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Abstract Background The chorioretinal inflammatory lesions occurring in punctate inner choroiditis evolve into punched-out atrophic scars. Typically, the progression is gradual. We report a case of highly myopic punctate inner choroiditis with rapid progression of chorioretinal atrophy. Case presentation A 48-year-old Japanese woman with high myopia presented with decreased visual acuity. Best-corrected visual acuity was 20/28 in the right eye and 20/16 in the left eye; axial length was 29.0 mm and 28.7 mm, respectively. Fundoscopy revealed an epiretinal membrane in the left eye. Three years later, the best-corrected visual acuity in the left eye had decreased to 20/33; at this time, the patient underwent vitrectomy with epiretinal membrane and internal limiting membrane peeling in this eye. Six months later, the best-corrected visual acuity in the left eye decreased suddenly to 20/100. Optical coherence tomography showed a nodule-like lesion in the outer retina with disruption of the retinal pigment epithelium and a focally thickened choroid, compatible with PIC. One month later, the choroidal thickness had decreased. The central chorioretinal atrophy expanded rapidly at a rate of 0.45 mm2/year over the next 3 years, and new areas of patchy focal chorioretinal atrophy developed in the perifovea. Conclusions Rapid progression of chorioretinal atrophy was observed in a patient with punctate inner choroiditis. Because punctate inner choroiditis is often associated with degenerative myopia, the retina is fragile and may be susceptible to mechanical damage. This case report alerts clinicians to the need for careful management of patients with punctate inner choroiditis, especially after vitrectomy.

Abstract Background Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. Case presentation A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 μm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. Conclusions Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.

Objective Rapid eye movement (REM) obstructive sleep apnea (OSA) is associated with the risk of cardiovascular events. Arterial stiffness and carotid artery intima-media thickness (IMT) predict these events, but few relevant studies have been conducted. We compared long-term changes in arterial stiffness and IMT between patients with REM OSA and non-REM (NREM) OSA receiving continuous positive airway pressure (CPAP) or oral appliance (OA) therapy. Methods Newly diagnosed female patients with OSA received CPAP (n = 6) or OA (n = 7). Pulse wave velocity (PWV) and carotid artery ultrasound were performed before and 60 months after treatment. Results There were no differences in baseline characteristics (mean age: 56.0 vs. 61.3 years; mean body mass index: 22.6 vs. 21.7 kg/m 2 ) between the REM OSA and non-REM OSA groups. The median apnea-hypopnea index was lower in the REM OSA group than in the non-REM OSA group. Increased PWV (12.92 ± 1.64 to 14.56 ± 2.73 m/s) and deteriorated glucose metabolism were observed in the REM OSA group after treatment. PWV, IMT, and cardiovascular risk factors were unaffected in the non-REM OSA group. Conclusion Arterial stiffness and glucose metabolism are deteriorated in patients with REM OSA compared with these parameters in patients with non-REM OSA after CPAP or OA treatment.

Background: Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is useful for detecting microperitoneal dissemination in gastric cancer. However, reports on its use in colorectal cancer are sparse. In this study, we performed PDD with 5-ALA to diagnose peritoneal dissemination in colorectal cancer during laparoscopic surgery. Methods: Between January 2018 and March 2019, we examined six patients scheduled laparoscopic surgery for colorectal cancer (cT3 or deeper) with suspected peritoneal dissemination. A solution of 5-ALA (20 mg/kg) in water was orally administered 3 to 4 hours before surgery. Intraoperatively, the peritoneal cavity was observed with white and fluorescent lights. Nodules suspected as dissemination lesions were resected and the presence or absence of seeding was confirmed histopathologically. Results: The median time from oral 5-ALA administration to observation was 226 minutes. Peritoneal nodules found in four of six cases using white light were collected. In Case 5, white nodules were observed in white light and luminescence in fluorescent light. Of the nodules collected, only that of Case 5 was pathologically diagnosed as disseminating. No adverse events were observed. Conclusions: We attempted PDD using 5-ALA during laparoscopic surgery for colorectal cancer. Observing more cases and optimizing observation conditions are required to improve accuracy. This study was registered at the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN Exam ID: UMIN000030531).

Abstract Background Pouch volvulus after proctocolectomy for ulcerative colitis is a very rare postoperative complication. The common site of pouch volvulus has been reported to be the ileal pouch–anal anastomosis and the middle part of the pouch, but no reports on pouch volvulus in the afferent limb of the pouch have been observed. Here, we report the case of a patient with afferent limb volvulus who underwent afferent limbpexy, but required reoperation 7 months later. Case presentation A 38-year-old man with refractory ulcerative colitis had undergone open proctocolectomy 10 years ago at another hospital. He had been aware of lower abdominal pain and bowel movement difficulty for 2 years. After repeated bowel obstruction, he was referred to our hospital for surgery. Based on the radiographic findings, we diagnosed a pouch volvulus and performed an operation. Laparoscopically, counterclockwise rotation of the afferent limb of the pouch was recognized. Moreover, the ileal mesentery was adhered and fixed to the presacral space 20 cm from the oral side of the pouch. The antimesenteric side of the afferent limb was fixed using interrupted stiches on the left peritoneal wall of the pelvis. He was discharged uneventfully 18 days after surgery, and defecation improved immediately. However, he was readmitted 7 months after surgery with the same abdominal pain and defecation difficulty. A similar finding was found and diagnosed as recurrent volvulus. Therefore, we performed a laparoscopic surgery. The same volvulus as in the previous surgery was confirmed. The site fixed during the previous surgery showed scars, but the afferent limb was free. The dilated ileum that contained the volvulus was excised only on the oral side of the pouch and an intraluminal anastomosis was performed on the anterior wall of the pouch. He had a good postoperative course and was discharged. Conclusion Proper diagnosis of volvulus based on the characteristic imaging findings is important. In principle, bilateral row fixation of the rotated ileum is the basic procedure for volvulus. However, fixation with this technique is sometimes difficult. Therefore, this procedure is one of the useful options for the fixation of difficult or recurrent cases.

Galactosialidosis is a rare metabolic disorder resulting from mutations in the CTSA gene. Few studies have reported on the ocular findings of galactosialidosis type IIb in detail. We report on a case of galactosialidosis, the diagnosis of which was suggested by bilateral macular cherry-red spots, which is an indication of lysosomal storage disease. In this case, retinal and systemic dysfunctions were mild. Genetic studies revealed an abnormality of relevant protective proteins, and thus a definitive diagnosis was made. The patient was a 35-year-old man who had blurred vision from young age, but he did not seek any therapy due to good visual acuity. He visited a local clinic after the blurred vision in the left eye worsened and was referred to us for bilateral macular cherry-red spots. He had no family history of note. We observed fine grayish-white deposits in the corneal stroma and fine opacity of the lens. Optical coherence tomography showed a hyperreflective region and a thick bilateral retinal ganglion cell layer. Goldmann perimetry showed focal loss of sensitivity. There was almost no functional decline noted on multifocal electroretinography. Lysosomal storage disease was suspected due to corneal clouding and macular cherry-red spots, and so further evaluation was performed. Though neurological abnormality was mild, we made a diagnosis of galactosialidosis because of decreased activity of β-galactosidase and sialidase. Genetic studies revealed an abnormality of relevant protective proteins. Since the onset was later in life and clinical symptoms were mild, we expect that the ophthalmological findings will remain stable. Long-term observation is necessary for this case.

We report a case of full-thickness macular hole (FTMH) which developed during follow-up for Coats disease. To our knowledge, this is the first report on a case of FTMH which developed during follow-up for Coats disease. A 17-year-old boy was referred to our institution with blurred vision in his left eye. Fundus examination showed yellowish subretinal exudates with overlying telangiectatic retinal vessels in the temporal periphery in the left eye; the right eye was normal. Fluorescein angiography revealed diffusion indicative of temporal peripheral vascular leakage. We made a diagnosis of stage 2A Coats disease and performed argon laser photocoagulation (PC). Moreover, he received intravitreal injection of anti-vascular endothelial growth factor. At 30 months after the first visit, the best-corrected visual acuity (BCVA) of the left eye worsened to 20/50. We observed tensioned internal limiting membrane (ILM), serous macular detachment (SMD) and retinal thinning; the intraretinal exudate remained. We performed PC and at 36 months after the first visit, BCVA further declined to 20/63 in his left eye and FTMH was observed. We then performed a 27-gauge pars plana vitrectomy and ILM peeling following which the FTMH was found to have closed by 4 days after vitrectomy. SMD gradually decreased, and BCVA improved to 20/20. Chronic inflammation by peripheral vascular leakage and PC application might have caused FTMH. In this case, the vitrectomy for FTMH with Coats disease provided good visual and anatomic outcomes.

Background: The Japanese guidelines for the treatment of alopecia areata list topical immunotherapies as a drug therapy for this condition. However, there is insufficient evidence of its efficacy to support this recommendation. Thus, we sought to clarify the effect of topical immunotherapy on the progression and severity of alopecia areata in Japanese patients. Methods: To evaluate the effect of topical immunotherapy with squaric acid dibutylester (SADBE) in alopecia areata patients, we performed a retrospective cohort study on 49 alopecia patients who had received topical immunotherapy with SADBE. Patients were evaluated by the change in alopecia severity at 6 and 12 months after the initiation of topical immunotherapy. The improvement rate was calculated by determination of the complete and partial responses rate to treatment with topical immunotherapy by application of SADBE. Results: The improvement rate in all alopecia patients treated with SADBE topical immunotherapy was 57.8% (complete response; 11.1% and partial response; 46.7%). Conclusions: Topical immunotherapy with SADBE is an effective treatment for alopecia areata. Therefore, the current treatment recommendations for alopecia areata with topical immunotherapies are appropriate. Keywords: Alopecia, Cohort study, Severity, Topical immunotherapy, Response rate

Background and Aim Although colorectal laterally spreading tumors (LSTs) can be classified into four subtypes, the histopathological characteristics are known to differ among these subtypes. We therefore performed a logistic regression analysis to determine whether the risk of pathological T1 cancer of large colorectal LSTs can be predicted based on factors such as endoscopic findings in a large group of patients enrolled in a multicenter study in Japan. Methods In the main study, we assessed 1236 colorectal adenomas or early cancers that were classified as LSTs measuring 20 mm or more in diameter and treated endoscopically. Logistic regression analysis was performed to determine whether factors such as the subtype of LST could be used to predict the risk of pathological T1 cancer. A validation study of 356 large colorectal LSTs was conducted to confirm the validity of the results obtained in the main study. Results The locations and tumor diameter of the LSTs in the main study were found to differ significantly according to the LST subclassification (P

Particle manipulation is still challenging even with the many tools available, especially manipulating particles on a surface. Here, the authors report a technique for nanomanipulation of various objects on solid substrates by modulating particle-substrate interactions through laser-induced opto-thermal dynamics.

Abstract Background The use of laparoscopic surgery has become widespread, and many surgeons are striving to acquire the necessary techniques for it. The Endoscopic Surgical Skill Qualification System (ESSQS), established by the Japan Society for Endoscopic Surgery, serves to maintain and improve the quality of laparoscopic surgery in Japan. In this study, we aimed to determine whether ESSQS certification is useful in maintaining and improving the quality of surgical techniques and in standardization of laparoscopic surgery in Japan. Methods This retrospective study used data from the Institute for Integrated Medical Sciences, Tokyo Women’s Medical University, Japan. From January 2016 to October 2017, 241 patients with colorectal cancer underwent laparoscopic surgery. Of them, 220 patients were selected and divided into two groups on the basis of surgery performed by an ESSQS-qualified surgeon (QS group) (n = 170) and a non-ESSQS-QS (NQS) (n = 50). We compared the short-term results in the two groups and examined those before and after propensity score matching (PSM). Results Mean operation time was longer in the NQS group than in the QS group. Furthermore, mean blood loss was significantly less in the QS group. These were similar before and after PSM. The rate of conversion to open surgery was significantly higher in the NQS group before PSM. However, the rate of postoperative complications was not different between the two groups. Conclusions A laparoscopic procedure performed by ESSQS-QS often leads to good short-term outcomes. Thus, the ESSQS system works and is potentially useful in maintaining and improving the quality of surgical techniques and in standardization of laparoscopic surgery in Japan.

We report a case of giant macular hole progression after rupture of giant retinal pigment epithelial detachment (PED). The patient was a 91-year-old man who had a giant PED in the left eye. He had bilateral hypermetropia (+2.00 dpt), and he had developed posterior vitreous detachment. The PED was 5,800 μm in diameter and 800 μm in height and ruptured during follow-up. A macular hole was formed, with a diameter of 400 μm, and the height of the PED had reduced to 360 μm. After 5 months, the macular hole expanded up to a diameter of 600 μm. Therefore, some cases of giant PED may lead to macular hole.

Eye checkups have become increasingly important to maintain good vision and quality of life. As the population requiring eye checkups increases, so does the clinical work burden of clinicians. An automatic screening algorithm to reduce the clinicians’ workload is necessary. Machine learning (ML) has recently become one of the chief techniques for automated image recognition and is a helpful tool for identifying ocular diseases. However, the accuracy of ML models is lower in a clinical setting than in the laboratory. The performance of ML models depends on the training dataset. Eye checkups often prioritize speed and minimize image processing. Data distribution differs from the training dataset and, consequently, decreases prediction performance. The study aim was to investigate an ML model to screen for retinal diseases from low-quality optical coherence tomography (OCT) images captured during actual eye chechups to prevent a dataset shift. The ensemble model with convolutional neural networks (CNNs) and random forest models showed high screening performance in the single-shot OCT images captured during the actual eye checkups. Our study indicates the strong potential of the ensemble model combining the CNN and random forest models in accurately predicting abnormalities during eye checkups.

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (β coefficient = -0.088, P = 0.040) and central retinal thickness (β coefficient = 0.00051 per μm, P = 0.027), MCP-1 (β coefficient = 0.44, P < 0.001) and IL-10 (β coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (β coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (β coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (β coefficient = 0.56, P = 0.01), CXCL12 at the third injection (β coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (β coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.

Abstract Background Various types of preoperative chemoradiotherapy (CRT) have been established for rectal cancer; thus,Physicians will need to refine the selection of appropriate preoperative CRT for different patients since there are various treatment regimens. Oral tegafur-uracil (UFT) plus leucovorin (LV) is commonly used to treat rectal cancer in Japan. Oral chemotherapy offers patients many potential advantages. Since 2008, we have been performing preoperative CRT with intermittent oral UFT plus LV in locally advanced rectal cancer patients to prevent postoperative local recurrence. Here, in a retrospective analysis, we evaluated the efficacy and short-term outcomes of preoperative CRT with intermittent oral UFT plus LV. Methods We analyzed data from 62 patients with locally advanced rectal cancer, including 31 patients who underwent preoperative CRT between 2009 and 2013 (the CRT group) and 31 patients who were treated with surgery alone between 2001 and 2008 (the non-CRT group). Clinicopathologically, both groups included patients with rectal cancer at clinical tumor stages 3-4 or clinical node stages 0-3. In the CRT group, curative operations were performed ≥8 weeks after CRT. Patients were concomitantly treated with 2 cycles of oral UFT (300 mg/m2/day, days 1–14 and 29–42) plus LV (75 mg/day, days 1–14 and 29–42) and 45 Gy of radiotherapy. Chemotherapy was repeated every 28 days, followed by a 2-week break. Results The completion rate of CRT was high at 94% (n = 29/31). The downstaging rate of CRT was 61% (n = 19/31). The pathological complete response rate was 6.5% (n = 2/31). Significant differences were observed in the 3-year local recurrence rate between the two groups (P < 0.05). Conclusions Preoperative CRT with intermittent oral UFT plus LV appears to be a tolerable and effective treatment for Japanese patients with rectal cancer. A further investigation of a diversification of preoperative CRT for Japanese rectal cancer patients is required.

Disease staging involves the assessment of disease severity or progression and is used for treatment selection. In diabetic retinopathy, disease staging using a wide area is more desirable than that using a limited area. We investigated if deep learning artificial intelligence (AI) could be used to grade diabetic retinopathy and determine treatment and prognosis.The retrospective study analyzed 9,939 posterior pole photographs of 2,740 patients with diabetes. Nonmydriatic 45° field color fundus photographs were taken of four fields in each eye annually at Jichi Medical University between May 2011 and June 2015. A modified fully randomly initialized GoogLeNet deep learning neural network was trained on 95% of the photographs using manual modified Davis grading of three additional adjacent photographs. We graded 4,709 of the 9,939 posterior pole fundus photographs using real prognoses. In addition, 95% of the photographs were learned by the modified GoogLeNet. Main outcome measures were prevalence and bias-adjusted Fleiss' kappa (PABAK) of AI staging of the remaining 5% of the photographs.The PABAK to modified Davis grading was 0.64 (accuracy, 81%; correct answer in 402 of 496 photographs). The PABAK to real prognosis grading was 0.37 (accuracy, 96%).We propose a novel AI disease-staging system for grading diabetic retinopathy that involves a retinal area not typically visualized on fundoscopy and another AI that directly suggests treatments and determines prognoses.

BACKGROUND: The gender-specific influences of various confounding factors, including apnea, age, BMI, and cigarette consumption, on the function of the parasympathetic nerve system (PNS) during sleep in OSA patients has never been investigated. METHODS: One hundred ninety-seven males and 63 females with OSA were subjected to full PSG examinations including assessment of R-R intervals (RRIs) during an overnight ECG. The PNS-derived modulatory effect on the RRIs and the variability of this effect were quantified during REM and NREM using instantaneous time-frequency analysis with complex demodulation. The spectral domain with the maximum instantaneous amplitude in the high-frequency band between 0.15 and 0.4 Hz was defined as the main HF peak and used as a surrogate marker of PNS discharge. Based on density-spectrum-array maps of the main HF peaks (HF-DSA map), shifts in the central frequency of the main HF peak over time were continuously observed. When the main HF peaks on the HF-DSA maps maintained the same central frequency for more than 20 sec or 5 min, the PNS functions were considered to be "stable" or "very stable", respectively. RESULTS: Apneas enhanced PNS-derived cardiac-modulation during REM in males, but more importantly, they made PNS-function unstable during both REM and NREM in males and during NREM in females. Aging blunted the PNS-derived cardiac-modulation during both REM and NREM regardless of gender, but aging had no impact on the stability of PNS-function. BMI blunted PNS-eliciting cardiac-modulation during REM in males and during NREM in both males and females. BMI made the PNS unstable during REM in females. Neither height nor cigarette consumption influenced any PNS-related parameter. CONCLUSIONS: The PNS-derived cardiac-modulation was generally inhibited by aging and obesity, in which the effect of obesity was gender-specific. The PNS instability at nighttime was mainly induced by apneas but by obesity particularly during REM in females.

A lot of skin diseases can occur on children’s faces. We report two children with unique flushing on their faces, sometimes accompanied with headache. Their eruption did not meet various differential diagnoses. Many dermatologists may have seen a similar condition but did not think much about it. Thus, it should be worth regarding such symptom as the benign new clinical entity, which may comfort patients with similar conditions and merit further attention in clinical practice.

BackgroundSenile hemangioma, so-called cherry angioma, is known as the most common vascular anomalies specifically seen in the aged skin. The pathogenesis of its abnormal angiogenesis is still unclear.Methodology/principal findingsIn this study, we found that senile hemangioma consisted of clusters of proliferated small vascular channels in upper dermis, indicating that this tumor is categorized as a vascular tumor. We then investigated the mechanism of endothelial proliferation in senile hemangioma, focusing on microRNA (miRNA). miRNA PCR array analysis revealed the mir-424 level in senile hemangioma was lower than in other vascular anomalies. Protein expression of MEK1 and cyclin E1, the predicted target genes of mir-424, was increased in senile hemangioma compared to normal skin or other anomalies, but their mRNA levels were not. The inhibition of mir-424 in normal human dermal microvascular ECs (HDMECs) using specific inhibitor in vitro resulted in the increase of protein expression of MEK1 or cyclin E1, while mRNA levels were not affected by the inhibitor. Specific inhibitor of mir-424 also induced the cell proliferation of HDMECs significantly, while the cell number was decreased by the transfection of siRNA for MEK1 or cyclin E1.Conclusions/significanceTaken together, decreased mir-424 expression and increased levels of MEK1 or cyclin E1 in senile hemangioma may cause abnormal cell proliferation in the tumor. Senile hemangioma may be the good model for cutaneous angiogenesis. Investigation of senile hemangioma and the regulatory mechanisms of angiogenesis by miRNA in the aged skin may lead to new treatments using miRNA by the transfection into senile hemangioma.

Background and study aims: Diagnostic performance of a computer-aided diagnosis (CAD) system for deep submucosally invasive (T1b) colorectal cancer was excellent, but the “regions of interest” (ROI) within images are not obvious. Class activation mapping (CAM) enables identification of the ROI that CAD utilizes for diagnosis. The purpose of this study was a quantitative investigation of the difference between CAD and endoscopists. Patients and methods: Endoscopic images collected for validation of a previous study were used, including histologically proven T1b colorectal cancers (n = 82; morphology: flat 36, polypoid 46; median maximum diameter 20 mm, interquartile range 15-25 mm; histological subtype: papillary 5, well 51, moderate 24, poor 2; location: proximal colon 26, distal colon 27, rectum 29). Application of CAM was limited to one white light endoscopic image (per lesion) to demonstrate findings of T1b cancers. The CAM images were generated from the weights of the previously fine-tuned ResNet50. Two expert endoscopists depicted the ROI in identical images. Concordance of the ROI was rated by intersection over union (IoU) analysis. Results: Pixel counts of ROIs were significantly lower using CAD (188.9K[x103] ± 109.1K) than by endoscopists (354.5K ± 223.6K; P < 0.0001) and mean ± standard deviation of the IoU was 0.203 ± 0.170. IoU was significantly higher in correctly identified lesions (n = 54, 0.234 ± 0.172) than incorrect ones (n=28, 0.144 ± 0.153, P = 0.0215). Concusions: IoU was larger in correctly diagnosed T1b colorectal cancers. Optimal annotation of the ROI may be the key to improving diagnostic sensitivity of CAD for T1b colorectal cancers.