Prognostic factors for esophageal squamous cell carcinoma without pathological lymph node metastasis after neoadjuvant therapy and surgery.

BACKGROUND: Pathological lymph node metastasis (LNM) following multimodal therapy is an important indicator of poor prognosis in patients with esophageal cancer. However, a significant number of patients without LNM are still at high risk for recurrence. METHODS: We assessed prognostic factors in 143 patients without pathological LNM who were diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) and underwent neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT), followed by surgery. RESULTS: Using univariate and multivariate analyses of recurrence-free survival, carcinoembryonic antigen (CEA) levels (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.12-4.23, and p = 0.02) and neutrophil-to-lymphocyte ratio (NLR) (HR: 1.22, 95% CI: 1.04-1.43, and p = 0.02) were significant independent covariates. Furthermore, pretherapeutic LNM (HR: 1.94, 95% CI: 1.003-3.76, and p = 0.049), NACRT (HR: 3.29, 95% CI: 1.30-8.33, and p = 0.01), poorly differentiated tumors (HR: 2.52, 95% CI: 1.28-4.98, and p = 0.01), and lymphovascular invasion (LVI) (HR: 2.78, 95% CI: 1.27-6.09, and p = 0.01) were also significant independent covariates. The recurrence rates among patients with 0/1, 2, 3, and 4/5 poor prognostic factors were significantly different (5.0%, 25.0%, 35.7%, and 53.8%, respectively; p = 0.001); the survival rates were stratified among these prognostic groups. CONCLUSIONS: Pretherapeutic CEA and NLR levels, pretherapeutic LNM, NACRT, poorly differentiated tumors, and LVI were significantly correlated with survivals in patients without pathological LNM after neoadjuvant therapy and surgery. Postoperative therapy should be considered in patients with ESCC with several indicators of recurrence, even in those without pathological LNM who underwent surgery following neoadjuvant therapy.

Multifaceted ORganizational InterventiONs (M-ORION) project for prevention of depression and anxiety among workers: study protocol for a five-arm cluster randomized controlled trial.

BACKGROUND: Depression and anxiety are the most common mental health issues experienced by workers. Although organizational intervention has been extensively evaluated as a primary prevention of depression and anxiety, the corresponding scientific evidence remains limited because of the lack of cluster randomized controlled trials (cRCT) and failure to detect organizational-level effects. Therefore, the present study aims to assess the preventive effects of four types of interventions on depression and anxiety among workers in an open, five-arm, parallel-group cRCT. METHODS: Overall, 140 worksites and 18,200 nested employees will be recruited from September 2023. The eligible worksites will be randomly assigned to each of the five arms, and programs will be offered for 6-12 months. The five arms are 1) psychoeducation for workers, 2) psychoeducation for supervisors, 3) work environment improvement, 4) physical activity promotion, and 5) active control. The primary outcomes of interest are depression and anxiety. We will also assess psychosocial factors at work, work engagement, health-related quality of life, well-being, economic outcomes, physiological outcomes of health checkups, cortisol levels extracted from fingernails, and indices representing the process and implementation outcomes, including program completion rates. Follow-up surveys will be conducted at 6, 12, and 18 months from baseline, and the primary endpoint is set at the 6-month follow-up. Repeated-measures multi-level mixed modeling will be used to evaluate the effect of each intervention compared with the control. ETHICS AND DISSEMINATION: The study protocol was approved by the Research Ethics Committee of the Kitasato University Medical Ethics Organization (C22-082). The results and findings of this study will be published in a scientific journal and disseminated to companies that participate in the study. TRIAL REGISTRATION NUMBER: UMIN000050949.

Characteristics of mental disorders among information technology workers in 238 compensated cases in Japan.

This study aimed to investigate the circumstances, characteristics, and background factors of mental disorders within the information technology (IT) industry, which is known for the frequent occurrence of mental disorders from overwork and poor psychosocial work environment. The study analyzed 238 cases of mental disorders and suicides in the IT industry from fiscal years 2010 to 2018 on the database constructed by the Japan Research Center for Overwork-Related Disorders. The results showed a higher number of cases among men (n=178, 74.8%) and an increasing number among women. The data for diagnosis of mental diseases indicated a high number of depressive episodes (150 cases, 63.0%). Regarding work-induced psychological burden, 37 cases (15.5%) reported "extremely long working hours" for "special events" and 65 cases (27.3%) reported "constantly long working hours". For "specific events", 87 cases (36.6%) reportedly "caused (major) changes in the content and amount of work". Among women, 13 cases (21.7%) of "sexual harassment" (SH), which showed an increasing trend. Therefore, in the IT industry, the working hours must be properly managed. Mental health measures should also accompany improved psychosocial environment in the workplace, and prohibition of SH at work in particular.

Cross-sectional associations of weekly time, social context, and motivation of exercise with mental health among workers.

PURPOSE: Exercise is considered a strategy to promote mental health among workers. However, the optimal exercise conditions that promote mental health benefits for workers are still unclear. This study examined the cross-sectional associations of weekly exercise time duration, social context of exercise, and exercise motivation levels with the mental health among Japanese workers. METHODS: A web-based cross-sectional questionnaire survey was conducted among 18,902 workers, aged 20-59 years. The mental health variables (psychological distress, psychological stress reaction, physical stress reaction, job satisfaction, and work engagement), exercise participation (non-exercisers, exercisers), and demographic factors of all responders were measured. Weekly exercise time, social context of exercise (alone only, with others only, both alone and with others), and exercise motivation (non-regulation, external/introjected regulation, identified regulation, integrated regulation, and internal regulation) were also measured amongst exercisers. After adjusting for demographic factors, multiple regression analyses were conducted. RESULTS: Exercisers had significantly lower psychological distress, lower psychological and physical stress reactions, higher job satisfaction, and higher work engagement than non-exercisers. Among exercisers, while weekly exercise time duration and social context of exercise were not clearly and robustly associated with mental health variables, respondents with intrinsic regulation had significantly lower psychological distress, lower psychological and physical stress reaction, higher job satisfaction, and higher work engagement than those with lower self-determined motivations. CONCLUSIONS: This study found that more self-determined exercise motivation is closely associated with advantageous mental health variables, than the duration or the social context of exercise among Japanese workers.

The treatment efficacy and prognosis of each treatment in early postoperative recurrence of esophageal squamous cell carcinoma.

PURPOSE: Various treatments are used for early postoperative recurrence of esophageal cancer, which has a poor prognosis. We evaluated the differences in outcomes and prognoses of each treatment modality between patients with early and late recurrence. METHODS: Early and late recurrence were defined as recurrence within and after six postoperative months, respectively. Of the 351 patients with esophageal squamous cell carcinoma who underwent R0 resection esophagectomy, 98 experienced postoperative recurrence (early recurrence, n = 41; late recurrence, n = 57). We evaluated the characteristics of patients with early and late recurrence and compared their treatment responses and prognoses. RESULTS: Regarding treatment responses for chemotherapy or immunotherapy, the objective response rate was not significantly different between the early- and late-recurrence groups. For chemoradiotherapy, the objective response rate was significantly lower in the early-recurrence group than in the late-recurrence group. The overall survival was significantly worse in the early-recurrence group than in the late-recurrence group. An analysis by treatment type showed that the early-recurrence group had significantly worse overall survival for chemoradiotherapy, surgery, and radiotherapy than the late-recurrence group. CONCLUSIONS: Patients with early recurrence had particularly poor prognoses with worse post recurrence treatment efficacy than those with late recurrence. The differences in the treatment efficacy and prognosis were particularly pronounced for local therapy.

Improvement of mnemonic discrimination with acute light exercise is mediated by pupil-linked arousal in healthy older adults.

Physical exercise has positive impacts on hippocampal memory decline with aging. One of the postulated neurobiological mechanisms of the decline is reduced catecholaminergic projections from the locus coeruleus to the hippocampus. Recent human studies revealed that very light exercise rapidly enhances memory and pupil diameter, which suggests that light exercise may improve memory via neural circuits involved in the ascending arousal system, including the locus coeruleus, even in older adults. Thus, we aimed to clarify the effects of a single bout of light-intensity exercise (60% ventilatory threshold) on mnemonic discrimination performance, an index of hippocampal memory function, in healthy older adults using a randomized crossover design. Pupil diameter was measured during exercise as a physiological marker of the ascending arousal system. Discrimination of highly similar stimuli to the targets improved after exercise when compared to the resting control performance. Importantly, causal mediation analysis showed that pupil dilation during exercise mediated the memory improvement. These results suggest that brief light exercise rapidly enhances memory, possibly by upregulating the ascending arousal system.

Risk factors for aortoesophageal fistula in cT4b esophageal squamous cell carcinoma after definitive radiation therapy.

Background: Esophageal fistula (EF) is a serious complication in patients with cT4b esophageal squamous cell carcinoma (ESCC) with adjacent organ involvement. Among EFs, aortoesophageal fistula (AEF), forming a fistula with the aorta, could be fatal. This study aimed to identify the risk factors for AEF in patients with cT4b ESCC with obvious or suspected aortic invasion who underwent definitive radiotherapy (DRT). Methods: Forty-four patients with cT4b ESCC with obvious or suspected invasion to the aorta who underwent DRT were included. Blood tests and computed tomography (CT) findings before and after DRT were compared between the patients with and without AEF to identify the potential risk factors for AEF. Results: Nine patients (20.5%) developed AEF after DRT. Comparing between patients with and without AEF, pre-DRT white blood cell counts and post-DRT C-reactive protein (CRP) levels were significantly higher in patients with AEF. Furthermore, pre-DRT CT findings were similar between the two groups. However, post-DRT CT findings demonstrated significantly larger picus angle and lower esophageal wall thickness on the aortic side in patients with AEF. Multivariate analysis identified elevated post-DRT CRP levels [<3.3 versus ≥3.3 mg/dL; odds ratio (OR): 30.7; 95% confidence interval (CI): 2.92-323.2; P=0.004] and esophageal wall thinning on post-DRT CT scans (>6 versus ≤6 mm; OR: 13.2; 95% CI: 1.24-140.1; P=0.033) as risk factors for AEF. Conclusions: We found that post-DRT esophageal wall thinning on the aortic side, as observed on CT scans, and elevated CRP levels were predictive factors for AEF in patients with cT4b ESCC with obvious or suspected invasion to the aorta.

Long working hours and risk of hypertensive intracerebral haemorrhage among Japanese workers claiming compensation for overwork-related intracerebral haemorrhage: an unmatched case-control study.

OBJECTIVES: Overwork-related cerebrovascular and cardiovascular diseases (CCVDs) constitute a major occupational and public health issue worldwide. However, to our knowledge, few studies have reported the underlying pathophysiological mechanisms. We aimed to determine whether patients with extreme workload have a greater risk of developing hypertensive intracerebral haemorrhage (ICH) located in the deep brain areas than patients without extreme workload. We also determined the association between the number of hours of overtime work and the risk of developing hypertensive ICH. DESIGN: Unmatched case-control study. SETTING: Database of patients claiming compensation for overwork-related CCVDs in Japan. PARTICIPANTS: A total of 1215 patients who claimed overwork-related ICH in Japan, of whom 621 had their compensation claim approved (patients with extreme workload) and 622 did not. PRIMARY AND SECONDARY OUTCOME MEASURES: Logistic regression analysis was performed to calculate the risk of developing hypertensive ICH in patients with extreme workload compared with those without extreme workload, adjusted for confounders such as age, occupation, smoking status, alcohol consumption and medical history. We also calculated the risk of developing hypertensive ICH in compensated patients by average monthly overtime working hours. RESULTS: Patients with extreme workloads had a significantly higher odds ratio (OR) for developing hypertensive ICH (1.44, 95% CI: 1.10 to 1.88) than those without extreme workloads. ORs for developing hypertensive ICH according to overtime working hours showed a dose-response relationship; an overtime of 100 hours/month was associated with a significantly higher OR (1.31, 95% CI: 0.89 to 1.91; 1.41, 95% CI: 0.95 to 2.11; and 1.50, 95% CI: 1.01 to 2.22 for 60-79.9, 80-99.9 and≥100 hours/month, respectively) than that for workloads of less than 60 hours/month. CONCLUSIONS: Regarding Japanese workers, overtime work could be associated with the risk of developing hypertensive ICH, and hypertension may play an important role in overwork-related ICH.

Protocol for a web-based study on the work environment and daily lifestyle of Japanese employees.

Mental health problems are prevalent among the working population and must be resolved. We conducted a web-based large-scale study of workers, including a baseline survey and two follow-up surveys, to investigate the associations between self-care behaviors in daily life (e.g., stress coping, sleep, diet, and exercise), work environment improvements, and mental health among Japanese employees from various industries. In this protocol, we demonstrate the study design and demographic data of the participants in the baseline survey. Invitations to participate in this study were sent to 421,825 internet monitor registrants in February 2022. Overall, 20,000 registrants who met the inclusion criteria participated in the survey. There were large variations in occupations and working styles (e.g., physical work, night work, and teleworking) among the participants, and we also found significant differences between male and female participants in the demographic data. An overview of the survey data suggests that the demographic characteristics of the participants in this study are comparable to those reported in previous studies on Japanese employees. We plan to use these survey data in the future to examine the associations of daily lifestyles and work environments with the mental health of Japanese employees.

Esophageal Neuroendocrine Carcinoma With Pathological Complete Response After Neoadjuvant Chemotherapy Followed by Robot-assisted Surgery: A Case Report.

BACKGROUND/AIM: Malignant esophageal neuroendocrine carcinoma (ENEC) is rare, and its prognosis is poor. Therefore, a standard strategy for treating ENEC remains controversial, and few reports have described a pathological complete response of ENEC to neoadjuvant chemotherapy (NAC) followed by surgery. CASE REPORT: A 74-year-old woman presented with an esophageal tumor, discovered as a result of dysphagia, that was clinically diagnosed as ENEC (small-cell type). The clinical stage was cT2N1M0 stage II (Union for International Cancer Control, eighth edition). Two cycles of carboplatin and etoposide were administered as NAC, and the overall treatment response to NAC was judged as a partial response according to Response Evaluation Criteria for Solid Tumors v.1.1. The patient then underwent robot-assisted, minimally-invasive esophagectomy with thoracoabdominal lymph node dissection. Postoperative histopathology revealed no residual tumor or lymph node metastasis, and pathological complete response to NAC was achieved. The postoperative course was free of major complications, and the patient has remained recurrence-free for 1 year. CONCLUSION: We treated ENEC with NAC and robotic surgery. To our knowledge, this is the first report of a pathological complete response for ENEC after NAC with carboplatin and etoposide.

Real-world clinical outcomes of nivolumab and taxane as a second- or later-line therapy for recurrent or unresectable advanced esophageal squamous cell carcinoma.

Background: Nivolumab is approved in Japan as a second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC) resistant to fluoropyrimidine and platinum-based drugs. It is also used in adjuvant and primary postoperative therapies. This study aimed to report real-world data on nivolumab use for esophageal cancer treatment. Methods: In total, 171 patients with recurrent or unresectable advanced ESCC who received nivolumab (n = 61) or taxane (n = 110) were included. We collected real-world data of patients treated with nivolumab as a second- or later-line therapy and evaluated treatment outcomes and safety. Results: Median overall survival was longer and progression-free survival (PFS) was significantly longer (p = 0.0172) in patients who received nivolumab than in patients who received taxane as a second- or later-line therapy. Furthermore, subgroup analysis for second-line treatment only showed the superiority of nivolumab in increasing the PFS rate (p = 0.0056). No serious adverse events were observed. Conclusions: In real-world practice, nivolumab was safer and more effective than taxane in patients with ESCC with diverse clinical profiles who did not meet trial eligibility criteria, including those with poor Eastern Cooperative Oncology Group performance status, comorbidities, and receiving multiple treatments.

Association Between Workplace Social Support and Use of Health-Promoting Wearable Devices: A Prospective Cohort Study of Japanese Employees.

We examined the relationship between workplace environmental factors, including support from supervisors and colleagues, and the continued use of a wearable device meant to promote occupational health. One hundred employees at a Japanese manufacturing company participated in a 3-month study, and information related to their physical health status was recorded by a wearable device. We analyzed the results using the χ2 test and logistic regression analysis. We found that men aged 40-49 years and employees reporting low support from supervisors and colleagues were significantly more likely to be continuing device users. Participants with low workplace support had adjusted odds ratios approximately two to three times higher than those with high levels of support, which was significant. Employees with low workplace support were able to communicate at work, access appropriate support, and enthusiastically participate in occupational health promotion with little psychological difficulty in using the device. Occupational health promotion using wearable devices can complement traditional face-to-face occupational health promotion.

Ability of Blood Cell Parameters to Predict Clinical Outcomes of Nivolumab Monotherapy in Advanced Esophageal Squamous Cell Carcinoma.

Purpose: Various blood cell parameters have been identified as predictive markers of tumor responses and the survival of patients with cancer treated with immune checkpoint inhibitors. The purpose of this study is to assess the ability of various blood cell parameters to predict therapeutic effects and survival in patients with esophageal squamous cell carcinoma (ESCC) treated with nivolumab monotherapy. Patients and Methods: We evaluated neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios as predictive markers of patients' survival and effects of nivolumab monotherapy after one or more prior chemotherapies for unresectable advanced or recurrent ESCC. Results: The objective response and disease control rates were 20.3% and 47.5%, respectively. The LMRs before, and 14 and 28 days after nivolumab initiation were significantly higher in patients with complete response (CR)/partial response (PR)/stable disease (SD) than those with progressive disease (PD). The NLRs at 14 and 28 days after nivolumab initiation were significantly lower in patients with CR/PR/SD than with PD. The optimal cutoffs for these parameters significantly discriminated patients with CR/PR/SD and PD. Univariate and multivariate analyses identified pretreatment NLRs as a significant independent factor for progression-free and overall survival (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07-1.32, and HR 1.23, 95% CI: 1.11-1.37, respectively; p ≤ 0.001 for both). Conclusion: The pretreatment LMRs, and NLR and LMR at 14 and 28 days after starting nivolumab monotherapy were significantly associated with the clinical therapeutic effect. The pretreatment NLR was significantly associated with patients' survival. These blood cell parameters before and during the early days of nivolumab monotherapy can help to identify patients with ESCC who would most likely benefit from nivolumab monotherapy.

Presenteeism in front-line physicians involved in COVID-19-related clinical practice: a national survey of employed physician members of the Japan Medical Association.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have increased the rate of presenteeism among front-line physicians. Presenteeism is the term used to describe attendance at work despite ill health that would normally prompt rest or absence from work. This study aimed to examine the associations between COVID-19 clinical practice and presenteeism among physicians. METHODS: A cross-sectional study was conducted from December 2021 to January 2022. The questionnaires were distributed to 21,737 employed physicians who were members of the Japan Medical Association. Presenteeism was measured by the Work Functioning Impairment Scale. Multiple logistic regression analysis was used to evaluate the association between COVID-19 clinical practice and presenteeism. RESULTS: Overall, 3,968 participants were included in the analysis, and presenteeism was observed in 13.9% of them. The rate of presenteeism significantly increased with both the number of COVID-19 patients treated and the percentage of work time spent treating these patients (both P values for trend < 0.001). In comparison to those not currently engaged in the treatment of COVID-19 patients, presenteeism was significantly higher among front-line (adjusted odds ratio [aOR] = 1.71, 95% confidence interval [CI]: 1.16-2.53) and second-line physicians supporting those in the front-line (aOR = 1.45, 95% CI: 1.17-1.78). There was no association between involvement in COVID-19 vaccination services and presenteeism. CONCLUSIONS: The burden on front-line and second-line physicians in COVID-19 clinical practice must be minimized. Employed physicians also need to recognize the importance of communicating with their workplaces about presenteeism.

Characteristics of needlestick and sharps injuries of the hands in the operating room among orthopedic surgeons in Japan.

Among the reports on needlestick and sharps injuries (NSIs), many are orthopedic-related due to the frequent use of sharp devices such as pins and wires. This study aimed to identify high-risk instruments, the most common injury sites for each instrument, and the circumstances of NSIs of the hand during orthopedic surgeries in Japan. Incidents of exposure to blood or bodily fluids among physicians during orthopedic surgeries reported to the Japan-EPINet between 2000 and 2015 were included in this study. The four most common devices were identified and the associations among years of experience, equipment users, and injured sites were analyzed. We identified 666 cases of NSIs affecting orthopedic surgeons in the operating room. The instrument most frequently responsible for NSIs was suture needles, which were involved in 265 cases (39.7%). The second most common instrument was pins/wires, which was involved in 111 cases (16.6%). NSIs of the hands of orthopedic surgeons were frequently caused by suture needles used in all surgeries, but relatively often caused by orthopedic devices. Orthopedic surgeons must be aware that they are at risk of NSIs and must take appropriate measures and always be cautious when performing surgery, regardless of their years of experience.

Eccentric exercise improves myocardial oxygen supply/demand balance with decelerating aortic diastolic pressure decay: The acute and chronic studies.

Both eccentric (ECC) and concentric (CON) exercises improve energy expenditure and blood lipid profile. Although ECC exercise has a more beneficial effect on these factors than CON exercise, its benefits on vital organs are still unclear. This study investigated the mode-of-action-dependent effects on myocardial perfusion index. Seventeen healthy men (age: 26 ± 5 years) were randomly enrolled in CON (n = 9) and ECC (n = 8) groups. Transient exercise and regular training (three-day a week for 4-week) included bicep curl comprising 5-set of 10-repetition, each using 75% one-repetition maximum concentric loading. The ECC group performed one-repetition of ECC for 3-s and CON for 1-s, while the CON group performed one-repetition of CON for 3-s and ECC for 1-s. All participants were assessed for subendocardial viability ratio (SEVR, myocardial perfusion index) and aortic diastolic pressure decay. Before study, these were found to be same for both groups. Transient (ΔSEVR: 20.3 ± 13.3%, p = 0.01; Δdecay: -0.07 ± 0.02 s-1, p < .001) and regular (ΔSEVR: 18.5 ± 12.8%, p = .001; Δdecay: -0.06 ± 0.05 s-1, p = .004) ECC (but not CON) exercises significantly increased SEVR and decelerated decay. Increased SEVR with ECC exercise was associated with decelerated decay (transient ECC: r2 = 0.56, 95% confidence interval [CI] = -0.95 to -0.10, p = .03; regular ECC: r2 = 0.53, 95% CI = -0.95 to -0.05, p = .04). These findings suggest that ECC exercise improves myocardial perfusion and diastolic pressure contour is involved in physiological mechanisms.

Mediating and Moderating Effects of Psychological Detachment on the Association Between Stressors and Depression: A Longitudinal Study of Japanese Workers.

OBJECTIVES: This study examines the mediating and moderating effects of psychological detachment (PD) based on the stressor-detachment model in the long term. METHODS: Two waves of Web-based surveys, 28 months apart, yielded 3556 responses from Japanese workers. Comparisons between models that included mediating and moderating effects of PD and reverse direction mediating effects (strain → PD → stressor) were made by structural equation modeling. Differences in depression as a strain between combinations of high and low stressors and PD were also examined. RESULTS: The best-fitting model was the moderation/reciprocal partial-mediation model. The effect of PD was significant in the group with stable or decreasing stressor. CONCLUSION: According to the worker's level of stressors, PD, and depression, targeted interventions may effectively prevent physical and mental health problems caused by chronic stress.