Impact of preprocedure simethicone on adenoma detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized controlled trial.

BACKGROUND AND STUDY AIMS: Ideal bowel preparation for colonoscopy requires complete removal of fluid and foam from the colon. Polyethylene glycol (PEG) is widely used for bowel preparation, with antifoaming agents such as simethicone commonly used in combination with PEG. Data on the effect of simethicone on the adenoma detection rate (ADR) were limited. This study therefore aimed to investigate whether preprocedure simethicone could increase the ADR. PATIENTS AND METHODS: This was a prospective, multicenter, endoscopist-blinded randomized controlled trial involving consecutive patients who underwent colonoscopy in six centers in China. Patients were randomly assigned to one of two groups: PEG plus simethicone or PEG alone. The primary outcome was ADR; secondary outcomes were quality of bowel preparation, measured by the Boston bowel preparation scale (BBPS) and bubble scores. RESULTS: 583 patients were included. More adenomas were detected in the PEG plus simethicone group than in the PEG alone group (ADR 21.0 % vs. 14.3 %, P = 0.04; advanced ADR 9.0 % vs. 7.0 %, P = 0.38). The mean number of adenomas detected was 2.20 ±â€Š1.36 vs. 1.63 ±â€Š0.89 (P = 0.02). Patients in the PEG plus simethicone group showed better bowel cleansing efficacy: BBPS ≥ 6 in 88.3 % vs. 75.2 % (P < 0.001) and bubble scores of 1.00 ±â€Š1.26 vs. 3.98 ±â€Š2.50 (P < 0.001). Abdominal bloating was reported less frequently in the PEG plus simethicone group (7.8 % vs. 19.7 %, P < 0.001) than in the PEG alone group. CONCLUSION: Combined use of PEG and simethicone is associated with a significantly increased ADR in a Chinese population.

In vivo pharmacokinetic and tissue distribution investigation of sustained-release cisplatin implants in the normal esophageal submucosa of 12 beagle dogs.

PURPOSE: The aim of this study was to clarify the pharmacokinetic, tissue distribution, hematologic, and histopathologic characteristics of sustained-release cisplatin from implants [CDDP-nanoparticle (NP) implants]. METHODS: Eighteen dogs (six hybrids and twelve beagles) were divided into three groups. In Group A, the six hybrid dogs were intravenously administered 20 mg CDDP via a hind limb vein. In Groups B and C, CDDP-NP implants containing CDDP doses of 40 and 60 mg, respectively, were embedded into the esophageal submucosa of beagles via painless gastroscopy with an endoscopic booster. Graphite frameless atomic absorption spectrophotometry was used to measure total platinum in plasma and tissues at various timepoints. In addition, free platinum levels in Group B were determined using inductively coupled plasma mass spectrometry. Toxicologic evaluation was also conducted. RESULTS: Pharmacokinetic results indicated that the CDDP-NP implant could achieve a smooth pharmacokinetic curve, with the plasma invalid concentration reached after almost 480 h, which is approximately ten times longer than that of standard CDDP (48 h). The peak time, peak concentration, clearance, elimination half-life, area under the curve, volume of distribution at steady state, and mean residence time of Groups B and C were 494 and 211, 0.39 and 0.42, 0.044 and 0.059, 80.11 and 87.70, 44 and 49, 38.8 and 57.9, and 12.29 and 12.39 times those of Group A, respectively (all P < 0.05). The ratio of free/total platinum concentration was 2.0-3.1% in plasma, 14.2% in liver tissue, and 14.3% in kidney tissue. Tissue distribution studies showed that the highest platinum concentrations were found in the esophagus, followed by the kidney and liver. Compared with pre-implantation (day 0), there were no significant differences in most hematological indicators in Groups B and C (P > 0.05). Furthermore, histopathologic examination of the kidneys of dogs from Group C revealed no significant kidney damage. Unlike the intravenous CDDP group (Group A), no animals in the implantation groups showed any clinical signs of toxicity. CONCLUSION: CDDP-NP implants can be used to achieve a smooth pharmacokinetic curve and higher drug concentration, as well as a longer mean residence time at the implantation site, with reduced side effects compared with intravenous CDDP.

NANOG: a promising target for digestive malignant tumors.

NANOG has been extensively researched since its discovery by Chambers et al. NANOG is a homeodomain transcription factor and an essential regulator of embryonic stem cell (ESC) self-renewal, which inhibits differentiation. Cancer stem cells (CSCs) are a small subset of cells that are thought to drive uncontrolled tumor growth; CSCs retain the tumor capabilities of self-renewal and propagation. The existence of CSCs was recently shown by direct experimental evidence. NANOG is expressed in CSCs and ESCs, although it remains unclear whether ESCs and CSCs share similar mechanisms in the regulation of physical and biological processes. Several studies suggest that the expression level of NANOG is high in cancer tissues and low or absent in normal tissues. High levels of NANOG expression are associated with advanced stages of cancer and a poor prognosis, indicating that it plays a vital role in tumor transformation, tumorigenesis, and tumor metastasis. NANOG is part of a complex regulatory network that controls cell fate determination, proliferation, and apoptosis. NANOG cooperates with other regulators, such as microflora, transcription factors, and kinases, in cancer cells. NANOG might have a promising future in anti-cancer and other therapeutic treatments, which could improve human health.

Mismatch repair gene mutation analysis and colonoscopy surveillance in Chinese Lynch syndrome families.

BACKGROUND: Lynch syndrome (or HNPCC) is a colorectal cancer syndrome caused by germline mutations in either one of the DNA mismatch repair (MMR) genes hMLH1, hMSH2, hMSH6 or hPMS2. Mutations in hMLH1 and hMSH2 are most prevalent. Here we aimed to determine the cancer risk of MMR gene mutation carriers and, in addition, the efficacy of colonoscopy surveillance in Chinese Lynch syndrome family members with and without MMR gene mutations. METHODS: A Lynch syndrome family registry encompassing 106 families in Northern China was recently established. Detailed pedigree data for each family were collected and hMLH1 and hMSH2 gene mutation analyses were performed. Germ-line mutations were identified in probands from 42 of these families, and additional genetic analyses were performed in each member of these 42 families to identify mutation and non-mutation carriers. Among the family members included, 180 received colonoscopy and the remaining cases were followed without colonoscopy. RESULTS: Overall 54.8 % of the Lynch syndrome family members carried MMR gene mutations, and these mutation carriers exhibited significantly higher colorectal cancer and other Lynch syndrome-associated cancer risks as compared to non-mutation carriers. The cumulative risk for all Lynch syndrome-related cancers at age 70 was 93.8 % for both hMLH1 and hMSH2 mutation carriers, and 81.7 % and 93.1 % for colorectal cancer at this age, respectively. Whereas 43 of 102 (42.2 %) mutation carriers exhibited significant colonoscopy findings, including 10 colorectal cancers, none of 78 non-mutation carriers exhibited significant findings, and no cancers were detected. In addition, in the mutation carriers, colonoscopy surveillance led to the detection of more early stage cancers than in the non-surveillance group (70.0 % versus 36.5 %, p < 0.01). CONCLUSION: In Lynch syndrome family members, we recommend pre-symptomatic MMR gene mutation analysis in order to identify high risk individuals for colonoscopy surveillance.

[Expression of manganese superoxide dismutase in colorectal carcinoma and its relationship with clinicopathological findings].

OBJECTIVE: To explore the expression of manganese superoxide dismutase (MnSOD) in colorectal carcinoma and its relationship with the clinicopathological findings. METHODS: The expressions of MnSOD in colorectal carcinoma, adenoma, and adjacent corresponding intestinal mucosal tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between MnSOD expression level in colorectal adenoma and clinical parameters was analyzed. RESULTS: The expression of MnSOD was negative in adjacent corresponding colorectal tissues. The positive expression rate of MnSOD was 44% (11/25) in colorectal adenoma and 76% (19/25) in colorectal carcinoma (P < 0.05 when compared with the colorectal adenoma and its adjacent tissues). The expression of MnSOD was positively correlated with histopathological grades (P < 0.05) but not with other clinicopathological findings (P > 0.05). CONCLUSION: The expression of MnSOD may be associated with the carcinogenesis and progression of colorectal carcinoma, and therefore may be used as a new biomarker.

Fecal cytology in conjunction with immunofecal occult blood test for colorectal cancer screening.

OBJECTIVE: To develop a simple method to extract and analyze the cytomorphology of epithelial cells from fecal samples and to compare the efficacy of fecal cytology with the immunofecal occult blood test (IFOBT) in colorectal cancer screening. STUDY DESIGN: Fecal cytology and IFOBT were performed on fecal samples obtained from 41 patients with colorectal cancer; 34 patients with a small, single adenoma (<0.5 cm); and 20 without abnormality. The samples were obtained prior to colonoscopic examination. For fecal cytology, epithelial cells were exacted through filtration, centrifugation and cytocentrifugation and stained with hematoxylin-eosin prior to morphologic analysis. RESULTS: Fecal cytology and IFOBT test had similar levels of sensitivity for detecting colorectal cancer (75.6% vs. 68.3%, respectively), but fecal cytology had higher specificity than IFOBT (100% as compared to 85.2%, respectively, p<0.05 by chi2 test). Seven of 41 colorectal cancer patients (17.1%) with negative IFOBT were positive by fecal cytology analysis. Combining fecal cytology with the IFOBT test in an either/or scenario significantly increased the sensitivity of IFOBT test to 92.68% for colorectal cancer detection (p<0.05 by chi2 test) without compromising the specificity. CONCLUSION: Fecal cytology augments the sensitivity of IFOBT in detecting colorectal cancers, and combining fecal cytology and IFOBT may provide an important simple and cost-effective alternative for colon cancer screening.

Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer.

AIM: To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS: A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation detection. RESULTS: High frequency microsatellite instability occurred in 25 probands (83.3%) of HNPCC family. Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability. Pathogenic mutation occurred in 14 samples and 3 novel mutational sites were discovered. Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1. Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands. The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%. The rate of the two methods in combination with methylation detection was 63.3%. CONCLUSION: Scientific and rational detection strategy can improve the detection rate of HNPCC. Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC.

[Mutation of hMLH1 and hMSH2 genes in hereditary nonpolyposis colorectal cancer: analysis of 76 probands].

OBJECTIVE: To investigate the mutations of the mismatch repair genes hMLH1 and hMSH2 in hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: The DNA samples of 76 probands of HNPCC families underwent PCR amplification and sequencing on 35 exons in hMLH1 and hMSH2 genes. RESULTS: (1) The overall mutation rate of the hMLH1 and hMSH2 genes was 33% (25/76). (2) 22 mutations were found, 16 in the hMLH1 gene and 6 in the hMSH2 gene. (3) The spectrum of mutation type included frame shift, nonsense, splice site, and missense mutations. Missense mutation was the most common mutation type. CONCLUSION: The hMLH1 and hMSH2 mutations in Chinese HNPCC families show a wide spectrum. It seems that hMLH1 gene is involved more frequently than hMSH2 gene. A certain number of HNPCC families can be benefited from the genetic screening for mutation of the mismatch repair genes.

A modified percutaneous transhepatic variceal embolization with 2-octyl cyanoacrylate versus endoscopic ligation in esophageal variceal bleeding management: randomized controlled trial.

BACKGROUND: Conventional percutaneous transhepatic varices embolization (PTVE) has rarely been used in recent years due to high rates of variceal recurrence and rebleeding. Herein we report a modified PTVE with 2-octyl cyanoacrylate (2-OCA) in which the whole lower esophageal and peri or para-esophageal varices, the submucosal varices, and the advertitial plexus of the cardia and fundus were sufficiently obliterated. We compared this PTVE with endoscopic band ligation (EVL) in the treatment of esophageal variceal bleeding. METHODS: In this prospective randomized controlled trial, cirrhotic patients with acute or recent esophageal variceal bleeding were assigned randomly to PTVE (52 patients) or EVL (50 patients) groups. Upper gastrointestinal (UGI) rebleeding, esophageal variceal rebleeding, and survival were followed-up. Computerized tomography (CT) scanning and portal venography were used to observe 2-OCA distribution. RESULTS: During the follow-up period (median 24 and 25 months in the PTVE and EVL groups, respectively) UGI rebleeding developed in eight patients in the PTVE group and 21 patients in EVL group (P = 0.004). Recurrent bleeding from esophageal varices occurred in three patients in the PTVE group and twelve in the EVL group (P = 0.012, relative risk 0.24, 95% confidence interval 0.05-0.74). Multivariate Cox analysis indicated that the treatment was the only factor predictive of rebleeding. A Kaplan-Meier curve showed there was no significant difference between survival in the two groups (P = 0.054). CONCLUSIONS: With the whole lower esophageal and peri or para-esophageal varices, the submucosal varices, and the adventitial plexus of the cardia and fundus sufficiently obliterated by 2-OCA, this modified PTVE was more effective than EVL in the management of esophageal varices recurrence and rebleeding. Survival in these two groups was not significantly different, however.

Systemic immune responses to oral administration of recombinant attenuated Salmonella typhimurium expressing Helicobacter pylori urease in mice.

AIM: To evaluate whether attenuated Salmonella typhimurium producing Helicobacter pylori (H pylori) urease subunit B (UreB) could induce systemic immune responses against H pylori infection. METHODS: Attenuated S. typhimurium SL3261 was used as a live carrier of plasmid pTC01-UreB, which encodes recombinant H pylori UreB protein. Balb/c mice were given oral immunization with two doses of SL3261/pTC01-UreB at a 3-wk interval. Twelve weeks after oral immunization of mice, serum IgG antibodies were evaluated by ELISA assay. Gamma interferon (IFN-gamma) and interleukin 10 (IL-10) in the supernatant of spleen cell culture were also assessed by ELISA. RESULTS: After oral immunization of mice, serum specific IgG antibodies against UreB in vaccine group were much higher than that in PBS and native Salmonella SL3261 control groups (A450, 0.373+/-0.100 vs 0.053+/-0.022, 0.142+/-0.039, respectively, P<0.01). Moreover, IFN-gamma in vaccine group was on average 167.53+/-29.93 pg/mL, which showed a significant increase vs that of PBS control group (35.68+/-3.55 pg/mL, P<0.01). There was also a tremendous increase of IL-10 in vaccine group compared to PBS and SL3261 control groups (275.13+/-27.65 pg/mL vs 56.00+/-7.15 pg/mL, 68.02+/-15.03 pg/mL, respectively, P<0.01). In addition, no obvious side effects in mice and no change in gastric inflammation were observed. CONCLUSION: The multiple oral immunizations with the attenuated S. typhimurium expressing H pylori UreB could induce significant systemic immune responses, suggesting it may be used as oral vaccine against H pylori infection.

[Development of a multiple ligator and its endoscopic therapy for patients with esophageal varices].

The ligators we have developed is a kind of economical and effective six-ring ligator. Endoscopic variceal ligation (EVL) was performed to treat bleeding from esophageal varices in patients with liver cirrhosis using self-made ligator and foreign multiple ligator. There are similar effects with both self-made ligator and foreign mutiple ligator in the control of variceal bleeding, variceal obliteration and rebleeding (93.8%, 87.5%, 0 in the group with self-made ligator, 94.5%, 87.1%, 2.4% in the group with foreign multiple ligator, P>0.05). In terms of the quality index, successful operation rate, hemastatic rate, variceal obliteration rate, rebleeding rate, complications and variceal recurrence rate, the self-made ligator is as good as the foreign multiple ligator, but much cheaper.