Papers - NANASHIMA Atsushi
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Liver-expressed antimicrobial peptide 2 is a hepatokine regulated by ghrelin, nutrients, and body weight Reviewed International coauthorship
Islam M.N., Nabekura H., Ueno H., Nishida T., Nanashima A., Sakoda H., Zhang W., Nakazato M.
Scientific Reports 14 ( 1 ) 24782 2024.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
Liver-expressed antimicrobial peptide 2 (LEAP2) is a peptide that counteracts the hunger hormone ghrelin-induced functions. Recently, we showed that vertical sleeve gastrectomy (VSG) did not alter the serum LEAP2 concentration in individuals with obesity. Here, we investigated the effects of VSG in both chow diet (CD)-fed and high-fat diet (HFD)-fed mice. In CD-fed mice, VSG increased plasma LEAP2 levels and hepatic Leap2 mRNA levels while decreasing body weight, blood glucose levels, and ghrelin levels. Intraperitoneal (ip) administration of ghrelin reversed these changes. These effects were found in both male and female mice. In contrast, VSG or weight loss in HFD-induced obese mice decreased LEAP2 levels. After fasting, the plasma LEAP2 concentration was in the following order: hepatic vein > abdominal aorta > portal vein. A high glucose concentration robustly increased the plasma LEAP2 concentration in the hepatic vein and abdominal aorta but not in the portal vein. In addition, corn oil or palmitate increased LEAP2 expression and secretion. The increase in LEAP2 levels after the meal tolerance test was delayed in the human subjects with diabetes. Our data suggest that various factors (metabolic, hormonal, and nutritional) regulate LEAP2, and the liver is the predominant site for the production and secretion of LEAP2. Furthermore, the interaction between ghrelin and LEAP2 is involved in the pathogenesis of obesity and diabetes.
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経肛門的小腸バルーン内視鏡で術前に病理診断した小腸原発悪性黒色腫の1例 Reviewed
清水一晃，内勢由佳子，市来伸彦，濵田聖暁，市原明子，七島篤志，中村恵理子，都築 諒
日本臨床外科学会雑誌 85 ( 11 ) 1551 - 1555 2024.10
Authorship：Last author Language：Japanese Publishing type：Research paper (scientific journal)
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Hosokawa A., Tamura H., Ichihara A., Imamura N., Kai K., Fukushima T., Nanashima A., Komohara Y.
Anticancer Research 44 ( 9 ) 4119 - 4125 2024.9
Language：English Publishing type：Case report Publisher：Anticancer Research
Background/Aim: Immune checkpoint inhibitors are effective in treating microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). Pathological complete response to immune checkpoint inhibitors for MSI-H metastatic CRC have been described in several reports. Liver metastasis is known to predict resistance to ani-programmed death 1 (PD-1)/PD-1 ligand 1 (PD-L1) therapy in several cancers, including CRC. Case Report: Herein, we report the case of a 23-year-old man with MSI-H colorectal liver metastasis who exhibited a pathological complete response to pembrolizumab following systemic chemotherapies. Pathological examination of the primary lesion revealed strong HLA-class I and HLA-DR expression in cancer cells. Elevated PD-L1 expression was observed in areas of increased CD8-postive T cell infiltration. Additional pathological study of regional lymph nodes showed increased PD-L1 and CD169 expression. Conclusion: A detailed pathological examination revealed PD-L1 expression not only in the primary CRC lesion but also in regional lymph nodes. Recent studies have highlighted the significance of regional lymph nodes in anti-cancer immune responses. Therefore, pathological studies using resected lymph nodes might be beneficial for predicting the response of anti-PD-1/PD-L1 therapy.
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臨床研究 術前治療後に骨盤内臓全摘術を施行した局所進行直腸癌の治療成績 Reviewed
市原明子，市来伸彦，千代反田顕，濵田聖暁，武野慎祐，七島篤志，賀本敏行，細川 歩，陣内 崇，池田拓人
宮崎医師会医学会誌 48 ( 2 ) 129 - 136 2024.9
Language：Japanese Publishing type：Research paper (scientific journal)
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A case of late-presenting congenital diaphragmatic hernia diagnosed at 5 years with acute abdomen. Reviewed
Masuya R, Nakame K, Munakata S, Takeno S, Nanashima A, Ieiri S
Surgical Case Reports 10 ( 1 ) 177 2024.7
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Acceptance of Virtual Reality Simulation Training for Stoma Care by Healthcare Providers: A Pilot Questionnaire Study After Viewing Prototype Imagings. Reviewed
Kai K, Shinoda H, Takeiri E, Hamada T, Chikubu M, Kodama Y, Higuchi K, Nanashima A
Cureus 16 ( 7 ) e65465 2024.7
Language：English Publishing type：Research paper (scientific journal)
DOI： 10.7759/cureus.65465
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Soyama A., Yamamoto H., Eguchi S., Nanashima A., Kakeji Y., Kitagawa Y., Nakamura M., Endo I.
Journal of Hepato-Biliary-Pancreatic Sciences 31 ( 7 ) 425 - 436 2024.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Hepato-Biliary-Pancreatic Sciences
Background: Although curative resection with vascular reconstruction improves the prognosis of blood-invading locally advanced hepatobiliary tumors, the mortality and morbidity of the procedure remains unclear. This study aimed to clarify the risk factors associated with mortality and morbidity in patients undergoing liver resection with vascular reconstruction. Methods: This retrospective observational study included 1215 patients undergoing hepatectomy of more than one section with vascular reconstruction, except for left lateral sectionectomy registered in the National Clinical Database (NCD) between 2015 and 2019. The rates of surgical mortality and relevant clinical factors were evaluated. Results: Among the four types of vascular reconstruction, portal venous reconstruction was frequently performed in 724 patients (59.6% of the enrolled patients). Surgical mortality was 8.1%. Patients with hepatic artery reconstruction had the highest surgical mortality rate of 15.8%. In other types of reconstruction, surgical mortality was 9.1% in the portal vein, 5.2% in inferior vena cava, and 4.9% in hepatic vein. Factors significantly associated with surgical mortality include age, sex (male), preoperative comorbidity (American Society of Anesthesiologists grade >3, respiratory distress, diabetes, preoperative pneumonia, weight loss, and obstructive jaundice), poorer liver functional reserve (indocyanine green retention rate at 15 min and prothrombin time/international normalized ratio >1.1) and accompanying biliary reconstruction. Conclusions: The NCD revealed the detailed status of liver resection combined with vascular reconstruction in Japan. Based on the results of this analysis, understanding the factors that influence the outcome and postoperative course of each procedure will provide patients with accurate information and opportunities to improve future outcomes.
DOI： 10.1002/jhbp.1435
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Masuya R., Muraji T., Harumatsu T., Machigashira S., Iwamoto Y., Ogata M., Takada L., Nishida N., Kedoin C., Nagano A., Matsui M., Murakami M., Sugita K., Yano K., Onishi S., Yamada K., Yamada W., Matsukubo M., Kawano T., Muto M., Nakame K., Kaji T., Nanashima A., Ieiri S.
Surgery Today 54 ( 5 ) 452 - 458 2024.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Surgery Today
Purpose: We compared the clinical features of patients with biliary atresia (BA) associated with a bleeding tendency (BT) at the time of the diagnosis with those of patients without a bleeding tendency (NBT). Methods: The patients’ background characteristics, age in days at the first visit, Kasai portoenterostomy (KPE), and postoperative course were retrospectively analyzed. Results: Nine of the 93 BA patients (9.7%) showed a BT, including 7 with intracranial hemorrhaging (ICH), 1 with gastrointestinal bleeding, and 1 with a prothrombin time (PT) of 0%. The age at the first visit was 62 ± 12 days old for BT patients and 53 ± 27 days old for NBT patients (p = 0.4); the age at KPE was 77 ± 9 days old for BT patients and 65 ± 24 days old for NBT patients (p = 0.2); the time from the first visit to surgery was 13 ± 7 days for BT patients and 11 ± 10 days for NBT patients (p = 0.5); and the native liver survival rate was 56% for BT patients and 58% for NBT patients (p = 1), with no significant difference in any of the parameters. The neurological outcomes of survivors of ICH were favorable. Conclusions: Appropriate BT correction allowed early KPE even after ICH, resulting in native liver survival rates comparable to those of NBT patients without significant neurological complications.
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MANGOU (Miyazaki Advanced New General Surgery of University) Wet Lab Training Relieves Anxiety About Surgical Skills in Surgical Education: A Cross-Sectional Study. Reviewed
Hiyoshi M, Kai K, Wada T, Tsuchimochi Y, Nishida T, Hamada T, Yano K, Imamura N, Kawano F, Nanashima A
Cureus 16 ( 5 ) e61273 2024.5
Authorship：Last author Language：English Publishing type：Research paper (scientific journal)
DOI： 10.7759/cureus.61273
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Kai Kengo, Nakashima Koji, Kawakami Hiroshi, Takeno Shinsuke, Hishikawa Yoshitaka, Ikenoue Makoto, Hamada Takeomi, Imamura Naoya, Shibata Tomotaka, Noritomi Tomoaki, Sasaki Fumisato, Nakamura Yoshitaka, Nanashima Atsushi
Internal Medicine 63 ( 7 ) 903 - 910 2024.4
Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Internal Medicine
<b>Introduction </b>Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available for vulnerable patients with various comorbidities at risk of salvage esophagectomy. This study assessed the impact of the Charlson comorbidity index (CCI) on the outcomes of salvage PDT using talaporfin sodium (TS) for esophageal cancer. <b>Metohds </b>Consecutive patients with esophageal cancer who underwent salvage TS-PDT from 2016 to 2022 were included in this retrospective study. We investigated the local complete response (L-CR), progression-free survival (PFS) and overall survival (OS) and evaluated the relationship between the CCI and therapeutic efficacy. <b>Results </b>In total, 25 patients were enrolled in this study. Overall, 12 patients (48%) achieved an L-CR, and the 2-year PFS and OS rates were 24.9% and 59.4%, respectively. In a multivariate analysis, a CCI ≥1 (p=0.041) and deeper invasion (p=0.048) were found to be significant independent risk factors for not achieving an L-CR. To evaluate the efficacy associated with comorbidities, we divided the patients into the CCI=0 group (n=11) and the CCI ≥1 group (n=14). The rate of an L-CR (p=0.035) and the 2-year PFS (p=0.029) and OS (p=0.018) rates in the CCI ≥1 group were significantly lower than those in the CCI=0 group. <b>Conclusion </b>This study found that the CCI was negatively associated with the efficacy of salvage TS-PDT for esophageal cancer.
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小児血液・悪性固形腫瘍患者に対する鎖骨上アプローチを用いた腕頭静脈穿刺による中心静脈カテーテル挿入術の検討 Reviewed
中目和彦，桝屋隆太，永澤 俊，中川 緑，山田 愛，木下真理子，上村幸代，盛武 浩，家入里志，七島篤志
日本小児外科学会雑誌 60 ( 2 ) 158 - 165 2024.4
Authorship：Last author Language：Japanese Publishing type：Research paper (scientific journal)
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Kai K., Hamada T., Sakae T., Sato Y., Hiyoshi M., Inomata M., Suzuki Y., Nakamura S., Azuma M., Nanashima A.
Clinical Journal of Gastroenterology 17 ( 1 ) 198 - 203 2024.2
Authorship：Last author Language：English Publishing type：Case report Publisher：Clinical Journal of Gastroenterology
A 48-year-old woman underwent transcatheter arterial embolization (TAE) for a splenic artery aneurysm, which resulted in a partial splenic infarction in the middle lobe. Five years after TAE, a 20-mm diameter mass in the noninfarcted area of the spleen was detected on imaging, which grew to 25 mm in diameter after 6 months. MRI after gadolinium administration showed a 35 × 34 mm mass within the superior pole and 15 × 12 mm mass within the inferior pole. The patient underwent laparoscopic splenectomy and had an uneventful postoperative recovery. No evidence of recurrence was observed during the 2-year follow-up period after surgery. The mass was pathologically confirmed to be sclerosing angiomatoid nodular transformation (SANT) of the spleen. While some studies hypothesize that SANT is a response to vascular injury or trauma, to the best of our knowledge, there have been no previous reports of SANT occurring after procedures directly affecting splenic blood flow. Additionally, multifocal SANTs are reported to be very rare, accounting for only 4.7% of all reported SANTs of the spleen. We highlight a rare course of SANT of the spleen and discuss the possible relationship between blood flow abnormalities and the appearance of SANT.
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The crucial role of SETDB1 in structural and functional transformation of epithelial cells during regeneration after intestinal ischemia reperfusion injury Reviewed International coauthorship
Ikenoue M., Choijookhuu N., Yano K., Fidya , Takahashi N., Ishizuka T., Shirouzu S., Yamaguma Y., Kai K., Higuchi K., Sawaguchi A., Nanashima A., Hishikawa Y.
Histochemistry and Cell Biology 161 ( 4 ) 325 - 336 2024.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Histochemistry and Cell Biology
Su (var) 3–9, enhancer of seste, trithorax (SET)-domain bifurcated histone lysine methyltransferase (SETDB1) plays a crucial role in maintaining intestinal stem cell homeostasis; however, its physiological function in epithelial injury is largely unknown. In this study, we investigated the role of SETDB1 in epithelial regeneration using an intestinal ischemia/reperfusion injury (IRI) mouse model. Jejunum tissues were sampled after 75 min of ischemia followed by 3, 24, and 48 h of reperfusion. Morphological evaluations were performed using light microscopy and electron microscopy, and the involvement of SETDB1 in epithelial remodeling was investigated by immunohistochemistry. Expression of SETDB1 was increased following 24 h of reperfusion and localized in not only the crypt bottom but also in the transit amplifying zone and part of the villi. Changes in cell lineage, repression of cell adhesion molecule expression, and decreased histone H3 methylation status were detected in the crypts at the same time. Electron microscopy also revealed aberrant alignment of crypt nuclei and fusion of adjacent villi. Furthermore, increased SETDB1 expression and epithelial remodeling were confirmed with loss of stem cells, suggesting SETDB1 affects epithelial cell plasticity. In addition, crypt elongation and increased numbers of Ki-67 positive cells indicated active cell proliferation after IRI; however, the expression of PCNA was decreased compared to sham mouse jejunum. These morphological changes and the aberrant expression of proliferation markers were prevented by sinefungin, a histone methyltransferase inhibitor. In summary, SETDB1 plays a crucial role in changes in the epithelial structure after IRI-induced stem cell loss.
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Hirashita T., Ikenaga N., Nakata K., Nakamura M., Kurahara H., Ohtsuka T., Tatsuguchi T., Nishihara K., Hayashi H., Nakagawa S., Ide T., Noshiro H., Adachi T., Eguchi S., Miyoshi A., Kohi S., Nanashima A., Nagano H., Takatsuki M., Inomata M.
Annals of Gastroenterological Surgery 8 ( 4 ) 681 - 690 2024.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Gastroenterological Surgery
Background: Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC. Patients and method: This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated. Results: There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33–3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival. Conclusions: LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.
DOI： 10.1002/ags3.12771
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Masuya R., Nakame K., Kai K., Tsuchimochi Y., Hamada T., Imamura N., Hiyoshi M., Nanashima A., Ieiri S.
Asian Journal of Endoscopic Surgery 17 ( 1 ) e13264 2024.1
Language：English Publishing type：Case report Publisher：Asian Journal of Endoscopic Surgery
A 15-year-old girl with recurrent upper abdominal pain was diagnosed with congenital biliary dilatation. Abdominal enhanced computed tomography (CT) showed the anterior segmental branch of the right hepatic artery (RHA) running across the ventral aspect of the dilated common hepatic duct (CHD). Laparoscopic extrahepatic dilated biliary duct excision and Roux-en-Y hepaticojejunostomy were planned. Intraoperatively, the dilated CHD was observed to bifurcate into the ventral and dorsal ducts, between which the anterior segmental branch of the RHA crossed through the CHD. The CHD rejoined on the distal side as one duct. We transected the CHD just above the cystic duct. The patency of the ventral and dorsal sides of the bifurcated CHD was confirmed. Laparoscopic hepaticojejunostomy was performed at the distal side of the rejoined CHD, without sacrificing the anterior segmental branch of the RHA. There was no postoperative blood flow impairment in the right hepatic lobe or anastomotic stenosis.
DOI： 10.1111/ases.13264
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咽頭喉頭頸部食道切除術後フォロー中に診断された胸部食道癌に対して経裂孔的食道切除術を施行した1例 Reviewed
落合貴裕，河野文彰，田代耕盛，武野慎祐，七島篤志
日本外科系連合学会誌 49 ( 4 ) 367 - 373 2024
Authorship：Last author Language：Japanese Publishing type：Case report
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Nanashima A., Kai K., Hamada T., Munakata S., İmamura N., Hiyoshi M., Hamada K., Shimizu I., Tsuchimochi Y., Tsuneyoshi I.
Turkish Journal of Surgery 39 ( 4 ) 328 - 335 2023.12
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Turkish Journal of Surgery
We developed a prototype VR platform, VECTORS L&M (VLM), aiming to enhance the understanding of digestive surgery for students, interns, and young surgeons by limiting costs. Its efficacy was assessed via questionnaires before implementation in surgical education. The VLM provides nine-minute VR views of surgeries, from both 180- and 360-degree angles. It was created with L.A.B. Co., Ltd. and incorporates surgery videos from biliary malignancy patients. Following VLM development, a survey was conducted among surgeons who had experienced it. Twenty-eight participants (32% of observers) responded to the survey. A majority (81%) reported positive experiences with the VR content and showed interest in VR video production, though some reported sickness. Most respondents were experienced surgeons, and nearly all believed VR was important for medical education with a mean score of 4.14 on a scale of up to 5. VR was preferred over 3D printed models due to its application versatility. Participants expressed the desire for future VR improvements, such as increased mobility, cloud connectivity, cost reduction, and better resolution. The VLM platform, coupled with this innovative teaching approach, offers experiential learning in intraabdominal surgery, effectively enriching the knowledge of students and surgeons ahead of surgical education and training.
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Terasaki F., Hirakawa S., Tachimori H., Sugiura T., Nanashima A., Komatsu S., Miyata H., Kakeji Y., Kitagawa Y., Nakamura M., Endo I.
Journal of Hepato-Biliary-Pancreatic Sciences 30 ( 12 ) 1304 - 1315 2023.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Hepato-Biliary-Pancreatic Sciences
Background: The aim of this study was to analyze the nationwide surgical outcome of a left trisectionectomy (LT) and to identify the perioperative risk factors associated with its morbidity. Methods: Cases of LT for hepato-biliary malignancies registered at the Japanese National Clinical Database between 2013 and 2019 were retrospectively reviewed. Statistical analyses were performed to identify the perioperative risk factors associated with a morbidity of Clavien–Dindo classification (CD) ≥III. Results: Left trisectionectomy was performed on 473 and 238 cases of biliary and nonbiliary cancers, respectively. Morbidity of CD ≥III and V occurred in 45% and 5% of cases with biliary cancer, respectively, compared with 26% and 2% of cases with nonbiliary cancer, respectively. In multivariable analyses, biliary cancer was significantly associated with a morbidity of CD ≥III (odds ratio, 1.87; p =.018). In subgroup analyses for biliary cancer, classification of American Society of Anesthesiologists physical status (ASA-PS) 2, portal vein resection (PVR), and intraoperative blood loss ≥30 mL/kg were significantly associated with a morbidity of CD ≥III. Conclusions: Biliary cancer induces severe morbidity after LT. The ASA-PS classification, PVR, and intraoperative blood loss indicate severe morbidity after LT for biliary cancer.
DOI： 10.1002/jhbp.1358
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Measuring intraoperative anesthetic parameters during hepatectomy with inferior vena cava clamping Reviewed
Nanashima A., Hiyoshi M., Imamura N., Hamada T., Tsuchimochi Y., Shimizu I., Ota Y., Furukawa K., Tsuneyoshi I.
Langenbeck's Archives of Surgery 408 ( 1 ) 455 2023.12
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Langenbeck's Archives of Surgery
Purpose: Uncontrollable bleeding remained problematic in anatomical hepatectomy exposing hepatic veins. Based on the inferior vena cava (IVC) anatomy, we attempted to analyze the hemodynamic and surgical effects of the combined IVC-partial clamp (PC) accompanied with the Trendelenburg position (TP). Methods: We prospectively assessed 26 consecutive patients who underwent anatomical hepatectomies exposing HV trunks between 2020 and 2023. Patients were divided into three groups: use of IVC-PC (group 1), no use of IVC-PC (group 2), and use of IVC-PC accompanied with TP (group 3). In 10 of 26 patients (38%), hepatic venous pressure was examined using transhepatic catheter insertion. Results: IVC-PC was performed in 15 patients (58%). Operating time and procedures did not significantly differ between groups. A direct hemostatic effect on hepatic veins was evaluated in 60% and 70% of patients in groups 1 and 3, respectively. Group 1 showed significantly more unstable vital status and vasopressor use (p < 0.01). Blood or fluid transfusion and urinary output were similar between groups. Group 2 had a significantly lower baseline central venous pressure (CVP), while group 3 showed a significant increase in CVP in TP. CVP under IVC-PC seemed lower than under TP; however, not significantly. Hepatic venous pressure did not significantly differ between groups. Systolic arterial blood pressure significantly decreased via IVC-PC in group 1 and to a similar extent in group 3. Heart rate significantly increased during IVC-PC (p < 0.05). Conclusion: IVC-PC combined with the TP may be an alternative procedure to control intrahepatic venous bleeding during anatomical hepatectomy exposing hepatic venous trunks.
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Successful treatment of esophageal perforation due to black esophagus (acute esophageal necrosis): a case report.
Ochiai T, Takeno S, Kawano F, Tashiro K, Nanashima A, Tsuzuki R, Doi K
General thoracic and cardiovascular surgery cases 2 ( 1 ) 96 2023.11