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Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

The number of gastric cancer (GC) patients with other diseases is increasing due to the aging of the population. In particular, in stage IA GC patients who have multiple diseases, surgical indications should be considered after identifying prognostic factors. We therefore investigated prognostic factors for stage IA GC in the elderly.Patient characteristics were collected and analyzed retrospectively for elderly patients with stage IA GC who underwent curative surgical treatment at Okayama University Hospital between 2010 and 2015, and an elderly group (EG; 75-79 years old) and very elderly group (VEG; ≥80 years old) were compared.Fifty-three patient in the EG and 31 patients in the VEG were compared. No factors associated with clinicopathological characteristics or surgical or postoperative short-term outcomes differed significantly between groups. Although no factors in the EG appeared significantly associated with poor overall survival (OS), severe comorbidity [Charlson Comorbidity Index (CCI) ≥2; P=0.019], open gastrectomy (P=0.012), high volume of blood loss (≥300 mL; P=0.013) and long postoperative hospital stay (≥14 days; P=0.041) were significantly associated with poor OS. Furthermore, only CCI ≥2 [hazard ratio (HR) =9.2; 95% confidence interval (CI): 1.2-68.9; P=0.032] was an independent prognostic factor associated with poor OS. Five-year OS was 88.9% for CCI 0/1 patients and 62.3% for CCI ≥2 patients, representing very impressive results.CCI ≥2 is an important prognostic factor in clinical decisions in stage IA GC patients ≥2, so careful determination of surgical indications is desirable.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are associated with the establishment and progression of peritoneal metastasis. This study investigated the efficacy of replicative oncolytic adenovirus-mediated p53 gene therapy (OBP-702) against CAFs and peritoneal metastasis of gastric cancer (GC). Higher CAF expression in the primary tumor was associated with poor prognosis of GC, and higher CAF expression was also observed with peritoneal metastasis in immunohistochemical analysis of clinical samples. And, we found transcriptional alteration of p53 in CAFs relative to normal gastric fibroblasts (NGFs). CAFs increased the secretion of cancer-promoting cytokines, including interleukin-6, and gained resistance to chemotherapy relative to NGFs. OBP-702 showed cytotoxicity to both GC cells and CAFs but not to NGFs. Overexpression of wild-type p53 by OBP-702 infection caused apoptosis and autophagy of CAFs and decreased the secretion of cancer-promoting cytokines by CAFs. Combination therapy using intraperitoneal administration of OBP-702 and paclitaxel synergistically inhibited the tumor growth of peritoneal metastases and decreased CAFs in peritoneal metastases. OBP-702, a replicative oncolytic adenovirus-mediated p53 gene therapy, offers a promising biological therapeutic strategy for peritoneal metastasis, modulating CAFs in addition to achieving tumor lysis.

Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature of tumors in the brain. To address this challenge, we first established PTEN-deficient melanoma brain metastasis mouse models and characterized them to be more immunosuppressive compared with primary melanoma, mimicking the clinical settings. Next, we developed an allogeneic twin stem cell (TSC) system composed of two tumor-targeting stem cell (SC) populations. One SC was loaded with oncolytic herpes simplex virus (oHSV), and the other SC was CRISPR-Cas9 gene-edited to knock out nectin 1 (N1) receptor (N1 KO ) to acquire resistance to oHSV and release immunomodulators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). Using mouse models of brain metastatic BRAF V600E /PTEN −/− and BRAF V600E/wt /PTEN −/− mutant melanomas, we show that locoregional delivery of TSCs releasing oHSV and GM-CSF (TSC-G) activated dendritic cell– and T cell–mediated immune responses. In addition, our strategy exhibited greater therapeutic efficacy when compared with the existing oncolytic viral therapeutic approaches. Moreover, the TSCs composed of SC-oHSV and SC N1KO –releasing GM-CSF and single-chain variable fragment anti–PD-1 (TSC-G/P) had therapeutic efficacy in both syngeneic and patient-derived humanized mouse models of leptomeningeal metastasis. Our findings provide a promising allogeneic SC-based immunotherapeutic strategy against melanomas in the CNS and a road map toward clinical translation.

H1299 cells stably co-transfected with KillerRed- and EGFP-expressing vectors (H1299-KillerRed-EGFP) were irradiated for 12 hours. Cells showed morphological changes following photobleaching and started to die, which could be visualized with GFP expression.

Supplementary Fig. S1: Schematic diagrams of the structures of replication-deficient and conditionally; Supplementary Fig. S2: The GFP fluorescence intensity of metastatic lymph nodes in HCT116-GFP-bearing mice after treatment with TelomKiller and laser irradiation. replicating adenovirus vectors; Supplementary Fig. S2: The GFP fluorescence intensity of metastatic lymph nodes in HCT116-GFP-bearing mice after treatment with TelomKiller and laser irradiation.

Supplementary Movie S1- MOV file 6383K, Time-lapse imaging of FUCCI-expressing CD133+ cells treated with OBP-301 or control on monolayer culture. Images were acquired every 20 min. The playback speed is 10, 800 x real time. Total imaging time = 48 hours. The cells in G0/ G1, S, or G2/M phases appear red, yellow, or green, respectively

Supplementary Movie S3 - MOV file 6227K, Time-lapse imaging of treatment dynamics of FUCCI-expressing dormant tumor spheres treated with OBP-301 or conventional therapy in three-dimensional culture. Tumor spheres were treated with mock (upper left), OBP-301 (upper right), cisplatin (lower left) or radiation (lower right). Images were acquired every 20 min. The playback speed is 30,240 x real time. Total imaging time = 7days. The cells in G0/ G1, S, or G2/M phases appear red, yellow, or green, respectively

Supplementary Fig. S1 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer

PDF file 1712K, Supplementary Methods Fig. S1. OBP-301 efficiently kills CD133+ cells from MKN7 cells resistant to conventional therapies. Fig. S2. CD133+ CS-like cells can produce CD133+ CS-like cells and CD133- non-CS-like cells. Fig. S3. CD133+ MKN7 cells produce larger colonies than CD133- MKN7 cells in vitro. Fig. S4. CD133+ cells have higher tumorigenicity in nude mice than CD133− cells. Fig. S5. Flow cytometry analysis shows that OBP-301 induces a significant increase in the percentage of both CD133+ CS-like and CD133- non-CS-like cells in S phase. Fig. S6. Expression of CD133 mRNA is associated with the population of CD133+ cells. Fig. S7. OBP-301 reduces the expression of CD133 mRNA. Fig. S8. CD133+ cells show higher expressions of p53, p21 and p27 proteins compared with CD133− cells. Fig. S9. Adenoviral E1A alters cell-cycle related proteins. Fig. S10. Experimental setup in vivo. Fig. S11. Experimental setup for combination therapy of OBP-301 plus cisplatin or paclitaxel in vitro. Fig. S12. The combination therapy of OBP-301 and chemotherapy is more effective than OBP-301 monotherapy on monolayer culture. Fig. S13. OBP-301 reduces the potentiality of stemness in CD133 positive cells. Fig. S14. The combination therapy of OBP-301 and chemotherapy is more effective against larger tumors. Fig. S15. A scheme for oncolytic adenovirus killing quiescent human cancer cells

A phase I dose-escalation study of telomerase-specific oncolytic adenovirus, OBP-301 (Telomelysin), is now under way in the United States to assess feasibility and to characterize its pharmacokinetics in patients with advanced solid tumors. The present preclinical study investigates whether OBP-301 and a chemotherapeutic agent that is commonly used for lung cancer treatment, gemcitabine, are able to enhance antitumor effects in vitro and in vivo. The antitumor effects of OBP-301 infection and gemcitabine were evaluated by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt assay. In vivo antitumor effects of intratumoral injection of OBP-301 in combination with systemic administration of gemcitabine were assessed on nu/nu mice s.c. xenografted with human lung tumors. OBP-301 infection combined with gemcitabine resulted in very potent synergistic cytotoxicity in human lung cancer cells. The three human lung cancer cell lines treated with OBP-301 for 24 hours tended to accumulate in S phase compared with controls. The proportion of cells in S phase increased from 43.85% to 56.41% in H460 cells, from 46.72% to 67.09% in H322 cells, and from 38.22% to 57.67% in H358 cells. Intratumoral injection of OBP-301 combined with systemic administration of gemcitabine showed therapeutic synergism in human lung tumor xenografts. Our data suggest that the combination of OBP-301 and gemcitabine enhances the antitumor effects against human lung cancer. We also found that the synergistic mechanism may be due to OBP-301–mediated cell cycle accumulation in S phase. These results have important implications for the treatment of human lung cancer.[Mol Cancer Ther 2009;8(4):980–7]

Supplementary Movie S2 - MOV file 4338K, Time-lapse imaging of FUCCI-expressing tumor spheres cultured in three-dimensional culture without serum (3D culture), or tumor sphere in monolayer culture with serum (monolayer culture). Images were acquired every 20 min. The playback speed is 12,342 x real time. Total imaging time = 48 hours. The cells in G0/ G1, S, or G2/M phases appear red, yellow, or green, respectively.

Supplementary Fig. S3 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer

Purpose: Because chemoradiotherapy selectively targets proliferating cancer cells, quiescent cancer stem–like cells are resistant. Mobilization of the cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of the cell cycle can eliminate quiescent cancer stem–like cells in solid cancers. Thus, we explored the use of a genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to mobilize the cell cycle and kill quiescent cancer stem–like cells.Experimental Design: We established CD133+ cancer stem–like cells from human gastric cancer MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent cancer stem–like cells. We visualized the treatment dynamics of OBP-301 killing of quiescent cancer stem–like cells in dormant tumor spheres and xenografts using a fluorescent ubiquitination cell-cycle indicator (FUCCI).Results: CD133+ gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133+ cancer stem–like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle mobilization from G0–G1 to S/G2/M phases and subsequent cell death in quiescent CD133+ cancer stem–like cells by mobilizing cell-cycle–related proteins. FUCCI enabled visualization of quiescent CD133+ cancer stem–like cells and proliferating CD133− non–cancer stem–like cells. Three-dimensional visualization of the cell-cycle behavior in tumor spheres showed that CD133+ cancer stem–like cells maintained stemness by remaining in G0–G1 phase. We showed that OBP-301 mobilized quiescent cancer stem–like cells in tumor spheres and xenografts into S/G2/M phases where they lost viability and cancer stem–like cell properties and became chemosensitive.Conclusion: Oncolytic adenoviral infection is an effective mechanism of cancer cell killing in solid cancer and can be a new therapeutic paradigm to eliminate quiescent cancer stem–like cells. Clin Cancer Res; 19(23); 6495–505. ©2013 AACR.

Supplementary Fig. S4 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer

Supplementary Fig. S2 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer

Supplementary Methods, Figures 1-10 from Telomerase-Dependent Oncolytic Adenovirus Sensitizes Human Cancer Cells to Ionizing Radiation via Inhibition of DNA Repair Machinery

The physics related to Berry curvature is now a central research topic in condensed matter physics. The Berry curvature dipole (BCD) is a significant and intriguing condensed matter phenomenon that involves inversion symmetry breaking. However, the creation and controllability of BCDs have so far been limited to far below room temperature (RT) and non-volatile (i.e., ferroic) BCDs have not yet been discovered, hindering further progress in topological physics. In this work, we demonstrate a switchable and non-volatile BCD effect at RT in a topological crystalline insulator, Pb1-xSnxTe (PST), which is attributed to ferroic distortion. Surprisingly, the magnitude of the ferroic BCD is several orders of magnitude greater than that of the non-ferroic BCDs that appear, for example, in transition metal dichalcogenides. The discovery of this ferroic and extraordinarily large BCD in PST could pave the way for further progress in topological material science and the engineering of novel topological devices., 23 pages, 3 figures

Objective This study aimed to identify factors associated with outlet obstruction and high-output stoma (HOS) after ileostomy creation. Summary of background data Ileostomy creation is effective in preventing leakage among patients undergoing low anterior resection for rectal cancer. However, major complications such as outlet obstruction and HOS can occur after surgery. Moreover, these complications cannot be prevented. Methods This retrospective study included 34 patients with rectal cancer who underwent low anterior resection and ileostomy creation at Okayama University Hospital from January 2015 to December 2018. Then, the risk factors associated with outlet obstruction and HOS were analyzed. Results Of 34 patients, 7 (21%) experienced outlet obstruction. In a multivariate logistic regression analysis, advanced T stage (P = 0.10), ileostomy with a short horizontal diameter (P = 0.01), and thick rectus abdominis (RA) muscle (P = 0.0005) were considered independent risk factors for outlet obstruction. There was a significant correlation between outlet obstruction and HOS (P = 0.03). Meanwhile, the independent risk factors of HOS were advanced T stage (P = 0.03) and thick RA muscle (P = 0.04). Conclusions Thick RA muscle and advanced T stage were the common risk factors of outlet obstruction and HOS. Therefore, in high-risk patients, these complications can be prevented by choosing an appropriate ileostomy location according to RA muscle thickness and by preventing tubing into the ileostomy.

The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression.

Pancreatic cancer has poor prognosis despite the various developed multimodal treatment strategies. Currently, neoadjuvant chemotherapy and immunotherapy have attracted substantial attention as effective treatment strategies. However, amplifying immune response with existing treatments is difficult. We developed telomerase-specific oncolytic adenoviruses (OAs), including OBP-301 that is currently tested in a clinical trial of combined anti-PD-1 antibody and p53-armed OBP- 301 variant(OBP-702). OAs have immune-modulation functions and induce CD8+ T cells into tumors by releasing immunogenic cell death markers, such as extracellular adenosine triphosphate. Here, we investigated the effectiveness of OBP- 702 in pancreatic cancer treatments, focusing on the influence on CD8+ memory T cells.

Remnant gastric cancer (RGC) has been increasing for various reasons such as a longer life span, medical progress, and others. It generally has a poor prognosis, and its mechanism of occurrence is unknown. The purpose of this study was to evaluate the clinicopathological features of and clarify the oncological features of RGC.Between January 2002 and January 2017, 39 patients with RGC following distal gastrectomy underwent curative surgical resection at the Okayama University Hospital; their medical records and immunohistochemically stained extracted specimens were used for retrospective analysis.On univariate analysis, initial gastric disease, pathological lymph node metastasis, and pathological stage were the significant factors associated with poor overall survival (p=0.014, 0.0061, and 0.016, respectively). Multivariate analysis of these 3 factors showed that only initial gastric disease caused by malignant disease was an independent factor associated with a poor prognosis (p=0.014, hazard ratio: 4.2, 95% confidence interval: 1.3-13.0). In addition, tumor-infiltrating CD8Initial gastrectomy caused by malignant disease was an independent poor prognostic factor of RGC, and as one of the causes, lower level of tumor-infiltrating CD8

Background Salivary alpha-amylase (sAA) activity is thought to be an indicator of mental stress. However, the relationship between sAA activity and mental stress in patients undergoing dental implant treatment has not been investigated. The present study aimed to examine the correlation between sAA activity and changes in the patient’s vital signs during dental implant surgery. Results sAA activity was higher after surgery compared to the pre-surgical measurements. A significant positive correlation was observed between sAA activity and heart rate (HR) (rs=0.434, p=0.007), as well as the peripheral blood oxygen (SpO2) (rs=0.392, p=0.016). Conclusion sAA activity and the patient’s stress levels tended to increase after the surgical procedure. A positive correlation was observed between SpO2 and sAA activity. A significant positive correlation was also observed between the between the HR and sAA activity, although there was no correlation between blood pressure and sAA activity. Thus, sAA may be a valuable indicator of the stress and anxiety accumulated during dental implant surgery.

Introducing magnetic order into a topological insulator (TI) system has been attracting much attention with an expectation of realizing exotic phenomena such as quantum anomalous Hall effect (QAHE) or axion insulator states. The magnetic proximity effect (MPE) is one of the promising schemes to induce the magnetic order on the surface of TI without introducing disorder accompanied by doping magnetic impurities in TI. In this study, we investigate the MPE at the interface of a heterostructure consisting of a topological crystalline insulator (TCI) SnTe and Fe by employing polarized neutron reflectometry. The ferromagnetic order penetrates $\sim$ 3 nm deep into the SnTe layer from the interface with Fe, which persists up to room temperature. Our findings demonstrate that the interfacial magnetism is induced by the MPE on the surface of TCI preserving the coherent topological states, which is essential for the bulk-edge correspondence, without introducing disorder arising from a random distribution magnetic impurities. This opens up a way for realizing next generation electronics, spintronics, and quantum computational devices by making use of the characteristics of TCI.

This study evaluated the three vibration characteristics, namely, natural frequency, damping ratio, and natural mode, together with maximum displacement of a two-implant-supported overdenture (IOD) at different locator attachment positions using experimental modal analysis (EMA). Edentulous mandibular models with a gingival thickness of 1 mm or 3 mm were prepared, into which dental implants were placed using a fully guided surgical template designed with simulation software, the locator abutments were fastened, and the IODs were then fabricated. The implant positions were bilaterally marked at the lateral incisor, first premolar, and first molar regions. EMA was performed by hammering the test structures to measure the impulse response and obtain the vibration characteristics (n = 5). The Kruskal-Wallis test was performed for natural frequency and maximum displacement, and the Games-Howell test for damping ratio. The significance level was set at α = 0.05. The study indicated that the gingival thickness had a significant effect on the vibration characteristics. Moreover, the natural frequency and damping ratio results showed that the vibration subsided faster when the attachment was placed on the molar implants in the thick gingival model. Furthermore, according to the effect of lateral force on IODs, the difference in maximum displacement between the anterior and posterior regions of the IOD was smaller when the attachments were designed on the pair of lateral incisors. Thus, within the limits of this experiment, our results suggested that two anterior implant-supported IODs are preferable treatment designs in terms of vibration engineering, especially when the gingiva is thick; the molar attachment design could be considered for thin gingival conditions. The differences in gingival thickness and abutment position affected the vibration characteristics of the IOD. Further in vivo studies would be necessary to validate the implant positions and their IOD designs for the mandibular edentulous shapes and the occlusal relationship.

Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

Purpose: The Endoscopic Surgical Skill Quantification System for qualified surgeons (QSs) was introduced in Japan to improve surgical outcomes. This study reviewed the surgical outcomes after initial experience performing laparoscopic distal gastrectomy (LDG) and evaluated the improvement in surgical outcomes following accreditation as a QS. Methods: Eighty-seven consecutive patients who underwent LDG for gastric cancer by a single surgeon were enrolled in this study. The cumulative sum method was used to analyze the learning curve for LDG. The surgical outcomes were evaluated according to the two phases of the learning curve (learning period vs. mastery period) and accreditation (non-QS period vs. QS period). Results: The learning period for LDG was 48 cases. Accreditation was approved at the 67th case. The operation time and estimated blood loss were significantly reduced in the QS period compared to the non-QS period (230 vs. 270 min, p Conclusions: Experience performing approximately 50 cases is required to reach proficiency in LDG. After receiving accreditation as a QS, the surgical outcomes, including the complication rate, were improved.

Background Gastric yolk sac tumor (YST)-like carcinoma is extremely rare, and its prognosis is poor, because most patients have widespread metastases at the time of diagnosis. We report a case of gastric YST-like carcinoma with an adenocarcinoma component without metastases in which curative resection was performed. Case presentation A 77-year-old man complaining of melena and dizziness due to anemia was diagnosed with poorly differentiated adenocarcinoma in the gastric cardia, with a benign ulcer in the gastric body. He underwent total gastrectomy with D2 lymph node dissection for the tumor. Histological examination of the resected specimens revealed a mixture of reticular and glandular neoplastic components morphologically. In the reticular area, an endodermal sinus pattern and some Schiller–Duval bodies were confirmed. Gastric YST-like carcinoma with adenocarcinoma components, T2N0M0 Stage IB, was diagnosed. Immunohistochemical analysis showed that the YST was positive for carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and p53. In contrast, the adenocarcinoma was positive for p53 and negative for CEA and AFP. The patient remained healthy as of 7 years postoperatively, with no recurrence. Conclusions Routine medical examinations or endoscopic examinations for accidental symptom may be helpful for early diagnosis and good prognosis for gastric YST-like carcinoma, although the prognosis is generally poor.

The usefulness of laparoscopic and endoscopic cooperative surgery (LECS) for gastric submucosal tumors in the cardiac region has been reported in recent years. However, LECS for submucosal tumors at the esophagogastric junction with hiatal sliding esophageal hernia has not been reported, and its validity as a treatment method is unknown. The patient was a 51-year-old man with a growing submucosal tumor in the cardiac region. Surgical resection was indicated because a definitive diagnosis of the tumor was not determined. The lesion was a luminal protrusion tumor, located on the posterior wall of the stomach 20 mm from the esophagogastric junction, and had a maximum diameter of 16.3 mm on endoscopic ultrasound examination. Because of the hiatal hernia, the lesion could not be detected from the gastric side by endoscopy. Local resection was considered to be feasible because the resection line did not extend into the esophageal mucosa and the resection site could be less than half the circumference of the lumen. The submucosal tumor was resected completely and safely by LECS. The tumor was diagnosed as a gastric smooth muscle tumor finally. Nine months after surgery, a follow-up endoscopy showed reflux esophagitis. LECS was a useful technique for submucosal tumors of the cardiac region with hiatal hernia, but fundoplication might be considered for preventing backflow of gastric acid.

Adequate bone volume is required for osseointegrated implants to restore lost teeth and oral function. Several studies have demonstrated potential advantage of stem cells in regenerative medicine using osteoblasts. The periosteum is composed of osteoblasts, fibroblasts, and osteoprogenitor cells. It may be an alternative source for bone tissue engineering because of easy isolation and rapid proliferation

Background: Body weight loss (BWL) and skeletal muscle loss (SML) are inevitable after gastrectomy for gastric cancer (GC), and can decrease patients’ quality of life (QOL) and survival. The aim of this retrospective study was to evaluate the effect of perioperative and post-discharge patient participation in continuous nutritional counseling (CNC) on post-gastrectomy BWL and SML. Methods: Ninety-three patients with GC who underwent curative gastrectomy between March 2018 and July 2019 were analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n=49) or patient-participation CNC (CNC group, n=44) after gastrectomy. Difference between percentage BWL (%BWL), percentage SML (%SML), and nutrition-related blood parameters between the preoperative values and those at 12 months after surgery were compared between the groups. Results: Compared with the control group, %BWL was significantly lower in the CNC group at 1 month (–6.2±2.5% vs. –7.9±3.3%, p=0.005), 6 months (–7.8±6.6% vs. –12.3±6.4%, p=0.001) and 12 months (–7.9±7.6% vs. –13.2±8.2%, p=0.002); and %SML was significantly lower in the CNC group at 12 months (–5.3±10.3% vs. –12.8±12%, p=0.002). Regarding nutrition-related blood parameters, change in total cholesterol was significantly lower in the CNC group than the control group at 12 months after surgery (p=0.02). Multivariate analysis identified no CNC as an independent risk factor for severe BWL (p = 0.001) and SML (p = 0.006) at 12 months after surgery. Conclusions: Following gastrectomy, patient-participation CNC prevented postoperative BWL and SML after surgery. These results support the induction of such a CNC program in these patients.

Despite numerous treatment methods, there is no gold standard for the treatment of peri-implantitis—an infectious peri-implant disease. Here, we examined selenium nanoparticles (SeNPs) at a wide range of concentrations to investigate their cytotoxicity, regulation of osteoblastic differentiation, and assessed the antibacterial effect against Porphyromonas gingivalis. SeNPs (mean size: 70 nm; shape: near-spherical; concentration: 0–2048 ppm) were tested against the MC3T3-E1 osteoblast precursor cell line and P. gingivalis red complex pathogen. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis was used to evaluate the bone morphogenetic protein 2 (BMP-2) signaling pathway. SeNPs at concentrations of 2–16 ppm showed no obvious cytotoxicity and promoted good mineralization and calcification. SeNPs at concentrations 64 ppm and below influenced gene expression promoting osteoblastic differentiation, whereas at high concentrations inhibited the expression of Runt-related transcription factor 2 (Runx2). The growth of P. gingivalis was significantly inhibited at SeNP concentrations of more than 4 ppm. SeNPs at low concentrations promoted osteoblastic differentiation while strongly inhibiting peri-implantitis pathogen growth. This study represents one of the few in vitro assessments of SeNPs against a red complex pathogen and the regulatory effect on osteoblastic differentiation. The findings demonstrate SeNPs could potentially be used for future application on implant coating.

Despite numerous treatment methods, there is no gold standard for the treatment of peri-implantitis-an infectious peri-implant disease. Here, we examined selenium nanoparticles (SeNPs) at a wide range of concentrations to investigate their cytotoxicity, regulation of osteoblastic differentiation, and assessed the antibacterial effect against

Postoperative body weight loss (BWL) and skeletal muscle loss (SML) after gastrectomy are associated with a decline in quality of life and worse longterm prognosis in gastric cancer (GC) patients. This study aimed to evaluate the efficacy of amino acids nutrition on BWL and SML in the early period following gastrectomy.The parameters of body composition were measured by bioelectrical impedance analysis in the patients undergoing radical gastrectomy for GC and analyzed retrospectively. Patients received either peripheral parenteral nutrition (PPN) of 4.3% glucose fluid with regular diet (control group, n=43) or PPN of 7.5% glucose fluid containing amino acids plus oral nutritional supplement (ONS) rich in protein with regular diet (amino acids group, n=40) following gastrectomy. The percentages of BWL and SML from preoperative values to those at 7 days and 1 month after surgery were compared between the two groups.The %BWL and %SML at 7 days after surgery were significantly lower in the amino acids group than those in the control group (%BWL, -2.4±1.7% vs. -4.2±1.8%; p0.0001, %SML, -4.1±3.8 vs. -6.5±3.8; p=0.006). Moreover, the %BWL at 1 month after surgery was significantly lower in the amino acids group compared to that in the control group (- 4.6±2.9% vs. -6.1±2.6%; p=0.01); however, the %SML was similar between the two groups. The hematological nutritional parameters were similar between the two groups.Amino acids nutrition by PPN and ONS following gastrectomy prevented postoperative BWL and SML in the early period after surgery in GC patients.

To evaluate the performance of sealing materials used in the screw-access holes of screw-retained implant final superstructures in vivo and in vitro.Twenty-one screw-access holes in the final superstructures were randomly divided into three groups (each group, n = 7). Following disinfection and isolation, all access holes were initially filled with sterilised cotton pellets of the same weight. Depending on the group, the access holes were finally sealed with either provisional composite restorations (group A), self-curing resin for provisional sealing (group B), or acrylic resin (group C). After one month of the functional period, the inner cotton pellets were collected as bacterial reservoirs.Total aerobic bacteria and total gram-negative anaerobic bacteria were measured after bacterial culture for 48 h and 72 h, respectively. In vitro evaluation of porosity using scanning electron microscopy (SEM) was also performed. Samples from superstructures sealed with provisional composite restorations showed fewer bacteria and less porosity than samples from superstructures sealed with self-curing resin for provisional sealing and acrylic resin. In this study, provisional composite restorations showed the best sealing properties. Provisional composite restorations may prevent bacterial invasion of the access holes of the final superstructures.In this study, provisional composite restorations showed the best sealing properties. Provisional composite restorations may prevent bacterial invasion of the access holes of the final superstructures.

Introduction Intracorporeal Billroth I (B‐I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi‐hand‐sewn (SHS) B‐I reconstruction. Materials and surgical technique After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B‐I anastomosis. All the transection line of the duodenum and one‐third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand‐sewn technique. Discussion SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra‐abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32‐63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill.

Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer., Graphical Abstract, Paclitaxel (PTX) enhanced the replication of telomerase-specific oncolytic adenovirus in cancer cells and the penetration of the virus into the disseminated nodules of gastric cancer (GC) in the abdominal cavity. The intraperitoneal virotherapy combined with PTX may be a novel promising therapy for peritoneal metastasis of GC.

We have investigated the structural and magnetic properties of (Zn,Fe)Te:N thin films grown under Zn-rich condition with Fe composition fixed at 1.4% and N concentrations varying in the range [N] = 1.8 × 1018–5.1 × 1019 cm−3. Structural analysis by x-ray diffraction (XRD) detects some additional extrinsic diffraction peaks possibly from Fe-N compounds in the N-doped film with [N] = 5.1 × 1019 cm−3 only. Accordingly, x-ray absorption fine structure (XAFS) analysis reveals the shifting of Fe atoms from substitutional position for N-doped films with high N concentrations, [N] ≥ 1.8 × 1019 cm−3, whereas N-doped films with intermediate N concentrations [N] ≤ 4.3 × 1018 cm−3 are composed of pure diluted phase with substitutional Fe atoms in the valence state deviating from Fe2+. Magnetization measurement using SQUID confirms drastic change of magnetic properties; the linear dependence of magnetization on magnetic field, typical of van Vleck-type paramagnetism in the film without N-doping changes into room temperature ferromagnetic behaviors with hysteretic magnetization curves for N-doped films. The observed weak room temperature ferromagnetic behavior of the N-doped films with [N] ≤ 4.3 × 1018 cm−3 may reflect the deviation of substitutional Fe valence state from Fe2+ to Fe2+/3+ mixed states. On the other hand, the robust room temperature ferromagnetic behavior exhibited by N-doped films with [N] ≥ 1.8 × 1019 cm−3 may originate from precipitates of Fe-N compounds with Fe being in Fe2+/3+ or other valence state.

Pancreatic ductal adenocarcinoma (PDAC) cells have an exceptional ability to invade nerves through pronounced crosstalk between nerves and cancer cells; however, the mechanism of PDAC cell invasion remains to be elucidated. Here, we demonstrate the therapeutic potential of telomerase-specific oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, against human PDAC cells. Highly invasive PDAC cells exhibited higher levels of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) expression independent of KRAS expression; ERK1/2 inhibitor or small interfering RNA (siRNA) treatment significantly reduced the migration and invasion of PDAC cells, suggesting that the ERK signaling pathway is associated with the invasiveness of PDAC cells. OBP-702 infection suppressed ERK signaling and inhibited PDAC cell migration and invasion more efficiently than OBP-301. OBP-702 also effectively inhibited PDAC cell invasion even when invasiveness was enhanced by administration of motility stimulators, such as nerve and neurosecretory factors. Moreover, noninvasive whole-body imaging analyses showed that OBP-702 significantly suppressed tumor growth in an orthotopic PDAC xenograft model, although both viruses were equally effective against subcutaneous tumors, suggesting that OBP-702 can influence the orthotopic tumor microenvironment. Our data suggest that oncolytic virus-mediated disruption of ERK signaling is a promising antitumor strategy for attenuating the invasiveness of PDAC cells., Graphical Abstract, Telomerase-specific oncolytic adenovirus OBP-702 armed with the wild-type p53 tumor suppressor suppressed ERK signaling and inhibited pancreatic ductal adenocarcinoma (PDAC) cell migration and invasion, even when enhanced by nerve-derived motility stimulators. OBP-702 also significantly suppressed tumor growth in an orthotopic PDAC xenograft model by influencing the tumor microenvironment.

Background and Objectives: Oral implant restorations are an excellent treatment option for edentulous patients; however, periodontopathogenic bacteria have been found in the microgaps between implant−abutment junctions. Implant designs to limit the microgaps have been extensively studied. However, studies have shown microgaps continue to exist, allowing for the leakage of bacteria into the implant system. Screw access hole materials are used to fill the access hole void. The use of materials with beneficial properties could provide bacterial leakage prevention. The aim of this study was to examine the surface free energy, cytotoxicity, and bacterial adhesion of selected screw access hole materials such as cotton, polytetrafluoroethylene (PTFE) tape, paraffin wax−polyolefin thermoplastic (PF), paraffin wax (Wax), gutta-percha (GP), and caviton EX (CE). Materials and Methods: A sessile drop test was performed to observe the contact angle and calculate the surface free energy of each material in order to determine the level of hydrophobicity. Cytotoxicity was examined in a mouse gingival epithelial cell line for day 1 and day 3. Bacterial adhesion was tested with Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. Results: PTFE, PF, and wax presented low surface free energies of 19.34, 23.041, and 24.883 mN.m-1, respectively. No cytotoxicity was observed, except for GP and CE. Concurrently, the bacterial adhesion was also the lowest in PTFE and PF. Conclusions: Within the limits of this study, PTFE and PF showed an excellent biocompatibility with few bacterial adhesions. These materials could be potential screw access hole materials in clinical settings.

TPS479 Background: The standard treatment for locally advanced proximal gastric cancer invading the greater curvature is “open total gastrectomy combined with splenectomy” (OTG+S) aiming for whole clearance of the splenic hilar lymph nodes. However, its pertinent postoperative severe complication (e.g. pancreatic fistula) is problematic. An objective of this study is to evaluate the safety of “laparoscopic or robotic total gastrectomy with spleen-preserving splenic hilar dissection” (LRSHD) as a new treatment option which has a potential to reduce surgical morbidity, subsequently to replace the current standard treatment, OTG+S. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria are as follows; clinical T2-4a resectable locally advanced proximal gastric adenocarcinoma that invades the greater curvature; without obvious lymph node metastasis at the splenic hilum nor direct invasion to the spleen/splenogastric ligament. Protocol treatment is laparoscopic or robotic total gastrectomy with splenic hilar lymph node dissection (D2 + No.10 lymphadenectomy according to the Japanese guidelines) in which the spleen is preserved with skeletonizing the splenic vessels. Quality control of surgery is assured by surgeon’s qualification and central peer review of intraoperative photo at the splenic hilum after dissection. The primary endpoint is the proportion of postoperative pancreatic fistula and/or intra-abdominal abscess formation with Clavien-Dindo Grade III or higher (within 30 days after surgery). Secondary endpoints are intraoperative blood loss, operation time, mortality, overall postoperative complication, number of yield splenic hilar nodes, number of metastatic splenic hilar nodes, conversion to splenectomy, conversion to laparotomy, relapse-free survival, and overall survival. Sample size was set as 85 patients to obtain 80% power considering that 15% of patients are judged as unresectable intraoperatively, with the hypothesis that the primary endpoint would have an expected value of 7% and a threshold value of 16% in one-sided alpha of 0.1. Planned accrual period is 5 years. The accrual began in August 2019. As of August 2022, 53 of the planned 85 patients (62.4%) have been enrolled. When the safety of LRSHD is proved by this study, a non-inferiority phase III trial will be consequently launched. Clinical trial registry number: UMIN000037580. Clinical trial information: UMIN000037580 .

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are associated with the establishment and progression of peritoneal metastasis. This study investigated the efficacy of replicative oncolytic adenovirus-mediated