Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the multicenter study. We investigated the relationship between various AFP response thresholds (relative decline ≥ 20%, ≥ 50%, and ≥ 75%) and treatment response and progression-free survival (PFS). An AFP relative decrease of ≥ 50% was associated with an overall response rate (ORR) with an odds ratio (95% confidence interval [CI]) of 5.7 (1.9-17). Disease control rate (DCR) was associated with an AFP relative decrease of ≥ 20%, with a 100% positive predictive value and a 52.0% sensitivity. AFP relative decreases of ≥ 50% and ≥ 20% were significantly associated with PFS with a hazard ratio (HR) of 5.60 (95% CI: 1.6-19, p = 0.006) and a HR of 4.44 (95% CI: 1.9-10, p < 0.001), respectively. AFP response of ≥ 50% and ≥ 20% were related to ORR and DCR, respectively, and both of these responses were also associated with PFS. AFP can be used as a real-time monitor during Atez/Bev treatment and is helpful for treatment optimization.

Nutrition knowledge related to breakfast skipping among Japanese adults aged 18-64 years: a cross-sectional study.

OBJECTIVE: Breakfast skipping is regarded as a public health issue among adults worldwide. Nutrition knowledge has been reported to be one of predictors of dietary behaviour. Therefore, the aim of the present study was to examine the association between nutrition knowledge and breakfast skipping. DESIGN: Data regarding nutrition knowledge were obtained by using a validated, self-administered general nutrition knowledge questionnaire for Japanese adults (JGNKQ). Participants were classified into three nutrition knowledge level groups according to total JGNKQ score: Low, Middle and High. In addition, participants reported the frequency of meal consumption per week and rated the difficulty in finding time to eat breakfast, lunch and dinner in the lifestyle questionnaire. The differences in frequency of breakfast, lunch and dinner consumption among Low, Middle and High nutrition knowledge groups were determined by using ANCOVA adjusted for potential confounding factors. SETTING: Kanto region, Japan.ParticipantsJapanese adults aged 18-64 years (n 1165, 57·3% women). RESULTS: Mean age of the participants was 43·8 (sd 8·9) years. There were no significant differences found in the proportion of respondents reporting difficulty in finding time to eat each meal among the three groups. However, the frequency of breakfast consumption was significantly different among Low, Middle and High groups, while lunch and dinner frequency did not differ among the three groups. CONCLUSIONS: The present study suggests that nutrition knowledge level is related to breakfast skipping among Japanese adults.

Effect of treatment with branched-chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma.

AIM: To examine the effect of branched-chain amino acid (BCAA) therapy for patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: Seventy-eight subjects with unresectable HCC with a serum level of albumin of 3.5 g/dL or less treated with sorafenib were evaluated. They were classified into two groups: those receiving BCAA granules (n = 34; BCAA group) or a regular diet (n = 44; control group). We compared overall survival and administration period of sorafenib, and analyzed absolute changes in serum levels of albumin during sorafenib therapy in 41 patients who continued sorafenib therapy for 1 month or more with a follow up of more than 3 months. RESULTS: Median survival time (MST) in BCAA and control groups was 350 and 143 days (P = 0.007), respectively. Median administration period of sorafenib in the two groups was 59 and 41 days (P = 0.018). In the 41 patients described above, at 1 month, there was no significant change in the serum level of albumin between the two groups, but at 3 months, the difference in the absolute change in the serum level of albumin in the two groups reached significance (P = 0.023). In these subgroup analyses, the administration period of sorafenib as well as the MST in the BCAA group were significantly longer than those in the control group (P = 0.020 and = 0.004). CONCLUSION: BCAA treatment during sorafenib therapy in HCC patients is useful for maintaining hepatic functional reserve, which may help to avoid early discontinuance of sorafenib therapy and improve survival.

Clinical characteristics of collagenous colitis with linear ulcerations.

BACKGROUND: The relationship between the thickness of subepithelial collagen bands (CB) and the development of linear ulcerations (LU) in collagenous colitis (CC) remains unclear. The aim of the present study was to compare the clinical and pathological features, including the thickness of CB, in CC patients with and without LU. PATIENTS AND METHODS: Twenty-five patients with CC diagnosed by pathological examination of biopsy specimens were analyzed. Eleven patients with LU (LU group) and 14 patients without LU (non-LU group) were compared. RESULTS: Ten patients in the LU group and seven in the non-LU group were taking lansoprazole (P = 0.038). Seven patients in the LU group and one in the non-LU group were taking non-steroidal anti-inflammatory drugs (NSAIDs) (P = 0.004). All LU were locatedin the transverse or left colon. Patients in the LU group were older than those in the non-LU group (P = 0.015). CB were significantly thicker in the LU group than in the non-LU group (mean ± SD, 40 ± 21 µm vs 20 ± 11 µm, P = 0.004). Multivariate analysis showed that NSAIDs use (odds ratio, 19.236; 95% confidence interval, 1.341-275.869) and CB thickness (odds ratio, 0.893; 95% confidence interval, 0.804-0.999) were independently associated with the development of LU. CONCLUSION: Use of lansoprazole and NSAIDs, thick CB, and advanced age are associated with the development of LU in CC patients.

[Three cases of hepatocellular carcinoma with nodules showing different signal intensities in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI].

We report three cases of resected hepatocellular carcinomas with nodules showing different signal intensities in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI). One case involved a nodule-in-nodule type hepatocellular carcinoma that showed high signal intensity for the outer tumor and low intensity for the inner tumor in the hepatobiliary phase of EOB-MRI. The inner tumor was more dedifferentiated than the outer. The other two cases involved similar nodules, which showed different signal intensities in the hepatobiliary phase of EOB-MRI. In all three cases, the expression of OATP8 showed good correlation with high signal intensity in the hepatobiliary phase of EOB-MRI, whereas MRP2, MRP3, or both were also highly expressed. However, in the two nodules showing low intensities, the expression of one excreting transporter was independently high even though that of OATP8 was not high. The expression of excreting transporters is usually characterized by passive correspondence to OATP8 expression levels; nevertheless, it sometimes shows expression independent of OATP8.

The effect of long-term supplementation with branched-chain amino acid granules in patients with hepatitis C virus-related hepatocellular carcinoma after radiofrequency thermal ablation.

GOALS: To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ≤3.5 g/dL. BACKGROUND: Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear. STUDY: We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS. RESULTS: The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively. CONCLUSIONS: BCAA treatment may improve OS and RFS after RFA in patients with HCV-related HCC≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL.

Hypovascular hepatic nodules showing hypointense on the hepatobiliary-phase image of Gd-EOB-DTPA-enhanced MRI to develop a hypervascular hepatocellular carcinoma: a nationwide retrospective study on their natural course and risk factors.

OBJECTIVE: We aimed to investigate the natural outcome of nonhypervascular lesions detected in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI by performing a longitudinal study retrospectively enrolled in a nationwide manner. METHODS: Between February 2008 and March 2011, 224 patients with 504 nodules that were diagnosed as nonhypervascular by imaging were recruited from institutions that participated in the present study. We examined the natural outcome of nonhypervascular lesions and evaluated the risk factors. RESULTS: Of the 504 nodules, 173 (34.3%) showed hypervascular transformation. The overall cumulative incidence of hypervascular transformation was 14.9% at 12 months and 45.8% at 24 months. Multivariate analysis using the Cox regression model revealed previous treatment history for hepatocellular carcinoma (HCC; relative risk = 1.498; p = 0.036, 95% CI 1.03-2.19) and hyperintensity on T2-weighted images (relative risk = 1.724; p = 0.015, 95% CI 1.11-2.67) were identified as independent factors for hypervascular transformation. CONCLUSIONS: Patients who have a previous treatment history for HCC and with hypointense nodules showing hyperintensity on T2-weighted images need careful follow-up because of the high incidence of hypervascular transformation.

[A case of α-fetoprotein-producing hepatoid adenocarcinoma of the stomach with spontaneous rupture of multiple liver metastases].

An 85-year-old man with epigastric pain and anorexia was admitted to our hospital. His serum α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA II) levels were markedly elevated. Gastrointestinal endoscopy revealed a large mass near the fundus, and computed tomography revealed multiple liver tumors. Intraperitoneal bleeding followed rupture of a liver tumor and was successfully stopped by transarterial embolization; however, regrowth of multiple tumors followed, resulting in liver failure and death within a short period. Autopsy revealed hepatoid adenocarcinomas originating in the stomach that had metastasized to the liver. Hepatoid adenocarcinomas are hypervascular, rapidly growing tumors that may result in the spontaneous rupture of metastatic liver lesions. Transarterial embolization may be a feasible option for the treatment of these ruptured tumors.

Unexpected anti-tumor effect of immune checkpoint inhibitors followed by transcatheter arterial chemoembolization for hepatocellular carcinoma.

The abscopal effect has recently attracted much attention because this effect is enhanced by immune checkpoint inhibitors (ICIs). However, little is known about the association between induction of the abscopal effect and local treatment against hepatocellular carcinoma (HCC). We describe a patient with advanced HCC who underwent selective transcatheter arterial chemoembolization (TACE) after treatment with an ICI that was found to remarkably regress in lesions in areas outside that targeted by selective TACE. An 82-year-old man had multiple recurrences in both lobes of the liver despite of repeated TACE and radiofrequency ablation, after resection of an HCC five years previously. After chemotherapy with atezolizumab and bevacizumab, his des-gamma-carboxy prothrombin (DCP) increased. CT during hepatic arteriography revealed multiple recurrent HCCs in both lobes of the liver. TACE with selective embolization at the level of the medial segmental arteries was performed against an approximately 50 mm-diameter tumor in the right lobe. Hepatic arterial phase imaging of contrast-enhanced CT performed 6 days after TACE showed hypo-enhancement of tumors in segment II and III in the left lobe. This case highlights that abscopal effects can be induced by local treatment against HCCs in combination with treatment with ICIs.

Prospective comparison of diagnostic performance of magnifying endoscopy and biopsy for sessile serrated adenoma/polyp.

Background: Magnifying narrow-band imaging (M-NBI) has recently improved the accuracy of endoscopic diagnosis of gastrointestinal tumors, including colorectal polyps. However, it can be difficult to distinguish between sessile serrated adenoma/polyps (SSA/Ps) and other polyps, especially hyperplastic polyps (HPs), by histological biopsy, because diagnostic features of SSA/Ps can be detected around the colon crypt bases. We aimed to evaluate the accuracy of endoscopic diagnosis of SSA/Ps using M-NBI compared with histological biopsy. Methods: We prospectively enrolled patients diagnosed with SSA/Ps by preoperative endoscopy and assessed the diagnostic accuracy. The primary outcome was the diagnostic accuracy of endoscopy and biopsy. Results: Between August 2015 and October 2017, 295 lesions were resected by polypectomy or endoscopic mucosal resection, and 79 endoscopically resected specimens that were endoscopically diagnosed as SSA/P underwent biopsy for histological examination. Two lesions were excluded because the specimens were too small for histological examination. Finally, 77 endoscopically resected specimens and 77 biopsy specimens were included in the analysis. Histopathological examination showed 67 SSA/Ps, 8 HPs, and 2 adenomas. The sensitivity, specificity and accuracy of endoscopic M-NBI diagnosis for SSA/Ps were 95.7%, 95.5% and 95.6%, respectively. The sensitivity, specificity and accuracy of histological diagnosis of a single biopsy specimen were 71.6%, 90.0% and 74.0%, respectively. The McNemar test showed significant differences between biopsy and endoscopy diagnoses (P=0.001). Conclusion: This study shows that biopsy may be avoided by using M-NBI in patients with suspected SSA/Ps.

Complete response of advanced hepatocellular carcinoma with multiple lung metastases treated with sorafenib: a case report.

Sorafenib, an oral multikinase inhibitor, has demonstrated clinical efficacy in patients with advanced hepatocellular carcinoma (HCC). However, in the SHARP trial (Sorafenib HCC Assessment Randomized Protocol trial) and the Asia-Pacific trial (conducted in the Asia-Pacific region), no cases of complete response (CR) were reported. Thereafter, only a relatively small number of CR cases were reported worldwide for sorafenib therapy. We herein report a case of CR in a patient treated with sorafenib for 4 months. The patient had advanced HCC with multiple lung metastases, and there has been no recurrence after 8 months following cessation of administration. To our knowledge, this is the first time a female treated with sorafenib alone for HCC has had a CR.

Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma.

BACKGROUND: The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC). METHODS: We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests. RESULTS: The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013). CONCLUSIONS: PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.

The Association between Milk Intake and Nutrient Intake Adequacy among Japanese Female Junior High School Students: A Cross-Sectional Study.

The consumption of dairy products, including milk, may be important for improving the overall quality of a diet. The aim of this study was to examine the relationship between milk intake and nutritional adequacy among Japanese female junior high school students. The participants of this study were Japanese female junior high school students aged between 12 and 15 years. Dietary habits over the past month were assessed by a brief self-administered diet history questionnaire. The adequacy of each nutrient intake was determined based on the Dietary Reference Intakes for Japanese 2020, with two goals: the estimated average requirement for fourteen nutrients and tentative dietary goals for preventing lifestyle-related diseases for six nutrients. The participants were classified into five groups according to milk intake (Q1 (lowest) to Q5 (highest)) by quintile. The adequacy of vitamin B2, calcium, magnesium, and potassium were higher among students with a higher milk consumption than among those with a lower milk consumption. However, the intake of saturated fatty acids was in excess among higher milk consumers. The present study suggests that milk intake was related to an adequate intake of some vitamins and minerals and an inadequate intake of saturated fatty acids among Japanese female junior high school students.

The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study.

BACKGROUND: Lenvatinib (LEN) has been approved for patients with unresectable hepatocellular carcinoma (u-HCC) since March 2018 in Japan. We performed a retrospective nationwide multicenter study to clarify the clinical characteristics of LEN in real-world practice. METHODS: A total of 343 u-HCC patients who received LEN from March 2018 to May 2020 at 23 sites in Japan were registered. RESULTS: During the median observation period of 10.5 months, 143 patients died. In Child-Pugh A (n = 276) and Child-Pugh B (n = 67) patients, the median overall survival (OS) was 21.0 and 9.0 months. The median progression-free survival (PFS) was 8.8 months in Child-Pugh A patients. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors (RECIST criteria) were 42.1% and 82.1%. The independent pretreatment factors associated with mortality in all patients were AFP ≥ 400 ng/mL (hazard ratio (HR) 2.00, 95% confidential interval (95% CI) 1.08-2.09, p < 0.0001), modified albumin-bilirubin (ALBI) grade 2b or 3 (HR 1.56, 95% CI 1.09-2.17, p = 0.012), major vascular invasion (HR 1.91, 95% CI 1.26-2.89, p = 0.0022), PS > 0 (HR 1.50, 95% CI 1.09-2.08, p = 0.014), and MTT (molecular targeted therapy) experience (HR 2.22, 95% CI 1.56-3.13, p = 0.00038). In the MTT naïve patients with ALBI grade 1 or modified ALBI 2a and BCLC stage B (n = 68), median OS and PFS were 25.3 and 12.3 months. Liver-related adverse events during LEN were the only significant adverse event associated with OS (HR 2.74, 95% CI 1.93-3.88, p < 0.0001). Among the Child-Pugh A patients with extrahepatic metastasis and no major vascular invasion, median PFS in the patients with bone metastasis was significantly shorter than those with lung or adrenal grand metastasis (6.3 vs. 12.5 months, p = 0.0025). CONCLUSION: LEN showed a high response rate in real-world practice. Pretreatment factors, including ALBI score, AFP, and major vascular invasion are important in making a treatment strategy for patients with u-HCC. The patients with bone metastasis would be candidates for new therapeutic approaches.

[A case of primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype: comparison of hemodynamics and histopathology].

A 58-year-old man was followed up for HBV-associated chronic hepatitis. A low echoic hepatic nodule 1.6cm in diameter developed in segment 8 of the liver. The tumor was hypervascular and showed enhancement on CV during hepatic arteriography (CTHA) and a defect on CT during arterial portography (CTAP). Strong enhancement, which lasted for 30 seconds, was observed at the margin of the tumor on single-level dynamic CTHA. The resected tumor was whitish, had no capsule, and consisted mainly of intermediate immature cells together with HCC-like and CCC-like tumor cells. These findings led to the diagnosis of primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype. Cytokeratin (CK) 7, CK8, CK19, EMA and vimentin were positive and HP-1 and c-kit tests were negative on immunohistochemical staining. Staining with CD34+alphaSMA showed more muscular arterial vessels and sinusoid-like vessels in the peripheral zone of the tumor than in the central zone. Six months after the resection of the tumor, swollen abdominal lymph nodes were observed on US and CT, which aspiration needle biopsy showed to be metastasis of a hepatic tumor.

Mothers' Nutrition Knowledge Is Unlikely to Be Related to Adolescents' Habitual Nutrient Intake Inadequacy in Japan: A Cross-Sectional Study of Japanese Junior High School Students.

Dietary habits in adolescence persist into adulthood; thus, it is important to identify the factors that influence adolescent diet and establish a healthy diet. This study aimed to examine the association between mothers' nutrition knowledge and their children's nutrient intake inadequacy among Japanese junior high school student-mother dyads. The participants were 288 students and their mothers. Data regarding mothers' nutrition knowledge were obtained using a validated, self-administered general nutrition knowledge questionnaire for Japanese adults (JGNKQ). Participants were categorised into two groups according to the mothers' total JGNKQ scores. Adolescents' dietary habits during the preceding month were assessed using a brief self-administered diet history questionnaire. Inadequacy of each nutrient intake was assessed using the cut-point method, which showed that 14 nutrients were below "estimated average requirement (EAR)" and five nutrients were outside the range of "tentative dietary goal to prevent lifestyle-related diseases (DG)". In the habitual daily nutrient intakes and the proportion of nutrient intake inadequacy of the students, no differences were observed according to mother's nutritional knowledge level. Our findings suggest that mothers' nutrition knowledge may not be directly associated with adolescents' nutrient intake among Japanese junior high school student-mother dyads.

Breakfast skipping is related to inadequacy of vitamin and mineral intakes among Japanese female junior high school students: a cross-sectional study.

Breakfast skipping is a public health issue which affects nutrient intake among adolescents worldwide. However, there have been few reports comparing intake and reference values to assess the deficiency of nutrient intake between breakfast consumers and skippers. Therefore, the present study aimed to examine the relationship between breakfast skipping and adequacy of total habitual nutrient intake among junior high school female students. The participants were 516 Japanese female junior high school students. Dietary habits during the preceding month were assessed using a brief self-administered diet history questionnaire. Inadequacy of each nutrient intake was assessed by the cut-point method, based on the estimated average requirement for fourteen nutrients and on dietary goal values for five nutrients. The overall nutritional inadequacy in participants was assessed by the number of consumed nutrients which did not meet the requirements as per the dietary reference intakes for Japanese, 2015 version. The participants were classified into two groups according to the frequency of breakfast eating: breakfast consumers (seven times/week) and breakfast skippers (0-6 times/week). Adequacy of vitamin A, vitamin B1, vitamin B2, vitamin C, Ca, Fe, Zn and K was higher among breakfast consumers than among skippers. Breakfast consumers had more intakes of fruits, vegetables and dairy products. Our findings suggest that breakfast skipping was related to deficiencies in vitamin and mineral intakes, and to an unfavourable dietary pattern, among Japanese female junior high school students.

Expression of liver X receptor alpha and lipid metabolism in granulocyte-macrophage colony-stimulating factor-induced human monocyte-derived macrophage.

Liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. The foam cell transformation of macrophages (Mvarphi) is considered a critical process in atherosclerotic lesions. The relationship, however, of the foam cell transformation of Mvarphi and LXR is not fully understood. The purpose of the present study was to examine the expression of LXRalpha, retinoid X receptor (RXR)alpha, ATP-binding cassette transporter (ABCA1), and macrophage scavenger receptor A (MSR-A), and lipid accumulation in human monocyte-derived Mvarphi. The expression of LXRalpha, ABCA1, MSR-A in 7 day cultured granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced Mvarphi (GM-Mvarphi) was significantly higher than that in 7 day cultured M-CSF-induced Mvarphi (M-Mvarphi). The expression levels of LXRalpha, ABCA1 and MSR-A protein decreased from 48 h to 5 days after the addition of lipopolysaccharide (LPS) in GM-Mvarphi, but only MSR-A protein decreased at 5 days after the addition of LPS in M-Mvarphi. Intracellular lipid accumulation was clearly observed when GM-Mvarphi was pre-stimulated with LPS for 48 h and incubated with oxidized LDL for an additional 5 days. These findings suggest that the inhibitory activity of LXRalpha, ABCA1 and MSR-A by LPS may be related to the transformation of Mvarphis, especially GM-Mvarphi into foam cells.

Underwater endoscopic mucosal resection: a new endoscopic method for resection of rectal neuroendocrine tumor grade 1 (carcinoid) ≤ 10 mm in diameter.

Background and study aims Rectal neuroendocrine tumors grade 1 (NET G1; carcinoid) ≤ 10 mm in diameter often extend into the submucosa, making their complete histological resection difficult using endoscopic techniques. Endoscopic submucosal resection with a ligation device (ESMR-L) and endoscopic submucosal dissection (ESD) are commonly used to overcome these difficulties. We also previously reported that underwater endoscopic mucosal resection (UEMR) could facilitate resection of rectal NET G1. This study aimed to evaluate the safety and efficacy of UEMR for removing rectal NET G1 ≤ 10 mm in diameter. 6 consecutive patients with rectal NET G1 ≤ 10 mm in diameter underwent UEMR at our hospital. The rate of en bloc resection was 100 %, and the rate of R0 resection was 83 %. The median procedure time was 8 min (range 5 - 12 min). No perforations or delayed bleeding occurred in this study. In conclusion, UEMR allows the safe and reliable resection of rectal NET G1 ≤ 10 mm in diameter with comparable results to ESMR-L or ESD, including high en bloc and R0 resection rates with no increase in significant adverse events. A multicenter trial is required to confirm the validity of the present results.

Expression of liver X receptor alpha in rat fetal tissues at different developmental stages.

The liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. Using a novel LXRalpha-specific antibody for immunohistochemistry, we evaluated cellular expression of LXRalpha in fetal rat tissues. In the fetal liver, LXRalpha-positive macrophages appeared at 12 days and their number peaked at 18 days of gestation. In contrast, hepatocytes expressed LXRalpha during the later stage of gestation, suggesting the functional development of the liver during ontogeny. Later, macrophages in spleen and thymus expressed LXRalpha, and some mononuclear cells in the vascular lumen compatible to primitive/fetal macrophages in the fetal circulation were found to express LXRalpha. In vitro, rat monocytes did not express LXRalpha, but monocyte-derived macrophages cultured in the presence of macrophage-colony stimulating factor revealed the distinct expression of LXRalpha in nucleoli. These findings suggest that LXRalpha plays a role in the differentiation of fetal macrophages, particularly hepatic macrophages, in rat development.