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.

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.

Photodynamic therapy and cancer of the esophagus.

Esophageal carcinoma usually is diagnosed at an advanced, incurable stage. In patients with good operative risk, surgery is still considered the ideal treatment. Patients with coexisting major medical conditions in whom resective surgery is precluded may benefit from several therapeutic options, including photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), dilation, thermal destruction, Nd:YAG laser ablation, injection therapy, and placement of prosthetic tubes. Photodynamic therapy with porfimer sodium is thought to have a direct toxic effect on malignant cells via the production of singlet oxygen, which damages the microvasculature of the tumor and renders it ischemic. The 630 nm wavelength used for clinical PDT exhibits the greatest relative degree of light penetration into tissue, with corresponding activation of retained photosensitizer. The efficacy of PDT with porfimer sodium is closely related to stage of disease. It should be emphasized that PDT has been shown to be potentially curative in patients with early, noninvasive tumors of both squamous and glandular (adenocarcinoma) histologies. Eighty-three patients with esophageal carcinoma were treated using PDT. At presentation, 60% of patients had recurrence following previous radiotherapy or chemotherapy. Patients with less advanced disease had a better response to PDT with regard to relief of dysphagia and prolongation of survival. Photodynamic therapy was found to be more useful than Nd:YAG laser therapy for high, upper third lesions, especially circumferential ones. For tumors larger than 8 cm, PDT was twice as effective as Nd:YAG laser therapy in establishing prolonged lumen patency, especially for adenocarcinomas. Photodynamic therapy appears to have the added advantages of fewer treatments and less pain. The role of PDT in gastrointestinal malignancies continues to evolve.

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.

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.

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.

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.

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.

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.

Photodynamic therapy and cancer of the esophagus.

Esophageal cancer is a tumor that, at diagnosis, is often advanced and not curable. In patients with good operative risk, surgery is still considered the ideal treatment. As many patients are elderly and have complicating serious medical conditions which preclude major resective surgery, endoscopic treatment (endoscopic oncology) has become a recent alternative. The endoscopic approach includes dilation, thermal destruction with Bicap probes, Nd. Yag laser, injection therapy, photodynamic therapy (PDT) and prostheses. This work is focused on photodynamic therapy which is safe but continues to be an experimental treatment. Its role in gastrointestinal malignancies is evolving. Currently the best results are to be expected in early lesions where the treatment could be curative.

The endoscopic management of esophageal cancer.

Cancer of the esophagus is a tumor that, at diagnosis, is often advanced and not curable. The traditional treatment for cancer of the esophagus is still surgery. Assessment of palliative treatments including radiation, YAG laser, photodynamic therapy, prosthesis is done.

Injection therapy for colonic diverticular bleeding. A case study.

We report a successful colonoscopic identification of acute massive diverticular bleeding in an elderly patient and successful injection therapy with epinephrine. Colonoscopy is a valuable diagnostic tool in acute lower gastrointestinal (LGI) bleeding when the colon can be adequately visualized. Peridiverticular injection therapy should be considered a safe and effective therapeutic option when the bleeding site can be established.

Pyogenic liver abscess: new concepts of an old disease.

Early recognition of pyogenic liver abscess requires a high index of suspicion. The abrupt onset of hectic fevers and jaundice is rarely seen today; instead, an insidious progression of malaise, abdominal pain, and night sweats is more common. Biliary tract disease is the most frequent underlying disorder. An elevated alkaline phosphatase is a useful clue to the condition, but diagnosis depends on imaging of an abscess cavity followed by aspiration. Treatment involves antibiotics together with drainage, which can often be performed successfully by a nonsurgical percutaneous approach. However, prognosis continues to be poor unless the diagnosis is made promptly.

Appendiceal mucocele: endoscopic appearance.

Appendiceal mucocele is a rare disorder of the vermiform appendix, occurring predominantly in the sixth or seventh decades, and has a distinct female predominance. Very few cases have been reported in the endoscopic literature. We report two patients with appendiceal mucocele, describe and show the colonoscopic appearance of these tumors, and review the literature.

Mucinous ductal ectasia: cholangiopancreatographic and endoscopic findings.

Mucinous ductal ectasia (MDE) is an uncommon disease characterized by a patulous duodenal papilla extruding mucus, and a pancreatogram showing dilation with amorphous filling defects, communication of the mass with the pancreatic duct, the mass usually being located in the head of the pancreas. We have recently treated three men and three women, mean age 66 years, with MDE. All had abdominal pain, while 33% had the clinical picture of pancreatic insufficiency. Three patients had recurrent pancreatitis, and three had biliary obstruction. Endoscopic retrograde cholangiopancreatography and imaging studies showed a patulous papilla draining mucus in six, pancreatic duct dilation in six, filling defects in six, and communication between the cystic mass and the pancreatic duct in five. A distinct finding not previously reported was a separate pancreatic and biliary orifice in two. Three patients had cancer, two cases being metastatic and one being found at surgery (not suspected preoperatively). Therapy included endoscopic biliary drainage in two, surgery in three, while one refused surgery. Of the operated patients, two underwent resection, one of whom had benign disease and the other cancer; both patients are doing well 14 and 32 months after surgery, respectively. One patient underwent pancreatojejunostomy without symptomatic relief, and developed cholangitis 18 months after surgery that was successfully treated with endoscopic drainage. The other two patients treated with biliary drainage died one and 13 months later, respectively. We conclude that MDE has characteristic pancreatographic and endoscopic findings, and that it is commonly associated with malignant degeneration. Surgical resection is the treatment of choice, since MDE is premalignant, and surgery may be curative when the malignancy is resectable.

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.