Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer.

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's dysplasia: results of the National Cryospray Registry.

Retrospective series have shown the efficacy of endoscopic spray cryotherapy in eradicating high-grade dysplasia (HGD) in Barrett's esophagus (BE); however, prospective data are lacking, and efficacy for low-grade dysplasia (LGD) is unclear. The aim of this study was to assess the efficacy and safety of spray cryotherapy in patients with LGD or HGD. A multicenter, prospective open-label registry enrolled patients with dysplastic BE. Spray cryotherapy was performed every 2-3 months until there was no endoscopic evidence of BE and no histological evidence of dysplasia, followed by surveillance endoscopies up to 2 years. Primary outcome measures were complete eradication of dysplasia (CE-D) and complete eradication of all intestinal metaplasia (CE-IM). Ninety-six subjects with Barrett's dysplasia (67% HGD; 65% long-segment BE; mean length 4.5 cm) underwent 321 treatments (mean 3.3 per subject). Mean age was 67 years, 83% were male. Eighty patients (83%) completed treatment with follow-up endoscopy (mean duration 21 months). In patients with LGD, rate of CE-D was 91% (21/23) and rate of CE-IM was 61% (14/23). In HGD, CE-D rate was 81% (46/57) and CE-IM was 65% (37/57). In patients with short-segment BE (SSBE) with any dysplasia, CE-D was achieved in 97% (30/31) and CE-IM in 77% (24/31). There were no esophageal perforations or related deaths. One subject developed a stricture, which did not require dilation. One patient was hospitalized for bleeding in the setting of non-steroidal anti-inflammatory drug use. In the largest prospective cohort to date, data suggest endoscopic spray cryotherapy is a safe and effective modality for eradication of BE with LGD or HGD, particularly with SSBE.

The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial.

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to underlying insulin resistance. The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH. This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH. Patients were randomized to either group A or B. Group A received placebo, dietary counseling, recommendations for weight loss and exercise four times per week. Group B received long-acting metformin 500 mg daily (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight loss and exercise four times per week. Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data. Twenty-three subjects were screened and 19 were randomized to either group A (n »10) or group B (n» 9). Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study. Body mass index improved in both groups decreasing by 1.7 kg/m(2) in group A and 0.9 kg/m(2) in group B (not significant, control versus treatment). Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B (not significant, control versus treatment). No significant difference in histopathology was seen between groups on follow-up liver biopsy. Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA-IR scores, serum aminotransferases and liver histology.

Evaluation of unexplained acute and acute recurrent pancreatitis using endoscopic retrograde cholangiopancreatography, sphincter of Oddi manometry and endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: Unexplained pancreatitis represents a diagnostic challenge. The aim of this study was to determine the diagnostic utility of endoscopic retrograde cholangiopancreatography (ERCP) with sphincter of Oddi manometry (SOM), bile analysis, and endoscopic ultrasound (EUS) in evaluating such patients. PATIENTS AND METHODS: Of 162 patients referred for evaluation of pancreatitis, 72 with a known cause were excluded. The remainder ( n=90) was classified as having prior acute ( n=24) or recurrent acute pancreatitis ( n=66). Bile sampling and SOM were performed at the time of ERCP. EUS was used to assess for tumors and for chronic pancreatitis. Clinical outcomes were evaluated by questionnaire. RESULTS: ERCP was successful in 88/89 patients (99 %). Manometry was successful in 63/67 patients (94 %), and 56 patients underwent EUS. Findings were categorized into five distinct etiologies: sphincter of Oddi dysfunction (SOD) ( n=28; 31 %), pancreas divisum ( n=18; 20 %), biliary ( n=18; 20 %), idiopathic ( n=18; 20 %) and tumor-related ( n=8; 9 %). Features of moderate or severe chronic pancreatitis by EUS and ERCP criteria were found in 18 patients (21 %); an additional nine patients had chronic pancreatitis by EUS criteria alone. EUS identified all the tumors. The condition was improved in 96 % of all patients undergoing endoscopic therapy. CONCLUSION: An etiology was identified in the majority of patients with unexplained pancreatitis. SOD represented the most common finding. Moderate to severe chronic pancreatitis was found in over one-fifth of these patients. Bile analysis, SOM, and EUS are useful tools in the evaluation of unexplained acute pancreatitis.

EUS and fine-needle aspiration in the evaluation of mediastinal masses superior to the aortic arch.

BACKGROUND: Mediastinal lesions require a tissue diagnosis. This cannot be obtained with CT-guided biopsy or bronchoscopy in many patients. Co-morbid diseases increase the risk of mediastinoscopy in some of these patients. EUS with fine-needle aspiration (FNA) is frequently used to obtain tissue from the mediastinum, but there have been no case series published of FNA of lesions superior to the aortic arch. METHODS: This is the report of a case series of 4 patients with mediastinal masses superior to the aortic arch. EUS with a linear array echoendoscope and FNA were performed to evaluate each lesion. OBSERVATIONS: All 4 patients underwent the procedure without complication, and cytologic material obtained in 3 was diagnostic. One patient had a nondiagnostic aspirate and underwent mediastinoscopy. CONCLUSIONS: EUS with FNA is a safe and effective method for tissue diagnosis of mediastinal lesions. Heretofore, mediastinoscopy or transtracheal biopsy was required for diagnosis in patients with lesions superior to the aortic arch. However, for such lesions EUS with FNA appears to be an excellent alternative for establishing a diagnosis.

Eradication of Helicobacter pylori normalizes elevated mucosal levels of epidermal growth factor and its receptor.

OBJECTIVE: Helicobacter pylori (H. pylori) infection has been linked to gastric cancer. The factors that promote carcinogenesis remain unknown. Epidermal growth factor (EGF) has been shown to be a potent epithelial mitogen and oncoprotein when sustained over expression occurs. Our aim was to compare gastric mucosal levels of EGF and its receptor (EGFR) among controls, H. pylori infected subjects, and subjects following H. pylori eradication using quantitative flow cytometric analysis. METHODS: Patients referred for evaluation of dyspepsia underwent EGD and six antral biopsies were performed (two each for rapid urease testing (RUT), histopathology, and flow cytometry). Controls were those found to be H. pylori negative while subjects had confirmed infection. The study patients were treated, then had repeat EGD with biopsies. RESULTS: There were 17 controls and 28 cases. Mean EGF and EGFR values were 2.69 and 2.46 for controls and 4.67 and 4.64 for subjects. Subjects' mean EGF was 73% higher (p = .035) and EGFR was 88% higher (p = 0.029) than controls. After treatment, the subjects' mean values declined 55% (p = 0.0001) for EGF and 40% (p = 0.002) for EGFR. Three subjects had persistent infection and showed no change in their EGF/EGFR levels. No difference was found among factor levels with respect to endoscopic findings. CONCLUSIONS: Both EGF and EGFR from gastric antral biopsies are increased nearly 2-fold in infection with H. pylori. Infection eradication reduces levels of both factors to those of controls. One major pathogenic mechanism for gastric mucosal hyperproliferation and possibly carcinogenesis related to H. pylori may be the over expression of EGF and increased receptor density of EGFR on gastric mucosal cells.

Upper gastrointestinal tract bleeding.

Upper GI bleeding is a serious and common emergency. Most upper GI bleeding will stop spontaneously but determining which patients will continue to bleed or rebleed is very difficult in the ED. Resuscitation and stabilization are the primary goals of the emergency physician. Hemorrhage control with pharmacotherapy or balloon tamponade may be necessary until urgent or emergent consultation with a gastroenterologist or surgeon is obtained. Early detection and treatment of H. pylori and the development of safer NSAIDs should alter the future of upper GI bleeding dramatically.