Low-Intensity Pulsed Ultrasound Maintains Bone Mass After Withdrawal of Human Parathyroid Hormone in Ovariectomized Mice.

The intermittent injection of teriparatide, a recombinant fragment of human parathyroid hormone (PTH 1-34), activates anabolic activity on bone turnover. However, the PTH administration period is limited to 2 years. Thus, sequential therapy after discontinuation of PTH is required. Low-intensity pulsed ultrasound (LIPUS) has been widely used for bone fracture healing. In this study, we examined the effects of LIPUS on bone mass after PTH withdrawal in ovariectomized (OVX) model mice. The LIPUS-non-irradiated femoral trabecular bone mineral density (BMD) in the treated after PTH withdrawal was significantly decreased. Meanwhile, the femoral BMD in the OVX + PTH-LIPUS group was remarkably higher than that of the OVX group. Additionally, mRNA expression of Runx2, Osterix, Col1a1, and ALP increased significantly following LIPUS irradiation after PTH withdrawal. These results suggest that LIPUS protected against femoral trabecular BMD loss and up-regulated the osteogenic factors following PTH withdrawal in OVX mice.

Impact of DNA double-strand breaks on pancreaticobiliary maljunction carcinogenesis.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a condition characterized by chronic inflammation due to refluxed pancreatic juice into the biliary tract that is associated with an elevated risk of biliary tract cancer. DNA double-strand breaks (DSBs) are considered the most serious form of DNA damage. DSBs are provoked by inflammatory cell damage and are recognized as an important oncogenic event in several cancers. This study used γ-H2AX, an established marker of DSB formation, to evaluate the impact of DNA damage on carcinogenesis in PBM. METHODS: We investigated γ-H2AX expression immunohistochemically in gallbladder epithelium samples obtained from 71 PBM cases and 19 control cases. RESULTS: Fourteen PBM cases with gallbladder adenocarcinoma were evaluated at non-neoplastic regions. A wide range of nuclear γ-H2AX staining was detected in all PBM and control specimens. γ-H2AX expression was significantly higher in PBM cases versus controls (median γ-H2AX-positive proportion: 14.4 % vs. 4.4 %, p = 0.001). Among the PBM cases, γ-H2AX expression was significantly higher in patients with carcinoma than in those without (median γ-H2AX-positive proportion: 21.4 % vs. 11.0 %, p = 0.031). CONCLUSIONS: DSBs occurred significantly more abundantly in the PBM gallbladder mucosa, especially in the context of cancer, indicating an involvement in PBM-related carcinogenesis.

[Pancreatic adenocarcinoma:a case containing a cyst enclosing a dilated tubular gland duct].

This case report describes a 73-year-old woman with pancreatic adenocarcinoma who had undergone a colectomy for colorectal cancer in 1995 and a right mastectomy and axillary dissection for breast cancer in 2013. In January 2019, a tumor, approximately 20mm in diameter, was detected in the pancreatic body. It contained a cyst noted to have delayed perfusion towards the center on abdominal computed tomography. On T1-weighted magnetic resonance imaging (MRI), almost the entire tumor exhibited low intensity. On T2-weighted MRI, however, the tumor center displayed high intensity, the tumor wall displayed low intensity, and the outermost layer displayed high intensity. On endoscopic ultrasound, the tumor center displayed low echo density, the tumor wall had a slightly elevated echo density, and the outermost layer had a low echo density. A distal pancreatectomy was performed for a suspected metastatic pancreatic cancer, pancreatic neuroendocrine neoplasm, or invasive ductal carcinoma without tubular adenocarcinoma. Histopathological examination revealed that the tumor cells had formed atypical tubular gland ducts with a fibrous stroma in the background. The lesion differed from the histopathological findings of her previous colorectal and breast cancers, and it was ultimately diagnosed as a pancreatic ductal adenocarcinoma. The lumen of the cyst was covered with tumor cells identical to those of the atypical tubular gland ducts in the tumor parenchyma, suggesting that the cyst was a dilated tubular gland duct.

Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.

Sequential treatment with endocrine or chemotherapy is generally used in the treatment of estrogen receptor (ER)-positive recurrent breast cancer. To date, few studies have investigated the effect of long-term endocrine therapy on the response to subsequent chemotherapy in ER-positive breast cancer. We examined whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER-positive breast cancer cells. Three ER-positive breast cancer cell lines (T47D, MCF7, BT474) and tamoxifen-resistant sublines (T47D/T, MCF7/T, BT474/T) were analyzed for sensitivity to 5-fluorouracil, paclitaxel, and doxorubicin. The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. MCF7/T cells became more sensitive to 5-fluorouracil than wild-type (wt)-MCF7 cells. In addition, the apoptosis induced by 5-fluorouracil was significantly increased in MCF7/T cells. However, no difference in sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T cells compared with their wt cells. Dihydropyrimidine dehydrogenase (DPYD) mRNA expression was significantly decreased in MCF7/T cells compared with wt-MCF7 cells. The expression of DPYD mRNA was restored with 5-azacytidine treatment in MCF7/T cells. In addition, DPYD 3'-UTR luciferase activity was significantly reduced in MCF7/T cells. These data indicated that the expression of DPYD mRNA was repressed by methylation of the DPYD promoter region and post-transcriptional regulation by miRNA in MCF7/T cells. In the mouse xenograft model, capecitabine significantly reduced the tumor volume in MCF7/T compared with MCF7. The results of this study indicate that endocrine therapy could alter the sensitivity to chemotherapeutic agents in a subset of breast cancers, and 5-fluorouracil may be effective in tamoxifen-resistant breast cancers.

Inverse correlation between PD-L1 expression and LGR5 expression in tumor budding of stage II/III colorectal cancer.

We investigated the expression of LGR5, the most robust and reliable known cancer stem cell (CSC) marker of colorectal cancer, and PD-L1 in tumor budding (TB), as well as clinicopathological features. Tissue microarrays (TMAs) were generated from TB samples from 32 stage II/III colorectal adenocarcinoma patients, and LGR5 expression in TMAs was evaluated by RNAscope, an extremely sensitive RNA in situ hybridization technique. LGR5 expression was significantly lower in the PD-L1-positive group than in the PD-L1-negative group (P = 0.0256). In the PD-L1-positive group, the tumor-infiltrating lymphocytes (TILs) score tended to be higher while the TNM stage was lower compared with the PD-L1 negative group (P = 0.0822 and P = 0.0765, respectively). There was no significant difference in Overall Survival between the PD-L1-positive and PD-L1-negative groups (log-rank test, P = 0.8218). This study showed that PD-L1-positive patients are a unique population with low LGR5 expression, and that LGR5-positive cells may be a promising therapeutic target in PD-L1-negative patients.

Reinforced Polyphenylene Ionomer Membranes Exhibiting High Fuel Cell Performance and Mechanical Durability.

We report on the preparation of reinforced membranes (SPP-QP-PE, where SPP stands for sulfonated polyphenylene), composed of an in-house proton-conductive polyphenylene ionomer (SPP-QP) and a flexible porous polyethylene (PE) mechanical support layer. By applying the push coating method, dense, uniform, transparent, and thin SPP-QP-PE membranes were obtainable. The use of SPP-QP with higher ion exchange capacity induced very high proton conductivity of SPP-QP-PE, leading to high fuel cell performance even at low humidified conditions (e.g., at 80 °C and 30% relative humidity), which had not been attainable with the existing reinforced aromatic ionomer membranes. The flexible porous PE substrate improved the mechanical toughness of the membranes; the elongation at break increased by a factor of 7.1 for SPP-QP-PE compared to that with the bare SPP-QP membrane, leading to mechanical durability at least 3850 wet-dry cycles under practical fuel cell operating conditions (the United States Department of Energy protocol). Overall, the reinforced aromatic ionomer membranes, SPP-QP-PE with balanced proton conductivity, mechanical toughness, and gas impermeability, functioned well in fuel cells with high performance and durability.

Screening and follow-up of chronic liver diseases with understanding their etiology in clinics and hospitals.

BACKGROUND AND AIM: Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. METHODS: Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119). RESULTS: FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 104/µL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients. CONCLUSIONS: Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.

Blocking sphingosine 1-phosphate receptor 2 accelerates hepatocellular carcinoma progression in a mouse model of NASH.

The role of sphingosine 1-phosphate (S1P) and its sphingosine-1-phosphate receptors (S1PRs) in non-alcoholic steatohepatitis (NASH) is unclear. We aimed to analyze the role of S1P/S1PRs in a Melanocortin-4 receptor (Mc4r)-deficient NASH murine model using FTY720, the functional antagonist of S1PR1, S1PR3, S1PR4, and S1PR5, and JTE-013, the antagonist of S1PR2. We observed that, compared to that in the control, the mRNA of S1pr1 tended to decrease, whereas those of S1pr2 and S1pr3 significantly increased in Mc4r-knockout (KO) mice subjected to a Western diet (WD). While the fat area did not differ, fibrosis progression differed significantly between control mice and mice in which liver S1PRs were blocked. Lipidomic and metabolomic analysis of liver tissues showed that JTE-013-administered mice showed elevation of S-adenosyl-l-methionine level, which can induce aberrant methylation due to reduction in glycine N-methyltransferase (GNMT) and elevation in diacylglycerol (DG) and triacylglycerol (TG) levels, leading to increased susceptibility to hepatocellular carcinoma (HCC). These phenotypes are similar to those of Gnmt-KO mice, suggesting that blocking the S1P/S1PR2 axis triggers aberrant methylation, which may increase DG and TG, and hepatocarcinogenesis. Our observations that the S1P/S1PR2 axis averts HCC occurrence may assist in HCC prevention in NASH.

Corticosteroids prevent the progression of autoimmune pancreatitis to chronic pancreatitis.

BACKGROUND/OBJECTIVES: Patients with autoimmune pancreatitis (AIP) sometimes progress to chronic pancreatitis (CP). We evaluated the ability of corticosteroids to prevent the progression to CP. METHODS: We defined patients with definitive findings of CP (stones in the main pancreatic duct [MPD] or multiple pancreatic calcifications) as having severe calcification (SC). A total of 145 AIP patients were enrolled. We measured the duration between AIP diagnosis and SC development and retrospectively compared the time to SC development between patients with and without steroids. Multivariate analysis for factors associated with SC were performed. RESULTS: Nineteen (13%) patients progressed to SC. Since 95 patients had pancreatic head swelling and SC was found in these patients only, our analysis focused mainly on these at-risk populations. In Kaplan-Meier analysis limited to patients with pancreatic head swelling, the incidence of SC was significantly lower in patients with steroids than in those without (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.07-0.52; p < 0.001). Multivariate testing of patients with pancreatic head swelling confirmed that steroid therapy was significantly associated with a lower incidence of SC (HR 0.11, 95% CI 0.03-0.34; p < 0.001), while MPD dilation at AIP diagnosis was related to a higher incidence of SC (HR 4.02, 95% CI 1.43-11.7; p = 0.009). CONCLUSIONS: Corticosteroids appeared to prevent progression to CP in AIP patients, especially in those with pancreatic head swelling. Patients with both pancreatic head swelling and MPD dilation at diagnosis have a higher incidence of progression to CP. Steroid therapy is suggested for these high-risk cases.

Correlation of Pancreatic T1 Values Using Modified Look-Locker Inversion Recovery Sequence (MOLLI) with Pancreatic Exocrine and Endocrine Function.

Quantifying myocardial T1 values has been useful for detecting and characterizing fibrotic appearance in myocardial infarction, focal scars, and non-ischemic cardiomyopathies. Since pancreatic exocrine function decreases with chronic pancreatic fibrosis advancement, this study examined the correlation between pancreatic T1 values and pancreatic exocrine and endocrine insufficiency. METHODS: Thirty-two patients underwent abdominal contrast-enhanced MRI in our department between October 2017 and February 2019. We evaluated the T1 values of the pancreas using a modified Look-Locker inversion recovery sequence (MOLLI), pancreatic exocrine insufficiency (PEI) by fecal elastase 1 (FE1) values, and pancreatic endocrine insufficiency using fasting insulin and blood glucose levels to calculate the HOMA-ß. This trial is registered in the UMIN Clinical Trials Registry as UMIN 000030067. RESULTS: The median cohort (9 males and 23 females) age was 71 (range: 49-84) years. Eighteen patients had pancreatic cysts, three had alcohol-induced chronic pancreatitis, three had pancreatic cancer, and eight possessed other pancreatic features (two patients each with autoimmune pancreatitis, acute pancreatitis, or a bile duct tumor, one with idiopathic chronic pancreatitis, and one healthy control with negative findings). The median pancreatic T1 value measured by the MOLLI was 857.5 ms (597-2569). A significant negative correlation was found between the T1 mapping and FE1 values (r = 0.69, p < 0.01), with none for the T1 with HOMA-ß or serum albumin, triglycerides, or body mass index. CONCLUSIONS: the pancreatic T1 values correlated significantly with pancreatic exocrine function and might be useful in PEI diagnosis.

Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles.

INTRODUCTION: Currently, there are no approved drugs for treating non-alcoholic steatohepatitis (NASH); however, mesenchymal stem cells (MSCs) and their small extracellular vesicles (sEVs), which possess immunomodulatory activities, are potential candidates. This study aimed to develop a mouse model of NASH with rapid accumulation of fibrosis using the pre-established melanocortin type-4 receptor knockout (Mc4r-KO) NASH mouse model and lipopolysaccharide (LPS), and to evaluate the therapeutic effect of MSCs and their sEVs. METHODS: Mc4r-KO mice (8 weeks old, male) were fed a western diet (WD) for 8 weeks. Next, the mice were intraperitoneally injected with lipopolysaccharide (LPS) twice a week for 4 weeks while continuing the WD. To confirm the therapeutic effect of MSCs and sEVs, human adipose tissue-derived MSCs or their sEVs were administered 12 weeks after initiation of the WD, and serum testing, quantitative analysis of fibrosis, and quantitative reverse transcription-polymerase chain reaction qRT-PCR were performed. RESULTS: By providing a WD combined with LPS treatment, we successfully developed a NASH model with rapid accumulation of fibrosis. Both human MSCs and their sEVs decreased serum alanine transaminase levels and inflammatory markers based on qRT-PCR. Histological analysis showed that MSC or sEV treatment did not affect fat accumulation. However, an improvement in fibrosis in the groups treated with MSCs and their sEVs was observed. Furthermore, after administering MSCs and sEVs, there was a significant increase in anti-inflammatory macrophages in the liver. CONCLUSION: We successfully developed a NASH model with rapid accumulation of fibrosis and confirmed the anti-inflammatory and anti-fibrotic effects of MSCs and their sEVs, which may be options for future therapy.

Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model.

Mesenchymal stem cells (MSCs) can be acquired from medical waste. MSCs are easily expanded and have multiple functions, including anti-inflammatory effects. We evaluated the effects of human adipose tissue-derived MSCs (AD-MSCs) and umbilical cord tissue-derived MSCs (UC-MSCs) in a dextran sulfate sodium (DSS)-induced mouse model. Human AD-MSCs and UC-MSCs (1 × 106 cells) were injected intravenously into a 7-day DSS-induced colitis model. The therapeutic effects of cell origin, injection timing, and supernatants obtained from MSC cultures were evaluated. We also analyzed messenger RNA (mRNA) expression in MSCs, tissues, and intestinal flora. AD-MSCs and UC-MSCs were found to show strong anti-inflammatory effects when injected on day 3 in a mouse model. On day 11, the mRNA levels of inflammatory factors in colon tissues were significantly decreased after injection of MSCs on day 3. Supernatants from MSCs culture decreased mRNA levels of tumor necrosis factor (Tnf)-α, but had reduced therapeutic effects compared with MSC cell injection. RNA sequencing using colon tissues obtained the day after cell injection revealed changes in the TNF-α/nuclear factor-κB and T cell receptor signaling pathways. Additional analyses showed that several factors, including chromosome 10 open reading frame 54, stanniocalcin-1, and TNF receptor superfamily member 11b were increased in MSCs after adding serum from DSS colitis mice. Furthermore, both AD-MSCs and UC-MSCs maintained the balance of intestinal flora. In conclusion, AD-MSCs and UC-MSCs showed therapeutic effects against inflammation after early cell injection while maintaining the intestinal flora. Although supernatants showed therapeutic effects, cell injection was more effective against inflammation.

Correlation of clinicopathological features and leucine-rich repeat-containing G-protein-coupled receptor 5 expression in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. Previous studies have established leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) as a cancer stem cell marker in gastrointestinal cancers. However, few reports have examined LGR5 in PDAC. Here we examined LGR5 expression and its clinicopathological significance in PDAC. We evaluated LGR5 expression in 78 PDAC patients who underwent surgical resection in our institution using RNAscope, a newly described RNA in situ hybridization technique. All 78 PDAC cases expressed LGR5 in cancer tissues, and LGR5 expression was prominent in the gland-forming part. LGR5 expression was significantly higher in patients with low histological grade (G1-G2) (p < 0.001) and early clinical stage (p = 0.004). Univariate analysis showed that low LGR5 expression (p = 0.034) was significantly associated with worse overall survival. However, LGR5 expression did not remain a predictor of prognosis in multivariate analysis (p = 0.639). All PDAC cases showed LGR5 expression to varying degrees, indicating LGR5 might be a cancer stem cell marker of PDAC, as in gastrointestinal cancer. Reduced LGR5 expression in tumor cells was associated with worse prognosis in PDAC. Further studies are required to elucidate the relationship between tumor progression and LGR5 expression in PDAC.

Effectiveness of steroid therapy for pancreatic cysts complicating autoimmune pancreatitis and management strategy for cyst-related complications.

Objectives: Autoimmune pancreatitis (AIP) sometimes becomes complicated with pancreatic cysts, although their detailed characteristics and management strategy have not been fully determined. We aimed to clarify the efficiency of steroid therapy and the risk factors for cyst formation and cyst-related complications. Methods: One hundred sixty-three AIP patients were retrospectively analyzed for relevant factors of cyst formation. We compared subjects with and without steroids to evaluate drug effectiveness on cyst size change and investigated the factors associated with cyst-related complications. Results: Thirty-two patients (19.6%) had complicating pancreatic cyst formation, and 40 cystic lesions of ≥10 mm in size were detected. Multivariate analysis revealed a drinking habit, abdominal/back pain, and elevated serum amylase to be significantly associated with cyst formation. Steroid-treated cysts became significantly reduced in size in the short-term and disappeared significantly more frequently within 1-year as compared with non-treated ones, which was confirmed by multivariate analysis. Six of 40 cysts exhibited cyst-related complications significantly associated with multilocular morphology and larger size. Conclusions: Steroid therapy is an effective choice for cysts developing in AIP to promote the release of pancreatic juice stasis. Larger lesions with multilocular morphology should be monitored closely for cyst-related complications and be considered strong candidates for steroid therapy.

Diverse perspectives to address for the future treatment of heterogeneous hepatocellular carcinoma.

Hepatocellular carcinomas (HCCs), which often arise from chronic liver damage, have poor conditional 5-year survival and are recognized as heterogeneous tumors. Considering the heterogeneity of HCCs, diverse perspectives need to be addressed for treating such tumors, besides the findings of conventional imaging modalities and tumor markers. Data from the latest technologies, such as liquid biopsy, and the detection of the presence of cancer cells with stem/progenitor cell markers, gene mutations and diverse pathways, crosstalk with immune cells and cancer-associated fibroblasts, and mechanisms of epithelial-mesenchymal transition provide diverse lines of information. Integration of these data with clinical data might be necessary to develop effective therapies for precision medicine. Here, we review several aspects of dealing with the complexity of heterogeneous HCCs.

Preparation of Nickel Nanoparticles by Direct Current Arc Discharge Method and Their Catalytic Application in Hybrid Na-Air Battery.

Nickel nanoparticles were prepared by the arc discharge method. Argon and argon/hydrogen mixtures were used as plasma gas; the evaporation of anode material chiefly resulted in the formation of different arc-anode attachments at different hydrogen concentrations. The concentration of hydrogen was fixed at 0, 30, and 50 vol% in argon arc, corresponding to diffuse, multiple, and constricted arc-anode attachments, respectively, which were observed by using a high-speed camera. The images of the cathode and anode jets were observed with a suitable band-pass filter. The relationship between the area change of the cathode/anode jet and the synchronous voltage/current waveform was studied. By investigating diverse arc-anode attachments, the effect of hydrogen concentration on the features of nickel nanoparticles were investigated, finding that 50 vol% H2 concentration has high productivity, fine crystallinity, and appropriate size distribution. The synthesized nickel nanoparticles were then used as catalysts in a hybrid sodium⁻air battery. Compared with commercial a silver nanoparticle catalyst and carbon black, nickel nanoparticles have better electrocatalytic performance. The promising electrocatalytic activity of nickel nanoparticles can be ascribed to their good crystallinity, effective activation sites, and Ni/NiO composite structures. Nickel nanoparticles prepared by the direct current (DC) arc discharge method have the potential to be applied as catalysts on a large scale.

Early Detection of Hepatocellular Carcinoma Recurrence Using the Highly Sensitive Fucosylated Fraction of Alpha-Fetoprotein.

Alpha-fetoprotein (AFP)-L3 was originally reported as a hepatocellular carcinoma (HCC)-specific tumor marker, and recent accumulation of evidence has revealed that AFP-L3 frequency predicts the biological malignancy potential of HCC. However, AFP-L3 elevation from undetectable levels after curative treatment could not be discussed due to the difficulties of calculating AFP-L3 concentrations when serum AFP levels were low. Here, as a novel method, we used highly sensitive AFP-L3 frequency to predict HCC recurrence after curative treatment. Our cases illustrate that recognizing elevation of AFP-L3 from undetectable levels led to the early detection of recurrent HCC due to more careful surveillance.

Usefulness of three-dimensional magnetic resonance cholangiopancreatography with partial maximum intensity projection for diagnosing autoimmune pancreatitis.

PURPOSE: To compare three-dimensional magnetic resonance cholangiopancreatography (MRCP) with/without partial maximum intensity projection (MIP) and endoscopic retrograde cholangiopancreatography (ERCP) in patients with autoimmune pancreatitis (AIP). MATERIALS AND METHODS: Three-dimensional MRCP and ERCP images were retrospectively analyzed in 24 patients with AIP. We evaluated the narrowing length of the main pancreatic duct (NR-MPD), multiple skipped MPD narrowing (SK-MPD), and side branches arising from the narrowed portion of the MPD (SB-MPD) using four MRCP datasets: 5 original images (MIP5), 10 original images (MIP10), all original images (full-MIP), and a combination of these three datasets (a-MIP). The images were scored using a 3- or 5-point scale. The scores of the four MRCP datasets were statistically analyzed, and the positive rate of each finding was compared between MRCP and ERCP. RESULTS: The median scores for SB-MPD on MIP5 and a-MIP were significantly higher than those on MIP10 and full-MIP. In other words, partial MIP is superior to full-MIP for visualization of detailed structures. The positive rate for SB-MPD on full-MIP was significantly lower than that on ERCP, whereas the positive rate on MIP5, MIP10, and a-MIP was not significantly different from that on ERCP. Moreover, the positive rate for NR-MPD and SK-MPD on the MRCP images was significantly higher than that on the ERCP images. CONCLUSION: Partial MIP is useful for evaluating the MPD and is comparable with ERCP for diagnosing AIP.

Lusutrombopag increases hematocytes in a compensated liver cirrhosis patient.

A 56-year-old Japanese man with liver cirrhosis (LC) due to hepatitis C virus was admitted to our hospital for radiofrequency ablation of residual tumor following lusutrombopag administration. Laboratory tests revealed thrombocytopenia and leukopenia. The patient's LC was managed, and he was classified as Child-Pugh A. After admission, lusutrombopag was administered for 7 days. The platelet count increased to over 50,000/mm3 after 7-14 days and returned to previous levels 50 days after administration. Leukocyte and erythrocyte counts also increased in response to the treatment and stayed elevated for over 120 days. Lusutrombopag acts selectively on human thrombopoietin (TPO) receptors and activates signaling pathways that promote the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes, consequently increasing the blood platelet count. However, the patient treated with lusutrombopag in our case study showed increased blood leukocyte and erythrocyte counts as well. Given that TPO receptors are reportedly expressed in not only megakaryocyte progenitor cells but also hematopoietic progenitors, lusutrombopag may potentially improve pancytopenia caused by LC and can be used for the recovery of blood counts before other treatments.