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This paper presents commentaries on how endoluminal antireflux procedures compare to laparoscopic fundoplication; new endoscopic procedures being studied to treat refractory gastroesophageal reflux disease (GERD); the new Stretta; the relationship between obesity and proton pump inhibitor (PPI) resistance; data concerning acid hypersensitivity and sensory receptors (vallinoid, TRPV1) causing refractory GERD; whether microscopic esophagitis is relevant in determining symptoms of non-erosive reflux disease (NERD); how concomitant functional gastrointestinal disorders affect the PPI response in NERD; the evidence that a functional esophagus is associated with inflammatory bowel syndrome (IBS); the role of GABA agonists in the treatment of refractory GERD; the role of biofeedback and antidepressants in refractory GERD; and endoluminal fundoplication using the EsophyX device.

The study of lymph as a biofluid is lacking because of absence of a safe site and technique for lymph acquisition. Injury to the thoracic duct during surgery is known to cause chylothorax. The aim of this interventional study was to puncture the thoracic duct under endoscopic ultrasound (EUS) guidance and observe for complications in a swine model.Three female Yorkshire pigs underwent EUS. The thoracic duct was identified by the previously described technique, punctured, and confirmed with a lymphangiogram. Postoperatively, animals were fed and monitored closely for any complications or signs of abnormal behavior indicating pain and/or disease. The animals were euthanized at 1 week, and necropsy was performed per protocol. Main outcome measurements included complications (chylothorax, mediastinitis, perforation, and hemorrhage) during the post-EUS-guided thoracic duct puncture period.No animals developed any complications during the survival period. The thoracic duct was identified and punctured in all animals. A lymphangiogram was additionally obtained to confirm ductal access. No chylothorax, mediastinitis, hematoma, abscess, or fistula formation was identified in any animal on necropsy.EUS-guided transesophageal thoracic duct puncture is safe as demonstrated by this survival study.

The following on surveillance and reversal of Barrett's esophagus (BE) includes commentaries on criteria for surveillance even when squamous epithelium stains normally with a variety of biomarkers; the long-term follow-up of surgery versus endoscopic ablation of BE; the recommended surveillance intervals in patients without dysplasia; the sampling problems related to anatomic changes following fundoplication; the value of tissue spectroscopy and optical coherence tomography; the cost-effectiveness of biopsy protocols for surveillance; the quality of life of Barrett's patients; and risk stratification and surveillance strategies.

The following on endoscopic treatments of Barrett's esophagus includes commentaries on animal experiments on cryotherapy; indications for cryotherapy, choice of dosimetry, number of sessions, and role in Barrett's esophagus and adenocarcinoma; recent technical developments of RFA technology and long-term effects; the comparative effects of diverse ablation procedures and the rate of recurrence following treatment; and the indications for treatment of dysplasia and the role of radiofrequency ablation.

Methylene blue (MB) selectively stains specialized intestinal metaplasia (SIM) and may assist in surveying a columnar-lined esophagus for Barrett's esophagus associated dysplasia.This is a prospective, randomized crossover study comparing 4-quadrant random biopsies (4QB) versus MB-directed biopsies for the detection of SIM and dysplasia in 48 patients with long segment Barrett's esophagus (LSBE). Patients randomly underwent two endoscopies over a 4-wk time period with either 4QB or MB-directed biopsies as their first or second exam. Our aim was to correlate stain intensity with histology.The sensitivity of MB for SIM and dysplasia was 75.2% and 83.1%, respectively. The yield of 4QB for identifying nondysplasia SIM was 57.6% (523/917) and for dysplasia was 12% (111/917). Dark staining was significantly associated with histologic grade (P0.007). The final diagnosis was correct in 43 (90%) patients using MB and in 45 (94%) using 4QB. The 4QB technique missed dysplasia in 3 of 21 patients while MB biopsies missed dysplasia in 5 of 21 patients. The discordance between the two techniques was not significant (P= 0.727, McNemar's test). The mean number of biopsies taken during 4QB was 18.92 +/- 6.36 and with MB was 9.23 +/- 2.89 (P0.001).MB requires significantly fewer biopsies than 4QB to evaluate for SIM and dysplasia. Dark staining correlates more with HGD than LGD in our experience. While MB is not more accurate than 4QB, MB may help to define areas to target for biopsy during surveillance endoscopy in patients with LSBE.

Background and study aim: Data are limited on the natural history of patients with Barrett’s esophagus with a diagnosis of “indefinite for dysplasia” (IND). The aims of this study were to: (i) determine rates of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma, and compare these with rates for low grade dysplasia (LGD); and (ii) determine the proportion of patients whose histological IND diagnosis changed on follow-up endoscopy. Patients and methods: Demographic, endoscopic, and histologic information of patients with diagnoses of IND and LGD and at least 12 months of follow-up were extracted from the database of a multicenter Barrett’s esophagus study. Rates and times for progression to HGD and esophageal adenocarcinoma and regression to nondysplastic epithelium were calculated. Proportions of diagnoses upgraded to HGD/esophageal adenocarcinoma or downgraded to nondysplastic epithelium at first follow-up endoscopy were evaluated. Results: Amongst 2264 patients, 83 with a diagnosis of IND (mean age 60 years, 95 % men, 95 % white; mean follow-up 5.6 years) and 79 with diagnosis of LGD were identified. In the IND group, annual incidences of esophageal adenocarcinoma and HGD were 0.21 % and 0.64 %, respectively, representing a combined incidence of 0.8 %. Mean time to progression was 4.72 years. Within the IND group 55 % patients showed regression to nondysplastic epithelium at first follow-up endoscopy and the overall regression rate was 80 %. Corresponding rates in LGD patients were similar. Conclusions: Lesions diagnosed as IND and LGD show similar biological behavior and can be treated as a single category with respect to surveillance and follow-up.

Background Diagnosing pancreatic cancer by EUS-FNA is a potentially appealing alternative to percutaneous biopsy. Aim To compare EUS-FNA with CT or US-guided FNA for diagnosing pancreatic cancer. Design Single center, prospective, randomized, cross-over. Setting Duke University Medical Center. Population Eighty-four patients referred with suspicious solid pancreatic mass lesions randomized to CT/US-FNA (n = 43) or EUS-FNA (n = 41). Intervention Patients underwent an imaging procedure/FNA. If cytology was nondiagnostic, cross over to the other modality was offered. Final outcome was determined by clinical follow-up every 6 months for 2 years and/or surgical pathology for patients with negative FNA. Main Outcome Measurements Sensitivity and accuracy of EUS-FNA versus CT/US-FNA for pancreatic cancer. Results There were 16 true positive (TP) by CT/US-FNA and 21 TP by EUS-FNA. Sixteen of the 20 CT/US-FNA negative patients crossed over to EUS-FNA; 12 underwent FNA, 4 had no mass at EUS. Seven of the 12 had positive EUS-FNA. Eight EUS-FNA negative crossed over to CT/US; 4 had no mass at CT/US, 3 remained true negative throughout follow-up, 1 had chronic pancreatitis at surgery. The sensitivity of CT/US-FNA and EUS-FNA for detecting malignancy was 62% and 84%, respectively. A comparison of the accuracy for CT/US-FNA and EUS-FNA was not statistically significant (P = .074, χ 2 ). Limitations Failure to meet target enrollment resulted in an inability to demonstrate a statistically significant difference between the 2 modalities. Conclusions EUS-FNA is numerically (though not quite statistically) superior to CT/US-FNA for the diagnosis of pancreatic malignancy.

Background Numerous ablative modalities have demonstrated varying degrees of efficacy in the eradication of Barrett's esophagus (BE). However, they are associated with either high cost, patient discomfort, complications, tedious application, residual underlying BE, or some combination of the above. The aim of this study was to evaluate the safety and the efficacy of a new cryogenic device by using liquid nitrogen sprayed through an open tipped cryogenic catheter placed through the accessory channel of an upper endoscope. Methods A prospective, single center study was performed on patients with a long-standing history of BE followed in a Barrett's registry. Patients with degrees of dysplasia ranging from none to multifocal high-grade dysplasia were treated. All patients were treated with 40 mg rabeprazole 3 times per day during the treatment period. Elimination of acid reflux was confirmed via 24-hour esophageal pH studies. Cryoablation was applied hemicircumferentially to 4-cm-long segments at monthly intervals, until the entire segment of BE was eliminated. Results Eleven patients were treated. There was reversal of BE in all patients. In 9 of 11 (78%) patients who completed the protocol, there was complete endoscopic and histologic reversal of BE. There was no subsquamous specialized intestinal metaplasia at the 6-month follow-up. No complications occurred. Conclusions Based on preliminary results, low-pressure spray cryoablation of BE under direct endoscopic visualization is safe and easy to perform. Its relative lack of patient discomfort and its simplicity and demonstrated efficacy make it a modality that should be further explored in the ablation of GI mucosal lesions such as BE and perhaps early esophageal cancer.

Background & Aims Recent population-based studies have shown a low risk of esophageal adenocarcinoma (EAC) in patients with nondysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with Barrett's esophagus (BE). Methods We performed a multicenter outcomes study of a large cohort of patients with BE. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE on their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE on 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against development of cancer. Results Of a total of 3515 patients with BE, 1401 patients met the inclusion criteria (93.3% white; 87.5% men; median age, 60 ±17 years). The median follow-up period was 5 ± 3.9 years (7846 patient-years). The annual risk of EAC in groups 1 to 5 was 0.32%, 0.27%, 0.16%, 0.2%, and 0.11%, respectively ( P for trend = .03). After adjusting for age, sex, and length of BE, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood of progression to EAC. Conclusions Persistence of NDBE over several endoscopic examinations identifies patients who are at low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE.

The following on surveillance and reversal of Barrett's esophagus (BE) includes commentaries on criteria for surveillance even when squamous epithelium stains normally with a variety of biomarkers; the long-term follow-up of surgery versus endoscopic ablation of BE; the recommended surveillance intervals in patients without dysplasia; the sampling problems related to anatomic changes following fundoplication; the value of tissue spectroscopy and optical coherence tomography; the cost-effectiveness of biopsy protocols for surveillance; the quality of life of Barrett's patients; and risk stratification and surveillance strategies.

Background Splenic complications of pancreatitis are exceedingly rare, occurring in only 2.2% of cases. Patients typically present in a dramatic fashion and often need an urgent procedure to prevent overwhelming infection or hemorrhage. Historically, the procedures involve surgery (distal pancreatectomy and splenectomy) or percutaneous drainage. Setting Walter Reed Army Medical Center. Patient A patient with acute or chronic pancreatitis presented with pleuritic chest pain and fever up to 105°F (40.6°C). A CT of the abdomen and the pelvis demonstrated a splenic abscess. Intervention Because of the technical inability to perform transpapillary drainage, EUS-guided transgastric drainage resolved the splenic abscess. Conclusions This is the first reported case of a splenic abscess treated definitively with endoscopic therapy. In the face of a worsening clinical picture and reported morbidities up to 79% with surgical and percutaneous drainage procedures, endoscopic therapies should be considered in the management of splenic complications of pancreatitis.

Fulminant (peri)myocarditis is a very infrequent EIM of IBD and oft en presents with sudden-onset severe congestive heart failure (4,5) . Clinical presentation is variable, but in the 2 – 4 weeks before presentation, patients oft en have fl u-like (e.g., fevers, arthalgias and malaise) and gastrointestinal symptoms. Laboratory fi ndings may include leukocytosis, eosinophilia, and elevated levels of ESR, cardiac troponin, and C-reactive protein. Myocarditis in these patients appears not to correlate with disease activity (2,3) . Early recognition of myo(peri)carditis is crucial and needs prompt treatment. Treatment of fulminant disease includes aggressive inotropic support possibly accompanied by the placement of an intra-aortic balloon pump and / or a ventricular assist device. In conclusion, this case report demonstrates the occurrence of lymphocytic myocarditis in a patient with previously undiagnosed Crohn ’ s disease. It cannot be fully excluded that the myocarditis found in this patient was unrelated to his Crohn ’ s disease. However, the reported occurrence of perimyocarditis in Crohn ’ s disease in the absence of another explanation for the myocarditis strongly suggests that the two are related. Awareness of the possibility of this rare and potentially life-threatening EIM of IBD is therefore important.

Objective: Transpyloric small intestine feeding tube placement can be difficult and tedious. Currently accepted techniques are associated with disadvantages and risk. The purpose of this study is to describe the development of a new technique: bedside videoscopic placement using fiberoptics through the tube. Design: Prospective, descriptive case study. Setting: Intensive care unit in a teaching hospital. Patients: Subjects were divided into two groups: a) group 1: eight healthy volunteers (seven male, one female); b) group 2: nine critically ill patients (six male, three female; eight of these patients were intubated). Interventions: Standard 12-Fr (4.0-mm) feeding tubes (n = 19) were placed. Two patients from group 2 had feeding tubes placed on two separate occasions. The feeding tubes were inserted by the oral (n = 8) or nasal (n = 11) route under direct vision, using a 6.7-Fr (2.2-mm) fiberoptic scope through the feeding tube. Measurements and Main Results: We visualized enteric structures clearly through the feeding tube in all subjects and patients. Based on visual landmarks, we advanced the feeding tube through the pylorus and into the duodenum in all individuals. Transpyloric tube placement was confirmed videoscopically (n = 19) and radiographically (n = 18). In three subjects from group 1, the feeding tube entered the first part of the duodenum, while, in the remainder of the subjects, the tube passed into or beyond the second portion of the duodenum. In eight (73%) of 11 attempts on the nine critically ill patients from group 2, the feeding tubes were advanced to the distal duodenum or jejunum. The time required for placement in group 2 ranged from 2 to 43 mins (mean 18 ± 12 [SD]). The feeding tubes remained in place 10 ± 4 days and patients met their estimated caloric needs within 24 hrs. Residual volumes of nutrition in the small bowel were

Predicting High-Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients With Non-Dysplastic Barrett's Esophagus (BE): Results From a Large, Multicenter Cohort Study Srinivas Gaddam, Patrick E. Young, Amy Wang, Ajay Bansal, Neil Gupta, Sachin B. Wani, Mandeep Singh, Vikas Singh, Keng-Yu Chuang, Vikram Boolchand, Hemanth Gavini, Priti Sud, John Kuczynski, April D. Higbee, Amit Rastogi, Sharad C. Mathur, Brooks D. Cash, Gary W. Falk, Richard E. Sampliner, Prateek Sharma

BACKGROUND: The current treatment of benign esophageal strictures often relies on the use of successively larger reusable Savary dilators or disposable balloon catheters. Recently, a new balloon catheter has been designed in which the balloon material has been preprogrammed to reach three successively larger sizes, depending upon the inflation pressure. This allows one balloon to provide dilatation to three different diameters (CRE TM balloon, Microvasive). AIM: To provide a prospective, multi-center, randomized comparison of the CRE TM balloon to a standard balloon dilator with regards to ease of use, complications, and effectiveness in patients with benign esophageal strictures. METHODS: A total of 60 patients were studied. Forty men and 20 women, mean age of 67 (range 24-87), with benign esophageal strictures were randomized based on stricture severity. At the time of entry, the two groups were comparable with regards to age, gender, history of previous dilatation, presence of esophagitis, use of antireflux medication, severity of dysphagia, and stricture severity. The mean lumen diameter prior to dilatation was 12.3 mm in the CRE TM group and the standard group was 12.7 mm. RESULTS: In comparing the effectiveness of the two groups, the dysphagia score within the first day was reduced by 3.5 in the CRE TM group vs. 2.6 in the standard group, p=0.07. Maximum dilatation obtained was 17.3 mm in the CRE TM group versus 17.1 mm in the standard group. Dilatation time was comparable, although the CRE TM balloon deflated more quickly than the standard, 6 versus 28 seconds. A slightly smaller number of CRE TM balloons were used per case than standard dilators, 1.2 versus 1.4. There was a trend in favor of the CRE TM balloon in regards to effectiveness at one month with an improvement in dysphagia score of 2.8 vs. 1.9 (p=0.07). CONCLUSIONS: The CRE TM balloon works at least as well as the standard balloon in dilatation of benign esophageal strictures. The CRE TM balloon allows dilatation to progressively larger diameters using a single catheter. There is a trend that suggests the CRE TM balloon might allow more effective dilatation with an increase in lumen size and reduction of symptoms. These trends should be explored in the context of a larger-scale randomized trial.