Publications by authors named "Takashi Motomura"

Article Synopsis
  • TM6SF2 rs58542926 (E167K) is linked to an increased risk of metabolic liver disease, prompting the need for a human model to study the mutation's effects due to conflicting animal study results.
  • A human in vitro model was developed using gene editing on induced pluripotent stem cells, leading to observations of liver cell dysfunction, including lipid accumulation and reduced VLDL secretion associated with the mutation.
  • The model demonstrated similarities to human conditions, facilitating future research on potential clinical interventions by addressing protein misfolding and ER stress related to the TM6SF2-E167K mutation.
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Introduction: This study aimed to clarify the validity of laparoscopic surgery for lower gastrointestinal perforation by comparing the clinical outcomes of laparoscopic and open emergency surgery.

Methods: We reviewed the data of patients who underwent surgery for lower gastrointestinal perforation. Patients were categorized into two groups: the laparoscopic group who underwent laparoscopic surgery, and the open group who underwent laparotomy.

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Article Synopsis
  • Colorectal perforation leads to high risks of complications and death post-surgery, prompting an investigation into patient features and risk factors.
  • A study of 147 patients revealed that complications like wound infections and abscesses were most common, with certain clinical indicators (like time to surgery and nutritional status) linked to these issues.
  • Key findings suggest that delays in surgery and specific blood test results (PNI, NLR, PLR) can predict severe complications and increased mortality rates following surgery for colorectal perforation.
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Background And Aims: Chronic liver injury that results in cirrhosis and end-stage liver disease (ESLD) causes more than 1 million deaths annually worldwide. Although the impact of genetic factors on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) has been previously studied, their contribution to the development of ESLD remains largely unexplored.

Methods: We genotyped 6 MASLD-associated polymorphisms in healthy (n = 123), metabolic dysfunction-associated steatohepatitis (MASH) (n = 145), MASLD-associated ESLD (n = 72), and ALD-associated ESLD (n = 57) cohorts and performed multinomial logistic regression to determine the combined contribution of genetic, demographic, and clinical factors to the progression of ESLD.

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Article Synopsis
  • The TM6SF2 E167K mutation is linked to increased prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), prompting the need for a human model to study its effects.
  • Researchers edited human-induced pluripotent stem cells (iPSC) to carry this mutation and observed changes like reduced TM6SF2 protein levels, increased lipid droplets, and altered cholesterol management in the resulting liver cells.
  • The study provides a reliable in vitro model for further research into the TM6SF2 E167K mutation, aiming to identify potential treatments and better understand its role in MASLD vulnerability.
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Advances in cellular engineering, as well as gene, and cell therapy, may be used to produce human tissues with programmable genetically enhanced functions designed to model and/or treat specific diseases. Fabrication of synthetic human liver tissue with these programmable functions has not been described. By generating human iPSCs with target gene expression controlled by a guide RNA-directed CRISPR-Cas9 synergistic-activation-mediator, we produced synthetic human liver tissues with programmable functions.

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Although the underlying cause may vary across countries and demographic groups, liver disease is a major cause of morbidity and mortality globally. Orthotopic liver transplantation is the only definitive treatment for liver failure but is limited by the lack of donor livers. The development of drugs that prevent the progression of liver disease and the generation of alternative liver constructs for transplantation could help alleviate the burden of liver disease.

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The initial creation of human-induced pluripotent stem cells (iPSCs) set the foundation for the future of regenerative medicine. Human iPSCs can be differentiated into a variety of cell types in order to study normal and pathological molecular mechanisms. Currently, there are well-defined protocols for the differentiation, characterization, and establishment of functionality in human iPSC-derived hepatocytes (iHep) and iPSC-derived cholangiocytes (iCho).

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The prevalence of end-stage liver disease (ESLD) in the US is increasing at an alarming rate. It can be caused by several factors; however, one of the most common routes begins with nonalcoholic fatty liver disease (NAFLD). ESLD is diagnosed by the presence of irreversible damage to the liver.

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The use of primary human hepatocytes has been hampered by limited availability of adequate numbers of fresh and viable cells due to the ongoing shortage of liver donors. Thus, there is no surplus of healthy organs from which freshly isolated cells can be prepared when needed. However, primary hepatocytes can be successfully isolated from explanted liver specimens obtained from patients receiving orthotopic liver transplantation for decompensated liver cirrhosis or for metabolic liver disease without end-stage liver disease and are a valuable resource for the pharmaceutical industry research.

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Purpose: Excessive working hours have been reported to contribute to burnout among surgeons. In Japan, work-style reform is a problem that needs immediate attention. Acute appendectomy, which often occurs at nighttime, is one of the most common emergency surgeries.

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Introduction: Pancreatic duct stents are widely used to reduce the incidence of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD); however, small stents may cause adverse effects, such as occlusion. Recently, we have tried placing a 7.5-Fr pancreatic duct stent to achieve more effective exocrine output from the pancreas; however, the association between pancreatic duct stent size and POPF remains unknown.

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Background: The role of preoperative neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CRLM) remains undetermined. This study aimed to assess the efficacy of NAC in patients with resectable CRLM, especially in high-risk subgroups for recurrence, with special reference to synchronicity and the CRLM grade in the Japanese classification system.

Methods: A retrospective analysis of a multi-institutional cohort who was diagnosed with resectable CRLM was performed.

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As diet and lifestyle have changed, fatty liver disease (FLD) has become more and more prevalent. Many genetic risk factors, such as variants of PNPLA3, TM6SF2, GCKR, and MBOAT7, have previously been uncovered via genome wide association studies (GWAS) to be associated with FLD. In 2018, a genetic variant (rs72613567, T > TA) of hydroxysteroid 17-β dehydrogenase family 13 (HSD17B13) was first associated with a lower risk of developing alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) in minor allele carriers.

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Background: Invasive aspergillosis (IA) is one of the most serious causes of death after liver transplantation (LT). IA is the second most common fungal infection, and its mortality rate exceeds 80%.

Case Presentation: A 67-year-old man presented to our hospital because of fulminant hepatitis caused by hepatitis B virus.

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Background/aim: We evaluated the relationship between low bone mineral density (BMD), also called osteopenia, and prognosis in patients who underwent resection for pancreatic cancer (PC).

Patients And Methods: We enrolled 91 consecutive patients who underwent curative resections for PC between May 2009 and January 2019. Their BMDs were measured at the Th11 vertebra using computed tomography.

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Background/aim: The Geriatric Nutritional Risk Index (GNRI) is a prognostic indicator for several cancers; however, the association between the GNRI and colorectal liver metastasis (CRLM) remains unknown.

Patients And Methods: Eighty patients who underwent hepatectomy for synchronous CRLM were divided into two groups based on the GNRI.

Results: The preoperative CA19-9 levels were significantly higher in the low (GNRI ≤98; n=30) than the normal GNRI group (GNRI >98; n=50).

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Background/aim: In order to overcome postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP), we have developed a new simple technique-Clip on Staple method.

Patients And Methods: In Clip on Staple method, pancreatic parenchyma was divided using a stapling device with a stepped-height staple design to make linear compression line, and thereafter, the full length of the staple line was reinforced by multiple clips. Clinical outcomes were retrospectively compared between Clip on Staple group (n=23) and Non-Clip group (n=38).

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Purpose: Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are reportedly predictive of the long-term outcomes of several cancers. We evaluated their correlations with the post-surgical long-term outcomes of patients with mass-forming (MF) intrahepatic cholangiocarcinoma (ICC).

Methods: The subjects of this study were 52 patients who underwent hepatic resection for MF-ICC at our hospital.

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Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL); however, the mechanism of its development has yet to be uncovered. A few ATL cases have been reported in HTLV-1-positive recipients after living donor liver transplantation. A 57-year-old HTLV-1-positive Japanese male suffered acute liver failure due to hepatitis B infection.

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Background/aim: Computed tomography (CT) has recently been applied to measure bone mineral density (BMD). However, the definition of osteopenia, which means depletion of BMD, using CT remains controversial. The aim of this study was to establish formulae to calculate standard BMD.

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Purpose: The aims of this study were to clarify the relationship of gait speed, hand grip strength, and skeletal muscle mass with complications after hepatic resection and to identify risk factors for complications in patients who underwent hepatic resection.

Methods: We evaluated the risk factors for complications after hepatic resection in 154 consecutive patients. Preoperative factors included gait speed, hand grip strength, and skeletal muscle mass.

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Background: Hemophagocytic syndrome (HPS) is a rare and potentially fatal complication following liver transplantation.

Case Presentation: A 63-year-old woman with decompensated liver cirrhosis secondary to hepatitis B virus infection underwent living donor liver transplantation using the right posterior section of her husband's liver (graft volume, 581 g; 56.8% of the recipient's standard liver volume).

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Background: Hepatic sclerosing hemangioma, a very rare benign tumor, is characterized by fibrosis and hyalinization occurring in association with degeneration of a hepatic cavernous hemangioma. Such atypical hemangiomas can be diagnosed incorrectly as primary or metastatic malignancies based on imaging characteristics. We present herein a rare case of giant and multiple hepatic sclerosing hemangiomas that are difficult to differentiate from hepatic malignancies and review the relevant literature.

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