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.

It is not necessary to resect all mucinous cystic neoplasms of the pancreas: current guidelines do not reflect the actual risk of malignancy.

BACKGROUND: Mucinous Cystic Neoplasms (MCN) of the pancreas are premalignant cysts for which current guidelines support pancreatic resection. The primary aim of this systematic review and meta-analysis is to define the pooled rate of malignancy for MCN. METHODS: A systematic review of eligible studies published between 2000 and 2021 was performed on PubMed and Embase. Primary outcome was rate of malignancy. Data regarding high-risk features, including cyst size and mural nodules, were collected and analyzed. RESULTS: A total of 40 studies and 3292 patients with resected MCN were included in the final analysis. The pooled rate of malignancy was 16.1% (95%CI 13.1-19.0). The rate of malignant MCN in studies published before 2012 was significantly higher than that of studies published after recent guidelines were published (21.0% vs 14.9%, p < 0.001). Malignant MCN were larger than benign (mean difference 25.9 mm 95%CI 14.50-37.43, p < 0.001) with a direct correlation between size and presence of malignant MCN (R2 = 0.28, p = 0.020). A SROC identified a threshold of 65 mm to be associated with the diagnosis of malignant MCN. Presence of mural nodules was associated with the diagnosis of a malignant MCN (OR = 4.34, 95%CI 3.00-6.29, p < 0.001). CONCLUSION: Whereas guidelines recommend resection of all MCN, the rate of malignancy in resected MCN is 16%, implying that surveillance has a role in most cases, and that surgical selection criteria are warranted. Size and presence of mural nodules are significantly associated with an increased risk of malignant degeneration, small MCN and without mural nodules can be considered for surveillance.

Serous Cystic Neoplasms of the Pancreas Management in the Real-world: Still Operating on a Benign Entity.

OBJECTIVE: Our aim is to provide a real-life picture of serous cystic neoplasms (SCNs) management once a presumptive diagnosis is made. SUMMARY OF BACKGROUND DATA: SCNs of the pancreas are invariably benign entities. While consensus about their management is lacking, surgical resection still plays a role. METHODS: Presumed SCNs evaluated from 1990 to 2018 were included. Indications for surgery, predictors of resection, rate, and predictors of misdiagnosis in the surgical cohort and time trends of management strategies were the main outcomes. RESULTS: A total of 672 presumed SCNs were included. Presence of symptoms (37%) and large size (34.1%) were the most frequent indications for surgery. Symptoms (60.4% vs 19.0%, P < 0.001), size (45 vs 30 mm, P < 0.001), solid components (19.7% vs 6.2%, P < 0.001), thick walls (14.4 vs 5.6%, P = 0.001) and main pancreatic duct dilation (13.4% vs 5.6%, P = 0.004) were associated with upfront resection (n = 134, 19.9%). Upfront resection decreased over time and 15.4% of patients eventually crossed over to surgery. Increase in size (6.9 vs 1.3 mm/yr), development of symptoms (25.3% vs 3.4%, P < 0.001), solid component (6.0% vs 1.4%, P = 0.010) or jaundice (3.6% vs 0.7%, P = 0.028) were associated with crossing over to surgery. Major morbidity and mortality occurred in 17.1% and 1.7% of patients, respectively. Misdiagnosis occurred mostly in case of macrocystic/unilocular lesions of the body-tail. CONCLUSIONS: In the real-life scenario, SCNs still represent an indication for surgery particularly once large and symptomatic. During surveillance, resection occurs mostly in younger individuals for body/tail lesions. Evidence-based consensus on appropriate indications for surgery is urgently needed.

The use of a mobile application to disseminate guidelines on cystic neoplasms of the pancreas - A snapshot study of 1000 case-simulations.

BACKGROUND: No data exist on the actual application of pancreatic cystic neoplasm (PCN) guidelines in clinical practice. AIM: Disseminate knowledge on existing PCN guidelines and determine which guidelines are prospectively chosen by iCyst app users for different case scenarios. METHODS: iCyst is a digital tool providing access to the three main existing guidelines (European, IAP, and AGA). Through a case simulation system, for one year, the app prospectively registered users' guideline choices. RESULTS: During the study period, 276 users downloaded iCyst and entered 1020 completed simulations. Most users were European (88%) and were either surgeons (69%) or gastroenterologists (29%). Six different representative scenarios were identified. Overall, the European guidelines were the most commonly preferred (52%). In 16% of cases, the users did not choose any of the available guidelines. CONCLUSION: Digital apps can be used to disseminate guidelines in clinical practice. Guideline dissemination might serve as the basis for future research lines on specific clinical scenarios that iCyst identifies as critical.

Progression vs Cyst Stability of Branch-Duct Intraductal Papillary Mucinous Neoplasms After Observation and Surgery.

Importance: The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information. Objective: To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations. Design, Setting, and Participants: The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months). Main Outcomes and Measures: Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination. Results: A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) 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 [95% CI, 2.94-87.40]; P = .001). Conclusions and Relevance: These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.

"Trivial" Cysts Redefine the Risk of Cancer in Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Potential Target for Follow-Up Discontinuation?

OBJECTIVES: The management of small and incidental branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) still is of concern. The aim is assessing the safety of a surveillance protocol through the evaluation of their progression to malignancy. METHODS: All presumed BD-IPMNs observed from 2000 to 2016 were included. Only patients presenting without worrisome features (WFs) and high-risk stigmata (HRS) at diagnosis were included. Development of WF, HRS, pancreatic cancer (PC), and survival were analyzed. BD-IPMNs were defined as trivial in the continuing absence of WF/HRS after 5 years of surveillance. The age-specific standardized incidence ratio of PC in the general population was used for comparison. RESULTS: A total of 1,036 BD-IPMNs without WF/HRS at diagnosis were included, 4.2% developed WF or HRS, and 1.1% developed PC after a median of 62 months. The median cyst growth rate was 0 mm/yr. A growth rate ≥2.5 mm/yr and the development of WF resulted independent predictors of PC. The standardized incidence ratio of PC for trivial BD-IPMN (n = 378) was 22.45 (95% confidence interval 8.19-48.86), but considering only patients aged >65 years (n = 198), it decreased to 3.84 (95% confidence interval 0.77-11.20). DISCUSSION: Surveillance of the vast majority of presumed BD-IPMNs is safe, as the risk of PC is comparable to postoperative mortality of pancreatic surgery. A growth rate ≥2.5 mm/yr is the main predictor of PC, reinforcing the role of repeated observations. A trivial BD-IPMN in patients aged >65 years might not increase the risk of developing PC compared with general population, identifying potential targets for follow-up discontinuation.