Safety Parameters for the Use of Holmium:YAG Laser in the Treatment of Biliary Calculi: The Ex-Vivo Model.

Background and Objectives: While studies have demonstrated the efficacy of cholangioscopy-guided Holmium-Yttrium aluminum garnet (Ho:YAG) laser lithotripsy for the treatment of refractory bile duct stones, data regarding the safety of the operating parameters for laser lithotripsy are lacking. The aim of this study was to determine safe, yet effective, energy settings for Ho:YAG laser in the ex-vivo model. Materials and Methods: This ex vivo experimental study utilized the Ho:YAG laser on porcine bile duct epithelium and human gallstones. Ho:YAG laser lithotripsy was applied in different power settings from 8 to 15 Watts (W) to six explanted porcine bile ducts. Settings that appeared safe were then utilized to fragment seventy-three human gallstones. Results: The median bile duct perforation times with the Ho:YAG laser between 8-15 W were: >60 s (8 W); 23 s (9 W); 29 s (10 W); 27 s (12 W); 12 s (14 W); and 8 s (15 W). Statistically significant differences in the median perforation times were noted between 8 W vs. 15 W, 9 W vs. 15 W, 10 W vs. 15 W, and 12 W vs. 15 W (p < 0.05). When using a 365 µm Ho:YAG laser probe at 8-12 W, the fragmentation rates on various size stones were: 100% (<1.5 cm); 80-100% (1.6-2.0 cm) and 0-32% (>2.0 cm). Optimal fragmentation was seen utilizing 12 W with high energy (2.4 J) and low frequency (5 Hz) settings. Using a larger 550 µm probe at these settings resulted in 100% fragmentation of stones larger than 2 cm. Conclusions: The Ho:YAG laser appears to be safe and effective in the treatment of large bile duct stones when used between 8-12 W in 5 s bursts in an ex vivo model utilizing porcine bile ducts and human gallstones.

Endoscopy versus early surgery for the management of chronic pancreatitis: a systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic stone removal and stenting of pancreatic strictures are the initial treatment for treating chronic pancreatitis-related pain. Surgery is considered when endoscopic interventions fail to improve symptoms. In this meta-analysis, we have compared early surgery versus endoscopic interventions. METHODS: The study was performed as per the PRISMA statement. The literature search was conducted on online databases to identify studies that compared endoscopy and surgery for the management of chronic pancreatitis symptoms. Primary outcomes of interest were pain relief, complications, and exocrine/endocrine insufficiency. Secondary outcomes were mean length of stay and mean number of procedures. Pooled odds ratio (OR) was calculated using random-effects model with 95% confidence interval (CI). RESULTS: Of a total of 9880 articles that were screened, three randomized controlled trials and two retrospective studies with 602 patients (71.4% males) were found to be eligible. Endoscopic interventions were performed in 317 patients and 285 patients underwent early surgery. Early surgery provided significantly better pain relief compared to endoscopy (OR 0.46; 95%CI 0.27-0.80; p = 0.01; I2 = 17.65%) and required less number of procedures (Mean difference 1.66; 95%CI 0.9-2.43; p = 0.00; I2 = 96.46%). There was no significant difference in procedure-related complication (OR 0.91; 95%CI 0.51-1.61; p = 0.74; I2 = 38.8%), endocrine (OR 1.18; 95%CI 0.63-2.20; p = 0.61; I2 = 28.24%), or exocrine insufficiency (OR 1.78; 95%CI 0.66-4.79; p = 0.25; I2 = 30.97%) or the length of stay (Mean difference 1.21; 95%CI -7.12 to 4.70; p = 0.69). CONCLUSION: Compared to endoscopy, early surgery appears to be better in controlling chronic pancreatitis-related pain, with no significant difference in procedure-related complications. However, larger randomized controlled trials are needed to ascertain their efficacy.

Pancreatic Stones and Extracorporeal Shockwave Lithotripsy: A Review of the Literature.

ABSTRACT: Pancreatic stones are sequelae of chronic pancreatitis, resulting in poor quality of life, frequent hospitalizations, and a significant economic burden. Extracorporeal shock wave lithotripsy (ESWL) can be used to treat pancreatic stones and is less invasive when compared to other modalities. In this review article, we have discussed the role of ESWL in the treatment of pancreatic stones and how it differs from other modalities. Databases were searched electronically for articles discussing the treatment of pancreatic ductal stones by ESWL or other modalities. Articles discussing or comparing treatment success rates were preferentially included. An inductive approach was used to identify articles related to the treatment of pancreatic stones with ESWL throughout the review process. Although laser lithotripsy and electrohydraulic lithotripsy appear to have higher success rates, the potential for ESWL to affect clinical outcomes is substantial, especially in individuals with a higher risk for invasive procedures. The decision to perform ESWL should be considered if the outcome will substantially alter the clinical management when performed by an experienced endoscopist. Further randomized controlled trials are needed to compare ESWL and peroral pancreatic lithotripsy methods.

Management of Hepatolithiasis: Review of the Literature.

PURPOSE OF REVIEW: Hepatolithiasis is a disease characterized by intrahepatic stone formation. In this article, we review the features of this disease and explore the established and emerging treatment modalities. RECENT FINDINGS: Recent reports show an increasing prevalence of hepatolithiasis, likely owed to increased immigration and shifts in the Western diet. New pharmacotherapy options are limited and are often only supportive. Endoscopic intervention still cruxes on removal of impacted stones, though new techniques such as bile duct exploratory lithotomy and lithotripsy continue to advance management. Although hepatectomy of the effected portion of the liver offers definitive therapy, alternative less invasive modalities such as combined endoscopic/interventional radiology modalities have been utilized in select patients. Additionally, liver transplant serves as an option for otherwise incurable hepatolithiasis with coexisting liver dysfunction. Multiple emerging pharmacologic and procedural interventions may provide novel treatment for hepatolithiasis. While definitive therapy remains resection of affected liver segments, these modalities offer hope for less invasive approaches in the future.

Talking Genes in Breast and Pancreatic Malignancies.

INTRODUCTION: Both breast and pancreatic cancers have high mortality rates. Breast cancer is the second leading cause of cancer death in females, while pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death. Almost 4-16 % of individuals with pancreatic cancer have a family history of the disease. Intra-ductal papillary mucinous neoplasms (IPMNs) are cystic lesions that received more attention lately due to their associations with PDAC and other solid organ tumors, such as breast cancer. AIM: The purpose of this article is to discuss the association of the familiar pancreatic cancer (FPC), sporadic pancreatic cancer, and IPMNs with the breast cancer. RESULTS: Mutations in BRCA2, BRCA1, p16 and PALB2 play a major role in the genetic etiologies of familial pancreatic cancer. In familial and sporadic pancreatic cancers, mutations in BRCA2 are associated with a high incidence of PDAC, while mutations in BRCA1have shown inconsistent results. Data is insufficient to prove an association between IPMNs and breast cancer. CONCLUSION: The familial clustering of PDAC is not well understood. Further studies are required for greater comprehension of the genetic basis of PDAC and the association between IPMNs and breast cancer.

Dilemma of elevated CA 19-9 in biliary pathology.

Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker which has been extensively evaluated and widely utilized primarily in diagnosing and prognosticating pancreaticobiliary malignancies. Levels may be significantly influenced and elevated in cases of benign biliary conditions however, especially in obstructive jaundice, thereby posing difficulty in distinguishing between benign and malignant cholestasis. A myriad of studies have focused on elucidating proper use and interpretation of CA 19-9 in pancreatic cancer as well as in the setting of cholestasis. These studies have demonstrated that many factors influence CA 19-9 values and various methods for interpreting CA 19-9 in obstructive jaundice have been proposed. With improvements in diagnostic imaging, advancements in endoscopic modalities, and likelihood that management will not change based on the results of the test, clinicians should be cautious when ordering CA 19-9 and consider the reasons for measuring the tumor marker.

Acute Pancreatitis in Chronic Dialysis Patients.

The annual incidence of acute pancreatitis (AP) ranges from 4.9 to 73.4 cases per 100,000 worldwide. Patients with end-stage renal disease on dialysis have an increased risk for developing AP compared with patients without renal disease. In addition to the general population risk factors, there are factors related to renal insufficiency and dialysis process that might predispose to AP in this population. Clinical features and diagnosis are the same as those in patients without renal failure; however, amylase and lipase levels should be interpreted cautiously as they might be falsely elevated in renal failure. In this article, we will describe the risk factors that are exclusive to this population. In addition, we will also focus on the laboratory indices and clinical features that are unique to this population with patients with end-stage renal disease.

The Emerging Role of Endoscopists in Treating Unresectable Pancreatic Cancer.

Pancreatic adenocarcinoma is the eighth leading cause of cancer deaths worldwide in men and ninth leading cause in women. Surgical resection offers the only chance of potential cure; however, only 9.4% of patients present at the localized, resectable stage, whereas the rest present at the locally advanced or metastatic, unresectable stages. Because of the guarded outcomes following systemic chemoradiation and the associated systemic toxicities, locoregional therapies have recently gained popularity. Various endoscopic techniques (endoscopic ultrasound [EUS]-guided ablative therapies, fine-needle instillation of antitumor agents, stereotactic body radiation therapy with EUS-guided fiducial marker placement, and EUS-guided brachytherapy) have been explored over the past several years. Endoscopic therapy plays a role in the treatment of unresectable pancreatic adenocarcinoma. Its minimal invasiveness and increased precision of delivering oncologic treatments under EUS guidance render it as a favorable option for patients who do not benefit from surgical resection. New endoscopic therapies are currently under investigation, and the emerging role of the endoscopist in the treatment of unresectable pancreatic cancer continues to grow.

A Prospective Multicenter Study Evaluating Learning Curves and Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography Among Advanced Endoscopy Trainees: The Rapid Assessment of Trainee Endoscopy Skills Study.

BACKGROUND & AIMS: On the basis of the Next Accreditation System, trainee assessment should occur on a continuous basis with individualized feedback. We aimed to validate endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) learning curves among advanced endoscopy trainees (AETs) by using a large national sample of training programs and to develop a centralized database that allows assessment of performance in relation to peers. METHODS: ASGE recognized training programs were invited to participate, and AETs were graded on ERCP and EUS exams by using a validated competency assessment tool that assesses technical and cognitive competence in a continuous fashion. Grading for each skill was done by using a 4-point scoring system, and a comprehensive data collection and reporting system was built to create learning curves by using cumulative sum analysis. Individual results and benchmarking to peers were shared with AETs and trainers quarterly. RESULTS: Of the 62 programs invited, 20 programs and 22 AETs participated in this study. At the end of training, median number of EUS and ERCP performed/AET was 300 (range, 155-650) and 350 (125-500), respectively. Overall, 3786 exams were graded (EUS, 1137; ERCP-biliary, 2280; ERCP-pancreatic, 369). Learning curves for individual end points and overall technical/cognitive aspects in EUS and ERCP demonstrated substantial variability and were successfully shared with all programs. The majority of trainees achieved overall technical (EUS, 82%; ERCP, 60%) and cognitive (EUS, 76%; ERCP, 100%) competence at conclusion of training. CONCLUSIONS: These results demonstrate the feasibility of establishing a centralized database to report individualized learning curves and confirm the substantial variability in time to achieve competence among AETs in EUS and ERCP. ClinicalTrials.gov: NCT02509416.

Autoimmune Pancreatitis and Inflammatory Bowel Disease: An Updated Review.

Autoimmune pancreatitis (AIP) occurring in association with inflammatory bowel disease (IBD) is rather rare and carries a worse prognosis and greater disease severity compared with IBD alone. Although it is an infrequently documented association, progress over the last 20 years has led to better understanding of the association between AIP and IBD. IBD has a stronger association with type 2 than with type 1 AIP. Clinical and histologic features of AIP-IBD more often reveal features of type 2 AIP. Imaging is not helpful in facilitating the diagnosis of AIP and IBD. Similarly, attempts to identify a serological marker have not yielded better result. A proposed lymphocyte homing mechanism provides some insight into the mechanism of pathogenesis. This review represents an update of our current knowledge of the association between AIP and IBD.

A Concurrent Case of Ménétrier's Disease and Signet Ring Carcinoma.

Ménétrier's disease, also known as hyperplastic protein-losing gastropathy, is a rare, idiopathic, acquired, premalignant condition associated with gastric carcinoma. Its association with signet ring cell cancer of the stomach has been previously reported only twice. We present the third case of histologically confirmed concurrent Ménétrier's disease with signet ring carcinoma of the stomach, interrogated by esophagogastroduodenoscopy and endoscopic ultrasound.

Management of Patients With Pancreatic Cysts: Analysis of Possible False-Negative Cases of Malignancy.

GOALS: To examine the utility of integrated molecular pathology (IMP) in managing surveillance of pancreatic cysts based on outcomes and analysis of false negatives (FNs) from a previously published cohort (n=492). BACKGROUND: In endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of cyst fluid lacking malignant cytology, IMP demonstrated better risk stratification for malignancy at approximately 3 years' follow-up than International Consensus Guideline (Fukuoka) 2012 management recommendations in such cases. STUDY: Patient outcomes and clinical features of Fukuoka and IMP FN cases were reviewed. Practical guidance for appropriate surveillance intervals and surgery decisions using IMP were derived from follow-up data, considering EUS-FNA sampling limitations and high-risk clinical circumstances observed. Surveillance intervals for patients based on IMP predictive value were compared with those of Fukuoka. RESULTS: Outcomes at follow-up for IMP low-risk diagnoses supported surveillance every 2 to 3 years, independent of cyst size, when EUS-FNA sampling limitations or high-risk clinical circumstances were absent. In 10 of 11 patients with FN IMP diagnoses (2% of cohort), EUS-FNA sampling limitations existed; Fukuoka identified high risk in 9 of 11 cases. In 4 of 6 FN cases by Fukuoka (1% of cohort), IMP identified high risk. Overall, 55% of cases had possible sampling limitations and 37% had high-risk clinical circumstances. Outcomes support more cautious management in such cases when using IMP. CONCLUSIONS: Adjunct use of IMP can provide evidence for relaxed surveillance of patients with benign cysts that meet Fukuoka criteria for closer observation or surgery. Although infrequent, FN results with IMP can be associated with EUS-FNA sampling limitations or high-risk clinical circumstances.

Endoscopic Ultrasound Elastography: Current Clinical Use in Pancreas.

Elastography is a newer technique for the assessment of tissue elasticity using ultrasound. Cancerous tissue is known to be stiffer (hence, less elastic) than corresponding healthy tissue, and as a result, could be identified in an elasticity-based imaging. Ultrasound elastography has been used in the breast, thyroid, and cervix to differentiate malignant from benign neoplasms and to guide or avoid unnecessary biopsies. In the liver, elastography has enabled a noninvasive and reliable estimate of fibrosis. Endoscopic ultrasound has become a robust diagnostic and therapeutic tool for the management of pancreatic diseases. The addition of elastography to endoscopic ultrasound enabled further characterization of pancreas lesions, and several European and Asian studies have reported encouraging results. The current clinical role of endoscopic ultrasound elastography in the management of pancreas disorders and related literature are reviewed.

Endoscopic drainage of pancreatic fluid collections using a fully covered expandable metal stent with antimigratory fins.

BACKGROUND AND OBJECTIVES: Endoscopic drainage is the first consideration in treating pancreatic fluid collections (PFCs). Recent data suggests it may be useful in complicated PFCs as well. Most of the available data assess the use of plastic stents, but scarce data exists on metal stent management of PFCs. The aim of our study to evaluate the efficacy and safety of a metal stent in the management of PFCs. PATIENTS AND METHODS: Data were collected prospectively on 47 patients diagnosed with PFCs from March 2007 to August 2011 at 3 tertiary care centers. These patients underwent endoscopic transmural placement of a fully covered self-expanding metal stent (FCSEMS) with antimigratory fins of 10 mm diameter. RESULTS: The stent was successfully placed in all patients, and left in place an average of 13 weeks (range 0.4-36 weeks). Etiology of the PFC was biliary pancreatitis (23), pancreas divisum (2), trauma (4), hyperlipidemia (3), alcoholic (8), smoking (2), idiopathic (4), and medication-induced (1). PFCs resolved in 36 patients, for an overall success rate of 77%. Complications included fever (3), stent migration (2) and abdominal pain (1). CONCLUSIONS: The use of FCSEMS is successful in the majority of patients with low complication rates. A large sample-sized RCT is needed to confirm if the resolution of PFCs is long-standing.

Cavernous hemangioma of adult pancreas: A case report and literature review.

Pancreatic hemangioma is a rare type of benign vascular tumor. Low clinical suspicion and inability of current cross sectional imaging techniques to differentiate it from other pancreatic lesions, contribute to the difficulty in making the correct diagnosis. Without a definitive diagnosis, and due to concern for malignancy, in many instances, surgery is performed. We report a case of pancreas cavernous hemangioma in an 18-year-old female. The patient presented with three-month history of epigastric pain. Physical examination and routine blood tests were normal. Abdominal Computed Tomography scan revealed a 5 cm × 6 cm complex non-enhancing cystic mass in the head of pancreas. Magnetic resonance imaging, endoscopic ultrasonography (EUS) and EUS guided fine needle aspiration cytology were non-diagnostic. Because of uncontrolled symptoms, the patient underwent surgical resection. Histopathology and Immunohistochemical staining confirmed the diagnosis of cavernous hemangioma of pancreas.

Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts.

BACKGROUND AND STUDY AIMS: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. PATIENTS AND METHODS: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis ("benign"/"statistically indolent" vs. "statistically higher risk [SHR]"/ "aggressive") or an International Consensus Guideline (Sendai 2012) criteria model for "surveillance" vs. "surgery." The Cox proportional hazards model determined hazard ratios for malignancy. RESULTS: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001). CONCLUSION: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.

How do we manage post-OLT redundant bile duct?

AIM: To address endoscopic outcomes of post-Orthotopic liver transplantation (OLT) patients diagnosed with a "redundant bile duct" (RBD). METHODS: Medical records of patients who underwent OLT at the Liver Transplant Center, University Texas Health Science Center at San Antonio Texas were retrospectively analyzed. Patients with suspected biliary tract complications (BTC) underwent endoscopic retrograde cholangiopancreatography (ERCP). All ERCP were performed by experienced biliary endoscopist. RBD was defined as a looped, sigmoid-shaped bile duct on cholangiogram with associated cholestatic liver biomarkers. Patients with biliary T-tube placement, biliary anastomotic strictures, bile leaks, bile-duct stones-sludge and suspected sphincter of oddi dysfunction were excluded. Therapy included single or multiple biliary stents with or without sphincterotomy. The incidence of RBD, the number of ERCP corrective sessions, and the type of endoscopic interventions were recorded. Successful response to endoscopic therapy was defined as resolution of RBD with normalization of associated cholestasis. Laboratory data and pertinent radiographic imaging noted included the pre-ERCP period and a follow up period of 6-12 mo after the last ERCP intervention. RESULTS: One thousand two hundred and eighty-two patient records who received OLT from 1992 through 2011 were reviewed. Two hundred and twenty-four patients underwent ERCP for suspected BTC. RBD was reported in each of the initial cholangiograms. Twenty-one out of 1282 (1.6%) were identified as having RBD. There were 12 men and 9 women, average age of 59.6 years. Primary indication for ERCP was cholestatic pattern of liver associated biomarkers. Nineteen out of 21 patients underwent endoscopic therapy and 2/21 required immediate surgical intervention. In the endoscopically managed group: 65 ERCP procedures were performed with an average of 3.4 per patient and 1.1 stent per session. Fifteen out of 19 (78.9%) patients were successfully managed with biliary stenting. All stents were plastic. Selection of stent size and length were based upon endoscopist preference. Stent size ranged from 7 to 11.5 Fr (average stent size 10 Fr); Stent length ranged from 6 to 15 cm (average length 9 cm). Concurrent biliary sphincterotomy was performed in 10/19 patients. Single ERCP session was sufficient in 6/15 (40.0%) patients, whereas 4/15 (26.7%) patients needed two ERCP sessions and 5/15 (33.3%) patients required more than two (average of 5.4 ERCP procedures). Single biliary stent was sufficient in 5 patients; the remaining patients required an average of 4.9 stents. Four out of 19 (21.1%) patients failed endotherapy (lack of resolution of RBD and recurrent cholestasis in the absence of biliary stent) and required either choledocojejunostomy (2/4) or percutaneous biliary drainage (2/4). Endoscopic complications included: 2/65 (3%) post-ERCP pancreatitis and 2/10 (20%) non-complicated post-sphincterotomy bleeding. No endoscopic related mortality was found. The medical records of the 15 successful endoscopically managed patients were reviewed for a period of one year after removal of all biliary stents. Eleven patients had continued resolution of cholestatic biomarkers (73%). One patient had recurrent hepatitis C, 2 patients suffered septic shock which was not associated with ERCP and 1 patient was transferred care to an outside provider and records were not available for our review. CONCLUSION: Although surgical biliary reconstruction techniques have improved, RBD represents a post-OLT complication. This entity is rare however, endoscopic management of RBD represents a reasonable initial approach.