Identification of SOCS2 and SOCS6 as biomarkers in human colorectal cancer.

BACKGROUND: Over the past years, some members of the family of suppressor of cytokine signalling (SOCS) proteins have emerged as potential tumour suppressors. This study aimed at investigating the clinical significance of SOCS proteins in colorectal carcinoma (CRC). METHODS: We integrated publicly available microarray expression data on CRC in humans, analysed the expression pattern of SOCSs and assessed the predictive power of SOCS2 and SOCS6 for diagnostic purposes by generating receiver operating characteristic curves. Using laser microdissected patient material we assessed SOCS expression on RNA and protein levels as well as their methylation status in an independent CRC patient cohort. Finally, we investigated the prognostic value of SOCS2 and SOCS6. RESULTS: The meta-analysis as well as the independent patient cohort analysis reveal a stage-independent downregulation of SOCS2 and SOCS6 and identify both molecules as diagnostic biomarkers for CRC. We demonstrate a different methylation pattern within the SOCS2 promoter between tumour tissue and normal control tissue in 25% of CRC patients. Furthermore, early CRC stage patients with low expression of SOCS2 display significantly shorter disease-free survival. CONCLUSIONS: Our data offers evidence that SOCS2 and SOCS6 levels are reduced in CRC and may serve as diagnostic biomarkers for CRC patients.

Endoscopic mucosal imaging of gastrointestinal neoplasia in 2013.

The holy grail of gastrointestinal endoscopy consists of the detection, in vivo characterization, and endoscopic removal of early or premalignant mucosal lesions. While our ability to achieve this goal has improved substantially since the development of the modern video-endoscope, inadequate visual inspection, errors of interpretation, and lesion subtlety all contribute to the continued suboptimal detection and assessment of early neoplasia. A myriad of new technologies has thus emerged that may help resolve these shortcomings; high magnification endoscopes, as well as the techniques of dye-based and virtual chromoendoscopy, are now widely available, while confocal laser endomicroscopy and endocystoscopy, optical coherence tomography, and autofluorescence imaging are generally applicable only in a research setting. Such technologies can be broadly categorized according to whether they potentially afford endoscopists improved detection, or real-time characterization, of mucosal lesions. Enhanced detection of otherwise "invisible" lesions, such as a flat area of intramucosal adenocarcinoma within Barrett's esophagus, carries the potential of an endoscopic cure prior to the development into a more advanced or metastatic disease. The ability to characterize a lesion to achieve an in vivo diagnosis, such as a colonic polyp, potentially affords endoscopists the ability to decide which lesions require removal and which can be safely left behind or discarded without histological assessment. Furthermore targeted biopsies, such as in the surveillance of chronic colitis, may prove to be more accurate and efficacious than the current protocol of random biopsies. An important caveat in the discussion of developing technologies in early cancer detection is the fundamental importance of a health-care system that promotes screening programs to recruit at-risk individuals. The ideal tool to optimize the use of endoscopy in population screening would be a panel of reliable biomarkers (blood, stool, or urine) that could effectively select a high-risk group, thus reducing the indiscriminate use of an expensive technology. The following review summarizes the current endoscopic imaging techniques available, and in development, for the early identification of gastrointestinal neoplasia.

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.

'Short' double-balloon enteroscope endoscopic retrograde cholangiopancreatography in patients with a surgically altered upper gastrointestinal tract.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) remains a challenge for endoscopists in patients with surgically altered anatomy of the upper gastrointestinal tract. Double-balloon enteroscopes (DBEs) have revolutionized the ability to access the small bowel. The indication for its therapeutic use is expanding to include ERCP for patients who have undergone small bowel reconstruction. Most of the published experiences in DBE-assisted ERCP have used conventional double-balloon enteroscopes that are 200 cm in length, which do not permit use of the standard ERCP accessories. The authors report their experience with DBE-assisted ERCP using a 'short' DBE in patients with surgically altered anatomy. METHODS: A retrospective review of patients with previous small bowel reconstruction who underwent ERCP with a 'short' DBE at the Centre for Therapeutic Endoscopy and Endoscopic Oncology (Toronto, Ontario) between February 2007 and November 2008 was performed. RESULTS: A total of 20 patients (10 men) with a mean age of 57.9 years (range 26 to 85 years) underwent 29 sessions of ERCP with a DBE. Six patients underwent Billroth II gastroenterostomy, seven patients Roux-en-Y hepaticojejunostomy, five patients Roux-en-Y gastrojejunostomy, one patient Roux-en-Y esophagojejunostomy and one patient a Whipple's operation with choledochojejunostomy. Some patients (n=12 [60%]) underwent previous attempts at ERCP in which the papilla of Vater or bilioenteric anastomosis could not be reached with either a duodenoscope or pediatric colonoscope. All procedures were performed with a commercially available DBE (working length 152 cm, distal end diameter 9.4 mm, channel diameter 2.8 mm). The procedures were performed under conscious sedation with intravenous midazolam, fentanyl and diazepam, except in one patient in whom general anesthesia was administered. Either the papilla of Vater or bilioenteric anastomosis was reached in 25 of 29 cases (86.2%) in a mean duration of 20.8 min (range 5 min to 82 min). Bile duct cannulation was successful in 24 of 25 cases in which the papilla or bilioenteric anastomosis was reached. Therapeutic interventions were successful in 15 patients (24 procedures) including sphincterotomy (n=7), stone extraction (n=9), biliary dilation (n=8), stent placement (n=9) and stent removal (n=8). The mean total duration of the procedures was 70.7 min (range 30 min to 117 min). There were no procedure-related complications. CONCLUSION: DBEs enable successful diagnostic and therapeutic ERCP in patients with a surgically altered anatomy of the upper gastrointestinal tract. It is a safe, feasible and less invasive therapeutic option in this group of patients. Standard 'long' DBEs have limitations of long working length and the need for modified ERCP accessories. 'Short' DBEs are equally as effective in reaching the target limb as standard 'long' DBEs, and overcomes some limitations of long DBEs to result in high success rates for endoscopic therapy.

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.

[Erectile function after permanent prostate brachytherapy: A long term prospective study about 157 cases]. / Etude de la fonction sexuelle à long terme après curiethérapie pour un cancer localisé de la prostate.

INTRODUCTION: The objective of this study was to determine the impact of the preservation of sexual function in the long-term in patients treated with brachytherapy using a validated self-questionnaire and determine the role of different clinical and therapeutic parameters. MATERIAL AND METHOD: From December 1999 to June 2002, 157 consecutive patients treated by prostate brachytherapy have been selected for the study. A questionnaire of the EORTC "QLQ C30" assorted with the module "PR25" has been submitted before treatment and in the second quarter 2007. Hundred and twenty-eight patients returned their questionnaires (81.5 %). Statistical analysis was made with 64 patients. The median follow-up was 6 years (+/-0.57 year). The settings can interfere with sexual function were assessed: age, prostate volume, co-morbidity, adjuvant hormonal therapy, D 90, V 150 and V 240. Statistical analysis was made by way univariate ANOVA procedure and mode Chi(2) and multivariate (logistic regression), the variable being studied "conservation of sexual activity YES/NO". RESULTS: The conservation rate of sexual function was 64 %. No variable can explain the loss of sexual function is reflected statistically significant (p<0.05). The most informative variable in the statistical analysis was the D 90 but is not seen as likely by a significant lack of power (p=0.08 in univariate analysis and p=0.2 in multivariate analysis). CONCLUSION: Brachytherapy for prostate preserved sexual function in the long-term in 64 % of cases (64 patients) and is therefore an attractive alternative for patients wishing to preserve it.

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.

[Primary leiomyosarcoma of the epididymis: a case report with review of the literature]. / Léiomyosarcome de l'épididyme : à propos d'un cas avec revue de la littérature.

Primary epididymal leiomyosarcoma is uncommon: only 16 cases has been reported in the literature. We present an additionnal case in a 78-year-old man, treated for a prostatic adenocarcinoma by gonadorelin (LH-RH) analogue, who had an epididymal tumor. A right orchidectomy with high ligation of the spermatic cord was performed. The diagnostic of primary leiomyosarcoma of the epididymis was made. The patient is dead 2 years later with no recurrence of disease. A review of reported cases is made.

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.

Reproducibility of wireless capsule endoscopy in the investigation of chronic obscure gastrointestinal bleeding.

BACKGROUND: Capsule endoscopy (CE) is a valuable tool in the diagnostic evaluation of obscure gastrointestinal bleeding, but limited information is available on the reproducibility of CE findings. OBJECTIVE: To compare two successive CE studies with push enteroscopy (PE) in patients presenting with chronic obscure gastrointestinal bleeding. METHODS: A prospective study was conducted. Ten patients (seven men and three women) with chronic obscure gastrointestinal bleeding and no contraindications for CE were eligible and completed the trial. For each patient, the first capsule was administered on day 1, the second capsule was administered on day 2 and PE was performed on day 3. Endoscopists were blinded to the capsule findings. Capsule findings were assessed independently by two investigators blinded to PE findings. RESULTS: A potential small intestinal bleeding source was found in 60% of the patients when all the studies were combined. A bleeding source was found in four patients in both CE studies. The second CE also identified a bleeding source in a fifth patient. Interobserver agreement by kappa analysis was 0.642 to 1.000 (P < or 05) for the CE studies. PE identified a potential small bowel bleeding site in four patients, including one patient who had negative CE studies. CONCLUSIONS: This study confirmed the reproducibility of CE findings on successive studies. Some patients did not have a source of bleeding in the small intestine, and all studies found this.

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.

Colonic fermentation and markers of colorectal-cancer risk.

The aim of this study was to determine the effect of soluble fiber on indexes of colon-cancer risk in postpolypectomy and nonpolyp patients. Forty-five postpolypectomy and 49 nonpolyp volunteers completed 2-wk metabolic studies where half of the group received oat-bran supplements and the other half took wheat-brain supplements. Colonic biopsies taken before and after the intervention showed no difference in the index of thymidine colonic-crypt-cell labeling, thymidine-labeling pattern, or nuclear aberrations. Nevertheless, fecal pH was significantly reduced by 0.23 +/- 0.07 pH units (P less than 0.002) as an index of increased colonic fermentation on oat bran. This was not associated with increased basal breath hydrogen concentrations; fecal butyrate concentrations were higher on wheat bran. We conclude that soluble fiber as oat brain appears to have no advantage over wheat bran in modifying putative risk factors for colonic cancer.

Wheat-bran and oat-bran supplements' effects on blood lipids and lipoproteins.

To compare the effects of oat-bran fiber on blood lipids, we studied 84 healthy middle-aged men and women who were placed on metabolic diets, for 2 wk, that were supplemented with either wheat bran (n = 42) or oat bran (n = 42). Fiber supplementation was 1.6 micrograms dietary fiber/J (6.8 g dietary fiber/1000 kcal) to a maximum of 16.4 g fiber/d. Significantly greater decrease with oat than with wheat were seen in total cholesterol (0.56 +/- 0.08 mmol/L and 0.29 +/- 0.08 mmol/L, P = 0.022) and low-density-lipoprotein cholesterol (0.39 +/- 0.07 mmol/L and 0.15 +/- 0.07 mmol/L, P = 0.024). No significant differences were seen in high-density lipoprotein, apolipoproteins A-1 and B, or triglyceride. We conclude that oat bran has an advantage over wheat bran in lowering serum lipids when tested in metabolic diets on large numbers of individuals with an initial mean serum cholesterol concentration above the desirable range, at 5.61 +/- 0.16 mmol/L.

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.

Mixed hyperplastic adenomatous polyps--an underdiagnosed entity. Report of a case of adenocarcinoma arising within a mixed hyperplastic adenomatous polyp.

We report a case of colonic adenocarcinoma arising within a polyp with mixed morphology of a hyperplastic polyp and tubular adenoma. Despite the relatively small size of the polyp, two isolated foci of adenocarcinoma in situ were present and tumor islands invaded the submucosa. Isolated areas, morphologically resembling hyperplastic glands, and varying degrees of atypia. Though rare, some hyperplastic polyps may be precursors of adenomas.

Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer.

Rectal biopsies and fecal collections were obtained from a consecutive series of 34 outpatients prior to colonoscopy at a gastroenterology clinic. Subsequently, 14 were found to have no colonic pathology, 13 had adenomatous polyps, (3 of those had a previous history of colon cancer) and 7 were diagnosed with colon cancer. In confirmation of earlier studies the tritiated thymidine labelling index was higher in patients with tumors than in those without pathology (7.9% vs. 5.8% with P = 0.06). The patients with colonic tumors also had significantly higher levels of deoxycholic acid (P = 0.01) and lithocholic acid (P = 0.005) in the aqueous extract of their feces. This study shows that these biochemical measures may indicate colon cancer risk.

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.