Search

Objective: Acute Physiology and Chronic Health Evaluation II (APACHE II) is based on the data of intensive care unit (ICU) patients and often correlates with disease severity and prognosis. However, no prognostic predictors exist based on ICU admission data for patients with brain tumors, and no studies have reported an association between APACHE II and prognosis in patients with brain tumors. The Japanese Intensive Care Patients Database (JIPAD) was established to improve the quality of care delivered in intensive care medicine in Japan. We used JIPAD to examine factors associated with in-hospital mortality based on available data of postoperative patients with brain tumors admitted to the ICU., Methods: Patients aged ≥16 years enrolled in JIPAD between April 2015 and March 2018 after surgical brain tumor resection or biopsy of brain tumors. We examined factors related to outcomes at discharge based on blood tests and medical procedures performed during ICU admission, tumor type, and APACHE II score., Results: Among the 1454 patients (male:female ratio: 1:1.1, mean age: 62 years) in the study, 32 (2.2 %) died during hospital stay. In multivariate analysis, male sex (odds ratio [OR] 2.70, [95 % confidence interval, CI 1.22-6.00]), malignant tumor (OR 2.51 [95 % CI 1.13-5.55]), and APACHE II score ≥15 (OR 2.51 [95 % CI 3.08-14.3]) were significantly associated with in-hospital mortality., Conclusion: By picking up cases with a high risk of in-hospital death at an early stage, it is possible to improve methods of treatment and support for the patient's family., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ovarian clear cell carcinoma (OCCC) is a unique clinicopathological subtype of epithelial ovarian cancer that is resistant to standard chemotherapy. Eribulin, a microtubule dynamics inhibitor of halichondrin class, has unique effects in the cancer microenvironment such as induction of epithelization and reduction in metastatic potential in breast cancer cells; however, nothing is known about the effect of eribulin and the detailed mechanisms in OCCC. This study aimed to investigate the involvement of ferroptosis and its mechanism in the antitumor activity of eribulin in OCCC cells and a mouse xenograft model. We found that eribulin-induced cell death was reduced by ferroptosis inhibitors; deferoxamine, an iron chelator and ferrostatin-1, a lipid peroxidation inhibitor. Eribulin increased the levels of intracellular iron, reactive oxygen species (ROS), and lipid peroxides, and increased the mitochondrial membrane potential. Eribulin downregulated the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), and superoxide dismutase (SOD) activity. The combination of eribulin and ML210, a glutathione peroxidase 4-inhibiting ferroptosis inducer, had a synergistic effect on ferroptosis. Taken together, our findings show firstly that eribulin triggers ferroptosis in OCCC and this effect occurs via the suppression of the Nrf2-HO-1 signaling pathway, SOD activity and the promotion of lipid peroxidation. These findings suggest that eribulin-induced ferroptosis is associated with its anti-tumor effect and also could be a potential therapeutic target in OCCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Non-convulsive status epilepticus (NCSE) is characterized by repetitive or continuous seizures without convulsions. Arterial spin labeling (ASL) is useful for assessing hyperperfusion due to neurovascular unit coupling in patients with NCSE; subarachnoid hemorrhage (SAH) impairs the neurovascular unit. We hypothesized that the sensitivity of ASL in detecting NCSE is low in patients with SAH during the acute phase., Methods: Based on ASL findings obtained within 48 h after the clinical suspicion of focal-onset NCSE, we divided 34 patients into ASL-negative (no hyperperfusion; n = 10) and ASL-positive (confirmed hyperperfusion; n = 24) groups. We further divided the two groups according to the NCSE etiology: patients who were diagnosed with NCSE within 14 days after SAH onset (acute SAH, n = 11) and patients with NCSE due to factors other acute SAH (n = 23) and compared their characteristics., Results: In 10 of the 34 patients (29.4 %) the ASL findings were normal. The rate of acute SAH was significantly higher in ASL-negative- (n = 8, 80.0 %) than ASL-positive patients (n = 3, 12.5 %). The rate of patients in aphasic status was significantly lower in ASL-negative patients (n = 1, 10 %) than in ASL-positive patients (n = 12, 50.0 %)., Conclusion: Normal ASL findings alone should not be used to exclude a diagnosis of NCSE particularly in patients in the acute phase of SAH with deterioration or no improvement in consciousness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Mononuclear cytotrophoblasts (CTs) differentiate and fuse to form multinuclear syncytiotrophoblasts (STs), which produce human chorionic gonadotropin (hCG) and progesterone to maintain pregnancy. Impaired differentiation and fusion of CTs to form STs are associated with hypertensive disorders of pregnancy and fetal growth restriction. Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional single transmembrane heme-binding protein. We previously demonstrated that downregulation of PGRMC1 promotes endometrial stromal cell differentiation (decidualization). Here, we explored the role of PGRMC1 in trophoblast differentiation and fusion. PGRMC1 expression was lower in STs than in CTs of first-trimester placental tissues. PGRMC1 expression in BeWo cells (a trophoblast-derived choriocarcinoma cell line) decreased upon dibutyryl-cAMP (db-cAMP)-induced differentiation. Both inhibition and knockdown of PGRMC1 stimulated hCG production in the presence of db-cAMP. Furthermore, a quantitative cell fusion assay we developed revealed that inhibition and knockdown of PGRMC1 enhanced db-cAMP-stimulated cell fusion. Peroxisome proliferator-activated receptor γ (PPARγ) agonists decreased PGRMC1 expression and stimulated the cell fusion in BeWo cells. These findings suggest that downregulation of PGRMC1 expression in part through activation of PPARγ during trophoblast differentiation promotes hCG production and cell fusion for formation and maintenance of placental villi during pregnancy.

Human endometrial stromal cells (ESCs) undergo differentiation, known as decidualization, and endometrial epithelial cells mature around the embryo implantation stage. In the uterus, cyclooxygenase 2 (COX2), the rate-limiting enzyme that produces prostaglandin E2, is expressed in endometrial stromal and epithelial cells, and promotes decidualization of the former cells. Our recent study demonstrated that progesterone receptor membrane component 1 (PGRMC1) is downregulated during decidualization and may be involved in cellular senescence associated with decidualization via the transcription factor forkhead box protein O1 (FOXO1). Therefore, we investigated the role of PGRMC1 in COX2 expression during differentiation and maturation of endometrial stromal and epithelial cells. Inhibition or knockdown of PGRMC1 significantly enhanced differentiation stimuli-induced COX2 expression in both cell types. However, this COX2 expression was suppressed by FOXO1 knockdown or nuclear factor-kappa B (NF-κB) inhibition. Silencing of COX2 expression inhibited PGRMC1 knockdown-induced expression of decidual markers in ESCs. Thus, PGRMC1 may be linked to FOXO1- and NF-κB-mediated COX2 expression in endometrial cells. Taken together, our data suggest that downregulation of PGRMC1 expression facilitates differentiation of endometrial cells, i.e., decidualization and glandular maturation, via upregulation of COX2 expression., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest associated with this manuscript., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

This study aimed to investigate the risk factors for difficult endoscopic hemostasis in patients with colonic diverticular bleeding and to evaluate the efficacy and safety of transcatheter arterial embolization (TAE) for colonic diverticular bleeding. This study included 208 patients with colorectal diverticular hemorrhage. The non-interventional radiotherapy group consisted of patients who underwent successful spontaneous hemostasis (n = 131) or endoscopic hemostasis (n = 56), whereas the interventional radiotherapy group consisted of patients who underwent TAE (n = 21). Patient clinical characteristics were compared to identify independent risk factors for the interventional radiotherapy group. Furthermore, the hemostasis success rate, rebleeding rate, complications, and recurrence-free survival were compared between patients who underwent endoscopic hemostasis and those who underwent TAE. Bleeding from the right colon (odds ratio [OR]: 7.86; 95% confidence interval [CI]: 1.6-38.8; P = .0113) and systolic blood pressure <80 mm Hg (OR: 0.108; 95% CI: 0.0189-0.62; P = .0126) were identified as independent risk factors for the interventional radiology group. The hemostasis success rate (P = 1.00), early rebleeding rate (within 30 days) (P = .736), late rebleeding rate (P = 1.00), and recurrence-free survival rate (P = .717) were not significantly different between the patients who underwent TAE and those who underwent endoscopic hemostasis. Patients in the TAE group experienced more complications than those in the endoscopic hemostasis group (P < .001). Complications included mild intestinal ischemia (19.0%) and perforation requiring surgery (4.8%). Patients who required interventional radiotherapy were more likely to bleed from the right colon and presented with a systolic blood pressure of <80 mm Hg. TAE is an effective treatment for patients with colonic diverticular hemorrhage that is refractory to endoscopic hemostasis. However, complications must be monitored carefully., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Extravillous trophoblasts (EVTs) invade the endometrium to establish a fetomaternal interaction during pregnancy. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) stimulate EVT invasion by binding to the EGF receptor (EGFR). We examined the role of the small GTP-binding protein Rap1 in EGF- and HB-EGF-stimulated EVT invasion., Methods: Expression of Rap1 in the first-trimester placenta was examined by immunohistochemistry. Effect of EGF or HB-EGF on Rap1 activation (GTP-Rap1) and Rap1 knockdown on invasion was assessed in EVT cell line (HTR-8/SVneo). In addition, effect of Rap1 knockdown and Rap1GAP (a Rap1 inactivator) overexpression on the activation of EGF signaling and EGFR expression were examined., Results: Rap1 was expressed by EVTs, villous cytotrophoblasts, and syncytiotrophoblasts in the placenta. EGF and HB-EGF activated Rap1 and promoted invasion of HTR-8/SVneo, and these effects were inhibited by Rap1 knockdown. The EGF- and HB-EGF-induced phosphorylation of AKT, ERK1/2, p38MAPK, and Src was inhibited by Rap1 knockdown. Furthermore, the knockdown of Rap1 reduced the EGFR protein level. Overexpression of Rap1GAP repressed EGF- and HB-EGF-induced Rap1 activation and reduced EGFR expression., Conclusion: Rap1 may function as a mediator of EGF and HB-EGF signaling pathways and can modulate EGFR expression in EVTs during placental development., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Background: Transarterial chemoembolization (TACE) is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B hepatocellular carcinoma (HCC). A novel glass membrane emulsification device (GMD) produces a high percentage of water/oil emulsions with homogeneous and stable droplets. There are few reports on the efficacy of GMD-conventional-TACE (GMD-c-TACE); therefore, we aimed to evaluate the effectiveness of GMD-c-TACE., Methods: Seventy-one patients with HCC with tumor diameter <5 cm who underwent c-TACE with and without GMD were included in this study to investigate local recurrence and hepatic functional reserve., Results: The local recurrence rates of TACE without GMD were 3.0% at 6 months, 16.7% at 12 months, and 35.0% at 18 months, around where it plateaued. In contrast, the local recurrence rates in the GMD-c-TACE group were 0.0% at 12 months and 15.4% at 18 months, respectively. Thus, GMD-c-TAE had a significantly lower local recurrence. ALBI score of c-TACE with GMD significantly preserved hepatic reserve. Multivariate analysis showed that GMD-c-TACE could suppress local recurrence and maintain hepatic reserve., Conclusions: GMD-c-TACE allows dense lipiodol accumulation in the tumor and the attainment of good local control. Additionally, in vitro evaluation of the sustained release properties of GMD, the inhibition of the release of anticancer drugs may lead to maintain hepatic reserve. GMD-c-TACE is useful in preventing local recurrence and is expected to become the standard treatment form of c-TACE in the future.

The pathogenesis of hypertensive disorder of pregnancy (HDP), which affects about 10% of pregnant women, is still incompletely understood. Our previous study showed that endoplasmic reticulum (ER) stress influences high-temperature requirement A serine peptidase 1 (HTRA1) expression and trophoblast invasion. However, the involvement of ER stress in the regulation of HTRA subtype expression and pathophysiology of HDP has not been characterized in extravillous trophoblasts (EVTs). To investigate this, HTR8/SVneo EVTs cell line was treated with the ER stress inducers Thapsigargin (Thap) or Tunicamycin (Tuni). Treatment with either Thap or Tuni inhibited trophoblast invasion, reduced HTRA1 and HTRA3 expression, but did not alter HTRA2 or HTRA4 expression. Knockdown of HTRA1 or HTRA3 also inhibited trophoblast invasion. Furthermore, treatment with either ER stress inducer or HTRA1 silencing increased the ratio of soluble fms-like tyrosine kinase-1/placental growth factor (sFLT1/PlGF), which is a marker of HDP. Immunohistochemical analysis revealed that HTRA1 is localized to EVTs and the endometrial decidua in the placenta of patients with HDP. These results suggest that factors that cause ER stress could result in the inhibition of EVTs invasion via HTRA1., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Uterine leiomyosarcoma is an aggressive soft tissue tumor. Stathmin, a phosphoprotein that modulates microtubule dynamics, is highly expressed in many malignancies including leiomyosarcoma. The microtubule-depolymerizing agent eribulin has been recently approved for treating malignant soft tissue tumors. Although eribulin inhibits microtubule polymerization, little is known about the relationship between eribulin treatment and stathmin dynamics. In this study, we explored the role of stathmin expression in the action of eribulin in leiomyosarcoma cells. Eribulin induced phosphorylation of stathmin and reduced expression of subunits A and C of protein phosphatase 2A (PP2A) in a leiomyosarcoma cell line. The PP2A activator FTY720 reduced levels of phosphorylated stathmin. Eribulin decreased stathmin protein levels without affecting stathmin mRNA expression. Furthermore, stathmin knockdown attenuated the inhibitory effects of eribulin on cell viability, whereas stathmin overexpression enhanced the anti-proliferative effect of eribulin. Eribulin-resistant leiomyosarcoma cell lines had enhanced expression of the class Ⅰ β-tubulin TUBB1, multi-drug resistance 1 protein MDR1 and breast cancer-resistance protein BCRP, and decreased expression of stathmin. Taken together, these results suggest that stathmin expression modulates the pharmacological efficacy of eribulin in uterine leiomyosarcoma cells., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest associated with this manuscript., (Copyright © 2022 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Blood transfusion, splenectomy, and partial splenic embolization (PSE) are generally performed for thrombocytopenia in patients with cirrhosis. Recently, thrombopoietin (TPO) agonists have become available, and investigations of patients who would benefit from them are necessary. Therefore, it is important to understand the fluctuations in cytokine levels associated with PSE. Therefore, fluctuations in platelet-associated immunoglobulin G (PAIgG), interleukin 6 (IL-6), and TPO levels with PSE were analyzed in this study. The study included 110 patients with liver cirrhosis and thrombocytopenia, with the aim of improving platelet counts. Fluctuations in PAIgG, IL-6, and TPO levels were investigated. The average splenic embolization ratio was 58.0% in patients with PSE. The platelet count rose significantly from 6.95 [5.40, 8.60] × 104/mL to 14.05 [10.43, 18.05] × 104/mL (P < .01), IL-6 rose significantly from 3.56 [2.53, 7.33] pg/mL to 18.90 [9.17, 32.95] pg/mL (P < .01), TPO rose significantly from 0.82 [0.52, 1.21] fmol/mL to 1.58 [0.97, 2.26] fmol/mL (P < .01), and PAIgG decreased significantly from 64.20 [38.33, 118.75] ng/107 cells to 37.50 [22.25, 70.00] ng/107 cells (P < .01). On multivariate analysis of factors related to the rate of platelet increase with PSE, primary biliary cholangitis (B = 0.475, P < .01), splenic embolization ratio (B = 0.75, P < .01), IL-6 change ratio (B = 0.019, P < .01), and PAIgG change ratio (B = -0.325, P < .01) were significant. When attempting to improve thrombocytopenia with PSE, adequate splenic embolization needs to be obtained together with improvements in IL-6, PAIgG, and TPO levels. With unsatisfactory improvement in thrombocytopenia, TPO agonist administration was considered., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Endometriosis is characterized by the presence of inflamed and fibrotic endometrial tissue outside the uterine cavity. Previously, we found decreased SERPINA1 (alpha-1 antitrypsin) expression in endometriosis-like lesions in a mouse model of endometriosis, suggesting that it exacerbated inflammation in these lesions. However, the molecular mechanism(s) by which SERPINA1 affects expression of inflammatory factors and development of endometriotic lesions have not been fully characterized. To investigate the role of intracellular SERPINA1 in endometrial stromal cells (ESCs), we performed RNA sequence analysis using RNA extracted from ESCs in which SERPINA1 was knocked down. The analysis identified several toll-like receptor (TLR)-related factors as being upregulated. Silencing of SERPINA1 increased expression of TLR3 and TLR4 in ESCs, as well as several TLR signaling pathway components, including MYD88, IRAK1/4, interleukin (IL)-1β, and interferon (IFN)-β. TLR3 or TLR4 agonists increased expression of inflammatory factors in SERPINA1-knockdown ESCs, whereas TLR3 or TLR4 inhibitors decreased expression. In addition, treatment with recombinant IL-1β or IFN-β increased expression of MYD88 and inflammatory factors in ESCs. Immunohistochemical analysis of endometriotic tissues showed that TLR3, TLR4, and MYD88 were localized in endometriosis lesions. Taken together, the data suggest that reduced expression of SERPINA1 induces expression of inflammatory factors by ESCs, which in turn are associated with TLR3/4, IL-1β, and IFN-β signaling. Regulation of intracellular SERPINA1 levels in ESCs may be a strategy to inhibit inflammatory responses in endometriotic lesions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kusama, Satoyoshi, Azumi, Yoshie, Kojima, Mizuno, Ono, Nishi, Kajihara and Tamura.)

Background: Mac-2-binding protein glycosylation isomer (M2BPGi), a novel noninvasive biomarker for fibrosis, is a prognostic factor for liver disease; however, its relationship with hepatic function reserve and nutritional status remains unclear. Furthermore, the cut-off value of this marker varies with the underlying liver disease. This study aims to clarify that M2BPGi can be clinically used as a hepatic function reserve marker and nutritional index without pushing the search for alternative markers to the forefront in clinical practice as an important biomarker., Methods: Seven hundred and forty-three outpatients with chronic liver disease (CLD) were enrolled. We evaluated the relationship among M2BPGi, albumin-bilirubin (ALBI) grade, and Controlling Nutritional Status (CONUT) score as nutritional status markers. Diagnostic performance of M2BPGi values in distinguishing different modified ALBI (mALBI) grade and CONUT score were compared using receiver operating characteristic (ROC) curve analysis., Results: The M2BPGi level increased with ALBI and mALBI grades. The correlation coefficient (r2) between M2BPGi and ALBI grade was 0.40 (r=0.63), indicating a positive correlation between M2BPGi and ALBI grade. The cut-off for M2BPGi to predict mALBI G1 vs. G2-G3 was 1.07, G1-2a vs. G2b-3 was 1.73, and mALBI G1-2 vs. G3 was 5.83 under the ROC curves. The cut-off for M2BPGi to predict CONUT score normal vs. light-severe was 1.60, normal-light vs. moderate-severe was 1.74, and normal-moderate vs. severe was 5.83 under the ROC curves. M2BPGi correlates with ALBI grade and is useful for diagnosing ROC analysis results, especially G2 and above. M2BPGi also correlates with the CONUT score and is useful for diagnosing ROC analysis results, especially moderate or higher. These results showed similar diagnostic performance regardless of the etiology of the background liver disease., Conclusions: Although the predictive cut-off value varied with the type of liver disease, M2BPGi was found to be a single predict biomarker of ALBI and CONUT, and thus, is an effective indicator of CLD status. Further investigation is warranted to determine the clinical utility of this marker.

The appropriate differentiation of endometrial stromal cells (ESCs) into decidual cells is required for embryo implantation and subsequent placentation into humans. Decidualization is accompanied by the appearance of senescent-like cells. We recently reported the secretory phase-specific downregulation of endometrial progesterone receptor membrane component 1 (PGRMC1) and enhanced decidualization upon PGRMC1 knockdown and inhibition in cultured ESCs. However, it remains unknown whether PGRMC1 is involved in cellular senescence during decidualization. Here, we showed that the small interfering RNA (siRNA)-mediated knockdown of PGRMC1 and the inhibition of PGRMC1 by AG-205 increased the expression of the transcription factor forkhead box protein O1 (FOXO1) and the senescence-associated β-galactosidase activity in cAMP analog- and progesterone-treated ESCs. Furthermore, the knockdown of FOXO1 repressed the decidual senescence induced by siRNA-based PGRMC1 knockdown or AG-205 treatment. Taken together, the decreased PGRMC1 expression in ESCs may accelerate decidualization and cellular senescence via the upregulation of FOXO1 expression for appropriate endometrial remodeling and embryo implantation during the secretory phase.

Background: Interventional radiology (IVR), including balloon-occluded retrograde transvenous obliteration (BRTO) and percutaneous transhepatic obliteration (PTO), is performed for patients with intractable hepatic encephalopathy (HE). However, information on the appropriate coil for endovascular coiling for preventing recanalization is lacking. This study aimed to compare the different types of coils for endovascular coiling used in BRTO and PTO for cases of intractable HE., Methods: This retrospective study included patients who underwent endovascular coiling with BRTO or PTO for HE caused by portosystemic shunts. The number of coils required for complete occlusion was compared among bare, fiber, and hydrogel-coated coils, and the expansion types that close the gap between and inside the hydrogel-coated coils were also compared., Results: Of 38 patients (age range, 30-86 years), 16 and 22 underwent BRTO and PTO, respectively, using bare (19 patients), fiber (8 patients), and hydrogel-coated coils (10 patients; external expansion type, 4; internal expansion type, 6). No significant differences in the size of portosystemic shunts were observed according to the type of coil. The mean number of coils required for complete occlusion varied (bare coils, 19.32; fiber coils, 18.11; hydrogel-coated coils, 10.70). Significantly fewer coils were required for endovascular coiling with hydrogel-coated coils. In the internal expansion type, a mean of 8.5 coils was required for occlusion., Conclusions: In some patients who underwent portal vein embolization, complete occlusion was not achieved with the scheduled type of coil because of slight expansion of blood vessels due to coil pressure. The findings suggested that hydrogel-coated coils were effective in endovascular coiling for HE caused by a portosystemic shunt, and internal expansion-type hydrogel-coated coils may be effective for the first-line procedure.

Background and Aims: The prognosis of acute liver failure (ALF) treated with conservative therapy is extremely poor. Histologic diagnosis at the time ALF occurs provides important clues for determining the prognosis, including indications for liver transplant. Transjugular liver biopsy (TJLB), which helps clarify the pathology of ALF, may be an effective clinical parameter that contributes to prognosis prediction, including indications for liver transplant., Methods: In this prospective study, 79 patients who underwent TJLB with ALF were enrolled between May 2002 and March 2021. The relationships between prognosis and the extent of tissue necrosis on TJLB specimens, serum parameters related to the cause, and clinical parameters were investigated., Results: Model for end-stage liver disease-sodium, hepatic encephalopathy predicting, total bilirubin, hepatocyte growth factor, ammonia, coma rate, and histologic diagnosis were identified as prognostic factors on univariate analysis. Histologically, 13 of 16 patients with massive hepatic necrosis died or had a liver transplant. On multivariate analysis, the only prognostic factor was massive hepatic necrosis. There were no treatment-related complications, and TJLB was technically successful in all patients., Conclusion: In diagnosing the cause of ALF and understanding its pathology, TJLB contributes to predicting the prognosis of ALF based on histologic findings together with liver function tests and imaging findings, and it is an important diagnostic technique for determining diagnostic and treatment eligibility, including indications for liver transplant. When determining the best timing for patient selection and liver transplant, the finding of massive hepatic necrosis on TJLB specimens at the time ALF occurred was the most important prognostic factor., (© 2022 The Authors.)

Eribulin, an inhibitor of microtubule dynamics, is used for treating breast cancers and sarcomas. The microtubule-destabilizing protein stathmin may modulate the antiproliferative activity of eribulin on breast cancer cells and leiomyosarcoma cells. The antitumor activity of eribulin in ovarian cancers has not been fully explored, so the present study aimed to determine the antitumor efficacy of eribulin and the involvement of stathmin in ovarian cancers. In a xenograft model of ovarian cancer, eribulin treatment reduced the tumor weight, which was accompanied by an increased level of phosphorylated stathmin. Eribulin stimulated the phosphorylation of stathmin in cultured cancer cell lines. The eribulin-induced phosphorylation of stathmin was inhibited by treatment with FTY720, an activator of protein phosphatase 2A (PP2A), and eribulin downregulated the expression of PP2A subunits. Furthermore, stathmin knockdown abrogated the inhibitory effects of eribulin on cell viability. Eribulin enhanced the antiproliferative effects of paclitaxel and concomitantly decreased stathmin expression. These results suggest that eribulin-induced phosphorylation of stathmin, mediated in part by PP2A downregulation, reduces stathmin activity and enhances the antiproliferative effects of paclitaxel in ovarian cancer. Collectively, the results of this study indicate that eribulin may suppress the proliferation of ovarian cancer cells partly by regulating the activity of stathmin.

Background: Navigation system devices have been developed to allow precise resection of brain tumor. The fence-post catheter techniques that use a navigation system have been used in many neurosurgery centers. However, an exclusive catheter for the fence-post catheter techniques have not been made, and substituted silicon tube of the cerebral ventricle drainage or a Nelaton catheter is widely used., Objective: In this brief technical note, we describe a new fence-post catheter with steel tip device that was designed for more precise tissue resection and is useful in tumor resection., Methods: The newly designed fence-post catheter helps to visually gauge the accurate depth from the tumor bottom during tumor resection. Furthermore, the catheter tip has moderate weight and is made of a non-magnetic material., Results: Using our fence-post catheter, which has a metal part at the tip of the tube (length, 13 mm), operators can clearly notice that they are getting closer to base of the tumor by checking the metal part during the resection of deep tumors., Conclusion: Our newly developed fence-post tube enables easy confirmation of the distance to deep-tissue regions and improves the degree of safety during tumor removal. J. Med. Invest. 69 : 117-119, February, 2022.

Endometriosis is characterized by inflammation and fibrotic changes. Our previous study using a mouse model showed that proinflammatory factors present in peritoneal hemorrhage exacerbated inflammation in endometriosis-like grafts, at least in part through the activation of prostaglandin (PG) E2 receptor and protease-activated receptor (PAR). In addition, menstruation-related factors, PGE2 and thrombin (P/T), a PAR1 agonist induced epithelial-mesenchymal transition (EMT) of endometrial cells under hypoxia. However, the molecular mechanisms by which P/T induce development of endometriosis have not been fully characterized. To investigate the effects of P/T, RNA extracted from endometrial stromal cells (ESCs) treated with P/T were subjected to RNA sequence analysis, and identified activin A, FOS, and GATA2 as upregulated genes. Activin A increased the expression of connective tissue growth factor (CTGF) and mesenchymal marker genes in ESCs. CTGF induced the expression of fibrosis marker type I collagen, fibronectin, and α-smooth muscle actin (αSMA), indicating fibroblast to myofibroblast transdifferentiation (FMT) of ESCs. In addition, activin A, FOS, GATA2, CTGF, and αSMA were localized in endometriosis lesions. Taken together, our data show that P/T induces changes resembling EMT and FMT in ectopic ESCs derived from retrograde menstruation, and that these are associated with fibrotic changes in the lesions. Pharmacological means that block P/T-induced activin A and CTGF signaling may be strategies to inhibit fibrosis in endometriotic lesions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Tolvaptan (TVP) is an effective treatment for patients with cirrhotic ascites; however, studies have indicated that a sufficient effect is difficult to obtain in patients with hepatocellular carcinoma (HCC). This study evaluates the efficacy of TVP in patients with HCC with refractory ascites., Methods: We retrospectively enrolled 32 patients with liver cirrhosis and refractory ascites [mean age: 74 years (range, 47-86 years), men: 78.1% (25/32)]. All patients had HCC and were treated with TVP at our hospital. A TVP responder was defined as a patient who experienced decrease in body weight by ≥1.5 kg within 1 week of treatment. Univariate and multivariate analyses were performed to evaluate clinical and laboratory predictive factors of TVP response., Results: The TVP response rate was 46.9% (15/32 patients) after 1 week of treatment. HCC treatment (transcatheter arterial chemoembolization and/or radiofrequency ablation) was administered to 11/15 (73.3%) responders. In the multivariate analysis, the reduction of urine osmolality was higher in responders than nonresponders (202 mOsm/l vs. 65 mOsm/l, P = 0.040), and the tumor stage (P = 0.043) was worse in nonresponders. Multivariate Cox proportional hazards regression analysis indicated a significantly better prognosis among responders than among nonresponders (P < 0.01)., Conclusion: The HCC tumor stage and the reduction in urine osmolality can predict the efficacy of TVP in patients with refractory ascites complicated with HCC. TVP may allow therapeutic intervention for HCC and improve prognosis, even in patients with Child-Pugh class C., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction Transjugular liver biopsy (TJLB) is indicated for patients in whom percutaneous liver biopsy is contraindicated, such as those with hematological diseases complicated by liver dysfunction. However, the clinical utility of TJLB in this group of patients has not been thoroughly investigated. The objective of this study is to evaluate the clinical efficacy of TJLB in patients with hematological diseases complicated by liver dysfunction. Methods We analyzed the data of patients who developed liver disorders during treatment for hematological diseases at our hospital and required tissue diagnosis via TJLB. The clinical features of patients were analyzed. Results Twenty-seven patients (mean age, 60.07 years; 12 men, 15 women) requiring tissue diagnoses via TJLB after developing liver disorders while undergoing treatment for hematological diseases were enrolled. One patient with autoimmune hemolytic anemia was diagnosed with drug-induced liver injury; two patients with amyloidosis had nonalcoholic steatohepatitis; one patient with acute promyelocytic leukemia had a drug-induced liver injury; one patient with chronic myelomonocytic leukemia had liver infiltration caused by an underlying disease; three patients with idiopathic thrombocytopenic purpura had autoimmune hepatitis; four patients with malignant lymphoma had liver infiltration by the underlying disease, and one patient with multiple myeloma had liver disorder caused by disseminated intravascular coagulation. Moreover, one patient had hepatitis B reactivation, another had hepatitis E, and six patients had a drug-induced liver injury. The treatment regimen was altered in cases of liver infiltration caused by the underlying disease, and the drug was changed for patients with drug-induced liver injury. Conclusion The etiology of liver disorders in patients with hematological diseases varies widely. Therefore, histological diagnosis using TJLB is useful to determine an appropriate therapeutic strategy for underlying hematological diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ishikawa et al.)

Background/aim: Tumor biopsy are needed frequency for accurate diagnosis. However, percutaneous liver tumor biopsy presents a risk of complications such as bleeding and tumor seeding. We investigated the feasibility of liver tumor biopsy, followed by cauterization with expandable radiofrequency ablation., Patients and Methods: Tumor biopsies using a co-access needle were performed in 102 patients. Expandable radiofrequency ablation was used to ensure cauterization and hemostasis of the puncture route. We evaluated the clinical background and complications., Results: The average (±standard deviation) tumor diameter was 56.87±39.45 mm. Pathological diagnosis was possible in all cases. In 20 patients, the postoperative pathological diagnosis differed from the preoperative diagnosis. No significant anemia progression was observed in any patients after biopsy, and no peritoneal seeding was observed during a mean follow-up observation period of 18.5 months., Conclusion: Liver tumor biopsy, followed by cauterization with expandable radiofrequency ablation via a co-access needle, is safe and useful for obtaining reliable diagnoses., Competing Interests: None declared., (Copyright 2021, International Institute of Anticancer Research.)

Radiotherapy (RT) is used to manage cervical cancer, and pelvic insufficiency fracture (PIF) is known as a late complication of RT. The present study identified risk factors for PIF after radiotherapy for cervical cancer, and investigated its incidence rate. It also considered the usefulness of positron emission tomography/magnetic resonance imaging (PET/MRI) in PIF diagnosis. A total of 149 patients with cervical cancer who received definitive or adjuvant RT with/without concurrent chemotherapy between January 2013 and December 2018 were investigated in the present study and followed up for more than one month after RT at Kobe University Hospital. The median follow-up period was 32 months (range, 1-87 months), and the median age of all patients was 66 years (age range, 34-90 years). Computed tomography (CT), MRI, PET/CT or PET/MRI were used for image examination. Among the 149 patients, 31 (20.8%) developed PIF. The median age of these patients was 69 years (age range, 44-87 years). Univariate analysis using the log-rank test demonstrated that age (≥60 years) was significantly associated with PIF. The median maximum standardized uptake value of PIF sites on PET/CT was 4.32 (range, 3.04-4.81), and that on PET/MRI was 3.97 (range, 1.21-5.96) (P=0.162). Notably, the detection time of PIF by PET/MRI was significantly earlier compared with PET/CT (P<0.05). The incidence of PIF after RT for cervical cancer was 20.8%, and age was significantly associated with risk factors for such fractures. Taken together, these results suggest that PET/MRI, which offers the advantage of decreased radiation exposure to the patient, is useful for diagnosing PIF and can detect it earlier than PET/CT imaging., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Azumi et al.)

Decidualization - the differentiation of endometrial stromal cells (ESCs) into decidual cells - is a crucial step for successful embryo implantation and placentation that is initiated in the secretory phase of the menstrual cycle. During decidualization, ESCs undergo proliferation arrest and secrete inflammatory mediators, including senescence-associated secretory phenotype (SASP). Although several senolytic agents improve age-related diseases, their effects on cellular senescence in decidualizing ESCs has not been explored. To do this, we treated decidualized ESCs with the senolytic agents Quercetin (Que), Dasatinib (Das), and BPTES. Que decreased the number of senescence-associated β-galactosidase (SA-β-Gal) positive cells and expression of senescence markers in ESCs treated with the decidual stimulus (dibutyryl-cAMP plus progesterone: DP). Concomitantly, Que markedly increased the expression of the decidualization markers IGFBP1, PRL, and FOXO1, in decidualizing ESCs. Similar to Que, Das also stimulated decidualization. Treatment with a combination of Que and Das synergistically increased the expression of decidualization markers and senescence markers compared with treatment with Que or Das alone. However, BPTES did not enhance the expression of decidualization markers. These results imply that treatment with Que and/or Das can remove senescent decidual cells and enhance the decidualization of the rest of ESCs. Thus, senolytic modulation of abnormal ESC decidualization could alleviate infertility caused by dysfunctions of endometrial receptivity and embryo implantation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Stathmin, a phosphoprotein that modulates microtubule dynamics, is highly expressed in breast cancer cells. Eribulin, a microtubule-depolymerizing agent, is used to treat patients with advanced breast cancer. However, the detailed mechanisms underlying the action of eribulin during microtubule catastrophe, and the interaction between eribulin and stathmin dynamics, remain unclear. Here, we investigated the role of stathmin in the antiproliferative activity of eribulin in breast cancer cells. Eribulin induced phosphorylation of stathmin in MCF7 and MDA-MB-231 cells; this was attenuated by an inhibitor of protein kinase A (H89) and an inhibitor of Ca 2+ /calmodulin-dependent kinase II (KN62). In addition, expression of phosphorylated stathmin was reduced by the protein phosphatase PP2A activator FTY720 but increased by the PP2A inhibitor okadaic acid. Of note, expression of PP2A subunits in eribulin-treated cells decreased, although eribulin did not affect the phosphatase activity of recombinant PP2A directly. Furthermore, the antiproliferative effect of eribulin was stronger in stathmin-overexpressing cells. These results suggest that stathmin dynamics are closely associated with the antiproliferative effects of eribulin and stathmin is a possible biomarker for predicting the therapeutic effects of eribulin in breast cancer patients., (© 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Background: Current guidelines recommend the temporary discontinuation of anticoagulants before colonoscopic polypectomy, but the effect of this practice on reducing the risk of delayed bleeding after hot snare polypectomy (HSP) and endoscopic mucosal resection (EMR) remains unclear. Our aim was to assess the impact of anticoagulants on the risk of colorectal delayed bleeding after HSP and EMR, and evaluate the necessity of drug withdrawal., Methods: We reviewed the clinical data of patients with colorectal polyps using antithrombotic drugs who underwent HSP and/or EMR between January 2016 and September 2020 at Nagaoka Red Cross Hospital. After excluding antiplatelet users, patients were classified into those who continued anticoagulants [continuation group: 50 patients (93 lesions)] and those who discontinued anticoagulants [discontinuation group: 87 patients (190 lesions)]., Results: Delayed bleeding occurred in 12 lesions, and there was no significant difference in the incidence rates between the continuation and the discontinuation groups (3.2% vs. 4.7%; P=0.756). Logistic regression analysis showed that continued use of anticoagulants was not a significant risk factor for delayed bleeding compared to anticoagulant discontinuation (odds ratio, 0.670; 95% CI, 0.177-2.537; P=0.556). There was no significant difference in the incidence rate and risk of delayed bleeding, regardless of the length of the anticoagulant withdrawal period., Conclusions: Continued use of anticoagulants, compared to their discontinuation, did not increase the risk of colorectal delayed bleeding after HSP and EMR. Our results suggest that current guideline recommendations for anticoagulant withdrawal before colonoscopic polypectomy may be reconsidered., Trial Registration: UMIN000040449., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (Available at https://dx.doi.org/10.21037/jgo-21-3). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

The current study aimed to compare the safety and effectiveness of self-expandable metallic stent placement among patients with extracolonic malignancy and those with colorectal cancer. Patient information, technical and clinical success rates and complication rates were compared between patients with colorectal cancer and extracolonic malignancy. The Kaplan-Meier method was used to compare the time elapsed before the onset of complications. Risk factors for re-obstruction in patients with self-expandable metallic stents were evaluated by multivariate analysis. A total of 68 patients who underwent self-expandable metallic stent placement at Saiseikai Niigata Hospital between January 2012 and September 2019 were included. The clinical success rate was significantly different between the colorectal cancer (96.6%) and extracolonic malignancy (66.7%) groups (P=0.01). The incidence of complications was significantly higher in the extracolonic malignancy group (66.7%) than in the colorectal cancer group (25.4%; P=0.02). Additionally, the time elapsed before the onset of complications was shorter in the extracolonic malignancy group than in the colorectal cancer group (P=0.0008). Risk factors for re-obstruction were higher in the extracolonic malignancy group [odds ratio, 7.76 (1.02-57.2)] than in the palliative stent placement group [odds ratio, 5.45 (1.01-29.5); P=0.04]. In extracolonic malignancy, self-expandable metallic stent placement was associated with lower clinical success rates and increased risk of complications. The time elapsed before the onset of complications was short, and extracolonic malignancy was a risk factor for re-obstruction, suggesting that the placement of self-expandable metallic stents for malignant colorectal obstruction in extracolonic malignancy is not optimal., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Sano et al.)

Background: Serous endometrial intraepithelial carcinoma (SEIC) is now considered to represent an early stage of uterine serous carcinoma (USC). It is an intraepithelial lesion but has been reported to cause extrauterine metastases. We report a case of SEIC with serous ovarian carcinoma and lymph node metastasis., Case Presentation: A 57-year-old post-menopausal woman (gravida 3, para 2, SA1) was referred to our hospital with lower abdominal pain. An ultrasound and MRI showed that the ovary had swollen to 8 cm in size and had a solid lesion. The uterus was normal. The patient underwent exploratory laparoscopy on the suspicion of torsion of the ovarian tumor. Intraoperative findings showed a right ovarian tumor, but no ovarian tumor torsion was observed. A small amount of bloody ascites was found in the Douglas fossa, and bleeding was observed from the tumor itself. A right salpingo-oophorectomy was then performed. Histopathological results revealed a high-grade serous carcinoma. Forty days after the first surgery, we performed a staging laparotomy: a total abdominal hysterectomy, left salpingo-oophorectomy, systematic pelvic and paraaortic lymphadenectomy, and a partial omentectomy. A complete cytoreduction was achieved. In the pathological examination, the invasion of the serous carcinoma was observed in the left ovarian ligament, and lymph node metastasis was found in the paraaortic lymph nodes. Atypical columnar cells formed irregular papillary lesions which had proliferated in the endometrium, and this was diagnosed as SEIC. The final diagnosis was serous ovarian cancer, FIGO stage IIIA1(ii), pT2bN1M0, with SEIC., Conclusion: We report a case of SEIC with synchronous serous carcinoma of the adnexa uteri. Both were serous carcinomas and, thus, it was difficult to identify the primary lesion. The distinction between metastatic cancer and two independent primary tumors is important for an accurate diagnosis and tumor staging. Histological diagnostic criteria remain controversial, and further development of a method for differentiating between both diseases is required.

It remains unclear whether therapeutic drug monitoring (TDM) of pazopanib improves treatment outcomes in routine clinical practice. We did a prospective cohort study to evaluate the benefits of TDM for pazopanib therapy in real-world practice. Among 25 patients with pharmacokinetically guided dosing, only 5 (20%, 95% confidence interval 6.8-40.7%) discontinued treatment because of adverse events. However, 5 (41.7%, 95% confidence interval 15.2-72.3%) of historical controls including 12 patients not receiving such a strategy experienced adverse events leading to early termination. PK-guided dosing significantly increased median time-to-treatment discontinuation (252 vs 74 days, P = .012) with reduced toxicity and improved overall survival (not reached vs 313 days, P = .002) relative to conventional dosing in the control group. In conclusion, PK-guided dose adaptation through the use of TDM has the potential to improve treatment outcomes of pazopanib in routine clinical practice, warranting larger, randomized studies., (© 2020 British Pharmacological Society.)

Purpose Axitinib is an orally active multikinase inhibitor currently used to treat patients with metastatic renal cell carcinoma (RCC). This study examined the pharmacokinetics of axitinib and the relationship between peak drug concentration (C max ) and clinical outcomes in real-world practice. Methods Twenty patients with metastatic RCC treated with axitinib monotherapy were enrolled. Post-dose (1-4 h) blood samples were obtained, and axitinib C max in plasma was measured by liquid chromatography-tandem mass spectrometry. Efficacy endpoints were best overall response (per RECIST 1.1) and progression-free survival (PFS). The safety endpoint was the cumulative incidence of dose-limiting toxicities (DLTs). Results Large inter- and intra-individual variability in dose-adjusted C max was observed (0.02-11.2 ng/mL/mg). Axitinib absorption was significantly influenced by glucuronidation activity (P = 0.040). C max at steady state was significantly higher in responders than in non-responders (P = 0.013). The optimal C max cutoff to predict a clinical response was 12.4 ng/mL. The median PFS was significantly longer in patients who achieved an average steady state C max above the threshold than in those who did not (799 vs. 336 days; P = 0.047). The cumulative incidence of DLTs was significantly higher in patients with C max  ≥ 40.2 ng/mL than in other patients (sub-hazard ratio, 4.13; 95% confidence interval, 1.27-13.5; P = 0.019). Conclusions The potential therapeutic window of axitinib C max in metastatic RCC was estimated at 12.4-40.2 ng/mL. Pharmacokinetically guided dose titration using therapeutic drug monitoring may improve the efficacy and safety of axitinib, warranting further investigation in a larger patient population.

Background: PCNSL is mainly treated with HD-MTX-based chemotherapy with or without WBRT. However, As WBRT is associated with delayed neurotoxicity leading to dementia in the elderly, many institutes reported benefits of intensive chemotherapy or high-dose chemotherapy with ASCT. We investigated whether treatment with HD-MTX and rituximab, followed by continued-maintenance HD-MTX monotherapy (3.5g / m2), improves overall survival (OS)., Methods: In this retrospective, single-center trial 52 immunocompetent patients with newly diagnosed PCNSL were included. All were treated between January 2005 and December 2017. The controls were 18 patients who, between 2005 and 2011, had received 3 cycles of HD-MTX and then adjuvant treatment with WBRT. In 2011 we started HD-MTX continued-maintenance therapy to treat 34 PCNSL patients. In the induction phase, these patients received HD-MTX every 14 days until a complete response (CR) was observed. When CR was obtained, maintenance therapy with HD-MTX (3.5g / m2) was delivered every three months., Results: In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT. J. Med. Invest. 68 : 286-291, August, 2021.

Purpose: Hydranencephaly is a rare condition that occurs during embryogenesis after neurogenesis and is characterized by the near complete absence of the cerebral hemispheres. In general, patients with hydranencephaly have been considered to have a markedly reduced life expectancy. We present 4 patients with hydranencephaly who have survived for over 5 years. The management and problems encountered in these cases are discussed., Methods: A retrospective review was conducted at our institution. Medical charts and radiographic studies were reviewed. Data including age at follow-up, sex, clinical complications, and surgical procedures were recorded., Results: Six patients were radiologically diagnosed with hydranencephaly during the period from January 2000 to December 2012. Two patients were excluded from our study: one because of death from pneumonia at 1 year of age and another because of transfer to another hospital. Four patients (3 males and 1 female) were included in the analysis. All 4 patients underwent ventriculoperitoneal shunt (VPS) placement and shunt revision. VPS infection occurred in 3 of 4 cases, and bloody cerebrospinal fluid (CSF) was observed in 2 of 4 cases. One patient underwent successful choroid plexus cauterization (CPC) and shunt removal after shunt infection., Conclusions: Prolonged survival with hydranencephaly is not unusual in the modern treatment era. CSF shunt problems, such as recurring shunt malfunction and shunt infection, represent one of the major problems, and avoiding CSF shunt with CPC is particularly desirable in patients with hydranencephaly.

Penetrating head injuries are rare, but can cause severe morbidity in children. In particular, penetrating head trauma with a wooden foreign body is considered to be likely to cause central nervous system infections because of its porosity and softness. However, actually confirming minute contaminations, such as skin debris or hair, in the brain parenchyma is rare. We report the case of a 2-year-old boy who presented with a penetrating head injury by a chopstick. During surgical removal of the chopstick, intraparenchymal hair contamination was confirmed under a surgical microscope. The postoperative course of the patient was uneventful. After 13 months of follow-up without any infectious events, the patient remains well and asymptomatic. The findings in the present case demonstrate that in the case of a penetrating head trauma with a wooden foreign body, surgical removal and active debridement should be the treatment of first choice.

Objective Rifaximin has become available for treating hyperammonemia in patients with hepatic encephalopathy. This study analyzed the changes in the body composition and nutritional status after long-term rifaximin therapy. Methods Twenty-one patients who underwent rifaximin therapy at 1,200 mg/day for more than 24 weeks were evaluated for the changes in the controlling nutritional status (CONUT) scores for the nutritional assessment, albumin-bilirubin (ALBI) scores for the liver function assessment, and skeletal muscle index (SMI) for the body composition assessment. Results There were 17 men and 4 women, with a mean age of 67.14±8.32 years. Eleven cases had a portosystemic shunt (52.3%), and 10 had hepatocellular carcinoma (47.6%). The Child-Pugh class was A in 9 cases (42.9%), B in 9 cases (42.9%), and C in 3 cases (14.2%). The blood ammonia levels in the rifaximin group improved significantly upon rifaximin therapy, from 124.76±28.68 μg/dL at baseline to 47.00±14.43 μg/dL after 2 weeks (p<0.001) and 49.81±15.02 μg/dL after 24 weeks (p<0.001). The CONUT scores improved significantly during rifaximin therapy, from 6.47±3.25 at baseline to 3.33±2.65 after 24 weeks (p=0.0007). The ALBI scores also improved significantly from -0.39±1.89 at baseline to -2.20±0.55 after 24 weeks (p=0.0002). The SMI scores showed that the body composition had been maintained in response to rifaximin therapy (50.20±7.67 at baseline and 51.29±7.62 after 24 weeks). Conclusion Rifaximin administration for hepatic encephalopathy improved the CONUT and ALBI scores. It may have a secondary effect on the improvement in the nutritional status and hepatic reserve.

Objectives: This study aimed to evaluate whether coating tooth surfaces with sodium fluoride (NaF) or silver diamine fluoride (SDF) inhibits bacteria-induced pH reductions at the bacteria/tooth interface., Methods: Specimens of coronal enamel (CE) or root dentin (RD) were prepared. The surfaces of the specimens were treated with 2% NaF or 38% SDF solution. Some specimens were aged for 1 week after being treated. A tooth specimen was fixed to the bottom of the well of the experimental apparatus. A miniature pH electrode was placed on the specimen and the well was filled with Streptococcus mutans (SM) cells. The pH was monitored after the addition of 0.5% glucose. SM cells were recovered from the wells, and the amounts of lactate, calcium, fluoride, and silver were measured., Results: The fluoride-treated tooth specimens exhibited significantly higher pH values than the untreated controls, irrespective of the tooth substrate at 120 min (CE: NaF 4.62 ± 0.06 vs 4.34 ± 0.10 and SDF 5.23 ± 0.29 vs 4.44 ± 0.16, RD: NaF 5.10 ± 0.11 vs 4.54 ± 0.33 and SDF 6.65 ± 0.47 vs 4.64 ± 0.39). The SDF-coated RD specimens released the greatest amounts of fluoride (103.3 ± 48.1 nmol/well) and silver (70.4 ± 36.9 nmol/well), while they exhibited significantly lower lactate production and decalcification (calcium release) than the control samples (lactate: 4.0 ± 0.7 vs 7.4 ± 0.3 mmol/l, calcium: 2.2 ± 0.4 vs 3.7 ± 0.5 μg/ml). This antimicrobial effect was weakened by 1 week's aging, while the acid resistance of the fluoride-treated surfaces seemed to increase with aging., Conclusions: Fluoride-treated tooth surfaces inhibit bacterial acid production at the bacteria/tooth interface. The SDF-coated RD had the strongest inhibitory effect., Clinical Significance: Coating RD with SDF could help to prevent root caries., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Delayed bleeding is an important complication after gastric endoscopic submucosal dissection (ESD). The search, coagulation, and clipping (SCC) method can be used to prevent delayed bleeding after ESD. However, its safety and efficacy are unclear. We compared the SCC method with post-ESD coagulation (PEC) to clarify the safety and efficacy of the SCC method for preventing delayed bleeding after gastric ESD., Methods: This retrospective study included 438 patients (478 lesions) who underwent gastric ESD. Multivariate logistic regression analysis was performed to identify the significant independent factors associated with delayed bleeding and we performed propensity-score matching (PSM) to reduce the effect of procedure-selection bias of SCC method., Results: Of the 438 patients, 216 underwent PEC and 222 underwent SCC. Delayed bleeding was significantly less common in the SCC than in the PEC (2.6% vs. 7.2%; P = 0.013). Among patients treated with antithrombotic therapy, the delayed bleeding rate was lower in the SCC group than in the PEC group; however, the difference was not significant (P = 0.15). The SCC method was found to be a significant independent factor for the prevention of delayed bleeding. PSM was performed in 156 patients in the PEC group and SCC group. There was a significant difference in the incidence of bleeding in the PEC and SCC groups (P = 0.013). No patient had perforation/bleeding associated with the SCC method., Conclusions: Our findings suggest that the SCC method is a simple, safe, and effective approach for preventing delayed bleeding after gastric ESD.

The article "The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection", written by Motoi Azumi, Manabu Takeuchi, Youhei Koseki, Masaru Kumagai, Yoko Kobayashi, Masafumi Takatsuna, Aiko Yoshioka, Seiichi Yoshikawa, Tsutomu Miura, and Shuji Terai, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 28 September 2018 without open access.

Background: The initial symptoms of Guillain-Barre Syndrome (GBS) can be similar to a case of spontaneous spinal epidural hematoma (SSEH) located at the cervicothoracic junction. Therefore, SSEH may be misdiagnosed as GBS., Case Report: A previously healthy 6-year-old girl presented with a 2-day history of progressive pain in the lower extremities and an inability to walk. On initial evaluation, she was completely paraparetic in the lower extremities. Deep tendon reflexes were absent in the lower extremities, and Babinski reflexes were positive on both sides. She exhibited reduced response to light touch and pinprick with a sensory level below T10, and experienced difficulty during urination. However, the strength, sensation and flexion of upper extremities were normal. Because her presentation and examinations were consistent with GBS, we initiated intravenous immunoglobulin therapy. The next day, she also developed pain and muscle weakness of the right upper extremity. Three days after admission, respiratory depression progressed rapidly. Spinal MRI showed a mass extending from the level of C7-T3, with spinal cord compression. The patient underwent an emergency laminectomy with evacuation of hematoma, and was diagnosed with SSEH. Sixty days after admission, she was transferred to the rehabilitation hospital with severe neurologic sequelae of paralysis in both legs., Conclusion: SSEH might have severe consequences, including neurologic deficits and risk of death. This case report serves to raise the awareness of SSEH that mimics the initial presentation of GBS., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Spontaneous intracranial hypotension (SIH) has been increasingly recognized as a phenomenon caused by cerebrospinal fluid (CSF) leaks; however, its pathogenesis remains unclear., Case Description: We report 2 cases of SIH resulting from CSF leak from a meningeal diverticulum at the C2 nerve root sleeve. The first case is that of a 46-year-old man who experienced orthostatic headache after a bicycle accident at age 45. Computed tomography (CT) myelography revealed CSF leaks at the C1-2 level. He underwent epidural blood patch therapy, but it was unsuccessful. Next, we performed direct surgery and found a meningeal diverticulum originating from the left C2 nerve root; therefore, we ligated the diverticulum. His symptoms and image findings strikingly improved after surgery. The second case is that of a 45-year-old man who experienced orthostatic headache 1 month after jumping into a river. Magnetic resonance imaging of the head showed bilateral subdural hematoma. CT myelography revealed CSF leaks at the C1-2 level and multiple cyst formations at the cervical and thoracic nerve root sleeves. epidural blood patch was performed, and his symptoms immediately improved., Conclusions: Recent studies have reported that meningeal diverticulum is involved in various cases of CSF leaks. The 2 cases indicate that traumatic accidents, such as back-and-forth neck movement or falls, presumably induce an increase in CSF pressure, followed by the rupture of an existing meningeal diverticulum, leading to CSF leak., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In Japan, this "ABC method" is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its cost-effectiveness for assessing gastric cancer risk., Methods: A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of HPA and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer., Results: According to base-case analysis, the ABC method cost less than annual endoscopic screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997., Conclusions: A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.

Objectives: To examine the long-term persistence rate with mirabegron in a real-world clinical setting., Methods: We retrospectively collected the data of patients who were prescribed mirabegron. We investigated the persistence rate and the reason for the discontinuation. The analysis included patient's age, diagnosis, Overactive Bladder Symptom Score, prostatic volume, the prescription by specialists for lower urinary tract dysfunction, drug-naïve patients, replacement of antimuscarinics or add-on therapy to antimuscarinics., Results: A total of 556 patients were included. Among them, 401 patients (72%) had overactive bladder and the other 155 (28%) were categorized as having other storage symptoms. During the observation period, 170 patients (42%) with overactive bladder discontinued mirabegron. The reasons for discontinuation in patients with overactive bladder included unmet expectation of treatment (45 patients, 26%), any adverse events (38 patients, 22%) or symptom improvement (37 patients, 22%). The persistence or discontinuation was not related with age, Overactive Bladder Symptom Score, prostatic volume or the prescription by specialists, while older male patients tended to continue mirabegron. The 3-year persistence rates in female and male overactive bladder patients were 46% and 51%, respectively, and these were better than those in patients with storage symptoms without urgency. In female overactive bladder patients, the persistence rate with mirabegron used as add-on therapy to antimuscarinics was higher than that in the drug-naïve patients on the Kaplan-Meier curve., Conclusions: The present study shows a relatively good long-term persistence rate with mirabegron in overactive bladder patients, notwithstanding the retrospective study in an academic hospital. The combined treatment with antimuscarinics could result in a good persistence rate with mirabegron., (© 2018 The Japanese Urological Association.)

Objectives: To evaluate the diagnostic efficacy of percutaneous renal tumor biopsy., Methods: We retrospectively investigated 23 patients who underwent percutaneous renal tumor biopsy since 2008 at Department of Renal and Urologic Surgery, Asahikawa Medical University Hospital. We examined indications of biopsy, diagnostic concordance rate between urologists, radiologists and biopsy findings, pathological findings and biopsy-related complications., Results: Renal tumor biopsy was performed under ultrasonography guidance in 21 patients and computed tomography guidance in 2. The most frequent indication to perform biopsy was to determine histological subtype of renal cell carcinoma(RCC)before treatment. The second indication was to clarify the nature of renal tumor. Biopsy findings revealed RCC in 17 patients and urothelial carcino- ma(UC)in 6. Diagnostic concordance rate between urologist's diagnosis and biopsy findings was 91%(21/23), which showed the same result between radiologists and biopsy findings. Biopsy-related adverse event included needle tract implantation in 1 patient with UC. Another patient who had central necrosis in the tumor showed insufficient material causing repeat biopsy with frozen section. Except this patient, initial renal tumor biopsy was successful in all patients by concomitant use of frozen section for tumor with central necrosis. The overall diagnostic rate of initial biopsy was 95.7%(22/23)., Conclusions: Despite a small number of patients and a retrospective nature, the present study shows that renal tumor biopsy plays an important role in diagnosis of renal tumor. Concomitant use of frozen section might be considered at the time of renal tumor biopsy in patients with necrotic renal tumor to avoid repeat biopsy. However, we should take into consideration that there are some possible risks of needle tract implantation in cases with UC when we perform percutaneous renal tumor biopsy.

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

Background and Study Aims: We previously reported that narrow-band imaging with magnifying endoscopy (NBI-ME) revealed a unique "gastritis-like" appearance in approximately 40 % of early gastric cancers after Helicobacter pylori eradication. Because rates of gastric cancer are increasing in patients with non-persistent infection of H. pylori, we aimed to clarify contribution factors to obscure tumors after therapeutic or spontaneous eradication., Patients and Methods: NBI-ME findings were examined retrospectively in 194 differentiated-type adenocarcinomas from H. pylori-negative patients with prior eradication therapy (83 patients) or without prior eradication therapy (72 patients). A gastritis-like appearance under NBI-ME was defined as an orderly microsurface structure and/or loss of clear demarcation with resemblance to the adjacent, non-cancerous mucosa. The correlation of this phenomenon with the degree of atrophic gastritis, determined both histologically in the adjacent mucosa and endoscopically, was evaluated., Results: The tumor-obscuring gastritis-like appearance was observed in 42 % and 23 % of the patients in the H. pylori eradication and non-eradication groups, respectively. The development of this appearance was affected by the histological grade of atrophy (P = 0.003) and intestinal metaplasia (P < 0.001) on univariate analysis. Multivariate analysis revealed an odds ratio of 0.25 (95 % confidence interval 0.10 - 0.61, P = 0.002) for an endoscopically severe extent of atrophy, independently of eradication therapy., Conclusions: An endoscopically mild or moderate extent of atrophy is associated with a gastritis-like appearance under NBI-ME in currently H. pylori-negative gastric cancers. Surveillance endoscopy should be performed carefully after successful eradication or spontaneous elimination of H. pylori, particularly in patients with non-severe atrophic background mucosa.

Objectives: To investigate the efficacy of combination treatment of degarelix and antiandrogen in patients with prostate cancer., Methods: We prospectively investigated the efficacy of combination treatment of degarelix and antiandrogen in 12 patients with treatment-naive prostate cancer. We surveyed PSA, LH, FSH and testosterone at day 3, 7, 14 and 28 during the initial month and thereafter once a month for 1 year. In cases with bone metastasis, we analyzed serum bone markers such as alkaline phosphatase(ALP), bone-type ALP and carboxyterminal telopeptide of type- I collagen once a month. Skeletal related events (SREs) were also monitored., Results: PSA progression free survival was 65%. PSA was reduced from baseline by 80% at day 14 and by 93% at day 28. In all patients serum testosterone immediately reached castrate level at day 3 and was maintained for 1 year without breakthrough escape. Both LH and FSH were reduced to within normal range at day 3. In contrast, all bone markers temporarily increased at day 28, and thereafter decreased. Although 2 patients had suffered from SREs before treatment, there were no SREs after combination treatment., Conclusions: The present study showed that combination of degarelix and antiandrogen could lead to favorable PSA reduction and immediate castrate level at an earlier phase. However, further study is needed to compare the difference between degarelix monotherapy and these combinations.

An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.