Impact of age, comorbidities and relevant changes on surveillance strategy of intraductal papillary mucinous neoplasms: a competing risk analysis.

OBJECTIVE: Cost-effectiveness of surveillance for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. We combined different categories of risks of IPMN progression and of IPMN-unrelated mortality to improve surveillance strategies. DESIGN: Retrospective analysis of 926 presumed BD-IPMNs lacking worrisome features (WFs)/high-risk stigmata (HRS) under surveillance. Charlson Comorbidity Index (CACI) defined the severity of comorbidities. IPMN relevant changes included development of WF/HRS, pancreatectomy or death for IPMN or pancreatic cancer. Pancreatic malignancy-unrelated death was recorded. Cumulative incidence of IPMN relevant changes were estimated using the competing risk approach. RESULTS: 5-year cumulative incidence of relevant changes was 17.83% and 1.6% developed pancreatic malignancy. 5-year cumulative incidences for IPMN relevant changes were 13.73%, 19.93% and 25.04% in low-risk, intermediate-risk and high-risk groups, respectively. Age ≥75 (HR: 4.15) and CACI >3 (HR: 3.61) were independent predictors of pancreatic malignancy-unrelated death. 5-year cumulative incidence for death for other causes was 15.93% for age ≥75+CACI >3 group and 1.49% for age <75+CACI ≤3. 5-year cumulative incidence of IPMN relevant changes were 13.94% in patients with age <75+CACI ≤3 compared with 29.60% in those with age ≥75+CACI >3. In this group 5-year rate of malignancy-free patients was 95.56% with a 5-year survival of 79.51%. CONCLUSION: Although it is not uncommon the occurrence of changes considered by current guidelines as relevant during surveillance of low risk BD-IPMNs, malignancy rate is low and survival is significantly affected by competing patients' age and comorbidities. IPMN surveillance strategy should be tailored based on these features and modulated over time.

Surveillance for Presumed BD-IPMN of the Pancreas: Stability, Size, and Age Identify Targets for Discontinuation.

BACKGROUND & AIMS: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance. METHODS: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer. RESULTS: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5). CONCLUSIONS: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm.

High-risk Pancreatic Anastomosis Versus Total Pancreatectomy After Pancreatoduodenectomy: Postoperative Outcomes and Quality of Life Analysis.

OBJECTIVE: To evaluate TP as an alternative to PD in patients at high-risk for popf. BACKGROUND: Outcomes of high-risk PD (HR-PD) and TP have never been compared. METHODS: All patients who underwent PD or TP between July 2017 and December 2019 were identified. HR-PD was defined according to the alternative fistula risk score. Postoperative outcomes (primary endpoint), pancreatic insufficiency, and quality of life after 12 months of follow-up (QoL) were compared between HR-PD or planned PD intraoperatively converted to TP (C-TP). RESULTS: A total of 566 patients underwent PD and 136 underwent TP during the study period. One hundred one (18%) PD patients underwent HR-PD, whereas 86 (63%) TP patients underwent C-TP. Postoperatively, the patients in the C-TP group exhibited lower rates of postpancreatectomy hemorrhage (15% vs 28%), delayed gastric emptying (16% vs 34%), sepsis (10% vs 31%), and Clavien-Dindo ≥3 morbidity (19% vs 31%) and had shorter median lengths of hospital stay (10 vs 21 days) (all P < 0.05). The rate of POPF in the HR-PD group was 39%. Mortality was comparable between the 2 groups (3% vs 4%). Although general, cancer- and pancreas-specific QoL were comparable between the HR-PD and C-TP groups, endocrine and exocrine insufficiency occurred in all the C-TP patients, compared to only 13% and 63% of the HR-PD patients, respectively, and C-TP patients had worse diabetesspecific QoL. CONCLUSIONS: C-TP may be considered rather than HR-PD only in few selected cases and after adequate counseling.

State-of-the-art surgical treatment of IPMNs.

BACKGROUND: A "pandemic" of incidentally discovered pancreatic cyst neoplasms (PCNs) is ongoing. Among PCNs, intraductal papillary mucinous cystic neoplasms (IPMNs) are the most common and with their complex biology could represent a precursor lesion of pancreatic cancer. Although multiple guidelines exist to guide their treatment, there are still many "gray areas" on indications for surgery for IPMNs. METHODS: The current indications for surgery of IPMNs were reappraised, considering potential discrepancies between available evidence and guidelines policies. The practice at a high-volume center for the diagnosis and treatment of PCN was presented and discussed. RESULTS: Most IPMNs do not and will never require surgery, as they won't progress to malignancy. The current literature is solid in identifying high-grade dysplasia (HGD) as the right and timely target for IPMN resection, but how to precisely assess its presence remains controversial and guidelines lack of accuracy in this regard. Multiple tumorigenic pathways of progression of IPMNs exist, and their knowledge will likely lead to more accurate tests for malignancy prediction in the future. CONCLUSIONS: The surgical management of IPMNs still is a matter of debate. Indication for resection should be considered only in highly selected cases with the ideal target of HGD. Clinicians should critically interpret the guidelines' indications, refer to a multidisciplinary team discussion, and always consider the outcome of an adequate counselling with the patient.

Pancreatic cystic neoplasms: Still high rates of preoperative misdiagnosis in the guidelines and endoscopic ultrasound era.

BACKGROUND: A wrong diagnosis of nature is common in pancreatic cystic neoplasms. The aim of the current study is to reappraise the diagnostic errors for presumed pancreatic cystic neoplasms in patients undergoing surgery. METHODS: All pancreatic resections for presumed pancreatic cystic neoplasms following international guidelines between 2011 and 2020 were analyzed. Misdiagnosis was defined as the discrepancy between preoperative diagnosis of nature and final pathology. Mismatch was defined as the discrepancy between the preoperative suspect of malignancy (or its absence) and final pathology. RESULTS: A total of 601 patients were included. Endoscopic ultrasound was performed in 301 (50%) patients. Overall misdiagnosis and mismatch were 19% and 34%, respectively, with no significant benefit for those patients who underwent endoscopic ultrasound. The highest rate of misdiagnosis was reached for cystic neuroendocrine tumors (61%) and the lowest for solid pseudopapillary tumors (6%). Several diagnostic errors had clinical relevance, including 7 (13%) presumed serous cystic neoplasms eventually found to be other malignant entities, 50 (24%) intraductal papillary mucinous neoplasms with high-risk stigmata revealed to be non-malignant, and 38 (33%) intraductal papillary mucinous neoplasms without high-risk stigmata revealed to be malignant at final pathology. A preoperative presumption of malignant mucinous cystic neoplasm was correct in only 20 (16%) patients. CONCLUSIONS: Despite not always being clinically relevant, diagnostic errors are still common among resected pancreatic cystic neoplasms when applying international guidelines. New diagnostic tools beyond endoscopic ultrasound are needed to refine the diagnosis of those lesions at higher risk for unnecessary surgery or accidentally observed, nevertheless being malignant.