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1.
Dis Colon Rectum ; 61(2): 239-249, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29337780

RESUMO

BACKGROUND: Because of its volume, adequate bowel preparation remains problematic in physically unfit patients. OBJECTIVE: This study aimed to compare a small-volume sodium picosulfate/magnesium citrate preparation with a 2-L ascorbic acid-enriched polyethylene glycol solution plus bisacodyl. DESIGN: This study has a noninferiority design, assuming that ascorbic acid-enriched polyethylene glycol solution plus bisacodyl is 70% efficacious in achieving an Ottawa score ≤7 and accepting a difference in success rate of <15% with a target enrollment of 146 patients per group. SETTING: This study was conducted in an outpatient department. PATIENTS: Patients referred for diagnostic colonoscopy were randomly assigned. Key exclusion criteria were severe kidney disease, ASA class ≥III, and hospital admission. INTERVENTION: Patients were randomly assigned to receive sodium picosulfate/magnesium citrate or ascorbic acid-enriched polyethylene glycol solution plus bisacodyl according to a split-dose regimen. Patients in the sodium picosulfate/magnesium citrate group received advice on the recommended 4-L fluid intake. Patients in the ascorbic acid-enriched polyethylene glycol solution plus bisacodyl group received 2 bisacodyl tablets 2 days before and advice on the additionally recommended 2-L fluid intake. MAIN OUTCOME MEASURES: To assess bowel-cleansing adequacy, the Ottawa, Aronchick, and Boston scores were used. Colonoscopy quality measures were obtained. Safety was assessed for a 30-day follow-up period. RESULTS: Overall, 341 patients (169 men, mean age 57.0 years; BMI 26.2 kg/m) were included. Comorbidities were present in 76.2% of patients, and 75.4% of patients used medication. An adequate Ottawa score was obtained in 81.4% and 75.8% of patients receiving ascorbic acid-enriched polyethylene glycol solution plus bisacodyl and sodium picosulfate/magnesium citrate (difference of 5.6% (95% CI, -3.5 to -14.6; p = 0.023)), showing noninferiority of the sodium picosulfate/magnesium citrate therapy. Ottawa segmental scores were lower for sodium picosulfate/magnesium citrate in the right and transverse colon. In both groups, successful ileocecal intubation was achieved in 95%. No medication-related adverse events were reported. LIMITATIONS: These results in a physically disabled ambulant population cannot be extrapolated to immobile, hospitalized patients. CONCLUSIONS: Sodium picosulfate/magnesium citrate proved to be noninferior to ascorbic acid-enriched polyethylene glycol solution plus bisacodyl in efficacy and safety. Timing of the colonoscopy and addition of bisacodyl to sodium picosulfate/magnesium citrate warrants further consideration. See Video Abstract at http://links.lww.com/DCR/A461.


Assuntos
Ácido Ascórbico/farmacologia , Bisacodil/farmacologia , Catárticos/farmacologia , Citratos/farmacologia , Ácido Cítrico/farmacologia , Neoplasias do Colo/diagnóstico por imagem , Colonoscopia/métodos , Compostos Organometálicos/farmacologia , Picolinas/farmacologia , Polietilenoglicóis/farmacologia , Adulto , Idoso , Ácido Ascórbico/administração & dosagem , Conscientização , Bisacodil/administração & dosagem , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Citratos/administração & dosagem , Ácido Cítrico/administração & dosagem , Pessoas com Deficiência , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Cooperação do Paciente , Picolinas/administração & dosagem , Polietilenoglicóis/administração & dosagem
2.
Gastroenterology ; 149(1): 110-118.e4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25836986

RESUMO

BACKGROUND & AIMS: Several case series have reported the effects of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). We assessed the efficacy and safety of FMT for patients with UC in a double-blind randomized trial. METHODS: Patients with mild to moderately active UC (n = 50) were assigned to groups that underwent FMT with feces from healthy donors or were given autologous fecal microbiota (control); each transplant was administered via nasoduodenal tube at the start of the study and 3 weeks later. The study was performed at the Academic Medical Center in Amsterdam from June 2011 through May 2014. The composite primary end point was clinical remission (simple clinical colitis activity index scores ≤2) combined with ≥1-point decrease in the Mayo endoscopic score at week 12. Secondary end points were safety and microbiota composition by phylogenetic microarray in fecal samples. RESULTS: Thirty-seven patients completed the primary end point assessment. In the intention-to-treat analysis, 7 of 23 patients who received fecal transplants from healthy donors (30.4%) and 5 of 25 controls (20.0%) achieved the primary end point (P = .51). In the per-protocol analysis, 7 of 17 patients who received fecal transplants from healthy donors (41.2%) and 5 of 20 controls (25.0%) achieved the primary end point (P = .29). Serious adverse events occurred in 4 patients (2 in the FMT group), but these were not considered to be related to the FMT. At 12 weeks, the microbiota of responders in the FMT group was similar to that of their healthy donors; remission was associated with proportions of Clostridium clusters IV and XIVa. CONCLUSIONS: In this phase 2 trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors and those who received their own fecal microbiota, which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. ClinicalTrials.gov Number: NCT01650038.


Assuntos
Terapia Biológica/métodos , Colite Ulcerativa/terapia , Fezes/microbiologia , Microbiota , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Intubação Gastrointestinal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
3.
Am J Gastroenterol ; 111(8): 1123-32, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27272012

RESUMO

OBJECTIVES: Electromagnetic (EM)-guided bedside placement of nasoenteral feeding tubes by nurses may improve efficiency and reduce patient discomfort and costs compared with endoscopic placement by gastroenterologists. However, evidence supporting this task shift from gastroenterologists to nurses is limited. We aimed to compare the effectiveness of EM-guided and endoscopic nasoenteral feeding tube placement. METHODS: We performed a multicenter randomized controlled non-inferiority trial in 154 adult patients who required nasoenteral feeding and were admitted to gastrointestinal surgical wards in five Dutch hospitals. Patients were randomly assigned (1:1) to undergo EM-guided or endoscopic nasoenteral feeding tube placement. The primary end point was the need for reinsertion of the feeding tube (e.g., after failed initial placement or owing to tube-related complications) with a prespecified non-inferiority margin of 10%. RESULTS: Reinsertion was required in 29 (36%) of the 80 patients in the EM-guided group and 31 (42%) of the 74 patients in the endoscopy group (absolute risk difference -6%, upper limit of one-sided 95% confidence interval 7%; P for non-inferiority=0.022). No differences were noted in success and complication rates. In the EM-guided group, there was a reduced time to start of feeding (424 vs. 535 min, P=0.001). Although the level of discomfort was higher in the EM-guided group (Visual Analog Scale (VAS) 3.9 vs. 2.0, P=0.009), EM-guided placement received higher recommendation scores (VAS 8.2 vs. 5.5, P=0.008). CONCLUSIONS: EM-guided bedside placement of nasoenteral feeding tubes by nurses was non-inferior to endoscopic placement by gastroenterologists in surgical patients and may be considered the preferred technique for nasoenteral feeding tube placement.


Assuntos
Endoscopia do Sistema Digestório/métodos , Nutrição Enteral/métodos , Gastroenterologistas , Gastroparesia/terapia , Intubação Gastrointestinal/métodos , Desnutrição/terapia , Enfermeiras e Enfermeiros , Complicações Pós-Operatórias/terapia , Idoso , Feminino , Humanos , Íleus/terapia , Imãs , Masculino , Pessoa de Meia-Idade , Pancreatite/terapia , Sistemas Automatizados de Assistência Junto ao Leito
4.
J Pediatr Gastroenterol Nutr ; 62(2): 353-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26252919

RESUMO

OBJECTIVES: Postpyloric feeding tube (PPFT) placement can be cumbersome. Fluoroscopic and endoscopic placements are required when unguided placement fails. We aimed to evaluate the feasibility and safety of PPFT placement in children, using an electromagnetic (EM) guided system as a rescue strategy in case unguided tube insertion fails. METHODS: In a single-center prospective study, we included all the children (weight >2.5 kg) in whom unguided PPFT placement failed between 2009 and 2012. EM guided PPFT placement was attempted before regular fluoroscopic and endoscopic placement was attempted, respectively. RESULTS: Forty-nine children were included (mean age 3.5 years). EM guided PPFT placement was successful in 82% of the children. No adverse events occurred. Age or indication for the PPFT did not influence the success rate of the procedure. A trend of a learning curve of 25 patients was noticed. Costs of EM placement were slightly higher than those of fluoroscopic placement in our hospital setting. CONCLUSION: With enough expertise, EM guided PPFT placement seems safe and can prevent fluoroscopic or endoscopic tube placement in 82% of children.


Assuntos
Duodeno , Fenômenos Eletromagnéticos , Endoscopia , Nutrição Enteral/métodos , Fluoroscopia , Intubação Gastrointestinal/métodos , Adolescente , Criança , Pré-Escolar , Análise Custo-Benefício , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos
5.
Gut ; 64(10): 1578-83, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25209657

RESUMO

OBJECTIVE: The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). DESIGN: After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in the Netherlands. Patients with previous small-bowel surgery were excluded. After bowel preparation, VCE was performed. The videos were read by two independent investigators. If significant lesions were detected, an endoscopic procedure was subsequently performed to obtain histology and, if possible, remove the lesion. RESULTS: In total, 200 patients (mean age 50 years (range 35-69), M/F 88/112), with proven mutations were included. These concerned MLH1 (n = 50), MSH2 (n = 68), MSH6 (n = 76), PMS2 (n = 3) and Epcam (n = 3) mutation carriers. In 95% of the procedures, caecal visualisation was achieved. Small-bowel neoplasia was detected in two patients: one adenocarcinoma (TisN0Mx) and one adenoma, both located in the duodenum. In another patient, a duodenal cancer (T2N0Mx) was diagnosed 7 months after a negative VCE. This was considered a lesion missed by VCE. All three neoplastic lesions were within reach of a conventional gastroduodenoscope. All patients with neoplasia were men, over 50 years of age and without a family history of small-bowel cancer. CONCLUSIONS: The prevalence of small-bowel neoplasia in asymptomatic patients with LS was 1.5%. All neoplastic lesions were located in the duodenum and within reach of conventional gastroduodenoscopy. Although VCE has the potential to detect these neoplastic lesions, small-bowel neoplasia may be missed. TRIAL REGISTRATION NUMBER: NCT00898768.


Assuntos
Endoscopia por Cápsula/métodos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Duodeno/patologia , Intestino Delgado/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos
6.
Gastrointest Endosc ; 81(2): 312-20, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25085333

RESUMO

BACKGROUND: Endoscopic volume reduction of the stomach may provide a minimally invasive alternative for surgical procedures in the treatment of obesity. OBJECTIVE: To assess safety and preliminary effectiveness in the first human application of a novel endoscopic stapling technique. DESIGN: Prospective, observational, phase 1 study. SETTING: Two university hospitals in The Netherlands. PATIENTS: Patients with a body mass index (BMI) of 40 to 45 kg/m(2) or 30 to 39.9 kg/m(2) with obesity-related comorbidity. INTERVENTIONS: Gastric volume reduction with an endoscopic stapler. MAIN OUTCOME MEASUREMENTS: Primary outcome measure was the prevalence of serious or mild adverse events. Reduction of excess body weight after 12 months was assessed as a secondary outcome measure for effectiveness of the procedure. RESULTS: Seventeen patients with a median BMI of 40.2 kg/m(2) (interquartile range [IQR] 37.6-42.8) underwent an endoscopic stapling procedure. Median procedure time was 123 minutes (IQR 95-129). No serious adverse events occurred. Adverse events were gastric pain (n = 7, range 1-3 days), sore throat (n = 4, 2-3 days), diarrhea (n = 4, 2-15 days), nausea (n = 3, 2-4 days), constipation (n = 4, 3-14 days), and vomiting (n = 3, 1-4 days). All adverse events were mild and resolved with conservative treatment within 15 days after surgery. The median percentage excess weight loss in the first year was 34.9% (IQR 17.8-46.6). LIMITATIONS: Limited number of patients. CONCLUSION: This first human application of this endoscopic stapler demonstrates that the procedure is technically feasible and safe. One hundred sixty plications were created in 17 patients without significant problems. Weight loss after 1 year is promising, but long-term follow-up and randomized, controlled studies should evaluate whether this procedure is an effective and durable minimally invasive endoscopic treatment for obesity. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01429194.).


Assuntos
Endoscopia , Gastroplastia/instrumentação , Obesidade/cirurgia , Grampeadores Cirúrgicos , Grampeamento Cirúrgico , Adulto , Índice de Massa Corporal , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Redução de Peso
7.
Gastrointest Endosc ; 81(4): 836-47.e2, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25660947

RESUMO

BACKGROUND: Nasoenteral tube feeding is frequently required in hospitalized patients to either prevent or treat malnutrition, but data on the optimal strategy of tube placement are lacking. OBJECTIVE: To compare the efficacy and safety of bedside electromagnetic (EM)-guided, endoscopic, and fluoroscopic placement of nasoenteral feeding tubes in adults. DESIGN: Systematic review of the literature. PATIENTS: Adult hospitalized patients requiring nasoenteral feeding. INTERVENTIONS: EM-guided, endoscopic, and/or fluoroscopic nasoenteral feeding tube placement. MAIN OUTCOME MEASUREMENTS: Success rate of tube placement and procedure- or tube-related adverse events. RESULTS: Of 354 screened articles, 28 studies were included. Data on 4056 patients undergoing EM-guided (n = 2921), endoscopic (n = 730), and/or fluoroscopic (n = 405) nasoenteral feeding tube placement were extracted. Tube placement was successful in 3202 of 3789 (85%) EM-guided procedures compared with 706 of 793 (89%) endoscopic and 413 of 446 (93%) fluoroscopic procedures. Reinsertion rates were similar for EM-guidance (270 of 1279 [21%] patients) and endoscopy (64 of 394 [16%] patients) or fluoroscopy (10 of 38 [26%] patients). The mean (standard deviation) procedure time was shortest with EM-guided placement (13.4 [12.9] minutes), followed by endoscopy and fluoroscopy (14.9 [8.7] and 16.2 [23.6] minutes, respectively). Procedure-related adverse events were infrequent (0.4%, 4%, and 3%, respectively) and included mainly epistaxis. The tube-related adverse event rate was lowest in the EM-guided group (36 of 242 [15%] patients), followed by fluoroscopy (40 of 191 [21%] patients) and endoscopy (115 of 384 [30%] patients) and included mainly dislodgment and blockage of the tube. LIMITATIONS: Heterogeneity and limited methodological quality of the included studies. CONCLUSION: Bedside EM-guided placement of nasoenteral feeding tubes appears to be as safe and effective as fluoroscopic or endoscopic placement. EM-guided tube placement by nurses may be preferred over more costly procedures performed by endoscopists or radiologists, but randomized studies are lacking.


Assuntos
Endoscopia Gastrointestinal , Fluoroscopia , Intubação Gastrointestinal/efeitos adversos , Intubação Gastrointestinal/métodos , Campos Magnéticos , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Duração da Cirurgia , Retratamento
8.
Endoscopy ; 47(4): 302-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25479562

RESUMO

BACKGROUND AND STUDY AIM: Intragastric balloons are used as a treatment for obesity. Much of the data collected on balloons has been in the context of clinical trials in academic medical centers or as a bridge to bariatric surgery in obesity centers. The aim of this study was to investigate the efficacy and safety of balloon treatment in private practice. PATIENTS AND METHODS: This was a retrospective analysis of 6-month weight loss data and balloon-related complications of patients referred to three private centers for obesity treatment. RESULTS: A total of 815 patients (131 males) were referred for balloon treatment (mean age 36.5 years, mean body weight 111.7 kg, mean body mass index [BMI] 38.1 kg/m(2)). The 6-month weight loss data were available for 672 patients. Mean weight loss was 20.9 kg (7.2 BMI units). A total of 372 patients visited the center only once following balloon placement (i. e. for balloon removal), but these patients still achieved a mean weight loss of 19.4 kg (6.6 BMI units). Successful weight loss (i. e. ≥ 10 %) was achieved in 85.0 %. Severe complications consisted of dehydration requiring hospital admission (n = 2; 0.2 %), and intestinal obstruction caused by balloon deflation, which required surgery (n = 2; 0.2 %). A total of 35 deflated balloons (4.3 %) were passed rectally without any adverse events. Severe esophagitis following balloon placement was diagnosed in 12 patients (1.5 %). A total of 53 patients (6.5 %) requested balloon removal during the first month. Nine balloons (1.1 %) were removed for medical reasons. CONCLUSION: In the private practice setting, intragastric balloons on their own, without an intensive lifestyle program and supportive consultations, resulted in safe and substantial weight losses, and may fill the therapeutic gap between pharmacotherapy and surgery.


Assuntos
Balão Gástrico , Obstrução Intestinal/etiologia , Obesidade Mórbida/terapia , Prática Privada , Redução de Peso , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Criança , Desidratação/etiologia , Endoscopia Gastrointestinal/efeitos adversos , Falha de Equipamento , Esofagite/etiologia , Feminino , Balão Gástrico/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Dig Dis Sci ; 59(8): 1717-25, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24563235

RESUMO

BACKGROUND: Endoscopy under midazolam sedation requires a 2-h recovery facility. AIM: To study the potential of shortening patients' stay without jeopardizing patients' safety by the use of the benzodiazepine-antagonist flumazenil in the everyday practice and to investigate the feasibility of a study comparing midazolam with recovery with midazolam-flumazenil and immediate discharge. METHODS: Consecutive ambulatory patients referred for endoscopy under midazolam sedation with ASA I or II, escorted by a person, were eligible. Flumazenil was given on arrival in the recovery room. Patients were discharged when adequate Aldrete scores and physical mobility were present. The next day, they were contacted by telephone. RESULTS: A total of 1,506 patients participated. They received 5 mg midazolam, while 887 patients also received 50 mcg fentanyl. The median dose of flumazenil was 0.2 mg. Oxygen desaturation (sO2 <92%) occurred in 15% during the procedure without an effect on recovery and discharge times. Patients left the department 65 min after the last midazolam administration. The majority (82.7%) were fully alert during their journey home. At home, 2.7% went to bed, 45.2% took a nap, and 40% undertook activities. Almost every patient (98.8%) liked the shortened recovery time. Three patients had an incident (fainting, fall, and near-fall) without consequences. Based on this low incidence, a non-inferiority comparison of midazolam-flumazenil with midazolam-recovery would require a total of 32,650 patients. CONCLUSIONS: Administration of flumazenil resulted in a safe shortening of the recovery period and offers the possibility for substantial savings in time, space, and nurse resources. A non-inferiority comparison will not be practicable.


Assuntos
Antídotos/administração & dosagem , Sedação Consciente/métodos , Endoscopia do Sistema Digestório , Flumazenil/administração & dosagem , Hipnóticos e Sedativos/antagonistas & inibidores , Midazolam/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sedação Consciente/efeitos adversos , Endoscopia do Sistema Digestório/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Satisfação do Paciente , Recuperação de Função Fisiológica , Adulto Jovem
11.
J Med Genet ; 50(1): 59-64, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23240097

RESUMO

BACKGROUND: Although Peutz-Jeghers syndrome (PJS) is known to be associated with pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We therefore aimed to determine the PC risk in a large cohort of Dutch PJS patients. METHODS: PJS was defined by diagnostic criteria recommended by the WHO, a proven LKB1 mutation, or both. All patients with a presumptive diagnosis of pancreatic, ampullary or distal bile duct cancer were identified. Cases were reviewed clinically, radiologically and immunohistochemically. Cumulative PC risks were calculated by Kaplan-Meier analysis and relative risks by Poisson regression analysis. RESULTS: We included 144 PJS patients (49% male) from 61 families (5640 person years follow-up). Seven (5%) patients developed PC at a median age of 54 years. Four patients (3%) were diagnosed with distal bile duct (n=2) or ampullary cancer (n=2) at a median age of 55 years. The cumulative risk for PC was 26% (95% CI 4% to 47%) at age 70 years and relative risk was 76 (95% CI 36 to 160; p<0.001). The cumulative risk for pancreatico-biliary cancer was 32% (95% CI 11% to 52%) at age 70 years, with a relative risk of 96 (95% CI 53 to 174; p<0.001). CONCLUSIONS: PJS patients have a highly increased risk for pancreatico-biliary cancer. Therefore, patients are eligible for surveillance within well defined research programmes to establish the benefit of such surveillance.


Assuntos
Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/epidemiologia , Síndrome de Peutz-Jeghers/complicações , Risco , Adulto , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Síndrome de Peutz-Jeghers/epidemiologia , Vigilância da População , Adulto Jovem
12.
Carcinogenesis ; 34(7): 1611-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23430953

RESUMO

Peutz-Jeghers syndrome (PJS) is caused by mutations in the LKB1 gene. It is characterized by gastrointestinal polyposis and an increased cancer risk, mainly in the gastrointestinal tract. Mechanisms of PJS-associated carcinogenesis are unclear. We investigated the involvement of candidate genes and molecular pathways in PJS-associated gastrointestinal cancers and dysplastic hamartomas. Cases were selected from the Dutch PJS cohort. Available tissue was immunostained for phospho-S6, ß-catenin, P53 and SMAD4. DNA was isolated from carcinoma tissue and dysplastic and non-dysplastic areas of hamartomas specifically. Mutation analyses were done for BRAF, KRAS and P53, and loss of heterozygosity (LOH) analyses for LKB1 and P53. Twenty-four of 144 patients (17%) developed 26 gastrointestinal malignancies at a median age of 49 years (interquartile range: 35-60). Eleven of 792 hamartomas (1.4%) of 9 patients were classified as dysplastic. LOH of LKB1 was detected in three of six (50%) carcinomas and in the dysplastic part of three of five (60%) hamartomas. Aberrant P53 expression was observed in 8 of 15 (53%) carcinomas. Six carcinomas with P53 overexpression harboured a P53 mutation, with loss of the remaining wild-type allele in four. Two hamartomas showing P53 overexpression in high-grade dysplastic foci harboured a P53 mutation with LOH. Loss of nuclear SMAD4 was observed in high-grade dysplastic foci of two of four (50%) hamartomas, in contrast to low-grade dysplastic foci (0/4) and non-dysplastic epithelium. Our findings suggest a role for mutant P53 in PJS-associated gastrointestinal carcinogenesis. Inactivation of transforming growth factor-ß/bone morphogenetic protein signalling and complete loss of LKB1 might be involved in dysplastic transformation of gastrointestinal hamartomas specifically.


Assuntos
Neoplasias Gastrointestinais/genética , Regulação Neoplásica da Expressão Gênica , Hamartoma/genética , Síndrome de Peutz-Jeghers/genética , Quinases Proteína-Quinases Ativadas por AMP , Adulto , Alelos , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Neoplasias Gastrointestinais/patologia , Mutação em Linhagem Germinativa , Hamartoma/patologia , Humanos , Imuno-Histoquímica , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Países Baixos , Linhagem , Síndrome de Peutz-Jeghers/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Gastrointest Endosc ; 77(4): 542-50, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23352497

RESUMO

BACKGROUND: The Spigelman classification stratifies cancer risk in familial adenomatous polyposis (FAP) patients with duodenal adenomatosis. High-resolution endoscopy (HRE) and narrow-band imaging (NBI) may identify lesions at high risk. OBJECTIVE: To compare HRE and NBI for the detection of duodenal and gastric polyps and to characterize duodenal adenomas harboring advanced histology with HRE and NBI. DESIGN: Prospective, nonrandomized, comparative study. Retrospective image evaluation study. SETTING: Tertiary-care center. PATIENTS: Thirty-seven FAP patients undergoing surveillance upper endoscopies. INTERVENTION: HRE endoscopy was followed by NBI. The number of gastric polyps and Spigelman staging were compared. Duodenal polyp images were systematically reviewed in a learning and validation phase. MAIN OUTCOME MEASUREMENTS: Number of gastric and duodenal polyps detected by HRE and NBI and prevalence of specific endoscopic features in duodenal adenomas with advanced histology. RESULTS: NBI did not identify additional gastric polyps but detected more duodenal adenomas in 16 examinations, resulting in upgrades of the Spigelman stage in 2 cases (4.4%). Pictures of 168 duodenal adenomas (44% advanced histology) were assessed. In the learning phase, 3 endoscopic features were associated with advanced histology: white color, enlarged villi, and size ≥1 cm. Only size ≥1 cm was confirmed in the validation phase (odds ratio 3.0; 95% confidence interval, 1.2-7.4). LIMITATIONS: Nonrandomized study, scant number of high-grade dysplasia adenomas. CONCLUSION: Inspection with NBI did not lead to a clinically relevant upgrade in the Spigelman classification and did not improve the detection of gastric polyps in comparison with HRE. The only endoscopic feature that predicted advanced histology of a duodenal adenoma was size ≥1 cm.


Assuntos
Polipose Adenomatosa do Colo/patologia , Neoplasias Duodenais/patologia , Endoscopia Gastrointestinal/métodos , Pólipos Intestinais/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos/patologia , Estudos Prospectivos , Estudos Retrospectivos
14.
Gastrointest Endosc ; 77(4): 617-23, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23321338

RESUMO

BACKGROUND: Insufficient detection of proximal serrated polyps (PSP) might explain the occurrence of a proportion of interval carcinomas in colonoscopy surveillance programs. OBJECTIVE: To compare PSP detection among endoscopists and to identify patient-related and endoscopist-related factors associated with PSP detection. DESIGN: Prospective study in unselected patients. SETTING: Colonoscopy screening program for colorectal cancer at two academic medical centers. PATIENTS: Asymptomatic consecutive screening participants (aged 50-75 years). INTERVENTION: Colonoscopies were performed by 5 experienced endoscopists. All detected polyps were removed. Multiple colonoscopy quality indicators were prospectively recorded. MAIN OUTCOME MEASUREMENTS: We compared PSP detection among endoscopists by calculating odds ratios (OR) with logistic regression analysis. Logistic regression also was used to identify patient features and colonoscopy factors associated with PSP detection. RESULTS: A total of 1354 patients underwent a complete screening colonoscopy: 1635 polyps were detected, of which 707 (43%) were adenomas and 685 (42%) were serrated polyps, including 215 PSPs. In 167 patients (12%) 1 or more PSPs were detected. The PSP detection rate differed significantly among endoscopists, ranging from 6% to 22% (P < .001). Longer withdrawal time (OR 1.12; 95% confidence interval, 1.10-1.16) was significantly associated with better PSP detection, whereas patient age, sex, and quality of bowel preparation were not. LIMITATIONS: Limited number of highly experienced endoscopists. CONCLUSION: The PSP detection rate differs among endoscopists. Longer withdrawal times are associated with better PSP detection, but patient features are not. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR1888.).


Assuntos
Adenoma/patologia , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Idoso , Colonoscopia/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Fatores de Tempo
15.
Gut ; 61(10): 1426-34, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22187070

RESUMO

OBJECTIVE: Conventional colonoscopy (CC) is considered the reference standard for detection of colorectal neoplasia, but it can still miss a substantial number of adenomas. The use of a transparent plastic cap may improve colonic visualisation. Cap-assisted colonoscopy (CAC) was compared with CC for adenoma detection. Secondary outcomes were caecal intubation time, caecal intubation rate and the degree of discomfort of colonoscopy. DESIGN: This is a parallel, randomised, controlled trial at two centres. Asymptomatic participants (aged 50-75 years) in a primary colonoscopy screening programme were consecutively invited. Consenting subjects were 1:1 randomised to either CAC or CC. All colonoscopies were performed by experienced endoscopists (≥ 1000 colonoscopies) who were trained in CAC. Colonoscopy quality indicators were prospectively recorded. RESULTS: A total of 1380 participants were randomly allocated to CC (N=694) or CAC (N=686). Caecal intubation rate was comparable in the two groups (98% vs 99%; p=0.29). Caecal intubation time was significantly lower in the CAC group: 7.7 ± 5.0 min with CAC vs 8.9 ± 6.2 min with CC (p<0.001) (values mean ± SD). Adenoma detection rates of all endoscopists were ≥ 20%. The proportion of subjects with at least one adenoma was similar in the two groups (28% vs 28%; RR 0.98; 95% CI 0.82 to 1.16), as well as the mean number of adenomas per subject (0.49 ± 1.05 vs 0.50 ± 1.03; p=0.91). Detection of small size, flat and proximally located adenomas was comparable. CAC participants had lower Gloucester Comfort Scores during colonoscopy (2.2 ± 1.0 vs 2.0 ± 1.0; p=0.03). CONCLUSION: CAC does not improve adenoma detection, but does reduce caecal intubation time by more than 1 min and does lessen the degree of discomfort during colonoscopy.


Assuntos
Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Colonoscopia/instrumentação , Idoso , Colonoscopia/métodos , Colonoscopia/normas , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Satisfação do Paciente/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde , Fatores de Tempo
16.
J Clin Gastroenterol ; 46(7): 533-44, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22772735

RESUMO

The prevalence of obesity is rising progressively, even among older age groups. By the year 2030 to 2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years or older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20% and 30% dependent on the model used. This means 20.9 million obese 60 years or older people in the United States in 2010 and 32 million obese elders in 2015 in EU. Although cutoff values of body mass index, waist circumference, and percentages of fat mass have not been defined for the elderly, it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a body mass index >30 kg/m(2). Thus, treatment should only be offered to patients who are obese rather than overweight and who have functional impairments, metabolic complications, or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should minimize muscle and bone loss and vigilance as regards the development of sarcopenic obesity--a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone--is important. Lifestyle intervention should be the first step and consists of a diet with a 500 kcal energy deficit and an adequate intake of protein of high biological quality, together with calcium and vitamin D, behavioral therapy, and multicomponent exercise. Multicomponent exercise includes flexibility training, balance training, aerobic exercise, and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older were excluded.


Assuntos
Envelhecimento/fisiologia , Obesidade/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Comportamental , Índice de Massa Corporal , Dieta , Europa (Continente)/epidemiologia , Exercício Físico/fisiologia , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Obesidade/terapia , Sarcopenia/epidemiologia , Estados Unidos/epidemiologia
17.
Gut ; 60(2): 141-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21205875

RESUMO

BACKGROUND: Peutz-Jeghers syndrome (PJS) is associated with an increased cancer risk. As the determination of optimal surveillance strategies is hampered by wide ranges in cancer risk estimates and lack of data on cancer-related mortality, we assessed cancer risks and mortality in a large cohort of patients with PJS. METHODS: Dutch PJS patients were included in this cohort study. Patients were followed prospectively between January 1995 and July 2009, and clinical data from the period before 1995 were collected retrospectively. Data were obtained by interview and chart review. Cumulative cancer risks were calculated by Kaplan-Meier analysis and relative cancer and mortality risks by Poisson regression analysis. RESULTS: We included 133 PJS patients (48% males) from 54 families, contributing 5004 person-years of follow-up. 49 cancers were diagnosed in 42 patients (32%), including 25 gastrointestinal (GI) cancers. The median age at first cancer diagnosis was 45 years. The cumulative cancer risk was 20% at age 40 (GI cancer 12%), increasing to 76% at age 70 (GI cancer 51%). Cumulative cancer risks were higher for females than for males (p=0.005). The relative cancer risk was higher in PJS patients than in the general population (HR 8.96; 95% CI 6.46 to 12.42), and higher among female (HR 20.40; 95% CI 13.43 to 30.99) than among male patients (HR 4.76; 95% CI 2.82 to 8.04). 42 patients had died at a median age of 45 years, including 28 cancer-related deaths (67%). Mortality was increased in our cohort compared to the general population (HR 3.50; 95% CI 2.57 to 4.75). CONCLUSIONS: PJS patients carry high cancer risks, leading to increased mortality. The malignancies occur particularly in the GI tract and develop at young age. These results justify surveillance in order to detect malignancies in an early phase to improve outcome.


Assuntos
Síndrome de Peutz-Jeghers/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Neoplasias da Mama/epidemiologia , Métodos Epidemiológicos , Feminino , Neoplasias Gastrointestinais/epidemiologia , Neoplasias dos Genitais Femininos/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/epidemiologia , Países Baixos/epidemiologia , Síndrome de Peutz-Jeghers/diagnóstico
18.
Gut ; 59(8): 1094-100, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19710031

RESUMO

BACKGROUND AND AIMS: Patients with hyperplastic polyposis syndrome (HPS) receive endoscopic surveillance to prevent malignant progression of polyps. However, the optimal treatment and surveillance protocol for these patients is unknown. The aim of this study was to describe the clinical and pathological features of a large HPS cohort during multiple years of endoscopic surveillance. METHODS: Databases were searched for patients with HPS, who were analysed retrospectively. Endoscopy reports and histopathology reports were collected to evaluate frequency of endoscopic surveillance and to obtain information regarding polyp and the presence of colorectal cancer (CRC). RESULTS: In 77 patients with HPS, 1984 polyps were identified during a mean follow-up period of 5.6 years (range: 0.5-26.6). In 27 (35%) patients CRC was detected of which 22 (28.5%) at initial endoscopy. CRC was detected during surveillance in five patients (cumulative incidence: 6.5%) after a median follow-up time of 1.3 years and a median interval of 11 months. Of these interval CRCs, 4/5 were detected in diminutive serrated polyps (range: 4-16 mm). The cumulative risk of CRC under surveillance was 7% at 5 years. At multivariate logistic regression, an increasing number of hyperplastic polyps (OR 1.05, p=0.013) and serrated adenomas (OR 1.09, p=0.048) was significantly associated with CRC presence. CONCLUSIONS: HPS patients undergoing endoscopic surveillance have an increased CRC risk. The number of serrated polyps is positively correlated with the presence of CRC in HPS, thus supporting a 'serrated pathway' to CRC. To prevent malignant progression, adequate detection and removal of all polyps seems advisable. If this is not feasible, surgical resection should be considered.


Assuntos
Neoplasias Colorretais/diagnóstico , Polipose Intestinal/diagnóstico , Adulto , Idoso , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Progressão da Doença , Métodos Epidemiológicos , Feminino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/epidemiologia , Hiperplasia/patologia , Polipose Intestinal/epidemiologia , Polipose Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Síndrome
19.
Clin Gastroenterol Hepatol ; 8(8): 731-3, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20399906

RESUMO

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is an inherited disease affecting approximately 1:10,000 newborns, characterized by the formation of numerous adenomas in the digestive tract. Surveillance and prophylactic treatment of colonic and duodenal manifestations of this disease have much influenced disease course and survival. In more recent years, it has become clear that adenoma formation in FAP patients is not restricted to the colon and duodenum. Accordingly, these adenomas might have malignant potential, although the actual risk is unknown. METHODS: We report 3 cases of jejunal carcinoma in FAP patients and review data on incidence, prognosis, and risk factors of jejunoileal adenoma and carcinoma development in FAP. RESULTS: Three patients with FAP aged 71, 57, and 59 years developed advanced duodenal adenomatosis and a jejunal carcinoma, which was associated with poor prognosis in 2 patients. CONCLUSIONS: Jejunal adenomas in FAP patients are reported occasionally and can progress into adenocarcinoma with a poor prognosis. In the future a subset of FAP patients benefitting from jejunal surveillance should be identified.


Assuntos
Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Polipose Adenomatosa do Colo/complicações , Neoplasias do Jejuno/diagnóstico , Adenocarcinoma/epidemiologia , Adenoma/epidemiologia , Polipose Adenomatosa do Colo/epidemiologia , Adulto , Humanos , Incidência , Neoplasias do Jejuno/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
20.
Gastrointest Endosc ; 71(4): 728-36, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20170911

RESUMO

BACKGROUND: The early institution of feeding in patients who need postpyloric feeding tubes is often hampered by a limited availability of endoscopists experienced in safe tube positioning. OBJECTIVE: To test the feasibility of having nurses place postpyloric feeding tubes by using a universal path finding system device. DESIGN: Prospective study. SETTING: Academic hospital. PATIENTS: The success rate and learning curve of a senior nurse placing postpyloric feeding tubes in 50 patients was studied, followed by a study in 160 patients on the success rates and learning curves of 4 inexperienced nurses instructed by the senior nurse. Finally, the success rate of postpyloric feeding tube placement by the senior nurse in 50 critically ill patients was investigated. INTERVENTION: Postpyloric feeding tube positioning by nurses using an electromagnetic universal path-finding system device enabling them to follow the path of the tip of the feeding tube on a monitor screen. MAIN OUTCOME MEASUREMENTS: Success was defined by postpyloric positioning of the feeding tube. The ultimate aim was to reach at least the duodenojejunal flexure. RESULTS: In the first part, the senior nurse was successful in 72% of cases. There was a clear learning curve. In the second part, the 4 newly instructed nurses had a success rate of 89.4% without an evident learning curve. In the third part, successful feeding tube positioning was achieved in 78% of critically ill patients. Of the 217 successfully positioned tubes, 74% reached at least the duodenojejunal flexure. In half of the unsuccessful cases, an explanation for the failure was found at endoscopy. No complications were seen. LIMITATIONS: The generalization to less-specialized hospitals should be investigated. CONCLUSION: Postpyloric positioning of feeding tubes by nurses at the bedside without endoscopy is feasible and safe. Nurses may take over some of the tasks of doctors in a time of high endoscopic needs.


Assuntos
Cuidados Críticos , Fenômenos Eletromagnéticos , Nutrição Enteral/instrumentação , Nutrição Enteral/enfermagem , Processamento de Imagem Assistida por Computador/instrumentação , Intubação Gastrointestinal/instrumentação , Intubação Gastrointestinal/enfermagem , Gravação em Vídeo , Adulto , Idoso , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Capacitação em Serviço , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Antro Pilórico
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