National Defense Medical College Research Articles

Urinary N-acetyl-D-glucosaminidase can predict bleeding after a percutaneous kidney biopsy

BackgroundA percutaneous kidney biopsy (PKB) allows nephrologists to make informed decisions for treating various kidney diseases; however, the risk of bleeding complications should be considered, given the vascularity of the kidney. Many studies have reported risk factors for bleeding events after a PKB. However, while urinary N-acetyl-β-D-glucosaminidase (NAG) is a useful biomarker of kidney disease severity, little is known about whether or not urinary NAG is related to the bleeding risk.MethodsMedical records of patients who underwent a PKB at the National Defense Medical College Hospital between October 2018 and October 2023 were retrospectively studied. Hemoglobin (Hb) loss ≥ 1 g/dL was defined as a bleeding event.ResultsOf the 213 patients, 110 (51.6%) were men, and the median age was 56 years old (interquartile range 40–71). The most frequent diagnosis on a PKB was IgA nephropathy (N = 72; 34.0%). Fifty-four patients (25.3%) experienced Hb loss ≥ 1 g/dL after a PKB, and urinary NAG/Cr levels before the biopsy were able to predict a bleeding event, with an area under the receiver operating characteristic curve of 0.65 (p = 0.005). Using the optimal cutoff value of 35 U/gCr, urinary NAG/Cr was found to be an independent risk factor by multiple logistic regression analysis (odds ratio 3.21, 95% confidence interval 1.42–7.27, p = 0.005). Even after adjusting for previously-reported risk factors, the elevated urinary NAG/Cr ratio remained a statistically significant variable. Compared with the pathological findings, only the severity of multilayered elastic laminae of the small muscular artery was associated with both urinary NAG/Cr levels (p = 0.008) and bleeding events (p = 0.03).ConclusionUrinary NAG successfully predicted not only the severity of kidney disorders but also bleeding events after a PKB. Arteriosclerosis in the kidneys may be the mechanism underlying these increased bleeding events.

Is the Bulbar Urethral Stricture a Single and Uniform Disease?

Objectives: Proximal and distal bulbar urethral strictures (BUS) have different disease characteristics and require different treatment strategies despite being regarded as a single condition. To clarify the differences, we analyzed our database by distinguishing the two types of BUS. Methods: We retrospectively reviewed the data of 196 patients with BUS who underwent urethroplasty at the National Defense Medical College (Japan) between August 2004 and March 2022. We divided patients into proximal (group 1) or distal (group 2) groups based on the stricture segment and compared patient background and surgical techniques for each group. We assessed whether the stricture segment was an independent predictive factor for substitution urethroplasty selection using multivariate logistic regression analysis. The recurrence rates were calculated and compared using the Kaplan–Meier method and log-rank test, respectively. Results: Patients in group 1 had a less frequent non-obliterated lumen (73% vs. 94%, p = 0.020) and significantly shorter strictures (10 mm vs. 23 mm, p < 0.001) more frequently caused by external traumas (47% vs. 26%, p = 0.010) than those in group 2. Logistic regression analysis revealed that the stricture segment (distal) (p < 0.001), stricture length (≥20 mm) (p < 0.001), ≥2 prior transurethral procedures (p = 0.030), and a non-obliterated lumen (p = 0.020) were independent predictive factors for substitution urethroplasty. However, the recurrence rate (p = 0.18) did not significantly differ between the two groups. Conclusions: Proximal and distal BUS have substantially different anatomical characteristics and etiologies and require different reconstructive techniques.

Effectiveness of Body Armor Against Shock Waves: Preventing Blast Injury in a Confined Space.

Introduction Blast injuries in modern society often occur owing to terrorist attacks in confined spaces, particularly in urban settings, indoors, and in vehicles, leading to significant damage. Therefore, it is important to focus on blast injuries in confined spaces rather than in conventional open-field experiments. Materials and methods We used an air-driven shock wave generator (blast tube) established indoors in 2017 and conducted basic research to potentially save the lives of patients with blast injuries. Under general anesthesia, pigs were divided into with body armor (BA) and without BA groups. The pigs were fixed in the measurement chamber with their dorsal chest directly exposed to the shock wave. The driving pressure was set at 3.0 MPa to achieve a mortality rate of approximately 50%. A generated shock wave was directly applied to the pigs. Comparisons were made between the groups with respect to cardiac arrest and survival, as well as apnea, bradycardia, and hypotension, which are the triad of blast lung. Autopsies were performed to confirm the extent of the organ damage. Statistical analysis was performed using Fisher's exact test, and statistical significance was set at p<0.05. The animal experimentation was conducted according to the protocol reviewed and approved by the Animal Ethics Committee of the National Defense Medical College Hospital (approval number 19041). Results Eight pigs were assigned to the BA group and seven pigs to the non-BA group. In the non-BA group, apnea was observed in four of seven cases, three of which resulted in death. None of the eight pigs in the BA group had respiratory arrest; notably, all survived. Hypotension was observed in some pigs in each group; however, there were no cases of bradycardia in either group. Statistical analysis showed that wearing BA significantly reduced the occurrence of respiratory and cardiac arrest (p=0.026) but not survival (p=0.077). No significant differences were found in other vital signs. Conclusions Wearing BA with adequate neck and chest protection reduced mortality and it was effective to reduce cardiac and respiratory arrest against shock wave exposure. Mortality from shock wave injury appears to be associated with respiratory arrest, and the avoidance of respiratory arrest may lead to survival.

Clinical significance of retained products of conception in placenta previa: a retrospective analysis

BackgroundRetained products of conception (RPOC) often cause severe postpartum hemorrhage (PPH) but the clinical significance of RPOC in placenta previa is unclear. This study aimed to investigate the clinical significance of RPOC in women with placenta previa. The primary outcome was to evaluate risk factors of RPOC and the secondary outcome was to consider risk factors of severe PPH.MethodsSingleton pregnant women with placenta previa who underwent cesarean section (CS) and placenta removal during the operation at the National Defense Medical College Hospital between January 2004 and December 2021 were identified. A retrospective analysis was performed to examine the frequency and risk factors of RPOC and the association of RPOC with severe PPH in pregnant women with placenta previa.ResultsThis study included 335 pregnant women. Among these, 24 (7.2%) pregnant women developed RPOC. Pregnant women with prior CS (Odds Ratio (OR) 5.98; 95% Confidence Interval (CI) 2.35–15.20, p < 0.01), major previa (OR 3.15; 95% CI 1.19–8.32, p < 0.01), and placenta accreta spectrum (PAS) (OR 92.7; 95% CI 18.39–467.22, p < 0.01) were more frequent in the RPOC group. Multivariate analysis revealed that prior CS (OR 10.70; 95% CI 3.47–33.00, p < 0.01,) and PAS (OR 140.32; 95% CI 23.84–825.79, p < 0.01) were risk factors for RPOC. In pregnant women who have placenta previa with RPOC or without RPOC, the ratio of severe PPH were 58.3% and 4.5%, respectively (p < 0.01). Furthermore, the occurrence of prior CS (OR 9.23; 95% CI 4.02–21.20, p < 0.01), major previa (OR 11.35; 95% CI 3.35–38.38, p < 0.01), placenta at the anterior wall (OR 3.44; 95% CI 1.40–8.44, p = 0.01), PAS (OR 16.47; 95% CI 4.66–58.26, p < 0.01), and RPOC (OR 29.70; 95% CI 11.23–78.55, p < 0.01) was more in pregnant women with severe PPH. In the multivariate analysis for severe PPH, prior CS (OR 4.71; 95% CI 1.29–17.13, p = 0.02), major previa (OR 7.50; 95% CI 1.98–28.43, p < 0.01), and RPOC (OR 13.26; 95% CI 3.61–48.63, p < 0.01) were identified as risk factors.ConclusionsPrior CS and PAS were identified as risk factors for RPOC in placenta previa and RPOC is closely associated with severe PPH. Therefore, a new strategy for RPOC in placenta previa is needed.

Case of neuropathic itch‐associated prurigo nodules on the bilateral upper arms after unilateral herpes zoster in a patient with cervical herniated discs: Successful treatment with mirogabalin

The Journal of DermatologyVolume 48, Issue 12 p. e585-e586 LETTER TO THE EDITOR Case of neuropathic itch-associated prurigo nodules on the bilateral upper arms after unilateral herpes zoster in a patient with cervical herniated discs: Successful treatment with mirogabalin Satoshi Okuno, Satoshi Okuno orcid.org/0000-0003-0456-1852 Department of Dermatology, National Defense Medical College, Tokorozawa, JapanSearch for more papers by this authorTakashi Hashimoto, Corresponding Author Takashi Hashimoto hashderm@ndmc.ac.jp orcid.org/0000-0001-6779-5598 Department of Dermatology, National Defense Medical College, Tokorozawa, Japan Correspondence Takashi Hashimoto, Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-0042, Japan. Email: hashderm@ndmc.ac.jpSearch for more papers by this authorTakahiro Satoh, Takahiro Satoh orcid.org/0000-0002-2244-6332 Department of Dermatology, National Defense Medical College, Tokorozawa, JapanSearch for more papers by this author Satoshi Okuno, Satoshi Okuno orcid.org/0000-0003-0456-1852 Department of Dermatology, National Defense Medical College, Tokorozawa, JapanSearch for more papers by this authorTakashi Hashimoto, Corresponding Author Takashi Hashimoto hashderm@ndmc.ac.jp orcid.org/0000-0001-6779-5598 Department of Dermatology, National Defense Medical College, Tokorozawa, Japan Correspondence Takashi Hashimoto, Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-0042, Japan. Email: hashderm@ndmc.ac.jpSearch for more papers by this authorTakahiro Satoh, Takahiro Satoh orcid.org/0000-0002-2244-6332 Department of Dermatology, National Defense Medical College, Tokorozawa, JapanSearch for more papers by this author First published: 05 September 2021 https://doi.org/10.1111/1346-8138.16147Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume48, Issue12December 2021Pages e585-e586 RelatedInformation

Psoas muscle index at the fifth lumbar vertebra as a predictor of survival in epithelial ovarian cancers.

Almost a quarter of a century has passed since the term sarcopenia was defined. Sarcopenia is recognized as a poor prognostic factor in a variety of cancer types. In ovarian cancer, it remains controversial whether sarcopenia affects prognosis and how it should be evaluated. The present study aimed to evaluate the association between the volume of the psoas major muscle and survival in patients with epithelial ovarian cancer. Medical charts of patients with epithelial ovarian cancer who received first-line chemotherapy with paclitaxel and carboplatin at the National Defense Medical College Hospital (Tokorozawa, Japan) between April 2010 and January 2015 were retrospectively reviewed. The bilateral psoas major muscle areas at the fifth lumbar vertebra were measured using computed tomography images. The Institutional Review Board at National Defense Medical College Hospital (Tokorozawa, Japan) approved the study protocol. A total of 72 patients with epithelial ovarian cancer who received combination therapy with paclitaxel and carboplatin were identified and enrolled. The median psoas muscle index (PMI; psoas muscle major cross-sectional area divided by height squared) was 5.4 cm2/m2 (range, 3.3-10.0). Patients with higher PMI had significantly improved overall survival (OS) compared with those with lower PMI [log-rank test P=0.014; hazard ratio (HR), 2.61; 95% confidence interval (CI), 1.21-6.06]. Multivariate analysis for OS revealed that lower PMI was an independent unfavorable prognostic factor (HR, 3.87; 95% CI, 1.37-12.1; P=0.0098). The volume of psoas major muscle mass could be a potential biomarker for prognosis in patients with epithelial ovarian cancer.

Evaluation of emotional arousal level and depression severity using voice-derived sound pressure change acceleration

In this research, we propose a new index of emotional arousal level using sound pressure change acceleration, called the emotional arousal level voice index (EALVI), and investigate the relationship between this index and depression severity. First, EALVI values were calculated from various speech recordings in the interactive emotional dyadic motion capture database, and the correlation with the emotional arousal level of each voice was examined. The resulting correlation coefficient was 0.52 (n = 10,039, p < 2.2 × 10−16). We collected a total of 178 datasets comprising 10 speech phrases and the Hamilton Rating Scale for Depression (HAM-D) score of outpatients with major depression at the Ginza Taimei Clinic (GTC) and the National Defense Medical College (NDMC) Hospital. The correlation coefficients between the EALVI and HAM-D scores were − 0.33 (n = 88, p = 1.8 × 10−3) and − 0.43 (n = 90, p = 2.2 × 10−5) at the GTC and NDMC, respectively. Next, the dataset was divided into “no depression” (HAM-D < 8) and “depression” groups (HAM-D ≥ 8) according to the HAM-D score. The number of patients in the “no depression” and “depression” groups were 10 and 78 in the GTC data, and 65 and 25 in the NDMC data, respectively. There was a significant difference in the mean EALVI values between the two groups in both the GTC and NDMC data (p = 8.9 × 10−3, Cliff’s delta = 0.51 and p = 1.6 × 10−3; Cliff’s delta = 0.43, respectively). The area under the curve of the receiver operating characteristic curve when discriminating both groups by EALVI was 0.76 in GTC data and 0.72 in NDMC data. Indirectly, the data suggest that there is some relationship between emotional arousal level and depression severity.

Efficacy of Body Armor in Protection Against Blast Injuries Using a Swine Model in a Confined Space with a Blast Tube

The purpose of this study was to clarify whether or not body armor would protect the body of a swine model using a blast tube built at National Defense Medical College, which is the first such blast tube in Japan. Seventeen pigs were divided into two groups: the body armor group and the non-body armor group. Under intravenous anesthesia, the pigs were tightly fixed in the left lateral position on a table and exposed from the back neck to the upper lumbar back to the blast wave and wind with or without body armor, with the driving pressure of the blast tube set to 3.0 MPa. When the surviving and dead pigs were compared, blood gas analyses revealed significant differences in PaO2, PaCO2, and pH in the super-early phase. All pigs injured by the blast wave and wind had lung hemorrhage. All 6 animals in the body armor group and 6 of the 11 animals in the control group survived for 3 hours after injury. Respiratory arrest immediately after exposure to the blast wave was considered to influence the mortality in our pig model. Body armor may have a beneficial effect in protecting against respiratory arrest immediately after an explosion.

Clear cell borderline tumor without fibromatous component: Pathological and literature review and report of two cases.

The aim of the present study was to examine the clinical outcome of ovarian clear cell borderline tumor (CCBT) through pathological review for cases with clear cell carcinoma (CCC) and CCBT between 1984 and 2015 who received surgery at the National Defense Medical College Hospital using 2020 World Health Organization (WHO) criteria. In addition to the definition of CCBT in 2020 WHO criteria, clear cell with atypia of the glandular epithelium without fibromatous component was added to the diagnostic criteria of CCBT. Two cases with CCBT were identified through review in the current study. There were no cases that changed from the initial CCBT diagnosis that were included in the current study. Case 1 was a 43-year-old woman who received total hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy. Pathologically, cysts were lined by cuboidal, hobnail and clear cells with eosinophilic cytoplasm and moderate nuclear atypia without the fibromatous component. These cells were adjacent to atypical endometriosis and non-atypical endometriosis, and the patient was diagnosed with CCBT. She exhibited no evidence of the disease for 37 months following surgery. Case 2 was a 42-year-old woman who received left salpingo-oophorectomy, partial omentectomy and pelvic lymphadenectomy. The tumor exhibited a cyst (80 mm) and nodular component. Pathologically, the tumor cells were lined by hobnail cells with mild atypia and eosinophilic cytoplasm without the fibromatous component. This patient was diagnosed with CCBT and exhibited no evidence of disease for 20 months following surgery. CCBT without fibromatous component is a rare and non-aggressive histological subtype. Additionally, regardless of fibromatous component, CCBT was able to be diagnosed.

Microdevice for the Measurement of Respiratory Activity of Cells

Monitoring of the respiratory activity of animal and microbial cells in solutions of small volumes is required in many situations. For this purpose, devices based on electrochemical principles are advantageous, because miniaturization, batch-fabrication, and integration are easily realized. In our previous work, a device with integrated Clark-type oxygen electrode was developed to measure the bactericidal activity of neutrophils [1][2]. However, problems remain in the preparation of the device by non-experts. In addition, the output current often became unstable by evaporation of water in the electrolyte solution.To solve these problems, we propose a novel structure shown in Figure 1. The structure including a platinum cathode, an Ag/AgCl anode, an electrolyte layer, and a silicone rubber oxygen-permeable membrane were completed in a dry state. The electrolyte and other solution components were impregnated in a thin paper disc. Prior to use, water which is necessary for the reduction of oxygen was introduced into the electrolyte layer through the oxygen-permeable membrane in the form of water vapor simply by immersing the device in water for 8 – 12 hours.In operating the device, −0.8 V was applied to the cathode with respect to the anode using a potentiostat. The response of the oxygen electrode was checked by immersing the active area into air-saturated pure water and removing dissolved oxygen by adding Na2SO3. After the activation, the output current in the air-saturated water was stabilized and the current response to the change in the dissolved oxygen concentration became distinct. The 90% response time of a fully activated device was approximately 30 seconds.To measure the respiratory activity of cells, a chamber made with PMMA (polymethyl methacrylate) was placed on the oxygen permeable membrane of a fully activated device, and a suspension of cells was injected into the chamber. E. coli and MSSA (methicillin-susceptible Staphylococcus aureus) used in this study were purchased from Sigma Aldrich. MRSA (methicillin-resistant Staphylococcus aureus) was isolated from the clinical specimens of a patient in the National Defense Medical College Hospital and grown on the brain heart infusion (BHI) agar supplemented with oxacillin for 48 h at 37 °C under aerobic conditions. Suspensions of bacteria mentioned above were all stored in 20% glycerin at −80 ºC until usage. Prior to the experiments, suspensions of bacteria were thawed and were finally prepared in BHI medium with the desirable concentration. Incubation for the cells was carried out by placing the device on a hotplate maintained at 37 ºC.The respiratory activity of E. coli was first monitored using suspensions of different concentrations. Distinct current changes were observed at E. coli concentrations higher than 106 CFU/mL, and the current decrease was larger with E. coli of higher concentrations. Next, change in the respiratory activity of Staphylococcus aureus suspensions treated with or without antibiotics was monitored for 80 minutes. In this experiment, 1×107 CFU/mL Staphylococcus aureus suspensions of susceptible strain (MSSA) and resistant strain (MRSA) treated with or without 1 µg/mL oxacillin were used as samples. As time elapsed, current decreased distinctly due to the oxygen consumption of bacteria both in the MSSA and MRSA suspensions without oxacillin. Distinct current decrease was also observed in the MRSA suspension treated with oxacillin. On the other hand, in the MSSA suspensions treated with oxacillin, the current decrease was smaller and was almost suppressed following the incubation. These results demonstrated that our device can detect the change in dissolved oxygen concentration caused by the respiration of bacteria.[1] K. Tanabe, M. Kinoshita, M. Nakashima, K. Kariya, M. Yokokawa, Y. Morimoto, H. Suzuki, Med. Devices Sens., 2, 1–7 (2019).[2] A. Yamagishi, K. Tanabe, M. Yokokawa, Y. Morimoto, M. Kinoshita, and H. Suzuki, Anal. Chim. Acta., 985, 1–6 (2017). Figure 1

Evaluation of the Severity of Major Depression Using a Voice Index for Emotional Arousal.

Recently, the relationship between emotional arousal and depression has been studied. Focusing on this relationship, we first developed an arousal level voice index (ALVI) to measure arousal levels using the Interactive Emotional Dyadic Motion Capture database. Then, we calculated ALVI from the voices of depressed patients from two hospitals (Ginza Taimei Clinic (H1) and National Defense Medical College hospital (H2)) and compared them with the severity of depression as measured by the Hamilton Rating Scale for Depression (HAM-D). Depending on the HAM-D score, the datasets were classified into a no depression (HAM-D < 8) and a depression group (HAM-D ≥ 8) for each hospital. A comparison of the mean ALVI between the groups was performed using the Wilcoxon rank-sum test and a significant difference at the level of 10% (p = 0.094) at H1 and 1% (p = 0.0038) at H2 was determined. The area under the curve (AUC) of the receiver operating characteristic was 0.66 when categorizing between the two groups for H1, and the AUC for H2 was 0.70. The relationship between arousal level and depression severity was indirectly suggested via the ALVI.

Effect of continuous saline bladder irrigation with concomitant single instillation of chemotherapy after transurethral resection on intravesical recurrence in patients with non-muscle-invasive bladder cancer.

A single immediate instillation of chemotherapy following transurethral resection of bladder tumor (TURBT) is effective in preventing intravesical recurrence (IVR) in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). However, continuous saline bladder irrigation (CSBI) is also performed with a single instillation of chemotherapy (SIC), but its inhibitory effect on IVR remains unclear. In the present study, the effect of CSBI with concomitant SIC following TUR on IVR was evaluated in patients with NMIBC. A retrospective review of 253 patients who underwent TURBT and were clinically and histologically diagnosed with NMIBC at National Defense Medical College Hospital was performed. Doxorubicin (DXR) was administered to all patients. Methods of DXR administration included a single instillation of DXR (60 mg in 30-40 ml saline) in 34 patients (group A), continuous irrigation of the bladder with saline including DXR (80 mg in 1 liter saline) in 40 patients (group B) and overnight CSBI after a single instillation of DXR in 179 patients (group C). The difference in IVR-free survival rates was compared after adjusting for significant differences in several covariates between the groups by nearest-neighbor propensity score matching. Prior to propensity score matching, it was identified that time to IVR was significantly longer in group A than in groups B and C; however, it was observed that several factors significantly differed among the three groups. By using nearest neighbor matching, 18 pairs were matched between groups A and B and 33 pairs between the groups A and C. No significant difference was identified in any covariates between these two matched group pairsTime to IVR was significantly longer in the matched group A than in the matched groups B and C (P=0.0255 and P=0.0023, respectively). In conclusion, SIC alone could provide a higher IVR-free survival rate than CSBI with DXR or CSBI with SIC.

Aquaporin 3 Expression in Endometrioid Carcinoma of the Uterine Body Correlated With Early Stage and Lower Grade.

Aquaporins (AQPs) are a family of transmembrane water channel proteins distributed in various human tissues. Recent studies revealed that AQPs play important roles in cancer biology. Few studies have documented the relationship between the prognosis, stage, and histological grade of uterine endometrioid carcinoma, with AQP expression. Hence, the present study aimed to investigate this relationship between uterine endometrioid carcinoma and AQP expression. We retrospectively reviewed records of the patients who underwent surgery for uterine body cancer between 1990 and 2010 at the National Defense Medical College Hospital, Saitama, Japan. In 241 cases of endometrioid carcinoma, we immunohistochemically examined the expression of AQP 1, 2, 3, 4, and 5, and their relationship with clinicopathological parameters and the patients' prognosis. We investigated the relationship between the clinicopathological parameters and AQP3 expression, and found that as the FIGO stage and histological grade progressed, the percentage of AQP3 expression tends to decrease. Furthermore, we analyzed progression-free survival/overall survival (PFS/OS) using the log-rank test, and found that the AQP3-positive group had a better prognosis than AQP3-negative group (PFS: P < 0.001, OS: P = 0.002, respectively). Using Cox's univariate proportional hazard model, we revealed that AQP3 had a low hazard ratio. However, according to Cox's multivariate proportional hazard model, AQP3 was not an independent prognostic factor. Among the endometrioid carcinoma patients, the AQP3-positive group was associated with early stage and lower grade compared to the AQP3-negative group. Therefore, AQP3 has the potential to serve as a predictor of prognosis, although further investigation is necessary to elucidate the biological mechanism of AQP3 in endometrioid carcinoma.

Posttrauma Symptoms after the 2011 Great East Japan Earthquake: A 6-Year Prospective Cohort Study in 56 388 First Responders

Background: First responders are at risk for developing symptoms of post-traumatic stress disorder (PTSD). Especially, body recovery duties and nuclear disaster response were known as challenging missions that can induce severe adverse psychological responses for a long time. The 2011 Great East Japan Earthquake (GEJE), an unprecedented complex disaster (i.e., earthquake/tsunami/nuclear accident), provided us with a unique opportunity to explore these risk factors and their relative influence for PTSD. Methods: Of approximately 70 000 eligible Japan Ground Self-Defense Force (JGSDF) first responders, 56 388 enrolled in this 6-year prospective cohort study. The data were collected at eight time points: one, six, 12, 24, 36, 48, 60, and 72 months post-mission completion. The Impact of Event Scale–Revised assessed PTSD symptoms; scores of ≥25 were defined as probable PTSD. Professional disaster experience (i.e., duties with body recovery or radiation exposure risk), sociodemographic factors (e.g., disaster–victim status) and working conditions (e.g., deployment length) were investigated. Cox proportional hazard models assessed the risk factors for incidences of probable PTSD. Findings: The cumulative incidence of probable PTSD was 6·75%. The classes categorized by baseline severity of PTSD symptoms demonstrated a high degree of rank-order stability over time. Rather than professional disaster experience, sociodemographic factors and working conditions showed strong independent association with the incidence of probable PTSD: disaster-victim status (hazard ratio [HR]=1·96; 95% CI 1·72-2·24), deployment length of ≥3 months (vs. <1 month; HR=1·75; 95% CI 1·52-2·03), older age (≥46 vs. ≤25 years; HR=2·28; 95% CI 1·79-2·91), and post-deployment overwork of ≥3 months (vs. little to none; HR=1·61; 95% CI 1·39-1·87). Interpretation: In the future, first responders’ PTSD symptoms might be mitigated by shortening deployment length, avoiding post-deployment overwork, and paying special attention to personnel with disaster-victim status or older age. Efforts to alleviate responders’ initial symptoms will be required. Funding Statement: This study was supported by the Japanese Society for the Promotion of Science KAKENHI Grant Number: 26461779. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Approval to perform this research was obtained from the Ethics Committee of the National Defense Medical College (Approval No. 2108). All data were anonymized before the statistical analyses.

Clinical Significance of Programmed Death Ligand-1 Expression in Esophageal Squamous Cell Carcinoma

BackgroundThe aim of this study was to evaluate the association between the expression of programmed death ligand-1 (PD-L1) and clinical outcomes in patients with surgically resected esophageal squamous cell carcinoma (ESCC). Materials and methodsWe included 76 patients with primary ESCC who underwent surgical resection between January 2009 and December 2014 at National Defense Medical College Hospital. Using the tumor tissues, we evaluated PD-L1 expression in tumor cells and stromal reactive lymphocytes via immunohistochemistry. Furthermore, the relationship between PD-L1 expression and the clinicopathological status of patients with ESCC was investigated. ResultsPD-L1 expression in tumor cells was detected in 39.5% of the patients. In addition, 51.3% of the patients had PD-L1–positive stromal reactive lymphocytes and exhibited significantly longer overall survival than those with lack of PD-L1 expression in stromal reactive lymphocytes (median survival time, 56.0 versus 27.3 mo; log-rank test, P = 0.04). Patients with lack of PD-L1 expression in both tumor cells and stromal reactive lymphocytes showed worse overall survival than those with the PD-L1–positive expression in tumor cells and/or stromal reactive lymphocytes (P = 0.02). ConclusionsPD-L1–positive expression in stromal reactive lymphocytes, rather than in tumor cells, is associated with a longer survival in patients with ESCC.

Nadir lymphocytopenia as a risk factor of bloodstream infection during molecular targeting pharmacotherapy in multiple myeloma.

Molecular targeting pharmacotherapy (MTP) with proteasome inhibitors and immunomodulatory drugs has led to a remarkable improvement in the effectiveness of multiple myeloma (MM) therapy. However, the effect of MTP on the occurrence of infections in patients with MM remains unclear. We aimed to identify the incidence of and risk factors for bloodstream infection (BSI) in patients with MM undergoing MTP. We conducted a retrospective cohort study. We reviewed the medical records of 108 inpatients with MM at the National Defense Medical College Hospital between January 2010 and January 2017. Univariate and multivariate analyses were conducted to identify risk factors for BSI. The incidence of BSI in patients with MM receiving MTP (n = 188) was 6.9%, which was significantly lower than the 52.6% in patients receiving cytotoxic chemotherapy (n = 57). We found that the most important risk factor for BSI in patients receiving MTP was lymphocytopenia at nadir (< 200/µL). In contrast, the risk factor for BSI in patients receiving cytotoxic chemotherapy was the number of regimens performed. Our study suggests that the incidence of BSI is lower in patients with MM receiving MTP than in those receiving cytotoxic chemotherapy and that lymphocytopenia at nadir may be a risk factor for BSI in patients with MM receiving MTP. Since previous clinical trials with MTP showed that the frequency of myelosuppression and infections was high in the Japanese population, these findings might provide novel insights into MTP for Japanese patients with MM. .

Prognostic significance of histological categorization of desmoplastic reaction in colorectal liver metastases.

Desmoplastic reaction (DR) involves the growth of fibrous or connective tissues around a tumor and has recently attracted attention as an indicator of malignant potential. Previous studies have confirmed that histological categorization of DR in the primary tumor is an independent prognostic factor in patients with colorectal liver metastases (CRLM). However, it remains unclear whether the DR status of the metastatic liver lesion (DRliver) is a useful prognostic factor. This pathological review evaluated records from 204 patients who underwent hepatectomy for CRLM at the National Defense Medical College Hospital in Japan. Each case's DRliver was classified as mature, intermediate, or immature based on the presence of keloid-like collagen and myxoid stroma in the metastatic liver lesion. This resulted in 12 cases of mature DRliver, 101 cases of intermediate DRliver, and 91 cases of immature DRliver. There was a significant correlation between the DR statuses of the primary tumor and the metastatic liver lesion (Spearman's rho = 0.3, P = 0.0001). The 5-year relapse-free survival rates after hepatectomy were 33.8% for mature/intermediate DRliver and 16.7% for immature DRliver (P = 0.0021). The 5-year overall survival rate after hepatectomy was higher in the mature/intermediate DRliver group (64.8%) than in the immature DRliver group (35.0%; P = 0.0012). The multivariate analysis confirmed that DRliver categorization could independently predict relapse-free survival and overall survival. In conclusion, DRliver categorization may be valuable for predicting prognosis after hepatectomy among patients with CRLM.

Cancer-induced spiculation on computed tomography: a significant preoperative prognostic factor for colorectal cancer.

Cancer-induced spiculation (CIS) on computed tomography, which is reticular or linear opacification of the pericolorectal fat tissues around the cancer site, is generally regarded as cancer infiltration into T3 or T4, but its clinicopathological significance is unknown. This study examines the correlation between CIS and clinicopathological findings to establish its prognostic value. The subjects of this retrospective study were 335 patients with colorectal cancer (CRC), who underwent curative surgery between January, 2010 and December, 2011, at the National Defense Medical College Hospital in Saitama Prefecture, Japan. The level of interobserver agreement in the evaluation of CIS was substantial (83%; kappa value, 0.65). The presence of CIS was specific for T3/T4 disease (positive predictive value, 88.3%), and was significantly associated with tumor size and venous invasion. The 5-year relapse-free survival rate was significantly lower in patients with CIS than in those without CIS (68.6% and 84.0%, respectively, p = 0.001). Subgroup analysis revealed remarkable prognostic differences in patients with stage III and T3 disease. Multivariate analysis revealed that CIS was a significant independent prognostic factor. CIS was a significant preoperative prognostic factor and could be useful in the selection of preoperative therapy for patients with CRC.

A case of intrahepatic cholangiocarcinoma that was difficult to diagnose prior to surgery: A case report.

The present study reports a case of mass-forming intrahepatic cholangiocarcinoma (ICC), which mimicked cholangiocellular carcinoma (CoCC) during imaging and a needle biopsy examination. A 51-year-old female with no relevant medical history was referred to the National Defense Medical College hospital with an intrahepatic tumor. Computed tomography demonstrated non-homogeneous enhancement in the early arterial phase and persistent enhancement in the portal and equilibrium phases, together with notable swelling of the para-aortic lymph nodes. Gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid-enhanced magnetic resonance imaging revealed low signal intensity in the hepatobiliary phase. The liver tumor and lymph nodes exhibited increased radiotracer uptake (maximum standardized uptake value=14.0) with positron emission tomography. A histological examination of a percutaneous needle biopsy specimen of the liver tumor indicated a diagnosis of CoCC. The patient underwent left hepatectomy and lymphadenectomy. The surgical specimen contained a poorly differentiated adenocarcinoma with anaplastic changes, which was immunohistochemically positive for epithelial membrane antigen (at the luminal membrane), cytokeratins 7 and 19, and negative for α-fetoprotein, hepatocyte-specific antigen, cluster of differentiation 56 and KIT. Based on these histopathological and immunohistochemical findings, the patient was diagnosed with ICC.

JAK2/STAT3 pathway as a therapeutic target in ovarian cancers.

The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression-free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p-STAT3 was observed in 95 cases (28%). Positive p-STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p-STAT3 expression was related with overall survival in patients with clear-cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear-cell cancer cells, and niclosamide treatment decreased expression of p-STAT3, leading to increased apoptosis in a dose-dependent manner in vitro. The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear-cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers.