Biomedical subjects

Takeshi Iwasaki

Publications and source records attributed to Takeshi Iwasaki.

13 recordsLinked to original sources

PubMed2026

Germline noncoding risk variants influence clonal hematopoiesis through altered hematopoietic enhancer activity.

Clonal hematopoiesis of indeterminate potential (CHIP) is a precursor condition characterized by the expansion of mutant hematopoietic stem and progenitor cell (HSPC) clones that increases the risk of hematologic malignancies. Although genome-wide association studies have identified multiple non-coding loci associated with CHIP susceptibility, their mechanisms remain unclear. We hypothesized that CHIP risk variants alter enhancer activity in HSPCs. To test this, we screened 1,374 non-coding variants from 51 CHIP-associated loci using a Massively Parallel Reporter Assay (MPRA) in the CD34+ fraction of MUTZ-3 cells. We identified 87 regulatory variants across 32 loci. Targeted genome editing in hematopoietic cells and complementary reporter assays in primary human HSPCs validated enhancer activity for variants regulating NKD2, FLT3, and MSI2. Functional studies demonstrated that increased MSI2 expression, modeling the effect of the CHIP risk allele, promotes clonal expansion of TET2-deficient HSPCs, providing a mechanistic link between inherited non-coding variation and CHIP clonal expansion.

Journal Article↗

PubMed2024

Muscle Tissue Transcriptome of Idiopathic Inflammatory Myopathy Reflects the Muscle Damage Process by Monocytes and Presence of Skin Lesions.

OBJECTIVE: We aim to investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM). METHODS: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl transfer RNA synthetase antibodies in the patients with DM (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach. RESULTS: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and negative monocytes and myeloid dendritic cells. Notably, patients with DM demonstrated enrichment of complement and interferon-α and γ pathway genes compared with those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and the transforming growth factor-β signaling pathway. CONCLUSION: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathologic differences among IIM subtypes. DM was characterized by complement and interferon-α and γ signaling, whereas ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.

Humans↗

PubMed2006

Relative adrenal insufficiency manifested with multiple organ dysfunction in a liver transplant patient.

Relative adrenal insufficiency is now a well-known clinical condition that occurs in critically ill patients particularly with septic complication. However, this pathology has long been unrecognized until recently in liver transplantation patients, for whom postoperative immunosuppressive therapies almost always comprise corticosteroids. We report an obvious case of relative adrenal insufficiency manifested by severe multiple organ dysfunction in a recipient after living donor liver transplantation (LDLT). A 38-year-old woman with multiple hepatocellular carcinoma developed refractory liver failure 2 months after the completion of the dual treatment; namely a cytoreductive right hepatectomy for bulky main tumors followed by 2 courses of percutaneous isolated hepatic perfusion for residual tumors in the remnant liver. She underwent a right-lobe LDLT, and postoperative immunosuppression was initiated with a low-dose tacrolimus monotherapy without corticosteroid because of a severe septic condition before transplantation. Postoperatively, she developed progressive hyperbilirubinemia, renal dysfunction, and coagulopathy. As the corticotropin stimulation test suggested the relative adrenal insufficiency, corticosteroid was commenced 40 days after LDLT. Thereafter, multiple organ dysfunction resolved dramatically and promptly. The patient is presently alive and well with completely normalized liver function 45 months after LDLT.

Adrenal Insufficiency↗

PubMed2005

Some engineering countermeasures to reduce exposure to welding fumes and gases avoiding occurrence of blow holes in welded material.

Recently, open-type push-pull ventilation systems have been widely employed as effective substitutes for the conventional local exhaust ventilation system, and have prevailed at many welding workshops in Japan. In this study, the effect of the uniform velocity on carbon dioxide (CO2) shielding arc welding was examined by laboratory experiments. The ventilation system examined in the experiments successfully fulfilled the requirement for open-type push-pull ventilators prescribed in Japanese regulations (ordinances). It was proved that the velocity at any points in the capture zone fell in the range of 50 to 150% of the average capture zone velocity. Welding defects could be avoided by controlling the flow rate of shielding gas. Unless the capture velocity exceeded a 0.8 m/s, the formation of blow-holes in the welded metal could be prevented at the shielding gas flow rate of 20 L/min. If the flow rate was provided at 30 L/min and 40 L/min, blow-holes didn't form at the capture velocity of 1.2 m/s and 1.6 m/s, respectively. At a capture velocity of faster than 0.3 m/s, the fume concentration at welder's breathing zone was reduced to a level below the limit values: ACGIH (TLV) and Japan Welding Engineering Society (CLV#). These data are important for designing open-type push-pull ventilation in the welding workshop. The other engineering countermeasures currently employed in the welding work in Japan, such as fume collecting torch and general ventilation, are also concerned in this report. #: Control Limit Value.

Air Pollutants, Occupational↗

PubMed2005

[Sustained complete remission with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for bilobar multiple hepatocellular carcinoma with portal venous tumor thrombus--a case report].

For patients with multiple bilobar hepatocellular carcinoma (m-HCC) and/or advanced portal venous tumor thrombus (Vp3, 4), there has been no effective therapy, and the survival of more than 6 months was exceptional. Under these circumstances, we have developed a dual treatment (dual Tx) that combines reductive hepatectomy with percutaneous isolated hepatic perfusion (PIHP) for such patients. This dual Tx offers the high-rate of mid- and long-term survival in a subset of patients who had previously a dismal prognosis. Herein, we report a patient with Vp4 m-HCC who was successfully treated with dual Tx and survived for more than 2 years with a complete remission of hepatic tumors. A 53-year-old man had main tumors in the right lobe liver and multiple bilobar intrahepatic metastases (IM) with portal venous tumor thrombus reaching the portal trunk. He underwent an extended right hepatectomy with portal venous tumor thrombectomy, and subsequently PIHP twice in a 3-month period after reductive hepatectomy. After dual Tx, he had sustained complete remission for more than 2 years. He died because of obstruction of the superior vena cava by recurrent tumors in the mediastinum. His clinical course after treatment strongly indicates that the dual Tx should become a major treatment option for patients with Vp3, 4 m-HCC.

Carcinoma, Hepatocellular↗

PubMed2005

[A case of multiple hepatocellular carcinoma with rapidly progressing bilateral portal vein tumor thrombosis--a complete remission achieved with dual treatment of reductive surgery plus percutaneous isolated hepatic perfusion].

We herein report a case of multiple advanced hepatocellular carcinoma (HCC) with rapidly progressing portal vein tumor thrombosis (PVTT). All of the hepatic tumors have completely disappeared for more than two years by a dual treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP). A 55-year-old man was referred to our institution on June 30, 2003. The abdominal CT scan demonstrated multiple massive HCC in the entire liver with PVTT reaching the portal trunk (Vp4). Two weeks later, the PVTT rapidly progressed to the umbilical portion of the left portal vein, and to the confluence of the superior mesenteric vein and to the splenic vein. Thus, we semi electively performed an extended right hepatectomy together with thrombectomy of the PVTT. Subsequently, he underwent a repeated PIHP (1st; doxorubicin 90 mg/m2, 2nd doxorubicin 65 mg/m2). This treatment produced complete tumor clearance of all of the residual tumors in the left liver. In March 2005, he underwent partial pneumonectomy for a metastatic lung. This again resulted in normalization of serum AFP and PIVKA-II levels. Dual treatment is considered to be the strongest therapeutic modality for multiple advanced HCC with severe PVTT. In addition, a close follow-up is required because in such far advanced cases, metastatic lesions most likely recur in the liver but also in the distant organs.

Carcinoma, Hepatocellular↗

PubMed2004

Neoadjuvant high-dose intraarterial infusion chemotherapy under percutaneous pelvic perfusion with extracorporeal chemofiltration in patients with stages IIIa-IVa cervical cancer.

OBJECTIVE: The objective of this study was to evaluate the response rate and survival of patients with locally advanced uterine cervical cancer who were treated with intraarterial infusion chemotherapy under percutaneous pelvic perfusion with extracorporeal chemofiltration (PPPEC). METHODS: Twenty-three untreated patients with stages IIIa-IVa cervical cancer were enrolled in the study. PPPEC was administered twice at 2 weeks interval using high-dose cisplatin alone (140-250 mg/m(2)) or high-dose cisplatin plus mitomycin C (7 mg/m(2)), pepleomycin (7 mg/m(2)) and 5-fluorouracil (700 mg/m(2)). Eighteen patients in whom the tumor downstaging was confirmed underwent radical surgery following PPPEC, whereas in the remaining five patients, radiotherapy was administered. RESULTS: Two weeks after the second PPPEC, the median volumetric tumor reduction and tumor response were 76% and 87%, respectively. Histologic response was 96%, while the tumor downstaging reached 83%. The curative surgery rate achieved was 89%. Five-year progression-free survival was 47% and 5-year survival rate was 74%. CONCLUSION: High-dose intraarterial infusion chemotherapy under PPPEC effectively achieved tumor downstaging and resulted in the favorable performance of the subsequent radical surgery and improved the 5-year survival rate of patients with locally advanced uterine cervical cancer.

Adult↗

PubMed2004

Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma.

OBJECTIVE: To evaluate the efficacy of a novel 2-stage treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for multiple hepatocellular carcinoma (HCC), which was previously unresectable. SUMMARY BACKGROUND DATA: Surgical resection is the treatment of choice for HCC, but the majority of patients with advanced HCC are not suitable candidates. PIHP is a minimally invasive surgery that allows high-dose regional chemotherapy of the liver, and our phase II studies have shown its profound efficacy for the local control of advanced HCC. METHODS: Twenty-five patients with multiple advanced HCC were enrolled in this prospective study. In the first stage, all patients underwent reductive hepatectomy: major hepatectomy in 13 patients and segmentectomy or less in 12. In 2 patients with subsegmentectomy, the retropancreatic and periportal metastatic lymph nodes were synchronously resected. Regardless of the type of hepatectomy, all patients routinely underwent cholecystectomy, and ligations of the right gastric artery and arterial collaterals of the remnant liver to increase the safety and efficacy of PIHP. In the second stage, PIHP with doxorubicin 60-120 mg/m2/treatment was planned for a period of 1 to 3 months after surgery. RESULTS: Of 25 enrolled patients, 22 successfully underwent PIHP an average of 1.8 times for the local control of residual liver tumors. In the remaining 3 patients, PIHP was abandoned because 2 had rapid disease progression and 1 had liver failure after surgery. In 22 patients with the 2-stage treatment, 19 (86%) had objective local tumor control (10 complete remissions and 9 partial responses with a median response duration of 16 months). The actuarial survival rate of all 25 patients was 42% at 5 years. CONCLUSIONS: Reductive surgery plus PIHP produced a strong antitumoral effect on multiple advanced HCC, when liver function allows this concentrated treatment approach, and offers long-term survival in a subset of patients who were previously deemed to have unresectable disease.

Adult↗

PubMed2003

Significant role of middle hepatic vein in remnant liver regeneration of right-lobe living donors.

For adult patients with end-stage liver disease, living-donor liver transplantation (LDLT) of right-lobe grafts with or without the middle hepatic vein (MHV) has been increasingly used in recent years. We investigated the role of the MHV in donor remnant liver regeneration after right-lobe LDLT, which has not been described in previous studies. A total of eight living donors were included in this study of right-lobe LDLT. Four donors underwent right lobectomy (without MHV), and the remaining four underwent extended right lobectomy (with MHV). Regeneration of the donor remnant liver was assessed by volumetric computed tomography studies before and 90 days after LDLT. Comparison between the right-lobe and extended right-lobe donors did not show a clear-cut difference in the net increase of remnant liver volume at 3 months. However, the mean volume increase of the medial segment at the 90th postoperative day was 7% in the extended right-lobe donors and 61% in the right-lobe donors, showing a lower value in the remnant livers without MHV. The MHV plays a specific role in remnant liver regeneration of right-lobe living donors. We expect that this knowledge will contribute to securing a margin of safety in right-lobe LDLT.

Adult↗

PubMed2003

Isolated gastric varices resulting from iatrogenic splenic vein occlusion: report of a case.

Iatrogenic splenic vein occlusion is known to be a rare cause of left-sided portal hypertension. We herein describe the clinical course of a 43-year-old woman with isolated gastric varices, which proved to be attributable to a segmental splenic vein resection during an operation for a benign pancreatic tumor 11 years previously. Seven years after the initial operation, prominent gastric varices due to left-sided portal hypertension were first noted. During the follow-up period of 4 years, she had no episodes of gastrointestinal hemorrhaging. Although the size of the gastric varices did not change, she decided to have a splenectomy considering the potential risk of variceal hemorrhaging. It may be reasonable to perform a splenectomy concomitantly when the splenic vein is to be resected or ligated during pancreatic surgery to avoid the future development of left-sided portal hypertension. However, the role of prophylactic surgery in asymptomatic patients with iatrogenic splenic vein occlusion remains to be determined.

Esophageal and Gastric Varices↗

PubMed2002

Isolated hepatic perfusion chemotherapy for unresectable malignant hepatic tumors.

Treatment failure with conventional approaches, including systemic and regional chemotherapy, for refractory advanced primary or metastatic hepatic cancers has evoked periodic waves of enthusiasm for isolated hepatic perfusion (IHP) over the past 50 years. With technical refinements of the procedure and the introduction of a novel biochemical regimen combining tumor necrosis factor and melphalan, several hepatobiliary-oncological centers initiated clinical trials of IHP in the 1990s. In parallel, a percutaneous technique of IHP has been developed in this era as a minimally invasive, simple form of IHP, and phase I and II studies have been done in some specialized centers. This study attempts to review past and current techniques of IHP, and to outline their possible role in the treatment of unresectable hepatic tumors, with special reference to hepatocellular carcinoma and colorectal hepatic metastases.

Antineoplastic Agents↗

PubMed2002

Effect of portal vein embolization on function of the nonembolized lobes of the liver: Evaluation by first-pass hepatic lidocaine extraction in dogs.

BACKGROUND: Portal vein embolization (PVE) of hepatic lobes planned for resection is known to increase the margin of safety in extended hepatic resection. We examined whether volume gain could directly translate into functional gain in the nonembolized hepatic lobes after PVE, using a unique pharmacologic model of hepatic venous isolation and charcoal hemoperfusion. METHODS: Lidocaine hydrochloride (8 mg/kg) was infused over 10 minutes in the portal vein of beagles with hepatic venous isolation and charcoal hemoperfusion, which prevented hepatic recirculation of the drug, and the lidocaine first-pass hepatic extraction ratio (Lid-HER) was determined to assess the selective lobar function of the liver. First, the correlation between Lid-HER and hepatic parenchymal weight of the lidocaine perfusion area was studied. Second, PVE was performed of the left portal branch, and Lid-HER of the nonembolized lobes was determined 1 hour or 2 weeks after PVE. RESULTS: Hepatic venous isolation and charcoal hemoperfusion reduced (>95%) the postfilter and systemic lidocaine concentrations compared with prefilter concentrations. In the first study, a significant correlation was demonstrated between Lid-HER and hepatic parenchymal weight (P =.0023, r(2) = 0.992). In the second study, both weight ratio of the nonembolized lobes relative to the whole liver and Lid-HER of the nonembolized lobes showed significant increases 2 weeks after PVE of 1.7- and 1.9-fold, respectively. CONCLUSIONS: Hepatic-weight increase paralleled functional increase, as determined by Lid-HER, in the nonembolized hepatic lobes 2 weeks after PVE. Thus, volume change directly translated into functional change in future remnant noncirrhotic liver after PVE.

Alanine Transaminase↗

PubMedDate not supplied

Safety of portal vein resection using centrifugal pump-assisted venous bypass between the superior mesenteric vein and the umbilical vein.

BACKGROUND/AIMS: To achieve complete resection of pancreatic cancer, portal vein resection has been performed with increasing frequency at the time of pancreaticoduodenal resection (pancreaticoduodenectomy or total pancreatectomy). In the meantime, visceral congestion and liver ischemia are of great concern during the procedure. We investigated safety of portal vein resection using a centrifugal pump-assisted bypass between the superior mesenteric vein and the umbilical vein. METHODOLOGY: A retrospective comparison was performed in 49 consecutive patients who underwent pancreatoduodenal resection with or without portal vein resection using the bypass for pancreatic cancer. Twenty-two patients underwent portal vein resection using the bypass (group 1). The other 27 patients undergoing pancreatoduodenal resection without portal vein resection comprise the control group (group 2). RESULTS: Total operative time was 756 +/- 159 min and 526 +/- 109 min (p<0.001) and median blood loss was 2090 mL and 1200 mL in groups 1 and 2, respectively. However, the centrifugal pump-assisted bypass allowed stable bypass flow, and neither intestinal edema nor ischemic change of the liver was observed during portal vein resection and the subsequent reconstruction. Postoperatively, the peak postoperative AST, ALT and total bilirubin levels showed no significant difference and postoperative day of starting a liquid diet was similar between the groups (9.0 +/- 5.4 vs. 9.8 +/- 3.8 days, p=0.48). In addition, the rates of morbidity (55% vs. 48%) including biliary and pancreatic leak as well as mortality (9% vs. 4%) did not significantly differ between the 2 groups. CONCLUSIONS: The centrifugal pump-assisted bypass may be useful to prevent hepatic ischemia and visceral congestion during portal vein resection procedures, resulting in similar postoperative outcomes to the control after pancreaticoduodenal resection for pancreatic cancer.

Aged↗