Project description:Tumor cells circulate in low numbers in peripheral blood; their detection is used predominantly in metastatic disease. We evaluated the feasibility and safety of sampling portal venous blood via endoscopic ultrasound (EUS) to count portal venous circulating tumor cells (CTCs), compared with paired peripheral CTCs, in patients with pancreaticobiliary cancers (PBCs).In a single-center cohort study, we evaluated 18 patients with suspected PBCs. Under EUS guidance, a 19-gauge EUS fine needle was advanced transhepatically into the portal vein and as many as four 7.5-mL aliquots of blood were aspirated. Paired peripheral blood samples were obtained. Epithelial-derived CTCs were sorted magnetically based on expression of epithelial cell adhesion molecules; only those with a proper morphology and found to be CD45 negative and positive for cytokeratins 8, 18, and/or 19 and 4',6-diamidino-2-phenylindole were considered to be CTCs. For 5 samples, CTCs also were isolated by flow cytometry and based on CD45 depletion. ImageStream was used to determine the relative protein levels of P16, SMAD4, and P53. DNA was extracted from CTCs for sequencing of select KRAS codons.There were no complications from portal vein blood acquisition. We detected CTCs in portal vein samples from all 18 patients (100%) vs peripheral blood samples from only 4 patients (22.2%). Patients with confirmed PBCs had a mean of 118.4 ± 36.8 CTCs/7.5 mL portal vein blood, compared with a mean of 0.8 ± 0.4 CTCs/7.5 mL peripheral blood (P < .01). The 9 patients with nonmetastatic, resectable, or borderline-resectable PBCs had a mean of 83.2 CTCs/7.5 mL portal vein blood (median, 62.0 CTCs/7.5 mL portal vein blood). In a selected patient, portal vein CTCs were found to carry the same mutations as those detected in a metastatic lymph node and expressed similar levels of P16, SMAD4, and P53 proteins.It is feasible and safe to collect portal venous blood from patients undergoing EUS. We identified CTCs in all portal vein blood samples from patients with PBCs, but less than 25% of peripheral blood samples. Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue. This technique might be used to study the pathogenesis and progression of PBCs, as well as a diagnostic or prognostic tool to stratify risk of cancer recurrence or developing metastases.
Project description:This article reviews the development of the hepatopancreatobiliary (HPB) endoscopic ultrasound (EUS) service at Freeman Hospital and seeks to identify from our experience learning points for good practice and pitfalls to avoid. The Freeman HPB EUS service has expanded rapidly over the past 10 years in response to the consolidation of cancer care and aligned to the needs of the cancer network. Effective multidisciplinary teamwork and increased subspecialisation by the endosonographers has allowed the efficient use of capacity and development of skills. Mechanisms for monitoring diagnostic performance put in place at the outset of the EUS-fine needle aspiration programme have helped to identify interventions that have led to improved test performance. An excellent working relationship between all stakeholders is critical to the success of such a service as is a preparedness to seek and respond to the views of patients and referrers.
Project description:Endoscopic ultrasonography (EUS) is widely used to evaluate pancreaticobiliary diseases, especially pancreatic masses. EUS has a good ability to detect pancreatic masses, but it is not sufficient for the differential diagnosis of various types of lesions. In order to address the limitations of EUS, new techniques have been developed to improve the characterization of the lesions detected by EUS. EUS-guided fine needle aspiration (EUS-FNA) has been used for diagnosing pancreatic tumors. In order to improve the histological diagnostic yield, a EUS-FNA needle with a core trap has recently been developed. Contrast-enhanced harmonic EUS is a new imaging modality that uses an ultrasonographic contrast agent to visualize blood flow in fine vessels. This technique is useful in the diagnosis of pancreatic solid lesions and in confirming the presence of vascularity in mural nodules for cystic lesions. EUS elastography analyzes several different variables to measure tissue elasticity, color patterns, and strain ratio, using analytical techniques such as hue-histogram analysis, and artificial neural networks, which are useful for the diagnosis of chronic pancreatitis and pancreatic cancer.
Project description:Background & aimsIt 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.MethodsWe 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.ResultsBy 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).ConclusionsIn 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.
Project description:Background and study aims Pancreatic cancer (PC) is the fourth most common cause of cancer death in the United States. Previous studies have suggested a survival benefit for endoscopic ultrasound (EUS), an important tool for diagnosis and staging of PC. This study aims to describe EUS use over time and identify factors associated with EUS use and its impact on survival. Patients and methods This was a retrospective review of the Surveillance, Epidemiology and End Results (SEER) database linked with Medicare claims. EUS use, clinical and demographic characteristics were evaluated. Chi-squared analysis, Cochran-Armitage test for trend, and logistic regression were used to identify associations between sociodemographic and clinical factors and EUS. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. Results EUS use rose during the time period, from 7.4 % of patients in 2000 to 32.4 % in 2015. Patient diversity increased, with a rising share of older, non-White patients with higher Charlson comorbidity scores. Both clinical (receipt of other therapies, PC stage) and nonclinical factors (region of country, year of diagnosis) were associated with receipt of EUS. While EUS was associated with a survival improvement early in the study period, this effect did not persist for PC patients diagnosed in 2012 to 2015 (median survival 3 month ± standard deviation [SD] 9.8 months without vs. 4 months ± SD 8 months with EUS). Conclusions Our data support previous studies, which suggest a survival benefit for EUS when it was infrequently used, but finds that benefit was attenuated as EUS became more widely available.
Project description:Background & aimsAlthough treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied trends in age-standardized mortality of chronic liver diseases in adults at least 20 years old in the United States from 2007 through 2016.MethodsWe collected data from the US Census and National Center for Health Statistics mortality records and identified individuals with HCV infection, ALD, nonalcoholic fatty liver disease, or hepatitis B virus infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC).ResultsAge-standardized HCV-related mortality increased from 7.17 per 100,000 persons in 2007 to 8.14 per 100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09 per 100,000 persons in 2014 to 7.15 per 100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014 but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC 2.3% from 2007 through 2013 and APC 5.5% from 2013 through 2016) and nonalcoholic fatty liver disease (APC 6.1% from 2007 through 2013 and APC 11.3% from 2013 through 2016). Mortality related to hepatitis B virus decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI -3.0 to -1.2). Etiology-based mortality in minority populations was higher. HCV-related mortality (per 100,000 persons) was highest in non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest in non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for hepatitis B virus infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks and 0.47 for non-Hispanic whites).ConclusionIn our population-based analysis of chronic liver disease mortality in the United States, the decrease in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, whereas mortality from ALD and nonalcoholic fatty liver disease increased during the same period. Minorities in the United States have disproportionately higher mortality related to chronic liver disease.
Project description:(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.
Project description:Data on the experience of endoscopic retrograde cholangiopancreatography (ERCP) in the management of pancreaticobiliary maljunction (PBM) is limited.A retrospective review of patients with PBM who underwent therapeutic ERCP at our endoscopy center between January 2008 and January 2016 was performed. Demographic, clinical, radiological and endoscopic data was documented. Patients who underwent sphincterotomy were divided into dilated group and undilated group based on their common channel diameter.Sixty-three PBM patients underwent 74 ERCP procedures. The technical success rate was 97.3%. ERCP therapy significantly decreased the levels of elevated liver enzymes and bilirubin. After an average of 27 months follow-up, 7 patients (11.1%) were lost. The overall effective rate of ERCP therapy was 60.7% (34/56). Decline in severity and frequency of abdominal pain was significant. Procedure-related complications were observed in 5 (6.8%) cases. Between the dilated group and undilated group, no significant difference was observed in effective rate, adverse events and follow-up results.ERCP can serve as a transitional step to stabilize PBM patients before definitive surgery. PBM patients with undilated common channel could benefit from sphincterotomy as well as those with dilated common channel.
Project description:The study aimed to compare the molecular profiles of metastatic, locally advanced, and resected primary pancreatic adenocarcinoma at the genomic and transcriptomic levels. DNA and mRNA were extracted from endoscopic ultrasound-guided fine needle aspiration-biopsy material of primary tumors from 397 patients, and they were subsequently analyzed by targeted deep sequencing and RNAseq.
Project description:The 2016 annual meeting of the American Society of Hematology took place in San Diego, California, 3–6 December. At the meeting, results from key studies on the first-line treatment of follicular lymphoma were presented. Of those studies, key oral presentations included two analyzing data from the gallium study, which evaluated the efficacy and safety of obinutuzumab plus chemotherapy (G-chemo) compared with rituximab plus chemotherapy (R-chemo), followed, in responding patients with follicular lymphoma, by obinutuzumab or rituximab maintenance; results from the sabrina study, which evaluated the efficacy and safety of subcutaneous compared with intravenous rituximab; results of a cost-effectiveness analysis of first-line treatment with bendamustine and rituximab from a Canadian perspective; and results from the SAKK 35/10 study, which evaluated the safety and efficacy of rituximab plus lenalidomide compared with rituximab monotherapy. Our meeting report describes the foregoing studies and includes interviews with the Canadian investigators, plus commentaries by those investigators about the potential impact on Canadian practice.