Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Gas Leak and Mucosal Injury During Endoscopic Esophageal Myotomy After Previous Myotomy: A Single-Center Experience.

PURPOSE: Peroral endoscopic myotomy (POEM) after prior myotomy (PM-POEM) can be technically challenging with possible increased adverse events. We aimed to assess gas leak and mucosal injury incidence during PM-POEM, compared to an index POEM (iPOEM), and post-procedure extubation time. PATIENTS AND METHODS: A retrospective study comparing PM-POEM to iPOEM from March 2016 to August 2018. RESULTS: There were 21 subjects in the PM-POEM and 56 subjects in the iPOEM. The PM-POEM group was younger (average age 44.33 vs 57.57 years, p=0.0082). Gas leak incidence did not differ between groups (28.6% in PM-POEM vs 14.3% in iPOEM, p=0.148). For cases with imaging available postoperatively, there was a trend towards higher incidence of gas leak in the PM-POEM, but it was not statistically significant (60% vs 42.1%, p=0.359). The post-procedure extubation time was not different between PM-POEM and iPOEM (11.38 vs 9.46 minutes, p=0.93), but it was longer when gas leak occurred (15.92 vs 8.67 minutes, p=0.027). The odds of mucosal injury were four-fold higher (OR, 4.31; 95% CI, 1.32-14.08), and more clips were used to close mucosal injuries (0.62 vs 0.14 clips, p=0.0053) in the PM-POEM group. More procedures were deemed difficult or challenging in the PM-POEM (33.3% vs 7.1%, p=0.007). The number of clips used to close the mucosotomy was not different between groups (4.05 vs 3.84 clips, p=0.498). Although the myotomy was shorter in PM-POEM, it was not statistically significant (6.38 vs 7.14 cm, p=0.074). However, the procedure was longer in PM-POEM (61.28 vs 45.39 minutes, p=0.0017). There was no intervention or ICU admission required pertinent to the procedure. CONCLUSION: Performing PM-POEM can be more difficult with more mucosal injuries. Gas leak was associated with a slightly longer post-procedure extubation time, but clinical relevance is unclear given incidence of gas leak was unknown at time of extubation.

Direct Endoscopic Necrosectomy With and Without Hydrogen Peroxide for Walled-off Pancreatic Necrosis: A Multicenter Comparative Study.

INTRODUCTION: Endoscopic necrosectomy has emerged as the preferred treatment modality for walled-off pancreatic necrosis. This study was designed to evaluate the safety and efficacy of direct endoscopic necrosectomy with and without hydrogen peroxide (H2O2) lavage. METHODS: Retrospective chart reviews were performed for all patients undergoing endoscopic transmural management of walled-off pancreatic necrosis at 9 major medical centers from November 2011 to August 2018. Clinical success was defined as the resolution of the collection by imaging within 6 months, without requiring non-endoscopic procedures or surgery. RESULTS: Of 293 patients, 204 met the inclusion criteria. Technical and clinical success rates were 100% (204/204) and 81% (166/189), respectively. For patients, 122 (59.8%) patients had at least one H2O2 necrosectomy (H2O2 group) and 82 (40.2%) patients had standard endoscopic necrosectomy. Clinical success was higher in the H2O2 group: 106/113 (93.8%) vs 60/76 (78.9%), P = 0.002. On a multivariate analysis, the use of H2O2 was associated with higher clinical success rate (odds ratio 3.30, P = 0.033) and earlier resolution (odds ratio 2.27, P < 0.001). During a mean follow-up of 274 days, 27 complications occurred. Comparing procedures performed with and without H2O2 (n = 250 vs 183), there was no difference in post-procedure bleeding (7 vs 9, P = 0.25), perforation (2 vs 3, P = 0.66), infection (1 vs 2, P = 0.58), or overall complication rate (n = 13 [5.2%] vs 14 [7.7%], P = 0.30). DISCUSSION: H2O2-assisted endoscopic necrosectomy had a higher clinical success rate and a shorter time to resolution with equivalent complication rates relative to standard necrosectomy.See the visual abstract at http://links.lww.com/AJG/B714.(Equation is included in full-text article.).

Utilizing functional lumen imaging probe in directing treatment for post-fundoplication dysphagia.

BACKGROUND: Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia. METHODS: We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist's description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI) < 2.8 mm2/mmHg on real-time FLIP. In patients with EGJO and dysphagia, EGJ dilation was performed to 20 mm, 30 mm, or 35 mm in a stepwise fashion. Outcome was assessed as % dysphagia improvement during phone call or on brief esophageal dysphagia questionnaire (BEDQ) score. RESULTS: Twenty-six patients were included, of whom 17 (65%) had a low EGJ-DI. No patients had a hiatal hernia greater than 3 cm. Dysphagia was the primary symptom in 17/26 (65%). In 85% (κ = 0.677) of cases, EGJ assessment (tight vs. open) was congruent between the combination of endoscopy (n = 26) and esophagram (n = 21) vs. EGJ-DI (n = 26) on FLIP. Follow-up data were available in 11 patients who had dilation based on a low EGJ-DI (4 with 20 mm balloon and 7 with ≥ 30 mm balloon). Overall, the mean % improvement in dysphagia was 60% (95% CI 37.7-82.3%, p = 0.0001). Nine out of 11 patients, including 6 out of 7 undergoing pneumatic dilation, had improvement ≥ 50% in dysphagia (mean % improvement 72.2%; 95% CI 56.1-88.4%, p = 0.0001). CONCLUSIONS AND INFERENCES: Functional lumen imaging probe is an accurate modality for evaluating for EGJ obstruction PF. FLIP may be used to select patients who may benefit from larger diameter dilation.

Practice Patterns and Use of Endoscopic Retrograde Cholangiopancreatography in the Management of Recurrent Acute Pancreatitis.

BACKGROUND/AIMS: There are conflicting opinions regarding the management of recurrent acute pancreatitis (RAP). While some physicians recommend endoscopic retrograde cholangiopancreatography (ERCP) in this setting, others consider it to be contraindicated in patients with RAP. The aim of this study was to assess the practice patterns and clinical features influencing the management of RAP in the US. METHODS: An anonymous 35-question survey instrument was developed and refined through multiple iterations, and its use was approved by our Institutional Review Board. The survey was distributed via email to 408 gastroenterologists to assess the practice patterns in the management of RAP in multiple clinical scenarios. RESULTS: The survey was completed by 65 participants representing 36 of the top academic/tertiary care centers across the country. Approximately 90.8% of the participants indicated that they might offer or recommend ERCP in the management of RAP. Multinomial logistic regression analysis revealed that ductal dilatation and presence of symptoms were the most predictive variables (p<0.001) for offering ERCP. CONCLUSION: A preponderance of the respondents would consider ERCP among patients with RAP presenting to tertiary care centers in the US. Ductal dilatation, presence of symptoms, and pancreas divisum significantly increased the likelihood of a recommendation for ERCP.

Performance Characteristics of Magnetic Resonance Imaging in Patients With Pancreas Divisum.

OBJECTIVE: This study was designed to assess the diagnostic accuracy of standard nonsecretin-enhanced preprocedural magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) in patients with and without pancreas divisum. METHODS: Patients undergoing MRI/MRCP followed by endoscopic retrograde cholangiopancreatography with between 2009 and 2016 were reviewed. The diagnostic accuracy of the MRI/MRCP was evaluated against the pancreatography. A subsequent independent blinded re-review performed by an expert abdominal radiologist was also evaluated. Multivariate binary logistic regression was performed to assess the impact of clinicopathologic factors on the diagnostic accuracy. RESULTS: A total of 189 patients were included in analysis. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI/MRCP for pancreas divisum were 63%, 97%, 94%, and 82% initially and 81%, 91%, 91%, and 82% on the expert review. Motion artifact, the presence of pancreatic tumor, and pancreatic necrosis were not found to significantly impact the accuracy. A normal diameter pancreatic duct (P = 0.04) and complete divisum anatomy were correlated with improved accuracy (P = 0.001). CONCLUSIONS: Although expert review, normal duct diameter, and complete divisum are associated with increased sensitivity, pancreas divisum may be uncharacterized by preprocedural MRI in 19% to 37% of patients before the index endoscopic retrograde cholangiopancreatography.

The efficacy of rapid on-site evaluation during endoscopic ultrasound-guided fine needle aspiration of pancreatic masses.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has become the preferred method to diagnose pancreatic masses due to its minimally invasive approach and diagnostic accuracy. Many studies have shown that rapid on-site evaluation (ROSE) improves diagnostic yield by 10-30%; however, more recent studies have demonstrated effective diagnostic accuracy rates without ROSE. Our study aims to examine whether the current standard of performing ROSE after each FNA pass adds diagnostic value during EUS-guided FNA of pancreatic masses. METHODS: We conducted a retrospective case series on patients who underwent EUS-guided FNA of pancreatic masses between February 2011 and October 2014. All cases were performed by one of three endoscopists at Emory University Hospital. Patient demographics, radiologic details of pancreatic masses and pathology reports of the biopsied pancreatic masses were examined. RESULTS: A total of 184 procedures performed in 171 patients were reviewed. The final pathology reports of the biopsied pancreatic masses showed 128 (70%) with confirmed malignancy. Only 64 (50%) of these 128 cases initially showed malignant cells during ROSE. Among these 64 cases, 23% required 5 or more FNA passes to first detect malignant cells. CONCLUSIONS: The use of ROSE during EUS-guided FNA of pancreatic masses may increase the diagnostic yield, since malignant cells were often detected during later FNA passes that would otherwise be missed if tissue sampling stopped prematurely. In addition, sample preparation for ROSE may be suboptimal, since malignant cells were only detected in 50% of cases.

Outcomes and quality of life assessment after per oral endoscopic myotomy (POEM) performed in the endoscopy unit with trainees.

BACKGROUND: Per oral endoscopic myotomy (POEM) has emerged as a promising option for the treatment of achalasia. This study assessed POEM training process, outcomes, and improvement in quality of life after POEM performed by an interventional endoscopist (mentor) with trainees. METHODS: We performed a retrospective review of data for patients who underwent POEM with involvement of trainees. Trainees were trained in performing mucosotomy, submucosal dissection, creating submucosal tunnel, identifying gastroesophageal junction, myotomy, and closure of mucosal incision in a step-by-step fashion. Trainees' performance on each step was evaluated by the mentor based on several key points in each step. The short form 36 (SF36) was obtained before and certain times after the primary POEM procedure was performed. RESULTS: Sixty-two patients, 26 males and 36 females with a mean age of 59 years, who underwent POEM were enrolled. A checklist included all related items for each step was established. All trainees obtained competence within 6 cases for each step. 61/62 (98.3%) patients had a significant improvement in the Eckardt's score post POEM: 9.3 ± 1.5 prior to POEM and 2.6 ± 1.2 after the POEM (P = 0.001) and a decrease in mean lower esophageal sphincter pressure (LES): pre- and post-procedure mean LES pressures were 28.5 ± 11.4 and 12.1 ± 4.5 mmHg, respectively (P = 0.001). The SF-36 questionnaire demonstrated a significant improvement in quality of life and comparable with those without trainees in other studies. CONCLUSION: This preliminary study showed for the first time that training for POEM can be performed in a step-by-step fashion, learning mucosal incision, submucosal dissection, myotomy, and mucosal incision closure from an expert interventional endoscopist without increasing adverse events. The checklist for each step could be used as an important guide in training POEM. The outcomes of POEM in this study were similar to those reported by others without trainees. Further multiple center studies are needed to verify this training process and to establish a formal training protocol.

Incidence, Survival, and Predictors of Lymph Node Involvement in Early-Stage Gastric Signet Ring Cell Carcinoma in the US.

INTRODUCTION: The incidence, survival, and propensity for nodal metastasis in early-stage gastric signet ring cell carcinoma have not been defined in the United States. These data are critical determinants for treatment allocation. METHODS: Cases of gastric signet ring cell carcinoma were extracted from the national SEER database for the years 2004-2013. Age-standardized incidence was derived. Survival was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of nodal metastasis. Exclusion criteria included neoadjuvant radiotherapy and lack of histologic or nodal data. RESULTS: A total of 10,624 cases were initially identified. The analysis cohort included 506 cases with early T-stage N0M0 disease following exclusions. The incidence was 0.094 per 100,000 person-years. The 5-year survival rate was 82.8%. Tumor stage (p < 0.001) and size (p < 0.001) were independent predictors of nodal metastasis. The incidence of nodal involvement for T1a tumors <2 cm was 5.4% (p < 0.004). CONCLUSION: The incidence of potentially resectable signet ring gastric carcinoma has not changed significantly over the past decade. While presenting with predominantly high-grade histology, early T-stage disease has a high survival rate. Small T1a tumors have low rates of nodal metastasis, suggesting that an endoscopic resection could be considered in this subset.

Lymph node metastasis in early gastric adenocarcinoma in the United States of America.

BACKGROUND AND STUDY AIMS: Localized approaches are being increasingly used in the management of early gastric adenocarcinoma; however, there are limited data on lymph node metastasis in the US population. This study examined the incidence and predictors of lymph node involvement for early-stage gastric adenocarcinomas in the USA. PATIENTS AND METHODS: Data were abstracted from the national SEER database from 2004 to 2013. Exclusion criteria included: cases with unknown tumor characteristics, unknown patient characteristics, metastatic disease, neoadjuvant radiation, and lack of surgical resection or lymph node evaluation. Univariate and multivariable analyses were conducted to assess the relationship of tumor stage, grade, and size, and patient sex, race, and age with nodal involvement. RESULTS: 43 769 cases of gastric adenocarcinoma were initially abstracted. After exclusions, 1577 patients remained for analysis. Multivariable analysis revealed that tumor stage (P < 0.001), grade (P = 0.008), and size (P < 0.001) were independent predictors of nodal metastasis. For low grade T1a tumors, nodal metastasis was present in 1.7 %, 1.7 %, 4.5 %, 4.1 %, and 20 % of tumors 0 - 1 cm, 1 - 2 cm, 2 - 3 cm, 3 - 4 cm, and ≥ 4 cm in size, respectively (P < 0.001), and in 8.4 %, 18.0 %, 19.5 %, 22.0 %, and 35.8 % of T1b tumors, respectively (P < 0.001). CONCLUSIONS: Low grade T1a tumors < 4 cm in size have low rates of nodal metastasis in the US population and may warrant consideration for local resection. Larger, higher grade T1b tumors have high rates of nodal metastasis in the US population and lymph node dissection may be indicated for patients who are surgical candidates.

Long-Term Survival in Stage IV Esophageal Adenocarcinoma with Chemoradiation and Serial Endoscopic Cryoablation.

Esophageal cancer has a poor overall prognosis and is frequently diagnosed at a late stage. Conventional treatment for metastatic esophageal cancer involves chemotherapy and radiation. Local disease control plays a significant role in improving survival. Endoscopic spray cryotherapy is a novel modality that involves freezing and thawing to produce local ablation of malignant tissue via ischemic mechanisms. Spray cryotherapy has been shown to be effective, particularly for early T-stage, superficial esophageal adenocarcinomas. We present the case of a 72-year-old-male with locally recurrent stage IV esophageal adenocarcinoma and long-term survival of 7 years to date, with concurrent chemoradiation and serial cryoablation. He remains asymptomatic and continues to undergo chemotherapy and sequential cryoablation. The findings highlight the long-term safety and efficacy of cryotherapy in combination with chemoradiation, and suggest that cryoablation may have an additive role in the treatment of advanced stage esophageal adenocarcinoma.

Endoscopic retrograde cholangiopancreatography with ampullary biopsy vs ERCP alone: a matched-pairs controlled evaluation of outcomes and complications.

BACKGROUND AND AIMS: Biopsy of the ampulla of Vater may be performed to evaluate for ampullary adenomas, suspected ampullary tumors and immunohistological staining for autoimmune pancreatitis. Ampullary biopsies are commonly performed at the time of endoscopic retrograde cholangiopancreatography (ERCP). Due to the well-established complication rate following ERCP, the contribution of ampullary biopsy as a potential independent risk factor would require a controlled comparison. METHODS: A matched-pairs, case-control analysis was performed for patients undergoing ERCP with or without ampullary biopsy. The analysis involved a retrospective review of adult patients at a tertiary-care center who underwent ampullary biopsies during ERCP compared (via procedural complexity) with a matched control group who underwent ERCP without ampullary biopsies. RESULTS: Of 159 procedures involving ampullary biopsy, 54 ERCPs that met the inclusion criteria were performed with ampullary biopsy and included in the analysis cohort. This cohort was compared with 54 patients undergoing ERCP without ampullary biopsy, matched by American Society for Gastrointestinal Endoscopy (ASGE) grade of procedural complexity. There were no patients with sphincter of Oddi dysfunction. Ampullary biopsies suggested a diagnosis in 75.9% of the procedures including 12 adenomas, 5 adenocarcinomas and 1 intraductal papillary mucinous neoplasm. Including major and minor complications, the overall complication rate with biopsy (9.3%) was equivalent to the complication rate in the control group without ampullary biopsy (9.3%, P>0.99). The incidence of post-procedure pancreatitis was not significantly different between the two groups (5.6% vs 3.7%, P=0.6). Age and pancreatic duct manipulation, but not ampullary biopsy, were associated with complications on multivariate analysis in the study population. CONCLUSIONS: Ampullary biopsy performed during ERCP had a high diagnostic yield and was not associated with an increased rate of post-procedure complications or pancreatitis when compared with ERCP alone.

Pancreatic Insufficiency Secondary to Tobacco Exposure: A Controlled Cross-Sectional Evaluation.

OBJECTIVES: Tobacco exposure is an established risk factor for pancreatic cancer and chronic pancreatitis; however, its role in pancreatic insufficiency is not clear. METHODS: This controlled, cross-sectional study examined smokers and nonsmokers with no history of pancreatic disease. Histories and validated inventories of alcohol and tobacco use were obtained, and pancreatic insufficiency was assessed using the fecal elastase-1 assay. RESULTS: Of 7854 patients approached, 226 were interviewed and 200 enrolled. The rates of pancreatic insufficiency [18% (18/100)] and severe pancreatic insufficiency [10% (10/100)] were significantly higher in smokers than in controls [6% (6/100), P = 0.009 and 1% (1/100), P = 0.010, respectively]. On multivariate logistic regression, the risk of pancreatic insufficiency in smokers was significantly increased [odds ratio, 4.34 (1.37-13.75); P = 0.012], controlling for alcohol use and relevant covariates. Tobacco exposure was associated with the highest odds ratio for pancreatic insufficiency. Alcohol consumption was strongly associated with tobacco exposure (P < 0.001), but not with pancreatic insufficiency by multivariate analysis (P = 0.792). CONCLUSIONS: This study suggests that tobacco exposure is independently associated with pancreatic exocrine insufficiency in patients without a prior diagnosis of pancreatic disease. Tobacco exposure seems to have greater detrimental effects on pancreatic function than alcohol in this population.

Treatment allocation in patients with early-stage esophageal adenocarcinoma: Prevalence and predictors of lymph node involvement.

BACKGROUND: In considering treatment allocation for patients with early esophageal adenocarcinoma, the incidence of lymph node metastasis is a critical determinant; however, this has not been well defined or stratified by the relevant clinical predictors of lymph node spread. METHODS: Data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute were abstracted from 2004 to 2010 for patients with early-stage esophageal adenocarcinoma. The incidence of lymph node involvement for patients with Tis, T1a, and T1b tumors was examined and was stratified by predictors of spread. RESULTS: A total of 13,996 patients with esophageal adenocarcinoma were evaluated. Excluding those with advanced, metastatic, and/or invasive (T2-T4) disease, 715 patients with Tis, T1a, and T1b tumors were included. On multivariate analysis, tumor grade (odds ratio [OR], 2.76; 95% confidence interval [95% CI], 1.58-4.82 [P<.001]), T classification (OR, 0.47; 95% CI, 0.24-0.91 [P =.025]), and tumor size (OR, 2.68; 95% CI, 1.48-4.85 [P = .001]) were found to be independently associated with lymph node metastases. There was no lymph node spread noted with Tis tumors. For patients with low-grade (well or moderately differentiated) tumors measuring <2 cm in size, the risk of lymph node metastasis was 1.7% for T1a (P<.001) and 8.6% for T1b (P = .001) tumors. CONCLUSIONS: For patients with low-grade Tis or T1 tumors measuring ≤2 cm in size, the incidence of lymph node metastasis appears to be comparable to the mortality rate associated with esophagectomy. For highly selected patients with early esophageal adenocarcinomas, the results of the current study support the recommendation that local endoscopic resection can be considered as an alternative to surgical management when followed by rigorous endoscopic and radiographic surveillance. Cancer 2016;122:2150-7. © 2016 American Cancer Society.

Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma.

OBJECTIVES: Brush cytology has a low sensitivity for the diagnosis of cholangiocarcinoma. This study aimed to compare the standard approach (brush cytology) with a triple modality approach utilizing brush cytology, forceps biopsy and fluorescence in situ hybridization in terms of sensitivity and specificity for the diagnosis of cholangiocarcinoma. METHODS: In a retrospective study at a single academic center, 50 patients underwent triple modality testing. Additionally, 61 patients underwent brush cytology alone. Intervention was endoscopic retrograde cholangiopancreatography with brush cytology, fluorescence in situ hybridization, and forceps biopsy. The main outcome measures included sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Overall, 50 patients underwent triple tissue sampling, and 61 patients underwent brush cytology alone. Twenty-two patients were eventually diagnosed with cholangiocarcinoma. Brush cytology had a sensitivity of 42%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%. Triple tissue sampling had an overall sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 87%. Within the triple test group, brush cytology had a sensitivity of 27%, forceps biopsy had a sensitivity of 50%, and fluorescence in situ hybridization analysis had a sensitivity of 59%. CONCLUSIONS: A triple modality approach results in a marked increase in sensitivity for the diagnosis of cholangiocarcinoma compared with single modality testing such as brush cytology and should be considered in the evaluation of indeterminate or suspicious biliary strictures.

Health resource utilization and multidisciplinary impact of endoscopic ultrasonography in a tertiary referral medical center.

BACKGROUND: Endoscopic ultrasound (EUS) is a resource-intensive endoscopic procedure, but may result in high downstream health resource utilization and multispecialty impact. Our aim was to examine the downstream impact of EUS by specialty and by indication. METHODS: A retrospective chart review was performed at an academic medical center for patients for whom EUS represented the first point of contact at the study institution within a 20-month period. RESULTS: A total of 552 EUS procedures were reviewed and 208 represented the first point of contact. The most common principle indication involved the pancreas (n = 117, 56%). Downstream health utilization was calculated for an average of 313 days postprocedure (range: 35-632 days). Following unique referral for endoscopic ultrasound, 52% of the patients in the study were retained within the institution for further management and, of these, 34% had a major intervention in the form of surgery or chemoradiotherapy. Compared with other indications, patients presenting with a pancreatic mass were significantly more likely to remain in the study institution for further management (62% versus 39%, p = 0.005), were more likely to have a downstream surgery (29% versus 14%, p = 0.020) and were more likely to have downstream chemo-radiotherapy (11% versus 3%, p = 0.012). CONCLUSIONS: EUS represents a unique portal of entry into tertiary referral medical centers. First point of contact EUS referrals are associated with major downstream health resource utilization and significantly increased utilization for mass lesions of the pancreas.

Increased diagnostic yield of endoscopic ultrasound-guided fine needle aspirates with flow cytometry and immunohistochemistry.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most sensitive and specific test for establishing a tissue diagnosis for many gastrointestinal malignancies; however, cytologic morphology alone may not be definitive for subsets of tumors. Our aim was to quantify the impact of the broad application of flow cytometry (FC) and immunohistochemistry (IHC) on EUS-FNA diagnostic yield. A retrospective chart review was performed on EUS procedures at a tertiary referral, academic medical center. All EUS-FNA cases performed over a 21-month period were examined. Of 606 EUS procedures reviewed during the period of study, 264 utilized FNA. After pancreatic cyst cases were excluded, 235 EUS-FNA cases for 221 patients were selected for analysis. For cases with subsequent histological evaluation, including the subset utilizing FC/IHC, the sensitivity of EUS-FNA was 89%, specificity was 100%, and accuracy was 91%. One quarter (58/235, 25%) of the tissue specimens underwent further testing by FC/IHC. There were 48 definitive diagnoses made in the subset utilizing FC/IHC. In 20 of the 48 diagnoses (42%), FC/IHC was deemed critical to the diagnosis, and without FC/IHC testing in those cases, the overall sensitivity and accuracy of EUS-FNA would be reduced to 74 and 77%, respectively. FC/IHC allowed for six diagnoses rarely or not previously described by EUS-FNA. Application of FC/IHC improves characterization predominantly for nonadenocarcinoma tumor subtypes and may lead to a diagnostic result for tumors not previously characterized by EUS-FNA. With an adequate tissue sample, broad application of FC/IHC increases the diagnostic yield of EUS-FNA.

Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis.

Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis. For steroid-dependent disease, azathioprine has been used for maintenance of remission. Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis; however, there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis. A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil, which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production. Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events. The patient was managed without a biliary stent. However, there was a return of symptoms, jaundice, increase in transaminases, and hyperbilirubinemia when the prednisone dose reached 11 mg per day. In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis, the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events, but it did not enable discontinuation of the steroids. Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.