Faculty Bibliography

Purpose: Barrett's esophagus (BE) with high grade dysplasia (HGD) has the potential to progress to esophageal cancer if left untreated. Endoscopic ablation is an acceptable form of therapy oft en done with radiofrequency ablation (RFA). There is a subset of patients who continue to have persistent disease despite therapy and may benefit from low-pressure liquid nitrogen cryotherapy. Methods: A retrospective cohort of patients initially treated with RFA, but continued to have BE- HGD were analyzed in this study. Variables included patient demographics, initial BE length, total RFA sessions, degree of persistent BE after RFA, and results after cryotherapy. Results: A total of 12 patients were treated with RFA followed by cryotherapy for BE-HGD. The mean age was 69 years (range 53-84 years) and all were males. The mean BE segment was 5.6 cm (range 1-13 cm). In 25% (n=3) of BE-HGD patients endoscopic mucosal resection was done prior to ablation. The mean number of RFA sessions were 2.1 (range 1-4 treatments). In 11/12 (92%) patients BE-HGD persisted after RFA therapy based on biopsies. One patient was downgraded to BE without dysplasia. Patients were then treated with cryotherapy ablation for a mean of 2.3 treatments (range 1-5 treatments). Dosimetry freeze time had a mean of 19 seconds (range 10-30 seconds) repeated 2.6 cycles (range 2-4 cycles) per treatment session. Post cryotherapy biopsies of previous BE-HGD patients were available in 7/12 patients. Complete eradication of BE-HGD was seen in 4/7 patients and these patients were biopsy negative. Two patients only had BE without dysplasia and one patient was downgraded to low grade dysplasia based on biopsies. The remaining five patients demonstrated endoscopic improvement, but biopsies were still pending at time of analysis. Conclusion: There appears to be a subset of patients who fail RFA ablation for BE-HGD. Low pressure liquid nitrogen should be considered for refractory BE-HGD patients who fail RFA. Futures studies are needed to better define the role of cryotherapy for the endoscopic treatment of BE with dysplasia

GOALS: To measure esophageal wall thickness (EWT) with endoscopic ultrasound (EUS) in patients with and without Barrett's esophagus (BE). BACKGROUND: Segment length and histology are used to evaluate BE. The development of varying depths of ablation therapy has renewed interest in using EUS for BE. STUDY: In this prospective study, EWT measurements were taken from the balloon-mucosal interface to the outer most hyper-echoic line. These measurements were correlated with the highest grade of BE dysplasia and segment length, and then compared with the measurements from control group. RESULTS: Between 2004 to 2007, 76 BE patients (69 men, mean age 68 y, 4 ND, 14 low-grade dysplasia, 52 high-grade dysplasia, 6 carcinoma in situ) and 53 normal controls (18 men, mean age 60 y) underwent EUS. The mean EWT was 2.4 mm for controls, 3.1 mm for nondysplastic BE, 3.2 mm for low-grade dysplasia, 3.4 mm for high-grade dysplasia, and 3.9 mm for carcinoma in situ. In the control group of 53 patients, the mean EWT was 2.4 mm. Compared with normal controls, the mean EWT was significantly greater in all histologic subgroups of BE patients (P<0.001). No statistically significant correlation was seen between EWT and BE histology grade. There were no correlations between age, gender, or BE segment length and EWT (P=0.55). CONCLUSIONS: EWT is greater among patients with BE compared with control patients; however, there were no systematic differences in EWT were found among BE patients, based on histology and segment length.

BACKGROUND: The factors associated with maximizing the cytological adequacy of EUS-guided FNA (EUS-FNA) in pancreatic tumor evaluation are not well-known. OBJECTIVE: To examine associations of physician and procedural factors with the endpoint: the presence of an adequate cytological specimen found by using EUS-FNA in patients with pancreatic tumors and lymph nodes. DESIGN: Retrospective cohort study. SETTING: A U.S. tertiary care center. PATIENTS: Patients undergoing EUS-FNA of pancreatic masses and lymph nodes. INTERVENTIONS: Analysis of EUS-FNA procedures performed in our institution from 1997 to 2007. MAIN OUTCOME MEASUREMENTS: Associations were evaluated between the primary endpoint of cytological adequacy and factors including the endoscopist, needle gauge, the number of needle passes attempted, the pathologist, and the presence of an onsite cytotechnologist to confirm an adequate specimen. EUS-FNA adequacy was determined by a pathologist based on the presence of definite benign or malignant tissue. RESULTS: EUS-FNA was performed in 247 pancreatic masses and 276 lymph nodes. An adequate cytological sample was obtained in 240 (97%) pancreatic tumors (95% CI, 94%-99%) and 252 (91%) lymph nodes (95% CI, 87%-94%). For pancreatic tumors, there was no evidence of any associations between factors and cytological adequacy. For lymph nodes, cytological adequacy was improved when an onsite cytotechnologist was present (96% vs 84%, P = .002); no other factors showed statistically significant associations with cytological adequacy. LIMITATIONS: Retrospective study, low power to detect associations. CONCLUSIONS: The presence of an onsite cytotechnologist is an important factor in achieving successful EUS-FNA of suspicious lymph nodes in patients with pancreatic masses.

BACKGROUND & AIMS: Adenoma detection rates might be improved through use of high-definition colonoscopy, which can detect subtle mucosal changes. We investigated whether the use of high-definition white-light (HDWL) colonoscopy resulted in a higher rate of adenoma detection than standard-definition white-light (SDWL) colonoscopy in a clinical practice setting. METHODS: This retrospective study included 2430 patients who underwent colonoscopies from September 2006 to December 2007; 1226 received SDWL colonoscopy and 1204 received HDWL colonoscopy. We analyzed data from consecutive screening, surveillance, and diagnostic colonoscopies, comparing adenoma and overall polyp detection between procedures. Potentially confounding variables were controlled using multivariable logistic regression analysis. RESULTS: The adenoma detection rate was higher among patients who underwent HDWL compared with SDWL colonoscopies (28.8% vs 24.3%; P = .012), as was the polyp detection rate (42.2% vs 37.8%; P = .026). These findings remained after adjustments for potentially confounding variables (P = .018 and .022, respectively). CONCLUSIONS: In a general clinical practice setting, HDWL colonoscopy resulted in a higher adenoma detection rate compared with SDWL colonoscopy. The use of SDWL colonoscopy could reduce the number of missed adenomas and the subsequent risk for colorectal cancer.

Photodynamic therapy (PDT) is a drug and device therapy using photosensitizer drugs activated by laser light for mucosal ablation. Porfimer sodium PDT has been used extensively with proven long-term efficacy and durability for the ablation of Barrett esophagus and high-grade dysplasia. and early esophageal adenocarcinoma. However, continued use is hampered by an associated stricture risk and prolonged photosensitivity (4-6 weeks). Promising single-center European studies using other forms of PDT, such as aminolevulinic acid PDT, have not been replicated elsewhere, limiting the widespread use of other forms of PDT. Future use of PDT in esophageal disease depends on the development of improved dosimetry and patient selection to optimize treatment outcomes, while minimizing adverse events and complications.

PURPOSE: Photodynamic therapy (PDT) is used to treat Barrett's esophagus with high-grade dysplasia and mucosal carcinoma. Outcomes are variable with some patients having persistent disease, whereas others develop strictures. The aims of this study were (a) to compare porfimer sodium tissue uptake, light dose, and esophageal thickness with clinical outcomes and (b) to determine the selectivity of porfimer sodium uptake in diseased and normal epithelium. EXPERIMENTAL DESIGN: Forty-eight hours after porfimer sodium infusion, patients underwent mucosal biopsy for quantification of the porfimer sodium. Laser light was delivered at 48 hours and again 24 or 48 hours later. Porfimer sodium was extracted from the biopsy samples and quantified using fluorescence spectroscopy. The enhanced photodynamic dose was determined as [porfimer sodium content * light dose/esophageal thickness]. PDT efficacy was determined 6 to 8 weeks later based on persistence or complete ablation of dysplasia or carcinoma. RESULTS: Mean porfimer sodium content of 6.2 mg/kg (range, 2.6-11.2 mg/kg) and mean total light dose of 278 J/cm (range, 225-360 J/cm) resulted in a complete treatment. Mean porfimer sodium tissue content of 3.9 mg/kg (range, 2.1-8.1 mg/kg) and mean total light dose of 268 J/cm (range, 250-350 J/cm) resulted in an incomplete treatment. The total esophageal thickness (range, 1.7-6.0 mm) and enhanced photodynamic dose were correlated with treatment outcome. CONCLUSIONS: Esophageal thickness is the strongest predictor of treatment outcome. The porfimer sodium content of Barrett's and normal tissue is not significantly different. "Photodynamic dose" for esophageal PDT should incorporate the esophageal thickness.

BACKGROUND: An American Society for Gastrointestinal Endoscopy-American College of Gastroenterology (ASGE-ACG) task force recently developed quality indicators for the preprocedure, intraprocedure, and postprocedure phases of each endoscopic procedure. Benchmark rates and clinical significance of compliance have not been determined. OBJECTIVES: To establish baseline compliance rates to the preprocedure and intraprocedure quality indicators in our EUS cases, identify indicators with the lowest compliance rates, and establish change in compliance rates with a targeted performance improvement plan. METHODS: We measured baseline compliance to each of the preprocedure and intraprocedure EUS quality indicators in the EUS procedures performed at Mayo Clinic Jacksonville from March 1996 through August 2006. We developed a performance improvement plan that targeted the 4 indicators with the lowest compliance over the entire time period. Compliance rates in the year after plan implementation were compared with those from January 2004 to August 2006, when adjusting for endoscopist and direct access. RESULTS: We demonstrated areas of high quality as well as areas for improvement in compliance with the ASGE-ACG quality metrics in a large cohort of EUS cases. We achieved improvement in all 4 areas targeted for quality improvement, statistically significant at the 5% level for two of the quality indicators. LIMITATIONS: Limitations included our retrospective design and the use of unstructured procedure dictations that may limit application of our results. It is also unclear whether compliance was truly synonymous with performance. CONCLUSIONS: We established reference levels of compliance rate within our practice and showed that a targeted performance improvement plan that consisted of awareness, individual accountability, and documentation can result in improvement.

BACKGROUND: Double-balloon enteroscopy (DBE) allows direct visualization and intervention in the entire small intestine. Concerns include long procedure times and a long learning curve after training. OBJECTIVES: To analyze the initial experience of a single endoscopist when using DBE; assess resource utilization, safety, clinical utility, and the learning curve. DESIGN: Prospective study. SETTING: Tertiary-referral center. PATIENTS: A total of 137 consecutive patients with bleeding or other small-intestine disorders. MAIN OUTCOME MEASURES: Clinical impact at the time of DBE and changes in the procedure time and extent with experience. RESULTS: Two hundred DBE procedures were performed without major complications. For 115 oral DBEs, the mean (SD) procedure duration was 101 +/- 35 minutes and length of examined small intestine was 220 +/- 80 cm, with no significant change with experience. For 85 anal DBEs, the mean (SD) procedure duration was 96 +/- 33 minutes, and the length examined was 124 +/- 60 cm; the length examined increased with experience, but the duration did not decrease. The percentage of patients in which a DBE had a helpful clinical impact rose from 58% in the first 50 DBEs, to 86% in the last 50 of 200 DBEs. The total enteroscopy rose from 8% in the first 50 DBEs, to 63% in the last 50 of 200 DBEs. LIMITATIONS: No follow-up data on outcomes. CONCLUSIONS: DBEs required significant time and did not always allow for a total enteroscopy. DBEs were safe and helpful in the management of most patients. An experienced endoscopist may perform a safe and useful DBE after limited training, but the development of expertise may require more than 100 to 150 DBE procedures.

CONTEXT: In patients with suspected lung cancer, the presence of mediastinal lymph node metastasis is a critical determinant of therapy and prognosis. Invasive staging with pathologic confirmation is recommended. Many methods for staging exist; mediastinoscopy, an invasive procedure requiring general anesthesia, is currently regarded as the diagnostic standard. OBJECTIVE: To compare the diagnostic accuracy of 3 methods of minimally invasive endoscopic staging (and their combinations): traditional transbronchial needle aspiration (TBNA), endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA), and transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). In particular, we aimed to compare EBUS-FNA with TBNA. DESIGN, SETTING, AND PARTICIPANTS: Invasive staging of the mediastinum among consecutive patients with suspected lung cancer at a US academic medical center from November 2004 through October 2006. INTERVENTION: TBNA, EBUS-FNA, and EUS-FNA performed sequentially as a single combined procedure. MAIN OUTCOME MEASURE: Sensitivity for detecting mediastinal lymph node metastases, using pathologic confirmation and 6- to 12-month clinical follow-up as the criterion standard. RESULTS: Among 138 patients who met all study criteria, 42 (30%) had malignant lymph nodes. EBUS-FNA was more sensitive than TBNA, detecting 29 (69%) vs 15 (36%) malignant lymph nodes (P = .003). The combination of EUS-FNA and EBUS-FNA (EUS plus EBUS) had higher estimated sensitivity (93% [39/42]; 95% confidence interval, 81%-99%) and negative predictive value (97% [96/99]; 95% confidence interval, 91%-99%) compared with either method alone. EUS plus EBUS also had higher sensitivity and higher negative predictive value for detecting lymph nodes in any mediastinal location and for patients without lymph node enlargement on chest computed tomography. CONCLUSIONS: These findings suggest that EBUS-FNA has higher sensitivity than TBNA and that EUS plus EBUS may allow near-complete minimally invasive mediastinal staging in patients with suspected lung cancer. These results require confirmation in other studies but suggest that EUS plus EBUS may be an alternative approach for mediastinal staging in patients with suspected lung cancer.