Brian G. Turner

Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts.

Objectives: Endoscopic ultrasound (EUS) may offer a diagnostic tool through the combination of imaging and guided fine-needle aspiration of pancreatic cysts. The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cysts. Methods: The results of EUS imaging, cytology, and cyst fluid biochemical markers were prospectively collected and compared in a large single-center study (776 patients) using histology or malignant cytology as the final diagnostic standard in 198 patients. Results: The mean cyst fluid carcinoembryonic antigen (CEA) was greater in mucinous cysts (4703.0 ng/mL) compared with nonmucinous cysts (25.8 ng/mL) (P = 0.008). When using the optimal cutoff value of 109.9 ng/mL, the CEA was more accurate (86%, receiver operating characteristic area = 0.928) than EUS imaging (48%) and cytology (58%) in predicting a mucinous cyst (P < 0.0001). Malignant cysts had a mean cyst fluid CEA value (2558.2 ng/mL) similar to benign cysts (4700.2 ng/mL). Cytology (75%) more accurately diagnosed malignant cysts than EUS (66%) and CEA (62%) (P < 0.05). Conclusions: Cyst fluid CEA concentration provides a highly accurate test for the diagnosis of a mucinous cyst, but does not distinguish benign from malignant cysts. Cytology is the most accurate test for the diagnosis of a malignant cyst.Abbreviations: EUS - endoscopic ultrasound, CEA - carcinoembryonic antigen, MCN - mucinous cystic neoplasm, IPMN - intraductal papillary mucinous neoplasm

Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes

Objective Invasive cancers arising from intraductal papillary mucinous neoplasm (IPMN) are recognised as a morphologically and biologically heterogeneous group of neoplasms. Less is known about the epithelial subtypes of the precursor IPMN from which these lesions arise. The authors investigate the clinicopathological characteristics and the impact on survival of both the invasive component and its background IPMN. Design and patients The study cohort comprised 61 patients with invasive IPMN (study group) and 570 patients with pancreatic ductal adenocarcinoma (PDAC, control group) resected at a single institution. Multivariate analyses were performed using a stage-matched Cox proportional hazard model. Results The histology of invasive components of the IPMN cohort was tubular in 38 (62%), colloid in 16 (26%), and oncocytic in seven (12%). Compared with PDAC, invasive IPMNs were associated with a lower incidence of adverse pathological features and improved mortality by multivariate analysis (HR 0.58; 95% CI 0.39 to 0.86). In subtype analysis, this favourable outcome remained only for colloid and oncocytic carcinomas, while tubular adenocarcinoma was associated with worse overall survival, not significantly different from that of PDAC (HR 0.85; 95% CI 0.53 to 1.36). Colloid and oncocytic carcinomas arose only from intestinal- and oncocytic-type IPMNs, respectively, and were mostly of the main-duct type, whereas tubular adenocarcinomas primarily originated in the gastric background, which was often associated with branch-duct IPMN. Overall survival of patients with invasive adenocarcinomas arising from gastric-type IPMN was significantly worse than that of patients with non-gastric-type IPMN (p=0.016). Conclusions Tubular, colloid and oncocytic invasive IPMNs have varying prognosis, and arise from different epithelial subtypes. Colloid and oncocytic types have markedly improved biology, whereas the tubular type has a course that resembles PDAC. Analysis of these subtypes indicates that the background epithelium plays an equally, if not more, important role in defining the biology and prognosis of invasive IPMNs.

High‐grade atypical epithelial cells in pancreatic mucinous cysts are a more accurate predictor of malignancy than “positive” cytology

The Sendai guidelines for risk assessment of malignancy in patients with mucinous cysts lists “positive” cytology as a high‐risk feature. In the current study, the authors hypothesized that a cytological threshold of high‐grade atypical epithelial cells (AEC) is a more accurate predictor of malignancy.

Accuracy of EUS in the evaluation of small gastric subepithelial lesions

BACKGROUND EUS combined with endoluminal resection techniques is increasingly used to provide a definitive diagnosis of small gastric subepithelial lesions seen on standard upper endoscopy. OBJECTIVE To evaluate the accuracy of EUS in diagnosing small gastric subepithelial lesions by using histology as the criterion standard. DESIGN A retrospective study. SETTING Academic tertiary care center. PATIENTS A total of 22 patients (15 women, mean age 62.2 years) with an endoscopically resected gastric subepithelial lesion were included in this 3-year retrospective study. MAIN OUTCOME MEASUREMENTS The size, echogenicity, the layer of origin, and presumptive diagnosis were determined by EUS. The diagnostic accuracy of EUS was determined by using histology as the criterion standard. RESULTS The mean size of the 22 lesions was 13.6 mm (range 8-20 mm). An endoscopic cap band mucosectomy device was used to resect 16 (72.7%) lesions, whereas 6 (27.3%) were resected with a saline solution-assisted and snare technique. Using histology as a criterion standard, we found that the accuracy of the EUS diagnosis was 10 of 22 (45.5%). EUS alone had an accuracy rate of 30.8% and 66.7%, respectively, in the diagnosis of neoplastic and non-neoplastic lesions. LIMITATIONS A single-center, retrospective analysis. CONCLUSION EUS imaging had a low accuracy rate in the diagnosis of gastric subepithelial lesions, and endoscopic submucosal resection should be performed to provide a histologic diagnosis. Resection of small subepithelial lesions of 20 mm or less can be accomplished en bloc with an endoscopic cap band mucosectomy device.

Pancreatic cystic lesions: clinical predictors of malignancy in patients undergoing surgery

Background  Despite advances in cross‐sectional imaging and the use of molecular markers, distinguishing between benign and malignant cysts remains a clinical challenge.

Feasibility of endoscopic transesophageal thoracic sympathectomy (with video)

BACKGROUND Thoracoscopic sympathectomy is the preferred surgical treatment for patients with disabling palmar hyperhidrosis. Current methods require a transthoracic approach to permit ablation of the thoracic sympathetic chain. OBJECTIVE To develop a minimally invasive, transesophageal endoscopic technique for a sympathectomy in a swine model. DESIGN Nonsurvival animal study. SETTING Animal trial at a tertiary care academic center. SUBJECTS This study involved 8 healthy Yorkshire swine. INTERVENTIONS After insertion of a double-channel gastroscope, a Duette Band mucosectomy device was used to create a small esophageal mucosal defect. A short, 5-cm submucosal tunnel was created by using the tip of the endoscope and biopsy forceps. Within the submucosal space, a needle-knife was used to incise the muscular esophageal wall and permit entry into the mediastinum and chest. The sympathetic chain was identified at the desired thoracic level and was ablated or transected. The animals were killed at the completion of the procedure. MAIN OUTCOME MEASUREMENTS Feasibility of endoscopic transesophageal thoracic sympathectomy. RESULTS The sympathetic chain was successfully ablated in 7 of 8 swine, as confirmed by gross surgical pathology and histology. In 1 swine, muscle fibers were inadvertently transected. On average, the procedure took 61.4+/-24.5 minutes to gain access to the chest, whereas the sympathectomy was performed in less than 3 minutes in all cases. One animal was killed immediately after sympathectomy, before the completion of the observation period, because of hemodynamic instability. LIMITATIONS Nonsurvival series, animal study. CONCLUSIONS Endoscopic transesophageal thoracic sympathectomy is technically feasible, simple, and can be performed in a porcine model.

Pancreatic Cystic Lesions: When to Watch, When to Operate, and When to Ignore

Pancreatic cystic lesions are being increasingly identified with the widespread use of state-of-the-art imaging. These lesions are categorized into a broad range of neoplastic cysts and inflammatory pseudocysts. Identification of a pancreatic cyst requires the clinician to focus on the main clinical challenge of the benign or malignant nature of the cyst. Neoplastic cysts range the spectrum from benign, to premalignant, to frank malignancy. The management of these lesions is difficult, and the decision to resect or observe a lesion is hampered by limitations in current imaging and tissue sampling techniques that prevent the accurate characterization of all lesions. This article reviews current guidelines for the evaluation of pancreatic cystic lesions, underscores the challenges posed by these lesions, and discusses current and future studies that will aid in patient management.

Feasibility of EUS-guided injection of irinotecan-loaded microspheres into the swine pancreas

BACKGROUND LC beads (Biocompatibles International plc) are designed for the time-released delivery of the chemotherapeutic agent irinotecan into focal, hypervascularized, hepatic tumors. OBJECTIVE To determine the feasibility of EUS-guided injection of LC beads (with/without irinotecan) into the swine pancreas. DESIGN Survival animal study. SETTING Academic center. SUBJECTS This study involved 12 Yorkshire swine. INTERVENTION LC beads without irinotecan and loaded with up to 300 mg of irinotecan were injected under EUS guidance with a 19-gauge needle into the tail of the pancreas. CT scanning and necropsy with histology were performed at day 7. MAIN OUTCOME MEASUREMENTS Feasibility of the injections, gross and microscopic evidence of pancreatic inflammation, and clinical tolerance by the animals. RESULTS After injection of LC beads with/without irinotecan, in 10 of 12 animals an intrapancreatic, hyperechoic focus with an average diameter of 2.2 cm was visible by EUS, and a hypodense area in the tail of the pancreas was visible by contrast CT. In 2 animals (1 with irinotecan and 1 without) no beads were seen on CT. In 10 of 12 animals, a depot of beads was located in the tail of the pancreas on gross inspection and histology. Drug depot with only localized pancreatic tissue reactions was seen on histopathologic review. LIMITATIONS Animal study. CONCLUSION The EUS-guided injection of LC beads (with/without irinotecan) into the pancreas of the pig is feasible and safe. This technique is a potential minimally invasive local treatment option for locally advanced pancreatic cancer.

A prospective, randomized trial of esophageal submucosal tunnel closure with a stent versus no closure to secure a transesophageal natural orifice transluminal endoscopic surgery access site

BACKGROUND Secure esophagotomy closure methods are a critical element in the advancement of transesophageal natural orifice transluminal endoscopic surgery (NOTES) procedures. OBJECTIVE To compare the clinical outcomes in swine receiving an esophageal stent or no stent after a submucosal tunnel NOTES access procedure. DESIGN Prospective, randomized, controlled trial in 10 Yorkshire swine. SETTING Academic center. INTERVENTION An endoscopic mucosectomy device was used to create an esophageal mucosal defect. An endoscope was advanced through a submucosal tunnel into the mediastinum and thorax, and diagnostic mediastinoscopy and thoracoscopy were performed. Ten animals were randomized to no stenting (n = 5) or stenting (n = 5) with a prototype small-intestine submucosa-covered stent. MAIN OUTCOME MEASUREMENTS Gross and histologic appearance of the mucosectomy and esophagotomy sites as well as clinical outcomes. RESULTS There was a significant difference in the overall procedure time between the animals that received a stent (35.0 min, range 27-46.0 min) and those with no closure (19.0 min, range 17-32 min) (P value = .018). The unstented group achieved endoscopic and histologic evidence of complete re-epithelialization and healing (100%) at the mucosectomy site compared with the stented group (20%, P = .048). Stent migration into the stomach occurred in two swine. Both groups had complete closure of the submucosal tunnel and well-healed esophagotomy sites. LIMITATIONS Animal study, small number of subjects. CONCLUSION The placement of a covered esophageal stent significantly interferes with mucosectomy site healing.

Diagnostic and therapeutic endoscopic approaches to intraductal papillary mucinous neoplasm

Pancreatic cystic lesions are increasingly identified on routine imaging. One specific lesion, known as intraductal papillary mucinous neoplasm (IPMN), is a mucinous, pancreatic lesion characterized by papillary cells projecting from the pancreatic ductal epithelium. The finding of mucin extruding from the ampulla is essentially pathognomonic for diagnosing these lesions. IPMNs are of particular interest due to their malignant potential. Lesions range from benign, adenomatous growths to high-grade dysplasia and invasive cancer. These mucinous lesions therefore require immediate attention to determine the probability of malignancy and whether observation or resection is the best management choice. Unresected lesions need long-term surveillance monitoring for malignant transformation. The accurate diagnosis of these lesions is particularly challenging due to the substantial similarities in morphology of pancreatic cystic lesions and limitations in current imaging technologies. Endoscopic evaluation of these lesions provides additional imaging, molecular, and histologic data to aid in the identification of IPMN and to determine treatment course. The aim of this article is to focus on the diagnostic and therapeutic endoscopic approaches to IPMN.