Paul A. Akerman

Effect of a retrograde-viewing device on adenoma detection rate during colonoscopy: the TERRACE study

BACKGROUND Although colonoscopy is currently the optimal method for detecting colorectal polyps, some are missed. The Third Eye Retroscope provides an additional retrograde view that may detect polyps behind folds. OBJECTIVE To determine whether the addition of the Third Eye Retroscope to colonoscopy improves the adenoma detection rate. DESIGN Prospective, multicenter, randomized, controlled trial. SETTING Nine European and U.S. centers. PATIENTS Of 448 enrolled subjects, 395 had data for 2 procedures. INTERVENTIONS Subjects underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC). Subjects were randomized to SC followed by TEC or TEC followed by SC. MAIN OUTCOME MEASUREMENTS Detection rates for all polyps and adenomas with each method. RESULTS In the per-protocol population, 173 subjects underwent SC and then TEC, and TEC yielded 78 additional polyps (48.8%), including 49 adenomas (45.8%). In 176 subjects undergoing TEC and then SC, SC yielded 31 additional polyps (19.0%), including 26 adenomas (22.6%). Net additional detection rates with TEC were 29.8% for polyps and 23.2% for adenomas. The relative risk of missing with SC compared with TEC was 2.56 for polyps (P < .001) and 1.92 for adenomas (P = .029). Mean withdrawal times for SC and TEC were 7.58 and 9.52 minutes, respectively (P < .001). The median difference in withdrawal times was 1 minute (P < .001). The mean total procedure times for SC and TEC were 16.97 and 20.87 minutes, respectively (P < .001). LIMITATIONS Despite randomization and a large cohort, there was disparity in polyp prevalence between the 2 groups of subjects. CONCLUSION The Third Eye Retroscope increases adenoma detection rate by visualizing areas behind folds. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01044732.).

Spiral enteroscopy: a novel method of enteroscopy by using the Endo-Ease Discovery SB overtube and a pediatric colonoscope

BACKGROUND Pathologic diagnosis and therapeutic interventions on the small bowel have been difficult and challenging for gastroenterologists. In the last few years, significant advances have been made in this direction. New diagnostic and therapeutic modalities for visualizing the small bowel have been introduced. Furthermore, increased indications for small-bowel imaging and therapeutics have been recognized. However, the currently available methods have limitations, and development of newer, rapid, minimally invasive, safe, and readily available techniques is needed. OBJECTIVE Our purpose was to evaluate the safety and efficacy of a novel method of spiral enteroscopy using a specialized overtube (Endo-Ease Discovery SB) with a pediatric colonoscope (PCF-140L). DESIGN Case series. SETTING Two international tertiary referral centers. PATIENTS Twenty-seven adult patients with obscure GI bleeding were enrolled in this study. INTERVENTION Spiral enteroscopy with the Endo-Ease Discovery SB overtube and a pediatric colonoscope. MAIN OUTCOME MEASUREMENTS Depth of insertion, time of procedure, and complications. RESULTS Average depth of insertion was 176 cm (range 80-340 cm) from ligament of Treitz, and average time of procedure was 36.5 minutes (range 90-65 minutes). Eleven patients had minor complications, which included minimal mucosal trauma and sore throat. LIMITATIONS Small number of patients with a case series study design. CONCLUSIONS Preliminary data suggest that use of Endo-Ease Discovery SB overtube for enteroscopy is a safe and effective technique for visualization of the small bowel.

Erlotinib and chemoradiation followed by maintenance erlotinib for locally advanced pancreatic cancer: a phase I study.

Objectives:A phase I trial was conducted to determine the maximally tolerated dose of erlotinib with concurrent gemcitabine, paclitaxel, and radiation for patients with locally advanced pancreatic cancer and to gather preliminary data on maintenance erlotinib after chemoradiation. Methods:Patients received gemcitabine, 75 mg/m2, and paclitaxel, 40 mg/m2, weekly for 6 weeks with 50.4 radiation to the primary tumor and draining lymph nodes with a 2- to 3-cm margin. Erlotinib was administered over 3-dose levels (50–100 mg/d) with chemoradiation then all patients received 150 mg/d maintenance until disease progression. Results:Seventeen patients were assessable for toxicity; 13 with locally advanced disease and 4 who had undergone resection but had positive margins. At erlotinib dosages ≥75 mg/d with chemoradiation the dose-limiting toxicities were diarrhea, dehydration, rash, myelosuppression, and small bowel stricture. Maintenance erlotinib, 150 mg/d, was well tolerated. The median survival of the 13 patients with locally advanced disease was 14.0 months and 6 of 13 (46%) had a partial response. Conclusions:The maximum tolerated dose of erlotinib with gemcitabine, paclitaxel and concurrent radiation is 50 mg/d for patients with locally advanced pancreatic cancer. Full dose maintenance erlotinib is well tolerated. Promising preliminary activity and overall survival were demonstrated.

Paclitaxel and concurrent radiation for locally advanced pancreatic cancer

PURPOSE To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer. METHODS AND MATERIALS Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m(2) by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments. RESULTS Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%. CONCLUSION Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.

Paclitaxel, Cisplatin, and Concurrent Radiation for Esophageal Cancer

Paclitaxel is an active agent for adenocarcinomas and squamous cell carcinomas of the esophagus and is a radiation sensitizer. We sought to investigate the toxicity and complete response rate of paclitaxel, cisplatin, and concurrent radiation for esophageal cancer. Forty-one patients with esophageal cancer were studied, 29 with adenocarcinomas and 12 with squamous cell cancers. Twelve patients had tumor extension into the proximal stomach and/or abdominal adenopathy. Patients received paclitaxel 60 mg/m2 by 3-hour intravenous (IV) infusion, and cisplatin 25 mg/m2 weekly on days 1, 8, 15, and 22. Radiation was administered concurrently to a total dose of 39.60 Gy, in 1.80 Gy fractions, for 22 treatments. Patients with medical or surgical contraindications to esophagectomy received 2 additional weeks of paclitaxel with a radiation boost to 50.4 Gy. Neutropenia was the most common grade 3/4 toxicity occurring in 10 patients (24%). Only 2 patients (5%) had grade 4 esophagitis requiring parenteral nutrition. Twelve patients (29%) obtained a complete response. The 2-year progression-free and overall survival rates were 40% and 42%, respectively. Esophagitis was less severe than expected and prophylactic enteral feeding tubes were not necessary. Additional effective systemic treatments are needed to reduce the development of distant metastases.

Paclitaxel poliglumex (PPX-Xyotax) and concurrent radiation for esophageal and gastric cancer: a phase I study.

Objectives:To determine the maximal tolerated dose (MTD) and dose limiting toxicities of poly(l-glutamic acid)-paclitaxel (PPX) and concurrent radiation (PPX/RT) for patients with esophageal and gastric cancer. Methods:Patients with esophageal or gastric cancer receiving chemoradiation for loco-regional, adjuvant, or palliative intent were eligible. The initial dose of PPX was 40 mg/m2/wk, for 6 weeks with 50.4 Gy radiation. Dose levels were increased in increments of 10 mg/m2/wk of PPX. Results:Twenty-one patients were enrolled over 5 dose levels. Sixteen patients had esophageal cancer and 5 had gastric cancer. Twelve patients received PPX/RT as definitive loco-regional therapy, 4 patients had undergone resection and received adjuvant PPX/RT, and 5 patients had metastatic disease and received PPX/RT for palliation of dysphagia. Dose limiting toxicities of gastritis, esophagitis, neutropenia, and dehydration developed in 3 of 4 patients treated at the 80 mg/m2 dose level. Four of 12 patients (33%) with loco-regional disease had a complete clinical response. Conclusions:The maximally tolerated dose of PPX with concurrent radiotherapy is 70 mg/m2/wk for patients with esophageal and gastric cancer.

Gemcitabine, paclitaxel and radiation for locally advanced pancreatic cancer: a phase I trial

PURPOSE To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of gemcitabine, paclitaxel, and concurrent radiation for pancreatic cancer. METHODS AND MATERIALS Twenty patients with locally unresectable pancreatic cancer were studied. The initial dose level was gemcitabine 75 mg/m(2) and paclitaxel 40 mg/m(2) weekly for 6 weeks. Concurrent radiation to 50.4 Gy was delivered in 1.8 Gy fractions. The radiation fields included the primary tumor, plus the regional peripancreatic, celiac, and porta hepatis lymph nodes. RESULTS Dose-limiting toxicities of diarrhea, dehydration, nausea, and anorexia occurred in 3 of 3 patients at the second dose level of gemcitabine, 150 mg/m(2)/week. An intermediate dose level of gemcitabine, 110 mg/m(2)/week, was added, but gastrointestinal toxicity and pulmonary pneumonitis were encountered. The MTD therefore was gemcitabine 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and concurrent radiation. Two of 11 patients treated at the MTD had Grade 3/4 toxicity. Four of 10 assessable patients treated at the MTD responded (40%), including one pathologic complete response. CONCLUSION The maximum tolerated dosage of gemcitabine is 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and conventional 50.4 Gy radiation fields. A Phase II Radiation Therapy Oncology Group study is under way.

Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup

AIM To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized, controlled trial data. METHODS The Third Eye® Retroscope® Randomized Clinical Evaluation (TERRACE) was a randomized, controlled, multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscopes forward view. We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device. Subjects were patients scheduled for colonoscopy for screening, surveillance or diagnostic workup, and each underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC), randomized to SC followed by TEC or vice versa. RESULTS Indication for colonoscopy was screening in 176/345 subjects (51.0%), surveillance after previous polypectomy in 87 (25.2%) and diagnostic workup in 82 (23.8%). In 4 subjects no indication was specified. Previously reported overall results had shown a net additional adenoma detection rate (ADR) with TEC of 23.2% compared to SC. Relative risk (RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92 (P = 0.029). Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening, 35.7% for surveillance, 55.4% for diagnostic and 40.7% for surveillance and diagnostic combined. The RR of missing adenomas with SC vs TEC was 1.11 (P = 0.815) for screening, 3.15 (P = 0.014) for surveillance, 8.64 (P = 0.039) for diagnostic and 3.34 (P = 0.003) for surveillance and diagnostic combined. Although a multivariate Poisson regression suggested gender as a possibly significant factor, subset analysis showed that the difference between genders was not statistically significant. Age, bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC. Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm, respectively (P = NS). CONCLUSION TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup, but not in screening patients (ClinicalTrials.gov Identifier: NCT01044732).

Spiral Enteroscopy and Push Enteroscopy

Spiral enteroscopy is a new technique for endoscopic evaluation of the small bowel. Currently, more than 3000 cases have been performed worldwide. The Discovery SB device has been approved by the Food and Drug Administration and has been granted a CE mark. The technique is safe and effective for management and detection of small bowel pathology. Recent studies of spiral enteroscopy have demonstrated diagnostic yield, total time of procedure, and depth of insertion that compare favorably with double and single balloon enteroscopy. The strengths of spiral enteroscopy are rapid advancement in the small bowel and controlled, stable withdrawal that facilitates therapy. Future studies will be needed to compare competing technologies. Push enteroscopy is a readily available, safe and effective technique for detecting and treating proximal gut pathology. If performed without an overtube, complications are rare. Use of a dedicated push enteroscope with an overtube is generally reserved for specific indications in which a moderate increase in depth of insertion into the small bowel is required. When capsule endoscopy and deep small bowel enteroscopy are not available, push enteroscopy is a reasonable option with low risk and moderate yield. Push enteroscopy will remain an important part of the armamentarium of the modern endoscopist.

Paclitaxel and concurrent radiation for gastric cancer

PURPOSE To determine the activity and toxicity of paclitaxel and concurrent radiation for gastric cancer. METHODS AND MATERIALS Twenty-seven patients were studied. Twenty-five had proximal gastric cancers, two had distal cancers. Eight had esophageal extension, 6 had celiac adenopathy, and 7 had retroperitoneal adenopathy. Patients received paclitaxel, 50 mg/m(2) by 3-hour intravenous (IV) infusion, weekly, on days 1, 8, 15, 22, and 29. Radiation was administered concurrently to a total dose of 45.0 Gy, in 1.80 Gy fractions, for 25 treatments. Patients who were medically or surgically inoperable received a sixth week of paclitaxel with a radiation boost to 50.4 Gy. RESULTS Esophagitis and gastritis were the most important toxicities, Grade 3 in four patients (15%), and Grade 4 in three patients (11%). Five patients (19%) had Grade 3 nausea. The overall response rate was 56%, including three patients (11%) with a complete response. The 2-year progression-free and overall survival rates were 29% and 31%, respectively. CONCLUSION Concurrent paclitaxel and radiation demonstrates substantial local-regional activity in gastric cancer. Future investigations combining paclitaxel and radiation with other local-regional and systemic treatments are warranted.