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Autoimmune pancreatitis (AIP) shows a unique spectrum of histologic features and commonly presents with an abundant IgG4-positive (IgG4+) plasma cell infiltration. However, differentiating AIP from other mass lesions, particularly pancreatic cancer [invasive ductal carcinoma (IDC)] can be clinically challenging. In this study, we evaluated the validity of IgG4 and IgG immunohistochemistry of ampullary and periampullary tissue for the diagnosis of AIP. Our study group consisted of 14 resected AIP cases with appropriate ampullary sections. Superficial ampullary tissue and "shouldering" duodenal mucosa were evaluated for several histologic variables. Immunohistochemistry for IgG4 and IgG was performed. The number of IgG4 and IgG-positive plasma cells was counted and an IgG4+ to IgG+ plasma cells ratio (IgG4/IgG ratio) was evaluated. A control cohort was composed of IDC (n=30) and chronic pancreatitis (CP) (n=29). Although an overlap was present between the groups, the overall inflammation and number of plasma cells in and around the ampulla was significantly increased in AIP compared with CP and IDC. Furthermore, although there was some overlap in the crude number of IgG4+ plasma cells of the ampullary and duodenal tissue between AIP, IDC, and CP, an IgG4/IgG ratio, especially of the ampulla, seems diagnostically useful in differentiating AIP from other "mass forming" lesions. When a cut-off of 0.10 was applied, the diagnostic sensitivity and specificity of the ampullary IgG4/IgG ratio was 86% and 95%, respectively. In conclusion, evaluation of ampullary histology and IgG4/IgG ratio might be proven beneficial in discriminating AIP from other mass forming pancreatic lesions.

The management of pancreatic cystic lesions offers a challenge to clinicians. Mucinous cystic lesions pose a low risk of the development of neoplasia that must be taken into account in long-term management. Although the natural history has not been well defined, it is likely that malignant change in the mucinous epithelium takes place over years, very similar to what is observed with Barrett's esophagus. The traditional therapy of mucinous cystic lesions has been surgical resection. Lesions in the head of the pancreas will require a Whipple resection whereas tail lesions are managed with a distal pancreatectomy and splenectomy. In patients at high risk for surgical resection, the risk/benefit ratio may be excessively high, not supporting the use of resection therapy. Ethanol ablation therapy has been thoroughly studied in hepatic, renal, and thyroid cysts. Epithelial ablation with ethanol appears to be highly effective and relatively safe. Recently, ethanol ablation has been evaluated in pancreatic cystic neoplasms. In macrocystic lesions between 1 and 5 cm, ethanol lavage will result in epithelial ablation and cyst resolution in a high percentage of patients. Pancreatitis is rarely observed clinically and is not present in resection specimens. A randomised prospective clinical trial is currently underway.

Introduction: Transanal endoscopic microsurgery (TEM) provides direct endoscopic access to the rectum and peritoneal cavity. The feasibility of natural orifice translumenal endoscopic surgery (NOTES) rectosigmoid resection using TEM was evaluated in swine. Transgastric endoscopic assistance to extend transanal colon mobilization was also investigated. Full-thickness circumferential rectal dissection was performed and extended proximally. After maximal sigmoid mobilization, the specimen was exteriorized and transected, and the proximal colon was stapled to the distal rectum. In a subset of animals, transgastric endoscopic access was used to mobilize the colon further., Results: Rectosigmoid resection using TEM was performed in two non-survival and seven swine cadavers (n = 9). The mean procedure time was 3 h (2.5-4 h), and mean length of resected colon was 16.7 cm (10-25 cm). Transgastric endoscopic assistance was used in three cadavers and two non-survival swine (n = 5) with a mean operative time of 3.5 h (3.5-3.75 h). The mean length of colon mobilized with transgastric and transanal endoscopic access was 24.4 cm (20-27 cm) vs. 16.7 cm which mobilized the transanal approach alone (p = 0.016). A posterior anastomotic defect was noted in two animals., Conclusion: Transanal rectosigmoid resection with TEM is feasible in swine. Combined transgastric and TEM access is a promising new technique for NOTES colorectal resection.

Introduction: Transesophageal endoscopic mediastinoscopy (MX) and thoracoscopy (TX) could reduce pain, eliminate intercostal neuralgia, provide better access to the posterior mediastinal compartment and pulmonary hilum, and improve cosmesis. The purpose of this study was to demonstrate the feasibility of transesophageal natural orifice translumenal endoscopic surgery (NOTES) and to determine the complications that might be seen in surviving animals., Methods: Using cap endoscopic mucosal resection and blunt dissection, a 15-20 cm submucosal tunnel was created in the esophagus and an endoscope passed through the tunnel into the mediastinum. One swine underwent MX; three swine underwent both MX and TX. The mediastinal compartment, hilar lymph nodes, pleura, lung, and esophagus were identified. Esophageal closure was obtained via submucosal tunnel flap-valve alone (two swine) or reinforcement with mucosal clips (two swine). The esophagus, mediastinum, and thorax were examined at necropsy. The esophagus was excised and sent for pathological examination., Results: NOTES MX and TX provided excellent visualization of mediastinal and thoracic structures. Pleural biopsy was easily accomplished. All animals survived the procedure, ate well, and showed no ill effects. Swine were sacrificed at either 8 or 12 days postoperatively. At necropsy, mild atelectasis was noted in each animal. One animal (mucosal clip closure) developed a fluid collection in the submucosal tunnel. There was no evidence of mediastinitis or thoracic contamination in any animals., Conclusions: Transesophageal endoscopic mediastinoscopy and thoracoscopy provide excellent visualization of mediastinal and intrathoracic structures. Pleural biopsy can be easily obtained under direct visualization. Structures that are difficult to visualize via traditional cervical mediastinoscopy and thoracoscopy are seen well with this approach. The submucosal tunnel creates a flap-valve that, alone, may be sufficient for preventing esophageal leak. These procedures can be performed safely in swine with short-term survival. Further study with a larger sample size and longer survival is warranted.

Background: It is common practice to empirically limit the radiofrequency (RF) power when ablating the posterior left atrium during atrial fibrillation ablation to avoid thermal injury to the esophagus. The objective of this study was to determine whether RF energy delivery limited by luminal esophageal temperature (LET) monitoring is associated with a reduction in esophageal injury compared with a strategy of RF power limitation alone., Methods and Results: Eighty-one consecutive patients who underwent atrial fibrillation ablation followed by esophageal endoscopy were included in this observational study. All patients underwent extraostial electric pulmonary vein isolation by using an electroanatomic mapping system and irrigated RF ablation. All RF applications on the posterior left atrium were limited to 35 W. A commercially available, single-thermocouple esophageal probe was used to monitor LET in a subset of patients (n=67). In these cases, applications were promptly interrupted when LET was > or =38.5 degrees C; further applications were performed at reduced power to obtain a LET < 38.5 degrees C. Esophageal endoscopy was performed 1 to 3 days after the procedure. Ablation-related esophageal ulcerations were identified in 9 of 81 (11%) patients. All patients were asymptomatic. Of these 81 patients, LET monitoring during ablation occurred in 67 (83%) of patients. Esophageal injury was observed more frequently (36% versus 6%, P<0.006) in the group without LET monitoring., Conclusions: These data suggest that LET monitoring may be associated with a reduction in esophageal injury compared with power limitation alone.

Pancreatic cystic neoplasms have emerged as an important new opportunity for many disciplines to participate in the diagnosis and management of early pancreatic neoplasia. With an increase in an understanding of these lesions and their potential for malignant transformation, there has been a dramatic increase in the frequency of diagnosis. We critically examined the literature on diagnostic methods for pancreatic cystic lesions over the past 5 years. The methods of endoscopic pancreatic pseudocyst drainage and clinical outcomes are also discussed. Morphologic studies of cystic lesions using cross-sectional imaging or endoscopic ultrasound have a low diagnostic rate. Cyst fluid analysis with the use of tumor markers (eg, carcinoembryonic antigen) increases the accuracy of diagnosis. The management of cystic lesions is heavily dependent on the type of cyst, the neoplastic potential, and the risk of surgery. The traditional therapy is pancreatic resection and not cyst enucleation. In contrast to cystic neoplasms, pseudocysts are localized collections of inflammatory fluid that mimic cystic neoplasms. The fluid collections arise from chronic pancreatitis and ductal leaks. Because pseudocysts have no neoplastic potential, they can be drained rather than resected. Drainage can be safely accomplished with external catheters or endoscopically with internal catheters. As we learn more about the pathophysiology of the various cystic lesions, treatment will be tailored to the specific cyst lesion. Endoscopic ultrasound has an important role in the characterization of pancreatic cystic lesions and helps in selection of the optimal treatment modality.

Background: Expectant management of serous cystadenoma (SCA) of the pancreas requires an accurate preoperative diagnosis. Previously published cytologic diagnostic sensitivities have ranged widely, from 10% to 100%. In the current study, the authors evaluated the diagnostic sensitivity of endoscopic ultrasound (EUS)-guided fine-needle aspiration biopsy (FNAB) and cross-sectional imaging for SCA., Methods: Group I consisted of 21 histologically confirmed SCAs. Group II (n = 7 lesions) lacked histologic confirmation and was defined by EUS findings that were consistent with SCA and a cyst fluid carcinoembryonic antigen (CEA) level <5 ng/mL. Group III was comprised of 2 nonserous and potentially malignant cysts of the pancreas for which a preoperative diagnosis of SCA was considered. Cross-sectional imaging data were recorded. The smears were evaluated for the presence of serous lining epithelium, gastrointestinal-contaminating epithelium, and inflammatory cells including hemosiderin-laden macrophages. The authors also evaluated the presence of hemosiderin-laden macrophages in a series of 110 FNA specimens from histologically confirmed neoplastic mucinous cysts of the pancreas and 45 pseudocysts of the pancreas., Results: Prospectively among Group I lesions, the appearance on computed tomography (CT) was considered definitive for SCA in 3 of 12 cases (25%). The histologically confirmed SCA cases had CEA levels of <5 ng/mL, except for 1 case for which the CEA level was 176.5 ng/mL. A cytologic diagnosis of SCA was made prospectively in only 1 CT-guided case. Retrospectively, 3 intraoperative FNAs and 1 additional CT-guided aspirate contained rare epithelial cells of a SCA. None of the EUS-guided aspirates demonstrated serous epithelium. Among Group II aspiration specimens, only 1 contained serous epithelial cells. Approximately 52% of the EUS-guided aspirates demonstrated gastrointestinal contamination. This glandular epithelium was categorized as atypical in 2 cases. Hemosiderin-laden macrophages were identified in 43% of the SCAs. Conversely, only 2% of neoplastic mucinous cysts and 9% of pseudocysts produced hemosiderin-laden macrophages in aspirate fluid., Conclusions: In the current study, serous epithelial cells were identified in <20% of cases. Gastrointestinal-contaminating epithelium, often observed in EUS-guided aspirates, further contributes to difficulties in interpretation. The presence of hemosiderin-laden macrophages as a surrogate marker for SCA requires further study. A preoperative diagnosis of SCA remains a challenge, and an EUS-guided FNAB is unlikely to provide the high level of diagnostic accuracy necessary to permit a nonoperative approach., (Copyright (c) American Cancer Society.)

Background: Thoracoscopy and mediastinoscopy are common procedures with painful incisions and prominent scars. A natural orifice transesophageal endoscopic surgical (NOTES) approach could reduce pain, eliminate intercostal neuralgia, provide access to the posterior mediastinal compartment, and improve cosmesis. In addition NOTES esophageal access routes also have the potential to replace conventional thoracoscopic approaches for medial or hilar lesions., Methods: Five healthy Yorkshire swine underwent nonsurvival natural orifice transesophageal mediastinoscopy and thoracoscopy under general anesthesia. An 8- to 9.8-mm video endoscope was introduced into the esophagus, and a 10-cm submucosal tunnel was created with blunt dissection. The endoscope then was passed through the muscular layers of the esophagus into the mediastinal space. The mediastinal compartment, pleura, lung, mediastinal lymph nodes, thoracic duct, vagus nerves, and exterior surface of the esophagus were identified. Mediastinal lymph node resection was easily accomplished. For thoracoscopy, a small incision was created through the pleura, and the endoscope was introduced into the thoracic cavity. The lung, chest wall, pleura, pericardium, and diaphragmatic surface were identified. Pleural biopsies were obtained with endoscopic forceps. The endoscope was withdrawn and the procedure terminated., Results: Mediastinal and thoracic structures could be identified without difficulty via a transesophageal approach. Lymph node resection was easily accomplished. Pleural biopsy under direct visualization was feasible. Selective mainstem bronchus intubation and collapse of the ipsilateral lung facilitated thoracoscopy. In one animal, an inadvertent 4-mm lung incision resulted in a pneumothorax. This was decompressed with a small venting intercostal incision, and the remainder of the procedure was completed without difficulty., Conclusions: Transesophageal endoscopic mediastinoscopy, lymph node resection, thoracoscopy, and pleural biopsy are feasible and provide excellent visualization of mediastinal and intrathoracic structures. Survival studies will be needed to confirm the safety of this approach.

One of the most important causes of relapsing pancreatitis is a cystic neoplasm of the pancreas. These low grade malignancies may cause pancreatitis by obstructing or communicating with a pancreatic duct. Patients with relapsing pancreatitis and a focal fluid fluid collection should be investigated for the possibility of a mucinous cystic neoplasm. Cross sectional imaging can provide a diagnosis with the imaging findings of a low attenuation cystic lesion containing mural calcification (CT scanning) or a lobular T2 enhancing lesion (MRCP). Endoscopic ultrasound can provide more detailed imaging with the ability to guide fine needle aspiration of the cyst fluid. Cyst fluid analysis can provide a diagnosis of a mucinous cystic lesion with the combination of cytology (mucinous epithelium), elevated carcinoembryonic antigen (CEA), and the presence of DNA mutations. Management of these patients consists of surgical resection and monitoring in patients not able to withstand surgery.

Pancreatic adenocarcinoma is one of the leading causes of cancer death in the West, with a poor overall 5-year survival rate of only 4%. Late clinical presentation with an advanced disease results in a low rate of surgical intervention. Tumor serum marker CA 19-9 is sensitive, although not specific for the diagnosis of adenocarcinomas of the pancreas. The treatment approach is based on whether the tumor is resectable or non-resectable at presentation. Therefore, imaging plays a crucial role in the management of this disease. Many modalities are available to image the pancreas. They include non-invasive techniques, like ultrasound, contrast-enhanced multidetector computed tomography, magnetic resonance imaging and integrated positron emission tomography/computed tomography, and invasive techniques, like endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. Each of these modalities has its peculiar strengths and weaknesses.

Background/aim: Management of patients with small (1-3 cm) branch duct intraductal papillary mucinous neoplasms (IPMN) is a challenge. Symptoms, dilated duct, mural nodule or positive cytology have been proposed as parameters for resection. The aim of our study was to compare this proposed algorithm to one that incorporates cytology with less than malignant epithelial cells and cyst fluid carcinoembryonic antigen (CEA)., Methods: A retrospective study was conducted., Results: There were 14 nonmalignant and 6 malignant cysts with 3 invasive IPMN. None were associated with a dilated duct and none had positive cytology. Only a mural nodule was significant by univariate analysis for the detection of malignancy (p = 0.01) and invasion (p = 0.009). The detection of atypical epithelial cells or a cyst fluid CEA of >2,500 ng/ml was more accurate for the detection of malignancy than using the recommended algorithm., Conclusions: The presence of a mural nodule in a small branch duct IPMN is a predictor of malignancy and invasion by univariate analysis. Recognition of an atypical epithelial cell component in contrast to positive cytology or a cyst fluid CEA of >2,500 ng/ml is more accurate than the recommended algorithm and adds value to the preoperative assessment of clinically diagnosed small branch duct IPMN. and IAP., (Copyright 2008 S. Karger AG, Basel.)

Background: In contrast to laparoscopic tubal ligation, oophorectomy, and appendectomy, laparoscopic distal pancreatectomy is associated with a morbidity rate of more than 50% and a mortality rate of more than 3%., Objective: To develop a minimally invasive, transgastric endoscopic technique for distal pancreatectomy in a nonsurvival series in swine., Design: Experimental study., Setting: Animal trial at a tertiary-care academic hospital., Subjects: Six healthy Yorkshire swine under general anesthesia., Interventions: A double-channel gastroscope was introduced into the stomach, and a gastric incision was created by using a triple-lumen, 4-mm, cutting-wire needle knife. The peritoneal cavity was accessed. An Endoloop was placed endoscopically around the distal aspect of the pancreas, and the tail of the pancreas was transected by using a diathermic snare. One to 3 hemoclips were placed across the pancreatic duct. The pancreatic specimen was retrieved, and the gastrotomy was closed endoscopically with metal clips. The animals were euthanized after the procedure. The abdominal cavity was examined grossly, and the resected pancreas was examined histologically., Main Outcome and Measurements: Feasibility of endoscopic transgastric distal pancreatectomy and rate of complications., Results: The pancreatic tail was successfully resected via a transgastric endoscopic approach in all animals. The procedure took an average (standard deviation) of 77.3 +/- 18.9 minutes. There was 1 complication, an episode of bleeding from a splenic laceration, which resulted in the loss of 250 mL of blood., Limitations: Nonsurvival series, animal study., Conclusions: Transgastric endoscopic distal pancreatectomy is technically feasible and can be performed in the porcine animal model.

Purpose of Review: To review the current state of natural orifice surgery and examine the concerns, challenges, and opportunities presented by translumenal research., Recent Findings: Translumenal endoscopic procedures have been the focus of extensive research. Researchers have reported natural orifice translumenal endoscopic surgery in a swine model in several areas involving the abdominal cavity. Diagnostic procedures have included endoscopic peritoneoscopy, liver biopsy, lymphadenectomy, and abdominal exploration. Several gynecologic procedures including tubal ligation, oophorectomy, and partial hysterectomy have been demonstrated using current commercial endoscopes. Gastrointestinal surgical procedures, including gastrojejunostomy, cholecystectomy, splenectomy, and distal pancreatectomy have been performed successfully via transgastric and/or transcolonic approaches. There have been no studies of natural orifice translumenal endoscopic surgery procedures published in humans. While fundamental questions about the emerging technology have not been scrutinized, limitations of the large animal model will pose a challenge to the development of large randomized trials., Summary: While natural orifice translumenal endoscopic surgery may represent a paradigm shift and may offer significant benefits to patients, rigorous testing of the techniques is lacking and current data have been drawn from case series.

Pancreatic cystic lesions are detected more frequently as a result of increasing use of high-resolution cross-sectional imaging. The ability of imaging and cyst fluid analysis to predict the biologic behavior of the lesions has aroused much interest recently. A precise diagnosis is critical to help guide further management. The diagnostic criteria and the management principles have evolved dramatically over the past 10 years with the advent of endoscopic ultrasound and fine-needle aspiration. In this review, we summarize the recent publications that have examined the key issues in the diagnosis and management of cystic lesions of the pancreas.

Background: OncoGel (ReGel/paclitaxel) is an intralesional injectable formulation of the chemotherapeutic drug, paclitaxel, for local tumor management., Objective: The aim of this study was to determine if a minimally invasive EUS-guided injection of paclitaxel, bound to a thermosensitive gel carrier, would lead to therapeutic tissue concentrations of the chemotherapeutic agent in the porcine pancreas., Design: Eight Yorkshire breed pigs were sedated by general anesthesia and OncoGel was injected, under EUS-guidance, with a 22-gauge needle into the tail of the pancreas., Main Outcome Measurements: During the 7-day (n = 4) or 14-day (n = 4) observational period, the animals were monitored by serum levels of amylase and lipase, and by a CT on day 4. The outcome was determined by gross and microscopic evidence of inflammation of the pancreas, clinical tolerance, and quantitation of tissue paclitaxel concentrations., Results: Eight pigs underwent injection of 1, 2, 3, or 4 mL OncoGel (6 mg paclitaxel per 1 mL OncoGel) (n = 2 per group). An intrapancreatic hyperechoic focus, with an average diameter of 2.1 +/- 0.8 cm, was visible by EUS, and a hypodense area in the tail of the pancreas was visible by contrast CT. Clinically, the animals appeared to tolerate the procedure without sequelae. Blood levels of amylase and lipase were normal. At euthanasia, a depot of OncoGel, with an average diameter of 14.7 +/- 5.0 mm), was located both grossly and histologically in the pancreatic tail. After 14 days, clinically significant tissue concentrations of paclitaxel were detected at a distance of 30 to 50 mm from the depot in the animals that underwent an injection of 3 and 4 mL of the agent (n = 2)., Conclusions: The EUS-guided injection of OncoGel into the pancreas of the pig provided high and sustained localized concentrations of paclitaxel. This technique is a potential minimally invasive local treatment option for unresectable pancreatic tumors.

Background: Ethanol is a commonly available agent and has been used to successfully and safely ablate cystic lesions of various organs., Objective: The aim of this study was to determine the short-term effects of an EUS-guided injection of ethanol into the pancreas of pigs by using 2 mL ethanol, in increasing concentration of 0% to 100%., Design: Six pigs were sedated by general anesthesia, and ethanol was injected, under EUS-guidance, with a 22-gauge needle into the pancreatic tail., Main Outcome Measurements: End points of this study were gross and microscopic evidence of pancreatitis and clinical tolerance. During the 7-day observational period, the animals were monitored by serum levels of amylase and lipase and by a CT on day 4., Results: At euthanasia, there was no pancreatic lesion in the animals that received normal saline solution or 20% ethanol. The injection of 40% to 100% ethanol led to a visible necrotic area in the pancreatic tail. By histology, the average maximal diameter of the lesions was 20.8 +/- 4.3 mm. The cross-sectional area of necrosis was proportional to the concentration of ethanol (r = 0.961). CT demonstrated a localized site of nonenhancing pancreatic tissue, with an average diameter of 19.4 +/- 10.5 mm; 40% to 100% ethanol. Clinically, the animals appeared to tolerate the procedure without sequelae. Serum levels of amylase and lipase were normal., Conclusions: The EUS-guided injection of ethanol into the pig pancreas resulted in a localized concentration-dependent tissue necrosis without complications.

Autoimmune pancreatitis (AIP) is a mass forming inflammatory pancreatobiliary-centric disease. Recent reports of multiorgan inflammatory mass forming lesions with increased numbers of IgG4 positive plasma cells suggest that AIP may have a systemic component. In this study, we explore the systemic nature of AIP, investigate the relevance of subtyping AIP, perform a systematic study of tissue IgG4 immunoperoxidase, and ultrastructurally evaluate the presence of immune complexes. Our study group consisted of 36 patients with AIP, 21 of whom underwent a Whipple procedure. On the basis of the pattern of inflammation, pancreatic involvement was subtyped as ductocentric (AIP-D) or lobulocentric (AIP-L). Extrapancreatic lesions included bile duct (n=3), salivary glands (n=3), lung (n=2), gallbladder (n=11), and kidney (n=4). Clinical and radiologic data was recorded. Immunohistochemistry for IgG4 was performed on both pancreatic and extrapancreatic tissues and the numbers of IgG4 positive plasma cells were semiquantitatively scored. A control cohort composed of pancreatic adenocarcinoma (n=19) and chronic pancreatitis-not otherwise specified (NOS) (n=14) was also evaluated. Eleven pancreatic specimens, including 2 cases of chronic pancreatitis-NOS and 4 kidneys were evaluated ultrastructurally. The pancreas, bile duct, gall bladder, salivary gland, kidney, and lung lesions were characterized by dense lymphoplasmacytic infiltrates with reactive fibroblasts and venulitis. IgG4 positive plasma cells were identified in all pancreatic and extrapancreatic lesions. The AIP cases showed significantly more pancreatic IgG4 positive plasma cells than chronic pancreatitis-NOS or adenocarcinoma (P=0.001). However, IgG4 positive cells were identified in 57.1% of chronic pancreatitis-NOS and 47.4% of ductal adenocarcinoma. Fifteen of 21 resected cases were classified as AIP-D, and 6 as AIP-L, the latter notably showing significantly more IgG4 positive plasma cells than the former (P=0.02). Additionally, clinical and radiologic differences emerged between the 2 groups. Ultrastructurally, electron dense deposits of immune complexes were identified in the basement membranes of 7 of the 9 AIP cases and in 3 of the 4 renal biopsies evaluated. AIP represents the pancreatic manifestation of a systemic autoimmune disease. Clinical and immunologic findings justify the recognition of pancreatic lobulocentric and ductocentric subtypes. Documentation of increased numbers of tissue IgG4 positive plasma cells, although not an entirely specific marker for AIP, may provide ancillary evidence for the diagnosis of a IgG4-related systemic disease.

Major advances in endoscopic techniques to diagnose and manage pancreatic biliary diseases have fundamentally changed the approach to these difficult clinical challenges. The diagnosis of benign and malignant pancreatic-biliary diseases is much more readily obtained through a combination of cross-sectional imaging and endoscopic procedures. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are the most important endoscopic tools for imaging and accessing the pancreatic biliary system. The review summarizes the major imaging methods for providing a diagnosis of bile duct malignancy, including ERCP, transhepatic cholangiography (THC), and magnetic resonance cholangiopancreatography (MRCP). High quality image examples of cholangiocarcinoma are provided. EUS has provided a new imaging modality for the detection of pancreatic and biliary malignancy. EUS is particularly sensitive for the detection of early pancreatic malignancy. Furthermore, EUS excels at the guidance of fine needle aspiration of pancreatic lesions. Diagnostic tissue acquisition for cholangiocarcinoma remains an important challenge. The endoscopic therapy for pancreatic-biliary malignancy involves the use of stenting which relieves the biliary obstruction commonly seen in these patients.

Background: Electronic 270 degrees transverse-array EUS (TA-EUS) provides high-quality cross-sectional images but cannot guide FNA. Linear EUS (L-EUS) provides longitudinal images of malignancies and the ability to guide FNA., Objective: We conducted a prospective randomized comparison of TA-EUS and L-EUS for the staging of upper-GI (UGI) malignancies., Design: Forty-three patients underwent L-EUS immediately followed by TA-EUS (N = 27, 63%) or TA-EUS immediately followed by L-EUS (N = 16, 37%)., Patients: Forty-three subjects (mean age, 64 years; 37 men) with an UGI malignancy (4 stomach and 38 esophageal) were evaluated with both TA-EUS and L-EUS., Interventions: Abnormal lymph nodes were sampled by FNA for cytology., Results: There was agreement on the T stage by linear and radial techniques in 38 of 43 subjects (88%). Twenty-seven of 43 patients (63%) had abnormal lymph nodes by linear or transverse-array imaging. L-EUS demonstrated 66 abnormal lymph nodes in 27 subjects (average of 2.4 nodes/subject). TA-EUS demonstrated 90 abnormal lymph nodes in 27 subjects (average of 3.3 nodes/subject, P = .009, compared with L-EUS). In 16 of the 27 subjects, an FNA was performed, which was positive in 13 cases (81%) and negative in 3 cases (10%) for malignancy., Conclusions: TA-EUS and L-EUS provide similar results of T staging of UGI malignancies. However, the number of abnormal lymph nodes detected by TA-EUS was more than by L-EUS. These findings suggest that radial or transverse-array EUS imaging should be the primary method for staging of UGI malignancies.

Background: Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall. To the authors' knowledge, the cytologic features of this neoplasm are poorly characterized, especially with respect to tumor grade., Methods: Thirty-three endoscopic ultrasound (EUS)-guided pancreatic fine-needle aspiration biopsy (FNAB) samples and 1 pancreatic duct brush specimen from 25 patients with a histologically confirmed IPMN were retrospectively reviewed. Blinded to tumor grade, background mucin, inflammation, necrosis, overall cellularity, the presence of gastrointestinal-contaminating epithelium, architecture of cell clusters, and nuclear and cellular morphology were evaluated. In cases in which special stains for mucin were performed, the diagnostic utility of these stains was assessed. These cytologic features were subsequently correlated with the histologic diagnosis., Results: The 34 cytology samples represented 4 adenomas, 15 IPMN-moderate dysplasias, 7 intraductal carcinomas, and 8 IPMNs with invasive carcinoma. Extracellular mucin was present in 97% of all cases; 53% had thick, viscous, "colloid-like" mucin. Special stains for mucin were positive in 6 of 11 cases (54%), helping to identify thin mucin in only 2 cases. Gastrointestinal contamination did not appear to create diagnostic difficulty due to an apparent dual (dysplastic-nondysplastic) epithelial population, but only 4 adenomas were evaluated in this study. Necrosis distinguished IPMN with carcinoma from IPMN-adenomas and IPMN with moderate dysplasia (P < .00001), and was more often observed with invasion than IPMN-carcinoma in situ (P < .05). Tight epithelial cell clusters with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio was more significant in IPMN of at least moderate dysplasia (P = .03). Pale nuclei with parachromatin clearing was found to be a nuclear feature that was suspicious for at least carcinoma in situ (P < .001). In addition, significant background inflammation (neutrophils and histiocytes) was found to be more characteristic of IPMN with at least carcinoma in situ (P = .002)., Conclusions: The presence of thick, "colloid-like" mucin is noted in half of the IPMN cases, but was not found to be specific to grade. The absence of such mucin does not exclude an IPMN. The presence of tight epithelial cell clusters is consistent with a neoplasm of at least moderate dysplasia, and abundant background inflammation and parachromatin clearing correlated with the presence of at least carcinoma in situ. Necrosis was the only feature found to be strongly suggestive of invasion.

Purpose: To retrospectively determine the frequency of malignancy in small (< or =3 cm) pancreatic cysts, to evaluate whether cyst morphologic features can help predict the presence of malignancy, and to determine the natural history of small pancreatic cysts at follow-up imaging., Materials and Methods: Institutional review board approval was obtained; informed patient consent was not required. By means of a computerized search, 510 patients with pancreatic cysts that had been detected at computed tomography (CT) or magnetic resonance (MR) imaging were identified. Cysts that were 3 cm or smaller at surgery or endoscopic ultrasonography (US)-guided cyst fluid aspiration and biopsy were included. Eighty-six patients-31 men and 55 women aged 24-89 years-fulfilled the criteria. Patients underwent surgery or were monitored with endoscopic US-guided cyst fluid analysis, cytologic analysis, and follow-up imaging. Imaging findings were compared with surgical and pathology records and with endoscopic US features. Positive predictive values (PPVs) for benignity and malignancy were calculated on the basis of cyst size and absence or presence of septa in the cysts., Results: Forty-eight patients underwent surgery, and 38 were treated nonsurgically. Seventy-five patients had benign cysts; eight, borderline (malignant) neoplasms; and three, carcinoma in situ lesions. The PPV of small pancreatic cysts for prediction of benignity was 87% (75 of 86 patients). Thirty-six patients had unilocular cysts (35 with benign lesions, one with borderline neoplasm). The PPV of unilocular cysts for prediction of benignity was 97% (35 of 36 patients). Fifty patients had septated cysts; seven of these patients had borderline neoplasms, and three had carcinoma in situ lesions. For prediction of malignancy in small cysts, the PPV of septa was 20% (10 of 50 patients), which was significantly higher than the 3% (one of 36 patients) PPV of unilocular cysts (P = .042). No significant changes in cyst morphologic features were seen in patients who were followed up with imaging for a mean period of 21.8 months., Conclusion: The majority (n = 75) of small pancreatic cysts were benign. Thirty-six cysts were unilocular, and virtually all of these (n = 35) were benign. The presence of septa was associated with borderline or in situ malignancy in 20% (10 of 50) of cases., (Copyright RSNA, 2006.)

Endoscopic mucosal resection (EMR), which is advocated for the treatment of early (superficial) gastroesophageal neoplasms, has also been alluded to represent a superior diagnostic and staging modality. We compared the diagnostic concordance of preceding biopsies with EMR specimens in 31 gastric and 10 esophageal EMRs consisting of 6 low-grade and 12 high-grade dysplasias, 21 intramucosal adenocarcinomas, and 2 submucosal invasive adenocarcinomas. Discrepancies were considered as either major or minor if the histologic grades differed by 2 or more, or by only 1, respectively. Discrepant and concordant cases were compared with regard to the size of lesion (maximum dimension and surface area), number of biopsy fragments, and extent of biopsy sampling (ratio between lesion size and number of biopsy fragments). These same variables were used to evaluate the differences seen between gastric and esophageal cases. Of the 41 cases, 16 (39%) had discrepant diagnoses, including 14 gastric and 2 esophageal neoplasms. A major discrepancy was seen in 2% of the cases (n = 1, gastric) and a minor discrepancy, in 15 cases. All but 2 of the discrepant cases were found to have a higher grade on EMR. The average number of biopsy fragments was 4.4 in both concordant and discrepant groups. The maximal dimension, surface area, and biopsy sampling ratios of the lesion were significantly greater in the discrepant cases than in the concordant cases. The esophageal cases trended toward having smaller size and a significantly extensive biopsy sampling. We conclude that EMR is superior to biopsy for diagnosing superficial gastroesophageal tumors. Discrepancies between the specimens occur in larger lesions (>10 mm) with less extensive biopsy sampling. EMR can substantially modify the diagnostic grade of a lesion and therefore facilitate optimal therapeutic decisions by avoiding undertreatment and overtreatment based on inaccurate grading and staging.

Background: Endoscopic mucosal resection using a cap-fitted endoscope (EMRC) has been proposed to be significantly better and safer for tissue resection compared with standard snare EMR. However, there are no valid animal or clinical data to support this. We aimed to compare EMRC with standard snare EMR in a porcine model with respect to tissue resected, ease of procedure, and degree of diathermic injury to the resected specimen., Methods: Gastric EMRs were randomly performed in pigs using a variety of techniques, including EMRC (1mm and 17-mm cap) and the standard snare technique, using a single-channel method without a grasping forceps. Geometric and histological assessment of the resection specimen for size, histological depth, and diathermic injury were performed by a single pathologist, blinded to the endoscopic techniques used., Results: Thirty-six gastric mucosal resections were randomly performed in three pigs. Use of EMRC resulted in a statistically significant greater resection specimen by weight, size, and histological depth compared with standard EMR (P < 0.04). Large-cap EMRC resulted in a statistically significant greater resection weight and size compared to small-cap EMRC (P < 0.05). There was a statistically significant greater degree of diathermic injury in the specimens resected using the standard snare EMR technique compared with EMRC (P < 0.006). There were no acute complications with either technique., Conclusion: Gastric EMRC is more technically effective than and as safe and easy as standard snare EMR. Use of the cap, especially the larger cap, is associated with larger and deeper mucosal resection and less diathermic injury compared with the standard snare technique, making the pathologic assessment of depth and margin involvement more reliable. When possible, EMRC should be the EMR method of choice.

Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of cross-sectional imaging. The initial evaluation of a pancreatic cyst should be directed toward exclusion of a pseudocyst. Patients with pseudocysts generally have a history of acute or chronic pancreatitis, whereas those with cystic tumors most often lack such a history. Several types of cystic lesions are encountered in the pancreas. Because of morphologic overlap at imaging, accurate characterization of these lesions can be difficult. Computed tomography and magnetic resonance imaging are excellent modalities for both initial detection and characterization of cystic pancreatic lesions. An imaging classification system for these lesions has been proposed that is based on the morphologic features of the lesion. This system can be helpful in characterizing lesions, narrowing the differential diagnosis, and making decisions regarding the treatment of affected patients. Endoscopic ultrasonography-guided aspiration and biopsy is useful in cases that are indeterminate at cross-sectional imaging or that require observation., (RSNA, 2005.)

Autoimmune pancreatitis (AIP) is a benign inflammatory disease of the pancreas that mimics pancreatic malignancy both clinically and radiologically. The fine needle aspiration biopsy (FNAB) features of AIP have not previously been documented. We report our experience with AIP, highlight pitfalls, and perform a comprehensive analysis of the cytomorphologic features of this condition. We identified 16 patients with AIP, initially evaluated by endoscopic ultrasound (EUS)-guided FNAB, 11 of whom subsequently underwent a pancreatoduodenectomy. We compared these to a cohort of EUS-guided aspirates from ductal carcinoma of the pancreas (n = 16) and chronic pancreatitis, not otherwise specified (NOS) (n = 19). On all 51 cases, we semiquantitatively evaluated presence and atypia of ductal cells, presence and cellularity of stromal fragments, and inflammatory cells, type and distribution. Fifty percent (8 of 16) of the AIP cases presented as obstructive jaundice. EUS and CT scan showed mass lesions in 10 and 6 cases, respectively. There were three false-positive cytologic diagnoses, an adenocarcinoma, a solid-pseudopapillary tumor and a mucinous neoplasm. Ductal epithelium was inconspicuous and was seen in 6 cases. The FNAB samples showed background lymphocytes in three AIP cases, a feature absent in the control cohort. Stromal fragments with embedded lymphocytes (greater than 30 per 60x) were seen in 37.5% of AIP cases and only rarely with adenocarcinoma (12.5%) and pancreatitis, NOS (0%). The cellularity of stromal fragments was significantly higher in AIP than in the control group. The presence of stromal fragments of high cellularity with a lymphoid infiltrate in conjunction with clinical and radiology findings could potentially both establish a diagnosis of AIP and exclude carcinoma, thus preventing pancreatic resection.

Background: Portal vein embolization (PVE) has been used as a preoperative strategy to induce hepatic lobar atrophy and contralateral lobe hypertrophy. We determined the feasibility of endoscopic ultrasound (EUS)-guided Enteryx (EVAL/ethylene-vinyl alcohol copolymer) embolization of the portal vein (EUS-PVE) in an animal model as a potential, minimally invasive, endoscopic technique., Methods: EUS-guided embolization of the portal vein (EUS-PVE) using Enteryx was performed in a Yorkshire breed swine. Portal pressure measurements were obtained before and after vascular embolization. The animal was carefully monitored for seven days for evidence of abdominal pain, shock, or bleeding. An upper abdominal contrast-CT scan was performed to verify the location of the embolus., Results: The PV pressure increased from 3 mmHg at baseline to a mean of 15 mmHg after EUS-PVE. The CT-scan on day 4 demonstrated Enteryx in the main portal vein with extension into the left branch. At sacrifice on day 7, a solid thrombus was visible grossly and histologically inside the main portal vein and the left branch of the portal vein., Conclusions: Selective embolization of the portal vein by EUS guidance appears to be feasible and a potential, minimally invasive, preoperative treatment option for patients undergoing extensive hepatectomy.

Purpose of Review: Exciting new developments and applications of imaging techniques in pancreatic diseases have emerged. This review discusses these new advances and how they are improving our ability to diagnose malignancies and inflammatory lesions, to grade severity of pancreatitis, and to stage pancreatic cancer accurately., Recent Findings: A new computed tomography severity index shows promise for grading the severity of acute pancreatitis. Magnetic resonance imaging is comparable with computed tomography in staging acute pancreatitis. Analysis of pancreatograms and textural changes of the parenchyma may prove helpful in diagnosing chronic pancreatitis. Contrast enhanced ultrasonography may prove to be a useful way to judge the degree of inflammation and fibrosis in autoimmune pancreatitis and to monitor response to steroid therapy. The debate over the best means of staging pancreatic cancer has focused on endoscopic ultrasound and computed tomography. Preliminary studies with contrast enhanced ultrasonography report improved diagnostic and staging capabilities with pancreatic cystic and solid neoplasms. Improvements in positron emission tomography/computed tomography scans may improve the detection of neuroendocrine tumors., Summary: These new advances will help refine the diagnosis and staging of pancreatic diseases.

Malignancies of the bile duct are often suspected in patients with abnormal serum hepatic enzyme levels and obstruction of the biliary system. Although cross-sectional imaging can provide evidence for biliary obstruction and a malignancy arising from the bile duct, a definitive diagnosis is often obtained through the use of endoscopic procedures. Endoscopic retrograde cholangiopancreatography (ERCP), the most commonly performed procedure for cholangiocarcinoma, can provide a tissue diagnosis through brush cytology of the bile duct. Relief from biliary obstruction can be provided with temporary plastic stenting or permanent metal stenting. Photodynamic therapy guided by ERCP may provide improved palliation from biliary obstruction in the future. Endoscopic ultrasonography complements the role of ERCP and may provide a tissue diagnosis through fine-needle aspiration and staging through ultrasound imaging. High-resolution ultrasound images can provide detailed information regarding the relationship between a mass and the bile duct wall. Despite these advances in endoscopic techniques and imaging of the bile duct, a tissue diagnosis often remains elusive in many patients. In the future, molecular markers will be employed to improve the sensitivity for the detection of malignancy in bile duct samples obtained through brushing, aspiration, and biopsy.

Cystic neoplasms of the pancreas represent the best example of a malignant precursor in the pancreas. There are many parallels between pancreatic cystic neoplasms and the colon polyp-cancer sequence. In the past, cystic neoplasms of the pancreas were thought to be relatively rare, composing less than 10% of cancers of the pancreas. With the greater use of cross-sectional imaging, an increasing number of these neoplasms are being seen.

Background and Study Aims: The widespread use of cholangioscopy in the management of difficult choledocholithiasis has been limited by the need for two expert operators. This report describes the use of a technique of single-operator duodenoscope-assisted cholangioscopy (SODAC) in the successful management of 75 patients with choledocholithiasis., Patients and Methods: The single-operator technique, allowing simultaneous control of both the duodenoscope and cholangioscope, was prospectively studied between June 1999 and June 2001 in the diagnosis and treatment of choledocholithiasis., Results: A total of 109 SODAC procedures were conducted in 75 patients to manage choledocholithiasis. The indications were: firstly, SODAC-guided electrohydraulic lithotripsy (EHL) of stones in which conventional methods, including mechanical lithotripsy, had not been successful (52 SODAC procedures in 26 patients); and secondly, direct visualization of the biliary tree after cholangiography to assess the presence of stones (57 SODAC procedures in 49 patients). The locations and numbers of the stones, but not their size, were predictive of the number of SODAC-guided lithotripsy sessions required. All of the patients were free of stones at the end of the study period, and no complications were recorded., Conclusions: Single-operator SODAC-guided electrohydraulic lithotripsy was effective in the treatment of difficult cases of choledocholithiasis in which conventional methods had previously failed. The technique may allow increased use of cholangioscopy in the management of choledocholithiasis.

Endoscopic mucosal resection (EMR), a relatively new endoluminal therapeutic technique with low morbidity and no mortality reported to date, is advocated for the treatment of Barrett's esophagus (BE)-related superficial neoplasms. However, recent studies revise its success downward, particularly regarding the ability to achieve complete excision. To evaluate what remains an evolving technique, we analyzed our experience with a series of 27 esophageal EMRs (20 lesions in 18 patients). Our goal was to evaluate the diagnostic, staging, and therapeutic advantages of EMR separately by correlating the initial biopsies and pre-EMR endoscopic ultrasound (EUS) staging with the final histologic diagnoses and stage. Persistence/recurrence of neoplastic tissue was also correlated with the margin status of the resections. The mean size of the neoplasms, which included low-grade dysplasias (n=2), high-grade dysplasias (n=8), intramucosal carcinomas (n=14), and submucosal invasive carcinomas (n=3), was 11 mm. EUS correctly reported an intramucosal or submucosal lesion in 70% of the cases while it overstaged 18% and understaged 12% of the cases. The biopsy diagnosis corresponded to the EMR diagnosis in 63% of the cases. The biopsy underestimated the grade of the lesion in 21% of the cases. EMR revealed a lower histologic grade compared with the biopsy in 16% of the cases. The resection was microscopically complete in only 4% of the cases. No residual/recurrent disease was observed in 10 lesions (9 patients) at 4 to 63 months (mean, 23 months) post-EMR. However, 9 lesions (8 patients) persisted/recurred 28 days to 25 months (mean, 6 months) after treatment; 56% of the cases with positive lateral margin(s) and negative deep margin persisted/recurred. However, 86% of the EMRs with positive deep margin showed residual tumor/recurrence on follow-up biopsies. In conclusion, we observed that EMR offers improved diagnosis and staging as compared with biopsy and EUS. This is a significant advantage since it can modify patients' management. However, frequent incompleteness of resection and high persistence/recurrence are significant pitfalls that dictate continued endoscopic surveillance.

Background: Ethanol lavage has been used to successfully and safely ablate cystic lesions of the liver, the kidneys, and the thyroid., Methods: Asymptomatic patients who undergo EUS examination for a pancreatic cystic lesion were eligible. Patients underwent complete examination with a linear-array echoendoscope, and cyst characteristics were documented. After evacuation of the cyst with needle aspiration, the cyst cavity was lavaged with ethanol for 3 to 5 minutes. The concentration (5%-80%) of ethanol was gradually increased over the course of the study. Patients were monitored for complications during 2 hours after the procedure, and further follow-up was obtained at 72 hours and 1 year after lavage., Observations: Twenty-five patients were enrolled, 80% were women, and the mean age of all patients was 64.5 years. Cysts had a mean diameter of 19.4 mm and were equally located in the head, the body, and the tail of the pancreas. Cyst-fluid characteristics included high viscosity in 13 (52%) and a mean carcinoembryonic antigen and amylase of 5916 ng/mL and 11,506 U/L, respectively. None of the patients reported any symptoms in short- and long-term follow-up. Of the 23/25 patients with complete follow-up, 8 patients (35%) had complete resolution of their cysts on follow-up imaging. Five patients underwent resection, and histologic evidence of epithelial ablation was seen., Conclusions: Ethanol lavage of pancreatic cystic lesions is safe and feasible. A subset of patients undergoing ethanol lavage appears to have long-term resolution on follow-up imaging. Further prospective studies are required to determine if ethanol lavage is an effective treatment for pancreatic cystic lesions.