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Assessment of therapeutic effects of combined treatment with cisplatin and anti-mouse programmed death (PD) -1 antibody in a mouse urothelial cancer model
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
Is oral Streptococcus mutans with collagen-binding protein a risk factor for intracranial aneurysm rupture or formation?
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
A comparison of two types of contrast media used in endoscopic retrograde cholangiopancreatography: A retrospective study
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Background
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most serious complications of ERCP. Various procedures can reduce the incidence of PEP, such as wire-guided cannulation, prophylactic pancreatic stent placement, and pretreatment anal insertion of NSAIDs. Recently, iso-osmolar contrast media (IOCM) have been used for ERCP in several hospitals to reduce the risk of PEP in Japan. However, the effect of IOCM is uncertain because few reports have examined IOCM in relation to PEP.
Aim
This study aimed to investigate the relationship between contrast media used and the incidence of PEP.
Methods
This retrospective study included all qualifying patients who had undergone ERCP at Hamamatsu University Hospital between January 2012 and January 2020. This study examined whether there was a difference in the onset of PEP between patients administered IOCM and high osmolar contrast medium (HOCM). Propensity score matching was used to analyze patient characteristics and ERCP procedures. Amidotrizoic acid was used as HOCM and iodixanol as IOCM.
Results
ERCP was performed on 458 patients, and 830 procedures were conducted. After propensity score matching, 162 patients from the amidotrizoic acid group and 162 patients from the iodixanol group were selected. The incidence of PEP was 10.5% (17) in the amidotrizoic acid group and 9.3% (15) in the iodixanol group (P=0.71). Changes in serum amylase levels post- and pre-ERCP were 240.6 ± 573.8 U/L and 142.7 ± 382.1 U/L in the amidotrizoic acid and iodixanol groups, respectively (P=0.072).
Conclusion
Iodixanol had no prophylactic effect on PEP and clinical outcomes.doctoral thesi
Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Background/Objectives: Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single-center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses.
Methods: Forty-eight patients being treated with naldemedine for opioidinduced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed.
Results: Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4β-hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin-6 (IL-6) and acute-phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements.
Conclusion: Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL-6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements.doctoral thesi
Development of a novel airbag system of abdominal compression for reducing respiratory motion: preliminary results in healthy volunteers
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）This study used cine-magnetic resonance imaging (cine-MRI) to evaluate the safety and efficacy of a novel airbag system combined with a shell-type body fixation system in reducing respiratory motion in normal volunteers. The airbag system consists of a six-sided polygon inflatable airbag, a same shape plate, a stiff air supply tube, an air-supply pump and a digital pressure load cell monitor. Piezoelectric sensors were installed in the plate to detect compression pressure load changes; pressure load data were transferred to the digital pressure load cell monitor through Bluetooth. Five volunteers underwent cine-MRI with and without airbag compression to detect differences in the respiratory motion of the organs. The volunteers’ physiologic signs were stable during the experiment. The maximum inspiration pressure load was 4.48 ± 0.86 kgf (range, 4.00–6.00 kgf), while the minimum expiration pressure load was 3.69 ± 0.95 kgf (range, 2.8–5.3 kgf). Under airbag compression, the right diaphragm movement was reduced from 19.50 ± 6.43 mm to 9.60 ± 3.61 mm (P<0.05) in the coronal plane and 23.12 ± 6.30 mm to 11.00 ± 3.69 mm (P<0.05) in the sagittal plane. The left diaphragm, pancreas and liver in the coronal plane and the right kidney and liver in the sagittal plane also showed significant movement reduction. This novel airbag abdominal compression system was found to be safe during the experiment and successful in the reduction of internal organ respiratory motion and promises to be a convenient and efficient tool for clinical radiotherapy
Prognostic outcomes in patients with metastatic renal cell carcinoma receiving second-line treatment with tyrosine kinase inhibitor following first-line immune-oncology combination therapy
Get PDFObjectives: This study aimed to assess the prognostic outcomes in mRCC patients receiving second-line TKI following first-line IO combination therapy.
Methods: This study retrospectively included 243 mRCC patients receiving second-line TKI after first-line IO combination therapy: nivolumab plus ipilimumab (n=189, IO-IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n=54, IO-TKI group). Oncological outcomes between the 2 groups were compared, and prognostication systems were developed for these patients.
Results: In the IO-IO and IO-TKI groups, the objective response rates to second-line TKI were 34.4% and 25.9% (P=0.26), the median PFS periods were 9.7 and 7.1 months (P=0.79), and the median OS periods after the introduction of second-line TKI were 23.1 and 33.5 months (P=0.93), respectively. Among the several factors examined, non-CCRCC, high CRP and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c-indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC and MSKCC systems, respectively.
Conclusions: There were no significant differences in the prognostic outcomes after introducing second-line TKI between the IO-IO and IO-TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second-line TKI, irrespective of first-line IO combination therapies
Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia status and clinical responses in head and neck cancer patients
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
CLEC10A expression defines functionally distinct subsets of conventional type 2 dendritic cells (cDC2) in the mouse lung
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi