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Background: Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP., Methods: This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C)., Discussion: The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety., Trial Registration: This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120)., (© 2024. The Author(s).)

Background: Multiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists' current practices and experiences in delivering the diagnosis of MSA., Methods: We conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique., Results: Among the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA., Conclusions: Our findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient's personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term "sudden death" in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement., (© 2024. The Author(s).)

Background: Minimally invasive distal pancreatectomy (MIDP), including laparoscopic and robotic distal pancreatectomy, has gained widespread acceptance over the last decade owing to its favorable short-term outcomes. However, evidence regarding its oncologic safety is insufficient. In March 2023, a randomized phase III study was launched in Japan to confirm the non-inferiority of overall survival in patients with resectable pancreatic cancer undergoing MIDP compared with that of patients undergoing open distal pancreatectomy (ODP)., Methods: This is a multi-institutional, randomized, phase III study. A total of 370 patients will be enrolled from 40 institutions within 4 years. The primary endpoint of this study is overall survival, and the secondary endpoints include relapse-free survival, proportion of patients undergoing radical resection, proportion of patients undergoing complete laparoscopic surgery, incidence of adverse surgical events, and length of postoperative hospital stay. Only a credentialed surgeon is eligible to perform both ODP and MIDP. All ODP and MIDP procedures will undergo centralized review using intraoperative photographs. The non-inferiority of MIDP to ODP in terms of overall survival will be statistically analyzed. Only if non-inferiority is confirmed will the analysis assess the superiority of MIDP over ODP., Discussion: If our study demonstrates the non-inferiority of MIDP in terms of overall survival, it would validate its short-term advantages and establish its long-term clinical efficacy., Trial Registration: This trial is registered with the Japan Registry of Clinical Trials as jRCT 1,031,220,705 [ https://jrct.niph.go.jp/en-latest-detail/jRCT1031220705 ]., (© 2024. The Author(s).)

Background: This study aimed to identify the current risk factors for coronavirus disease 2019 severity and examine its association with medication use., Methods: We used data from a large United States electronic health record database to conduct an anonymized cohort study of 171,491 patients with coronavirus disease 2019. The study was conducted from January 1, 2020, to August 27, 2021. Data on age, race, sex, history of diseases, and history of medication prescriptions were analyzed using the Cox proportional hazards model analysis to calculate hazard ratios for hospitalization and severe risk., Results: Factors that increased the risk of hospitalization and critical care were age ≥ 65 years, male sex, type 2 diabetes, hypertension, interstitial pneumonia, and cardiovascular disease. In particular, age ≥ 65 years significantly increased the risk of hospitalization (hazard ratio, 2.81 [95% confidence interval, 2.58-3.07]; P < 0.001) and critical care (hazard ratio, 3.45 [2.88-4.14]; P < 0.001). In contrast, patients with hyperlipidemia had a reduced risk. However, patients with hyperlipidemia who were not taking statins had a significantly increased risk of hospitalization (hazard ratio, 1.24 [1.16-1.34]; P < 0.001). Sodium-glucose cotransporter-2 inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, glucocorticoids, and statins significantly reduced the risk of hospitalization and critical care. The risk of hospitalization and critical care increased in patients of all ethnicities with type 2 diabetes. The factors that significantly increased the risk of hospitalization in all regions were older age, hypertension, chronic obstructive pulmonary disease, and cardiovascular disease., Conclusion: This study identified factors that increase or reduce the risk of severe coronavirus disease. The provision of appropriate drug treatment and modification of lifestyle-related risk factors may reduce coronavirus disease severity., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The current standard of care for patients with unresectable locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) combined with durvalumab consolidation therapy. However, radiotherapy (RT) always carries the risk of radiation pneumonitis (RP), which can preclude durvalumab continuation. In particular, the spread of interstitial lung disease (ILD) in low-dose areas or extending beyond the RT field often makes it difficult to determine the safety of continuation or rechallenging of durvalumab. Thus, we retrospectively analyzed ILD/RP after definitive RT with and without durvalumab, with assessment of radiologic features and dose distribution in RT., Methods: We retrospectively evaluated the clinical records, CT imaging, and radiotherapy planning data of 74 patients with NSCLC who underwent definitive RT at our institution between July 2016 and July 2020. We assessed the risk factors for recurrence within one year and occurrence of ILD/RP., Results: Kaplan-Meier method showed that ≥ 7 cycles of durvalumab significantly improved 1-year progression free survival (PFS) (p < 0.001). Nineteen patients (26%) were diagnosed with ≥ Grade 2 and 7 (9.5%) with ≥ Grade 3 ILD/RP after completing RT. There was no significant correlation between durvalumab administration and ≥ Grade 2 ILD/RP. Twelve patients (16%) developed ILD/RP that spread outside the high-dose (> 40 Gy) area, of whom 8 (67%) had ≥ Grade 2 and 3 (25%) had Grade 3 symptoms. In unadjusted and multivariate Cox proportional-hazards models adjusted for V 20 (proportion of the lung volume receiving ≥ 20 Gy), high HbA1c level was significantly correlated with ILD/RP pattern spreading outside the high-dose area (hazard ratio, 1.842; 95% confidence interval, 1.35-2.51)., Conclusions: Durvalumab improved 1-year PFS without increasing the risk of ILD/RP. Diabetic factors were associated with ILD/RP distribution pattern spreading in the lower dose area or outside RT fields, with a high rate of symptoms. Further study of the clinical background of patients including diabetes is needed to safely increase the number of durvalumab doses after CRT., (© 2023. The Author(s).)

Background: Evidence has demonstrated that excess sodium intake is associated with development of several non-communicable diseases. The main source of sodium is salt. Therefore, reducing salt intake in foods is an important global public health effort to achieve sodium reduction and improve health. This study aimed to model salt intake reduction with 'umami' substances among Japanese adults. The umami substances considered in this study include glutamate or monosodium glutamates (MSG), calcium diglutamate (CDG), inosinate, and guanylate., Methods: A total of 21,805 participants aged 57.8 years on average from the National Health and Nutrition Survey was used in the analysis. First, we employed a multivariable linear regression approach with overall salt intake (g/day) as a dependent variable, adjusting for food items and other covariates to estimate the contribution of salt intake from each food item that was selected through an extensive literature review. Assuming the participants already consume low-sodium products, we considered three scenarios in which salt intake could be reduced with the additional umami substances up to 30%, 60% and 100%. We estimated the total amount of population-level salt reduction for each scenario by age and gender. Under the 100% scenario, the Japan's achievement rates against the national and global salt intake reduction goals were also calculated., Results: Without compromising the taste, the 100% or universal incorporation of umami substances into food items reduced the salt intake of Japanese adults by 12.8-22.3% at the population-level average, which is equivalent to 1.27-2.22 g of salt reduction. The universal incorporation of umami substances into food items changed daily mean salt intake of the total population from 9.95 g to 7.73 g: 10.83 g to 8.40 g for men and 9.21 g to 7.17 g for women, respectively. This study suggested that approximately 60% of Japanese adults could achieve the national dietary goal of 8 g/day, while only 7.6% would meet the global recommendation of 5.0 g/day., Conclusions: Our study provides essential information on the potential salt reduction with umami substances. The universal incorporation of umami substances into food items would enable the Japanese to achieve the national dietary goal. However, the reduced salt intake level still falls short of the global dietary recommendation., (© 2023. The Author(s).)

Background: Hospital physician workforce in Japan is the lowest among developed countries. Many patients with novel coronavirus disease 2019 (COVID-19) with high risk of mortality could not be hospitalized during case surges in Japan and only about 5% of total acute care beds were used as COVID-19 beds nationwide. However, the relationship between the number of hospital physicians and patient admissions remains unclear. Thus, we aimed to evaluate this relationship in areas with the highest incidences during the surges., Methods: Data collection was performed for teaching hospitals accredited with the specialty of internal medicine in three prefectures which experienced the highest COVID-19 incidences in Japan (Tokyo, Osaka, Okinawa). Association was examined between the number of full-time physicians (internal medicine staff physicians and residents) and admissions of internal medicine patients through ambulance transport from April 2020 to March 2021. Analysis was conducted separately for community hospitals and university hospitals because the latter have roles as research institutions in Japan. Community hospitals included private, public, and semi-public hospitals., Results: Of 117 teaching hospitals in three prefectures, data from 108 teaching hospitals (83 community hospitals and 25 university hospitals) were available. A total of 102,400 internal medicine patients were admitted to these hospitals during the one-year period. Private hospitals received the greatest mean number of patient admissions (290 per 100 beds), followed by public hospitals (227) and semi-public hospitals (201), and university hospitals (94). Among community hospitals, a higher number of resident physicians per 100 beds was significantly associated with a greater number of patient admissions per 100 beds with beta coefficient of 11.6 (95% CI, 1.5 to 21.2, p = 0.025) admissions by one physician increase per 100 beds. There was no such association among university hospitals., Conclusions: Community hospitals with many resident physicians accepted more internal medicine admissions through ambulance transport during the COVID-19 pandemic. An effective policy to counter physician shortage in hospitals in Japan may be to increase internal medicine resident physicians among community hospitals to save more lives., (© 2023. The Author(s).)

Background: Local duodenectomy and primary closure is a simple option for some nonampullary duodenal neoplasms. Minimizing the resection area while ensuring curability is necessary for safe primary duodenal closure. However, it is often difficult to determine the appropriate resection line from the serosal side. We developed clip-guided local duodenectomy to easily determine the resection range and perform local duodenectomy safely, then performed a retrospective observational study to confirm the safety of clip-guided local duodenectomy., Methods: The procedure is as follows: placing endoscopic metal clips at four points on the margin around the tumor within 3 days before surgery, identifying the tumor extent with the clips under X-ray imaging during surgery, making an incision to the duodenum just outside of the clips visualized by X-ray imaging, full-thickness resection of the duodenum with the clips as guides of tumor demarcation, and transversely closure by Gambee suture. We evaluated clinicopathological data and surgical outcomes of patients who underwent clip-guided local duodenectomy at two surgical centers between January 2010 and May 2020., Results: Eighteen patients were included. The pathological diagnosis was adenoma (11 cases), adenocarcinoma (6 cases), and GIST (1 case). The mean ± SD tumor size was 18 ± 6 mm, and the tumor was mainly located in the second portion of the duodenum (66%). In all cases, the duodenal defect was closed with primary sutures. The mean operation time and blood loss were 191 min and 79 mL, respectively. The morbidity was 22%, and all complications were Clavien-Dindo grade II. No anastomotic leakage or stenosis was observed. In the 6 adenocarcinoma patients, all were diagnosed with pT1a, and postoperative recurrence was not observed. The 1-year overall and recurrence free survival rate was 100%., Conclusions: Clip-guided local duodenectomy is a safe and useful surgical option for minimally local resection of nonampullary duodenal neoplasms such as duodenal adenoma, GIST, and early adenocarcinoma., (© 2022. The Author(s).)

Background: Multiple waves of the COVID-19 epidemic have hit most countries by the end of 2021. Most of those waves are caused by emergence and importation of new variants. To prevent importation of new variants, combination of border control and contact tracing is essential. However, the timing of infection inferred by interview is influenced by recall bias and hinders the contact tracing process., Methods: We propose a novel approach to infer the timing of infection, by employing a within-host model to capture viral load dynamics after the onset of symptoms. We applied this approach to ascertain secondary transmission which can trigger outbreaks. As a demonstration, the 12 initial reported cases in Singapore, which were considered as imported because of their recent travel history to Wuhan, were analyzed to assess whether they are truly imported., Results: Our approach suggested that 6 cases were infected prior to the arrival in Singapore, whereas other 6 cases might have been secondary local infection. Three among the 6 potential secondary transmission cases revealed that they had contact history to previously confirmed cases., Conclusions: Contact trace combined with our approach using viral load data could be the key to mitigate the risk of importation of new variants by identifying cases as early as possible and inferring the timing of infection with high accuracy., (© 2022. The Author(s).)

Background: Plaque hardness in carotid artery stenosis correlates with cerebral infarction. This study aimed to quantitatively compare plaque hardness with histopathological findings and identify the pathological factors involved in plaque hardness., Methods: This study included 84 patients (89 lesions) undergoing carotid endarterectomy (CEA) at our institution. Plaque hardness was quantitatively measured immediately after excision using a hardness meter. Collagen and calcification were evaluated as the pathological factors. Collagen was stained with Elastica van Gieson stain, converted to a gray-scale image, and displayed in a 256-step histogram. The median gray-scale median (GSM) was used as the collagen content. The degree of calcification was defined by the hematoxylin-eosin stain as follows: "0:" no calcification, "1:" scattered microcalcification, or "2:" calcification greater than 1 mm or more than 2% of the total calcification. Carotid echocardiographic findings, specifically echoluminance or the brightness of the narrowest lesion of the plaque, classified as hypo-, iso-, or hyper-echoic by comparison with the intima-media complex surrounding the plaque, and clinical data were reviewed., Results: Plaque hardness was significantly negatively correlated with GSM [Spearman's correlation coefficient: -0.7137 (p < 0.0001)]: the harder the plaque, the higher the collagen content. There were significant differences between plaque hardness and degree of calcification between "0" and "2" (p = 0.0206). For plaque hardness and echoluminance (hypo-iso-hyper), significant differences were found between hypo-iso (p = 0.0220), hypo-hyper (p = 0.0006), and iso-hyper (p = 0.0015): the harder the plaque, the higher the luminance. In single regression analysis, GSM, sex, and diabetes mellitus were significant variables, and in multiple regression analysis, only GSM was extracted as a significant variable., Conclusions: Plaque hardness was associated with a higher amount of collagen, which is the main component of the fibrous cap. Greater plaque hardness was associated with increased plaque stability. The degree of calcification may also be associated with plaque hardness., (© 2022. The Author(s).)

Background: Curative treatment of inoperable post-irradiation sarcoma is often challenging, especially using radiotherapy, wherein curative dose administration is difficult because the organs around the tumor have already been irradiated during the first cancer treatment. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of post-irradiation sarcomas because it allows re-irradiation with high-dose localization properties and also demonstrates higher cytotoxic effects on radioresistant tumors compared with X-rays. This study presents the long-term survival of two patients with inoperable post-irradiation pelvic osteosarcoma treated with C-ion RT after uterine cervical cancer treatment., Case Presentation: The durations from prior radiotherapy to the diagnosis of post-irradiation osteosarcoma were 112.8 and 172.2 months, respectively. Both patients received 70.4 Gy (relative biological effectiveness) in 16 fractions of C-ion RT, and chemotherapy was performed before and after C-ion RT. Both patients achieved a complete response 1 year after the initiation of C-ion RT. However, one patient developed single lung metastasis 12.6 months after the initiation of C-ion RT and underwent thoracoscopic lobectomy. After 63.7 and 89.0 months from the initiation of C-ion RT, respectively, the patients were alive with no evidence of local recurrence, other distant metastasis, or fatal toxicities., Conclusions: The study findings suggest that C-ion RT is a suitable treatment option for inoperable post-irradiation osteosarcoma., (© 2022. The Author(s).)

Background and Purpose: Muscle ultrasonography has been increasingly recognized as a useful tool for detection of fasciculations. Separately, concordance between dominant hand and onset side has been reported in amyotrophic lateral sclerosis (ALS). The aim of this study was to reveal the distribution of fasciculations in the whole body, focusing on handedness., Methods: In 106 consecutive patients with ALS, muscle ultrasonography was systematically performed in 11 muscles (the tongue, and bilateral biceps brachii, 1st dorsal interosseous [FDI], T10-paraspinalis, vastus lateralis and tibialis anterior muscles). The fasciculation intensity was scored from 0 to 3 for each muscle., Results: Fasciculations were more frequently found in the limb muscles than the tongue and paraspinalis. Side and handedness analyses revealed that fasciculation intensity in FDI was significantly more prominent on the right (median [inter-quartile range] 2 [0 - 3]) than left (1.5 [0 - 3]; p = 0.016), and in the dominant hand (2 [1 - 3]) than non-dominant side (1.5 [0 - 3]; p = 0.025). The differences were greater in patients with upper limb onset. There were no side differences in the lower limb muscles. Multivariate analyses showed that male patients had more frequent fasciculations in the dominant FDI (β = 0.22, p < 0.05)., Conclusion: More intensive fasciculations are present in the FDI in the dominant hand and gender might be associated with fasciculation intensities. This distribution pattern of fasciculations might be associated with pathogenesis of ALS., (© 2022. The Author(s).)

Background: Japan strives to strengthen its development cooperation by mobilizing various resources to assist partner countries advance on Universal Health Coverage by 2030. However, the involvement and roles of various actors for health are not clear. This study is the first to map Japan's publicly funded projects by both Official Development Assistance (ODA) and other non-ODA public funds, and to describe the intervention areas. Further, the policy implications for country-specific cooperation strategies are discussed. The development cooperation for health in Vietnam is used as a case in this study., Methods: A cross-sectional analysis of the Japanese publicly funded health projects that were being implemented in Vietnam during December 2016 was conducted. A framework of analysis based on the World Health Organization six health systems building blocks was adopted. The projects' qualitative information was also assessed., Results: Overall, 68 projects implemented through Japanese public funding were analyzed. These 68 projects under 15 types of schemes were managed by seven different scheme-operating organizations and funded by five ministries. Of these 44 (64.7%) were ODA and 24 (35.3%) were non-ODA projects. Among the recategorized six building blocks of the health system, the largest proportion of projects was health service delivery (44%), followed by health workforces (25%), and health information systems (15%). Almost half the projects were implemented together with the central hospitals as Vietnamese counterparts, which suggests that this is one area in which the specificities of Japanese cooperation are demonstrated. No synergetic effects of potential collaboration or harmonization among Japanese funded projects were captured., Conclusions: Several Japanese-funded projects addressed a wide range of health issues across all six building blocks of the health system in Vietnam. However, there is room for improvement in developing coordination and harmonization among the diversified Japanese projects. Establishing a country-specific mechanism for strategic coordination across Japanese ministries' schemes can yield efficient and effective development cooperation for health. While Vietnam's dependence on external funding is low, the importance of coordination across domestic actors of the donor countries can serve as an important lesson, especially in beneficiary countries with high external funding dependency., (© 2021. The Author(s).)

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach., Methods/design: Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival., Discussion: If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view., Trial Registration: UMIN Clinical Trials Registry UMIN000041381 . Registered on 10 August 2020. ClinicalTrials.gov NCT04600063 . Registered on 22 October 2020., (© 2021. The Author(s).)

Background: Equity is one of three dimensions of universal health coverage (UHC). However, Iraq has had capital-focused health services and successive conflicts and political turmoil have hampered health services around the country. Iraq has embarked on a new reconstruction process since 2018 and it could be time to aim for equitable healthcare access to realise UHC. We aimed to examine inequality and determinants associated with Iraq's progress towards UHC targets., Methods: We assessed the progress toward UHC in the context of equity using six nationally representative population-based household surveys in Iraq in 2000-2018. We included 14 health service indicators and two financial risk protection indicators in our UHC progress assessment. Bayesian hierarchical regression model was used to estimate the trend, projection, and determinant analyses. Slope and relative index of inequality were used to assess wealth-based inequality., Results: In the national-level health service indicators, inequality indices decreased substantially from 2000 to 2030. However, the wide inequalities are projected to remain in DTP3, measles, full immunisations, and antenatal care in 2030. The pro-rich inequality gap in catastrophic health expenditure increased significantly in all governorates except Sulaimaniya from 2007 to 2012. The higher increases in pro-rich inequality were found in Missan, Karbala, Erbil, and Diala. Mothers' higher education and more antenatal care visits were possible factors for increased coverage of health service indicators. The higher number of children and elderly population in the households were potential risk factors for an increased risk of catastrophic and impoverishing health payment in Iraq., Conclusions: To reduce inequality in Iraq, urgent health-system reform is needed, with consideration for vulnerable households having female-heads, less educated mothers, and more children and/or elderly people. Considering varying inequity between and within governorates in Iraq, reconstruction of primary healthcare across the country and cross-sectoral targeted interventions for women should be prioritised., (© 2021. The Author(s).)

Background: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS., Case Presentation: A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient., Conclusions: We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes., (© 2021. The Author(s).)

Background: In clinical practice, a mixed suspension of clopidogrel bisulfate and magnesium oxide (MgO) tablets is administered frequently via a feeding tube. However, there is no report on the changes occurring when suspensions of these two drugs are combined, including the effects or potential decrease in dose following tube administration. Thus, the purpose of our study was to investigate the (i) changes caused by mixing clopidogrel bisulfate (ion form) and MgO tablets and (ii) effects on the administered clopidogrel dose after passing through a feeding tube., Methods: The molecular structure of clopidogrel generated in a mixture of clopidogrel bisulfate and a basic compound, such as sodium bicarbonate or MgO tablet, was determined by 1 H-NMR after extraction and purification. The suspension of clopidogrel bisulfate tablet alone and the mixed suspension of clopidogrel bisulfate tablet and MgO tablet were passed through a feeding tube. We compared the yield of the molecular form of clopidogrel from each passed fraction., Results: The substance obtained from the mixture of clopidogrel bisulfate tablet and sodium bicarbonate or MgO tablet was identified as the molecular form of clopidogrel, and chemical degradation did not occur under these conditions. In the tube passage test, the yield of clopidogrel (molecular form) from the mixture of clopidogrel bisulfate and MgO tablets was lower than that from the suspension of clopidogrel bisulfate tablet alone., Conclusions: The mixture of clopidogrel bisulfate and MgO tablets caused a considerable reduction in the administered dose passed through the feeding tube. Therefore, it is recommended to administer the suspensions of clopidogrel bisulfate and MgO tablets separately for safe and effective pharmacotherapy.

Background: Disability weights (DWs) are weight factors that reflect the severity of health states for estimates of disability-adjusted life years. A new set of global DWs was published for the Global Burden of Diseases and Injuries (GBD) 2013 study, which relied on sampling from various world regions, but included little data for countries in East Asia. This study aimed to measure DWs in Japan using comparable methods, and compare the results with previous estimates from the GBD 2013 DW study., Methods: We conducted a web-based survey in 2019 to estimate DWs for 231 health states for the Japanese population. The survey included five new health states but otherwise followed the method of the GBD DW measurement study. The survey consisted of 15 paired comparison (PC) questions and 3 population health equivalence questions (PHE) per respondent. We analyzed PC data using probit regression and rescaled results to DW units between 0 (equivalent to full health) and 1 (equivalent to death)., Findings: We considered 37,318 nationally representative respondents. The values of the resulting DWs ranged from 0.707 (95% uncertainty interval (UI) 0.527-0.842) for spinal cord injury at neck level (untreated) to 0.004 (UI 0.001-0.009) for mild anemia. High correlation between Japanese DW and GBD 2013 DW was observed, but there was considerable disagreement. Out of 226 comparable health states, 55 (24.3%) showed more than a factor-of-two difference, of which 41 (74.6%) had a higher value in Japanese DW. Many of the health states with higher DW in the Japan study were injuries, including amputation and fracture, and hearing and vision loss, while mental, behavioral, and substance use disorders generally tended to be lower., Conclusions: This study has created an empirical basis for assessment of Japanese DWs of health status. The findings from this study based on the Japanese population suggest that there might be contextual differences in rating the severity of health states compared to previous surveys conducted elsewhere.

Background: Low vegetable intake is one of the key dietary risk factors known to be associated with a range of health problems, including cardiovascular diseases (CVDs), cancer, and diabetes and kidney diseases (DKDs). Using data from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017, this study aimed to forecast the impact of change in vegetable intake on disability-adjusted life years (DALYs) between 2017 and 2040 for three diseases., Methods: We generated a three-component model of cause-specific DALYs, including changes in major behavioural and metabolic risk predictors, the socio-demographic index and an autoregressive integrated moving average model to project future DALY rates for 2017-2040 using the data between 1990 and 2016. Data on Vegetable consumption and risk predictors, and DALY rate were obtained from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases Study in 2017. We also modelled three scenarios of better, moderate and worse cases to evaluate the impact of change in vegetable consumption on the DALY rates for three diseases (CVDs, cancer, and DKDs)., Results: Projected mean vegetable intake in the total population showed a decreasing trend through 2040 to 237.7 g/day. A significant difference between the reference scenario and the better case scenario was observed with un-overlapped 95% prediction intervals of DALY rates in females aged 20-49 years (- 8.0%) for CVDs, the total population for cancer (- 5.6%), and in males (- 8.2%) and females (- 13.7%) for DKDs., Conclusions: Our analysis indicates that increased vegetable consumption would have a significant reduction in the burdens of CVDs, cancer and DKDs in Japan. By estimating the disease burden attributable to low vegetable intake under different scenarios of future vegetable consumption, our study can inform the design of targeted interventions for public health challenges.

Background: Conflicting results between bacterial mutagenicity tests (the Ames test) and mammalian carcinogenicity tests might be due to species differences in metabolism, genome structure, and DNA repair systems. Mutagenicity assays using human cells are thought to be an advantage as follow-up studies for positive results in Ames tests. In this collaborative study, a thymidine kinase gene mutation study (TK6 assay) using human lymphoblastoid TK6 cells, established in OECD TG490, was used to examine 10 chemicals that have conflicting results in mutagenicity studies (a positive Ames test and a negative result in rodent carcinogenicity studies)., Results: Two of 10 test substances were negative in the overall judgment (20% effective as a follow-up test). Three of these eight positive substances were negative after the short-term treatment and positive after the 24 h treatment, despite identical treatment conditions without S9. A toxicoproteomic analysis of TK6 cells treated with 4-nitroanthranilic acid was thus used to aid the interpretation of the test results. This analysis using differentially expressed proteins after the 24 h treatment indicated that in vitro specific oxidative stress is involved in false positive response in the TK6 assay., Conclusions: The usefulness of the TK6 assay, by current methods that have not been combined with new technologies such as proteomics, was found to be limited as a follow-up test, although it still may help to reduce some false positive results (20%) in Ames tests. Thus, the combination analysis with toxicoproteomics may be useful for interpreting false positive results raised by 24 h specific reactions in the assay, resulting in the more reduction (> 20%) of false positives in Ames test.

Background: It is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC., Methods: We retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed., Results: Fifteen patients received treatment during the study period. The median age was 78 years (range 75-86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0-1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3-36.8] and 13.5 (95% CI 6.4-20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50-93.1%) and 66.7% (95% CI 37.5-84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4-36.8) and 14.9 (95% CI 7.0-20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6-89.1%) and 66.7% (95% CI 37.5-84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4-5 non-haematologic acute or late toxicities were not observed., Conclusions: The OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.

Background: In Japan, a high-sodium diet is the most important dietary risk factor and is known to cause a range of health problems. This study aimed to forecast Japan's disability-adjusted life year (DALYs) for chronic diseases that would be associated with high-sodium diet in different future scenarios of salt intake. We modelled DALY forecast and alternative future scenarios of salt intake for cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and stomach cancer (SC) from 2017 to 2040., Methods: We developed a three-component model of disease-specific DALYs: a component on the changes in major behavioural and metabolic risk predictors including salt intake; a component on the income per person, educational attainment, and total fertility rate under 25 years; and an autoregressive integrated moving average model to capture the unexplained component correlated over time. Data on risk predictors were obtained from Japan's National Health and Nutrition Surveys and from the Global Burden of Disease Study 2017. To generate a reference forecast of disease-specific DALY rates for 2017-2040, we modelled the three diseases using the data for 1990-2016. Additionally, we generated better, moderate, and worse scenarios to evaluate the impact of change in salt intake on the DALY rate for the diseases., Results: In our reference forecast, the DALY rates across all ages were predicted to be stable for CVDs, continuously increasing for CKDs, and continuously decreasing for SC. Meanwhile, the age group-specific DALY rates for these three diseases were forecasted to decrease, with some exceptions. Except for the ≥70 age group, there were remarkable differences in DALY rates between scenarios, with the best scenario having the lowest DALY rates in 2040 for SC. This represents a wide scope of future trajectories by 2040 with a potential for tremendous decrease in SC burden., Conclusions: The gap between scenarios provides some quantification of the range of policy impacts on future trajectories of salt intake. Even though we do not yet know the policy mix used to achieve these scenarios, the result that there can be differences between scenarios means that policies today can have a significant impact on the future DALYs.

Background: A national endoscopic screening program for gastric cancer was rolled out in Japan in 2015. We used a microsimulation model to estimate the cost-effectiveness of current screening guidelines and alternative screening strategies in Japan., Methods: We developed a microsimulation model that simulated a virtual population corresponding to the Japanese population in risk factor profile and life expectancy. We evaluated 15 endoscopic screening scenarios with various starting ages, stopping ages, and screening intervals. The primary outcomes were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio. Cost-effective screening strategies were determined using a willingness-to-pay threshold of $50,000 per QALY gained. One-way sensitivity and probabilistic sensitivity analyses were done to explore model uncertainty., Results: Using the threshold of $50,000 per QALY, a triennial screening program for individuals aged 50 to 75 years was the cost-effective strategy, with an incremental cost-effectiveness ratio of $45,665. Compared with no endoscopic screening, this strategy is predicted to prevent 63% of gastric cancer mortality and confer 27.2 QALYs gained per 1000 individuals over a lifetime period. Current screening guidelines were not on the cost-effectiveness efficient frontier. The results were robust on one-way sensitivity analyses and probabilistic sensitivity analysis., Conclusions: This modeling study suggests that the endoscopic screening program in Japan would be cost-effective when implemented between age 50 and 75 years, with the screening repeated every 3 years. These findings underscore the need for further evaluation of the current gastric cancer screening recommendations.

Background: Hypertension is one of the leading risk factors for cardiovascular diseases in India and Nepal. Socio-economic disparity in these two countries has created wide gap in management of hypertension. However, inequalities in prevalence and management (awareness, treatment, and control) of hypertension is poorly assessed. This study analyzes the risk factors associated with prevalence and management of hypertension in India and Nepal and assesses the wealth-and education-based inequalities in them., Methods: This study used data from the Demographic and Health Survey; a cross-sectional survey conducted between January 2015 to December 2016 in India and June 2016 to January 2017 in Nepal. A total of 787,713 individuals in India and 14,454 individuals in Nepal aged between 15 and 49 years were included in the study. Respondents were classified as being hypertensive if their systolic blood pressure (SBP) readings were at least 140 mmHg or diastolic blood pressure (DBP) readings were at least 90 mmHg, or if they reported currently taking anti-hypertensive medication. Multilevel logistic regression models with random intercepts at household-and community-levels were used to identify the risk factors associated with prevalence and management of hypertension. For inequality assessment, slope index and relative index of inequalities in prevalence and management of hypertension were estimated., Results: Overall prevalence of hypertension in India and Nepal were 11.4% (95% confidence interval (CI), 11.4-11.5) and 19.6% (95% CI, 18.9-20.2), respectively. Less than one-third of the hypertensive population received treatment and below 20% among them had their blood pressure controlled. In both countries, wealth-and education-based inequalities in awareness, treatment, and control of hypertension were significantly high in urban and rural areas., Conclusion: Wealth- and education-based inequalities in prevalence and management of hypertension were high among different socio-economic groups at national and sub-national levels. Tailored strategies are required to effectively manage hypertension in different regions by considering socio-economic and demographic factors.

Background: Hepatocellular carcinoma (HCC) involving a major branch of the portal or hepatic vein is in a locally advanced stage and remains difficult to cure. This study aimed to evaluate the clinical effects of carbon ion radiotherapy (C-ion RT) in locally advanced HCC (LAHCC)., Methods: The data of 11 consecutive patients with LAHCC who received C-ion RT were analyzed. The C-ion RT doses of 52.8 Gy (relative biological effectiveness [RBE]) and 60.0 Gy (RBE) were delivered in 4 fractions for standard cases, and the 60.0 Gy dose was delivered in 12 fractions for close-to-gastrointestinal-tract cases. Survival and local control probabilities were calculated using the Kaplan-Meier method., Results: The median follow-up duration after C-ion RT was 36.4 months. The median age at the time of registration for C-ion RT was 76 years. The median tumor size was 53 mm. The numbers of treatment-naive and recurrent HCC patients were 1 and 10, respectively. Direct invasion of the major branch of the portal vein, hepatic vein, or both portal and hepatic veins was observed in three, five, and three patients, respectively. The 3-year overall survival, local control, and progression-free survival rates were 64, 78, and 18%, respectively. No patient developed radiation-induced liver diseases or grade 3 or higher toxicities in the acute and late phases., Conclusions: C-ion RT showed favorable clinical outcomes with a high rate of local control and minimal toxicities in LAHCC. Our findings suggest that C-ion RT is a promising multidisciplinary treatment option in LAHCC.

Background: Demographic changes in the pattern of disease burden, escalating health expenditures and inequitable access to healthcare are global challenges. Irrespective of their level of development, all countries need to reform their health systems to prepare for the future emerging health needs, in order to meet their commitments of health systems strengthening, universal health coverage (UHC) and explicit targets in the Sustainable Development Goals (SDGs). We propose three core principles for the future health system as described herein. A health system is not simply a 'cure delivery machine' but part of a 'social security system' that engages all stakeholders through a shared vision and value of health and well-being, not merely an absence of diseases. The future health system shall provide people-centred, affordable care, tailored to the individual's needs, accessible at any time and any place, and reflect the notion of leaving no one behind through a life course approach - underpinned by the SDGs. Information and communications technology (ICT) offers the potential to facilitate the realisation of these principles by improving the information flow between different parts of the health system through electronic means. We introduce Japan's new data platform - Person-centred Open PLatform for wellbeing (PeOPLe) - planned to be introduced in 2020 as one example of an ICT-based intervention to realise the three proposed principles. PeOPLe integrates data collected throughout the life course to enable all people to receive affordable, personalised health and social care at any time and any place throughout their lifetime. Furthermore, we discuss the applicability of these principles and PeOPLe to the health systems context of Thailand and the Philippines, including elaborations on ICT transformation challenges., Conclusion: Current rising momentum and scale for ICTs in the UHC era offers a great opportunity to make a difference for countries. The PeOPLe concept is not only relevant to resource-rich countries; its applicability to other Asian countries could be feasible though it will need to be adapted to the various country contexts. We hope that this paper contributes to wider discussion around policy choices of ICT application for future health systems strengthening and UHC in order to achieve the SDGs.

Background: Tuberculosis is associated with increased risk of cancer. However, the impact of tuberculosis on global cancer burden is unknown., Methods: We performed random-effects meta-analyses and meta-regressions of studies reporting the association between tuberculosis and cancer risks by searching PubMed, Web of Science, Embase, Cochrane library, and CINAHL from inception to 1 June 2019. Population attributable fractions (PAFs) of cancer incidence attributable to tuberculosis were calculated using relative risks from our meta-analyses and tuberculosis prevalence data from Global Health Data Exchange by age, sex, and country. The study has been registered with PROSPERO (CRD42016050691)., Results: Fourty nine studies with 52,480 cancer cases met pre-specified inclusion criteria. Tuberculosis was associated with head and neck cancer (RR 2.64[95% CI 2.00-3.48]), hepatobiliary cancer (2.43[1.82-3.25]), Hodgkin's lymphoma (2.19[1.62-2.97]), lung cancer (1.69[1.46-1.95]), gastrointestinal cancer (1.62[1.26-2.08]), non-Hodgkin's lymphoma (1.61[1.34-1.94]), pancreatic cancer (1.58[1.28-1.96]), leukaemia (1.55[1.25-1.93]), kidney and bladder cancer (1.54[1.21-1.97]), and ovarian cancer (1.43[1.04-1.97]). We estimated that 2.33%(1.14-3.81) or 381,035(187145-623,404) of global cancer incidences in 2015 were attributable to tuberculosis. The PAFs varied by Socio-demographic Index (SDI)-ranging from 1.28% (0.57-2.31%) in the high-SDI countries to 3.51% (1.84-5.42%) in the middle-SDI countries. Individually, China and India accounted for 47% of all tuberculosis-related cancer cases., Conclusions: Tuberculosis is associated with increased risk of cancer at ten sites. The burden of tuberculosis attributable cancer skewed towards lower resource countries. Research priorities are to better understand regional disparities and underlying mechanism linking tuberculosis and cancer development.

Background: Development assistance for health (DAH) is one of the most important means for Japan to promote diplomacy with developing countries and contribute to the international community. This study, for the first time, estimated the gross disbursement of Japan's DAH from 2012 to 2016 and clarified its flows, including source, aid type, channel, target region, and target health focus area., Methods: Data on Japan Tracker, the first data platform of Japan's DAH, were used. The DAH definition was based on the Organisation for Economic Co-operation and Development's (OECD) sector classification. Regarding core funding to non-health-specific multilateral agencies, we estimated DAH and its flows based on the OECD methodology for calculating imputed multilateral official development assistance (ODA)., Results: Japan's DAH was estimated at 1472.94 (2012), 823.15 (2013), 832.06 (2014), 701.98 (2015), and 894.57 million USD (2016) in constant prices of 2016. Multilateral agencies received the largest DAH share of 44.96-57.01% in these periods, followed by bilateral grants (34.59-53.08%) and bilateral loans (1.96-15.04%). Ministry of Foreign Affairs (MOFA) was the largest contributors to the DAH (76.26-82.68%), followed by Ministry of Finance (MOF) (10.86-16.25%). Japan's DAH was most heavily distributed in the African region with 41.64-53.48% share. The channel through which the most DAH went was Global Fund to Fight AIDS, Tuberculosis, and Malaria (20.04-34.89%). Between 2012 and 2016, approximately 70% was allocated to primary health care and the rest to health system strengthening., Conclusions: With many major high-level health related meetings ahead, coming years will play a powerful opportunity to reevaluate DAH and shape the future of DAH for Japan. We hope that the results of this study will enhance the social debate for and contribute to the implementation of Japan's DAH with a more efficient and effective strategy.

Background: Partial pancreatoduodenectomy is performed for malignant and benign diseases of the pancreatic head region. The procedure is considered highly difficult and highly invasive. Postoperative pancreatic fistula (POPF) is an important complication because of several consequent complications, including intraabdominal haemorrhage, often increasing hospital stays and surgical mortality. Although many kinds of pancreaticojejunostomy aimed at reducing POPF have been examined to date, the technique has not yet been standardized. We devised a new method using double-coated polyglycolic acid felt after pancreaticojejunostomy. The aim of the PLANET-PJ trial is to evaluate the superiority of polyglycolic acid felt reinforcement in preventing POPF after pancreaticojejunostomy in patients undergoing partial pancreatoduodenectomy to previous anastomosis methods., Methods: Patients diagnosed with pancreatic or periampullary lesions in whom it is judged that the main pancreatic duct diameter was 3 mm or less on the left side of the portal vein without pancreatic parenchymal atrophy due to obstructive pancreatitis are considered eligible for inclusion. This study is designed as a multicentre randomized phase III trial in Japan and the Republic of Korea. Eligible patients will be centrally randomized to either group A (polyglycolic acid felt reinforcement) or group B (control). In total, 514 patients will be randomized in 31 high-volume centres in Japan and Republic of Korea. The primary endpoint is the incidence of POPF (International Study Group of Pancreatic Surgery grade B/C)., Discussion: The PLANET-PJ trial evaluates the efficacy of a new method using double-coated polyglycolic acid felt reinforcement for preventing POPF after pancreaticojejunostomy. This new method may reduce POPF., Trial Registration: ClinicalTrials.gov, NCT03331718 . University Hospital Medical Information Network Clinical Trials Registry, UMIN000029647. Registered on 30 November 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000033874.

Background: We compared clinical outcomes of carbon ion radiotherapy and transarterial chemoembolization in the treatment of hepatocellular carcinoma., Methods: Data of 477 patients with hepatocellular carcinoma who had undergone carbon ion radiotherapy or transarterial chemoembolization between April 2007 and September 2016 were retrospectively reviewed. Treatment naïve patients with single HCC, who underwent carbon ion radiotherapy or transarterial chemoembolization as a primary treatment were included. Clinical outcomes of the treatments were compared after utilizing propensity score matching., Results: Of 124 patients who received carbon ion radiotherapy and 353 patients who received transarterial chemoembolization, 31 and 23 patients met our inclusion criteria, respectively. After utilizing propensity score matching, 17 matched pairs of patients from each treatment group were analyzed. The median follow-up durations after carbon ion radiotherapy and transarterial chemoembolization were 43 and 32 months, respectively. The 3-year overall survival, local control, and progression-free survival rates in the carbon ion radiotherapy versus transarterial chemoembolization groups were 88% versus 58% (p < 0.05), 80% versus 26% (p < 0.01), and 51% versus 15% (p < 0.05), respectively., Conclusions: Carbon ion radiotherapy showed more favorable clinical outcomes than did transarterial chemoembolization for patients with single hepatocellular carcinoma after matching patient characteristics utilizing propensity score matching. Further studies with larger patient numbers are required to confirm our results., Trial Registration: UMIN000036455 : date of registration 22 March 2019, retrospectively registered.

Background: It has been suggested that an increasing number of Japanese adults remain sexually inexperienced; however, no study has assessed this issue using nationally representative data., Methods: We used data from seven rounds of the National Fertility Survey of Japan, 1987-2015, and included adults aged 18-39 years (18-34 years in the 1987 survey) in the analyses (sample size 11,553-17,850 [1987-2010]; response rate 70.0-92.5%). For each survey year, sex and age group, we estimated the age-adjusted prevalence of heterosexual inexperience, defined as reporting no experience of sexual intercourse with someone of the opposite sex. We used logistic regression, adjusted for age, to identify factors associated with heterosexual inexperience in the 2010 survey. Information about same-sex sexual experience was not available., Results: Between 1992 and 2015, the age-standardized prevalence of heterosexual inexperience in adults aged 18-39 years increased from 21.7 to 24.6% for women (p-values for linear and quadratic trend < 0.05) and from 20.0 to 25.8% for men (p-values for trend < 0.05). Among those aged 30-34 years, the prevalence was 6.2% in 1987 and 11.9% in 2015 for women (p-values for trend ≥0.05) and 8.8% (1987) and 12.7% (2015) for men (p-values for trend ≥0.05). Among those aged 35-39 years, prevalence increased from 4.0% in 1992 to 8.9% in 2015 among women (p-values for trend < 0.05). The corresponding numbers for men in the same age group were 5.5 and 9.5%, respectively (p-values for trend ≥0.05). Among men aged 25-39 years, unemployment, temporary/part-time employment and lower income were associated with heterosexual inexperience., Conclusions: The proportion of young Japanese adults with no experience of heterosexual intercourse had increased in the past two decades. Among adults in their thirties, around one in ten had no heterosexual experience. Unemployment, temporary/part-time employment and low income were associated with heterosexual inexperience among men. Further research is needed on the factors contributing to and the potential public health and demographic implications of the high proportion of the Japanese population that remains sexually inexperienced well into adult age.

Background: As demonstrated by the United Nations High-Level Meeting on tuberculosis (TB) held in September 2018, the political momentum for TB has been increasing. The aim of this study was to analyze the current challenges and opportunities for global TB control and, with specific focus on policies surrounding TB control, to reveal what kinds of efforts are needed to accelerate global TB control., Methods: We organized two expert meetings with the purposes of assessing the current situation and analyzing challenges regarding TB control. By applying Shiffman and Smith's framework which contains four categories; Actor, Ideas, Political context, and Issue characteristics, we analyzed the challenges and opportunities for global TB control based on the findings from the two expert meetings., Results: In the Actor Category, we found that although there has already been active engagement by non-governmental organizations (NGOs), civil society organizations (CSOs) and private sectors, there still remained an area with room for improvement. In particular, the complexities behind varying drug regulatory and procurement systems per country hindered the active participation of the private sector in this area. As for the Ideas category, due to an increasing threat of antimicrobial resistance and growing number of global migrations, TB is now widely recognized as a health security issue rather than a purely health issue. This makes TB an easier target for political attention. As for the Political category, having the UN High-Level Meeting itself is not enough; such meetings must be followed up by actual commitments from heads of states. Lastly the issue characteristic indicates that the amount of funding for R&D for new drugs, vaccines and diagnostics for TB is not at an adequate level, and investment in childhood TB and missing cases are particularly in need., Conclusions: This study provides important insight into the current status of global efforts toward end TB epidemic. The outcomes from the UN high-level meeting on TB need to be closely monitored will be crucial for the progress towards this goal.

Background: The purpose was to retrospectively evaluate the effect of intensity-modulated radiotherapy (IMRT) on gastrointestinal (GI) toxicities and outcomes compared to three-dimensional conformal radiotherapy (3DCRT) for locally advanced pancreatic cancer (LAPC)., Methods: We included 107 consecutive patients who underwent CRT for LAPC from September 2001 to March 2015; 80 patients underwent 3DCRT and 27 patients underwent IMRT. They were compared for GI toxicities, locoregional progression free survival (LRPFS), distant metastasis free survival (DMS), and overall survival (OS)., Results: Median radiation dose and fractions for 3DCRT and IMRT were 54 Gy/30 fr. and 48 Gy/15 fr. The regimens of CRT consisted of weekly gemcitabine 250 mg/m 2 (for 3DCRT) or 1000 mg/m 2 (for IMRT). Acute GI toxicity ≥grade 2 occurred in 32 patients (40%) treated with 3DCRT compared with five patients (19%) treated with IMRT. Late GI toxicity of grade 3 occurred in 10 patients (12%) treated with 3DCRT and one patient (4%) treated with IMRT. Patients who underwent IMRT had superior 1-year LRPFS (73.1% vs. 63.2%, p = 0.035) and 1-year OS (92.3% vs. 68.2%, p = 0.037) as compared with those treated with 3DCRT. Multivariate analysis showed that in IMRT patients, higher dose (≥45 Gy) was an independent factor for better LRPFS and OS., Conclusions: LAPC patients treated with hypofractionated full-dose gemcitabine IMRT had improved OS and LRPFS without increased GI toxicities when compared to those of patients treated with conventionally fractionated low dose gemcitabine 3DCRT. In IMRT patients, higher dose was an independent favorable prognostic factor for better LRPFS and OS, which suggests that dose escalation with IMRT for LAPC is a promising strategy.

Background: Some patients with thymoma present with a very large mass in the thoracic cavity. Although the most effective treatment for thymoma is surgical resection, it is difficult to perform because of the size of the tumor and the infiltration of tumor into the surrounding organs and vessels. We report a patient with a giant thymoma that was completely resected via a median sternotomy and left anterolateral thoracotomy., Case Presentation: A 63-year-old woman presented with a mass in the left thoracic cavity that was incidentally found on a chest X-ray. Chest computed tomography revealed a giant mass (16 × 10 cm) touching the chest wall and diaphragm and pressed against the heart and left upper pulmonary lobe. Complete resection was performed via a median sternotomy and left anterolateral thoracotomy. The tumor was histologically diagnosed as a WHO type B2 thymoma, Masaoka stage II., Conclusions: Giant thymomas tend to grow expansively without invasion into surrounding organs and vessels. Surgical resection that employs an adequate approach must be considered, regardless of the size of the tumor.

Background: To evaluate the safety and efficacy of carbon ion radiotherapy (C-ion RT) for 80 years or older patients with hepatocellular carcinoma (HCC)., Methods: Eligibility criteria of this retrospective study were: 1) HCC confirmed by histology or typical hallmarks of HCC by imaging techniques of four-phase multidetector-row computed tomography or dynamic contrast-enhanced magnetic resonance imaging; 2) no intrahepatic metastasis or distant metastasis; 3) no findings suggesting direct infiltration of the gastrointestinal tract; 4) performance status ≤2 by Eastern Cooperative Oncology Group classification; and 5) Child-Pugh classification A or B. Patients received C-ion RT with 52.8 Gy (RBE) or 60.0 Gy (RBE) in four fractions for usual cases and 60.0 Gy (RBE) in 12 fractions for close-to-gastrointestinal tract cases. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (Version 4.0)., Results: Between March 2011 and November 2015, 31 patients were treated. The median follow-up period of all patients was 23.2 months (range: 8.4-55.3 months). Median age at the time of registration of C-ion RT was 83 years (range: 80-95 years). Child-Pugh grade A and B were 27 patients and 4 patients, respectively. The 2-year estimated overall survival, local control, and progression-free survival rates were 82.3%, 89.2%, and 51.3%, respectively. No patients had Grade 2 or higher acute toxicities (within 3 months after C-ion RT). One patient experienced progression in Child-Pugh classification from A to B within 3 months after C-ion RT. In late toxicities, Grade 3 encephalopathy was observed in 3 patients, and 2 improved with medication., Conclusions: C-ion RT was effective with minimal toxicities for 80 years or older patients with hepatocellular carcinoma., Trial Registration: UMIN000020571 : date of registration, 14 January 2016, retrospectively registered.

Background: Despite achievement of universal health coverage in Thailand, socioeconomic inequality in health has been a major policy concern. This study examined mortality patterns across different socioeconomic strata in Thailand., Methods: We conducted a cross-sectional analysis of the 2010 Population and Housing Census on area-level socioeconomic deprivation against the 2010 mortality from the vital registration database at the super-district level. We used principal components analysis to construct a socioeconomic deprivation index and K-mean cluster analysis to group socioeconomic status and cause-specific mortality., Results: Excess mortality rates from all diseases, except colorectal cancer, were observed among super-districts with low socioeconomic status. Spatial clustering was evident in the distribution of socioeconomic status and mortality rates. Cluster analysis revealed that super-districts which were predominantly urban tended to have low all-cause standardize mortality ratio but a high colorectal cancer-specific mortality rate. Deaths due to liver cancer, diabetes, and renal diseases were common in the low socioeconomic super-districts which hosted one third of the total Thai population., Conclusion: Socially deprived areas have an excess of overall and cause specific deaths. Populations living in more affluent areas, despite low general mortality, still have many preventable deaths such as colorectal cancer. These findings warrant future epidemiological studies investigating various causes of excessive deaths in non-deprived areas and implementation of policies to reduce the mortality gap between rich and poor areas.

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins-namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)-in pulmonary arteries., Methods: We analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained from 9 IPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary arterial abnormalities. Results of microscopic observation were analyzed in relation to the cellular components and size of pulmonary arteries., Results: Varying rates of positive reactivity to Dvl-2 and Daam-1 were confirmed in all cellular components of pulmonary arteries, namely, endothelial cells, myofibroblasts, and medial smooth muscle cells. In contrast, none of these components was reactive to Wnt-11. No specific expression patterns were observed for endothelial cells or myofibroblasts under any experimental conditions. However, marked expression of Dvl-2 and Daam-1 was confirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in contrast with specimens from associated pulmonary arterial hypertension cases and controls., Conclusions: High Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH.

Background: Kikuchi-Fujimoto disease is a self-limited clinicopathologic entity that is increasingly recognized worldwide. Kikuchi-Fujimoto disease is characterized by cervical lymphadenopathy occurring in young adults. Neurologic involvement is rare, and testitis directly caused by Kikuchi-Fujimoto disease has not yet been reported., Case Presentation: A 19-year-old man was brought to our clinic with complaints of fever, headache, fatigue, and left lower quadrant pain that had persisted for 3 weeks. On physical examination, painful cervical lymphadenopathies were observed. Meningitis was suspected based on a cerebrospinal fluid examination, and left-sided orchitis was diagnosed based on findings from magnetic resonance imaging and ultrasonography. However, neither antibiotics nor antiviral drugs were effective in treating the patient's symptoms. On the 20 th day of hospitalization, the patient experienced a loss of consciousness, and brain T2-weighted magnetic resonance imaging showed asymmetrical, high-signal intensities in both basal nuclei and the left temporal lobe. Encephalitis was suspected, and the patient was treated with intravenous prednisolone pulse therapy (1 g/day) for 3 days and intravenous immunoglobulin therapy for 5 days. A left cervical lymph node biopsy showed apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which had irregular nuclei suggestive of Kikuchi-Fujimoto disease; the pathological findings from a brain biopsy were the same as those of the cervical lymph node biopsy. The encephalitis and cervical lymphadenopathies followed a benign course, as did the testitis., Conclusions: This is the first report of Kikuchi-Fujimoto disease involving painful testitis and pathologically proven asymmetrical brain regions. Kikuchi-Fujimoto disease should be included in the differential diagnosis when a patient presents with encephalitis, testitis, and fever of unknown origin.

Background: Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B cell lymphoma that is a type of non-Hodgkin lymphoma and a type of primary pulmonary malignant lymphoma. MALT lymphomas affecting the lung show various findings on chest computed tomography, which range from typical nodules or areas of consolidation to findings that are extremely rare in pulmonary MALT lymphomas, such as pure ground-glass opacities throughout the lung., Case Presentation: A 35-year-old woman was found to have a few shadows with ground glass opacities on chest computed tomography (CT) in 2012. A shadow in right S10 that was initially very small increased in size over time, and was 14 × 8 mm in 2015. Other shadows also appeared. Because lung adenocarcinoma was suspected, the patient underwent video-assisted thoracoscopic surgery with a right wedge resection of the lower lobe that included the largest nodule in S10 and other nodules. Histopathological examination of the right S10 and other lesions revealed small- or medium-sized lymphocyte-like cells that were located in the alveolar interseptal spaces. The alveolar walls remained intact. Immunohistochemical staining showed that tumor cells were positive for CD20, CD79a, and BCL2 expression. The lesions were diagnosed as extranodal marginal zone B-cell lymphoma of MALT., Conclusions: We think that the ground glass opacities on CT were accounted for by MALT lesions that contained intact alveolar air spaces. The patient has remained well during 12 months of follow up after surgery. Although she did not receive chemotherapy because the MALT lymphoma lesions have been stable without progression, the patient is kept under close observation because of potential progression of the disease.

Purpose: To investigate the clinical outcomes of stage I and IIA non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using a real-time tumor-tracking radiotherapy (RTRT) system., Materials and Methods: Patterns-of-care in SBRT using RTRT for histologically proven, peripherally located, stage I and IIA NSCLC was retrospectively investigated in four institutions by an identical clinical report format. Patterns-of-outcomes was also investigated in the same manner., Results: From September 2000 to April 2012, 283 patients with 286 tumors were identified. The median age was 78 years (52-90) and the maximum tumor diameters were 9 to 65 mm with a median of 24 mm. The calculated biologically effective dose (10) at the isocenter using the linear-quadratic model was from 66 Gy to 126 Gy with a median of 106 Gy. With a median follow-up period of 28 months (range 0-127), the overall survival rate for the entire group, for stage IA, and for stage IB + IIA was 75%, 79%, and 65% at 2 years, and 64%, 70%, and 50% at 3 years, respectively. In the multivariate analysis, the favorable predictive factor was female for overall survival. There were no differences between the clinical outcomes at the four institutions. Grade 2, 3, 4, and 5 radiation pneumonitis was experienced by 29 (10.2%), 9 (3.2%), 0, and 0 patients. The subgroup analyses revealed that compared to margins from gross tumor volume (GTV) to planning target volume (PTV) ≥ 10 mm, margins < 10 mm did not worsen the overall survival and local control rates, while reducing the risk of radiation pneumonitis., Conclusions: This multi-institutional retrospective study showed that the results were consistent with the recent patterns-of-care and patterns-of-outcome analysis of SBRT. A prospective study will be required to evaluate SBRT using a RTRT system with margins from GTV to PTV < 10mm.

Background: Thailand has achieved remarkable improvement in health status since the achievement of universal health coverage in 2002. Health equity has improved significantly. However, challenges on health inequity still remain.This study aimed to determine the trends of geographical inequalities in disease specific mortality in Thailand after the country achieved universal health coverage., Methods: National vital registration data from 2001 to 2014 were used to calculate age-adjusted mortality rate and standardized mortality ratio (SMR). To minimize large variations in mortality across administrative districts, the adjacent districts were systematically grouped into "super-districts" by taking into account the population size and proximity. Geographical mortality inequality among super-districts was measured by the coefficient of variation. Mixed effects modeling was used to test the difference in trends between super-districts., Results: The overall SMR steadily declined from 1.2 in 2001 to 0.9 in 2014. The upper north and upper northeast regions had higher SMR whereas Greater Bangkok achieved the lowest SMR. Decreases in SMR were mostly seen in Greater Bangkok and the upper northern region. Coefficient of variation of SMR rapidly decreased from 20.0 in 2001 to 12.5 in 2007 and remained close to this value until 2014. The mixed effects modelling revealed significant differences in trends of SMR across super-districts. Inequality in mortality declined among adults (≥15 years old) but increased in children (0-14 years old). A declining trend in inequality of mortality was seen in almost all regions except Greater Bangkok where the inequality in SMR remained high throughout the study period., Conclusions: A decline in the adult mortality inequality across almost all regions of Thailand followed universal health coverage. Inequalities in child mortality rates and among residents of Greater Bangkok need further exploration.

Background: Myelolipoma is a rare benign tumor composed of mature adipose tissue and normal hematopoietic tissue. Although surgical resection has been recommended due to the potential of progressive enlargement, the natural history of mediastinal myelolipoma has not yet been described. Herein we report a surgically resected mediastinal myelolipoma showing gradual enlargement over a period of 9 years., Case Presentation: A 70-year-old woman presented with a posterior mediastinal mass shadow detected by computed tomography (CT) examination. She had a medical history of sigmoidectomy for colon cancer 13 years previously. A CT scan showed a smooth, well-demarcated 2.8 × 2.1-cm paravertebral mass shadow, composed of a fat density area and a soft tissue density area, which showed gradual enlargement from a 1.6 × 1.0-cm nodule 9 years previously. This was not accompanied by chronic anemia or hematologic disease including thalassemia, and no abnormal accumulation was observed on bone marrow scintigraphy or fluoro-2-deoxyglucose positron emission tomography. With a clinical diagnosis of mediastinal myelolipoma, surgical resection was performed, and pathological examination confirmed the diagnosis., Conclusions: We experienced a rare case with mediastinal myelolipoma showing gradual enlargement, with a tumor doubling time of 1,212 days.

Background: Calciphylaxis is a syndrome consisting of vascular calcification, thrombosis, and skin necrosis. The syndrome develops often in chronic hemodialysis patients. However, there have been several case reports on calciphylaxis in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, a systemic disease associated with plasma cell dyscrasia and upregulation of vascular endothelial growth factor (VEGF)., Methods: In 76 POEMS patients and 86 age- and gender-matched disease controls, we studied abnormal small vessel calcification by computed tomography (CT) of the soft tissues. Clinical and laboratory profiles were compared between POEMS patients with and without calciphylaxis. Histological examination was performed in six autopsy cases., Results: Small vessel calcification on CT was found in 17 % of POEMS patients and in none of the controls (P < 0.001). Autopsy confirmed calciphylaxis in 2 (33 %) patients. Among POEMS patients, higher disease activity, including more severe neuropathy and ascites, higher serum levels of interleukin-6, and lower serum albumin levels, was associated with the development of calciphylaxis. Serum levels of creatinine, calcium, and phosphate were not related to the presence of calciphylaxis., Conclusions: Calciphylaxis is often present in patients with POEMS syndrome. Upregulation of multiple inflammatory cytokines such as VEGF and interleukin-6 may contribute to the development of calciphylaxis, by entirely different mechanism from that in chronic dialysis. POEMS syndrome should be recognized as a potential cause of calciphylaxis.

Background: The simultaneous surgical treatment of thoracic aortic arch aneurysm (TAA) and lung carcinoma is extremely rare., Case Presentation: We report the simultaneous surgical treatment of TAA and squamous cell carcinoma of the lung in a 72-year-old Japanese man. We performed a one-stage operation that consisted of aortic arch replacement for aortic arch aneurysm with a 3-branched artificial vessel under separate cerebral and systemic extracorporeal circulation, and left upper lobectomy for lung cancer via a left lateral thoracotomy., Conclusions: Although patients should be carefully selected for this procedure, the simultaneous surgical treatment of TAA and lung carcinoma can be performed safely.

Background: Costal exostosis is a benign condition that sometimes requires emergent surgery because of associated hemothorax; in addition, there have been cases with malignant transformation to chondrosarcoma. Here, we describe an asymptomatic patient who underwent thoracoscopic resection for primary costal exostosis., Case Presentation: A 16-year-old male was found to have a bow-shaped shadow on a chest X-ray. Chest computed tomography revealed a rod-like mass with a soft tissue shadow adjacent to the left fifth rib. A thoracoscopic partial resection of the left fifth rib was performed. Intraoperative findings included thickening of the pericardium near the tip of the growth and erosion of the visceral pleura of the left lung. The resected specimen was diagnosed as a primary costal exostosis based on histopathological findings., Conclusions: We review the published literature on costal exostosis and discuss the surgical indications of asymptomatic cases.

Injury to the inferior phrenic artery after blunt trauma is an extremely rare event, and it may occur under unanticipated conditions. This case report describes an injury to the left inferior phrenic artery caused by blunt trauma, which was complicated by massive hemothorax, and treated with transcatheter arterial embolization (TAE). An 81 year-old female hit by a car while walking at the traffic intersection was transferred to the emergency department, computed tomography scanning revealed active extravasations of the contrast medium within the retrocrural space and from branches of the internal iliac artery. The patient underwent repeated angiography, and active extravasation of contrast medium was observed between the retrocrural space and the right pleural space originating from the left inferior phrenic artery. The injured left inferior phrenic artery was successfully embolized with N-butyl cyanoacrylate, resulting in stabilization of the patient's clinical condition. Inferior phrenic artery injury should be recognized as a rare phenomenon and causative factor for hemothorax. TAE represents a safe and effective treatment for this complication and obviates the need for a thoracotomy.

Background: Ossification in the posterior longitudinal ligament (PLL) correlates with changes of enthesis during the early stages of development, but this issue remains controversial, as little is known regarding the details of this process. The aim of the present study was to elucidate part of the ossification mechanism. Thus, in the present study, we observed and evaluated minute ossifications in the PLL that did not exhibit symptoms of ossification of the posterior longitudinal ligament (OPLL)., Methods: The subjects in the present study were derived from serial autopsy cases from January 2009 to December 2013 at Toho University Omori Medical Center, Japan. Minute ossifications in the PLL from autopsy subjects without any history of OPLL were screened as high-density areas using micro-focus X-ray CT, and the foci were histologically examined. Subsequently, we conducted both micro-focus X-ray CT image analysis and histological examination, and evaluated the correlation between these findings and putative predictive factors reported in previous studies., Results: A total of 103 individuals among the 267 subjects involved in the present study were analyzed within the study period. There were no cases involving OPLL identification prior to death, and no subjects presented with neurological symptoms of myelopathy. The incidence of cases involving high-density areas greater than 0.1 mm(2) in the PLL was 46.6 %, half of which revealed mature bone structures inside this area. Thus, the high-density areas comprised three types: a continuous posterior-annular fibrosus type (23 cases), an isolated posterior-annular fibrosus type (11 cases), and a posterior-vertebral type (29 cases). However, a positive correlation was observed between the proportion of high-density areas, age (Pearson r = 0.265, p < 0.01), and HbA1c (Pearson r = 0.294, p < 0.01). Histological examination confirmed that these high-density areas involved calcification with or without mature bone formation., Conclusions: We evaluated minute foci of calcification with and without ossification in the PLL from 103 cadavers, generating the following observations: 1. Minute calcification foci greater than 0.1 mm(2) were observed in the PLL of 48 cases (46.6 %), half of which revealed mature bone structures inside this area (23.3 %). 2. The proportion of minute calcification foci observed in the present study was correlated with age and glucose tolerance, suggesting changes in the OPLL in the early stage. 3. Three different mechanisms of ossification were suggested: The two structures developed behind the disc might reflect the elongation of enthesis or rupture of annular fibrosus, while the remaining structure developed behind the vertebral body might reflect a dystrophic calcification-based bony metaplasia sequence.

Background: Surgery for chronic pulmonary aspergillosis is often technically risky. The choice of immediate thoracoplasty or muscle flap plombage to prevent postoperative space problems remains controversial. This study focused on the use of muscle flaps to prevent postoperative complications., Methods: During an 8-year period (2004 to 2012), all patients surgically treated for chronic pulmonary aspergillosis were enrolled in this retrospective study. Concomitant intrathoracic transposition of the latissimus dorsi muscle flap has been performed since 2011. The clinical records of these patients were reviewed retrospectively., Results: From 2004 to 2012, 16 patients were treated for chronic pulmonary aspergillosis. Fifteen patients received lobectomies and one had a partial resection. A preventive latissimus dorsi muscle flap was used in 6 patients (37 %). No postoperative deaths occurred. Prolonged air leaks appeared in 2 patients without muscle flaps, resulting in empyema in both. None of the patients with preventive muscle flaps suffered prolonged air leaks and subsequent empyema. In the outpatient clinic, late onset air leaks developed in 2 patients, one of whom had a lobectomy with muscle flap while the other had a lobectomy without muscle flap. Residual pleural space persisted in these two patients and Aspergillus infection later recurred., Conclusions: Concomitant latissimus dorsi muscle flaps may be effective for the prevention of prolonged air leaks and subsequent empyema. Late onset air leaks are problematic.