Sex disparities in prehospital advanced cardiac life support in out-of-hospital cardiac arrests in Japan.

OBJECTIVE: Sex disparities in out-of-hospital cardiac arrest (OHCA) care processes have been reported. This study aimed to investigate the association between sex and prehospital advanced cardiac life support (ACLS) interventions provided by emergency medical services in Japan. METHODS: We analyzed data from January 1, 2013, to December 31, 2020, from the All-Japan Utstein Registry of patients with OHCA aged ≥18 years who were resuscitated by bystanders. The primary outcomes were prehospital ACLS interventions, including advanced airway management (AAM) and epinephrine administration. Sex-based disparities in receiving prehospital ACLS interventions were assessed via multivariable logistic regression analyses. RESULTS: Among 314,460 eligible patients, females with OHCA received fewer prehospital ACLS interventions than males: 83,571/187,834 (44.5%) males vs. 55,086/126,626 (43.5%) females (adjusted odds ratio [AOR] = 0.94, 95% confidence interval [CI] = 0.93-0.96) for AAM and 60,097/187,834 (32.0%) males vs. 35,501/126,626 (28.0%) females (AOR = 0.84, 95% CI = 0.83-0.85) for epinephrine administration. Similar results were also obtained in the subgroup analysis (groups included patients aged 18-74 years and ≥75 years and those with cardiac origin, ventricular fibrillation (VF), non-VF, non-family member witnessed, and family member witnessed). CONCLUSION: Compared with males, females were less likely to receive prehospital ACLS. Emergency medical service staff must be made aware of this disparity, and off-the-job training on intravenous cannulation or AAM replacement must be conducted. Investigation of the impact of sex disparity on OHCA care processes can facilitate planning of future public health policies to improve survival outcomes.

Association of sex with post-arrest care and outcomes after out-of-hospital cardiac arrest of initial shockable rhythm: a nationwide cohort study.

Background: Research has described differences in the provision of prehospital treatment for women who experience out-of-hospital cardiac arrest. However, studies have reported conflicting results regarding survival outcomes or in-hospital interventions between sexes. Thus, this study aimed to investigate the association of sex with survival outcomes and in-hospital treatments in Japan. Methods: We retrospectively analyzed data from the Japanese Association for Acute Medicine-Out-of-Hospital Cardiac Arrest Registry. Patients aged ≥18 years who presented with a shockable rhythm at the scene between June 2014 and December 2020 were included in our analysis. Outcome measures were 30-day survival and in-hospital interventions. We compared the outcomes between the sexes using multivariable logistic regression. Results: In total, 5,926 patients (4,270 men; 1,026 women) with out-of-hospital cardiac arrest were eligible for our analysis. The proportions of patients with 30-day survival outcomes were 39.5% (1685/4,270) and 37.4% (384/1,026) in the male and female groups, respectively (crude odds ratio, 0.92; 95% confidence interval, 0.80-1.06). Although there were no significant differences, survival outcomes tended to be better in women than in men in the multiple regression analysis (adjusted odds ratio: 1.38; 95% confidence interval: 0.82-2.33). Furthermore, there was no significant difference between the sexes in terms of patients who received extracorporeal cardiopulmonary resuscitation (adjusted odds ratio: 0.81; 95% confidence interval: 0.49-1.33) or targeted temperature management (adjusted odds ratio: 0.99; 95% confidence interval: 0.68-1.46). Conclusions: After adjusting for prognostic factors, there were no differences in survival rates and in-hospital interventions between men and women.

Association of the COVID-19 Pandemic With Prehospital Characteristics and Outcomes of Pediatric Patients With Out-of-Hospital Cardiac Arrest in Japan, 2005-2020.

This cohort study investigates the association of the COVID-19 pandemic with prehospital characteristics and outcomes of pediatric patients with out-of-hospital-cardiac arrest in Japan.

Survival following an out-of-hospital cardiac arrest in Japan in 2020 versus 2019 according to the cause.

Aim: The coronavirus disease (COVID-19) pandemic has led to an increase in out-of-hospital cardiac arrests (OHCAs) and mortality. However, there has been no reports in Japan using nationwide registry data. We compared survival among patients with OHCAs and detailed information on the cause during the COVID-19 pandemic (2020), and during the pre-pandemic period (2019). Methods: Using a Japanese population-based retrospective cohort study design, we analyzed registry data on 39,324 and 39,170 patients with OHCAs in 2019 and 2020, respectively. We compared patient outcomes in 2019 and 2020 using univariable and multivariable logistic regression analyses. Results: The proportion of OHCAs of cardiac origin increased significantly from 61.6% in 2019 to 62.7% in 2020 (P = 0.001). The use of bystander CPR (6.9% versus 5.7%, P < 0.001) and publicaccess automated external defibrillator pads (3.7% versus 3.0%, P < 0.001) decreased significantly from 2019 to 2020. The 1-month survival for OHCA of cardiac origin (12.1% versus 10.7%; adjusted odds ratio [OR] 0.93, 95% confidence interval [CI] 0.87-1.00), asphyxia (10.9% versus 8.8%; adjusted OR 0.80, 95% CI 0.70-0.92), and external causes (adjusted OR 0.66; 95% CI 0.46-0.96), also decreased significantly from 2019 to 2020. Conclusions: In Japan, the 1-month survival after OHCA of cardiac origin, or due to asphyxia or external causes, decreased significantly during the COVID-19 pandemic period.

Impact of the COVID-19 pandemic on out-of-hospital cardiac arrest outcomes in older adults in Japan.

Aim: The coronavirus disease (COVID-19) pandemic has negatively affected access to healthcare and treatment. This study aimed to explore the impact of the COVID-19 pandemic on older adults with out-of-hospital cardiac arrest (OHCA) in Japan, a country with a super-aging society. Methods: This secondary analysis of the All-Japan Utstein Registry included patients aged 65 years and older with bystander-witnessed OHCA between January 1, 2005, and December 31, 2020. Survival outcomes were compared by time period using multivariable logistic regression analyses. The primary outcome measured was the one-month survival rate with neurologically favorable outcomes. Results: Before the COVID-19 pandemic, survival outcomes were steadily improving, and 32,024 patients in 2019 and 31,894 in 2020 were eligible for analysis. The proportions of conventional cardiopulmonary resuscitation and shock by public-access automated external defibrillators were lower in 2020 than in 2019 (6.7% versus 5.7%, p < 0.001 and 2.5% versus 2.1%, p < 0.001, respectively). Compared to 2019, the one-month survival after OHCA and prehospital return of spontaneous circulation decreased significantly in 2020 than in 2019 (7.7% versus 6.6%, adjusted odds ratio [AOR]: 0.88, 95% confidence interval [CI]: 0.83-0.94, and 16.8% versus 14.9%, AOR: 0.87, 95% CI: 0.83-0.91, respectively). The proportion of neurologically favorable outcomes also decreased, but the decrease was not statistically significant (3.4% versus 2.8%, AOR: 0.92, 95% CI: 0.83-1.01). Conclusion: In this population-focused, bystander-witnessed study regarding OHCA, the analysis of nationwide registry data revealed that the COVID-19 pandemic was associated with reduced survival among older adults with OHCA in Japan.

Sepsis-Associated Encephalopathy: A Mini-Review of Inflammation in the Brain and Body.

Sepsis is defined as a life-threatening multi-organ dysfunction triggered by an uncontrolled host response to infectious disease. Systemic inflammation elicited by sepsis can cause acute cerebral dysfunction, characterized by delirium, coma, and cognitive dysfunction, known as septic encephalopathy. Recent evidence has reported the underlying mechanisms of sepsis. However, the reasons for the development of inflammation and degeneration in some brain regions and the persistence of neuroinflammation remain unclear. This mini-review describes the pathophysiology of region-specific inflammation after sepsis-associated encephalopathy (SAE), clinical features, and future prospects for SAE treatment. The hippocampus is highly susceptible to inflammation, and studies that perform treatments with antibodies to cytokine receptors, such as interleukin-1ß, are in progress. Future development of clinically applicable therapies is expected.

Association between Timing of Epinephrine Administration and Outcomes of Traumatic Out-of-Hospital Cardiac Arrest following Traffic Collisions.

The effects of epinephrine administration timing on patients with out-of-hospital cardiac arrest (OHCA) following traffic collisions are unknown. We analyzed the 2013-2019 All-Japan Utstein Registry data of 2024 such patients aged ≥18 years who were resuscitated by emergency medical service (EMS) personnel or bystanders and then transported to medical institutions. Time from 119 call to epinephrine administration was classified into quartiles: Q1 (6-21 min), Q2 (22-26 min), Q3 (27-34 min), and Q4 (35-60 min). Multivariable logistic regression analysis was used to assess the effects of epinephrine administration timing on one-month survival after OHCA. Overall, the one-month survival rates were 3.2% (15/466) in Q1, 1.1% (5/472) in Q2, 1.9% (11/577) in Q3, and 0.2% (1/509) in Q4. Additionally, the one-month survival rate decreased significantly in the Q4 group (adjusted odds ratio, 0.07; 95% confidence interval, 0.01-0.57) compared with the Q1 group, and the probability of one-month survival decreased as the time from the EMS call to epinephrine administration increased (p-value for trend = 0.009). Only four patients (0.9% [4/466]) with the earliest epinephrine administration showed a good neurological outcome.

Nationwide improvements in geriatric mortality due to traumatic brain injury in Japan.

BACKGROUND: Traumatic brain injury (TBI), both isolated and in combination with extracranial lesions, is a global health problem associated with high mortality. Among various risk factors for poor clinical outcomes, age is the most important independent predictor of mortality in patients with TBI. TBI-related mortality is expected to increase as the society ages. However, in a super-aged society such as Japan, little is known about the trend of TBI-related mortality among older adults. Herein, we assessed the nationwide trend of the incidence and clinical outcomes of geriatric patients with TBI in Japan using the national Japanese Trauma Data Bank (JTDB) registry. METHODS: In this retrospective cohort study, cases of TBI (aged ≥65 years) in hospitals registered with the JTDB database between January 2004 and December 2018 were included. In-hospital mortality was the primary outcome, and mortality in the emergency department was the secondary outcome. The odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital deaths with respect to 3-year periods were assessed using multivariable analysis after adjusting for potential confounders. RESULTS: The main cause of TBI in older individuals was falls. The proportion of patients who died after hospitalization during the study period decreased markedly from 29.5% (194/657) during 2004-2006 to 14.2% (1309/9240) during 2016-2018 in the isolated TBI group (adjusted OR = 0.42, 95% CI: 0.33-0.53) and from 48.0% (119/248) during 2004-2006 to 21.7% (689/3172) during 2016-2018 in the multiple trauma group (adjusted OR = 0.32, 95% CI: 0.23-0.45). The adjusted ORs for the 3-year increment were 0.84 (95% CI: 0.81-0.88) and 0.78 (95% CI: 0.75-0.83) for the isolated TBI and multiple trauma groups, respectively. CONCLUSIONS: Using the national JTDB registry, we demonstrated a nationwide reduction in TBI-related mortality. Our findings in the super-aged society of Japan may provide insight for the treatment of geriatric patients with TBI worldwide.

Survival Trends in Adults with Out-of-Hospital Cardiac Arrests after Traffic Collisions in Japan: A Population-Based Study.

The 1-month survival rate from out-of-hospital cardiac arrest (OHCA) of cardiac origin has reportedly improved recently, at ≥5%. However, the characteristics of patients with OHCA after a traffic collision have not been adequately evaluated in Japan. We analyzed the All-Japan Utstein Registry data of 12,577 adult patients aged ≥ 20 years with OHCA due to traffic collisions who were resuscitated by emergency medical service personnel or bystanders and were then transported to medical institutions between 2013 and 2019. Multiple logistic regression analysis was used to assess factors potentially associated with the 1-month survival rate after OHCA. The 1-month survival rate was 1.4% (174/12,577). The proportion of 1-month survival of all OHCAs after a traffic collision origin did not increase significantly (from 1.6% [30/1919] in 2013 to 1.8% [25/1702] in 2019), and the adjusted odds ratio for 1-year increments was 1.04 (95% confidence interval, 0.96-1.12). In multivariate analysis, men who received ventricular fibrillation, pulseless electrical activity, intravenous fluid replacement, or early emergency medical service response and had a traffic collision during daytime had significantly favorable 1-month outcomes. In Japan, the 1-month survival after OHCA of a traffic collision origin was lower than that of a cardiac origin and remains stable.

Epidemiology and Outcome of Pediatric Out-of-Hospital Cardiac Arrest after Traffic Collision in Japan: A Population-Based Study.

The epidemiological and clinical characteristics, treatments, and outcomes of patients with traumatic out-of-hospital cardiac arrests (OHCAs) following traffic collisions have not been adequately investigated in Japan. We analyzed the All-Japan Utstein Registry data of 918 pediatric patients aged <20 years with OHCAs following traffic collisions who were resuscitated by bystanders or emergency medical service personnel and were subsequently transported to hospitals between 2013 and 2019. Multiple logistic regression analysis was used to assess factors potentially associated with 1-month survival after OHCA. The 1-month survival rate was 3.3% (30/918), and the rate of neurologically favorable outcomes was 0.7% (60/918). The proportion of 1-month survival of all OHCAs after traffic collision origin did not significantly increase (from 1.9% (3/162) in 2013 to 4.5% (5/111) in 2019), and the adjusted odds ratio (OR) for a 1-year increment was 1.13 (95% confidence interval (CI) 0.93 to 1.37). In a multivariate analysis, ventricular fibrillation arrests and pulseless electrical activity (PEA) were significant predictors of 1-month outcome after OHCAs due to traffic collision. From a large OHCA registry in Japan, we demonstrated that 1-month survival after OHCAs due to traffic collision origin was approximately 3%, and some children even gained full recovery of neurological function.

Association of Pre-Hospital Helicopter Transport with Reduced Mortality in Traumatic Brain Injury in Japan: A Nationwide Retrospective Cohort Study.

Patients with traumatic brain injury (TBI) are severely injured patients who require timely, efficient, and specialized care. The effectiveness of helicopter emergency medical services (HEMS) for patients with TBI remains unclear. This study aimed to compare the mortality of patients with TBI transported by HEMS and ground ambulance using propensity score-matching analysis, and to analyze the effects of HEMS in various subpopulations. We conducted a retrospective analysis of the Japan Trauma Data Bank. The study period was from January 2004 to December 2018. The participants were divided into two groups: the helicopter group (patients transported by HEMS) and ground group (patients transported by ground ambulance). The principal outcome was death at hospital discharge. In total, 58,532 patients were eligible for analysis (ground group, n = 54,820 [93.7%]; helicopter group, n = 3712 [6.3%]). Helicopter transport decreased patient mortality at hospital discharge (adjusted odds ratio [OR], 0.83; 95% confidence interval [CI], 0.74-0.92). In propensity score-matched patients, the proportion of deaths at hospital discharge was lower in the helicopter (18.76%) than in the ground (21.21%) group (crude OR, 0.86; 95% CI, 0.77-0.96). The mortality rate in the helicopter group was significantly reduced in many subpopulations, especially in cases of severe TBI with a decreased level of consciousness or higher Injury Severity Score (ISS; Japan Coma Scale score 2 [adjusted OR, 0.60; 95% CI, 0.45-0.80] and ISS ≥50 [adjusted OR, 0.69; 95% CI, 0.48-0.99]). Although the study design was non-randomized, our findings in patients with TBI showed that HEMS conferred a mortality benefit over ground ambulance.

Association between vasopressor use and mortality in patients with severe traumatic brain injury: a nationwide retrospective cohort study in Japan.

AIM: Vasopressors are frequently incorporated into severe traumatic brain injury management algorithms. However, evidence regarding their clinical effectiveness is lacking. We undertook a nationwide retrospective cohort study to determine the association between vasopressor use and mortality in patients with severe traumatic brain injury. METHODS: Data were collected between January 2004 and December 2018 from the Japanese Trauma Data Bank, which includes data from 272 emergency hospitals in Japan. Adults aged 16 years and over with severe traumatic brain injury but without major extracranial injuries were examined. A severe traumatic brain injury was defined based on a Glasgow Coma Scale score of 3-8 on admission. Multivariable analysis and propensity score matching were carried out. Statistical significance was assessed using 95% confidence intervals. RESULTS: In total, 10,295 patients were eligible for analysis, with 654 included in the vasopressor group and 9,641 included in the nonvasopressor group. The proportion of deaths at hospital discharge was higher in the vasopressor group than in the nonvasopressor group (81.80% [535/654] versus 40.24% [3,880/9,641]). This finding was confirmed in a multivariable logistic regression analysis (adjusted odds ratio, 5.37; 95% confidence interval, 4.23-6.81). Among propensity score-matched patients adjusted for severity, the proportion of deaths at hospital discharge remained higher in the vasopressor group than in the nonvasopressor group (81.87% [533/651] versus 56.22% [366/651]) (odds ratio, 3.52; 95% confidence interval, 2.73-4.53). CONCLUSION: The study results suggest that vasopressor use in patients with severe isolated traumatic brain injury is associated with a higher mortality at hospital discharge.

Sex and age differences in isolated traumatic brain injury: a retrospective observational study.

BACKGROUND: Among the many factors that may influence traumatic brain injury (TBI) progression, sex is one of the most controversial. The objective of this study was to investigate sex differences in TBI-associated morbidity and mortality using data from the largest trauma registry in Japan. METHODS: This retrospective, population-based observational study included patients with isolated TBI, who were registered in a nationwide database between 2004 and 2018. We excluded patients with extracranial injury (Abbreviated Injury Scale score ≥ 3) and removed potential confounding factors, such as non-neurological causes of mortality. Patients were stratified by age and mortality and post-injury complications were compared between males and females. RESULTS: A total of 51,726 patients with isolated TBI were included (16,901 females and 34,825 males). Mortality across all ages was documented in 12.01% (2030/16901) and 12.76% (4445/34825) of males and females, respectively. The adjusted odds ratio (OR) of TBI mortality for males compared to females was 1.32 (95% confidence interval [CI], 1.22-1.42]. Males aged 10-19 years and ≥ 60 years had a significantly higher mortality than females in the same age groups (10-19 years: adjusted OR, 1.97 [95% CI, 1.08-3.61]; 60-69 years: adjusted OR, 1.24 [95% CI, 1.02-1.50]; 70-79 years: adjusted OR, 1.20 [95% CI, 1.03-1.40]; 80-89 years: adjusted OR, 1.50 [95% CI, 1.31-1.73], and 90-99 years: adjusted OR, 1.72 [95% CI, 1.28-2.32]). In terms of the incidence of post-TBI neurologic and non-neurologic complications, the crude ORs were 1.29 (95% CI, 1.19-1.39) and 1.14 (95% CI, 1.07-1.22), respectively, for males versus females. This difference was especially evident among elderly patients (neurologic complications: OR, 1.27 [95% CI, 1.14-1.41]; non-neurologic complications: OR, 1.29 [95% CI, 1.19-1.39]). CONCLUSIONS: In a nationwide sample of patients with TBI in Japan, males had a higher mortality than females. This disparity was particularly evident among younger and older generations. Furthermore, elderly males experienced more TBI complications than females of the same age.

Survival outcomes after traumatic brain injury during national academic meeting days in Japan.

Surgeons and medical staff attend academic meetings several times a year. However, there is insufficient evidence on the influence of the "meeting effect" on traumatic brain injury (TBI) treatments and outcomes. Using the Japan Trauma Data Bank, we analyzed the data of TBI patients admitted to the hospital from 2004 to 2018 during the national academic meeting days of the Japanese Association for Acute Medicine, the Japanese Society of Intensive Care Medicine, the Japanese Association for the surgery of trauma, the Japan Society of Neurotraumatology and the Japan Neurosurgical Society. The data of these patients were compared with those of TBI patients admitted 1 week before and after the meetings. The primary outcome was in-hospital death. We included 7320 patients in our analyses, with 5139 and 2181 patients admitted during the non-meeting and meeting days, respectively; their in-hospital mortality rates were 15.7% and 14.5%, respectively. No significant differences in in-hospital mortality were found (adjusted odds ratio, 0.93; 95% confidence interval, 0.78-1.11). In addition, there were no significant differences in in-hospital mortality during the meeting and non-meeting days by the type of national meeting. In Japan, it is acceptable for medical professionals involved in TBI treatments to attend national academic meetings without impacting the outcomes of TBI patients.

Original experimental rat model of blast-induced mild traumatic brain injury: a pilot study.

OBJECTIVE: Diagnosing blast-induced mild traumatic brain injury (mTBI) is difficult due to minimal imaging findings. This study aimed to establish a rat model of behavioral abnormality caused by blast-induced mTBI and detect new findings for therapeutic intervention. METHODS: We used a bench-top blast wave generator with the blast wave exiting through a 20-mm I.D. nozzle aimed at the focused target. The blast wave was directed at the head of male Wistar rats under general anesthesia positioned prone 2.5 cm below the nozzle. Peak shock wave pressure was 646.2 ± 70.3 kPa. RESULTS: After blast injury, mTBI rats did not show the findings of brain hemorrhage or contusion macroscopically and on hematoxylin-eosin-stained frozen sections but did show anorexia and weight loss in the early post-injury phase. Behavioral experiments revealed short-term memory impairment at 2 weeks and depression-like behavior at 2 and 6 weeks. Diffusion-weighted ex vivo MRI showed high-intensity areas in layers of the bilateral hippocampus. Immunohistochemical analysis revealed accumulation of reactive microglia and GFAP-positive astrocytes in the same region and loss of NeuN-positive neurons in the hippocampal pyramidal cell layer. CONCLUSIONS: This model can reflect the pathophysiology of blast-induced mTBI and could potentially be used to develop therapeutic interventions in the future.

Traumatic brain injury-related inflammatory projection: beyond local inflammatory responses.

Acute neuroinflammation induced by microglial activation is key for repair and recovery after traumatic brain injury (TBI) and could be necessary for the clearance of harmful substances, such as cell debris. However, recent clinical and preclinical data have shown that TBI causes chronic neuroinflammation, lasting many years in some cases, and leading to chronic neurodegeneration, dementia, and encephalopathy. To evaluate neuroinflammation in vivo, positron-emission tomography has been used to target translocator protein, which is upregulated in activated glial cells. Such studies have suggested that remote neuroinflammation induced by regional microglia persists even after reduced inflammatory responses at the injury site. Furthermore, unregulated inflammatory responses are associated with neurodegeneration. Therefore, elucidation of the role of neuroinflammation in TBI pathology is essential for developing new therapeutic targets for TBI. Treatment of associated progressive disorders requires a deeper understanding of how inflammatory responses to injury are triggered, sustained, and resolved and how they impact neuronal function. In this review, we provide a general overview of the dynamics of immune responses to TBI, from acute to chronic neuroinflammation. We discuss the clinical significance of remote ongoing neuroinflammation, termed "brain injury-related inflammatory projection". We also highlight positron-emission tomography imaging as a promising approach needing further development to facilitate an understanding of post-TBI inflammatory and neurodegenerative processes and to monitor the clinical effects of corresponding new therapeutic strategies.

Myeloid-Derived Suppressor Cells Infiltrate the Brain and Suppress Neuroinflammation in a Mouse Model of Focal Traumatic Brain Injury.

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive characteristics, which allow them to limit inflammation and facilitate wound healing and recovery. Although MDSCs are a newly-determined cell type that is gaining attention in the immunology field, their neuroimmunological characteristics remain unstudied. In this study, we explored the suppressive role of MDSCs in cerebral inflammatory reactions after focal traumatic brain injury (TBI) using in vivo imaging. Through morphological, functional, and phenotypic analyses we determined that CD11b+/Gr-1+ cells infiltrating the contusion area are MDSCs. MDSCs are among the first responders to tissue injury, responding even prior to microglial activation. Positron emission tomography imaging of translocator protein results suggest that infiltrating MDSCs suppress neuronal inflammation and interact with resident immune cells, like microglia, following focal TBI.

Inflammatory projections after focal brain injury trigger neuronal network disruption: An 18F-DPA714 PET study in mice.

Due to the heterogeneous pathology of traumatic brain injury (TBI), the exact mechanism of how initial brain damage leads to chronic inflammation and its effects on the whole brain remain unclear. Here, we report on long-term neuroinflammation, remote from the initial injury site, even after subsiding of the original inflammatory response, in a focal TBI mouse model. The use of translocator protein-positron emission tomography in conjunction with specialised magnetic resonance imaging modalities enabled us to visualize "previously undetected areas" of spreading inflammation after focal cortical injury. These clinically available modalities further revealed the pathophysiology of thalamic neuronal degeneration occurring as resident microglia sense damage to corticothalamic neuronal tracts and become activated. The resulting microglial activation plays a major role in prolonged inflammatory processes, which are deleterious to the thalamic network. In light of the association of this mechanism with neuronal tracts, we propose it can be termed "brain injury related inflammatory projection". Our findings on multiple spatial and temporal scales provide insight into the chronic inflammation present in neurodegenerative diseases after TBI.

[Two Cases of Colon Metastasis of Gastric Cancer by Different Metastasis Pathway].

We treated 2 cases ofcolon metastasis ofgastric cancer considered to be caused by different pathway. Case 1 was a 55- year-old male with gastric cancer associated with metastases for lymph node, gallbladder, and liver. Curative surgical treatment of distal gastrectomy, partial hepatectomy, cholecystectomy and lymph node dissection was performed. The final find- ing was, L, Less, Type 3, pT4b(GB), tub2, pN3a(10/20), sP0, CY0, pH1, pM1, Stage IV , R0. Ten months after, ileocecal resection was performed, as a tumor was detected in the cecum. It was a submucosal tumor of well to moderately differentiated adenocarcinoma, and diagnosed as a metastasis ofgastric cancer. Case 2 was a 59-year-old male who received total gastrectomy. The final finding was UE, Less, Type 4, tub2-por2, pT4a, pN2(5/19), cM0, sP0, CY0, Stage III B, R1. One year and 10 months later, unevenness and redness in the mucosal membrane ofthe transverse colon occurred. Signet-ring cells were observed by the endoscopic biopsy, and colon metastasis ofstomach cancer was diagnosed. Consequently, transverse colectomy was performed. Diffused invasion of cancer cells was observed in all layers of the wall, which was considered as metastasis via gastrocolic ligament. Although colon metastasis ofstomach cancer is rare, its pathway varies, such as infiltration, direct invasion, hematogenous, and lymphogenous. Form oflesion also varies. For diagnosis ofcolon lesion occurring during follow-up after gastric cancer, these points should be noted.

[A Very Elderly Patient Successfully Treated by Multimodality Treatment for Pancreas Cancer with Synchronous Multiple Liver Metastases and Liver Dysfunction].

We report an 86-year-old patient successfully treated by multimodality treatment for advanced pancreatic cancer with synchronous multiple liver metastases and liver dysfunction. Systemic chemotherapy(SC)(gemcitabine[GEM]1 g and 5-FU 1 g biweekly)was initiated. Two weeks after, the radiation therapy(55 Gy/25 days)was added. Three weeks after, the short period's high dose hepatic artery infusion(SPHDHAI)(5-FU[1 g]×3 days: 1 day rest: 5-FU[1 g]×3 days)was started. By these treatments, liver dysfunction was completely improved and abdominal pain was disappeared. After 2 times of weekly high dose hepatic artery infusion(WHDHAI)(5-FU 1,500mg), the mixed chemotherapy(MC)(GEM 800 mg[systemic] and 5-FU 1,500 mg hepatic artery infusion:[HAI]biweekly)were started. She could live without admission for about 1 year. About 13 months after lung metastases was appeared and she died about 19 months after first chemotherapy. Our multimodality treatment(systemic and HAI therapy and radiation)was effective for keeping patient quality of life and for improving the survival even if the patient was a very old age and showed liver dysfunction.