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Higher volume growth rate is associated with development of worrisome features in patients with branch duct-intraductal papillary mucinous neoplasms

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World Journal of Clinical Cases 2022年第17期10卷 5667-5679页

作者： Tommaso Innocenti Ginevra Danti Erica Nicola Lynch Gabriele Dragoni Matteo Gottin Filippo Fedeli Daniele Palatresi Maria Rosa Biagini Stefano Milani Vittorio Miele Andrea Galli Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences"Mario Serio"University of FlorenceFlorence 50134Italy Emergency Radiology Unit Department of ServicesCareggi University HospitalFlorence 50134Italy Department of Medical Biotechnologies University of SienaSiena 53100Italy

BACKGROUND Branch duct-intraductal papillary mucinous neoplasms(BD-IPMNs)are the most common pancreatic cystic tumours and have a low risk of malignant transformation.Current guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure,especially when comparing different methods.On the other side,cyst volume is a new parameter with low interobserver variability and is highly reproducible over time.AIM To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant characteristics.METHODS Computed tomography scans and magnetic resonance imaging exams were retrospectively reviewed.The diameter was measured on three planes,while the volume was calculated by segmentation:The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion;therefore,a threedimensional volume of interest was finally obtained with the calculated value expressed in cm^(3).Changes in size over time were measured.The development of worrisome features was evaluated.RESULTS We evaluated exams of 98 patients across a 40.5-mo median follow-up time.Ten patients developed worrisome features.Cysts at baseline were significantly larger in patients who developed worrisome features(diameters P=0.0035,P=0.00652,P=0.00424;volume P=0.00222).Volume growth rate was significantly higher in patients who developed worrisome features(1.12 cm^(3)/year vs 0 cm^(3)/year,P=0.0001);diameter growth rate was higher as well,but the difference did not always reach statistical significance.Volume but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features(0.46 cm^(3)/year vs 0 cm^(3)/year,P=0.00634).CONCLUSION The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of BD-IPMNs.Volume measurement could be a better tool than diameter measurement to predict the development

关键词： intraductal papillary mucinous neoplasms Cyst Volume Growth Worrisome features Malignancies

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Predictive factors associated with malignancy of intraductal papillary mucinous pancreatic neoplasms

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World Journal of Gastroenterology 2010年第42期16卷 5353-5358页

作者： Jin Hee Lee Kyu Taek Lee Jongwook Park Sun Youn Bae Kwang Hyuck Lee Jong Kyun Lee Kee-Taek Jang Jin Seok Heo Seong Ho Choi Dong Wook Choi Jong Chul Rhee Department of Medicine Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 135710South Korea Department of Pathology Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 135710South Korea Department of Surgery Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 135710South Korea

AIM:To identify preoperative predictive factors associated with malignancy of intraductal papillary mucinous neoplasms(IPMNs) of the pancreas.METHODS:Between April 1995 and April 2010,129 patients underwent surgical resection for IPMNs at our institute and had confirmed pathologic diagnoses.The medical records were retrospectively reviewed and immunohistochemical staining for mucin(MUC) in pancreatic tissues was performed.RESULTS:Univariate analysis showed that the following five variables were closely associated with malignant IPMNs preoperatively:absence of extrapancreatic malignancy;symptoms;tumor size > 4 cm;main pancreaticduct(MPD) size > 7 mm;and lymph node enlargement on preoperative computed tomography(CT).Multivariate analysis revealed that the following two factors were significantly associated with malignant IPMNs preoperatively:MPD size > 7 mm [odds ratio(OR) = 2.50];and lymph node enlargement on preoperative CT(OR = 3.57).No significant differences in the expression of MUC1,MUC2 and MUC5AC were observed between benign and malignant IPMNs.CONCLUSION:MPD size > 7 mm and preoperative lymph node enlargement on CT are useful predictive factors associated with malignancy of IPMNs.

关键词： intraductal papillary mucinous neoplasms Malignancy Predictive factors Pancreatic neoplasms

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Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

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World Journal of Gastroenterology 2020年第23期26卷 3201-3212页

作者： Andrew Eiterman Ali Lahooti Somashekar G Krishna Department of Internal Medicine The Ohio State University Wexner Medical CenterColumbusOH 43210United States Division of Gastroenterology Hepatologyand NutritionThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

Pancreatic cancer has a high mortality rate with minimal proven interventions.intraductal papillary mucinous neoplasms(IPMNs) are known precursor lesions for pancreatic cancer. Identification of pancreatic cysts has improved from advances in abdominal imaging. Despite multiple revisions of the international consensus recommendations and various guidelines by other major societies,successful risk stratification of the malignant potential of mucinous pancreatic cysts remains challenging. Specifically, detection and accurate classification of advanced neoplasia(high-grade dysplasia and/or adenocarcinoma) in IPMNs is suboptimal with current diagnostic strategies. Development of interventional techniques utilizing endoscopic ultrasound include-through-the-needle microforceps biopsy, next-generation or whole genome molecular analysis of cyst fluid, and needle-based confocal laser endomicroscopy. These techniques suffer from a series of limitations in technical success, diagnostic yield, and clinical feasibility, but a combination approach may offer a solution that optimizes their cyst evaluation and risk stratification. Assessment and comparison of these techniques is restricted by lack of adequate surgical specimens for testing of diagnostic accuracy, resulting in a possible sample bias. Additional large-scale multicenter studies are needed to accumulate evidence for the utility and feasibility of their translation into clinical practice. Great strides have been made in pancreatic cyst evaluation, but further research is required to improve diagnostic accuracy and clinical management of IPMNs.

关键词： Pancreatic cyst Confocal endomicroscopy Microforceps biopsy Cyst fluid molecular analysis Endoscopic ultrasound intraductal papillary mucinous neoplasms

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Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

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Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 581-589页

作者： Yuichi Hori Tsukasa Ikeura Takashi Yamaguchi Katsunori Yoshida Koichi Matsuzaki Mitsuaki Ishida Sohei Satoi Kazuichi Okazaki Department of Gastroenterology and Hepatology Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan Department of Pathology Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan Department of Surgery Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan

Background:Malignant intraductal papillary mucinous neoplasm(IPMN)has poor prognosis.The carcinogenesis of IPMN is not clear.The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods:By using immunohistochemistry,we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013.We also examined the expression of Ki-67,c-Myc and p-JNK.Results:The median immunostaining index of pSmad3C was 79.2%in low-grade dysplasia,74.9%in highgrade dysplasia,and 42.0%in invasive carcinoma(P<0.01),whereas that of pSmad3L was 3.4%,4.3%,and 42.4%,respectively(P<0.01).There was a negative relationship between the expression of pSmad3C and c-Myc(P<0.001,r=-0.615)and a positive relationship between the expression of pSmad3L and c-Myc(P<0.001,r=0.696).Negative relationship between the expression of pSmad3C and Ki-67(P<0.01,r=-0.610)and positive relationship between the expression of pSmad3L and Ki-67(P<0.01,r=0.731)were confirmed.p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells.The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58(range,0.05–0.93),3.83(range,0.85–5.96),respectively(P=0.02).The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91(range,0–36.9)and 82.1(range,46.2–97.1),respectively(P=0.02).The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9(range 5.7–30.8)and 90.9(range 52.9–98.5),respectively(P=0.02).Conclusions:pSmad3L was upregulated in malignant IPMN.pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

关键词： intraductal papillary mucinous neoplasms of the pancreas Immunohistochemistry Phosphorylated Smad Carcinogenesis Prognosis

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Recent advances in the diagnostic evaluation of pancreatic cystic lesions

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World Journal of Gastroenterology 2022年第6期28卷 624-634页

作者： Devarshi R Ardeshna Troy Cao Brandon Rodgers Chidiebere Onongaya Dan Jones Wei Chen Eugene J Koay Somashekar G Krishna Department of Internal Medicine Ohio State University Wexner Medical CenterColumbusOH 43210United States College of Medicine Ohio State UniversityColumbusOH 43210United States James Molecular Laboratory Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of Pathology Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of GI Radiation Oncology The University of Texas MD AndersonHoustonTX77030United States Division of Gastroenterology Department of Internal MedicineOhio State University Wexner Medical CenterColumbusOH 43210United States

Pancreatic cystic lesions(PCLs)are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population.It has become crucial to identify these PCLs and subsequently risk stratify them to guide management.Given the high morbidity associated with pancreatic surgery,only those PCLs at high risk for malignancy should undergo such treatment.However,current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs.Therefore,research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy.Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing.While cyst fluid glucose has reemerged as a potential biomarker,cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs.Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs.While most of these recent diagnostics are only practiced at selective tertiary care centers,they hold a promise that management of PCLs will only get better in the future.

关键词： Pancreatic cystic lesion intraductal papillary mucinous neoplasms mucinous cystic neoplasm Microforceps biopsy Radiomics Confocal laser endomicroscopy

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Deficient Rnf43 potentiates hyperactive Kras-mediated pancreatic preneoplasia initiation and malignant transformation

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Animal Models and Experimental Medicine 2022年第1期5卷 61-71页

作者： Xian Zhou Zhichao Sun Mengdi Zhang Xiaoyu Qu Shuhui Yang Lianmei Wang Yanling Jing Li Li Weiwei Deng Fangming Liu Jin Di Jie Chen Jian Wu Hongbing Zhang State Key Laboratory of Medical Molecular Biology Department of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Institute of Cancer Stem Cell Dalian Medical UniversityDalianChina Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijingChina Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina MyGenostics Inc. BeijingChina

Background:Largely due to incidental detection,asymptomatic pancreatic cystic le-sions(PCLs)have become prevalent in recent years.Among them,intraductal papillary mucinous neoplasm(IPMN)infrequently advances to pancreatic ductal adenocarcinoma(PDAC).Conservative surveillance versus surgical intervention is a difficult clinical decision for both caregivers and PCL patients.Because RNF43 loss-of-function mutations and KRAS gain-of-function mutations concur in a subset of IPMN and PDAC,their biological significance and therapeutic potential should be elucidated.Methods:Pancreatic Rnf43 knockout and Kras activated mice(Rnf43^(−/−);Kras^(G12D))were generated to evaluate their clinical significance in pancreatic pre-neoplastic initiation and malignant transformation.Results:Loss of Rnf43 potentiated the occurrence and severity of IPMN and PDAC in oncogenic Kras mice.The Wnt/β-catenin signaling pathway was activated in pan-creatic Kras^(G12D)and Rnf43 knockout mice and the PORCN inhibitor LGK974 blocked pancreatic IPMN initiation and progression to PDAC accordingly.Conclusions:Rnf43 is a tumor suppressor in the prevention of pancreatic malignant transformation.This genetically reconstituted autochthonous pancreatic Rnf43^(−/−);Kras^(G12D)preclinical cancer model recapitulates the pathological process from pancreatic cyst to cancer in humans and can be treated with inhibitors of Wnt/β-catenin signaling.Since the presence of RNF43 and KRAS mutations in IPMNs predicts future development of advanced neoplasia from PCLs,patients with these genetic anomalies warrant surveillance,surgery,and/or targeted therapeutics such as Wnt/β-catenin inhibitors.

关键词： intraductal papillary mucinous neoplasms KRAS pancreatic ductal adenocarcinoma RNF43 Wnt

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High-grade pancreatic intraepithelial lesions： prevalence and implications in pancreatic neoplasia

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Hepatobiliary & Pancreatic Diseases International 2017年第2期16卷 202-208页

作者： Jean R Park Feng Li Veeral M Oza Brett C Sklaw Kevin M Cronley Michael Wellner Benjamin Swanson Somashekar G Krishna Division of Hospital Medicine The Ohio State University Wexner Medical Center Columbus Ohio USA Division of Gastroenterology Hepatology and Nutrition The Ohio State University Wexner Medical Center Columbus Ohio USA Department of Pathology The Ohio State University Wexner Medical Center Columbus Ohio USA

BACKGROUND： High-grade pancreatic intraepithelial neoplasia（Pan IN-3）, a precursor of pancreatic ductal adenocarcinoma（PDAC）, is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms（IPMNs）.METHODS： A retrospective review of a tertiary care center pathology database（1/2000-6/2014） was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.RESULTS： A total of 458 patients who underwent primary pancreatic resection were included. “Pan IN-3” lesions were found in 74（16.2%） patients who either had PDAC（n=67） or main duct（MD）-IPMN（n=7）. Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival（OS） for pancreata with Pan IN-3 lesions was significantly better than those without（OS 1.12 years, interquartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64,1.60 years respectively; P=0.04）. Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death（HR=0.43; 95% CI： 0.23-0.82; P=0.01）.CONCLUSIONS： Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.

关键词： pancreatic intraepithelial neoplasia intraductal papillary mucinous neoplasms pancreatic neoplasia pancreatic ductal adenocarcinoma

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Validation of serum tumor biomarkers in predicting advanced cystic mucinous neoplasm of the pancreas

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World Journal of Gastroenterology 2021年第6期27卷 501-512页

作者： Li-Qi Sun Li-Si Peng Jie-Fang Guo Fei Jiang Fang Cui Hao-Jie Huang Zhen-Dong Jin Department of Gastroenterology Changhai HospitalSecond Military Medical UniversityShanghai 200433China

BACKGROUND Early detection of advanced cystic mucinous neoplasms[(A-cMNs),defined as high-grade dysplasia or malignancy]of the pancreas is of great significance.As a simple and feasible detection method,serum tumor markers(STMs)may be used to predict advanced intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms(MCNs).However,there are few studies on the usefulness of STMs other than carbohydrate antigen(CA)19-9 for early detection of A-cMNs.AIM To study the ability of five STMs-CA19-9,carcinoembryonic antigen(CEA),CA125,CA724,and CA242 to predict A-cMNs and distinguish IPMNs and MCNs.METHODS We mainly measured the levels of each STM in patients pathologically diagnosed with cMNs.The mean levels of STMs and the number of A-cMN subjects with a higher STM level than the cutoff were compared respectively to identify the ability of STMs to predict A-cMNs and distinguish MCNs from IPMNs.A receiver operating characteristic curve with the area under curve(AUC)was also created to identify the performance of the five STMs.RESULTS A total of 187 patients with cMNs were identified and 72 of them showed AcMNs.We found that CA19-9 exhibited the highest sensitivity(SE)(54.2%)and accuracy(76.5%)and a moderate ability(AUC=0.766)to predict A-cMNs.In predicting high-grade dysplasia IPMNs,the SE of CA19-9 decreased to 38.5%.The ability of CEA,CA125,and CA724 to predict A-cMNs was low(AUC=0.651,0.583,and 0.618,respectively).The predictive ability of CA242 was not identified.The combination of STMs improved the SE to 62.5%.CA125 may be specific to the diagnosis of advanced MCNs.CONCLUSION CA19-9 has a moderate ability,and CEA,CA125,and CA724 have a low ability to predict A-cMNs.The combination of STM testing could improve SE in predicting A-cMNs.

关键词： Serum tumor markers Diagnosis Advanced cystic mucinous neoplasms mucinous cystic neoplasms intraductal papillary mucinous neoplasms

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Methylation changes at the GNAS imprinted locus in pancreatic cystic neoplasms are important for the diagnosis of malignant cysts

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World Journal of Gastrointestinal Oncology 2020年第9期12卷 1056-1064页

作者： Sandra Faias Marlene Duarte Luísa Pereira Paula Chaves Marília Cravo Antonio Dias Pereira Cristina Albuquerque Department of Gastroenterology Instituto Português de Oncologia de Lisboa Francisco GentilEPELisboa 1099-023Portugal Faculty of Health Sciences University of Beira InteriorCovilhã6200-506Portugal Unidade de Investigação em Patobiologia Molecular(UIPM) Instituto Português de Oncologia de Lisboa Francisco GentilEPELisboa 1099-023Portugal Centro de Matemática e Aplicações(CMA-UBI) Universidade da Beira InteriorCovilhã6200-506Portugal Department of Pathology Instituto Português de Oncologia de Lisboa Francisco GentilEPELisboa 1099-023Portugal Department of Gastroenterology Hospital BeatrizÂngeloLoures 2674-514Portugal

BACKGROUND Guanine nucleotide-binding protein,alpha stimulating(GNAS)mutations are characteristic of intraductal papillary mucinous neoplasms(IPMNs).Pancreatic ductal adenocarcinomas(PDACs)harboring GNAS mutations originate in IPMNs.GNAS is a complex imprinted locus that produces five transcripts regulated by differential methylated regions,NESP55,GNASAS,GNASXL,GNAS1A,and GNAS.AIM To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic cysts.METHODS GNAS locus methylation was analyzed in archival pancreatic cyst fluid(PCF)obtained by endoscopic ultrasound with fine-needle aspiration by methylation specific–multiplex ligation dependent probe amplification.Results were normalized and analyzed using *** software.RESULTS Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for KRAS and GNAS mutations were studied.The final diagnoses were surgical(11)and clinicopathological(41),including 30 benign cysts,14 pre-malignant cyst,and eight malignant cysts.Methylation changes at NESP55,GNASAS,GNAS1A,and especially GNASXL were more frequent in malignant cysts,and NESP55 and GNASAS were useful for diagnosis.A combined variable defined as“GNAS locus methylation changes”was significantly associated with malignancy(6/8 malignant cysts and only 2/20 benign cysts)and improved classification.Hypermethylation in both maternally(NESP55)and paternally(GNASXL)derived promoters was found in 3/3 PDACs.CONCLUSION This is the first study to identify methylation changes in the GNAS locus,improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC.

关键词： intraductal papillary mucinous neoplasms Pancreas cyst Methylation Biomarker GNAS locus Pancreatic neoplasm

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Validation of American Joint Committee on Cancer 8th edition of TNM staging in resected distal pancreatic cancer

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2020年第2期11卷 25-39页

作者： Feng Yin Mohammed Saad Hao Xie Jingmei Lin Christopher R Jackson Bing Ren Cynthia Lawson Dipti M Karamchandani Belen Quereda Bernabeu Wei Jiang Teena Dhir Richard Zheng Christopher W Schultz Dongwei Zhang Courtney L Thomas Xuchen Zhang Jinping Lai Michael Schild Xuefeng Zhang Xiuli Liu Department of Pathology and Anatomical Sciences University of MissouriColumbiaMO 65212United States Department of Pathology Indiana UniversityIndianapolisIN 46202United States Division of Medical Oncology Mayo ClinicRochesterMN 55905United States Department of Pathology Dartmouth-Hitchcock Medical CenterLebanonPA 03766United States Department of Pathology Pennsylvania State Health Milton S.Hershey Medical CenterHersheyPA 17033United States Department of Pathology Thomas Jefferson University HospitalPhiladelphiaPA 19107United States Department of Pathology and Lab Medicine University of Rochester Medical CenterRochesterNY 14642United States Department of Pathology Yale UniversityNew HavenCT 06510United States Department of Pathology and Laboratory Medicine Kaiser Permanente Sacramento Medical CenterSacramentoCA 95825United States Department of Pathology Duke UniversityDurhamNC 27710United States Department of Pathology Cleveland ClinicClevelandOH 44195United States Department of Pathology Immunology and Lab MedicineUniversity of FloridaGainesvilleFL 32610United States

BACKGROUND In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma(PDAC),the American Joint Committee on Cancer(AJCC)has published its eighth edition staging manual.Some major changes have been introduced in the new staging system for both T and N categories.Given the rarity of resectable disease,distal pancreatic cancer is likely underrepresented in the published clinical studies,and how the impact of the staging system actually reflects on to clinical outcomes remain unclear.AIM To validate the AJCC 8th edition of TNM staging in distal PDAC.METHODS A retrospective cohort study was performed in seven academic medical centers in the United States.Clinicopathological prognostic factors associated with progression-free survival(PFS)and overall survival(OS)were evaluated through univariate and multivariate analyses.RESULTS Overall,454 patients were enrolled in the study,and were divided into 2 subgroups:Invasive intraductal papillary mucinous neoplasms(IPMN)(115 cases)and non-IPMN associated adenocarcinoma(339 cases).Compared to invasive IPMN,non-IPMN associated adenocarcinomas are more common in relatively younger patients,have larger tumor size,are more likely to have positive lymph nodes,and are associated with a higher tumor(T)stage and nodal(N)stage,lymphovascular invasion,perineural invasion,tumor recurrence,and a worse PFS and OS.The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual,and it’s more evenly distributed based on 8th edition staging manual.T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort,although dividing into N1 and N2 according to the 8th edition does not show additional stratification.For PDAC arising in IPMN,T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS.For PDAC without an IPMN component,T staging from both versions fails to stratify PFS and OS.CONCLUSION The AJCC 8th edition TNM staging system provides even

关键词： Pancreatic cancer Pancreatic ductal adenocarcinoma Prognosis intraductal papillary mucinous neoplasms Survival American Joint Committee on Cancer

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