[A Case in Which Multiple Post-Operatively Recurring Hepatocellular Carcinomas Showed a Positive Response to Sorafenib-Hepatic Arterial Infusion Chemotherapy (HAIC)Sequential Therapy].

A male patient in his 70s underwent a right lobectomy because of a hepatocellular carcinoma(HCC)located in the right lobe(S6)of his liver. Eleven months after surgery, contrast-enhanced CT showed multiple masses in the residual liver, which were diagnosed as HCC recurrence. He was then treated with hepatic arterial infusion chemotherapy(HAIC). Ten months after the recurrence, the liver tumors progressed. Therefore, treatment was switched to sorafenib(400 mg/day orally)and HAIC(low-dose FP: 5-FU 250 mg plus CDDP 5 mg 5 days/week 4 weeks)sequential therapy. The patient received 2 cycles of sorafenib-HAIC sequential therapy for 11 months, and his liver tumors shrunk considerably. Unfortunately, 24 months after the recurrence of HCC, he died of respiratory failure. The cause of his death was officially determined to be primary lung cancer. An autopsy revealed that most tissues were necrotic, and only a small number of viable tumor cells were present in the liver tumors. This suggests that sorafenib-HAIC sequential therapy was significantly effective in targeting the multiple HCCs in this case.

[Coexistence of IgG4-related autoimmune hepatitis and inflammatory pseudotumors of the liver:a case report].

IgG4-related autoimmune hepatitis (IgG4-AIH) is characterized by hepatic inflammation and is considered an IgG4-related disease. Several inflammatory pseudotumors (IPTs) are also considered as IgG4-related diseases;however, there have been no reports of cases wherein both diseases occurred concurrently. An older adult with liver dysfunction was admitted to the hospital and was diagnosed with IgG4-AIH following a liver biopsy;IgG4-positive plasma cell infiltration in the portal tract and high serum IgG4 concentration were detected. A few months following biopsy, imaging studies revealed two IPTs in the liver. The patient was diagnosed with cryptogenic organized pneumonia several months after imaging and was treated with steroids in a different hospital. Her liver dysfunction improved, and one of the two IPTs disappeared in response to steroid treatment. The following is an account of a rare case of IgG4-AIH with IPTs of the liver.

The influence of visual field position induced by a retinal prosthesis simulator on mobility.

PURPOSE: Our aim is to develop a new generation of suprachoroidal-transretinal stimulation (STS) retinal prosthesis using a dual-stimulating electrode array to enlarge the visual field. In the present study, we aimed to examine how position and size of the visual field-created by a retinal prosthesis simulator-influenced mobility. METHODS: Twelve healthy subjects wore retinal prosthesis simulators. Images captured by a web camera attached to a head-mounted display (HMD) were processed by a computer and displayed on the HMD. Three types of artificial visual fields-designed to imitate phosphenes-obtained by a single (5 × 5 electrodes; visual angle, 15°) or dual (5 × 5 electrodes ×2; visual angle, 30°) electrode array were created. Visual field (VF)1 is an inferior visual field, which corresponds to a dual-electrode array implanted in the superior hemisphere. VF2 is a superior visual field, which corresponds to a single-electrode array implanted in the inferior hemisphere. VF3 is a superior visual field, which corresponds to a dual-electrode array implanted in the inferior hemisphere. In each type of artificial visual field, a natural circular visual field (visual angle, 5°) which imitated the vision of patients with advanced retinitis pigmentosa existed at the center. Subjects were instructed to walk along a black carpet (6 m long × 2.2 m wide) without stepping on attached white circular obstacles. Each obstacle was 20 cm in diameter, and obstacles were installed at 40-cm intervals. We measured the number of footsteps on the obstacles, the time taken to complete the obstacle course, and the extent of head movement to scan the area (head-scanning). We then compared the results recorded from these 3 types of artificial visual field. RESULTS: The number of footsteps on obstacles was lowest in VF3 (One-way ANOVA; P = 0.028, Fisher's LSD; VF 1 versus 3 P = 0.039, 2 versus 3 P = 0.012). No significant difference was observed for the time to complete the obstacle course or the extent of head movement between the 3 visual fields. CONCLUSION: The superior and wide visual field (VF3) obtained by the retinal prosthesis simulator resulted in better mobility performance than the other visual fields.

Comparison of visual fatigue caused by head-mounted display for virtual reality and two-dimensional display using objective and subjective evaluation.

This study aimed to evaluate objective and subjective visual fatigue experienced before and after performing a visual task while using a head-mounted display for virtual reality (VR-HMD) and two-dimensional (2D) display. Binocular fusion maintenance (BFM) was measured using a binocular open-view Shack-Hartmann wavefront aberrometer equipped with liquid crystal shutters. Twelve healthy subjects performed the BFM test and completed a questionnaire regarding subjective symptoms before and after performing a visual task that induces low visually induced motion sickness (VIMS). BFM (p = .87) and total subjective eye symptom scores (p = .38) were not significantly different between both groups, although these values were significantly lower after the visual task than before the task within both groups (p < .05). These findings suggest that visual fatigue after using a VR-HMD is not significantly different from that after using a 2D display in the presence of low-VIMS VR content. Practitioner summary: Objective and subjective evaluation of visual fatigue were not significantly different with the use of a head-mounted display for virtual reality (VR-HMD) and two-dimensional display. These results should be valuable not only to engineers developing VR content but also to researchers involved in the evaluation of visual fatigue using VR-HMD. Abbreviations: VR: virtual reality; VR-HMD: head-mounted display for virtual reality; BFM: binocular fusion maintenance; BWFA: binocular open-view Shack-Hartmann wavefront aberrometer.

Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

PURPOSE: To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a suprachoroidal-transretinal stimulation (STS) retinal prosthesis. METHODS: An STS retinal prosthesis was implanted in the right eye of a 42-year-old man with advanced Stargardt disease (visual acuity: right eye, light perception; left eye, hand motion). In localization tests during the 1-year follow-up period, the patient attempted to touch the center of a white square target (visual angle, 10°; contrast, 96, 85, or 74%) displayed at a random position on a monitor. The distance between the touched point and the center of the target (the absolute deviation) was averaged over 20 trials with the STS system on or off. RESULTS: With the left eye occluded, the absolute deviation was not consistently lower with the system on than off for high-contrast (96%) targets, but was consistently lower with the system on for low-contrast (74%) targets. With both eyes open, the absolute deviation was consistently lower with the system on than off for 85%-contrast targets. With the system on and 96%-contrast targets, we detected a shorter response time while covering the right eye, which was being implanted with the STS, compared to covering the left eye (2.41 ± 2.52 vs 8.45 ± 3.78 s, p < 0.01). CONCLUSIONS: Performance of a reaching movement improved in a patient with an STS retinal prosthesis implanted in an eye with residual natural vision. Patients with a retinal prosthesis may be able to improve their visual performance by using both artificial vision and their residual natural vision. CLINICAL TRIAL REGISTRATION: Beginning date of the trial: Feb. 20, 2014 Date of registration: Jan. 4, 2014 Trial registration number: UMIN000012754 Registration site: UMIN Clinical Trials Registry (UMIN-CTR) http://www.umin.ac.jp/ctr/index.htm.

Correction to: Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

The original publication of this paper contain an error because of an incorrect captured corresponding author.

Surveillance of patients with long-segment Barrett's esophagus: A multicenter prospective cohort study in Japan.

BACKGROUND AND AIM: The incidence of esophageal adenocarcinoma (EAC) in cases with long-segment Barrett's esophagus (BE) has not been investigated in Japan. The aim of this study is to investigate the incidence of EAC in Japanese cases with long-segment BE prospectively. METHODS: This is a multicenter prospective cohort study investigating the incidence rate of EAC in patients with BE with a length of at least 3 cm. Study subjects received index esophagogastroduodenoscopy at the time of enrollment, and they were instructed to undergo yearly follow-up esophagogastroduodenoscopy. Patients in whom EAC was diagnosed in the endoscopic examinations underwent subsequent treatment, and their prognosis was observed. RESULTS: Of 215 enrolled patients, six (2.8%) were initially diagnosed with EAC at the enrollment. Among the remaining 209 patients, 132 received at least one follow-up esophagogastroduodenoscopy. In this follow-up, three EACs developed in 251 observed patient-years (incidence rate: 1.2% per year). Most of the EACs detected at the initial endoscopic examination (5/6, 83%) were already at advanced stages. Meanwhile, all the three lesions detected in the follow-up esophagogastroduodenoscopies were identified as early cancers and subjected to curative resection. CONCLUSIONS: The incidence rate of EAC in Japanese cases with long-segment BE was calculated to be 1.2% in a year.

Insulin-like growth factor-related components and the risk of liver cancer in a nested case-control study.

Insulin-like growth factor-1 (IGF1) is a potent mitogen. IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 levels and low IGFBP3 levels are associated with increased risk of several cancers. We examined relationships between serum levels of these factors and hepatoma risk in a case-control study nested in a prospective cohort study (the Japan Collaborative Cohort Study (JACC Study)). A baseline survey was conducted from 1988 to 1990, and 39,242 subjects donated blood samples. Participants diagnosed with hepatoma by 1997 were considered cases for nested case-control studies. Ninety-one cases and 263 sex- and age-matched controls were analyzed. A conditional logistic model was used to estimate odds ratios (ORs) for the incidence of hepatoma associated with serum IGF1 and IGFBP3 levels. Neither IGF1 nor the molar ratio of IGF1/IGFBP3 was correlated with hepatoma risk. After adjustment for hepatitis viral infection, body mass index, smoking, and alcohol intake, a higher molar difference of (IGFBP3 - IGF1) was associated with a decreased hepatoma risk more than IGFBP3 alone (p for trend <0.001 and = 0.003, respectively). People in the highest quartile had a lower risk (OR = 0.098; 95 % confidence interval = 0.026-0.368). In subgroup analyses of males and females, the molar difference was associated with a decreased hepatoma risk (p for trend <0.05). In non-elderly individuals, the difference was inversely correlated with the incidence of hepatoma (p for trend <0.01). The molar difference of (IGFBP3 - IGF1) may be inversely associated with the incidence of hepatoma.

Systemic Prophylactic Antibiotics for the Modified Introducer Method for Percutaneous Endoscopic Gastrostomy: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the most common method of enteral nutrition in patients who require long-term tube feeding. According to meta-analyses, administration of systemic prophylactic antibiotics for PEG reduces peristomal infection. However, with several recent developments in the procedure and instruments, the risk of infection might have been reduced. The aim of this study was to evaluate the use of systemic antibiotic prophylaxis for a modified introducer method of PEG. METHODS: This prospective, randomized, double-blind trial assessed 278 patients undergoing PEG for inclusion. Ninety-one patients with an indication for PEG who gave informed consent to participate were randomized. Forty-six patients received prophylactic ampicillin and 45 patients received a placebo. A modified introducer method of PEG using a Seldinger PEG kit was performed. The primary outcome was the occurrence of clinically evident wound infection within 3 days after PEG. RESULTS: Wound infection within 3 days was observed in none in the prophylaxis group and in 1 patient in the control group (P=0.4945). There was no significant difference between 2 groups in the other parameters, including peristomal infection within 7 days, overall infection, white blood cell counts, C-reactive protein level, and successive rate of finishing antibiotics. CONCLUSIONS: For wound infection within 3 days, noninferiority of the placebo group to the antibiotics group was preliminarily suggested with our criteria, but not for peristomal infection within 7 days. More strict criteria for noninferiority should be examined in a further large sample study.

Associations between polymorphisms in folate-metabolizing genes and pancreatic cancer risk in Japanese subjects.

BACKGROUND: Evidence supporting the associations between folate metabolizing gene polymorphisms and pancreatic cancer has been inconclusive. We examined their associations in a case-control study of Japanese subjects. METHODS: Our case-control study involved 360 newly diagnosed pancreatic cancer cases and 400 frequency-matched, non-cancer control subjects. We genotyped four folate metabolizing gene polymorphisms, including two polymorphisms (rs1801133 and rs1801131) in the methylenetetrahydrofolate (MTHFR) gene, one polymorphism (rs1801394) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene and one polymorphism (rs1805087) in the 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between folate metabolizing gene variants and pancreatic cancer risk. RESULTS: Overall we did not observe a significant association between these four genotypes and pancreatic cancer risk. For rs1801133, compared with individuals with the CC genotype of MTHFR C677T, the OR for those with the CT genotype and TT genotype was 0.87 (0.62-1.22) and 0.99 (0.65-1.51), respectively. For rs1801131, individuals with the CC genotype had approximately 1.2-fold increased risk compared with those with the AA genotype, but the association was not statistically significant. In analyses stratified by smoking and drinking status, no significant associations were noted for C677T genotypes. No significant interactions were observed with smoking and drinking with respect to pancreatic cancer risk. CONCLUSIONS: Our data did not support the hypothesis that MTHFR polymorphisms or other polymorphisms in the folate metabolizing pathway are associated with pancreatic cancer risk.

False reaching movements in localization test and effect of auditory feedback in simulated ultra-low vision subjects and patients with retinitis pigmentosa.

PURPOSE: To determine the accuracy of reaching movements with localization tests in subjects with simulated ultra-low vision, and to examine the effectiveness of auditory feedback training in improving the accuracy of the reaching movements. METHODS: Twenty-one subjects with simulated ultra-low vision and three patients with advanced retinitis pigmentosa (RP) were studied with the localization tester. The localization tester had white square targets with a visual angle of 10° that were projected randomly on a computer monitor screen. The subjects or RP patients were instructed to touch the center of the target. Each subject was tested 20 trials. The distance from the center of the target to the point where subjects touched, the deviation, was calculated automatically by the computer. We also examined the effect of auditory feedback on improving the accuracy of reaching movements. RESULTS: The average angle of deviation in the subjects was not significantly correlated with visual acuity. The points touched by subjects with simulated low vision were located downward and horizontally toward the hand they used. They were condensed around the barycenter of the touched points (paired t tests; *p = 0.037). The touched points of the patients also deviated downward and condensed around the barycenter. The deviations decreased significantly with auditory feedback when trained over 100 trials. CONCLUSIONS: The subjects with simulated ultra-low vision and the advanced RP patients had false orientations against the position of localized target systematically. An auditory feedback system may help to correct the false orientations for reaching movements in patients with very low vision.

Surgical feasibility and biocompatibility of wide-field dual-array suprachoroidal-transretinal stimulation prosthesis in middle-sized animals.

PURPOSE: To investigate the safety and efficacy of a newly-developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in middle-sized animals. METHODS: The prosthesis consisted of two arrays with 50 to 74 electrodes. To test the feasibility of implanting the prosthesis and its efficacy, the prosthesis was implanted for 14 days into two rabbits. Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14 days after the implantation. Then the rabbits were euthanized, eyes were enucleated, and the posterior segment of the eye was examined histologically. In a second experiment, the arrays were implanted into two cats, and their ability to elicit neural responses was determined by electrically evoked potentials (EEPs) at the chiasm and by optical imaging of the retina. RESULTS: All arrays were successfully implanted, and no major complications occurred during the surgery or during the 2-week postoperative period. Neither OCT nor ophthalmoscopy showed any major complications or instability of the arrays. Histological evaluations showed only mild cellular infiltration and overall good retinal preservation. Stimulation of the retina by the arrays evoked EEPs recorded from the chiasm. Retinal imaging showed that the electrical pulses from the arrays altered the retinal images indicating an activation of retinal neurons. The thresholds were as low as 100 µA for a chiasm response and 300 µA for the retinal imaging. CONCLUSION: Implantation of a newly-developed dual-array STS prosthesis for 2 weeks in rabbits was feasible surgically, and safe. The results of retinal imaging showed that the dual-array system was able to activate retinal neurons. We conclude that the dual-array design can be implanted without complication and is able to activate retinal neurons and optic nerve axons.

[National clinical investigation of anti-aquaporin-4 seropositive optic neuritis].

PURPOSE: We carried out a national clinical investigation of anti-aquaporin-4 seropositive optic neuritis which is resistant to steroid pulse therapy. METHODS: A questionnaire of clinical training institutions authorized by the Japanese Ophthalmological Society regarding anti-aquaporin-4 seropositive optic neuritis. RESULTS: We received responses from 44 facilities (40%). There were 188 anti-aquaporin-4 seropositive cases (24 men, 162 women), with a mean age of 52.4 +/- 15.5 (14-88 years old, median 54). Visual acuity at the time of the first medical examination was 3.4 to -0.18 logMAR (median 1.30) and at the last 3.4 to -0.18 logMAR (median 0.70). The average number of times of recurrence and steroid pulse therapy were 1.5 +/- 2.3 (median 1) and 3.3 +/- 4.1 (median 2) respectively. There was no significant difference in visual acuity between patients who received additional therapy such as plasma exchange therapy and immunoadsorption therapy and patients who were not treated additionally. CONCLUSIONS: Clinical characteristics of anti-aquaporin-4 seropositive optic neuritis were revealed. A well-designed prospective study is needed to obtain evidence of availability of plasma exchange therapy and other related issues.

Retinal Blood Vessel Formation in the Macula Following Intravitreal Ranibizumab Injection for Aggressive Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Recently, anti-vascular endothelial growth factor (VEGF) drugs have been widely used for ROP to inhibit abnormal retinal angiogenesis. However, there is a concern that such drugs potentially also affect normal retinal vascular development. We report a case of blood vessel growth across the macula after anti-VEGF treatment for zone I aggressive ROP. A 25-week-old female infant was administered 0.2 mg of ranibizumab for bilateral aggressive ROP in both eyes at 33 weeks of postmenstrual age. Under normal development, retinal blood vessels do not grow into the center of the future macular region. After five weeks, however, a horizontal blood vessel sprouted from the optic disc and extended across the macula in the right eye. The blood vessel ran straight to the vascular-avascular juncture by 41 weeks of postmenstrual age during the follow-up period. While the focus has been on arresting retinal vascular development through VEGF inhibition, anti-VEGF treatment may induce vascular abnormalities in patients with severe ROP. Infants with retinal vascular abnormalities should be carefully monitored for their visual prognosis.

Continuous oxygen saturation and risk of retinopathy of prematurity in a Japanese cohort.

BACKGROUND/AIMS: We assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO2), and developed a risk prediction model for severe ROP using birth data and SpO2 data. METHODS: This retrospective study included infants who were born before 30 weeks of gestation between August 2009 and January 2019 and who were screened for ROP at a single hospital in Japan. We extracted data on birth weight (BW), birth length, gestational age (GA) and minute-by-minute SpO2 during the first 20 days from the medical records. We defined four SpO2 variables using sequential measurements. Multivariate logistic regression was used to develop a model that combined birth data and SpO2 data to predict treatment-requiring ROP (TR-ROP). The model's performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Among 350 infants, 83 (23.7%) required ROP treatment. The SpO2 variables in infants with TR-ROP differed significantly from those with non-TR-ROP. The average SpO2 and high SpO2 showed strong associations with GA (r=0.73 and r=0.70, respectively). The model incorporating birth data and the four SpO2 variables demonstrated good discriminative ability (AUC=0.83), but it did not outperform the model incorporating BW and GA (AUC=0.82). CONCLUSION: Data obtained by continuous SpO2 monitoring demonstrated valuable associations with severe ROP, as well as with GA. Differences in the distribution of average SpO2 and high SpO2 between infants with TR-ROP and non-TR-ROP could be used to establish efficient cut-off values for risk determination.

Ten-year outcomes of congenital cataract surgery performed within the first six months of life.

PURPOSE: To investigate the long-term outcomes of congenital cataract surgery performed within the first 6 months of life. SETTING: 11 ophthalmic surgical sites in Japan. DESIGN: Retrospective chart review. METHODS: Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia. RESULTS: Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this time frame. The incidence of secondary glaucoma was similar between groups while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes. CONCLUSIONS: In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of IOL with sophisticated surgical techniques shows promise even in congenital cataract surgery.