Background: Currently endoscopic ultrasound with fine needle aspiration (EUS-FNA) complements Mediastinoscopy (MED) in staging of patients with NSCLC who have enlarged or abnormal appearing mediastinal lymph nodes on noninvasive imaging such as CT scan. Endobronchial ulstrasound (EBUS) is an emerging technology that can access lymph node stations traditionally accessible only by surgical intervention. The use of combined EUS-FNA+EBUS-FNA has been shown to be feasible and reaches 95% sensitivity with specificity near 100%. The cost-benefit ratio of this procedure, which can be done on the same day under conscious sedation with discharge after standard recovery time, has not been compared to MED, which requires general anesthesia and operating room time.

Background: Pancreatic cancer is the fourth leading cause of cancer death in the United States. It frequently presents at an advanced stage and treatment options are very limited. Recently, EUS guided injection (EUS-FNI) of chemotherapeutic agents and gene therapy into pancreatic tumors has been investigated with promising results. Nanoparticles are currently under investigation as potential carriers for chemotherapeutic agents in brain tumors. They may have properties that enhance the quality of ultrasound imaging which could be advantageous in EUS-FNI therapy. Curcumin is a non-toxic phytochemical that has been shown to decrease the expression of NF-kappaB-regulated gene products, including cyclooxygenase-2, prostaglandin E2, and interleukin-8, all of which have been implicated in the growth and invasiveness of pancreatic carcinoma. Short pieces of double-stranded RNA (short, interfering RNAs or siRNA) are used by cells to degrade messenger RNA and if siRNAs are matched to the mRNA of a faulty gene, the abnormal protein product of that gene will not be produced.

Purpose/Objective(s)We initiated an IRB-approved phase II study to estimate progression-free survival (PFS) of patients with nonmetastatic, locally advanced pancreatic cancer (LAPC) treated with induction gemcitabine (Gem)/oxaliplatin (Ox) and cetuximab (Cet) followed by intensity-modulated radiotherapy (IMRT) with concurrent capecitabine (Cap). IMRT was used to deliver the radiotherapy (RT) in an attempt to minimize RT-related morbidity. Dosimetric parameters and toxicity outcomes are investigated.Materials/MethodsAll patients had unresectable or borderline-resectable LAPC based on endoscopic ultrasound (EUS), CT, or MRI findings, no evidence of metastatic disease, and ECOG performance status 0-2. All patients were started on induction chemotherapy with Gem 1000mg/m2 IV d1, Ox 100mg/m2 IV d2, repeated every 14 days for 6 cycles, with Cet 400mg/m2 IV d1 followed by 11 weekly infusions of 250mg/m2. Patients then were restaged with EUS and CT/MRI. If they became resectable they were taken to surgery. If not, they went on to chemoradiation. IMRT delivered 45.9 Gy at 1.53 Gy per fraction to the elective nodal region while simultaneously delivering 54 Gy at 1.8 Gy per fraction to gross disease. Cap was taken (800 mg/m2 po BID, 5 days per week) concurrently with IMRT. 6 weeks after chemoradiation, patients were restaged with EUS and CT/MRI. Patients deemed resectable were taken for curative resection; others were observed.ResultsTrial accrual is complete with 39 patients initiated on protocol therapy. The final 2 patients are receiving radiotherapy at the time of this analysis. 9 of 35 patients (25.7%) who have completed treatment and restaging were taken for R0 resection. 15 patients did not receive protocol RT at this institution. The remaining 24 patients all received IMRT on protocol at MUSC. Of these 24 patients the median values achieved for dosimetric parameters are as follows: PTV45.9Gy V100% = 96.8%, V93% = 100%, max dose =104.5%; PTV54Gy V100% = 95.6%, V93% = 100%, max dose = 104.6%; liver: V20Gy = 44.3%, V30Gy = 21.9%; stomach: V30Gy = 21.6%, V45Gy = 12.2%; small bowel: mean = 13.1Gy, V45Gy = 12.3%, V30Gy = 18.7%; ipsilateral kidney: V18Gy = 36.1%; contralateral kidney: V18Gy = 22.3%; spinal cord: max dose (to .1cc) = 43.1Gy. Only 2 patients (8.3%) suffered acute toxicity>grade 2 during chemoradiation. These 2 patients required IV fluids for dehydration. Median weight loss during chemoradiation is 4 lbs. or 3%. The median change in performance status is 0. Median overall survival is 12.2 mo, median PFS is 9.1 mo, and 6-mo PFS is 80% based on intent-to-treat analysis.ConclusionsThis phase II study demonstrates that IMRT with concurrent capecitabine after multi-agent induction chemotherapy with Gem/Ox/Cet is well tolerated with relatively mild acute toxicity. Purpose/Objective(s)We initiated an IRB-approved phase II study to estimate progression-free survival (PFS) of patients with nonmetastatic, locally advanced pancreatic cancer (LAPC) treated with induction gemcitabine (Gem)/oxaliplatin (Ox) and cetuximab (Cet) followed by intensity-modulated radiotherapy (IMRT) with concurrent capecitabine (Cap). IMRT was used to deliver the radiotherapy (RT) in an attempt to minimize RT-related morbidity. Dosimetric parameters and toxicity outcomes are investigated. We initiated an IRB-approved phase II study to estimate progression-free survival (PFS) of patients with nonmetastatic, locally advanced pancreatic cancer (LAPC) treated with induction gemcitabine (Gem)/oxaliplatin (Ox) and cetuximab (Cet) followed by intensity-modulated radiotherapy (IMRT) with concurrent capecitabine (Cap). IMRT was used to deliver the radiotherapy (RT) in an attempt to minimize RT-related morbidity. Dosimetric parameters and toxicity outcomes are investigated. Materials/MethodsAll patients had unresectable or borderline-resectable LAPC based on endoscopic ultrasound (EUS), CT, or MRI findings, no evidence of metastatic disease, and ECOG performance status 0-2. All patients were started on induction chemotherapy with Gem 1000mg/m2 IV d1, Ox 100mg/m2 IV d2, repeated every 14 days for 6 cycles, with Cet 400mg/m2 IV d1 followed by 11 weekly infusions of 250mg/m2. Patients then were restaged with EUS and CT/MRI. If they became resectable they were taken to surgery. If not, they went on to chemoradiation. IMRT delivered 45.9 Gy at 1.53 Gy per fraction to the elective nodal region while simultaneously delivering 54 Gy at 1.8 Gy per fraction to gross disease. Cap was taken (800 mg/m2 po BID, 5 days per week) concurrently with IMRT. 6 weeks after chemoradiation, patients were restaged with EUS and CT/MRI. Patients deemed resectable were taken for curative resection; others were observed. All patients had unresectable or borderline-resectable LAPC based on endoscopic ultrasound (EUS), CT, or MRI findings, no evidence of metastatic disease, and ECOG performance status 0-2. All patients were started on induction chemotherapy with Gem 1000mg/m2 IV d1, Ox 100mg/m2 IV d2, repeated every 14 days for 6 cycles, with Cet 400mg/m2 IV d1 followed by 11 weekly infusions of 250mg/m2. Patients then were restaged with EUS and CT/MRI. If they became resectable they were taken to surgery. If not, they went on to chemoradiation. IMRT delivered 45.9 Gy at 1.53 Gy per fraction to the elective nodal region while simultaneously delivering 54 Gy at 1.8 Gy per fraction to gross disease. Cap was taken (800 mg/m2 po BID, 5 days per week) concurrently with IMRT. 6 weeks after chemoradiation, patients were restaged with EUS and CT/MRI. Patients deemed resectable were taken for curative resection; others were observed. ResultsTrial accrual is complete with 39 patients initiated on protocol therapy. The final 2 patients are receiving radiotherapy at the time of this analysis. 9 of 35 patients (25.7%) who have completed treatment and restaging were taken for R0 resection. 15 patients did not receive protocol RT at this institution. The remaining 24 patients all received IMRT on protocol at MUSC. Of these 24 patients the median values achieved for dosimetric parameters are as follows: PTV45.9Gy V100% = 96.8%, V93% = 100%, max dose =104.5%; PTV54Gy V100% = 95.6%, V93% = 100%, max dose = 104.6%; liver: V20Gy = 44.3%, V30Gy = 21.9%; stomach: V30Gy = 21.6%, V45Gy = 12.2%; small bowel: mean = 13.1Gy, V45Gy = 12.3%, V30Gy = 18.7%; ipsilateral kidney: V18Gy = 36.1%; contralateral kidney: V18Gy = 22.3%; spinal cord: max dose (to .1cc) = 43.1Gy. Only 2 patients (8.3%) suffered acute toxicity>grade 2 during chemoradiation. These 2 patients required IV fluids for dehydration. Median weight loss during chemoradiation is 4 lbs. or 3%. The median change in performance status is 0. Median overall survival is 12.2 mo, median PFS is 9.1 mo, and 6-mo PFS is 80% based on intent-to-treat analysis. Trial accrual is complete with 39 patients initiated on protocol therapy. The final 2 patients are receiving radiotherapy at the time of this analysis. 9 of 35 patients (25.7%) who have completed treatment and restaging were taken for R0 resection. 15 patients did not receive protocol RT at this institution. The remaining 24 patients all received IMRT on protocol at MUSC. Of these 24 patients the median values achieved for dosimetric parameters are as follows: PTV45.9Gy V100% = 96.8%, V93% = 100%, max dose =104.5%; PTV54Gy V100% = 95.6%, V93% = 100%, max dose = 104.6%; liver: V20Gy = 44.3%, V30Gy = 21.9%; stomach: V30Gy = 21.6%, V45Gy = 12.2%; small bowel: mean = 13.1Gy, V45Gy = 12.3%, V30Gy = 18.7%; ipsilateral kidney: V18Gy = 36.1%; contralateral kidney: V18Gy = 22.3%; spinal cord: max dose (to .1cc) = 43.1Gy. Only 2 patients (8.3%) suffered acute toxicity>grade 2 during chemoradiation. These 2 patients required IV fluids for dehydration. Median weight loss during chemoradiation is 4 lbs. or 3%. The median change in performance status is 0. Median overall survival is 12.2 mo, median PFS is 9.1 mo, and 6-mo PFS is 80% based on intent-to-treat analysis. ConclusionsThis phase II study demonstrates that IMRT with concurrent capecitabine after multi-agent induction chemotherapy with Gem/Ox/Cet is well tolerated with relatively mild acute toxicity. This phase II study demonstrates that IMRT with concurrent capecitabine after multi-agent induction chemotherapy with Gem/Ox/Cet is well tolerated with relatively mild acute toxicity.

Background and study alms: Solid pseudopapillary tumors of the pancreas are rare, low-grade, epithelial neoplasms that are usually discovered incidentally in young women. Distinguishing solid pseudopapillary tumors from other pancreatic tumors, especially pancreatic endocrine tumors, can be challenging. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in this context remains unclear. The purpose of this study was to describe the endoscopic ultrasound features of solid pseudopapillary tumors and the role of EUS-FNA in the preoperative diagnosis of these tumors.Patients and methods: Patients from five tertiary referral centers with surgically confirmed solid pseudopapillary tumors who had undergone preoperative EUS-FNA were included. The endoscopic ultrasound findings, cytologic descriptions, immunostaining results, operative records, surgical pathology, and results of the most recent clinical follow-up were reviewed.Results: A total of 28 patients were identified (four men [14%], 24 women [86%], mean age +/- standard deviation [SD] 35 +/- 10 years). Solid pseudopapillary tumors had been found as incidental findings on cross-sectional imaging in 50% of cases. The mean tumor size +/- SD was 42 +/- 19.5 mm and the majority were located in the pancreatic body and tail. The endoscopic ultrasound report described a well-defined, echo-poor mass in 86%; the tumors were solid in 14 patients (50%), mixed solid and cystic in 11 patients (39%), and cystic in three patients (11%). A preoperative diagnosis of solid pseudopapillary tumor was made in 21 patients (75%) on the basis of EUS-FNA cytology. Surgical resection was performed in all cases. Laparoscopic resection was performed in eight of these patients (29%).Conclusions: A solid pseudopapillary tumor should be included in the differential diagnosis of any well-demarcated, echo-poor, solid or mixed solid/cystic pancreatic lesion seen during endoscopic ultrasound, particularly in young women. The diagnostic accuracy of EUS-FNA for solid pseudopapillary tumors was 75% in this study. A definitive preoperative diagnosis can guide the surgical approach in selected cases.

15506 Background: The treatment of patients with locally advanced pancreatic cancer remains challenging with median survival in the range of 10 months. This study seeks to establish whether neoadjuvant therapy with cetuximab in combination with oxaliplatin and gemcitabine improves the rate of progression free survival (PFS) at 6 months. Methods: Pts received preoperative gemcitabine (G) 1,000 mg/m2 iv d1, oxaliplatin (O) 100 mg/m2 iv d2 every 14d for 6 cycles with cetuximab (C) 400 mg/m2 iv d1 followed by 11 weekly infusions of 250 mg/m2. Staging by CT scan and endoscopic ultrasound occurred prior to enrolment and 4 weeks after completion. Pts who were considered surgically resectable underwent surgical exploration while patients with unresectable disease were treated with IMRT at 54 Gy with concurrent capecitabine at 800 mg/m2 by mouth twice daily. Results: 26 pts have been enrolled and 15 pts have completed chemotherapy and are evaluated for response. 3 pts were taken off from the protocol prior to completing chemotherapy: allergic reaction to cetuximab(1pt), decrease in performance status(1pt), and personal preference (1pt). The median progression-free is 9.5 months 95% CI (7.23-Inf) and median overall survival is not reached. No patients had progressed at six months. 7 pts were borderline resectable while 8 had unresectable disease. 14 pts completed neoadjuvant therapy with 5 of 14 (36%) able to undergo an R0 surgical resection. 1 pt was able to undergo R0 resection after concurrent chemoradiation, for a resectability rate of 6/14 (43%). IMRT was delivered to 8 of 9 pts unresectable after GOC. 7 of 8 pts were able to complete IMRT. During GOC, 2 of 14 pts had grade 3 hematologic toxicities and 1 pt had grade 4 allergic reaction to cetuximab. During IMRT 3 of 8 pts had a maximum RTOG grade 3 acute GI toxicity. Conclusions: Early results from this study indicate that neoadjuvant GOC followed by IMRT is well tolerated with a very promising R0 resectability rate. Trial accrual continues and updated results will be presented. No significant financial relationships to disclose.

Chylothorax due to thoracic duct (TD) trauma is traditionally treated with duct ligation at thoracotomy. We describe a novel endoscopic approach to this difficult management dilemma using endoscopic ultrasound (EUS) and fine needle injection (FNI) of the TD. A 41 year-old male was involved in a high-speed motor vehicle accident resulting in ejection from the vehicle and severe chest injuries. During his hospitalization refractory hiccups and nausea prompted a chest CT scan. A 4.9 × 3.1 cm focal fluid collection was identified between the esophagus and aorta in the subcarinal region. Bilateral pleural effusions were seen but no pulmonary mass or adenopathy was present. Rupture of the thoracic duct was considered and an EUS confirmed a 6 cm fluid collection under the aortic arch. A dilated 2.2 mm thoracic duct could be tracked into the collection and 35 ml of milky, straw colored fluid was aspirated; pathology confirmed a chyloma. In preparation for thoracic duct occlusion the following day and to optimize TD visualization, the patient was fed 2 canisters of high fat Ensure. The next day the fluid had fully re-accumulated and the thoracic duct was again identified. Color flow Doppler interrogation of surrounding structures confirmed its relation to the azygous vein. Twenty ml was again aspirated, fully collapsing the collection. Because of its safety profile and sclerosant properties, 1.5 ml of sodium morrhuate (NaM) was directly into the TD under EUS control. There were no complications. The nausea and hiccups resolved and the patient was discharged uneventfully. No surgical intervention or chest tube placement was required. To our knowledge, this represents a novel and minimally invasive approach to manage traumatic chylothorax. We have replicated this approach in swine models and will present gross and histopathologic proof of principle.

It is widely recognized that endoscopic ultrasonography (EUS) in combination with fine-needle aspiration (FNA) has a specificity of almost 100 % in the diagnosis of pancreatic cancer. While EUS is in our view a very sensitive diagnostic tool, the diagnosis of pancreatic cancer can be overlooked even by expert endosonographers. Short of direct procedure-related complications, missed gastrointestinal cancers are the most dreaded and most humbling consequence to face the practicing endoscopist. In a study published in this issue of Endoscopy, Bhutani et al. [1] sought to identify factors leading to a missed or delayed diagnosis of pancreatic cancer on EUS. While this cautionary study identified practical limitations of EUS-FNA in detecting pancreatic cancer, there are several important caveats regarding it which need to be addressed.

BACKGROUND:The long-term efficacy of sequential insertion of multiple plastic stents for benign biliary strictures is poorly defined. The aims of this study were to evaluate the long-term outcome (bile duct patency, complications) of this therapy and to identify predictors of a good outcome.METHODS:Retrospective review of 29 cases of benign biliary strictures treated with sequential plastic stent insertion in progressively increasing numbers and/or of increasing diameter.RESULTS:Stricture etiology was as follows: postoperative 19 (66%), chronic pancreatitis 9 (31%), and idiopathic 1 (3%). Therapy succeeded in 18 patients (62%) (mean follow-up 48.0 [11.56] months after stent removal). Therapy failed in 11 patients (38%) (mean interval to failure 11.59 [9.79] months after stent removal). The 2 groups of patients in which therapy failed had either a hilar stricture (n = 4, 25% success) or distal common bile duct stricture caused by chronic pancreatitis (n = 9, 44% success). In the remaining cases, therapy succeeded in 13 of 16 (81% success). The observed differences in success rate among subgroups were not statistically significant. There were no ERCP-related deaths. One episode of mild pancreatitis and 2 episodes of cholangitis developed during 126 ERCPs over a period of stent insertion of 36 patient years.CONCLUSIONS:In selected patients with benign biliary strictures, sequential endoscopic insertion of multiple biliary stents may lead to long-term success that could be equal to or superior to surgery with minimal morbidity. Hilar strictures and those caused by chronic pancreatitis appear to respond poorly to this therapy.

Eosinophilic gastroenteritis is a rare gastrointestinal disorder of undetermined etiology that is characterized by eosinophilic infiltration of the gut wall. The presenting symptoms depend on the site and depth of intestinal involvement and varies from nausea, vomiting, and abdominal pain to acute bowel obstruction. Pancreaticobiliary obstruction caused by eosinophilic gastroenteritis is rare. We report a 39-year-old man who presented with abdominal pain, vomiting, abnormal liver tests, and a duodenal mass on upper endoscopy. Blood tests showed peripheral eosinophilia. Abdominal computed tomography scan showed a suspected mass in ampullary region. At endoscopic retrograde cholangiopancreatography, both pancreatic and common bile duct were dilated with no obvious ductal strictures. Biopsies from the duodenal mass showed evidence of eosinophilic gastroenteritis. He was successfully treated with prednisone, and his liver test results returned to normal. In conclusion, this unusual case of eosinophilic gastroenteritis presented with duodenal mass that was masquerading as an ampullary adenoma causing pancreaticobiliary obstruction.

INTRODUCTIONEUS is an accurate means of evaluating and diagnosing submucosal lesions of the GI tract. The aim of this study was to prospectively determine interobserver agreement for the EUS classification of submucosal masses among endosonographers with different levels of training and experience from multiple centers.METHODSTwenty patients with submucosal mass lesions diagnosed by upper endoscopy underwent EUS. Surgical findings were available for 16 patients. In 4 patients with obvious cystic/vascular structures (i.e., varices) no surgical specimen was necessary. A blinded observer developed a study videotape of critical endoscopic and EUS real-time imaging for each lesion. The videotape was distributed to 10 endosonographers, each with at least 1 year of experience, who independently reviewed the videotape and recorded their diagnosis based on EUS features. These endosonographers used previously agreed-upon standardized EUS diagnostic criteria for each category of lesion. A kappa (kappa) statistic, used to evaluate agreement, was calculated for each lesion category for the 10 endosonographers as a group and individually. An overall kappa statistic was also calculated. Significance was analyzed with a two-tailed t test.RESULTSAgreement was excellent for cystic lesions (kappa = 0.80) and extrinsic compressions (kappa = 0.94), good for lipoma (kappa = 0.65), fair for leiomyoma and vascular lesions (kappa = 0.53 and 0.54, respectively), and poor for other submucosal lesions (kappa = 0.34). Overall agreement among observers was good (kappa = 0.63). Furthermore, a significant association was noted between total years of EUS experience and the number of correct answers (p = 0.01).CONCLUSIONSInterobserver agreement is good for characterizing submucosal masses by EUS. However, it appears to be better for some lesions than others. The overall length of experience with EUS appears to play an important role in the accuracy of this modality in the evaluation of submucosal lesions.

Background and Study Aims: The use of endoscopic ultrasonography (EUS) guidance for fine-needle aspiration (FNA) of mediastinal lymph nodes has become an important aid in the staging of bronchogenic carcinoma. In many cases, it may be an alternative to mediastinoscopy/mediastinotomy (MED), but the cost-effectiveness of the two techniques has not been compared. The aim of this study was to apply a decision-analysis model to compare the cost-effectiveness of EUS and MED in the preoperative staging of patients with non-small-cell lung cancer.Patients and Methods: A decision-analysis model was designed, taking as entry criteria lung cancer and abnormal mediastinal lymph nodes verified by computerized tomography (CT), Performance characteristics of MED and EUS were retrieved from the published literature, as were life expectancy data. Direct actual costs of the relevant procedures were retrieved from the billing system of our hospital.Results: The cost per year of expected survival is US$ 1.729 with the EUS strategy, and US% 2.411 with the MED strategy. The advantage conferred by EUS remains even when the negative predictive value of EUS is as low as 0.22,Conclusion: Because of its low cost and high yield, EUS-guided FNA is a cost-effective aid assessing mediastinal lymphadenopathy.

BACKGROUND:The ability to identify common bile duct stones by noninvasive means in patients with acute biliary pancreatitis is limited. The aim of this study was to prospectively evaluate the ability of endosonography (EUS) to identify cholelithiasis and choledocholithiasis and predict disease severity in patients with nonalcoholic pancreatitis.METHODS:EUS was performed immediately before endoscopic retrograde cholangiopancreatography (ERCP) by separate blinded examiners within 72 hours of admission. Gallbladder findings were compared between EUS and transabdominal ultrasonography (US). Using endoscopic extraction of a bile duct stone as the reference standard for choledocholithiasis, the diagnostic yield of EUS was compared with transabdominal US and ERCP. Features identified during endosonographic imaging of the pancreas were correlated with length of hospitalization.RESULTS:Thirty-six patients were studied. EUS and transabdominal US were concordant in their interpretation of gallbladder findings in 92% of patients. The sensitivity of transabdominal US, EUS, and ERCP for identifying choledocholithiasis was 50%, 91%, and 92% and the accuracy was 83%, 97%, and 89%, respectively. Length of hospital stay was longer in patients with peripancreatic fluid (9.2 vs. 5.7 days, p < 0.1) and shorter in patients with coarse echo texture (2.6 vs. 7.2 days, p < 0.05) demonstrated on EUS.CONCLUSIONS:EUS can reliably identify cholelithiasis and is more sensitive than transabdominal US in detecting choledocholithiasis in patients with biliary pancreatitis. EUS may be used early in the management of patients with acute pancreatitis to select those who would benefit from endoscopic stone extraction. The utility of EUS for predicting pancreatitis severity requires further investigation.