Noninvasive Discrimination of Low and High-risk Pancreatic Intraductal Papillary Mucinous Neoplasms.


Journal

Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354

Informations de publication

Date de publication:
01 06 2021
Historique:
pubmed: 11 7 2020
medline: 13 8 2021
entrez: 11 7 2020
Statut: ppublish

Résumé

To propose a noninvasive diagnostic approach, which allows reliable distinction between low- and high-risk pancreatic intraductal papillary mucinous neoplasms (IPMNs). IPMNs are identifiable precursor lesions of pancreatic cancer, of which surgical resection is warranted prior to the development of invasive carcinoma, but low-grade IPMNs should not be unnecessarily resected. However, diagnostic tools that preoperatively enable accurate risk stratification of IPMNs are missing. This single-center, retrospective cohort study included 56 patients who underwent surgical resection for IPMN including 18 low-risk (low-grade) and 38 high-risk (high-grade/invasive carcinoma) IPMNs, from whom clinical features and serum samples were prospectively obtained. An antibody microarray platform was used to analyze the serum proteome. Based on serum markers and selected clinical characteristics support vector machine models were constructed to predict the risk of IPMN malignancy. A serum protein signature discriminating low- and high-risk IPMN patients was identified. Combinations of established clinical features and the newly identified serum biomarkers correctly distinguished low- and high-risk IPMNs in 93% on 1000-fold cross-validation. This study highlights the synergistic predictive value of combining a novel serum protein signature with conventional clinical characteristics to risk-stratify IPMN patients. If these findings are supported by larger validation studies, they might enable more rational decision-making in clinical management of IPMN patients in conjunction with clinical guidelines.

Sections du résumé

OBJECTIVE
To propose a noninvasive diagnostic approach, which allows reliable distinction between low- and high-risk pancreatic intraductal papillary mucinous neoplasms (IPMNs).
BACKGROUND
IPMNs are identifiable precursor lesions of pancreatic cancer, of which surgical resection is warranted prior to the development of invasive carcinoma, but low-grade IPMNs should not be unnecessarily resected. However, diagnostic tools that preoperatively enable accurate risk stratification of IPMNs are missing.
METHODS
This single-center, retrospective cohort study included 56 patients who underwent surgical resection for IPMN including 18 low-risk (low-grade) and 38 high-risk (high-grade/invasive carcinoma) IPMNs, from whom clinical features and serum samples were prospectively obtained. An antibody microarray platform was used to analyze the serum proteome. Based on serum markers and selected clinical characteristics support vector machine models were constructed to predict the risk of IPMN malignancy.
RESULTS
A serum protein signature discriminating low- and high-risk IPMN patients was identified. Combinations of established clinical features and the newly identified serum biomarkers correctly distinguished low- and high-risk IPMNs in 93% on 1000-fold cross-validation.
CONCLUSIONS
This study highlights the synergistic predictive value of combining a novel serum protein signature with conventional clinical characteristics to risk-stratify IPMN patients. If these findings are supported by larger validation studies, they might enable more rational decision-making in clinical management of IPMN patients in conjunction with clinical guidelines.

Identifiants

pubmed: 32649457
pii: 00000658-202106000-00043
doi: 10.1097/SLA.0000000000004066
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e273-e275

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Déclaration de conflit d'intérêts

The authors report no conflicts of interest.

Références

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69:7–34.
Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 2004; 28:977–987.
Basturk O, Hong SM, Wood LD, et al. A Revised classification system and recommendations from the baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol 2015; 39:1730–1741.
Koh YX, Zheng HL, Chok AY, et al. Systematic review and meta-analysis of the spectrum and outcomes of different histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms. Surgery 2015; 157:496–509.
Pulvirenti A, Margonis GA, Morales-Oyarvide V, et al. Intraductal papillary mucinous neoplasms: have IAP consensus guidelines changed our approach?: Results from a multi-institutional study. Ann Surg 2020; [Epub ahead of print].
Xu MM, Yin S, Siddiqui AA, et al. Comparison of the diagnostic accuracy of three current guidelines for the evaluation of asymptomatic pancreatic cystic neoplasms. Medicine (Baltimore) 2017; 96:e7900.
Mustafa S, Pan L, Marzoq A, et al. Comparison of the tumor cell secretome and patient sera for an accurate serum-based diagnosis of pancreatic ductal adenocarcinoma. Oncotarget 2017; 8:11963–11976.
Springer S, Masica DL, Dal Molin M, et al. A multimodality test to guide the management of patients with a pancreatic cyst. Sci Transl Med 2019; 11:eaav4772.
Das KK, Geng X, Brown JW, et al. Cross validation of the monoclonal antibody das-1 in identification of high-risk mucinous pancreatic cystic lesions. Gastroenterology 2019; 157: 720–730.e2.
Maker AV, Hu V, Kadkol SS, et al. Cyst fluid biosignature to predict intraductal papillary mucinous neoplasms of the pancreas with high malignant potential. J Am Coll Surg 2019; 228:721–729.

Auteurs

Susanne Roth (S)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Promita Bose (P)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Mohamed S S Alhamdani (MSS)

Division of Functional Genome Analysis, German Cancer Research Center, Heidelberg (DKFZ), Germany.

Shakhawan A Mustafa (SA)

Division of Functional Genome Analysis, German Cancer Research Center, Heidelberg (DKFZ), Germany.

Christine Tjaden (C)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Katharina Zamzow (K)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Ulf Hinz (U)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Christoph W Michalski (CW)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.
Department of Surgery, Halle University Hospital, Halle (Saale), Germany.

John P Neoptolemos (JP)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Jörg D Hoheisel (JD)

Division of Functional Genome Analysis, German Cancer Research Center, Heidelberg (DKFZ), Germany.

Markus W Büchler (MW)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Thilo Hackert (T)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

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