Length of Barrett's segment predicts success of extensive endomucosal resection for eradication of Barrett's esophagus with early neoplasia.

BACKGROUND: Although the efficacy and safety of extensive endomucosal resection (EMR) in eradicating Barrett's esophagus (BE) harbouring early neoplasia have been established, factors predicting efficacy remains unclear. AIM: To determine the complete eradication rate of Barrett's esophagus with high-grade intraepithelial neoplasia (HGIN) or intramucosal carcinoma (IMC), safety, and factors predicting complete eradication by EMR. METHODS: Patients with histological confirmation of Barrett's HGIN/IMC were prospectively identified. EMR was performed using Duette multiband ligator or cap technique by a single operator (NEM). RESULTS: 99 patients (81 males) with median age 67 years [interquartile range (IQR) 60-77 years] and median Barrett's length 4 cm (IQR 2-6 cm) were included. Of 628 index EMRs [mean 6.3, median 5 (IQR 3-8)], 23% showed IMC, 58.5% showed HGIN, and 16% showed low-grade dysplasia only. A median of 8 EMR resections per patient (IQR 6-16, 1,064 resections in 89 patients) resulted in complete eradication of BE harboring neoplasia in 49.4% and eradication of HGIN/IMC in 81% (BE <5 cm subgroup: 65% complete eradication and 91% HGIN eradication) at median follow-up of 18 months (range 6-27 months). On univariate analysis, focal dysplasia (P = 0.003) and Barrett's length <5 cm (P = 0.001) were predictors of complete BE eradication. Barrett's length <5 cm was the only significant predictor [odds ratio (OR) 3.4, standard error (SE) 0.11, P = 0.0006] on multiple logistic regression analysis. Strictures developed in 27% and major bleeding in 2% with no procedure-related perforations or mortality. CONCLUSIONS: Extensive EMR for removal of BE with early neoplasia is safe. Outcomes for complete BE eradication are modest at 49.4% and eradication of high-grade dysplasia at 81%. Barrett's length <5 cm is the only significant predictor of complete response.

Fluticasone propionate for treatment of esophageal lichen planus. A case series.

Esophageal lichen planus is a rare condition, and although the majority of cases occur in conjunction with lichen planus at other sites, the endoscopic features are often misinterpreted resulting in a delay in diagnosis. We report a series of five patients presenting to our unit between 2005 and 2009. All five patients were female and presented with dysphagia. Endoscopy demonstrated proximal esophageal stricturing in four patients. Characteristic histological findings were found in four patients. Lichen planus was diagnosed at other sites, and preceded gastrointestinal symptoms, in all patients; five had oral involvement, two had genital involvement, and one had dermal involvement. All patients received proton pump inhibitor therapy without demonstrable benefit. Administration of oral fluticasone proprionate resulted in symptomatic improvement in three patients.

Esophageal papillomatosis complicated by squamous cell carcinoma.

Esophageal papillomatosis is a very rare condition that is believed to have a benign clinical course. Recent reports underscore the potential development of a malignancy in association with squamous papillomatosis of the esophagus. A case of esophageal papillomatosis complicated by the development of esophageal invasive squamous cell carcinoma diagnosed after esophagectomy, despite multiple nondiagnostic endoscopic biopsies, is described. The patient also developed squamous cell carcinoma in the oral cavity and pyloric channel. The finding of extensive esophageal papillomatosis and unremitting dysphagia symptoms should prompt investigations into an underlying associated malignancy.

Characterization of tissue autofluorescence in Barrett's esophagus by confocal fluorescence microscopy.

High grade dysplasia and early cancer in Barrett's esophagus can be distinguished in vivo by endoscopic autofluorescence point spectroscopy and imaging from non-dysplastic Barrett's mucosa. We used confocal fluorescence microscopy for ex vivo comparison of autofluorescence in non-dysplastic and dysplastic Barrett's esophagus. Unstained frozen sections were obtained from snap-frozen Barrett's esophagus biopsy samples and scanned with confocal fluorescence microscopy (458 nm excitation; 505-550 nm [green] and > 560 nm [red] emission). Digital micrographs were taken from areas with homogenous and specific histopathology. Visual inspection and statistical analysis were used to evaluate the image datasets. Dysplastic and non-dysplastic Barrett's esophagus epithelia fluoresced mainly in the green spectrum and the main sources of autofluorescence were the cytoplasm and lamina propria. High-grade dysplasia was differentiated from non-dysplastic Barrett's esophagus by microstructural tissue changes. However, there were no specific changes in either the locations or average intensities of intrinsic green and red autofluorescence at the epithelial level that could differentiate between dysplastic and non-dysplastic Barrett's esophagus epithelia, ex vivo. Detectable differences in autofluorescence between BE and dysplasia/cancer in vivo are probably not caused by specific changes in epithelial fluorophores but are likely due to other inherent changes (e.g. mucosal thickening and increased microvascularity) attenuating autofluorescence from the collagen-rich submucosa. Furthermore, confocal fluorescence microscopy provides 'histology-like' imaging of Barrett's tissues and may offer a unique opportunity to exploit microstructural tissue changes occurring during neoplastic transformation for in vivo detection of high-grade dysplasia in Barrett's patients using newly developed confocal fluorescence microendoscopy devices.

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.

Endoscopy in the elderly patient.

In the elderly who require endoscopy for diagnosis and /or intervention, the endoscopist should be aware of the special risks related to the presence of concomitant systemic diseases. This is especially pertinent in the use of sedatives and analgesics due to the altered physiological functions related to ageing. This can be further complicated by the fact that elderly patients are often prescribed multiple drugs, which makes for the possibility of serious drug interactions. Endoscopy is a minimally invasive technique that is safer than conventional surgery in many conditions. The endoscopist must take into consideration the important factors related to quality of life, as well as the wishes of the patients and their families. The endoscopist must be sympathetic to their wishes and realize when investigation and treatment are not appropriate.

In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy.

Raman spectroscopy (RS) has potential for disease classification within the gastrointestinal tract (GI). A near-infrared (NIR) fiber-optic RS system has been developed previously. This study reports the first in vivo Raman spectra of human gastrointestinal tissues measured during routine clinical endoscopy. This was achieved by using this system with a fiber-optic probe that was passed through the endoscope instrument channel and placed in contact with the tissue surface. Spectra could be obtained with good signal-to-noise ratio in 5 s. The effects on the spectra of varying the pressure of the probe tip on the tissue and of the probe-tissue angle were determined and shown to be insignificant. The limited set of spectra from normal and diseased tissues revealed only subtle differences. Therefore, powerful spectral-sorting algorithms, successfully implemented in prior ex vivo studies, are required to realize the full diagnostic potential of RS for tissue classification in the GI.

A randomized, double-blind study of the use of droperidol for conscious sedation during therapeutic endoscopy in difficult to sedate patients.

BACKGROUND: Droperidol has been used in combination with narcotics and benzodiazepines to achieve conscious sedation. We performed a randomized, double-blind, study of droperidol in patients at risk for difficult sedation scheduled for therapeutic endoscopy. METHODS: Patients with regular ethanol, narcotic, or benzodiazepine usage, suspected sphincter of Oddi dysfunction, or a history of difficult sedation were eligible for the study. Patients were randomized to receive either droperidol or placebo along with midazolam and meperidine as preprocedure sedation. Time to achieve sedation, interruptions due to undersedation, medication dosages, recovery time, and subjective assessments of sedation were recorded. RESULTS: One hundred one patients were randomized. The droperidol group had significantly fewer procedure interruptions and observer ratings of difficulty with sedation and required significantly less midazolam (23%) and meperidine (16%) than the placebo group. There were no significant differences in time to achieve sedation, incomplete procedures, procedure length, recovery room time, or complications. There were significantly higher observer ratings of the quality of sedation for patients who received droperidol. CONCLUSIONS: Droperidol is a useful adjunct to conscious sedation in patients who are difficult to sedate. Its use results in significantly fewer interruptions due to poor sedation and improved sedation ratings compared with sedation using midazolam and meperidine alone.

Light-induced fluorescence endoscopy of the gastrointestinal tract.

The early detection of dysplasia and superficial malignant lesions of the gastrointestinal tract is of significant clinical importance. Recent advances in fluorescence-based endoscopic imaging and spectroscopy of the gastrointestinal tract may offer alternative means of detecting and identifying premalignant and malignant lesions that were otherwise occult or nonspecific on conventional white-light endoscopy. The purpose of this article is to present a general overview of the current developments and possible clinical roles of light-induced fluorescence endoscopy as an adjunct to routine diagnostic endoscopy to enhance screening and surveillance for premalignant and malignant gastrointestinal lesions.

Expandable metal stents for benign esophageal obstruction.

Extensive experience with expandable metal stents for benign esophageal obstruction is limited. A review of the literature demonstrates a high incidence of complications varying from stent migration to stent-induced trauma leading to fistulization. The most common complication (41%) is that of stent-induced stenosis caused by granulation tissue and fibrosis. Currently, the authors do not recommend the routine use of expandable metal stents for benign obstruction. Each case must be assessed on its own merits and risks. The solution in the future may well have to be new stent configuration and esophagus-friendly materials.

Is light-induced fluorescence better than the endoscopist's eye?

While recognizing advanced tumours with endoscopy does not generally pose a challenge, cure rates are relatively low, depending on the size and stage of the tumour. Screening tests for cancer are advantageous for diagnosing cancers before the date after which a cure is no longer an option. Many gastrointestinal cancers are diagnosed after the date on which a cure is possible. The present article discusses some of the limitations of conventional white light endoscopy in screening and presents some of the fluorescent-based diagnostics that are being investigated as complements to white light endoscopy. Autofluorescence and fluorescence due to exogenous photosensitizers or precursors are two sources of fluorescence that are being studied. Preliminary results of current investigations are presented, and future research directions are described.

Nonthermal ablation of malignant esophageal strictures. Photodynamic therapy, endoscopic intratumoral injections, and novel modalities.

Several novel nonthermal ablative modalities for the palliation of malignant esophageal stenoses have been developed over the past decade. In this article, the authors review techniques and clinical experience with photodynamic therapy as well as the intratumoral injection of alcohol, cytotoxins, and immunomodulators.

Idiopathic colonic inflammation in AIDS: an open trial of prednisone.

OBJECTIVES: Idiopathic colonic inflammation and ulceration have been described in HIV infection, but only as isolated case reports. We have been treating this condition with a uniform corticosteroid protocol and now report our results. METHODS: We describe the cases of eight patients with HIV infection who had diarrhea for more than 4 wk and inflammation and/or ulceration in the colon at endoscopy, confirmed by biopsy, without any invasive pathogens despite extensive evaluation. Each patient was treated with prednisone, starting at 40 mg/day, then tapered according to a standardized protocol. RESULTS: The diarrhea completely resolved in three patients and partially improved in five. One patient had some improvement but was unable to tolerate the prednisone because of a severe exacerbation of anal warts. He responded to subtotal colectomy. After a minimum follow-up of 8 months (mean, 17 months), only one patient (complete response to prednisone) was found to have an enteric pathogen. In this patient, cytomegalovirus colitis was diagnosed 15 months after prednisone was started. CONCLUSION: Idiopathic colonic inflammation or ulceration in HIV infection (1) may respond to corticosteroid therapy without life-threatening side effects and (2) is only rarely followed by the detection of a recognized pathogen. These observations suggest that enteric pathogens are not missed by standard techniques.

Photodynamic therapy for the treatment of tumor ingrowth in expandable esophageal stents.

BACKGROUND AND STUDY AIMS: Tumor ingrowth through self-expanding metal stents presents a difficult problem for management. The techniques for treating tumor ingrowth have not yet been well described, and the optimal endoscopic approach is not clear. We have recently used photodynamic therapy (PDT) to treat tumor ingrowth through uncovered nitinol mesh stents. PATIENTS AND METHODS: Four patients (mean age 73) with obstructive adenocarcinomas of the distal esophagus had received self-expanding stents for palliation of their dysphagia. After stent placement, tumor ingrowth had caused progressive dysphagia in all of the patients; the dysphagia was graded on a scale from 0 (normal) to 4 (inability to swallow liquids). All of the patients received PDT treatment. RESULTS: After PDT, excellent palliation of the dysphagia was seen in all of the patients, with a mean improvement in the dysphagia score of 2.25 and a mean dysphagia-free interval of 92 days. There were no major complications. CONCLUSION: The use of PDT to treat tumor ingrowth through self-expanding metal esophageal stents is effective and safe.

Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial.

BACKGROUND: Photodynamic therapy (PDT) is a different type of laser treatment from Nd:YAG thermal ablation for palliation of dysphagia from esophageal cancer. METHODS: In this prospective, multicenter study, patients with advanced esophageal cancer were randomized to receive PDT with porfimer sodium and argon-pumped dye laser or Nd:YAG laser therapy. RESULTS: Two hundred thirty-six patients were randomized and 218 treated (PDT 110, Nd:YAG 108) at 24 centers. Improvement in dysphagia was equivalent between the two treatment groups. Objective tumor response was also equivalent at week 1, but at month 1 was 32% after PDT and 20% after Nd:YAG (p < 0.05). Nine complete tumor responses occurred after PDT and two after Nd:YAG. Trends for improved responses for PDT were seen in tumors located in the upper and lower third of the esophagus, in long tumors, and in patients who had prior therapy. More mild to moderate complications followed PDT, including sunburn in 19% of patients. Perforations from laser treatments or associated dilations occurred after PDT in 1%, Nd:YAG 7% (p < 0.05). Termination of laser sessions due to adverse events occurred in 3% with PDT and in 19% with Nd:YAG (p < 0.05). CONCLUSIONS: Photodynamic therapy with porfimer sodium has overall equal efficacy to Nd:YAG laser thermal ablation for palliation of dysphagia in esophageal cancer, and equal or better objective tumor response rate. Temporary photosensitivity is a limitation, but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd:YAG laser therapy.