Incidence of colorectal neoplasms among male pilots

AIM: To assess the prevalence of colorectal neoplasms (adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots.METHODS: Initial screening colonoscopy was performed on average-risk (no symptoms and no family history) airline pilots at the Integrated Cancer Prevention Center (ICPC) in the Tel-Aviv Medical Center. Visualized polyps were excised and sent for pathological examination. Advanced adenoma was defined as a lesion >10 mm in diameter, with high-grade dysplasia or villous histology. The results were compared with those of an age- and gender-matched random sample of healthy adults undergoing routine screening at the ICPC.RESULTS: There were 270 pilots (mean age 55.2 ± 7.4 years) and 1150 controls (mean age 55.7 ± 7.8 years). The prevalence of colorectal neoplasms was 15.9% among the pilots and 20.6% among the controls (P = 0.097, χ² test). There were significantly more hyperplastic polyps among pilots (15.5% vs 9.4%, P = 0.004) and a trend towards fewer adenomas (14.8% vs 20.3% P = 0.06). The prevalence of advanced lesions among pilots and control groups was 5.9% and 4.7%, respectively (P = 0.49), and the prevalence of cancer was 0.7% and 0.69%, respectively (P = 0.93).CONCLUSION: There tends to be a lower colorectal adenoma, advanced adenoma and cancer prevalence but a higher hyperplastic polyp prevalence among pilots than the general population.     

Difference in the prevalence of advanced colon adenoma between patients with gastric neoplasm and healthy people: A STROBE-compliant study

We compared the prevalence of adenoma and cancerous colon polyps in patients undergoing endoscopic removal or gastric surgery for gastric adenoma or gastric cancer and in healthy individuals.The medical records of 707 patients with gastric neoplasm and 798 age- and sex-matched healthy subjects were retrospectively analyzed between January 2010 and July 2018. The clinicopathological characteristics, prevalence of colorectal neoplasm diagnosed by colonoscopy, and risk factors for colorectal polyps were also investigated.When comparing the two groups, the prevalence of overall colorectal polyps and its distribution was not different between the two groups (54.0% vs.49.5%, P = .079), whereas, the number of colon polyps (1.20 ± 1.71 vs 0.99 ± 1.54, P = .015) and the maximal size (3.53 ± 6.14 vs 2.08 ± 2.88, P < .001) were significantly larger in the gastric neoplasm group. The prevalence of advanced colon adenoma was significantly higher in the gastric neoplasm group (10.7% vs 3.8%, P < .001). Risk factors such as elevated glucose levels and the presence of gastric neoplasm were related to the prevalence of all colon polyps. The presence of gastric neoplasm is an important risk factor for advanced colon polyps.Patients with gastric neoplasms had a significantly higher prevalence of advanced colon adenoma. Advanced colon adenoma is associated with the chain from benign adenomas through malignant altered adenomas to advanced colon cancer. Thus, patients with gastric neoplasm are regarded as a high-risk group for colorectal cancer and are recommended for screening colonoscopy at the time of diagnosis.     

Cap-Assisted Colonoscopy Increases Detection of Advanced Adenomas and Polyps

Background

Cap-assisted colonoscopy (CAC) has been reported to increase the adenoma detection rate (ADR) in Asian population. However, CAC trials in non-Asian population have had conflicting results. Studies in North America have shown an improvement in ADRs with the use of CAC, but it mainly included white and African American patients. Given the lack of prospective studies of CAC in Hispanics, we conducted this randomized controlled trial.

Polyp detection rates using magnification with narrow band imaging and white light

AIM: To compare the yield of adenomas between narrow band imaging and white light when using high definition/magnification. METHODS: This prospective, non-randomized comparative study was performed at the endoscopy unit of veteran affairs medical center in Phoenix, Arizona. Consecutive patients undergoing first average risk colorectal cancer screening colonoscopy were selected. Two experienced gastroenterologists performed all the procedures that were blinded to each other's findings. Demographic details were recorded. Data are presented as mean ± SEM. Proportional data were compared using the χ2 test and means were compared using the Student's t test. Tandem colonoscopy was performed in a sequential and segmental fashion using one of 3 strategies: white light followed by narrow band imaging [Group A: white light(WL) → narrow band imaging(NBI)]; narrow band imaging followed by white light(Group B: NBI → WL) and, white light followed by white light(Group C: WL → WL). Detection rate of missed polyps and adenomas were evaluated in all three groups. RESULTS: Three hundred patients were studied(100 in each Group). Although the total time for the colonoscopy was similar in the 3 groups(23.8 ± 0.7, 22.2 ± 0.5 and 24.1 ± 0.7 min for Groups A, B and C, respectively), it reached statistical significance between Groups B and C(P 0.05). The cecal intubation time in Groups B and C was longer than for Group A(6.5 ± 0.4 min and 6.5 ± 0.4 min vs 4.9 ± 0.3 min; P 0.05). The withdrawal time for Groups A and C was longer than Group B(18.9 ± 0.7 min and 17.6 ± 0.6min vs 15.7 ± 0.4 min; P 0.05). Overall miss rate for polyps and adenomas detected in three groups during the second look was 18% and 17%, respectively(P = NS). Detection rate for polyps and adenomas after first look with white light was similar irrespective of the light used during the second look(WL → WL: 13.7% for polyps, 12.6% for adenomas; WL → NBI: 14.2% for polyps, 11.3% for adenomas). Miss rate of polyps and adenomas however was significantly higher when NBI was used first(29.3% and 30.3%, respectively; P 0.05). Most missed adenomas were ≤ 5 mm in size. There was only one advanced neoplasia(defined by size only) missed during the first look. CONCLUSION: Our data suggest that the tandem nature of the procedure rather than the optical techniques was associated with the detection of additional polyps' and adenomas.     

phytoestrogens/insoluble fibers and colonic estrogen receptor β: randomized,double-blind,placebo-controlled study

AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.     

A simple method to improve adenoma detection rate during colonoscopy: Altering patient position

BACKGROUND:

Colonoscopy is currently considered to be the gold standard method for detecting and removing adenomatous polyps. However, tandem colonoscopy studies reveal a pooled polyp miss rate of 22%.

OBJECTIVE:

A prospective randomized trial was conducted to assess whether alteration of patient position during colonoscopy withdrawal increases the adenoma detection rate (ADR).

METHOD:

The study group included 120 patients who presented for elective colonoscopic examination. After reaching the cecum, patients were randomly assigned in a 1:1 ratio to examination in either the left lateral position or other positions (left lateral position for the cecum, ascending colon and hepatic flexure; supine for transverse colon; and supine and right lateral position for splenic flexure, descending and sigmoid colon) first. Examination of the colon was performed segment by segment. The size, morphology and location of all polyps were recorded. Polyps were removed immediately after examination of a colon segment when all positions were completed. ADR and polyp detection rates (PDR) were calculated.

RESULTS:

A total of 102 patients completed the study. Examination in the left lateral position revealed 66 polyps in 31 patients (PDR 30.3%) and 42 adenomas in 24 patients (ADR 23.5%). PDR increased to 43.1% (81 polyps in 44 patients) and the ADR to 33.3% (53 adenomas in 34 patients) after the colon was examined in the additional positions (P<0.001 and P=0.002, respectively). The increase in the number of adenomas detected was statistically significant in the transverse and sigmoid colon. The addition of position changes led to a 9.8% increase in the ADR in the transverse colon, splenic flexure, and descending and sigmoid colon. The frequency of surveillance interval was shortened in nine (8.8%) patients after examination of the colon in dynamic positions.

CONCLUSION:

Alteration of patient position during colonoscopy withdrawal is a simple and effective method to improve ADR.     

Low red blood cell levels of deglycating enzymes in colorectal cancer patients

AIM: To investigate Glyoxalase Ⅰ and fructosamine-3-kinase (FN3K) activity in red blood cells from patients with colorectal adenomas and cancer. METHODS: Thirty three consecutive subjects with one or more histologically confirmed colorectal adenomatous polyps, 16 colorectal cancer patients and a group of 11 control subjects with normal colonoscopy were included in the study. Glyoxalase Ⅰ and FN3K activities were measured in red blood cells using a spectrophotometric and radiometric assay, respectively. RESU...     

Low-dose CT coronary angiography using iterative reconstruction with a 256-slice CT scanner

AIM: To explore whether computer tomography coronary angiography (CTCA) using iterative reconstruction (IR) leads to significant radiation dose reduction without a significant loss in image interpretability compared to conventional filtered back projection (FBP).METHODS: A consecutive series of 200 patients referred to our institution to undergo CTCA constituted the study population. Patients were sequentially assigned to FBP or IR. All studies were acquired with a 256-slice CT scanner. A coronary segment was considered interpretable if image quality was adequate for evaluation of coronary lesions in all segments ≥ 1.5 mm.RESULTS: The mean age was 56.3 ± 9.6 years and 165 (83%) were male, with no significant differences between groups. Most scans were acquired using prospective ECG triggering, without differences between groups (FBP 84% vs IR 82%; P = 0.71). A total of 3198 (94%) coronary segments were deemed of diagnostic quality. The percent assessable coronary segments was similar between groups (FBP 91.7% ± 4.0% vs IR 92.5% ± 2.8%; P = 0.12). Radiation dose was significantly lower in the IR group (2.8 ± 1.4 mSv vs 4.6 ± 3.0 mSv; P < 0.0001). Image noise (37.8 ± 1.4 HU vs 38.2 ± 2.4 HU; P = 0.20) and signal density (461.7 ± 51.9 HU vs 462.2 ± 51.2 HU; P = 0.54) levels did not differ between FBP and IR groups, respectively. The IR group was associated to significant effective dose reductions, irrespective of the acquisition mode.CONCLUSION: Application of IR in CTCA preserves image interpretability despite a significant reduction in radiation dose.     

Impact of sedation type on adenoma detection rate by colonoscopy

Background & AimsEndoscopic detection of polyps and adenomas decreases the incidence and mortality of colorectal cancer. The available data concerning the relationship between the sedation type and adenoma detection rate (ADR) or polyp detection rate (PDR) is inconclusive. The aim of our study was to evaluate the impact of conscious vs. deep (propofol) sedation on the ADR/PDR in diagnostic and screening colonoscopies.MethodsThis was a retrospective cohort study. Patients aged 50–75 years old presenting for a first screening or diagnostic colonoscopy were included. Baseline demographic characteristics were collected, as well as PDR and ADR. Endoscopic withdrawal time and quality of bowel preparation rated in a binary fashion were also collected. Two multivariate logistic regression models were used to evaluate the independent predictors of endoscopic detection of polyps and adenomas.Results574 patients met our inclusion criteria. Mean age was 59.26 ± 7.21 with 52.4% females and an average BMI of 28.08 ± 4.89. 374 patients (65.2%) underwent screening colonoscopies, and deep sedation was performed in 200 patients (34.8%). Only 4.7% had bad bowel preparation. PDR was 70% and ADR was 52%. On bivariate analysis, no significant difference was shown in PDR and ADR between conscious and deep sedation groups (0.70, 0.71; p = 0.712 and 0.50, 0.54; p = 0.394, respectively). On multivariate analysis for PDR, age and withdrawal time were independent predictors. For ADR, age, female sex, and withdrawal time were independent predictors. Sedation type and the indication did not reach statistical significance in both models.ConclusionThe use of deep sedation didn't influence the ADR/PDR quality metrics in our mixed cohort of screening and diagnostic colonoscopies.     

Local corticosterone production and angiotensin-I?converting enzyme shedding in a mouse model of intestinal inflammation

AIM: To investigate local corticosterone production and angiotensin-I converting enzyme (ACE) protein expression and their interaction in healthy and inflamed intestine.METHODS: Acute intestinal inflammation was induced to six weeks old male Balb/c mice by administration of either 3% or 5% dextran sodium sulfate (DSS) in drinking water for 7 d (n = 12 in each group). Healthy controls (n = 12) were given tap water. Corticosterone production and ACE protein shedding were measured from ex vivo incubates of the small and large intestine using EIA and ELISA, respectively. Morphological changes of the intestinal wall were assessed in hematoxylin-eosin stained tissue preparations of jejunum and distal colon. Effects of angiotensin II, captopril and metyrapone on corticosterone production was assessed by incubating pieces of small intestine of healthy mice in the presence of 0.1, 1 or 10 μmol/L angiotensin II, 1, 10 or 100 μmol/L captopril or 1, 10 or 100 μmol/L metyrapone solutions and measuring corticosterone released to the incubation buffer after 90 min (n = 5 in each group).RESULTS: Both concentrations of DSS induced inflammation and morphological changes in large intestines but not in small intestines. Changes were observed as distortions of the crypt structure, mucosal erosion, immune cell infiltration to the mucosa and submucosal edema. Ex vivo corticosterone production (2.9 ± 1.0 ng/mL vs 2.0 ± 0.8 ng/mL, P = 0.034) and ACE shedding (269.2 ± 97.1 ng/mL vs 175.7 ± 52.2 ng/mL, P = 0.016) were increased in small intestines in 3% DSS group compared to the controls. In large intestine, corticosterone production was increased compared to the controls in both 3% DSS (229 ± 81 pg/mL vs 158 ± 30 pg/mL, P = 0.017) and 5% DSS groups (366 ± 163 pg/mL vs 158 ± 30 pg/mL, P = 0.002). Large intestine ACE shedding was increased in 5% DSS group (41.5 ± 9.0 ng/mL vs 20.9 ± 5.2 ng/mL, P = 0.034). Angiotensin II treatment augmented corticosterone production in small intestine at concentration of 10 μmol/L (0.97 ± 0.21 ng/mg protein vs 0.40 ± 0.09 ng/mg protein, P = 0.036).CONCLUSION: Intestinal ACE shedding is increased by DSS-induced intestinal inflammation and parallels local corticosterone production. ACE product angiotensin II stimulates corticosterone formation in healthy intestine.     

Selection of appropriate endoscopic therapies for duodenal tumors: An open-label study,single-center experience

AIM: To determine an appropriate compartmentalization of endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) for duodenal tumors.METHODS: Forty-six duodenal lesions (excluding papillary lesions) from 44 patients with duodenal tumors treated endoscopically between 2005 and 2013 were divided into the ESD and EMR groups for retrospective comparison and analysis.RESULTS: The mean age was 65 ± 9 years (35-79 years). There were 24 lesions from men and 22 from women. The lesions consisted of 6 early cancers, 31 adenomas and 9 neuroendocrine tumors. Lesion location was the duodenal bulb in 15 cases and the descending part of the duodenum in 31 cases. The most common macroscopic morphology was elevated type in 21 cases (45.6%). Mean tumor diameter was 11.9 ± 9.7 mm (3-60 mm). Treatment procedure was ESD (15 cases) vs EMR (31 cases). The examined parameters in the ESD vs EMR groups were as follows: mean tumor diameter, 12.9 ± 14.3 mm (3-60 mm) vs 11.4 ± 6.7 mm (4-25 mm); en bloc resection rate, 86.7% vs 83.9%; complete resection rate, 86.7% vs 74.2%; procedure time, 86.5 ± 63.1 min (15-217 min) vs 13.2 ± 17.0 min (2-89 min) (P < 0.0001); intraprocedural perforation, 3 cases vs none (P = 0.0300); delayed perforation, none in either group; postprocedural bleeding, 1 case vs none; mean postoperative length of hospitalization, 8.2 ± 2.9 d (5-16 d) vs 6.1 ± 2.0 d (2-12 d) (P = 0.0067); recurrence, none vs 1 case (occurring at 7 mo postoperatively).CONCLUSION: ESD was associated with a longer procedure time and a higher incidence of intraprocedural perforation; EMR was associated with a lower rate of complete resection.     

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period.RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 10⁹/L vs 63.3 ± 15.7 × 10⁹/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation.CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.     

Magnifying narrow-band imaging with acetic acid to diagnose early colorectal cancer

AIM:To evaluate the diagnostic characteristics of magnifying endoscopy with acetic acid spray and narrowband imaging(MA-NBI)for early colorectal cancer.METHODS:We conducted a prospective study to evaluate the diagnostic characteristics of MA-NBI in differentiating early colorectal adenocarcinomas from adenomas.To compare the results,we used magnifying endoscopy with NBI(M-NBI)and magnifying endoscopy with crystal violet staining(M-CV).The study was performed in 2 phases.In phase 1,10 colonoscopists at our institution were shown still photographs of 35colorectal polyps(24 adenocarcinomas and 11 adenomas)in M-NBI,MA-NBI,and M-CV.They made diagnostic predictions using a five-grade scoring evaluation.We plotted receiver operating characteristic curves and compared the areas under the curves(AUCs).In phase2,colorectal polyps measuring≥8 mm were prospectively enrolled.During real-time colonoscopy,one ofthe 7 colonoscopists scored the lesion as an adenocarcinoma or an adenoma and assigned a level of confidence to the prediction(high or low).We calculated the accuracy,sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for each method and compared the proportions of highconfidence predictions.RESULTS:In phase 1,the mean±SD AUCs were 0.64±0.031 in M-NBI,0.71±0.066 in MA-NBI,and 0.76±0.059 in M-CV(P<0.05 for M-NBI vs MA-NBI,P<0.001 for M-NBI vs M-CV,and not significant for MANBI vs M-CV).In phase 2,84 patients with 91 lesions(46 adenocarcinomas and 45 adenomas)were enrolled.The diagnostic characteristics were as follows:73%accuracy,85%sensitivity,60%specificity,68%PPV,and 79%NPV in M-NBI;73%accuracy,80%sensitivity,64%specificity,70%PPV,and 76%NPV in MA-NBI;and 73%accuracy,83%sensitivity,62%specificity,69%PPV,and 78%NPV in M-CV.The proportions of high-confidence predictions were 57%in M-NBI,75%in MA-NBI,and 76%in M-CV(P<0.005 for M-NBI vs MA-NBI,P<0.0005 for M-NBI vs M-CV,and P=1.0 for MA-NBI vs M-CV).CONCLUSION:MA-NBI is useful for differentiating early colorectal adenocarcinomas from adenomas.     

Comparison of different gastric bypass procedures in gastric carcinoma patients with type 2 diabetes mellitus

AIM: To determine the effect of different Roux-en-Y gastric bypass procedures in gastric carcinoma patients with type 2 diabetes mellitus.METHODS: A retrospective analysis of the clinical data of 54 patients with gastric cancer and type 2 diabetes mellitus treated in the Department of General Surgery from January 2006 to June 2013 was conducted. The patients underwent gastrectomy using different Roux-en-Y gastric bypass procedures (traditional, n = 26; modified, n = 28). Fasting plasma glucose (FPG), two hour postprandial blood glucose (2 h PBG) and hemoglobin A1c (HbA1c) were analyzed before surgery (0 mo) and 1, 3 and 6 mo after surgery.RESULTS: FPG and 2 h PBG levels were significantly decreased 1 mo after surgery in the traditional Roux-en-Y gastric bypass group (FPG 7.5 ± 1.3 vs 10.7 ± 1.2, P < 0.05) (2 h PBG 10.2 ± 1.8 vs 13.8 ± 3.2, P < 0.05). FPG and 2 h PBG levels were significantly decreased after surgery in the modified Roux-en-Y gastric bypass group (FPG 6.9 ± 1.2 vs 10.5 ± 1.1, 6.5 ± 1.3 vs 10.5 ± 1.1, 6.4 ± 1.2 vs 10.5 ± 1.1, P < 0.05) (2 h PBG 9.9 ± 2.2 vs 14.1 ± 2.9, 9.2 ± 2.4 vs 14.1 ± 2.9, 8.9 ± 2.6 vs 14.1 ± 2.9, P < 0.05). Compared with the levels before surgery, HbA1c levels were significantly decreased 3 and 6 mo after surgery (7.2 ± 1.1 vs 10.5 ± 1.1, 5.5 ± 1.1 vs 10.5 ± 1.1, P < 0.05). Significant differences between the two groups regarding FPG, 2 h PBG and HbA1c concentration were observed 3 and 6 mo after surgery (FPG 10.1 ± 1.5 vs 6.5 ± 1.3, 10.3 ± 1.4 vs 6.4 ± 1.2, P < 0.05) (2 h PBG 13.1 ± 2.8 vs 9.2 ± 2.4, 13.6 ± 3.1 vs 8.9 ± 2.6, P < 0.05) (HbA1c 10.1 ± 1.4 vs 7.2 ± 1.1, 10.5 ± 1.3 vs 5.5 ± 1.1, P < 0.05).CONCLUSION: Modified Roux-en-Y gastric bypass can improve glucose metabolism in type 2 diabetic patients with gastric cancer.     

Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup

AIM: To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized, controlled trial data.METHODS: The Third Eye^® Retroscope^® Randomized Clinical Evaluation (TERRACE) was a randomized, controlled, multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope’s forward view. We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device. Subjects were patients scheduled for colonoscopy for screening, surveillance or diagnostic workup, and each underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC), randomized to SC followed by TEC or vice versa.RESULTS: Indication for colonoscopy was screening in 176/345 subjects (51.0%), surveillance after previous polypectomy in 87 (25.2%) and diagnostic workup in 82 (23.8%). In 4 subjects no indication was specified. Previously reported overall results had shown a net additional adenoma detection rate (ADR) with TEC of 23.2% compared to SC. Relative risk (RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92 (P = 0.029). Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening, 35.7% for surveillance, 55.4% for diagnostic and 40.7% for surveillance and diagnostic combined. The RR of missing adenomas with SC vs TEC was 1.11 (P = 0.815) for screening, 3.15 (P = 0.014) for surveillance, 8.64 (P = 0.039) for diagnostic and 3.34 (P = 0.003) for surveillance and diagnostic combined. Although a multivariate Poisson regression suggested gender as a possibly significant factor, subset analysis showed that the difference between genders was not statistically significant. Age, bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC. Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm, respectively (P = NS).CONCLUSION: TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup, but not in screening patients (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01044732","term_id":"NCT01044732"}}NCT01044732).     

Alterations in gut microbiota during remission and recurrence of diabetes after duodenal-jejunal bypass in rats

AIM: To observe the alterations in gut microbiota in high-fat diet(HFD)-induced diabetes recurrence after duodenal-jejunal bypass(DJB) in rats. METHODS: We assigned HDF- and low-dose streptozotocin-induced diabetic rats into two major groups to receive DJB and sham operation respectively. When the DJB was completed, we used HFD to induce diabetes recurrence. Then, we grouped the DJB-operated rats by blood glucose level into the DJB-remission(DJB-RM) group and the DJB-recurrence(DJB-RC) group. At a sequence of time points after operations, we compared calorie content in the food intake(calorie intake), oral glucose tolerance test, homeostasis model assessment of insulin resistance(HOMA-IR), concentrations of glucagon-like peptide 1(GLP-1), serum insulin, total bile acids(TBAs) and lipopolysaccharide(LPS) and alterations in colonic microbiota.RESULTS: The relative abundance of Firmicutes in the control(58.06% ± 11.12%; P 0.05 vs sham; P 0.05 vs DJB-RC) and DJB-RM(55.58% ± 6.16%; P 0.05 vs sham; P 0.05 vs DJB-RC) groups was higher than that in the sham(29.04% ± 1.36%) and DJB-RC(27.44% ± 2.17%) groups; but the relative abundance of Bacteroidetes was lower(control group: 33.46% ± 10.52%, P 0.05 vs sham 46.88% ± 2.34%, P 0.05 vs DJB-RC 47.41% ± 5.67%. DJB-RM group: 34.63% ± 3.37%, P 0.05 vs sham; P 0.05 vs DJB-RC). Escherichia coli was higher in the sham(15.72% ± 1.67%, P 0.05 vs control, P 0.05 vs DJB-RM) and DJB-RC(16.42% ± 3.00%; P 0.05 vs control; P 0.05 vs DJB-RM) groups than in the control(3.58% ± 3.67%) and DJB-RM(4.15% ± 2.76%) groups. Improved HOMA-IR(2.82 ± 0.73, P 0.05 vs DJB-RC 4.23 ± 0.72), increased TBAs(27803.17 ± 4673.42 ng/m L; P 0.05 vs DJB-RC 18744.00 ± 3047.26 ng/m L) and decreased LPS(0.12 ± 0.04 ng/m L, P 0.05 vs DJBRC 0.19 ± 0.03 ng/m L) were observed the in DJB-RM group; however, these improvements were reversed in the DJB-RC group, with the exception of GLP-1(DJB-RM vs DJB-RC P 0.05). CONCLUSION: Alterations in gut microbiota may be responsible for the diabetes remission and recurrence after DJB, possibly by influencing serum LPS and TBAs.     

Intravoxel incoherent motion diffusion-weighted imaging for monitoring chemotherapeutic efficacy in gastric cancer

AIM: To assess intravoxel incoherent motion diffusionweighted imaging(IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.METHODS: IVIM-DWI was performed with 12 b-values(0-800 s/mm2) in 25 human gastric cancer-bearing nude mice at baseline(day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups(n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calciumfolinate treatment. Together with tumor volumes(TV), the apparent diffusion coefficient(ADC) and IVIM parameters [true water molecular diffusion coefficient(D), perfusion fraction(f) and pseudo-related diffusion coefficient(D*)] were measured. The differences in those parameters from baseline to each measurement(ΔTV%, ΔADC%, ΔD%, Δf% and ΔD*%) were calculated. After image acquisition, tumor necrosis, microvessel density(MVD) and cellular apoptosis were evaluated by hematoxylin-eosin(HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman's correlation coefficient analysis were performed.RESULTS: The observed relative volume increase(ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5(ΔTV_(treatment)% = 19.63% ± 3.01% and ΔTVcontrol% = 83.60% ± 14.87%, P = 0.008) and day 7(ΔTV_(treatment)% = 29.07% ± 10.01% and ΔTV_(control)% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group(ΔADC%_(treatment), median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group(ΔADC%_(control), median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7(P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group(ΔD%_(treatment), median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group(ΔD%_(control), median-0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5(P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up(median,-34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016;-50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008;-49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and-46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points(median,-32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008;-44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008;-59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and-47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis(r_s = 0.720, P 0.001; r_s = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D(r_s = 0.626, P = 0.001; r_s = 0.542, P = 0.005, respectively). Perfusionrelated parameters(f and D*) were positively correlated to MVD(r_s = 0.618, P = 0.001; r_s = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor(r_s =-0.550, P = 0.004; r_s =-0.692, P 0.001, respectively).CONCLUSION: IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.     

Aloe vera attenuated gastric injury on indomethacin-induced gastropathy in rats

AIM: To evaluate the protective effects of Aloe vera on gastric injury in rats with indomethacin (IMN)-induced gastropathy.METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 6) was given distilled water (DW) orally. Group 2 (IMN, n = 6) was given oral IMN (150 mg/kg) dissolved in 5% sodium bicarbonate (NaHCO₃^-) at time 0 and 4 h. Group 3 (Aloe vera-treated, n = 6) was given oral Aloe vera (150 mg/kg) dissolved in DW and IMN at time 0 and 4 h. Eight hours later, the stomach was removed to determine gastric malondialdehyde (MDA), the number of interleukin (IL)-18 positive stained cells (%) by immunohistochemistry, and for histopathological examination. Then, the serum was collected to determine tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 by sandwich enzyme linked immunosorbent assay method.RESULTS: In the IMN group, serum TNF-α, CINC-1 and gastric MDA were significantly increased when compared to the control group (27.78 ± 1.52 pg/mL vs 85.07 ± 49.11 pg/mL, P = 0.009; 104.55 ± 45.80 pg/mL vs 1054.70 ± 20.38 pg/mL, and 1.74 ± 0.21 nmol/mg vs 9.36 ± 1.07 nmol/mg protein, P = 0.000, respectively). The mean level of TNF-α, CINC-1 and gastric MDA in the Aloe vera-treated group were improved as compared with the IMN group (85.07 ± 49.11 pg/mL vs 35.19 ± 1.61 pg/mL, P = 0.021; 1054.70 ± 20.38 pg/mL vs 813.56 ± 239.04 pg/mL, P = 0.025; and 9.36 ± 1.07 nmol/mg vs 2.67 ± 0.64 nmol/mg protein, P = 0.000, respectively). The number of IL-18 positive stained cells (%) in the gastric epithelial cells of the IMN group was significantly higher than the control group (5.01% ± 3.73% vs 30.67% ± 2.03%, P = 0.000, respectively). In contrast, Aloe vera treatment decreased the number of IL-18 positive stained cells (%) significantly when compared with the IMN group (30.67% ± 2.03% vs 13.21% ± 1.10%, P = 0.000, respectively). Most rats in the IMN group developed moderate to severe gastric inflammation and erosions. The gastric erosions and neutrophil infiltration scores were significantly reduced in the Aloe vera-treated group.CONCLUSION: Aloe vera attenuated IMN-induced gastropathy in rats by the reduction of oxidative stress, inflammation, and improvement of gastric histopathology.     

1H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy

AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics.METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using ¹H - nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients (FID’s) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups.RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate (0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate (0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine (0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine (0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine (0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate (1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate (1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01), pyruvate (0.11 ± 0.02 vs 0.03 ± 0.00, P < 0.01) threonine (0.39 ± 0.02 vs 0.08 ± 0.01, P < 0.01) and aspartate (0.37 ± 0.03 vs 0.03 ± 0.01). A five metabolite signature by stepwise discriminant analysis could separate between controls and cirrhotic patients with an accuracy of 98%. In patients with encephalopathy we observed further derangement of ketone body metabolism, impaired production of glycerol and myoinositol, reversal of Fischer’s ratio and impaired glutamine production as demonstrated by lower b-hydroxybutyrate (0.58 ± 0.14 vs 0.16 ± 0.02, P < 0.0002), higher acetoacetate (0.23 ± 0.02 vs 0.41 ± 0.16, P < 0.05), leucine (0.33 ± 0.02 vs 0.49 ± 0.05, P < 0.005) and isoleucine (0.12 ± 0.02 vs 0.27 ± 0.02, P < 0.0004) and lower glutamine (0.44 ± 0.08 vs 0.36 ± 0.04, P < 0.013), glycerol (0.53 ± 0.03 vs 0.19 ± 0.02, P < 0.000) and myoinositol (0.36 ± 0.04 vs 0.18 ± 0.02, P < 0.010) concentrations. A four metabolite signature by stepwise discriminant analysis could separate between encephalopathic and cirrhotic patients with an accuracy of 87%.CONCLUSION: Patients with cirrhosis and patients with hepatic encephalopathy exhibit distinct metabolic abnormalities and the use of metabonomics can select biomarkers for these diseases.     

Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver ischemia/reperfusion injury

AIM: To investigate the effect of diazoxide administration on liver ischemia/reperfusion injury.METHODS: Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from the medium and left anterior lateral segments for 1 h under mechanical ventilation. They were divided into 3 groups: Control Group, rats submitted to liver manipulation, Saline Group, rats received saline, and Diazoxide Group, rats received intravenous injection diazoxide (3.5 mg/kg) 15 min before liver reperfusion. 4 h and 24 h after reperfusion, blood was collected for determination of aspartate transaminase (AST), alanine transaminase (ALT), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), nitrite/nitrate, creatinine and tumor growth factor-β1 (TGF-β1). Liver tissues were assembled for mitochondrial oxidation and phosphorylation, malondialdehyde (MDA) content, and histologic analysis. Pulmonary vascular permeability and myeloperoxidase (MPO) were also determined.RESULTS: Four hours after reperfusion the diazoxide group presented with significant reduction of AST (2009 ± 257 U/L vs 3523 ± 424 U/L, P = 0.005); ALT (1794 ± 295 U/L vs 3316 ± 413 U/L, P = 0.005); TNF-α (17 ± 9 pg/mL vs 152 ± 43 pg/mL, P = 0.013; IL-6 (62 ± 18 pg/mL vs 281 ± 92 pg/mL); IL-10 (40 ± 9 pg/mL vs 78 ± 10 pg/mL P = 0.03), and nitrite/nitrate (3.8 ± 0.9 μmol/L vs 10.2 ± 2.4 μmol/L, P = 0.025) when compared to the saline group. A significant reduction in liver mitochondrial dysfunction was observed in the diazoxide group compared to the saline group (P < 0.05). No differences in liver MDA content, serum creatinine, pulmonary vascular permeability and MPO activity were observed between groups. Twenty four hours after reperfusion the diazoxide group showed a reduction of AST (495 ± 78 U/L vs 978 ± 192 U/L, P = 0.032); ALT (335 ± 59 U/L vs 742 ± 182 U/L, P = 0.048), and TGF-β1 (11 ± 1 ng/mL vs 17 ± 0.5 ng/mL, P = 0.004) serum levels when compared to the saline group. The control group did not present alterations when compared to the diazoxide and saline groups.CONCLUSION: Diazoxide maintains liver mitochondrial function, increases liver tolerance to ischemia/reperfusion injury, and reduces the systemic inflammatory response. These effects require further evaluation for using in a clinical setting.