P0021 - Association Between Pancreatic Intraductal Papillary Mucinous Neoplasms and Extrapancreatic Malignancies: A Systematic Review and Meta-Analysis

Daryl Ramai, MD, MSc¹, Antonio Facciorusso, MD, PhD², Stefano Crinò, MD³, Giovanni Marchegiani, MD³, Andrea Lisotti, MD⁴, Pietro Fusaroli, MD⁵, Renato Cannizzaro, ⁶, Paraskevas Gkolfakis, ⁷, Ioannis S. Papanikolaou, MD, PhD⁸, Konstantinos Triantafyllou, MD⁸, Siddharth Singh, MD^9
1University of Utah, Salt Lake City, UT; ²University of Foggia, Foggia, Puglia, Italy; ³University Hospital of Verona, Verona, Veneto, Italy; ⁴Hospital of Imola, Bologna, Emilia-Romagna, Italy; ⁵University of Bologna, Bologna, Emilia-Romagna, Italy; ⁶Centro Riferimento Oncologico, Aviano, Friuli-Venezia Giulia, Italy; ⁷Erasme University Hospital, Brussels, Brussels Hoofdstedelijk Gewest, Belgium; ⁸Attikon University General Hospital, Athens, Attiki, Greece; ⁹UC San Diego Health, La Jolla, CA

Introduction: It is still unclear whether patients with intraductal papillary mucinous neoplasia (IPMN) harbor a higher risk of developing extrapancreatic malignancies (EPMs). Aim of this meta-analysis is to provide a pooled estimate of the incidence of EPM in patients with IPMN, with a particular focus on the comparison to the general population.

Methods: Computerized bibliographic search on the main databases was performed through February 2021. Pooled effects were calculated using a random-effects model by means of DerSimonian and Laird test. Primary endpoint was the pooled incidence of EPM in IPMN patients. Additional outcome was the comparison of EPM occurrence between IPMN patients and general population, expressed in terms of standardized incidence ration (SIR) along with 95% confidence intervals (CIs).

Results: Eighteen studies with 8709 patients were included. Pooled rate of EPM in patients with IPMN was 27.3% (95% CI: 20.5%-34.1%), with a pooled rate of 14.7% (9.4%-20.1%) of EPM detected previous to IPMN diagnosis and 6.6% (4.5%-8.7%) of synchronous EPM. Pooled rate of metachronous EPM was 10 (95% CI: 6-13)/1000 persons-year. No difference was observed according to IPMN histology and sex, whereas a significantly superior incidence of EPM was observed in patients with main-duct IPMN (36.7%, 25.4%-48% as compared to 26.2%, 17.6%-34.8% in branch-duct IPMN; p=0.03) and in Eastern studies (36.1%, 31.1%-41.1% versus 20.8%, 12.7%-28.9%; p=0.02).

Pooled SIR of comparison with expected rates in general population was 1.01 (0.79-1.29); no difference was observed concerning rates of metachronous gastric cancer (SIR 1.60, 0.72-3.54) and colorectal cancer (SIR 1.29, 0.92-1.18), whereas biliary cancer was observed more frequently in IPMN patients (SIR 2.29, 1.07-4.93). EPM-related and IPMN-related mortality rates were 6% (3%-9.1%) and 6.3% (4.2%-8.5%), respectively.

Discussion: Our meta-analysis demonstrates that IPMN patients harbor an overall rate of EPM as high as 27.3%, but rate of

metachronous EPM is not superior to the general population.


Figure: Forest plot comparing observed/expected incidence of metachronous extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasia. Standardized incidence ratio was 1.01 (0.79-1.29), with moderate evidence of heterogeneity (I2=22%).

Tumor	Endpoint	No. of Studies	No. of patients	Summary measure (95% CI)	Within-group heterogeneity (I2)
Gastric cancer	Overall rate	17	7478	1.1% (0.6%-1.6%)	45.56%
	Metachronous*	11	10889 P/Y	1 (0-2)	14.87%
	Comparison with general population+	5	1038	1.60 (0.72-3.54)	33%
Colorectal cancer	Overall rate	17	7868	4.5% (3%-6.1%)	41.97%
	Metachronous*	7	9211 P/Y	2 (1-3)	0%
	Comparison with general population+	7	1034	1.29 (0.92-1.18)	38%
Biliary cancer	Overall rate	12	6214	0.5% (0.2%-0.8%)	33.9%
	Metachronous*	9	28233 P/Y	0.2 (0-0.4)	0%
	Comparison with general population+	4	745	2.29 (1.07-4.93)	0%
EPM-related mortality	Overall rate	6	522	6% (3%-9.1%)	54.28%
	Rate/1000 persons/Y	6	1592 P/Y	20 (9-30)	39%
IPMN-related mortality	Overall rate	7	573	6.3% (4.2%-8.5%)	13.06%
	Rate/1000 persons/Y	6	1684 P/Y	21 (14-28)	0%
* Results expressed as N/1000 persons/year + Results expressed as standardized incidence ratio. Previous cancers were excluded from the comparative analysis. Abbreviations: EPM, Extra-pancreatic malignancy; IPMN, Intraductal Papillary Mucinous Neoplasm

Table: Analysis concerning gastric, colorectal, biliary cancer, and mortality.


Disclosures:
Daryl Ramai indicated no relevant financial relationships.
Antonio Facciorusso indicated no relevant financial relationships.
Stefano Crinò indicated no relevant financial relationships.
Giovanni Marchegiani indicated no relevant financial relationships.
Andrea Lisotti indicated no relevant financial relationships.
Pietro Fusaroli indicated no relevant financial relationships.
Renato Cannizzaro indicated no relevant financial relationships.
Paraskevas Gkolfakis indicated no relevant financial relationships.
Ioannis Papanikolaou indicated no relevant financial relationships.
Konstantinos Triantafyllou indicated no relevant financial relationships.
Siddharth Singh indicated no relevant financial relationships.


Daryl Ramai, MD, MSc¹, Antonio Facciorusso, MD, PhD², Stefano Crinò, MD³, Giovanni Marchegiani, MD³, Andrea Lisotti, MD⁴, Pietro Fusaroli, MD⁵, Renato Cannizzaro, ⁶, Paraskevas Gkolfakis, ⁷, Ioannis S. Papanikolaou, MD, PhD⁸, Konstantinos Triantafyllou, MD⁸, Siddharth Singh, MD⁹. P0021 - Association Between Pancreatic Intraductal Papillary Mucinous Neoplasms and Extrapancreatic Malignancies: A Systematic Review and Meta-Analysis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.