Periodontal Tissue Regeneration Using Fibroblast Growth Factor -2: Randomized Controlled Phase II Clinical Trial

Background: The options for medical use of signaling molecules as stimulators of tissue regeneration are currently limited. Preclinical evidence suggests that fibroblast growth factor (FGF)-2 can promote periodontal regeneration. This study aimed to clarify the activity of FGF-2 in stimulating regeneration of periodontal tissue lost by periodontitis and to evaluate the safety of such stimulation. Methodology/Principal Findings: We used recombinant human FGF-2 with 3% hydroxypropylcellulose (HPC) as vehicle and conducted a randomized double-blinded controlled trial involving 13 facilities. Subjects comprised 74 patients displaying a 2- or 3-walled vertical bone defect as measured ?3 mm apical to the bone crest. Patients were randomly assigned to 4 groups: Group P, given HPC with no FGF-2; Group L, given HPC containing 0.03% FGF-2; Group M, given HPC cotaining 0.1% FGF-2; and Group H, given HPC Containing 0.3% FGF-2. Each patient underwent flap operation during which we administered 200 μL of the appropriate investigational drug to the bone defect. Before and for 36 weeks following administration, patients underwent periodontal tissue inspections and standardized radiography of the region under investigation. As a result, a significant difference (p = 0.021) in rate of increase in alveolar bone height was identified between Group P (23.92%) and Group H (58.62%) at 36 weeks. The linear increase in alveolar bone height at 36 weeks in Group P and H was 0.95 mm and 1.85 mm, respectively (p = 0.132). No serious adverse events attribute to the investigational drug were identified. Conclusions: Although no statistically significant differences were noted for gains in clinical attachment level and alveolar bone gain for FGF-2 groups versus Group P, the significant difference in rate of increase in alveolar bone height (p = 0.021) between Groups P and H at 36 weeks suggests that some efficacy could be expected from FGF-2 in stimulating regeneration of periodontal tissue in patients with periodontitis

A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successful <i>Helicobacter pylori</i> eradication

<div><p>Background</p><p><i>Helicobacter pylori</i> (<i>H</i>. <i>pylori)</i> eradication is usually assessed using the ¹³C-urea breath test (UBT), anti-<i>H</i>. <i>pylori</i> antibody and the <i>H</i>. <i>pylori</i> stool antigen test. However, a few reports have used pepsinogen (PG), in particular, the percentage change in the PG I/II ratio. Here, we evaluated the usefulness of the percentage changes in serum PG I/II ratios for determining the success of eradication therapy for <i>H</i>. <i>pylori</i>.</p><p>Materials and methods</p><p>In total, 650 patients received eradication therapy from October 2008 to March 2013 in our Cancer Institute Hospital. We evaluated the relationship between <i>H</i>. <i>pylori</i> eradication and percentage changes in serum PG I/II ratios before and 3 months after treatment with CLEIA^® (FUJIREBIO Inc, Tokyo, Japan). The gold standard of <i>H</i>. <i>pylori</i> eradication was defined as negative by the UBT performed 3 months after completion of eradication treatment. Cut-off values for percentage changes in serum PG I/II ratios were set as +40, +25 and +10% when the serum PG I/II ratio before treatment was below 3.0, above 3.0 but below 5.0 and 5.0 or above, respectively.</p><p>Results</p><p>Serum PG I and PG II levels were measured in 562 patients with <i>H</i>. <i>pylori</i> infection before and after eradication therapy. Eradication of <i>H</i>. <i>pylori</i> was achieved in 433 patients studied (77.0%). The ratios of first, second, third-line and penicillin allergy eradication treatment were 73.8% (317/429), 88.3% (99/112), 75% (12/16) and 100% (5/5), respectively. An increasing percentage in the serum levels of the PG I/II ratios after treatment compared with the values before treatment clearly distinguished success from failure of eradication (108.2±57.2 vs. 6.8±30.7, <i>p</i><0.05). Using the above cut-off values, the sensitivity, specificity and validity for determination of <i>H</i>. <i>pylori</i> were 93.1, 93.8 and 93.2%, respectively.</p><p>Conclusion</p><p>In conclusion, the percentage changes in serum PG I/II ratios are useful as evaluation criteria for assessing the success of eradication therapy for <i>H</i>. <i>pylori</i>.</p></div

Correlation between the percentage change in the PG I/II ratio and the PG I/II ratio before treatment.

<p>Correlation between the percentage change in the PG I/II ratio and the PG I/II ratio before treatment.</p

Low risk of local recurrence after a successful en bloc endoscopic submucosal dissection for noninvasive colorectal lesions with positive horizontal resection margins (R-ESD study)

Background During endoscopic submucosal dissection (ESD), the normal mucosa is cut under constant optical control. We studied whether a positive horizontal resection margin after a complete en bloc ESD predicts local recurrence. Methods In this European multicenter cohort study, patients with a complete en bloc colorectal ESD were selected from prospective registries. Cases were defined by a horizontal resection margin that was positive or indeterminate for dysplasia (HM1), whereas controls had a free resection margin (HM0). Low risk lesions with submucosal invasion (T1) and margins free of carcinoma were analyzed separately. The main outcome was local recurrence. Results From 928 consecutive ESDs (2011–2020), 354 patients (40% female; mean age 67 years, median follow-up 23.6 months), with 308 noninvasive lesions and 46 T1 lesions, were included. The recurrence rate for noninvasive lesions was 1/212 (0.5 %; 95 %CI 0.02%–2.6%) for HM0 vs. 2/96 (2.1 %; 95 %CI 0.57%–7.3%) for HM1.The recurrence rate for T1 lesions was 1/38 (2.6%; 95%CI 0.14%–13.5%) for HM0 vs. 2/8 (25%; 95%CI 7.2%–59.1 %) for HM1. Conclusion A positive horizontal resection margin after an en bloc ESD for noninvasive lesions is associated with a marginal nonsignificant increase in the local recurrence rate, equal to an ESD with clear horizontal margins. This could not be confirmed for T1 lesions

Patient characteristics.

<p>Patient characteristics.</p

Development and validation of the international Blue Light Imaging for Barrett's Neoplasia Classification

BACKGROUND AND AIMS: Detecting subtle Barrett's neoplasia during surveillance endoscopy can be challenging. Blue-light imaging (BLI) is a novel advanced endoscopic technology with high-intensity contrast imaging that may improve the identification of Barrett's neoplasia. The aim of this study was to develop and validate the first classification to enable characterization of neoplastic and non-neoplastic Barrett's esophagus using BLI. METHODS: In phase 1, descriptors pertaining to neoplastic and non-neoplastic Barrett's esophagus were identified to form the classification, named the Blue Light Imaging for Barrett's Neoplasia Classification (BLINC). Phase 2 involved validation of these component criteria by 10 expert endoscopists assessing 50 BLI images. In phase 3, a web-based training module was developed to enable 15 general (nonexpert) endoscopists to use BLINC. They then validated the classification with an image assessment exercise in phase 4, and their pre- and post-training results were compared. RESULTS: In phase 1 the descriptors were grouped into color, pit, and vessel pattern categories to form the classification. In phase 2 the sensitivity of neoplasia identification was 96.0% with a very good level of agreement among the experts (κ = .83). In phase 3, 15 general endoscopists completed the training module. In phase 4 their pretraining sensitivity (85.3%) improved significantly to 95.7% post-training with a good level of agreement (κ = .67). CONCLUSIONS: We developed and validated a new classification system (BLINC) for the optical diagnosis of Barrett's neoplasia using BLI. Despite the limitations of this image-based study with a high prevalence of neoplasia, we believe it has the potential to improve the optical diagnosis of Barrett's neoplasia given the high degree of sensitivity (96%) noted. It is also a promising tool for training in Barrett's esophagus optical diagnosis using BLI.status: publishe

A computer-assisted algorithm for narrow-band imaging-based tissue characterization in Barrett's esophagus

Background and Aims: The endoscopic evaluation of narrow-band imaging (NBI) zoom imagery in Barrett's esophagus (BE) is associated with suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CAD) systems may assist endoscopists in the characterization of Barrett's mucosa. Our aim was to demonstrate the feasibility of a deep-learning CAD system for tissue characterization of NBI zoom imagery in BE. Methods: The CAD system was first trained using 494,364 endoscopic images of general endoscopic imagery. Next, 690 neoplastic BE and 557 nondysplastic BE (NDBE) white-light endoscopy overview images were used for refinement training. Subsequently, a third dataset of 112 neoplastic and 71 NDBE NBI zoom images with histologic correlation was used for training and internal validation. Finally, the CAD system was further trained and validated with a fourth, histologically confirmed dataset of 59 neoplastic and 98 NDBE NBI zoom videos. Performance was evaluated using fourfold cross-validation. The primary outcome was the diagnostic performance of the CAD system for classification of neoplasia in NBI zoom videos. Results: The CAD system demonstrated accuracy, sensitivity, and specificity for detection of BE neoplasia using NBI zoom images of 84%, 88%, and 78%, respectively. In total, 30,021 individual video frames were analyzed by the CAD system. Accuracy, sensitivity, and specificity of the video-based CAD system were 83% (95% confidence interval [CI], 78%-89%), 85% (95% CI, 76%-94%), and 83% (95% CI, 76%-90%), respectively. The mean assessment speed was 38 frames per second. Conclusion: We have demonstrated promising diagnostic accuracy of predicting the presence/absence of Barrett's neoplasia on histologically confirmed unaltered NBI zoom videos with fast corresponding assessment time

A computer-assisted algorithm for narrow-band imaging-based tissue characterization in Barrett's esophagus.

BACKGROUND AND AIMS: The endoscopic evaluation of narrow-band imaging (NBI) zoom imagery in Barrett's esophagus (BE) is associated with suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CAD) systems may assist endoscopists in the characterization of Barrett's mucosa. Our aim was to demonstrate the feasibility of a deep-learning CAD system for tissue characterization of NBI zoom imagery in BE. METHODS: The CAD system was first trained using 494,364 endoscopic images of general endoscopic imagery. Next, 690 neoplastic BE and 557 nondysplastic BE (NDBE) white-light endoscopy overview images were used for refinement training. Subsequently, a third dataset of 112 neoplastic and 71 NDBE NBI zoom images with histologic correlation was used for training and internal validation. Finally, the CAD system was further trained and validated with a fourth, histologically confirmed dataset of 59 neoplastic and 98 NDBE NBI zoom videos. Performance was evaluated using fourfold cross-validation. The primary outcome was the diagnostic performance of the CAD system for classification of neoplasia in NBI zoom videos. RESULTS: The CAD system demonstrated accuracy, sensitivity, and specificity for detection of BE neoplasia using NBI zoom images of 84%, 88%, and 78%, respectively. In total, 30,021 individual video frames were analyzed by the CAD system. Accuracy, sensitivity, and specificity of the video-based CAD system were 83% (95% confidence interval [CI], 78%-89%), 85% (95% CI, 76%-94%), and 83% (95% CI, 76%-90%), respectively. The mean assessment speed was 38 frames per second. CONCLUSION: We have demonstrated promising diagnostic accuracy of predicting the presence/absence of Barrett's neoplasia on histologically confirmed unaltered NBI zoom videos with fast corresponding assessment time.status: Published onlin