Purpose: Re-irradiation is a treatment option for recurrent esophageal cancer patients with a history of radiotherapy, but there is a risk of severe late adverse effects. This study focused on the efficacy and safety of re-irradiation using hyperfractionated radiotherapy. Materials and Methods: Twenty-six patients who underwent re-irradiation by the hyperfraction technique using twice-daily irradiation of 1.2 Gy per fraction for recurrent esophageal cancer were retrospectively included in this study. The overall survival period after the start of secondary radiotherapy and the occurrence of late adverse effects were investigated. Results: Of 26 patients, 21 (81%) received re-irradiation with definitive intention and 21 (81%) underwent concurrent chemotherapy. The median re-irradiation dose was 60 Gy in 50 fractions in 25 treatment days, and the median accumulated irradiation dose in equivalent dose in 2 Gy per fraction was 85.4 Gy with an α/β value of 3. The median interval between two courses of radiotherapy was 21.0 months. The median overall survival period was 15.8 months and the 1-year and 3-year overall survival rates were 64.3% and 28.3%, respectively. Higher dose of re-irradiation and concurrent chemotherapy significantly improved survival (p < 0.001 and p = 0.019, respectively). Severe late adverse effects with the Common Terminology Criteria for Adverse Events grade 3 or higher were observed in 5 (19.2%) patients, and 2 (7.7%) of them developed a grade 5 late adverse effect. Conclusion High-dose re-irradiation using a hyperfractionated schedule with concurrent chemotherapy might be related to good prognosis, while the rate of late severe adverse effects is not high compared with the rates in past reports.

Purpose: Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. Materials and Methods: Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. Results: Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLIbright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. Conclusions Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.

Conventional endoscopy often misses early gastric cancers with minimal red discoloration because they cannot be distinguished from inflamed mucosa. We treated a patient with a small early gastric cancer that was difficult to diagnose using conventional endoscopy. Conventional endoscopy using a small-caliber endoscope showed only subtle red discoloration of the gastric mucosa. However, blue laser imaging showed a clearly discolored area measuring 10 mm in diameter around the red lesion, which was distinct from the surrounding inflamed mucosa. Irregular vessels on the tumor surface (suspicious for early gastric cancer) were observed even with small-caliber endoscopy. Biopsy revealed a well-moderately differentiated tubular adenocarcinoma, and endoscopic submucosal dissection was performed. Histopathological examination of the specimen confirmed well-moderately differentiated adenocarcinoma localized to the mucosa with slight depression compared to the surrounding mucosa, consistent with the endoscopic findings. This small early gastric cancer became clearly visible with blue laser imaging using small-caliber endoscopy.
Adenocarcinoma ; Biopsy ; Depression ; Endoscopes ; Endoscopy ; Gastric Mucosa ; Humans ; Mucous Membrane ; Stomach Neoplasms

Objective: Instructions contained in over-the-counter medicine package inserts can be hard to read because of the limited printing space.  Pictograms are one means of helping users to understand important information.  However, few pictogram systems have been reliably and validly evaluated.  Therefore, a new method was developed to improve the clarity of each illustration and the legitimacy as a pictogram for conveying information important.
Methods: Four creators developed 69 illustrations, each of which expressed one of 24 instructions in the package insert of an H2 blocker.  In a survey, participants (449 university undergraduate and graduate students and 103 pharmacy users) were asked to describe the possible meaning of each illustration and to provide their personal suggestions for improvement.  To evaluate comprehension of information, each instruction was broken into two or three different parts.  Comprehension level was calculated by: (number of people who answered correctly) × 100 / (total number of respondents).  Existing pictograms were included to compare comprehension levels for the same instructions.
Results: Using 67% as the minimum standard for comprehension, we classified each illustration into one of three categories: “no need for improvement,” “need for partial improvement,” and “need for total improvement.”  The students and pharmacy users tended to accurately interpret the possible meanings of illustrations that were familiar to them.
Conclusion: Breaking one instruction of the package insert into a few important pieces of information was useful for determining the level of improvement needed for each illustration.  Evaluating how well each illustration conveys important information in the instructions through two steps was also beneficial, which are to improve the illustration’s clarity with students and its legitimacy among pharmacy users for fulfilling the intended functions of a pictogram.

We developed pancreatic and duodenal homeobox1 (Pdx1) knockout mice to improve a compensatory hyperinsulinemia, which was induced by hyperplasia in the beta cells or Langerhans' islands, as the diabetic model mice. For targeting of Pdx1 gene by homologous recombination, ES cells derived from a 129(+Ter)/SvJclxC57BL/6JJcl hybrid mouse were electroporated and subjected to positive-negative selection with hygromycin B and ganciclovir. As these results, one of the three chimeric mice succeeded to produce the next or F1 generation. Then, the mouse fetuses were extracted from the mother's uterus and analyzed immunohistologically for the existence of a pancreas. The fetuses were analyzed at embryonic day 14.5 (E14.5) because Pdx1 knockout could not alive after birth in this study. Immunohistochemical staining revealed that 10 fetuses out of 26 did not have any PDX1 positive primordium of the pancreas and that the PDX1 expresses in both the interior and exterior regions of intestine. In particular, one the exterior of the intestine PDX1 was expressed in glands that would be expected to form the pancreas. The result of PCR genotyping with extracted DNA from the paraffin sections showed existence of 10 Pdx1-knockout mice and corresponded to results of immunostaining. Thus, we succeeded to establish a Pdx1-knockout (Pdx1-/-) mice.
Animals ; DNA ; Fetus ; Ganciclovir ; Homologous Recombination ; Hygromycin B ; Hyperinsulinism ; Hyperplasia ; Intestines* ; Islands ; Mice ; Mice, Knockout* ; Pancreas ; Paraffin ; Parturition ; Polymerase Chain Reaction ; Uterus

OBJECTIVES: The number of patients with bilateral cochlear implant (CI) has gradually increased as patients and/or parents recognize its effectiveness. The purpose of this report is to evaluate the efficacy of 29 bilateral CI out of 169 pediatric CI users, who received auditory-verbal/oral habilitation at our hearing center. METHODS: We evaluated the audiological abilities 29 Japanese children with bilateral CIs including wearing threshold, word recognition score, speech discrimination score at 1 m from front speaker (SP), 1 m from second CI side SP, speech discrimination score under the noise (S/N ratio=80 dB sound pressure level [SPL]/70 dB SPL, 10 dB) at 1 m from front SP, word recognition score under the noise (S/N ratio=80 dB SPL/70 dB SPL, 10 dB) at 1 m from front SP. RESULTS: Binaural hearing using bilateral CI is better than first CI in all speech understanding tests. Especially, there were significant differences between the results of first CI and bilateral CI on SDS at 70 dB SPL (P=0.02), SDS at 1 m from second CI side SP at 60 dB SPL (P=0.02), word recognition score (WRS) at 1 m from second CI side SP at 60 dB SPL (P=0.02), speech discrimination score (SDS) at 1 m from front SP under the noise (S/N=80/70; P=0.01) and WRS at 1 m from front SP under the noise (S/N=80/70; P=0.002). At every age, a second CI is very effective. However, the results of under 9 years old were better than of over 9 years old on the mean SDS under the noise (S/N=80/70) on second CI (P=0.04). About use of a hearing aid (HA) in their opposite side of first CI, on the WRS and SDS under the noise, there were significant differences between the group of over 3 years and the group of under 10 months of HA non user before second CI. CONCLUSION: These results may show important binaural effectiveness such as binaural summation and head shadow effect. Bilateral CI is very useful medical intervention for many children with severe-to-profound hearing loss in Japan as well as elsewhere.
Asian Continental Ancestry Group ; Child ; Cochlear Implantation ; Cochlear Implants ; Head ; Hearing ; Hearing Aids ; Hearing Loss ; Humans ; Japan ; Noise ; Parents ; Speech Perception

OBJECTIVES: We conducted multi-directional language development tests as a part of the Research on Sensory and Communicative Disorders (RSVD) in Japan. This report discusses findings as well as factors that led to better results in children with severe-profound hearing loss. METHODS: We evaluated multiple language development tests in 33 Japanese children with cochlear implants (32 patients) and hearing aid (1 patient), including 1) Test for question and answer interaction development, 2) Word fluency test, 3) Japanese version of the Peabody picture vocabulary test-revised, 4) The standardized comprehension test of abstract words, 5) The screening test of reading and writing for Japanese primary school children, 6) The syntactic processing test of aphasia, 7) Criterion-referenced testing (CRT) for Japanese language and mathematics, 8) Pervasive development disorders ASJ rating scales, and 9) Raven's colored progressive matrices. Furthermore, we investigated the factors believed to account for the better performances in these tests. The first group, group A, consisted of 14 children with higher scores in all tests than the national average for children with hearing difficulty. The second group, group B, included 19 children that scored below the national average in any of the tests. RESULTS: Overall, the results show that 76.2% of the scores obtained by the children in these tests exceeded the national average scores of children with hearing difficulty. The children who finished above average on all tests had undergone a longer period of regular habilitation in our rehabilitation center, had their implants earlier in life, were exposed to more auditory verbal/oral communication in their education at affiliated institutions, and were more likely to have been integrated in a regular kindergarten before moving on to elementary school. CONCLUSION: In this study, we suggest that taking the above four factors into consideration will have an affect on the language development of children with severe-profound hearing loss.
Aphasia ; Asian Continental Ancestry Group ; Child ; Child Development Disorders, Pervasive ; Cochlear Implants ; Communication Disorders ; Comprehension ; Hearing ; Hearing Aids ; Hearing Loss ; Humans ; Japan ; Language Development ; Mass Screening ; Mathematics ; Rehabilitation Centers ; Vocabulary ; Weights and Measures ; Writing

OBJECTIVES: It is not unusual for a cochlear implantation (CI) candidate to have some type of ear malformation, in particular an abnormal course of the facial nerve (FN). In this study, we attempted to reconstruct a three-dimensional (3D) image of temporal bone structures with malformation using computed tomography (CT) imaging and examined its usefulness in the surgical planning of CI in a malformed ear. METHODS: We prepared 3D images for 6 separate CI cases before surgery. First, we manually colored preoperative CT images using Photoshop CS Extended. We then converted the colored CT images to 3D images using Delta Viewer, free-ware for Macintosh. Before surgery, we discussed any problems anticipated based on the 3D images and plans for surgery with those who would be performing the CI. RESULTS: Case 1: The subject was a 3-year-old boy with malformed ossicles, semicircular canal (SC) hypoplasia, internal auditory canal stenosis, and an abnormal course of the FN. 3D image indicated that the stapes were absent, and the FN was more anteriorly displaced, so that it was difficult to perform cochleostomy. The surgical findings were similar to those depicted on the 3D image, so we could insert an electrode based on the preoperative image simulation without complications. Case 2: The subject was a 7-year-old boy with malformed stapes, atresia of the round window, cochlear and SC aplasia, and an abnormal course of the FN with bifurcation. CI was performed with no problems, in the same manner as in Case 1. CONCLUSION: We were able to successfully depict the structures of the inner ear, ossicles, and FN as 3D images, which are very easy to understand visually and intuitively. These 3D images of the malformed ear are useful in preoperative image simulation and in surgical planning for those performing a CI procedure.
Child ; Cochlear Implantation ; Cochlear Implants ; Constriction, Pathologic ; Ear ; Ear, Inner ; Electrodes ; Facial Nerve ; Humans ; Imaging, Three-Dimensional ; Preschool Child ; Round Window, Ear ; Semicircular Canals ; Stapes ; Temporal Bone

Since the reexamination system of new drugs has been in place for about thirty years, it is necessary to reconsider its management. The time from the reexamination application of new drugs until issuance of the results takes several years recently. General drugs are applied during the reexamination application and are approved before reconfirmation of the efficacy and safety of new drugs. Therefore, the reexamination system is not effectively operated. Although the informations for proper use collected from post-marketing investigations and clinical trials, and spontaneous adverse reaction reports of new drugs, etc. during the reexamination period are utilized for its safety measures, the plan for effective use is not systematically managed. We propose an improved plan for a future reexamination system. Further, we propose the introduction of a risk management plan in Japan; the current one of which lags behind EU and US.

BACKGROUND: Use of complementary and alternative medicine (CAM) has become popular in Japan.
OBJECTIVE: To investigate associations of symptom-related CAM use with sociodemographic factors in Japan.
DESIGN AND SETTING: A prospective cohort study of a nationally representative sample of households in Japan.
PARTICIPANTS: Community-dwelling adults who developed at least one symptom during a 31-day period.
MAIN OUTCOME MEASURES: Self-reported, symptom-related use of CAM, either physical CAM or oral CAM.
RESULTS: Of 2, 453 adults, 2, 103 participants (86%) developed at least one symptom. Of these symptomatic adults, 156 (7.4% ; 95% CI: 6.3-8.5%) used physical CAM therapy. The likelihood of using physical CAM was not significantly influenced by annual household income, employment, or education. Participants living in large cities had an increased likelihood of using physical CAM with an odds ratio (OR) of 2.6 (95% CI: 1.2-5.8), compared to those living in rural areas. Oral CAM therapy was used by 480 participants (22.8%; 95% CI: 21.0-24.6%) among the symptomatic adults. An age of 60 years old and older (OR 2.0; 95% CI: 1.2-3.3) and female gender (OR 1.8; 95% CI: 1.3-2.6) were significantly associated with an increased use of oral CAM. The unemployed participants had a lower likelihood of using oral CAM, with an OR of 0.6 (95% CI: 0.4-0.9), compared to the employed.
CONCLUSIONS: Oral CAM use is common among Japanese patients and is associated with older age, female gender, and employed status, while physical CAM use is less common and is associated with living in a large city.