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  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

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    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
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    All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
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Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: The Follow-up Strategy Is Still Evolving

Tae Yoon Lee

Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, Korea

Correspondence to: Tae Yoon Lee
ORCID https://orcid.org/0000-0003-1008-9814
E-mail widebrow@empal.com

See “Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: Clinical Outcome after Long-term Follow-up” by Dong-Won Ahn, et al. on page 328, Vol. 18, No. 2, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2024;18(2):199-200. https://doi.org/10.5009/gnl240080

Published online March 15, 2024, Published date March 15, 2024

Copyright © Gut and Liver.

Surveillance of incidental pancreatic cysts, particularly presumed branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains a challenge. The likelihood of malignancy is generally low in pancreatic cysts, which are more commonly found in elderly patients who often die from nonpancreatic-related diseases. In clinical practice, there is currently no consensus on the optimal method to surveil pancreatic cystic lesions, including the duration, interval, and discontinuation of the follow-up. Excessive surveillance frequency may cause a considerable burden on healthcare resources due to imaging costs and the risks associated with unnecessary procedures such as endoscopic ultrasound.1 However, inadequate lengthening of the surveillance interval poses a significant concern for the malignant risk of the cyst itself or concomitant pancreatic ductal adenocarcinoma elsewhere in the pancreas. It is also unclear whether surveillance can be discontinued in patients with prolonged, stable incidental pancreatic cysts.

Therefore, it is welcome to see in this issue of the Journal, a study by Ahn et al.2 from Korea evaluating the long-term clinical outcomes of incidental pancreatic cystic lesions for more than 10 years. The study showed that there was still a chance for malignancy to progress after 5 years of follow-up, and the majority of pancreatic cystic lesions without the development of worrisome features (WF) or high-risk stigmata (HRS) within 10 years had a good clinical prognosis even after 10 years. Optimal surveillance duration is an area of significant controversy. The American Gastroenterological Association proposes stopping surveillance after 5 years, if there are no changes in the cysts for 5 years after diagnosis.3 In contrast, the American College of Gastroenterology, European Study Group, and International Association of Pancreatology recommend ongoing surveillance even after 5 years.4 Although current guidelines have no consistency regarding follow-up intervals and the duration of surveillance, there is growing evidence to suggest that pancreatic cystic lesions may have a considerable risk of developing cancer, even after 5 years.

In this study, only 0.4% of the patients (1/227) had a risk of malignancy within 5 years; however, after 5 years, 1.4% of patients (3/210) developed malignancy. The findings of this study support the need for ongoing surveillance beyond 5 years for patients with pancreatic cystic lesions. However, it is difficult to draw definite conclusions from this study because not only the total number of enrolled patients (n=227) but also the number of patients with pancreatic cancer (n=4) was small. From a biological perspective, the risk of pancreatic cancer is anticipated to increase over time, not decrease. Studies have demonstrated that it can take 20 years for pancreatic cancer to develop after an initial mutation, providing a rationale for prolonging surveillance beyond 5 years. A multicenter prospective study in Japan, which evaluated 1,404 patients with IPMNs, found a cumulative incidence of pancreatic cancer of 3.3% at 5 years, 6.6% at 10 years, and 15% at 15 years.5 However, the argument for stopping surveillance is that most patients with incidental pancreatic cysts will not develop pancreatic cancer and it is not feasible to follow patients indefinitely given the large number of patients with pancreatic cystic lesions. The approach of stopping surveillance after 5 years is supported by a retrospective study of 7,211 patients with pancreatic cysts in which only 79 (1.1%) developed pancreatic cancer.6 Similarly, a recent meta-analysis of 41 cohort studies reported that the malignant conversion rate during extended surveillance after 5 years for patients with stable BD-IPMN without WF or HRS at the 5-year time point was only 0.2%.7

The key question is how to identify the subgroup of patients, who are less or more likely to undergo malignant conversion after 5 years when considering the economic burden. The identification of this subgroup must be based on strong evidence of the natural history of BD-IPMN. Recently, a large-scale international cohort study by Han et al.8 reported that malignant conversion was not observed in stable cysts that did not develop WFs during the initial 5-year surveillance, whereas it was observed in 12 changing cysts (1.7%). This finding suggests that patients with cysts smaller than 20 mm and who do not experience morphologic changes during the first 5 years of surveillance may consider stopping surveillance if they are unable to undergo surgery or have a life expectancy of 10 years or less.

At this time, there is not enough evidence to justify continuing surveillance for all incidental pancreatic cysts after 5 years according to the findings of this study. Equally, there are not enough data to support stopping surveillance universally after 5 years of stability based on the American Gastroenterological Association guidelines. The era of precision medicine can give a possibility that a combination of patient factors (age and comorbidity), cyst factors (histology subtype, presence of WF/HRS, cyst size), and more precise pancreatic cyst fluid biomarkers, will result in a more detailed and well-informed approach for stopping or continuing incidental pancreatic cysts surveillance.

No potential conflict of interest relevant to this article was reported.

  1. Chong J, Wee NK, Tan CH, et al. Pancreatic cysts: can surveillance interval for small low-risk lesions be lengthened?. Acta Radiol. Epub 2024 Jan 9. https://doi.org/10.1177/02841851231222799
    Pubmed CrossRef
  2. Ahn DW, Lee SH, Choi JH, et al. Optimal follow-up of incidental pancreatic cystic lesions without worrisome features: clinical outcome after long-term follow-up. Gut Liver 2024;18:328-337.
    Pubmed CrossRef
  3. Vege SS, Ziring B, Jain R, Moayyedi P; Clinical Guidelines Committee; American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:819-822.
    Pubmed CrossRef
  4. Lennon AM, Vege SS. Pancreatic cyst surveillance. Clin Gastroenterol Hepatol 2022;20:1663-1667.
    Pubmed KoreaMed CrossRef
  5. Oyama H, Tada M, Takagi K, et al. Long-term risk of malignancy in branch-duct intraductal papillary mucinous neoplasms. Gastroenterology 2020;158:226-237.
    Pubmed CrossRef
  6. Anand GS, Youssef F, Liu L, et al. Pancreas cancer incidence and pancreas cancer-associated mortality are low in national cohort of 7211 pancreas cyst patients. Dig Dis Sci 2022;67:1065-1072.
    Pubmed KoreaMed CrossRef
  7. Chhoda A, Singh S, Sheth AH, et al. Benefit of extended surveillance of low-risk pancreatic cysts after 5-year stability: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2023;21:1430-1446.
    Pubmed CrossRef
  8. Han Y, Kwon W, Lee M, et al. Optimal surveillance interval of branch duct intraductal papillary mucinous neoplasm of the pancreas. JAMA Surg. Epub 2024 Jan 17. https://doi.org/10.1001/jamasurg.2023.7010
    CrossRef

Article

Editorial

Gut and Liver 2024; 18(2): 199-200

Published online March 15, 2024 https://doi.org/10.5009/gnl240080

Copyright © Gut and Liver.

Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: The Follow-up Strategy Is Still Evolving

Tae Yoon Lee

Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, Korea

Correspondence to:Tae Yoon Lee
ORCID https://orcid.org/0000-0003-1008-9814
E-mail widebrow@empal.com

See “Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: Clinical Outcome after Long-term Follow-up” by Dong-Won Ahn, et al. on page 328, Vol. 18, No. 2, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Body

Surveillance of incidental pancreatic cysts, particularly presumed branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains a challenge. The likelihood of malignancy is generally low in pancreatic cysts, which are more commonly found in elderly patients who often die from nonpancreatic-related diseases. In clinical practice, there is currently no consensus on the optimal method to surveil pancreatic cystic lesions, including the duration, interval, and discontinuation of the follow-up. Excessive surveillance frequency may cause a considerable burden on healthcare resources due to imaging costs and the risks associated with unnecessary procedures such as endoscopic ultrasound.1 However, inadequate lengthening of the surveillance interval poses a significant concern for the malignant risk of the cyst itself or concomitant pancreatic ductal adenocarcinoma elsewhere in the pancreas. It is also unclear whether surveillance can be discontinued in patients with prolonged, stable incidental pancreatic cysts.

Therefore, it is welcome to see in this issue of the Journal, a study by Ahn et al.2 from Korea evaluating the long-term clinical outcomes of incidental pancreatic cystic lesions for more than 10 years. The study showed that there was still a chance for malignancy to progress after 5 years of follow-up, and the majority of pancreatic cystic lesions without the development of worrisome features (WF) or high-risk stigmata (HRS) within 10 years had a good clinical prognosis even after 10 years. Optimal surveillance duration is an area of significant controversy. The American Gastroenterological Association proposes stopping surveillance after 5 years, if there are no changes in the cysts for 5 years after diagnosis.3 In contrast, the American College of Gastroenterology, European Study Group, and International Association of Pancreatology recommend ongoing surveillance even after 5 years.4 Although current guidelines have no consistency regarding follow-up intervals and the duration of surveillance, there is growing evidence to suggest that pancreatic cystic lesions may have a considerable risk of developing cancer, even after 5 years.

In this study, only 0.4% of the patients (1/227) had a risk of malignancy within 5 years; however, after 5 years, 1.4% of patients (3/210) developed malignancy. The findings of this study support the need for ongoing surveillance beyond 5 years for patients with pancreatic cystic lesions. However, it is difficult to draw definite conclusions from this study because not only the total number of enrolled patients (n=227) but also the number of patients with pancreatic cancer (n=4) was small. From a biological perspective, the risk of pancreatic cancer is anticipated to increase over time, not decrease. Studies have demonstrated that it can take 20 years for pancreatic cancer to develop after an initial mutation, providing a rationale for prolonging surveillance beyond 5 years. A multicenter prospective study in Japan, which evaluated 1,404 patients with IPMNs, found a cumulative incidence of pancreatic cancer of 3.3% at 5 years, 6.6% at 10 years, and 15% at 15 years.5 However, the argument for stopping surveillance is that most patients with incidental pancreatic cysts will not develop pancreatic cancer and it is not feasible to follow patients indefinitely given the large number of patients with pancreatic cystic lesions. The approach of stopping surveillance after 5 years is supported by a retrospective study of 7,211 patients with pancreatic cysts in which only 79 (1.1%) developed pancreatic cancer.6 Similarly, a recent meta-analysis of 41 cohort studies reported that the malignant conversion rate during extended surveillance after 5 years for patients with stable BD-IPMN without WF or HRS at the 5-year time point was only 0.2%.7

The key question is how to identify the subgroup of patients, who are less or more likely to undergo malignant conversion after 5 years when considering the economic burden. The identification of this subgroup must be based on strong evidence of the natural history of BD-IPMN. Recently, a large-scale international cohort study by Han et al.8 reported that malignant conversion was not observed in stable cysts that did not develop WFs during the initial 5-year surveillance, whereas it was observed in 12 changing cysts (1.7%). This finding suggests that patients with cysts smaller than 20 mm and who do not experience morphologic changes during the first 5 years of surveillance may consider stopping surveillance if they are unable to undergo surgery or have a life expectancy of 10 years or less.

At this time, there is not enough evidence to justify continuing surveillance for all incidental pancreatic cysts after 5 years according to the findings of this study. Equally, there are not enough data to support stopping surveillance universally after 5 years of stability based on the American Gastroenterological Association guidelines. The era of precision medicine can give a possibility that a combination of patient factors (age and comorbidity), cyst factors (histology subtype, presence of WF/HRS, cyst size), and more precise pancreatic cyst fluid biomarkers, will result in a more detailed and well-informed approach for stopping or continuing incidental pancreatic cysts surveillance.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

References

  1. Chong J, Wee NK, Tan CH, et al. Pancreatic cysts: can surveillance interval for small low-risk lesions be lengthened?. Acta Radiol. Epub 2024 Jan 9. https://doi.org/10.1177/02841851231222799
    Pubmed CrossRef
  2. Ahn DW, Lee SH, Choi JH, et al. Optimal follow-up of incidental pancreatic cystic lesions without worrisome features: clinical outcome after long-term follow-up. Gut Liver 2024;18:328-337.
    Pubmed CrossRef
  3. Vege SS, Ziring B, Jain R, Moayyedi P; Clinical Guidelines Committee; American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:819-822.
    Pubmed CrossRef
  4. Lennon AM, Vege SS. Pancreatic cyst surveillance. Clin Gastroenterol Hepatol 2022;20:1663-1667.
    Pubmed KoreaMed CrossRef
  5. Oyama H, Tada M, Takagi K, et al. Long-term risk of malignancy in branch-duct intraductal papillary mucinous neoplasms. Gastroenterology 2020;158:226-237.
    Pubmed CrossRef
  6. Anand GS, Youssef F, Liu L, et al. Pancreas cancer incidence and pancreas cancer-associated mortality are low in national cohort of 7211 pancreas cyst patients. Dig Dis Sci 2022;67:1065-1072.
    Pubmed KoreaMed CrossRef
  7. Chhoda A, Singh S, Sheth AH, et al. Benefit of extended surveillance of low-risk pancreatic cysts after 5-year stability: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2023;21:1430-1446.
    Pubmed CrossRef
  8. Han Y, Kwon W, Lee M, et al. Optimal surveillance interval of branch duct intraductal papillary mucinous neoplasm of the pancreas. JAMA Surg. Epub 2024 Jan 17. https://doi.org/10.1001/jamasurg.2023.7010
    CrossRef
Gut and Liver

Vol.18 No.2
March, 2024

pISSN 1976-2283
eISSN 2005-1212

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