Autonomic nervous responses in colorectal polypectomy: Randomized controlled trial comparing air and carbon dioxide insufflation.

BACKGROUND AND AIM: Carbon dioxide (CO2) insufflation devices are commonly used for endoscopic examination and treatment. In this prospective randomized controlled trial (RCT), we compared patient acceptance, cardiovascular tolerance,and autonomic nervous responses between patients receiving air insufflation and CO2 insufflation. METHODS: We initially enrolled 170 patients and, of these, 158 patients in total were analyzed (air group, 83; CO2 group, 75). Autonomic nervous responses were evaluated by analysis of heart rate variability (HRV). Primary end point was superiority in the effects of CO2 insufflation on the autonomic nervous system by HRV analysis. RESULTS: Visual analog scale disclosed significantly less abdominal pain and abdominal fullness with CO2. Percentage heart rate change rate at 1 h and 4 h after the procedure was also significantly lower in the CO2 group than in the air group (1 h after: P < 0.01, 4 h after: P < 0.05). Comparison based on age showed that % heart rate change was significantly lower in the younger CO2 patients (just after colonoscopy and 1 h after: P < 0.01, 4 h after: P < 0.05), but this difference was not apparent in an older group of patients. CONCLUSIONS: This is the first RCT showing that colorectal polypectomy using CO2 insufflation significantly decreases abdominal pain and abdominal fullness common in such patients with lowered stress to the autonomous nervous system. The effects using CO2 insufflation on the sympathetic nervous system also seemed to be more prominent among younger patients.

Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer.

BACKGROUND: Our recent prospective study found equivalent accuracy of magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) for diagnosing the invasion depth of colorectal cancer (CRC); however, whether these tools show diagnostic differences in categories such as tumor size and morphology remains unclear. Hence, we conducted detailed subset analysis of the prospective data. METHODS: In this multicenter, prospective, comparative trial, a total of 70 patients with early, flat CRC were enrolled from February 2011 to December 2012, and the results of 66 lesions were finally analyzed. Patients were randomly allocated to primary MC followed by EUS or to primary EUS followed by MC. Diagnoses of invasion depth by each tool were divided into intramucosal to slight submucosal invasion (invasion depth <1000 µm) and deep submucosal invasion (invasion depth ≥1000 µm), and then compared with the final pathological diagnosis by an independent pathologist blinded to clinical data. To standardize diagnoses among examiners, this trial was started after achievement of a mean κ value of ≥0.6 which was calculated from the average of κ values between each pair of participating endoscopists. RESULTS: Both MC and EUS showed similar diagnostic outcomes, with no significant differences in prediction of invasion depth in subset analyses according to tumor size, location, and morphology. Lesions that were consistently diagnosed as Tis/T1-SMS or ≥T1-SMD with both tools revealed accuracy of 76-78%. Accuracy was low in borderline lesions with irregular pit pattern in MC and distorted findings of the third layer in EUS (MC, 58.5%; EUS, 50.0%). CONCLUSIONS: MC and EUS showed the same limited accuracy for predicting invasion depth in all categories of early CRC. Since the irregular pit pattern in MC, distorted findings to the third layer in EUS and inconsistent diagnosis between both tools were associated with low accuracy, further refinements or even novel methods are still needed for such lesions. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trials Registry UMIN 000005085.

Therapeutic effects of biobran, modified arabinoxylan rice bran, in improving symptoms of diarrhea predominant or mixed type irritable bowel syndrome: a pilot, randomized controlled study.

Background. Recently, it was revealed that low grade mucosal inflammation and/or immune imbalance of the lower digestive tract is one of the mechanisms involved in symptom generation in patients with irritable bowel syndrome (IBS). Biobran, arabinoxylan compound derived from rice bran, has been reported to have several biological actions such as anti-inflammatory and immune modulatory effects. So we investigated the therapeutic effects of Biobran in patients with IBS. Method. Forty patients with diarrhea predominant or mixed type IBS were randomly assigned to either a Biobran group for treatment with Biobran or a placebo group. Therapeutic efficacy and IBS symptoms were assessed subjectively by the patients after 4 weeks of administration. Results. The global assessment was effective in 63.2% of the Biobran group and in 30% of the placebo group (P < 0.05, Biobran group versus placebo group). Biobran group showed a significant decrease in the score of diarrhea and constipation and in CRP value. However, no significant changes were observed in the placebo group. Conclusion. The administration of Biobran improved IBS symptoms. It is likely that anti-inflammatory and/or immune modulatory effects of Biobran might be useful in IBS patients.

Adalimumab Treatment in Biologically Naïve Crohn's Disease: Relationship with Ectopic MUC5AC Expression and Endoscopic Improvement.

Background. Adalimumab (ADA) is effective for patients with Crohn's disease (CD). However, there have been few reports on ADA therapy with respect to its relationship with pathologic findings and drug efficacy in biologically naïve CD cases. Methods. Fifteen patients with active biologically naïve CD were treated with ADA. We examined them clinically and pathologically with ectopic MUC5AC expression in the lesions before and after 12 and 52 weeks of ADA therapy, retrospectively. Results. Both mean CD activity index scores and serum C-reactive protein values were significantly lower after ADA therapy (P < 0.001). In the MUC5AC negative group, all cases exhibited clinical remission (CR) and endoscopic improvement at 52 weeks. In MUC5AC positive groups, loss of MUC5AC expression was detected in cases having CR and endoscopic improvement at 52 weeks, while remnant ectopic MUC5AC expression was observed in those exhibiting no endoscopic improvement and flare up after 52 weeks. Conclusions. ADA leads to CR and endoscopic improvement in biologically naïve CD cases. In addition, ectopic MUC5AC expression may be a predictive marker of flare up and endoscopic improvement in the intestines of CD patients.

Management of systolic blood pressure after endoscopic submucosal dissection is crucial for prevention of post-ESD gastric bleeding.

OBJECTIVE: Endoscopic submucosal dissection (ESD) is a useful technique for early gastric neoplasms without lymph node metastasis. However, a critical complication is unpredictable post-ESD bleeding. Some risk factors for post-ESD bleeding have been reported previously, although those risk factors have not directly contributed toward prevention of post-ESD bleeding. MATERIALS AND METHODS: We retrospectively identified 186 gastric neoplasms in 183 consecutive patients treated with ESD from 2005 to 2012 at Nagoya City University Hospital, and divided them into two groups on the basis of the presence or absence of post-ESD bleeding. RESULTS: Of the 186 lesions, eight lesions (4.2%) developed post-ESD bleeding. Univariate analysis identified hypertension (38.8% in nonbleeding vs. 87.5% in bleeding; P=0.009) and depressed-type tumors (26.4% in nonbleeding vs. 62.5% in bleeding; P=0.040) as significantly related to the incidence of post-ESD bleeding. On multivariate analysis, hypertension (odds ratio, 11.55; 95% confidence interval, 1.20-111.66; P=0.034) and depressed-type tumors (odds ratio, 5.36; 95% confidence interval, 1.12-25.73; P=0.036) were independent risk factors for post-ESD bleeding. Systolic blood pressure (SBP) after ESD was significantly higher in the post-ESD bleeding group than in the post-ESD non-bleeding group (P=0.021), with the comorbidity of hypertension significantly correlating with SBP after ESD (ρ=0.332, P<0.001). CONCLUSION: Control of SBP after ESD is important for the prevention of post-ESD bleeding because hypertension as a comorbidity, which is associated positively with SBP after ESD, is a significant risk factor for post-ESD bleeding.

Magnifying chromoendoscopy and endoscopic ultrasonography measure invasion depth of early stage colorectal cancer with equal accuracy on the basis of a prospective trial.

BACKGROUND & AIMS: Magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) are used to estimate the depth of colorectal cancer (CRC) invasion, but it is not clear which procedure is more accurate. We performed a prospective study to compare MC and EUS. METHODS: A total of 70 patients with an early stage flat CRC lesion were enrolled at 6 institutions in Japan and randomly assigned to groups assessed by MC followed by EUS or EUS followed by MC. Results from MC and EUS measurements of 66 lesions were included in the final analysis. The invasion depth of each lesion was measured by each procedure and categorized as mucosal to slight submucosal (depth <1000 µm) or deep submucosal (depth ≥ 1000 µm); measurements were compared with the final diagnosis on the basis of the pathology analysis. All participating examiners achieved a mean κ value ≥ 0.6 for both MC and EUS before this trial. RESULTS: MC and EUS each measured the depth of lesion invasion with 71.2% accuracy (correctly for 47 of 66 lesions). MC identified lesions with deep submucosal invasion with 74.2% sensitivity and 68.6% specificity, whereas EUS identified them with 67.7% sensitivity and 74.3% specificity. The differences between MC and EUS measurements did not differ significantly. However, MC required significantly shorter observation time than EUS (361.7 ± 164.5 seconds vs 451.2 ± 209.4 seconds, P = .002). CONCLUSIONS: MC and EUS are equally accurate in estimating the invasion depth of early stage CRC lesions. However, neither procedure has sufficient diagnostic accuracy to be used as the standard. University Hospital Medical Network Clinical Trials Registry, Number: UMIN 000005085.

Diagnostic utility of small-caliber and conventional endoscopes for gastric cancer and analysis of endoscopic false-negative gastric cancers.

AIM: To analyze the diagnostic utility of a small-caliber endoscope (SC-E) and clinicopathological features of false-negative gastric cancers (FN-GCs). METHODS: A total of 21638 esophagogastroduodenoscopy (EGD) gastric cancer (GC) screening examinations were analyzed. Secondary endoscopic examinations (n = 3352) were excluded because most secondary examinations tended to be included in the conventional endoscopy (C-E) group. Detection rates of GCs and FN-GCs were compared between SC-E and C-E groups. FN-GC was defined as GC performed with EGD within the past 3 years without GC detection. Macroscopic types, histopathological characteristics and locations of FN-GCs were compared with firstly found-gastric cancers (FF-GCs) in detail. RESULTS: SC-E cases (n = 6657) and C-E cases (n = 11644), a total of 18301 cases, were analyzed. GCs were detected in 16 (0.24%) SC-E cases and 40 C-E (0.34%) cases (P = 0.23) and there were 4 FN-GCs (0.06%) in SC-E and 13 (0.11%) in C-E (P = 0.27), with no significant difference. FN-GCs/GCs ratio between SC-E and C-E groups was not significantly different (P = 0.75). The comparison of endoscopic macroscopic types of FN-GCs tended to be a less advanced type (P = 0.02). Histopathologically, 70.6% of FN-GCs were differentiated and 29.4% undifferentiated type. On the other hand, 43.0% of FF-GCs were differentiated and 53.8% undifferentiated type, so FN-GCs tended to be more differentiated type (P = 0.048). CONCLUSION: The diagnostic utility of SC-E for the detection of GCs and FN-GCs was not inferior to that of C-E. Careful observation for superficially depressed type lesions in the upper lesser curvature region is needed to decrease FN-GCs.

[Efficacy and safety of S-1 plus docetaxel combination therapy for patients with advanced gastric cancer].

Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP combination therapy has been reported. Docetaxel also has been reported to have favorable efficacy in gastric cancer. In addition, docetaxel can be administered in outpatient clinics. We investigated the efficacy and safety of S-1 plus docetaxel combination therapy for 35 naive patients with advanced gastric cancer. Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by one week rest. MST was 300 days, and the response rate was 42. 9%. Although leucopenia was observed in 31%, all patients were able to be continue this therapy. In conclusion, we considered that this S-1 plus docetaxel combination therapy was effective and safe in advanced gastric cancer, and convenient for outpatients.