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1.
Sci Rep ; 10(1): 7793, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385343

RESUMO

BACKGROUND: Diabetes is associated with an increased risk of colorectal cancer (CRC). We conducted a retrospective analysis of adenoma detection rates (ADR) in initial screening colonoscopies to further investigate the role of diabetes in adenoma detection. METHODS: A chart review was performed on initial average risk screening colonoscopies (ages 45-75) during 2012-2015. Data collected included basic demographics, insurance, BMI, family history of CRC, smoking, diabetes, and aspirin use. Multivariable generalized linear mixed models for binary outcomes were used to examine the relationship between diabetes and variables associated with CRC risk and ADR. RESULTS: Of 2865 screening colonoscopies, 282 were performed on patients with type 2 diabetes (T2DM). Multivariable analysis suggested that T2DM (OR = 1.49, 95% CI:1.13-1.97, p = 0.0047) was associated with an increased ADR, as well as smoking, older age, higher BMI and male sex (all p < 0.05). For patients with T2DM, those not taking diabetes medications were more likely to have an adenoma than those taking medication (OR = 2.38, 95% CI:1.09-5.2, p = 0.03). CONCLUSION: T2DM has an effect on ADR after controlling for multiple confounding variables. Early interventions for prevention of T2DM and prescribing anti-diabetes medications may reduce development of colonic adenomas and may contribute to CRC prevention.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32119924

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancies, with a 5-year survival rate <8%.1,2 Suspicious lesions are typically diagnosed via endoscopic ultrasound-guided fine-needle aspiration or endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).3 Fewer needle passes decreases the risk of postprocedure complications, including pancreatitis and hemorrhage, while allowing additional needle passes to be used for adjuvant tissue testing, such as organoid creation and DNA sequencing.

5.
Clin Gastroenterol Hepatol ; 18(3): 739-740, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31228568

RESUMO

Placement of a pancreatic duct (PD) stent for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP)1-3 often necessitates a second procedure for stent removal, generally within 2-4 weeks to avoid stent occlusion or injury to the duct.4 These procedures are associated with increased costs and may result in procedure-related complications. Stents without internal anchoring flaps were developed to allow spontaneous migration into the duodenum,5 thus obviating the need for a repeat procedure. However, radiographic confirmation of a migrated stent can be challenging.6.

6.
Endosc Int Open ; 7(11): E1419-E1423, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31673613

RESUMO

Background and study aims Fully covered self-expanding metal stents (FCSEMS) have been used to treat refractory pancreatic duct strictures. We aimed to evaluate the feasibility, safety, and efficacy of FCSEMS in chronic pancreatitis with refractory pancreatic duct strictures. Patients and methods This was a retrospective multicenter cases series of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with FCSEMS placement in the main pancreatic duct (MPD) at five tertiary care centers between February 2010 and June 2016. Primary endpoints were technical success, clinical success, and procedure-related morbidity. Secondary endpoints were pain relief at the end of follow-up and resolution of the pancreatic stricture on ERCP. Results Thirty-three patients with previously drained stents, 76 % of whom were male, underwent ERCP with FCSEMS placement. Mean duration of follow-up was 14 months. All of the patients had prior therapy. The technical success rate for FCSEMS placement was 100 % (n = 33) and the clinical success rate was 93 % (was n = 31). Stents were removed after a median duration of 14.4 weeks. After stent removal, the diameter of the narrowest MPD stricture had increased significantly from 1 mm to 4.5 mm ( P  < 0.001). There was a statistically significant improvement on the Visual Analogue Scale (VAS) from a median of 8.5 to 2.5. At the end of the study, (n = 27) 87.1 % of patients reported significant pain reduction with reduced narcotic use. Conclusion FCSEMS appeared to be a feasible, safe, and potentially effective Intervention in patients who had not responded to endoscopic therapy with plastic stents.

8.
Gastrointest Endosc Clin N Am ; 29(2): 161-171, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30846146

RESUMO

Isolated biliary dilation, as an incidental diagnosis, is increasing owing to an increase in the use of noninvasive abdominal imaging and poses a diagnostic challenge to physicians especially when further noninvasive diagnostic testing fails to reveal an etiology. This article reviews available data describing the natural history of this clinical scenario and the impact of endoscopic ultrasound examination in the evaluation of unexplained dilation of the common bile duct.


Assuntos
Ductos Biliares/diagnóstico por imagem , Endossonografia , Ductos Biliares/patologia , Dilatação Patológica/sangue , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/etiologia , Humanos , Testes de Função Hepática , Imagem por Ressonância Magnética , Tomografia Computadorizada por Raios X
9.
Gastrointest Endosc ; 89(6): 1160-1168.e9, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30738985

RESUMO

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Competência Clínica , Educação de Pós-Graduação em Medicina/normas , Endoscopia do Sistema Digestório/educação , Endossonografia , Bolsas de Estudo/normas , Gastroenterologia/educação , Curva de Aprendizado , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Estudos Prospectivos , Esfinterotomia Endoscópica/educação
10.
Gastrointest Endosc ; 89(2): 329-339, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30367877

RESUMO

BACKGROUND AND AIMS: Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle. METHODS: Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders. RESULTS: A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P < .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836). CONCLUSION: The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).


Assuntos
Biópsia com Agulha de Grande Calibre/instrumentação , Carcinoma/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Intestinais/patologia , Linfadenopatia/patologia , Linfoma/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Idoso , Carcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Endossonografia , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Biópsia Guiada por Imagem/instrumentação , Neoplasias Intestinais/diagnóstico , Linfadenopatia/diagnóstico , Metástase Linfática , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Agulhas , Tumores Neuroendócrinos/diagnóstico , Razão de Chances , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/patologia , Sensibilidade e Especificidade
11.
J Clin Gastroenterol ; 53(4): 298-303, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29570171

RESUMO

BACKGROUND: The incidence of infection due to Clostridium difficile infection (CDI) and subsequent economic burden are substantial. GOALS: The impact of changing practice patterns on demographics at risk and utilization of health care resources for recurrence of CDI remains unclear. STUDY: A total of 291,163 patients hospitalized for CDI were identified from 1995 to 2014 from the New York SPARCS database. The χ test, the Welch t test, and multivariable logistic regression analysis were performed to evaluate factors related to readmission. RESULTS: Hospital admissions and readmissions for CDI peaked in 2008 at 20,487 and 13,795, respectively, and have since decreased (linear trend, 0.9706 and 0.9464, respectively; P<0.0001). In total, 60,077 (21%) patients required ≥2 admissions. Risk factors for readmission included: age 55 to 74, government insurance, hypertension, diabetes, anemia, hypothyroidism, chronic pulmonary disease, rheumatoid arthritis, renal failure, peripheral vascular disease, and depression (all P<0.05). Trends in surgery showed a similar peak in 2008 at 165 and have since decreased (linear trend, 0.8660; P<0.0001). A total of 1830 (0.63%) patients with CDI underwent surgery, with emergent being more common than elective (71% vs. 29%). CONCLUSIONS: Hospital admissions and readmissions for CDI peaked in 2008 and have since been steadily declining. These trends may be secondary to improved diagnostic capabilities and evolving antibiotic regimens. More than 1 in 5 hospitalized patients had at least 1 readmission. Numerous risk factors for these patients have been identified. Although <1% of all patients with CDI undergo surgery, these rates have also been declining.

12.
Endosc Ultrasound ; 8(2): 99-104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29623911

RESUMO

Background and Objectives: We present a multicenter study of a new endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) needle (Acquire, Boston Scientific, Natick, MA). The aim of the study was to analyze the needle's clinical performance when sampling solid lesions and to assess the safety of this device. Methods: We performed a multicenter retrospective study of patients undergoing EUS-FNB during July 1-November 15, 2016. Results: Two hundred patients (121 males and 79 females) underwent EUS-FNB of solid lesions with the Acquire needle. Lesions included solid pancreatic masses (n = 109), adenopathy (n = 45), submucosal lesions (n = 34), cholangiocarcinoma (n = 8), liver lesions (n = 6), and other (n = 8). Mean lesion size was 30.6 mm (range: 3-100 mm). The mean number of passes per target lesion was 3 (range: 1-7). Rapid onsite cytologic evaluation (ROSE) by a cytologist was performed in all cases. Tissue obtained by EUS-FNB was adequate for evaluation and diagnosis by ROSE in 197/200 cases (98.5%). Data regarding the presence or absence of a core of tissue obtained after EUS-FNB were available in 145/200 procedures. In 131/145 (90%) of cases, a core of tissue was obtained. Thirteen out of 200 patients (6.5%) underwent some form of repeat EUS-based tissue acquisition after EUS-FNB with the Acquire needle. There were no adverse events. Conclusion: Overall, this study showed a high rate of tissue adequacy and production of a tissue core with this device with no adverse events seen in 200 patients. Comparative studies of different FNB needles are warranted in the future to help identify which needle type and size is ideal in different clinical settings.

13.
Endosc Int Open ; 6(10): E1267-E1275, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30302385

RESUMO

Background and study aims Endoscopic drainage with dedicated lumen-apposing metal stents (LAMS) is routinely performed for symptomatic pancreatic fluid collections (PFCs), walled-off necrosis (WON) and pseudocyst (PP). There has been increasing concern regarding delayed adverse events associated with the indwelling LAMS.  Patients and methods Multicenter retrospective analysis of consecutive patients who underwent endoscopic ultrasound (EUS)-guided LAMS placement for PFC from January 2010 to May 2017. Main outcomes included: (1) resolution of the PFC, (2) rate of delayed adverse events at follow-up, and (3) predictors of treatment failure and delayed adverse events on logistic regression. Results A total of 122 patients (mean age 50.9 years, 68 % male) underwent LAMS insertion for 64 WON (98.4 %) and 58 PP (98.3 %). PFC mean size was 10.6 cm. PFC resolution was significantly lower for WON (62.3 %) vs. PP (96.5 %) ( P  < 0.001) on imaging at a median of 4 weeks. Stent occlusion was identified in 18 (29.5 %) and 10 (17.5 %) patients with WON and PP, respectively ( P  = 0.13). There were no cases of delayed bleeding or buried stent on follow-up endoscopy. Use of electrocautery-enhanced LAMS was the only factor associated with treatment failure of WON (OR = 13.2; 95 % ci: 3.33 - 51.82, P  = 0.02) on logistic regression. There were no patient, operator, or procedure-related factors predictive of stent occlusion. Conclusions EUS-guided LAMS for PFC is associated with a low incidence of delayed adverse events. While nearly all PPs resolve at 4 weeks permitting LAMS removal shortly thereafter, many WON persist, with use of electrocautery-enhanced LAMS being the sole predictor of treatment failure.

14.
Ann Surg Oncol ; 25(9): 2767-2775, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30003451

RESUMO

BACKGROUND: Organoids are three-dimensional in vitro models of human disease developed from benign and malignant gastrointestinal tissues with tremendous potential for personalized medicine applications. We sought to determine whether gastric cancer patient-derived organoids (PDOs) could be safely established from endoscopic biopsies for rapid drug screening. METHODS: Patients underwent esophagogastroduodenoscopy (EGD) for surveillance or staging and had additional forceps biopsies taken for PDO creation. Cancer tissues from operative specimens were also used to create PDOs. To address potential tumor heterogeneity, we performed low-coverage whole-genome sequencing of endoscopic-derived PDOs with paired surgical PDOs and whole-tumor lysates. The stability of genomic alterations in endoscopic organoids was assessed by next-generation sequencing and nested polymerase chain reaction (PCR) assay. The feasibility and potential accuracy of drug sensitivity screening with endoscopic-derived PDOs were also evaluated. RESULTS: Gastric cancer PDOs (n = 15) were successfully established from EGD forceps biopsies (n = 8) and surgical tissues (n = 7) from five patients with gastric adenocarcinoma. Low-coverage whole-genomic profiling of paired EGD and surgical PDOs along with whole-tumor lysates demonstrated absence of tumor heterogeneity. Nested PCR assay identified similar KRAS alterations in primary tumor and paired organoids. Drug sensitivity testing of endoscopic-derived PDOs displayed standard dose-response curves to current gastric cancer cytotoxic therapies. CONCLUSIONS: Our study results demonstrate the feasibility of developing gastric cancer PDOs from EGD biopsies. These results also indicate that endoscopic-derived PDOs are accurate surrogates of the primary tumor and have the potential for drug sensitivity screening and personalized medicine applications.


Assuntos
Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Endoscopia do Sistema Digestório/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Cultura de Órgãos/métodos , Organoides/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/genética , Biópsia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Organoides/efeitos dos fármacos , Organoides/metabolismo , Medicina de Precisão , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Células Tumorais Cultivadas
15.
Gastroenterology ; 155(5): 1483-1494.e7, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30056094

RESUMO

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Competência Clínica , Endossonografia , Colangiopancreatografia Retrógrada Endoscópica/normas , Endossonografia/normas , Humanos , Curva de Aprendizado , Estudos Prospectivos , Indicadores de Qualidade em Assistência à Saúde
16.
Cancer Discov ; 8(9): 1112-1129, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29853643

RESUMO

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.


Assuntos
Antineoplásicos/farmacologia , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/efeitos dos fármacos , Organoides/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Organoides/química , Organoides/citologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Medicina de Precisão , Estudos Prospectivos , Análise de Sequência de RNA , Padrão de Cuidado , Células Tumorais Cultivadas
18.
PLoS One ; 13(1): e0190997, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29385143

RESUMO

BACKGROUND: Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). METHOD: V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. RESULTS: Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. CONCLUSION: The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.


Assuntos
Infecções por Clostridium/terapia , Clostridium difficile/isolamento & purificação , Colite Ulcerativa/terapia , Transplante de Microbiota Fecal , Fezes/microbiologia , Microbiota , Infecções por Clostridium/microbiologia , Humanos , Estudos Longitudinais , Reação em Cadeia da Polimerase , Estudos Prospectivos , Recidiva , Resultado do Tratamento
19.
Trials ; 19(1): 108, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29444707

RESUMO

BACKGROUND: The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). METHODS: The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. DISCUSSION: The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.


Assuntos
Neoplasias dos Ductos Biliares/complicações , Colangiopancreatografia Retrógrada Endoscópica , Colestase/terapia , Drenagem/métodos , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colestase/diagnóstico por imagem , Colestase/etiologia , Pesquisa Comparativa da Efetividade , Drenagem/efeitos adversos , Estudos de Equivalência como Asunto , Humanos , Estudos Multicêntricos como Assunto , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
20.
Gastrointest Endosc ; 87(6): 1474-1480, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29325707

RESUMO

BACKGROUND AND AIMS: Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately, most patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) sampling in patients with PDA. METHODS: In this prospective clinical trial in patients referred to evaluate a pancreatic mass, EUS-FNA was performed for initial onsite diagnosis. Two additional needle passes were performed with a 22-gauge FNB needle for organoid creation. Primary outcome was successful isolation of organoids within 2 weeks of EUS-FNB sampling (P0, no passages), confirmed by organoid morphology and positive genotyping. RESULTS: Thirty-seven patients with 38 PDA tumors were enrolled. Successful isolation of organoids (P0) was achieved in 33 of 38 tumors (87%). Establishment of PDA organoid lines for ≥5 passages of growth (P5, five passages) was reached in 25 of 38 tumors (66%). In the single patient with successful P5 FNB sampling-derived and P5 surgically derived organoids, there was identical matching of specimens. There were no serious adverse events. Two patients developed bleeding at the EUS-FNB puncture site requiring hemostasis clips. CONCLUSIONS: Pancreatic cancer organoids can be successfully and rapidly created by means of EUS-FNB sampling using a 22-gauge needle at the time of initial diagnosis. Successful organoid generation is essential for precision medicine in patients with pancreatic cancer in whom most are not surgically resectable. (Clinical trial registration number: NCT03140592.).


Assuntos
Carcinoma Ductal Pancreático , Organoides , Neoplasias Pancreáticas , Idoso , Idoso de 80 Anos ou mais , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Técnicas de Cultura de Tecidos , Células Tumorais Cultivadas
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