Sightline ColonoSight system for a disposable, power-assisted, non-fiber-optic colonoscopy (with video).

BACKGROUND: The Sightline ColonoSight (CS) colonoscopy system presents 3 technologic advances: (1) disposable components protect the reusable parts from contact with colonic contents, eliminating the need for disinfection between procedures, (2) an air-pressure-powered engine assists in colonoscope advancement, (3) light emitting diode (LED) illumination eliminates the need for fiber optics and an external light source. OBJECTIVES: To study the operation, performance, and safety of the Sightline CS colonoscopy system. DESIGN: The system was tested during colonoscopy in animals and in human pilot studies. An in vitro dye diffusion test, and bacterial cultures (obtained after using the colonoscope in animals and humans) were performed to ascertain the protective integrity of the disposable components. SETTING: Animal centers, hospitals in Israel and Italy, and office endoscopy centers in the United States. PATIENTS: Thirty-three volunteers and 145 patients who required a colonoscopy for various indications. INTERVENTIONS: Colonoscopy, polypectomy, biopsy, and coagulation. MAIN OUTCOME MEASURES: Complications, system function, cecal intubation, and colonoscopy time. RESULTS: The Sightline CS system performed well during a colonoscopy in 19 animals and 178 patients, without complications. Dye studies and bacterial cultures showed no transfer of dye molecules or bacterial organisms across the protective, disposable components. LIMITATIONS: This is an observational pilot study, with no comparative group. CONCLUSIONS: The new Sightline CS colonoscopy system performed well. The disposable components eliminated the need for disinfection of the colonoscope between procedures. Advancement of the colonoscope in the colon was helped by self propulsion of the instrument affected by an air-pressure-powered engine. LED illumination eliminated the need for fiber optics and an external light source.

Small bowel capsule endoscopy: have we conquered the last frontier?

Capsule endoscopy was launched at the beginning of this millennium and has since become a well-established tool for evaluating the entire small bowel for manifold pathologies. CE far exceeded our early expectations by providing us with a tool to establish the correct diagnosis for such elusive gastrointestinal conditions as obscure gastrointestinal bleeding, Crohn's disease, polyposis syndrome and others. Recent evidence has shown CE to be superior to other imaging modalities - such as small bowel follow-through X-ray, colonoscopy with ileoscopy, computerized tomographic enterography, magnetic resonance enteroclysis and push enteroscopy--for diagnosing small bowel pathologies. Since the emergence of CE, more than 650,000 capsules have been swallowed worldwide, and more than 700 peer-reviewed publications have appeared in the literature. This review summarizes the essential data that emerged from these studies.

Hydrogen peroxide in exhaled breath condensate (EBC) vs eosinophil count in induced sputum (IS) in parenchymal vs airways lung diseases.

We compared exhaled breath condensate (EBC) and induced sputum (IS) for assessing inflammation in pulmonary diseases in patients with obstructive lung disease (n = 20), persistent cough >6 months (n = 20), interstitial lung disease (n = 25) and controls (n = 10). EBC was collected by suspending a Teflon perfluoroalkoxy tube installed in an ice-filled container and connected to a polypropylene test tube. IS was recovered after 20' inhalation of 3% saline with an ultrasonic nebulizer, and 300 cells were differentially counted in cytospin Giemsa-stained slides. H(2)0(2) was measured by a method based on oxidation of phenolsulfonphthalein (phenol red) mediated by horseradish peroxidases and H(2)0(2). Pulmonary function tests were performed by conventional methods. H(2)0(2) levels in EBC and % eosinophils in IS were significantly different between groups. A positive and significant correlation was found between % eosinophils in IS and the levels of H(2)0(2) in EBC for each group and for all patients combined.

The role of endoscopy in the evaluation of iron deficiency anemia in premenopausal women.

BACKGROUND: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement under the assumption that the condition is due to excessive menstrual blood loss. OBJECTIVES: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia. METHODS: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes. RESULTS: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 +/- 15 years and their mean hemoglobin level 9.3 +/- 2.3 g/dl. Twenty-eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts. CONCLUSIONS: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi-directional endoscopic evaluation of the gastrointestinal tract.

Mutational analysis of hMsh6 in Israeli HNPCC and HNPCC-like families.

Germline mutations in DNA mismatch repair (DNA-MMR) genes, mainly hMlh1 and hMsh2, underlie Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Germline hMSH6 gene mutations have been reported in a small subset of HNPCC families. In the present study, ethnically diverse individuals with HNPCC and HNPCC-like features were genotyped for hMsh6 germline mutations using exon-specific PCR, DGGE, and DNA sequencing. The study encompassed 92 individuals representing 88 unrelated families who were previously analyzed for Msh2 and Mlh1 mutations: Jewish Ashkenazim (n = 44), non-Ashkenazim (n = 27), Israeli Moslem-Arab (n = 15), Druze (n=3), and Cypriot non-Jews (n = 3). Of the study population, 71 had colon cancer (CRC), mean age at diagnosis was 50.9+/-13.2 years (range 16-73 years), 5 had endometrial cancer (two with concurrent CRC), (mean 43.6+/-3.26 years, range 38-45 years), and unaffected individuals (n = 18) were first degree relatives within HNPCC families and were genotyped at a mean age of 48.3+/-11.7 years (range 30-69 years). Of the 92 individuals analyzed, none showed a truncating hMsh6 mutation, and 6 (6.6%) harbored one of three germline missense mutations: a previously reported one (V878A), and two novel mutations (V509A, S227I). The pathogenic significance of these three missense mutations is yet unclear. In addition, 5 polymorphisms were detected, 2 of which were novel. We conclude that the rate of pathogenic hMsh6 mutations in HNPCC families of Jewish and Mediterranean origin is low, and that mutations in other genes probably account for the phenotype in these families.

Capsule endoscopy: improving transit time and image view.

AIM: To evaluate the effect of various methods of small bowel preparation on the transit time and the quality of visualization of the entire small bowel mucosa. METHODS: Ninety-five patients underwent capsule endoscopy (CE) by easily swallowing the capsule. They were divided into three study groups according to the preparation used: group A (n = 26) by polyethylene glycol (PEG) liter or with sodium phosphate (SP) 12 h prior to the CE study; group B (n = 29) by erythromycin 1 h prior to the CE study; and group C (n = 40) without any preparation. Visualization ranged from good to satisfactory to poor. RESULTS: The gastric emptying time in the group prepared with erythromycin was shorter but without statistical significance and the small bowel transit time was unaffected. In elderly subjects prepared by PEG or SP, the gastric emptying time was significantly longer (163.7 min, P = 0.05). The transit times of the three sub-groups were not affected by gender or pathology. The grade of cleaning of the entire study group was 3.27+/-1.1. The erythromycin group presented significantly the worst quality of images (P = 0.05) compared to the other sub-groups. Age, gender, and pathology had no effect on the quality of the cleaning of the small bowel in the sub-groups. One (1.05%) case had no natural excretion. CONCLUSION: Erythromycin markedly reduces gastric emptying time, but has a negative effect on the quality of the image in the small bowel. The preparation of elderly subjects with PEG or SP has a negative effect on the small bowel transit time.

Genetic analysis of familial colorectal cancer in Israeli Arabs.

Colorectal cancers (CRC) among Israeli Arabs differ from those diagnosed in Jewish Israeli individuals in two manners: an earlier age of occurrence and a low frequency. These differences are unaccounted for and thus prompted us to perform genetic analysis in Israeli Arab CRC patients. Analysis included the major Hereditary non-polyposis colorectal cancer (HNPCC) genes and the APC I1307K mutation (MIM# 175100.0029). Twenty-five patients and 25 relatives from 24 unrelated families were clinically classified according to personal and familial cancer history. If MSI (microsatellite instability) was displayed in tumor tissue, patients underwent mutation analysis of the MSH2 and MLH1 genes using DGGE (denaturing gradient gel electrophoresis) and sequencing. MSI was detected in 9/21 of the tumors tested (43%). Two novel missense mutations were diagnosed among 11 fully analyzed patients: a change of A to G at position 380 in MSH2 (N127S), and a D601G mutation in MLH1. The I1307K mutation was detected in 8 families (8/24, 33.3%). This is the first report of genetic analysis in familial CRC associated genes among Israeli Arabs. We suggest that the I1307K mutation may contribute to CRC in Israeli Arabs and that inactivating mutations of MSH2 and MLH1 may not be a major cause for early onset CRC.

Capsule endoscopy in real life: a four-centre experience of 160 consecutive patients in Israel.

OBJECTIVE: The Given Capsule procedure is a new system designed to aid the gastroenterologist in diagnosing small-bowel disease. Capsule endoscopy has provided gastroenterologists with easy access to small-bowel mucosa for examination by direct visualisation. The aim of our prospective study was to determine the indication for capsule endoscopy and to describe the identified pathology within the gastrointestinal tract. METHODS: Patients with unexplained gastrointestinal bleeding from suspected small-bowel pathology of an undisclosed nature or with unexplained abdominal pain for more than 6 months were eligible to undergo capsule endoscopy. Patients with suspected intestinal obstruction or with a history of major abdominal surgery were excluded. RESULTS: One hundred and sixty patients (70 women, 90 men; mean age 49.0 +/- 19.8 years, range 13-91 years) ingested the capsule easily. They had undergone 6 +/- 2.9 investigative procedures before capsule endoscopy. Two (1.25%) patients who had non-natural excretions underwent surgery: one was found to have Meckel's diverticulum and the other had stricturing Crohn's disease. The mean haemoglobin in iron-deficiency anaemia patients was 9.1 +/- 2.2 g%. The diagnostic yield of capsule endoscopy was 57.7% in iron-deficiency anaemia and 52.4% in suspected Crohn's disease. CONCLUSIONS: Capsule endoscopy detected the more clinically significant intestinal lesions. It was of diagnostic value in patients with obscure bleeding, suspected Crohn's disease and malabsorption, but the diagnostic yield in patients with chronic pain or irritable bowel syndrome-type symptoms was low.

First histologic confirmation of the diagnosis made by the new wireless-capsule endoscopy.

Wireless-capsule endoscopy is a new painless technique for endoscopic imaging of the small bowel. A 63-year-old male with iron deficiency anemia and thrombocytosis and extensive negative workup was examined twice with the capsule and was found to have multiple bluish polypoid lesions with a villous-appearing texture. Some of these lesions actually were seen to be bleeding. This is the first time that we have obtained histologic evidence for lesions seen only on the video-capsule endoscopy. The lesion was reached by deep ileoscopy via colonoscopy. On histologic analysis, there was acute and chronic ileitis.

Effect of oral purgatives on gastric and small bowel transit time in capsule endoscopy.

BACKGROUND: During ingestible capsule endoscopy, video images are recorded throughout the device's natural propulsion through the digestive system. Shortening the transit time of the wireless video capsule through the stomach and small bowel could reduce the time needed to read and analyze the resultant images, utilize more effectively the short life of the capsule battery (7 +/- 1 hours) and make it possible to image the entire small bowel. OBJECTIVE: To measure gastric and small bowel transit times, with and without preparation, using capsule endoscopy. METHODS: Capsule transit times through the stomach, small bowel and colon were evaluated by analysis of the videos generated during the capsule's passage. The study group included 62 patients with small and large bowel pathologies (e.g., iron deficiency anemia, Crohn's disease). The patients were divided into three groups: prepared with polyethylene glycol (Group A, n = 9), prepared with sodium phosphate (Group B, n = 13), and with no preparation (Group C, n = 40). RESULTS: The gastric emptying times were 20.4 +/- 15.2 minutes in group A, 55.7 +/- 45.1 in group B, and 48.3 +/- 28.7 in group C (P = 0.01). The capsule produced views of the cecum in only 49 of the 62 patients. The mean small bowel transit time for these 49 patients was 238.8 +/- 82.1 minutes, making the mean times for the groups (A,B,C) 148.9 +/- 32.6, 289.4 +/- 77.2 and 249.3 +/- 73.9 minutes respectively (P = 0.0001). CONCLUSION: Compared to both SP and no preparation, preparation of the colon with PEG significantly shortened the transit time of the capsule through the stomach and small bowel.

Ensure preparation and capsule endoscopy: a two-center prospective study.

AIM: To compare small bowel (SB) cleanliness and capsule endoscopy (CE) image quality following Ensure(®), polyethylene glycol (PEG) and standard preparations. METHODS: A preparation protocol for CE that is both efficacious and acceptable to patients remains elusive. Considering the physiological function of the SB as a site for the digestion and absorption of food and not as a stool reservoir, preparation consisting of a liquid, fiber-free formula ingested one day before a CE study might have an advantage over other kinds of preparations. We conducted a prospective, blind-to-preparation, two-center study that compared four types of preparations. The participants' demographic and clinical data were collected. Gastric and SB transit times were calculated. The presence of bile in the duodenum was scored by a single, blinded-to-preparation gastroenterologist expert in CE, as was cleanliness within the proximal, middle and distal part of the SB. A four-point scale was used (grade 1 = no bile or residue, grade 4 ≥ 90% of lumen full of bile or residual material). RESULTS: The 198 consecutive patients who were referred to CE studies due to routine medical reasons were divided into four groups. They all observed a 12-h overnight fast before undergoing CE. Throughout the 24 h preceding the fast, control group 1 (n = 45 patients) ate light unrestricted meals, control group 2 (n = 81) also ate light meals but free of fruits and vegetables, the PEG group (n = 50) ate unrestricted light meals and ingested the PEG preparation, and the Ensure group (n = 22) ingested only the Ensure formula. Preparation with Ensure improved the visualization of duodenal mucosa (a score of 1.76) by decreasing the bile content compared to preparation with PEG (a score of 2.9) (P = 0.053). Overall, as expected, there was less residue and stool in the proximal part of the SB than in the middle and distal parts in all groups. The total score of cleanliness throughout the length of the SB showed some benefit for Ensure (a score of 1.8) over control group 2 (a score of 2) (P = 0.06). The cleanliness grading of the proximal and distal parts of the SB was similar in all four groups (P = 0.6 for both). The cleanliness in the middle part of the SB in the PEG (a score of 1.8) and Ensure groups (a score of 1.7) was equally better than that of control group 2 (a score of 2.1) (P = 0.057 and P = 0.07, respectively). All 50 PEG patients had diarrhea as an anticipated side effect, compared with only one patient in the Ensure group. CONCLUSION: Preparation with Ensure, a liquid, fiber-free formula has advantages over standard and PEG preparations, with significantly fewer side effects than PEG.

Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naïve patients.

AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 µg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by real-time polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean body mass index (27 ± 4 kg/m² vs 24 ± 3 kg/m²; P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-naïve patients with chronic HCV genotype 1 infection significantly improves the viral response.

Capsule endoscopy: Future horizons.

Capsule endoscopy (CE) was launched at the beginning of this millennium and has since become a well established methodology for evaluating the entire small bowel for manifold pathologies. CE far exceeded early expectations by providing a tool for establishing the correct diagnosis for elusive gastrointestinal (GI) conditions such as obscure GI bleeding, Crohn's disease, polyposis syndrome and others. Contemporary CE, like radiology, gives results that can only be read, unlike conventional endoscopic procedures which enable concomitant biopsy when indicated. This is one of the major limitations of the technique. The ideal CE should improve the quality of the image and have a faster frame rate than the currently available one. There should be a therapeutic capsule capable of performing a biopsy, aspirating fluid, delivering drugs as well as measuring the motility of the small bowel wall. Another major leap forward would be the capability of remote control of the capsule's movement in order to navigate it to reach designated anatomical areas for carrying out a variety of therapeutic options. Technology for improving the capability of the future generation capsule is almost within grasp and it would not be surprising to witness the realization of these giant steps within the coming decade.

Post-pyloric feeding.

Postpyloric feeding is an important and promising alternative to parenteral nutrition. The indications for this kind of feeding are increasing and include a variety of clinical conditions, such as gastroparesis, acute pancreatitis, gastric outlet stenosis, hyperemesis (including gravida), recurrent aspiration, tracheoesophageal fistula and stenosis in gastroenterostomy. This review discusses the differences between pre- and postpyloric feeding, indications and contraindications, advantages and disadvantages, and provides an overview of the techniques of placement of various postpyloric devices.

Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel.

BACKGROUND: The molecular mechanisms that underlie colorectal cancer (CRC) include microsatellite instability (MSI), chromosomal instability, and the CpG island methylator phenotype. There is evidence to suggest that CRC incidence varies among different ethnic populations worldwide. The authors of this report hypothesized that environmental factors and lifestyle differences among various ethnic groups may differentially influence the epigenetic regulation of tumor suppressor genes in CRC. METHODS: In the current study, microdissection and DNA extraction were performed on 128 samples of CRC from Israeli patients (85 Jews and 43 Arabs). MSI analysis, mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) protein expression levels, and MLH1 promoter methylation were investigated by combined bisulfite restriction analysis. The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) valine-to-glutamic acid mutation at residue 600 was investigated by direct DNA sequencing. RESULTS: High MSI (MSI-H), MLH1 methylation, and BRAF mutations were observed in 11.6%, 9.4%, and 23.5% of Jews, respectively, and in 16.2%, 17.6%, and 20.9% of Arabs, respectively (P value nonsignificant). MLH1 promoter methylation was observed in 22.6% of microsatellite-stable (MSS) tumors and in 53.8% of MSI-H tumors (P < .015). Extensive methylation (covering both 5' and 3' promoter regions) was present in all MSI-H tumors with loss of MLH1 expression. BRAF mutation was observed in 15.6% and 46.1% of MSS tumors and MSI-H tumors, respectively (P < .007). BRAF mutation was observed in 66%, 22.2%, and 14.7% of patients who had tumors with extensive MLH1 promoter methylation, methylation of the 5' region alone, or without methylation, respectively (P < .006). CONCLUSIONS: There was no difference in molecular signatures examined between Jewish and Arab patients with CRC in Israel. Extensive promoter methylation was associated with MLH1 inactivation, MSI, and BRAF mutation.

Induced sputum eosinophilia in ulcerative colitis patients: the lung as a mirror image of intestine?

BACKGROUND: Ulcerative colitis (UC) is a systemic disease of unknown etiology with extra-intestinal manifestation. Induced sputum (IS) non-invasively assesses extrapulmonary involvement in Crohn's disease. We sought to determine whether there is a cellular marker of lung injury in UC patients detectable by IS. METHODS: Nineteen UC patients (mean age 46.4+/-11.3 years, disease duration 8.6+/-7.5 years [range 1-25 years] 68.4% males) were studied, 6 with active disease and 13 in remission. Eleven received 5-ASA, 5 received steroids and/or azathioprine and 3 patients were untreated. UC patients were compared with 27 healthy non-smoker controls. IS was recovered after 20 min inhalation of 3% saline with an ultrasonic nebulizer by the selecting plugs method, and 300 cells were differentially cell counted in cytospin Giemsa-stained slides. CD4/CD8 subsets were identified by FACS. Pulmonary function tests were performed by the Jaeger Masterlab spirometer. RESULTS: UC patients' IS contained higher %eosinophils than controls (p=0.05) and lower FEV(1)/FVC ratios (p=0.001). Steroid- and/or azathioprine-treated patients had significantly lower FEV(1)/FVC ratios than only 5-ASA-treated patients (p=0.019). Eosinophil infiltration in airways was high in 5-ASA-treated patients compared to those receiving steroids and/or azathioprine (p=0.046) and those with less extensive disease (p=0.05). Using a cutoff of 3% eosinophils, IS had a sensitivity of 67% and specificity of 73% to differentiate patients with a cutoff of 70 eosinophils/mm(2) in biopsy. CONCLUSIONS: The percentage of sputum eosinophils is significantly different between UC patients with proctitis and pancolitis. These immune abnormalities may be a common pattern that is present throughout the mucosae.

Macroamylasemia as the first manifestation of celiac disease.

Macroamylasemia is a biochemical disorder characterized by an elevated serum amylase activity resulting from the circulation of a macromolecular complex of amylase with a serum component, often an immunoglobulin. The increased molecular weight of this complex prevents the normal renal excretion of the enzyme. A few cases of celiac patients with macroamylasemia have been published in whom the biochemical disorder disappeared after treatment with a gluten-free diet.

Effect of erythromycin on image quality and transit time of capsule endoscopy: a two-center study.

AIM: To compare the effect of oral erythromycin vs no preparation with prokinetics on the transit time and the image quality of capsule endoscopy (CE) in evaluating small bowel (SB) pathology. METHODS: We conducted a retrospective, blinded (to the type of preparation) review of 100 CE studies, 50 with no preparation with prokinetics from one medical center (Group A) and 50 from another center with administration of a single dose of 200 mg oral erythromycin 1 h prior to CE (Group B). Gastric, SB and total transit times were calculated, the presence of bile in the duodenum was scored, as was cleanliness within the proximal, middle and distal intestine. RESULTS: The erythromycin group had a slightly shorter gastric transit time (21 min vs 28 min, with no statistical significance). SB transit time was similar for both groups (all P > 0.05). Total transit time was almost identical in both groups. The rate of incomplete examination was 16% for Group A and 10% for Group B (P = 0.37). Bile and cleanliness scores in different parts of the intestine were similar for the two groups (P > 0.05). CONCLUSION: Preparation for capsule endoscopy with erythromycin does not affect SB or total transit time. It tends to reduce gastric transit time, but it does not increase the cecum-reaching rate. Erythromycin does not adversely affect image quality. We consider the routine use of oral erythromycin preparation as being unjustified, although it might be considered in patients with known prolonged gastric emptying time.