Commentary

Point/Counterpoint: Should all suspected mucinous cystic neoplasms be resected?


 

 

Dr. Pawlik is a pretty clever guy and a strong adversary. Mucinous cystic neoplasm is literally the only topic in hepato-pancreato-biliary surgery he has not written about – yet.1

But I will argue that all suspected mucinous cystic neoplasms (MCNs) should be surgically removed. Reasons include: the natural history of a benign MCN in a typical 45-year-old remains unknown, clinical features are not always reliable, and it’s difficult to distinguish benign from malignant neoplasms without surgery.

Dr. Matthew H. Katz, MD Anderson Cancer Center
Dr. Matthew H. Katz
The pertinent questions in 2017 are: Can we accurately discriminate benign from malignant MCNs? And, do we understand the natural history of how benign MCNs behave over time? I would argue no.

Although many MCNs are benign when resected, all have malignant potential.

The prevalence of cancer at time of diagnosis with an MCN is fairly low, about 15%. This means most of these cysts are benign when resected. However, discrimination between benign and malignant is difficult without surgery, and the degree of epithelial dysplasia at time of resection ranges from mild to severe with invasive carcinoma.

When cancer is present, patients tend to do poorly. In one study where 44 out of 344 patients developed invasive cancer, the group with cancer had a 3-year overall survival rate of 59%.2

In addition, aspiration of cyst fluid is often of limited utility. It is poor at distinguishing whether a cyst is benign or malignant. For example, in a series of 55 patients with MCNs that underwent fine-needle aspiration of cyst epithelium, 71% of assays were nondiagnostic.3 So this diagnostic test is very insensitive and may miss at least half of cancers – another point in favor of surgical resection for all MCNs.

It is true that evidence in the literature associates certain clinical factors with a higher risk for malignancy in suspected MCNs. These include male gender, larger cysts, and location in the pancreatic head or neck or larger cyst diameter and presence of nodules.2,4 However, use of clinical features is not perfect.

In another study, of 163 resected MCNs, those with invasive cancer were often – but not always – larger than 4 cm with nodules.5 These same series revealed that those with invasive cancer were often, but again not always, larger than 4 cm.

We see this in our practice as well – that a large cyst or presence of nodules is not a foolproof indicator of malignancy. We had a 38-year-old woman with a large cyst and nodules who did not have cancer. In contrast, a 45-year-old woman at our institution presented with small cysts and no cancer on fine-needle aspiration. However, final pathology in her case revealed high-grade dysplasia.

Also, we only know what happens to cysts that have been resected. We know nothing about duration or other best practices for following patients who do not undergo surgery. For this reason, we really don’t know what these tumors will do if left alone.

Surgery is curative and carries a pretty low risk. Following resection, these patients do well. We’re talking about curative operations.

Dr. Katz is an Associate Professor, Department of Surgical Oncology, Division of Surgery at the University of Texas MD Anderson Cancer Center in Houston. He is also Chief of the Pancreas Surgery Service at MD Anderson. Dr. Katz noted he was asked to provide the pro side of the argument, and he may not necessarily uphold these positions in his own practice. Dr. Katz had no relevant financial disclosures.

References:

1. Dr. Pawlik’s list of selected publications: http://pathology.jhu.edu/liver/pawlik.cfm.

2. JAMA Surg. 2017;152:19-25.

3. Cancer. 2017;125:169-77.

4. Pancreas. 2011;40:67-71.

5. Ann Surg. 2008;247:571-9.

Some mucinous cystic neoplasms can be safely followed.

Data in the literature suggest some of these suspected mucinous cystic neoplasms can be followed; surgery may not be indicated solely because “as surgeons we tend to take all masses out” and because operative complications occur. Therefore, resection is not a benign procedure.

Dr. Katz, you were done before you got started. The evidence shows that some of the MCNs can be followed rather than resected.

Dr. Timothy M. Pawlik of the Ohio State Wexner Medical Center
Dr. Timothy M. Pawlik
Pancreatic cysts are very common. A surgical approach to remove every one of these cysts – whether they are MCNs, intraductal papillary mucinous neoplasms (IPMNs), or another type – is logistically challenging and inappropriate.

Most of the published studies focus on IPMN, but I think the topic of MCNs is becoming increasingly important; they follow IPMNs as the second most common type of cystic neoplasms. So we’re going to be finding more small MCNs. In this debate, we are not talking about an 8-cm MCN, but rather what do we do when we see a 2- to 3-cm MCN. Do these patients all need to undergo resection?

What Dr. Katz is concerned about is that we are going to miss a cancer. We should operate on all patients because – at least as Dr. Katz’s argues – the surgery can always be done without complications.

However, even at the very, very experienced centers, morbidity was 30%-50%, and a pancreatic fistula developed for 1 in 10 patients. So it’s not a benign procedure.1

As surgeons, we tend to take every mass out. Although operative mortality is low, it is still in a measurable range, 1%-2%, and that is even at expert centers. Many of these small cysts are being found at smaller and community hospitals, and undue morbidity and mortality may weigh more heavily in these settings.2

Rather than “being a hammer and seeing everything as a nail,” we need a more rational approach. For example, we should identify a subgroup that will the most benefit from resection.

Investigators from Memorial Sloan Kettering Cancer Center reported that certain clinical factors identify patients at higher risk for mortality, such as nodules.3 Patients with invasive cancer almost all had nodules. And all patients with invasive cancer without nodules had a tumor larger than 4 cm.

Maybe using both presence of nodules and size is the right approach to identifying underling malignancy in suspected MCNs. Again, size is important, as is male gender, presence of solid nodules, and duct dilatation.4

We are arguing whether all MCNs should be resected. I’m positing that many 2-cm to 3-cm MCNs can be followed. There is only a small chance they will grow over time, and it’s unlikely they are harboring a malignancy.

Dr. Pawlik is Chair of Surgery at the Ohio State Wexner Medical Center in Columbus. He is also the Urban Meyer III and Shelley Meyer Chair for Cancer Research at Ohio State. He has no disclosures.

References

1. HPB (Oxford). 2007;9:8-15.

2. Diagnosis and Management of Cystic Lesions of the Pancreas. Diagnostic and Therapeutic Endoscopy Volume 2011 (2011), Article ID 478913.

3. JAMA Surg. 2017;152:19-25.

4. Ann Surg. 2006;244:572-82.

This Point/Counterpoint feature is based on comments Dr. Katz and Dr. Pawlik made during a debate at AHPBA 2017, the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

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