Surgery for Small Pancreatic Duct Dilatation to Prevent Cancer

Liam Davenport

May 28, 2019

Patients with intraductal papillary mucinous neoplasms (IPMNs) should undergo surgery if there is even a small dilatation of the main pancreatic duct (MPD), say US researchers. They argue that such surgery could help prevent the development of pancreatic cancer.

"Changing to more aggressive guidelines will lead to more surgeries but would likely save more lives," said Ross Beckman, MD, a resident and postdoctoral fellow at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

He was lead author of a study published earlier this year in the Annals of Surgery.

The study set out to examine factors that predict the development of pancreatic cancer. The researchers reviewed the records of almost 800 patients with IPMN who underwent pancreatic resection at leading centers in Sweden and the United States.

Their review revealed that of all the preoperative patient and disease-related factors examined, only dilatation of the MPD significantly predicted the presence of high-grade or invasive IPMN, a condition associated with cancer progression.

As expected, dilatation of ≥10 mm was associated with a more than sixfold increased risk for high-grade IPMN and 15-fold increased risk for invasive IPMN.

However, even a dilatation of 5 mm – 9.9 mm, which is not universally regarded as an indication for surgery, was linked to an almost threefold increased risk for high-grade IPMN and a more than fourfold increased risk for invasive IPMN.

"If we continue using the more conservative cutoff point of 10-mm dilation for deciding when to remove these cysts, this study suggests we will miss a lot of people who will go on to develop cancer," Beckman commented in a press statement.

Beckman told Medscape Medical News that this is important because IPMNs in cysts represent "the only type of precancerous lesion in pancreatic cancer that can be identified before it becomes cancer."

Because few symptoms indicate the presence of IPMNs, they are usually detected incidentally during, for example, CT of the abdomen.

However, "If we do notice something like this incidentally, then we have some data that show that even these incidental lesions that have significant dilation are at risk of pancreatic cancer," Beckman said.

This can then form the basis of a conversation with the patient and their family as to whether to proceed to surgery.

Beckman said: "It's not an operation that has no risk, so it's always a conversation about weighing the risks and benefits of having the operation vs ongoing surveillance.

"But at this point, we feel the risk is high enough with this mid-range of >5 mm dilatation that we would recommend this to patients who are appropriate for an operation," he said.

Second Most Common Cause of Cancer Death

It is predicted that pancreatic cancer will become the second most common cause of cancer death by 2030.

Beckman explained that this is partly due to a slight increase in the incidence of the disease.

The main reason, however, is that there have been "great strides" in the management of lung, colon, breast, and prostate cancer, "whereas we're not progressing at the same rate in pancreatic cancer, mainly because of the difficulties with the aggressiveness of the cancer," he said.

Until recently, it was not possible to predict who would develop pancreatic cancer other than individuals who have a family history of the disease or rare genetic syndromes.

It has been shown, however, that some pancreatic cystic neoplasms (PCNs), which are seen in 20% to 30% of the population, are associated with the development of cancer.

In particular, IPMNs, which account for around half of PCNs, can progress from adenoma with low-grade dysplasia to cancer. The risk increases over time.

Because only a small minority of patients with IPMNs experience progression to cancer and because pancreatic surgery is associated with high perioperative morbidity, guidelines recommend that, before offering resection, the risk of developing cancer be assessed using radiologic and clinical criteria.

There is disagreement, however, as to what these criteria should be.

For example, the International Cancer of the Pancreas Screening Consortium recommends the surgical removal of cysts when dilatation of the MPD is ≥10 mm, whereas the European Study Group on Cystic Tumours of the Pancreas indicates that a diameter ≥5 mm is a relative indication for surgery.

Study Details

The study involved a retrospective analysis of patients who underwent pancreatic resection for IPMN at two centers between 2004 and 2017.

The team collated data on patient sex, age, body mass index, smoking history, diabetes status, family history of pancreatic cancer, abdominal symptoms, IPMN radiologic characteristics, and serum levels of the tumor marker Ca 19–9.

The team excluded from the study patients found to have concomitant pancreatic cancer and also patients for whom that could not be established. The researchers then assessed 796 patients (51.8% women).

The mean age of the patents was 68.8 years. The majority (58.2%) underwent pancreaticoduodenectomy; 28.6% underwent distal pancreatectomy; and 11% underwent total pancreatectomy.

Information regarding complete preoperative workup was available for 741 patients. Among those patients, the diameter of the MPD was <5 mm in 41.2%; from 5 mm – 9.9 mm in 38.6%; and ≥10 mm in 20.2%. In 19.9% of patients, the maximum diameter was >40 mm.

Serum levels of Ca 19–9 were abnormally high in 43.3% of patients, and 40.2% had high-grade or invasive IPMN on histologic analysis.

Univariate analysis indicated that male sex, age >70 years, high serum Ca 19–9 levels, jaundice, weight loss, diabetes mellitus, main-duct or mixed-type IPMN, single lesions, and a clinically relevant lesion in the pancreatic head were all associated with invasive IPMN.

In contrast, increasing dilatation of the MPD was strongly associated with both high-grade and invasive IPMN. A diameter ≥10 mm was linked to a twofold increased risk for high-grade IPMN and a sixfold increased risk for invasive IMPN, vs a diameter <5 mm.

On multivariate analysis, only MPD dilatation was significantly and positively associated with both high-grade and invasive IPMN (P < .001 for both).

In comparison with dilatation <5 mm, dilation of 5 mm – 9.9 mm was associated with an increased risk for both high-grade IPMN (odds ratio [OR], 2.74) and invasive IPMN (OR, 4.42).

For dilation ≥10 mm, the risk for high-grade IPMN vs dilation <5 mm was even higher (OR, 6.57). For invasive IPMN among these patients, the OR was 15.07.

Further analysis indicated that MPD dilatation of 5–7 mm was the most accurate cutoff for identifying patients at the highest risk for high-grade and invasive IPMN.

The team writes that their study confirms that "even small pancreatic dilatation is associated with a significantly increased risk of high grade/invasive IPMN" and that their findings support a proposed recommendation in the European guidelines that such lesions be considered for surgical resection.

Noting, however, that the diameter of the MPD cannot be used to distinguish between high-grade and invasive IMPN, they call for more studies to help "improve the ability to shift from cancer surgery to preemptive surgery."

The research was supported by the National Cancer Institute, Cancerfonden Sweden, and ALF Medel Stockholm. The authors have disclosed no relevant financial relationships.

Ann Surg. Jan 18, 2019. doi: 10.1097/SLA.0000000000003174. Abstract

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