Tethered capsule endomicroscopy (TCE) is a recently developed form of in vivo microscopy based on optical coherence tomography (OCT). With TCE, a small tethered pill is swallowed, procuring high resolution microscopic images of the esophageal wall. TCE does not require sedation and is thus a more rapid and convenient procedure comparing to traditional endoscopic examination. Our group and others have successfully conducted OCT-TCE in pilot, single-center studies that demonstrated the potential of this technology for upper GI tract diagnosis. Here, we demonstrate and evaluate the feasibility and safety of a next generation OCT-TCE system and device in patients with Barrett’s esophagus (BE) and report the initial longitudinal analysis of the natural history of BE.
While the most common method used to evaluate and survey patients with Barrett’s Esophagus (BE) is endoscopic biopsy, this procedure is invasive, time-consuming, and suffers from sampling errors. Moreover, it requires patient sedation that increases cost and mandates its operation in specialized settings. Our lab has developed a new imaging tool termed tethered capsule endomicroscopy (TCE) that involves swallowing a tethered capsule which utilizes optical coherence tomography (OCT) to obtain three-dimensional microscopic (10µm) images of the entire esophageal wall as it traverses the luminal organ via peristalsis or is retrieved by pulling up tether. As opposed to endoscopy, TCE procedure is non-invasive, doesn’t require patient sedation and mitigates sampling error by evaluating the microscopic structure of the entire esophagus. The merits of TCE make it a suitable device to investigate the microscopic natural history of BE in a longitudinal manner.
Here, we present our initial experience of a multicenter (5-site) clinical trial to study the microscopic natural history of BE. The TCE device used for the study is the new generation capsule with the ball lens optical configuration and a distal scan stepper motor, which provides 30µm (lateral) resolution and 40Hz imaging rate. The portable OCT imaging system is a custom in-house built swept source system and provides 7µm (axial) at a 100 kHz A-line rate with a center wavelength of ~1310 nm. To date, we have successfully enrolled 69 subjects at all sites (MGH: 33, Columbia University: 11, Kansas City VA: 10, Mayo Jacksonville: 8, Mayo Rochester: 7) and 59 have swallowed the capsule (85.5%). There have been no reported adverse events associated with TCE procedure. High-quality OCT images were reliably obtained from patients who swallowed the device, and BE tissues were identified by expert readers. Our initial experience with TCE in a multicenter study demonstrates that this technology is easy to use and efficient in multiple clinical settings. Completion of this longitudinal study is likely to provide new insights on the temporal progression of BE that may impact management strategies.
Background: There are few data available comparing endoscopic ablation methods for Barrett's esophagus with high-grade
dysplasia (BE-HGD).
Objective: To determine differences in symptoms and complications associated with endoscopic ablation.
Design: Prospective observational study.
Setting: Two tertiary care centers in USA.
Patients: Consecutive patients with BE-HGD
Interventions: In this pilot study, symptoms profile data were collected for BE-HGD patients among 3 endoscopic
ablation methods: porfimer sodium photodynamic therapy, radiofrequency ablation and low-pressure liquid nitrogen
spray cryotherapy.
Main Outcome Measurements: Symptom profiles and complications from the procedures were assessed 1-8 weeks after
treatment.
Results: Ten BE-HGD patients were treated with each ablation modality (30 patients total; 25 men, median age: 69
years (range 53-81). All procedures were performed in the clinic setting and none required subsequent hospitalization.
The most common symptoms among all therapies were chest pain, dysphagia and odynophagia. More patients (n=8) in
the porfimer sodium photodynamic therapy group reported weight loss compared to radio-frequency ablactation (n=2)
and cryotherapy (n=0). Four patients in the porfimer sodium photodynamic therapy group developed phototoxicity
requiring medical treatment. Strictures, each requiring a single dilation, were found in radiofrequency ablactation (n=1)
and porfimer sodium photodynamic therapy (n=2) patients.
Limitations: Small sample size, non-randomized study.
Conclusions: These three endoscopic therapies are associated with different types and severity of post-ablation
symptoms and complications.
Photodynamic therapy with porfimer sodium (PS) is a treatment option for high grade dysplasia associated with Barrett's
esophagus. This study sought to investigate the optical properties of Barrett's dysplasia that may be useful in light
dosimetry planning and to determine the effect of PS on tissue absorption and scattering. Fiber optic reflectance spectra
were collected before and 48 hours after administration of 2 mg/kg PS. Mucosal biopsies were collected at the same
locations. According to Monte Carlo analysis, the fiber optic probe sampled only the mucosal layer. A mathematical fit
of the reflectance spectra was performed as a function of blood volume fraction, oxygen saturation and scattering. The
average calculated blood volume was 100% higher in Barrett's tissue than normal esophageal tissue. The average
scattering slope from 620 to 750 nm was 26% higher for Barrett's dysplasia than normal esophageal tissue, indicating an
increase in the size of scattering particles. The difference in the scattering amplitude was not statistically significant,
suggesting no significant increase in the number of scattering particles. PS tissue content was determined with extraction
methods. Changes in the scattering slope due to PS sensitization were observed; however they were not proportional to
the extracted PS concentration.
Background: Photodynamic therapy using porfimer sodium (Ps-PDT) is approved for use in patients with Barrett's highgrade dysplasia and esophageal carcinoma. Ps-PDT light dosimetry, however, is critically important to treatment outcomes since insufficient ablation results in residual dysplasia and carcinoma while excessive treatment results in stricture formation. Aim: The aim of this study was to model esophageal PDT with optical absorption and scattering coefficients derived from an ex-vivo porcine multilayer esophagus model. Methods: Optical coefficients were derived for the mucosal and muscle layers of normal pig esophagus. The mucosal layer (mucosa, muscularis mucosa and submucosa) was separated from the muscle layer. Diffuse reflectance and transmittance were measured with an integrating sphere spectrophotometer. Absorption and reduced scattering coefficients were determined with the inverse adding doubling method.
(Table not available in abstract, see pdf of paper) Multilayer Monte Carlo simulation and single-layer mathematical dosimetry equations were employed to model esophageal PDT with the derived coefficients. Porfimer sodium addition was modeled with an increase in both absorption and scattering. Depth of injury, assumed to require a threshold light dose, was estimated for various light doses commonly used in clinical practice. Depth of injury was then compared to clinical outcomes reported in the literature for various light doses.
In 1995, PDT was approved for palliative use in patients with esophageal cancer. We report our experience using PDT to treat esophageal cancer patients previously treated with combination chemotherapy and radiation therapy. In our series, nine patients referred for PDT with persistent esophageal cancer after chemo-radiation therapy. We found: (1) All patients were men with a mean age of 63 years and eight out of nine had adenocarcinoma with Barrett's esophagus; (2) All patients required endoscopic dilation after PDT; (3) At a mean follow up of 4 months, two T2N0 patients had no demonstrable tumor and all three T3N0 patients had greater than 50% tumor reduction (the partially responsive T3N0 patients will be offered repeat PDT); (4) Patients with metastatic disease (T3N1 or M1) had effective dysphagia palliation. Thus, PDT is safe and effective in ablating all or most tumor in patients with persistent esophageal cancer after chemotherapy and radiation therapy.
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