Numerous lesions of gastric adenocarcinoma of fundic-gland and fundic gland-mucosa type in a patient.

A man in his 60 s underwent upper gastrointestinal endoscopy at our hospital, which revealed a 30-mm elevated lesion in the upper stomach (main lesion). There were several discolored, flat mucosal lesions and slightly elevated, reddish, subepithelial mass-like lesions (multiple secondary lesions) in the gastric fornix and body. Histopathological examination of several biopsied secondary lesions revealed gastric adenocarcinoma of fundic-gland type (GA-FG) or gastric adenocarcinoma of fundic gland-mucosa type (GA-FGM). The main lesion was suspected to be GA-FGM on magnifying endoscopy with narrow-band imaging. It was removed using endoscopic submucosal dissection for therapeutic and diagnostic purposes. The histopathological diagnosis of the resected lesion was GA-FGM, which was surrounded by two GA-FGM and > 30 GA-FG lesions. Total gastrectomy was considered; however, the patient declined further surgical treatment. Therefore, he was followed up with biannual endoscopy and computed tomography. At five years postoperatively, no tumor growth or metastasis has been observed.

Magnifying endoscopy with narrow-band imaging for diagnosis of subtype of gastric intestinal metaplasia.

BACKGROUND AND AIM: Patients with incomplete gastric intestinal metaplasia (GIM) have a higher risk of gastric cancer (GC) than those with complete GIM. We aimed to clarify whether micromucosal patterns of GIM in magnifying endoscopy with narrow-band imaging (M-NBI) were useful for diagnosis of incomplete GIM. METHODS: We enrolled patients with a history of endoscopic resection of GC or detailed inspection for suspicious or definite GC. The antrum greater curvature and corpus lesser curvature were regions of interest. Areas with endoscopic findings of light blue crest and/or white opaque substance (WOS) were defined as endoscopic GIM, and subsequent M-NBI was applied. Micromucosal patterns were classified into Foveola and Groove types, and targeted biopsies were performed on GIM with each pattern. GIM was classified into complete and incomplete types using mucin (MUC)2, MUC5AC, MUC6, and CD10 immunohistochemical staining. The primary endpoint was the association between micromucosal pattern and histological subtype. The secondary endpoint was endoscopic findings associated with incomplete GIM. RESULTS: We analyzed 98 patients with 156 GIMs. Univariate analysis (odds ratio [OR] 3.4, P = 0.004), but not multivariate analysis (OR 0.87, P = 0.822), demonstrated a significant association between micromucosal pattern and subtype. The antrum (OR 3.7, P = 0.006) and WOS (OR 43, P = 0.002) were independent predictors for incomplete GIM. The WOS had 69% sensitivity and 93% specificity. CONCLUSIONS: The M-NBI micromucosal pattern is not useful for diagnosis of GIM subtype. WOS is a promising endoscopic indicator for diagnosis of incomplete GIM. (UMIN-CTR000041119).

Periodontal Regenerative Therapy with Recombinant Human Fibroblast Growth Factor (rhFGF) -2 for Stage III Grade C Periodontitis: A Case Report with 6-month Follow-up.

This report describes a case of generalized chronic periodontitis requiring periodontal regenerative therapy. The patient was a 56-year-old woman visiting the Tokyo Dental College Suidobashi Hospital with the chief complaint of swelling in the maxillary right gingiva. An initial examination revealed 34.0% of sites with a probing depth (PD) of ≥4 mm. The prevalence of sites with bleeding on probing was 32.7%. The plaque control record (PCR) score was 65.7%. Radiographic examination revealed angular bone resorption at #18 and 48. Horizontal absorption was also observed in other areas. The percent bone loss/age at #48 was 1.07. A clinical diagnosis of generalized chronic periodontitis (Stage III, Grade C) was made. Based on the clinical diagnosis of severe chronic periodontitis, initial periodontal therapy was performed. An improvement was observed in periodontal conditions at re-evaluation. The PCR score was 16.7%. Periodontal surgery was performed for teeth with a residual PD of ≥4 mm. Periodontal regenerative therapy using rhFGF-2 were performed on intrabony defects in #18 and 48. Open flap debridement was performed on #16, 26, and 27. Following evaluation, oral function was restored using all-ceramic crowns (#46). At 6 months postoperatively, the patient was transitioned to supportive periodontal therapy (SPT). During the 6-month SPT, stable periodontal conditions that facilitated a favourable level of plaque control were maintained.

Treatment of Stage III Grade C Periodontitis with Periodontal Regenerative Therapy including Guided Tissue Regeneration (GTR) and Recombinant Human Fibroblast Growth Factor (rhFGF)-2: A Case Report.

This report describes a case of periodontitis treated with periodontal surgery including guided tissue regeneration (GTR) and recombinant human fibroblast growth factor (rhFGF)-2. The patient was a 54-year-old woman who visited the Tokyo Dental College Suidobashi Hospital with the chief complaint of swelling in the maxillary right gingiva. An initial examination revealed 30.4% of sites with a probing depth (PD) of ≥4 mm. The prevalence of sites with bleeding on probing was 57.7%. The plaque control record (PCR) score was 66.1%. Radiographic examination revealed vertical bone defects in the molar region. Based on these findings, the clinical diagnosis was generalized chronic periodontitis (Stage III, Grade C). Initial periodontal therapy yielded an improvement in periodontal conditions, with the PCR score reducing to 13.8%. Periodontal surgery was performed for teeth with a residual PD ≥4 mm. Guided tissue regeneration was performed on #37 and 47. A series of periodontal regenerative treatments comprising application of rhFGF-2 was performed on angular bone defects in #14, 15, 25, and 27. Open flap debridement was performed on #16, 17, 26, 36, and 46. Following evaluation, oral function was restored by placing all-ceramic crowns on #21 and 26. The patient was then placed on supportive periodontal therapy. In the present case of generalized chronic periodontitis, periodontal regenerative therapy with GTR and rhFGF-2 yielded stable periodontal conditions.

A comparative study of demarcation line diagnostic performance between non-magnifying observation with white light and non-magnifying observation with narrow-band light for early gastric cancer.

BACKGROUND AND AIMS: With the improvement in endoscopic equipment functions, narrow-band imaging (NBI) for endoscopic observation of the stomach, which is an organ with a large lumen, is now feasible. Studies evaluating the NBI utility without magnifying endoscopy to diagnose the invasion extent for the demarcation line identification in early gastric cancer have not been reported. This study aimed to investigate the demarcation line diagnostic performance of NBI in early gastric cancer compared to that of white-light imaging (WLI) using prospectively collected consecutive specimens from early gastric cancer patients. METHODS: Thirty consecutive lesions were collected from patients who underwent endoscopic submucosal dissection for early gastric cancer. Next, 30 NBI and 30 WLI images, each with the same degree of gastric wall extension, angle, and layout for one lesion, were selected, and a total of 60 images were prepared for testing. The early gastric cancer invasion ranges in the endoscopic images was plotted using the web-developed software, and 264 independent endoscopists, unaware of the diagnosis, performed the web tests, with the concordance rates between the ranges of responses. After estimating the actual early gastric cancer invasion ranges, the NBI and WLI results were compared. RESULTS: The concordance rates for NBI and WLI images were 43.1% (95% confidence interval [CI] 42.5-43.7%) and 37.2% (95% CI 36.6-37.7%), respectively, showing that the concordance rate for NBI was significantly higher than that for WLI. CONCLUSION: This study suggested that NBI was more useful for identifying demarcation lines than WLI.

Treatment of Chronic Periodontitis with Periodontal Surgery Including Regenerative Therapy Using Recombinant Human Fibroblast Growth Factor-2 and Papilla Preservation Technique: A Case Report with a Two-year Follow-up.

This report describes a case of generalized chronic periodontitis requiring periodontal therapy including periodontal regeneration. The patient was a 59-year-old man who visited the Tokyo Dental College Suidobashi Hospital with the chief complaint of mobility in tooth #47. Periodontal examination at the first visit revealed that 32.1% of sites had a probing depth of ≥4 mm and 32.7% of sites bleeding on probing. Radiographic examination revealed vertical bone resorption in #26 and horizontal resorption in #12, 13, 42, and 43. Based on a clinical diagnosis of severe chronic periodontitis, initial periodontal therapy consisting of plaque control, scaling and root planing, occlusal adjustment, caries treatment, and placement of an occlusal splint was performed. Tooth #47 was extracted due to bone resorption extending as far as the root apex. After reevaluation, surgical periodontal treatment was performed at the selected site. Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 and papilla preservation technique was performed for #26. To reduce periodontal pockets, open flap debridement was implemented for #12, 13, 42, and 43. After reevaluation, the patient was placed on supportive periodontal therapy (SPT). Periodontal regenerative therapy with rhFGF-2 and modified papilla preservation technique yielded an improvement in angular bone resorption which has been properly maintained for two years. Periodontal therapy with open flap debridement resulted in an improvement in horizontal bone resorption. Continued SPT is needed to maintain a stable periodontal condition.

Surgical Periodontal Therapy Using Recombinant Human Fibroblast Growth Factor-2 in Combination with Carbonate Apatite Granules for Stage III Grade B Periodontitis: A Case Report with 1-year Follow-up.

This report describes a case of generalized chronic periodontitis requiring periodontal treatment including regenerative therapy. The patient was a 60-year-old woman who visited the Tokyo Dental College Suidobashi Hospital with the chief complaint of tooth mobility and pain in tooth #26. Periodontal examination at the first visit revealed that 32.0% of sites had a probing depth of ≥4 mm and 43.8% bleeding on probing. Radiographic examination revealed vertical bone resorption in #17. Horizontal resorption was noted in other areas. Initial periodontal therapy consisting of plaque control, scaling and root planing, and caries treatment was performed based on a clinical diagnosis of Stage III Grade B periodontitis. Tooth #26 was extracted due to bone resorption extending as far as the root apex. After reevaluation, periodontal regenerative therapy using recombinant human fibroblast growth factor-2 (rhFGF-2) in combination with carbonate apatite (CO3Ap) granules was performed for #17. Following reevaluation, a zirconia crown (#16) and zirconia bridge (#24-27) were placed. Following further reevaluation, the patient was placed on supportive periodontal therapy (SPT). The periodontal regenerative therapy using rhFGF-2 with CO3Ap granules yielded an improvement in the vertical bone resorption observed in #17. This improvement has been adequately maintained over a 1-year period postoperatively. Continued SPT is needed to maintain stable periodontal conditions.

Characteristic endoscopic findings of gastric adenocarcinoma of fundic-gland mucosa type.

BACKGROUND AND STUDY AIMS: Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) was reported as a subtype of gastric adenocarcinoma. This study aimed to investigate the endoscopic findings of GA-FGM and to evaluate the differences between GA-FGM and GA-FG. PATIENTS AND METHODS: This was a single-center retrospective study. Participants were selected from patients with gastric cancer treated at Fukuoka University Chikushi Hospital, between September 2007 and May 2020. Patients histologically diagnosed with GA-FGM or GA-FG were enrolled, and endoscopic findings were analyzed in detail. RESULTS: A total of 12 GA-FGM lesions (12 patients) and 14 GA-FG lesions (13 patients) were analyzed. The two lesion types showed similar features: most lesions were of elevated type, located in the upper stomach, and developed in the stomach without Helicobacter pylori infection. On conventional endoscopy using the dye-spraying method, well-demarcated fine granular areas were observed in 7 GA-FGM lesions (58%) but not in any GA-FG lesions, with a significant difference between the two groups (P = 0.001). Magnifying endoscopy with narrow-band imaging (NBI) showed that 11 GA-FGM lesions (92%) met the diagnostic criteria for cancer according to the vessel plus surface classification system, whereas none of the GA-FG lesions met the same criteria (0%, 0/14) (P = 0.001). CONCLUSION: Our results suggest that magnifying endoscopy with NBI is a potentially useful method for the diagnosis of GA-FGM.

Systemic administration of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation.

BACKGROUND/OBJECTIVES: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule expressed on T cells. CTLA-4 also binds to the surfaces of monocytes and macrophages, precursors of osteoclasts. Research on rheumatoid arthritis demonstrated that CTLA-4 suppresses inflammation and bone resorption. However, its effects on alveolar bone have yet to be understood. The purpose of this study was to investigate the role and potential mechanism of CTLA-4 in bone resorption in periodontitis. MATERIALS AND METHODS: In vivo, the effects of systemic administration of CTLA-4 immunoglobulin fusion protein (CTLA-4-Ig) on alveolar bone resorption were investigated using a periodontitis mouse model. A total of 20 C57BL/6J mice were randomly assigned to two groups according to the administration modes. Periodontitis was induced by placing a ligature around the left maxillary second molar. The contralateral tooth was left un-ligated. In the CTLA-4-Ig (+) group, CTLA-4-Ig was administered by intraperitoneal injection at 1 and 3 days after ligature placement. Animals in the CTLA-4-Ig (-) group were given only phosphate-buffered saline each time. At 5 days after ligature placement, bone resorption was assessed by micro-computed tomography and histological examination, and the prevalence of osteoclast-like cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining. In vitro, the effects of CTLA-4-Ig on osteoclasts were evaluated. Viability of RAW 264.7 cells treated with receptor activator of nuclear factor-κB ligand (RANKL) and CTLA-4-Ig was tested by WST-1 assay. Osteoclast-like cells were enumerated by TRAP staining, and osteoclast activity was evaluated by resorption pit assay. Gene expression levels of osteoclast differentiation markers (macrophage-colony stimulating factor receptor, carbonic anhydrase II, cathepsin K, and Trap) and protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, were assessed by quantitative real-time polymerase chain reaction. The effect of CTLA-4-Ig on the nuclear factor-κB (NF-κB) activation was assessed by enzyme-linked immunosorbent assay. RESULTS: In vivo, ligature-induced bone resorption and the numbers of osteoclast-like cells were significantly decreased by the administration of CTLA-4-Ig. In vitro, treatment with RANKL and CTLA-4-Ig had no significant effect on cell viability. CTLA-4-Ig significantly reduced the prevalence and activation of osteoclast-like cells and decreased the expressions of osteoclast differentiation markers, compared with the RANKL-treated control. CTLA-4-Ig significantly suppressed RANKL-induced phosphorylation of NF-κB p65 but increased PP2A expression. CONCLUSION: These results suggest that CTLA-4-Ig abrogates bone resorption in induced periodontitis, possibly via inhibition of osteoclast differentiation and activation. The regulation of the NF-κB pathway and PP2A expression may be one mechanism by which CTLA-4-Ig suppresses osteoclast behavior.

Treatment with functionalized designer self-assembling peptide hydrogels promotes healing of experimental periodontal defects.

BACKGROUND/OBJECTIVES: It has been reported that self-assembling peptide (SAP) hydrogels with functionalized motifs enhance proliferation and migration of host cells. How these designer SAP hydrogels perform in the treatment of periodontal defects remains unknown. This study aimed to test the potential of local application of designer SAP hydrogels with two different functionalized motifs in the treatment of experimental periodontal defects. MATERIAL AND METHODS: In vitro, viability/proliferation of rat periodontal ligament-derived cells (PDLCs) cultured on an SAP hydrogel RADA16 and RADA16 with functionalized motifs, PRG (integrin binding sequence) and PDS (laminin cell adhesion motif), was assessed. Cell morphology was analyzed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In vivo, standardized periodontal defects were made mesially in the maxillary first molars of Wistar rats. Defects received RADA16, PRG, PDS or left unfilled. At 2 or 4 weeks postoperatively, healing was assessed by microcomputed tomography, histological and immunohistochemical methods. RESULTS: Viability/proliferation of PDLCs was significantly greater on PRG than on RADA16 or PDS at 72 hours. rPDLCs in the PRG group showed enhanced elongations and cell protrusions. In vivo, at 4 weeks, bone volume fractions in the PRG and PDS groups were significantly greater than the RADA16 group. Histologically, bone formation was more clearly observed in the PRG and PDS groups compared with the RADA16 group. At 4 weeks, epithelial downgrowth in the hydrogel groups was significantly reduced compared to the Unfilled group. In Azan-Mallory staining, PDL-like bundles ran in oblique direction in the hydrogel groups. At 2 weeks, in the area near the root, proliferating cell nuclear antigen (PCNA)-positive cells were detected significantly more in the PRG group than other groups. At 4 weeks, in the middle part of the defect, a significantly greater level of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (SMA)-positive blood vessels were observed in the PRG group than in other groups. CONCLUSION: The results indicate that local application of the functionalized designer SAP hydrogels, especially PRG, promotes periodontal healing by increasing cell proliferation and angiogenesis.

Periodontal surgery using rhFGF-2 with deproteinized bovine bone mineral or rhFGF-2 alone: 2-year follow-up of a randomized controlled trial.

AIM: To compare outcomes of rhFGF-2 + DBBM therapy with rhFGF-2 alone in the treatment of intrabony defects. This study provides 2-year follow-up results from the previous randomized controlled trial. MATERIALS AND METHODS: Defects were randomly allocated to receive rhFGF-2 + DBBM (test) or rhFGF-2 (control). Treated sites were re-evaluated at 2 years postoperatively, using original clinical and patient-centred measures. RESULTS: Thirty-eight sites were available for re-evaluation. At 2 years, both groups showed a significant improvement in clinical attachment level (CAL) from baseline. A gain in CAL of 3.4 ± 1.3 mm in the test group and 3.1 ± 1.5 mm in the control group was found. No significant inter-group difference was noted. Both groups showed a progressive increase in radiographic bone fill (RBF). The test treatment yielded greater RBF (56%) compared with the control group (41%). The control treatment performed better in contained defects in terms of CAL and RBF. There was no significant difference in patient-reported outcomes between groups. CONCLUSIONS: At 2-year follow-up, the test and cotrol treatments were similarly effective in improving CAL, whereas the test treatment achieved a significantly greater RBF. In both treatments, favourable clinical, radiographic, and patient-reported outcomes can be sustained for at least 2 years. TRIAL REGISTRATION: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) 000025257.

Root Coverage with Connective Tissue Graft in Patients with Thin Periodontal Biotype: A Case Series with 12-month Follow-up.

Preoperative gingival thickness is an important factor in the success of complete root coverage. Here, two cases are reported in which a biotype probe was used to assess the periodontal biotype before performance of a root coverage procedure. Clinical examinations were performed at baseline and at 3, 6, and 12 months postoperatively. The following clinical parameters were evaluated: probing depth, recession height, clinical attachment level, bleeding on probing, and width of keratinized gingiva. At baseline and at 12 months postoperatively, periodontal biotype was estimated using the biotype probe. The root coverage esthetic score was assessed to determine esthetic outcome at baseline and at 3, 6, and 12 months postoperatively. The periodontal biotypes in the mandibular central and lateral incisors were judged to be thin. These teeth presented with Miller Class II gingival recession after orthodontic therapy. Gingival recession was treated with a coronally advanced flap and autogenous connective tissue graft. In both cases, improvements in all clinical parameters and root coverage esthetic scores were evaluated at 3, 6, and 12 months postoperatively. The treated recession showed 100% root coverage. The periodontal biotype changed from one that was thin to one that was thick at the surgical sites. In both the present cases, objective preoperative assessment of the periodontal biotype allowed the appropriate surgical procedure to be selected.

Treatment of Chronic Periodontitis with Recombinant Human Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral in Wide Intrabony Defects:12-month Follow-up Case Series.

Clinical use of 0.3% recombinant human fibroblast growth factor (rhFGF)-2 for periodontal regeneration received formal approval in Japan in 2016. The combination of growth factor and bone graft material is used to enhance periodontal healing in regenerative therapy. The exact effects of combination therapy on periodontal healing remain unknown, however. Here, we report three cases of chronic periodontitis treated with the combination of rhFGF-2 and deproteinized bovine bone mineral (DBBM). Following initial periodontal therapy, periodontal regenerative therapy using rhFGF-2 in combination with DBBM was performed to treat wide intrabony defects. Periodontal parameters and radiographic bone fill were reevaluated at 3 months, 6 months, and 1 year postoperatively. Oral health-related quality of life (OHRQL) was assessed as a patient-reported measure of outcome. At 1 year postoperatively, probing pocket depth and clinical attachment level showed a significant improvement in comparison with at baseline. An improvement was also noted in radiographic evidence of bone fill and total OHRQL scores. Combination therapy yielded clinically favorable results in the present cases.

Surgical Treatment of Furcation Involvement Associated with Recurrence of Aggressive Periodontitis: A Case Report.

Here, we report a case of generalized chronic periodontitis with furcation involvement that was treated successfully by means of surgical intervention. The patient was a 43-year-old man requesting treatment for periodontal disease. An initial examination revealed 42% of sites with a probing depth of ≥4 mm and 42.9% of sites with bleeding on probing. The maxillary molars showed varying degrees of furcation involvement. Radiographic examination revealed bone resorption in the molar and mandibular anterior teeth regions. Microbiological examination of subgingival plaque revealed the presence of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia. The patient's oral health-related quality of life (OHRQL) was also assessed. Based on a clinical diagnosis of severe chronic periodontitis, initial periodontal therapy was performed. Plaque control, scaling and root planing, extraction, temporary fixed restoration, occlusal adjustment, and root canal treatment were implemented. Following reevaluation, open flap debridement was performed at selected sites. Root resection was performed on the distal root of #16. Prosthetic treatment was then initiated for recovery of oral function. After confirmation of appropriate occlusion and cleanability, the patient was placed on supportive periodontal therapy. Root resection improved cleanability. This clinical improvement has been adequately maintained over a 2-year period. The patient's OHRQL score showed a slight deterioration during the supportive periodontal therapy OK period, however. This indicates the need for further careful monitoring of periodontal conditions, as well as of how they are perceived by the patient themselves.

Combined effects of systemic parathyroid hormone (1-34) and locally delivered neutral self-assembling peptide hydrogel in the treatment of periodontal defects: An experimental in vivo investigation.

AIM: To evaluate in vivo combination therapy of systemic parathyroid hormone (PTH) and locally delivered neutral self-assembling peptide (SAP) hydrogel for periodontal treatment. MATERIALS AND METHODS: Viability/proliferation of rat periodontal ligament cells in a neutral SAP nanofibre hydrogel (SPG-178) was evaluated using WST-1 assay. Periodontal defects were created mesially to the maxillary first molars in 40 Wistar rats. Defects were filled with 1.5% SPG-178 or left unfilled. Animals received PTH (1-34) or saline injections every 2 days. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing at 2 or 4 weeks postoperative. RESULTS: At 72 hr, cells in 1.5% SPG-178 showed increased viability/proliferation compared to cells in 0.8% SPG-178 or untreated controls. In vivo, systemic PTH resulted in significantly greater bone volume in the Unfilled group at 2 weeks (p = .01) and 4 weeks (p < .0001) than in the saline control. At 4 weeks, a significantly greater bone volume was observed in the PTH/SPG-178 (p = .0003) and PTH/Unfilled (p = .004) groups than in Saline/SPG-178 group. Histologically, greater bone formation was observed in PTH/SPG-178 at 4 weeks than in other groups. In the PTH/SPG-178 group, increased proportions of PCNA-, VEGF-, and Osterix-positive cells were observed in the treated sites. CONCLUSIONS: These findings suggest that intermittent systemic PTH and locally delivered neutral SAP hydrogel enhance periodontal healing.

Treatment of intrabony periodontal defects using rhFGF-2 in combination with deproteinized bovine bone mineral or rhFGF-2 alone: A 6-month randomized controlled trial.

AIM: To evaluate the use of recombinant human fibroblast growth factor (rhFGF)-2 in combination with deproteinized bovine bone mineral (DBBM) compared with rhFGF-2 alone, in the treatment of intrabony periodontal defects. MATERIALS AND METHODS: Patients with periodontitis who had received initial periodontal therapy and had intrabony defects of ≥ 3 mm in depth were enrolled. Sites were randomly assigned to receive a commercial formulation of 0.3% rhFGF-2 + DBBM (test) or rhFGF-2 alone (control). Clinical parameters and a patient-reported outcome measure (PROM) were evaluated at baseline and at 3 and 6 months postoperatively. RESULTS: Twenty-two sites in each group were evaluated. A significant improvement in clinical attachment level (CAL) from baseline was observed in both groups at 6 months postoperatively. CAL gain was 3.16 ± 1.45 mm in the test group and 2.77 ± 1.15 mm in the control group, showing no significant difference between groups. Radiographic bone fill was significantly greater in the test group (47.2%) than in the control group (29.3%). No significant difference in PROM between groups was observed. CONCLUSIONS: At 6 months, no significant difference in CAL gain or PROM between the two treatments was observed, although combination therapy yielded an enhanced radiographic outcome.

Efficient siRNA delivery and gene silencing using a lipopolypeptide hybrid vector mediated by a caveolae-mediated and temperature-dependent endocytic pathway.

BACKGROUND: We developed a non-viral vector, a combination of HIV-1 Tat peptide modified with histidine and cysteine (mTat) and polyethylenimine, jetPEI (PEI), displaying the high efficiency of plasmid DNA transfection with little toxicity. Since the highest efficiency of INTERFERin (INT), a cationic amphiphilic lipid-based reagent, for small interfering RNA (siRNA) transfection among six commercial reagents was shown, we hypothesized that combining mTat/PEI with INT would improve transfection efficiency of siRNA delivery. To elucidate the efficacy of the hybrid vector for siRNA silencing, ß-actin expression was measured after siRNA ß-actin was transfected with mTat/PEI/INT or other vectors in HSC-3 human oral squamous carcinoma cells. RESULTS: mTat/PEI/INT/siRNA produced significant improvement in transfection efficiency with little cytotoxicity compared to other vectors and achieved ≈ 100% knockdown of ß-actin expression compared to non-treated cells. The electric charge of mTat/PEI/INT/siRNA was significantly higher than INT/siRNA. The particle size of mTat/PEI/INT/siRNA was significantly smaller than INT/siRNA. Filipin III and ß-cyclodextrin, an inhibitor of caveolae-mediated endocytosis, significantly inhibited mTat/PEI/INT/siRNA transfection, while chlorpromazine, an inhibitor of clathrin-mediated endocytosis, did not inhibit mTat/PEI/INT/siRNA transfection. Furthermore, the transfection efficiency of mTat/PEI/INT at 4 °C was significantly lower than 37 °C. CONCLUSIONS: These findings demonstrated the feasibility of using mTat/PEI/INT as a potentially attractive non-viral vector for siRNA delivery.

Clinical predictors of histologic type of gastric cancer.

BACKGROUND AND AIMS: Gastric cancer is classified into differentiated and undifferentiated types according to the degree of glandular differentiation. Undifferentiated-type early gastric cancer (EGC) carries a higher risk of lymph-node metastasis than differentiated type, and therefore the indication criteria for endoscopic resection differ. This study aimed to clarify the ability of clinical predictors to distinguish between differentiated-type and undifferentiated-type EGCs. METHODS: This was a post hoc study of a multicenter prospective trial carried out in 5 Japanese hospitals, including 343 patients with cT1 EGC of ≥10 mm. According to the protocol, age, sex, and endoscopic findings of cancer (diameter, location, macroscopic type, and invasion depth) were evaluated, and the final diagnosis was confirmed from resected specimens. We evaluated the associations between these clinical factors and the histologic type of cancer and calculated the ability of the factors to diagnose differentiated-type EGC. The diagnostic ability of forceps biopsy was also calculated as a reference. RESULTS: Multivariate analysis identified older age (≥72 years), male sex, larger tumor size (>30 mm), elevated type, and shallower invasion depth (cT1a) as independent significant predictors for differentiated-type EGC, with elevated type showing the highest positive likelihood ratio. The sensitivity, specificity, accuracy, and positive and negative likelihood ratios of elevated type for differentiated-type EGC were 24%, 99%, 38%, 15.7, and 0.77, respectively, compared with 96%, 86%, 95%, 7.0, and 0.04 for forceps biopsy. CONCLUSIONS: Endoscopic elevated type is a significant predictor for differentiated-type EGC and may exclude undifferentiated-type EGC without the need for forceps biopsy.

Delineation of the extent of early gastric cancer by magnifying narrow-band imaging and chromoendoscopy: a multicenter randomized controlled trial.

BACKGROUND: Accurate delineation of tumor margins is necessary for curative resection of early gastric cancer (EGC). The objective of this multicenter, randomized, controlled study was to compare the accuracy with which magnifying narrow-band imaging (M-NBI) and indigo carmine chromoendoscopy delineate EGC margins. METHODS: Patients with EGC ≥ 10 mm undergoing endoscopic or surgical resection were enrolled. The oral-side margins of the lesions were first evaluated with conventional white-light endoscopy in both groups and then delineated by either chromoendoscopy or M-NBI. Biopsies were taken from noncancerous and cancerous mucosa, each at 5 mm from the margin. Accurate delineation was judged to have been achieved when the histological findings in all biopsy samples were consistent with endoscopic diagnoses. The primary end point was the difference in rate of accurate delineation between the two techniques. RESULTS: Data on 343 patients were analyzed. The accurate delineation rate (95 % confidence interval) was 85.7 % (80.4 - 91.0) in the chromoendoscopy group (n = 168), and 88.0 % (83.2 - 92.8) in the M-NBI group (n = 175; P = 0.63). Lower third tumor location (odds ratio [OR] 2.9; P = 0.01), nonflat macroscopic type (OR 4.4; P < 0.01), and high diagnostic confidence (OR 3.6; P < 0.001) were associated with accurate delineation, whereas use of M-NBI was not (OR 1.2; P = 0.39). Even after adjustment for identified confounders, the difference in accurate delineation between the groups was not significant (OR 1.0; P = 0.82). CONCLUSIONS: M-NBI does not offer superior delineation of EGC margins compared with chromoendoscopy; the two methods appear to be clinically equivalent.

Extending magnifying NBI diagnosis of intestinal metaplasia in the stomach: the white opaque substance marker.

Background and aims Intestinal metaplasia (IM) of the stomach is associated with an increased risk of differentiated gastric cancer. While it is important to diagnose IM endoscopically, it can be difficult to observe by white-light endoscopy. In magnifying endoscopy with narrow-band imaging (M-NBI) of the stomach, a light-blue crest (LBC) is widely known to be a useful marker in the endoscopic diagnosis of IM. However, IM that exhibits only white opaque substance (WOS) without an LBC can also occur. The aim of this study was to elucidate whether the presence of WOS on M-NBI of the stomach could serve as a marker of IM in the same way that an LBC does. Methods The subjects were 40 consecutive patients who underwent M-NBI between July and December 2014. The primary endpoint in this study was to evaluate the diagnostic performance of M-NBI for histologically observed IM in WOS- and LBC-positive mucosa. Results The sensitivity and specificity of WOS for histologically diagnosed IM were 50.0 % (95 % confidence interval [CI] 40.0 % - 50.0 %) and 100.0 % (95 %CI 85.0 % - 100.0 %), respectively. Meanwhile, the sensitivity and specificity of LBC were 62.5 % (95 %CI 51.1 % - 65.9 %) and 93.8 % (95 %CI 76.7 % - 98.9 %), respectively. The sensitivity and specificity of WOS and/or LBC (WOS positive and LBC positive, WOS positive and LBC negative, or WOS negative and LBC positive) for histologically diagnosed IM were 87.5 % (95 %CI 76.9 % - 90.9 %) and 93.8 % (95 %CI 77.9 % - 98.9 %), respectively. Conclusions LBC and WOS are both useful markers for endoscopic diagnosis of IM. Combining both markers improves the sensitivity.Clinical trial number: UMINCTR000014453.