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Yuka Ohe, Sachio Fushida, Takahisa Yamaguchi, Jun Kinoshita, Hiroto Saito, Koichi Okamoto, Keishi Nakamura, Hidehiro Tajima, Itasu Ninomiya, Tetsuo Ohta Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, JapanCorrespondence: Sachio FushidaDepartment of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8641, JapanTel +8176-265-2362Email fushida@staff.kanazawa-u.ac.jpIntroduction: Platelets are one factor promoting tumor development. Conversely, lymphocytes are one factor for immune protection. The peripheral blood platelets–lymphocyte ratio (PLR) is useful as an inflammation/immune indicator to predict postoperative recurrence and prognosis of a variety of malignancies. The peripheral blood neutrophil–lymphocyte ratio (NLR) has also been reported as a useful inflammation/immune indicator. However, there are few studies evaluating the relationship between these peripheral blood indicators and the effectiveness of chemotherapy. Thus, we examined these relationships in gastric cancer patients.Patients and Methods: Between 2005 and 2018, 41 gastric cancer patients treated with preoperative DCS therapy (docetaxel, cisplatin, and S-1) therapy followed by gastrectomy were evaluated. Data for peripheral blood tests prior to the initiation of chemotherapy were used. The effectiveness of chemotherapy was determined using Response Evaluation Criteria in Solid Tumors (RECIST) and the pathological response of primary lesions (Ef grade). The relationship between the blood test results and the effectiveness of chemotherapy was evaluated.Results: Each optimal cut-off value of peripheral inflammation/immune indicators was calculated through ROC curves. Although the pathological responder (Ef grade 2 or 3) revealed significantly better prognosis than the non-responder (Ef grade 0-1b), no relationship was found between responder according to RECIST and prognosis (P=0.014, P=0.992). In univariate analysis, a low PLR (< 180, P=0.005), low NLR (< 2.6, P=0.019), high lymphocyte (≥ 1.43, P=0.019) and high PNI (≥ 40, P=0.032) were identified as prognostic markers, whereas PLR was the only marker correlated with pathological response (P=0.031).Conclusion: PLR obtained prior to chemotherapy might be a useful indicator for predicting chemosensitivity owing to the simplicity of its procedure.Keywords: gastric cancer, preoperative chemotherapy, chemosensitivity, platelet-lymphocyte ratio

Sachio Fushida,1 Jun Kinoshita,1 Katsunobu Oyama,1 Takashi Fujimura,2 Tomoya Tsukada,3 Takahisa Yamaguchi,1 Itasu Ninomiya,1 Tetsuo Ohta1 1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan; 2Department of Surgery, Toyama City Hospital, Toyama, Japan; 3Department of Surgery, Toyama Prefectural Central Hospital, Toyama, Japan Background: Scirrhous gastric cancer (SGC) is highly invasive and metastatic because of its interactions with stromal cells, such as fibroblasts and macrophages, and extracellular matrix, leading to a higher incidence of peritoneal metastasis (PM) than other gastric cancers (GCs). Taxane-based intraperitoneal chemotherapy (IPC) is a promising therapy for PM. We retrospectively analyzed outcomes of multidisciplinary therapies that included IPC for SGC. Patients and therapy: Of 1,679 GC patients treated between 1990 and 2012, we analyzed 119 patients who underwent multidisciplinary therapy for SGC. Patients without PM received gastrectomy with lymphadenectomy and resection of involved adjacent organs followed by intraoperative IPC using cisplatin. Patients with PM received chemotherapy using fluorouracil, with or without methotrexate plus IPC using cisplatin before 2000, and S-1 plus IPC using paclitaxel or docetaxel since 2000. Results: Of the 119 patients, 73 (61%) had PM and 63 (53%) had positive peritoneal lavage cytology. Of the 89 gastrectomy patients, 30 (34%) had macroscopic residual tumors (R2). Of the patients treated since 2000, 66 (100%) received S-1 plus taxanes and 44 patients (67%) received taxane-based IPC. Median survival time was significantly longer in the post-2000 group (22.8 months) than in the pre-2000 group (9.5 months). In univariate analysis, lavage cytology, PM, taxane-based IPC, gastrectomy, and R2 resection were significant prognostic factors. However, only R2 resection was an independent prognostic factor in multivariate analysis (hazard ratio: 5.53, 95% CI: 2.05–14.93). Conclusion: As use of taxane-based IPC is not an independent prognostic factor, new multidisciplinary therapies are necessary to avoid R2 resections. Keywords: peritoneal metastasis, intraperitoneal chemotherapy, taxanes

Toru Kurata, Sachio Fushida, Jun Kinoshita, Katsunobu Oyama, Takahisa Yamaguchi, Mitsuyoshi Okazaki, Tomoharu Miyashita, Hidehiro Tajima, Itasu Ninomiya, Tetsuo Ohta Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan Background: Characterized by aggressive proliferation, extensive stromal fibrosis, and resulting drug resistance, peritoneal dissemination in gastric cancer remains associated with poor prognosis. Interaction between cancer and stromal cells accelerates tumor progression via epithelial–mesenchymal transition (EMT), which is one of the major causes of tissue fibrosis, and human peritoneal mesothelial cells (HPMCs) play important roles as cancer stroma in peritoneal dissemination. Transforming growth factor-β (TGF-β) has a pivotal function in the progression of EMT, and Smad proteins play an important role in the TGF-β signaling pathway. Eribulin mesylate (eribulin), a nontaxane microtubule dynamics inhibitor used for the treatment of advanced breast cancer, inhibits EMT changes in triple-negative breast cancer cells. We examined its ability to inhibit tumor progression and EMT changes resulting from the interaction between gastric cancer cells and HPMCs and to act synergistically with 5-fluorouracil (5-FU), a key drug for gastric cancer. Materials and methods: Proliferation of gastric cancer cells and HPMCs isolated from healthy omentum was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Following gastric cancer cell/HPMC coculture, EMT markers were detected by immunofluorescence, immunohistochemistry, and Western blotting; invasion assays were performed; and TGF-β and Smad phosphorylation were assessed by Western blotting and enzyme-linked immunosorbent assay. A mouse fibrotic tumor xenograft model was established using gastric cancer cell/HPMC cocultures. The effect of eribulin and/or 5-FU was tested in each case. Results: Eribulin significantly suppressed gastric cancer cell proliferation and EMT changes in MKN-45 gastric cancer cells and HPMCs induced by their interaction in vitro. Eribulin inhibited EMT at much lower concentrations (≥0.5 nM for MKN-45 and ≥0.1 nM for HPMCs) than its half maximal inhibitory concentrations (2.2 nM for MKN-45 and 8.1 nM for HPMCs), and this resulted, at least partly, from the downregulation of TGF-β/Smad signaling. Eribulin administration of ≥0.1 mg/kg suppressed tumor progression (0.1 mg/kg, p=0.02), and fibrosis was inhibited by lower dose (0.05 mg/kg, p=0.008) in the xenograft model. Furthermore, 0.05 mg/kg administration with 5-FU brought about synergistic antitumor effects (p=0.006). Conclusion: Low-dose eribulin combined with 5-FU might be a promising therapy for peritoneal dissemination in gastric cancer. Keywords: peritoneal dissemination, cancer–stromal interaction, human peritoneal mesothelial cell, TGF-β, Smad, synergism

Mitsuyoshi Okazaki,1 Sachio Fushida,1 Tomoya Tsukada,1 Jun Kinoshita,1 Katsunobu Oyama,1 Tomoharu Miyashita,1 Itasu Ninomiya,1 Shinichi Harada,2 Tetsuo Ohta1 1Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan; 2Center for Biomedical Research and Education, School of Medicine, Kanazawa University, Ishikawa, Japan Background: In patients with gastric cancer, one of the greatest obstacles to effective chemotherapy is the development of chemoresistance. It has been previously reported that hypoxia-inducible factor-1 alpha (HIF-1α) is associated with acquisition of chemoresistance, and more recent studies have also noted an association of pyruvate kinase muscle 1 (PKM1) and chemoresistance. The purpose of this study was to identify the effect of HIF-1α and PKM1 expression on the development of acquired chemoresistance using a paclitaxel (PTX)-resistant gastric cancer cell line.Materials and methods: A cancer cell line resistant to PTX was established from MKN45 cells by stepwise exposure to drug (rMKN45-PTX). The expressions of HIF-1α, apoptosis, vascular endothelial growth factor (VEGF), multidrug transporters and glycolytic enzyme were examined by Western blotting, enzyme-linked immunosorbent assay and immunohistochemistry. We also assessed the tumor proliferation by subcutaneous tumor and peritoneal dissemination of mouse xenograft model.Results: The resistance index was 6.1 by determining as the ratio of the 50% growth inhibition (IC50) of rMKN45-PTX/IC50 of MKN45. Expression of nuclear factor kappa B and HIF-1α was increased in rMKN45-PTX cells compared with the parent cells. Expression of Bax and caspase-3 was significantly downregulated, whereas expression of Bcl-xL, P-glycoprotein, multidrug resistance-associated protein and VEGF was increased in rMKN45-PTX. The expression level of PKM1 was upregulated in rMKN45-PTX, leading to an increase in the PKM1/PKM2 ratio. Using xenograft models, we demonstrated that mouse subcutaneous tumors derived from rMKN45-PTX were significantly larger than those derived from MKN45 cells.Conclusion: Under the stress of chemotherapeutic agent exposure, high expression of HIF-1α affects various downstream genes. Although the underlying mechanism is unknown, our data suggest that PKM1 is also a molecular target for gastric cancer treatment. Keywords: HIF-1α, PKM1, chemoresistance, gastric cancer

Maria Miura-Karasawa,1 Hiroshi Toshida,1 Toshihiko Ohta,1 Akira Murakami2 1Department of Ophthalmology, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka, Japan; 2Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan Objective: To report a case of coincidence of sebaceous gland hyperplasia and papilloma with detection of human papillomavirus-51 in the apical portion by in situ hybridization.Case presentation: A 75-year-old man noted discomfort at the inner canthus of his left eye when he blinked. A tumor of the lacrimal caruncle was identified and resected. The base of the tumor had a smooth surface and was whitish. In addition, a “navel-like structure” was seen, and the findings strongly suggested sebaceous gland hyperplasia of the lacrimal caruncle. The apical portion of the tumor was a papillomatous lesion. Histological examination of the resected tumor led to a diagnosis of sebaceous gland hyperplasia. Human papillomavirus-51 was detected in the apical portion by in situ hybridization. Based on these results, the final diagnosis was sebaceous gland hyperplasia with papilloma. No recurrence of either tumor has been observed up to 3 years postoperatively.Conclusion: This might be the first report of a case of coincidence of sebaceous gland hyperplasia and papilloma, even though the association between these two lesions was unclear, including which developed first. Keywords: lacrimal caruncle, sebaceous gland hyperplasia, papilloma, human papilloma virus, HPV-51

Ai Toride,1,2 Hiroshi Toshida,1 Asaki Matsui,1 Yusuke Matsuzaki,1 Rio Honda,1,3 Toshihiko Ohta,1 Akira Murakami3 1Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka, 2Department of Ophthalmology, Juntendo University Nerima Hospital, 3Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan Background: Most patients with open globe eye injury are brought to hospital as emergency patients and usually require admission for emergency surgery. We analyzed the visual outcome in patients with open globe eye injury at our hospital over a 4-year period.Patients and methods: This study reviewed 40 eyes of 40 patients with open globe eye injury who were presented to Juntendo University Shizuoka Hospital and required emergency surgery during the 4 years from January 2010 to December 2014. Retrospective evaluation of the visual outcome was performed using data from the medical records, including assessment of the influence of sex, side of the eye injury, cause of injury, and site/severity of injury.Results: The mean age (SD) at the time of the injury was 58.9 years (±25.1 years). There were 28 males (70.0%) and 12 females (30.0%). Statistically significant improvement in visual acuity after treatment was noted in the males (P=0.0015, Wilcoxon test), but not in the females. Twenty-five patients had injury to the right eye (62.5%) and 15 had injury to the left eye (37.5%). A significant improvement in visual acuity was achieved after treatment of injury to the right eye (P=0.021), but not the left eye (P=0.109). The most frequent cause of injury was an accident (15 eyes; 37.5%). The second most frequent cause was work-related injury (14 eyes; 35.0%), which only occurred in males, and the third cause was accident due to negligence (eleven eyes; 27.5%). Two patients developed sympathetic ophthalmia and one patient developed postoperative endophthalmitis. Conclusion: The majority of patients with open globe eye injury were male workers in Japan. The visual outcome of work-related injury was better than that of injury due to other causes. The visual outcome was also better if the right eye was injured compared with the left eye. Patients with injuries due to negligence were older than the other groups, and this finding might be characteristic of an aging society. Keywords: ocular trauma, visual outcome, accident, work-related injury, negligence

Sachio Fushida,1 Jun Kinoshita,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Tomoya Tsukada,2 Takashi Fujimura,4 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization Study Group 1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, 2Department of Surgery, Toyama Prefectural Central Hospital, Toyama, 3First Department of Surgery, Fukui University Hospital, Fukui, 4Department of Surgery, Toyama City Hospital, Toyama, Japan Background: Weekly paclitaxel (wPTX) is the preferred second-line chemotherapy for gastric cancer in Japan. Histone deacetylase inhibitors have been shown to decrease proliferation through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One histone deacetylase inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis and enhances the efficacy of paclitaxel (PTX), shown in a murine gastric cancer model. This Phase II trial was designed to evaluate the benefits of adding VPA to wPTX in patients with gastric cancer refractory to first-line treatment with fluoropyrimidine.Patients and methods: The patients were randomly assigned in a 1:1 ratio to receive PTX 80 mg/m2 intravenously on days 1, 8, and 15, every 4 weeks, or a dose of PTX plus VPA taken everyday at 7.5 mg/kg twice daily. Random assignment was carried out at the data center with a minimization method adjusted by the Eastern Cooperative Oncology Group performance status (0–1 vs 2), prior chemotherapy (first-line vs second-line), and measurable lesions (presence vs absence). The primary end point was the overall survival (OS) rate, and the secondary end points were the progression-free survival rate and safety analysis.Results: Sixty-six patients were randomly assigned to receive wPTX (n=33) or wPTX plus VPA (n=33). The median OS was 9.8 months in the wPTX group and 8.7 months in the wPTX plus VPA group (hazard ratio 1.19; 95% CI 0.702–2.026; P=0.51). The median progression-free survival was 4.5 months in the wPTX group and 3.0 months in the wPTX plus VPA group (hazard ratio 1.29; 95% CI 0.753–2.211; P=0.35). Grade 3–4 adverse events were neutropenia (3.1%), pneumonia (1.6%), liver injury (1.6%), brain infarction (1.6%), and rupture of aorta (1.6%).Conclusion: No statistically significant difference was observed between wPTX and wPTX plus VPA for OS. Keywords: valproic acid, paclitaxel, second- or third-line therapy, advanced gastric cancer

Yusuke Hayashi, Hiroshi Toshida, Yusuke Matsuzaki, Asaki Matsui, Toshihiko Ohta Department of Ophthalmology, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka, Japan Objective: Rebamipide ophthalmic suspension was developed for the treatment of dry eyes and for other corneal diseases, promoting the secretion of both mucin in tear fluid and membrane-associated mucin, increasing the number of goblet cells, and restoring the barrier function of the corneal epithelium. We report a case of a persistent corneal epithelial defect in a patient with diabetes treated with topical application of rebamipide ophthalmic suspension. Case presentation: A 73-year-old woman had a history of type 2 diabetes for 35 years and nonproliferative diabetic retinopathy for 23 years. She presented to our department with discharge and ophthalmalgia in the left eye. A corneal ulcer was detected, and culture of corneal scrapings was performed, with Staphylococcus aureus and Streptococcus canis being isolated. The infection was treated with levofloxacin eye drops and ofloxacin ophthalmic ointment based on the sensitivity profile of the isolate. However, a corneal epithelial defect persisted for approximately 2 months despite continuing treatment with 0.1% hyaluronic acid ophthalmic suspension and 0.3% ofloxacin eye ointment. Her hemoglobin A1c was 7.3%. The persistent corneal epithelial defect showed improvement at 2 weeks after treatment with rebamipide unit dose 2% ophthalmic suspension, and it did not recur even when vitrectomy was subsequently performed for vitreous hemorrhage due to progression of diabetic retinopathy. Conclusion: This is the first report about efficacy of rebamipide unit dose 2% ophthalmic suspension for presenting persistent corneal epithelial defect in a patient with diabetes. In the present case, the suggested mechanisms are the following: improving the corneal barrier function, stabilization of mucin on the keratoconjunctival epithelium, and improving the wettability and stability of the tear film, which resulted in the promotion of healing of the corneal epithelial defect in a short time period. Keywords: rebamipide, diabetic keratitis, corneal epithelium, wound healing

Sachio Fushida,1,2 Katsunobu Oyama,1,2 Masahide Kaji,2 Yasuo Hirono,2 Jun Kinoshita,1,2 Tomoya Tsukada,1,2 Hideaki Nezuka,2 Tatsuo Nakano,2 Masahiro Noto,2 Koji Nishijima,2 Takashi Fujimura,2 Tetsuo Ohta1,2 1Department of Gastroenterological Surgery, Kanazawa University Hospital, 2Digestive Disease Support Organization (DDSO), Kanazawa, Japan Background: Tiotropium, a long-acting inhaled anticholinergic drug, has been widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the issue of whether perioperative tiotropium improves postoperative outcomes for gastric cancer patients with COPD remains unclear. Thus, the aim of this study was to determine the efficacy of perioperative tiotropium intervention for gastric cancer patients with COPD.Patients and methods: Eighty-four gastric cancer patients with mild-to-moderate COPD were randomly assigned to receive perioperative pulmonary rehabilitation alone (control group) or pulmonary rehabilitation with 18 µg of tiotropium once daily (tiotropium group). The patients in the tiotropium group received tiotropium for more than 1 week before surgery and for 2 weeks after surgery. Spirometry was performed prior to group assignment and at 2 weeks after surgery. Postoperative complications, forced expiratory volume in 1 second, forced vital capacity, and the ratio of forced expiratory volume in second to forced vital capacity (%) were compared between the two groups.Results: There were no significant differences between the two groups in terms of age, body mass index, smoking, gastrectomy incision, operation time, and bleeding volume (all P>0.05). Postoperative complications and pulmonary functions did not differ significantly between the control and tiotropium groups. A subgroup analysis of gastric cancer patients with moderate COPD showed that perioperative tiotropium intervention significantly decreased the rate of postoperative complications compared with the control group (P=0.046). However, even after gastrectomy, many patients with mild COPD in both the control and tiotropium groups showed improved pulmonary function.Conclusion: Although perioperative tiotropium intervention had no significant effects in gastric cancer patients with mild COPD, it may be beneficial in those with moderate COPD. Therefore, the next prospective study should further evaluate perioperative tiotropium intervention for gastric cancer patients with moderate-to-severe COPD. Keywords: gastric cancer, COPD, tiotropium

Yusuke Shimizu,1 Hiroshi Toshida,1 Rio Honda,1 Asaki Matsui,1 Toshihiko Ohta,1 Yousuke Asada,2 Akira Murakami2 1Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka, Japan; 2Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan Purpose: To investigate the microbial isolates from patients with ocular infections and the trend in the emergence of levofloxacin-resistant strains over the past four years from 2006 to 2009 retrospectively. Patients and methods: The subjects were 242 patients with ocular infections or traumas treated in our hospital including outpatients, inpatients, and emergency room patients. Most of them needed urgent care presenting with eye complaints, traumas, or decreased vision. Clinical samples were obtained from discharges, corneal, conjunctival tissues or vitreous fluid or aqueous humor, and cultured. Items for assessment included the patient’s age, the diagnosis, the prevalence of isolated bacteria, and the results of susceptibility tests for levofloxacin (LVFX) cefamezin (CEZ), gentamicin (GM) and vancomycin. This information was obtained from the patients’ medical records. Results: There were 156 male patients and 86 female patients who were aged from 2 months old to 94 years old and mean age was 56.8 ± 24.2 years. Of the 242 patients, 78 (32.2%) had positive cultures. The culture-positive rate was significantly higher in male patients than female in total (P = 0.002) and in patients with corneal perforation (P = 0.005). Corneal perforation was the highest culture-positive rate (60.0%), followed by orbital cellulitis (56.5%), blepharitis (50.0%), dacryoadenitis (45.5%), conjunctivitis (38.2%), infectious corneal ulcer (28.5%) and endophthalmitis (24.7%). LVFX-resistant strains accounted for 40 out of a total of 122 strains (32.8%), and the minimum inhibitory concentration (MIC) was significantly higher in LVFX and GM compared with the other antibiotics. There were no vancomycin-resistant strains. Conclusion: Attention should be paid to a possible future increase of strains with resistance to LVFX, as commonly prescribed ocular antibiotics bring emergence of resistant bacteria. Although no vancomycin-resistant strains were isolated this drug should be reserved as the last resort, in order to prevent the emergence of vancomycin resistance. Keywords: ocular infections, drug resistance, levofloxacin, vancomycin, minimum inhibitory concentration

Akito Odaka,1 Hiroshi Toshida,2 Toshihiko Ohta,2 Nobuhito Tabuchi,3,4 Daisuke Koike,4 Chikako Suto,3 Akira Murakami31Human and Environmental Safety Evaluation Center, Lion Corporation, Kanagawa, Japan; 2Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka, Japan; 3Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan; 4Pharmaceutical Research Laboratories No 1, Research and Development Headquarters, Lion Corporation, Kanagawa, JapanPurpose: We examined the efficacy of retinol palmitate (VApal) for dry eyes using dry eye model rabbits whose lacrimal glands were resected.Materials and methods: After alkaline injury on keratoconjunctival epithelium, VApal eye drops were administered 6 times a day for 7 days. The efficacy of VApal was also compared with that of 0.1% hyaluronic acid eye drops.Results: The fluorescein staining and rose bengal scores showed a significant decrease compared with the score in the vehicle group at 7 days (P < 0.05) in the 1000 IU/mL VApal group and at both 3 days (P < 0.05) and 7 days (P < 0.01) in the 1500 IU/mL VApal group. Histological examination revealed recovery of the corneal epithelium, and PAS staining disclosed the recovery of mucin-producing lower palpebral conjunctival goblet cells after 7 days in the 1500 IU/mL VApal group compared with the vehicle group. Results from impression cytology showed a significant increase in density of conjunctival goblet cells compared with that in the vehicle group after 7 days in the 1000 IU/mL VApal group and after 3 and 7 days in the 1500 IU/mL VApal group. There were no significant changes in tear flow in either group. Topical application of VApal at 1500 IU/mL showed greater improvement than 0.1% hyaluronic acid in both fluorescein and rose bengal score and in the density of conjunctival goblet cells.Conclusion: It is suggested that VApal is effective for the improvement of keratoconjunctival epithelial damage associated with tear abnormalities, such as dry eyes.Keywords: cornea, dry eye, hyaluronic acid, vitamin A, wound healing, retinol palmitate

Hiroshi Toshida1,2, Yoshiaki Kadota3, Chikako Suto2, Toshihiko Ohta1, Akira Murakami21Juntendo University Shizuoka Hospital, Department of Ophthalmology, Shizuoka, 2Juntendo University School of Medicine, Department of Ophthalmology, Tokyo, 3Bausch & Lomb Japan Co, Ltd, Research and Development, Tokyo, JapanPurpose: To assess the use of multipurpose lens care products via an online survey conducted among soft contact lens (SCL) wearers in Japan.Methods: The subjects were 1000 men and women aged 15–44 years who reported that they cleaned their SCL by using multipurpose solution at least twice a week. Via the internet, they were asked questions about SCL care, the use of a rubbing step when cleaning SCL, cleaning and replacing lens cases, and recommended SCL care methods.Results: Of the 1000 SCL wearers enrolled, 94.3% performed lens care every day lenses were worn, 64.2% reported rubbing the lenses every time, 57.9% rubbed the lenses for at least 10 seconds per side, and 64.7% reported they rubbed the lenses on both sides. Further, 61.2% reported that they had been given an explanation of SCL cleaning at an eye clinic or contact lens store. Only 49.8% of subjects reported that they cleaned the lens case every time and 61.7% replaced the case within 3 months. Only 19.5% had been given an explanation about lens case care. Half of the subjects reported they had been given no recommendation to use specific SCL care products or could not remember whether or not they had. The most common reason for the recommendation was good compatibility with their type of lens.Conclusion: More education is needed in Japan regarding methods of SCL care to ensure correct lens cleaning with inclusion of a rubbing step, as well as sufficient cleaning and replacement of the lens case. Of particular interest is the finding that many subjects were not given an explanation about proper SCL care and lens case cleaning and replacement at the time of lens purchase or prescription.Keywords: soft contact lens, multipurpose solutions, compliance, questionnaire survey, contact lens care

Rio Honda1, Hiroshi Toshida1, Chikako Suto2, Takuro Fujimaki2, Tairo Kimura2, Toshihiko Ohta1, Akira Murakami2 1Department of Ophthalmology, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka, 2Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan Objective: The effect of eyedrops for glaucoma on conjunctival bacterial flora was investigated by comparing a group of patients treated with such eyedrops for at least 1 year to a control group that did not use eyedrops. Methods: In both groups, bacterial culture came from scrapings of the conjunctival sac, and the bacterial infection rate and pattern of drug resistance were determined. Findings were analyzed in various subgroups stratified by age, frequency of instillation, and concentration of antiseptic benzalkonium chloride in the eyedrops. Results: The culture-positive rate was significantly lower in the glaucoma eyedrop group (43/119 eyes, 40.3%) than in the control group (19/28 eyes, 67.8%) (P < 0.05). No differences in infection rate were found among the different age groups. The most frequent bacteria in both groups was coagulase-negative staphylococci. Gram-negative bacteria were only detected in the glaucoma eyedrop group. Retrospective evaluation was possible for 86 eyes of patients from the glaucoma eyedrop group, among which 45 eyes (52.3%) showed some corneal epithelium damage. There was no difference in the culture-positive rate of bacteria between patients who used eyedrops containing 0.01% or higher dose of benzalkonium chloride and those containing less than 0.01%. Strains that showed resistance to levofloxacin were significantly less frequent in the glaucoma eyedrop group (six strains, 15.0%) than in the control group (11 strains, 39.3%) (P < 0.05). Conclusion: Patients using eyedrops for glaucoma had a lower culture-positive rate of bacteria in the conjunctival sac, probably due to being washed out by the eyedrops. However, Gram-negative bacteria were detected in the eyedrop group. Bacteria isolated from the eyedrop group had lower resistance to levofloxacin, a finding that may have clinical relevance. Keywords: glaucoma, eyedrop, benzalkonium chloride, conjunctival flora, levofloxacin

Groundwater contains dissolved He, and its concentration increases with the residence time of the groundwater. Thus, if the 4He accumulation rate is constant, the dissolved 4He concentration in ground-water is equivalent to the residence time. Since accumulation mechanisms are not easily separated in the field, we estimate the total He accumulation rate during the half-life of 36Cl (3.01 × 105 years). We estimated the 4He accumulation rate, calibrated using both cosmogenic and subsurface-produced 36Cl, in the Great Artesian Basin (GAB), Australia, and the subsurface-produced 36Cl increase at the Äspö Hard Rock Laboratory, Sweden. 4He accumulation rates range from (1.9±0.3) × 10−11 to (15±6) × 10−11 ccSTP·cm−3·y−1 in GAB and (1.8 ±0.7) × 10−8 ccSTP·cm−3·y−1 at Äspö. We confirmed a ground-water flow with a residence time of 0.7-1.06 Ma in GAB and stagnant groundwater with the long residence time of 4.5 Ma at Äspö. Therefore, the groundwater residence time can be deduced from the dissolved 4He concentration and the 4He accumulation rate calibrated by 36Cl, provided that 4He accumulation, groundwater flow, and other geo-environmental conditions have remained unchanged for the required amount of geological time.