Extensive intraoperative peritoneal lavage (EIPL) for gastric cancer with positive peritoneal lavage and/or stamp cytology: An exploratory phase II study

by Gen Tsujio, Masakazu Yashiro, Yuichiro Miki, Kohei Matsuoka, Koji Maruo, Mami Yoshii, Tatsuro Tamura, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Shigeru Lee, Tomohisa Okuno, Kishu Kitayama, Go Masuda, Masaichi Ohira, Kiyoshi Maeda

Background

Our group revealed that the combination of intra-operative stamp cytology and peritoneal lavage cytology (CY) improved the identification of individuals with high risk of peritoneal metastasis. In this exploratory Phase II study, we aimed to evaluate the effect on relapse-free survival (RFS) of extensive intraoperative peritoneal lavage (EIPL) for gastric cancer with positive peritoneal cytology (CY1) and/or stamp cytology positive (stamp+).

Materials and methods

This study was a single arm, multi-institutional, exploratory phase 2 trial to assess the effects of EIPL after open gastrectomy for gastric cancer with CY1 and/ or stamp+. The primary endpoint was RFS. Secondary endpoints were overall survival (OS), postoperative recurrence site and incidence of postoperative adverse events.

Results

Between 2017 and 2021, 13 patients from 2 institutions were enrolled in this study. Because of the recent decline in open abdominal surgery, the number of cases did not increase and the trial was closed due to lack of applicants at 13 cases. Median 3-year RFS was 14.5 months (95% CI 5.4-NA), median 3-year OS was not reached (95% CI 14.5-NA) and median3-year peritoneal RFS was 16.0 months (95% CI 5.4-NA). Median 3-year peritoneal RFS rate was 83% in CY0 and stamp+ cases (n=6), and 0% in CY1 and stamp+/- cases (n=7). (Log-rank p=0.015).

Conclusion

Because of the slow accrual pace and early stop of the trial, we were not able to evaluate the prespecified endpoints thoroughly. However, EIPL might be effective to prevent perineal recurrence, especially in CY0 and stamp+ case.

Caregiving activities causing occupational low back pain in Japanese social welfare facilities and hospitals

by Kazuyuki Iwakiri, Keiichi Miki, Takeshi Sasaki

Background

Occupational low back pain (LBP) has increased in Japanese social welfare facilities and hospitals. Understanding its occurrence is the first step in addressing this issue.

Aim

This study investigated the caregiving activities that cause occupational LBP incidents in these contexts.

Methods

The study analyzed 2,722 incidents of occupational LBP among staff in social welfare facilities and hospitals resulting in four or more days absent from work. Data were extracted from accident occurrences and causes in the 2018–2019 Reports of Worker Casualties. The caregiving situations related to the occupational LBP incidents at each facility were then analyzed.

Results

Approximately half of the occupational LBP incidents surveyed occurred during transfer assistance. This assistance was mainly associated with eating, bathing, and toileting in both facilities and frequently occurred during patient transfers between a bed and a wheelchair. In social welfare facilities, nontransfer assistance also contributed significantly, which included bathing, toileting, childcare, diaper changing, lying, standing, sitting, walking, and car transportation. In hospitals, nontransfer assistance such as providing support for lying, diaper changing, medical care, and sitting were occupational LBP risk factors. Furthermore, most incidents of occupational LBP occurred among staff who worked alone during day shifts.

Conclusion

Caregiving activities involving transfer assistance, such as bathing, toileting, and eating, were common risk factors in social welfare facilities and hospitals. However, the specific nontransfer assistance activities contributing to occupational LBP varied by facility. To effectively reduce the incidence of occupational LBP, prevention strategies should focus on these high-risk activities according to facility type and the types of caregiving required.

Dupilumab attenuates the expression of TSLP and IL-8 induced by dsRNA and IL-4/IL-13 co-stimulation in human small airway epithelial cells

by Aditya Sri Listyoko, Ryota Okazaki, Tomoya Harada, Genki Inui, Hiroki Kohno, Miyu Nishigami, Miki Takata, Masato Morita, Akira Yamasaki

Background

The interaction between viral components and type 1 or type 2 cytokines during asthma exacerbations in the airway epithelium may contribute to worsening inflammation. However, these interactions in the small airway epithelium—particularly those involving alarmins (TSLP, IL-25, and IL-33) and IL-8—remain unclear. Dupilumab, a biologic agent used in severe asthma, blocks IL-4 receptor alpha (IL-4Rα) and may offer therapeutic benefits in virus-induced asthma exacerbations. In this study, we evaluate the effects of double-stranded RNA (dsRNA), in combination with various cytokines and dupilumab, on the Human Small Airway Epithelial Cells (HSAECs) line.

Methods

Primary HSAECs were preincubated with dsRNA to induce the gene and protein expression of alarmins and IL-8. To evaluate the effects of cytokines on dsRNA-induced alarmin and IL-8 expression, various type 1 and type 2 cytokines were co-stimulated with dsRNA. Dupilumab was used as a pretreatment prior to co-stimulation with dsRNA and IL-4 or IL-13. Gene expression of TSLP, IL-25, IL-33, and IL-8 was assessed by quantitative PCR, and protein expression was evaluated by Western Blotting.

Results

dsRNA significantly increased the expression of TSLP and IL-8. IL-4 and IL-13 further enhanced dsRNA-induced TSLP and IL-8 gene and protein expression. In contrast, TNF-α reduced dsRNA-induced TSLP expression but enhanced IL-8 gene and protein expression. Dupilumab attenuated the expression of TSLP and IL-8 induced by co-stimulation with dsRNA and IL-4 or IL-13 in HSAECs.

Conclusion

In the microenvironment of small airway epithelial cells, particularly during viral infections, the presence of IL-4 or IL-13 may enhance the expression of TSLP and IL-8. Dupilumab attenuates this expression, potentially offering additional benefits in the treatment of asthma, especially during virus-induced asthma exacerbations.

A simulation study of the cost of cerebral vasospasm treatments with clazosentan: A mathematical model using time-driven activity-based costing

by Jieyu Zhao, Kota Kurisu, Kazuki Ohashi, Toshiya Osanai, Katsuhiko Ogasawara, Miki Fujimura

In this work, we aimed to assess the impact of clazosentan on clinical labour time costs within Japan’s value-based healthcare system using time-driven activity-based costing. Time-driven activity-based costing was employed to analyse the labour time costs associated with preventing cerebral vasospasm following aneurysmal subarachnoid haemorrhage. Time-driven activity-based costing simplifies cost analysis by utilising time as the primary cost driver. We compared two treatment approaches: conventional therapy with fasudil hydrochloride and postoperative therapy with clazosentan. Scenario and sensitivity analyses were performed to assess the impact of physicians’ costs on the results. The use of clazosentan for the prevention of cerebral vasospasm significantly reduced human resource costs, particularly in cases where symptomatic vasospasm did not occur, yielding savings of approximately 51,343 yen. The greatest cost reductions were observed among nursing staff, with a 30% decrease in the absence of symptomatic vasospasm and a 15% reduction when symptomatic vasospasm was present. The cost reductions for physicians were comparatively smaller, particularly in cases where symptomatic vasospasm occurred. Sensitivity analyses indicated that clazosentan reduced overall costs by approximately 35,000–50,000 yen; however, costs increased in the presence of symptomatic vasospasm. Clazosentan for subarachnoid haemorrhage treatment significantly reduces human resource costs, especially in nursing staff. These findings support the potential of clazosentan for broader clinical use, given its cost-savings and clinical benefits in reducing cerebral vasospasm following aneurysmal subarachnoid haemorrhage.