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Article ; Online: Risk Factors Associated with the Development of Metastases in Patients with Gastroenteropancreatic Neuroendocrine Tumors

Shuzo Kohno / Masahiro Ikegami / Toru Ikegami / Hiroaki Aoki / Masaichi Ogawa / Fumiaki Yano / Ken Eto

Journal of Clinical Medicine, Vol 11, Iss 60, p

A Retrospective Analysis

2022 Volume 60

Abstract: Neuroendocrine tumors develop from systemic endocrine and nerve cells, and their occurrence has increased recently. Since these tumors are heterogeneous, pathological classification has been based on the affected organ. In 2019, the World Health ... ...

Abstract	Neuroendocrine tumors develop from systemic endocrine and nerve cells, and their occurrence has increased recently. Since these tumors are heterogeneous, pathological classification has been based on the affected organ. In 2019, the World Health Organization introduced a change expected to influence neuroendocrine tumor research, as gastroenteropancreatic neuroendocrine tumors are now included within a unified classification. This retrospective study aimed to investigate the characteristics (e.g., lymph node metastases and all other metastases) of gastroenteropancreatic neuroendocrine tumors using this new classification in 50 cases. Tumor size, depth, MIB-1 index, lymphatic invasion, venous invasion, and neuroendocrine tumor grade were significantly correlated with lymph node metastasis and other metastases. The venous invasion was more strongly correlated with lymph node metastasis and all other types of metastases than with lymphatic invasion. Identification rates for lymphatic invasion were considered lower because of structural problems such as lymphatic vessels being much thinner than veins. However, venous invasion was considered effective in compensating for the low identification rate in cases of lymphatic invasion. In future research, a unified classification and standardized framework for assessment will be important when analyzing the characteristics of neuroendocrine tumors, and large-scale studies are required.
Keywords	neuroendocrine tumor ; metastasis ; lymphatic invasion ; venous invasion ; Medicine ; R
Subject code	616 ; 630
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Efficacy of Portal Vein Embolization with a Procedure of Sheath Injection and Balloon Occlusion with Gelatin Sponge

Yosuke Nozawa / Hirokazu Ashida / Kenkichi Michimoto / Shunsuke Kisaki / Rui Kano / Hiroya Ojiri / Toru Ikegami

Journal of the Belgian Society of Radiology, Vol 105, Iss

2021 Volume 1

Abstract: Introduction: To evaluate the efficacy, safety, and associated complications of a novel and simple approach to portal vein embolization that utilizes sheath injection and balloon occlusion (PVE-SIBO) with gelatin sponge (GS) for the purpose of increasing ...

Abstract	Introduction: To evaluate the efficacy, safety, and associated complications of a novel and simple approach to portal vein embolization that utilizes sheath injection and balloon occlusion (PVE-SIBO) with gelatin sponge (GS) for the purpose of increasing future liver remnant (FLR) volume. Methods: Between 1 January, 2006, and 31 August, 2020, 20 patients (15 men, 5 women, aged 64.6 ± 10.2 years) diagnosed with hepatobiliary malignancy underwent presurgical PVE-SIBO at our institution via a percutaneous transhepatic approach to the right portal vein and embolization of the portal vein with GS. We evaluated the increased ratio of FLR volume, operation duration, recanalization rate, and complications following this procedure. Results: All procedures were successful and without complications such as subcapsular hematoma, intra-abdominal bleeding, and bile leakage. The increased ratio of FLR volume was 34.7 ± 23.7% after a mean of 14.3 ± 2.57 days, and there was a significant difference in the FLR volume before and after PVE (P < 0.01). Procedure time was 52.7 ± 11.4 minutes. Conclusion: PVE-SIBO with GS is a simple, effective, and safe procedure to increase the ratio of FLR volume prior to hepatic surgeries.
Keywords	future liver remnant ; gelatin sponge ; hepatic resection ; portal vein embolization ; balloon occlusion ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Ubiquity Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phase II trial of nafamostat mesilate/gemcitabin/S-1 for unresectable pancreatic cancer

Tadashi Uwagawa / Taro Sakamoto / Takeshi Gocho / Hiroaki Shiba / Shinji Onda / Jungo Yasuda / Yoshihiro Shirai / Ryoga Hamura / Kenei Furukawa / Katsuhiko Yanaga / Toru Ikegami

PLoS ONE, Vol 17, Iss

2022 Volume 5

Abstract: Purpose To assess the efficacy of combination chemotherapy with nafamostat mesilate, gemcitabine and S-1 for unresectable pancreatic cancer patients. Materials and methods The study was conducted as a single-arm, single center, institutional review board- ...

Abstract	Purpose To assess the efficacy of combination chemotherapy with nafamostat mesilate, gemcitabine and S-1 for unresectable pancreatic cancer patients. Materials and methods The study was conducted as a single-arm, single center, institutional review board-approved phase II trial. Patients received nafamosntat mesilate (4.8 mg/kg continuous transregional arterial infusion) with gemcitabine (1000 mg/m2 transvenous) on days 1 and15, and with oral S-1 [(80 mg/day (BSA<1.25 m2), 100 mg/day (1.25 ≤ BSA<1.5 m2), or 120 mg/day (BSA ≥1.5 m2)] on days 1–14 or, days 1–7 and 15–21. This regimen was repeated at 28-day intervals. Results Forty-seven evaluable patients (Male/Female: 31/16, Age (median): 66 (range 35–78) yrs, Stage III/IV 10/37.) were candidates in this study. Two patients in stage III (20%) could undergo conversion surgery. Twenty-four patients (51%) underwent subsequent treatment (1st line/ 2nd line / 4th line, 13/ 10/ 1, FOLFIRINOX: 12, GEM/nab-PTX: 18, TAS-118: 3, chemoradiation with S-1: 2, GEM/Erlotinib: 1, nal-IRI: 1, surgery: 2). Median PFS and OS were 9.7 (95% CI, 8.9–14.7 mo) and 14.2 months (99% CI, 13.3–23.9 mo), respectively. Median PFS in stage IV patients was 9.2 months (95% CI, 8.4–12.0 mo). Median OS in patients without subsequent treatment was 10.8 months (95% CI, 9.1–13.8 mo). Median OS in patients with subsequent treatment was 19.3 months (95% CI, 18.9–31.9 mo). Grade 4 treatment-related hematological toxicities were encountered in 7 patients. Two patients developed grade 3 allergic reaction after 6 cycles or later. No febrile neutropenia has been observed. Conclusion NAM/GEM/S-1 therapy is safe and could be promising option for unresectable pancreatic cancer, especially for stage IV cancer.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phase II trial of nafamostat mesilate/gemcitabin/S-1 for unresectable pancreatic cancer.

Tadashi Uwagawa / Taro Sakamoto / Takeshi Gocho / Hiroaki Shiba / Shinji Onda / Jungo Yasuda / Yoshihiro Shirai / Ryoga Hamura / Kenei Furukawa / Katsuhiko Yanaga / Toru Ikegami

PLoS ONE, Vol 17, Iss 5, p e

2022 Volume 0267623

Abstract	Purpose To assess the efficacy of combination chemotherapy with nafamostat mesilate, gemcitabine and S-1 for unresectable pancreatic cancer patients. Materials and methods The study was conducted as a single-arm, single center, institutional review board-approved phase II trial. Patients received nafamosntat mesilate (4.8 mg/kg continuous transregional arterial infusion) with gemcitabine (1000 mg/m2 transvenous) on days 1 and15, and with oral S-1 [(80 mg/day (BSA<1.25 m2), 100 mg/day (1.25 ≤ BSA<1.5 m2), or 120 mg/day (BSA ≥1.5 m2)] on days 1-14 or, days 1-7 and 15-21. This regimen was repeated at 28-day intervals. Results Forty-seven evaluable patients (Male/Female: 31/16, Age (median): 66 (range 35-78) yrs, Stage III/IV 10/37.) were candidates in this study. Two patients in stage III (20%) could undergo conversion surgery. Twenty-four patients (51%) underwent subsequent treatment (1st line/ 2nd line / 4th line, 13/ 10/ 1, FOLFIRINOX: 12, GEM/nab-PTX: 18, TAS-118: 3, chemoradiation with S-1: 2, GEM/Erlotinib: 1, nal-IRI: 1, surgery: 2). Median PFS and OS were 9.7 (95% CI, 8.9-14.7 mo) and 14.2 months (99% CI, 13.3-23.9 mo), respectively. Median PFS in stage IV patients was 9.2 months (95% CI, 8.4-12.0 mo). Median OS in patients without subsequent treatment was 10.8 months (95% CI, 9.1-13.8 mo). Median OS in patients with subsequent treatment was 19.3 months (95% CI, 18.9-31.9 mo). Grade 4 treatment-related hematological toxicities were encountered in 7 patients. Two patients developed grade 3 allergic reaction after 6 cycles or later. No febrile neutropenia has been observed. Conclusion NAM/GEM/S-1 therapy is safe and could be promising option for unresectable pancreatic cancer, especially for stage IV cancer.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nafamostat mesilate, a nuclear factor kappa B inhibitor, enhances the antitumor action of radiotherapy on gallbladder cancer cells.

Naoki Takada / Hiroshi Sugano / Yoshihiro Shirai / Nobuhiro Saito / Ryoga Hamura / Tomohiko Taniai / Tadashi Uwagawa / Katsuhiko Yanaga / Toru Ikegami / Toya Ohashi / Ken Eto

PLoS ONE, Vol 16, Iss 9, p e

2021 Volume 0257019

Abstract: Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. ... ...

Abstract	Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 μg/mL and 40 μg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Efficient butanol recovery from acetone–butanol–ethanol fermentation cultures grown on sweet sorghum juice by pervaporation using silicalite-1 membrane

Kanemoto, Miho / Hideyuki Negishi / Hiroyuki Ohta / Keiji Sakaki / Shigeru Chohnan / Toru Ikegami / Yasurou Kurusu / Youji Nitta

The Society for Biotechnology, Japan Journal of bioscience and bioengineering. 2016 June, v. 121, no. 6

2016

Abstract: We investigated butanol recovery by pervaporation separation, using a silicalite-1 membrane, from batch cultures of butanol-producing Clostridium beijerinckii SBP2 grown on sweet sorghum juice as a fermentation medium. The pervaporation system yielded 73% ...

Abstract	We investigated butanol recovery by pervaporation separation, using a silicalite-1 membrane, from batch cultures of butanol-producing Clostridium beijerinckii SBP2 grown on sweet sorghum juice as a fermentation medium. The pervaporation system yielded 73% (w/v) butanol from intact feed cultures containing 1% (w/v) butanol, and had a butanol permeation flux of 11 g m−2 h−1. Upon neutralization and activated charcoal treatment of the feed cultures, butanol yield and total flux increased to 82% (w/v) and 40 g m−2 h−1, respectively. This system is applicable to refining processes for practical biobutanol production from a promising energy crop, sweet sorghum.
Keywords	activated carbon ; butanol ; Clostridium beijerinckii ; energy crops ; fermentation ; juices ; neutralization ; pervaporation ; refining ; sweet sorghum
Language	English
Dates of publication	2016-06
Size	p. 697-700.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1465387-4
ISSN	1347-4421 ; 1389-1723
ISSN (online)	1347-4421
ISSN	1389-1723
DOI	10.1016/j.jbiosc.2015.11.008
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Histological architectural classification determines recurrence pattern and prognosis after curative hepatectomy in patients with hepatocellular carcinoma.

Hirohisa Okabe / Tomoharu Yoshizumi / Yo-Ichi Yamashita / Katsunori Imai / Hiromitsu Hayashi / Shigeki Nakagawa / Shinji Itoh / Norifumi Harimoto / Toru Ikegami / Hideaki Uchiyama / Toru Beppu / Shinichi Aishima / Ken Shirabe / Hideo Baba / Yoshihiko Maehara

PLoS ONE, Vol 13, Iss 9, p e

2018 Volume 0203856

Abstract: AIM:The clinical impact of pathological classification based on architectural pattern in hepatocellular carcinoma (HCC) remains elusive in spite of its well-known and common feature. METHODS:The prognostic impact of pathological classification was ... ...

Abstract	AIM:The clinical impact of pathological classification based on architectural pattern in hepatocellular carcinoma (HCC) remains elusive in spite of its well-known and common feature. METHODS:The prognostic impact of pathological classification was examined with prospective database. Three hundred and eighty HCC patients who underwent curative hepatectomy as an initial treatment in Kumamoto University were enrolled as a test cohort. The outcome was confirmed with a validation cohort in Kyushu University. RESULTS:Macrotrabecular (macro-T) subtype (n = 38) and compact subtype (n = 43) showed similar biological and prognostic features. Both showed higher AFP level and worse overall survival than microrabecular (micro-T) subtype (n = 266). Multivariate analysis for overall survival revealed that DCP ≥ 40, multiple tumor and macro-T/compact subtype were associated with poor overall survival (risk ratio = 2.2, 1.6 and 1.6; p = 0.002, 0.020, and 0.047, respectively). Of note, 32% of macro-T/compact subtype showed early recurrence within 1 year, which showed substantially low (5%) 5 year overall survival, whereas 16% of micro-T/PG subtype did. Twenty-one percent of macro-T/compact subtype showed multiple intrahepatic metastases (≥ 4) or distant metastases, which resulted in non-curative treatment, whereas 5% of micro-T/PG subtype did. In validation cohort, macro-T/compact subtype was an independent predictor of worse overall survival. CONCLUSION:Macro-T/compact subtype is biologically discriminated from micro-T and PG subtypes due to its aggressive features and poor prognosis after curative treatment. Additional treatment with curative hepatectomy on Macro-T/compact subtype should be discussed because of high possibility of systemic residual cancer cell.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan

Jun Muto / Masaya Sugiyama / Ken Shirabe / Motokazu Mukaide / Ikue Kirikae-Muto / Toru Ikegami / Tomoharu Yoshizumi / Yo-ichi Yamashita / Yoshihiko Maehara / Masashi Mizokami

Annals of Hepatology, Vol 17, Iss 4, Pp 596-

2018 Volume 603

Abstract: Introduction and aim. Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is ... ...

Abstract	Introduction and aim. Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients.Material and methods. DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalently-closed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI.Results. HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies.Conclusions. OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI.
Keywords	Occult hepatitis B virus infection ; Hepatocellular carcinoma ; Inflammation ; Specialties of internal medicine ; RC581-951
Subject code	610 ; 616
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diverse Basis of β-Catenin Activation in Human Hepatocellular Carcinoma

Hirohisa Okabe / Hiroki Kinoshita / Katsunori Imai / Shigeki Nakagawa / Takaaki Higashi / Kota Arima / Hideaki Uchiyama / Toru Ikegami / Norifumi Harimoto / Shinji Itoh / Takatoshi Ishiko / Tomoharu Yoshizumi / Toru Beppu / Satdarshan P S Monga / Hideo Baba / Yoshihiko Maehara

PLoS ONE, Vol 11, Iss 4, p e

Implications in Biology and Prognosis.

2016 Volume 0152695

Abstract: β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation ... ...

Abstract	β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC.Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues.Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001).This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diverse Basis of β-Catenin Activation in Human Hepatocellular Carcinoma

PLoS ONE, Vol 11, Iss 4, p e

Implications in Biology and Prognosis.

2016 Volume 0152695

Abstract	β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC.Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues.Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001).This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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