The MDM2-p53 Axis Represents a Therapeutic Vulnerability Unique to Glioma Stem Cells.

The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests that they have unique vulnerabilities that may be therapeutically targeted. We investigated MDM2 expression levels in glioma stem cells and their non-stem cell counterparts and the effects of the genetic and pharmacological inhibition of MDM2 on the viability of these cells as well as downstream molecular pathways. The results obtained showed that MDM2 expression was substantially higher in glioma stem cells than in their non-stem cell counterparts and also that the inhibition of MDM2, either genetically or pharmacologically, induced a more pronounced activation of the p53 pathway and apoptotic cell death in the former than in the latter. Specifically, the inhibition of MDM2 caused a p53-dependent increase in the expression of BAX and PUMA and a decrease in the expression of survivin, both of which significantly contributed to the apoptotic death of glioma stem cells. The present study identified the MDM2-p53 axis as a novel therapeutic vulnerability, or an Achilles' heel, which is unique to glioma stem cells. Our results, which suggest that non-stem, bulk tumor cells are less sensitive to MDM2 inhibitors, may help guide the selection of glioblastoma patients suitable for MDM2 inhibitor therapy.

The effect of a polymer capping agent on electrodeposited silver nanoparticles in a silver deposition-based electrochromic device.

In this study, polyvinylpyrrolidone (PVP) was introduced into an Ag deposition-based electrochromic (EC) device as a capping agent for electrodeposited Ag nanoparticles (AgNPs) to improve the coloration characteristics of EC devices and to precisely control the size and shape of the AgNPs. Through the coordination of PVP molecules with Ag+ ions in the EC electrolyte, the critical voltage for the deposition of AgNPs decreased, resulting in a lower operating voltage of the EC device in comparison with the conventional one. Because particle growth and AgNP aggregation were suppressed by the capping effect of PVP, uniform electrodeposition of AgNPs was achieved. Aggregation suppression enabled vivid cyan, yellow, and red coloration using a simple driving procedure. The suppression of AgNP aggregation by PVP was demonstrated even in an electrochemical system. Furthermore, the capping effect of PVP also improved image retention. Better color retention properties were achieved even without the use of any counter-modified electrode cells.

Association of ADC of hyperintense lesions on FLAIR images with TERT promoter mutation status in glioblastoma IDH wild type.

Background: Although mutations in telomerase reverse transcriptase (TERT) promoter (TERTp) are the most common alterations in glioblastoma (GBM), predicting TERTp mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing TERTp mutation status using magnetic resonance imaging (MRI). Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)-wild-type GBM. The apparent diffusion coefficient (ADC) and volume of CELs and FLAIR hyperintense lesions (FHLs) were determined, and the correlation between MRI features and TERTp mutation status was analyzed. In a subset of cases, FHLs were histopathologically analyzed to determine the correlation between tumor cell density and ADC. Results: TERTp mutations were present in 77 (67.5%) patients. The minimum ADC of FHLs was significantly lower in the TERTp-mutant group than in the TERTp-wild-type group (mean, 958.9 × 10-3 and 1092.1 × 10-3 mm2/s, respectively, P < 0.01). However, other MRI features, such as CEL and FHL volumes, minimum ADC of CELs, and FHL/CEL ratio, were not significantly different between the two groups. Histopathologic analysis indicated high tumor cell density in FHLs with low ADC. Conclusion: The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning.

Recent developments in machine learning modeling methods for hypertension treatment.

Hypertension is the leading cause of cardiovascular complications. This review focuses on the advancements in medical artificial intelligence (AI) models aimed at individualized treatment for hypertension, with particular emphasis on the approach to time-series big data on blood pressure and the development of interpretable medical AI models. The digitalization of daily blood pressure records and the downsizing of measurement devices enable the accumulation and utilization of time-series data. As mainstream blood pressure data shift from snapshots to time series, the clinical significance of blood pressure variability will be clarified. The time-series blood pressure prediction model demonstrated the capability to forecast blood pressure variabilities with a reasonable degree of accuracy for up to four weeks in advance. In recent years, various explainable AI techniques have been proposed for different purposes of model interpretation. It is essential to select the appropriate technique based on the clinical aspects; for example, actionable path-planning techniques can present individualized intervention plans to efficiently improve outcomes such as hypertension. Despite considerable progress in this field, challenges remain, such as the need for the prospective validation of AI-driven interventions and the development of comprehensive systems that integrate multiple AI methods. Future research should focus on addressing these challenges and refining the AI models to ensure their practical applicability in real-world clinical settings. Furthermore, the implementation of interdisciplinary collaborations among AI experts, clinicians, and healthcare providers are crucial to further optimizing and validate AI-driven solutions for hypertension management.

A case of congenital biliary dilatation without pancreaticobiliary maljunction, so-called Type Ib according to Todani's classification.

Congenital biliary dilatation (CBD) is a congenital malformation of focal dilatation of the extrahepatic bile ducts, including the common bile duct, and is often associated with pancreaticobiliary maljunction (PBM). In this article, we report a CBD case that presented with focal dilation of the common bile duct without PBM (Todani's classification type Ib). The patient was a 32-year-old man who visited a doctor with a chief complaint of abdominal distension. Computed tomography revealed cystic dilatation of the common bile duct, and the patient was referred to our institution. Magnetic resonance cholangiopancreatography showed cystic dilatation of the common bile duct with a maximum diameter of 7 cm; however, evaluating the presence of PBM was challenging. Endoscopic ultrasonography showed small gallstones and debris in the dilated common bile duct and no thickening of the gallbladder wall. Endoscopic retrograde cholangiopancreatography revealed no PBM or markedly elevated bile amylase levels. Based on these findings, the patient was diagnosed with Todani Type Ib CBD. Since this patient did not have pancreatobiliary reflux, it was unclear whether the risk of developing biliary tract cancer was high, and since the treatment was highly invasive, the decision was to follow up without surgical treatment.

LC-MS identification, isolation, and structural elucidation of anti-HIV macrocyclic daphnane orthoesters from Edgeworthia chrysantha.

The occurrence of macrocyclic daphnane orthoesters (MDOs) with a 1-alkyl group originating from a C14 aliphatic chain is extremely limited in the plant kingdom and has only been isolated from Edgeworthia chrysantha. In the present study, LC-ESI-MS/MS analysis was performed on different parts of E. chrysantha, including flower buds, flowers, leaves, and stems, and resulted in the identification of seven MDOs in all the four plant parts, including two previously unreported compounds 1 and 7. Further LC-MS guided isolation was carried out to afford compounds 1 and 7, and their structures were determined by various spectroscopic analyses. These compounds were also evaluated for anti-HIV activity, thus expanding insights into the structure-activity relationships for MDOs.

Selective microbial production of lacto-N-fucopentaose I in Escherichia coli using engineered α-1,2-fucosyltransferases.

Lacto-N-fucopentaose I (LNFP I) is the second most abundant fucosylated human milk oligosaccharide (HMO) in breast milk after 2'-fucosyllactose (2'-FL). Studies have reported that LNFP I exhibits antimicrobial activity against group B Streptococcus and antiviral effects against Enterovirus and Norovirus. Microbial production of HMOs by engineered Escherichia coli is an attractive, low-cost process, but few studies have investigated production of long-chain HMOs, including the pentasaccharide LNFP I. LNFP I is synthesized by α1,2-fucosyltransfer reaction to the N-acetylglucosamine moiety of the lacto-N-tetraose skeleton, which is catalyzed by α1,2-fucosyltransferase (α1,2-FucT). However, α1,2-FucTs competitively transfer fucose to lactose, resulting in formation of the byproduct 2'-FL. In this study, we constructed LNFP I-producing strains of E. coli with various α1,2-fucTs, and observed undesired 2'-FL accumulation during fed-batch fermentation, although, in test tube assays, some strains produced LNFP I without 2'-FL. We hypothesized that promiscuous substrate selectivity of α1,2-FucT was responsible for 2'-FL production. Therefore, to decrease the formation of byproduct 2'-FL, we designed 15 variants of FsFucT from Francisella sp. FSC1006 by rational and semi-rational design approaches. Five of these variants of FsFucT surpassed a twofold reduction in 2'-FL production compared with wild-type FsFucT while maintaining comparable levels of LNFP I production. These designs encompassed substitutions in either a loop region of the enzyme (residues 154-171), or in specific residues (Q7, H162, and L164) that influence substrate binding either directly or indirectly. In particular, the E. coli strain that expressed FsFucT_S3 variants, with a substituted loop region (residues 154-171) forming an α-helix structure, achieved an accumulation of 19.6 g/L of LNFP I and 0.04 g/L of 2'-FL, while the E. coli strain expressing the wild-type FsFucT accumulated 12.2 g/L of LNFP I and 5.85 g/L of 2'-FL during Fed-bach fermentation. Therefore, we have successfully demonstrated the selective and efficient production of the pentasaccharide LNFP I without the byproduct 2'-FL by combining protein engineering of α1,2-FucT designed through in silico structural modeling of an α1,2-FucT and docking simulation with various ligands, with metabolic engineering of the host cell.

Enhanced Circularly Polarized Luminescence by a Homochiral Guest-Host Interaction in Gyroidal MOFs, [Ru(bpy)3] [M2(ox)3] (bpy = 2,2'-Bipyridyl, ox = Oxalate, M = Zn, Mn).

We report the circularly polarized luminescence (CPL) for [Ru(bpy)3]I2 (1) and [Ru(bpy)3][M2(ox)3] (M = Zn (2), Mn (3)). Whereas compound 1 is a simple salt of [Ru(bpy)3]2+, 2 and 3 are MOFs in which the chiral [Ru(bpy)3]2+ ions are encapsulated in a homochiral gyroidal skeleton of [M2(ox)3]2-. Whereas the solution of 1 exhibited weak CPL with a luminescence dissymmetry factor of |glum| ∼ 10-4, the CPL was significantly enhanced in solid-state 1-3 with |glum| = 2 × 10-2 for 1, 4 × 10-2 for 2, and 1 × 10-1 for 3. The enhanced CPL in 3 was attributable to an energy transfer between the homochiral guest and host in 3.

The Significance of Histopathological Findings on Clinical Outcomes in Endoscopic Papillectomy with Endocut.

This study aimed to evaluate primary clinical outcomes in patients who underwent endoscopic papillectomy (EP) using the Endocut mode while examining the pathological characteristics of the margin of the resected specimen. To this end, 70 patients who underwent Endocut EP were included. Resection margins were classified according to pathological findings as "negative", "positive", or "uncertain (difficult pathological evaluation)". The effect of pathological resection margins on residual tumor recurrence rates was evaluated. The median follow-up was 47 months (range, 22-84). Eleven patients (15.7%) were diagnosed with residual tumors, ten of whom were diagnosed within 6 months after EP. The resection margins were pathologically negative in 27 patients, positive in 15, and uncertain in 28; residual tumors occurred in 5 patients (33.3%) in the positive group, 5 (17.9%) in the uncertain group, and 1 (3.7%) in the negative group. The patient in the negative group had familial adenomatous polyposis (FAP). Female sex, FAP, and uncertain or positive resection margins were significantly more common in residual patients (p = 0.009, 0.044, and 0.041, respectively). Pathological resection margins can be used to infer the residual tumor incidence, leading to early post-treatment of residual tumors.

Utility of Covered Self-Expanding Metal Stents for Biliary Drainage during Neoadjuvant Chemotherapy in Patients with Borderline Resectable Pancreatic Cancer.

OBJECTIVES: We aimed to compare the utility of covered self-expanding metal stents (CSEMSs) with that of plastic stents (PSs) for biliary drainage during neoadjuvant chemotherapy in patients with borderline resectable pancreatic cancer. METHODS: Forty patients with borderline resectable pancreatic cancer underwent biliary stenting during neoadjuvant chemotherapy at Hiroshima University Hospital. PSs and CSEMSs were placed in 19 and 21 patients, respectively. Two gemcitabine-based regimens for chemotherapy were used. Treatment outcomes and postoperative complications were compared between both groups. RESULTS: The incidence of recurrent biliary obstruction was significantly lower in the CSEMS group (0% vs. 47.4%, p < 0.001), and the median time to recurrent biliary obstruction in the PS group was 47 days. There was no difference in the incidence of other complications such as non-occlusive cholangitis, pancreatitis, and cholecystitis between the two groups. Delays in the chemotherapy schedule due to stent-related complications were significantly frequent in the PS group (52.6% vs. 4.8%, p = 0.001). There was no significant difference in the incidence of postoperative complications between the two groups. CONCLUSIONS: CSEMSs may be the best choice for safely performing neoadjuvant chemotherapy for several months in patients with borderline resectable pancreatic cancer with bile duct stricture.

Electrochemically regulated luminescence of europium complexes with ß-diketone in polyether matrices.

This study investigates the electrochemical modulation of luminescence color, i.e., electrofluorochromism, of an Eu complex in a polyether solvent. The electrofluorochromic (EFC) reaction of the Eu complex occurred via a reversible redox reaction between Eu3+ and Eu2+. Initially, the intrinsically stable Eu3+ complex showed intense red photoluminescence (PL) induced by f-f transitions. After the electrochemical reduction of Eu3+ to Eu2+, broad blue PL was observed attributed to the d-f transitions in the Eu2+ complex. This distinct blue luminescence from the Eu2+ complex was attributed to the effective stabilization of the Eu2+ state by the polyether solvent. The dynamic EFC reaction that changes the valence state of the Eu ion can be potentially applied to novel chemical sensors, security devices, and display devices.

Individual health-disease phase diagrams for disease prevention based on machine learning.

Early disease detection and prevention methods based on effective interventions are gaining attention worldwide. Progress in precision medicine has revealed that substantial heterogeneity exists in health data at the individual level and that complex health factors are involved in chronic disease development. Machine-learning techniques have enabled precise personal-level disease prediction by capturing individual differences in multivariate data. However, it is challenging to identify what aspects should be improved for disease prevention based on future disease-onset prediction because of the complex relationships among multiple biomarkers. Here, we present a health-disease phase diagram (HDPD) that represents an individual's health state by visualizing the future-onset boundary values of multiple biomarkers that fluctuate early in the disease progression process. In HDPDs, future-onset predictions are represented by perturbing multiple biomarker values while accounting for dependencies among variables. We constructed HDPDs for 11 diseases using longitudinal health checkup cohort data of 3,238 individuals, comprising 3,215 measurement items and genetic data. The improvement of biomarker values to the non-onset region in HDPD remarkably prevented future disease onset in 7 out of 11 diseases. HDPDs can represent individual physiological states in the onset process and be used as intervention goals for disease prevention.

Late-onset aqueductal membranous occlusion treated neuroendoscopic procedure and consideration of its pathological findings: A case report.

Background: Aqueduct of Sylvius stenosis/obstruction interferes with cerebrospinal fluid (CSF) flow and leads to the non-communicating hydrocephalus. Acquired non-neoplastic causes of aqueduct of Sylvius stenosis/ obstruction include simple stenosis, gliosis, slit-like stenosis, and septal formation, but the detailed mechanisms are not clear. In the present study, we experienced a case of late-onset aqueductal membranous occlusion (LAMO) successfully treated by neuroendoscopic procedure, which allowed us to examine the pathology of the membranous structures of the aqueduct of Sylvius occlusion. Case Description: A 66-year-old woman presented with gradually progressive gait disturbance, cognitive dysfunction, and urinary incontinenc. Brain magnetic resonance imaging (MRI) showed enlargement of the bilateral lateral ventricles and the third ventricle without dilatation of fourth ventricle, and heavily T2-weighted images showed an enlarged aqueduct of Sylvius and a membranous structure at its caudal end. Gadolinium contrast-enhanced T1-weighted images showed no neoplastic lesions. We diagnosed this case that the hydrocephalus due to late-onset idiopathic aqueductal stenosis or LAMO and the patient underwent endoscopic third ventriculostomy and endoscopic aqueduct oplasty. Membranous tissue specimens were obtained from the occluded aqueduct of Sylvius at the time of treatment. Histopathological examination revealed gliosis, and inside the gliosis, there were cell clusters that appeared to be ependymal cells and were corpora amylacea. We confirmed CSF flow at the site of obstruction of the aqueduct of Sylvius and the stoma of the third ventricle floor by MRI images. Her symptoms were improved immediately. Conclusion: We experienced a case of LAMO successfully treated by neuroendoscopic procedure, which allowed us to examine the pathology of the membranous structure of the aqueduct of Sylvius. The pathological study of LAMO is rare, and we report it, including a review of the literature.

A case of middle-aged male with multicentric solid pseudopapillary neoplasm of the pancreas.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a low-grade, malignant pancreatic tumor that occurs predominantly in young females. In this report, an extremely rare case of multicentric SPNs in a middle-aged male is discussed. A 55-year-old man was incidentally found to have a mass in the pancreatic body on abdominal ultrasonography during a medical checkup. Contrast-enhanced computed tomography (CT) revealed masses with 50-mm and 25-mm diameters with internal calcification in the pancreatic body and tail, respectively. These masses had a gradually increasing enhancement pattern though the center of the pancreatic body mass and the periphery of the pancreatic tail lesion were non-enhancing. Magnetic resonance imaging revealed a hyperintense signal in the mass of the pancreatic tail suggestive of hemorrhage on T1-weighted imaging. Positron emission tomography-CT revealed abnormal uptake of fluorodeoxyglucose in both lesions. Endoscopic ultrasound-guided fine needle aspiration was performed on both lesions, and tumor tissue with a solid proliferation of poorly pleomorphic small cells was observed. The tumor cells were positive for CD10 in the cytoplasm and ß-catenin in the nucleus. The patient was diagnosed with SPNs and underwent a successful distal pancreatectomy.

Nicotine- and tar-removed cigarette smoke extract modulates the antigen presentation function of mouse bone marrow-derived dendritic cells.

Dendritic cells (DCs) take up antigens derived from pathogens such as bacteria and viruses, and from tumor cells and induce the activation of antigen-specific T cells through major histocompatibility complex (MHC)-mediated antigen presentation. Mainstream cigarette smoke extract (CSE) has various effects, and the effects of its major components, nicotine and tar, have been analyzed extensively. Recently, the physiological effects of nicotine- and tar-removed CSE (cCSE) have also been reported. However, the effects of cCSE on DC-mediated immune responses remain unknown. In this study, we found that cCSE enhanced lipopolysaccharide (LPS)-stimulated induction of the expression of MHC-I and MHC-II on the cell surface of mouse bone marrow-derived DCs (BMDCs). In contrast, cCSE suppressed the induction of CD86 induced by stimulation with curdlan and interferon-γ (IFN-γ). In addition, cCSE suppressed the production of IL-12, IL-23, and IL-10 by LPS and curdlan stimulation. In the presence of cCSE, LPS-stimulated BMDCs showed enhanced activation of CD4 and CD8 T cells and increased IL-2 production from T cells by antigen presentation in a mixed-leukocyte reaction assay. In contrast, cCSE did not affect the activation of T cells by curdlan- or IFN-γ-stimulated BMDCs, and curdlan-stimulated BMDCs suppressed IL-17 production from T cells and enhanced IFN-γ production. These results suggest that cCSE has different effects on the activation signals induced by LPS, curdlan, and IFN-γ in BMDCs and modulates the antigen presentation function of BMDCs.

Preoperative serum interleukin-6 level in head and neck cancer reflects systemic inflammatory response and is a predictor of postoperative prognosis.

BACKGROUND: The outcome of head and neck cancer has improved in recent years but survival is not yet satisfactory. Interleukin (IL)-6 is a representative inflammatory cytokine and inducer of systemic inflammatory response. It is not known whether preoperative serum level of IL-6 is a prognostic factor in head and neck cancer surgery. METHODS: We studied 181 consecutive patients who underwent head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) between September 2016 and December 2020. Whether preoperative serum IL-6 level was a prognostic risk factor was retrospectively investigated by univariate and multivariate analyses. We also investigated the association between preoperative IL-6 level and representative systemic inflammatory response markers. RESULTS: The preoperative IL-6 ≥ 8 pg/mL group had a significantly worse prognosis than the preoperative IL-6 < 8 pg/mL group (overall survival [OS]: hazard ratio [HR] 3.098, P = 0.0006; disease-specific survival [DSS]: HR 3.335, P = 0.0008). In multivariate analysis, IL-6 ≥ 8 pg/mL and age ≥ 70 years were independent poor prognostic factors for OS (HR 1.860, P = 0.0435 and HR 1.883, P = 0.0233, respectively). The only independent poor prognostic factor for DSS was IL-6 ≥ 8 pg/mL (HR 2.052, P = 0.0329). Serum albumin was significantly lower and serum C-reactive protein and neutrophil-to-lymphocyte ratio were significantly higher in the IL-6 ≥ 8 pg/mL group than in the IL-6 < 8 pg/mL group (all P < 0.0001). CONCLUSIONS: Preoperative serum IL-6 level is an independent poor prognostic factor for both OS and DSS after HNS-FTTR, reflecting the degree of preoperative systemic inflammatory response.

Magenta-Blue Electrofluorochromic Device Incorporating Eu(III) Complex, Anthracene Derivative, and Viologen Molecule.

Electrochemical switching of luminescence color between magenta and blue using two types of luminescent materials and electrochromic molecules was demonstrated based on the control of excited energy transfer through an electrochromic reaction. The magenta photoluminescence, due to the integration of red luminescence from the Eu(III) complex and blue fluorescence from the anthracene derivative, was reversibly modulated to a pure-blue luminescence color by an electrochemical redox reaction. Electrofluorochromism is induced by effective excited energy transfer from the Eu(III) complex to the electrochromic molecule under a redox reaction.

Ingenuity using 3D-MRI fusion image in evaluation before and after microvascular decompression for hemifacial spasm.

Background: Hemifacial spasm (HFS) is most often caused by blood vessels touching a facial nerve. In particular, responsible vessels compress the root exit zone (REZ) of the facial nerve. Although we recognize these causes of HFS, it is difficult to evaluate the findings of precise lesion in radiological imaging when vessels compress REZ. Hence, we tried to obtain precise images of pre- and postoperative neuroradiological findings of HFS by creating a fusion image of MR angiography and the REZ of facial nerve extracted by magnetic resonance imaging (MRI) diffusion tensor image (DTI). Case Description: A 52-year-old woman had a 2-year history of HFS on the left side of her face. It was confirmed that the left vertebral artery and anterior inferior cerebellar artery were presented near the facial nerve on MRI. REZ of the facial nerve was visualized using DTI and fusion image was created with vascular components, making it possible to recognize the relationship between compression vessels and REZ of the facial nerve in detail. She underwent microvascular decompression and her HFS completely disappeared. We confirmed that the REZ of the facial nerve was decompressed by MRI imaging, in the same way as before surgery. Conclusion: We describe that the REZ of facial nerve and compressive vessels was delineated in detail on MRI and this technique is useful for pre- and postoperative evaluation of HFS.

High-Pressure Synthesis of Superconducting Sn3S4 Using a Diamond Anvil Cell with a Boron-Doped Diamond Heater.

High-pressure techniques open exploration of functional materials in broad research fields. An established diamond anvil cell with a boron-doped diamond heater and transport measurement terminals has performed the high-pressure synthesis of a cubic Sn3S4 superconductor. X-ray diffraction and Raman spectroscopy reveal that the Sn3S4 phase is stable in the pressure range of P > 5 GPa in a decompression process. Transport measurement terminals in the diamond anvil cell detect a metallic nature and superconductivity in the synthesized Sn3S4 with a maximum onset transition temperature (Tconset) of 13.3 K at 5.6 GPa. The observed pressure-Tc relationship is consistent with that from the first-principles calculation. The observation of superconductivity in Sn3S4 opens further materials exploration under high-temperature and -pressure conditions.

Optimal indication of endoscopic retrograde pancreatography-based cytology in the preoperative pathological diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is extremely useful for pathological diagnosis of pancreatic ductal adenocarcinoma (PDAC); however, puncturing is difficult in some cases, and there is a risk of needle tract seeding. This study evaluated the indications for endoscopic retrograde pancreatography-based (ERP)-based cytology for the preoperative diagnosis of PDAC. METHODS: This study included 267 patients with PDAC who underwent preoperative ERP. The diagnostic performance of ERP-based cytology for PDAC was evaluated based on the sample collection method (pancreatic juice cytology [PJC] during ERP, brush cytology, PJC via endoscopic nasopancreatic drainage [ENPD] catheter), lesion site (pancreatic head, body/tail), and lesion size (≤10 mm, 10-20 mm, >20 mm), and compared with the diagnostic performance of EUS-FNA. RESULTS: The overall sensitivity of ERP-based cytology was 54.9%; sensitivity by the sampling method was 34.7% for PJC during ERP, 65.8% for brush cytology, and 30.8% for PJC via an ENPD catheter. The sensitivity of EUS-FNA was 85.3%. Brush cytology and PJC via an ENPD catheter were performed more often in pancreatic body/tail lesions than in head lesions (P = 0.016 and P < 0.001, respectively), and the overall sensitivity of ERP-based cytology was better for body/tail lesions (63.2% vs. 49.0%, P = 0.025). The sensitivities of ERP-based cytology and EUS-FNA in diagnosing PDAC ≤10 mm were 92.3% and 33.3%, respectively. Post-ERP pancreatitis was observed in 22 patients (8.2%) and significantly less common with ENPD catheters (P = 0.002). CONCLUSIONS: ERP-based cytology may be considered the first choice for pathological diagnosis of PDAC ≤10 mm and in the pancreatic body/tail.