Hanada K, Okazaki A, Hirano N, Izumi Y, Minami T, Ikemoto J, Kanemitsu K, Hino F.
Effective screening for early diagnosis of pancreatic cancer.
Best Pract Res Clin Gastroenterol. 2015 Dec;29(6):929-39. doi: 10.1016/j.bpg.2015.09.017. Epub 2015 Sep 26.
Abstract/Text
Diagnosis of pancreatic cancer (PC) at an early stage with curative surgery should improve long-term patient outcome. At present, improving survival should lie in identifying those cases with high-risk factors or precursor lesions through an effective screening including ultrasonography, some biological markers, or national familial pancreatic cancer registration. Recently, cases with PC < 10 mm with a favorable prognosis have been reported. For the diagnoses of cases with PC < 10 mm, the rate of tumor detection was higher on endoscopic ultrasonography (EUS) than on CT or other modalities, and EUS-guided fine needle aspiration was helpful in confirming the histologic diagnosis. Additionally, for the diagnosis of cases with PC in situ, EUS and magnetic resonance cholangiopancreatography (MRCP) may play important roles in detecting the local irregular stenosis of the pancreatic duct. Cytodiagnosis of pancreatic juice using endoscopic nasopancreatic drainage multiple times may be useful in the final diagnosis.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Yamada Y, Mori H, Matsumoto S, Kiyosue H, Hori Y, Hongo N.
Pancreatic adenocarcinoma versus chronic pancreatitis: differentiation with triple-phase helical CT.
Abdom Imaging. 2010 Apr;35(2):163-71. doi: 10.1007/s00261-009-9579-7.
Abstract/Text
BACKGROUND: Chronic pancreatitis and pancreatic adenocarcinoma often show similar clinical and imaging appearances. This study aims to differentiate chronic pancreatitis from pancreatic adenocarcinoma by defining enhancement patterns in both pathologic conditions during triple-phase helical CT.
METHODS: The study included 42 patients with chronic pancreatitis and 85 patients with pancreatic adenocarcinoma. CT images obtained according to protocol A (scan delays, 30, 60, and 150 s; 300 mg I/mL contrast material) or protocol B (scan delays, 40, 70, and 150 s; 370 mg I/mL contrast material) were retrospectively evaluated.
RESULTS: Mean contrast enhancement value of normal pancreas peaked in the first phase (early-washout pattern) while that of chronic pancreatitis peaked in the second phase (delayed-washout pattern), and that of pancreatic adenocarcinoma gradually rose (increasing pattern) in both protocols. Diagnostic indices for pancreatic adenocarcinoma were 82.4% and 94.1% for sensitivity, 83% and 83% for specificity, 82.7% and 90.4% for accuracy in protocols A and B, respectively, when differentiation between chronic pancreatitis and pancreatic adenocarcinoma was performed based on time-attenuation curve patterns.
CONCLUSION: Our results indicate that time attenuation curves obtained from triple-phase helical CT in protocol B provide useful information in differentiating chronic pancreatitis from pancreatic adenocarcinoma.
Gangi S, Fletcher JG, Nathan MA, Christensen JA, Harmsen WS, Crownhart BS, Chari ST.
Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis.
AJR Am J Roentgenol. 2004 Apr;182(4):897-903. doi: 10.2214/ajr.182.4.1820897.
Abstract/Text
OBJECTIVE: Our purpose was to determine whether abdominal CT can detect pancreatic cancer before its clinical diagnosis.
SUBJECTS AND METHODS: Two radiologists interpreted in a blinded manner 62 CT scans in 28 pancreatic cancer patients that were obtained before histologic diagnosis and 89 CT scans in 89 control subjects and noted specific CT findings. The presence of pancreatic cancer was characterized as definite, suspicious, low probability, or normal. The scans of the pancreatic cancer patients were divided into four groups on the basis of the time interval preceding cancer diagnosis (0-2, 2-6, 6-18, or > 18 months), and one scan (closest to 18 months) was selected per patient per time interval. Sensitivity and specificity for pancreatic cancer and interobserver agreement for CT findings were calculated.
RESULTS: Radiologists agreed that CT findings definite or suspicious for pancreatic cancer were present in 50% of the scans obtained 2-6 and 6-18 months before the diagnosis of pancreatic cancer (3/6 and 4/8 scans, respectively), but they noted such CT findings in only 7% (1/15) of the scans obtained more than 18 months before diagnosis. Pancreatic duct dilatation and cutoff were early CT findings identified by both radiologists and were associated with near-perfect and substantial interobserver agreement (kappa = 0.84 and 0.76, respectively). Ninety-five percent confidence intervals of specificity for tumor absence ranged from 92% to 100%.
CONCLUSION: CT can detect a significant proportion of asymptomatic incident pancreatic cancers before the clinical diagnosis of pancreatic cancer. CT should be considered in screening at-risk patient populations. Pancreatic duct dilatation and cutoff are early findings associated with the development of pancreatic cancer and can be detected on CT with a high degree of reproducibility.
Catalano C, Laghi A, Fraioli F, Pediconi F, Napoli A, Danti M, Reitano I, Passariello R.
Pancreatic carcinoma: the role of high-resolution multislice spiral CT in the diagnosis and assessment of resectability.
Eur Radiol. 2003 Jan;13(1):149-56. doi: 10.1007/s00330-002-1473-4. Epub 2002 Jul 18.
Abstract/Text
The purpose of our study was to evaluate multislice computed tomography (MSCT) in the assessment of patients with clinical, laboratory, and US suspicion of pancreatic neoplasm, and to evaluate resectability status. Forty-six patients with a suspected pancreatic tumor underwent MSCT. After a preliminary precontrast survey, a postcontrast scan was performed in the arterial and portal venous phase with the following protocol: 4 x 1-mm collimation; 1.25- and 5-mm slice thickness width, respectively, and 1- and 5-mm reconstruction interval. In all patients pathological correlation was obtained. The evaluation of all images provided a diagnosis in 44 patients, with a sensitivity, specificity, and accuracy of 97, 80, and 96%, respectively. The MSCT correctly provided a diagnosis of unresectability with sensitivity of 96%, specificity of 86%, and accuracy of 93%. Evaluation of 1-mm slices demonstrated 83 of the 91 liver metastases found at surgery; conversely, the 5-mm slices detected only 76 of these lesions. Infiltration of peripancreatic major vessels was demonstrated, and was confirmed at surgery in 18 patients. High-resolution MSCT improves prediction of resectability in patients with suspected pancreatic carcinoma. Parenchymal and vascular information can be achieved with a single MSCT examination.
Treadwell JR, Zafar HM, Mitchell MD, Tipton K, Teitelbaum U, Jue J.
Imaging Tests for the Diagnosis and Staging of Pancreatic Adenocarcinoma: A Meta-Analysis.
Pancreas. 2016 Jul;45(6):789-95. doi: 10.1097/MPA.0000000000000524.
Abstract/Text
Imaging tests are central to the diagnosis and staging of pancreatic adenocarcinoma. We performed a systematic review and meta-analysis of the pertinent evidence on 5 imaging tests (computed tomography (CT), magnetic resonance imaging, CT angiography, endoscopic ultrasound with fine-needle aspiration, and combined positron emission tomography with CT). Searches of several databases up to March 1, 2014, yielded 9776 articles, and 24 provided comparative effectiveness of 2 or more imaging tests. Multiple reviewers applied study inclusion criteria, extracted data from each study, rated the risk of bias, and graded the strength of evidence. Data included accuracy of diagnosis and resectability in primary untreated pancreatic adenocarcinoma, including tumor stage, nodal stage, metastases, and vascular involvement. Where possible, study results were combined using bivariate meta-analysis. Studies were at low or moderate risk of bias. Most comparisons between imaging tests were insufficient to permit conclusions, due to imprecision or inconsistency among study results. However, moderate-grade evidence revealed that CT and magnetic resonance imaging had similar sensitivities and specificities for both diagnosis and vascular involvement. Other conclusions were based on low-grade evidence. In general, more direct evidence is needed to inform decisions about imaging tests for pancreatic adenocarcinoma.
Ikemoto J, Serikawa M, Hanada K, Eguchi N, Sasaki T, Fujimoto Y, Sugiyama S, Yamaguchi A, Noma B, Kamigaki M, Minami T, Okazaki A, Yukutake M, Ishii Y, Mouri T, Shimizu A, Tsuboi T, Arihiro K, Chayama K.
Clinical Analysis of Early-Stage Pancreatic Cancer and Proposal for a New Diagnostic Algorithm: A Multicenter Observational Study.
Diagnostics (Basel). 2021 Feb 12;11(2). doi: 10.3390/diagnostics11020287. Epub 2021 Feb 12.
Abstract/Text
Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.
Li H, Hu Z, Chen J, Guo X.
Comparison of ERCP, EUS, and ERCP combined with EUS in diagnosing pancreatic neoplasms: a systematic review and meta-analysis.
Tumour Biol. 2014 Sep;35(9):8867-74. doi: 10.1007/s13277-014-2154-z. Epub 2014 Jun 3.
Abstract/Text
In the current study, we performed a systematic review of literature pertaining to the diagnostic value of endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography (EUS), and combined ERCP plus EUS to pancreatic cancer. We searched MEDLINE, OVID, and the Cochrane Library for studies evaluating diagnostic validity of ERCP, EUS, and ERCP plus EUS between January 1989 and May 2014. We obtained pooled estimates of sensitivity, specificity, and summary receiver operating characteristic curves (SROC). A total of 10 studies that included 669 patients who fulfilled all of the inclusion criteria were considered for inclusion in the analysis. The pooled sensitivities of EUS, ERCP, and EUS plus ERCP were 76.7, 57.9, and 79.9 %, respectively. The pooled specificities were 91.7, 90.6, and 94.2 %, respectively. The *Q index estimates were 0.828, 0.862, and 0.896, respectively. The *Q indices for EUS and EUS plus ERCP were significantly higher compared with ERCP (P = 0.010 and 0.008, respectively). Our meta-analysis showed that ERCP plus EUS was associated with a high diagnostic value for the detection of pancreatic neoplasms compared with ERCP and EUS alone.
Mikata R, Ishihara T, Tada M, Tawada K, Saito M, Kurosawa J, Sugiyama H, Sakai Y, Tsuyuguchi T, Miyazaki M, Yokosuka O.
Clinical usefulness of repeated pancreatic juice cytology via endoscopic naso-pancreatic drainage tube in patients with pancreatic cancer.
J Gastroenterol. 2013 Jul;48(7):866-73. doi: 10.1007/s00535-012-0684-y. Epub 2012 Oct 10.
Abstract/Text
BACKGROUND: Cytological examination of pancreatic juice obtained during endoscopic retrograde cholangiopancreatography (ERCP) is well established, but its sensitivity for pancreatic cancer has not been satisfactory. The aim of this study was to evaluate the usefulness of repeated pancreatic juice cytology (PJC) via the endoscopic naso-pancreatic drainage (ENPD) tube in patients with pancreatic cancer compared with conventional PJC.
METHODS: We retrospectively investigated 139 patients with pancreatic disease. Between April 2004 and November 2007, conventional PJC was performed in 56 patients with pancreatic cancer and 23 with benign pancreatic stricture. Between January 2008 and November 2010, ENPD was used in 40 patients with pancreatic cancer and 20 with benign pancreatic stricture. The ENPD tube was placed into the main pancreatic duct for up to 3 days, and cytological samples of pancreatic juice were collected up to 6 times in total.
RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ENPD method for pancreatic cancer were 80, 100, 100, 71, and 87 %, respectively, revealing significantly higher sensitivity than the conventional method (p = 0.0001). Sensitivities according to tumor location and size were 90 % (19/21), 69 % (9/13), and 67 % (4/6) in the head, body, and tail of the pancreas, 88 % (7/8), 79 % (19/24), and 75 % (6/8) in tumors with a diameter less than 20 mm including carcinoma in situ, 21-40, and greater than 41 mm, respectively.
CONCLUSIONS: The ENPD method was found to have high diagnostic yield, especially for tumors less than 20 mm or located in the pancreatic head, and might be useful for the diagnosis of early-stage pancreatic cancer.
Iiboshi T, Hanada K, Fukuda T, Yonehara S, Sasaki T, Chayama K.
Value of cytodiagnosis using endoscopic nasopancreatic drainage for early diagnosis of pancreatic cancer: establishing a new method for the early detection of pancreatic carcinoma in situ.
Pancreas. 2012 May;41(4):523-9. doi: 10.1097/MPA.0b013e31823c0b05.
Abstract/Text
OBJECTIVES: We examined the results of pancreatic juice cytodiagnosis using the method of endoscopic nasopancreatic drainage (ENPD) to identify pancreatic carcinoma in situ and compared the images and pathologic diagnosis of pancreatic carcinoma in situ as well as clinicopathologic characteristics.
METHODS: In patients who underwent endoscopic retrograde cholangiopancreatography and had ENPD place, only patients presenting with focal stenosis and distal dilatation of the main pancreatic duct were included in the ENPD placement group. Endoscopic nasopancreatic drainage was conducted 27 times in 20 patients in the ENPD placement group. In an average session, cytodiagnosis of the pancreatic juice was conducted 5.3 times (range, 2-11 times).
RESULTS: Results of cytodiagnosis were positive in 15 of 20 patients. Results of ENPD cytodiagnosis and diagnosis of pancreatic cancer showed sensitivity of 100%, specificity of 83.3%, and accuracy of 95%. Seven of 15 patients were diagnosed with carcinoma in situ. In these 7 patients, tumor markers (carcinoembryonic antigen, CA-19-9) were within reference limits, and the tumors were not visible on imaging tests. Pathologic histology revealed a propensity for the cancer to proliferate around the stenosis of the pancreatic duct.
CONCLUSIONS: Cytodiagnosis of pancreatic juice using ENPD multiple times proved to be useful in the diagnosis of pancreatic carcinoma in situ.
Kanno A, Masamune A, Hanada K, Maguchi H, Shimizu Y, Ueki T, Hasebe O, Ohtsuka T, Nakamura M, Takenaka M, Kitano M, Kikuyama M, Gabata T, Yoshida K, Sasaki T, Serikawa M, Furukawa T, Yanagisawa A, Shimosegawa T; Japan Study Group on the Early Detection of Pancreatic Cancer (JEDPAC).
Multicenter study of early pancreatic cancer in Japan.
Pancreatology. 2018 Jan;18(1):61-67. doi: 10.1016/j.pan.2017.11.007. Epub 2017 Nov 20.
Abstract/Text
BACKGROUND/OBJECTIVES: The diagnosis of early-stage pancreatic ductal adenocarcinoma (PDAC) is still challenging. We conducted a multicenter study to clarify the clinical features of early-stage PDAC in Japan.
METHODS: We collected patients with stage 0 and stage I PDAC according to the sixth edition of the Japanese Classification of Pancreatic Carcinoma. We retrospectively analyzed the clinical profiles including opportunities for medical examination, imaging modalities and findings, methods of cytological diagnosis, and prognosis according to the stages at diagnosis.
RESULTS: Two hundred cases with Stage 0 and stage I PDAC were reported from 14 institutions, which accounted for approximately 0.7% and 3% of all PDAC cases, respectively. Overall, 20% of the early-stage PDAC cases were symptomatic. Indirect imaging findings such as dilatation of the main pancreatic duct were useful to detect early-stage PDAC. In particular, local fatty changes may be specific to early-stage PDAC. For preoperative pathologic diagnosis, cytology during endoscopic retrograde cholangiopancreatography was more commonly applied than endoscopic ultrasound fine-needle aspiration. Although the overall prognosis was favorable, new PDAC lesions developed in the remnant pancreas in 11.5% cases.
CONCLUSIONS: This multicenter study revealed several key points concerning the diagnosis and management of early-stage PDAC, including screening of asymptomatic cases, importance of indirect imaging findings, application of cytology during endoscopic retrograde cholangiopancreatography, and the risk of carcinogenesis in the remnant pancreas.
Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.
日本膵臓学会、膵癌診療ガイドライン改訂委員会編:膵癌診療ガイドライン 2022年版 第6版、金原出版、2022.
Egawa S, Toma H, Ohigashi H, Okusaka T, Nakao A, Hatori T, Maguchi H, Yanagisawa A, Tanaka M.
Japan Pancreatic Cancer Registry; 30th year anniversary: Japan Pancreas Society.
Pancreas. 2012 Oct;41(7):985-92. doi: 10.1097/MPA.0b013e318258055c.
Abstract/Text
OBJECTIVES: Since 1981, the Japan Pancreas Society has been hosting a nationwide pancreatic cancer registry. To commemorate its 30th anniversary, we review its history and latest achievement.
METHODS: During 3 decades, more than 350 leading institutions in Japan contributed voluntarily to register and periodic follow-up. The registry was modified to protect privacy by encrypting and hash algorithm.
RESULTS: From 1981 to 2007, 32,619 cumulative records were analyzed. The overall survival of invasive cancer was improved significantly. More patients with earlier stage or with intraductal and cystic neoplasms underwent resection. The strongest prognostic factor of Union for International Cancer Control (UICC) stage IIA and IIB tubular adenocarcinoma in the pancreatic head was histological grade, followed by tumor size, extent of lymph node dissection, and postoperative chemotherapy. The 5-year survival rate of Union for International Cancer Control stage 0 reached 85%. The improvement of survival of patients with invasive cancer in Japan can be attributed to the introduction of effective chemotherapies, regionalization, and the earlier diagnosis and treatment. Simple definition of "early pancreatic cancer" is needed.
CONCLUSIONS: At the 30th year anniversary, the Japan Pancreas Society nationwide pancreatic cancer registry is more shining than ever for current perspectives and for future diagnostic and treatment tactics.
Hanada K, Shimizu A, Kurihara K, Ikeda M, Yamamoto T, Okuda Y, Tazuma S.
Endoscopic approach in the diagnosis of high-grade pancreatic intraepithelial neoplasia.
Dig Endosc. 2022 Jul;34(5):927-937. doi: 10.1111/den.14240. Epub 2022 Feb 14.
Abstract/Text
Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is essential for improving prognosis; however, diagnosing PDAC at an early stage is challenging. In patients with localized high-grade pancreatic intraepithelial neoplasia (HG-PanIN), whose tumorous lesion is undetectable on cross-sectional images such as computed tomography or magnetic resonance image, long-term survival is expected. Pancreatic cystic lesions or main pancreatic duct (MPD) dilatation are important indirect findings for the initial diagnosis of HG-PanIN. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) should play important roles in detecting abnormal image findings, such as local irregular MPD stenosis, caliber MPD changes, small cystic lesions, or branch duct dilatation. Additionally, EUS could detect hypoechoic areas around the MPD stenosis in some patients with HG-PanIN. Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) and its associated pancreatic juice cytology, including serial pancreatic juice aspiration cytologic examination (SPACE) after placement of an endoscopic nasopancreatic drainage (ENPD) tube, may have high diagnostic accuracy for confirming the malignancy in HG-PanIN. Although ERCP and its associated pancreatic cytology, including SPACE, may be associated with post-ERCP pancreatitis (PEP), a recent randomized trial suggested that a 4-Fr ENPD tube may reduce the incidence of PEP. In the future, further prospective multicenter studies are required to establish a standard method of SPACE. Additionally, further studies for novel biomarkers could help to establish evolutionary methods with duodenal fluid and pancreatic juice for the early and accurate diagnosis of early-stage PDAC.
© 2022 Japan Gastroenterological Endoscopy Society.
Kawamura R, Ishii Y, Serikawa M, Tsuboi T, Tsushima K, Nakamura S, Hirano T, Ikemoto J, Kiyoshita Y, Saeki S, Tamura Y, Miyamoto S, Nakamura K, Furukawa M, Ishida K, Arihiro K, Uemura K, Aikata H.
Optimal indication of endoscopic retrograde pancreatography-based cytology in the preoperative pathological diagnosis of pancreatic ductal adenocarcinoma.
Pancreatology. 2022 Apr;22(3):414-420. doi: 10.1016/j.pan.2022.02.001. Epub 2022 Feb 8.
Abstract/Text
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.
Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Chen J, Yang R, LU Y, et al. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesion: a systematic review. J Cancer Res Clin Oncol 2012; 138: 1433-41.
Chen G, Liu S, Zhao Y, Dai M, Zhang T.
Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer: a meta-analysis.
Pancreatology. 2013 May-Jun;13(3):298-304. doi: 10.1016/j.pan.2013.01.013. Epub 2013 Feb 10.
Abstract/Text
BACKGROUND AND OBJECTIVE: EUS-FNA of pancreatic lesion has been put into clinical use widely in many centers. The present meta-analysis was conducted to study the diagnostic role of EUS-FNA in pancreatic cancer.
METHODS: A comprehensive review of study on the precision of EUS-FNA in the diagnosis of pancreatic cancer. A random effects model was used to pool the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR). A summary receiver-operating characteristic (SROC) was constructed to summarize the overall test performance.
RESULTS: Thirty-one articles were eligible for the meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR of EUS-FNA in the diagnosis of pancreatic cancer were 0.89 (95% CI: 0.88-0.90), 0.96 (95% CI: 0.95-0.97), 16.88 (95% CI: 10.63-26.79), 0.13 (95%CI: 0.10-0.16) and 150.80 (95%CI: 95.94-237.03) respectively. In subgroup meta-analysis of the prospective studies, the pooled sensitivity, specificity, PLR, NLR and DOR were 0.91 (95% CI: 0.90-0.93), 0.94 (95% CI: 0.91-0.96), 11.19 (95% CI: 6.36-19.69), 0.10 (95% CI: 0.07-0.15) and 125.22 (62.37-251.41). The area under the curve (AUC) was 0.97, indicating a good performance of overall accuracy.
CONCLUSION: EUS-FNA has the high sensitivity and specificity in differentiating pancreatic cancer. Moreover, it is also a safe diagnostic modality with little complications.
Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Banafea O, Mghanga FP, Zhao J, Zhao R, Zhu L.
Endoscopic ultrasonography with fine-needle aspiration for histological diagnosis of solid pancreatic masses: a meta-analysis of diagnostic accuracy studies.
BMC Gastroenterol. 2016 Aug 31;16(1):108. doi: 10.1186/s12876-016-0519-z. Epub 2016 Aug 31.
Abstract/Text
BACKGROUND: Previous studies have demonstrated that endoscopic ultrasound-fine needle aspiration (EUS-FNA) is a reliable tool for diagnosing pancreatic lesions; however, the reported sensitivity and specificity vary greatly across studies. The aim of this study was to pool the existing literature and assess the overall performance of EUS-FNA in the diagnosis of solid pancreatic lesions.
METHODS: A systematic search of MEDLINE, Cochrane Database for Systematic Reviews, and EMBASE was performed to identify original and review articles published between January 1995 and January 2014 that reported the accuracy of EUS-FNA in the diagnosis of pancreatic masses. Quality of the included studies was assessed using the quality assessment of diagnosis accuracy studies score tool. Meta-DiSc software was used to calculate the pooled sensitivity and specificity, positive and negative likelihood ratios, and to construct the summary receiver operating characteristics curve.
RESULTS: Twenty studies involving a total of 2,761 patients were included in the study. The pooled sensitivity and specificity of EUS-FNA in the diagnosis of solid pancreatic lesions were 90.8 % [95 % confidence interval (CI), 89.4-92 %] and 96.5 % (95 % CI, 94.8-97.7 %), respectively. The positive and negative likelihood ratios were 14.8 (95 % CI, 8.0-27.3) and 0.12 (95 % CI, 0.09-0.16), respectively. The overall diagnostic accuracy was 91.0 %.
CONCLUSIONS: Our findings suggest that EUS-FNA has high sensitivity and specificity in the diagnosis of solid pancreatic lesions.
花田敬士, 南智之, 岡崎彰仁ほか:乳頭的胆管・膵管生検と細胞診. 消化器内視鏡, 2017; 29(5): 847-52.
南智之, 花田敬士, 平野巨道ほか:膵上皮内癌の診断. 膵臓, 2017; 32(1): 50-5.
Kurihara K, Hanada K, Shimizu A.
Endoscopic Ultrasonography Diagnosis of Early Pancreatic Cancer.
Diagnostics (Basel). 2020 Dec 14;10(12). doi: 10.3390/diagnostics10121086. Epub 2020 Dec 14.
Abstract/Text
Early diagnosis of pancreatic cancer (PC) can improve patients' prognosis. We aimed to investigate the utility of endoscopic ultrasonography (EUS) for the early diagnosis of PC. This study included 64 patients with PC at an early stage treated at Onomichi General Hospital between January 2007 and January 2020. Diagnostic procedures included contrast computed tomography (CT), magnetic resonance cholangiopancreatography, EUS fine-needle aspiration, and endoscopic retrograde cholangiopancreatography (ERCP) for pancreatic juice cytology. The mean age was 71.3 years. In all, 32 patients were stage 0, and 32 were stage I. As for image findings, the main pancreatic duct (MPD) stenosis was detected in several cases, although CT and MRCP seldom detected tumors. EUS had a high detection rate for stage 0 tumor lesions. The median observation period was 3.9 years. In cases with stage 0, the 1 year and 5 year survival rates were 100% and 78.9%, respectively. In cases with stage I, the 1 year and 5 year survival rates were 96.4% and 66.7%, respectively. EUS has the highest sensitivity among all imaging modalities for detecting small pancreatic tumors. Cases with MPD dilation or stenosis, especially with tumors that cannot be identified on CT and MRI, should have EUS performed. In some cases, EUS was not able to detect any tumor lesions, and ERCP-based pancreatic juice cytology should be useful for pathological diagnosis.
Izumi Y, Hanada K, Okazaki A, Minami T, Hirano N, Ikemoto J, Kanemitsu K, Nakadoi K, Shishido T, Katamura Y, Onogawa S, Amano H, Hino F, Amano H, Yonehara S.
Endoscopic ultrasound findings and pathological features of pancreatic carcinoma in situ.
Endosc Int Open. 2019 Apr;7(4):E585-E593. doi: 10.1055/a-0839-4312. Epub 2019 Apr 12.
Abstract/Text
日本膵臓学会編:膵癌取扱い規約 第8版、金原出版、2023.
Motoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M, Honda G, Matsumoto I, Wada K, Furuse J, Matsuyama Y, Unno M; Study Group of Preoperative Therapy for Pancreatic Cancer (Prep) and Japanese Study Group of Adjuvant Therapy for Pancreatic cancer (JSAP).
Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05).
Jpn J Clin Oncol. 2019 Feb 1;49(2):190-194. doi: 10.1093/jjco/hyy190.
Abstract/Text
A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with curative resection who fully recovered within 10 weeks after surgery in both arms. The primary endpoint is overall survival; secondary endpoints include adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases and tumor marker kinetics. The target sample size was required to be at least 163 (alpha-error 0.05; power 0.8) in both arms. A total of 360 patients were required after considering ineligible cases. This trial began in January 2013 and was registered with the UMIN Clinical Trials Registry (UMIN000009634).
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr.
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8.
Abstract/Text
The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators.
Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials.
Lancet Oncol. 2020 Feb;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6. Epub 2019 Dec 11.
Abstract/Text
BACKGROUND: Entrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood-brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials.
METHODS: An integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0-2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG (NCT02650401; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012-000148-88 (ALKA-372-001).
FINDINGS: Patients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018) the efficacy-evaluable population comprised 54 adults with advanced or metastatic NTRK fusion-positive solid tumours comprising ten different tumour types and 19 different histologies. Median follow-up was 12.9 months (IQR 8·77-18·76). 31 (57%; 95% CI 43·2-70·8) of 54 patients had an objective response, of which four (7%) were complete responses and 27 (50%) partial reponses. Median duration of response was 10 months (95% CI 7·1 to not estimable). The most common grade 3 or 4 treatment-related adverse events in both safety populations were increased weight (seven [10%] of 68 patients in the NTRK fusion-positive safety population and in 18 [5%] of 355 patients in the overall safety-evaluable population) and anaemia (8 [12%] and 16 [5%]). The most common serious treatment-related adverse events were nervous system disorders (three [4%] of 68 patients and ten [3%] of 355 patients). No treatment-related deaths occurred.
INTERPRETATION: Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours.
FUNDING: Ignyta/F Hoffmann-La Roche.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL.
Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer.
N Engl J Med. 2019 Jul 25;381(4):317-327. doi: 10.1056/NEJMoa1903387. Epub 2019 Jun 2.
Abstract/Text
BACKGROUND: Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib has had antitumor activity in this population.
METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients who had a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy. Patients were randomly assigned, in a 3:2 ratio, to receive maintenance olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival, which was assessed by blinded independent central review.
RESULTS: Of the 3315 patients who underwent screening, 154 underwent randomization and were assigned to a trial intervention (92 to receive olaparib and 62 to receive placebo). The median progression-free survival was significantly longer in the olaparib group than in the placebo group (7.4 months vs. 3.8 months; hazard ratio for disease progression or death, 0.53; 95% confidence interval [CI], 0.35 to 0.82; P = 0.004). An interim analysis of overall survival, at a data maturity of 46%, showed no difference between the olaparib and placebo groups (median, 18.9 months vs. 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P = 0.68). There was no significant between-group difference in health-related quality of life, as indicated by the overall change from baseline in the global quality-of-life score (on a 100-point scale, with higher scores indicating better quality of life) based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (between-group difference, -2.47 points; 95% CI, -7.27 to 2.33). The incidence of grade 3 or higher adverse events was 40% in the olaparib group and 23% in the placebo group (between-group difference, 16 percentage points; 95% CI, -0.02 to 31); 5% and 2% of the patients, respectively, discontinued the trial intervention because of an adverse event.
CONCLUSIONS: Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo. (Funded by AstraZeneca and others; POLO ClinicalTrials.gov number, NCT02184195.).
Copyright © 2019 Massachusetts Medical Society.