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1.
Ann Surg ; 279(4): 671-678, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37450701

RESUMO

OBJECTIVE: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis. BACKGROUND: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention. METHODS: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications. RESULTS: Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33-2.28; P =0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56-7.37; P =0.34). The median number of additional interventions was 0 (IQR 0-0) in both groups ( P =0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P =0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar. CONCLUSIONS: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach. TRIAL REGISTRATION: ISRCTN33682933.


Assuntos
Pancreatite Necrosante Aguda , Qualidade de Vida , Humanos , Resultado do Tratamento , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/cirurgia , Antibacterianos/uso terapêutico , Drenagem/métodos
2.
Fam Cancer ; 22(4): 403-411, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37171677

RESUMO

Individuals with Lynch syndrome have an increased colorectal cancer risk, hence, biennial colonoscopy surveillance is recommended. We aimed to investigate patients' perception and preferences regarding surveillance, and to further explore compliance behaviour. Individuals with Lynch syndrome received a validated survey evaluating experiences of their three most recent colonoscopies. Individuals were non-compliant to surveillance if the interval between colonoscopies differed ≥ 6 months from the recommended interval. In total, 197 of 291 (68%) invited individuals returned the survey. They mostly underwent colonoscopy biennially (99%), under mild sedation (79%) and with bowel preparation performed by Moviprep® (99%). Surveillance was perceived as impacting quality of life in 21%, and as moderately to extremely burdensome in 57%, particularly in those below age 40. To lower the burden, patients prioritised improvements in volume and taste of bowel preparation, laxation-related bowel movements, waiting times, and a more personal and respectful approach of endoscopic staff. Additionally, many individuals (60%) would favour less-invasive surveillance modalities such as biomarkers. In total, 28% of individuals had delayed colonoscopy surveillance, predominantly for patient-related reasons. An additional 10% considered quitting/postponing surveillance. Upon multivariable analysis, patient-related delay was associated with low and medium education, history of ≤ 4 colonoscopies and having no hospital recall-system. Colonoscopy surveillance in Lynch syndrome is often experienced as burdensome, and frequently delayed. We identified determinants of surveillance behaviour in this population, and present potential interventions to reduce the burden and non-compliance rates.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Humanos , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Qualidade de Vida , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle
3.
HPB (Oxford) ; 24(10): 1634-1641, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35562255

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography-guided tissue acquisition (EUS-TA) are increasingly performed in the same session in patients with malignant biliary obstruction. In this retrospective analysis, we investigated adverse events (AE) after same session ERCP and EUS-TA. METHODS: Patients with malignant distal biliary obstruction who underwent EUS-TA and/or ERCP with self-expandable metal stent (SEMS) placement from January 2015 to April 2020 were included. Primary outcome was post-procedural pancreatitis (PPP). Secondary outcomes were other procedure-related AE. RESULTS: We included 494 patients, of which 118 patients (24%) underwent same session EUS-TA+ERCP, 51 patients (10%) underwent separate session EUS-TA & ERCP, 90 patients (18%) ERCP-only and 235 patients (48%) EUS-TA only. PPP occurred in 22 patients (19%) after same session EUS-TA+ERCP and in 6 patients (12%) after separate EUS-TA & ERCP (p = 0.270). When adjusted for other known risk factors (i.e., difficult procedure), the difference in PPP remained non-significant (adjusted odds ratio 1.74 (95%-CI 0.65-4.67, p = 0.268). The incidence of other AE was similar, although the overall AE rate was significantly higher after same session EUS-TA+ERCP (36% vs. 20%, p = 0.030). CONCLUSION: Same session EUS-TA+ERCP did not significantly increase the incidence of PPP, although overall AE were significantly higher. These data warrant further prospective studies.


Assuntos
Colestase , Anormalidades do Sistema Digestório , Pancreatite , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Endossonografia , Colestase/etiologia , Colestase/complicações , Estudos Prospectivos , Estudos Retrospectivos , Ultrassonografia de Intervenção/efeitos adversos , Pancreatite/complicações , Pancreatite/diagnóstico por imagem
4.
JGH Open ; 6(1): 57-62, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35071789

RESUMO

BACKGROUND AND AIMS: Percutaneous endoscopic gastrostomy (PEG) is indicated for prolonged enteral nutrition. This study aimed to analyze the outcome and to identify potential risk factors for complications in PEG procedures. METHODS: A single-center retrospective analysis of the performed PEG procedures during the period January 2010 till January 2020. RESULTS: A PEG placement procedure was performed in 854 patients (64.1% male) and was successful in 833 (97.5%). In total, 513 push (61.6%) and 320 pull (38.6%) PEGs were placed. The mean age was 60.7 years, and the median follow-up was 267 days. The push PEG was associated with peri-procedural bleeding (P = 0.002) and tube dislodgements (P < 0.001), while the pull PEG was significantly associated with buried bumpers (P < 0.001), infected placement sites (P = 0.019), and granulation tissue formation (P = 0.044). The PEG-related mortality rate was 0.2%, but the overall 30-day mortality was 4.0%. CONCLUSION: The current study showed that the push and pull PEG placements are both safe and feasible procedures, with a low PEG-related mortality. Buried bumpers, infected placement sites, and granulation tissue formation are more often seen in the pull PEG, while the push PEG is associated with periprocedural bleeding and tube dislodgements. These complications should be taken into account and there is a need for a prospective trial to identify superiority between the PEG methods.

5.
Gut ; 71(3): 553-560, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34086597

RESUMO

OBJECTIVE: Despite regular colonoscopy surveillance, colorectal cancers still occur in patients with Lynch syndrome. Thus, detection of all relevant precancerous lesions remains very important. The present study investigates Linked Colour imaging (LCI), an image-enhancing technique, as compared with high-definition white light endoscopy (HD-WLE) for the detection of polyps in this patient group. DESIGN: This prospective, randomised controlled trial was performed by 22 experienced endoscopists from eight centres in six countries. Consecutive Lynch syndrome patients ≥18 years undergoing surveillance colonoscopy were randomised (1:1) and stratified by centre for inspection with either LCI or HD-WLE. Primary outcome was the polyp detection rate (PDR). RESULTS: Between January 2018 and March 2020, 357 patients were randomised and 332 patients analysed (160 LCI, 172 HD-WLE; 6 excluded due to incomplete colonoscopies and 19 due to insufficient bowel cleanliness). No significant difference was observed in PDR with LCI (44.4%; 95% CI 36.5% to 52.4%) compared with HD-WLE (36.0%; 95% CI 28.9% to 43.7%) (p=0.12). Of the secondary outcome parameters, more adenomas were found on a patient (adenoma detection rate 36.3%; vs 25.6%; p=0.04) and a colonoscopy basis (mean adenomas per colonoscopy 0.65 vs 0.42; p=0.04). The median withdrawal time was not statistically different between LCI and HD-WLE (12 vs 11 min; p=0.16). CONCLUSION: LCI did not improve the PDR compared with HD-WLE in patients with Lynch syndrome undergoing surveillance. The relevance of findings more adenomas by LCI has to be examined further. TRIAL REGISTRATION NUMBER: NCT03344289.


Assuntos
Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico por imagem , Aumento da Imagem , Adenoma/patologia , Adulto , Idoso , Cor , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
N Engl J Med ; 385(15): 1372-1381, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34614330

RESUMO

BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).


Assuntos
Antibacterianos/uso terapêutico , Drenagem , Pâncreas/patologia , Pancreatite Necrosante Aguda/terapia , Tempo para o Tratamento , Idoso , Terapia Combinada , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/patologia , Pancreatite Necrosante Aguda/cirurgia
7.
J Exp Clin Cancer Res ; 40(1): 161, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964942

RESUMO

BACKGROUND: Improvement of radiotherapy efficacy requires better insight in the dynamic responses that occur during irradiation. Here, we aimed to identify the molecular responses that are triggered during clinically applied fractionated irradiation. METHODS: Gene expression analysis was performed by RNAseq or microarray analysis of cancer cells or xenograft tumors, respectively, subjected to 3-5 weeks of 5 × 2 Gy/week. Validation of altered gene expression was performed by qPCR and/or ELISA in multiple cancer cell lines as well as in pre- and on-treatment biopsies from esophageal cancer patients ( NCT02072720 ). Targeted protein inhibition and CRISPR/Cas-induced gene knockout was used to analyze the role of type I interferons and cGAS/STING signaling pathway in the molecular and cellular response to fractionated irradiation. RESULTS: Gene expression analysis identified type I interferon signaling as the most significantly enriched biological process induced during fractionated irradiation. The commonality of this response was confirmed in all irradiated cell lines, the xenograft tumors and in biopsies from esophageal cancer patients. Time-course analyses demonstrated a peak in interferon-stimulated gene (ISG) expression within 2-3 weeks of treatment. The response was accompanied by a variable induction of predominantly interferon-beta and/or -lambda, but blocking these interferons did not affect ISG expression induction. The same was true for targeted inhibition of the upstream regulatory STING protein while knockout of STING expression only delayed the ISG expression induction. CONCLUSIONS: Collectively, the presented data show that clinically applied fractionated low-dose irradiation can induce a delayed type I interferon response that occurs independently of interferon expression or STING signaling. These findings have implications for current efforts that aim to target the type I interferon response for cancer treatment.


Assuntos
Neoplasias Esofágicas/radioterapia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Interferon Tipo I/genética , Proteínas de Membrana/genética , Animais , Astrocitoma/genética , Astrocitoma/imunologia , Astrocitoma/metabolismo , Astrocitoma/radioterapia , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Feminino , Células HT29 , Humanos , Imunidade/efeitos da radiação , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Mol Oncol ; 15(4): 901-914, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33506581

RESUMO

Identification of molecular predictive markers of response to neoadjuvant chemoradiation could aid clinical decision-making in patients with localized oesophageal cancer. Therefore, we subjected pretreatment biopsies of 75 adenocarcinoma (OAC) and 16 squamous cell carcinoma (OSCC) patients to targeted next-generation DNA sequencing, as well as biopsies of 85 OAC and 20 OSCC patients to promoter methylation analysis of eight GI-specific genes, and subsequently searched for associations with histopathological response and disease-free (DFS) and overall survival (OS). Thereby, we found that in OAC, CSMD1 deletion (8%) and ETV4 amplification (5%) were associated with a favourable histopathological response, whereas SMURF1 amplification (5%) and SMARCA4 mutation (7%) were associated with an unfavourable histopathological response. KRAS (15%) and GATA4 (7%) amplification were associated with shorter OS. In OSCC, TP63 amplification (25%) and TFPI2 (10%) gene promoter methylation were associated with an unfavourable histopathological response and shorter DFS (TP63) and OS (TFPI2), whereas CDKN2A deletion (38%) was associated with prolonged OS. In conclusion, this study identified candidate genetic biomarkers associated with response to neoadjuvant chemoradiotherapy in patients with localized oesophageal cancer.


Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Terapia Neoadjuvante , Medicina de Precisão , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Ilhas de CpG , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Helicases/genética , Metilação de DNA , Intervalo Livre de Doença , Neoplasias Esofágicas/genética , Feminino , Fator de Transcrição GATA4/genética , Glicoproteínas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Proteínas Nucleares/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética
9.
Gastroenterology ; 158(5): 1326-1333, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31926173

RESUMO

BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Proteínas de Ligação a DNA/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Adenoma/diagnóstico , Adenoma/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , Feminino , Finlândia/epidemiologia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Países Baixos/epidemiologia , Estudos Prospectivos , beta Catenina/genética
10.
Gastroenterology ; 155(5): 1400-1409.e2, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30063918

RESUMO

BACKGROUND & AIMS: Patients with Lynch syndrome are at high risk for developing colorectal cancer (CRC). Regular colonoscopic surveillance is recommended, but there is no international consensus on the appropriate interval. We investigated whether shorter intervals are associated with lower CRC incidence and detection at earlier stages by comparing the surveillance policies in Germany, which evaluates patients by colonoscopy annually, in the Netherlands (patients evaluated at 1-2-year intervals), and Finland (patients evaluated at 2-3-year intervals). METHODS: We collected data from 16,327 colonoscopic examinations (conducted from 1984 through 2015) of 2747 patients with Lynch syndrome (pathogenic variants in the MLH1, MSH2, or MSH6 genes) from the German HNPCC Consortium, the Dutch Lynch Syndrome Registry, and the Finnish Lynch Syndrome Registry. Our analysis included 23,309 person-years of cumulative observation time. Time from the index colonoscopy to incident CRC or adenoma was analyzed using the Kaplan-Meier method; groups were compared using the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk (diagnosis of CRC before the index colonoscopy, sex, mutation, age, and presence of adenoma at the index colonoscopy). RESULTS: The 10-year cumulative CRC incidence ranged from 4.1% to 18.4% in patients with low- and high-risk profiles, respectively, and varied with age, sex, mutation, and prior detection of CRC or adenoma. Observed colonoscopy intervals were largely in accordance with the country-specific recommendations. We found no significant differences in cumulative CRC incidence or CRC stage at detection among countries. There was no significant association between CRC stage and time since last colonoscopy. CONCLUSIONS: We did not find a significant reduction in CRC incidence or stage of detection in Germany (annual colonoscopic surveillance) than in countries with longer surveillance intervals (the Netherlands, with 1-2-year intervals, and Finland, with 2-3-year intervals). Overall, we did not find a significant association of the interval with CRC risk, although age, sex, mutation, and prior neoplasia were used to individually modify colonoscopy intervals. Studies are needed to develop and validate risk-adapted surveillance strategies and to identify patients who benefit from shorter surveillance intervals.


Assuntos
Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais/diagnóstico , Adulto , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais
12.
Endosc Int Open ; 3(5): E400-4, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26528492

RESUMO

BACKGROUND AND STUDY AIMS: Ultra-thin caliber endoscopes (UTCEs) are versatile and applicable in various conditions. However, only limited data exist on the actual daily clinical use of UTCEs. The aim of our study was to determine indications for UTCEs in a large patient cohort. In turn, our 2 main objectives were (1) to evaluate patient comfort and safety and (2) to determine benefits and potential advantages associated with the use of UTCEs in this same cohort. PATIENTS AND METHODS: We performed a retrospective analysis of our prospective database of 1028 procedures with UTCEs in 457 patients. All procedures were carried out in the Department of Gastroenterology and Hepatology, VU University Medical Center, in Amsterdam, the Netherlands, between May 2008 and May 2014. In these procedures, either the Fujinon (Tokyo, Japan) EG-530N UTCE or the Olympus (Tokyo, Japan) GIF N-180 UTCE was used. RESULTS: Mean (standard deviation [SD]) age of patients was 64 (20) years, and most (60 %) of the patients were men. Most (61 %) of the underlying diseases, requiring endoscopic procedures, were found in the esophagus. Of the procedures performed, 91 % were successful, and 82 % were therapeutic. In comparison with regular endoscopes, the most important advantage of the UTCE was the ability to pass a stenosis (37 %), followed by nasogastric feeding tube placement (13 %). Newer and more innovative uses of the UTCE were percutaneous endoscopic gastrostomy (PEG)-jejunal extension placement with endoscope introduction through existing PEG tract, retrograde esophageal introduction through existing PEG tract, inspection of colonic neovagina stenosis, and direct inspection of the common bile duct. CONCLUSIONS: In everyday clinical practice, the UTCE has specific advantages over conventional endoscopes because of its small caliber. The 3 main advantages are (1) introduction of high-grade strictures; (2) introduction of fistulas, including PEG fistula; and (3) increased patient comfort. The endoscopist should appreciate these advantages and consider use of the UTCE accordingly.

13.
Clin Cancer Res ; 21(20): 4569-75, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26056353

RESUMO

PURPOSE: Epidermal growth factor receptor (EGFR) inhibitors may improve both the therapeutic efficacy of radiotherapy and the radiosensitizing activity of gemcitabine. Based on this rationale and the nonoverlapping toxicity profiles of gemcitabine and the monoclonal EGFR antibody panitumumab, we designed a phase I trial to investigate the maximum-tolerated dose (MTD), safety, and activity of panitumumab added to gemcitabine-based chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer (LAPC). EXPERIMENTAL DESIGN: Patients with LAPC and WHO performance status 0 to 1 were treated with weekly panitumumab at four dose levels (1-2.5 mg/kg), combined with weekly gemcitabine 300 mg/m(2) and radiotherapy (50.4 Gy in 28 fractions) for 6 weeks, followed by gemcitabine 1,000 mg/m(2) weekly for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. Each cohort was monitored during the combination therapy to establish dose limiting toxicity. Tumor evaluation was performed after CRT and during gemcitabine monotherapy. RESULTS: Fourteen patients were enrolled; 14 were evaluable for toxicity and 13 for response. The MTD for panitumumab was 1.5 mg/kg. Three of the 6 patients, treated at MTD, experienced grade 3 adverse events during the combination therapy; neutropenia (n = 2; 33%), fatigue (n = 1; 17%), nausea (n = 1; 17%), and vomiting (n = 1; 17%). Partial response was achieved by 3 patients (23%), 1 in each dose cohort. Median progression free survival of the three cohorts together was 8.9 months. CONCLUSIONS: The addition of panitumumab to gemcitabine-based chemoradiotherapy in LAPC has manageable toxicity and potential clinical efficacy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Idoso , Anticorpos Monoclonais/efeitos adversos , Quimiorradioterapia/métodos , Terapia Combinada/métodos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Receptores ErbB/metabolismo , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Panitumumabe , Radiossensibilizantes/administração & dosagem , Gencitabina
14.
Ned Tijdschr Geneeskd ; 158: A7398, 2014.
Artigo em Holandês | MEDLINE | ID: mdl-25269631

RESUMO

BACKGROUND: Germline mutations in the SMAD4 gene lead to both juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia (HHT). CASE DESCRIPTION: A 23-year-old man underwent colectomy with ileo-anal pouch anastomosis at the age of 12 due to colorectal juvenile polyposis. At follow-up, recurrent juvenile polyps in the pouch were removed. No gastric polyps were found. The family history was negative for intestinal polyposis. In addition, the patient had recurrent epistaxis. DNA testing revealed a pathogenic SMAD4 mutation: c.1558G>T; p.(Glu520*). Further examination confirmed suspected HHT. CONCLUSION: DNA testing in patients with juvenile polyposis is important for subclassification of this syndrome with implications for the management of patients and family members.


Assuntos
Polipose Intestinal/congênito , Síndromes Neoplásicas Hereditárias/diagnóstico , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/diagnóstico , Colectomia , Epistaxe/diagnóstico , Epistaxe/genética , Testes Genéticos , Humanos , Polipose Intestinal/diagnóstico , Polipose Intestinal/genética , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/genética , Masculino , Mutação , Síndromes Neoplásicas Hereditárias/genética , Telangiectasia Hemorrágica Hereditária/genética , Adulto Jovem
15.
Dig Endosc ; 25(4): 365-75, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23701732

RESUMO

A dedicated digestive disease endoscopy unit is structurally and functionally differentiating rapidly as a result of increasing diagnostic and therapeutic possibilities in the last 10-20 years. Publications with practical details are scarce, imposing a challenge in the construction of such a unit. The lack of authoritative information about endoscopy unit design means that architects produce their own design with or without consulting endoscopists working in such a unit. A working group of the World Endoscopy Organization discussed and outlined a practical approach fordesign and construction of a modern endoscopy unit. Designing the layout is extremely important, necessitating thoughtful planning to provide comfort to the endoscopy staff and patients, and efficient data archiving and transmission during endoscopic services.


Assuntos
Serviços de Diagnóstico/provisão & distribuição , Endoscopia Gastrointestinal/estatística & dados numéricos , Gastroenteropatias/diagnóstico , Guias como Assunto , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Departamentos Hospitalares/organização & administração , Sociedades Médicas , Humanos
16.
Abdom Imaging ; 38(1): 42-51, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22527155

RESUMO

PURPOSE: To evaluate the diagnostic accuracy of MR enteroclysis and to compare it to video capsule endoscopy (VCE) in the analysis of suspected small-bowel disease. METHODS: We performed a retrospective analysis of 77 patients who underwent both MR enteroclysis and VCE and compared the findings of these studies with the findings of enteroscopy, surgery, or with the results of clinical follow-up lasting ≥2 years. RESULTS: Findings included malignant neoplasms (n = 13), benign neoplasms (n = 10), refractory celiac disease (n = 4), Crohn's disease (n = 2) and miscellaneous conditions (n = 10). Specificity of MR enteroclysis was higher than that of VCE (0.97 vs. 0.84, P = 0.047), whereas sensitivity was similar (0.79 vs. 0.74, P = 0.591). In 2/32 (6.3%) patients with both negative VCE and negative MR enteroclysis a positive diagnosis was established, compared to 5/11 (45.5%) patients in whom VCE was positive and MR enteroclysis was negative (likelihood ratio 8.1; P = 0.004), 9/11 (81.8%) patients in whom MR enteroclysis was positive and VCE was negative (likelihood ratio 23.5; P < 0.0001), and all 23 patients in whom both VCE and MR enteroclysis showed abnormalities (likelihood ratio 60.8; P < 0.0001). CONCLUSIONS: VCE and MR enteroclysis are complementary modalities. In our study-population, MR enteroclysis was more specific than VCE, while both produced the same sensitivity.


Assuntos
Endoscopia por Cápsula , Enteropatias/diagnóstico , Intestino Delgado , Imageamento por Ressonância Magnética/métodos , Distribuição de Qui-Quadrado , Meios de Contraste , Feminino , Humanos , Enteropatias/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
J Clin Gastroenterol ; 47(5): 393-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23164686

RESUMO

GOALS AND BACKGROUND: Discriminating between patients with nonresponsive but otherwise uncomplicated celiac disease (CD) and patients with refractory celiac disease (RCD) and/or lymphoma is difficult, especially as many abnormalities encountered in complicated CD are not within reach of conventional gastroduodenoscopy. We aimed to describe video capsule endoscopy (VCE) findings in patients with CD and persisting or relapsing symptoms despite a gluten-free diet and to identify VCE findings associated with poor prognosis. METHODS: We retrospectively analyzed 48 VCE studies performed in adult patients with CD because of persisting or relapsing symptoms despite adherence to a gluten-free diet. Patients with either uncomplicated CD or RCD type I were considered to have a good prognosis, whereas patients with either RCD type II or enteropathy-associated T-cell lymphoma were considered to have a poor prognosis. Multivariate analysis was performed to identify VCE findings independently associated with either good or poor prognosis. RESULTS: Proximal focal erythema (odds ratio, 6.7; 95% confidence interval, 1.2-38.7; P=0.033) and absence of progression of the capsule to the distal intestine (odds ratio, 16.5; 95% confidence interval, 1.2-224.9; P=0.035) were independently associated with poor prognosis. Of the 28 patients with none of these 2 features, none died during follow-up, compared with 2 (13.3%) of the 15 patients with one of both features, and 4 (80.0%) of the 5 patients with both the features. CONCLUSIONS: VCE is a minimally invasive endoscopic modality that could be of use in identifying patients with nonresponsive CD who are at risk of poor prognosis.


Assuntos
Endoscopia por Cápsula/métodos , Doença Celíaca/diagnóstico , Intestino Delgado/patologia , Adulto , Doença Celíaca/patologia , Dieta Livre de Glúten , Progressão da Doença , Linfoma de Células T Associado a Enteropatia/complicações , Linfoma de Células T Associado a Enteropatia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos
18.
Ned Tijdschr Geneeskd ; 156(39): A5175, 2012.
Artigo em Holandês | MEDLINE | ID: mdl-23009822

RESUMO

BACKGROUND: Double-balloon enteroscopy is a technique that utilises an endoscope equipped with an overtube to inspect the entire small bowel. Diagnostic and therapeutic procedures can be performed during this type of endoscopy. So far, the use of this technique in children has been limited. In this article, we present a case illustrating the indication, efficacy and safety of this technique in the paediatric setting. CASE DESCRIPTION: In a 17-year-old girl with chronic abdominal pain and iron deficiency anaemia, neither gastroduodenoscopy nor ileocolonoscopy revealed any abnormality. Video capsule endoscopy revealed a few suspicious erosive lesions and ulcerations, presumed to be located in the ileum. A double-balloon enteroscopy was then performed during which an ulcer was seen on a small-bowel stenosis; this was consistent with the diagnosis of Crohn's disease. The symptoms diminished after treatment with budesonide and azathioprine was initiated. CONCLUSION: Double-balloon enteroscopy also appears to be an effective and safe method of diagnosing and performing therapeutic interventions in paediatric small bowel pathology.


Assuntos
Dor Abdominal/diagnóstico , Anemia Ferropriva/diagnóstico , Doença de Crohn/diagnóstico , Enteroscopia de Duplo Balão/métodos , Dor Abdominal/etiologia , Adolescente , Anemia Ferropriva/etiologia , Doença de Crohn/complicações , Diagnóstico Diferencial , Enteroscopia de Duplo Balão/efeitos adversos , Feminino , Gastroenteropatias/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos
19.
Dig Endosc ; 24(4): 247-54, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22725110

RESUMO

BACKGROUND AND AIM: Little is known about the causes of overt obscure gastrointestinal bleeding (OGIB) in patients using anti-thrombotic therapy. We aimed to describe video capsule endoscopy (VCE) findings and to identify factors associated with positive findings in these patients. METHODS: We carried out a retrospective study of 56 patients who underwent VCE for evaluation of previous overt OGIB during anti-thrombotic therapy. VCE studies were re-evaluated by a gastroenterologist blinded to clinical details. Clinical data included in the multivariate analysis were sex, age, indication for and type of anti-thrombotic therapy, hemodynamic instability on admission, type of blood loss, hemoglobin on admission, use of a proton pump inhibitor, NSAID use, time between bleeding episodes and VCE, and whether or not anti-thrombotic therapy was resumed before the VCE study. RESULTS: A probable cause for gastrointestinal bleeding was identified in 28 (50%) of the 56 studies. Angiodysplasia was found in 19 patients. Twenty-two studies showed a possible cause in the small bowel. Multivariate logistic regression analysis showed that reinstitution of anti-thrombotic therapy before VCE was carried out was the only independent predictor of positive VCE findings (OR: 8.61, 95% CI: 1.20-60.42, P=0.032). CONCLUSIONS: Small intestinal angiodysplasia was the most common cause for overt OGIB. Reinstitution of withdrawn anti-thrombotic drugs before the VCE examination was carried out was associated with positive VCE findings in multivariate analysis.


Assuntos
Endoscopia por Cápsula , Fibrinolíticos/efeitos adversos , Hemorragia Gastrointestinal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiodisplasia/complicações , Feminino , Fibrinolíticos/uso terapêutico , Hemorragia Gastrointestinal/etiologia , Trato Gastrointestinal/irrigação sanguínea , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
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