Clinical outcomes of challenging out-of-hospital hypothermia management: A retrospective assessment of DOKEI protocol.

BACKGROUND: Accidental hypothermia (AH) is a major cause of death in mountainous areas globally, and the second highest of mountaineering deaths in Japan, accounting for 37 % in Hokkaido. Managing AH is a significant challenge, particularly when adverse weather complicates the application of recommended rewarming and rapid transfer. To address this, the Hokkaido Police Organization (DOKEI) AH protocol was applied in Hokkaido's remote areas from 2011 to 2022, integrating high-temperature active external rewarming (HT-AER) with on-site sustained treatment. METHODS: This study retrospectively analyzed the rescue reports and hospital records of hypothermia patients treated postprotocol, excluding patients with cold exposure, undetectable vital signs at rescue, and inadequate documentation. Protocol adherence and outcomes-hypothermia stage, cardiocirculatory collapse, survival, and neurological status-were assessed. RESULTS: Among the 60 protocol-treated patients (19-74 years, 85 % male), 14 had stage 2 hypothermia, and 3 had stage 3 hypothermia. HT-AER was applied in 96.7 % of the patients. A total of 98.3 % of patients improved before handover without cardiac arrest (CA) or extracorporeal life support (ECLS). Comparatively, ten preprotocol patients (18-60 years, 70 % male) had two CAs, one fatal and six with no improvement. CONCLUSION: The DOKEI AH protocol demonstrates feasibility in managing stages 1-3 hypothermia, enhancing survival and neurological recovery, and can offer a vital option in challenging AH rescue scenarios.

Response to pembrolizumab in a patient with primary lung adenocarcinoma originated from indium lung.

BACKGROUND: Indium is a metal used as a compound called indium-tin oxide for liquid crystal display. Its inhalation causes lung toxicity, resulting in a new occupational lung disease called indium lung. Although the carcinogenicity of indium has been reported in an animal model, its carcinogenicity in humans is unknown. CASE PRESENTATION: This is the first reported case of a primary lung cancer originating from indium lung. In this report, we describe a 46-year-old man with interstitial pneumonia-type indium lung diagnosed 16 years ago. The initial symptom was left chest pain, and computed tomography showed a mass adjacent to the aorta with left pleural effusion. Specimens collected using video-assisted thoracoscopy revealed an adenocarcinoma with a high expression of programmed cell death-ligand 1 (cT4N0M1a stage IVA). Although the lesions showed a remarkable aggressive nature, the patient benefited from pembrolizumab, a monoclonal antibody against programmed cell death 1, which was used as second-line therapy for 2 years. CONCLUSIONS: It is important for clinicians to be aware of lung cancer development in indium-exposed workers or in patients with indium lung, as this could have an aggressive behavior. Treatment with immune checkpoint inhibitors is an option even in patients with interstitial pneumonia-type indium lung.

A population-based cohort study to evaluate the effectiveness of lung cancer screening using low-dose CT in Hitachi city, Japan.

OBJECTIVES: To evaluate the effectiveness of lung cancer screening using low-dose computed tomography for the general population, we conducted a retrospective cohort study of screening for participants among Hitachi residents. MATERIALS AND METHODS: Citizens aged 50-74 who underwent low-dose computed tomography screening at least once during 1998-2006 were defined as the computed tomography group, and those who underwent X-ray screening at least once during the same period, but did not receive low-dose computed tomography screening throughout the follow-up period, were defined as the XP group. We investigated the lung cancer incidence rate, mortality rate and all-cause mortality rate for both groups from the first lung cancer screening to the end of 2012. RESULTS: In the computed tomography group (17 935 residents; 9790 males and 8145 females), 273 cases of lung cancer (1.5%), 72 cases of lung cancer death (0.4%), and 885 cases of all-cause death (4.9%) were observed. On the other hand, 164 cases (1.1%) of lung cancer, 80 cases (0.5%) of lung cancer death and 1188 cases (7.6%) of all-cause death were observed in the XP group (15 548 residents; 6526 males and 9022 females). The hazard ratios of the computed tomography group to the XP group adjusted for gender, age and smoking history were 1.23 for lung cancer incidence rate, 0.49 for lung cancer mortality rate and 0.57 for all-cause mortality rate. Non-smokers and light smokers (<30 pack-years) had a significantly lower lung cancer mortality (0.41 and 0.21, respectively). CONCLUSION: low-dose computed tomography screening for a population including non-smokers and light smokers may be effective.

[Outcomes of an Independent Clinical Study to Compare Branded and Generic Formulations of Sustained-Release Oxycodone].

To evaluate the potential for the adoption of a generic formulation of sustained-release oxycodone(Oxycodone SR Capsules), an independent clinical study was planned to accurately evaluate the efficacy and safety during a 9-day period. After a 3-day pretreatment period, the generic formulation was administered to patients with progressive cancer, who had been treated with a branded formulation(OxyContin®Tablets)of the drug for 5 days at the same dose. This was followed by a 1- day observation period. Drug administration to 3 patients with pulmonary cancer achieved the primary(dose, pain level, and adverse drug reactions)and secondary(rescue dose frequency and quality of life)endpoints, as well as safety goals. The merits of adopting a different dosage form were also noted. Independent data collection using an appropriate evaluation method consequently promoted the understanding of generic opioids in the clinical setting.

[A case of angiosarcoma of the scalp with severe fluid retention after administering docetaxel].

A 7 3-year-old man with angiosarcoma was treated with concurrent chemoradiotherapy, using docetaxel (25mg/m(2) weekly). While the size of the tumor reduced rapidly, fluid retention, considered as an adverse effect of docetaxel, appeared at the cumulative dose of 325mg/m(2). He required chest drainage for prolonged pleural effusion. Though fluid retention due to docetaxel is infrequently reported in Japan, it may lead to severe illness and require discontinuation of chemotherapy. When we administer docetaxel over a prolonged period, we should be aware of this adverse effect.

Associated Factors and Comorbidities of Airflow Limitation in Subjects Undergoing Comprehensive Health Examination in Japan - Survey of Chronic Obstructive Pulmonary Disease Patients Epidemiology in Japan (SCOPE- J).

Purpose: To identify associated factors of having at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases in health examinees, and to describe the characteristics of each subgroup classified by comorbidities. Subjects and Methods: This was an observational cross-sectional survey carried out in multiple regions of Japan. Subjects aged 40 years older, undergoing comprehensive health examination, were recruited. Airflow limitation was defined as having forced expiratory volume in 1 s/forced vital capacity lower than 70%. Associated factors of having at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases were examined by logistic regression analysis. Subgroup classification by comorbidity patterns was conducted by hierarchical cluster analysis. Results: In a total of 22,293 subjects, 1520 (6.8%) had at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases. With this objective variable, the following explanatory variables were significantly associated: older age, higher total score in the chronic obstructive pulmonary disease assessment test (CAT) and coexistence of lung cancer (common in ever-smokers and never-smokers), higher pack-years, lower body mass index, higher C-reactive protein, without coexistence of diabetes mellitus (specific in ever-smokers), male sex, coexistence of anxiety, and sleep disorder (specific in never-smokers). Among the 1520 subjects, 1512 subjects with smoking history data were classified by comorbidity patterns into subgroups of "no comorbidities," "mixed comorbidities," "inflammatory comorbidities," "overweight," "underweight," and "chronic kidney disease." "Inflammatory comorbidities" were specific in ever-smokers, and "underweight" was specific in never-smokers. Conclusion: Several factors were identified as associated factors of having at least one of airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases and they were different between ever-smokers and never-smokers. Different comorbidity patterns were observed by smoking history. These findings could provide information to assist the management of subjects with COPD or at risk for COPD in the general population.

Chronic Cough and Phlegm in Subjects Undergoing Comprehensive Health Examination in Japan - Survey of Chronic Obstructive Pulmonary Disease Patients Epidemiology in Japan (SCOPE-J).

Purpose: The purpose of this study was to estimate the prevalence of subjects with chronic cough and phlegm and describe their characteristics including the presence or absence of airflow limitation among the general population in Japan. Subjects and Methods: This was an observational cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited. The existence of chronic cough and phlegm, airflow limitation, and treatment for respiratory diseases were examined. Chronic cough and phlegm were defined as having both symptoms for at least 3 months of the year and for at least 2 consecutive years, or as receiving any treatment for chronic bronchitis at the time of recruitment. Airflow limitation was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) less than 0.7. Results: In a total of 22,293 subjects, 380 subjects (1.7%) had chronic cough and phlegm. Among these 380 subjects, 21.8% received treatment for a respiratory disease, and 11.6% had airflow limitation. Compared to subjects without both chronic cough and phlegm but with airflow limitation, subjects with chronic cough and phlegm without airflow limitation were younger, more likely to be current smokers (39.6%), and had higher total scores on a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Scores of CAT questions 1-4 (cough, phlegm, chest tightness, breathlessness, respectively) were higher in subjects with chronic cough and phlegm regardless of airflow limitation. Conclusion: This study demonstrated that subjects identified to have chronic cough and phlegm in comprehensive health examination settings were symptomatic, while most of them did not receive any treatment for respiratory diseases and did not have airflow limitation. Screening subjects for chronic cough and phlegm in a comprehensive health examination followed by a detailed examination of screened subjects could be an effective approach for better management of chronic cough and phlegm. Smoking cessation should be included in the management, in consideration that around 40% of subjects with chronic cough and phlegm were current smokers.

A case of ROS1-rearranged lung adenocarcinoma exhibiting pleural effusion caused by crizotinib.

Reports of crizotinib-induced pleural effusion in non-small cell lung cancer (NSCLC) are limited. A 35-year-old Japanese woman was diagnosed with ROS1-rearranged lung adenocarcinoma (primary left lower lobe, cT4N3M1c). Crizotinib was administered as first-line therapy, and the primary and mediastinal hilar lymph node metastases rapidly shrank. On the fourth day of treatment, chest X-ray demonstrated contralateral pleural effusion. On the 41st day of treatment, crizotinib was discontinued because of grade 3 neutropenia. Examination including surgical thoracoscopy did not reveal causative findings, and the continued cessation of drug administration enabled the right pleural effusion to decrease gradually and disappear, suggesting that this event was a side effect of crizotinib. The disease did not progress even though the drug was withdrawn for more than one year. In conclusion, crizotinib was considered to cause pleural effusion as an adverse event in a case of ROS1-rearranged lung adenocarcinoma with a complete response.

Detection of circulating tumor cells in patients with lung cancer using metallic micro-cavity array filter: A pilot study.

We have developed a metallic micro-cavity array filter and an automated detection system for capturing circulating tumor cells (CTCs). In this single institutional pilot study, we assessed the ability of this device to detect CTCs in patients with lung cancer at each stage. Patients diagnosed with lung cancer, undergoing planned surgery for lung cancer, or suspected of having lung cancer were recruited (40 recruited and 2 excluded). Blood samples were obtained from the patients and 3 ml whole blood was applied to the device without any preparation. The captured cells were stained to differentiate the nucleus, and determine cytokeratin and CD45 expression. Subsequently, two operators blinded to clinical information counted the number of CTCs. Sample collection was performed at the time of recruitment, before treatment and ~3 months after initial blood collection. CTC counts at recruitment were 1.4±0.4, 1.8±1.2, 1.3±0.6 and 7.4±5.1 (mean ± SE) in clinical stages I, II, III and IV, respectively. No significant difference was observed among the stages. These data indicated the ability of this device to detect CTCs at early or non-metastatic stages of lung cancer. Further research on a larger scale is needed for a more accurate assessment of the device, and research on the utility of captured cells remains a future challenge.

Real Clinical Practice in ALK-rearranged NSCLC Patients: A Retrospective Observational Study.

BACKGROUND/AIM: To describe real clinical outcomes when using systemic therapy to treat non-small cell lung cancer (NSCLC) patients who have anaplastic lymphoma kinase (ALK) fusion gene mutation. PATIENTS AND METHODS: We performed a retrospective chart review from April 2008 to March 2019 sourced from 16 medical institutes that cover a population of three million people. RESULTS: There were 129 ALK rearranged NSCLC patients. Among them, 103 patients including 40 recurrent disease cases received ALK-tyrosine kinase inhibitors (TKI) and chemotherapy. Our treatment results were comparable to previously reported clinical trials and clinical practice studies. First-line alectinib, treatment sequence of ALK-TKI followed by another ALK-TKI, and pemetrexed-containing chemotherapy contributed to the outcome of treatment. CONCLUSION: By arrangement of treatment such as treatment sequence of ALK-TKI and chemotherapy regimen, it might be possible to obtain a treatment outcome almost equivalent to those of clinical trials even in real clinical practice.

A population-based study of gefitinib in patients with non-small cell lung cancer.

Survival data for non-small cell lung cancer is typically reported from clinical trials that include patients fit enough to meet treatment criteria. The denominator of all patients from which the gefitinib-treated population is derived has rarely been reported and the impact of gefitinib on population-based outcomes is difficult to measure. We have retrospectively reviewed data of 626 patients who received gefitinib in Ibaraki Prefecture (with a population of 3 million) in Japan from July 2002 until September 2007. Overall response rate was found to 30.8%, and the median survival time was 8.0 months (95% confidence interval: 7.0-9.0 months). Female gender, good PS, and adenocarcinoma were significantly associated with prolonged survival. Adverse events were generally mild and were mostly skin reactions and diarrhea. Our population-based study has generated similar results to those previously reported in published clinical trials, which had restrictive criteria for eligible patients.

[A case of postcardiac injury syndrome with repeated pleuritis after blunt chest trauma].

A 59-year-old man suffered blunt injury to the left chest during a fall in August 2004. He had 5 repeated episodes of back and left chest pain in three years since August 2005. Since these symptoms were accompanied by left pleural effusion and serum inflammatory reaction, the tentative diagnosis was pleuritis. Although examinations of pleural effusion showed exudation with marked augmentation of inflammatory cells, there were no findings that suggested the cause of repetitive pleuritis. All symptoms were relieved within one or two weeks following administration of non-steroid anti-inflammatory drugs. Surgical thoracoscopy was carried out to investigate the cause of repeated pleuritis, and an acquired deficit of the left pericardium was noted. We considered this case to be postcardiac injury syndrome causing repeated pleuritis following blunt chest injury.

Low-dose CT screening for lung cancer reduced lung cancer mortality in Hitachi City.

Purpose: To detect early, curable lung cancer, screening using low-dose CT (CT screening) was initiated in Japan and Western countries around the early 1990s. Material and methods: In 2013, the National Lung Screening Trial (NLST) reported that annual CT screening for high-risk participants leads to a 16% reduction in lung cancer death. In Hitachi City, CT screening for citizens 50 years of age or older was started in 1998, and 30% of the citizens had received a CT examination at least once by 2006. Results: We reported excellent survival (5-year survival of 90%) of 210 patients with lung cancer detected by CT screening. Based on a time trend analysis, a significant reduction (24%) in lung cancer mortality was observed 4 to 8 years after the introduction of CT screening among Hitachi residents. CT images can detect numerous smoking-related factors represented by pulmonary emphysematous change (CT emphysema). If we can evaluate the risk of respiratory disease according to these images, the benefits of screening are expected to increase further. Conclusion: To establish the effectiveness of CT screening for the general population, an optimum screening schedule is desired based on the risk of individuals. In addition, long-term follow-up is necessary to evaluate the effects of radiation exposure.

Real Clinical Practice of Using Afatinib Therapy in NSCLC Patients with an Acquired EGFR T790M Mutation.

BACKGROUND/AIM: To describe real clinical outcomes when using afatinib therapy to treat non-small cell lung cancer patients who have an acquired EGFR T790M mutation. MATERIALS AND METHODS: A retrospective chart review was conducted from January 2013 to November 2017 sourced from 15 medical institutes that cover a population of three million people. RESULTS: There were 74 patients who met the above-mentioned criteria. Treatment outcomes with afatinib, in patients with or without tyrosine kinase inhibitor (TKI) therapy prior to afatinib, were similar to previously reported clinical trials. Stratification of patients by the presence or absence of TKI pretreatment before afatinib, and the presence or absence of an acquired T790M mutation found no statistical difference in overall survival. CONCLUSION: This population-based study found that the disadvantages of pretreatment before afatinib, and absence of an acquired T790M EGFR mutation, could be overcome by an appropriate treatment strategy in clinical practice.

Acquired EGFR T790M Mutation After Relapse Following EGFR-TKI Therapy: A Population-based Multi-institutional Study.

AIM: To describe the prevalence and determinants of acquired epidermal growth factor receptor (EGFR) T790M gene mutation in a clinical practice setting. MATERIALS AND METHODS: We performed a retrospective chart review study between January 2013 and November 2017 across multiple institutes, covering a population of 3 million people. RESULTS: We reviewed the charts of 233 patients non-small cell lung cancer with EGFR mutations. Of them, 99 (42.5%) patients had acquired T790M mutations in EGFR. Patients ≥75 years old and patients with an exon 19 deletion had higher rates of acquired T790M mutation than did younger patients and those with an exon 21 L858R mutation. In 75 patients treated with afatinib, 34 (45.3%) patients had acquired T790M mutation. The sensitivity of T790M mutation detection was lower in plasma specimens than in biopsy specimens. CONCLUSION: This population-based study confirms previous studies and highlights potential determinants of acquired T790M mutation to be considered in clinical practice.

Efficacy of first-line erlotinib in non-small cell lung cancer patients undergoing dose reduction and those with a low body surface area: A population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The aim of the present study was to evaluate the efficacy of erlotinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), in patients undergoing dose reduction and in those with a low body surface area (BSA). The association between dose reduction, low BSA and efficacy, including response rate, disease control rate, time to treatment failure and overall survival, were evaluated in patients prescribed first-line erlotinib for EGFR mutated non-small cell lung cancer patients between April 2012 and March 2015. A total of 22 patients received first-line erlotinib during the study period. A dose reduction of erlotinib for the reason of low BSA and poor performance status occurred in 14 (63.6%) of the patients: 6 (27.3%) had initial dose reduction, 6 (27.3%) had dose reduction in their clinical courses, and 2 (9.1%) had both. Dose reduction of erlotinib with the initial dose of erlotinib/BSA was >80 mg/m2, and longest-term prescribed dose of erlotinib/BSA was >50 mg/m2, which may have no association with a survival disadvantage. Dose-reduction estimation studies for TKIs may be crucial, particularly for patients with a low BSA. Future prospective studies and confirmation of these results in population-based retrospective ones investigating the incidence of dose reduction in patients with AEs and those with low BSA may be required for the efficient use of erlotinib in common clinical practice.

S-1-containing chemotherapy for patients with non-small-cell lung cancer: A population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group.

To evaluate the efficacy and safety of S-1 monotherapy, S-1-containing combined chemotherapy and S-1 containing chemoradiotherapy for non-small cell lung cancer (NSCLC), a population-based observational study was performed. The efficacy and safety of the chemotherapies were evaluated at 13 institutes in a prefecture of Japan between April 2011 and March 2015. Datasets were obtained from 282 patients with NSCLC. For either wild-type or mutated epidermal growth factor receptor (EGFR), these three therapy groups generated almost identical response results and toxicity profiles as those in previously reported clinical trials, although the present study appeared to have slightly lower survival rates compared with those in the previous clinical trials. This may be due to the inclusion of patients in poor condition, and S-1 therapy being administered in the second, or later, line of therapy. In conclusion, the present study has confirmed that S-1-containing chemotherapy is effective against wild- and mutated-type EGFR NSCLC, and it is also tolerable in clinical practice.

[A Decrease in Lung Cancer Mortality Following the Implementation of CT Screening for General Population].

In Hitachi Medical Area, a large-scale lung cancer screening program using low-dose CT has been underway in two medical facilities since its introduction in 1998 and 2001. A total of 61,914 tests were performed among 25,385 participants until 2006. Two hundred and ten lung cancer patients had been identified on CT screening. The estimated 5-year survival rate for all patients was 90%. Among residents in Hitachi City, nearly 40% of inhabitants aged 50-69 years were estimated to have participated in the screening from 1998 through 2009. Cancer mortality data were obtained from a regional cancer registry and the standardized mortality ratio (SMR) of lung cancer was calculated for each 5-year period during 1995-2009. For residents aged 50-79 years, SMR was nearly unity between 1995 and 2004; however, there was a significant decrease during 2005-2009, with SMR (95% confidence interval) being 0.76 (0.67-0.86). These results suggest that the wide implementation of CT screening may reduce lung cancer mortality in the community, 4-8 years after introduction. It is desirable to continue to focus on future developments, including original research in Japan.

Low-dose computed tomography screening in Japan.

Lung cancer is a leading cause of cancer death in both male and female individuals in Japan. The effect of screening using chest radiography is assumed to be limited. In Japan, screening using low-dose computed tomography (CT) was initiated in 1993, and its dissemination has progressed with studies evaluating its efficacy, although it is not officially recommended. In addition to the academic activities of the Japanese Society of CT Screening, certification of physicians and radiologic technologists by the Japan Accreditation Council for CT Screening has been progressing. Currently, several hundred thousand low-dose CT screenings are performed annually in Japan. In Hitachi City, Ibaraki Prefecture, low-dose CT screening among employees and in communities started in 2001, and it was estimated that 40% of 50- to 69-year-old citizens had undergone screening at least once by March 2009. The lung cancer mortality rate in citizens in this age group decreased by 24% in 2005 to 2009 compared with the national statistics. Low-dose CT screening targeting the general population may be effective, but it is necessary to consider the target and interval of screening separately from those for the high-risk group. Observational study may play a role in evaluating the efficacy of screening in Japan.