Management of Intraductal Papillary Mucinous Neoplasms Still Unclear

By Marilynn Larkin

May 26, 2021

NEW YORK (Reuters Health) - Two studies addressing the management of intraductal papillary mucinous neoplasms (IPMNs) conclude that current guidelines don't provide enough evidence on when to observe and when to excise them.

Both studies were published in JAMA Surgery.

In one study, Dr. Markus Buchler of Heidelberg University Hospital and colleagues evaluated more than 1,400 IPMN patients who underwent pancreatic resection at a single center from 2001-2019. Based on preoperative imaging and medical history, timeliness of resection was determined to be too early (adenoma and low-grade dysplasia); timely (intermediate-grade dysplasia and in situ carcinoma); and too late (invasive cancer).

They found that in one-third of cases, malignant disease had already progressed to an advanced stage.

The authors conclude, "Until the true biological nature of IPMN is clarified, a precise estimation of the time to progression (becomes) possible and more accurate evidence-based guidelines are established, the blind pursuit of a watch-and-wait policy cannot be justified."

Dr. Joe Hines of the David Geffen School of Medicine at UCLA, coauthor of an accompanying editorial, commented in an email to Reuters Health, "IPMNs are identified with some frequency on CT scans or other imaging of the abdomen. Most commonly, these are benign cysts that are unlikely to become cancer over time."

"Identifying cysts that are or will become cancer remains a challenge," he said. "This study suggests that current IPMN management guidelines may not be sufficient and without improved diagnostic studies, more of these should be considered for removal," he said. "Whether this conclusion is true on a broader scale is in unknown."

"For some cysts, particular features require they be removed, but most do not manifest these and identifying which in this category require removal is uncertain," he said. "Most commonly, these are followed with serial imaging, looking for any changes that increase the likelihood a cancer is present."

Indeed, Dr. Giovanni Marchegiani of Verona University Hospital Trust in Italy, lead author of the other study, told Reuters Health by email, "When evaluating a patient with a branch-duct IPMN (BD-IPMN), what matters most is the information that we get from repeated observations. None of the so-called 'worrisome features' were associated with high-grade dysplasia (HGD) if considered statically at the time of surgery."

Worrisome features include, among others, acute pancreatitis, cyst of at least 30 mm, thickened/enhancing cyst wall, main pancreatic duct measuring 5.0 to 9.9 mm, and cyst growth of at least 5 mm in two years.

For the surveillance study, Dr. Marchegiani and colleagues studied data on 292 BD-IPMN patients (median age, 64; 53%, men) enrolled in a surveillance program from 2000 - 2019 (median perioperative surveillance, 37 months).

During surveillance, 9.2% developed a worrisome feature after five years, and 16.7% developed high-risk stigmata (HRS). At final pathological evaluation, 36.6% had HGD or invasive cancer, and 5.5% had IPMNs with concomitant pancreatic ductal adenocarcinoma.

Rates of HGD and invasive cancer differed significantly between those without worrisome features (27.3%) and those developing HRS from a previous worrisome feature (61.9%).

Developing an additional worrisome feature (odds ratio, 3.24) or an HRS from a baseline worrisome feature (OR, 2.87) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04).

Dr. Marchegiani noted, "Evidence supporting the safety of surveillance for BD-IPMN is in the literature, and it comes mostly from observational series, as it would be unlikely to find that surveillance is safe looking at cohorts of resected patients."

"Both our data and that from the Heidelberg team mainly show how inadequate our management of these tumors still is," he said. "Therefore, at the end of 2020, we launched an international consortium of more than 40 institutions worldwide on IPMNs called 'Verona 2020 EBM on IPMN.'"

"One of the first studies born out of this consortium is an international study on BD-IPMN under surveillance, aiming at identifying a subset of patients where surveillance can be safely discontinued," he said. "More than 20 centers across the world have joined, and we hope to present the results during 2022. Only in this way, we'll hopefully be able, one day, to be better doctors for our patients."

Dr. Buchler did not respond to requests for a comment.

SOURCES: https://bit.ly/3ukSF0b, https://bit.ly/3vkLMxi and https://bit.ly/2SvTKoQ JAMA Surgery, online May 19, 2021.

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