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1.
Gut ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849943

RESUMO

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

2.
Surg Endosc ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543349

RESUMO

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33278573

RESUMO

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

5.
Ann Surg ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33201115

RESUMO

OBJECTIVE: To evaluate the significance of UDD in IPMNs. BACKGROUND: The uncinate process of the pancreas has an independent ductal drainage system. International consensus guidelines of IPMNs still consider it as a branch-duct, even though it is the main drainage system for the uncinate process. METHODS: A retrospective review of all surgically treated IPMNs at our institution after 2008 was performed. Preoperative radiological studies were reviewed by an abdominal radiologist who was blinded to the pathological results. In addition to the Fukuoka criteria, presence of UDD was recorded. Using multivariate analysis, the pathological significance of UDD in predicting advanced neoplasia [high grade dysplasia or invasive carcinoma (HGD/IC)] was determined. RESULTS: Two hundred sixty patients were identified (mean age at diagnosis was 68 years and 49% were females): 122 (47%) had HGD/IC. UDD was noted in 59 (23%), of which 36 (61%) had HGD/IC (P < 0.003). On multivariate analysis, UDD was an independent predictor of HGD/IC (odds ratio = 2.99, P < 0.04). Subgroup analysis on patients with IPMNs confined to the dorsal portion of the gland (n = 161), also demonstrated UDD to be a significant predictor of HGD/IC in those remote lesions (odds ratio: 4.41, P = 0.039). CONCLUSIONS: This is the largest study to evaluate the significance of UDD in IPMNs and shows it to be a high-risk feature. This association persisted for remote IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive phenotype even in remote IPMN lesions.

6.
Gut ; 69(1): 52-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30971436

RESUMO

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Doenças Biliares/diagnóstico , Doenças Biliares/genética , Doenças Biliares/patologia , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Constrição Patológica/diagnóstico , Constrição Patológica/genética , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Adulto Jovem
7.
Clin Endosc ; 48(5): 411-20, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26473125

RESUMO

BACKGROUND/AIMS: Surgery is the mainstay of treatment for cholecystitis. However, gallbladder stenting (GBS) has shown promise in debilitated or high-risk patients. Endoscopic transpapillary GBS and endoscopic ultrasound-guided GBS (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage. METHODS: Data from patients with cholecystitis were prospectively collected from August 2004 to May 2013 from two United States academic university hospitals and analyzed retrospectively. The following treatment algorithm was adopted. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and cystic duct stenting was initially attempted. If deemed feasible by the endoscopist, EUS-GBS was then pursued. RESULTS: During the study period, 139 patients underwent endoscopic gallbladder drainage. Among these, drainage was performed in 94 and 45 cases for benign and malignant indications, respectively. Successful endoscopic gallbladder drainage was defined as decompression of the gallbladder without incidence of cholecystitis, and was achieved with ERCP and cystic duct stenting in 117 of 128 cases (91%). Successful endoscopic gallbladder drainage was also achieved with EUS-guided gallbladder drainage using transmural stent placement in 11 of 11 cases (100%). Complications occurred in 11 cases (8%). CONCLUSIONS: Endoscopic gallbladder drainage techniques are safe and efficacious methods for gallbladder decompression in non-surgical patients with comorbidities.

8.
Clin Gastroenterol Hepatol ; 13(2): 339-44, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25019698

RESUMO

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) often is used to stage rectal cancer and thereby guide treatment. Prior assessments of its accuracy have been limited by small sets of data collected from tumors of varying stages. We aimed to characterize the diagnostic performance of EUS analysis of rectal cancer, paying particular attention to determining whether patients should undergo primary surgical resection. METHODS: We performed a retrospective observational study using procedural databases and electronic medical records from 4 academic tertiary-care hospitals, collecting data on EUS analyses from 2000 through 2012. Data were analyzed from 86 patients with rectal cancer initially staged as T2N0 by EUS. The negative predictive value (NPV) was calculated by comparing initial stages determined by EUS with those determined by pathology analysis of surgical samples. Logistic regression models were used to assess variation in diagnostic performance with case attributes. RESULTS: EUS excluded advanced tumor depth with an NPV of 0.837 (95% confidence interval [CI], 0.742-0.908), nodal metastasis with an NPV of 0.872 (95% CI, 0.783-0.934), and both together with an NPV of 0.767 (95% CI, 0.664-0.852) compared with pathology analysis. Incorrect staging by EUS affected treatment decision making for 20 of 86 patients (23.3%). Patient age at time of the procedure correlated with the NPV for metastasis to lymph node, but no other patient features were associated significantly with diagnostic performance. CONCLUSIONS: Based on a multicenter retrospective study, EUS staging of rectal cancer as T2N0 excludes advanced tumor depth and nodal metastasis, respectively, with an approximate NPV of 85%, similar to that of other modalities. EUS has an error rate of approximately 23% in identifying disease appropriate for surgical resection, which is lower than previously reported.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Endossonografia/métodos , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Retais/cirurgia , Estudos Retrospectivos
9.
Dig Liver Dis ; 47(3): 202-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25499063

RESUMO

BACKGROUND: Confocal endomicroscopy provides real-time evaluation of various sites and has been used to provide detailed endomicroscopic imaging of the biliary tree. We aimed to evaluate the feasibility and utility of probe-based confocal laser endomicroscopy of the pancreatic duct as compared to cytologic and histologic results in patients with indeterminate pancreatic duct strictures. METHODS: Retrospective data on patients with indeterminate pancreatic strictures undergoing endoscopic retrograde cholangiopancreatography (ERCP) and confocal endomicroscopy were collected from two tertiary care centres. Real-time confocal endomicroscopy images were obtained during ERCP and immediate interpretation according to the Miami Classification was performed. RESULTS: 18 patients underwent confocal endomicroscopy for evaluation of pancreatic strictures from July 2011 to December 2012. Mean pancreatic duct size was 4.2mm (range 2.2-8mm). Eight cases were interpreted as benign, 4 as malignant, 4 suggestive of intraductal papillary mucinous neoplasms, and 2 appeared normal. Cytology/histopathology for 15/16 cases showed similar results to confocal endomicroscopy interpretation. Kappa coefficient of agreement between cyto/histopathology and confocal endomicroscopy was 0.8 (p=0.0001). Pancreatic confocal endomicroscopy changed management in four patients, changing the type of surgery from total pancreatectomy to whipple. CONCLUSIONS: Confocal endomicroscopy is effective in assisting with diagnosis of indeterminate pancreatic duct strictures as well as mapping of abnormal pancreatic ducts prior to surgery.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , Constrição Patológica/diagnóstico , Microscopia Confocal , Ductos Pancreáticos/patologia , Adulto , Idoso , Carcinoma Ductal Pancreático/cirurgia , Constrição Patológica/cirurgia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
J Clin Gastroenterol ; 48(2): 145-52, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23751853

RESUMO

BACKGROUND: Endoscopic necrosectomy for necrotizing pancreatitis has been increasingly used as an alternative to surgical or percutaneous interventions. The use of fully covered esophageal self-expandable metallic stents may provide a safer and more efficient route for internal drainage. The aim of this study was to evaluate the safety and efficacy of endoscopic treatment of pancreatic necrosis with these stents. METHODS: A retrospective study at 2 US academic hospitals included patients with infected pancreatic necrosis from July 2009 to November 2012. These patients underwent transgastric placement of fully covered esophageal metallic stents draining the necrosis. After necrosectomy, patients underwent regular sessions of endoscopic irrigation and debridement of cystic contents. The efficacy endpoint was successful resolution of infected pancreatic necrosis without the need for surgical or percutaneous interventions. RESULTS: Seventeen patients were included with the mean age of 41±12 years. A mean of 5.3±3.4 sessions were required for complete drainage and the follow-up period was 237.6±165 days. Etiology included gallstone pancreatitis (6), alcohol abuse (6), s/p distal pancreatectomy (2), postendoscopic retrograde cholangiopancreatography pancreatitis (1), medication-induced pancreatitis (1), and hyperlipidemia (1). Mean size of the necrosis was 14.8 cm (SD 5.6 cm), ranging from 8 to 19 cm. Two patients failed endoscopic intervention and required surgery. The only complication was a perforation during tract dilation, which was managed conservatively. Fifteen patients (88%) achieved complete resolution. CONCLUSIONS: Endoscopic necrosectomy with covered esophageal metal stents is a safe and successful treatment option for infected pancreatic necrosis.


Assuntos
Endoscopia do Sistema Digestório/métodos , Pancreatite Necrosante Aguda/cirurgia , Stents , Adolescente , Adulto , Desbridamento , Drenagem/métodos , Endoscopia do Sistema Digestório/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Necrosante Aguda/microbiologia , Pancreatite Necrosante Aguda/patologia , Estudos Retrospectivos , Stents/efeitos adversos , Irrigação Terapêutica , Adulto Jovem
11.
Dig Endosc ; 26(4): 577-80, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24344750

RESUMO

BACKGROUND AND AIM: Current diagnostic modalities for indeterminate biliary strictures offer low accuracy. Probe-based confocal laser endomicroscopy (pCLE) permits microscopic assessment of mucosal structures by obtaining real-time high-resolution images of the mucosal layers of the gastrointestinal tract. Previously, an interobserver study demonstrated poor to fair agreement even among experienced confocal endomicroscopy operators. Our objective was to assess interobserver agreement and diagnostic accuracy upon completion of a pCLE training session. METHODS: Forty de-identified pCLE video clips of indeterminate biliary strictures were sent to five endoscopists at four tertiary care centers for scoring. Observers subsequently attended a teaching session by an expert pCLE user that included 20 training clips and rescored the same pCLE video clips, which were randomized and renumbered. RESULTS: Pre-training interobserver agreement for all observers was 'fair' (Κ: 0.31, P-value: <0.0001) and diagnostic accuracy was 72% (55-80%). Post-training interobserver agreement for all observers was 'substantial' (Κ: 0.74, P-value: <0.0001) and diagnostic accuracy was 89% (80-95%). Using a paired t-test, we observed an increase of 17% (95% CI 7.6-26.4) in post-training diagnostic accuracy (t = 5.01, df = 4, P-value 0.007). CONCLUSIONS: Interobserver agreement and diagnostic accuracy improved after observers underwent training by an expert pCLE user with a specific sequence set. Users should participate in such training programs to maximize diagnostic accuracy of pCLE evaluation.


Assuntos
Colestase/terapia , Competência Clínica , Endoscopia Gastrointestinal/educação , Endoscopia Gastrointestinal/métodos , Microscopia Confocal/métodos , Colestase/patologia , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Gravação em Vídeo
12.
Gut Liver ; 7(2): 129-36, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23560147

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) has become the first-line therapy for bile duct drainage. In the hands of experienced endoscopists, conventional ERCP results in a failed cannulation rate of 3% to 5%. This failure can occur more commonly in the setting of altered anatomy or technically difficult cases due to either duodenal or biliary obstruction. In cases of ERCP failure, patients have traditionally been referred for either percutaneous transhepatic biliary drainage (PTBD) or surgery. However, both PTBD and surgery have higher than desirable complication rates. Within the last decade, endoscopic ultrasound-guided biliary drainage (EUS-BD) has become an attractive alternative to PTBD after failed ERCP. Many groups have reported on the feasibility, efficacy and safety of this technique. This article reviews the indications for ERCP and the currently practiced EUS-BD techniques, including EUS-guided rendezvous, EUS-guided choledochoduodenostomy and EUS-guided hepaticogastrostomy.

13.
Gastrointest Endosc Clin N Am ; 23(2): 435-52, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23540968

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) is currently the standard of care for biliary drainage. In the hands of experienced endoscopists, conventional ERCP has a failed cannulation rate of 3% to 5%. Failures have traditionally been referred for either percutaneous transhepatic biliary drainage (PTBD) or surgery. Both PTBD and surgery have higher than desirable complication rates. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a novel and attractive alternative after failed ERCP. Many groups have reported on the feasibility, efficacy, and safety of this technique. This article reviews the indications and technique currently practiced in EUS-BD, including EUS-guided rendezvous, EUS-guided choledochoduodenostomy, and EUS-guided hepaticogastrostomy.


Assuntos
Ducto Colédoco/diagnóstico por imagem , Drenagem/métodos , Endossonografia , Ultrassonografia de Intervenção/métodos , Colangiopancreatografia Retrógrada Endoscópica , Coledocostomia/métodos , Drenagem/efeitos adversos , Humanos , Stents , Falha de Tratamento , Ultrassonografia de Intervenção/efeitos adversos
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