Nakano, Yutaka

写真a

Affiliation

School of Medicine, Department of Surgery (General and Gastroenterological Surgery) （Shinanomachi）

Position

Project Assistant Professor (Non-tenured)/Project Research Associate (Non-tenured)/Project Instructor (Non-tenured)
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Papers 【 Display / hide 】

  • Reappraisal of liver transplantation for erythropoietic protoporphyria: A deadly combination of disease recurrence and biliary complication

    Endo Y., Hibi T., Shinoda M., Obara H., Kitago M., Yagi H., Abe Y., Hasegawa Y., Matsubara K., Hori S., Tanaka M., Makiuchi S., Nakano Y., Itano O., Kuroda T., Kitagawa Y.

    Pediatric Transplantation （Pediatric Transplantation)  26 （ 4 ）  2022.06

    ISSN  13973142

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    Background: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. Case presentation: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. Conclusion: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.

  • Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross-sectional study

    Abe K., Kitago M., Kosaki K., Yamada M., Iwasaki E., Kawasaki S., Mizukami K., Momozawa Y., Terao C., Yagi H., Abe Y., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Kitagawa Y.

    Cancer Science （Cancer Science)  113 （ 5 ） 1821 - 1829 2022.05

    ISSN  13479032

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    Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.

  • Decellularized Organ-Derived Scaffold Is a Promising Carrier for Human Induced Pluripotent Stem Cells-Derived Hepatocytes

    Kojima H., Yagi H., Kushige H., Toda Y., Takayama K., Masuda S., Morisaku T., Tsuchida T., Kuroda K., Hirukawa K., Inui J., Nishi K., Nakano Y., Tanaka M., Hori S., Hasegawa Y., Abe Y., Kitago M., Adachi S., Tomi M., Matsuura K., Mizuguchi H., Kitagawa Y.

    Cells （Cells)  11 （ 8 ）  2022.04

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    Human induced pluripotent stem cells (hiPSCs) are a promising cell source for elucidating disease pathology and therapy. The mass supply of hiPSC-derived cells is technically feasible. Carriers that can contain a large number of hiPSC-derived cells and evaluate their functions in vivo-like environments will become increasingly important for understanding disease pathogenesis or treating end-stage organ failure. hiPSC-derived hepatocyte-like cells (hiPSC-HLCs; 5 × 108) were seeded into decellularized organ-derived scaffolds under circumfusion culture. The scaffolds were implanted into immunodeficient microminiature pigs to examine their applicability in vivo. The seeded hiPSC-HLCs demonstrated increased albumin secretion and up-regulated cytochrome P450 activities compared with those in standard two-dimensional culture conditions. Moreover, they showed long-term survival accompanied by neovascularization in vivo. The decellularized organ-derived scaffold is a promising carrier for hiPSC-derived cells for ex vivo and in vivo use and is an essential platform for regenerative medicine and research.

  • KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer

    Suzuki T., Masugi Y., Inoue Y., Hamada T., Tanaka M., Takamatsu M., Arita J., Kato T., Kawaguchi Y., Kunita A., Nakai Y., Nakano Y., Ono Y., Sasahira N., Takeda T., Tateishi K., Uemura S., Koike K., Ushiku T., Takeuchi K., Sakamoto M., Hasegawa K., Kitago M., Takahashi Y., Fujishiro M.

    Cancer Science （Cancer Science)   2022

    ISSN  13479032

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    KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi-institutional cohort of 1162 pancreatic cancer patients with formalin-fixed paraffin-embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS-mutant to KRAS-wild-type tumors, 1.04 [95% CI, 0.62–1.75] and 1.05 [95% CI, 0.60–1.84], respectively). Among KRAS-mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13–1.42; ptrend <0.001) and 1.31 (95% CI, 1.16–1.48; ptrend <0.001), respectively. In summary, ddPCR detected KRAS mutations in clinical specimens of pancreatic cancer with high sensitivity irrespective of parameters potentially affecting mutation detections. KRAS VAF, but not mutation positivity, was associated with survival of pancreatic cancer patients.

  • Extrahepatic approach for taping the common trunk of the middle and left hepatic veins or the left hepatic vein alone in laparoscopic hepatectomy (with videos)

    Nakano Y., Abe Y., Kitago M., Yagi H., Hasegawa Y., Hori S., Koizumi W., Ojima H., Imanishi N., Kitagawa Y.

    Journal of Hepato-Biliary-Pancreatic Sciences （Journal of Hepato-Biliary-Pancreatic Sciences)   2022

    ISSN  18686974

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    Background: Outflow control is difficult, and techniques required for effectively handling intraoperative hemorrhage during laparoscopic hepatectomy have not previously been adequately reported. Methods: Sixteen patients underwent surgery, of which 15 underwent laparoscopic left hepatectomy and one underwent laparoscopic partial hepatectomy of the caudate lobe. Encircling and taping of the common trunk of the middle (MHV) and left hepatic veins (LHV) was performed in 12 patients, and that of the LHV alone in four patients. Surgical techniques based on anatomical landmarks and histological findings are presented with videos. Histological confirmation of the anatomical landmarks for these procedures was performed in fresh cadavers to understand the anatomical structures and layers involved. Results: The median procedure duration was 15 (6-25) minutes. All procedures were performed safely with no major bleeding. Histological findings showed fibrous connective tissue between the tunica adventitia of the inferior vena cava (IVC) and the Laennec’s capsule of the liver. The layer of dissection was along the tunica adventitia of the IVC. Conclusions: The surgical techniques for encircling and taping of the common trunk of the MHV and LHV and the LHV alone based on anatomical landmarks were feasible and could allow for efficient outflow control in laparoscopic hepatectomy.

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • レクチンアレイを用いたエクソソーム糖鎖解析による新規膵癌バイオマーカーの開発

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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