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Invasive features, positive margins tied to worse outcome of precancerous pancreas lesions

Annals of Surgery
Reuters Health - 16/10/2020 - Invasive pathology and positive surgical margins are associated with worse outcomes after resection of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, researchers in South Korea report.

"Outcomes of survival and recurrence differed according to initial pathology and margin status after resection in patients with IPMN," Dr. Hyeong Seok Kim of Seoul National University College of Medicine told Reuters Health by email.

"However, even in patients with low-grade dysplasia (LGD) or high-grade dysplasia (HGD), regular follow-up is required after resection of the lesions for the possibility of recurrence after five years and development of pancreatic ductal adenocarcinoma (PDAC) in the pancreas," he said.

IPMNs are precancerous lesions of the pancreas, and several studies have sought to identify risk factors to support decisions regarding which patients should undergo surgical resection. Little is known, however, about the course of patients who undergo resection.

Dr. Kim and colleagues used data from 577 consecutive patients who underwent surgery for IPMN to evaluate factors associated with recurrence and prognosis according to pathology and margin status.

Among the 548 patients included in the analysis, 353 had LGD, 78 had HGD, and 117 had invasive IPMN pathology.

After a median follow-up of 56 months, 50 patients (9.1%) developed recurrences, including six patients (1.7%) with LGD, four patients (5.1%) with HGD and 40 patients (34.2%) with invasive IPMN, the researchers report in Annals of Surgery.

Recurrence rates were higher among patients with positive margins than among patients with R0 resection, regardless of pathology.

Cumulative recurrence rates at five years were significantly higher in patients with invasive IPMN (37.6%) than in patients with LGD (0.7%) or HGD (4.3%), and recurrence risk increased continuously even after five years from resection in all three groups.

In multivariate analysis, invasive IPMN pathology was associated with an 18-fold increased risk of recurrence, and malignant margin was associated with a 2.6-fold increased risk of recurrence. Elevated CA19-9 was also associated with a significant 2.5-fold increased risk of recurrence.

Five-year survival rates were significantly worse among patients with invasive IPMN (48%) than among those with LGD (89%) or HGD (84%) and among patients with malignant margins (31%) than those with LGD margins (83%) or negative margins (81%).

Malignant margin, N1 stage, venous invasion, chemotherapy, and elevated CA19-9 were independent predictors of worse disease-free survival.

Among the 431 patients with noninvasive IPMN, four developed extrapancreatic recurrences: two patients who received supportive care due to poor general conditions and one who received chemotherapy died within several months; one patient with local recurrence of a mass around the superior mesenteric vein underwent excision and remained alive.

"According to the American Gastroenterological Association guidelines for the management of IPMN, surveillance of pancreatic cysts can be discontinued if there has been no significant change after 5 years, and surveillance of pancreatic cysts without high-grade dysplasia or invasive IPMN at surgical resection is extremely unlikely to be cost-effective," Dr. Kim said.

"However, results of our study indicate that even patients with low-grade dysplasia or high-grade dysplasia should undergo lifelong postoperative surveillance for any possibility of disease recurrence or development of a new pancreatic cancer, consistent with European guidelines on IPMN, which also recommend lifelong surveillance following resection."

He added, "Invasive IPMN developed more recurrences and had worse survival than low-grade dysplasia or high-grade dysplasia, indicating the need for more efficient postoperative treatment strategies including the novel adjuvant chemotherapy regimen for invasive IPMN."

"Malignant margins, which included margins with high-grade dysplasia and invasive IPMN, were associated with a higher cumulative risk of recurrence and worse prognosis. This margin status, therefore, needs additional resection to achieve negative, or at least low-grade dysplasia, margin status to guarantee better survival and recurrence outcomes," Dr. Kim said. "Otherwise, postoperative concurrent chemoradiotherapy should be considered for local control of the disease."

By Will Boggs MD

SOURCE: https://bit.ly/2S0fs0s Annals of Surgery, online September 15, 2020.

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