Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

BACKGROUND AND STUDY AIMS: The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. METHODS: This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. RESULTS: The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. CONCLUSION: A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.

The challenge of comparing digitally captured signatures registered with different software and hardware.

Along with the growing popularity of electronic documents authorised with digitally captured signatures, such evidence has appeared in the work of forensic practitioners. Many different vendors offer signature pads with varying specifications. It is therefore expected that forensic handwriting experts will be called upon to compare questioned and known samples captured with completely or partially different hardware and software combinations. Such cases may be challenging as numerical handwriting data produced by various equipment may differ not only in the type of information captured and its quality, but also in its structure and coding. In this research, numerical data of handwriting - i.e. spatial coordinates, force, and time values - were acquired with 26 different combinations of hardware and software to study characteristics of their coding. The analysis of samples revealed that scaling of numerical data is not only hardware but also software dependent. Therefore, their compliance with the ISO/IEC 19794-7 standard is recommended to improve the data interoperability. This standard emphasizes the importance of supplementing numerical signature data with scaling ratios of the used signing solution. The paper also includes descriptions of several phenomena observed in the acquired data to highlight possible pitfalls in performing inter-solution comparisons in casework.

Features of digitally captured signatures vs. pen and paper signatures: Similar or completely different?

The question of whether digitally captured signatures and conventional signatures executed with a pen on paper differ in their characteristics is of practical relevance for forensic handwriting examiners. Due to gaps in the current literature, the present research is dedicated to this issue. Eighty persons signed in three conditions: a) with a stylus on a pad, b) with an inking pen on a sticky note attached to a signature pad allowing to obtain a digital and an analogue version on paper of one and the same writing simultaneously, and c) with a pen on paper. The first step was to investigate to what extent the character shape and number of pen lifts differ between the digital and analogue representation of one and the same signature. This revealed minor differences which are due to technical characteristics of the devices used. The observed distortions are of minor practical relevance according to ratings by eight participating forensic handwriting examiners. Subsequently, signature characteristics were compared between the three different writing conditions in a casework-oriented way. Statistical multi-level models indicate significant differences between the three signature types, but minor effect sizes in most of the examined characteristics. From the point of view of the participating handwriting examiners, these factors do not fundamentally restrict the comparability between digitally captured and conventional signatures in practice. However, caution should be exercised when generalising the results, as several factors, such as the usage of different signature pads as well as signatures made with the finger instead of a stylus, could result in more important differences compared to pen and paper signatures.

Video-capsule endoscopy gastric and small bowel transit time and completeness of the examination in patients with diabetes mellitus.

BACKGROUND: Small intestine video-capsule endoscopy examination in patients with diabetes mellitus may be incomplete due to delayed gastric emptying. AIM: To measure video-capsule endoscopy gastric and small bowel transit time and to assess the completeness of the examination in diabetes mellitus patients. METHODS: In this retrospective, case-control study, we examined capsule endoscopy videos from 29 consecutive diabetes mellitus patients. Fifty-eight matched for sex, type of preparation, age and reason for referral non-diabetic controls were selected from our video-capsule endoscopy database. Two independent experienced investigators measured transit times and assessed examinations' completeness. RESULTS: Video-capsule endoscopy gastric transit time was significantly longer in diabetes mellitus (87, 1-478 min) compared to non-diabetic patients (24, 4-108 min, p<0.001). The caecum was visualized in 20/29 (69%) diabetes mellitus and 52/58 (89.6%) non-diabetic controls (p=0.02). In 16 diabetes mellitus patients that video-capsule endoscopy reached the caecum, small bowel transit time was significantly shorter (261.2+/-55.5 min) compared to their 32 non-diabetic matched controls (302+/-62.7 min, p=0.03). CONCLUSIONS: Patients with type 2 diabetes mellitus have prolonged video-capsule endoscopy gastric transit time compared to non-diabetic patients. Prospective studies are required to complete our understanding of video-capsule endoscopy transit times in the setting of diabetes mellitus.

Capsule endoscopy; the cumulative experience from its use in 193 patients with suspected small bowel disease.

BACKGROUND/AIMS: This study presents our cumulative clinical experience from the use of wireless capsule endoscopy (WCE) in a large series of Greek patients with suspected small bowel (SB) diseases. METHODOLOGY: Over an 18-month period, 193 patients were evaluated with WCE for suspected SB diseases [108 obscure gastrointestinal (GI) bleeding, 32 chronic diarrhea, 22 suspected and 6 diagnosed Crohn's disease, 16 abdominal pain, 4 refractory celiac disease, 3 polyposis syndromes, 1 Rendu-Osler-Weber disease and 1 Behcet disease]. All patients had undergone upper GI endoscopy and total colonoscopy. WCE findings were characterized as specific or non-specific, depending on whether the patient's signs and symptoms could be sufficiently attributed to them or not. RESULTS: One or more abnormal findings were detected in 161/193 (83%) patients; these were classified as specific in 91/193 (47%). The diagnostic yield of WCE (in terms of specific findings) was significantly higher when evaluating patients with obscure GI bleeding, compared to chronic diarrhea (52% vs. 25%, respectively, p=0.013, 95% CI: 1.33-7.83). Among obscure GI bleeders, specific findings were significantly more in the group of overt rather than occult bleeders (66% vs. 42% respectively, p=0.026, 95% CI: 1.19-5.88). In patients referred for diagnosed or suspected Crohn's disease, WCE findings were compatible with the diagnosis in 5/6 cases (83%) and in 8/22 cases (36%), respectively. In 9 more patients from other groups with a negative previous diagnostic work-up, WCE helped in diagnosing Crohn's disease. Among 16 patients evaluated for abdominal pain, specific findings were identified only in 1 (6%). CONCLUSIONS: WCE seems to be a very useful diagnostic tool in the evaluation of GI bleeding of obscure origin (in both overt and occult bleeders), as well as suspected Crohn's disease. In other indications, such as unexplained chronic diarrhea and abdominal pain, it completes the traditional work-up, but abnormal findings need to be better delineated before WCE can be widely recommended in these cases.

Cisapride, metoclopramide, and ranitidine in the treatment of severe nonulcer dyspepsia.

Cisapride, a prokinetic drug with a novel mechanism of action, was compared with another prokinetic drug, metoclopramide, and an H2-blocker, ranitidine, in the treatment of nonulcer dyspepsia. In a double-blind study, 60 patients with severe dyspeptic symptoms received cisapride 5 mg TID, metoclopramide 10 mg TID, or ranitidine 150 mg BID for 8 weeks. Symptoms were evaluated during treatment and 4 weeks after the end of therapy. All three drugs effectively controlled the symptoms of chronic functional upper gastrointestinal tract disorders. The prokinetic drugs, particularly cisapride, were significantly better than ranitidine in controlling symptoms, especially reflux symptoms. All three drugs were generally well tolerated; cisapride in particular was associated with fewer adverse effects.

A comparative trial of 400 mg cimetidine twice daily and 1000 mg daily in the short-term treatment of duodenal ulceration.

The therapeutic efficacy of cimetidine given as 400 mg twice daily was compared to that of cimetidine given as 1.0 g daily in 4 divided doses (200 mg 3-times daily and 400 mg at night) in two groups of 25 patients (total 50 patients) with active duodenal ulceration. After 4 weeks, healing rates of 72% and 76%, respectively, were observed for the two dosage regimens. Patients who remained unhealed at 4 weeks were treated for a further 4 weeks, after which cumulative healing rates of 84% and 92%, respectively, were obtained. None of the observed differences in healing rates were statistically significant. Symptomatic improvement was similar for the two dosage regimens. No significant adverse reactions were reported.

The role of endoscopic ultrasonography in diagnosis of benign lesions of the upper GI tract.

The contribution of endoscopic ultrasonography (EUS) in the diagnosis of benign lesions of the upper gastrointestinal (UGI) tract was studied in 46 patients with polypoid lesions which were not thought to have invaded adjacent tissues or organs. Precise visualization of the five layers of the UGI tract was possible with EUS. The site of origin of the tumour was also determined. The diameter of the hypochoic lesions ranged between 1-4 cm, with well-defined margins, and were demarcated precisely from adjacent tissues. Lesions included: (1) leiomyoma of the esophagus, stomach, duodenum (n = 7); (2) ectopic pancreatic tissues (n = 3); (3) polyp of the esophagus, stomach or duodenum (n = 12); (4) hypertrophic gastric folds (n = 19); (5) extra gastric compression (n = 5). Patients from groups 1, 2 and 3 had the diagnosis confirmed and staged surgically. It was possible to differentiate between polypoid lesions of the UGI tract and extra gastric compression. The sensitivity of EUS in the diagnosis of benign tumours was 92%.

Detection of interferon inhibitors or antagonists in gastrointestinal malignancies.

BACKGROUND/AIMS: The aim of this study was to investigate the IFN-inhibiting activity in sera from patients with gastrointestinal malignancies, exerted in a variety of cellular types, as well as to elucidate the determinants of cellular sensitivity to such IFN-inhibitors. METHODOLOGY: Sera from 16 patients with gastric cancer and 18 with colon cancer were tested, while sera from 37 healthy blood donors were used as controls. All serum samples, collected before any kind of treatment, were tested for IFN-blocking and endogenous IFN-like activity. These activities were determined by assaying the inhibition of the vesicular stomatitis virus specific cytopathic effect in three cell lines: A549 cells, intestine 407 and Chang liver cells. RESULTS: There was no endogenous IFN in any of the serum samples of patients or controls. Concerning the IFN blocking activity of serum, there was no significant difference between gastric and colon cancer, while a marked variability was prominent depending on the cell line used. 76.4% of serum samples exerted IFN-blocking activity in the A549 cells, 47.05% in the Int-407 cell line and 32.3% in the Chang Liver cells. No control sample had IFN-blocking activity in any of the cell lines tested. CONCLUSIONS: The results support a cytokine and cytokine inhibitors network, mediating pathophysiological events at the cellular level as well as the whole organism. The limited responsiveness of many neoplasias, including digestive system cancer, to IFN treatment might be due to the presence of IFN inhibitors in the patient's serum.

Ranitidine and antacids in the prevention of duodenal ulcer relapse in Greece.

The present study was undertaken to compare the efficacy of ranitidine 150 mg/nocte with that of antacids taken "on demand" in the prevention of recurrence of duodenal ulcer (DU). Two groups (A, B) of patients with DU recently healed by ranitidine or antacids were studied. Patients of Group A (110) healed by ranitidine were put on maintenance treatment with ranitide, and patients of Group B (32) healed by antacids were given antacids "on demand" for a period of one year. Endoscopy was performed at the end of the 6th and 12th months, as well as whenever symptoms appeared. Patients were followed up clinically at 2-month intervals. Relapse rates of 11% (group A) and 34% (group B) were found at the end of the 6th month, (p less than 0.005), while the total relapse rates at the end of the 12th month were 19% and 47%, respectively (p less than 0.005). Recurrences were asymptomatic in 62% (Group A) and 27% (Group B) of patients. No significant side effects were observed. It is concluded that ranitidine 150 mg nocte is significantly superior to antacids "on demand" as far as the recurrence of DU is concerned.

Acute amiodarone-induced hepatitis.

Two fatal cases of amiodarone-induced acute, confluent, necrotic hepatitis are described. The patients, aged 28 and 60, had received a high loading dose of amiodarone. After the first and second day respectively following the administration of amiodarone, the patients developed jaundice, hepatomegaly, high serum transaminases, a prolonged prothrombin time and low cholesterol concentration. They died of hepatic coma and acute renal failure on the fourteenth and fourth day respectively. Needle liver biopsy, performed immediately after death, revealed lesions of acute drug-induced hepatitis with confluent and bridging necrosis. It is proposed that rapid administration of a high loading dose of amiodarone can cause acute confluent necrotic hepatitis. The mode of administration and the dosage of the drug should be re-considered.

Endoscopic ultrasonography in the preoperative staging of colorectal cancer.

BACKGROUND/AIMS: Endoscopic ultrasonography presents a significant progress in imaging methods for the examination of the digestive system and is commonly used in cancer staging. The aim of this study was to quantify the potential of this modality for diagnosis and staging of colorectal cancer. METHODOLOGY: Eighty patients with histologically proven colorectal cancer were included in this study. All patients were preoperatively diagnosed by colonoscopy and biopsies, abdominal computed tomography and endoscopic ultrasonography. The latter was also used to evaluate the depth of tumor invasion and presence of lymph node or distant metastasis prior to surgery. RESULTS: Endoscopic ultrasonography presented 100% sensitivity in cancer detection versus 60% for computed tomography (P < 0.001). Endoscopic Ultrasonography sensitivity in T, N, M and TNM staging was 93.8%, 93.8%, 92.5% and 82.5% with corresponding specificities of 99.2%, 97.9%, 92.5% and 94.2%. Overall, Endoscopic Ultrasonography staging of the patients did not present statistically significant differences with histological staging (P > 0.05). CONCLUSIONS: Endoscopic ultrasonography is of satisfactory accuracy in diagnosis and preoperative staging of colorectal cancer.

Doppler US of superior mesenteric artery in the assessment of ulcerative colitis. A prospective study.

BACKGROUND/AIMS: The purpose of this study was to correlate blood flow velocity in the superior mesenteric artery and activity of ulcerative colitis. METHODOLOGY: Doppler spectral analysis of superior mesenteric artery blood flow velocities were obtained in a blind study from 28 patients after fasting (A1: 13 patients with pancolitis, A2: 5 patients with subtotal colitis, B: 10 patients with left-sided colitis) and 50 healthy volunteers (control group). Disease activity was determined with clinical and endoscopic findings. RESULTS: A significant increase in superior mesenteric artery blood flow measurements was observed in the active pancolitis group A1 [Vsyst = 3.64 +/- 0.18 m/sec and Vdiast = 0.94 +/- 0.09 m/sec as compared with healthy volunteers (Vsyst = 1.14 +/- 0.07 m/sec, Vdiast = 0.38 +/- 0.04 m/sec) P < 0.01. A minor increase in superior mesenteric artery blood flow velocity was observed in patients with subtotal colitis, group A2 (Vsyst = 2.06 +/- 0.14 m/sec, Vdiast = 0.45 +/- 0.05 m/sec) as compared with healthy volunteers P < 0.01. In group B with left sided colitis superior mesenteric artery velocity changes were not statistically significant (P > 0.05). CONCLUSIONS: Doppler US velocity measurement of superior mesenteric artery may be used as an adjunct in the assessment of ulcerative colitis extension and activity.

Eradication of Campylobacter pylori and recurrence of duodenal ulcer. A six-month follow-up study.

Fifty-four patients were studied, 41 men and 13 woman, aged 26-76 years, suffering from duodenal ulcer that healed 4-8 weeks after colloidal bismuth subcitrate therapy (360 mgr twice a day). All patients underwent endoscopy before treatment, 4-8 weeks and 6 months later. Biopsy was taken for campylobacter pylori (C.P.) detection by urease test. All patients were C.P. positive initially. The organisms were eradicated in 36/54 patients (67%) at the end of therapy. Ulcer healing was obtained after 8 weeks in 45/54 patients (83%). They were re-examined 6 months later or sooner if symptoms had recurred. Twenty seven (66%) were then C.P. negative and 14 were C.P. positive. Ulcer recurrence was observed in 15/41 patients (37%) whose ulcer had previously cured. All patients with recurrence were C.P. positive. There was a statistically significant positive correlation between persistence of C.P. and ulcer recurrence rate (p less than 0.001). It is concluded: a) that eradication of C.P. in duodenal ulcer patients has no influence on ulcer healing. b) Duodenal ulcer recurrence is correlated with persistence of C.P.

Clinical trial: effectiveness of chewing-gum in accelerating capsule endoscopy transit time--a prospective randomized, controlled pilot study.

BACKGROUND: Capsule endoscopy (CE) fails to reach the caecum in approximately 20% of patients. Data suggest that chewing-gum, simulating sham feeding, provokes the cephalic phase of gastrointestinal (GI) motor response and may increase GI motility. AIM: To determine whether chewing-gum increases the ability of CE reaching the caecum. METHODS: Prospective, randomized, single-blinded controlled trial. Ninety-three consecutive patients were randomized either to use chewing-gum (n = 47) or not (n = 46). All patients received the identical bowel preparation. Patients chewed one piece of gum for approximately 30 min every 2 h. Two blinded gastroenterologists examined all studies. The number of CE that reached the caecum within 8-h, gastric transit time (GTT) and small bowel transit time (SBTT) were evaluated in all patients. RESULTS: The CE percentage passed into the caecum was higher in the chewing-gum group compared with those in the other (83.0% vs. 71.7% respectively, P = 0.19). Both GTT and SBTT were significantly shorter in the chewing-gum vs. control group [40.8 min (interquartile range: 21-61 min) vs. 56.1 min (interquartile range: 22-78 min) (P = 0.045) and 229.1 min (interquartile range: 158-282 min) vs. 266.2 min (interquartile range: 204-307 min) (P = 0.032) respectively]. Chewing-gum did not adversely affect CE image quality. CONCLUSIONS: Chewing-gum significantly reduces GTT and SBTT during CE. Its use may improve the likelihood of the capsule reaching the caecum without affecting CE image quality.

The role of wireless capsule endoscopy in investigating unexplained iron deficiency anemia after negative endoscopic evaluation of the upper and lower gastrointestinal tract.

INTRODUCTION: Despite undergoing standard endoscopic diagnostic evaluation with eosophagogastroduodenoscopy and ileocolonoscopy, up to 30% of patients with iron deficiency anemia (IDA) have no definitive diagnosis. The aim of this study was to prospectively investigate the role of wireless capsule endoscopy (WCE) in detecting lesions of the small bowel in patients with unexplained IDA after a negative endoscopic work-up. PATIENTS AND METHODS: Between 1 December 2003 and 31 December 2004, 253 consecutive patients who had been referred because of unexplained IDA underwent eosophagogastroduodenoscopy with small-bowel biopsies and ileocolonoscopy. Endoscopic and histological investigations were negative in 51 of these patients (20.2%) and WCE was performed. Air double-contrast enteroclysis was performed following WCE in all these patients. RESULTS: Wireless capsule endoscopy revealed one or more small-bowel lesions that were considered to be a likely cause of the IDA in 29/51 patients (57%): angiodysplasias in twelve patients (23.5%), multiple jejunal and/or ileal ulcers in six patients (11.7%), multiple erosions in four patients (7.8%), a solitary ulcer in three patients (5.9%), polyps in two patients (3.9%), and tumors in two patients (3.9%). Enteroclysis revealed abnormal findings likely to cause IDA in only 6/51 patients (11.8%): multiple ileal ulcers in three patients (5.9%), tumors in two patients (3.9%), and polyps in one patient (1.9%) (enteroclysis VS. WCE, P < 0.0001). WCE revealed all of the radiographic findings and no adverse events were observed. CONCLUSIONS: This study demonstrates the importance of investigating the small bowel with WCE in patients with unexplained IDA after negative standard endoscopic evaluation. Wireless capsule endoscopy is superior to enteroclysis for detecting lesions of the small bowel in patients with unexplained IDA and should be the next diagnostic test of choice after unremarkable standard endoscopic evaluation.

Bowel preparation and the risk of explosion during colonoscopic polypectomy.

Concentration of oxygen, methane, and hydrogen were measured in intracolonic gas samples aspirated through the colonoscope at the time of colonoscopy from 46 patients. Of the above patients 20 prepared either with mannitol (n = 10) or with castor oil (n = 10) had the instrument passed to the caecum without air insufflation or suction. After mannitol, mean intracolonic hydrogen concentration (4.07%) was significantly higher (p less than 0.001) than after castor oil (0.51%). Mean oxygen and methane concentrations were approximately similar. Potentially explosive concentrations of hydrogen (greater than 4.1%) and or methane (greater than 5%) were present in 6/10 patients given mannitol and 2/10 patients given castor oil. Nevertheless only one patient from each group had coexisting oxygen concentrations of more than 5% producing thus a combustile mixture. Routine colonoscopy (using air insufflation and suction) was performed in 26 patients prepared with mannitol. Mean intracolonic hydrogen and methane was 0.63% and 0.88% respectively. The highest recorded concentration of hydrogen was 2.6%, and of methane 2.1%, while all patients had oxygen concentrations of more than 5%. It is suggested, therefore, that routine insufflation and suction before colonoscopic electrosurgical polypectomy should result in safe levels of these gases. The remote possibility of pockets of undiluted gas in explosive concentration, however, indicates the use of an inert gas such as carbon dioxide if mannitol preparation is used before electrosurgery.

Plasma lipoprotein pattern in relation to liver histology after toxic hepatitis and experimental biliary obstruction in rabbits.

Plasma lipoproteins were studied in relation to liver histology in rabbits in the course of toxic hepatitis and compared to those after experimental biliary obstruction. The lipoprotein electrophoretic pattern became deeply abnormal during the acute phase of toxic hepatitis and correlated with the degree of liver injury, improving during recovery. Liver damage was more severe after carbon tetrachloride than after alcohol and milder after allylo-isopropyl-acetamide, a porphyrinogenic substance. Lipoprotein abnormalities were not followed by significantly reduced levels of cholesterol esters in the plasma. In comparison, animals with biliary obstruction developed milder liver damage presented gross abnormalities of plasma lipids and lipoproteins, followed by relative deficiency of cholesterol esterification. It is concluded that lipoprotein changes in acute liver injury, although non-specific, are a sensitive index of liver damage and recovery. Serious acute liver injury can exist without significant fall in cholesterol esters.