Maria Cirocco

Endoscopic Doppler optical coherence tomography in the human GI tract: initial experience

BACKGROUND Expanding the current endoscopic optical coherence tomography (OCT) system with Doppler capability may augment this novel high-resolution cross-sectional imaging technique with functional blood flow information. The aim of this feasibility study was to assess the clinical feasibility of an endoscopic Doppler OCT (EDOCT) system in the human GI tract. METHODS During routine endoscopy, 22 patients were imaged by using a prototype EDOCT system, which provided color-Doppler and velocity-variance images of mucosal and submucosal blood flow at one frame per second, simultaneously with high-spatial-resolution (10-25 mum) images of tissue microstructure. The images were acquired from normal GI tract and pathologic tissues. OBSERVATIONS Subsurface microstructure and microcirculation images of normal and pathologic GI tissues, including Barretts esophagus, esophageal varices, portal hypertensive gastropathy, gastric antral vascular ectasia, gastric lymphoma, and duodenal adenocarcinoma, were obtained from 72 individual sites in vivo. Differences in vessel diameter, distribution, density, and blood-flow velocity were observed among the GI tissue pathologies imaged. CONCLUSIONS To our knowledge, this is the first study to demonstrate the feasibility of EDOCT imaging in the human GI tract during routine endoscopy procedures. EDOCT may detect the different microcirculation patterns exhibited by normal and diseased tissues, which may be useful for diagnostic imaging and treatment monitoring.

Autofluorescence characterisation of isolated whole crypts and primary cultured human epithelial cells from normal, hyperplastic, and adenomatous colonic mucosa.

Background/Aims: In vivo autofluorescence endoscopic imaging and spectroscopy have been used to detect and differentiate benign (hyperplastic) and preneoplastic (adenomatous) colonic lesions. This fluorescence is composed of contributions from the epithelium, lamina propria, and submucosa. Because epithelial autofluorescence in normal and diseased tissues is poorly understood, this was the focus of the present study. Methods: Whole colonic crypts were isolated, and short term primary cultures of epithelial cells were established from biopsies of normal, hyperplastic, and adenomatous colon. Autofluorescence (488 nm excitation) was examined by confocal fluorescence microscopy. Fluorescently labelled organelle probes and transmission electron microscopy were used to identify subcellular sources of fluorescence. Results: Mitochondria and lysosomes were identified as the main intracellular fluorescent components in all cell types. Normal and hyperplastic epithelial cells were weakly autofluorescent and had similar numbers of mitochondria and lysosomes, whereas adenomatous (dysplastic) epithelial cells showed much higher autofluorescence, and numerous highly autofluorescent lysosomal (lipofuscin) granules. Conclusions: Short term primary cell cultures from endoscopic biopsies provide a novel model to understand differences in colonic tissue autofluorescence at the glandular (crypt) and cellular levels. The differences between normal, hyperplastic, and adenomatous epithelial cells are attributed in part to differences in the intrinsic numbers of mitochondria and lysosomes. This suggests that the detection of colonic epithelial fluorescence alone, if possible, may be sufficient to differentiate benign (hyperplastic) from preneoplastic and neoplastic (adenomatous) colonic intramucosal lesions during in vivo fluorescence endoscopy. Furthermore, highly orange/red autofluorescent intracellular granules found only in dysplastic epithelial cells may serve as a potential biomarker.

Endoscopic cryotherapy for the management of gastric antral vascular ectasia.

BACKGROUND Gastric antral vascular ectasia (GAVE) is an uncommon but clinically significant cause of chronic GI bleeding. OBJECTIVE To assess the efficacy and safety of cryotherapy for endoscopic treatment of GAVE. DESIGN Patients received 3 sessions of endoscopic cryotherapy at 3-week to 6-week intervals and had a follow-up endoscopy 4 weeks thereafter. They were followed prospectively in terms of clinical and endoscopic response. SETTING Tertiary-care center, between October 2004 and April 2006. PATIENTS The patients were 43 to 89 years of age, with a diagnosis of GAVE and documented iron deficiency anemia. Eight patients had a history of overt GI bleeding. Eight patients (67%) had previously been treated with argon plasma coagulation (APC) (median 6 sessions, range 1-10 sessions) and failed to respond or had a recurrence. RESULTS Twelve patients were enrolled. Six patients (50%) had a complete response, and 6 patients had a partial response. The mean number of units of blood transfused in the period of 3 months before cryotherapy and during the period of follow-up of 3 months was 4.6 and 1.7 units, respectively. An increased mean Hb level, from 9.9 to 11.3 g/dL, was noted. The average duration of the cryotherapy was 5 minutes (range 1-15 minutes). In 32 of 36 cryotherapy treatment sessions performed (89%), it was technically possible to treat more than 90% of GAVE lesions. There were no immediate cryotherapy-related complications, and none of the patients required admission after the procedure. LIMITATIONS A pilot study from a single center. CONCLUSIONS Endoscopic cryotherapy is a safe and effective treatment for GAVE. It appears to be effective, even for GAVE refractory to APC therapy. Optimal cryogen, delivery device, and treatment protocols are yet to be determined.

Thalidomide for the treatment of chronic gastrointestinal bleeding from angiodysplasias: a case series

Background Mucosal angiodysplasias, either inherited or acquired, can cause gastrointestinal bleeding, sometimes refractory to treatment. From earlier case reports, thalidomide has been described to possess some benefits in this disease, but its benefits and risks nevertheless remain unclear. Objectives This pilot study assesses the efficacy, safety, and side-effect of thalidomide in the treatment of patients with chronic gastrointestinal bleeding from angiodysplasias. Methods Patients with chronic angiodysplasia bleeding and requiring ongoing transfusion were eligible for this open nonrandomized study. Thalidomide was started with 50 mg/day and then increased incrementally by 50 mg every week up to 200 mg/day, if tolerated, and continued for 6 months. Adverse events, hemoglobin, blood chemistry, and blood transfusion were monitored during the treatment and for 6-months posttreatment. Results Seven patients were recruited in this study. Four patients discontinued thalidomide within 3–8 weeks, because of fatigue (two patients), peripheral neuropathy (one patient), and skin rash (one patient). All side-effects resolved when thalidomide was discontinued. These four patients required the same volume of blood transfusions per month as pre-study. In contrast, the three patients who continued 100–200 mg/day of thalidomide for 6 months did not require any transfusions during the 6 months of medication. During 6-months posttreatment of these three patients, one maintained response without any transfusion for 2 months, then required 1 U of blood every 4 weeks, one patient required 2 U of blood every 3–4 weeks, and one patient died from diabetes complications. Conclusion Thalidomide should be considered as a therapeutic option in patients who are resistant to conventional therapy, but it has a high discontinuation rate because of its side-effects.

Double-Balloon Enteroscopy following Capsule Endoscopy in the Management of Obscure Gastrointestinal Bleeding: Outcome of a Combined Approach

BACKGROUND There is no consensus on the relative accuracy of capsule endoscopy (CE) versus double-balloon enteroscopy (DBE) to investigate obscure gastrointestinal bleeding (GIB). CE is less invasive, but DBE more directly examines the small bowel, and allows tissue sampling plus therapeutic intervention. OBJECTIVES To evaluate the yield and outcome of DBE following CE in patients with obscure GIB. METHODS After DBE became readily available at the Centre for Therapeutic Endoscopy and Endoscopic Oncology (St Michaels Hospital, Toronto, Ontario), all patients with obscure GIB seen from December 2002 to June 2007 were evaluated identically, first with CE, then with DBE (some with further interventions). Findings, adverse outcomes and interventions are reported. RESULTS Fifty-one patients (25 women) with a mean (range) age of 64.1 years (34 to 83 years) are reported. Eight patients underwent DBE twice, for a total of 59 DBEs. Fourteen patients had overt GIB and the median (range) number of red blood cell unit transfusions was 10 (0 to 100). The positive findings for each type of lesion were compared in these 51 patients: angiodysplasia (CE 64.7% and DBE 61%, P=0.3), ulcers (CE 19.6% and DBE 18.6%, P=0.5), bleeding lesions (CE 43.1% and DBE 15.3%, P=0.0004) and mass (CE 10.2% and DBE 8.5%, P=0.5). DBE provided the advantage of therapeutic intervention: argon plasma coagulation (33 of 59 DBEs), clipping (two of 59), both argon plasma coagulation and clipping (three of 59), polypectomy (two of 59), tattooing (52 of 59) and biopsies (11 of 59). DBE detected lesions not seen by CE in 21 patients; lesions were treated in 18 patients. However, CE detected 31 lesions not seen by DBE. No major complications occurred with either examination. CONCLUSION Overall detection rates for both techniques are similar. Each technique detected lesions not seen by the other. These data suggest that CE and DBE are complementary and that both evaluate obscure GIB more fully than either modality alone.

Unsedated transnasal endoscopy: A Canadian experience in daily practice

BACKGROUND Esophagogastroduodenoscopy (EGD) is the most frequently performed diagnostic procedure for upper gastrointestinal disorders. The procedure is routinely performed under conscious sedation in North America. A significant proportion of morbidity and mortality associated with EGD is related to hypoxia due to conscious sedation. The use of sedation is also associated with an increase in cost, loss of work on the day of endoscopy and the need for the patient to be accompanied home after the procedure. Transnasal endoscopy has advantages such as no sedation and less patient monitoring, nursing time and expenses than conventional per oral EGD. OBJECTIVES To assess the feasibility and acceptability of unsedated transnasal EGD in daily practice. METHODS Patients due to undergo EGD were given a choice of either unsedated transnasal EGD or per oral EGD with sedation. Patients who chose unsedated transnasal EGD had the procedure performed in the office by a senior gastroenterologist with experience in transnasal EGD. All procedures were performed using a small-calibre esophagogastroduodenoscope. All patients were surveyed using a patient satisfaction questionnaire, and were asked to give specific scores in terms of choking sensation, sore throat, nasal discomfort and abdominal discomfort. All variables were assessed by scores between 0 and 10, with 10 indicating the most severe degree of each variable. Any complications were also recorded. RESULTS Between March 2002 and August 2003, 231 patients underwent transnasal EGD. The median age of the patients was 57 years (range 15 to 87 years). Complete examinations were possible in 98% of patients. Patients reported a high degree of acceptability (mean score 6.6, range 1 to 10) and low degrees of choking sensation (mean 1.8, range 0 to 10), nasal discomfort (mean 1.7, range 0 to 10), sore throat (mean 0.8, range 0 to 9) and abdominal discomfort (mean 1.1, range 0 to 10). The only complications reported by the patients were epistaxis (n=2, 0.9%) and sinusitis (n=1, 0.4%). Some patients also reported transient light-headedness (n=12, 5%) and mucous discharge (n=2, 0.9%). When asked, 185 patients (88%) stated that they were willing to undergo the same procedure in the future if medically indicated. Of the 84 patients who had conventional EGD under conscious sedation in the past, 52 patients (62%) preferred transnasal EGD without sedation. CONCLUSIONS Transnasal EGD is generally well tolerated, feasible and safe. It can be performed with topical anesthesia in an outpatient setting. The low complication rate, high patient satisfaction and potential cost savings make transnasal endoscopy an attractive alternative to conventional EGD to screen patients for upper gastrointestinal tract diseases.

A prospective study of the repeated use of sterilized papillotomes and retrieval baskets for ERCP: quality and cost analysis

BACKGROUND The impact on instrument quality and cost of the practice of reusing ERCP accessories has not been fully addressed. METHODS Twenty-five new papillotomes and 15 new retrieval baskets were labeled and evaluated over time by staff blinded to the number of prior uses. Instruments were scored as to their function for the designated task. The cost of this practice was calculated from the purchase price of accessories and the costs of cleaning, sterilization, and disposal, and then compared with the estimated cost of a practice of one-time use of similar instruments. RESULTS Twenty-five papillotomes were used 246 times (median 8; mean 9.8). Fifteen retrieval baskets were used 193 times (median 13; mean 12.9). The median survival of both papillotomes and baskets before being considered inadequate (score < 6 out of 10) was 9 uses. There were no complications attributable to using reused equipment. The projected yearly cost savings of using reusable versus disposable instruments was

In Vivo Doppler Optical Coherence Tomography of Mucocutaneous Telangiectases in Hereditary Hemorrhagic Telangiectasia

94,095 for papillotomes and

Diffuse reflectance spectroscopy in Barrett’s Esophagus: developing a large field-of-view screening method discriminating dysplasia from metaplasia

61,809 for baskets, a 475% and 322% cost reduction, respectively. CONCLUSION The papillotomes and baskets in this study could be reused reliably and safely multiple times, with considerable cost savings compared with the practice of using disposable instruments.

Advanced Imaging Technologies for the Detection of Dysplasia and Early Cancer in Barrett Esophagus

BACKGROUND Hereditary hemorrhagic telangiectasia is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Knowledge is limited concerning the development hemodynamics of mucocutaneous telangiectases. Doppler optical coherence tomography can demonstrate microvascular blood flow at flow rates as low as 20 microm/second, which is up to approximately 100 times more sensitive than Doppler US. The aims of this study were to collect in vivo Doppler optical coherence tomography images of mucocutaneous telangiectases and normal surrounding mucosa and skin, and to gain experience for an in vivo GI endoscopic study. It was hypothesized that visibly normal areas may have occult telangiectases and that mucocutaneous telangiectases that have bled may have a higher rate of blood flow than mucocutaneous telangiectases with no history of bleeding. METHODS Twelve patients with hereditary hemorrhagic telangiectasia and mucocutaneous telangiectases were studied. Two to 3 visible mucocutaneous telangiectases on the digits, lips, and tongue were imaged with Doppler optical coherence tomography, along with visually normal surrounding areas at each site. The Doppler optical coherence tomography images were obtained in 0.5 second by using 1310 nm light. RESULTS A total of 67 mucocutaneous telangiectases from the 12 patients were imaged (38 digit, 16 lip, 13 tongue). Blood flow was demonstrated within every mucocutaneous telangiectasis imaged. Doppler optical coherence tomography did not identify any abnormal vasculature within visually normal areas. Mucocutaneous telangiectases with a history of bleeding (n = 18) were situated closer to the surface, compared with mucocutaneous telangiectases with no bleeding history (n = 49), but there was no difference in the Doppler flow appearance. CONCLUSIONS Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not appear to have abnormal vasculature. Mucocutaneous telangiectases with a history of bleeding were more superficial but were otherwise similar to mucocutaneous telangiectases with no bleeding history.