Publications by authors named "Soichiro Ako"

14 Publications

  • Page 1 of 1

Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells.

Pancreas 2021 04;50(4):524-528

From the Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Objectives: Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic endotoxemia), which is thought to mediate obesity-associated inflammation. However, the direct effects of LPS on PDAC cells are poorly understood.

Methods: The expression of toll-like receptor 4, the receptor for LPS, was confirmed in PDAC cell lines. AsPC-1 and PANC-1 cells were exposed to LPS, and differential gene expression was determined by RNA sequencing. The activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by LPS in PDAC cells was assessed by Western blotting.

Results: The expression of toll-like receptor 4 was confirmed in all PDAC cell lines. The exposure to LPS led to differential expression of 3083 genes (426 ≥5-fold) in AsPC-1 and 2584 genes (339 ≥5-fold) in PANC-1. A top canonical pathway affected by LPS in both cell lines was PI3K/Akt/mTOR. Western blotting confirmed activation of this pathway as measured by phosphorylation of the ribosomal protein S6 and Akt.

Conclusions: The exposure of PDAC cells to LPS led to differential gene expression. A top canonical pathway was PI3K/Akt/mTOR, a known oncogenic driver. Our findings provided evidence that LPS can directly induce differential gene expression in PDAC cells.
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http://dx.doi.org/10.1097/MPA.0000000000001790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097724PMC
April 2021

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach Occurring With Ball Valve Syndrome.

Clin Gastroenterol Hepatol 2020 Jul 23. Epub 2020 Jul 23.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

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http://dx.doi.org/10.1016/j.cgh.2020.07.044DOI Listing
July 2020

Human Telomerase Reverse Transcriptase Gene Promoter Mutation in Serum of Patients with Hepatocellular Carcinoma.

Oncology 2020 5;98(5):311-317. Epub 2020 Mar 5.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Background: Mutations in the human telomerase reverse transcriptase (hTERT) gene promoter have been reported in hepatocellular carcinoma (HCC); however, analyses of these mutations in liquid biopsies have been technically difficult because of the high GC content of the regions of interest within this promoter. We evaluated the feasibility and prognostic value of hTERT promoter mutations identified in circulating cell-free DNA (cfDNA) from the serum of patients with HCC.

Objective: A cohort of HCC patients (n = 36) who were curatively treated by surgical resection between June 2003 and September 2014 were enrolled in this study.

Methods: The presence of hTERT promoter mutations in cfDNA from the patients' serum was analyzed via modified droplet digital polymerase chain reaction, and associations were sought between specific promoter mutations and patients' disease-free survival (DFS).

Results: The G>A hTERT mutation at -124 bp was detected in the serum of 25 patients (69%). Although no marked differences were observed between the characteristics of the serum mutation-positive and serum mutation-negative patient groups, the DFS of patients with the mutation was significantly shorter than that of the serum mutation-negative patients (p = 0.02). Among 18 clinicopathologic and background liver factors examined, the presence of the -124 bp G>A mutation was an independent and significant predictor of patients' DFS (hazard ratio = 3.01, 95% confidence interval 1.11-10.5, p = 0.03) in multivariate analyses.

Conclusions: The -124 bp G>A hTERT promoter mutation was observed in the serum of 69% of HCC patients who underwent surgical resection and was an independent predictor of disease progression in HCC.
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http://dx.doi.org/10.1159/000506135DOI Listing
May 2020

Evaluation of Local Recurrence of Pancreatic Cancer by KRAS Mutation Analysis Using Washes from Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

Dig Dis Sci 2020 10 2;65(10):2907-2913. Epub 2020 Jan 2.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.

Background And Aims: The sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing the recurrence of pancreatic cancer is usually low because of difficulties in obtaining adequate samples for pathological examinations. We evaluated the efficacy of highly sensitive KRAS mutation analysis using EUS-FNA washes to detect cancer recurrence.

Methods: Nineteen consecutive patients with suspected pancreatic cancer recurrence after surgical resection were enrolled. All underwent EUS-FNA, and samples were obtained for pathological examination. After the first session, the inside of the FNA needle was washed with saline for DNA extraction. KRAS mutations were examined using digital droplet PCR (dPCR).

Results: The median needle puncture number used to obtain adequate pathological samples was two (range 1-6). In ten patients pathologically diagnosed with malignant pancreatic cancer, nine patients tested positive for a KRAS mutation. All patients who were not diagnosed with a malignant pancreatic cancer tested negative for a KRAS mutation. About half of surgically resected primary cancers (9/19) showed double KRAS mutations (G12V and G12D); however, all but one wash sample showed a single KRAS mutation, G12D. After including one patient who showed a malignant recurrence during follow-up, the sensitivities of a pathological diagnosis and KRAS analysis to detect recurrence were 90.9% and 81.8%, respectively.

Conclusions: KRAS mutation analysis of needle wash samples using dPCR is a new methodology for the diagnosis of the local recurrence of pancreatic cancer. The diagnostic ability of dPCR with a one-time needle wash sample was comparable to a pathological diagnosis with multiple samplings.
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http://dx.doi.org/10.1007/s10620-019-06006-6DOI Listing
October 2020

Utility of liquid biopsy using urine in patients with pancreatic ductal adenocarcinoma.

Cancer Biol Ther 2019;20(10):1348-1353. Epub 2019 Jul 22.

Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine , Okayama , Japan.

In recent years, liquid biopsy for blood and body fluid in cancer patients has attracted attention. However, there have been few reports of liquid biopsy focusing on urine of pancreatic ductal adenocarcinoma (PDAC). In 56 patients with PDAC, DNA was extracted from urine and plasma prior to treatment, and KRAS mutations were analyzed with droplet digital PCR to examine the mutation detection rate. Our study showed that KRAS mutations were found in 27 cases (48%) in urine and 27 cases (48%) in plasma. The detection rate of urine KRAS mutations varied by renal functions. The rates were 70% (14/20) and 36% (13/36) in the creatinine clearance rate (CCr) < 70 mL/min group and in the CCr ≥ 70 mL/min group, respectively ( = .024). Whereas, no influence of the CCr was observed in the detection rates of plasma KRAS mutations. The rates were 50% (10/20) and 47% (17/36) in cases with the CCr < 70 mL/min group and the CCr ≥ 70 mL/min group, respectively. Although the sample size was small, this study clearly indicated a new possibility of less invasive urine liquid biopsy in PDAC patients.
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http://dx.doi.org/10.1080/15384047.2019.1638685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783121PMC
August 2020

[Metachronous intraductal papillary mucinous carcinoma five years after cholecystectomy for gallbladder cancer in a patient with pancreaticobiliary maljunction].

Nihon Shokakibyo Gakkai Zasshi 2019;116(3):241-248

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

A 71-year-old female with non-dilated pancreaticobiliary maljunction (PBM) and gallbladder polypoid lesions underwent laparoscopic cholecystectomy. Histological examination of the polypoid lesions revealed gallbladder cancer. Five years after cholecystectomy, gradual dilatation of the main pancreatic duct (MPD) led to the identification of a papillary tumor growing in the MPD of the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Pathological examination revealed a papillary tumor with focal invasion to the MPD. Immunohistochemically, the tumor cells were positive for MUC1 and MUC5AC and negative for MUC2. Therefore, the definitive diagnosis was pancreatobiliary-type intraductal papillary mucinous carcinoma. This case emphasizes the significance of surveillance for potential cancer of the pancreas as well as the biliary tract in patients with PBM.
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http://dx.doi.org/10.11405/nisshoshi.116.241DOI Listing
June 2019

Liquid biopsy of bile for the molecular diagnosis of gallbladder cancer.

Cancer Biol Ther 2018 4;19(10):934-938. Epub 2018 May 4.

a Department of Gastroenterology and Hepatology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.

Introduction: Tissue sampling of gallbladder cancer (GBCa) is challenging because of the anatomy of the gallbladder. The aim of this study is to investigate the possibility of diagnosing GBCa patients by performing a liquid biopsy of bile in addition to current diagnostic methods.

Methods: Thirty patients with GBCa were enrolled in this study. Cytological examination was performed in all patients. Using next generation sequencing (NGS), DNA isolated from the bile and tumor tissue was analyzed for mutations in 49 oncogenes. We also compared these mutations with cytology results.

Results: 57.1% of DNA samples from tumor tissue were positive for a mutation. In these patients, 87.5% of the bile circulating tumor DNA (ctDNA) samples had the same mutation. The concordance rate between bile ctDNA and tissue DNA samples was 85.7%, and the mutation frequencies detected in ctDNA were approximately half of what was detected in tumor tissue DNA. On the other hand, the sensitivity of the cytological and bile ctDNA analyses was 45.8% and 58.3%, respectively. The concordance rate between cytology and bile ctDNA analyses was 87.5%.

Conclusions: Mutated tumor DNA could be detected in bile by NGS. Liquid biopsy of bile might help us to diagnose GBCa because of higher sensitivity and positive predict value compared to cytology with ERCP.
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http://dx.doi.org/10.1080/15384047.2018.1456604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300345PMC
September 2019

Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular Carcinoma before Radiofrequency Ablation.

Acta Med Okayama 2018 Feb;72(1):47-52

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Transcatheter arterial chemoembolization (TACE) is often performed before radiofrequency ablation (RFA) for the treatment of early-stage hepatocellular carcinoma (HCC). TACE prior to RFA can expand the ablated area and reduce the tumor size, facilitating complete ablation. However, the factors correlated with size reduction remain uncertain. The aim of this study was to identify the factors associated with size reduction by TACE and develop a formula to predict the reduction rate. A total of 100 HCC patients treated with TACE followed by RFA at least 20 days later were enrolled. The tumor size was measured at the time of TACE and RFA, and correlations between the reduction rate and 13 clinical factors were examined. A formula to predict the reduction rate was built using the factors obtained by the analysis. Reduction in the tumor size was observed in 69 nodules, and the median reduction rate was 16.2%. A multivariate regression analysis revealed that a large tumor size (p< 0.01) and a long interval between the therapies (p= 0.01) were factors for a high tumor reduction rate, with tumor size more strongly related to the degree of reduction. A size reduction of more than 10% can be expected by waiting 20 days after TACE when the size of the tumor at TACE is over 25 mm in diameter. The tumor size.
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http://dx.doi.org/10.18926/AMO/55662DOI Listing
February 2018

Comparing reduced-dose sodium phosphate tablets to 2 L of polyethylene glycol: A randomized study.

World J Gastroenterol 2017 Jun;23(24):4454-4461

Soichiro Ako, Koji Takemoto, Eriko Yasutomi, Chihiro Sakaguchi, Mayu Murakami, Tomoko Sunami, Shohei Oka, Hamada Kenta, Noriko Okazaki, Yuki Baba, Yasushi Yamasaki, Toshiyuki Asato, Daisuke Kawai, Ryuta Takenaka, Hirohumi Tsugeno, Shigeatsu Fujiki, Department of Gastroenterology, Tsuyama Chuo Hospital, Tsuyama City, Okayama 708-0841, Japan.

Aim: To compare the tolerability and quality of bowel cleansing between 2 L polyethylene glycol (PEG) and reduced-dose sodium phosphate (NaP) tablets as a preparation for colonoscopy.

Methods: Two hundred patients were randomly assigned to the PEG or NaP groups at the same ratio. The NaP group patients took 30 tablets with 2 L of clear liquid, while the PEG group patients took 2L of PEG. Tolerability was assessed by a questionnaire about taste, volume, and the overall impression. The bowel cleansing quality was evaluated by colonoscopists.

Results: Although NaP showed better tolerability in terms of taste, volume and overall impression ( < 0.01, < 0.01 and = 0.02, respectively), the overall cleansing quality was better in the PEG group ( < 0.01). A subgroup analysis, stratified by sex and age, indicated that NaP was associated with better tolerability and equivalent bowel cleansing quality in females of < 50 years of age.

Conclusion: Despite the better tolerability, the use of 30 NaP tablets with 2 L of clear liquid should be limited due to its lower cleansing quality; however, in certain cases the regimen may deserve consideration, particularly in cases involving young women.
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http://dx.doi.org/10.3748/wjg.v23.i24.4454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487510PMC
June 2017

Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue.

Pancreatology 2017 Mar - Apr;17(2):285-290. Epub 2016 Dec 27.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Background/objectives: The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR).

Methods: DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR.

Results: The amount of DNA isolated from the serum was much higher than that from plasma (1.0- to 42.0-fold). At least 1 KRAS mutation was observed in 93% of cancer tissues, whereas we detected the mutations in only 48% of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01).

Conclusions: Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.
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http://dx.doi.org/10.1016/j.pan.2016.12.011DOI Listing
October 2017

Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma.

J Gastroenterol Hepatol 2017 Mar;32(3):695-700

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.

Background And Aim: Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC.

Methods: Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching.

Results: About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (>30 mm, hazard ratio = 1.685, P = 0.043), high des-γ-carboxyprothrombin (>100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group.

Conclusions: RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.
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http://dx.doi.org/10.1111/jgh.13586DOI Listing
March 2017

[A case of diffuse cystic malformation in which submucosal tumor-like advanced gastric cancer was identified during 10-year follow-up].

Nihon Shokakibyo Gakkai Zasshi 2012 Nov;109(11):1910-9

Department of Hepatology and Gastroenterology, Osaka Red Cross Hospital.

A 66-year-old man with giant gastric folds had been followed up since February 2000. In March 2010, a submucosal tumor of 35mm was identified with endoscopy and a low echoic mass was identified with endoscopic ultrasonography. After histologic diagnosis by endosonography-guided fine needle aspiration biopsy, he underwent a total gastrectomy. Histologic examination of the resected specimen revealed a tumor 20mm in diameter consisting of well-to-moderately differentiated tubular adenocarcinoma in the thickened wall of the gastric greater curvature, which contained small cystic lesions in the lamina propria. Immunohistochemical staining showed thick gastric wall consisting of not only multiple cysts but also smooth muscle, elastic and collagen fibers. The histologic diagnosis was advanced gastric cancer accompanied by diffuse cystic malformation (DCM). Although it is a rare condition, DCM should be considered in the differential diagnosis of giant gastric folds and as a pre-cancerous lesion.
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November 2012

The effect of long-term supplementation with branched-chain amino acid granules in patients with hepatitis C virus-related hepatocellular carcinoma after radiofrequency thermal ablation.

J Clin Gastroenterol 2013 Apr;47(4):359-66

Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Tennoji-ku, Osaka, Japan.

Goals: To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ≤3.5 g/dL.

Background: Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear.

Study: We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS.

Results: The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively.

Conclusions: BCAA treatment may improve OS and RFS after RFA in patients with HCV-related HCC≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL.
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http://dx.doi.org/10.1097/MCG.0b013e31826be9adDOI Listing
April 2013

The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients.

BMC Res Notes 2012 Mar 10;5:135. Epub 2012 Mar 10.

Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.

Background: The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged < 65 years and 108 elderly patients aged ≥ 65 years. We also examined the factors contributing to a sustained virological response.

Results: There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; P = 0.378). There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040- 0.330, P < 0.001).

Conclusions: The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.
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http://dx.doi.org/10.1186/1756-0500-5-135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317866PMC
March 2012
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