Bleeding lesions within reach of conventional endoscopy in capsule endoscopy examinations for obscure gastrointestinal bleeding: is repeating endoscopy economically feasible?

BACKGROUND: Most tertiary gastroenterology centers currently offer an open-access capsule endoscopy (CE) service, including patients with obscure gastrointestinal bleeding. However, CE may identify lesions missed by conventional endoscopy. AIMS: To determine the incidence of bleeding lesions missed by the preceding gastroscopy/colonoscopy that were revealed by CE and compare potential differences in the rate of identifying such lesions in patients that we investigated as opposed to those investigated elsewhere. METHODS: We prospectively reviewed data from patients subjected to CE for obscure bleeding. We analyzed all cases where a source of bleeding was located in the stomach, duodenum, or colon. RESULTS: A total of 317 consecutive patients were subjected to CE for obscure gastrointestinal bleeding within 28 months. Prior to CE examination, 174 patients had gastroscopy and colonoscopy in our institutions and 143 were referrals, all with negative endoscopic investigation. We identified 11 (3.5%) cases where the source of bleeding was found in the stomach (n = 4) or the cecum (n = 7). There was a significant difference of extra small intestinal lesions diagnosed by CE between referrals (9/143, 6.3%) and endoscopic investigation performed in our institutions (2/174, 1.15%), (p = 0.026). The estimated cost of re-endoscoping in our institution all CE referrals would be 50,050 euro (143 patients × 350 euro), to avoid unnecessary CE examinations (9 patients × 600 euro = 5,400 euro). CONCLUSIONS: Reading the whole CE video is important, because small-bowel CE may identify lesions responsible for obscure bleeding missed by the preceding gastroscopy and colonoscopy. Repeating conventional endoscopy by experts before CE is not a cost-effective approach.

High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis.

Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins, which has been implicated in anti-apoptotic and anti-inflammatory pathways, via binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair in ulcerative colitis (UC) has not been studied. We investigated the systemic (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64 patients with UC and 56 healthy controls. DcR3 serum concentrations were highly elevated in patients with active UC (P<0.0001 vs. healthy controls). This elevation was clearly related to the presence of intestinal inflammation as it was less frequently observed in patients in remission (P=0.003 vs. active UC) whereas effective treatment resulted in disappearance or significant decrease of serum DcR3 (P=0.006 vs. pre-treatment). Furthermore, DcR3 mRNA transcripts were significantly elevated in inflamed areas of the colon (P=0.002 vs. non-affected of the same patient). In addition to DcR3 elevation, we found increased circulating levels of TL1A in patients with either active or inactive UC in comparison to healthy controls (P<0.001 for both). We conclude that elevated serum DcR3 may serve as an indicator of active colonic inflammation in patients with UC. TL1A/DcR3-mediated pathways may participate in the pathogenesis of UC.

Is there a role for second-look capsule endoscopy in patients with obscure GI bleeding after a nondiagnostic first test?

BACKGROUND: Long-term follow-up data on patients with obscure GI bleeding subjected to capsule endoscopy (CE) are missing. OBJECTIVE: Our purpose was to follow up patients with a nondiagnostic test and determine whether a second-look CE would be beneficial. PATIENTS: We enrolled 293 subjects. CE studies were classified as diagnostic (positive findings) or nondiagnostic (findings of uncertain significance/no findings). Patients were followed up for a mean (SD) 24.8 (5.2) months. Outcome was defined as continued or complete resolution of bleeding. INTERVENTIONS: Patients with a nondiagnostic test were subjected to a repeat CE if they manifested a new bleeding episode or a drop in hemoglobin >or=2 g/dL. RESULTS: Positive findings, findings of uncertain significance, and no findings were identified in 41.6%, 16.0%, and 42.3% of our patients, respectively. Therapeutic intervention was possible in 72.1% of those with positive findings and in 30% of those with findings of uncertain significance. Complete resolution of bleeding occurred more often in patients with a diagnostic test (65.2%) compared with those with a nondiagnostic test (35.4%, P < .001). Second-look CE was performed in a subgroup of our patients (n = 76) and was diagnostic in those whose presentation changed from occult to overt or those whose hemoglobin dropped >or=4 g/dL. CONCLUSIONS: In patients with obscure GI bleeding, a diagnostic CE leads to therapeutic interventions and a favorable outcome. Patients with a nondiagnostic test would definitely benefit from a second-look CE if the bleeding presentation changes from occult to overt or if the hemoglobin value drops >or=4 g/dL.

PillCam Colon capsule endoscopy does not always complement incomplete colonoscopy.

BACKGROUND: There are no data on the role of PillCam Colon capsule (PCC) endoscopy for examination of the colon in incomplete colonoscopy cases. OBJECTIVE: To evaluate whether PCC endoscopy can complete colon examination after failure of conventional colonoscopy to visualize the cecum. SETTING: Three tertiary centers. STUDY DESIGN: Retrospective case series. PATIENTS: Patients who underwent PCC endoscopy after incomplete colonoscopy from January to June 2008. INTERVENTIONS: Conventional colonoscopy and PCC endoscopy. RESULTS: By using PCC, we studied 12 patients who had incomplete colonoscopy. Six patients had an obstructing tumor of the left side of the colon, and, in 6 cases, there were technical difficulties to complete colonoscopy. PCC endoscopy visualized the rectum in 1 case. The capsule did not reach the site where colonoscopy stopped in 6 of the 12 cases, ie, 3 left sited tumors and 3 with technical difficulties. Moreover, in 1 of the 3 cases in which the capsule passed the site where colonoscopy stopped, poor bowel preparation precluded the accurate examination of the colon. Four patients underwent a third colon examination (3 barium enemas and 1 virtual CT colonoscopy). There were no adverse events related to PCC endoscopy. LIMITATIONS: A retrospective study and a selected patient population. Data may not be applicable to other settings. CONCLUSION: In this retrospective case series of patients with incomplete colonoscopy, PCC endoscopy did not always satisfactorily examine the colon.

Contribution of nuclear morphometry by confocal laser scanning microscopy to the diagnosis of malignant bile duct strictures.

OBJECTIVE: To determine the clinical utility of nuclear morphometry by confocal laser scanning microscopy for the diagnosis of malignant biliary strictures. STUDY DESIGN: The study included 51 patients with bile duct strictures who underwent endoscopic retrograde cholangiopancreatography (ERCP). Based on the initial workup, 6 patients were diagnosed with benign strictures, and 12 patients had malignant strictures, while in the remaining 33 cases the diagnoses were inconsistent, due mainly to inadequate samples. Smears from ERCP brushings were stained for DNA with propidium iodide. Nuclear morphometry was assessed on images acquired by a confocal laser scanning microscope. Three parameters-nuclear volume, nuclear shape and nuclear staining intensity-were calculated. Based on these features, a distinctive nuclear morphometric pattern was attributed to the malignant nuclei, and its predictive value was assessed prospectively in the 33 undiagnosed cases. RESULTS: After an overall median follow-up period of 8 months, 19 patients were diagnosed with malignant strictures, and 14 patients were considered to have benign strictures. With respect to the prediction of malignancy, the sensitivity of the described method was 78%, the specificity was 63%, the positive predictive value was 64%, and the negative predictive value was 80%. CONCLUSION: Nuclear morphometry may provide significant information for the diagnosis of malignant bile duct strictures when conventional cytology fails to.

Insulinlike growth factor I receptor and estrogen receptor beta expressions are inversely correlated in colorectal neoplasms and affected by the insulin resistance syndrome.

The present study aimed at evaluating the modulation of insulin-like growth factor I receptor (IGF-IR) and estrogen receptor beta (ER-beta) expression and their correlation during tumorigenesis of sporadic colorectal cancer, with particular interest in the insulin resistance syndrome. In a series of 100 individuals (54 men and 46 women; mean age, 67.3 +/- 9.4 years) with colorectal neoplasms, classified as early adenomas (n = 25), advanced adenomas (n = 44), and adenocarcinomas (n = 31), IGF-IR and ER-beta expression was quantified in formalin-fixed, paraffin-embedded biopsy specimens, using confocal laser scanning microscopy and a computer-based method for assessment of immunofluorescent staining. All individuals were evaluated for insulin resistance markers (hyperglycemia, dyslipidemia, central obesity, and arterial hypertension), and 50 (26 men and 24 women; mean age, 68.2 +/- 9.0 years) were diagnosed with the insulin resistance syndrome. For the sequence of early adenoma-advanced adenoma-adenocarcinoma, a gradual increase in IGF-IR expression and a gradual decrease in ER-beta expression were observed. The partial correlation coefficient between IGF-IR and ER-beta expression, controlled for age, sex, insulin resistance, type of lesion, and location of lesion was 0.295 (P = .004, 2-tailed significance). Analysis of variance demonstrated that the effect of the insulin resistance syndrome on IGF-IR and ER-beta expression was significant (P = .007 and P = .018, respectively). The results suggest the combined effect of IGF-I and estrogens in colorectal cancer, with a distinctive role in individuals with the insulin resistance syndrome.

Fibroblast activation protein and its prognostic significance in correlation with vascular endothelial growth factor in pancreatic adenocarcinoma.

Fibroblast activation protein (FAP), a selective protein for tumor stromal fibroblasts, is expressed in >90% of human epithelial carcinomas. A characteristic feature of pancreatic cancer is an extensive fibrotic or desmoplastic reaction surrounding the primary tumor. The present study aimed to evaluate the expression levels of FAP and vascular endothelial growth factor (VEGF) and determine their correlation in pancreatic adenocarcinoma. Confocal laser scanning microscopy and conventional immunohistochemical analysis were used to quantify FAP and VEGF expression levels in formalin­fixed and paraffin­embedded tissue biopsies from 46 patients (male, 26; female, 20; mean age, 66 years; age range, 53­80 years) with pancreatic adenocarcinoma stage IIA or IIB. The expression levels of FAP in the neoplastic and adjacent normal tissue were significantly higher in stage IIB patients, compared with stage IIA patients. FAP expression was correlated with positive lymph nodes, resulting in poor prognosis for stage IIB patients. The partial correlation coefficient between FAP and VEGF expression levels was 0.39 (P=0.007), and the two factors had an effect on patient survival. Multivariate analysis demonstrated the prognostic superiority of FAP over VEGF, which is considered to be the most consistently reproducible molecular marker with prognostic value in resected pancreatic adenocarcinoma. Due to the limited beneficial effect of current systemic therapies for pancreatic adenocarcinoma, targeting FAP may be a potential therapeutic strategy and requires further investigation.

Possible Strongyloides stercoralis infection diagnosed by videocapsule endoscopy in an immunocompetent patient with devastating diarrhea.

Strongyloides stercoralis is an endemic parasitic infection of tropical areas, but it is rare in Europe. Most infected immunocompetent patients are asymptomatic, but may present with abdominal pain and diarrhea even several years after acquiring the infection. However, in immunocompromized patients, hyperinfection syndrome has a high mortality rate. Risk factors for the hyperinfection syndrome are corticosteroids and infection with human T lymphotropic virus type 1. Diagnosis of strongyloidiasis is usually made by identifying the larvae in the stool or in duodenal biopsies. There are only four published cases of strongyloidiasis in Greek patients, three of them were immunocompromized. In our patient videocapsule endoscopy identified rhabditiform larvae suggestive of strongyloidiasis. This case report illustrates the difficulty in establishing a diagnosis of the disease in immunocompetent patients.

Two cameras detect more lesions in the small-bowel than one.

AIM: To explore the feasibility of dual camera capsule (DCC) small-bowel (SB) imaging and to examine if two cameras complement each other to detect more SB lesions. METHODS: Forty-one eligible, consecutive patients underwent DCC SB imaging. Two experienced investigators examined the videos and compared the total number of detected lesions to the number of lesions detected by each camera separately. Examination tolerability was assessed using a questionnaire. RESULTS: One patient was excluded. DCC cameras detected 68 positive findings (POS) in 20 (50%) cases. Fifty of them were detected by the "yellow" camera, 48 by the "green" and 28 by both cameras; 44% (n = 22) of the "yellow" camera's POS were not detected by the "green" camera and 42% (n = 20) of the "green" camera's POS were not detected by the "yellow" camera. In two cases, only one camera detected significant findings. All participants had 216 findings of unknown significance (FUS). The "yellow", "green" and both cameras detected 171, 161, and 116 FUS, respectively; 32% (n = 55) of the "yellow" camera's FUS were not detected by the "green" camera and 28% (n = 45) of the "green" camera's FUS were not detected by the "yellow" camera. There were no complications related to the examination, and 97.6% of the patients would repeat the examination, if necessary. CONCLUSION: DCC SB examination is feasible and well tolerated. The two cameras complement each other to detect more SB lesions.

Subsite-specific differences of estrogen receptor beta expression in the normal colonic epithelium: implications for carcinogenesis and colorectal cancer epidemiology.

OBJECTIVE: This study aimed at investigating whether a differential estrogen receptor beta (ER-beta) expression between the colonic subsites could correspond to a modification in proliferation, apoptosis, and adhesion of the normal colonocytes. METHODS: ER-beta, Ki-67, Bcl-2, and E-cadherin expressions were investigated immunohistochemically, in normal epithelium biopsies from the ascending and the descending colon of 53 individuals, who underwent colonoscopy for the investigation of anemia and in whom no local pathology was identified. RESULTS: ER-beta immunoreactivity has been shown to be stronger at the superficial epithelium than the crypts' base, the difference being important only for the ascending colon. In addition, ER-beta expression was higher in the superficial epithelium of the ascending colon than that of the descending colon. The variations of ER-beta expression did not correspond to the alterations in Ki-67, Bcl-2, and E-cadherin expression. CONCLUSION: A subsite-specific variation of ER-beta expression has been shown in the normal colonic epithelium. This modulation of ER-beta might account for some well established specificities of colorectal cancer epidemiology like the right-sided predominance of the neoplasm in women and its gradual shift to more proximal sites over time.

Impact of capsule endoscopy in obscure small-bowel bleeding: defining strict diagnostic criteria for a favorable outcome.

BACKGROUND: The most frequent indication for capsule endoscopy is to diagnose the cause of obscure GI bleeding. The objective of the study was to determine the impact of capsule endoscopy on the outcome of patients with GI bleeding of obscure origin. METHODS: Ninety-six patients (53 men, 43 women; mean [standard deviation] age, 60.84 years [16.55 years]) were enrolled in the study. All patients have been subjected to gastroscopy, colonoscopy, small-bowel barium follow-through or enteroclysis, and push enteroscopy; no bleeding site had been identified. Capsule endoscopy was performed with the Given M2A video capsule system. By using strict criteria, studies were classified as having positive findings, findings of uncertain significance, and no findings. Outcome was defined as continued or complete resolution of bleeding. RESULTS: Positive findings, findings of uncertain significance, and no findings were identified in 41.7%, 20.8%, and 37.5% of our study population, respectively. The most common lesions seen were angiodysplasias of the small intestine. Therapeutic intervention was possible in 82.5% of patients with positive findings and in 35.0% of patients with findings of uncertain significance. Complete resolution of bleeding, after a median (interquartile range) follow-up period of 14 months (9-17 months), occurred significantly more often in patients with positive findings (68.4%) compared with patients with findings of uncertain significance and no findings (40.8%, p = 0.009). CONCLUSIONS: Capsule endoscopy increases the diagnostic yield in the workup of patients with obscure small-bowel bleeding. Strictly defined positive findings are associated with a favorable outcome.

Somatostatin inhibits gastric acid secretion more effectively than pantoprazole in patients with peptic ulcer bleeding: a prospective, randomized, placebo-controlled trial.

OBJECTIVE: Gastric acid inhibition is beneficial in the management of peptic ulcer bleeding (PUB). The aim of this double-blind study was to test whether somatostatin (SST) increases intragastric pH in PUB as compared with pantoprazole (PAN) and placebo (PLA). MATERIAL AND METHODS: Eligible patients were randomized to receive SST (500 microg/h+250 microg bolus), or PAN (8 mg/h+80 mg bolus) or PLA (normal saline) i.v., for 24 h. All patients underwent gastric pH monitoring during the infusion of the trial drugs. RESULTS: The three groups (SST, n=14; PAN, n=14; PLA, n=15) were comparable for age, gender, aetiology of PUB and laboratory data at admission. Mean (+/-SE) baseline pH levels in the fundus increased during the administration of the trial drugs (SST: 1.94+/-0.18 to 6.13+/-0.37, p<0.0001; PAN: 1.93+/-0.16 to 5.65+/-0.37, p<0.0001; PLA: 1.86+/-0.12 to 2.10+/-0.15, p=0.0917). During the first 12 h of infusion, the mean (+/-SE) percentage time spent above pH 4.0 and 5.4 was higher with SST versus PAN (84.4%+/-4.8 versus 55.1%+/-8.3, p=0.0049 and 74.2%+/-6.5 versus 47.1%+/-8.3, p=0.0163, respectively) and there was a trend favouring the SST group regarding the time spent above pH 6.0 and 6.8 (65.7%+/-6.4 versus 43.3%+/-8.2, p=0.0669 and 49.2%+/-7.7 versus 28.4+/-6.6, p=0.0738, respectively). CONCLUSIONS: In PUB, both SST and PAN inhibit gastric acid secretion as compared with placebo. However, during the first 12 h of the infusion, SST was more effective than PAN in maintaining high intragastric pH. These results may provide a rationale for the administration of SST in PUB.

Bowel preparation increases the diagnostic yield of capsule endoscopy: a prospective, randomized, controlled study.

BACKGROUND: The aim of this study was to determine the value of small-bowel preparation for patients undergoing capsule endoscopy. METHODS: The study design was prospective, randomized, and controlled. Eighty patients referred for capsule endoscopy were randomized into two equal groups. Patients in Group A (mean age 54.40 [15.65] years) ingested 2 L of a polyethylene glycol/electrolyte solution 16 hours before the test, whereas patients in Group B (mean age 59.85 [14.58] years) prepared for the procedure by taking only clear liquids during the prior day. The primary outcome evaluated was the effect of bowel preparation on the quality of capsule images, as assessed with an objective scoring system in which cleansing was graded as "adequate" or "inadequate" by blinded examiners. A secondary outcome was the effect of bowel preparation on diagnostic yield. For this purpose, the results of capsule endoscopy were classified as positive findings, findings of uncertain significance, and no findings. RESULTS: Cleansing of the small intestine was considered "adequate" in 36 patients in Group A (90%) vs. 24 patients of Group B (60%) (p = 0.004). A diagnosis was established in 26 patients in Group A (65%) compared with 12 patients in Group B (30%) (p = 0.003). CONCLUSIONS: Bowel preparation before capsule endoscopy improves visualization of the small intestine, which may lead to an improvement in diagnostic yield.