Novel mutation of transferrin receptor 2 causing hereditary hemochromatosis type 3 in a Japanese patient.

Hereditary hemochromatosis (HH) is recognized as a progressive iron-storage disorder, and leading to severe organ impairments, including liver cirrhosis. Hereditary hemochromatosis type 3 arises from mutations in the transferrin receptor 2 (TFR2) gene. However, HH type 3 is rare in Asia, and information regarding genetic mutations and associated phenotypes remains limited. Here, we reported the case of a Japanese patient with HH type 3, with a novel homozygous mutation of the TFR2 gene. A 69-year-old woman presented to our hospital with hand joint pain and was referred due to liver impairment. Viral hepatitis and autoimmune liver diseases were ruled out. However, the transferrin saturation was 92.2%, and the serum ferritin level was 1611.8 ng/mL. Additionally, abdominal computed tomography showed diffuse increased density of the liver parenchyma. Abdominal magnetic resonance imaging also suggested iron deposition. There is no history of prior treatments involving blood transfusions or iron agents. Her parents were involved in a consanguineous marriage, prompting genetic testing. She had a homozygous novel mutation, c.1337G>A (p.G446E), in the TFR2 gene. Serum hepcidin-25 level was decreased to 2.9 ng/mL. According to the American Society of Medical Genetics and Genomics guideline, the mutation was classified as likely pathogenic, leading to the diagnosis of HH type 3. Following phlebotomy, her arthritis resolved, and serum transaminase levels were normalized. This case marks the first demonstration of homozygous mutation, c.1337G>A (p.G446E), in the TFR2 gene in patients with HH type 3.

Inside stent placement is suitable for preoperative biliary drainage in patients with perihilar cholangiocarcinoma.

BACKGROUND/PURPOSE: Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the utility of inside stent (IS) and conventional stent (CS) for preoperative EBS in patients with LPHC. METHODS: EBS was performed in 56 patients with LPHC. EBS involved the placement of a CS (n = 32) or IS (n = 24). Treatment outcomes were compared between these two groups. RESULTS: Preoperative recurrent biliary obstruction (RBO) occurred in 23 patients (71.9%) in the CS group and 7 (29.2%) in the IS group, with a significant difference (p = 0.002). The time to RBO (TRBO) was significantly longer in IS than in CS (log-rank: p < 0.001). The number of stent replacements was significantly lower in IS than CS [0.38 (0-3) vs. 1.88 (0-8), respectively; p < 0.001]. Gemcitabine-based neoadjuvant chemotherapy (NAC) was administered to 26 patients (46.4%). Among patients who received NAC, TRBO was longer in IS than in CS group (log-rank: p < 0.001). The IS group had a significantly shorter preoperative and postoperative hospital stay than the CS group (20.0 vs. 37.0 days; p = 0.024, and 33.5 vs. 41.5 days; p = 0.016).　 Both the preoperative and the postoperative costs were significantly lower in the IS group than in the CS group (p = 0.049 and p = 0.0034, respectively). CONCLUSION: Compared with CS, IS for preoperative EBS in LPHC patients resulted in fewer complications and lower re-intervention rates. The fact that the IS group had shorter preoperative and postoperative hospital stays and lower costs both preoperatively and postoperatively compared to the CS group may suggest that the use of IS has the potential to benefit not only the patient but also the healthcare system.

The Diagnosis of Esophageal Tuberculosis Through an Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy: A Case Study.

A 54-year-old woman presented with an elevated esophageal lesion. Computed tomography (CT) and magnetic resonance imaging revealed a mass in the pancreatic head. Endoscopic ultrasound (EUS) showed a well-defined, round, hypoechoic mass, which was considered lymph node enlargement. An EUS-guided fine-needle aspiration biopsy (FNAB) was performed on the esophagus and the mass above the pancreatic head. The pathologically confirmed epithelial cells and multinucleated giant cells were positive for T-SPOT. Clinically, tuberculous lymphadenitis and esophageal tuberculosis were suspected, with successful treatment with anti-tuberculosis therapy resulting in a good response. Our findings suggest that an EUS-FNAB is useful for diagnosing esophageal tuberculosis.

Risk Factors Associated with Painful Colonoscopy and Prolonged Cecal Intubation Time in Female Patients.

Objectives: Few studies have examined risk factors leading to painful colonoscopy and prolonged cecal intubation time in female patients. We aimed to determine the factors associated with painful colonoscopy and prolonged cecal intubation time in female patients. Methods: This retrospective study analyzed prospectively collected data from a randomized controlled trial with female patients who underwent colonoscopy. Multivariate logistic and linear regression analyses were performed using the following factors that might be associated with painful colonoscopy and prolonged cecal intubation time, respectively: age, body mass index, history of colonoscopy, previous abdominal surgery, routine use of laxatives, inadequate bowel preparation, sigmoid colon diverticulosis, use of a small-caliber colonoscope, and an inexperienced operator. Results: The study enrolled 219 female patients aged >20 years. Using the receiver operating characteristic curve, painful colonoscopy was defined in cases where the visual analogue scale of overall pain was ≥50 mm. Logistic regression analysis for risk factors associated with painful colonoscopy revealed that sigmoid colon diverticulosis [odds ratio (OR), 2.496; 95% confidence interval (CI), 1.013-5.646; p=0.028] was a risk factor for painful colonoscopy; conversely, the use of a small-caliber colonoscope was a negative factor for painful colonoscopy (OR, 0.436; 95% CI, 0.214-0.889, p=0.022). In linear regression analysis, inadequate bowel preparation was significantly associated with prolonged cecal intubation time (ß-coefficient, 3.583; 95% confidence interval, 0.578-6.588; p=0.020). Conclusions: Female patients with sigmoid colon diverticulosis are more likely to experience severe pain during colonoscopy, and those with inadequate bowel preparation may require more time for cecal intubation.

Advances in the Early Diagnosis of Pancreatic Ductal Adenocarcinoma and Premalignant Pancreatic Lesions.

Pancreatic cancer is one of the most lethal human malignancies, in part because it is often diagnosed at late stages when surgery and systemic therapies are either unfeasible or ineffective. Therefore, diagnosing pancreatic cancer in earlier stages is important for effective treatment. However, because the signs and symptoms may be nonspecific and not apparent until the disease is at a late stage, the timely diagnoses of pancreatic cancer can be difficult to achieve. Recent studies have shown that selective screening and increased usage of biomarkers could improve the early diagnosis of pancreatic cancer. In this review, we discuss recent advancements in the early detection of pancreatic ductal carcinoma and precancerous lesions. These include innovations in imaging modalities, the diagnostic utility of various biomarkers, biopsy techniques, and population-based surveillance approaches. Additionally, we discuss how machine learning methods are being applied to develop integrated methods of identifying individuals at high risk of developing pancreatic disease. In the future, the overall survival of pancreatic cancer patients could be improved by the development and adoption of these new methods and techniques.

Pancreatic Mixed Acinar-neuroendocrine-ductal Carcinoma: A Case Report and Literature Review.

Pancreatic mixed neoplasms are very rare. We herein report a unique case of pancreatic mixed acinar-neuroendocrine-ductal carcinoma with trilineage differentiation. The patient was an 83-year-old woman referred to our hospital due to anemia and a pancreatic mass. Contrast-enhanced computed tomography revealed a 60-mm mass in the pancreas. Subtotal stomach-preserving pancreaticoduodenectomy was performed. The postoperative pathological diagnosis was mixed acinar-neuroendocrine-ductal carcinoma. Postoperative chemotherapy was conducted according to the adenocarcinoma and neuroendocrine carcinoma protocols. The patient died 26 months postoperatively. Choosing appropriate chemotherapy for mixed neoplasms is difficult. Cancer gene panel testing, if possible, may support the choice of therapeutic agents.

Endoscopic resection for a solitary Peutz-Jeghers type polyp in the duodenum: A case report with literature review.

A 68-year-old female patient was referred to our hospital with a 30-mm polyp in the second portion of the duodenum found via esophagogastroduodenoscopy. The polyp had an irregular, lobular surface and a thick stalk. In addition, white dots were detected on the surface. Magnifying endoscopy with narrow-band imaging showed a white material deep in the loop-shaped microvessels on the white dots. Endoscopic ultrasonography showed a hypoechoic elevated lesion from the mucosal layer, and a feeding vessel traversing the stalk to supply the head of the polyp. Endoscopic biopsy did not provide a definitive diagnosis. Endoscopic resection was conducted for a definitive diagnosis and treatment. The resected specimen showed a branching bundle of smooth muscle fibers covered by hyperplastic mucosa, consistent with a hamartomatous polyp. The patient had no mucocutaneous pigmentation or familial history of the hamartomatous polyp. The polyp was finally diagnosed as a solitary Peutz-Jeghers-type polyp. No recurrence has been observed for seven years postoperatively.

Factors Related to Difficulty in Endoscopic Submucosal Dissection for Superficial Esophageal Cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is technically challenging, and research on predictive factors related to the difficulty in the procedure is limited. This study aimed to investigate the factors predicting the difficulty in esophageal ESD. METHODS: This retrospective study analyzed 303 lesions treated at our institution between April 2005 and June 2021. The following 13 factors were evaluated: sex, age, tumor location, tumor localization, macroscopic type, tumor size, tumor circumference, preoperative diagnosis of histological type, preoperative diagnosis of invasion depth, previous radiotherapy for esophageal cancer, metachronous lesion located close to post-ESD scar, operator's skill, and use of a clip-and-thread traction method. Difficult esophageal ESD cases were defined as those requiring long procedure time (>120 min). RESULTS: Fifty-one lesions (16.8%) met the defined criterion for difficult cases of esophageal ESD. Logistic regression analysis identified tumor size larger than 30 mm (odds ratio: 9.17, 95% confidence interval: 4.27-19.69, p < 0.001) and tumor circumference more than half that of the esophagus (odds ratio 2.53, 95% confidence interval: 1.15-5.54, p = 0.021) as independent predictive factors related to difficulty in esophageal ESD. CONCLUSION: Tumor size larger than 30 mm and tumor circumference more than half that of the esophagus can predict difficulty in performing esophageal ESD. This knowledge can provide useful information for developing ESD strategies and selecting a suitable operator on a case-by-case basis to achieve favorable clinical outcomes.

The usefulness of image-enhanced endoscopy to distinguish gastric carcinoma in tumors initially diagnosed as adenomas by endoscopic biopsy: A retrospective study.

Superficial epithelial gastric neoplasms can be divided into adenomas and early carcinomas. Histological diagnosis by endoscopic forceps biopsy is crucial for the diagnosis and management of gastric neoplasms. It is difficult to distinguish features of gastric neoplasms in small biopsy specimens; hence, gastric carcinomas can be underdiagnosed as adenomas. Recent developments in image-enhanced endoscopy have improved the ability to differentiate between carcinomatous and non-carcinomatous lesions. To investigate the prevalence of gastric carcinoma in lesions initially diagnosed as adenomas by forceps biopsy and assess the usefulness of image-enhanced endoscopy in distinguishing carcinomas. A total of 142 lesions of gastric adenomas, diagnosed by biopsy and resected endoscopically between January 2010 and May 2020, were retrospectively evaluated. Images were captured by white-light endoscopy (WLE), magnifying endoscopy with narrow-band imaging (M-NBI), and magnifying endoscopy with acetic acid and narrow-band imaging (M-AANBI); they were analyzed and compared with histopathological results. The diagnostic performance of M-AANBI was compared with that of M-NBI. Of the 142 lesions, 58 (40.8%) were pathologically diagnosed as adenocarcinomas. On WLE images, a depressed macroscopic type and size ≥20 mm were significant predictors of carcinoma (P < .001); however, they displayed low sensitivities (32.8% and 41.4%, respectively). M-AANBI displayed significantly higher sensitivity, specificity, and accuracy for distinguishing carcinomas than M-NBI (94.8% vs 74.1%, 81.0% vs 72.6%, and 86.6% vs 73.2%, P < .05). In conclusion, carcinoma was prevalent in 40.8% of gastric lesions initially diagnosed as adenomas by forceps biopsy. M-AANBI may be more useful than M-NBI and WLE in distinguishing gastric carcinomas from adenomas.

Negative effect of prolonged cecal intubation time on adenoma detection in female patients.

Background and Aim: Withdrawal time of the colonoscope is associated with adenoma detection. However, the association between cecal intubation time and adenoma detection remains unclear. This study aimed to evaluate the association between cecal intubation time and adenoma detection. Methods: This retrospective study analyzed prospectively collected data from a randomized controlled trial on female patients who underwent colonoscopy in an academic hospital. The primary outcome was the mean number of all adenomas detected per patient. Secondary outcomes included the mean number of advanced, diminutive, small/large, right-sided colonic, and left-sided colonic adenomas detected per patient. Furthermore, the detection rates of all categories of adenoma were evaluated. Results: The analysis included 216 female patients aged ≥20 years. The correlation analysis did not reveal a significant relationship (P = 0.473) between cecal intubation and withdrawal times. The mean number of all adenomas detected per patient declined by approximately 30% (1.05-0.70) from the fastest to the slowest insertion time quartile. Adjusted regression analysis showed a significant decrease in the mean number of all adenomas detected per patient with increased intubation time (relative risk, RR = 0.87; 95% confidence interval, 0.76-0.99, P = 0.045), whereas the mean number of other categories of adenomas detected per patient and the detection rates of all categories of adenoma were not associated with the cecal intubation time. Conclusions: This study showed a significant association between prolonged cecal intubation time and decreased adenoma detection. The cecal intubation time may be a significant quality indicator for colonoscopy.

Autoimmune Pancreatitis with Massive Ascites and Multiple Pancreatic Cysts Successfully Treated with Prednisolone.

A 64-year-old man with a history of diabetes and gallstones was admitted to our institution with suspected pancreatic malignancy. Computed tomography (CT) revealed multiple pancreatic cysts and massive ascites, and endoscopic ultrasonography (EUS) revealed a 28×27-mm hypoechoic mass in the pancreatic head. An EUS-guided fine-needle aspiration biopsy was performed, and there were no malignant findings. Based on the test results and imaging findings, type 1 autoimmune pancreatitis was suspected. The patient was administered 30 mg of prednisolone daily. After 11 days, CT revealed that the pancreatic cysts and ascites had reduced in size.

Effect of adding acetic acid when performing magnifying endoscopy with narrow band imaging for diagnosis of Barrett's esophageal adenocarcinoma.

Background and study aims Magnifying endoscopy with narrow band imaging (M-NBI) was developed to diagnose Barrett's esophageal adenocarcinoma (BEA); however, this method remains challenging for inexperienced endoscopists. We aimed to evaluate a modified M-NBI technique that included spraying acetic acid (M-AANBI). Patients and methods Eight endoscopists retrospectively examined 456 endoscopic images obtained from 28 patients with 29 endoscopically resected BEA lesions using three validation schemes: Validation 1 (260 images), wherein the diagnostic performances of M-NBI and M-AANBI were compared - the dataset included 65 images each of BEA and non-neoplastic Barrett's esophagus (NNBE) obtained using each modality; validation 2 (112 images), wherein 56 pairs of M-NBI and M-AANBI images were prepared from the same BEA and NNBE lesions, and diagnoses derived using M-NBI alone were compared to those obtained using both M-NBI and M-AANBI; and validation 3 (84 images), wherein the ease of identifying the BEA demarcation line (DL) was scored via a visual analog scale in 28 patients using magnifying endoscopy with white-light imaging (M-WLI), M-NBI, and M-AANBI. Results For validation 1, M-AANBI was superior to M-NBI in terms of sensitivity (90.8 % vs. 64.6 %), specificity (98.5 % vs. 76.9 %), and accuracy (94.6 % vs. 70.4 %) (all P  < 0.05). For validation 2, the accuracy of M-NBI alone was significantly improved when combined with M-AANBI (from 70.5 % to 89.3 %; P  < 0.05). For validation 3, M-AANBI had the highest mean score for ease of DL recognition (8.75) compared to M-WLI (3.63) and M-NBI (6.25) (all P <  0.001). Conclusions Using M-AANBI might improve the accuracy of BEA diagnosis.

Cilia-Mediated Insulin/Akt and ST2/JNK Signaling Pathways Regulate the Recovery of Muscle Injury.

Following injury, skeletal muscle regenerates but fatty tissue accumulation is seen in aged muscle or muscular dystrophies. Fibro/adipogenic progenitors (FAPs) are key players in these events; however, the effect of primary cilia on FAPs remains unclear. Here, it is reported that genetic ablation of trichoplein (TCHP), a ciliary regulator, induces ciliary elongation on FAPs after injury, which promotes muscle regeneration while inhibiting adipogenesis. The defective adipogenic differentiation of FAPs is attributed to dysfunction of cilia-dependent lipid raft dynamics, which is critical for insulin/Akt signaling. It is also found that interleukin (IL) 13 is substantially produced by intramuscular FAPs, which are upregulated by ciliary elongation and contribute to regeneration. Mechanistically, upon injury, long cilia excessively activate the IL33/ST2/JNK axis to enhance IL13 production, facilitating myoblast proliferation and M2 macrophage polarization. The results indicate that FAPs organize the regenerative responses to skeletal muscle injury via cilia-mediated insulin/Akt and ST2/JNK signaling pathways.

Dedifferentiated liposarcoma in the abdominal cavity: a case report.

Liposarcoma adherent to the mesentery is extremely rare and difficult to diagnose. A 70-year-old woman presented to the hospital with a right lower abdominal mass. After surgical resection, the patient was diagnosed with dedifferentiated liposarcoma of the transverse colon with a mesenteric origin, and chemotherapy was administered. Diagnosing dedifferentiated liposarcoma of the transverse mesocolon based on imaging findings alone is challenging. Surgical resection can aid diagnosis. Moreover, cancer-specific genetic testing was performed in this case because dedifferentiated liposarcoma is a disease for which novel therapeutic agents are expected to be developed.

Propensity-score matched analysis to evaluate efficacy of endoscopic submucosal dissection for superficial esophageal cancer in gastrectomized patients.

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment option for superficial esophageal cancer (SEC) with high rates of complete resection. However, limited research exists on the efficacy of ESD for SEC in gastrectomized patients. This study aimed to evaluate the efficacy of ESD for SEC in gastrectomized patients. We included 318 patients of SEC treated at our institution between April 2005 and October 2021. To minimize bias between the gastrectomized and non-gastrectomized groups, we conducted a propensity-score matched analysis and compared the ESD outcomes for SEC of the two groups. Of the 318 patients included in the study, 48 and 270 patients were in the gastrectomized and non-gastrectomized groups, respectively. After 1:2 propensity-score matching, we matched 44 patients in the gastrectomized group to 88 patients in the non-gastrectomized group, and found no significant differences in the baseline clinicopathological characteristics. Regarding the ESD outcomes, there were no significant differences in the complete resection rate, procedure time, hospitalized period, and recurrence rates between the two groups. Multivariate analysis also cofirmed that the history of gastrectomy was not a risk factor of the difficult case of esophageal ESD. In conclusion, history of gastrectomy might not negatively affect the ESD outcomes of SECs.

Development of "Mathematical Technology for Cytopathology," an Image Analysis Algorithm for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. The accuracy of a PDAC diagnosis based on endoscopic ultrasonography-guided fine-needle aspiration cytology can be strengthened by performing a rapid on-site evaluation (ROSE). However, ROSE can only be performed in a limited number of facilities, due to a relative lack of available resources or cytologists with sufficient training. Therefore, we developed the Mathematical Technology for Cytopathology (MTC) algorithm, which does not require teaching data or large-scale computing. We applied the MTC algorithm to support the cytological diagnosis of pancreatic cancer tissues, by converting medical images into structured data, which rendered them suitable for artificial intelligence (AI) analysis. Using this approach, we successfully clarified ambiguous cell boundaries by solving a reaction-diffusion system and quantitating the cell nucleus status. A diffusion coefficient (D) of 150 showed the highest accuracy (i.e., 74%), based on a univariate analysis. A multivariate analysis was performed using 120 combinations of evaluation indices, and the highest accuracies for each D value studied (50, 100, and 150) were all ≥70%. Thus, our findings indicate that MTC can help distinguish between adenocarcinoma and benign pancreatic tissues, and imply its potential for facilitating rapid progress in clinical diagnostic applications.

Usefulness of magnifying endoscopy with acetic acid and narrow-band imaging for the diagnosis of duodenal neoplasms: proposal of a diagnostic algorithm.

BACKGROUND: This study aimed to clarify the features of superficial non-ampullary duodenal epithelial tumors (SNADETs) on magnifying endoscopy with narrow-band imaging (M-NBI) and magnifying endoscopy with acetic acid and narrow-band imaging (M-AANBI), and evaluate the efficacy of M-NBI/M-AANBI to distinguish high-grade adenomas or adenocarcinomas (HGA/AC) from low-grade adenomas (LGA). METHODS: Clinicopathological data on 62 SNADETs in 58 patients who underwent preoperative M-NBI/M-AANBI and endoscopic resection were retrospectively reviewed. The pathological results were classified into two categories, LGA and HGA/AC. We evaluated microvascular patterns (MVPs) and microsurface patterns (MSPs) observed by M-NBI and MSPs observed by M-AANBI for characterizing LGA and HGA/AC. The kappa value was calculated to assess the interobserver and intraobserver agreements of evaluation of M-AANBI images. RESULTS: Pathologically, 38 lesions (61.3%) were LGA and 24 lesions (38.7%) were HGA/AC. HGA/AC tended to have irregular MVP and/or MSP on M-NBI. M-NBI diagnostic performance to distinguish HGA/AC from LGA showed 62.5% sensitivity, 68.4% specificity, and 66.1% accuracy. SNADETs had irregular MSP on M-AANBI. Three irregularity grades (iG) of MSP were observed by M-AANBI as follows: iG1, mild; iG2, moderate; iG3, significant. HGA/AC lesions had a significantly higher rate of iG3 than LGA lesions (p < 0.001). The iG2 was associated with HGA/AC in elevated lesions and LGA in depressed lesions. The diagnostic performance of M-AANBI was as follows: 95.8% sensitivity, 97.4% specificity, and 96.8% accuracy. The diagnostic accuracy of M-AANBI was significantly higher than that of M-NBI (p < 0.001). The kappa value for interobserver agreement on the diagnosis and irregularity grading of M-AANBI images was 0.742 and 0.719, respectively. These data indicate substantial interobserver agreement. Based on the above-mentioned results, we developed a M-AANBI diagnostic algorithm for SNADETs. CONCLUSION: The diagnostic algorithm for SNADETs using M-AANBI may be useful for differentiating between LGA and HGA/AC.

Clinical utility of endoscopic submucosal dissection using the pocket-creation method with a HookKnife and preoperative evaluation by endoscopic ultrasonography for the treatment of rectal neuroendocrine tumors.

BACKGROUND: Various endoscopic methods have been developed to remove small rectal neuroendocrine tumors (NETs). This study aimed to evaluate the clinical utility of endoscopic submucosal dissection using the pocket-creation method (ESD-PCM) with a HookKnife, following preoperative evaluation by endoscopic ultrasonography (EUS), for the treatment of rectal NETs. METHODS: We analyzed retrospectively consecutive patients who underwent ESD-PCM with a HookKnife for the removal of rectal NETs, with a size less than 10 mm, at Mie University Hospital between June 2015 and December 2019. All the rectal NETs were resected by ESD-PCM with a HookKnife. The R0 resection rate, procedure time, adverse event rate, diagnostic accuracy of tumor size and invasion depth evaluated by preoperative EUS, and follow-up outcome were evaluated retrospectively. RESULTS: The study group comprised 12 patients with 12 resected lesions. The median tumor size of the resected specimens was 5 mm and the size and invasion depth of each tumor was approximately equal to that predicted by preoperative EUS. R0 resection was achieved in all cases, without adverse events. The median procedure time was 50.5 min, which did not differ from previous studies. No recurrence was observed during the median follow-up period of 34.4 months (range, 5.2-60.0 months). CONCLUSIONS: ESD-PCM with a HookKnife provides a favorable clinical utility for removing rectal NETs, with high R0 resection rate and good follow-up outcome. In addition, EUS is useful for evaluating preoperatively the size and invasion depth of rectal NETs.

Extracellular vesicles from pancreatic ductal adenocarcinoma endoscopic ultrasound-fine needle aspiration samples contain a protein barcode.

BACKGROUND: The survival rate of pancreatic ductal adenocarcinoma (PDAC) is very poor because early detection is difficult. Extracellular vesicles (EVs) are released from cells associating with the cellular condition and circulated in the blood. We aimed to identify EV proteins from endoscopic ultrasound-fine needle aspiration (EUS-FNA) biopsy samples in order to develop novel biomarkers for PDAC. METHODS: Extracellular vesicles were isolated from EUS-FNA samples of 40 PDAC patients and six autoimmune pancreatitis (AIP) patients to be used as a control. EV proteins were identified using nanoLC-MS/MS. RESULTS: Intact EVs approximately 200 nm in diameter were detected from EUS-FNA samples. We identified 2059 or 1032 EV proteins in PDAC or AIP, respectively, and 1071 EV proteins were detected only in PDAC. One hundred and fifty-three EV proteins were significantly different between PDAC and AIP: 64 proteins were down-regulated in PDAC whereas 89 EV proteins were up-regulated in PDAC including mucins, keratins, Ras-related proteins, and olfactomedin-4, which proteins have been reported to be elevated in PDAC tissue/blood, or cultured pancreatic cancer cell lines. Notably, in the 89 up-regulated PDAC EV proteins we identified novel proteins including ADP-ribosylation factor 3, CD55, pyruvate kinase, and lipopolysaccharide-induced tumor necrosis factor. Out of 89 proteins, a total of 13 proteins including Ras-related proteins were significantly elevated in PDAC stages II-IV compared to PDAC stage I, including Ras-related proteins, moesin, and CD55. CONCLUSIONS: The EV proteins obtained from EUS-FNA samples contain a PDAC-specific protein barcode. The EV proteins identified from EUS-FNA samples include promising biomarkers for the diagnosis and clinical staging of PDAC.