A multi-institutional study designed by members of Tokyo Guidelines (TG) Core Meeting to elucidate the clinical characteristics and pathogenesis of acute cholangitis after bilioenteric anastomosis and biliary stent insertion with a focus on biliary obstruction: Role of transient hepatic attenuation difference (THAD) and pneumobilia in improving TG diagnostic performance.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

Sclerosing meningioma with a large peritumoral cyst: Case report.

Meningioma morphology is diverse. Although unlisted in the WHO classification, sclerosing meningioma is a rare variation featuring an extremely low signal intensity on MRI T2-weighted imaging. About 50 cases of sclerosing meningiomas, including spinal tumors, have been reported; however, cases with an accompanying large peritumoral cyst remain unreported. Here, we first report a rare case of sclerosing meningioma with a large peritumoral cyst and review relevant literature.

Effects of switching from liraglutide to semaglutide or dulaglutide in patients with type 2 diabetes: A randomized controlled trial.

INTRODUCTION: Few studies have examined the effects of glucagon-like peptide-1 receptor agonist switching, particularly in Japanese patients. Therefore, we aimed to investigate the effects of switching from liraglutide to semaglutide or dulaglutide on blood glucose, body weight, and the occurrence of adverse effects in clinical practice. MATERIALS AND METHODS: This was an open-label, prospective, randomized, parallel-group controlled trial. Patients with type 2 diabetes treated with liraglutide (0.6 or 0.9 mg) at Yokosuka Kyosai Hospital in Japan were recruited from September 2020 to March 2022 and, after obtaining informed consent, randomly assigned to the semaglutide or dulaglutide group (1:1). Changes in the glycated hemoglobin level from baseline to weeks 8, 16, and 26 were evaluated post-treatment. RESULTS: Initially, 32 participants were enrolled, of whom 30 completed the study. Glycemic control was significantly better in the semaglutide group than in the dulaglutide group (-0.42 ± 0.49% vs -0.00 ± 0.34%, P = 0.0120). Body weight significantly decreased in the semaglutide group (-2.6 ± 3.6 kg, P = 0.0153), whereas no change was observed in the dulaglutide group (-0.1 ± 2.7 kg, P = 0.8432). We found a significant difference in body weight between the groups (P = 0.0469). The proportion of participants who reported adverse events was 75.0% and 18.8% in the semaglutide and dulaglutide groups, respectively. One patient in the semaglutide group had difficulty continuing treatment due to severe vomiting and weight loss. CONCLUSIONS: Switching from once-daily liraglutide to once-weekly semaglutide 0.5 mg significantly improved glycemic control and body weight compared with switching to once-weekly dulaglutide 0.75 mg.

Single-incision laparoscopic enucleation for pancreatic insulinoma with preoperative nasopancreatic stent placement: A case report.

INTRODUCTION AND IMPORTANCE: Most insulinomas are benign and solitary, with a tumor diameter less than 2 cm; therefore, laparoscopic enucleation, which is a minimally invasive procedure that can preserve the pancreatic parenchyma, is considered an optimal procedure. The key to enucleation is to avoid injury to the main pancreatic duct (MPD). Herein, we present a case in which single-incision laparoscopic enucleation (SILE) was performed for insulinomas, with preoperative nasopancreatic stent (NPS) placement. CASE PRESENTATION: A male patient in his fifties underwent SILE for insulinomas. To prevent injury to the MPD, an NPS was preoperatively placed. All surgical procedures were performed through a single mini-laparotomy site in the umbilicus. NPS placement facilitated identification of the MPD under laparoscopic ultrasonography. Enucleation was successfully completed without any injury to the MPD, and the NPS was removed immediately after confirming that there was no injury to the MPD by the NPS via pancreatography. The postoperative course was uneventful. CLINICAL DISCUSSION: This report serves to highlight the maximum safety and minimal invasiveness of SILE with the preoperative NPS placement. Preoperative NPS placement is useful for avoiding injury to the MPD during enucleation and has the merit of helping to recognize whether leakage occurs by intraoperative pancreatography via the NPS. CONCLUSION: Preoperative NPS placement helps to ensure the safe enucleation of pancreatic insulinomas even in single-incision laparoscopic surgery, with minimal invasiveness and better cosmetic outcomes.

The oligodendroglial histological features are not independently predictive of patient prognosis in lower-grade gliomas.

The relevance of oligodendroglial histological features to patient prognoses is controversial. 93 LrGGs resected for about 2 decades were re-assessed based on WHO2007 with special interest to pure oligodendroglial diagnosis (oligodendroglioma or anaplastic oligodendroglioma) and presence of CFO features. Those histological features, patients OS, and tumor chromosomal/genetic characteristics were correlated each other in each of the 3 IDH-1p/19q-based molecular groups. There was significant association between 1p19q status with the oligodendroglial histological diagnosis as well as presence of CFO in the entire cohort. The oligodendroglial diagnosis was associated with longer OS in IDHmut/codel group; however, this association was not significant in the multivariate analyses. In IDHmut/noncodel and IDH-wildtype groups, the oligodendroglial diagnosis was not associated with patient OS. Presence of CFO was not associated with patient OS in any molecular groups. Gain of 8q was associated with the oligodendroglial diagnosis in IDHmut/noncodel group. Neither the oligodendroglial diagnosis nor CFO was predictive for the methylation status of the MGMT gene in any molecular groups. The oligodendroglial histological features are not independently predictive of either patient prognosis or chemotherapeutic response in LrGGs, leaving the possibility of marginal favorable association only in IDHmut/codel tumors.

Tumor-to-tumor metastasis: an extremely rare combination with renal cell carcinoma as the donor and a pancreatic neuroendocrine tumor as the recipient.

BACKGROUND: Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another tumor. Herein, we report an extremely rare case of a renal cell carcinoma metastasis into a pancreatic neuroendocrine tumor exhibiting a tumor-to-tumor metastasis. Ours is the third reported case worldwide. CASE PRESENTATION: The patient, a 72-year-old male, was referred to our hospital for further examination and treatment due to high levels of prostate-specific antigen. A left renal tumor and pancreatic head tumor were revealed incidentally on screening computed tomography. There were suspected to be a renal cell carcinoma and primary pancreatic neuroendocrine tumor or pancreatic metastasis from the renal cell carcinoma according to preoperative examination. The left nephrectomy and subtotal stomach-preserving pancreaticoduodenectomy were performed because of the pancreatic tumor indicated for operation in either case of diagnosis. Postoperative pathological examination showed a diagnosis of clear cell renal cell carcinoma for the left renal tumor. The pancreatic tumor was diagnosed with clear cell renal cell carcinoma metastasis into the pancreatic neuroendocrine tumor, that is to say tumor-to-tumor metastasis. CONCLUSION: In some cases, conservative approach is selected for pancreatic neuroendocrine tumor patients who meet some requirements. However, if such patients exhibit tumor-to-tumor metastasis which combines with renal cell carcinoma and pancreatic neuroendocrine tumor as this case, conservative approach leads to progression of renal cell carcinoma. Therefore, conceiving the possibility of tumor-to-tumor metastasis, it is necessary to carefully choose a treatment plan for pancreatic neuroendocrine tumor patients associated with renal cell carcinoma, not easily choosing conservative approach.

Recurrence of cervical intramedullary gliofibroma.

INTRODUCTION: Gliofibroma is a rare tumor that develops in the brain and spinal cord. Due to the rarity of its nature, its pathophysiology and appropriate treatment remain elusive. We report a case of intramedullary spinal cord gliofibroma that was surgically treated multiple times. This report is of great significance because this is the first case of recurrence of this tumor. CASE PRESENTATION: A 32-year-old woman complained of gait disturbance and was referred to our institution. At the age of 13 years, she was diagnosed with intramedullary gliofibroma and underwent gross total resection (GTR) in another hospital. Based on imaging findings, tumor recurrence was suspected at the level of cervical spinal cord, and surgery was performed. However, the resection volume was limited to 50% because the boundary between the tumor and spinal cord tissue was unclear and intraoperative neuromonitoring alerted paralysis. At 1 year postoperatively, the second surgery was performed to try to resect the residual tumor, but subtotal resection was achieved at most. At 2 years after the final surgery, no tumor recurrence was observed, and neurologic function was maintained to gait with cane. DISCUSSION: Although complete resection is desirable for this rare tumor at the initial surgery, there is a possibility to recur even after GTR with long-term follow-up. During surgical treatment for tumor recurrence, fair adhesion to the spinal cord is expected, and reoperation and/or adjuvant therapy might be considered in the future if the tumor regrows and triggers neurological deterioration.

A case with massive hemobilia long-term after internal drainage surgery for congenital biliary dilation.

BACKGROUND: Currently, there is an unwavering consensus that the standard surgery for congenital biliary dilation (CBD) is extrahepatic bile duct resection and choledochojejunostomy. However, decades prior, choledochocyst-gastrointestinal anastomosis without extrahepatic bile duct resection (internal drainage surgery, IDS) was preferred for CBD because of its simplicity. Currently, there is almost no chance of a surgeon encountering a patient who has undergone old-fashioned IDS, which has been completely obsolete due to the risk of carcinogenesis from the remaining bile duct. Moreover, the pathological condition long after IDS is unclear. Herein, we report a case of life-threatening bile duct bleeding as well as carcinoma of the bile duct 62 years after IDS in a patient with CBD. CASE PRESENTATION: An 82-year-old Japanese woman with hemorrhagic shock due to gastrointestinal bleeding was transferred to our hospital. She had a medical history of unspecified surgery for CBD at the age of 20. Based on imaging findings and an understanding of the historical transition of the surgical procedure for CBD, the cause of gastrointestinal bleeding was determined to be rupture of the pseudoaneurysm of the dilated bile duct that remained after IDS. Hemostasis was successfully performed by transcatheter arterial embolization (TAE) in an emergency setting. Then, elective surgery for extrahepatic bile duct resection and choledochojejunostomy was performed to prevent rebleeding. Pathological examination revealed severely and chronically inflamed mucosa of the bile duct. Additionally, cholangiocarcinoma (Tis, N0, M0, pStage 0) was incidentally revealed. CONCLUSION: It has been indicated that not only carcinogenesis, but also a risk of life-threatening bleeding exists due to long-lasting chronic inflammation to the remnant bile duct after IDS for CBD. Additionally, both knowledge of which CBD operation was performed, and an accurate clinical history are important for the diagnosis of hemobilia.

TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma.

The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

Double Meningioma: A Case of Two Fibrous Meningiomas Coexisting Isolatedly in Meningothelial Meningioma.

Meningiomas are the most common intracranial primary neoplasm in adults, and show various histological subtypes, indicating heterogeneous clinical and molecular genetic characteristics. Different subtypes of meningioma coexisting independently within the main tumor of another different subtype is a quite rare clinical situation. A 69-year-old woman presented with a several- year history of dizziness as a non-specific complaint. Magnetic resonance imaging (MRI) revealed an extra-axial mass lesion in the left parieto-occipital region including two well-demarcated, round mass components. Total resection was performed via left parieto-occipital craniotomy. Two white masses were identified within the main tumor, with neither showing dural attachments. Pathological findings showed the main mass represented meningothelial meningioma and the demarcated mass lesions were both fibrous meningiomas. No transitional features existed between these subtypes. No differences in genetic characteristics were evident between subtypes of meningioma. We have described, apparently for the first time, a case of two fibrous meningiomas coexisting in an isolated manner in meningothelial meningioma with the similar molecular genetic profile.

TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations.

TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

Malignant transformation of pleomorphic xanthoastrocytoma and differential diagnosis: case report.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic glioma, characterized by large pleomorphic and frequently multinucleated cells, spindle and lipidized cells, a dense pericellular reticulin network, and numerous eosinophilic granular bodies according to the grade II glial tumor standards of the World Health Organization's (WHO) 2016 guidelines. PXA rarely transforms into anaplastic PXA or glioblastoma (GBM) and anaplastic PXA, classified as WHO grade III, has a more aggressive clinical behavior with poorer prognosis than PXA. CASE PRESENTATION: Here we describe an unusual case of PXA in a 19-year-old woman, first admitted with headache and a mass in the left temporal lobe in 2005 that was removed. Twelve years later, she returned with left temporal headache, diplopia and tinnitus. A local tumor recurrence was found, and a second resection was performed. The specimen showed highly malignant findings, such as necrosis, microvascular proliferation, and multiple mitoses. The integrated diagnosis was made as high grade glioma, probably derived from PXA. Immunohistochemical (IHC) stains were positive for oligo2, and approximately 21% positive for Ki-67, while negative for CD34, IDH1 R132H. INI1 and ATRX were retained. As the histological classification was glioblastoma, the patient received GBM-appropriate chemotherapy and radiation therapy and outpatient follow-ups have demonstrated no obvious symptoms for 1 year after surgery. Additional molecular analyses found BRAF V600E mutations in both resections, supporting the idea that the recurrent tumor had derived from PXA. CONCLUSIONS: This case highlights the complexities of differential diagnosis based on the World Health Organization's 2016 guidelines. More integrated criteria to differentiate anaplastic PXA from GBM and epithelioid GBM, combined with genetic screening results, might be needed.

Influence of Timing of Insulin Initiation on Long-term Glycemic Control in Japanese Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Objective Delays in insulin initiation can lead to the development of complications in the management of type 2 diabetes. Methods In this study, the effects of the timing of insulin initiation on glycemic control in patients with type 2 diabetes were evaluated retrospectively. Changes in the HbA1c levels of 237 patients were analyzed after insulin initiation. Results The patients were divided into 4 groups according to the duration of diabetes at the time of insulin initiation: ≤3 years, 4 to 6 years, 7 to 9 years, or ≥10 years. Patients with a diabetes duration of ≤3 years were more frequently hospitalized at the time of insulin initiation, had a higher HbA1c level before insulin initiation and a lower HbA1c level at 1 year after insulin initiation and exhibited significant decreases in HbA1c at 1, 3, or 5 years after insulin initiation than those in the other 3 groups with longer durations of diabetes. In the group receiving 4 insulin injections per day, the reduction in HbA1c after 5 years of treatment was larger in patients with a diabetes duration at the time of insulin initiation of ≤3 years than in those with a duration of 7 to 9 years or ≥10 years. Conclusion Our results suggested that an earlier initiation of insulin therapy was crucial for sustaining glycemic control in Japanese patients with type 2 diabetes, particularly in those with a history of obesity or receiving multiple insulin injections daily.

Biopolymer monolith for protein purification.

Porous glycopolymers, "glycomonoliths", were prepared by radical polymerization based on polymerization-induced phase separation with an acrylamide derivative of α-mannose, acrylamide and cross-linker in order to investigate protein adsorption and separation. The porous structure was induced by a porogenic alcohol. The pore diameter and surface area were controlled by the type of alcohol. The protein adsorption was measured in both batch and continuous flow systems. The glycomonoliths showed specific interaction with the sugar recognition protein of concanavalin A, and non-specific interaction to other proteins was negligible. The amount of protein adsorption to the materials was determined by the sugar density and the composition of the glycomonoliths. Fundamental knowledge regarding the glycomonoliths for protein separation was obtained.

Identification of shared genomic aberrations between angiomatous and microcystic meningiomas.

BACKGROUND: Angiomatous and microcytic meningiomas are classified as rare subtypes of grade I meningiomas by World Health Organization (WHO). They typically exhibit distinct histopathological features as indicated by their WHO titles; however, these angiomatous and microcystic features are often intermixed. Recently, angiomatous meningiomas were reported to show characteristic chromosomal polysomies unlike the other WHO grade I meningiomas. In the present study, we hypothesize that microcystic meningiomas share similar cytogenetic abnormalities with angiomatous meningioma. METHODS: We performed copy number analysis using single nucleotide polymorphism (SNP) arrays for three angiomatous and eight microcystic meningiomas. Of these, three angiomatous and three microcystic meningiomas were also analyzed by whole exome sequencing and RNA sequencing. RESULTS: We first analyzed three angiomatous and three microcystic meningiomas for which both frozen tissues and peripheral blood were accessible. Copy number analysis confirmed previously reported multiple polysomies in angiomatous meningiomas, which were entirely replicated in microcystic meningiomas when analyzed on different analytical platforms with five additional samples prepared from formalin-fixed paraffin-embedded tumors. Polysomy of chromosome 5 was found in all cases, along with chromosome 6, 12, 17, 18, and 20 in more than half of the cases including both angiomatous and microcystic meningiomas. Furthermore, next generation sequencing did not reveal any distinctive somatic point mutations or differences in gene expression characterizing either angiomatous or microcystic meningiomas, indicating a common genetic mechanism underlying tumorigenesis. CONCLUSIONS: Angiomatous and microcystic meningiomas have substantially similar genetic profiles represented by the characteristic patterns of multiple polysomies originating from chromosome 5 amplification.

Random Skin Biopsies Before Brain Biopsy for Intravascular Large B-Cell Lymphoma.

OBJECTIVE: To evaluate effectiveness of random skin biopsies for intravascular large B-cell lymphoma (IVLBCL) with or without central nervous system (CNS) involvement. METHODS: Data from 21 patients with suspected IVLBCL (7 with CNS involvement and 14 without CNS involvement) who underwent single (4 patients), double (1 patient), and random (16 patients) skin biopsies were retrospectively analyzed. RESULTS: IVLBCL was diagnosed in 16 patients (including 6 with CNS involvement). Sensitivity, specificity, and positive predictive value of random skin biopsies were 75%, 100%, and 100%. Ratio of tumor-positive biopsy samples to plasma soluble interleukin-2 receptor (sIL-2R) values was significantly correlated in cases with data on both variables. sIL-2R values in the 6 tumor-negative skin samples (median, 1415 U/mL; range, 487-3200 U/mL) were significantly lower than in tumor-positive skin samples (median, 3550 U/mL; range, 595-8700 U/mL) with at least 1 skin specimen obtained. Mean ratio of tumor-positive biopsy samples in IVLBCL cases with low sIL-2R (<3000 U/mL) was only 45%, indicating a requirement for 3-site multiple sampling. No differences in median sIL-2 values between cases of IVLBCL with and without CNS involvement were found (2795 U/mL vs. 3550 U/mL). Steroids administered before diagnosis yielded false-negative results in 3 of 5 IVLBCL cases (all false-negative cases were IVLBCL with CNS involvement), whereas none of 11 IVLBCL cases without steroid administration yielded false-negative results. CONCLUSIONS: Random skin biopsies before brain biopsy are recommended in patients with suspected IVLBCL regardless of CNS involvement, but low sIL-2R values and steroids may yield false-negative results.

Exosome-encapsulated microRNA-4525, microRNA-451a and microRNA-21 in portal vein blood is a high-sensitive liquid biomarker for the selection of high-risk pancreatic ductal adenocarcinoma patients.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis. This is due to late diagnosis and lack of reliable prognostic biomarkers. In this study, we focused on exosomal microRNA (miRNA) in portal vein blood (PVB) as a potential biomarker to identify patients at high-risk for recurrence and poor postoperative outcome. METHODS: Exosomal miR-4525, miR-451a and miR-21 expressions were assessed using PVB and peripheral blood (PB) collected from 55 PDAC patients during curative pancreatectomy. Correlation between the miRNA expressions and clinical outcomes, and target genes expressions was investigated. RESULTS: Exosomal miR-4525, miR-451a and miR-21 levels were upregulated in PVB, which were higher than those in the PB. High expression of miR-4525, miR-451a and miR-21 in PVB was associated with recurrence with a higher sensitivity, specificity, and accuracy than that in PB. Cox regression analysis showed miR-4525, miR-451a and miR-21 levels in PVB were independent prognostic factors for overall survival and disease-free survival. There was a negative correlation between the expressions of miR-4525 and MEN1 mRNA, miR-451a and CAB39 mRNA, and t miR-21 and PDCD4 mRNA. CONCLUSIONS: miR-4525, miR-451a and miR-21 in PVB are potential biomarkers identifying patients at high-risk for recurrence and poor survival in resected PDAC patients.

Progesterone Receptor Is Responsible for Benign Biology of Skull Base Meningioma.

OBJECTIVE: Many studies have been performed to evaluate the roles of estrogen receptor and progesterone receptor (PGR) in meningiomas, but their influence on tumor behavior remains unclear. METHODS: We retrospectively analyzed patients with meningioma who underwent surgical resection at our institute. Patients with data for immunohistochemical staining of estrogen receptor, PGR, and Ki-67 were included. RESULTS: The study included 161 patients comprising 61 skull base and 100 non-skull base meningiomas. Histologically, the number of patients with World Health Organization (WHO) grade I, II, and III disease were 132 (82.0%), 22 (14.7%), and 7 (4.4%), respectively. Tumor recurrence was observed in 21 (13.0%). Negative PGR, high Ki-67 index, incomplete resection, and WHO grade II or III were significantly correlated with tumor recurrence and shorter recurrence-free survival. Skull base meningiomas were difficult to remove entirely; 31 patients (50.8%) with skull base and 77 patients (77.0%) with non-skull base meningiomas had overall complete removal (P = 0.0006). Ki-67 indices, proportion of WHO grade II or III, and recurrence rate or recurrence-free survival did not differ between the tumor locations. The only difference was the proportion of patients with positive PGR, which was significantly higher for skull base meningiomas (61.5 ± 33.4% vs. 42.2 ± 35.7%, P = 0.0009). CONCLUSIONS: Although skull base meningiomas are often incompletely resected, there were no differences in recurrence-free survival or recurrence rate between skull base and non-skull base meningiomas. As the Ki-67 index and WHO grade were not different between these locations, the high rate of positive PGR may be responsible for the benign biology of skull base meningiomas.

Diffusely Infiltrating Cerebellar Anaplastic Astrocytoma Effectively Controlled with Bevacizumab: Case Report and Literature Review.

BACKGROUND: Gliomas that show extensive diffuse infiltration from the cerebellum to the brainstem without masslike expansion are extremely rare. The efficacy of bevacizumab treatment for diffusely infiltrating gliomas remains uncertain. CASE DESCRIPTION: A 75-year-old man presented with a cerebellar anaplastic astrocytoma showing diffuse infiltration to the brainstem without a definite mass. He had experienced rapidly progressive nausea and dysarthria, as well as vertigo and headache for 2 months. Magnetic resonance imaging (MRI) revealed a poorly demarcated T2 high-intensity area in the right cerebellum and brainstem. The tumor in the right cerebellum showed sparse enhancement with gadolinium (Gd). Suboccipital decompressive craniotomy and partial removal of the tumor was emergently performed because of the rapid progression of symptoms and severe tonsillar herniation demonstrated on MRI. The pathologic diagnosis was anaplastic astrocytoma, and genomic analyses revealed no mutation in IDH1, H3F3A, or BRAF. During concomitant chemoradiotherapy with temozolomide, rapid worsening of the neurologic symptoms developed and significant enlargement of the T2 high-intensity area extending to the cerebral peduncle was seen, as well as a new Gd-enhancing lesion in the midbrain. After administration of bevacizumab, the neurologic symptoms gradually improved, the T2 high-intensity area decreased, and the Gd-enhancing lesion disappeared. At follow-up 2 years after the operation, no worsening of neurologic symptoms was seen and the residual T2 high-intensity area remained unchanged on MRI. CONCLUSIONS: Bevacizumab treatment may be a salvage treatment option for patients with diffusely infiltrating cerebellar gliomas that exhibits rapid progression during standard treatment.

Welcoming the new WHO classification of pituitary tumors 2017: revolution in TTF-1-positive posterior pituitary tumors.

The fourth edition of the World Health Organization classification of endocrine tumors (EN-WHO2017) was released in 2017. In this new edition, changes in the classification of non-neuroendocrine tumors are proposed particularly in tumors arising in the posterior pituitary. These tumors are a distinct group of low-grade neoplasms of the sellar region that express thyroid transcription factor-1, and include pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and sellar ependymoma. This short review focuses on the classification of posterior pituitary tumors newly proposed in EN-WHO2017, and controversies in their pathological differential diagnosis are discussed based on recent cases.