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Background: Pancreatic cancer is highly aggressive and has a low survival rate primarily due to late-stage diagnosis and the lack of effective early detection methods. We introduce here a novel, noninvasive urinary extracellular vesicle miRNA-based assay for the detection of pancreatic cancer from early to late stages., Methods: From September 2019 to July 2023, Urine samples were collected from patients with pancreatic cancer (n = 153) from five distinct sites (Hokuto Hospital, Kawasaki Medical School Hospital, National Cancer Center Hospital, Kagoshima University Hospital, and Kumagaya General Hospital) and non-cancer participants (n = 309) from two separate sites (Hokuto Hospital and Omiya City Clinic). The main inclusion criteria included a diagnosis of pancreatic cancer based on pathological or imaging examination, while multiple primary cancers were excluded. Extracellular vesicles were enriched using a polymer-based precipitation method, and miRNAs were comprehensively analyzed by small RNA sequencing. A machine learning model for pancreatic cancer detection was developed using a training dataset (n = 315) consisting of 99 pancreatic cancer participants (of which 33 were early-stage [I/IIA]) and 216 non-cancer participants, and validated with a test dataset (n = 147) consisting of 54 pancreatic cancer participants (of which 9 were early-stage [I/IIA]) and 93 non-cancer participants., Findings: This method showed consistent performance, with areas under the receiver operating characteristic curves of 0.972 (95% confidence interval [CI], 0.928-0.996) and 0.963 (95% CI, 0.932-0.988) in the training and test sets, respectively. The sensitivities for pancreatic cancer detection were 93.9% (95% CI, 87.5%-97.3%) and 77.8% (95% CI, 64.9%-87.3%) overall and 97.0% (95% CI, 83.9%-99.8%) and 77.8% (95% CI, 44.2%-95.9%) for stage I/IIA pancreatic cancer, respectively. The specificities were 91.7% (95% CI, 87.1%-94.7%) and 95.7% (95% CI, 89.4%-98.5%), respectively. We also evaluated the sensitivity of CA19-9 for pancreatic cancer detection in 140 patients with pancreatic cancer, and it was 37.5% (95% CI, 23.5%-53.8%) for stages I/IIA pancreatic cancer. Performance in early-stage cancer detection was significantly higher for miRNA-based pancreatic cancer detection. Functional enrichment analysis of pancreatic cancer-associated urinary miRNAs revealed that the urinary miRNA signature reflects miRNA patterns of the pancreatic cancer tissue itself as well as those of the tumor microenvironment., Interpretation: Urinary extracellular vesicle miRNAs may reflect signals from both tumor cells and their microenvironment, offering a unique opportunity for detection of pancreatic cancer from early to late stages. While this study has a limitation due to the relatively small sample size, our approach has the potential to contribute to treatment outcomes through population screening. Our primary goal is to make this assay more accessible to a broader population, particularly in areas with limited hospital access where cancer is often detected at a late stage, leveraging the advantage of using urine samples that can be collected at home., Funding: This research was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Number JP24he2302007 and Craif Inc., Competing Interests: AMED supported KY, YI and YK. YK is an advisor and has stock options of Craif Inc. MM and YI are board members and shareholders of Craif Inc. HY and YA are employees and have stock options of Craif Inc. Other authors have no conflicts of interest., (© 2024 The Authors.)

Mature cystic teratomas (MCTs) of the ovary comprise tissues from all three germ layers. The coexistence of the complete intestinal tract, prostatic tissue, and bladder component within the same ovarian MCT is unprecedented. Here, we report the diagnosis and management of such a rare case. A 26-year-old woman presented with a right ovarian mass, which was later confirmed as an MCT by histopathological examination. The patient underwent a successful laparoscopic cystectomy with no evidence of malignancy or postoperative complications. Histological examination revealed that this MCT contained the complete organ structures including a lower intestinal tract and male genital tract with prostate, urethra, and bladder components, which is unusual. This case underscores the importance of understanding the pathogenesis of extensive organogenesis in MCTs and raises questions about the differentiation processes leading to such unique presentations., Competing Interests: Declarations. Conflict of Interest: None. Informed consent: The patient provided written consent for the publication of this case report. All personal identifiers have been removed to ensure privacy. Coexistence of Complete Intestinal Tract, Prostatic Tissue, Prostatic Urethra and Bladder., (© 2024. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Background: The scoring system for bile cytology (SSBC) aims to improve bile cytology diagnostic accuracy. Here, the practicality of SSBC was verified by multiple cytotechnologists., Methods: Bile cytological specimens were evaluated by 24 cytotechnologists using SSBC. The samples were assessed before using the SSBC (first-time assessment) according to three categories: benign, indeterminate, and malignant. A first scoring evaluation (FSE) was then performed using SSBC; each item in the scoring system was classified as present or absent. After distributing an instruction sheet with diagnostic criteria, a second scoring evaluation (SSE) was performed using SSBC. Each method was evaluated using diagnostic accuracy and interobserver and intraobserver agreement., Results: Several samples were assessed as indeterminate in the first-time assessment. Although the specificity of the SSE improved, the sensitivity and accuracy decreased compared with those of the FSE. The overall interobserver agreement was fair for all parameters, including abnormal chromatin, irregular internuclear distances, irregularly overlapped nuclei, irregular cluster margins, and final evaluation in the FSE and SSE. The final evaluation by histological type exhibited slight agreement for well-differentiated tubular adenocarcinoma and almost perfect agreement for poorly differentiated tubular adenocarcinoma in the FSE and SSE. For moderately differentiated tubular adenocarcinoma, agreement was moderate in the FSE and fair in the SSE. For cholangitis, a slight agreement was observed in the FSE, which improved to fair in the SSE., Conclusions: Although the SSBC is expected to improve specificity, there exists ambiguity regarding SSBC criteria and interindividual assessment differences. Therefore, the objective assessment method should be revised., (© 2024 Wiley Periodicals LLC.)

Background: The reported actual risk of rupture for vertebral artery dissection (VAD) in patients presenting with headache is very low, ranging from 0.4% to 1.0%. The authors report a case in which the dissection site dilated rapidly within several hours after the dissection occurred resulting in subarachnoid hemorrhage (SAH)., Observations: A 49-year-old healthy man who had participated in a marathon noticed a headache while running. Magnetic resonance imaging (MRI) performed 2 days later revealed no findings suspicious for right VAD, but a string sign was observed in the left side, suggesting left VAD. Three hours following MRI, he developed severe headaches and became unconscious at home, prompting emergency services to rush him to the hospital. A computed tomography scan showed diffuse SAH and a rapidly enlarged aneurysmal dilatation in the right vertebral artery. He underwent endovascular internal trapping to prevent rebleeding. He was discharged without any neurological symptoms. No recurrence or new dissection occurred after 2 years of follow-up., Lessons: Even in the absence of typical imaging findings, strict management, such as blood pressure control, is required when clinical findings strongly suggest VAD, and differentiation of VAD from primary headache is important. https://thejns.org/doi/10.3171/CASE24202.

The development of tumors in livers transplanted from hepatitis B virus (HBV)-negative donors to patients with hepatitis B and cirrhosis is rare. The present study describes the case of a woman in her 60s who developed hepatocellular carcinoma (HCC) in her grafted liver, 19 years after transplantation, as well as a metachronous colorectal tumor. The pathological findings, including clinical, immunohistochemical and molecular results, are described in the present case report. The liver tumor was a conventional HCC and the colorectal tumor comprised a tubular adenocarcinoma. Immunohistochemistry of both tumors showed a loss of expression of mutL homolog 1 and postmeiotic segregation increased 2 in the tumor cells, confirming microsatellite instability-high (MSI-H) status. Furthermore, a molecular study detected the presence of genes located on the Y chromosome in the normal and tumor tissues of the liver, proving that the HCC occurred in the grafted liver. The present report also discusses that prolonged use of immunosuppressive drugs to prevent post-transplant rejection, poorly controlled diabetes mellitus and MSI-H may have contributed to the risk of tumor development., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Sumiyoshi et al.)

Extranodal NK/T-cell lymphoma (ENKTL), nasal type, is often seen in the head and neck region, but there have been rare instances of this disease with initial presentation as a lesion in the oral mucosa. The patient, a woman in her seventh decade of life, presented with an ulcer in the maxillary gingiva, and scraping cytology and biopsy were performed. Cytological specimens showed solitary or small aggregating cells with marked atypia in a necrotic background. Tumor cells were detected that had various nuclear shapes and azure granules in the cytoplasm. Biopsy showed that the tumor cells had diffusely infiltrated or interdigitated into the subepithelium. Immunohistochemistry revealed that the tumor cells had T- and NK cell phenotypes and were Epstein-Barr virus-encoded small RNA (EBER) positive, leading to a diagnosis of ENKTL. Thus, when nonepithelial tumor cells in a necrotic background and prominent atypia are found, as in this case, it is important to carefully observe for azurophil granules in the cytoplasm for differential diagnosis considerations., (© 2023 Wiley Periodicals LLC.)

Human pancreatic tumors are hypovascular in nature, and their tumor microenvironment is often characterized by hypoxia and severe nutrient deprivation due to uncontrolled heterogeneous growth, a phenomenon known as "austerity". However, pancreatic tumor cells have the inherent ability to adapt and thrive even in such low nutrient and hypoxic microenvironments. Anticancer drugs such as gemcitabine and paclitaxel, which target rapidly proliferating cells, are often ineffective against nutrient-deprived pancreatic cancer cells. In order to overcome this limitation, the search for novel agents that can eliminate cancer cells' adaptations to nutrition starvation, also known as "antiausterity" agents, represents a promising strategy to make the cancer cells susceptible to treatment. The natural product (+)-nicolaioidesin C (Nic-C) was found to have potent antiausterity activity against the PANC-1 human pancreatic cancer cell line in a nutrient-deprived condition. However, its efficacy in vivo remained untested. To address this, we synthesized Nic-C in its racemic form and evaluated its antitumor potential in a human pancreatic cancer xenograft model. Nic-C inhibited pancreatic cancer cell migration and colony formation and significantly inhibited tumor growth in MIA PaCa-2 xenografts in a dose-dependent manner. Furthermore, Nic-C inhibited the Akt/mTOR and autophagy signaling pathways in both in vitro and in vivo studies. Metabolomic profiling of in vivo tumor samples suggests that Nic-C downregulates amino acid metabolism while upregulating sphingolipid metabolism.

Background and Aims: A novel EUS-guided fine-needle biopsy sampling (EUS-FNB) needle enabled physicians to obtain sufficient pathologic samples with fewer to-and-fro movements (TAFs) within the lesion. We compared the diagnostic yields of EUS-FNB with 3 and 12 TAFs at each puncture pass., Methods: The primary endpoint of this multicenter, noninferiority, crossover, randomized controlled trial involving 6 centers was diagnostic sensitivity. Secondary endpoints were diagnostic accuracy and quantity and quality evaluation of EUS-FNB specimens. Length of the macroscopically visible core (MVC) and microscopic histologic quantity were used for quantitative evaluation. Macroscopic visual and microscopic histologic evaluations were performed for qualitative evaluation., Results: Among 110 patients (220 punctures, 110 for 3 TAFs and 12 TAFs each), 105 (210 punctures) had malignant histology. Diagnostic sensitivity for malignancy of 3 TAFs (88.6%) was not inferior to that of 12 TAFs (89.5%; difference, -.9%; 95% confidence interval, -9.81 to 7.86). Diagnostic accuracy for malignancy was 92.7% for 3 TAFs and 94.6% for 12 TAFs. Overall median MVC length was 13.5 mm in both groups. The 3-TAF group had a significantly higher rate of score ≥3 on macroscopic visual quality evaluation than the 12-TAF group (71.8% vs 52.7%, P = .009). No significant intergroup differences existed in microscopic histologic quantity and quality evaluations (quantity evaluation, 88.2% for 3 TAFs vs 83.6% for 12 TAFs; quality evaluation, 90.0% for 3 TAFs vs 89.1% for 12 TAFs)., Conclusions: Diagnostic sensitivity and accuracy of EUS-FNB with 3 TAFs were not inferior to those with 12 TAFs for solid pancreatic lesions. The 3-TAF group showed significantly less blood contamination in sampled tissues than the 12-TAF group. (Clinical trial registration number: UMIN000037309.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206 + M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206 + M2-like macrophages or deletion of CD206 + M2-like macrophages-specific TGF-β1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206 + M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in impaired muscle stem cell function, enhanced fibrosis, and delayed muscle regeneration. Mechanistically, CD206 + M2-like macrophages inhibit the secretion of FAP-derived follistatin via TGF-β signaling. Here we show that CD206 + M2-like macrophages constitute a microenvironment for FAPs and may regulate the myogenic potential of muscle stem/satellite cells., (© 2022. The Author(s).)

BACKGROUND Distal pancreatectomy with en bloc celiac artery resection (DP-CAR) is a curative surgical method for locally advanced pancreatic body cancer; however, arterial reconstruction remains controversial in this procedure. This report presents the case of a 47-year-old man with advanced distal pancreatic carcinoma and initial partial response to chemotherapy who required celiac axis reconstruction of the common hepatic artery and left gastric artery. CASE REPORT A 47-year-old man had loss of appetite. He had a 40-mm hypovascular tumor extending from the pancreatic body to the tail, invading around the celiac artery, common hepatic artery, left gastric artery, and splenic artery. We initiated chemotherapy concurrent with chemo-radiotherapy with S-1 administration. After chemo-radiotherapy, computed tomography (CT) showed tumor shrinkage, indicating partial response, but soft tissue CT density surrounding the celiac axis arteries persisted. We conducted conversion surgery. When the common hepatic artery was clamped during surgery, the intrahepatic arterial blood flow reduced; thus, we reconstructed the middle hepatic artery to the common hepatic artery. The left gastric artery was also reconstructed using the second jejunal artery to prevent ischemic gastropathy. Histopathologic examination showed no tumor cells in the specimen; thus, R0 resection was achieved. CONCLUSIONS Arterial reconstruction can be an option for R0 resection in DP-CAR when hepatic arterial blood flow is reduced due to an intraoperative common hepatic artery clamping test.

Background: Spinal cord infarction is a rare but serious complication of neurointervention that has been rarely documented. An association between spinal cord infarction and the placement of large bore catheters in the vertebral artery (VA) has been mentioned, but the precise etiology remains unclear., Case Description: A 72-year-old female presented with the right hemiparesis and left thermal hypoalgesia directly after endovascular coil embolization for an unruptured basilar tip aneurysm. Magnetic resonance imaging demonstrated right-sided upper cervical (C2-3) spinal cord infarction. Conventional bilateral vertebral angiograms revealed no opacification of the anterior spinal arteries. Cone-beam computed tomography showed a watershed area of radiculomedullary arteries that was correlated with the extent of the ischemic lesion. Thus, the spinal cord ischemia may have had multifactorial causes combined with reduced perfusion pressure to the spinal cord, which was caused by the placement of the guiding catheter in the VA and intensive hypotension during general anesthesia., Conclusion: Spinal cord infarction should be recognized as a serious complication of endovascular treatment involving posterior circulation., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

We compared the preplanned histopathological responses of resected liver metastases from patients who received modified FOLFOX6 plus bevacizumab or modified FOLFOX6 plus cetuximab for liver-limited colorectal metastases in the ATOM trial. Fibrosis and viable tumor cells in tumor regression grade (TRG), infarct-like necrosis in modified TRG (mTRG), and dangerous halo (DH) were assessed. Fifty-five patients (28 and 27 patients in the bevacizumab and cetuximab arms, respectively) were divided into the low (viable tumor cells ≤ 50%) and high (>50%) TRG or mTRG groups. DH was characterized as absent/rare or focal/diffuse. Compared to the bevacizumab arm, the cetuximab arm was more effective, with respect to low TRG (13 vs. 23 patients) and absent/rare DH (14 vs. 19 patients), respectively. Low mTRG was similarly observed in both arms. Low TRG/mTRG and absent/rare DH showed better relapse-free survival (RFS) than high TRG/mTRG and focal/diffuse DH. In the bevacizumab arm, a significant difference in RFS existed between the low and high TRG groups, while in the cetuximab arm, for TRG, mTRG, and DH, the low and absent/rare groups demonstrated significantly longer RFS than the high and focal/diffuse groups, respectively. TRG could estimate RFS in patients who underwent liver metastasectomy after bevacizumab or cetuximab chemotherapy.

Among intracranial cystic lesions, dermoid cysts and epidermoid cysts are relatively common benign tumors. In a small number of these tumors, it is known that squamous cell carcinomas arise in the lining epithelium of the cysts. Among tumors derived from the appendage, only one case of hidradenoma within a dermoid cyst and no cases of sebaceous tumor have been reported previously. In the present case, a protruding lesion was present in the cystic wall, and it was composed of two cell types: sebaceous cells (sebocytes) and basaloid/germinated cells, being characteristic of this tumor. It is essential to distinguish it from other sebaceous lesions such as hyperplasia, sebaceoma, sebaceous carcinoma, and basal cell carcinoma with sebaceous differentiation derived from the epidermis. The critical distinguishing points in making a differential diagnosis among these lesions are the ratio of the two cell types and the presence or absence of other components such as hair sacs, invasion or cellular atypia. Immunohistochemical examination revealed that the tumor cells were positive for the epithelial markers, such as cytokeratin (CK)14, p63, p40, high-molecular CK, and adipophilin; these findings are peculiar to sebaceous adenoma. Although there have been several similar case reports of sebaceous tumors associated with dermmoid cysts in the ovaries, most of the intracranial lesions were squamous cell carcinomas that developed within the cysts, and there has been no precedent showing an association with a sebaceous tumor. The present report describes the first case of sebaceous adenoma that occurred in an intracranial dermoid cyst., (© 2022 Japanese Society of Neuropathology.)

Objectives: Measurement of the macroscopic visible core (MVC) length during macroscopic on-site quality evaluation (MOSE) may allow estimation of sample adequacy for next-generation sequencing (NGS), and prediction of correct diagnosis in endoscopic ultrasound-guided tissue acquisition (EUS-TA) of pancreatic masses., Methods: This multicenter prospective study included consecutive patients who underwent EUS-TA for pancreatic masses using a 22-G Franseen needle. MVC length and pathological samples obtained from two needle passes were analyzed on a per-pass basis. Outcome measures included respective correlations of MVC length with histological sample quantity and diagnostic yields., Results: The analysis included 204 passes from 102 EUS-TAs. MVC length correlated positively with histological sample quantity (P < 0.01). On the receiver operating characteristic curve for MVC length, the cut-off value and area under the curve for obtaining a candidate sample for NGS were 30 mm and 0.74 (95% confidence interval [CI] 0.65-0.83), respectively. On multivariate analysis, MVC length ≥30 mm was a significant factor affecting suitability for NGS (odds ratio 6.19; 95% CI 2.72-14.10). Histologic diagnostic yield correlated positively with MVC length (P = 0.01); however, there was no positive correlation between MVC length and overall (histology plus cytology) diagnostic yield., Conclusions: Measuring MVC length to predict histological sample quantity on MOSE may be of clinical significance during EUS-TA using a 22-G Franseen needle. It may be an effective method, particularly while submitting samples for NGS., Registration: University Hospital Medical Information Network Trials Registry (UMIN000036528)., (© 2021 Japan Gastroenterological Endoscopy Society.)

Aims: This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia., Methods and Results: The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD) or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of the HGD area with crypt differentiation, the HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma., Conclusions: Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends upon the presence or absence of crypt differentiation., (© 2021 John Wiley & Sons Ltd.)

Malignant melanoma is known to have an altered phenotype and loss of differentiation markers for melanoma due to metastasis. Here, we report a case in which the expression of the immunohistochemical markers for melanoma was changed due to lymph node metastasis of primary cutaneous malignant melanoma. The patient, a male in his 60s, was diagnosed with malignant melanoma after undergoing excision of a skin mass. The additional excision specimen showed a small number of tumor cell clusters infiltrating the dermis. The biopsied lymph node showed completely different histological findings from those of the skin lesion and consisted of spindle-shaped tumor cells. An immunohistochemical study revealed no significant positive reactions in the lymph node tissue indicative of melanoma. The additional genetic study revealed BRAF V600e mutations in both the primary tumor and a lymph node. Together with the histological findings, the diagnosis was of metastasis of dedifferentiated melanoma to a lymph node. In summary, there is a risk of underestimation or misdiagnosis of melanoma as undifferentiated sarcoma or other tumors when melanoma metastasizes to lymph nodes and findings show a dedifferentiated or undifferentiated tumor. Therefore, as in this case, it is necessary to add a genetic study in order to make a comprehensive judgment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kamata et al.)

Post-transplant lymphoproliferative diseases (PTLD) are potentially fatal complications after cardiac transplantation. Most cases are Epstein-Barr virus (EBV)-related B-cell tumors, and reduction of immunosuppression treatment as well as the use of rituximab in combination with other chemotherapy are effective. However, patients with T/NK-cell PTLD post-cardiac transplantation are rarely reported. We had a patient with a fever that lasted for three weeks, with lung infiltrations and hepatosplenomegaly, who had EBV-associated hemophagocytosis 7 years after heart transplantation and was eventually diagnosed with T/NK-cell PTLD by autopsy. Although rare diseases, regular monitoring of EBV-DNA levels might be crucial for early diagnosis and treatment of PTLD.

Pancreatic cancer is a malignant neoplasm with high invasiveness and poor prognosis. In a previous study, a highly invasive pancreatic cancer cell line was established and found to feature enhanced interleukin-32 (IL-32) expression. However, whether IL-32 promotes the invasiveness by enhancing or suppressing the expression of IL-32 through regulating downstream molecules was unclear. To investigate the effect of IL-32, cells were established with high levels of expression or downregulated IL-32; their invasive ability was measured using a real-time measurement system and the expression of some candidate downstream molecules involved in invasion was evaluated in the two cell types. The morphological changes in both cell types and the localization of IL-32 expression in pancreatic cancer tissues were studied using immunohistochemistry. Among the several splice variants of IL-32, cells transfected with the ε isoform had increased invasiveness, whereas the IL-32-suppressed cells had reduced invasiveness. Several downstream molecules, whose expression was changed in the two cell types, were monitored. Notably, changes of E-cadherin, CLDN1, CD44, CTGF and Wnt were documented. The morphologies of the two cell types differed from the original cell line. Immunohistochemically, the expression of IL-32 was observed only in tumor cells and not in normal pancreatic cells. In conclusion, IL-32 was found to promote the invasiveness of pancreatic cancer cells by regulating downstream molecules., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Takagi et al.)

Secondary bile acids (SBAs) with high hydrophobicity are abundant in the colonic lumen. However, both aggravating and protective roles of SBAs have been proposed in the pathogenesis of inflammatory bowel diseases (IBDs). We observed that oral administration of hyodeoxycholic acid (HDCA), a hydrophilic bile acid, prevented the development of dextran sulfate sodium (DSS)-induced colitis in mice. We then examined the individual effects of DSS and HDCA as well as their combined effects on fecal bile acid profile in mice. HDCA treatment increased the levels of most of fecal bile acids, whereas DSS treatment had limited effects on the levels of fecal bile acids. The combined treatment with DSS and HDCA synergistically increased the levels of fecal chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) in feces, which are potent activators of the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). The overall hydrophobicity of fecal bile acids was not modified by any treatments. Our data suggest that the preventive effect of HDCA on DSS-induced colitis in mice is due to the synergism between DSS and HDCA in increasing the levels of the fecal bile acids with potencies to activate FXR and TGR5.

Objective: Expansion of adipose tissue during obesity through the recruitment of newly generated adipocytes (hyperplasia) is metabolically healthy, whereas that through the enlargement of pre-existing adipocytes (hypertrophy) leads to metabolic complications. Accumulating evidence from genetic fate mapping studies suggests that in animal models receiving a high-fat diet (HFD), only adipocyte progenitors (APs) in gonadal white adipose tissue (gWAT) have proliferative potential. However, the proliferative potential and differentiating capacity of APs in the inguinal WAT (iWAT) of male mice remains controversial. The objective of this study was to investigate the proliferative and adipogenic potential of APs in the iWAT of HFD-fed male mice., Methods: We generated PDGFRα-GFP-Cre-ER T2 /tdTomato (KI/td) mice and traced PDGFRα-positive APs in male mice fed HFD for 8 weeks. We performed a comprehensive phenotypic analysis, including the histology, immunohistochemistry, flow cytometry, and gene expression analysis, of KI/td mice fed HFD., Results: Contrary to the findings of others, we found an increased number of newly generated tdTomato + adipocytes in the iWAT of male mice, which was smaller than that observed in the gWAT. We found that in male mice, the iWAT has more proliferating tdTomato + APs than the gWAT. We also found that tdTomato + APs showed a higher expression of Dpp4 and Pi16 than tdTomato - APs, and the expression of these genes was significantly higher in the iWAT than in the gWAT of mice fed HFD for 8 weeks. Collectively, our results reveal that HFD feeding induces the proliferation of tdTomato + APs in the iWAT of male mice., Conclusion: In male mice, compared with gWAT, iWAT undergoes hyperplasia in response to 8 weeks of HFD feeding through the recruitment of newly generated adipocytes due to an abundance of APs with a high potential for proliferation and differentiation., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Soft tissue calcifications are common findings in patients with various diseases, such as malignant tumors, collagen diseases, trauma, and chronic kidney disease. The majority of these lesions are not clinically significant; however, they can cause specific disorders within a limited space, such as the spinal canal. Here, we report the case of a patient undergoing fusion surgery for lumbar canal stenosis due to degenerative spondylolisthesis and multiple intraspinal canal calcifications associated with psoriatic arthritis (PsA). A 55-year-old female patient presented with pain in the left leg and intermittent claudication for 1 month. One year ago, she was diagnosed with PsA and received outpatient treatment, including biological medication, at the Division of Rheumatology, Department of Internal Medicine of our institution. She was referred to our department, and radiological examination revealed lumbar canal stenosis caused by spondylolisthesis and multiple calcifications in the lumbar spinal canal. We performed posterior lumbar interbody fusion (PLIF) with percutaneous pedicle screw fixation concomitant with removal of the calcifications. The postoperative course was uneventful, and her neurological symptoms improved. Although several prior case reports have noted intraspinal canal calcifications due to collagen disease or chronic kidney disease, calcifications associated with PsA are rare. We discuss the diagnosis of PsA and its relationship with intraspinal canal calcifications by reviewing the previous relevant literature., Competing Interests: Conflicts of Interest Disclosure None declared., (© 2021 The Japan Neurosurgical Society.)

Amyloidosis is a disorder of protein folding in which various proteins automatically aggregate into a highly abnormal fibrillar conformation. Amyloidosis is classified into systemic and localized forms depending on whether the abnormal proteins deposited in several different organs or only a single organ. In localized amyloidosis of the head and neck regions, laryngeal amyloidosis is common; however, localized amyloidosis of the nose is extremely rare. We herein report a case of localized amyloidosis of the nose and review the relevant literature on localized sinonasal amyloidosis. A 41-year-old man presented with a history of severe nasal obstruction, which had persisted for two decades. Nasal endoscopy and imaging studies showed extensive thickening of the bilateral nasal mucosa and diffuse submucosal deposition of calcification. After histopathological and systemic examinations, he was diagnosed with localized amyloidosis of the nasal mucosa. Septoplasty and bilateral inferior turbinoplasty, which consisted of mucosal resection using an ultrasonic bone curette, was performed and his symptoms markedly improved. Localized sinonasal amyloidosis has a good prognosis and surgical resection should be selected as a first-line treatment; however, clinicians should recognize the high probability of recurrence., 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 © 2021 Takakura, Tachino, Takii, Imura and Shojaku.)

Intraosseous mucoepidermoid carcinoma of the jaw is a rare lesion that has been suggested to originate from the odontogenic epithelium. We report an unusual case of central mucoepidermoid carcinoma in an 18-year-old Japanese man with an odontogenic cyst., Competing Interests: The authors made no disclosures., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

We report three cases in which endovascular treatment (EVT) was performed for anterior circulation large vessel occlusion (LVO) beyond 24 h from the onset of stroke. Case 1 experienced left hemispatial neglect and gait disorder due to right internal cerebral artery (ICA) occlusion and underlying atherosclerosis. After percutaneous transluminal angioplasty (PTA), revascularization with mild stenosis was achieved. Case 2 complained of reduced activity, motor aphasia, and right-sided hemiparesis due to left middle cerebral artery occlusion. After thrombectomy using a retrieval stent, revascularization with M1 stenosis and distal perfusion delay was observed, which improved after PTA. Case 3 arrived at our hospital 30 h after the onset of dysarthria and gait disturbance due to left ICA occlusion. Since the symptoms were mild, medical treatment was started; however, the patient's symptoms deteriorated 6 h later, and EVT was required. After thrombectomy using a retrieval stent, revascularization was achieved. LVO pathophysiology beyond 24 h of stroke onset varies and may require multimodal treatment. Preserving the pyramidal tract may lead to favorable outcomes, even in cases of anterior circulation LVO. EVT may be effective for anterior circulation LVO because, in some patients, infarct volume continues to increase >24 h after stroke onset., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Asian Journal of Neurosurgery.)

Ayu-narezushi , a traditional Japanese fermented food, comprises abundant levels of lactic acid bacteria (LAB) and free amino acids. This study aimed to examine the potential beneficial effects of ayu-narezushi and investigated whether ayu-narezushi led to improvements in the Tsumura Suzuki obese diabetes (TSOD) mice model of spontaneous metabolic syndrome because useful LAB are known as probiotics that regulate intestinal function. In the present study, the increased body weight of the TSOD mice was attenuated in those fed the ayu-narezushi -comprised chow ( ayu-narezushi group) compared with those fed the normal rodent chow (control group). Serum triglyceride and cholesterol levels were significantly lower in the Ayu-narezushi group than in the control group at 24 weeks of age. Furthermore, hepatic mRNA levels of carnitine-palmitoyl transferase 1 and acyl-CoA oxidase, which related to fatty acid oxidation, were significantly increased in the ayu-narezushi group than in the control group at 24 weeks of age. In conclusion, these results suggested that continuous feeding with ayu-narezushi improved obesity and dyslipidemia in the TSOD mice and that the activation of fatty acid oxidation in the liver might contribute to these improvements., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Takeshi Nishida et al.)