A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma.

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.

Autoimmunity against melanoma differentiation-associated gene 5 induces interstitial lung disease mimicking dermatomyositis in mice.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) is characterized by amyopathic DM with interstitial lung disease (ILD). Patients with anti-MDA5 antibody-associated ILD frequently develop rapidly progression and present high mortality rate in the acute phase. Here, we established a murine model of ILD mediated by autoimmunity against MDA5. Mice immunized with recombinant murine MDA5 whole protein, accompanied with complete Freund's adjuvant once a week for four times, developed MDA5-reactive T cells and anti-MDA5 antibodies. After acute lung injury induced by intranasal administration of polyinosinic-polycytidylic acid [poly (I:C)] mimicking viral infection, the MDA5-immunized mice developed fibrotic ILD representing prolonged respiratory inflammation accompanied by fibrotic changes 2 wk after poly (I:C)-administration, while the control mice had quickly and completely recovered from the respiratory inflammation. Treatment with anti-CD4 depleting antibody, but not anti-CD8 depleting antibody, suppressed the severity of MDA5-induced fibrotic ILD. Upregulation of interleukin (IL)-6 mRNA, which was temporarily observed in poly (I:C)-treated mice, was prolonged in MDA5-immunized mice. Treatment with anti-IL-6 receptor antibody ameliorated the MDA5-induced fibrotic ILD. These results suggested that autoimmunity against MDA5 exacerbates toll-like receptor 3-mediated acute lung injury, and prolongs inflammation resulting in the development of fibrotic ILD. IL-6 may play a key role initiating ILD in this model.

Relationship of plasma 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid concentration with OATP1B activity in patients with chronic kidney disease.

Organic anion-transporting polypeptides (OATP)1B are drug transporters mainly expressed in the sinusoidal membrane. Many studies have suggested that OATP1B activity is affected by genetic factor, the uremic toxin 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Coproporphyrin-I (CP-I) is spotlighted as a highly accurate endogenous substrate of OATP1B. We previously reported a positive correlation between plasma CMPF and CP-I concentrations in patients with chronic kidney disease (CKD). The present study evaluated the impact of genetic polymorphisms, CMPF, IL-6, TNF-α, and estimated glomerular filtration rate (eGFR) on individual differences in OATP1B activity in patients with CKD. Seventy-three patients with CKD who received kidney transplant at least 3 months earlier were analyzed. Plasma CP-I concentration was higher in OATP1B1*15 carriers than in non-carriers. In all patients, CP-I did not correlate significantly with CMPF, IL-6, TNF-α, or eGFR. However, when the dataset was cut off at CMPF concentration of 8 and 7 µg/mL, 4 µg/mL, 3 µg/mL or 2 µg/mL, CMPF correlated positively with CP-I, and correlation coefficient tended to be higher as plasma CMPF concentration was lower. In conclusion, OATP1B1*15 impacted OATP1B activity in patients with CKD, but IL-6 and TNF-α did not. However, the impact of CMPF on OATP1B activity was limited to low CMPF concentrations, and the effect could be saturated at high concentrations. When prescribing an OATP1B substrate drug for patients with CKD, the OATP1B1*15 carrier status and plasma CMPF concentration may need to be considered to decide the dose regimen.

Comparison of the diagnostic and prognostic abilities of flexible laryngoscopy and dynamic digital radiography for vocal cord paralysis: A prospective observational study.

BACKGROUND: Although flexible laryngoscopy (FL) is the reference modality for diagnosing vocal cord paralysis (VCP), FL involves patient discomfort and insertion intolerance. Dynamic digital radiography (DDR) with high spatial and temporal resolution is easier to use and less invasive when evaluating VCP. METHODS: Seventy-eight patients underwent FL and DDR before and after neck surgery. Qualitative and quantitative vocal cord movement (VCM) evaluations were conducted. Patients with postoperative VCP were followed-up regularly. RESULTS: DDR exhibited diagnostic performance with 67% sensitivity and 100% specificity. The cutoff for VCM was 2.4 mm, with DDR exhibiting 100% sensitivity and 78% specificity. All cords with transient VCP had positive VCM at both 3 weeks and 2 months. Additionally, 50% and 75% of cords with permanent VCP had negative VCM at 3 weeks and 2 months, respectively. CONCLUSIONS: DDR is promising for the diagnosis of postoperative VCP and early prediction of permanent postoperative VCP.

Evaluation of the usefulness of plasma 4ß-hydroxycholesterol concentration normalized by 4α-hydroxycholesterol for accurate CYP3A phenotyping.

Plasma 4ß-hydroxycholesterol (OHC) has drawn attention as an endogenous substrate indicating CYP3A activity. Plasma 4ß-OHC is produced by hydroxylation by CYP3A4 and CYP3A5 and by cholesterol autoxidation. Plasma 4α-OHC is produced by cholesterol autoxidation and not affected by CYP3A activity. This study aimed to evaluate the usefulness of plasma 4ß-OHC concentration minus plasma 4α-OHC concentration (4ß-OHC-4α-OHC) compared with plasma 4ß-OHC concentration and 4ß-OHC/total cholesterol (TC) ratio in cross-sectional evaluation of CYP3A activity. Four hundred sixteen general adults were divided into 191 CYP3A5*1 carriers and 225 non-carriers. Twenty-six patients with chronic kidney disease (CKD) with CYP3A5*1 allele were divided into 14 with CKD stage 3 and 12 with stage 4-5D. Area under the receiver operating characteristic curve (AUC) for the three indices were evaluated for predicting presence or absence of CYP3A5*1 allele in general adults, and for predicting CKD stage 3 or stage 4-5D in patients with CKD. There was no significant difference between AUC of 4ß-OHC-4α-OHC and AUC of plasma 4ß-OHC concentration in general adults and in patients with CKD. AUC of 4ß-OHC-4α-OHC was significantly smaller than that of 4ß-OHC/TC ratio in general adults (p = 0.025), but the two indices did not differ in patients with CKD. In conclusion, in the present cross-sectional evaluation of CYP3A activity in general adults and in patients with CKD with CYP3A5*1 allele, the usefulness of 4ß-OHC-4α-OHC was not different from plasma 4ß-OHC concentration or 4ß-OHC/TC ratio. However, because of the limitations in study design and subject selection of this research, these findings require verification in further studies.

Successful coil embolization of post-hepatectomy arterioportal fistula that reduced ascites and improved liver function.

A 71-year-old man had previously undergone S7 + S8 dorsal segmentectomy and S5 partial hepatectomy for hepatocellular carcinomas. Six months later, he experienced abdominal distention. Abdominal computed tomography (CT) showed massive ascites and a significant hepatic arterioportal shunt. The ascites was thought to be caused by portal hypertension due to a high-flow hepatic arterioportal fistula (HAPF). The fistula, located between the right hepatic artery A7 and the right portal vein, was embolized with microcoils under flow control using a balloon catheter. After embolization, the shunt blood flow disappeared and the hepatopetal venous flow was restored. His body weight and abdominal circumference decreased immediately, and his liver function on blood tests improved after the procedure. CT performed 11 days after embolization showed decreased ascites. A HAPF after hepatectomy is extremely rare. Balloon-assisted embolization using microcoils is a useful endovascular procedure for treating a high-flow HAPF.

Forecasting Fetal Buprenorphine Exposure through Maternal-Fetal Physiologically Based Pharmacokinetic Modeling.

Buprenorphine readily crosses the placenta, and with greater prenatal exposure, neonatal opioid withdrawal syndrome (NOWS) likely grows more severe. Current dosing strategies can be further improved by tailoring doses to expected NOWS severity. To allow the conceptualization of fetal buprenorphine exposure, a maternal-fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0). Buprenorphine transplacental passage was predicted from its physicochemical properties. The maternal-fetal PBPK model integrated reduced transmucosal absorption driven by lower salivary pH and induced metabolism observed during pregnancy. Maternal pharmacokinetics was adequately predicted in the second trimester, third trimester, and postpartum period, with the simulated area under the curve from 0 to 12 h, apparent clearance, and peak concentration falling within the 1.25-fold prediction error range. Following post hoc adjustment of the likely degree of individual maternal sublingual absorption, umbilical cord blood concentrations at delivery (n = 21) were adequately predicted, with a geometric mean ratio between predicted and observed fetal concentrations of 1.15 and with 95.2% falling within the 2-fold prediction error range. The maternal-fetal PBPK model developed in this study can be used to forecast fetal buprenorphine exposure and would be valuable to investigate its correlation to NOWS severity.

Modified open-thoracotomy-view approach in robotic-assisted thoracoscopic lung resection.

Robotic-assisted thoracoscopic surgery (RATS) is widely performed in thoracic surgery. The open-thoracotomy-view approach (OTVA) is one approach in RATS lung resection. OTVA is a good surgical approach that provides the same field of view as that with open thoracotomy and allows active participation of the assistant. However, the OTVA has certain limitations compared with other approaches, such as difficulty placing a robotic arm in the lower intercostal space, the assistant port is positioned further from the hilum, and CO2 insufflation is required. We have made some modifications to the OTVA by placing one of the robotic arms in the lower intercostal space, which enhances the operability for the surgeon without the need for CO2 insufflation. Additionally, by positioning the assistant port between the robotic arms, the assistant is closer to the hilum, and there is no requirement for a closed port owing to the absence of CO2 insufflation, resulting in improved performance by the assistant. Therefore, for the assistant to perform well, it is necessary to make modifications to the OTVA to widen the typically narrow space between the robotic arms. We performed lung resection using our modified 4-port 3-arm OTVA method in 20 patients from June 2022 to July 2023. Although we have not used our modified OTVA in a large number of cases, we have not observed critical issues to date. In this report, we introduce our modified OTVA as an option in RATS for lung resection.

Usefulness of Belimumab in Adult Patients With Systemic Lupus Erythematosus Evaluated Using Single Indexes: A Meta-Analysis and Systematic Review.

Background: Belimumab is the first antibody drug approved for systemic lupus erythematosus (SLE), and is a fully human monoclonal antibody that inhibits soluble B lymphocyte stimulator protein. In clinical trials, a composite index was used to assess efficacy of belimumab. However, clinical guidelines on SLE treatment currently use single efficacy indexes. Objective: The main objective of this study was to perform a meta-analysis to evaluate the efficacy of belimumab utilizing single indexes used in routine clinical practice, rather than the composite efficacy index used in clinical trials during the development phase. As a secondary endpoint, safety was also evaluated. Methods: Several databases were searched to identify reports published up to December 1, 2021 on randomized controlled trials examining the efficacy of belimumab in adult patients with SLE. From the clinical trial data, efficacy was evaluated using single indexes including the SLE Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group Index, and Physician Global Assessment. Safety was also assessed. Data were synthesized and analyzed using Review Manager 5.4. This study protocol was registered in the UMIN Clinical Trials Registry (Registration number: UMIN000052846). Results: The search identified 12 reports that met the inclusion criteria. Five reports were included in efficacy evaluation and 9 in safety evaluation. The primary endpoint was SLEDAI. Significantly more belimumab-treated patients achieved a ≥4-point reduction in SLEDAI (relative risk 1.28; 95% confidence interval, 1.16-1.40; P < 0.00001) compared with placebo. Other efficacy endpoints were also improved significantly in the belimumab group. No difference in safety was found between belimumab and placebo. Conclusions: The present meta-analysis evaluating clinical trial data using various single indexes recommended by clinical guidelines for SLE verifies that addition of belimumab to standard of care is efficacious for moderate-to-severe SLE.

The Impact of Phenological Gaps on Leaf Characteristics and Foliage Dynamics of an Understory Dwarf Bamboo, Sasa kurilensis.

Phenological gaps exert a significant influence on the growth of dwarf bamboos. However, how dwarf bamboos respond to and exploit these phenological gaps remain enigmatic. The light environment, soil nutrients, leaf morphology, maximum photosynthetic rate, foliage dynamics, and branching characteristics of Sasa kurilensis were examined under the canopies of Fagus crenata and Magnolia obovata. The goal was to elucidate the adaptive responses of S. kurilensis to phenological gaps in the forest understory. The findings suggest that phenological gaps under an M. obovata canopy augment the available biomass of S. kurilensis, enhancing leaf area, leaf thickness, and carbon content per unit area. However, these gaps do not appreciably influence the maximum photosynthetic rate, total leaf number, leaf lifespan, branch number, and average branch length. These findings underscore the significant impact of annually recurring phenological gaps on various aspects of S. kurilensis growth, such as its aboveground biomass, leaf morphology, and leaf biochemical characteristics. It appears that leaf morphology is a pivotal trait in the response of S. kurilensis to phenological gaps. Given the potential ubiquity of the influence of phenological gaps on dwarf bamboos across most deciduous broadleaf forests, this canopy phenomenon should not be overlooked.

Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear. PATIENTS AND METHODS: This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies. RESULTS: Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group. CONCLUSIONS: Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs.

Possible correlation between serum interleukin-8 levels and the activity of myositis in anti-NXP2 antibody-positive dermatomyositis.

Anti-nuclear matrix protein 2 (NXP2) antibody-positive dermatomyositis (DM) is characterized by extensive and severe myositis. In this study, we evaluated which cytokines/chemokines involved with the activity of the myositis. We performed quantitative immunoassays using the MILLIPLEX® Multiplex Assays Using Luminex to evaluate serum levels of interferon-γ, interleukin (IL)-1ß, IL-6, IL-8, IL-12p40, and tumor necrosis factor-α in samples collected over time from a 9-year-old female with anti-NXP2 antibody-positive DM. In our case, the serum level of IL-8 was elevated when the myositis worsened, and decreased in accordance with the improvement of myositis, suggesting that the serum IL-8 levels were correlated with the myositis activity. Serum levels of IL-8 in samples from five patients with anti-NXP2 antibody-positive DM and five patients with anti-transcriptional intermediary factor 1γ (TIF1γ) antibody-positive DM without both interstitial lung disease (ILD) and malignancy before starting treatments, along with five healthy controls, were also evaluate by an enzyme-linked immunosorbent assay. Serum IL-8 levels were significantly elevated in anti-NXP2 or anti-TIF1γ antibody-positive DM patients with myositis but not ILD, than healthy controls. It was suggested that serum levels of IL-8 correlate with the activity of myositis in DM including anti-NXP2 antibody-positive DM.

Rapid and simple quantification of belimumab in human plasma using ultra-high performance liquid chromatography with tandem mass spectrometry.

OBJECTIVE: Belimumab is a monoclonal antibody against the B-lymphocyte stimulating factor and is approved for the treatment of patients with systemic lupus erythematosus (SLE) not responding adequately to existing therapies. In this study, we established and validated an assay for quantifying belimumab in human plasma. METHODS: From the peptides generated by trypsin digestion of belimumab, in silico analysis was used to search for unique peptides to determine the surrogate peptides. Samples were trypsin digested, pretreated with solid phase extraction, and analyzed by ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) to quantify the surrogate peptide in the samples. The assay was validated according to the Food and Drug Administration (FDA) bioanalytical method validation guidance. We used the established assay to quantify plasma belimumab concentrations in two SLE patients treated with belimumab. RESULTS: Among the unique peptides identified by the in silico analysis, the peptide with the best peak shape when measured by UHPLC-MS/MS was selected as the surrogate peptide. The validation results of this assay met the acceptable criteria recommended by the FDA guidance. The lower limit of quantification (LLOQ) for belimumab was 2 µg/mL. Recovery rates and matrix effects when corrected for internal standards were 91.5-114.3 % and 96.9-108.4 %, respectively. Plasma concentrations of belimumab were measured in 12 samples from two belimumab-treated SLE patients. All concentrations were within the calibration range. CONCLUSIONS: We have established and validated a method for measuring plasma belimumab concentrations using UHPLC/MS-MS. By measuring plasma belimumab concentrations in more patients, this method is expected to contribute to appropriate use of belimumab.

Balloon-Assisted Portal Vein Embolization Using n-Butyl-2-Cyanoacrylate-Lipiodol-Iopamidol Mixture in Swine: A Comparison of 2 Formulations.

PURPOSE: To compare 2 ratios of n-butyl-2-cyanoacrylate (nBCA)-ethiodized oil (Lipiodol)-iopamidol (NLI) in balloon-assisted portal vein embolization (PVE) in swine. MATERIALS AND METHODS: In an in vitro study, NLI prepared at a ratio of 2:3:1 (NLI231) or 1:4:1 (NLI141) was injected into 2.5- or 10-mL syringes filled with swine blood, and the viscosity of NLI was measured to determine an appropriate balloon occlusion time. Two portal vein branches in 8 female swine (n = 16 vein branches) were embolized with NLI231 (n = 8) or NLI141 (n = 8) under balloon occlusion. Portal venography was performed before, immediately after, and 3 days after PVE to evaluate the migration of NLI and the recanalization of embolized portal vein branches. Then, the livers were removed for histopathologic evaluation. RESULTS: The times to peak viscosity of NLI231 in the 2.5- and 10-mL syringes were 55.8 seconds (SD ± 7.0) and 85.2 seconds (SD ± 6.3), and those to peak viscosity of NLI141 were 129.2 seconds (SD ± 11.8) and 254.0 seconds (SD ± 21.8), respectively. No migration of NLI231 was observed in all 8 procedures immediately or 3 days after PVE. Migration of NLI141 was observed in 6 of 8 procedures within 3 days after PVE. The migration frequency of the embolic material was lower in the NI231 group than in the NLI141 group (0/8 vs 6/8; P = .051). Histologically, NLI231 occupied the portal veins without any thrombi, whereas NLI141 was accompanied by thrombi in the portal veins. CONCLUSIONS: NLI231 may be more suitable than NLI141 for balloon-assisted PVE in swine.

Comparison of Renal Damage Following Renal Artery Embolization with Three Different Embolic Mixtures in Swine.

Purpose: Renal artery embolization is a minimally invasive and effective procedure for renal ablation, a complete necrosis of the renal parenchyma. This study aims to compare the extent of renal damage in swine following renal artery embolization with ethanol and N-butyl-2-cyanoacrylate, commonly used as embolic materials in renal ablation. Material and Methods: Three different embolic mixtures were prepared for renal artery embolization in swine: 33% ethanol-Lipiodol mixture (ethanol:Lipiodol = 1:2; Group A), 67% ethanol-Lipiodol mixture (ethanol:Lipiodol = 2:1; Group B), and 10% N-butyl-2-cyanoacrylate-Lipiodol mixture (N-butyl-2-cyanoacrylate:Lipiodol = 1:9; Group C). Three swine were assigned to each group and underwent embolization of the unilateral renal artery. Renal arteriography was performed before, immediately after, and two days after renal artery embolization. After two days, the kidneys were removed to determine the macroscopic necrosis rate and for histologic examination. Dark tissue regions were considered necrotic. Results: The macroscopic necrosis rate of the kidneys was 50.3%±7.4%, 100%±0%, and 100%±0% in Groups A, B, and C, respectively. The necrosis rates were higher in Groups B and C than in Group A. Histologically, the renal tubules were damaged in the necrotic areas. In addition, the glomeruli were damaged in Groups A and B but were preserved in Group C. Conclusions: Sixty-seven percent ethanol-Lipiodol mixture and 10% N-butyl-2-cyanoacrylate-Lipiodol mixture are effective embolic materials in renal artery embolization for renal ablation in swine. Also, ethanol caused partial glomerular necrosis, whereas N-butyl-2-cyanoacrylate preserved the glomeruli. Therefore, ethanol should be used for renal ablation.

Comparison of Incidence of Hyponatremia between Linezolid and Vancomycin by Propensity Score Matching Analysis.

Several cases of severe hyponatremia induced by linezolid (LZD) were reported. However, severe infections could also cause hyponatremia by increasing vasopressin secretion. To prove that hyponatremia is associated with LZD rather than infection, we compared the incidence and risk of developing hyponatremia between patients receiving LZD and those receiving vancomycin (VCM). A retrospective, single-center, observational cohort study was conducted in patients aged 18 years or older who received intravenous LZD or VCM for 7 d or longer. Hyponatremia was defined as serum sodium level lower than 134 mEq/L and more than 5% decrease from baseline after treatment initiation. The incidence and risk of developing hyponatremia were analyzed between LZD and VCM groups using chi-square test. Four hundred and fifty patients who satisfied the selection criteria were divided into LZD (n = 97) and VCM groups (n = 353). Significant differences in patient characteristics between LZD and VCM groups were observed before propensity score matching, but no significant differences were found after matching. LZD group showed a significantly higher incidence and risk of developing hyponatremia compared to VCM group both before (LZD: 16.5%, VCM: 5.4%; p < 0.001, odds ratio 3.472 [95% confidence interval (CI) 1.711-7.048]) and after (LZD: 17.8%, VCM: 5.5%; p = 0.020, odds ratio 3.738 [95% CI 1.157-12.076]) propensity score matching. In conclusion, propensity score analyses suggest that the risk of hyponatremia associated with LZD is approximately 3.7-fold higher than that associated with VCM, regardless of patient background.

Application of Indocyanine Green Fluorescence Imaging for Tumor Localization during Robot-Assisted Hepatectomy.

The efficacy of indocyanine green (ICG) fluorescence imaging for visualizing hepatic tumors in robot-assisted hepatectomy (RAH) should be validated. This study included 30 consecutive patients with 33 collective tumors who underwent RAH. ICG was administered at a dose of 0.5 mg/kg before surgery. ICG fluorescence imaging was performed intraoperatively. In total, 28 patients with a combined total of 31 tumors underwent ICG fluorescence imaging. Further, 26 (84%) tumors were identified on hepatic surfaces prior to hepatic transection. The fluorescence signals of eight tumors were detected on hepatic raw surfaces during parenchymal dissection, thereby enabling surgeons to adjust the transection planes to ensure appropriate surgical margins. One patient with intrahepatic cholangiocarcinoma tested positive for cancer cells at the dissected stump of the bile duct. However, in all patients in whom ICG fluorescence imaging was used, negative surgical margins were achieved at the site of the dissected hepatic parenchyma. On the other hand, one of two patients with ICG contraindications had a positive surgical margin surrounding the dissected hepatic parenchyma. The median operative time and volume of blood loss were 259 (range: 124-594) min and 150 (range: 1-1150) mL, respectively. ICG fluorescence imaging facilitates the easy identification of hepatic tumors, even in RAH. Hence, it can be useful for confirming appropriate surgical margins.

Pulmonary inflammatory leiomyosarcoma represents a potential diagnostic pitfall of DNA methylation-based classification of sarcomas: a case report.

BACKGROUND: Pulmonary inflammatory leiomyosarcoma (PILMS) is a rare type of myogenic tumor with prominent lymphohistiocytic infiltration. Despite their histological similarities, PILMS is immunohistochemically and genetically distinct from soft tissue inflammatory leiomyosarcoma, and its clinicopathological picture including DNA methylome data remains still unknown. CASE PRESENTATION: Here we present a case of PILMS in an 18-year-old male who underwent lobectomy. As reported previously, the current case demonstrated spindle myoid cell proliferation with smooth muscle differentiation within a prominent lymphohistiocytic infiltration and a diploid genome with a MUC3A gene alteration. DNA methylation analysis predicted this case to be an "inflammatory myofibroblastic tumor" (IMT) according to the Deutsches Krebsforschungszentrum (DKFZ) classifier. The data was analyzed by t-distributed stochastic neighbor embedding, which plotted the case tumor in the vicinity of IMT, however, there were no IMT histological features. These discordant results could be due to background non-neoplastic inflammatory cells. CONCLUSIONS: As the DNA methylation classification of PILMS might be a potential diagnostic pitfall, an integrative histological and genetic approach is required for its accurate diagnosis.

Duodenal bleeding outside covered stents identified by selective computed tomography during arteriography that was successfully treated by embolization: A case report.

The patient was a man in his 60s who previously underwent placement of covered stents in the duodenum for a duodenal stricture caused by pancreatic cancer invasion. He experienced multiple episodes of hematemesis and hematochezia during hospitalization. Emergency upper and lower gastrointestinal endoscopies were performed but were unable to reveal the bleeding source. Based on these findings, we suspected small intestinal bleeding and emergency angiography was performed for the purpose of hemostasis. Computed tomography during arteriography was performed from the superior mesenteric artery and revealed extravasation outside the covered stents in the descending portion of the duodenum. Angiography of the inferior pancreaticoduodenal artery revealed extravasation in the descending portion of the duodenum, and the inferior pancreaticoduodenal artery was embolized with n-butyl cyanoacrylate. There were no postoperative symptoms indicative of intestinal ischemia or pancreatitis, and there was no rebleeding after embolization. In patients with bleeding outside the duodenal-covered stents, it can be difficult to identify the bleeding source by upper gastrointestinal endoscopy. In this case, selective computed tomography during arteriography and angiography revealed bleeding outside the duodenal-covered stents that was successfully treated by arterial embolization with n-butyl cyanoacrylate.

Evaluation of effects of indoxyl sulfate and parathyroid hormone on CYP3A activity considering the influence of CYP3A5 gene polymorphisms.

AIMS: Indoxyl sulfate and parathyroid hormone (PTH), which accumulate in chronic kidney disease (CKD), have been reported to reduce cytochrome P450(CYP)3A activity. Homozygotes of the CYP3A5*3 allele have reduced CYP3A5 activity compared to carriers of at least one CYP3A5*1 allele. 4ß-Hydroxycholesterol (4ß-OHC) has been established as an endogenous substrate reflecting CYP3A activity. 4ß-OHC is produced through hydroxylation by CYP3A4 and CYP3A5 and by autoxidation of cholesterol, whereas 4α-hydroxycholesterol (4α-OHC) is produced solely by autoxidation of cholesterol. This study focused on CKD patients and evaluated the effects of plasma indoxyl sulfate and intact-PTH concentrations on plasma 4ß-OHC concentration, 4ß-OHC/total cholesterol ratio and 4ß-OHC-4α-OHC, with consideration of the influence of CYP3A5 polymorphism. METHODS: Sixty-three CKD patients were analysed and divided into CYP3A5 carrier group (n = 26) and non-carrier group (n = 37). RESULTS: Plasma indoxyl sulfate significantly correlated inversely with 4ß-OHC concentration and with 4ß-OHC-4α-OHC in both the CYP3A5*1 carrier group (r = -0.42, P = .034; r = -0.39, P = .050, respectively) and the non-carrier group (r = -0.45, P = .0054; r = -0.39, P = .019, respectively). However, multiple regression analysis did not identify plasma indoxyl sulfate concentration as a significant independent factor associated with any of the CYP3A activity indices. There was no significant correlation between plasma intact-PTH concentration and any of the CYP3A activity indices. CONCLUSIONS: The present results suggest that plasma indoxyl sulfate and intact-PTH concentrations do not have clinically significant effects on CYP3A activity in patients with CKD.