EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatic tissue: a pilot study in a porcine model (with video).

BACKGROUND: EUS-guided photodynamic therapy (PDT) with the photosensitizing agent porfimer sodium has been shown to be effective in ablation of pancreatic tissue. OBJECTIVE: The objective of this study was to determine the effectiveness and safety of EUS PDT with verteporfin, a photosensitizer associated with less photosensitivity. DESIGN: Prospective investigation of 6 swine that received an IV injection of 6 mg/m2 of verteporfin before EUS. SETTING: Hospital animal laboratory. INTERVENTIONS: The tail of the pancreas was located with EUS and was used to guide the placement of a light catheter. The pancreatic tail was exposed to 10, 15, or 20 minutes of laser light (689 nm). MAIN OUTCOME MEASUREMENTS: Follow-up abdominal CT, liver and renal function tests, and serum pancreatic enzymes levels were performed. Histology of the pancreas was obtained 7 days after the procedure on necropsy. RESULTS: Localized tissue necrosis within the pancreatic tail (range 6.6-30.5 mm in diameter) was seen in all animals. The diameter of the necrotic tissue was directly related to the dose of light. No post-procedural complications were observed. LIMITATIONS: Normal animal model (lack of malignant tissue). CONCLUSIONS: EUS-guided PDT of porcine pancreas with verteporfin achieved localized pancreatic tissue ablation in a dose-related fashion.

Utility of endoscopic ultrasound in the diagnosis of aberrant right subclavian artery.

BACKGROUND AND AIMS: Aberrant right subclavian artery (ARSA) is the most common congenital anomaly of the aortic arch occurring in 0.4-2.0% of the general population. Instead of arising from the brachiocephalic artery, the ARSA arises as the last branch from the aortic arch. The aim of this study was to determine the prevalence of ARSA in patients undergoing upper endoscopic ultrasound (EUS) and to describe the EUS characteristics of ARSA. METHODS: A retrospective review was conducted of 7513 upper EUS exams performed from 1 July 2000 to 1 February 2005. RESULTS: In total, 27 (0.36%, 95% CI 0.22-0.50%) of 7513 patients undergoing upper EUS were found to have an ARSA (10 male, 17 female; mean age 58 years, range 23-81 years). Of the 27 patients, 16 had only radial EUS, 10 had radial and linear EUS, and one had only linear EUS. In all 26 patients who underwent radial imaging, a well-defined, anechoic tubular structure was seen originating from the aortic arch and passing between the esophagus and spine. In all 11 patients undergoing linear imaging, the abnormal anatomy was detected and the vascular nature confirmed by Doppler. In one patient, both radial and linear imaging identified unsuspected aneurismal dilatation of the ARSA; a rare condition referred to as Kommerell's diverticulum (KD). None of the other 26 patients had symptoms to suggest an ARSA. Of the 14 patients who had computed tomography (CT) prior to EUS, only four were initially reported to have ARSA. However, later review of the CT scans verified an ARSA in all 14 patients. Of the two patients who underwent a barium swallow, only one had findings suggestive of ARSA. CONCLUSIONS: This report highlights the utility of both radial and linear EUS imaging in identifying previously unsuspected ARSA and associated anomalies. This report also suggests the need for careful review of the CT in patients suspected of having ARSA due to the frequent failure of radiologists to identify, or report, this anomaly when particular focus is not given.

Feasibility of endoscopic transgastric distal pancreatectomy in a porcine animal model.

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.

Endoscopic therapy of benign pyloric stenosis and gastric outlet obstruction.

PURPOSE OF REVIEW: To examine the short and long-term success rates of balloon dilation of pyloric stenosis. RECENT FINDINGS: Several large studies have demonstrated high rates of success for the relief of symptoms from pyloric stenosis using through-the-scope balloons. These dilating balloons readily increase the diameter of the stenotic pylorus on average from 6 to 16 mm. Patients who require more than two dilations are at high risk of endoscopic failure and the need for surgical intervention. Rapid re-stenosis rates are observed in patients with malignant pyloric obstruction. Since many patients with benign pyloric stenosis have underlying ulcer disease, helicobacter infection is a relatively common finding. Eradication of this infection at the time of balloon dilation will ensure higher long-term success rates. SUMMARY: In summary, benign pyloric stenosis can be readily treated with endoscopic balloon dilation and should be the first-line therapy.

Endoscopic transmural drainage of pancreatic pseudocysts: results of a national and an international survey of ASGE members.

BACKGROUND: Pancreatic pseudocysts can be drained endoscopically via the transpapillary or the transmural routes. We sought to assess endoscopic methods of pseudocyst drainage. METHODS: A web-based survey was sent to American Society for Gastrointestinal Endoscopy (ASGE) members in the United States (U.S.) and internationally. RESULTS: Of the 3054 endoscopists to whom the survey was sent, 266 (8.7%) replied; 198 performed pseudocyst drainage (103 [52%] ASGE members from the United States and 95 [48%] international members). The median of the total number of drainages per physician was 15 (range 1-364). The transgastric route was the most commonly used drainage route (65%). Transmural entry was performed by using a needle-knife in 53% of transmural drainages that were not EUS-guided. The number of stents placed ranged from 1 to 5 and these remained in place for 2 to 30 weeks. CT scan was used before drainage by 95% of all respondents. EUS imaging was used before drainage by 72 of 103 (70%) US endoscopists compared with 56 of 95 (59%) international endoscopists (p = 0.1). EUS-guided drainage was used by 56% of US endoscopists compared with 43% international endoscopists (p = 0.06). CONCLUSIONS: The most common site of transmural entry for drainage of pancreatic pseudocysts appears to be the transgastric route. Although CT is the most commonly used predrainage imaging modality, EUS is used before and during transmural drainage of pseudocysts in both the U.S. and abroad, particularly in academic medical centers. Use of EUS before or during drainage does not appear to be significantly different among endoscopists in the United States and internationally.

International survey of knowledge of indications for EUS.

BACKGROUND: The knowledge level for EUS indications among gastroenterologists across different locations and practices is not known. The aim of this study was to assess knowledge of EUS indications among a diverse group of gastroenterologists, both nationally and internationally. METHODS: A web-based survey was designed to assess knowledge of EUS with respect to 4 organ systems: esophagus, gastroduodenum, hepatopancreatobiliary, and colorectum. The survey was distributed by electronic mail (e-mail) to members of the American Society for Gastrointestinal Endoscopy. RESULTS: The survey was distributed to 3848 physicians, of whom 2848 had an active e-mail address. There were 323 respondents (11.3%), of whom 210 were U.S. members and 113 international. Overall, the mean score for the different organ systems for all respondents was highest for gastroduodenum (93% correct) and lowest for colorectum (71%) compared with esophagus (79%) and hepatopancreatobiliary (83%) systems. The mean total score was higher for U.S. respondents (84% correct) compared with international respondents (79%, p < 0.0001). Endosonographers fared better than those who were not endosonographers (85% vs. 81%, p = 0.0002). CONCLUSIONS: Knowledge levels of colorectal applications of EUS are poorest among the 4 organ systems studied. Future educational initiatives should focus on applications of EUS in this category. Studies are required to assess the impact of this education on the appropriateness of EUS referral patterns.

Clinical implications of the extent of invasion of T3 esophageal cancer by endoscopic ultrasound.

BACKGROUND: Endoscopic ultrasound (EUS) is an accurate imaging modality for local staging of esophageal cancer. We aimed to determine if depth of tumor invasion beyond muscularis propria (MP), as determined by preoperative EUS, is predictive of tumor recurrence or survival (a positive change in mortality) in patients with T3 esophageal cancer. METHODS: Records and images of all patients with T3 N1 M0 esophageal cancer staged with EUS at our institution between January 1999 and October 2003 were reviewed. EUS images were independently reviewed by five blinded endosonographers and tumors were classified as minimally invasive (invasion < 3 mm beyond MP) or advanced (invasion > or = 3 mm beyond MP) T3 disease. RESULTS: One hundred and sixty-five patients with esophageal cancer underwent EUS for staging and 39 patients with T3 N1 esophageal cancer were identified; 17 patients had minimally invasive T3 disease and 22 had advanced disease. All patients underwent neoadjuvant chemoradiation therapy followed by esophagectomy. Median follow up was 13 months. Adjusting for age and sex, minimally invasive disease was not associated with a statistically significant improvement in recurrence-free survival (hazard ratio, 1.45; 95% CI, 0.88-2.41, P = 0.14) or mortality (hazard ratio, 0.96; 95% CI: 0.49-1.78, P = 0.91). CONCLUSIONS: The extent of invasion of T3 esophageal cancer beyond MP, as determined by EUS, is not a significant predictor of tumor recurrence or mortality.

Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors.

BACKGROUND & AIMS: Nonoperative methods for diagnosis of pancreas cysts often lack sufficient accuracy. Accurate diagnosis is needed to determine prognosis and guide clinical management. The aim of this study was to determine whether the tissue obtained by endoscopic ultrasound-guided trucut biopsy (EUS TCB) is sufficient for histologic diagnosis of cystic pancreatic tumors (CPTs). METHODS: EUS TCB was performed in patients with a suspected CPT. A dedicated gastrointestinal pathologist reviewed the core biopsies. The final diagnosis was based on clinical, laboratory, imaging, and biopsy findings, and resected specimens when available. RESULTS: EUS TCB was performed in 10 patients with a suspected CPT. Final diagnoses included serous cystadenoma (SCA, n=5), islet cell tumor (n=2), mixed seromucinous lesion (n=1), polycystic disease of the pancreas (n=1), and pseudocyst (n=1). EUS TCB was nondiagnostic in 3 of 10 patients. Among the other 7 patients, TCB diagnosed 4 SCAs, obviating the need for planned surgery in 3 patients. In the fourth patient with an SCA, the TCB result ruled out metastatic disease from locally recurrent lung cancer, allowing a narrowed radiation field. EUS TCB confirmed the need for surgery in 2 patients with an islet cell tumor. In 1 patient, EUS TCB findings were "partially" diagnostic, leading to previously unplanned surgery. CONCLUSIONS: This report establishes the capability and safety of EUS TCB to collect sufficient tissue for diagnosing CPTs. The results might help guide clinical management.

Assessment of the impact of an educational course on knowledge of appropriate EUS indications.

BACKGROUND: The knowledge level of EUS among gastroenterologists likely influences the appropriateness of requested indications for EUS. It remains unknown what the impact is of a short EUS course, involving didactic teaching, on knowledge levels of EUS indications for EUS. The aim of this study was to assess the impact of a 3-day educational course on knowledge levels of attending gastroenterologists regarding the appropriateness of indications for EUS. METHODS: A questionnaire was designed that tested knowledge of indications for EUS in 4 anatomic sites: esophagus, gastroduodenum, hepatopancreatobiliary system, and colorectum. This questionnaire was distributed to all attendees of a 3-day EUS educational course. All attendees completed the survey before and immediately after the course. RESULTS: A total of 24 gastroenterologists completed the pre- and post-course survey. Before the course, respondents scored highest in questions on EUS applications in the gastroduodenum (94%) and the hepatopancreatobiliary system (88%) compared with the esophagus (72%) and the colorectum (74%). Statistically significant improvements in knowledge were recorded in all organ categories: gastroduodenum (100%, p = 0.002 vs. pretest score), hepatopancreatobiliary system (99%, p < 0.0001), esophagus (92%, p < 0.0001), and colorectum (93%, p = 0.0004). The biggest improvement was observed in knowledge levels for the esophagus (20%) and the colorectum (18%). CONCLUSIONS: There was a consistent improvement in the gastroenterologists' knowledge levels of EUS indications among all organ categories after an educational course. Our findings suggest that education enhances gastroenterologists' understanding of EUS. Future studies should seek to assess the impact of these improved knowledge levels on the appropriateness of EUS referral patterns.

EUS-guided trucut biopsy in establishing autoimmune pancreatitis as the cause of obstructive jaundice.

BACKGROUND: The diagnosis of autoimmune pancreatitis can be difficult and often requires a larger specimen than can be provided by FNA alone to determine if the tissue sample obtained with EUS trucut biopsy (TCB) is sufficient to allow adequate histologic review to establish the diagnosis of autoimmune pancreatitis. METHODS: EUS TCB was performed in patients presenting with obstructive jaundice who were suspected of having autoimmune pancreatitis based on their clinical, laboratory and imaging studies. The charts were retrospectively reviewed to determine the feasibility of TCB. RESULTS: Between August 2002 and June 2004, 3 patients with obstructive jaundice and suspected autoimmune pancreatitis (AIP) underwent EUS TCB. In each case, a diagnosis of pancreatic cancer also was considered, and surgical resection was the planned therapy before the patient underwent EUS TCB. Histologic review of the TCB specimens established the diagnosis of AIP in two patients and identified nonspecific changes of chronic pancreatitis in the third patient. EUS-guided FNA was performed in two of the 3 patients and failed to establish the diagnosis in either patient. Other than mild transient abdominal pain (n = 1), no complications were identified. CONCLUSIONS: This preliminary study suggests that EUS TCB can safely establish the diagnosis of AIP. Doing so helps guide management and may help to avoid unnecessary surgery. Prospective studies are needed to verify these findings and to more clearly define the role of EUS TCB in these patients.

EUS features of recurrent transitional cell bladder cancer metastatic to the GI tract.

BACKGROUND: Recurrent transitional cell bladder cancer (TCBC) can metastasize to the GI tract albeit uncommonly. This is the first report of the EUS appearance of metastatic TCBC to the GI tract. In addition to describing the EUS features of recurrent metastatic TCBC, this study determined the number of patients referred for evaluation of a primary GI luminal cancer in which EUS instead established the diagnosis of metastatic recurrent TCBC. METHODS: Patients referred from July 2000 through April 2004 for EUS evaluation of a suspected primary GI luminal cancer were retrospectively reviewed. For patients with an established diagnosis of recurrent metastatic TCBC, EUS images were retrospectively reviewed to identify characteristic features. RESULTS: Of 2216 patients undergoing EUS to evaluate a suspected primary GI luminal cancer, 3 men (0.14%: 95% confidence interval [0.02%, 0.29%]) (mean age 67 years, range 54-74 years) were found instead to have recurrent metastatic TCBC involving the duodenum (n = 1) or rectum (n = 2). The patients presented a mean of 32 months after diagnosis of the primary TCBC with change in bowel habit (n = 1) and symptoms of bowel obstruction (n = 2). In each patient, initial endoscopy revealed circumferential luminal stenosis and mucosal erythema, but mucosal biopsy specimens revealed normal tissue. EUS demonstrated hypoechoic, symmetric, circumferential wall thickening, loss of deep wall layers, and pseudopodia-like extensions into the peri-intestinal tissues. In the two patients with rectal involvement, no evidence of direct infiltration from the bladder bed was seen. EUS-guided FNA was diagnostic of metastatic TCBC in all patients. CONCLUSIONS: Although most cases of hypoechoic bowel-wall thickening and stenosis are from primary GI neoplasia, recurrent TCBC should be considered in patients with a history of this tumor. Correct diagnosis is important, because this allows selection of appropriate therapeutic interventions. Although firm EUS criteria for TCBC cannot be established based on findings in 3 patients, certain features may prove useful. EUS-guided FNA can confirm the diagnosis.

Knowledge of indications for EUS among gastroenterologists and non-gastroenterologists.

BACKGROUND: The level of awareness among non-gastroenterologists of the indications for EUS is unknown. This study assessed knowledge of the indications and the utility of EUS among gastroenterologists and non-gastroenterologists in a large multispecialty academic practice. METHODS: A questionnaire was designed that tested knowledge of the indications for EUS with respect to 4 organ systems: esophagus, gastroduodenum, hepatopancreatobiliary system and colorectum. The questionnaire was distributed by electronic mail to gastroenterologists, general internists, non-gastroenterologist subspecialists, and surgeons in a large multispecialty practice. RESULTS: The survey was distributed to 659 attending physicians of whom 227 (34%) replied: gastroenterologists (53%), internists (30%), non-gastroenterologist specialists (33%), and surgeons (28%). Knowledge of appropriate indications was highest among gastroenterologists (84.3%) compared with internists (68.9%), non-gastroenterologist specialists (65.4%), and surgeons (65.3%) (p < 0.0001). Among all non-gastroenterologists, knowledge of indications for hepatopancreatobiliary (mean 66.3% correct responses) and colorectal applications (64.0%) was inferior to knowledge of esophageal (71.5%) and gastroduodenal (83.5%) applications. CONCLUSIONS: Internists, non-gastroenterologist specialists, and surgeons in a large multispeciality practice have moderate knowledge of the indications and the utility of EUS. Knowledge was at the lowest level for hepatopancreatobiliary and colorectal applications of EUS for all 3 groups of non-gastroenterologists. Future studies should focus on the education of non-gastroenterologists regarding the role of EUS and assess the impact of such education on the appropriateness of EUS referral patterns.

AIDS Cholangiopathy.

AIDS is an advanced disease with systemic and infectious complications that can be fatal. When a patient with AIDS presents with right upper quadrant or midepigastric pain, cholestasis, and symptoms of cholangitis, AIDS cholangiopathy should be suspected and appropriate diagnostic and therapeutic interventions should be initiated. Opportunistic infections such as Cryptosporidium and cytomegalovirus are the most common cause of AIDS cholangiopathy. Four distinct cholangiographic abnormalities have been demonstrated by endoscopic retrograde cholangiopancreatography, the most common being papillary stenosis with sclerosing cholangitis. Antimicrobial therapy is often ineffective. Highly active antiretroviral therapy may enhance immune function and offers the best medical therapy to clear the opportunistic infections. Ursodeoxycholic acid has a limited benefit in patients with sclerosing cholangitis and cholestasis. Endoscopic sphincterotomy has been shown to relieve pain and biliary obstruction in patients with papillary stenosis. Balloon dilation of strictures and stent placement decompress the biliary system and may be helpful. Cholecystectomy is recommended to treat acalculous cholecystitis, and celiac plexus block may be offered to patients with terminal disease and intractable abdominal pain.

Role of endoscopic ultrasonography in diseases of the extrahepatic biliary system.

Endoscopic ultrasonography (EUS) is one of the most recent advances in gastrointestinal endoscopy. Available EUS devices include echoendoscopes, such as radial scanning and linear array echoendoscopes, and catheter ultrasound probes. Endoscopic ultrasonography has various applications, such as staging of gastrointestinal malignancy, evaluation of submucosal tumors, and has grown to be an important modality in evaluating the pancreaticobiliary system. With regard to the biliary system, EUS is useful for the detection and staging of ampullary tumors, detection of microlithiasis and choledocholithiasis and evaluation of benign and malignant bile-duct strictures. Endoscopic ultrasonography may be used as an adjunct to transabdominal ultrasound for the detection and characterization of gallbladder polyps. In addition, EUS is helpful in the staging of gallbladder cancer as well as in diagnosing anomalous pancreaticobiliary junction with its associated pancreatobiliary diseases. The present paper reviews the current applications of EUS for imaging and intervention in diseases of the extrahepatic biliary system.

Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats: implications for the pathogenesis and prevention of ERCP-induced pancreatitis.

INTRODUCTION: The neurogenic inflammatory mediator, substance P (SP), has been implicated in the pathogenesis of acute secretagogue-induced pancreatitis. We hypothesized that it may also play an important role in the development of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). AIMS Our aim was to evaluate the effectiveness of CP-96345, a NK1 receptor antagonist, in diminishing post-ERCP pancreatitis in a rat model. METHODS: The effects of CP-96345, when mixed with the contrast agent, were studied in a rat model of pancreatitis caused by retrograde contrast infusion. After 24 hours, histology, edema, and myeloperoxidase activity (MPO) of pancreas, plasma amylase, and NK1 receptor endocytosis in pancreatic acinar cells were evaluated. RESULTS: Intraductal contrast infusion caused increases in plasma amylase, edema, histologic grade, and MPO of pancreas, and NK1 receptor internalization in pancreatic acinar cells. The addition of CP-96345 to the infusate significantly reduced pancreatic edema, MPO activity, and the histologic grade of pancreatitis accompanied by a decrease in NK1 receptor internalization. CONCLUSIONS: When an NK1 receptor antagonist is delivered along with the contrast media there is significant reduction in the pancreatic inflammation caused by intraductal contrast infusion. These results provide some insight into the pathogenesis of ERCP induced pancreatitis as well as present novel pharmacological targets for its prevention.

Differentiating pancreatic cancer from pseudotumorous chronic pancreatitis.

The differentiation between pancreatic carcinoma and pseudotumorous pancreatitis continues to be a challenge. Several diagnostic imaging and endoscopic modalities can assist in making the differentiation, but the accuracy of each method varies. Radiologic imaging techniques include transabdominal ultrasound, computed tomography, magnetic resonance imaging, magnetic resonance cholangiopancreatography, and positron emission tomography. Endoscopic techniques include endoscopic ultrasonography, intraductal ultrasonography, and endoscopic retrograde cholangiopancreatography with brush cytology of pancreatobiliary strictures, endoscopic forceps biopsy, and analysis of pancreatic juices for malignant cells. Tumor markers appear to be promising, but further studies are needed to define the role of these markers.