Clinical Impact of Proton Pump Inhibitor and Potassium-Competitive Acid Blocker for Predicting the Curability of Endoscopic Resection in Ulcerative Early Gastric Cancer.

INTRODUCTION: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. METHODS: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. RESULTS: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). CONCLUSION: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection.

Metal-conjugated Maltotriose Chlorins as Novel Photosensitizers for Photodynamic Therapy.

BACKGROUND/AIM: Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light, causing a photochemical reaction that releases free radicals, thereby inducing tumor cell necrosis via oxidative stress. The oxygen molecule reaches the singlet excited state through efficient energy transfer from an excited triplet state of the photosensitizer. Heavy atoms are frequently introduced in photosensitizers for efficiently generating reactive oxygen species (ROS) in PDT, known as the heavy atom effect. However, metal-complexed photosensitizers often show low water-solubility. To overcome this limitation and produce ROS effectively, we focused on the better solubility of photosensitizers with heavy metals bound within the chlorin skeleton and conjugated with glucose in this study. MATERIALS AND METHODS: We established maltotriose (Mal3)-conjugation with heavy metallochlorins [M (Mal3-chlorin), M=Pt or Pd)] and evaluated its anti-tumor effect. RESULTS: M (Mal3-chlorin) showed effective ROS production and singlet oxygen induction. Consequently, these cytotoxic factors caused effective anti-tumor effects and induced morphological changes, followed by cell death in vitro. In a xenograft tumor mouse model, PDT with M (Mal3-chlorin) showed tumor growth suppression. CONCLUSION: M (Mal3-Chlorin) might be an excellent glucose-conjugated chlorin because of its strong anti-tumor PDT effect.

Estimation of genetic parameters for visceral diseases of fattening Japanese Black cattle in Shimane Prefecture, Japan.

In this study, the genetic parameters of major visceral diseases were estimated using the postmortem inspection records of 9057 fattening Japanese Black cattle in Shimane Prefecture, Japan, and the genetic correlation between visceral diseases and carcass traits was analyzed. There were six visceral diseases with a prevalence of 5% or higher, namely, pleurisy, pneumonia, bovine abdominal fat necrosis (BFN), rumenitis, hemorrhagic hepatitis, and perihepatitis. Variance components were estimated using the Gibbs sampling method, and the heritability of the visceral disease ranged from 0.07 to 0.49 for perihepatitis and BFN, respectively. Significant negative genetic correlations were identified between pleurisy and rib thickness (-0.32), BFN and carcass weight (-0.29), and BFN and rib eye area (-0.22). No significant genetic correlation was observed among the visceral diseases. The least squares analysis of variance suggested that some visceral diseases decrease the value of carcass traits. In particular, carcass weight and rib eye area in individuals with BFN were 11.7 kg and 1.87 cm2 lower than those of healthy cattle, respectively. Thus, it was inferred that genetic factors were involved in the visceral diseases of fattening Japanese Black cattle in Shimane Prefecture.

The reality of occupational harm incurred by Japanese home health care nurses, the hazardous situations they face, and protective measures: a cross-sectional study.

Objectives: To gain a comprehensive understanding of the occupational hazards encountered by home health care nurses in Japan and to elucidate the reality of harm they incur, the hazardous situations, and the protective measures taken.Methods:A questionnaire survey of managers of home health care nursing agencies in Japan was conducted, and 355 valid responses were obtained. The survey questions concerned the occupational hazards experienced by home health care nursing staff. The occupational hazards were classified into 6 categories, and responses were obtained regarding harm, hazardous situations, and protective measures in each category.Results: The types of harm that occurred at highest rates during the previous 3 years were emotional abuse by the patient or their family members, lower back pain resulting from improper posture while providing care, sexual harassment by the patients and their family members, automobile accidents while traveling to home care sites, and allergic reactions to the environment at home care sites. Some hazardous situations were caused by the unique environments of home care sites.Conclusions: In order to prevent the occurrence of harm, the development of risk assessment tools, educational initiatives to increase awareness of occupational hazards, and consideration of the financial and technical support that will enable the use of assistive devices in the practice of nursing techniques were considered necessary. The development of effective guidelines and manuals specific to the occupational hazards encountered by home health care nurses is an important challenge.

Induction of ferroptosis by photodynamic therapy and enhancement of antitumor effect with ferroptosis inducers.

BACKGROUND: Photodynamic therapy (PDT) is an effective tumor treatment that involves the administration of a photosensitizer to generate cytotoxic 1O2 [reactive oxygen species (ROS)] from molecular oxygen that is produced from energy absorption following tumor irradiation at specific wavelengths. Ferroptosis is induced by the disruption of the glutathione peroxidase 4 (GPX4) antioxidant system, leading to lipid peroxidation. We hypothesized that talaporfin sodium-photodynamic therapy (TS-PDT)-generated ROS would lead to ferroptosis via accumulation of lipid peroxidation. METHODS: Cell viability assay in TS-PDT-treated cells in combination with a ferroptosis inhibitor (ferrostatin-1: Fer-1) or ferroptosis inducers (imidazole ketone erastin: IKE, Ras-selective lethal 3: RSL3) was performed. Accumulation of lipid peroxidation, GPX4 antioxidant system and cystine/glutamate antiporter (system xc-) activity in TS-PDT-treated cells was investigated. In xenograft mice, the antitumor effect of TS-PDT in combination with ferroptosis inducers (IKE or sorafenib) was examined. RESULTS: TS-PDT-induced cell death was partly suppressed by Fer-1 and accompanied by lipid peroxidation. TS-PDT combined with IKE or RSL3 enhanced the induction of cell death. TS-PDT inhibited cystine uptake activity via system xc-. In vivo, the combination of TS-PDT and ferroptosis inducers (IKE or sorafenib) reduced tumor volume. CONCLUSION: This study found that the mechanism underlying TS-PDT-induced ferroptosis constitutes direct lipid peroxidation by the generated ROS, and the inhibition of system xc-, and that the combination of a ferroptosis inducer with TS-PDT enhances the antitumor effect of TS-PDT. Our findings suggest that ferroptosis-inducing therapies combined with PDT may benefit cancer patients.

Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody.

Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform a basic analysis of the anti-tumor effect of talaporfin sodium (TS)-PDT as well as its synergism with the immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate the cell death mechanism induced by TS-PDT and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT in vitro. We establish a syngeneic mouse model of bilateral flank tumors and verify the enhancement of the abscopal effect on the non-irradiated side. TS-PDT induced apoptosis, necrosis, and autophagy-associated cell death in vitro. TS-PDT induced the release and/or expression of DAMPs in vitro. Tumor growth was inhibited in the TS-PDT and anti-PD-1 antibody combination group compared with other single-treatment or non-treatment groups in vivo. In summary, TS-PDT induces the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhances the anti-tumor immunity induced by TS-PDT. Thus, our results demonstrate that the combination of TS-PDT and anti-PD-1 antibody can potentially be used for anti-tumor therapy.

[Evaluation of the "Health management guideline on occupational allergy in nursing occupations and its primary prevention" by nursing managers].

OBJECTIVE: Individuals in nursing occupations are often exposed to various materials such as rubber products and drugs, and they comprise a population at high risk of developing occupational allergies. We therefore created a "Health management guideline on occupational allergy in nursing occupations and its primary prevention" (hereinafter referred to as "HMG") and conducted a questionnaire survey to elucidate its potential use and the challenges of implementing it in clinical practice. SUBJECTS AND METHODS: The HMG includes the following content: A. Basic knowledge of occupational allergies; B. Common occupational allergies in nursing occupations; C. Occupational allergies triggered by specific antigens in nursing occupations; D. Eczema and skincare for hands; and E. Health management for occupational allergies. A questionnaire survey was conducted on one nursing manager each from 80 hospitals, with at least 400 beds. The survey included questions to gauge the level of understanding the content described in the HMG and opinions on incorporating the management method. The ethics committee of the researcher's institution approved the study. RESULTS: Responses were obtained from 30 nursing managers. Over 70% responded that they understood the instructions for [occupational allergies], [common occupational allergies in nursing occupations], and [eczema and skincare for hands] presented in the HMG, and 100% said they either understood or mostly understood them. For [work management], 57% said they understood the content and 90% wanted to incorporate it. Furthermore, 10% responded that they wanted to incorporate the guidelines but did not believe it was feasible, given that "achieving general awareness and efforts involving other occupations are difficult." For [work environment management], 53% said they understood the content and 83% wanted to incorporate it. Additionally, 17% responded that they wanted to incorporate it but did not believe it was feasible, amid concerns that "allergen monitoring is difficult in reality" and "installation of local ventilation systems seems difficult." DISCUSSION AND CONCLUSIONS: The HMG was postulated to be useful in providing knowledge on occupational allergy and health management methods, and for employing in clinical practice. The study recommended that in order to specifically incorporate the management methods, it is imperative that the entire hospital, including staff from other occupations, understand the guidelines and make adjustments accordingly.

Malignant gastrointestinal neuroectodermal tumor presenting with small intestinal obstruction: A case report.

Malignant gastrointestinal neuroectodermal tumors (GNETs) are rare malignant mesenchymal neoplasms. To our knowledge, only 99 cases have been reported worldwide. The tumor has an aggressive malignancy, with a rapid progression. The histological features of GNET overlap with those of clear cell sarcoma, which contain Ewing sarcoma breakpoint region 1 mutation. GNETs lack melanocyte-specific markers, while clear cell sarcoma exhibits melanocytic differentiation. Various symptoms have been reported previously, and the most reported lesion is in the small bowel. The patient was a 69-year-old man who presented with abdominal pain and vomiting. Computed tomography revealed a nodule in the small bowel, which induced small intestinal obstruction. Enteroscopic images revealed a submucosal tumor. Surgery was performed, and the patient was diagnosed with GNET. Only two patients whose primary lesions were in the small intestine, including the patient in this report, have undergone enteroscopy before surgery. This is a rare case of GNET in which a patient underwent enteroscopy before surgical treatment.

5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models.

Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.

Potential of Photodynamic Therapy Based on Sugar-Conjugated Photosensitizers.

In 2015, the Japanese health insurance approved the use of a second-generation photodynamic therapy (PDT) using talaporfin sodium (TS); however, its cancer cell selectivity and antitumor effects of TS PDT are not comprehensive. The Warburg effect describes the elevated rate of glycolysis in cancer cells, despite the presence of sufficient oxygen. Because cancer cells absorb considerable amounts of glucose, they are visible using positron emission tomography (PET). We developed a third-generation PDT based on the Warburg effect by synthesizing novel photosensitizers (PSs) in the form of sugar-conjugated chlorins. Glucose-conjugated (tetrafluorophenyl) chlorin (G-chlorin) PDT revealed significantly stronger antitumor effects than TS PDT and induced immunogenic cell death (ICD). ICD induced by PDT enhances cancer immunity, and a combination therapy of PDT and immune checkpoint blockers is expected to synergize antitumor effects. Mannose-conjugated (tetrafluorophenyl) chlorin (M-chlorin) PDT, which targets cancer cells and tumor-associated macrophages (TAMs), also shows strong antitumor effects. Finally, we synthesized a glucose-conjugated chlorin e6 (SC-N003HP) that showed 10,000-50,000 times stronger antitumor effects than TS (IC50) in vitro, and it was rapidly metabolized and excreted. In this review, we discuss the potential and the future of next-generation cancer cell-selective PDT and describe three types of sugar-conjugated PSs expected to be clinically developed in the future.

Combination of talaporfin photodynamic therapy and Poly (ADP-Ribose) polymerase (PARP) inhibitor in gastric cancer.

Photodynamic therapy (PDT) utilizes photochemical reactions induced by a photosensitizer and light in the target tissue and is used to treat various cancers. There is a high degree of anticipation of success regarding the application of PDT with talaporfin (photosensitizer) for gastric cancer. Olaparib is an oral inhibitor of Poly (ADP-Ribose) polymerase (PARP) and has demonstrated optimal efficacy and clinical activity in trials. Therefore, the aim of the present study was to investigate the efficacy of talaporfin PDT combined with olaparib for gastric cancer. MKN45, a gastric cancer cell line, was incubated with talaporfin, followed by irradiation, in the presence/absence of olaparib. Talaporfin PDT and olaparib exhibited excellent synergistic action in a concentration-dependent manner. PARP-DNA complexes were characterized based on bound chromatin using Western blot analyses. The combination of talaporfin PDT and olaparib enhanced PARP1 accumulation (the entrapment of PARP1-DNA complexes) in bound chromatin. The combination of talaporfin PDT and olaparib induced DNA double-strand breaks, which was confirmed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established, and antitumor effects were analyzed. In vivo, tumor growth was significantly suppressed following PDT with talaporfin and olaparib. Our results demonstrated that olaparib enhances the efficacy of talaporfin PDT by inducing the formation of PARP-DNA complexes. Therefore, our results suggest that the combination of talaporfin PDT and olaparib is a potential antitumor therapy for gastric cancer.

Vascular Shutdown by Photodynamic Therapy Using Talaporfin Sodium.

Photodynamic therapy (PDT) is an attractive cancer treatment modality. Talaporfin sodium, a second-generation photosensitizer, results in lower systemic toxicity and relatively better selective tumor destruction than first-generation photosensitizers. However, the mechanism through which PDT induces vascular shutdown is unclear. In this study, the in vitro effects of talaporfin sodium-based PDT on human umbilical vein endothelial cells (HUVECs) were determined through cell viability and endothelial tube formation assays, and evaluation of the tubulin and F-actin dynamics and myosin light chain (MLC) phosphorylation. Additionally, the effects on tumor blood flow and tumor vessel destruction were assessed in vivo. In the HUVECs, talaporfin sodium-based PDT induced endothelial tube destruction and microtubule depolymerization, triggering the formation of F-actin stress fibers and a significant increase in MLC phosphorylation. However, pretreatment with the Rho-associated protein kinase (ROCK) inhibitor, Y27632, completely prevented PDT-induced stress fiber formation and MLC phosphorylation. The in vivo analysis and pathological examination revealed that the PDT had significantly decreased the tumor blood flow and the active area of the tumor vessel. We concluded that talaporfin sodium-based PDT induces the shutdown of existing tumor vessels via the RhoA/ROCK pathway by activating the Rho-GTP pathway and decreasing the tumor blood flow.

Effect of a hand massage with a warm hand bath on sleep and relaxation in elderly women with disturbance of sleep: A crossover trial.

AIM: The purpose of the present study was to clarify the effects of a hand massage with a warm hand bath on sleep, autonomic nervous activity, subjective sleep quality, and relaxation in elderly women with sleep disturbance. METHODS: A crossover design was used. Participants were assigned to two groups: a structured control first and intervention second condition, or an intervention first and control second condition. The sleep index as assessed by actigraphy, autonomic nervous activity, subjective sleep quality, and relaxation was then recorded. RESULTS: The mean age of the participants was 77.8 ± 6.8 years (n = 28). According to the actigraph, the intervention day showed significantly improved sleep efficiency (p = .048) and sleep onset latency (p = .015). Regarding autonomic nervous activity, heart rate decreased significantly after the intervention (p = .001), but no significant differences were seen in the other indexes. Subjective sleep quality, which was investigated using the middle-age and aged version of the Oguri-Shirakawa-Azumi sleep questionnaire, was significantly higher after the intervention for four out of five factors. Subjective comfort and relaxation were significantly higher after the intervention for all items. CONCLUSIONS: A hand massage with a warm hand bath in the evening improved sleep efficiency and sleep onset latency in elderly women with sleep disturbance. These results suggest that a hand bath and massage may improve subjective sleep quality and relaxation.

Effects of a warm hand bath on the blood flow in the shoulder, skin and deep body temperature, autonomic nervous activity, and subjective comfort in healthy women: An experimental cross-over trial.

AIM: The present study was conducted in order to clarify the effects of a warm hand bath at 40°C for 10 min on the blood flow in the shoulder, skin and deep body temperature, autonomic nervous activity, and subjective comfort in healthy women. METHODS: The study's participants were 40 healthy adult women who were randomly assigned to either a structured hand bath first and no hand bath second (Group A) or to no hand bath first and a hand bath second (Group B). The blood flow in the shoulder, skin and deep body temperature, autonomic nervous activity, and subjective comfort then were recorded in all the participants. RESULTS: A repeated-measures ANOVA revealed no significant difference in the blood flow in the right shoulder or deep body temperature between groups. The skin temperature of the hands, forearms, and arms was significantly increased, but not of the face and upper back. The skin temperature of the forearms was maintained at 0.5°C-1°C higher for 30 min in the hand bath group, compared with the no hand bath group. The hand bath group had a significantly higher heart rate while bathing and a significantly lower parasympathetic nerve activity level during bathing. No significant difference was seen in the sympathetic activity level between groups. The hand bath group had a significantly higher subjective comfort level. CONCLUSION: Hand baths can improve the level of subjective comfort and increase the heart rate and might affect autonomic nervous activity. The skin temperature of the forearms was maintained for 30 min in the hand bath group.

Postpartum infective endocarditis with Enterococcus faecalis in Japan: a case report.

BACKGROUND: The clinical characteristics of infective endocarditis include the presence of predisposing cardiac disease, a history of illegal drug use, and high morbidity in the elderly. Only a few cases of the disease after delivery have been reported in the literature. We describe here a first case of enterococcal postpartum infective endocarditis without underlying disease in Japan. CASE PRESENTATION: We report the case of a 31-year-old Japanese woman with postpartum infective endocarditis by Enterococcus faecalis. She had no significant medical history or any unusual social history. After emergency surgery for severe mitral regurgitation and antimicrobial treatment for 6 weeks, she was discharged from our hospital and is now being monitored at an out-patient clinic. CONCLUSIONS: We encountered a case of Enterococcus faecalis infective endocarditis that occurred in the native valve of a postpartum healthy woman. Although the pathogenesis of this case remains unclear, it could be due to bacteremia arising from the administration of prophylactic broad-spectrum antibiotics used for cesarean section. Previous use of cefotiam and urinary catheter insertion may be risk factors for nosocomial enterococcal bacteremia in this case.

Occupational exposures among nurses caring for chemotherapy patients -Quantitative analysis of cyclophosphamide and α-fluoro-ß-alanine in urine.

OBJECTIVES: The aim of this study was to measure the antineoplastic drug content in urine and verify the situation of occupational exposure of the antineoplastic drug among nurses who care for patients undergoing chemotherapy. METHODS: Ten female nurses who were caring for patients receiving chemotherapy were the subjects of this study. Urine samples were collected over 24-hour periods, and each sample was analyzed. The excretion of cyclophosphamide (CP) and α-fluoro-ß-alanine (FBAL) were measured in the urine of the 10 nurses. CP and FBAL were detected separately using gas chromatography tandem mass spectrometry (GC-MSMS) methods (Exposure Control, the Netherlands). RESULT: CP was detected in 24 urine samples of 9 nurses. The total amount of CP excreted ranged from 5.4 to 44.2 ng/24-hours. The mean amount of CP excreted per nurse was 16.8 ng/24-hours. No significant difference was observed between the hospital I and II. FBAL was not detected in any of the urine samples. CP was detected in the urine of the nurses prior to their work shift. Moreover, CP was detected in the urine of the nurses who were not caring for patients in the intravenous drip of CP. There was most what answered that there was hair loss in health condition. CONCLUSION: The results reveal that almost all nurses were exposed to cyclophosphamide. Even when the patient in the intravenous drip of CP was not being cared for, it became clear that exposure by CP existed. As the route of the exposure to CP, the inhalation or dermal absorption can be considered. To ensure minimum exposed to antineoplastic drugs, suitable personal protective equipment needs to be equipped also of various scenes of caring for chemotherapy patients. Moreover, it is important to keep an eye on the monitoring of the antineoplastic drug in the environment and a nurse's health condition periodically going forward.

Cytopathologic characteristics of the primary strumal carcinoid tumor of the ovary: a case report with emphasis on differential diagnostic considerations.

Primary strumal carcinoid tumor of the ovary (SCTO) is an extremely rare entity, though the survival rate is excellent if the disease is confined to one ovary. A case is presented here in which intraoperative squash smears in a 45-year-old woman with a left adnexal mass revealed dispersed or small clusters of neoplastic cells forming loosely cohesive gland-like structures with abundant cytoplasm. The nuclear chromatin was finely granular with a "salt and pepper" appearance and occasional tiny nucleoli. The position of the nucleus presented a vaguely plasmacytoid appearance. Small fragments of thyroidal colloid-like structures were also identified. A cytopathologic diagnosis of a SCTO was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Cords or nests of uniform cells with abundant cytoplasm, and eccentric nuclei with coarse chromatin and occasional colloidal tissue were identified on H&E sections. The tumor cells showed diffuse and strong cytoplasmic staining for chromogranin A, synaptophysin, CD56, and vimentin but were negative for calretinin, α-inhibin or CDX2. The proliferative index with MIB-1 was around 3%. Thyroidal colloid-like structures were immunoreactive for thyroglobulin and TTF-1 stains. The diagnosis of primary SCTO was confirmed based on cytopathologic, histopathological, and immunohistochemical results, and the location of the tumor. Awareness of the cytopathological findings of SCTO can assist in diagnosing this rare entity correctly.

Assessment of DNA damage in Japanese nurses handling antineoplastic drugs by the comet assay.

To clarify genotoxic effects of occupational exposure to antineoplastic drugs in Japan, we examined DNA damage, assessed by the comet assay, in 121 female nurses and 46 female clerks working at three hospitals in the northeast of Japan. The comet assay is considered to be a sensitive and rapid method for DNA strand break detection in individual cells, and tail length and tail moment are used as the comet parameters. Concerning the basal characteristics, the 46 control subjects had higher rates of smoking and coffee-drinking habits and lower hemoglobin than the 121 nurses (p<0.05). The log-transformed tail length in the nurses was significantly longer than that in the control subjects after adjusting for possible covariates such as age and smoking habit (p<0.05). Also, the log-transformed tail length was significantly longer, in the 57 nurses who had handled antineoplastic drugs in the last six months, than that in the 46 control subjects (p<0.05); but, no significant difference in tail length or tail moment was seen between the two nurse groups with and without experience of handling hazardous drugs (p>0.05). These results suggest that Japanese nurses who have worked at hospitals using antineoplastic drugs may have a potential risk of DNA damage. To minimize this risk in Japan, use of biological safety cabinet and appropriate protective equipment, in addition to staff education and training, should be implemented in the healthcare environment.