Endoscopic diagnosis of Helicobacter pylori gastritis using white light imaging and texture and color enhancement imaging.

Background and study aims Texture and color enhancement imaging (TXI) is a new image-enhanced endoscopy that augments subtle tissue differences and color changes in gastric mucosa. This study aimed to compare the usefulness of TXI and white light imaging (WLI) for diagnosing Helicobacter pylori gastritis. Patients and methods We retrospectively prepared one image set with 22 endoscopic images acquired by WLI and TXI from 60 consecutive patients individually. Five endoscopists independently reviewed the randomly displayed image sets and assessed the H. pylori infection status on endoscopy according to the Kyoto Classification of Gastritis. The primary endpoints were the accuracies of WLI and TXI in diagnosing H. pylori -active gastritis. The correlation of the endoscopic features with the three H. pylori infection statuses (current infection, past infection, and noninfection) was also evaluated. Results Diagnostic accuracy for active gastritis was significantly higher in TXI than in WLI (85.3 % vs. 78.7 %; P  = 0.034). All the specific endoscopic features associated with H. pylori infection statuses had a higher odds ratio with TXI than with WLI. Additionally, interobserver agreement among the five reviewers was higher in TXI than in WLI, except for one pair. Conclusions TXI may improve the endoscopic diagnosis accuracy for H. pylori infection.

Mechanical Properties of a 3 Dimensional-Printed Transparent Flexible Resin Used for Vascular Model Simulation Compared with Those of Porcine Arteries.

PURPOSE: To develop a vascular intervention simulation model that replicates the characteristics of a human patient and to compare the mechanical properties of a 3-dimensional (3D)-printed transparent flexible resin with those of porcine arteries using the elastic modulus (E) and kinetic friction coefficient (µk). MATERIALS AND METHODS: Resin plates were created from a transparent flexible resin using a 3D printer. Porcine artery plates were prepared by excising the aorta. E values and the adhesive strengths of the resin and arterial surfaces toward a polyethylene plate, were measured with a tensile-compressive mechanical tester. Resin transparency was measured using an ultraviolet-visible light spectrometer. The µk value of the resin plate surface after applying silicone spray for 1-5 seconds and that of the artery were measured using a translational friction tester. RESULTS: E values differed significantly between the arteries and resin plates at each curing time (0.20 MPa ± 0.04 vs 8.53 MPa ± 2.37 for a curing time of 1 minute; P < .05). The resin was stiffer than the arteries, regardless of the curing times. The visible light transmittance and adhesive strength of the resin decreased as the curing time increased. The adhesive strength of the artery was the lowest. The µk value of the silicone-coated resin surface created by applying silicone for 2-3 seconds (thickness of the silicone layer, 1.6-2.0 µm) was comparable with that of the artery, indicating that the coating imparted a similar slippage to the resin as to the living artery. CONCLUSIONS: A transparent flexible resin is useful for creating a transparent and slippery vascular model for vascular intervention simulation.

Clinical outcome of the delineation-without-negative-biopsy strategy in magnifying image-enhanced endoscopy for identifying the extent of differentiated-type early gastric cancer.

BACKGROUND: The histologic evaluation of biopsy samples collected from the surrounding mucosa has conventionally been used to determine the horizontal extent of early gastric cancer. Recently, optical delineation using magnifying image-enhanced endoscopy (IEE) has been considered an alternative method to histologic evaluation. This study aimed to assess the clinical outcome and efficacy of this method in identifying cancer margins. METHODS: Overall, 921 patients with 1018 differentiated-type early gastric tumors who underwent endoscopic submucosal dissection (ESD) were examined. Before ESD, the lesions were classified based on whether they have clear or unclear margins on magnifying IEE. When the lesions had clear margins, the marking dots were placed outside the margins without a negative biopsy. Successful delineation was defined as lesions with clear margins and accurate delineation based on histopathological examination. The primary outcome was the accuracy of optical delineation without a negative biopsy compared with histopathological diagnosis. Moreover, the clinicopathological factors associated with an unsuccessful delineation were assessed. RESULTS: Of 1018 lesions, 820 had a clear margin and 198 an unclear margin. Of 820 lesions with a clear margin, 817 and 3 had an accurate and inaccurate delineation, respectively, according to the histological examination. Accordingly, the accuracy rate of optical delineation was 99.6% (817/820). The significant independent factors associated with an unsuccessful delineation were absence of Helicobacter pylori infection after eradication, tumor size > 20 mm, and moderate differentiation. CONCLUSIONS: Optical delineation may be an alternative method to histological evaluation in lesions with a clear margin on magnifying IEE.

Randomized study of two endo-knives for the traction-assisted endoscopic submucosal dissection of early esophageal squamous cell carcinoma.

Needle-type devices, such as the DualKnife (Olympus, Tokyo, Japan), are widely used for traction-assisted esophageal endoscopic submucosal dissection (ESD) but require a prolonged operation time. An improved model of the ITknife (Olympus), the ITknife nano, may allow faster and easier ESD than the DualKnife. We conducted a randomized study to compare the performances of the DualKnife and the ITknife nano for traction-assisted esophageal ESD. Patients with early esophageal squamous cell carcinoma were eligible for this study. The primary outcome was the total procedure time. The secondary outcomes were submucosal dissection time, en bloc, and complete resection rates, perforation rate, and adverse events. Results Fifty patients were equally divided into two groups: the DualKnife group (D-group) and the ITknife nano group (I-group), and all underwent the assigned treatment. The I-group had significantly shorter total procedure time (36.8 vs. 60.7 min; P < 0.01) and submucosal dissection time (17.2 vs. 35.8 min; P < 0.01) than the D-group. The en bloc and complete resection rates were sufficiently high in both groups (100% and 100% in the D-group and 100% and 96% in the I-group, respectively). Significantly fewer hemostatic procedures due to intraoperative bleeding were performed in the I-group than in the D-group (0.2 vs. 1.4; P < 0.01). Delayed bleeding, perforation, or esophageal stricture did not occur in either group. The ITknife nano exhibited lower procedure time for traction-assisted esophageal ESD than the DualKnife, without increasing adverse events.

Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study.

Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.

Comparison of endoscopic visibility and miss rate for early gastric cancers after Helicobacter pylori eradication with white-light imaging versus linked color imaging.

BACKGROUND AND AIM: We aimed to investigate whether linked color imaging (LCI) improves endoscopic visibility of early gastric cancers (EGC) after Helicobacter pylori eradication, which are often difficult to detect, and reduces the miss rate when compared with white-light imaging (WLI). METHODS: The visibility study used two images, one each with WLI and LCI, from 84 consecutive EGC after H. pylori eradication. Endoscopic visibility was evaluated using a visibility score and color difference (CD) value. To analyze miss rates, we studied a library of recorded videos using both WLI and LCI for 70 other consecutive patients after H. pylori eradication, among whom 19 had EGC. Endoscopic screening was done using the same protocol to map the entire stomach. Six endoscopists reviewed the videos in a randomized order. Miss rates of EGC were compared among the modalities. RESULTS: Mean [(±standard deviation) visibility scores with LCI were significantly higher than those with WLI (3.19 ± 0.84 vs 2.52 ± 0.98, P < 0.001), as were mean CD values (26.3 ± 9.1 vs 13.6 ± 6.3, P < 0.001). Miss rates of the six endoscopists were significantly lower with LCI than with WLI (30.7% vs 64.9%, P < 0.001). Both expert and trainee endoscopists had significantly better results with LCI than with WLI. CONCLUSIONS: Linked color imaging significantly improved the visibility of EGC after H. pylori eradication compared with WLI using both subjective and objective criteria. Furthermore, LCI significantly reduced miss rates of these lesions compared with WLI.

Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma.

The prognosis of advanced pancreatic adenocarcinoma is still extremely poor. This study sought to determine the efficacy of, and immunological response to, peptide vaccination therapy in patients with this disease. In this multicenter randomized phase II study, patients with advanced pancreatic adenocarcinoma after gemcitabine and/or tegafur/gimeracil/oteracil were randomly assigned to 3 groups that each received a 2-step treatment course. In Step 1, the groups received treatments of: (i) survivin 2B peptide (SVN-2B) plus interferon-ß (IFNß); (ii) SVN-2B only; or (iii) placebo until the patients show progression. In Step 2, all patients who consented to participate received 4 treatments with SVN-2B plus IFNß. The primary endpoint was progression-free survival (PFS) after initiation of Step 1 treatment. Secondary endpoints included immunological effects assessed by analysis of PBMCs after Step 1. Eighty-three patients were randomly assigned to receive SVN-2B plus IFNß (n = 30), SVN-2B (n = 34), or placebo (n = 19). No significant improvement in PFS was observed. Survivin 2B-specific CTLs were found to be increased in the SVN-2B plus IFNß group by tetramer assay. Among patients who participated in Step 2, those who had received SVN-2B plus IFNß in Step 1 showed better overall survival compared with those who had received placebo in Step 1. Patients vaccinated with SVN-2B plus IFNß did not have improved PFS, but showed significant immunological reaction after vaccination. Subgroup analysis suggested that a longer SVN-2B plus IFNß vaccination protocol might confer survival benefit. (Clinical trial registration number: UMIN 000012146).

Linked color imaging improves the endoscopic visibility of gastric mucosal cancers.

Background and study aims As a newly developed endoscopy technique, linked color imaging (LCI) provides very bright images with enhanced color tones. With the objective of improving the detection rate of gastric mucosal cancers, which are often difficult to detect, we examined the utility of LCI from the viewpoint of visibility. Patients and methods The current study used 100 consecutive gastric mucosal cancers ≤ 20 mm in diameter. For each lesion, we selected one endoscopic image acquired by white-light imaging (WLI), blue-laser imaging (BLI) -bright, and LCI modes. Four endoscopists interpreted the images; using a previously reported scale, we scored the visibility level on a scale of 1 - 4. Results The mean (±â€ŠSD) visibility scores were 2.54 ±â€Š1.10 for WLI, 3.02 ±â€Š1.07 for BLI-bright, and 3.28 ±â€Š0.97 for LCI. The score was significantly higher for BLI-bright compared with WLI ( P  < .001) and again higher for LCI compared with BLI-bright ( P  < .001). For the experts, the scores for BLI-bright and LCI were similar, but both were significantly higher than the score for WLI. For the trainees, there was no significant difference between the WLI and BLI-bright scores, but LCI score was significantly higher than those for WLI and BLI-bright scores. With regard to clinical characteristics, LCI particularly enhanced visibility of normochromic, flat and depressed lesions, which had the lowest visibility scores of all three modalities compared with those of the other lesions. Conclusion LCI increased visibility and may contribute to early detection of gastric mucosal cancers.

Linked-color imaging improves endoscopic visibility of colorectal nongranular flat lesions.

BACKGROUND AND AIMS: As a newly developed image-enhanced endoscopy (IEE) technique, linked-color imaging (LCI) provides very bright images with enhanced color tones. With the objective of improving the detection rate of colorectal flat tumor lesions, which are difficult to detect, we examined the usefulness of LCI from the viewpoint of visibility. METHODS: Fifty-three consecutive nongranular flat tumors were used in this study. Endoscopic images were acquired by white-light imaging (WLI), blue-laser imaging (BLI)-bright, and LCI modes. For each lesion, we selected 1 image each acquired by WLI, BLI-bright, and LCI modes. Six endoscopists interpreted the images. By using a previously reported visibility scale, we scored the visibility level on a scale of 1 to 4. RESULTS: The mean (± standard deviation) visibility scores were 2.74 ± 1.08 for WLI, 2.94 ± 0.97 for BLI-bright, and 3.36 ± 0.72 for LCI. The score was significantly higher for BLI-bright compared with WLI (P < .001) and again higher for LCI compared with BLI-bright (P < .001). When we compared between experts and trainees, the corresponding scores of experts were 2.83 ± 1.06, 3.17 ± 0.88, and 3.40 ± 0.74, with a tendency similar to the scores of all endoscopists. For the trainees, there was no difference between the scores for WLI (2.65 ± 1.10) and BLI-bright (2.71 ± 1.00), but the score for LCI (3.31 ± 0.69) was significantly higher than that for WLI or BLI-bright (P < .001). When only sessile serrated adenoma/polyp lesions were analyzed, LCI remained significantly higher than the other 2. CONCLUSIONS: The present findings suggest that LCI increases the visibility of colorectal flat lesions and contributes to improvement of the detection rate for these lesions.

[Antioxidant reactions and activities of teas and wines by the cumene hydroperoxide/hemoglobin * methylene blue method].

BACKGROUND: We reported a new method using cumene hydroperoxide to determine the antioxidant activity of polyphenols. METHODS: We measured antioxidant activities of a variety of different teas and wines by the cumene hydroperoxide/hemoglobin * methylene blue method. The activities of teas were observed by adding 100 ml of boiling water to 2g of tea leaves. The wine samples were mainly diluted 10 times. RESULTS: The average level of antioxidant activity of teas was as follows: wild plants (n = 6) were 59 micromol/l, heated green (n = 3) was 400 micromol/l, green (n = 8) was 550 micromol/l, powdered green (n = 2) was 960 micromol/l, and black (n = 11) was 405 micromol/l. The antioxidant activity of wines was as follows: red (n = 7) was 1,920 micromol/l, white (n = 7) was 1,010 micromol/l, additive-free red (n = 6) was 658 micromol/l, and additive-free white (n = 6) was 118 micromol/l. The correlation between the concentration of teas or wines and antioxidant activity was not a linear type. For this reason, the tea and wine were measured under comparable conditions. The concentration of free sulfur dioxide contained within red wine was 20 mg/l and, white wine was 55 mg/l. The apparent-antioxidant activity of these concentrations of free sulfur dioxide was 234 micromol/l and 651 micromol/l. CONCLUSIONS: Tea is the national drink of Japan, green tea and heated green tea are particularly favored. The antioxidant activities of these teas were lower than that of red wine. However larger quantities of tea than wine are consumed every day. Therefore, we concluded that the total antioxidant activity of tea is the same or higher than that of red wine.

A new method of measuring the antioxidant activity of polyphenols using cumene hydroperoxide.

BACKGROUND: It is well known that polyphenols lower the risk of chronic diseases such as heart disease and cancer. We describe a new method using cumene hydroperoxide (CHP) to determine the antioxidant activity of polyphenols. CHP is considered to be a model reactive lipid peroxidation product. METHODS: The method was based on two reactions: the reduction of a known concentration of CHP by polyphenols and the reaction of the remaining CHP with a methylene blue derivative (10-N-methylcarbamoyl-3,7 dimethylamino-10H-phenothiazine) in the presence of haemoglobin. Methylene blue was formed as a result of the two reactions and then measured by absorbance at 675 nm. We named this assay the 'cumene hydroperoxide/haemoglobin.methylene blue (CHP/Hb.MB) method'. We examined 13 polyphenols and nine compounds known to be antioxidants. RESULTS: Among the 13 polyphenols, milicetin, with the largest number of hydroxyl groups, had the highest antioxidant activity, followed by cyanidin, pelargonidin and quercetin. It is suggested that the increase in the number of hydroxyl groups induced a higher antioxidant activity. Within-run coefficients of variation were 3.6% and 3.5% at the mean antioxidant activity of 50 micromol/L and 151 micromol/L, respectively. CONCLUSION: We conclude that this CHP/Hb.MB assay is capable of measuring the antioxidant activity of polyphenols.

[Antioxidant activities of green and black teas determined by the cumene hydroperoxide/hemoglobin.methylene blue method].

Antioxidant activity in tea was measured by the new cumene hydroperoxide/hemoglobin.methylene blue(CHP/Hb.MB) method developed in our laboratory. Using the CHP/Hb.MB method, we investigated the activities of polyphenols(11 varieties) in order to determine their reactivity on CHP. According to the CHP/Hb.MB method, an increase in the number of hydroxyl groups in polyphenols induced high antioxidant activity. We found that this method was capable of measuring the antioxidant activity of polyphenols. Consequently, we were able to measure the antioxidant activities of heated, green, powdered and black teas by this method. The average of antioxidant activities of heated green tea was 207 nmol/ml, while that of green tea was 280 nmol/ml, powdered green tea was 481 nmol/ml and black tea was 215 nmol/ml respectively.

Molecular detection of von Hippel-Lindau gene mutations in urine and lymph node samples in patients with renal cell carcinoma: potential biomarkers for early diagnosis and postoperative metastatic status.

PURPOSE: Organ confined renal cell carcinoma can be cured in the majority of patients, whereas more extensive lesions have a poor prognosis. Therefore, the development of a useful biomarker for early diagnosis as well as postoperative metastatic status would contribute to the appropriate therapy for renal cell carcinoma. To diagnose renal cell carcinoma preoperatively we developed a novel urinary test and detected occult lymph node micrometastasis using a molecular approach. MATERIALS AND METHODS: Urine samples were obtained preoperatively from 27 patients with renal cell carcinoma and von Hippel-Lindau (VHL) gene mutations in the tumors, and were analyzed for VHL gene mutations using a nested single strand conformational polymorphism analysis. Lymph nodes without evidence of histological metastasis were obtained from 15 patients with renal cell carcinoma and VHL gene mutations, and analyzed for VHL gene mutations using mutation specific nested reverse transcription polymerase chain reaction method. RESULTS: In urine samples 5 of 27 VHL gene mutations (18.5%) were found and each mutation pattern was the same as that detected in each renal cell carcinoma. One lymph node micrometastasis was found. CONCLUSIONS: These data indicate the presence of detectable levels of tumor derived DNA in the urine of patients with renal cell carcinoma and suggest that nested single strand conformational polymorphism analysis of VHL gene of urine samples provides a possible tool for the early detection of renal cell carcinoma. Furthermore, mutation specific nested reverse transcription polymerase chain reaction is useful to detect occult lymph node micrometastasis and may predict patients at risk for local recurrence. These 2 combined approaches using VHL gene mutations may contribute to the total therapy for and prognosis of renal cell carcinoma.