Publications by authors named "Motoyasu Kan"

17 Publications

  • Page 1 of 1

"Salvage techniques" are the key to overcome difficult biliary cannulation in endoscopic retrograde cholangiopancreatography.

Sci Rep 2022 Aug 10;12(1):13627. Epub 2022 Aug 10.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba-City, 260-8670, Japan.

Although the efficacy and safety of salvage techniques for biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) have been reported, few reports analyzed the choice of techniques and their clinical outcomes in large cohorts. This study aimed to evaluate the outcomes of biliary cannulation in patients with native papillae. We retrospectively identified 1021 patients who underwent initial ERCP from January 2013 to March 2020. We investigated background factors, treatment details, cannulation success rates, and adverse event rates. Then we analyzed a series of treatment processes, including salvage techniques such as double guidewire technique (DGT), needle knife pre-cutting (NKP), and transpancreatic pre-cut papillotomy (TPPP). The initial ERCP success rate using standard technique alone was 62.8%, which increased to 94.3% including salvage techniques. Salvage techniques were frequently required in patients with long oral protrusions (OR 2.38; 95% CI 1.80-3.15; p < 0.001). A total of 503 cases (49.3%) had long oral protrusions, 47.5% of which required the salvage techniques, much higher than 27.5% of not-long cases. Patients with long oral protrusions had a higher frequency of NKP. In conclusion, patients with long oral protrusions frequently required salvage techniques. Salvage techniques may help to overcome many difficult biliary cannulation cases.
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http://dx.doi.org/10.1038/s41598-022-17809-5DOI Listing
August 2022

The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells.

Int J Mol Sci 2022 Jul 17;23(14). Epub 2022 Jul 17.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and -overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in -knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.
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http://dx.doi.org/10.3390/ijms23147878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316910PMC
July 2022

Feasibility of a Single Pigtail Stent Made by Cutting a Nasobiliary Drainage Tube in Endoscopic Transpapillary Gallbladder Stenting for Acute Cholecystitis.

Cureus 2022 May 17;14(5):e25072. Epub 2022 May 17.

Gastroenterology, Chiba University, Chiba, JPN.

Background and objective In this study, we aimed to evaluate the efficacy and safety of a single pigtail stent made by cutting a nasobiliary drainage tube (NBD stent) by comparing the clinical outcomes of using an NBD stent and those of using a ready-made double pigtail stent (RDP stent) in endoscopic gallbladder stenting (EGBS) for acute cholecystitis. Materials and methods This was a single-center retrospective study involving 20 cases that had technical success with EGBS for acute cholecystitis; the patients were divided into two groups: those using NBD stent (NBD group) and those using RDP stent (RDP group). The baseline characteristics and clinical outcomes were compared between the two groups. Results There were 13 patients in the NBD group and seven in the RDP group. The rates of clinical success (NBD group: 92% vs. RDP group: 100%, p=0.45) did not differ significantly between the groups. Regarding adverse events, gallbladder perforation occurred in one case in the NBD group; however, no other adverse events occurred in either group (NBD group: 7.7% vs. RDP group: 0%, p=0.45). The stent patency periods did not differ significantly between the groups [NBD group: 43 (12-64) days vs. RDP group: 97 (58-215) days, p=0.17]. The stent patency period in cases of long-term stent placement after EGBS was 1,381 days and 1,579 days in the NBD group and 305 days in the RDP group, respectively. Conclusion NBD stents are considered as effective as RDP stents in EGBS for acute cholecystitis. They are highly versatile and can be used for both bridging to surgery and long-term stent placement.
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http://dx.doi.org/10.7759/cureus.25072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202489PMC
May 2022

Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring Mutation in Early Clinical Experience.

J Cancer 2022 16;13(8):2656-2661. Epub 2022 May 16.

Department of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

Atezolizumab plus bevacizumab (ATZ/BV) treatment is a combined immunotherapy consisting of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor monoclonal antibody, which has brought a major paradigm shift in the treatment of unresectable hepatocellular carcinoma (HCC). Gain-of-function mutation of contributes to resistance of ICI monotherapy through the framework of non-T-cell-inflamed tumor microenvironment. However, whether mutation renders resistance to ATZ/BV similar to ICI monotherapy remains to be elucidated. In this study, a liquid biopsy sample in plasma of 33 patients with HCC treated with ATZ/BV was subjected to droplet digital PCR for detecting hotspot mutations at the exon 3 of locus. A total of eight patients (24.2%) exhibited at least one mutation. The objective response rate (ORR) in patients with wild-type (WT) and mutant (MT) was 8.0% and 12.5%, respectively, and the disease control rate (DCR) was 68.0% and 87.5%, respectively. No significant difference in both ORR and DCR has been observed between the two groups. The median progression-free survival in patients with WT and MT was 6.6 and 7.6 months, respectively (not statistically significant). Similarly, no significant difference in overall survival has been observed between patients with WT and MT (13.6 vs. 12.3 months). In conclusion, the treatment effect of ATZ/BV in patients with HCC with MT was comparable to those patients with WT . These results implicate that BV added to ATZ might improve immunosuppressive tumor microenvironment caused by mutation.
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http://dx.doi.org/10.7150/jca.71494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174847PMC
May 2022

A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis.

Lab Invest 2022 May 28. Epub 2022 May 28.

Department of Gastroenterology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential therapeutic target for NAFLD. The establishment of animal models with these metabolic comorbidities and with the rapid progression of the disease is needed for developing treatments for NAFLD but remains to be archived. In the present study, KK-A mice, widely used as T2DM models, or C57BL6 mice were fed a high-fat, high-fructose, and high-cholesterol diet supplemented with cholic acid (NAFLD diet). The KK-A mice fed a NAFLD diet exhibited remarkable obesity and insulin resistance. A prominent accumulation of triglycerides and cholesterol in the liver was observed at 4 weeks. These mice developed steatohepatitis at 4 weeks and fibrosis at 12 weeks. In contrast, C57BL6 mice fed a NAFLD diet remained lean, although they still developed steatohepatitis and fibrosis. In summary, we established a diet-induced murine NAFLD model with the rapid development of steatohepatitis and fibrosis, bearing obesity and insulin resistance. This model could be useful as preclinical models for drug development of NAFLD.
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http://dx.doi.org/10.1038/s41374-022-00807-6DOI Listing
May 2022

Liver cirrhosis is a risk factor for poor prognosis of acute cholangitis caused by choledocholithiasis.

Ann Hepatol 2022 May-Jun;27(3):100696. Epub 2022 Mar 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan. Electronic address:

Introduction And Objectives: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear.

Materials And Methods: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019.

Results: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02).

Conclusions: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.
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http://dx.doi.org/10.1016/j.aohep.2022.100696DOI Listing
May 2022

Diagnostic value of peroral cholangioscopy in addition to computed tomography for indeterminate biliary strictures.

Surg Endosc 2022 05 9;36(5):3408-3417. Epub 2021 Aug 9.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba-City, Chiba, 260-8670, Japan.

Background: Peroral cholangioscopy (POCS) has been used to overcome the difficulty in diagnosing indeterminate biliary stricture or tumor spread. However, the value of adding POCS to computed tomography (CT) remains unclear. Our aim was to evaluate the diagnostic value of adding POCS to CT for indeterminate biliary stricture and tumor spread by interpretation of images focusing on the high diagnostic accuracy of visual findings in POCS.

Methods: We retrospectively identified 52 patients with biliary stricture who underwent endoscopic retrograde cholangiography (ERC) at our institution between January 2013 and December 2018. Two teams, each composed of an expert endoscopist and surgeon, performed the interpretation independently, referring to the CT findings of the radiologist. The CT + ERC + POCS images (POCS group) were evaluated 4 weeks after the evaluation of CT + ERC images (CT group). A 5-point scale (1: definitely benign to 5: definitely malignant) was used to determine the confident diagnosis rate, which was defined as an evaluation value of 1 or 5. Tumor spread was also evaluated.

Results: In the evaluation of 45 malignant diagnoses, the score was significantly closer to 5 in the POCS group than in the CT group in both teams (P < 0.001). The confident diagnosis rate was significantly higher for the POCS group (92% and 73%) than for the CT group (25% and 12%) in teams 1 and 2, respectively (P < 0.001). We found no significant difference in diagnostic accuracy for tumor spread between the groups.

Conclusion: Visual POCS findings confirmed the diagnosis of biliary strictures. POCS was useful in cases of indefinite diagnosis of biliary strictures by CT.
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http://dx.doi.org/10.1007/s00464-021-08661-1DOI Listing
May 2022

Analysis of circulating cell-free DNA after endoscopic ultrasound-guided fine needle aspiration in pancreatic ductal adenocarcinoma.

Pancreatology 2021 Apr 15. Epub 2021 Apr 15.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background/objectives: Recently, increase in cell-free DNA (cfDNA) concentration or newly detected KRAS mutation after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy were reported to be related to the occurrence of new distant metastasis. In this study, we investigated whether cfDNA concentration increased with the release of tumor components into the blood after EUS-FNA and whether its increase was related to prognosis.

Methods: Sixty-eight patients underwent EUS-FNA and were pathologically confirmed as having pancreatic ductal adenocarcinoma (PDAC). We measured plasma cfDNA concentration and the copy number of KRAS mutation in 68 patients and circulating tumor cells in 8 before and after EUS-FNA.

Results: The average cfDNA concentration after EUS-FNA (672.5 ± 919.6 ng/mL) was significantly higher than that before EUS-FNA (527.7 ± 827.3 ng/mL) (P < 0.001). KRAS mutation in plasma was detected in 8 patients (11.8%), however a significant increase in cfDNA concentration after EUS-FNA was not related to the change in KRAS-mutant copy number. Minimal increase in circulating tumor cells was observed in 3 of 8 patients. New distant metastasis was observed within 286 days to initial metastasis detection in 6 of 12 patients with ≥2-fold increase in cfDNA concentration and 26 of 56 patients with <2-fold increase within 185 days. In 32 patients who underwent surgery, ≥2-fold increase in cfDNA did not affect early recurrence.

Conclusions: The increase in cfDNA concentration after EUS-FNA was not caused by tumor cell components released into blood vessels. Hence, the risk of seeding via the blood stream after EUS-FNA may need not be considered.
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http://dx.doi.org/10.1016/j.pan.2021.04.001DOI Listing
April 2021

Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma.

J Cancer 2021 5;12(9):2694-2701. Epub 2021 Mar 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Hepatocellular carcinoma (HCC) is typically accompanied by abundant arterial blood flow. Although angiogenic growth factors such as Angiopoietin 2 (Ang2) play a central role in tumor angiogenesis in HCC, the role of serum Ang2 as a biomarker in HCC remains unclear. In this study, we aimed to investigate the potential of Ang2 as a diagnostic and prognostic biomarker in HCC using a sandwich enzyme-linked immunosorbent assay (ELISA). The median Ang2 levels in controls (n=20), chronic liver disease patients (n=98), and HCC patients (n=275) were 1.58, 2.33, and 3.53 ng/mL, respectively. The optimal cut-off value of Ang2 was determined as 3.5 ng/mL by receiver operating curve analysis. The sensitivity, specificity, and accuracy of Ang2 for HCC detection were 50.9, 83.7, and 59.5%, respectively. Spearman's rank correlation coefficient analysis demonstrated only a weak correlation between Ang2 serum levels and alpha-fetoprotein (AFP) or des-gamma-carboxy prothrombin (DCP) serum levels. The diagnostic value of Ang2 was comparable to those of other existing markers. In addition, 24 out of 73 patients with normal AFP and DCP levels (32.9%) demonstrated abnormally high Ang2 levels (≥3.5 ng/mL). Although no significant difference in overall survival was found between Ang2 and Ang2 patients with curative ablation therapy, recurrence-free survival (RFS) in Ang2 patients was observed to be significantly shorter than those in Ang2 patients. Multivariate analysis demonstrated that high serum Ang2 levels (≥3.5 ng/mL) and the presence of multiple tumors were poor prognostic factors. In conclusion, our findings indicate that serum Ang2 is a potential novel biomarker for both diagnosis and prognosis in HCC.
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http://dx.doi.org/10.7150/jca.56436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040723PMC
March 2021

Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells.

Biochem Biophys Res Commun 2021 04 3;549:171-178. Epub 2021 Mar 3.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells. Lenvatinib-resistant HCC cell lines were established by exposure to serially escalated doses of lenvatinib over 2 months. The biological characteristics of these cells were examined by in vitro assays. To investigate the cytokine profile of lenvatinib-resistant HCC cells, the supernatant derived from lenvatinib-resistant Huh7 cells was subjected to nitrocellulose membrane-based sandwich immunoassay. Both activation of the MAPK/MEK/ERK signaling pathway and upregulation of epithelial mesenchymal transition markers were observed in lenvatinib-resistant cells. Concordant with these findings, proliferation and invasion abilities were enhanced in these cells compared with control cells. Screening of a cytokine array spotted with 105 different antibodies to human cytokines enabled us to identify 16 upregulated cytokines in lenvatinib-resistant cells. Among them, 3 angiogenic cytokines: vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and angiogenin, were increased significantly. Conditioned medium from lenvatinib-resistant cells accelerated tube formation of human umbilical vein cells. In conclusion, lenvatinib-resistant HCC cells were characterized by enhanced proliferation and invasion abilities. These findings might contribute to the establishment of new combination therapies with lenvatinib.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.097DOI Listing
April 2021

Chemotherapy-induced neutropenia as a prognostic factor in patients with pancreatic cancer treated with gemcitabine plus nab-paclitaxel: a retrospective cohort study.

Cancer Chemother Pharmacol 2020 08 6;86(2):203-210. Epub 2020 Jul 6.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan.

Objectives: Chemotherapy-induced neutropenia (CIN) is a common adverse event of chemotherapy. Several reports have suggested that CIN could be an important prognostic factor in chemotherapy of various cancers. However, whether CIN is a prognostic factor in unresectable pancreatic cancer (PC) treated with gemcitabine plus nab-paclitaxel (GnP) is unknown. The primary endpoint of this study was to compare overall survival (OS) between patients with severe CIN (grade ≥ 3) and those with absent/mild CIN (grade ≤ 2) in unresectable PC cases treated with GnP as first-line chemotherapy.

Methods: A retrospective, cohort study was conducted using data from a computerized database. A total of 290 patients with pathologically confirmed PC treated with GnP as first-line chemotherapy were analyzed (severe CIN: ≥ grade 3, n = 174; absent/mild CIN: ≤ grade 2, n = 116).

Results: The median OS was longer in the severe CIN group than in the absent/mild CIN group (19.2 months vs 11.3 months, respectively; P < 0.001). After adjustment, severe CIN was an independent predictive factor for OS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.74; P < 0.001). After adjustment by time-varying covariates, severe CIN was still a significant prognostic factor for OS (HR, 0.79; 95% CI 0.69-0.91, P = 0.001).

Conclusion: The present results show that severe CIN is an independent and useful prognostic factor in PC patients treated with GnP.
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http://dx.doi.org/10.1007/s00280-020-04110-3DOI Listing
August 2020

Skill-up study of systemic endoscopic examination technique using narrow band imaging of the head and neck region of patients with esophageal squamous cell carcinoma: Prospective multicenter study.

Dig Endosc 2019 Nov 20;31(6):653-661. Epub 2019 Jun 20.

Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan.

Objective: To evaluate the usefulness of a training program on endoscopic head and neck surveillance for beginner endoscopists.

Methods: This prospective multicenter study included 13 beginner endoscopists from 10 institutions who received training in systematic observation techniques and diagnostic criteria, and the training involved hands-on learning. Between May 2016 and February 2017, enrolled patients with current or previously diagnosed esophageal squamous cell carcinomas underwent head and neck surveillance using narrow band imaging (NBI) endoscopy, and histologically confirmed head and neck squamous cell carcinoma (HNSCC) detection rates, endoscopic image quality, and examination times were compared before (group A) and after (group B) the training program. Maximum possible score for the endoscopic images was 30 points.

Results: A total of 330 patients, comprising 181 in group A and 149 in group B, were enrolled. Three patients with HNSCC were detected in group A (1.7%) and in group B (2.0%; P = 1.000). Mean ± standard deviation (SD) examination times were 157 ± 71 s and 174 ± 109 s in groups A and B, respectively, (P = 0.073). Mean ± SD scores of the endoscopic images were 25.04 ± 5.47 points and 27.01 ± 4.35 points in groups A and B, respectively, (P < 0.001).

Conclusion: The HNSCC detection rate based on the use of NBI on patients with ESCC did not improve after the training program for beginner endoscopists; however, endoscopic image quality improved significantly after the training program.
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http://dx.doi.org/10.1111/den.13445DOI Listing
November 2019

Endoscopic Ultrasound-Guided Gallbladder Drainage for Aberrant Right Posterior Duct Obstruction Developing after Placement of a Covered Self-Expandable Metallic Stent in a Patient with Distal Biliary Obstruction.

Case Rep Gastroenterol 2018 Sep-Dec;12(3):722-728. Epub 2018 Nov 28.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been utilized as an alternative endoscopic technique for patients with acute cholecystitis. In addition to EUS-guided hepaticogastrostomy and EUS-guided cystogastrostomy, EUS-GBD has been reported as being useful for biliary drainage in cases with distal malignant biliary obstruction instead of conventional endoscopic retrograde cholangiopancreatography. We present a case of successful EUS-GBD for malignant obstruction of an aberrant hepatic duct draining directly into the cystic duct.
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http://dx.doi.org/10.1159/000492215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323387PMC
November 2018

Predictive factors of the treatment outcome in patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy.

J Gastroenterol 2019 Mar 8;54(3):281-290. Epub 2018 Oct 8.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.

Background: Few studies have clearly identified the prognostic factors in patients with advanced biliary tract cancer (BTC) receiving gemcitabine plus cisplatin (GC) which is acknowledged as standard chemotherapy regimen.

Objectives: The aim of this study was to identify predictive factors of the overall survival (OS) in advanced BTC patients receiving GC therapy.

Methods: Data of 307 patients with advanced BTC who received GC therapy as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. The patients were randomly assigned to the investigation or the validation dataset at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors, a prognostic index is proposed from the investigation dataset, and the usefulness of this index was confirmed in the validation dataset.

Results: Multivariate analysis identified poor performance status, elevated serum lactate dehydrogenase, and elevated neutrophil-to-lymphocyte ratio as independent unfavorable predictors. The patients could be classified into three groups according to these factors, and it was found that the outcomes differed significantly among the three groups (P = 0.0002, good- vs. intermediate-prognosis groups; P = 0.005, intermediate- vs. poor-prognosis groups). When this index was applied to the validation dataset, the OS was confirmed to differ significantly among the three groups (P = 0.04, good- vs. intermediate-prognosis groups, P < 0.0001, intermediate- vs. poor-prognosis groups).

Conclusions: We identified three predictors of the OS in patients with advanced BTC receiving GC therapy in this study, based on which we could classify the patients into three risk groups.
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http://dx.doi.org/10.1007/s00535-018-1518-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394712PMC
March 2019

Alternate Endpoints for Phase II Trials in Advanced Neuroendocrine Tumors.

Oncologist 2019 01 2;24(1):47-53. Epub 2018 Aug 2.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Background: In phase II trials for neuroendocrine tumors (NETs), the objective response rate (ORR) is traditionally used as a primary endpoint. However, the validity of the ORR as a primary endpoint has never been systematically examined. Therefore, a literature-based analysis of phase II trials for NETs was performed to identify valid alternative endpoints for predicting median progression-free survival (PFS) in clinical trials for NETs.

Materials And Methods: Phase II trials of medical treatment for advanced NETs were identified based on a systematic search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials.

Results: A total of 22 trials were identified, and 1,310 patients and 27 treatment arms were included in the analysis. There was no significant relationship between the ORR and median PFS ( = .374; 95% confidence interval [CI], -0.051 to 0.800; = .085). Conversely, 12-month PFS rates showed very strong correlations with median PFS ( = .929; 95% CI, 0.831-1.027; < .001).

Conclusion: The results of the present analysis indicate that the ORR is not significantly correlated with median PFS and suggest that 12-month PFS rates are good alternate endpoints for screening phase II trials for NETs.

Implications For Practice: Phase II trials are screening trials that seek to identify agents with sufficient activity to continue development. Thus, earlier endpoints are preferable, and the objective response rate (ORR) has been traditionally used as a surrogate endpoint in phase II trials for neuroendocrine tumors (NETs). However, the present study showed that the ORR was not significantly correlated with median progression-free survival (PFS). On the other hand, the 12-month PFS rate showed very strong correlation with median PFS and is considered a good alternate endpoint for screening phase II trials for NETs.
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http://dx.doi.org/10.1634/theoncologist.2017-0651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324626PMC
January 2019

Histopathology of immature (ongoing) squamous metaplasia of the stomach.

Pathol Int 2018 05 2;68(5):318-320. Epub 2018 Feb 2.

Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524, Japan.

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http://dx.doi.org/10.1111/pin.12636DOI Listing
May 2018

Metachronous early gastric cancer over a period of 13 years after eradication of Helicobacter pylori.

Clin J Gastroenterol 2014 Dec 4;7(6):490-5. Epub 2014 Nov 4.

Department of Endoscopy, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524, Japan,

Stomach cancer can occur during chronic inflammation from Helicobacter pylori (HP) infection, and its occurrence can be suppressed by eradication of HP. However, the effects of suppressing stomach cancer by HP eradication are limited, and the cancer is known to recur even after eradication of this infection. Here, we report the case of a 56-year-old male patient with gastric cancer who, although undergoing HP eradication after treatment of early gastric cancer with endoscopy, experienced five metachronous cancer recurrences over a period of 13 years. Whether observation of patients who undergo eradication of HP due to peptic ulcers or chronic gastritis and patients who undergo eradication after endoscopic treatment for early gastric cancer should be performed at the same interval is an issue that must be addressed in the future. The appropriate observation period for each patient must be established while considering the burdens to the patient and from the medical economic perspective.
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http://dx.doi.org/10.1007/s12328-014-0536-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261136PMC
December 2014
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