Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia.

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii-associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii-associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii-associated pulmonary infections.

A Japanese Case of Leber's Hereditary Optic Neuropathy with the m.13051G>A Pathogenic Variant.

Leber's hereditary optic neuropathy (LHON) is one of the hereditary optic neuropathies and is principally caused by three frequent mitochondria deoxyribonucleic acid (DNA) pathogenic variants (m.11778 G>A, m.3460 G>A, and m.14484T>C). These pathogenic variants account for 90% of LHON cases, with rare pathogenic variants accounting for the remaining cases. We report the first Japanese case of LHON with the m.13051 G>A pathogenic variant, which is a rare primary pathogenic variant of LHON. A 24-year-old woman developed subacute visual loss in both eyes over several months. The best corrected visual acuity (BCVA) was 6/120 in her right eye (OD) and 6/7.5 in her left eye (OS). A relative afferent pupillary defect was not detected. Humphrey visual field testing revealed a central scotoma OD and a temporal paracentral scotoma OS. Fundus examination showed the presence of a pale optic disc OD and optic disc swelling with peripapillary microangiopathy OS. Orbital magnetic resonance imaging showed no abnormal findings. As the mitochondrial DNA gene testing demonstrated the m.13051 G>A pathogenic variant, the patient was diagnosed with LHON. Subsequently, her BCVA worsened to 6/600 in each eye, followed by a nearly plateau-like progression thereafter. This mutation has been primarily reported in Europe but has not yet been confirmed in the Asian region. This case also indicates the importance of examining the whole mitochondrial DNA gene for pathogenic variants in cases where one of the three major pathogenic variants has not been not detected.

Outcomes of definitive carbon-ion radiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

BACKGROUND: A recent phase I/II study determined the optimal dose of definitive carbon-ion radiotherapy (CIRT) for cT1bN0M0 esophageal cancer. This study aimed to further confirm the efficacy and feasibility of the recommended dose fractionation of CIRT with long-term follow-up results in a larger sample size. METHODS: This single center retrospective study evaluated patients with cT1bN0M0 esophageal squamous cell carcinoma treated with the recommended dose fractionation of 50.4 Gy relative biological effectiveness in 12 fractions, between 2012 and 2022. RESULTS: Thirty-eight patients underwent CIRT at our hospital. Although eight (21.1%) patients were older than 80 years, 15 (39.5%) had high surgical risk, and seven (18.4%) were at high risk for chemotherapy, all patients underwent CIRT as scheduled. Grade 3 esophagitis occurred in eight (21.1%) patients and grade 3 pneumonia in one (2.6%) patient in this study, but no grade 4 adverse events occurred. The only grade 3 late adverse event was pneumonia in one patient (2.6%). The 5-year overall survival rate, local control rate, and disease-free survival rates were 76.6% (95% CI, 90.9-62.4), 74.9% (95% CI, 90.7-59.0), and 66.4% (95% CI, 83.3-49.5), respectively. Additionally, post CIRT recurrence was as follows: seven (18.4%) patients had recurrence in another part of the esophagus, three (7.9%) in the primary site, three (7.9%) in lymph nodes outside the irradiated area, and one (2.6%) patient had liver metastasis. CONCLUSIONS: Our study demonstrates that CIRT using the recommended dose fractionation is feasible and effective for cT1bN0M0 esophageal squamous cell carcinoma.

Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageals cell carcinoma: a multi-center retrospective Japanese cohort study.

BACKGROUND: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. METHODS: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. RESULTS: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA. CONCLUSIONS: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment.

Cone contrast test-HD: sensitivity and specificity in red-green dichromacy and the impact of age.

We report normative cone contrast sensitivity values, right-left eye agreement, and sensitivity and specificity values for the cone contrast test-HD (CCT-HD). We included 100 phakic eyes with color vision normal (CVN) and 20 dichromatic eyes (10 with protanopia and 10 with deuteranopia). The CCT-HD was used to measure L, M, and S-CCT-HD scores, and the right and left eyes were evaluated for agreement using Lin's concordance correlation coefficient (CCC) and Bland-Altman analysis to investigate the sensitivity and specificity of the CCT-HD based on diagnosis with an anomaloscope device. All cone types were in moderate agreement with the CCC (L-cone: 0.92, 95% CI, 0.86-0.95; M-cone: 0.91, 95% CI, 0.84-0.94; S-cone: 0.93, 95% CI, 0.88-0.96), whereas the Bland-Altman plots showed that the majority of cases (L-cone: 94%; M-cone: 92%; S-cone: 92%) fell within the 95% limits of agreement and showed good agreement. The m e a n±s t a n d a r d error L, M, and S-CCT-HD scores for protanopia were 0.6±1.4, 74.7±2.7, and 94.6±2.4, respectively; for deuteranopia, these were 84.0±3.4, 40.8±3.3, and 93.0±5.8, respectively; and for age-matched CVN eyes (m e a n±s t a n d a r d deviation age, 53.1±5.8 years; age range, 45-64 years), these were 98.5±3.4, 94.8±3.8, and 92.3±3.4, respectively, with significant differences between the groups except for S-CCT-HD score (Bonferroni corrected α=0.0167, p<0.0167). The sensitivity and specificity of the CCT-HD were 100% for protan and deutan in diagnosing abnormal types in those aged 20 to 64 years; however, the specificity decreased to 65% for protan and 55% for deutan in those aged >65 years. The CCT-HD is comparable to the diagnostic performance of the anomaloscope in the 20-64-year-old age group. However, the results should be interpreted cautiously in those ≥65 years, as these patients are more susceptible to acquired color vision deficiencies due to yellowing of the crystalline lens and other factors.

Relationship of Low-luminance Visual Acuity with Ocular Aberrations in Older Participants.

SIGNIFICANCE: This study highlights the importance of twilight adaptation for reliable assessment of low-luminance visual acuity and understanding the relationship between low-luminance visual acuity and ocular aberrations. PURPOSE: The human eye experiences reduced visual acuity as luminance decreases owing to reduced retinal and optical resolutions; however, the details are unclear. This study aimed to quantify the effects of refraction, pupil diameter, and ocular aberrations on visual acuity during the transition from high- to low-light environments, thereby contributing to the standardization of low-luminance visual acuity measurements. METHODS: In total, 27 older participants with a mean age of 70.0 ± 4.1 years were included in this study. Visual acuity was measured according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol with three luminance conditions: high luminance (300 cd/m 2 ), low luminance (10 cd/m 2 ), and low luminance with short-term (15-minute) twilight adaptation (10 cd/m 2 ). RESULTS: The mean logarithm of minimum angle of resolution values of visual acuity were -0.09 ± 0.09, 0.10 ± 0.13, and 0.03 ± 0.09 at 300, 10, and 10 cd/m 2 with twilight adaptation, respectively. Multiple regression analysis determined that spherical aberration ( P < .005) and tetrafoil ( P < .005) were significant factors associated with low-luminance visual acuity after twilight adaptation, with an adjusted R2 value of 0.35 for this model ( P < .005). CONCLUSIONS: Although the influence of ocular aberrations on low-luminance visual acuity may be relatively modest compared with neural effects, it remains a crucial factor that should not be overlooked. The absence of twilight (or dark) adaptation can cause ocular aberrations and neural effects, potentially leading to inaccuracies in the measurement of low-luminance visual acuity.

Decennial trends in hip fractures over 20 years in Yamagata Prefecture, Japan.

BACKGROUND: Hip fracture is among the most common injuries in elderly people. We aimed to investigate the decennial trends in hip fractures in patients ≥65 years of age. METHODS: A questionnaire was distributed to all hospitals with a Department of Orthopaedic Surgery in Yamagata Prefecture to collect data on hip fractures occurring in 1996, 2006 and 2016. RESULTS: The response rate was 100%. The total numbers of hip fractures in 1996, 2006 and 2016 were 665, 1169 and 1,728, respectively (crude incidence: 258, 373 and 494 per 100,000 person-year, respectively). Injuries frequently occurred in the early morning and daytime morning in 1996. In contrast, they frequently occurred in activity times (e.g., morning and afternoon) in 2006 and 2016. Among the patients, 80-90% were injured by simple falls, and 70-80% were injured indoors. The incidence of trochanteric fractures was approximately 1.8-1.9 times greater than incidence of neck fractures in all years. Especially, trochanteric fractures in females of ≥90 years of age markedly increased. The rate of surgical treatment was the same in 1996 and 2006, but was lower in 2016. In 1996, the percentage of independent walkers at discharge and 1 year later was almost the same. In 2006 and 2016, the rate of independent walkers was low at discharge, but increased 1 year later. The rate of discharge to home decreased gradually. The combined percentage of patients discharged to home and to rehabilitation institutions in 2006 and the percentage of patients who entered the regional referral clinical pathway in 2016 were both approximately 70%, with no marked changes observed. CONCLUSIONS: Hip fractures, especially trochanteric fractures in super-aged females, increased. Discharge to home decreased, and the use of the regional referral clinical pathway was widespread. Ambulation ability was reduced at discharge, but improved after 1 year.

Pathogenesis, Clinical Features, and Treatment of Patients with Myelin Oligodendrocyte Glycoprotein (MOG) Autoantibody-Associated Disorders Focusing on Optic Neuritis with Consideration of Autoantibody-Binding Sites: A Review.

Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG) autoantibody-associated disease (MOGAD), there is still uncertainty regarding the MOG protein function and the pathogenicity of anti-MOG autoantibodies in this disease. It is important to note that the disease characteristics, immunopathology, and treatment response of MOGAD patients differ from those of anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS). The clinical phenotypes of MOGAD are varied and can include acute disseminated encephalomyelitis, transverse myelitis, cerebral cortical encephalitis, brainstem or cerebellar symptoms, and optic neuritis. The frequency of optic neuritis suggests that the optic nerve is the most vulnerable lesion in MOGAD. During the acute stage, the optic nerve shows significant swelling with severe visual symptoms, and an MRI of the optic nerve and brain lesion tends to show an edematous appearance. These features can be alleviated with early extensive immune therapy, which may suggest that the initial attack of anti-MOG autoantibodies could target the structures on the blood-brain barrier or vessel membrane before reaching MOG protein on myelin or oligodendrocytes. To understand the pathogenesis of MOGAD, proper animal models are crucial. However, anti-MOG autoantibodies isolated from patients with MOGAD do not recognize mouse MOG efficiently. Several studies have identified two MOG epitopes that exhibit strong affinity with human anti-MOG autoantibodies, particularly those isolated from patients with the optic neuritis phenotype. Nonetheless, the relations between epitopes on MOG protein remain unclear and need to be identified in the future.

A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results.

We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.

Pupil assessment with a new handheld pupillometer in healthy subjects.

OBJECTIVE: To assess the pupil response with a new handheld pupillometer in healthy subjects. METHODS: Sixty-four eyes of 32 healthy subjects (mean age 21.2 years) were tested. After dark adaptation for 10 min, pupil responses to 1 s red and blue light stimuli at 100 cd/m2 were measured in the order from right to left eyes with a 1 min interval. The initial pupil size (D1, mm), minimum pupil size (D2, mm), and constriction rate (CR, %) were obtained. Intra-examiner reproducibility was examined using the coefficient of variation (CV, %) and the Bland-Altman plot. Inter-examiner consistency was examined using the interclass correlation coefficient (ICC) and the agreements with a conventional device, by Pearson's correlation coefficient (r). RESULTS: The CV of all parameters have high reproducibility in the red (11.0-20.7%) and blue (5.5-12.1%) light stimuli. Bland-Altman plot analysis showed no bias with both light stimuli. "Almost perfect" and "substantial" correlations between the examiners were obtained in the red (ICC = 0.78-0.94) and blue (ICC = 0.71-0.89) light stimuli. "Excellent" and "good" correlations between the devices were obtained, except for the CR parameter in the red (D1: r = 0.90; p < 0.001, D2: 0.72; p < 0.001, and CR: 0.08; p = 0.631, respectively) and blue (D1: r = 0.87; p < 0.001, D2: 0.70; p < 0.001, and CR: 0.19; p = 0.274, respectively) light stimuli. CONCLUSION: The novel pupillometer is useful for assessing pupil response. However, because of their different constructions, the CR values cannot be compared directly between the devices.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

Smoothness of gait in healthy older females and patients with postoperative proximal femur fracture.

[Purpose] This study aimed to investigate the usefulness of a quality index in gait for proximal femur fractures. [Participants and Methods] In this study, 20 females with postoperative proximal femur fracture in the preparation phase for discharge (femur fracture group) aged ≥60 years (63.0 ± 3.0 years) and 20 healthy older females (healthy group) participated (75.7 ± 7.7 years) (n=40). Measurements were conducted at comfortable and maximal gait speeds. Power spectrum entropy (PSE), harmonic ratio (HR), and modified HR (mHR), which are smoothness indices, were calculated from the measured data in each of the three axial directions and compared. [Results] The healthy and femur fracture groups showed significant differences in the PSE, HR, and mHR for comfortable and maximal gait speed in the lateral and vertical directions. Furthermore, all directions between the HR and mHR in the femur fracture group had significant differences. [Conclusion] The usefulness of the PSE, HR, and mHR as quality evaluation indices of gait was demonstrated in patients with postoperative femur fractures after unilateral disability.

PZLAST: an ultra-fast amino acid sequence similarity search server against public metagenomes.

SUMMARY: : Similarity searches of amino acid sequences against the public metagenomic data can provide users insights about the function of sequences based on the environmental distribution of similar sequences. However, a considerable reduction in the amount of data or the accuracy of the result was necessary to conduct sequence similarity searches against public metagenomic data, because of the vast data size more than Terabytes. Here, we present an ultra-fast service for the highly accurate amino acid sequence similarity search, called PZLAST, which can search the user's amino acid sequences to several Terabytes of public metagenomic sequences in ∼10-20 min. PZLAST accomplishes its search speed by using PEZY-SC2, which is a Multiple Instruction Multiple Data many-core processor. Results of PZLAST are summarized by the ontology-based environmental distribution of similar sequences. PZLAST can be used to predict the function of sequences and mine for homologs of functionally important gene sequences. AVAILABILITY AND IMPLEMENTATION: PZLAST is freely accessible at https://pzlast.riken.jp/meta without requiring registration. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

External validation of the Candiolo nomogram for high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy: a retrospective cohort study.

The aim of this study was to reclassify high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy using the Candiolo nomogram and evaluate usefulness to predict the following 10-year biochemical recurrence. Six hundred seventy-two high-risk prostate cancer patients were reclassified according to the Candiolo nomogram. The cumulative incidence curves for biochemical recurrence were compared by Gray's test. Furthermore, five predictors of the Candiolo nomogram in our patients were evaluated by Fine and Gray regression hazards model. The higher the Candiolo risk, the worse the biochemical recurrence, especially in high- and very high-risk patients. Out of five predictors, age ≥70 years, cT3 stage, biopsy Gleason score ≥9 or the percentage of positive biopsy cores ≥50% had significant impacts on 10-year biochemical recurrence in our patients. The Candiolo nomogram can reclassify our high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy and evaluate the biochemical recurrence preciously.

Comparison of subjective cyclofusion ranges and objective ocular torsion in normal participants according to age.

PURPOSE: To investigate the relationship between subjective cyclofusion ranges and objective ocular torsion in normal participants according to age. METHODS: This cross-sectional study included 120 participants aged ≥ 20 years with no ocular diseases. The subjective cyclofusion ranges were measured centrifugally and centripetally in the direction of excyclotorsion and incyclotorsion, respectively, concurrently with rotational diplopia production by rotation using synoptophore. Disc fovea angle (DFA) was defined as the angle formed by two lines: a line passing through the center of the optic nerve papilla and fovea and a horizontal line passing through the center of gravity of the optic papilla using fundus photographs. RESULTS: The participants were aged 49.1 ± 17.7 years. The total cyclofusion centrifugal (sum of extorsion and intorsion) and centripetal ranges were 10.9 ± 2.2° and 7.2 ± 1.8°, respectively, both of which decreased in participants in their 60 s and 70 s (p < 0.01). The DFA was - 7.0 ± 3.4° in the right eye (- : excyclo, + : incyclo) and - 8.0 ± 3.2° in the left, which was associated with age (p < 0.001). The correlation between the DFA and centrifugal (r = - 0.13, p = 0.16) and centripetal (r = - 0.002, p = 0.99) cyclofusion ranges of extorsion was not significantly different. The centrifugal (r = 0.37, p < 0.001) and centripetal (r = 0.40, p < 0.001) cyclofusion ranges of intorsion were positively correlated. CONCLUSION: Subjective cyclofusion ranges decreased in both extorsion and intorsion in the elderly. Objective ocular torsion showed excyclotorsion with age. When strabismus surgery is performed in elderly patients with torsional strabismus, the decrease in subjective cyclofusion ranges should be considered.

Morphological Changes and Potential Mechanisms of Intraocular Pressure Reduction after Micropulse Transscleral Cyclophotocoagulation in Rabbits.

INTRODUCTION: Micropulse transscleral cyclophotocoagulation (MP-TSCPC) is a method for intraocular pressure (IOP) reduction in patients with glaucoma; however, the specific mechanisms underlying its ability to reduce IOP remain unclear. We therefore investigated the morphological changes and mechanisms of IOP reduction after MP-TSCPC. METHODS: The right eyes of 4 pigmented rabbits were treated with MP-TSCPC with power setting corresponding to those used in glaucoma patients (1 power: 2,000 mW; time: 160 s; duty cycle: 31.3%). Power settings of 1, 1/8, 1/16, and 1/32 power were applied to the right eyes. The left eyes were used as controls. A light microscope and electron microscope were used to observe morphological findings after 1 week of MP-TSCPC. IOP and IOP reduction rate were compared before and after MP-TSCPC application on days 1, 3, and 5, and at 1 week. RESULTS: In the pre-MP-TSCPC, IOP was 16.7 ± 0.6 mm Hg. The IOP of rabbit treated with the 1 power was 3 mm Hg, with an IOP reduction rate of 80%; however, the eyes developed phthisis bulbi. The IOP was 7.0 ± 0.0 mm Hg 1 week after MP-TSCPC (IOP reduction rate: 59%) in rabbit treated with the 1/8 power. Reduction in IOP was observed, but there was significant tissue invasion to the ciliary body. The IOP was 10.3 ± 0.6 mm Hg (IOP reduction rate: 40%) 1 week after MP-TSCPC in rabbit treated with the 1/16 power, which was more effective to reduce IOP than that with the 1/8 power. Tissue invasion to the ciliary body was negligible, nonpigmented epithelial cells of the pars plicata were damaged, basal infoldings were destroyed, and repair was accompanied by proliferating tissue. No IOP reduction or tissue change was observed in rabbit treated with the 1/32 power. CONCLUSION: A potential mechanism for IOP reduction in pigmented rabbits is aqueous humor transport dysfunction due to damage to the nonpigmented epithelial cells of the pars plicata and destruction of basal infoldings. The power of MP-TSCPC was consistent with both morphological changes and IOP reduction.

Carbon-ion radiotherapy for urological cancers.

Carbon-ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon-ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon-ion radiotherapy as a standard cancer therapy, the Japan Carbon-ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon-ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon-ion radiotherapy and our efforts to disseminate the use of this new technology worldwide.

Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review.

Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.

The potential for reducing alcohol consumption to prevent esophageal cancer morbidity in Asian heavy drinkers: a systematic review and meta-analysis.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34-7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57-2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

Fruit and vegetable consumption and risk of esophageal cancer in the Asian region: a systematic review and meta-analysis.

The consumption of fruit and vegetables was reported to be associated with a reduced risk of esophageal cancer (EC) in many studies of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) from different regions worldwide. Therefore, to provide precise information to reduce the risk of EC in Asia, we performed a systematic review and meta-analysis of studies conducted in the Asian region about fruit and vegetable consumption and the risk of EC. We searched the MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases from January 2010 to December 2020. The summary relative risk (SRR) and 95% CI were calculated using a random-effects model. In addition, I2 statistics were used to detect heterogeneity. Twenty-two studies were eligible for meta-analysis (16 case-control studies and 6 cohort studies). The SRR for the lowest versus highest fruit consumption was 0.64 (95% CI 0.53-0.77, I2 = 82%). That for the lowest versus highest vegetable consumption was 0.61 (95% CI 0.50-0.74, I2 = 81%). Based on subgroup analysis, a validated Food Frequency Questionnaire (FFQ) was significantly associated (SRR for fruit: 0.54; 95% CI 0.40-0.74, SRR for vegetable: 0.60; 95% CI 0.48-0.76) with low heterogeneity (I2 = 48% for fruit, I2 = 0% for vegetables). Egger's funnel plot asymmetry test demonstrated publication bias (P < 0.001 for fruit, P = 0.009 for vegetables). Fruit and vegetable consumption might be associated with a lower risk of EC in the Asian region. However, further substantial prospective studies with a validated FFQ and well-controlled important confounding factors are required to confirm the association.