Douglas K. Pleskow

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND AND STUDY AIMS The AIM-II Trial included patients with nondysplastic Barretts esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barretts esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up

BACKGROUND For patients with Barretts esophagus (BE), life-long surveillance endoscopy is recommended because of an elevated risk for developing dysplasia and esophageal adenocarcinoma. Various endoscopic therapies have been used to eradicate BE. Recently circumferential radiofrequency ablation has been used with encouraging short-term results. OBJECTIVE To provide longer follow-up and to assess the long-term safety and efficacy of step-wise circumferential ablation with the addition of focal ablation for BE. DESIGN Prospective, multicenter clinical trial (NCT00489268). SETTING Eight U.S. centers, between May 2004 and February 2007. PATIENTS Seventy subjects with 2 to 6 cm of BE and histologic evidence of intestinal metaplasia (IM). INTERVENTIONS Circumferential ablation was performed at baseline and repeated at 4 months if there was residual IM. Follow-up biopsy specimens were obtained at 1, 3, 6, 12, and 30 months. Specimens were reviewed by a central pathology board. Focal ablation was performed after the 12-month follow-up for histological evidence of IM at the 12-month biopsy (absolute indication) or endoscopic appearance suggestive of columnar-lined esophagus (relative indication). Subjects received esomeprazole for control of esophageal reflux. MAIN OUTCOME MEASUREMENTS Complete absence of IM per patient from biopsy specimens obtained at 12 and 30 months, defined as complete remission-IM (CR-IM). RESULTS At 12 months, CR-IM was achieved in 48 of 69 available patients (70% per protocol [PP], 69% intention to treat [ITT]). At 30 months after additional focal ablative therapy, CR-IM was achieved in 60 of 61 available patients (98% PP, 97% ITT). There were no strictures or buried glandular mucosa detected by the standardized biopsy protocol at 12 or 30 months, and there were no serious adverse events. LIMITATIONS This was an uncontrolled clinical trial with 2.5-year follow-up. CONCLUSION Stepwise circumferential and focal ablation resulted in complete eradication of IM in 98% of patients at 2.5-year follow-up.

Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones (with videos)

BACKGROUND The feasibility of single-operator cholangioscopy (SOC) for biliary diagnostic and therapeutic procedures was previously reported. OBJECTIVE To confirm the utility of SOC in more widespread clinical use. DESIGN Prospective clinical cohort study. SETTING Fifteen endoscopy referral centers in the United States and Europe. PATIENTS Two hundred ninety-seven patients requiring evaluation of bile duct disease or biliary stone therapy. INTERVENTIONS SOC examination and, as indicated, SOC-directed stone therapy or forceps biopsy. MAIN OUTCOME MEASUREMENTS Procedural success defined as ability to (1) visualize target lesions and, if indicated, collect biopsy specimens adequate for histological evaluation or (2) visualize biliary stones and initiate fragmentation and removal. RESULTS The overall procedure success rate was 89% (95% CI, 84%-92%). Adequate tissue for histological examination was secured in 88% of 140 patients who underwent biopsy. Overall sensitivity in diagnosing malignancy was 78% for SOC visual impression and 49% for SOC-directed biopsy. Sensitivity was higher (84% and 66%, respectively) for intrinsic bile duct malignancies. Diagnostic SOC procedures altered clinical management in 64% of patients. Procedure success was achieved in 92% of 66 patients with stones and complete stone clearance during the study SOC session in 71%. The incidence of serious procedure-related adverse events was 7.5% for diagnostic SOC and 6.1% for SOC-directed stone therapy. LIMITATIONS The study was observational in design with no control group. CONCLUSIONS Evaluation of bile duct disease and biliary stone therapy can be safely performed with a high success rate by using the SOC system.

Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer

PURPOSE Patients with nonmetastatic locally advanced unresectable pancreatic cancer have a dismal prognosis. Conventional concurrent chemoradiotherapy requires 6 weeks of daily treatment and can be arduous. We explored the safety and effectiveness of a 3-day course of hypofractionated stereotactic body radiotherapy (SBRT) followed by gemcitabine in this population. PATIENTS AND METHODS A total of 36 patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with ≥12 months of follow-up were included. They received three fractions of 8, 10, or 12 Gy (total dose, 24-36 Gy) of SBRT according to the tumor location in relation to the stomach and duodenum, using fiducial-based respiratory motion tracking on a robotic radiosurgery system. The patients were then offered gemcitabine for 6 months or until tolerance or disease progression. RESULTS With an overall median follow-up of 24 months (range, 12-33), the local control rate was 78%, the median overall survival time was 14.3 months, the median carbohydrate antigen 19-9-determined progression-free survival time was 7.9 months, and the median computed tomography-determined progression-free survival time was 9.6 months. Of the 36 patients, 28 (78%) eventually developed distant metastases. Six patients (17%) were free of progression at the last follow-up visit (range, 13-30 months) as determined by normalized tumor markers with stable computed tomography findings. Nine Grade 2 (25%) and five Grade 3 (14%) toxicities attributable to SBRT occurred. CONCLUSION Hypofractionated SBRT can be delivered quickly and effectively in patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with acceptable side effects and minimal interference with gemcitabine chemotherapy.

Effect of Institution-Wide Policy of Colonoscopy Withdrawal Time ≥7 Minutes on Polyp Detection

BACKGROUND & AIMS Practice guidelines recommend that endoscopists spend at least 7 minutes examining the colonic mucosa during colonoscopy withdrawal to optimize polyp yield. The aim of this study was to determine if the implementation of an institution-wide policy of colonoscopy withdrawal time > or = 7 minutes was associated with an increase in colon polyp detection. METHODS All 42 endoscopists at our institute were asked to attain a colonoscopy withdrawal time of at least 7 minutes. Compliance with 7-minute withdrawal time was recorded for all nontherapeutic colonoscopies. Polyp detection ratio (number of polyps detected divided by number of colonoscopies performed) was computed. Regression models were used to assess the association between compliance with 7-minute withdrawal time and polyp detection. RESULTS During the study period, 23,910 colonoscopies were performed. The average age of patients was 56.8 years, and 54% were female. Colon cancer screening or surveillance was the indication for 42.5% of colonoscopies. At the beginning of the study, the polyp detection ratio was 0.48. Compliance with 7-minute withdrawal time for nontherapeutic procedures increased from 65% at the beginning of the initiative to almost 100%. However, no increase in polyp detection ratio was noted over the same period for all polyps (slope, 0.0006; P = .45) or for polyps 1-5 mm (slope, 0.001; P = .26), 6-9 mm (slope, 0.002; P = .43), or > or = 10 mm (slope, 0.006; P = .13). No association was detected when only colonoscopies performed for screening or surveillance were analyzed. CONCLUSIONS An institution-wide policy of colonoscopy withdrawal time > or = 7 minutes had no effect on colon polyp detection.

Evaluation of a Serologic Marker, CA19-9, in the Diagnosis of Pancreatic Cancer

STUDY OBJECTIVE To determine the utility of the serologic marker CA19-9 in the diagnosis of pancreatic cancer in patients suspected of having a pancreatic disorder. DESIGN Blinded study of frozen pedigreed serum samples collected at time of diagnostic evaluation with follow-up review at a mean of 8 years. SETTING A general university teaching hospital serving both primary and referral patient populations. MEASUREMENTS AND MAIN RESULTS Sera collected prospectively from 1978 to 1980 from 261 patients undergoing imaging studies of the pancreas (ultrasound, computed tomography, endoscopic retrograde cholangiopancreatography) for a variety of symptoms were assayed for CA19-9 levels, and the results were compared with earlier determinations of other potential markers for pancreatic cancer. In 54 patients ultimately shown to have pancreatic cancer, the CA19-9 assay showed a sensitivity of 70% with a median value of 349 u/mL (normal less than 70 u/mL) and range, 7.3 to 2,859,964 u/mL, whereas specificity of the marker in this population was 87%. The positive predictive value was 59%, and the negative predictive value was 92%. Results of CA19-9 testing in the small group of patients with definitive staging information showed no difference in sensitivity between patients with local/regional disease (n = 6) and those with distant metastases (n = 14), 50% compared with 71% (P = 0.613). CONCLUSION CA19-9 was found to be a more sensitive and specific marker of pancreatic cancer than other serologic markers and should be a useful test in the patient with suspected pancreatic disease.

Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: a multicenter experience.

BACKGROUND Because of the low sensitivity of current ERCP-guided tissue sampling methods, management of patients with indeterminate pancreaticobiliary strictures is a challenge. Probe-based confocal laser endomicroscopy (pCLE) enables real-time microscopic visualization of strictures during an ongoing ERCP. OBJECTIVE To document the utility, performance, and accuracy of real-time pCLE diagnosis compared with histopathology. DESIGN Prospective observational study within the framework of a multicenter registry. SETTING Five academic centers. PATIENTS This study involved 102 patients with indeterminate pancreaticobiliary strictures. INTERVENTION Clinical information, ERCP findings, tissue sampling results, and pCLE videos were collected prospectively. Investigators were asked to provide a presumptive diagnosis based on pCLE during the procedure before pathology results were available. All patients received at least 30 days of follow-up until definitive diagnosis of malignancy was established or 1-year follow-up if index tissue sampling was benign. MAIN OUTCOME MEASUREMENTS Diagnostic accuracy, sensitivity, specificity of ERCP-guided pCLE compared with ERCP with tissue acquisition. RESULTS There were no pCLE-related adverse events in the study. We were able to evaluate 89 patients, of whom 40 were proven to have cancer. The sensitivity, specificity, positive-predictive value, and negative-predictive value of pCLE for detecting cancerous strictures were 98%, 67%, 71%, and 97%, respectively, compared with 45%, 100%, 100%, and 69% for index pathology. This resulted in an overall accuracy of 81% for pCLE compared with 75% for index pathology. Accuracy for combination of ERCP and pCLE was significantly higher compared with ERCP with tissue acquisition (90% vs 73%; P = .001). LIMITATIONS Investigators had access to all relevant clinical information, which may have biased the predictive characteristics of pCLE. CONCLUSION Probe-based CLE provides reliable microscopic examination and has excellent sensitivity and negative predictive value. The significantly higher accuracy of ERCP and pCLE compared with ERCP with tissue acquisition may support supplementing ERCP with pCLE.

Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer.

PURPOSE Stereotactic body radiotherapy (SBRT) has been used successfully to treat patients with locally advanced pancreas cancer. However, many patients develop metastatic disease soon after diagnosis and may receive little benefit from such therapy. We therefore retrospectively analyzed a planned strategy of initial chemotherapy with restaging and then treatment for those patients with no evidence of metastatic progression with SBRT. METHODS AND MATERIALS Forty-seven patients received gemcitabine (1,000 mg/m(2) per week for 3 weeks then 1 week off) until tolerance, at least six cycles, or progression. Patients without metastases after two cycles were treated with SBRT (tolerance-based dose of 24-36 Gy in 3 fractions) between the third and fourth cycles without interrupting the chemotherapy cycles. RESULTS Eight of the 47 patients (17%) were found to have metastatic disease after two cycles of gemcitabine; the remaining 39 patients received SBRT. The median follow-up for survivors was 21 months (range, 6-36 months). The median overall survival for all patients who received SBRT was 20 months, and the median progression-free survival was 15 months. The local control rate was 85% (33 of 39 patients); and 54% of patients (21 of 39) developed metastases. Late Grade III toxicities such as GI bleeding and obstruction were observed in 9% (3/39) of patients. CONCLUSION For patients with locally advanced pancreas cancer, this strategy uses local therapy for those who are most likely to benefit from it and spares those patients with early metastatic progression from treatment. SBRT delivers such local therapy safely with minimal interruption to systemic chemotherapy, thereby potentially improving the outcome in these patients.

Large balloon dilation vs. mechanical lithotripsy for the management of large bile duct stones: a prospective randomized study.

OBJECTIVES:The removal of large bile duct stones (>12 mm) after endoscopic sphincterotomy (EST) remains a challenging issue in therapeutic endoscopy. The aim of this prospective, randomized, controlled trial was to compare the effectiveness and complications of EST followed by large balloon dilation (LBD) with that of EST followed by mechanical lithotripsy (ML) for the management of large bile duct stones.METHODS:A total of 90 patients with large bile duct stones (12–20 mm) were randomized to EST followed by LBD (n=45) or EST followed by ML (n=45). Success rate was determined with a final cholangiogram, whereas type and rate of post-procedure complications were assessed prospectively.RESULTS:Complete bile duct stone removal was accomplished in 97.7% of patients subjected to EST–LBD as compared with 91.1% of those subjected to EST–ML (P=0.36). Post-procedure complications were observed in two (4.4%) patients subjected to EST–LBD and in nine (20%) patients subjected to EST–ML (P=0.049). Rates of pancreatitis were similar between the two groups (one case in each), as was post-endoscopic retrograde cholangio pancreatography (ERCP) hemorrhage (one case in each group). None of the patients subjected to EST–LBD developed cholangitis, while this was seen in six patients subjected to EST–ML (0.0 vs. 13.3%, P=0.026). One patient subjected to EST–ML developed perforation, which was successfully managed conservatively. None of our patients with complications died.CONCLUSIONS:EST followed by LBD is equally effective as EST followed by ML for the removal of large bile duct stones, although it is associated with fewer complications.

Endoscopic full-thickness plication for the treatment of GERD: a multicenter trial

BACKGROUND A novel endoscopic full-thickness plication device has been designed to inhibit gastroesophageal reflux by placing a transmural plication near the gastroesophageal junction under direct endoscopic visualization. This study assessed the safety and efficacy of endoscopic full-thickness plication in the treatment of patients with symptoms caused by GERD. METHODS Patients with chronic heartburn requiring maintenance therapy with antisecretory medication were recruited. Exclusion criteria were the following: hiatal hernia (>2 cm), grade III and IV esophagitis, and Barretts esophagus. The following were assessed over a follow-up period of 6 months: GERD-Health-Related Quality of Life, Gastrointestinal Symptom Rating Scale, and SF-36 Health Survey, medication use, 24-hour esophageal pH monitoring and esophageal manometry. Patients underwent a single, full-thickness plication in the gastric cardia just distal to the gastroesophageal junction. Re-treatment was not permitted. RESULTS A total of 64 patients (mean age 46.3 years, range 23-71 years) underwent endoscopic full-thickness plication (mean procedure time 17.2 minutes). At 6 months after plication, proton pump inhibitor therapy had been eliminated in 74% of previously medication-dependent patients. Median GERD-Health-Related Quality of Life scores improved 67% (19.0 vs. 5.0; p<0.001). Improvements also were observed in median Gastrointestinal Symptom Rating Scale and SF-36 Health Survey mental and physical composite scores. Median esophageal acid exposure improved significantly (10 vs. 8; p<0.008) with normalization of pH noted in 30% of patients. No significant change in esophageal manometry was noted. One gastric perforation occurred and was managed conservatively without sequelae. CONCLUSIONS In this study, a single full-thickness plication placed at the gastroesophageal junction reduced symptoms, medication use, and esophageal acid exposure associated with GERD.