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Endoscopic therapy (ET) has been used to treat nonampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in size, but data on long-term outcomes are limited. In addition, management of 11- to 19-mm NAD-NETs is not well defined because of variable estimates of risk of metastasis. We aimed to determine the prevalence and risk factors of metastasis of NAD-NETs ≤19 mm and evaluate the long-term survival of patients after ET as compared with radical surgery. The Surveillance Epidemiology and End Result database was used to identify 1243 patients with T1-2 histologically confirmed NAD-NETs ≤19 mm in size. Cancer-specific survival (CSS) and overall survival (OS) were calculated. Overall, 4.8% of cases had metastasis at the time of diagnosis, with lower prevalence in ≤10-mm lesions (3.1%) versus 11- to 19-mm lesions (11.7%, P <.001). The risk factors for metastases included invasion to the muscularis propria (odds ratio, 25.95; 95% confidence interval, 9.01-76.70), age <65 years (odds ratio, 1.93), submucosal involvement (odds ratio, 3.1), and 11 to 19 mm in size (vs ≤10 mm). In patients with well- to moderately differentiated T1-2N0M0 NAD-NETs ≤19 mm confined to the mucosa/submucosa who underwent ET or surgery, the 5-year CSS was 100%. The 5-year OS was similar between the ≤10-mm and 11- to 19-mm groups (86.6% vs 91.0%, P =.31) and the ET and surgery groups (87.4% vs 87.5%, P =.823). In NAD-NETs, invasion to the muscularis propria is the strongest risk factor for metastasis. In the absence of metastasis, in lesions with well/moderate differentiation and without muscle invasion, ET is adequate for NAD-NETs ≤10 mm and is a viable option for 11- to 19-mm lesions. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to investigate whether inhibition of Sonic Hedgehog (SHH) pathway would prevent progression of Barrett’s Esophagus (BE) to esophageal adenocarcinoma. Background: The hedgehog signaling pathway is a leading candidate as a molecular mediator of BE and esophageal adenocarcinoma (EAC). Repurposed use of existing off-patent, safe and tolerable drugs that can inhibit hedgehog, such as itraconazole, could prevent progression of BE to EAC. Methods: The efficacy of itraconazole was investigated using a surgical rat reflux model of Barrett’s Metaplasia (BM). Weekly intraperitoneal injections of saline (control group) or itraconazole (treatment group; 200 mg/kg) were started at 24 weeks postsurgery. Esophageal tissue was harvested at 40 weeks. The role of the Hh pathway was also evaluated clinically. Esophageal tissue was harvested after 40 weeks for pathological examination and evaluation of the SHH pathway by immunohistochemistry. Results: BM was present in control animals 29 of 31 (93%) versus itraconazole 22 of 24 (91%). EAC was significantly lower in itraconazole 2 of 24 (8%) versus control 10 of 31 (32%), respectively (P = 0.033). Esophageal SHH levels were lower in itraconazole vs control (P = 0.12). In esophageal tissue from humans with recurrent or persistent dysplastic BE within 24 months of ablative treatment, strong SHH and Indian Hedgehog expression occurred in distal BE versus proximal squamous epithelium, odds ratio = 6.1 (95% confidence interval: 1.6, 23.4) and odds ratio = 6.4 (95% confidence interval: 1.2, 32.8), respectively. Conclusion: Itraconazole significantly decreases EAC development and SHH expression in a preclinical animal model of BM. In humans, BE tissue expresses higher SHH, Indian Hedgehog, and bone morphogenic protein levels than normal squamous esophageal epithelium [ABSTRACT FROM AUTHOR]

Background & Aims Esophageal adenocarcinoma (EAC) is resistant to standard chemoradiation treatments, and few targeted therapies are available. We used large-scale tissue profiling and pharmacogenetic analyses to identify deregulated signaling pathways in EAC tissues that might be targeted to slow tumor growth or progression. Methods We collected 397 biopsy specimens from patients with EAC and nonmalignant Barrett's esophagus (BE), with or without dysplasia. We performed RNA-sequencing analyses and used systems biology approaches to identify pathways that are differentially activated in EAC vs nonmalignant dysplastic tissues; pathway activities were confirmed with immunohistochemistry and quantitative real-time polymerase chain reaction analyses of signaling components in patient tissue samples. Human EAC (FLO-1 and EsoAd1), dysplastic BE (CP-B, CP-C, CP-D), and nondysplastic BE (CP-A) cells were incubated with pharmacologic inhibitors or transfected with small interfering RNAs. We measured effects on proliferation, colony formation, migration, and/or growth of xenograft tumors in nude mice. Results Comparisons of EAC vs nondysplastic BE tissues showed hyperactivation of transforming growth factor-β (TGFB) and/or Jun N-terminal kinase (JNK) signaling pathways in more than 80% of EAC samples. Immunohistochemical analyses showed increased nuclear localization of phosphorylated JUN and SMAD proteins in EAC tumor tissues compared with nonmalignant tissues. Genes regulated by the TGFB and JNK pathway were overexpressed specifically in EAC and dysplastic BE. Pharmacologic inhibition or knockdown of TGFB or JNK signaling components in EAC cells (FLO-1 or EsoAd1) significantly reduced cell proliferation, colony formation, cell migration, and/or growth of xenograft tumors in mice in a SMAD4-independent manner. Inhibition of the TGFB pathway in BE cell lines reduced the proliferation of dysplastic, but not nondysplastic, cells. Conclusions In a transcriptome analysis of EAC and nondysplastic BE tissues, we found the TGFB and JNK signaling pathways to be hyperactivated in EACs and the genes regulated by these pathways to be overexpressed in EAC and dysplastic BE. Inhibiting these pathways in EAC cells reduces their proliferation, migration, and formation of xenograft tumors. Strategies to block the TGFB and JNK signaling pathways might be developed for treatment of EAC. Graphical abstract [ABSTRACT FROM AUTHOR]

Background & Aims African American and European American individuals have a similar prevalence of gastroesophageal reflux disease (GERD), yet esophageal adenocarcinoma (EAC) disproportionately affects European American individuals. We investigated whether the esophageal squamous mucosa of African American individuals has features that protect against GERD-induced damage, compared with European American individuals. Methods We performed transcriptional profile analysis of esophageal squamous mucosa tissues from 20 African American and 20 European American individuals (24 with no disease and 16 with Barrett's esophagus and/or EAC). We confirmed our findings in a cohort of 56 patients and analyzed DNA samples from patients to identify associated variants. Observations were validated using matched genomic sequence and expression data from lymphoblasts from the 1000 Genomes Project. A panel of esophageal samples from African American and European American subjects was used to confirm allele-related differences in protein levels. The esophageal squamous-derived cell line Het-1A and a rat esophagogastroduodenal anastomosis model for reflux-generated esophageal damage were used to investigate the effects of the DNA-damaging agent cumene-hydroperoxide (cum-OOH) and a chemopreventive cranberry proanthocyanidin (C-PAC) extract, respectively, on levels of protein and messenger RNA (mRNA). Results We found significantly higher levels of glutathione S-transferase theta 2 (GSTT2) mRNA in squamous mucosa from African American compared with European American individuals and associated these with variants within the GSTT2 locus in African American individuals. We confirmed that 2 previously identified genomic variants at the GSTT2 locus, a 37-kb deletion and a 17-bp promoter duplication, reduce expression of GSTT2 in tissues from European American individuals. The nonduplicated 17-bp promoter was more common in tissue samples from populations of African descendant. GSTT2 protected Het-1A esophageal squamous cells from cum-OOH–induced DNA damage. Addition of C-PAC increased GSTT2 expression in Het-1A cells incubated with cum-OOH and in rats with reflux-induced esophageal damage. C-PAC also reduced levels of DNA damage in reflux-exposed rat esophagi, as observed by reduced levels of phospho-H2A histone family member X. Conclusions We found GSTT2 to protect esophageal squamous cells against DNA damage from genotoxic stress and that GSTT2 expression can be induced by C-PAC. Increased levels of GSTT2 in esophageal tissues of African American individuals might protect them from GERD-induced damage and contribute to the low incidence of EAC in this population. Graphical abstract [ABSTRACT FROM AUTHOR]

Background EUS-guided gastroenterostomy (EUS-GE) is a developing modality in the management of gastric outlet obstruction (GOO) with several technical approaches, including the direct and balloon-assisted techniques. The aim of this study was to compare the direct with the balloon-assisted modality while further defining the role of EUS-GE in GOO. Methods This multicenter, retrospective study involved consecutive patients who underwent EUS-GE with the direct or balloon-assisted technique for GOO (January 2014 to October 2016). The primary outcome was technical success. Secondary outcomes were success (ability to tolerate at least a full fluid diet), procedure time, and rate/severity of adverse events (AEs). Results A total of 74 patients (44.6% women; mean age 63.0 ± 11.7 years) underwent EUS-GE for GOO (direct gastroenterostomy, n = 52; balloon-assisted gastroenterostomy, n = 22). GOO was of malignant and benign etiology in 66.2% and 33.8% of patients, respectively. Technical success was achieved in 94.2% of the direct and 90.9% of the balloon-assisted approach ( P = .63). Mean procedure time was shorter with the direct technique (35.7 ± 32.1 minutes vs 89.9 ± 33.3 minutes, P < .001). The clinical success rate was 92.3% for the direct technique and 90.9% for the balloon-assisted modality ( P = 1.00), with a mean time to oral intake of 1.32 ± 2.76 days. The AE rate was 6.8% with only 1 severe AE noted. Rate of AEs, postprocedure length of stay, need for reintervention, and survival were similar between the 2 groups. Conclusions EUS-GE is effective and safe in the management of GOO. The direct technique may be the preferred method given its shorter procedure time when compared with the balloon-assisted approach. Prospective trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Because the esophagus is easily accessible with endoscopy, early diagnosis and curative treatment of esophageal cancer is possible. However, diagnosis is often delayed because symptoms are not specific during early stages of tumor development. The onset of dysphagia is associated with advanced disease, which has a survival at 5 years lower than 15%. Population screening by endoscopy is not cost-effective, but a number of alternative imaging and cell analysis technologies are under investigation. The ideal screening test should be inexpensive, well tolerated, and applicable to primary care. Over the past 10 years, significant progress has been made in endoscopic diagnosis and treatment of dysplasia (squamous and Barrett’s), and early esophageal cancer using resection and ablation technologies supported by evidence from randomized controlled trials. We review the state-of-the-art technologies for early diagnosis and minimally invasive treatment, which together could reduce the burden of disease. [ABSTRACT FROM AUTHOR]

Background and Aims Medical treatment options for gastroparesis are limited. Data from studies of botulinum toxin and surgical pyloroplasty suggest that disruption of the pylorus can result in symptomatic improvement in some patients with refractory gastroparetic symptoms. The aim of this study was to determine the clinical response to transpyloric stent (TPS) placement in patients with gastroparetic symptoms refractory to standard therapy. Methods Patients with gastroparesis refractory to medical treatment were referred for TPS placement for salvage therapy. Self-reported symptom improvement, stent migration rate, and pre– and post–stent gastric-emptying study results were collected. Results A total of 30 patients with refractory gastroparesis underwent 48 TPS procedures. Of these, 25 of 48 (52.1%) were performed in patients admitted to the hospital with intractable gastroparetic symptoms. Successful stent placement in the desired location across the pylorus (technical success) was achieved during 47 procedures (98%). Most (n = 24) stents were anchored to the gastric wall by using endoscopic suturing with a mean number of sutures of 2 (range 1-3) per procedure. Clinical response was observed in 75% of patients, and all inpatients were successfully discharged. Clinical success in patients with the predominant symptoms of nausea and vomiting was higher than in those patients with a predominant symptom of pain (79% vs 21%, P = .12). A repeat gastric-emptying study was performed in 16 patients, and the mean 4-hour gastric emptying normalized in 6 patients and significantly improved in 5 patients. Stent migration was least common (48%) when stents were sutured. Conclusion TPS placement is a feasible novel endoscopic treatment modality for gastroparesis and improves both symptoms and gastric emptying in patients who are refractory to medical treatment, especially those with nausea and vomiting. TPS placement may be considered as salvage therapy for inpatients with intractable symptoms or potentially as a method to select patients who may respond to more permanent therapies directed at the pylorus. [ABSTRACT FROM AUTHOR]

Background Studies comparing linear and radial EUS for the detection of pancreatic lesions in an asymptomatic population with increased risk for pancreatic cancer are lacking. Objectives To compare pancreatic lesion detection rates between radial and linear EUS and to determine the incremental diagnostic yield of a second EUS examination. Design Randomized controlled tandem study. Setting Five academic centers in the United States. Patients Asymptomatic high-risk individuals (HRIs) for pancreatic cancer undergoing screening EUS. Interventions Linear and radial EUS performed in randomized order. Main Outcome Measurements Pancreatic lesion detection rate by type of EUS, miss rate of 1 EUS examination, and incremental diagnostic yield of a second EUS examination (second-pass effect). Results Two hundred seventy-eight HRIs were enrolled, mean age 56 years (43.2%), and 90% were familial pancreatic cancer relatives. Two hundred twenty-four HRIs underwent tandem radial and linear EUS. When we used per-patient analysis, the overall prevalence of any pancreatic lesion was 45%. Overall, 16 of 224 HRIs (7.1%) had lesions missed during the initial EUS that were detected by the second EUS examination. The per-patient lesion miss rate was significantly greater for radial followed by linear EUS (9.8%) than for linear followed by radial EUS (4.5%) ( P = .03). When we used per-lesion analysis, 73 of 109 lesions (67%) were detected by radial EUS and 99 of 120 lesions (82%) were detected by linear EUS ( P < .001) during the first examination. The overall miss rate for a pancreatic lesion after 1 EUS examination was 47 of 229 (25%). The miss rate was significantly lower for linear EUS compared with radial EUS (17.5% vs 33.0%, P = .007). Limitations Most detected pancreatic lesions were not confirmed by pathology. Conclusion Linear EUS detects more pancreatic lesions than radial EUS. There was a “second-pass effect” with additional lesions detected with a second EUS examination. This effect was significantly greater when linear EUS was used after an initial radial EUS examination. [ABSTRACT FROM AUTHOR]

Background: Endoscopic drainage (ED) and percutaneous drainage (PD) have largely replaced surgical drainage as the initial approach for symptomatic pseudocysts. However, there are few studies comparing ED and PD. Objective: To compare the outcomes of ED and PD for symptomatic pseudocysts. Design: Retrospective cohort study. Setting: Academic center. Patients: Adult patients with symptomatic pseudocysts within ≤1 cm of the gastric or duodenal wall who underwent ED or PD between 1993 and 2011. Patients with walled-off pancreatic necrosis were excluded. Intervention: ED or PD. Main Outcome Measurements: Rates of technical success, procedural adverse events, clinical success, reinterventions, and failure. Other outcomes included the length of hospital stay and number of follow-up abdominal imaging studies. Results: There were 81 patients, 41 who underwent ED and 40 who underwent PD, with no differences in age, sex, and comorbidity between the 2 groups. There were no differences in the rates of technical success (90.2% vs 97.5%; P = .36), adverse events (14.6% vs 15%; P = .96), and clinical success (70.7% vs 72.5%; P = .86) between ED and PD, respectively. Patients who underwent PD had higher rates of reintervention (42.5% vs 9.8%; P = .001), longer length of hospital stay (14.8 ± 14.4 vs 6.5 ± 6.7 days; P = .001), and median number [quartiles] of follow-up abdominal imaging studies (6 [3.25, 10] vs 4 [2.5, 6]; P = .02) compared with patients who underwent ED. Limitations: Single center, retrospective study. Conclusion: ED and PD have similar clinical success rates for symptomatic pseudocysts. However, PD is associated with significantly higher rates of reintervention, longer length of hospital stay, and increased number of follow-up abdominal imaging studies. [Copyright &y& Elsevier]

Background & Aims: Acute ascending cholangitis usually is treated with antibiotics, and biliary drainage is treated by endoscopic retrograde cholangiopancreatography (ERCP). We investigated the effects of the timing of ERCP on outcomes of patients with acute cholangitis factors that predict prolonged hospital stays, increased costs of hospitalization, and composite clinical outcomes (death, persistent organ failure, and admission to the intensive care unit). Methods: We performed a retrospective analysis of data from 90 patients (mean age, 60 y; 48% female) admitted to Johns Hopkins Hospital from January 1994 to June 2010 who were diagnosed with acute cholangitis and underwent ERCP. A delayed ERCP was defined as one performed more than 72 hours after admission. Electronic and paper medical records were reviewed, and relevant data were abstracted. Results: ERCP was performed successfully in 92% of the patients, at a mean time period of 38 hours after admission (14% of ERCPs were delayed). Factors that were associated independently with prolonged length of hospital stay (top 10%) included unsuccessful ERCP (odds ratio [OR], 52.5; P = .002) and delayed ERCP (OR, 19.8; P = .008). Factors associated with increased hospitalization cost (top 10%) included unsuccessful ERCP (OR, 33.8; P = .004) and delayed ERCP (OR, 11.3; P = .03). Factors associated with composite clinical outcome included age (OR, 1.1; P = .01), total level of bilirubin (OR, 1.36; P = .002), and delayed ERCP (OR, 7.8; P = .04). Conclusions: Delayed and failed ERCP are associated with prolonged hospital stays and increased costs of hospitalization. Delayed ERCP is associated with composite clinical outcome (death, persistent organ failure, and/or intensive care unit stay). Older age and higher levels of bilirubin also are associated with patients'' composite end point. [Copyright &y& Elsevier]

The article presents a study to determine whether cancers develop at an earlier age in multiplex Familial Barrett's Esophagus (FBE) kindreds, defined by three or more members affected by Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC). Age of cancer diagnosis and other risk factors were compared in nonfamilial, duplex and multiplex FBE kindreds from eight tertiary care hospitals. Multiplex FBE kindreds are found to develop EAC at an earlier age compared to nonfamilial EAC cases.

Background: Precise localization of small pancreatic tumors during laparoscopic distal pancreatectomy (LDP) can be difficult because of decreased tactile ability of laparoscopy and the homogeneous appearance of the pancreas and surrounding retroperitoneal fat. Precise localization of the lesion is critical to achieving adequate margins of resection and preserving healthy pancreatic tissue. EUS-guided fine-needle tattooing (EUS-FNT) of a pancreatic lesion before LDP has been described in single case reports, but no large series have reported its effectiveness in patients undergoing LDP. Objective: To assess the feasibility, safety, and efficacy of EUS-FNT in consecutive patients undergoing LDP. Design: Retrospective cohort study. Setting: Tertiary-care referral hospital. Patients: This study involved 30 consecutive patients who underwent LDP from 2008 to 2010. Thirteen had EUS-FNT followed by LDP, and 17 had LDP alone. Interventions: LDP or EUS-FNT with a sterile carbon-particle tattoo followed by LDP. Main Outcome Measurements: The following features were examined: the technical success and complication rates of EUS-FNT, visibility of the tattoo at the time of laparoscopy, durability of the tattoo, and pathologic absence of tumor at the resection margin. Results: The final pathology of pancreatic lesions of patients who had EUS-FNT was similar to those who had LDP alone. The median resected tumor size was significantly larger for the LDP-alone patients (median 4.0 cm vs 1.3 cm; P = .03). Thirty-one percent (4/13) of lesions in the EUS-FNT group were not visualized by prior preoperative pancreatic protocol CT. EUS-FNT was feasible in all 13 patients at laparoscopy, with R0 resection and negative final pathology margins in all cases. The tattoo was visible in all 13 EUS-FNT cases, with mean time from EUS-FNT to surgery of 20.3 days (range, 3-69 days). There were no significant complications associated with EUS-FNT. Limitations: Small, retrospective, single-center study. Conclusions: Preoperative EUS-FNT of lesions was technically feasible and safe, and it assisted in the localization of lesions in patients before LDP. The carbon particle tattoo was durable and visible in all cases. [Copyright &y& Elsevier]

Background: Single-balloon enteroscopy (SBE) and spiral enteroscopy (SE) are recently described device-assisted techniques in endoluminal evaluation of the small bowel. No studies comparing SBE and SE in patients with suspected small-bowel disorders have previously been reported. Objective: The aims of this study were to compare SBE and SE in terms of diagnostic yield, procedure time, depth of maximal insertion, and complications. Design: Retrospective cohort study. Setting: Tertiary-care referral center. Patients: A retrospective analysis was performed on all patients at our institution undergoing anterograde SBE or SE between 2007 and 2009. Patients with altered anatomy or prior small-bowel surgery were excluded. Intervention: Deep enteroscopy. Main Outcome Measurement: Diagnostic yield. Results: During the study period, 92 patients underwent 105 procedures (52 SBE, 53 SE). The most common indication for small-bowel endoscopy was obscure GI bleeding (n = 42). The diagnostic yield was not statistically different between SBE and SE (59.6% and 43.4%, respectively, P = .12). The overall diagnostic yield in patients with obscure GI bleeding was 67%. There was no significant difference between mean SBE and SE procedure times (53 minutes [range 15-99 minutes] vs 47 minutes [range 20-125 minutes], respectively; P = .2). The mean depth of maximal insertion beyond the ligament of Treitz for SE was significantly higher than that for SBE (301 cm [range 175-400 cm] vs 222 cm [range 110-400 cm], respectively; P < .001). Perforation occurred in one SBE procedure. Limitations: Retrospective design and nonstandardized gas insufflation. Conclusion: This is the first report comparing SE and SBE. Although SE yielded greater depth of maximal insertion than SBE, both techniques had similar diagnostic yields and procedure times. In addition, both techniques were safe and were particularly useful in patients with obscure GI bleeding. [Copyright &y& Elsevier]

Background: Precise and expedient localization of small pancreatic tumors during laparoscopic distal pancreatectomy can be difficult owing to the decreased tactile ability of laparoscopy and the homogenous appearance of the surrounding retroperitoneal fat. Precise localization of the lesion is critical to achieving adequate margins of resection while preserving as much healthy pancreas as possible. The objective in this study was to determine the effect of endoscopic tattooing of the distal pancreas on operative time. Methods: We reviewed retrospectively 36 consecutive patients who had a laparoscopic distal pancreatectomy at our institution over a 4-year period (2006–2009). Ten patients underwent preoperative tattooing via an endoscopic transgastric technique using ultrasound guidance. The tattoo was performed using 2–4 cc of sterile purified carbon particles injected immediately proximal and anterior to the pancreatic lesion. Operative times were compared according to the presence of a tattoo. Results: The endoscopically placed tattoo was easily visible upon entering the lesser sac in all 10 patients at laparoscopy. Patients with a tattoo had a shorter operative time (median, 128.5 minutes; range, 53–180) compared with patients without a tattoo (median, 180 minutes; range, 120–240; P < .01). None of the tattoo group required repeat surgery, whereas 1 patient who was not tattooed required re-resection for a lesion missed in the initial specimen. There were no complications associated with the endoscopic ultrasound-guided tattoo. Conclusion: Endoscopic ultrasound-guided tattooing of pancreas lesions before a laparoscopic distal pancreatectomy is safe and is associated with decreased operative time compared with nontattooed patients. This technique can allow for quick and precise localization of the lesion, allowing for optimal preservation of pancreas parenchyma and demarcating an appropriate line of resection. [Copyright &y& Elsevier]

Confocal laser endomicroscopy (CLE) is a novel technique that allows in vivo microscopic imaging of the gastrointestinal mucosa. CLE has been used to study many gastrointestinal disorders, including Barrett''s esophagus (BE), gastrointestinal neoplasia, and inflammatory bowel disease. There are two endomicroscopy systems currently used, an endoscope-based system (eCLE) and a probe-based system (pCLE), each with different strengths and weaknesess. This article discusses the current technique for performing endomicroscopy as it is applied for evaluation of patients with BE and compares the two available systems. Learning endomicroscopy requires technical mastery to obtain stable images and cognitive mastery of endomicroscopy image interpretation. [Copyright &y& Elsevier]

Background & Aims: Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett''s esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. Methods: Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n = 138) or 20 mg omeprazole twice daily (n = 70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. Results: Histologic assessment of 33,658 biopsies showed no significant difference (P > .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. Conclusions: No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma. [Copyright &y& Elsevier]

Background: Endosonography (EUS) is widely used for locoregional staging of malignant GI tumors. Delineation of a tumor''s margins with a long-lasting fluoroscopically visible material will facilitate subsequent surgical and radiation therapy. Objective: To assess the feasibility of EUS-guided submucosal implantation of a radiopaque marker in a porcine model. Setting: Survival experiments on four 50-kg pigs. Methods: A linear array echoendoscope was introduced into the esophagus and advanced to the stomach. With a 19-gauge FNA needle, a submucosal bleb was created by injecting 3 mL of normal saline solution into the gastric and esophageal wall followed by injection of 1 mL of tantalum suspension under fluoroscopic observation. Fluoroscopy was repeated after 1, 2, and 4 weeks followed by euthanasia and necropsy. Main Outcome Measurements: Long-term depositions of the marker in the injection sites. Results: Submucosal injections of tantalum were easily performed through the 19-gauge FNA needle, resulting in good fluoroscopic opacification of injected material. Follow-up fluoroscopy in 1, 2, and 4 weeks demonstrated stable deposition of the tantalum at the sites of injection. There were no complications during and after the tantalum implantation. Histologic examination of the injection sites demonstrated submucosal tantalum depositions without signs of infection, inflammation, tissue damage, or necrosis. Limitations: Animal experiments with 4 weeks'' follow-up. Conclusions: EUS-guided implantation of tantalum as a radiopaque marker into the submucosal layer of the GI tract in a porcine model is technically feasible and safe. Long-lasting fluoroscopically visible tantalum markings could facilitate subsequent surgical and radiation therapy. [Copyright &y& Elsevier]

Background: EUS is the preferred modality for local staging of esophageal cancer. The presence of a long-lasting fluoroscopically visible marker of malignant lymph nodes would facilitate subsequent radiation and surgical therapy. Objective: To assess the feasibility of EUS-guided implantation of a radiopaque marker (tantalum) into mediastinal and celiac lymph nodes in a porcine model. Setting: Survival experiments on six 50-kg pigs. Design and Interventions: A linear-array echoendoscope was advanced into the esophagus and the stomach. Mediastinal and celiac lymph nodes were identified and injected with 1 mL tantalum suspension by using 19- and 22-gauge FNA needles under fluoroscopy. The pigs were recovered. Fluoroscopy was repeated after 1, 2, and 4 weeks, then a postmortem examination was performed. Main Outcome Measurements: Long-term opacification of lymph nodes. Results: It was not possible to inject tantalum through the 22-gauge FNA needle because of its rapid precipitation inside the needle, which caused needle occlusion. Intranodal injection with the 19-gauge FNA needle was easily accomplished and resulted in excellent fluoroscopic opacification of injected lymph nodes. Repeat fluoroscopy at 1, 2, and 4 weeks demonstrated stable tantalum deposition at the injection site. There were no complications. Histologic examination of harvested lymph nodes revealed intranodal tantalum depositions without signs of infection, inflammation, tissue damage, or necrosis. Conclusions: EUS-guided implantation of tantalum as a radiopaque marker into mediastinal and celiac lymph nodes in a porcine model is technically feasible, safe, and results in long-lasting intranodal depositions to facilitate subsequent surgical and radiotherapeutic interventions. [Copyright &y& Elsevier]

Background: Barrett''s esophagus (BE) may lead to high-grade dysplasia (HGD) and adenocarcinoma. The objective was to examine the impact of treating patients with BE and with HGD by using porfimer sodium (POR) and photodynamic therapy (PDT) for ablating HGD and reducing the incidence of esophageal adenocarcinoma. Methods: The design was a multicenter, partially blinded (pathology), randomized clinical trial conducted in patients with BE who have HGD. There were 30 contributing centers. A total of 485 patients were screened, with 208 in the intent-to-treat population and 202 in the safety population. Patients were randomized on a 2:1 basis to compare PDT with POR plus omeprazole (PORPDT) with omeprazole only (OM). The main outcome measurement was complete HGD ablation occurring at any time during the study period. Results: There was a significant difference (p < 0.0001) in favor of PORPDT (106/138 [77%]) compared with OM (27/70 [39%]) in complete ablation of HGD at any time during the study period. The occurrence of adenocarcinoma in the PORPDT group (13%) (n=18) was significantly lower (p < 0.006) compared with the OM group (20%) (n=20). The safety profile showed 94% of patients in the PORPDT group and 13% of patients in the OM group had treatment-related adverse effects. The limitations of the study were that PDT therapy may have had to be applied more than once and that patients spent more time in treatment. The patients and the physicians were not blinded to the treatment. Conclusions: PORPDT in conjunction with omeprazole is an effective therapy for ablating HGD in patients with BE and in reducing the incidence of esophageal adenocarcinoma. [Copyright &y& Elsevier]