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.

Surgery for Intraductal Papillary Mucinous Neoplasms of the Pancreas: Preoperative Factors Tipping the Scale of Decision-Making.

BACKGROUND: Decision-making in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas depends on scaling the risk of malignancy with the surgical burden of a pancreatectomy. This study aimed to develop a preoperative, disease-specific tool to predict surgical morbidity for IPMNs. METHODS: Based on preoperative variables of resected IPMNs at two high-volume institutions, classification tree analysis was applied to derive a predictive model identifying the risk factors for major morbidity (Clavien-Dindo ≥3) and postoperative pancreatic insufficiency. RESULTS: Among 524 patients, 289 (55.2%) underwent pancreaticoduodenectomy (PD), 144 (27.5%) underwent distal pancreatectomy (DP), and 91 (17.4%) underwent total pancreatectomy (TP) for main-duct (18.7%), branch-duct (12.6%), or mixed-type (68.7%) IPMN. For 98 (18.7%) of the patients, major morbidity developed. The classification tree distinguished different probabilities of major complications based on the type of surgery (area under the surve [AUC] 0.70; 95% confidence interval [CI], 0.63-0.77). Among the DP patients, the presence of preoperative diabetes identified two risk classes with respective probabilities of 5% and 25% for the development of major morbidity, whereas among the PD/TP patients, three different classes with respective probabilities of 15%, 20%, and 36% were identified according to age and body mass index (BMI). Overall, history of diabetes, age, and cyst size segregated three different risk classes for new-onset/worsening diabetes. CONCLUSIONS: In presumed IPMNs, the disease-specific risk of major morbidity and pancreatic insufficiency can be determined in the preoperative setting and used to personalize the possible surgical indication. Age and overweight status in case of PD/TP and diabetes in case of DP tip the scale toward less aggressive clinical management in the absence of features suggestive for malignancy.

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.

The Sequential Radiographic Effects of Preoperative Chemotherapy and (Chemo)Radiation on Tumor Anatomy in Patients with Localized Pancreatic Cancer.

BACKGROUND: The incidence and magnitude of indicators of radiographic response of pancreatic cancer to systemic chemotherapy and (chemo)radiation administered prior to anticipated pancreatectomy are unclear. METHODS: Sequential computed tomography scans of 226 patients with localized pancreatic cancer who received chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) or gemcitabine and nanoparticle albumin-bound paclitaxel (GA) with or without (chemo)radiation and who subsequently underwent surgery with curative intent from January 2010 to December 2018 at The University of Texas MD Anderson Cancer Center and Verona University Hospital were re-reviewed and compared. RESULTS: Overall, 141 patients (62%) received FOLFIRINOX, 70 (31%) received GA, and 15 (7%) received both; 164 patients (73%) received preoperative (chemo)radiation following chemotherapy and prior to surgery; and 151 (67%), 70 (31%), and 5 (2%) patients had Response Evaluation Criteria in Solid Tumors (RECIST) stable disease, partial response, and progressive disease, respectively. The tumors of 29% of patients with borderline resectable or locally advanced cancer were downstaged after preoperative therapy. Radiographic downstaging was more common with chemotherapy than with (chemo)radiation (24% vs. 6%; p = 0.04), and the median tumor volume loss after chemotherapy was significantly greater than that after (chemo)radiation (28% vs. 17%; p < 0.01). CONCLUSIONS: Less than one-third of patients treated with FOLFIRINOX or GA with or without (chemo)radiation experienced either RECIST partial response or radiographic downstaging prior to surgery. The incidence of tumor downstaging was higher and the magnitude of tumor volume loss was greater following chemotherapy than after (chemo)radiation.

The management of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are one of the most common preneoplastic entities among pancreatic cystic neoplasms (PCN). Their incidence is increasing due to an extensive use of cross-sectional imaging, but management still remains controversial. Among IPMNs, the main duct (MD-IPMN) and mixed (MT-IPMN) types harbor a high risk of malignant degeneration requiring resection in most of cases. The branch duct type (BD-IPMN), on the other side, can be safely surveilled as surgical resection is limited to selected cases deemed at high risk of malignant progression according to specific clinical and radiological features. An accurate diagnosis and a correct assessment of malignant potential are often hard to achieve, and clinical management still relies on the experience of the gastroenterologist/surgeon that is called to choose between a major pancreatic resection burdened by high morbidity and mortality rates and a life-long surveillance. The purpose of this report is to summarize the available evidence supporting the current practice for the management of IPMN and to offer a useful practical guide from first observation to postoperative follow-up.

"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.

The role of age in pancreatic intraductal papillary mucinous neoplasms of the pancreas: Same risk of death but different implications for management.

BACKGROUND: Current guidelines do not address the role of age in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. AIM: To evaluate whether clinical features and risk for malignancy are affected by patient's age at diagnosis. METHODS: In total, 2189 IPMNs, both surgically resected or surveilled, were dichotomized according to a 50-year-old cutoff and compared in terms of pathological features, cumulative risk of developing high-risk stigmata (HRS), overall survival (OS) and disease-specific survival (DSS). RESULTS: Patients <50 years had more frequent abdominal pain (38.5 vs. 22.4%; p < 0.01) and acute pancreatitis (20.4 vs. 9.3%; p < 0.01) at presentation. Patients ≥50 years old had more multifocal IPMNs (50 vs. 36.9%; p < 0.01), HRS (8.5% vs. 4.3%; p = 0.04) and invasive IPMNs (26.6% vs. 17.3%; p = 0.03) when resected. Moreover, patients ≥50 years old had a significantly higher cumulative risk of developing HRS over time, and a significantly lower OS, but similar DSS when compared with those <50 years old. CONCLUSIONS: IPMNs diagnosed in older patients are more likely to progress to HRS despite the fact that cancer-related death is not affected by age. The follow-up schedule should not be adjusted according to age, but one should take into account that IPMNs in younger individuals have more time to progress toward malignancy.