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High-Grade Dysplasia and Adenocarcinoma Are Frequent in Side-Branch Intraductal Papillary Mucinous Neoplasm Measuring Less than 3 cm on Endoscopic Ultrasound

  • 2012 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Surgical resection for intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the last decade. While IPMN with main duct communication are generally recommended for resection, indications for resection of side-branch IPMN (SDIPMN) have been less clear. We reviewed our single institutional experience with SDIPMN and indications for resection.

Methods

Patients who underwent resection for IPMN were identified from a prospectively maintained IRB-approved database. Patients with main pancreatic duct communication were excluded. Outcome, clinical and pathologic characteristics were correlated with endoscopic ultrasound (EUS) findings.

Results

From 2000 to 2010, 105 patients who underwent preoperative EUS evaluation and resection for SDIPMN were identified. The mean age was within the sixth decade of life, and there was a slight female predominance (55 vs. 45 %). The most common presenting symptom was abdominal pain (N = 47, 45 %), followed by jaundice (N = 24, 23 %) and weight loss (N = 24, 23 %). Only ten patients (10 %) were asymptomatic at presentation; seven (70 %) had suspicious features on EUS. Of the total cohort, few patients had intracystic septations (N = 27, 26 %) or presence of mural nodules (N = 2, 2 %) on EUS. Of 39 patients who had invasive pancreatic ductal adenocarcinoma (PDAC) on final pathology, EUS-fine needle aspiration (EUS-FNA) demonstrated malignancy in only 21 (54 %). An additional seven (18 %) had EUS-FNA findings of atypia or concern for mucinous neoplasm. EUS evaluation of cyst size was correlated with final pathology. Of 70 patients with EUS cyst size <3 cm, 12 (17 %) had a preoperative EUS diagnosis of malignancy. Final pathology revealed 24 (34 %) to have PDAC: 1 of 7 (14 %) patients with cyst size <1 cm, 2 of 19 (11 %) with cyst size 1–2 cm, and 21of 44 (48 %) with cyst size 2–3 cm. Fifteen of 35 (43 %) patients with cyst size >3 cm had PDAC on final pathology. Of the patients with cyst size <3 cm, 16 (23 %) had high-grade dysplasia on final pathology: 3 of 7 (43 %) with cyst size <1 cm, 3 of 19 (16 %) with cyst size 1–2 cm, and 10 of 44 (23 %) with cyst size 2–3 cm. Seven of 35 (20 %) patients with cyst size >3 cm had high-grade dysplasia on final pathology. Although overall survival (OS) at 48 months stratified by EUS cyst size did not significantly differ between groups, patients with PDAC on final pathology had significantly worse OS compared to noninvasive pathology. A total of eight patients (8 %) developed recurrent disease, all of whom had PDAC on final pathology.

Conclusion

EUS is a helpful modality for the diagnostic evaluation of SDIPMN. Considering the high incidence of malignancy as well as high-grade dysplasia in SDIPMN greater than 2 cm, EUS features should be used in conjunction with other clinical criteria to guide management decisions. Patients with SDIPMN greater than 2 cm that do not undergo surgical resection may benefit from more intensive surveillance.

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Author information

Authors and Affiliations

  1. Department of Surgery, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Joyce Wong, Jill Weber & Pamela Hodul

  2. Department of Gastroenterology, H. Lee Moffitt Cancer Center, Tampa, FL, United States

    Shivakumar Vignesh, Cynthia L. Harris & Jason B. Klapman

  3. Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, United States

    Barbara A. Centeno

  4. Department of Gastrointestinal Surgical Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Pamela Hodul

Authors
  1. Joyce Wong
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  2. Jill Weber
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  3. Barbara A. Centeno
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  4. Shivakumar Vignesh
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  5. Cynthia L. Harris
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Correspondence to Pamela Hodul.

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Discussant

Dr. Charles M. Vollmer, Jr. (Philadelphia, PA): Dr. Wong, thank you for bringing this provocative work to the SSAT. I appreciate your providing the manuscript ahead of time.

There is a building groundswell to determine better selection criteria for resection of SB-IPMN. Historically, our patters of care for this disease have swung like a pendulum from the “Have cyst, will operate” mantra of the early era (1990s) to the current enthusiasm for “observation.” Usually, the practical truth is found somewhere in the middle ground of the extremes. Many of us are dissatisfied with the current suggestions for resection as posed in the Sendai Criteria version 1.0. Few would quibble with criteria like symptoms or cytological proof of malignancy. Other parameters warrant closer scrutiny. For instance, change in size of a cyst over time (Is this really indicative of malignant degeneration?). But perhaps the most contentious of those suggested guidelines is the particular category of size of a cyst as an indicator of cancer.

Now to the findings of this present study…It is important to note that only 10 % of patients in this series were asymptomatic. A full quarter were jaundiced at presentation, and half experienced abdominal pain. The quoted rate of malignancy in this series of all comers of SB-IPMN who ultimately received EUS is a staggering 55 %, compared to the bulk of the literature which evens out around 15 % at most. I think the results of your study need to be reconciled with the inclusion criteria. We are not dealing with the most troubling question we tackle in our clinics week after week—that is “What to do with the incidentally identified cyst at various zones in the spectrum of size?”

Now, some questions:

1. Could there be a referral bias in that this work is derived from a cancer-center practice?

2. What are the indications for performing EUS in your practice—particularly when FNA is accurate in determining malignancy only half the time? Why is EUS employed in overtly jaundiced patients?

3. When is the surgeon involved in the decision-making process about diagnostic modalities? Do they have a stake in the choice and timing of these interventions?

4. In this series, 13 patients were ultimately deemed to have “benign” pathology. If not dysplastic, are these really IPMN? What were these after all?

Finally, a comment which I’d like you to rationalize… I’d argue that your data show a haphazard correlation of EUS size to the eventual pathologic diagnosis of malignancy. For invasion, the rates go 14 %, down to 11 %, then up to 48 %, and leveling off at 43 % for the various hash-marks from 0 to >3 cm. Similarly, for high-grade dysplasia, they range 43, 16, 23, and 20 %. So, does size matter? Is it a realistic indicator of a threatening cyst?

My overall impression from reading your work would be “Take ‘em all out!”, thus reverting us back to the initial aggressive mindset we employed 20 years ago and indicating that we have a long way to go in refining our decision making about surgical resection of this disease. Thank you for an excellent presentation and paper.

Closing Discussant

Dr. Joyce Wong:

1. Could there be a referral bias in that this work is derived from a cancer-center practice?

Yes, there could be a referral bias. At Moffitt, we see a significant number of patients with a strong family history for pancreatic cancer, and we are the tertiary referral center in a large area for pancreatic malignancy.

2. What are the indications for performing EUS in your practice—particularly when FNA is accurate in determining malignancy only half the time? Why is EUS employed in overtly jaundiced patients?

We employ EUS in conjunction with other imaging modalities, including CT and MRI, to evaluate the architecture of the pancreatic body and duct, to evaluate the cyst size, and to obtain fine needle aspiration of the cyst. We find that utilizing EUS with other imaging modalities gives us more information than either CT or MRI alone. In patients with jaundice, EUS can provide additional architectural information about the bile duct and potentially provide an opportunity for therapeutic intervention.

3. When is the surgeon involved in the decision-making process about diagnostic modalities? Do they have a stake in the choice and timing of these interventions?

Generally, all patients who present to Moffitt Cancer Center, whether initially to the gastroenterologist, medical oncologist, or surgeon, are presented at a weekly tumor board. The tumor board is represented by these specialists, along with radiation oncologists, radiologists, and pathologists. The patient’s history, imaging, and pathology are reviewed in collaboration. So surgeons are involved with patient care from initial presentation at tumor board and can contribute input regarding whether surgical resection would be appropriate.

4. In this series, 13 patients were ultimately deemed to have “benign” pathology. If not dysplastic, are these really IPMN? What were these after all?

These 13 patients had no evidence of malignancy or carcinoma on final pathology. They were all assessed to be side-branch IPMN by pre-resection imaging and EUS. While the pathology may demonstrate adenoma or benign pathology, the sensitivity of FNA is not great, and the majority of the resections performed in this series were for symptoms.

Finally, a comment which I’d like you to rationalize…I’d argue that your data show a haphazard correlation of EUS size to the eventual pathologic diagnosis of malignancy. For invasion, the rates go 14 %, down to 11 %, then up to 48 %, and leveling off at 43 % for the various hash-marks from 0 to >3 cm. Similarly, for high-grade dysplasia they range 43, 16, 23, and 20 %. So, does size matter? Is it a realistic indicator of a threatening cyst?

We observed a particularly high rate of invasive carcinoma in cysts greater than 2 cm in size. While the exact percentages are perhaps high, this observation has been reported by a number of other studies which also observe that a greater percentage of invasive malignancy is captured with cysts >2 cm in size. It is likely that cyst size does matter but should be utilized along with other factors, such as presence of symptoms. We are not at the point where cyst size alone can be defined as an independent predictor of malignancy.

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Wong, J., Weber, J., A. Centeno, B. et al. High-Grade Dysplasia and Adenocarcinoma Are Frequent in Side-Branch Intraductal Papillary Mucinous Neoplasm Measuring Less than 3 cm on Endoscopic Ultrasound. J Gastrointest Surg 17, 78–85 (2013). https://doi.org/10.1007/s11605-012-2017-0

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  • DOI: https://doi.org/10.1007/s11605-012-2017-0

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