The safety and benefit of pancreatic juice cytology under ERCP in IPMN patients

BackgroundInternational consensus guidelines 2012 for intraductal papillary mucinous neoplasia (IPMN), defined two characteristics: high-risk stigmata (HRS) and worrisome features (WF). Patients with WF require detailed examination including cytology. However, routine endoscopic retrograde cholangiopancreatography (ERCP) for cytology is not recommended in the guidelines due to risk of post-ERCP pancreatitis (PEP). Our aim was to clarify what types of IPMN were susceptible for PEP and gain benefit of ERCP.Patients/methodsWe examined 138 consecutive IPMN patients who underwent ERCP in our hospital, retrospectively. Patients were classified into HRS, WF and the others (N) based on imaging findings before ERCP. We assessed pancreatic juice cytology, PEP frequency and rate of malignant IPMN at 12 months after ERCP.ResultsThe rates of cytological malignancy were 0% (N), 4.8% (WF) and 19.5% (HRS). The PEP frequency was 14.5%, and these risk factors were branch duct (BD)-IPMN, body/tail cysts and brush cytology by multivariate logistic analysis. The rates of malignant IPMN were 0% (N), 16.4% (WF) and 48.8% (HRS). Furthermore, we examined patients with WF in detail. The PEP frequency/rate of malignancy were 3.6%/23.1% in patients with main pancreatic duct (MPD) dilatation (5–9 mm), and the sensitivity of cytology was 33.3%. On the other hand, the PEP frequency/rate of malignancy were 17.2%/0% in patients with BD-IPMN fulfilling only cyst size over 30 mm.ConclusionsRoutine ERCP for IPMN, especially for BD-IPMN, is not recommended. ERCP may be beneficial for WF patients with MPD dilatation based on a balance between PEP risk and presence of malignancy.     

Long-term follow-up of branch-duct intraductal papillary mucinous neoplasms with No change in first 5 Years of diagnosis

BackgroundDiscontinuation of branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) surveillance after 5 years of no change remains controversial. Long-term outcomes of BD-IPMN without significant changes in the first 5 years were evaluated.MethodsWe performed a multi-center retrospective analysis of patients with BD-IPMN diagnosis from 2005 to 2011 (follow-up until 2017). Significant changes were defined as pancreatic cancer (PC), pancreatectomy, high-risk stigmata (HRS), worrisome features (WF) and worrisome EUS features (WEUS).ResultsOf 982 patients who had no significant changes, 5 (0.5%), 7 (0.7%), 99 (10.1%), 4 (0.4%) patients developed PC, HRS, WF, WEUS, respectively, post-5 years. PC and HRS/WF/WEUS incidences at 12 years were 1.0% and 29.0%, respectively. Patients that developed HRS/WF/WEUS had larger cyst size in first 5 years compared to those that did not [16 (12–23) vs. 12 (9–17) mm, p = 0.0001], cyst size of >15 mm having higher cumulative incidence of HRS/WF/WEUS. PC mortality was 0.8%; all-cause mortality was 32%. Incidence of mortality due to PC was higher in HRS/WF/WEUS group, p < 0.0001. The mortality rate at 12 years for ACCI (age-adjusted Charlson Comorbidity Index) of ≤3, 4–6, and ≥7 were 3.5%, 19.9%, and 57.6% (p < 0.0001), respectively.ConclusionsIncidence of PC in patients with BD-IPMN without significant changes in first 5 years of diagnosis remains low at 1.0%. Incidence of HRS/WF/WEUS was higher at 29.0%. PC-related mortality was higher in HRS/WF/WEUS group. These risks should be weighed against patients’ overall mortality (utilizing scoring systems such as ACCI) when making surveillance decision of BD-IPMN beyond 5 years.     

Importance of each high-risk stigmata and worrisome features as a predictor of high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas

BackgroundHigh-risk stigmata (HRS) and ‘worrisome features’ (WFs) are defined as predictive factors for malignancies of intraductal papillary mucinous neoplasms (IPMNs). We performed this study to determine the importance and odds ratio (OR) of each HRS and WFs as predictors for high-grade dysplasia (HGD).MethodsWe analyzed 295 patients who underwent pancreatectomy for branch duct and mixed-type IPMN, and evaluated the association between HRS and WFs (as defined by the ‘2017 Fukuoka Consensus Guidelines’) and HGD.ResultsThe proportions of patients with low-grade dysplasia (LGD), HGD, and invasive carcinoma were 47%, 28%, and 25%, respectively. Multivariate analysis comparing patients with LGD and HGD using all HRS and WFs revealed that an enhancing mural nodule ≥5 mm (OR: 4.1), pancreatitis (OR: 2.2), and thickened/enhancing cyst walls (OR: 2.2) were independent predictive factors for HGD. Based on the OR (the former factor is two points and the latter two factors are each one point), the incidence of HGD in patients with none (n = 43), one (n = 82), two (n = 25), three (n = 52), and four (n = 19) of these predictive factors were 9%, 26%, 52%, 62%, and 63%, respectively. Assuming a score of one or higher as a surgical indication, the sensitivity, specificity, positive predict value, and negative predict value of HGD were 95, 38, 44, and 91%.ConclusionsOur derived scoring system using more important factors in HRS and WFs may be useful for predicting HGD and determining surgical indications of IPMN.     

New onset diabetes predicts progression of low risk pancreatic mucinous cysts

BackgroundPatients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts.MethodsWe evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method.ResultsThe 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5–57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%–20.2%), compared to only 0.8% (95%CI, 0.0%–2.3%) for patients without NODM. Among patients with the largest cysts (20–29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%–89.9%) compared to only 7.5% (95%CI, 1.6%–15.2%) for patients without NODM.ConclusionNew onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.     

Systematic review and meta-analysis of observational studies on BD-IPMNS progression to malignancy

BackgroundThe vast majority of presumed branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are referred to a surveillance program due to the relatively low risk of malignancy. We aim to evaluate all available data from observational studies focused on the risks of BD-IPMN progression and malignancy to provide vital insights into its management in clinical practice.MethodsA comprehensive search was conducted at PubMed, Cochrane, Web of Science and Embase for observational studies published before January 1st, 2020. The progression of BD-IPMN was defined as the development of worrisome features (WFs) or high-risk stigmata (HRS) during surveillance. Overall malignancy was defined as all malignancies, such as malignant IPMN, concomitant pancreatic ductal adenocarcinoma (PDAC) and other malignancies, including BD-IPMN with high-grade sec. Baltimore consensus 2015 or BD-IPMN with high-grade dysplasia (carcinoma in situ) sec. WHO 2010. A meta-analysis was performed to investigate the presence of a mural nodule as a possible predictor of malignancy.ResultsTwenty-four studies were included, with a total of 8941 patients with a presumed BD-IPMN. The progression rate was 20.2%, and 11.8% underwent surgery, 29.5% of whom showed malignancy at the final pathology. Of those, 78% had malignant IPMNs, and 22% had concomitant pancreatic cancer. Overall, 0.5% had distant metastasis. The meta-analysis showed that the risk of malignancy in the presence of a mural nodule >5 mm had a RR of 5.457 (95% CI 1.404–21.353), while a nonenhancing mural nodule or an enhancing mural nodule < 5 mm had a RR of 5.286 (95% CI 1.805–15.481) of harboring malignancy.ConclusionMost presumed BD-IPMNs entering surveillance do not become malignant. Of those submitted to surgery, concomitant PDAC adds to the overall risk of detecting malignancy.     

Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata

Background/ObjectivesAccording to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs.MethodsWe enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN.ResultsFifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45).ConclusionsLarge nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.     

A resected case of two branch duct-type intraductal papillary mucinous neoplasms showing different clinical courses after a two-year follow-up

The patient was a 60-year-old man without any particular complaints, but he underwent abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) due to a fatty liver, which revealed two similar cystic lesions regarded as branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) in the pancreatic body [BD-IPMN (b), 16 mm in size] and tail [BD-IPMN (t), 13 mm in size] without a “high-risk stigmata” or “worrisome features”. He subsequently received follow-up by MRCP every 6 months. Two years later, MRCP showed prominent dilation of the main pancreatic duct (MPD) and mural nodule formation within the dilated MPD adjacent to the BD-IPMN (b). Distal pancreatectomy specimens revealed that the BD-IPMN (b) was lined by low-papillary gastric mucinous epithelium with low-to-intermediate-grade dysplasia and involved the MPD, forming a malignant mural nodule showing pancreatobiliary-type IPMN. In contrast, the BD-IPMN (t) was lined by flat, monolayer columnar gastric mucinous epithelium without atypia, which suggested the possibility of a “simple mucinous cyst”. A genetic analysis showed KRAS mutation only in BD-IPMN (b). Differences in the histological and genetic findings between two similar BD-IPMNs in the present case may suggest what kinds of examinations should be performed in patients with BD-IPMNs without any worrisome features.     

Comorbidities Drive the Majority of Overall Mortality in Low-Risk Mucinous Pancreatic Cysts Under Surveillance

Background & AimsThe Charlson Comorbidity Index (CACI) has been suggested as a tool to determine comorbidity burden and guide management for patients with mucinous pancreatic cysts (Intrapapillary Mucinous Neoplasms and Mucinous Cystic Neoplasms), but has not been studied well among “low-risk” mucinous pancreatic cysts i.e. without worrisome features (WF) and high-risk stigmata (HRS). This study sought to determine the comorbidity burden among surveillance population of low-risk pancreatic cysts and provide their follow-up mortality outcomes.MethodsA single center study retrospectively reviewed a prospective pancreatic cyst database and included individuals with low-risk cysts undergoing serial imaging during 2016. Electronic medical records were reviewed to determine their baseline age-adjusted CACI (age-CACI). After 4 years, their progression to WF, disease specific (pancreatic malignancy-related, DSM), extra-pancreatic (EPM), and overall mortalities (OM) were determined using Kaplan-Meir Survival Analysis.Results502 individuals underwent prospective surveillance. The study included 440 individuals with low-risk suspected or presumed mucinous cysts and excluded 50 and 12 individuals with WF and HRS respectively. Over a median follow-up of 56 months, 12 WF progressions, 2 DSMs, 42 EPMs, and 44 OMs were observed. Baseline age-CACI had good predictive capacity for 4-year EPM (Area-Under Curve: 0.87; p< .0001). The median age-CACI of 4 enabled cohort stratification into Low (age-CACI <4) and High CACI (age-CACI ≥4) groups. A significantly higher OM (p< .001) was observed among the High CACI group as compared to the Low CACI group.ConclusionThrough real-time application of CACI to patient outcomes, our analysis supports incorporation of this comorbidity assessment tool in making shared surveillance decisions among low-risk pancreatic cyst population.     

Minimal main pancreatic duct dilatation in small branch duct intraductal papillary mucinous neoplasms associated with high-grade dysplasia or invasive carcinoma

BackgroundThe aim of this study was to determine the incidence of high-grade dysplasia (HGD) or invasive carcinoma in patients with small branch duct intraductal papillary mucinous neoplasms (BD-IPMNs).Methods923 patients who underwent surgical resection for an IPMN were identified. Sendai-negative patients were identified as those without history of pancreatitis or jaundice, main pancreatic duct size (MPD) <5 mm, cyst size <3 cm, no mural nodules, negative cyst fluid cytology for adenocarcinoma, or serum carbohydrate antigen 19-9 (CA 19-9) <37 U/L.ResultsBD-IPMN was identified in 388 (46.4%) patients and 89 (22.9%) were categorized as Sendai-negative. Overall, 68 (17.5%) of BD-IPMN had HGD and 62 (16.0%) had an associated invasive-carcinoma. Among the 89 Sendai-negative patients, 12 (13.5%) had IPMNs with HGD and only one patient (1.1%) had invasive-carcinoma. Of note, older age (OR 1.13, 95% CI 1.03–1.23; P = 0.008) and minimal dilation of MPD (OR 11.3, 95% CI 2.40–53.65; P = 0.002) were associated with high-risk disease in Sendai-negative patients after multivariable risk adjustment.ConclusionThe risk of harboring a high-risk disease remains low in small BD-IPMNs. However, Sendai-negative patients who are older than 65 years old and those with minimal dilation of MPD (3–5 mm) are at greater risk of high-risk lesions and should be given consideration to be included as a “worrisome feature” in a future guidelines update.     

International Consensus Guidelines parameters for the prediction of malignancy in intraductal papillary mucinous neoplasm are not properly weighted and are not cumulative

Background

The International Consensus Guidelines (ICG) stratify risk for malignancy in patients with intraductal papillary mucinous neoplasm (IPMN) into three progressive categories according to whether patients show ‘no criteria’, ‘worrisome features’ (WFs) or ‘high-risk stigmata’ (HRS).

Objectives

This study was conducted to test the hypothesis that type (clinical versus radiological) and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN.

Methods

A retrospective review of a prospectively maintained database of patients who underwent surgical resection for IPMN at a single, university-based medical centre during 1992–2012 was performed. Differences that achieved a P-value of <0.05 were considered significant.

Results

Of 362 patients, 340 were eligible for entry into the study and were categorized as demonstrating no criteria (n = 70), WFs (n = 185) or HRS (n = 85). Patients in the WFs group had higher rates of malignant and invasive IPMN than those in the no-criteria group [26.5% versus 4.3% (P < 0.0001) and 15.7% versus 4.3% (P = 0.02), respectively]. Patients in the HRS group had higher rates of malignant and invasive IPMN than those in the WFs group [56.5% versus 26.5% (P = 0.0001) and 42.4% versus 15.7% (P = 0.0001), respectively]. When radiological parameters only were considered for WFs versus HRS, no difference was found in rates of malignant or invasive IPMN. By contrast, when clinical parameters only were considered, patients in the HRS group had higher rates of malignant or invasive IPMN [66.7% versus 8.1% (P = 0.04) and 66.7% versus 2.7% (P = 0.01), respectively]. There was no stepwise increase in rates of malignant or invasive IPMN with the number of WFs. However, patients with only one WF had a lower risk for malignancy than patients with two or more WFs.

Conclusions

The type and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN.     

Age and cystic size are associated with clinical impact of endoscopic ultrasonography-guided fine-needle aspiration on the management of pancreatic cystic neoplasms

Objectives: The clinical impact of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in managing pancreatic cystic neoplasms (PCNs) remains controversial. The aim of this study was to identify which patients with PCNs would benefit from EUS-FNA.

Methods: A retrospective study was performed on patients with PCNs who underwent EUS-FNA between January 2009 and June 2018. A discordant or a consistent diagnosis after EUS-FNA was analyzed and was correlated with the clinical demographic data and cystic features. Predictors of the change in the diagnosis after EUS-FNA were analyzed.

Results: One hundred eighty-eight cases of PCNs were analyzed. EUS-FNA changed the diagnosis in 45.7% of all patients with PCNs and 54.5% patients with presumed branch ductal type intraductal papillary mucinous neoplasm (BD-IPMN) and impacted the recommendation in 35.6% of patients with PCNs and 50.5% patients with BD-IPMN. Patients with a discordant diagnosis after EUS-FNA were younger in age (54.8?±?12.6 vs. 61.2?±?14.2; p=.037) and had a cyst size larger than 3?cm than patients with a consistent diagnosis after EUS-FNA. The only worrisome feature (WF) that differed between patients with a discordant and a consistent diagnosis after EUS-FNA was the main pancreatic duct (MPD) between 5 and 9?mm (p=.013). In multivariate analysis, a cyst size >3?cm and age were independent predictors of diagnostic changes after EUS-FNA (OR: 5.33, 95% CI: 1.79–15.88, p?=?.003; OR: 0.96, 95% CI: 0.93–0.99, p = .031).

Conclusions: EUS-FNA made a significant change in the management of nearly half of the patients with PCNs, especially in younger patients and in patients with a cyst size larger than 3?cm.     

Cyst location and presence of high grade dysplasia or invasive cancer in intraductal papillary mucinous neoplasms of the pancreas: a seven institution study from the central pancreas consortium

Background

Traditionally, intraductal papillary mucinous neoplasms (IPMNs) of the pancreas with “high risk stigmata” (HRS) or “worrisome features” (WF) are referred for resection. We aim to assess if IPMN location is predictive of harboring either high grade dysplasia (HGD) or invasive cancer (IC).

Resection of pancreatic cystic neoplasms in recurrent acute pancreatitis prevents recurrent pancreatitis but does not identify more malignancies

BACKGROUNDRecurrent acute pancreatitis (RAP) may be a presenting feature of and an indication for resection of pancreatic cysts, including intra-ductal papillary mucinous neoplasm (IPMN). Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIMTo study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODSThis retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016. The prevalence of preoperative high-risk cyst features, and of neoplasia was compared between patients with and without RAP. To identify the cause of pancreatitis, all the patients had a detailed history of alcohol, smoking, medications obtained, and had cross-sectional imaging (contrast-enhanced computed tomography/magnetic resonance imaging) and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis. The incidence of RAP post-resection was the primary outcome.RESULTSIPMN accounted for 101 cases (58.7%) {[branch duct (BD) 59 (34.3%), main duct (MD) 42] (24.4%)}. Twenty-nine (16.9%) presented with RAP (mean 2.2 episodes): 15 had BD-IPMN, 8 MD-IPMN, 5 mucinous cystic neoplasm and 1 serous cystic neoplasm. Malignancy was similar among those with vs without RAP for all patients [6/29 (20.7%) vs 24/143 (16.8%)] and IPMN patients [6/23 (26.1%) vs 23/78 (29.5%)], although tended to be higher with RAP in BD-IPMN, [5/15 (33.3%) vs 3/44 (6.8%), P = 0.04]. At mean follow-up of 7.2 years, 1 (3.4%) RAP patient had post-resection RAP. The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02 (P < 0.0001). CONCLUSIONMalignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP. In addition, specific cyst charac-teristics were not clearly associated with RAP. The incidence of RAP was markedly decreased in almost all patients following cyst resection.     

Risk of additional pancreatic cancer in patients with branch duct intraductal papillary-mucinous neoplasm

Branch duct intraductal papillary-mucinous neoplasms of the pancreas (BD-IPMN) are being diagnosed with increasing frequency. Although BD-IPMN outcomes are generally good, pancreatic ductal adenocarcinoma (PDA) is found distant from the original BD-IPMN in about 3.3–9.2% of cases. These reports raise the question of whether a possible association exists between BD-IPMN and PDA. Recent findings from follow-up studies suggest that pancreases with BD-IPMNs have a high risk of developing additional pancreatic cancer, with standardized incidence ratios (SIRs) of 15.8- to 26-fold. These studies suggest that special attention should be paid to BD-IPMN patients who are ≥70 years. Furthermore, molecular evidence supports the hypothesis that field cancerization causing multiple primary neoplastic lesions exists in pancreases harboring IPMNs. Although more extensive studies are required to clarify the magnitude of this increased risk, clinicians should pay close attention to the development of PDA in patients with BD-IPMN, as well as to changes in BD-IPMN lesions.     

Main duct and mixed type intraductal papillary mucinous neoplasms without enhancing mural nodules: Duct diameter of less than 10 mm and segmental dilatation of main pancreatic duct are findings support surveillance rather than immediate surgery

ObjectiveThe guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMNs) recommend surgical resection of all main-duct (MD) and mixed-type IPMNs in surgically fit patients. We conducted this study to identify the rates of high-grade dysplasia (HGD) and invasive carcinoma according to the morphological features of the main pancreatic duct (MPD) in patients with MD and mixed IPMN.MethodsWe performed a retrospective study of 259 patients with histologically proven MD and mixed-type IPMNs who underwent surgery at six academic institutions.ResultsThe rate of HGD and invasive carcinoma was 11.1% (24/216) in patients without enhancing mural nodules (MNs) and 69.8% (30/43) in patients with MNs. Multivariate analysis showed that MPD diameter of ≥10 mm [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.155–5.505; P = 0.02], diffuse MPD dilatation (OR, 3.2; 95% CI, 1.152–8.998; P = 0.02), and presence of enhancing MNs in MPD (OR, 9.6; 95% CI, 3.928–23.833, P < 0.0001) were significant predictors of HGD and invasive carcinoma. Of the 216 patients without enhancing MNs, 79 patients (36.6%) having both segmental MPD dilatation and MPD diameter of <10 mm showed significantly lower rates of HGD and invasive carcinoma (3/79, 3.8%) than patients having both diffuse MPD dilatation and MPD diameter ≥10 mm (9/36, 25%, P = 0.001).ConclusionsMD and mixed-type IPMNs having segmental MPD dilatation with MPD dilation <10 mm and no enhancing MNs on imaging showed a significantly lower rate of HGD and invasive carcinoma, and watchful follow-up instead of immediate surgical resection might be possible in these patients.     

Incidence of Synchronous and Metachronous Pancreatic Carcinoma in 168 Patients with Branch Duct Intraductal Papillary Mucinous Neoplasm

Background/Aims: Although branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN) are being diagnosed with increasing frequency, the incidence of concomitant pancreatic carcinoma (PC) is not well known. We investigated the incidence and clinical features of synchronous and metachronous PC in patients with BD-IPMN. Methods: We studied 168 BD-IPMN patients diagnosed by various imaging modalities, including endoscopic retrograde pancreatography, between 1990 and 2008. We reviewed the medical records and clinical features in both patients developing and not developing PC. The diagnosis of PC was histologically verified in all patients. Results: PC was observed in 9 (5.4%) of 168 patients. Five were synchronously detected at the time of BD-IPMN diagnosis, whereas four were metachronously identified during the follow-up period. All PCs occurred in regions separate from the BD-IPMN lesion. All PCs represented histologically invasive ductal adenocarcinomas, whereas the BD-IPMN lesion was diagnosed as adenoma. Patients developing PC were significantly older than patients not developing PC (p = 0.017). The diameters of the BD-IPMN lesions and main pancreatic ducts were significantly smaller in patients developing PC than patients not developing PC (p = 0.013 and p<0.001, respectively). Conclusions: It was not infrequent for PC to occur in the pancreas with BD-IPMN. Particular attention should therefore be paid to the development of PC, even in low-risk BD-IPMN, as well as to changes in BD-IPMN.     

MRI features for differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma: A systematic review and meta-analysis

Background and AimsThe accurate differential diagnosis between autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC) is clinically important. We aimed to determine significant MRI features for differentiating AIP from PDAC, including assessment of diffusion-weighted imaging (DWI).MethodsWe performed a systematic search using three databases. The pooled diagnostic odds ratio was calculated using a bivariate random effects model to determine significant MRI features for differentiating AIP from PDAC. The pooled sensitivity and specificity were calculated. The qualitative systematic review for DWI assessment was performed.ResultsOf nine studies (775 patients), multiple main pancreatic duct (MPD) strictures, absence of upstream marked MPD dilatation, peripancreatic rim, and duct penetration sign were significant MRI features for differentiating AIP from PDAC. Absence of MPD dilatation had the highest pooled sensitivity (87%, 95% CI=68–96%), whereas peripancreatic rim had the highest pooled specificity (100%, 95% CI=88–100%). Of 12 studies evaluating DWI, seven reported statistically significant differences in apparent diffusion coefficient (ADC) values between AIP and PDAC; however, four reported lower ADC values in AIP than in PDAC, but three reported the opposite result.ConclusionThe four significant MRI features can be useful to differentiate AIP from PDAC, but DWI assessment might be limited.     

Chronic immunosuppression does not potentiate the malignant progression of mucinous pancreatic cystic lesions

BackgroundPremalignant mucinous pancreatic cystic lesions (mPCLs) are increasingly identified.AimsIn this study, we aim to assess the effect of selected immunosuppressive therapies on the progression of mPCLs, including side-branch intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.MethodsWe performed a retrospective cohort study of patients with mPCLs diagnosed over a 24-year period who received chronic immunosuppression. Controls were matched on age at cyst diagnosis (±11 yrs) and cyst size (±8 mm). Measured outcomes included increase in cyst size, development of “worrisome features” as defined by consensus guidelines, progression to malignancy, and rate of surgical resection.Results39 patients (mean age 60 yrs) with mPCLs were on immunosuppression. Leading indications for immunosuppression were solid organ transplant (n = 14), inflammatory bowel disease (n = 6), and rheumatoid arthritis (n = 5). 33% were on biologics, 77% on antimetabolites and 79% on multiple medications. Mean cyst size increased from 12.6 mm to 17.8 mm over a median of 16.5 months. 6 patients elected for surgical resection, and none ultimately developed malignancy. 26 cases with follow-up were matched to control subjects, with no significant differences among cases and controls in initial cyst size (12.8 mm vs 11.9 mm, P = 0.69), mean size increase (6.9 mm vs 5 mm, P = 0.47), follow-up interval (24.3 months vs 21.5 months, P = 0.44). No significant differences in the rate of worrisome features, malignancy, or surgical resection.ConclusionsPatients with mPCLs exposed to immunosuppressive medications did not have higher rates of malignancy or development worrisome features in the short term. This suggests that patients with mPCLs can be initiated or maintained on these agents without changes to surveillance practices.     

Can contrast-enhanced harmonic endoscopic ultrasonography accurately diagnose main pancreatic duct involvement in intraductal papillary mucinous neoplasms?

BackgroundMain pancreatic duct (MPD) involvement in branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is a high risk finding for malignant IPMNs. However, discrepancies exist in the identification of MPD involvement between imaging findings and pathological diagnosis. The purpose of this study was to evaluate the diagnostic accuracy of preoperative assessment of MPD involvement in IPMNs using contrast-enhanced harmonic endoscopic ultrasound (CH-EUS).MethodsThis study involved 166 consecutive patients with BD-IPMNs who underwent surgical resection. CH-EUS was used to evaluate the MPD involvement according to the presence of mural nodules (MN) that advanced into the MPD or involved the MPD. The CH-EUS findings were compared with the pathological findings. Additionally, we analyzed the risk factors for malignant BD-IPMNs using multivariate analysis.ResultsA total of 77, 51, and 38 patients were pathologically diagnosed with low-grade or intermediate-grade dysplasia, high-grade dysplasia and invasive IPMNs, respectively. MPD involvement was diagnosed using CH-EUS (MPD-inv.-EUS) in 90 (54.2%) patients with a sensitivity, specificity and accuracy of 83.5%, 87.0% and 84.9%, respectively. The malignancy rate in patients with MPD-inv.-EUS was 71.6% (63/90). Multivariate logistic regression analysis showed that MPD-inv.-EUS (OR, 3.61; 95% CI:1.45–8.98), age (OR, 5.70; 95% CI: 1.47–22.2), cyst size (OR, 2.45; 95% CI:1.04–5.78) and MN size (OR, 7.05; 95% CI:2.48–20.0) were significant for malignant BD-IPMNs.ConclusionsMPD-inv.-EUS accurately represents the pathological involvement of IPMN and may be a useful predictor of malignant BD-IPMNs.     

Follow-up of asymptomatic pancreatic cysts in clinical practice: A vignette questionnaire

Background/ObjectivesIn absence of evidence-based guidelines of pancreatic cystic neoplasms (PCN), the management might vary among physicians. The aim of this survey was to assess the attitude of Dutch gastroenterologists (GE) towards the management of asymptomatic PCNs.MethodsAn anonymous online questionnaire was distributed to all practicing GE (n = 381) in The Netherlands, in which four vignette patients with PCN were presented.ResultsIn total 45% of GE responded. Most respondents would perform surveillance for a 10 mm PCN (78%) mainly with an interval of one year (57%). A shorter interval of three (26%) or six (57%) months was chosen for a 25 mm BD-IPMN. Ultrasound was recommended for surveillance by 19% for a 10 mm cyst. GE with EUS experience were more likely to apply EUS for surveillance of 10 mm cyst than those without (56% vs 28%; p < 0.001). The presence of a branch-duct intraductal mucinous neoplasm (BD-IPMN) with a mural nodule, dilated pancreatic duct (8 mm) or increased serum CA 19.9 (300 U/ml) were considered an indication for resection by respectively 88%, 68% and 51% of respondents.ConclusionDutch GE demonstrate substantial variability in the management of asymptomatic PCNs. A significant proportion of general GE still use ultrasound for surveillance of small PCNs, while GE with EUS experience were more likely to perform EUS. The presence of risk factors for malignant degeneration of IPMN were not recognized by a substantial proportion of GE. Data on the natural history of PCNs is required to provide input for evidence-based guidelines, which should lead to a more uniform approach.