Pancreatic Juice Cytology Research Articles

Mixed ductal-acinar cell carcinoma of the pancreas: A case report.

Mixed carcinoma of the pancreas is defined as the concurrent existence of pancreatic ductal carcinoma, acinar cell carcinoma, and/or islet cell carcinoma within the same neoplasm. We herein report a rare case of mixed ductal-acinar cell carcinoma in a 74-year-old man who was undergoing treatment for hypertension and diabetes at another hospital. After an abrupt worsening of his blood glucose control, the patient was referred to our hospital for further evaluation. Abdominal contrast-enhanced computed tomography and magnetic resonance imaging revealed a tumor with a multilocular cystic lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography revealed obstruction of the main pancreatic duct and dilation of the dorsal pancreatic duct; in addition, adenocarcinoma was detected in the pancreatic juice cytology. Based on the abovementioned findings, the patient was diagnosed with carcinoma of the pancreatic head and underwent subtotal stomach-preserving pancreaticoduodenectomy. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with mixed ductal-acinar cell carcinoma. The patient was prescribed TS-1 as postoperative adjuvant chemotherapy upon discharge. However, treatment was discontinued 2 months later due to marked general malaise, and the patient succumbed to tumor recurrence in the residual pancreas 12 months after the surgery.

Evaluation of efficacy of pancreatic juice cytology for risk classification according to international consensus guidelines in patients with intraductal papillary mucinous neoplasm; a retrospective study

ObjectivesPancreatic juice cytology (PJC) for intraductal papillary mucinous neoplasm (IPMN) is a possible tool to enhance preoperative diagnostic ability by improving risk classification for malignant IPMN, but its efficacy is controversial. This study evaluated the efficacy of PJC for risk classification according to international guidelines. MethodsWe retrospectively analyzed 127 IPMN patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) preoperatively. PJC was performed in 125 of the 127 cases. High-risk stigmata (HRS, n = 57), worrisome features (WF, n = 64), and other characteristics (n = 6) were classified according to the 2017 international guidelines. ResultsAmong the 127 IPMN patients, 71 (55.9%) had malignant IPMN (invasive and non-invasive intraductal papillary mucinous carcinoma). The accuracy of WF for classifying malignant IPMN was increased by the addition of PJC, but the accuracy of HRS was not (WF to WF + PJC: 33.1% [42/127] to 48.8% [61/125], HRS to HRS + PJC: 65.4% [83/127] to 52.8% [66/125]). Post-ERCP pancreatitis (PEP) occurred in 32 (25.2%) of 127 IPMN patients. Severe PEP was not detected. Significant risk factors for PEP were female sex, obesity, and endoscopic naso-pancreatic drainage (ENPD) (P = .03, P = .0006, and P = .02, respectively). In patients with ENPD tube placement, a main pancreatic duct size of <5 mm was a significant risk factor for PEP (P = .02). ConclusionPJC could increase the accuracy of WF for classifying malignant IPMN. The additive effect of PJC for risk classification may be limited, however, and it is not recommended for all IPMN cases due to the high frequency of PEP.

Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Several studies have recently suggested that exosomes may have potential as novel biomarkers. This study aimed to isolate exosomes from pancreatic juice and to investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC. Pancreatic juice was collected from patients with PDAC and chronic pancreatitis (CP) by endoscopic retrograde pancreatography. Exosomes were extracted by ultracentrifugation. The presence of exosomes was confirmed by electron microscopy and Western blotting using anti-CD63, -CD81, and -TSG101 antibodies. Relative levels of ex-miR-21 and ex-miR-155 were quantified and compared between PDAC and CP patients. A total of 35 pancreatic juice samples (27 PDAC and 8 CP) were collected. Relative levels of both ex-miR-21 and ex-miR-155 were significantly higher in PDAC patients compared with CP patients (p < 0.001 and p = 0.008, respectively). By contrast, no significant difference was apparent in relative levels of miR-21 and miR-155 in whole pancreatic juice from PDAC patients compared with CP patients (p = 0.08 and p = 0.61, respectively). Ex-miR-21 and ex-miR-155 levels discriminated PDAC patients from CP patients with area under the curve values of 0.90 and 0.89, respectively. The accuracies of ex-miR-21 levels, ex-miR-155 levels, and pancreatic juice cytology were 83%, 89%, and 74%, respectively. When combining the results of ex-miR profiling with pancreatic juice cytology, the accuracy was improved to 91%. We successfully extracted exosomes from pancreatic juice. Ex-miRs, including ex-miR-21 and ex-miR-155, in pancreatic juice may be developed as biomarkers for PDAC.

Utility of “liquid biopsy” using pancreatic juice for early detection of pancreatic cancer

Background Despite advances in the diagnosis of pancreatic ductal adenocarcinoma (PDA), histological evaluation of small and poorly defined masses in the pancreas is uncomfortable and unsafe. Methods We herein report a case of early stage PDA, in which multiple KRAS mutations were detected in the pancreatic juice preoperatively. A small hypoechoic area adjacent to the portal vein was detected through endoscopic ultrasound in the pancreatic body. KRAS mutations were evaluated using plasma, and the pancreatic juice by digital PCR. Results Pancreatic duct biopsy and pancreatic juice cytology were performed with no evidence of malignancy; however, KRAS mutations, KRAS G12V and G12D, were detected in the pancreatic juice. Histological assessment of the resected specimen demonstrated a solid tumor with desmoplastic reaction accompanied by carcinoma in situ in the main pancreatic duct where KRAS G12V mutation was identified. More detailed analysis demonstrated KRAS G12D mutation in the cluster of low grade pancreatic intraepithelial neoplasia, implying that the lesion developed independently. Conclusions Our study indicates the potential of “endoscopic liquid biopsy” to capture the driver gene for PDA diagnosis.

10 Fr S-Type Plastic Pancreatic Stents in Chronic Pancreatitis Are Effective for the Treatment of Pancreatic Duct Strictures and Pancreatic Stones.

Aim Endoscopic pancreatic stenting for refractory pancreatic duct strictures associated with impacted pancreatic stones in chronic pancreatitis cases has yielded conflicting results. We retrospectively evaluated the efficacy of endoscopic treatment in chronic pancreatitis patients with pancreatic duct strictures. Methods Pancreatic sphincterotomy, dilatation procedures, pancreatic brush cytology, and pancreatic juice cytology were routinely performed, and malignant diseases were excluded. After gradual dilatation, a 10 Fr plastic pancreatic stent was inserted. The stents were replaced every 3 months and removed after the strictures were dilated. Statistical analyses were performed to determine the risk of main pancreatic duct restenosis. Results Endoscopic pancreatic stents were successfully placed in 41 of a total of 59 patients (69.5%). The median duration of pancreatic stenting was 276 days. Pain relief was obtained in 37 of 41 patients (90.2%). Seventeen patients (41.5%) had recurrence of main pancreatic duct stricture, and restenting was performed in 16 patients (average placement period 260 days). During the follow-up period, pancreatic cancer developed in three patients (5.1%). Multivariate analysis revealed that the presence of remnant stones after stenting treatment was significantly associated with a higher rate of main pancreatic duct restenosis (p = 0.03). Conclusion The use of 10 Fr S-type plastic pancreatic stents with routine exchange was effective for both short-term and long-term outcomes in chronic pancreatitis patients with benign pancreatic duct strictures and impacted pancreatic stones.

Efficacy and safety of pancreatic juice cytology by using synthetic secretin in the diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect in its early stages with the poorest prognosis of all cancers. To improve the prognosis, a precise diagnosis is needed when we suspect PDAC. Although endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is a widely accepted modality for the diagnosis of PDAC, its sensitivity is 85-89%, and approximately 10% of PDAC cases cannot be diagnosed. The main causes that interrupt the diagnosis of PDAC by using EUS-FNA are tumor size, presence of a vessel or the main pancreatic duct along the puncture route, and difficulty in withdrawing anticoagulant. Pancreatic juice cytology (PJC), the sensitivity of which is 33.3-65.8%, is a method for the diagnosis of PDAC cases in which carrying out of EUS-FNA is difficult. To diagnose PDAC appropriately, we need to improve the diagnostic ability of PJC. We examined PJC using synthetic secretin for 138 cases of pancreatic tumor and pancreatic non-cancerous diseases. Sensitivity of PJC improved from 50.9% to 74.0% as a result of synthetic secretin loading, and 13 PDAC cases that had not been able to be diagnosed with EUS-FNA could be diagnosed pathologically by PJC. Although there were 12 patients with mild pancreatitis (8.7%) as a complication, all were relieved with conservative treatment. Adding synthetic secretin to PJC is useful for cases in which it is difficult to carry out EUS-FNA for PDAC.

High-grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer.

This study aimed to identify the pathological features of high-grade PanIN that presents with imaging-detectable abnormalities. Ten cases of isolated, main-duct, high-grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with two being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all seven cases examined. In resected specimens, high-grade PanIN was present chiefly in the main pancreatic duct, with longitudinal extension ranging between 3 and 40 mm in length (median = 18 mm). In four cases, in which hypoechoic or hypovascular masses were observed on imaging, radiopathology correlations suggested that they represented parenchymal atrophy and subsequent fibrosis around affected ducts, but not invasive malignancy. On immunohistochemistry, the loss of p16 expression was found in five (50%), p53 overexpression in two (20%) and loss of SMAD4 expression in none (0%). KRAS mutations were detected in nine cases, with two dominant clones being found in three by ultrasensitive droplet digital polymerase chain reaction, suggesting the genetic heterogeneity of dysplastic cells composing individual lesions. Mutant GNAS was also observed in one case. Isolated high-grade PanIN may present with pancreatic duct stenosis. Therefore, intensive investigations including pancreatic juice cytology will be required for patients with unexplained pancreatic duct stenosis. The abnormal expression of p53 and SMAD4 is infrequent, while GNAS may be mutated in premalignant lesions mainly affecting the main pancreatic duct, similar to KRAS.

A case of a 6 mm-sized invasive ductal carcinoma (anaplastic carcinoma, spindle cell type) of the pancreas diagnosed by pancreatic juice cytology

A case of a 6 mm-sized invasive ductal carcinoma (anaplastic carcinoma, spindle cell type) of the pancreas diagnosed by pancreatic juice cytology

Prospective Follow-up Study of the Recurrence of Pancreatic Cancer Diagnosed at an Early Stage: The Value of Endoscopic Ultrasonography for Early Diagnosis of Recurrence in the Remnant Pancreas.

Most patients with pancreatic cancer (PC) demonstrate recurrences in the form of metastatic disease. We prospectively evaluated recurrence in PC cases diagnosed at an early stage. Thirty cases of PC stage 0 or IA were prospectively followed for at least 1 year after initial surgery. We performed blood tests and contrast-enhanced computed tomography (CT) every 3 to 6 months. Endoscopic ultrasonography (EUS) was performed if CT revealed abnormal findings in the remnant pancreas (RP). The median follow-up period was 53.9 months. Pancreatic cancer recurred in the RP (n = 8) and liver (n = 1). Computed tomography revealed mass lesions in 5 cases, a cystic lesion in 2 cases, and pancreatic duct dilatation in 1 case. Endoscopic ultrasonography detected mass lesions in 3 cases without a detectable mass on CT. The sensitivity of EUS-guided fine-needle aspiration and pancreatic juice cytology was 75%. Five of 8 cases underwent total resection of the RP, with pathologic findings revealing stage IA in 1 case, stage II in 1 case, and stage III in 3 cases. Careful long-term follow-up including EUS should be performed in resected PC cases diagnosed at an early stage to check recurrence in the RP.

Correction to: Diagnostic significance of SPACE for PCIS

In the original publication of the article, the first sentence of the listed point 2, in page 1 should read as "Advanced pancreatic cancer is diagnosed by pancreatic juice cytology in < 50% of cases."

The role of pancreatic juice cytology in the diagnosis of pancreatic intraductal papillary mucinous neoplasm.

pancreatic juice cytology (PJC) is an important predictor of malignant intraductal papillary mucinous neoplasm (IPMN). This study aimed to determine the role of PJC for the prediction of malignant IPMN (intraductal papillary mucinous cancer [IPMC]). medical records of IPMN patients who underwent surgery between 2012 and 2016 at the Nagasaki University Hospital were reviewed. Patients who underwent preoperative PJC were classified as high risk stigmata (HRS), worrisome features (WF) and no-criteria, based on imaging criteria. PJC class III or higher was considered as positive and only invasive IPMN was defined as IPMC. PJC was validated in each group with regard to sensitivity, specificity, accuracy with the corresponding 95% confidence intervals (95% CI) and area under receiver operating curve (AUROC) analysis. A p-value of < 0.05 was considered as statistically significant. preoperative pancreatic juice was obtained in 33/52 IPMN patients; only patients with adequate aspirate for cytology (n = 29) were included. In the HRS group (n = 9), 4/6 non-IPMC had a negative PJC and 3/3 IPMC had a positive PJC. In the WF group (n = 17), 9/11 non-IPMC had a negative PJC and 3/6 IPMC had a positive PJC. Adding PJC to imaging results improved the AUROCs of HRS and WF from 0.63 and 0.62 to 0.83 and 0.66, respectively. PJC was negative in all no-criteria cases (n = 3; one IPMC and two non-IPMC). In all 29 patients, PJC sensitivity was 60% (95% CI: 26%-88%), specificity was 79% (95% CI: 54%-94%), accuracy was 72% (95% CI: 63%-89%) and the AUROC was 0.69 (p = 0.03). PJC is a statistically significant IPMC predictor that can improve the validity of imaging for IPMC prediction.

209 Are the Pancreatic Specimens Preoperatively Obtained Useful for the Determination of Surgery in Patients With Branch Duct IPMN?: A Retrospective Study in 177 Patients in Whom Pancreatic Juice Cytology With Immunostaining Was Performed

209 Are the Pancreatic Specimens Preoperatively Obtained Useful for the Determination of Surgery in Patients With Branch Duct IPMN?: A Retrospective Study in 177 Patients in Whom Pancreatic Juice Cytology With Immunostaining Was Performed

Su1259 - The Efficacy and Safety of Pancreatic Juice Cytology by Using Synthetic Secretin in the Diagnosis of Pancreatic Ductal Adenocarcinoma

Su1259 - The Efficacy and Safety of Pancreatic Juice Cytology by Using Synthetic Secretin in the Diagnosis of Pancreatic Ductal Adenocarcinoma

5．膵液細胞診によるIPMN併存膵癌の早期診断

我々の施設では他の画像診断法では捉えられないIPMN併存膵上皮内癌はERCP下膵液細胞診でのみ診断可能であると考え，IPMN患者に対して積極的にERCP下膵液細胞診を行っている．実際，これまで経験したIPMN併存膵上皮内癌9例のうち4例をERCPのみで診断した．またworrisome featuresを持つIPMNの中から悪性IPMNを拾い上げるのにもERCP下膵液細胞診が有用である（感度100%，特異度92%）．局在がわからないIPMN併存膵上皮内癌の同定には術中残膵洗浄細胞診が有用であるが，洗浄液漏出による術後播種再発や，洗浄細胞診偽陰性の可能性が課題として残る．最近では膵癌を合併しやすいIPMNの特徴としてMUC2陰性，野生型GNASなどが指摘されており，これらを膵癌発症高危険群として重点的にERCP下膵液細胞診を行うことで，膵癌を効率よく早期に診断することができる可能性がある．

Pancreatic juice cytology with immunohistochemistry to detect malignancy and histologic subtypes in patients with branch duct type intraductal papillary mucinous neoplasms of the pancreas

The aim of this study was to elucidate the efficacy of pancreatic juice cytology with the cell-block method (CB-PJC) for the determination of surgery in patients with branch duct intraductal papillary mucinous neoplasm (BD-IPMN). In 138 patients with BD-IPMN from whom pancreatic juice was collected under ERCP for CB-PJC, we retrospectively evaluated the following: (1) the rate of successfully evaluated CB-PJC; (2) the ability of CB-PJC to diagnose malignancy and to identify pathologic subtypes in resected BD-IPMNs; (3) the rate of development into invasive cancer and progression of BD-IPMNs in patients with BD-IPMNs diagnosed as benignancy by CB-PJC; and (4) post-ERCP adverse events. (1) The success rate of CB-PJC was 89.9%. (2) The sensitivity and specificity of CB-PJC for preoperative diagnosis of malignancy were 50% and 100%, respectively, with only hematoxylin and eosin staining, whereas they were 79% and 100%, respectively, by adding immunohistologic staining. The agreement rate of the preoperative subtypes by CB-PJC with the subtypes of resected specimens was 93%. (3) The onset of invasive cancer was not detected at all on imaging studies, whereas the progression of IPMN was detected in 14 patients. Multivariate analysis revealed the risk factor of progression to be non-gastric type. The cumulative 5-year progression rate in this group was 89%. (4) Post-ERCP pancreatitis developed in 13 patients (7.7%). The diagnostic efficacy of preoperative CB-PJC for malignant BD-IPMN was excellent. The results may suggest the feasibility of applying preoperative subtyping by CB-PJC for decisions as to whether surgery is indicated.

Lymphoepithelial cyst with sebaceous glands of the pancreas: a case report.

BackgroundLymphoepithelial cyst (LEC) of the pancreas is a rare benign tumor. LEC with sebaceous glands of the pancreas is extremely rare, and its histogenesis remains unclear.Case presentationWe present a 66-year-old man with an incidental finding of a cystic lesion at the neck of the pancreas. Pancreatic juice cytology results and elevated serum carbohydrate antigen 19-9 and Dupan-2 levels indicated that the cyst was a potential adenocarcinoma. Therefore, a pancreaticoduodenectomy was performed. Macroscopically, the tumor was a unilocular cyst with a thin transparent wall, filled with soft yellow material. Pathological findings showed that the cyst was lined with squamous epithelium, accompanied by dense lymphoid tissue with scattered germinal centers. There were no hair follicles, but sebaceous glands were present in the lymphoid tissue just beneath the squamous epithelium. Therefore, the histopathological diagnosis was an LEC with sebaceous glands of the pancreas. Furthermore, the squamous epithelium surrounding the cyst was pathologically continuous with the tubular structure, indicating that the tubular structure transitioned into the squamous epithelium.ConclusionsWe report an extremely rare case of LEC with sebaceous glands of the pancreas. Moreover, the pathological findings, which showed that the tubular structure transitioned into the squamous epithelium, suggested that this was squamous metaplasia. In order to investigate the histogenesis of LEC of the pancreas, the pathological findings must be evaluated.

The safety and benefit of pancreatic juice cytology under ERCP in IPMN patients

BackgroundInternational consensus guidelines 2012 for intraductal papillary mucinous neoplasia (IPMN), defined two characteristics: high-risk stigmata (HRS) and worrisome features (WF). Patients with WF require detailed examination including cytology. However, routine endoscopic retrograde cholangiopancreatography (ERCP) for cytology is not recommended in the guidelines due to risk of post-ERCP pancreatitis (PEP). Our aim was to clarify what types of IPMN were susceptible for PEP and gain benefit of ERCP. Patients/methodsWe examined 138 consecutive IPMN patients who underwent ERCP in our hospital, retrospectively. Patients were classified into HRS, WF and the others (N) based on imaging findings before ERCP. We assessed pancreatic juice cytology, PEP frequency and rate of malignant IPMN at 12 months after ERCP. ResultsThe rates of cytological malignancy were 0% (N), 4.8% (WF) and 19.5% (HRS). The PEP frequency was 14.5%, and these risk factors were branch duct (BD)-IPMN, body/tail cysts and brush cytology by multivariate logistic analysis. The rates of malignant IPMN were 0% (N), 16.4% (WF) and 48.8% (HRS). Furthermore, we examined patients with WF in detail. The PEP frequency/rate of malignancy were 3.6%/23.1% in patients with main pancreatic duct (MPD) dilatation (5–9 mm), and the sensitivity of cytology was 33.3%. On the other hand, the PEP frequency/rate of malignancy were 17.2%/0% in patients with BD-IPMN fulfilling only cyst size over 30 mm. ConclusionsRoutine ERCP for IPMN, especially for BD-IPMN, is not recommended. ERCP may be beneficial for WF patients with MPD dilatation based on a balance between PEP risk and presence of malignancy.

Pancreatic juice cytology under ERCP for main duct or mixed type IPMN is feasible in view of post-ERCP pancreatitis rate and sensitivity of cytology

Pancreatic juice cytology under ERCP for main duct or mixed type IPMN is feasible in view of post-ERCP pancreatitis rate and sensitivity of cytology

Differentiation of malignant and benign IPMN by repeated pancreatic juice cytology combination with CEA level in pancreatic juice

Differentiation of malignant and benign IPMN by repeated pancreatic juice cytology combination with CEA level in pancreatic juice

The efficacy and safety of pancreatic juice cytology when used with synthetic secretin for the diagnosis of intra-ductal papillary mucinous carcinoma

The efficacy and safety of pancreatic juice cytology when used with synthetic secretin for the diagnosis of intra-ductal papillary mucinous carcinoma