Comparing per-pass performance of 2 types of needles for EUS-guided fine-needle biopsy sampling of pancreatobiliary masses in a randomized trial.

BACKGROUND AND AIMS: EUS-guided fine-needle biopsy sampling (EUS-FNB) has largely replaced FNA for tissue diagnosis of pancreatobiliary mass lesions. However, the optimal number of passes required for the diagnosis of malignancy is not clear. We aimed to compare the per-pass performance of 2 types of fine-needle biopsy (FNB) needles for the detection of malignancy. METHODS: One hundred fourteen patients referred for EUS evaluation of solid pancreatobiliary mass lesions underwent randomization between biopsy sampling with a Franseen needle and a 3-prong tip needle with an asymmetric cutting surfaces. Four passes of EUS-FNB were taken from each mass lesion. Two pathologists blinded to needle type analyzed the specimens. The final diagnosis of malignancy was made based on FNB specimen pathology, surgery, or a follow-up of at least 6 months after EUS-FNB. The sensitivity of EUS-FNB to diagnose malignancy was compared between the 2 groups. The cumulative sensitivity of detection of malignancy by EUS-FNB was calculated after each pass in each arm. Other characteristics of the specimens including cellularity and blood contents were also compared between the 2 groups. In the primary analysis, lesions categorized as suspicious on EUS-FNB were considered nondiagnostic for malignancy. RESULTS: Ninety-eight patients (86%) had a final diagnosis of malignancy, and 16 patients (14%) had benign disease. Four passes of EUS-FNB with the Franseen needle detected malignancy in 44 of 47 patients (sensitivity, 93.6%; 95% confidence interval [CI], 82.5-98.7) and with the 3-prong asymmetric-tip needle in 50 of 51 patients (sensitivity, 98%; 95% CI, 89.6-99.9; P = .35). Two passes of EUS-FNB detected malignancy with a sensitivity of 91.5% (95% CI, 79.6-97.6) with the Franseen needle and 90.2% (95% CI, 78.6-96.7) with the 3-prong asymmetric-tip needle. The cumulative sensitivities at pass 3 were 93.6% (95% CI, 82.5-98.6) and 96.1% (95% CI, 86.5-99.5), respectively. Samples collected with the Franseen needle had significantly higher cellularity than samples collected with the 3-prong asymmetric-tip needle (P < .01). However, no difference as found between the 2 types of needles in term of specimen bloodiness. CONCLUSIONS: No significant differences were found in the diagnostic performance of the Franseen needle versus the 3-prong asymmetric-tip needle in patients with suspected pancreatobiliary cancer. However, the Franseen needle yielded higher cellularity of the specimen. Two passes of EUS-FNB are required to detect malignancy with at least 90% sensitivity with either type of needle. (Clinical trial registration number: NCT04975620.).

Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma.

BACKGROUND & AIMS: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI). METHODS: Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis. Primary outcome was safety. Secondary outcomes were clinical efficacy, hospital stay, and recurrence rate after EUS-RFA. RESULTS: Using propensity score matching, 89 patients were allocated in each group (1:1), and were evenly distributed in terms of age, sex, Charlson comorbidity index, American Society of Anesthesiologists score, body mass index, distance between lesion and main pancreatic duct, lesion site, size, and grade. Adverse event (AE) rate was 18.0% and 61.8% after EUS-RFA and surgery, respectively (P < .001). No severe AEs were observed in the EUS-RFA group compared with 15.7% after surgery (P < .0001). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (P = .160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median, 23 months; interquartile range, 14-31 months vs 37 months; interquartile range, 17.5-67 months in the surgical group; P < .0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group; P < .0001). Fifteen lesions (16.9%) recurred after EUS-RFA and underwent a successful repeat EUS-RFA (11 patients) or surgical resection (4 patients). CONCLUSION: EUS-RFA is safer than surgery and highly effective for the treatment of PI. If confirmed in a randomized study, EUS-RFA treatment can become first-line therapy for sporadic PI.

Cell and cell-derivative-based therapy for liver diseases: current approaches and future promises.

INTRODUCTION: According to the recent updates from World Health Organization, liver diseases are the 12th most common cause of mortality. Currently, orthotopic liver transplantation (OLT) is the most effective and the only treatment for end-stage liver diseases. Owing to several shortcomings like finite numbers of healthy organ donors, lifelong immunosuppression, and complexity of the procedure, cell and cell-derivatives therapies have emerged as a potential therapeutic alternative for liver diseases. Various cell types and therapies have been proposed and their therapeutic effects evaluated in preclinical or clinical studies, including hepatocytes, hepatocyte-like cells (HLCs) derived from stem cells, human liver stem cells (HLSCs), combination therapies with various types of cells, organoids, and implantable cell-biomaterial constructs with synthetic and natural polymers or even decellularized extracellular matrix (ECM). AREAS COVERED: In this review, we highlighted the current status of cell and cell-derivative-based therapies for liver diseases. Furthermore, we discussed future prospects of using HLCs, liver organoids, and their combination therapies. EXPERT OPINION: Promising application of stem cell-based techniques including iPSC technology has been integrated into novel techniques such as gene editing, directed differentiation, and organoid technology. iPSCs offer promising prospects to represent novel therapeutic strategies and modeling liver diseases.

Intrahepatic aneurysmal portosystemic venous shunt diagnosed on EUS.

Video 1EUS demonstration of aneurysmal intrahepatic portosystemic venous shunt.

Endoscopic or surgical treatment for necrotizing pancreatitis: Comprehensive systematic review and meta-analysis.

Background and study aims Treatment of necrotizing pancreatitis is changed over the past two decades with the availability of endoscopic, and minimally invasive surgical approaches. The aim of this systematic review was to assess outcomes of endoscopic drainage, and different types of surgical drainage approaches in necrotizing pancreatitis. Methods Medline, Embase, Scopus, and Web of Science were searched from 1998 to 2020 to assess outcomes in endoscopic drainage and various surgical drainage procedures. The assessed variables consisted of mortality, development of pancreatic or enteric fistula, new onset diabetes mellitus, and exocrine pancreatic insufficiency. Results One hundred seventy studies comprising 11,807 patients were included in the final analysis. The pooled mortality rate was 22 % (95 % confidence interval [CI]: 19%-26 %) in the open surgery (OS), 8 % (95 %CI:5 %-11 %) in minimally invasive surgery (MIS), 13 % (95 %CI: 9 %-18 %) in step-up approach, and 3 % (95 %CI:2 %-4 %) in the endoscopic drainage (ED). The pooled rate of fistula formation was 35 % (95 %CI:28 %-41 %) in the OS, 17 % (95 %CI: 12%-23 %) in MIS, 17 % (95 %CI: 9 %-27 %) in step-up approach, and 2 % (95 %CI: 0 %-4 %) in ED. There were 17 comparative studies comparing various surgical drainage methods with ED. The mortality rate was significantly lower in ED compared to OS (risk ratio [RR]: 30; 95 %CI: 0.20-0.45), and compared to MIS (RR: 0.40; 95 %CI: 0.26-0.6). Also, the rate of fistula formation was lower in ED compared to all other surgical drainage approaches. Conclusions This systematic review demonstrated lower rate of fistula formation with ED compared to various surgical drainage methods. A lower rate of mortality with ED was also observed in observational studies. PROSPERO Identifier: CRD42020139354.

Mesenchymal Stromal Cell Therapy Improves Refractory Perianal Fistula in Crohn's Disease: Case Series Clinical Interventional Study.

Objective: Perianal fistulas in Crohn's disease (CD) are the main challenges in inflammatory bowel diseases (IBDs). Some of the fistulas are refractory to any therapeutic strategy. The aim of this study was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) as a novel promising modality for the treatment of fistulizing CD. Materials and Methods: This case series clinical interventional study was conducted from 2014 to 2017 at Shariati Hospital, an IBD referral center in Tehran, Iran. Refractory adult patients with CD who had draining perianal fistulas were enrolled in this study. All patients were examined by a colorectal surgeon and the fistula imaging studies were performed by pelvic magnetic resonance imaging (MRI). After autologous bone marrow (BM) aspiration and MSCs isolation, the cells were cultured and passaged under current good manufacturing practice (cGMP) conditions. Four intra-fistula injections of cells, each containing 40×106 MSCs suspended in fibrin glue, were administered by an expert surgeon every 4 weeks. Procedure safety, feasibility and closure of the perianal fistulas at week 24 were assessed. Clinical examination and MRI findings were considered as the primary end points. Results: In total, 5 patients (2 males and 3 females) were enrolled in this study. No adverse events were observed during the six-month follow-up in these patients. Both the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) scores decreased in all patients after cell injections and one patient achieved complete remission with closure of fistulas, discontinuation of fistula discharge, and closure of the external opening. Conclusion: Local injection of MSCs combined with fibrin glue is potentially a safe and effective therapeutic approach for complex perianal fistulas in patients with CD.

Dietary intake of fatty acids and risk of pancreatic cancer: Golestan cohort study.

BACKGROUND: As pancreatic cancer (PC) is a malignancy with poor prognosis, finding strategies for its prevention became a notable priority. Among all the factors influencing the risk of PC, dietary items especially fats are considered as the most modifiable risk factors.This study is designed to assess the associations of dietary intake of fatty acids with the risk of PC incidence. METHODS: A total of 50,045 adults between 40 and 75 years old participated in this cohort study in 2004-2008 and were followed up to the present. Intakes of fatty acids was evaluated by validated food-frequency questionnaire (FFQ). Cox proportional hazards regression model was used to estimate hazard ratio (HR) with 95 % confidence interval of differing levels of dietary intakes of fatty acids for incidence of PC. RESULTS: At the end of follow-up period, 76 cases of PC were identified and 46,904 participants without history of cancer, acute kidney disorders, fibrosis and cirrhosis were included in the study. Dietary total saturated fatty acids (SFAS) was associated with PC risk (HR = 1.05 (1.01-1.09), Ptrend=0.01), whereas dietary total monounsaturated fatty acids (MUFAS) was inversely associated with the risk of PC (HR = 0.92 (0.86-0.99), Ptrend=0.04). Dietary total polyunsaturated fatty acids (PUFAS) did show a protective but not significant association with the risk of PC (HR = 0.91(0.84-1.00), Ptrend=0.05). CONCLUSIONS: The amount of total fat intake is not a risk factor for PC in our study and focusing on the intake of specific fatty acids becomes more striking. Unsaturated fatty acids including PUFAS and especially MUFAS are considered as protective dietary factors in PC prevention. In contrast, total SFAS is positively associated with the increased risk of PC. However, very long chain and odd-chain saturated fatty acids intake may be protective against PC.

The Prevalence of Nonalcoholic Fatty Pancreas by Endoscopic Ultrasonography.

OBJECTIVES: Pancreatic steatosis or fatty pancreas refers to the fat accumulation in the pancreas, which can lead to inflammation and fibrosis, ß-cell dysfunction, fibrosis, and, possibly, pancreatic cancer. This study aimed to study the prevalence of fatty pancreas and its risk factors in patients referred to an endosonography center. METHODS: During 18 months, 228 patients who were referred to our endosonography center for various reasons were evaluated for fatty pancreas. Fatty pancreas was defined as hyperechoic pancreas echotexture compared with spleen echotexture. Demographic characteristics, past medical history, and laboratory measurements were compared between groups with and without fatty pancreas to determine the risk factors for fatty pancreas. RESULTS: The prevalence of fatty pancreas was 25.9%. Patients with fatty pancreas had a significantly higher mean level of uric acid (P = 0.04), frequency of ischemic heart disease (P = 0.03), hyperlipidemia (P = 0.04), frequency of fatty liver (P < 0.001), and aortic intima thickness (P = 0.01). There was no significant difference in age, sex, body mass index, smoking status, substance abuse, and use of oral contraceptives in the 2 groups. CONCLUSIONS: Fatty pancreas is a common disorder. There are meaningful relationships between coronary artery disease, nonalcoholic fatty liver, and atherosclerosis with fatty pancreas.

Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial.

BACKGROUND: Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients. METHODS: In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer's lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed. RESULTS: During 21 months, a total of 414 patients (mean age 55.5 ±â€Š17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % - 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % - 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % - 21.4 %] in group B). There was no significant difference between the two groups in PEP severity (P = 0.59), amylase levels after 2 hours (P = 0.31) or 24 hours (P = 0.08), and length of hospital stay (P = 0.07). CONCLUSIONS: The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.

Prevalence and Clinical Outcomes of Common Bile Duct Dilation in Patients Who Use Opium.

BACKGROUND: This study aimed to evaluate the association of various opium-related factors with common bile duct (CBD) diameter in individuals who use opium in the general population and investigate the clinical importance and long-term outcomes. MATERIALS AND METHODS: In this prospective study, 2,400 participants were randomly selected from the Golestan Cohort study. Opium consumption data were recorded. CBD diameter was measured by ultrasound. Transient elastography was performed at enrollment and 3 years later. Participants were followed up for at least 5 years. RESULTS: A total of 1,599 individuals, aged above 50 years, were enrolled and 167 subjects were users of opium. CBD diameter was significantly higher in users of opium than controls (mean ± standard deviation:5.54 ± 1.95 versus 4.74 ± 1.34mm, P < 0.001). This difference was noted with all opium types, but mostly by users of heroin (P < 0.001). Ingestion of opium caused greater CBD dilatation than inhalation (coefficient: 1.16; 95% CI: 0.05-2.27, P = 0.04 versus coefficient: 0.98; 95% CI: 0.75-1.20, P < 0.001). Transient elastography results did not show any association between fibroscan score change and CBD diameter. No major related malignancy was seen during follow-up. CONCLUSIONS: This study strengthened the evidence of an association of opium use with increased CBD diameter in a population-based setting without significantly increased risk of pancreaticobiliary malignancies or liver fibrosis. We cautiously suggest that opium-induced CBD dilatation may not require further diagnostic work-up.

Per-Pass Performance Characteristics of Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Malignant Solid Pancreatic Masses in a Large Multicenter Cohort.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely performed for the evaluation of pancreatic masses. We evaluated the performance characteristics of EUS-FNA in obtaining a diagnosis of pancreatic malignancy. METHODS: We performed a multicenter study of patients who underwent EUS-FNA for a solid pancreatic mass. Endoscopic ultrasound-guided FNA was standardized using a 25-gauge needle, slow-pull stylet technique for specimen acquisition, and on-site cytopathology. For the primary analysis, only malignant cytology was regarded as positive. A secondary analysis was performed in which malignant and/or suspicious cytology was regarded as positive. RESULTS: A total of 138 patients underwent EUS-FNA. In the primary analysis, the sensitivity of EUS-FNA for malignancy was 56.7% on first pass, 73.3% on second pass, 83.3% on third pass, 89.2% on fourth pass, and 90.8% on fifth pass, with no increase beyond the fifth pass. In the secondary analysis, the sensitivity was 75.0% on first pass, 89.2% on second pass, 93.3% on third pass, and 95.8% on fourth pass, with no increase beyond the fourth pass. No significant relationship was seen between lesion size and diagnostic yield. CONCLUSIONS: Using a 25-gauge needle, the maximal diagnostic yield of EUS-FNA for a solid pancreatic mass is reached after 4 needle passes.

Opium Use and Risk of Pancreatic Cancer: A Prospective Cohort Study.

Background: We examined the association between opium consumption and pancreatic cancer incidence in a large-scale prospective cohort of the general population in northeastern Iran.Methods: A total of 50,045 adults were systematically followed up (median of 7.4 years), and incident cases of pancreatic cancer were identified. Self-reported data on opium consumption was collected at baseline. Cumulative use (-year) was defined as number of nokhods (a local unit, approximately 0.2 g) of opium consumed per day multiplied by number of years consuming. Adjusted HRs and 95% confidence intervals (CIs) for the association between opium consumption and pancreatic cancer were calculated using Cox proportional hazards regression models.Results: Overall, 54 confirmed cases of pancreatic cancer were identified. Opium use of more than 81 nokhod-years (high cumulative use), compared with never use, was strongly associated with pancreatic cancer even after adjustments for multiple potential confounding factors [HR = 3.01; 95% CI, 1.25-7.26]. High cumulative consumption of opium was significantly associated with risk of pancreatic cancer after adjusting for cumulative dose of cigarette smoking [HR = 3.56; 95% CI, 1.49-8.50]. In a sensitivity analysis, we excluded participants (including 2 pancreatic cancer cases) who were recruited within the first 5 years of starting opium consumption; high cumulative use of opium was still associated with pancreatic cancer risk [HR = 2.75; 95% CI, 1.14-6.64].Conclusions: Our results showed a positive association between opium consumption and pancreatic cancer.Impact: This is the first prospective large-scale study to show the association of opium consumption with pancreatic cancer as a risk factor. Cancer Epidemiol Biomarkers Prev; 27(3); 268-73. ©2017 AACR.

Ulcerative Colitis Following Orthotopic Cardiac Transplantation.

Inflammatory bowel disease following a solid organ transplantation while the patient is receiving immunosuppressive therapy is a rare phenomenon. Here we present a 48-year-old man who underwent cardiac transplantation 9 years earlier and was receiving cyclosporine as immunosuppressive therapy since then, presenting with complaints of rectorrhagia and diarrhea. In follow-up, he was diagnosed as having ulcerative colitis. We also reviewed the literature for similar cases, which yielded very few similar ones.

Increasing Number of Passes Beyond 4 Does Not Increase Sensitivity of Detection of Pancreatic Malignancy by Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

BACKGROUND & AIMS: It is not clear exactly how many passes are required to determine whether pancreatic masses are malignant using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We aimed to define the per-pass diagnostic yield of EUS-FNA for establishing the malignancy of a pancreatic mass, and identify factors associated with detection of malignancies. METHODS: In a prospective study, 239 patients with solid pancreatic masses were randomly assigned to groups that underwent EUS-FNA, with the number of passes determined by an on-site cytopathology evaluation or set at 7 passes, at 3 tertiary referral centers. A final diagnosis of pancreatic malignancy was made based on findings from cytology, surgery, or a follow-up evaluation at least 1 year after EUS-FNA. The cumulative sensitivity of detection of malignancy by EUS-FNA was calculated after each pass; in the primary analysis, lesions categorized as malignant or suspicious were considered as positive findings. RESULTS: Pancreatic malignancies were found in 202 patients (84.5% of the study population). EUS-FNA detected malignancies with 96% sensitivity (95% confidence interval [CI], 92%-98%); 4 passes of EUS-FNA detected malignancies with 92% sensitivity (95% CI, 87%-95%). Tumor size greater than 2 cm was the only variable associated with positive results from cytology analysis (odds ratio, 7.8; 95% CI, 1.9-31.6). In masses larger than 2 cm, 4 passes of EUS-FNA detected malignancies with 93% sensitivity (95% CI, 89%-96%) and in masses ≤2 cm, 6 passes was associated with 82% sensitivity (95% CI, 61%-93%). Sensitivity of detection did not increase with increasing number of passes. CONCLUSIONS: In a prospective study, we found 4 passes of EUS-FNA to be sufficient to detect malignant pancreatic masses; increasing the number of passes did not increase the sensitivity of detection. Tumor size greater than 2 cm was associated with malignancy, and a greater number of passes may be required to evaluate masses 2 cm or less. ClinicalTrials.gov number, NCT01386931.