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AOKI TomoakiUniversity Hospital / Gastrointestinal SurgeryAssistant Professor
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■ Paper- BACKGROUND: Esophageal squamous cell carcinoma (ESCC) and hepatic cirrhosis (HC) share major risk factors, including alcohol consumption and smoking. Consequently, patients with HC exhibit an elevated incidence of ESCC. Although HC is widely recognized to contribute to poor prognosis following esophagectomy for ESCC, the underlying mechanisms remain poorly understood. This study aimed to investigate the association between hepatic fibrosis evaluated using the fibrosis-4 (FIB-4) index and postoperative outcomes among patients with ESCC undergoing esophagectomy. METHODS: We retrospectively analyzed 461 patients with ESCC who underwent minimally invasive esophagectomy at Kobe University Hospital. Hepatic fibrosis was evaluated using the FIB-4 index, which estimates liver fibrosis based on routine blood test parameters. Patients were stratified into two groups: fibrosis-positive (FIB-4 > 2.67) and fibrosis-negative (FIB-4 ≤ 2.67). RESULTS: Among patients with cT1 tumors, overall survival (OS) did not differ significantly between the two groups. However, among those with ≥cT2 tumors, the fibrosis-positive group showed significantly worse OS than the fibrosis-negative group (P = 0.0148). Additionally, the fibrosis-positive group had a significantly higher incidence of poor response to preoperative chemotherapy (P = 0.0075). Postoperative serum albumin levels were markedly lower at 3, 6, and 12 months in the fibrosis-positive group (P = 0.015, 0.043, and 0.0066, respectively). While albumin levels recovered to baseline in the fibrosis-negative group within 12 months, no such recovery was observed in the fibrosis-positive group. CONCLUSIONS: Preoperative hepatic fibrosis is associated with poor response to preoperative chemotherapy and prolonged postoperative malnutrition, contributing to poorer long-term survival outcomes among patients with ESCC undergoing minimally invasive esophagectomy.Jan. 2026, Annals of surgical oncology, 33(1) (1), 444 - 452, English, International magazineScientific journal
- BACKGROUND/AIM: Previous studies demonstrated the safety of laparoscopic gastrectomy in patients with locally advanced gastric cancer. However, the feasibility of minimally invasive surgery (MIS) following neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer remains unclear. To our knowledge, no previous study has conducted a comprehensive analysis that evaluated NAC and surgical approach simultaneously. This study aimed to assess the feasibility of MIS for locally advanced gastric cancer after NAC using a four-arm comparison. PATIENTS AND METHODS: This study retrospectively analyzed 174 patients who underwent gastrectomy at Kobe University Hospital between January 2011 and July 2024. The patients were categorized into four groups based on NAC and surgical approaches: No NAC/open surgery (n=63), no NAC/MIS (n=49), NAC/open surgery (n=20), and NAC/MIS (n=42). We compared surgical and survival outcomes among the four groups. RESULTS: Patients in the group treated with NAC/MIS experienced less blood loss, fewer transfusions, and a shorter hospital stay. Additionally, compared with the NAC/open (20%) and no NAC/MIS (6.1%) groups, the rate of severe postoperative complications (grade ≥III) was lowest in the group treated with NAC/MIS, with no incidence of pancreatic fistula. The R0 resection rate was highest (97.6%) in the group treated with NAC/MIS. Although 5-year relapse-free survival and overall survival were higher in the group treated with NAC/MIS, the differences were not statistically significant. CONCLUSION: This four-arm study suggests that minimally invasive surgery after NAC for locally advanced gastric cancer may be technically and oncologically safe.Dec. 2025, Anticancer research, 45(12) (12), 5557 - 5566, English, International magazineScientific journal
- PURPOSE: Minimally invasive esophagectomy (MIE) is the standard surgical procedure. Robot-assisted MIE (RAMIE) was developed to overcome the problems associated with conventional MIE. This study investigated whether or not standardizing surgical procedures for RAMIE using soft coagulation scissors and Maryland bipolar forceps could improve short-term outcomes. METHODS: This study included 130 patients who underwent RAMIE. Clinicopathological characteristics and surgical outcomes were compared before and after standardization by two expert surgeons as well as between the standardized and trainee groups. A cumulative sum control chart (CUSUM) was used to evaluate changes in operative time. RESULTS: The console time during the thoracic procedure was shorter in the standardized group than in the pre-standardized group (P < 0.001). The rate of recurrent laryngeal nerve palsy was lower in the standardized group than in the pre-standardized group (P = 0.039). No significant differences were observed between the standardized and trainee groups. In the standardized and trainee groups, CUSUM clearly indicated that the console time peak occurred in the 12th and 16th cases. CONCLUSIONS: Standardization of surgical procedures using an appropriate device for each surgical step could improve surgical outcomes in RAMIE. Furthermore, it may facilitate safer and more efficient surgical training.Nov. 2025, Surgery today, English, Domestic magazineScientific journal
- BACKGROUND & AIMS: Oral nutritional supplements (ONS) administered after gastrectomies can prevent postoperative weight loss. However, the amount of additional energy to be added to energy requirements after gastrectomy is unclear. This study aimed to clarify dietary energy intake and its association with weight loss in postgastrectomy patients. METHODS: We performed a single-center, single-arm, open-label, non-randomized clinical trial. Fifty patients with gastric cancer who underwent distal or total gastrectomy were included in this study. Until 3 months postoperatively, the patients continuously consumed ONS and their intake was recorded. Additionally, the patients took photos of their regular diets. Hospital visits were made every 2 weeks to investigate calorie intake (from regular diet plus ONS), physical findings, and nutritional status. The primary endpoint was the percentage of body weight loss (%BWL) at 3 months after gastrectomy. RESULTS: Data were available for 45 patients. %BWL was 7.5 ± 5.1 % at 3 months postoperatively. The group with ONS intake <200 kcal/day tended to show a lower %BWL; however, this was not significant. No correlation was observed between ONS and regular dietary calorie intake. The required calorie intake was 1588 ± 157 kcal/day. Calorie intake from regular diet alone and from regular diet plus ONS were 1330 ± 280 and 1487 ± 300 kcal/day, respectively. The sufficient group, whose total calorie intake met the requirements, had significantly reduced body weight loss, compared with the insufficient group. CONCLUSIONS: After gastrectomy, regular diet alone often fails to meet nutritional requirements, and ONS supplementation may reduce %BWL at 3 months postoperatively by correcting energy deficits. This study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR; UMIN000047451; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054111).Jul. 2025, Clinical nutrition ESPEN, 69, 449 - 457, English, International magazineScientific journal
- BACKGROUND: Several studies have compared robot-assisted minimally invasive esophagectomy (RAMIE) with conventional minimally invasive surgery (C-MIE). However, the anatomical factors that may make certain patients more suitable for RAMIE remains unclear. This study compared the surgical outcomes of RAMIE with those of C-MIE in patients with narrow mediastinum and left-shifted esophagus. METHODS: Between January 2017 and December 2023, 260 patients with esophageal squamous cell carcinoma (ESCC) who underwent MIE (C-MIE or RAMIE) at Kobe University Hospital were included in the study. We developed a new index to assess the narrow mediastinum and left-shifted esophagus at the tracheal bifurcation level using computed tomography imaging. Cox proportional hazards regression analyses were performed to identify the prognostic factors. RESULTS: Patients with a narrow mediastinum and left-shifted esophagus had a higher incidence of recurrent laryngeal nerve (RLN) palsy and fewer lymph nodes dissections than other patients (p = 0.026 and p = 0.051, respectively). In the entire cohort, the operative time in the RAMIE group was longer than that in the C-MIE group (< 0.0001). No significant differences in other variables, including RLN palsy, were observed between the two groups. Among patients with narrow mediastinum and left-shifted esophagus, RAMIE was associated with longer operative time and fewer lymph nodes dissected from the left and right sides of the upper mediastinum compared to C-MIE (p < 0.0001, 0.0001, and 0.0001, respectively). Regarding the RLN palsy, there was no significant difference (p = 0.79). CONCLUSIONS: There are challenges in performing RAMIE in patients with a narrow mediastinal and left-shifted esophagus. Therefore, establishing an effective procedure for these patients is important.Jul. 2025, Surgical endoscopy, 39(7) (7), 4156 - 4165, English, International magazineScientific journal
- Outcomes for advanced gastric cancer are improving with multidisciplinary treatment combining surgical resection and perioperative chemotherapy. In Asia, the standard of care for pathological Stage (pStage) II gastric cancer involves tegafur-gimeracil-oteracil potassium for 1 year postoperatively after gastrectomy with D2 lymph node dissection or capecitabine plus oxaliplatin for 6 months postoperatively. For pStage III gastric cancer, a combination of tegafur, gimeracil, and oteracil potassium combined with docetaxel remains the standard postoperative treatment. However, perioperative chemotherapy combined with surgery is being developed to further improve outcomes, similar to approaches in Europe. In addition, the perioperative use of molecularly targeted agents, such as trastuzumab, and immune checkpoint inhibitors, such as pembrolizumab, is expected to improve outcomes. Furthermore, improved chemotherapy outcomes have increased opportunities for surgical intervention in Stage IV gastric cancer, which was previously not indicated for surgery. In this article, we reviewed multidisciplinary treatments for Stage II-IV gastric cancer, combining surgery and chemotherapy.Jul. 2025, International journal of clinical oncology, 30(7) (7), 1268 - 1275, English, Domestic magazineScientific journal
- PURPOSE: Esophagectomy and chemoradiotherapy (CRT) are the mainstays of treatment for esophageal squamous cell carcinoma (ESCC). Older patients often do not receive full standard treatment due to physiological limitations. This study aimed to assess the long-term prognosis of surgery or non-surgery treatment for older patients with resectable ESCC. METHODS: This retrospective study included 114 patients who underwent esophagectomy (surgery group) and 65 patients who underwent CRT/radiotherapy (RT) (non-surgery group) at Kobe University Hospital. Propensity score matching was performed to identify matched patients in each tumor stage, including those with cT1N0 ESCC and cT1N-positive or cT2/3N-any ESCC. For cT1N0 ESCC, each group (surgery and non-surgery) had 14 patients. For cT1N-positive or cT2/3N-any ESCC, each group had 34 patients. RESULTS: After propensity score matching, for patients with cT1N0, the overall survival (OS) of the surgery group was significantly better than that of the non-surgery groups (p = 0.016). For cT1N-positive or cT2/3N-any patients, no significant differences were observed in OS between the two groups (p = 0.85). Before matching, in patients with cT1N0 ESCC, those who underwent RT alone had worse OS than patients who underwent surgery or CRT (p = 0.0003). In patients with cT1N-positive or cT2/3N-any ESCC, those who underwent RT alone or surgery alone had worse OS than those who underwent neoadjuvant chemotherapy plus surgery or CRT (p = 0.023). CONCLUSIONS: Patients who could not receive chemotherapy had poor survival. An appropriate treatment strategy should be considered, taking into account their general condition, especially their ability to receive chemotherapy.Jun. 2025, Esophagus : official journal of the Japan Esophageal Society, English, Domestic magazineScientific journal
- Mitochondrial transplantation (MTx) has emerged as a potential therapeutic approach for diseases associated with mitochondrial dysfunction, yet its scalability and cross-species feasibility remain underexplored. This study aimed to evaluate the dose-dependent uptake and molecular effects of xenogeneic mitochondrial transplantation (xeno-MTx) using rat-derived mitochondria in mouse neuronal systems. HT-22 hippocampal neuronal cells and a murine model of cardiac arrest-induced global cerebral ischemia were used to assess mitochondrial uptake, gene expression, and mitochondrial DNA presence. Donor mitochondria were isolated from rat pectoralis muscle and labeled with MitoTracker dyes. Flow cytometry and confocal microscopy revealed a dose-dependent increase in donor mitochondrial uptake in vitro. Quantitative PCR demonstrated a corresponding increase in rat-specific mitochondrial DNA and upregulation of Mfn2 and Bak1, with no changes in other fusion, fission, or apoptotic genes. Inhibitor studies indicated that mitochondrial internalization may involve actin-dependent macropinocytosis and cholesterol-sensitive endocytic pathways. In vivo, rat mitochondrial DNA was detected in mouse brains post-xeno-MTx, confirming donor mitochondrial delivery to ischemic tissue. These findings support the feasibility of xeno-MTx and its dose-responsive biological effects in neuronal systems while underscoring the need for further research to determine long-term functional outcomes and clinical applicability.Jun. 2025, Life (Basel, Switzerland), 15(7) (7), English, International magazineScientific journal
- Upper-extremity deep venous thrombosis (UEDVT) after whole blood donation is rarely reported. Blood donation has a low rate of complications and is typically safe. A small percentage of blood donors experience donation-related events such as UEDVT, which are extremely rare. We are reporting a rare case of a UEDVT following blood donation. This is an extremely rare event; only five cases were reported to our knowledge. A 22-year-old Caucasian woman with a past medical history of provoked pulmonary embolism completed 6 months of apixaban and negative thrombophilia workup presented to the hospital with complaints of progressive pain and swelling in her right arm. The patient reports donating blood using her right arm in January 2021. Phlebotomy duration for blood donation was approximately 10minutes. She reported pain and swelling several days after blood donation. Subsequently, a duplex ultrasound showed a thrombus in the right brachial vein. The patient was started on apixaban for 6 months. Although most whole blood donors do not experience complications, DVT is a rare complication from whole blood donation with severe consequences. It should be considered in a donor with worsening pain and swelling.Jun. 2025, The International journal of angiology : official publication of the International College of Angiology, Inc, 34(2) (2), 111 - 114, English, International magazineScientific journal
- BACKGROUND: Overlap anastomosis is widely used in gastrointestinal reconstruction during minimally invasive gastrectomy. The entry hole of the anastomosis is typically closed with hand-sewn sutures because of concerns about stenosis. This study aimed to compare the efficacy of linear stapler (LS) closure with that of hand-sewn closure of the entry hole in overlap anastomosis. METHODS: We included 172 patients who underwent overlap anastomosis during laparoscopic or robot-assisted total gastrectomy (TG, Roux-en-Y) or distal gastrectomy (DG, Roux-en-Y/Billroth II) between February 2020 and September 2024. The patients were divided into two groups based on the method of entry hole closure: the suturing group (S group) and the LS group. Surgical outcomes were retrospectively analyzed. RESULTS: There were no significant differences in patient characteristics or tumor staging between the two groups. TG was performed in 46 and 17 patients in the S and LS groups, respectively, whereas DG was performed in 41 and 68 patients in the S and LS groups, respectively. In TG patients, there was no significant difference in operative time, but the esophageal-jejunal overlap anastomosis time was significantly shorter in the LS group (38.3 vs. 20.5 min, P < 0.001). The incidence of postoperative complications was similar in both groups, and no cases of stenosis were observed in the LS group. In DG patients, the operative time and gastric-jejunal overlap anastomosis time were significantly shorter in the LS group (294 min vs. 253 min, P = 0.002; 28.5 vs. 9.0 min, P < 0.001). The length of postoperative hospital stay was significantly shorter in the LS group (13 vs. 11 days, P = 0.01). CONCLUSION: Using an LS to close the entry hole in an overlapping anastomosis during minimally invasive gastrectomy can reduce the anastomosis time and may be a safe option without increasing the risk of stenosis.May 2025, Surgical endoscopy, 39(5) (5), 3346 - 3353, English, International magazineScientific journal
- INTRODUCTION: Mitochondrial transplantation (MTx) is an emerging strategy for restoring cellular bioenergetics and mitigating ischemia-reperfusion (IR) injury. We previously demonstrated that MTx improved neurological outcomes and survival in a rat model of cardiac arrest (CA). However, the mechanisms underlying these benefits, particularly regarding immune modulation and transcriptional regulation, remain unclear. METHODS: Adult C57BL/6 mice and Sprague-Dawley rats underwent CA and resuscitation protocols, followed by intravenous MTx with species-matched donor mitochondria. Survival and neurological outcomes were assessed up to 72 h. Biodistribution and cellular uptake of fluorescent dye-labeled mitochondria were analyzed via in vivo imaging and flow cytometry. Gene expression related to mitochondrial dynamics, inflammation, and immune regulation was evaluated using qPCR. RESULTS: MTx improved 72-hour survival (33.3% vs. 0%, P = 0.006) and neurological scores compared to vehicle treatment. Reduced brain edema was observed in MTx-treated animals. Mitochondrial uptake was significantly enhanced in the brain and spleen post-CA, with key infiltrating and resident immune cell populations-including monocytes, macrophages, microglia, astrocytes, and endothelial cells-preferentially internalizing transplanted mitochondria. Circulating myeloid cells rapidly internalized functional mitochondria, with 53.9% uptake in MTx-treated CA animals versus 10.6% in controls (P < 0.001). MTx also modulated immune profiles, reducing pro-inflammatory macrophages and enhancing cytotoxic T cell numbers. Gene expression analysis showed that MTx downregulated Fission 1, preserved Mitofusin 2, and upregulated protective genes, including Hmox1, Sirt1, and Entpd1. CONCLUSIONS: MTx improves outcomes after CA, accompanied by mitochondrial uptake by immune cells and redistribution to injured tissues. This process likely modulates immune responses, enhances mitochondrial fusion, and activates cytoprotective gene expression.Mar. 2025, Resuscitation, 208, 110535 - 110535, English, International magazineScientific journal
- BACKGROUND: Post-cardiac arrest syndrome (PCAS) presents a multifaceted challenge in clinical practice, characterized by severe neurological injury and high mortality rates despite advancements in management strategies. One of the important critical aspects of PCAS is post-arrest lung injury (PALI), which significantly contributes to poor outcomes. PALI arises from a complex interplay of pathophysiological mechanisms, including trauma from chest compressions, pulmonary ischemia-reperfusion (IR) injury, aspiration, and systemic inflammation. Despite its clinical significance, the pathophysiology of PALI remains incompletely understood, necessitating further investigation to optimize therapeutic approaches. METHODS: This review comprehensively examines the existing literature to elucidate the epidemiology, pathophysiology, and therapeutic strategies for PALI. A comprehensive literature search was conducted to identify preclinical and clinical studies investigating PALI. Data from these studies were synthesized to provide a comprehensive overview of PALI and its management. RESULTS: Epidemiological studies have highlighted the substantial prevalence of PALI in post-cardiac arrest patients, with up to 50% of survivors experiencing acute lung injury. Diagnostic imaging modalities, including chest X-rays, computed tomography, and lung ultrasound, play a crucial role in identifying PALI and assessing its severity. Pathophysiologically, PALI encompasses a spectrum of factors, including chest compression-related trauma, pulmonary IR injury, aspiration, and systemic inflammation, which collectively contribute to lung dysfunction and poor outcomes. Therapeutically, lung-protective ventilation strategies, such as low tidal volume ventilation and optimization of positive end-expiratory pressure, have emerged as cornerstone approaches in the management of PALI. Additionally, therapeutic hypothermia and emerging therapies targeting mitochondrial dysfunction hold promise in mitigating PALI-related morbidity and mortality. CONCLUSION: PALI represents a significant clinical challenge in post-cardiac arrest care, necessitating prompt diagnosis and targeted interventions to improve outcomes. Mitochondrial-related therapies are among the novel therapeutic strategies for PALI. Further clinical research is warranted to optimize PALI management and enhance post-cardiac arrest care paradigms.Sep. 2024, Journal of intensive care, 12(1) (1), 32 - 32, English, International magazineScientific journal
- Background: Mitochondrial dysfunction, which is triggered by systemic ischemia–reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific mitochondrial dynamics. This review focuses on the organ-specific mitochondrial responses to IR injury, particularly examining the brain, heart, and kidneys, to highlight potential therapeutic strategies targeting mitochondrial dysfunction to enhance outcomes post-IR injury. Methods and Results: We conducted a narrative review examining recent advancements in mitochondrial research related to IR injury. Mitochondrial responses to IR injury exhibit considerable variation across different organ systems, influenced by unique mitochondrial structures, bioenergetics, and antioxidative capacities. Each organ demonstrates distinct mitochondrial behaviors that have evolved to fulfill specific metabolic and functional needs. For example, cerebral mitochondria display dynamic responses that can be both protective and detrimental to neuronal activity and function during ischemic events. Cardiac mitochondria show vulnerability to IR-induced oxidative stress, while renal mitochondria exhibit a unique pattern of fission and fusion, closely linked to their susceptibility to acute kidney injury. This organ-specific heterogeneity in mitochondrial responses requires the development of tailored interventions. Progress in mitochondrial medicine, especially in the realms of genomics and metabolomics, is paving the way for innovative strategies to combat mitochondrial dysfunction. Emerging techniques such as mitochondrial transplantation hold the potential to revolutionize the management of IR injury in resuscitation science. Conclusions: The investigation into organ-specific mitochondrial responses to IR injury is pivotal in the realm of resuscitation research, particularly within the context of PCAS. This nuanced understanding holds the promise of revolutionizing PCAS management, addressing the unique mitochondrial dysfunctions observed in critical organs affected by IR injury.MDPI AG, Apr. 2024, Life, 14(4) (4), 477 - 477Scientific journal
- Elsevier BV, Apr. 2024, The American Journal of Emergency Medicine, 78, 182 - 187Scientific journal
- Background Cardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia–reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction. Purinergic signaling, as regulated by CD39 and CD73, has emerged as centrally important in the context of organ-specific IRI. Hence, comprehensive understanding of such purinergic responses may be likewise imperative for improving outcomes in PCAS. Methods We have investigated alterations of immune cell populations after CA by utilizing rodent models of PCAS. Blood and spleen were collected after CA and resuscitation and underwent flow cytometry analysis to evaluate shifts in CD3+CD4+ helper T cells, CD3+CD8a+ cytotoxic T cells, and CD4/CD8a ratios. We then examined the expression of CD39 and CD73 across diverse cell types, including myeloid cells, T lymphocytes, and B lymphocytes. Results In both rat and mouse models, there were significant increases in the frequency of CD3+CD4+ T lymphocytes in PCAS (rat, P < 0.01; mouse, P < 0.001), with consequently elevated CD4/CD8a ratios in whole blood (both, P < 0.001). Moreover, CD39 and CD73 expression on blood leukocytes were markedly increased (rat, P < 0.05; mouse, P < 0.01 at 24h). Further analysis in the experimental mouse model revealed that CD11b+ myeloid cells, with significant increase in their population (P < 0.01), had high level of CD39 (88.80 ± 2.05 %) and increased expression of CD73 (P < 0.05). CD19+ B lymphocytes showed slight increases of CD39 (P < 0.05 at 2h) and CD73 (P < 0.05 at 2h), while, CD3+ T lymphocytes had decreased levels of them. These findings suggested a distinct patterns of expression of CD39 and CD73 in these specific immune cell populations after CA. Conclusions These data have provided comprehensive insights into the immune response after CA, highlighting high-level expressions of CD39 and CD73 in myeloid cells.Lead, Frontiers Media SA, Mar. 2024, Frontiers in Immunology, 15Scientific journal
- Abstract Background Mitochondrial transplantation (MTx) has emerged as a novel therapeutic strategy, particularly effective in diseases characterized by mitochondrial dysfunction. This review synthesizes current knowledge on MTx, focusing on its role in modulating immune responses and explores its potential in treating post-cardiac arrest syndrome (PCAS). Methods We conducted a comprehensive narrative review of animal and human studies that have investigated the effects of MTx in the context of immunomodulation. This included a review of the immune responses following critical condition such as ischemia reperfusion injury, the impact of MTx on these responses, and the therapeutic potential of MTx in various conditions. Results Recent studies indicate that MTx can modulate complex immune responses and reduce ischemia–reperfusion injury post-CA, suggesting MTx as a novel, potentially more effective approach. The review highlights the role of MTx in immune modulation, its potential synergistic effects with existing treatments such as therapeutic hypothermia, and the need for further research to optimize its application in PCAS. The safety and efficacy of autologous versus allogeneic MTx, particularly in the context of immune reactions, are critical areas for future investigation. Conclusion MTx represents a promising frontier in the treatment of PCAS, offering a novel approach to modulate immune responses and restore cellular energetics. Future research should focus on long-term effects, combination therapies, and personalized medicine approaches to fully harness the potential of MTx in improving patient outcomes in PCAS.Lead, Springer Science and Business Media LLC, Mar. 2024, Journal of Translational Medicine, 22(1) (1)Scientific journal
- Lead, Springer International Publishing, Oct. 2023, Advances in Experimental Medicine and Biology, 217 - 222In book
- Abstract Objective Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. Methods This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. Results We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. Conclusions We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.Springer Science and Business Media LLC, Oct. 2023, BMC Pulmonary Medicine, 23(1) (1)Scientific journal
- Springer Science and Business Media LLC, Jul. 2023, Purinergic Signalling, 20(4) (4), 345 - 357Scientific journal
- Abstract Cardiac arrest (CA) and concomitant post‐CA syndrome lead to a lethal condition characterized by systemic ischemia–reperfusion injury. Oxygen (O2) supply during cardiopulmonary resuscitation (CPR) is the key to success in resuscitation, but sustained hyperoxia can produce toxic effects post CA. However, only few studies have investigated the optimal duration and dosage of O2 administration. Herein, we aimed to determine whether high concentrations of O2 at resuscitation are beneficial or harmful. After rats were resuscitated from the 10‐min asphyxia, mechanical ventilation was restarted at an FIO2 of 1.0 or 0.3. From 10 min after initiating CPR, FIO2 of both groups were maintained at 0.3. Bio‐physiological parameters including O2 consumption (VO2) and mRNA gene expression in multiple organs were evaluated. The FIO2 0.3 group decreased VO2, delayed the time required to achieve peak MAP, lowered ejection fraction (75.1 ± 3.3% and 59.0 ± 5.7% with FIO2 1.0 and 0.3, respectively; p < .05), and increased blood lactate levels (4.9 ± 0.2 mmol/L and 5.6 ± 0.2 mmol/L, respectively; p < .05) at 10 min after CPR. FIO2 0.3 group had significant increases in hypoxia‐inducible factor, inflammatory, and apoptosis‐related mRNA gene expression in the brain. Likewise, significant upregulations of hypoxia‐inducible factor and apoptosis‐related gene expression were observed in the FIO2 0.3 group in the heart and lungs. Insufficient O2 supplementation in the first 10 min of resuscitation could prolong ischemia, and may result in unfavorable biological responses 2 h after CA. Faster recovery from the impairment of O2 metabolism might contribute to the improvement of hemodynamics during the early post‐resuscitation phase; therefore, it may be reasonable to provide the maximum feasible O2 concentrations during CPR.Lead, Wiley, May 2023, The FASEB Journal, 37(7) (7)Scientific journal
- Abstract Background Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia–reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation. Methods This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy. Results The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA. Conclusions MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.Springer Science and Business Media LLC, Mar. 2023, BMC Medicine, 21(1) (1)Scientific journal
- Abstract Cardiac arrest (CA) patients suffer from systemic ischemia–reperfusion (IR) injury leading to multiple organ failure; however, few studies have focused on tissue-specific pathophysiological responses to IR-induced oxidative stress. Herein, we investigated biological and physiological parameters of the brain and heart, and we particularly focused on the lung dysfunction that has not been well studied to date. We aimed to understand tissue-specific susceptibility to oxidative stress and tested how oxygen concentrations in the post-resuscitation setting would affect outcomes. Rats were resuscitated from 10 min of asphyxia CA. Mechanical ventilation was initiated at the beginning of cardiopulmonary resuscitation. We examined animals with or without CA, and those were further divided into the animals exposed to 100% oxygen (CA_Hypero) or those with 30% oxygen (CA_Normo) for 2 h after resuscitation. Biological and physiological parameters of the brain, heart, and lungs were assessed. The brain and lung functions were decreased after CA and resuscitation indicated by worse modified neurological score as compared to baseline (222 ± 33 vs. 500 ± 0, P < 0.05), and decreased PaO2 (20 min after resuscitation: 113 ± 9 vs. baseline: 128 ± 9 mmHg, P < 0.05) and increased airway pressure (2 h: 10.3 ± 0.3 vs. baseline: 8.1 ± 0.2 mmHg, P < 0.001), whereas the heart function measured by echocardiography did not show significant differences compared before and after CA (ejection fraction, 24 h: 77.9 ± 3.3% vs. baseline: 82.2 ± 1.9%, P = 0.2886; fractional shortening, 24 h: 42.9 ± 3.1% vs. baseline: 45.7 ± 1.9%, P = 0.4658). Likewise, increases of superoxide production in the brain and lungs were remarkable, while those in the heart were moderate. mRNA gene expression analysis revealed that CA_Hypero group had increases in Il1b as compared to CA_Normo group significantly in the brain (P < 0.01) and lungs (P < 0.001) but not the heart (P = 0.4848). Similarly, hyperoxia-induced increases in other inflammatory and apoptotic mRNA gene expression were observed in the brain, whereas no differences were found in the heart. Upon systemic IR injury initiated by asphyxia CA, hyperoxia-induced injury exacerbated inflammation/apoptosis signals in the brain and lungs but might not affect the heart. Hyperoxia following asphyxia CA is more damaging to the brain and lungs but not the heart.Lead, Springer Science and Business Media LLC, Feb. 2023, Scientific Reports, 13(1) (1)Scientific journal
- Springer International Publishing, Dec. 2022, Advances in Experimental Medicine and Biology, 385 - 390In book
- Elsevier BV, Nov. 2022, Clinical Therapeutics, 44(11) (11), 1471 - 1479Scientific journal
- Objective Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC‐DHA), was significantly decreased in plasma post‐CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC‐DHA supplementation on the brain post‐CA. Methods We first evaluated associations between the plasma level of LPC‐DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC‐DHA supplementation. Results We found that decreased plasma LPC‐DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC‐DHA was associated with decreased levels of brain LPC‐DHA after CA, and supplementing plasma LPC‐DHA normalized brain levels of LPC‐DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC‐DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. Interpretation The observed neuroprotection accompanied with normalized brain LPC‐DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC‐DHA post‐CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC‐DHA for brain damage after CA. ANN NEUROL 2022;91:389–403Wiley, Jan. 2022, Annals of Neurology, 91(3) (3), 389 - 403Scientific journal
- Objective: We recently reported that post-resuscitation normoxic therapy attenuates oxidative stress in multiple organs and improves post-cardiac arrest (CA) organ injury, oxygen metabolism, and survival. Yet, detailed mechanisms of gene expression patterns and signaling pathways mitigated by normoxic therapy have not been elucidated. Therefore, we assessed post-resuscitation normoxic therapy-modified gene expression of oxidative stress-related signaling molecules. Methods: Rats were resuscitated from 10 minutes of asphyxial CA and divided into 2 groups: those that inhaled 100% supplemental O 2 (CA-FIO2 1.0) and those that inhaled 30% supplemental O 2 (CA-FIO2 0.3). Control groups were also prepared for comparison (control-FIO2 1.0, control-FIO2 0.3). At 2 hours after resuscitation, brain and heart tissues were collected, and mRNA purifications followed by real-time PCR measurements were performed to compare gene expression of hyperoxia-induced inflammatory and apoptosis-related signaling pathways amongst these groups. Results: In the brain, relative IL-1 beta mRNA gene expression levels, which represent inflammatory signaling pathways, increased post-CA (8.1±2.3 in CA-FIO2 1.0 and 1.0±0.4 in control-FIO2 0.3, p<0.05), but were significantly attenuated by normoxic therapy (2.3±0.2 in CA-FIO2 0.3, p<0.05). Likewise, normoxic therapy significantly reduced oxidative stress-induced inflammatory (NFKB1, TGFB1, MAPK14, TRAF6) and apoptosis-related (BAX, EGF) mRNA gene expression levels in the brain, whereas no statistical differences were detected in the heart. Conclusions: Post-CA normoxic therapy significantly attenuated the gene expression of oxidative stress-induced inflammation and apoptosis in the brain, while there were no remarkable changes in the heart. Therefore, it is inferred that the heart is more tolerant to hyperoxic injury compared to the brain.Lead, Ovid Technologies (Wolters Kluwer Health), Nov. 2021, Circulation, 144(Suppl_2) (Suppl_2)Scientific journal
- Abstract Background Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. Methods Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. Results The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan–Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in d-glutamine and d-glutamate metabolism. Conclusions H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia–reperfusion injury in critically ill patients who require ECMO support.Springer Science and Business Media LLC, Nov. 2021, Journal of Translational Medicine, 19(1) (1)Scientific journal
- Abstract This case report describes a 52-year-old male patient, with the incidental finding of inferior vena cava filter (IVCF) fragments impacted into the right ventricle, secondary to IVCF fragmentation and subsequent embolization. While IVCFs are prescribed to prevent pulmonary embolizations when anticoagulation is either contraindicated, or has failed, IVCF embolizations to the heart represent an extremely rare, but potentially life-threatening complication. Of note, at the time of writing, the utility and effectiveness of IVCF are not fully established. Intracardiac embolizations of IVCF typically present with complications such as hypotension, cardiac tamponade, arrhythmias, ventricle perforation, bleeding, cardiac arrest, and death. To our knowledge, this is the first case report of an asymptomatic kidney transplant recipient found to have right ventricle embolizations of IVCF fragments through routine assessment. Additionally, this is also the first report of an asymptomatic patient who presented IVCF fragments embolized to the right ventricle and left gonadal vein in the same clinical setting.Georg Thieme Verlag KG, Jul. 2021, International Journal of AngiologyScientific journal
- Elsevier BV, Jul. 2021, Resuscitation, 164, 46 - 53Scientific journal
- Abstract Using a new method for measuring the molecular ratio (R) of inhalation to exhalation, we investigated the effect of high fraction of inspired oxygen (FIO2) on oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ) in mechanically ventilated rats. Twelve rats were equally assigned into two groups by anesthetics: intravenous midazolam/fentanyl vs. inhaled isoflurane. R, VO2, VCO2, and RQ were measured at FIO2 0.3 or 1.0. R error was ± 0.003. R was 1.0099 ± 0.0023 with isoflurane and 1.0074 ± 0.0018 with midazolam/fentanyl. R was 1.0081 ± 0.0017 at an FIO2 of 0.3 and 1.0092 ± 0.0029 at an FIO2 of 1.0. There were no differences in VCO2 among the groups. VO2 increased at FIO2 1.0, which was more notable when midazolam/fentanyl was used (isoflurane-FIO2 0.3: 15.4 ± 1.1; isoflurane-FIO2 1.0: 17.2 ± 1.8; midazolam/fentanyl-FIO2 0.3: 15.4 ± 1.1; midazolam/fentanyl-FIO2 1.0: 21.0 ± 2.2 mL/kg/min at STP). The RQ was lower at FIO2 1.0 than FIO2 0.3 (isoflurane-FIO2 0.3: 0.80 ± 0.07; isoflurane-FIO2 1.0: 0.71 ± 0.05; midazolam/fentanyl-FIO2 0.3: 0.79 ± 0.03; midazolam/fentanyl-FIO2 1.0: 0.59 ± 0.04). R was not affected by either anesthetics or FIO2. Inspired 100% O2 increased VO2 and decreased RQ, which might be more remarkable when midazolam/fentanyl was used.Springer Science and Business Media LLC, Jun. 2021, Scientific Reports, 11(1) (1)Scientific journal
- This case series reviews four critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [coronavirus disease 2019 (COVID-19)] suffering from pneumatosis intestinalis (PI) during their hospital admission. All patients received the biological agent tocilizumab (TCZ), an interleukin (IL)-6 antagonist, as an experimental treatment for COVID-19 before developing PI. COVID-19 and TCZ have been independently linked to PI risk, yet the cause of this relationship is unknown and under speculation. PI is a rare condition, defined as the presence of gas in the intestinal wall, and although its pathogenesis is poorly understood, intestinal ischemia is one of its causative agents. Based on COVID-19's association with vasculopathic and ischemic insults, and IL-6's protective role in intestinal epithelial ischemia–reperfusion injury, an adverse synergistic association of COVID-19 and TCZ can be proposed in the setting of PI. To our knowledge, this is the first published, single center, case series of pneumatosis intestinalis in COVID-19 patients who received tocilizumab therapy.Frontiers Media SA, Jun. 2021, Frontiers in Medicine, 8Scientific journal
- Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.Springer Science and Business Media LLC, May 2021, Journal of Translational Medicine, 19(1) (1)Scientific journal
- Background: Identification of the mechanisms underlying mitochondrial dysfunction is key to understanding the pathophysiology of acute injuries such as cardiac arrest (CA); however, effective methods for measurement of mitochondrial function associated with mitochondrial isolation have been debated for a long time. This study aimed to evaluate the dysregulation of mitochondrial respiratory function after CA while testing the sampling bias that might be induced by the mitochondrial isolation method. Materials and Methods: Adult rats were subjected to 10-min asphyxia-induced CA. 30 min after resuscitation, the brain and kidney mitochondria from animals in sham and CA groups were isolated (n = 8, each). The mitochondrial quantity, expressed as protein concentration (isolation yields), was determined, and the oxygen consumption rates were measured. ADP-dependent (state-3) and ADP-limited (state-4) respiration activities were compared between the groups. Mitochondrial quantity was evaluated based on citrate synthase (CS) activity and cytochrome c concentration, measured independent of the isolation yields. Results: The state-3 respiration activity and isolation yield in the CA group were significantly lower than those in the sham group (brain, p < 0.01; kidney, p < 0.001). The CS activity was significantly lower in the CA group as compared to that in the sham group (brain, p < 0.01; kidney, p < 0.01). Cytochrome c levels in the CA group showed a similar trend (brain, p = 0.08; kidney, p = 0.25). Conclusions: CA decreased mitochondrial respiration activity and the quantity of mitochondria isolated from the tissues. Owing to the nature of fragmented or damaged mitochondrial membranes caused by acute injury, there is a potential loss of disrupted mitochondria. Thus, it is plausible that the mitochondrial function in the acute-injury model may be underestimated as this loss is not considered.Lead, Frontiers Media SA, Apr. 2021, Frontiers in Medicine, 8Scientific journal
- Abstract The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = −0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.Springer Science and Business Media LLC, Jan. 2021, Scientific Reports, 11(1) (1)Scientific journal
- (一社)日本消化器外科学会, Dec. 2020, 日本消化器外科学会総会, 75回(Supplement1) (Supplement1), P103 - 4, Japanese短期間に再発した腹腔内遊離ガス及び縦隔気腫を伴う腸管嚢胞様気腫症の1例
- (一社)日本内視鏡外科学会, Dec. 2019, 日本内視鏡外科学会雑誌, 24(7) (7), MO155 - 2, Japanese当科における腸閉塞症に対する腹腔鏡下手術の検討
- 日本臨床外科学会, Oct. 2019, 日本臨床外科学会雑誌, 80(増刊) (増刊), 610 - 610, Japanese皮下埋め込み式中心静脈ポートのカテーテル先端の逸脱を繰り返した1例
- PURPOSE: The surgical indication of laparoscopic surgery for pT4 colon cancer remains to be established because only a few studies have investigated the short- and long-term outcomes of laparoscopic surgery for them to date. Therefore, we aimed to elucidate the validity of laparoscopic surgery for them. METHODS: We retrospectively analyzed 81 patients with pT4 colon cancer who underwent surgical resection with a curative intent at Kobe University Hospital from January 2007 to December 2015. The short- and long-term outcomes were compared between the propensity score-matched patients who underwent laparoscopic colectomy (LAP group, n = 25) and those who underwent open colectomy (OP group, n = 25). RESULTS: Intraoperative blood loss was significantly less in the LAP group than in the OP group (p = 0.029). Operative time, R0 resection rate, and morbidity did not significantly differ between the two groups. The 5-year overall survival (OS) and the 5-year recurrence-free survival (RFS) did not significantly differ between the propensity score-matched groups. Univariate and multivariate analyses of the entire cohort showed the surgical approach (LAP vs OP) selected was not a significant prognostic factor for OS or RFS. CONCLUSIONS: The short and the long-term outcomes were similar between the LAP and OP groups. Laparoscopic surgery might be a safe and feasible option for pT4 colon cancer patients.Lead, Jul. 2019, International journal of colorectal disease, 34(7) (7), 1259 - 1265, English, International magazineScientific journal
- (NPO)日本食道学会, Jun. 2019, 日本食道学会学術集会プログラム・抄録集, 73回, 288 - 288, Japaneseロボット支援下食道切除術の導入と初期治療成績
- (株)南江堂, Jun. 2019, 外科, 81(7) (7), 716 - 720, Japanese【消化管術後合併症-発症要因と対応】胃術後食物停滞の発症要因,予防対策と対応
- Collective invasion is an important strategy of cancers of epithelial origin, including colorectal cancer (CRC), to infiltrate efficiently into local tissues as collective cell groups. Within the groups, cells at the invasive front, called leader cells, are highly polarized and motile, thereby providing the migratory traction that guides the follower cells. However, its underlying mechanisms remain unclear. We have previously shown that signaling emanating from the receptor tyrosine kinase Ror2 can promote invasion of human osteosarcoma cells and that intraflagellar transport 20 (IFT20) mediates its signaling to regulate Golgi structure and transport. Herein, we investigated the role of Ror2 and IFT20 in collective invasion of CRC cells, where Ror2 expression is either silenced or nonsilenced. We show by cell biological analyses that IFT20 promotes collective invasion of CRC cells, irrespective of expression and function of Ror2. Intraflagellar transport 20 is required for organization of Golgi‐associated, stabilized microtubules, oriented toward the direction of invasion in leader cells. Our results also indicate that IFT20 promotes reorientation of the Golgi apparatus toward the front side of leader cells. Live cell imaging of the microtubule plus‐end binding protein EB1 revealed that IFT20 is required for continuous polarized microtubule growth in leader cells. These results indicate that IFT20 plays an important role in collective invasion of CRC cells by regulating organization of Golgi‐associated, stabilized microtubules and Golgi polarity in leader cells.Lead, Wiley, Feb. 2019, Cancer Science, 110(4) (4), 1306 - 1316Scientific journal
- (一社)日本癌学会, Sep. 2018, 日本癌学会総会記事, 77回, 1333 - 1333, EnglishIFT20は微小管ダイナミックスを制御することで大腸癌細胞の浸潤能亢進に寄与する(IFT20 promotes invasiveness of colorectal cancer cells by regulating microtubule dynamics)
- (一社)日本消化器外科学会, Jul. 2018, 日本消化器外科学会総会, 73回(Supplement1) (Supplement1), 661 - 661, JapanesepT4b症例における腹腔鏡手術の治療成績
- Lead, Springer Science and Business Media LLC, Jun. 2018, Esophagus, 15(4) (4), 286 - 293Scientific journal
- (一社)日本外科学会, Apr. 2018, 日本外科学会定期学術集会抄録集, 118回, 1370 - 1370, Japanese胸腔鏡下食道切除術に対する3D内視鏡の導入と治療成績
- 金原出版(株), Aug. 2017, 手術, 71(9) (9), 1335 - 1340, Japanese手術手技 3ステップ法による腹腔鏡下脾彎曲授動の定型化
- (NPO)日本食道学会, Jun. 2017, 日本食道学会学術集会プログラム・抄録集, 71回, W1 - 9, Japanese食道良性疾患の外科治療 食道非上皮性腫瘍の術前診断とその有用性
- (NPO)日本食道学会, Jun. 2017, 日本食道学会学術集会プログラム・抄録集, 71回, P8 - 6, Japanese食道癌同時性重複癌症例に対する同時手術治療症例の検討
- (一社)日本内視鏡外科学会, Dec. 2016, 日本内視鏡外科学会雑誌, 21(7) (7), OS50 - 5, Japanese3ステップ法による腹腔鏡下脾彎曲授動の定型化
- (NPO)日本食道学会, Jul. 2016, 日本食道学会学術集会プログラム・抄録集, 70回, 42 - 42, Japanese食道非上皮性腫瘍の治療 食道非上皮性腫瘍の診断と手術治療の検討
- 日本外科系連合学会, May 2016, 日本外科系連合学会誌, 41(3) (3), 401 - 401, Japanese各科手術におけるエネルギーデバイス使用の現状 腹臥位食道癌手術におけるエネルギーデバイスの使い分けとコツ
- 日本外科系連合学会, May 2016, 日本外科系連合学会誌, 41(3) (3), 443 - 443, Japaneseシミュレーションは手術をどこまで変えるか 食道癌手術における気管支動脈3D-CT術前ナビゲーションの有用性
- (一社)日本内視鏡外科学会, Dec. 2015, 日本内視鏡外科学会雑誌, 20(7) (7), OS209 - 5, Japanese腹腔鏡補助下・後縦隔経路再建術の手技と工夫
- (一社)日本内視鏡外科学会, Dec. 2015, 日本内視鏡外科学会雑誌, 20(7) (7), OS306 - 4, Japanese胸腔鏡下食道切除術の治療成績の検討
- (一社)日本消化器外科学会, Nov. 2015, 日本消化器外科学会雑誌, 48(11) (11), 952 - 960, Japanese
- Japanese Journal of Cancer and Chemotherapy Publishers Inc., Oct. 2015, Japanese Journal of Cancer and Chemotherapy, 42(10) (10), 1148 - 1151, JapaneseCurrent status and future prospects of chemoradiotherapy for esophageal cancer[Refereed]
- (株)癌と化学療法社, Oct. 2015, 癌と化学療法, 42(10) (10), 1148 - 1151, Japanese
- (一社)日本外科学会, Apr. 2015, 日本消化器外科学会雑誌(Web), 115回(11) (11), RS - 10, JapanesePancreaticoduodenectomy for the Periampullary Cancers Involving an Aberrant Right Hepatic Artery
- (一社)日本胃癌学会, Mar. 2015, 日本胃癌学会総会記事, 87回, 249 - 249, JapaneseStageIV胃癌に対する化学療法後Conversion surgeryの治療成績
- (一社)日本胃癌学会, Mar. 2015, 日本胃癌学会総会記事, 87回, 471 - 471, Japanese胃癌術後の閉塞性黄疸に対する内視鏡的胆管ステントの有用性
- 日本臨床外科学会, Oct. 2014, 日本臨床外科学会雑誌, 75(増刊) (増刊), 703 - 703, Japanese肝動脈走行異常を伴う遠位胆管癌に対し膵頭十二指腸切除を施行した2例
- 日本臨床外科学会, Oct. 2014, 日本臨床外科学会雑誌, 75(増刊) (増刊), 724 - 724, Japanese当院5年間における下部消化管穿孔手術例の検討 臨床的特徴と予後因子に関する検討
- (一社)日本消化器外科学会, Oct. 2014, 日本消化器外科学会雑誌, 47(Suppl.2) (Suppl.2), 197 - 197, Japanese血管合併切除ならびに血行再建により根治術が可能であった右外腸骨動静脈に浸潤した盲腸癌の一切除例
- (一社)日本胆道学会, Aug. 2014, 胆道, 28(3) (3), 532 - 532, Japanese胆嚢十二指腸瘻に対し胃空腸吻合術を施行した一例
- (NPO)日本食道学会, Jul. 2014, 日本食道学会学術集会プログラム・抄録集, 68回, 138 - 138, Japanese当院における食道癌術後胃管癌症例の検討
- (一社)日本消化器外科学会, Jul. 2014, 日本消化器外科学会総会, 69回(Supplement1) (Supplement1), P - 4, JapaneseAmyand's herniaに急性虫垂炎を合併し一期的に腹腔鏡下手術した一例
- (一社)日本外科学会, Mar. 2014, 日本外科学会雑誌, 115(臨増2) (臨増2), 992 - 992, Japanese当院における高齢者胃癌患者に対する腹腔鏡下胃切除の検討
- (一財)日本消化器病学会, Mar. 2014, 日本消化器病学会雑誌, 111(臨増総会) (臨増総会), A294 - A294, Japanese総胆管結石の既往が腹腔鏡下胆嚢摘出術へ及ぼす影響の検討
- (一財)日本消化器病学会, Mar. 2014, 日本消化器病学会雑誌, 111(臨増総会) (臨増総会), A345 - A345, Japanese胃癌術後に腹腔内出血をきたした症例の検討
- (一財)日本消化器病学会, Mar. 2014, 日本消化器病学会雑誌, 111(臨増総会) (臨増総会), A414 - A414, Japanese十二指腸潰瘍穿孔における腹腔鏡下穿孔部閉鎖・大網被覆術の検討
- (一社)日本胃癌学会, Mar. 2014, 日本胃癌学会総会記事, 86回, 276 - 276, Japanese当院でのLECS症例の検討
- (一社)日本胃癌学会, Mar. 2014, 日本胃癌学会総会記事, 86回, 294 - 294, Japanese胃癌術後早期に多発性脳梗塞を呈しTrousseau症候群と診断した1例
- (一社)日本胃癌学会, Mar. 2014, 日本胃癌学会総会記事, 86回, 328 - 328, Japanese術前CEA高値を呈した胃癌症例の検討
- (一社)日本胃癌学会, Mar. 2014, 日本胃癌学会総会記事, 86回, 358 - 358, Japanese胃腺癌、胃小細胞癌と胃粘膜下腫瘍が混在していた1症例
- (一社)日本胃癌学会, Mar. 2014, 日本胃癌学会総会記事, 86回, 377 - 377, JapanesecStageIV胃癌に対して胃切除後に化学療法を施行した症例と化学療法後に胃切除術を施行した症例の検討
- (一社)日本内視鏡外科学会, Nov. 2013, 日本内視鏡外科学会雑誌, 18(7) (7), 508 - 508, Japanese腹腔鏡補助下胃切除術と開腹下胃切除術の術後長期QOLの比較検討
- 日本臨床外科学会, Oct. 2013, 日本臨床外科学会雑誌, 74(増刊) (増刊), 437 - 437, Japanese女性外科医によるワークショップ(消化器) 急性期病院における育児と消化器外科勤務の両立とキャリア形成の現状
- 日本臨床外科学会, Oct. 2013, 日本臨床外科学会雑誌, 74(増刊) (増刊), 721 - 721, Japanese内視鏡的粘膜下層剥離術(ESD)後に施行した腹腔鏡下胃切除術(LAG)の安全性に関する検討
- 日本臨床外科学会, Oct. 2013, 日本臨床外科学会雑誌, 74(増刊) (増刊), 796 - 796, Japaneseリンパ節転移を伴った縦隔悪性嚢胞性胚細胞腫瘍の1例
- 日本臨床外科学会, Oct. 2013, 日本臨床外科学会雑誌, 74(増刊) (増刊), 847 - 847, Japanese3種の組織型から構成される後腹膜混合型脂肪肉腫の1例
- 日本臨床外科学会, Oct. 2013, 日本臨床外科学会雑誌, 74(増刊) (増刊), 962 - 962, Japanese腸閉塞を呈した非特異性小腸潰瘍の1切除例
- (一社)日本胆道学会, Aug. 2013, 胆道, 27(3) (3), 642 - 642, Japanese肝動脈走行異常を伴う膵頭部領域癌に対する膵頭十二指腸切除 癌腫の前面を肝動脈が異常走行していた症例
- (一財)日本消化器病学会, Feb. 2013, 日本消化器病学会雑誌, 110(臨増総会) (臨増総会), A338 - A338, Japanese肝動脈分岐異常を有する膵頭十二指腸切除術の7例 癌浸潤を疑う肝動脈温存の可否
- (一社)日本胃癌学会, Feb. 2013, 日本胃癌学会総会記事, 85回, 372 - 372, Japanese残胃の癌の臨床病理学的検討
- (一社)日本内視鏡外科学会, Dec. 2012, 日本内視鏡外科学会雑誌, 17(7) (7), 527 - 527, Japanese腹腔鏡下手術を施行した傍上行結腸窩ヘルニアの1例
- (一社)日本消化器外科学会, Jul. 2011, 日本消化器外科学会総会, 66回(Supplement1) (Supplement1), 940 - 940, Japanese腹腔鏡補助下に切除し得た魚骨による急性腹症の1例
- 2025, 日本外科系連合学会誌, 50(2) (2)高度進行胃癌に対する集学的治療戦略
- 2025, 制癌剤適応研究会プログラム・抄録集, 57th術前化学療法を施行した胸部食道癌における病理学的腫瘍径と予後の関係
- 2025, 制癌剤適応研究会プログラム・抄録集, 57thSOX+Nivolumab療法により病理学的完全奏効を得られた切除不能進行胃癌の1例
- 2025, 日本外科学会定期学術集会(Web), 125th根治的胃切除を行った高齢胃癌患者における予後因子としての周術期Geriatric Nutritional Risk Indexの有用性
- 2025, 日本外科学会定期学術集会(Web), 125th左側食道かつ狭縦隔症例におけるロボット支援下食道切除と胸腔鏡下食道切除術の比較
- 2025, 日本外科学会定期学術集会(Web), 125th腹腔鏡・ロボット支援胃切除術のoverlap吻合における自動縫合器による共通孔閉鎖の有用性についての検討
- 2025, 日本外科学会定期学術集会(Web), 125th表在性非乳頭部十二指腸上皮性腫瘍に対する十二指腸腹腔鏡内視鏡合同手術の有効性の検討
- 2025, 日本外科学会定期学術集会(Web), 125th食道癌に対するロボット支援下食道切除術のlearning curveと短期および長期成績
- 2025, 日本外科学会定期学術集会(Web), 125th胃癌に対する腹腔鏡手術と比較したロボット支援下胃切除術の中長期成績
- 2025, 手術, 79(3) (3)右上葉区域肺静脈分岐の破格を伴う食道癌に対してロボット支援食道切除術を行った1例
- 2025, 大腸癌研究会学術集会プログラム・抄録集, 102ndNACRT後直腸癌に対するTaTMEの手術成績
- 2018, 日本分子生物学会年会プログラム・要旨集(Web), 41stIFT20は大腸がん細胞の集団的浸潤における先導細胞の極性を制御する
- 2016, 日本消化器癌発生学会総会プログラム・抄録集, 27th手術治療をおこなった食道GISTの2例
- 2015, 日本ヘルニア学会学術集会プログラム・抄録集, 13thTAPP術後の再発症例に対する再TAPP3例の経験
- 2014, 日本肝胆膵外科学会学術集会プログラム・抄録集(CD-ROM), 26th術前後に黄疸が長期遷延した膵癌の一切除例
- 2013, 日本消化器病学会雑誌, 110当院における小腸悪性腫瘍の経験
- 2013, 日本外科学会雑誌, 114高齢者胃癌に対する腹腔鏡下胃切除術の検討
- 2013, 日本外科学会雑誌, 114総胆管結石の既往が腹腔鏡下胆嚢摘出術へ及ぼす影響の検討
- 2013, 日本胃癌学会総会記事, 85th当院における高齢者胃癌に対する腹腔鏡下胃切除の検討
- 2013, 日本消化器病学会雑誌, 110開腹既往歴のない小腸イレウスに対する手術の検討
- 2013, 日本外科学会雑誌, 114胃全摘後,空腸パウチ間置再建の長期成績
- 2013, 日本胃癌学会総会記事, 85th当院における腹腔鏡補助下噴門側胃切除症例の検討
- 2013, 日本胃癌学会総会記事, 85th胃癌手術症例におけるGlasgow proghostic score (GPS)の有用性
- 2013, 日本胃癌学会総会記事, 85th審査腹腔鏡にて腹膜播種を伴う胃GISTと診断後,イマチニブが奏効し原発巣切除を施行した1例
- 2012, 日本臨床外科学会雑誌, 73非切除後5年の長期生存が得られた膵癌の一剖検例
- 2012, 日本臨床外科学会雑誌, 73回腸原発神経内分泌細胞癌の一例
- 2012, 日本臨床外科学会雑誌, 73審査腹腔鏡にて腹膜播種を伴う胃GISTと診断後,イマチニブが奏功し原発巣切除を施行した1例
- 2011, 日本循環器学会近畿地方会(Web), 111thDICを伴った,超高齢者巨大腹部大動脈瘤の一例
- American Heart Association Scientific Sessions, English, National Center, Philadelphia, United States, International conferenceImmediate Internalization of Transplanted Mitochondria in Circulatory Immune Cells After Cardiac Arrest Resuscitation in RatsPublic symposium
- 45th Annual Conference on Shock 2022, English, University of Calgary, Toronto, Canada, International conferenceINSUFFICIENT OXYGEN INHALATION DURING CARDIOPULMONARY RESUSCITATION INDUCES UNFAVORABLE BIOLOGICAL RESPONSES IN POST-CARDIAC ARREST RATSPublic symposium
- American Heart Association Scientific Sessions, English, National Center, Web, International conferenceStress Related mRNA Gene Expressions in a Post-Cardiac Arrest Rat ModelPublic symposium
- 第73回日本食道学会学術集会, Japanese, 独立行政法人国立病院機構 九州がんセンター, 福岡, Japan, Domestic conferenceロボット支援下食道切除術の導入と初期治療成績Poster presentation
- 第77回日本癌学会学術総会, Japanese, 日本癌学会, 大阪, Japan, Domestic conferenceIFT20は微小管ダイナミックスを制御することで大腸癌細胞の浸潤能亢進に寄与するPoster presentation
- 第73回日本消化器外科学会総会, Japanese, 一般社団法人 日本消化器外科学会, 鹿児島, Japan, Domestic conferencepT4b症例における腹腔鏡手術の治療成績Oral presentation
- 第118回日本外科学会定期学術集会, Japanese, 一般社団法人日本外科学会, 東京, Japan, Domestic conference胸腔鏡下食道切除術に対する3D内視鏡の導入と治療成績Public symposium
- 第71回日本食道学会学術集会, Japanese, 佐久医療センター 内視鏡内科, 軽井沢, Japan, Domestic conference食道癌同時性重複癌症例に対する同時手術治療症例の検討Poster presentation
- 第71回日本食道学会学術集会, Japanese, 佐久医療センター 内視鏡内科, 軽井沢, Japan, Domestic conference食道非上皮性腫瘍の術前診断とその有用性Public symposium
- 第29回日本内視鏡外科学会総会, Japanese, 北里大学医学部外科, 横浜, Japan, Domestic conference3ステップ法による腹腔鏡下脾弯曲授動の定型化Oral presentation
- 第27回日本消化器癌発生学会総会, Japanese, 鹿児島大学大学院 消化器・乳腺甲状腺外科学, 鹿児島, Japan, Domestic conference手術治療をおこなった食道GISTの2例Oral presentation
- 第29回近畿内視鏡外科研究会, Japanese, 近畿内視鏡外科研究会事務局, 京都, Japan, Domestic conference3ステップ法による腹腔鏡下結腸脾弯曲授動Oral presentation
- 第70回日本食道学会学術集会, Japanese, 虎の門病院 消化器外科, 東京, Japan, Domestic conference食道非上皮性腫瘍の診断と手術治療の検討Public symposium
- 第41回日本外科系連合学会学術集会, Japanese, 兵庫医科大学外科学(肝・胆・膵外科), 大阪, Japan, Domestic conference食道癌手術における気管支動脈3D-CT術前ナビゲーションの有用性Public symposium
- 第41回日本外科系連合学会学術集会, Japanese, 兵庫医科大学外科学(肝・胆・膵外科), 大阪, Japan, Domestic conference腹臥位食道癌手術におけるエネルギーデバイスの使い分けとコツPublic symposium
- 第28回日本内視鏡外科学会総会, Japanese, 関西医科大学腎泌尿器外科学講座, 大阪, Japan, Domestic conference胸腔鏡下食道切除術の治療成績の検討Oral presentation
- 第28回日本内視鏡外科学会総会, Japanese, 関西医科大学腎泌尿器外科学講座, 大阪, Japan, Domestic conference腹腔鏡補助下・後縦隔経路再建術の手技と工夫Oral presentation
- 第68回日本胸部外科学会定期学術集会, Japanese, 神戸大学大学院医学研究科外科学講座 心臓血管外科分野, 神戸, Japan, Domestic conference食道癌に対する腹腔鏡補助下胃管作成・後縦隔再建術Public symposium
