Mural nodule of 10 mm or larger as predictor of malignancy for intraductal papillary mucinous neoplasm of the pancreas: Pathological and radiological evaluations

BackgroundWe had previously reported that mural nodule (MN) ≥10 mm was optimal predictor of malignancy for intraductal papillary mucinous neoplasm (IPMN). However, little is known about its microscopic findings and imaging detectability.MethodsMedical records and resected specimens of consecutive patients with IPMNs harboring MN ≥ 10 mm were reviewed. Imaging detectability was determined on reports basis. Malignant IPMNs (noninvasive + invasive carcinomas) were microscopically classified according to localization of high-grade dysplasia (HGD) within MN.ResultsThirty-six patients were included. Imaging detectability of MN ≥ 10 mm in CT, MRI, US and EUS were 64%, 68%, 89%, and 97%, respectively. Thirty-three (92%) IPMNs were histologically diagnosed as malignant. Thirty percent of malignant IPMNs were classified into “diffuse HGD within MN”, 40% into “focal HGD within MN”, and 30% into “HGD outside MN”, in which HGD was not located within MN but in low papillary epithelia around MN. Overall sensitivity of pancreatic juice cytology was calculated as 58%, and for “diffuse HGD within MN”, “focal HGD within MN”, and “HGD outside MN” as 80%, 62%, and 30%, respectively (p = 0.0237). Univariate-analysis showed localization of HGD within MN was associated with true positive cytology (OR = 5.33, p = 0.043).ConclusionsDetectability of MN ≥ 10 mm is excellent in US and EUS. Although HGD is observed within MN in 70% of malignant IPMNs, HGD is located only in low papillary epithelia around MN in the remaining 30%, in which sensitivity of pancreatic juice cytology is shown to be inadequate.     

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.     

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.     

A comparative study between computed tomography and endoscopic ultrasound in the detection of a mural nodule in intraductal papillary mucinous neoplasm –Multicenter observational study in Japan

Background/objectivesThe detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN.MethodsThis multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined.ResultsTwo-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001).ConclusionsEUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.     

Frequency and significance of calcification in IPMN

The frequency and significance of calcification in intraductal papillary mucinous neoplasms (IPMN) are unknown. We examined calcifications by computed tomography (CT) in a large cohort of IPMNs and correlated them with clinicopathologic characteristics.MethodsPreoperative contrast-enhanced CT imaging studies of 164 patients with surgically resected IPMN were retrospectively reviewed. Morphologic characteristics of IPMN, presence and type of calcifications, their location, the degree of dysplasia and the epithelial subtype were recorded. Symptoms at the time of diagnosis, history of smoking, and alcohol consumption were obtained from medical records.ResultsOf the 164 IPMNs, 68 were branch duct type (Br-IPMN) and 96 main duct (MD-IPMN) or combined type (CT-IPMN); 78 (48%) had a malignant component (CIS and Invasive). Calcifications were present in 33 cases (20%). By type, 16 calcifications were punctate, 11 coarse and 9 eggshell, and by location, 15 were mural, 3 septal, 2 ductal, 1 in the solid component, and 13 in multiple locations. Calcifications were seen more frequently in larger lesions (44 mm vs 32 mm p = 0.002), and when MPD dilation was noted (70% vs 45%, p = 0.023). There was no association between presence of calcification and malignancy, epithelial subtype, or other clinical data. However, malignancy was present in 9/11 IPMN with coarse calcification (p = 0.04), suggesting this may be a worrisome feature.ConclusionCalcification is found in 20% of IPMNs, and is more common in larger lesions. Although its overall presence has no correlation with malignancy, coarse calcification, when combined with other morphologic features, may be a radiologic sign of malignancy.     

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.     

Pancreatic juice cytology in IPMN of the pancreas.

BACKGROUND: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a disease ranging from adenoma to borderline (with moderate dysplasia) and further to carcinoma (noninvasive and invasive) and surgical strategy is different by the grades of dysplasia. METHODS: Preoperative pancreatic juice cytology in IPMN was reviewed in 71 patients with IPMN who underwent surgical resection. RESULTS: The IPMN was adenoma in 48 patients, borderline in 13 and carcinoma (invasive) in 10. The sensitivity of pancreatic juice cytology in malignant IPMN was 40% (4/10). In 4 patients with the 48 IPM adenomas, diagnosis of pancreatic juice cytology was class IV or V. One of the 4 cases was considered to be an overdiagnosis of cytology, but the other 3 cases were considered to be a consequence of accompanying carcinoma in situ (or PanIN-3) (2 patients) or invasive ductal adenocarcinoma (1 patient) apart from IPMN. Sensitivity of pancreatic juice cytology was higher in IPMN of the main duct type with mucin hypersecretion and with mural nodules. CONCLUSIONS: These findings suggest that pancreatic juice cytology in IPMN is useful especially in the main duct type with mucin hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic carcinoma should be suspected.     

Pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas: A investigation of those clinicopathological features by analyzing 48 patients who underwent surgery for those lesions

BackgroundDifferences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified.MethodsForty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups.Results1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%).ConclusionsBecause characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds.     

Intraductal papillary mucinous neoplasms: Does a family history of pancreatic cancer matter?

Background/ObjectivesThe purpose of this study is to compare surgically resected intraductal papillary mucinous neoplasms (IPMNs) in patients with and without a family history of pancreatic cancer to gain insight into differences that may suggest the need for differential management.MethodsA retrospective review of patients who underwent resection of an IPMN at the Massachusetts General Hospital (1990–2011) was conducted. Three hundred and twenty-four patients of whom 45 (13.9%) had a family history of pancreatic cancer were identified. Patients with (PFH) and without (NFH) a family history of pancreatic cancer were compared.ResultsThere were no differences in demographic characteristics between groups. Extra-pancreatic malignancies diagnosed prior to the IPMN were more common in those with a PFH (35.6% vs 20.1%, p = 0.03). There were no differences in IPMN characteristics between groups including no difference in the presence of invasive disease (p = 0.55). Concurrent pancreatic ductal adenocarcinomas were more common in those with a PFH (11.1% vs 2.9%, p = 0.02). The survival in the PFH group was marginally lower than the NFH group, a difference found to be attributable to the higher prevalence of extra-pancreatic malignancies.ConclusionCharacteristics of surgically resected IPMNs are not different between patients with and without a family history of pancreatic cancer. Most importantly, the incidence of invasive disease is not different, suggesting that these lesions may not be more aggressive when they occur in the presence of a family history of pancreatic cancer.     

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.     

Endoscopic ultrasonographic findings predict the risk of carcinoma in branch duct intraductal papillary mucinous neoplasms of the pancreas

BackgroundThe preoperative diagnosis of branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas can be very difficult, since low-risk and high-risk lesions can be difficult to differentiate even after cytological analysis. The purpose of this study was to evaluate the preoperative diagnostic value of endoscopic ultrasonography (EUS) in differentiating low-risk and high-risk IPMNs.MethodsWe retrospectively identified 36 patients who underwent preoperative EUS for branch duct IPMNs. The pathological diagnosis after surgical resection was low-grade dysplasia (n = 26), moderate dysplasia (n = 1), high-grade dysplasia or carcinoma in situ (n = 5), and invasive carcinoma (n = 4). We divided the patients into two groups: low risk (low-grade dysplasia or moderate dysplasia) and high risk (high-grade dysplasia or carcinoma). We focused on the diameter of the cystic dilated branch duct, the main pancreatic duct, and the mural nodule as measured using the EUS findings.ResultsThe cystic dilated branch duct diameter (31.5 mm vs. 41.9 mm, P = 0.0225) was significantly correlated with low-risk and high-risk IPMNs, but the main pancreatic duct diameter (5.37 mm vs. 5.44 mm, P = 0.9418) was not significantly correlated with the low-risk and high-risk IPMNs. The mural nodule diameter of the papillary protrusions (4.3 mm vs. 16.4 mm, P < 0.0001) and the width diameter of the mural nodule (5.7 mm vs. 23.2 mm, P < 0.0001) were significantly correlated with low-risk and high-risk IPMNs.ConclusionsThe mural nodule of papillary protrusions diameter and width diameter observed using EUS was a reliable preoperative diagnostic finding capable of distinguishing low-risk and high-risk IPMNs.     

Psychological distress in patients under surveillance for intraductal papillary mucinous neoplasms of the pancreas: The “Sword of Damocles” effect calls for an integrated medical and psychological approach a prospective analysis

IntroductionMost intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can be safely surveilled. Their psychological impact is not known. The aim of this study is to obtain a psychological profile of patients under surveillance and compare the results to patients undergoing surgery.MethodsPatients under surveillance for IPMNs evaluated between 2017 and 2019 at the pancreatic cysts clinic of The Pancreas Institute of Verona were compared to patients undergoing surgery for the same disease. Patients with high-risk stigmata were excluded in both groups. Patients were profiled with the Barratt Simplified Measure of Socio-Economic Status (BSMSS), the Brief Coping Orientation to Problems Experienced (Brief-COPE), the Perceived Stress Scale (PSS), the Symptom Checklist-90 and the Short Form Health Survey (SF-36). Age, sex, BSMSS and Brief-COPE were used to match patients with the propensity score as potential sources of bias.ResultsTwo hundred patients were profiled. After the matching, 74 patients under surveillance were compared to 74 patients who underwent surgery. Patients under surveillance reported significantly increased scores for symptoms such as somatization (0.71 vs. 0.54, p = 0.032), depression (0.45 vs 0.31, p = 0.047) and anxiety (0.45 vs. 0.27, p = 0.002). They also reported a reduced health perception in the domain of physical role functioning (54 vs. 68, p = 0.046).ConclusionPatients under surveillance for a presumed IPMN experience anxiety and stress and feel less healthy than do patients undergoing surgery. This reduction in quality of life should always be taken into account and warrants an integrated medical-psychological approach in selected cases.     

Acute pancreatitis in intraductal papillary mucinous neoplasms correlates with pancreatic volume and epithelial subtypes

BackgroundIntraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, however its causes have not been fully elucidated. We investigated the association of the incidence of AP with epithelial subtypes and pancreatic volume in IPMN.MethodsThis retrospective study included 182 consecutive surgically resected IPMN patients between January 2000 and December 2018. The relationship between the incidence of AP and epithelial subtypes of IPMN and pancreatic volume was investigated. Epithelial subtypes of IPMN were classified into gastric (G type: N = 116), intestinal (I type: N = 49), pancreatobiliary (PB type: N = 14), and oncocytic types (O type: N = 3). Pancreatic volume of the contrast-enhanced computed tomography scan was measured using Ziostation2 software. Histological pancreatic parenchymal atrophy was also evaluated.ResultsAP occurred more frequently in I-types (I-type vs. G-type, 22.4% [11/49] vs 3.4% [4/116], P = 0.003) and PB-types (PB type vs. G-type, 35.7% [5/14] vs. 3.4% [4/116], P = 0.007) in comparison with G-types, which constituted the majority of the resected IPMNs. AP occurred more frequently in I-type patients with high pancreatic volumes (I-type with high pancreatic volume vs. I-type with low pancreatic volume, 37.0% [10/27] vs. 4.7% [1/21], P = 0.02). However, histological atrophy did not show an additional influence on the association between the incidence of AP and epithelial subtypes. The elevation of serum pancreatic enzymes was not significantly related to epithelial subtypes.ConclusionEpithelial subtypes and the degree of pancreatic volume may be closely associated with the incidence of AP in IPMN.     

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.     

Risk factors and prevention of postoperative pancreatic fistula after insulinoma enucleation:a retrospective study from a high-volume center

Background/ObjectivesEnucleation is an effective surgical method to treat pancreatic insulinoma, however, the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) is high. We aim to investigate the risk factors for CR-POPF which have not been well characterized and develop effective methods to prevent CR-POPF after enucleation.MethodsThis retrospective cohort study included 161 patients diagnosed with insulinoma from June 2016 to July 2020 in Peking Union Medical College Hospital. The risk factors for CR-POPF were evaluated and the role of prophylactic pre-operative pancreatic stent to prevent the occurrence of CR-POPF after enucleation of pancreatic insulinoma were explored.ResultsA cohort of 161 insulinoma cases were reviewed. The CT or MRI imaging reports could be tracked in 108 cases. A total of 96 patients underwent surgery, while 81 experienced pancreatic enucleation. Univariate and multivariate analyses showed that the distance from insulinoma to the main pancreatic duct (MPD) ≤2 mm was an independent risk factor for CR-POPF (p = 0.003, OR = 6.011, 95% Cl 1.852–19.512). The pre-operative pancreatic stent substantially reduced the incidence of CR-POPF in patients with tumor located in proximity to (distance ≤2 mm) the MPD (CR-POPF of the stented group vs the non-stented group: 37.5% vs 71.4%, p = 0.028).ConclusionsThe distance from insulinoma to MPD ≤2 mm is a predictive factor for CR-POPF after enucleation. Pancreatic duct stenting may benefit patients with insulinoma in proximity to the MPD by enabling a lower CR-POPF rate, so it should be considered before the enucleation of the insulinoma in proximity to the MPD (distance ≤2 mm).     

Usefulness of cell block cytology for preoperative grading and typing of intraductal papillary mucinous neoplasms

BackgroundPrecise histological diagnosis is important for the successful management of intraductal papillary mucinous neoplasms (IPMNs).ObjectThe object of this study was to determine whether cell block cytology is useful for preoperative cytomorphological grading and typing of IPMNs.MethodsThe subjects were 23 patients with IPMN from whom pancreatic juice was collected via a pancreatic catheter and who subsequently underwent pancreatic resection.ResultsIn 20 of the 23 cases, the quantity of cells collected for cell block cytology was sufficient to enable typing and grading of the IPMN. The rates of consistency between the results of typing and grading by cell block cytology and histological examination of the surgical specimen were 95% and 80%, respectively. Typing of the 10 main-duct/mixed-duct-type IPMNs by cell block cytology yielded 5 gastric types, 3 intestinal types, 1 oncocytic type, and 1 pancreatobiliary type, and the typing was consistent with the surgical diagnosis in all 10 cases. The results of typing of the branch-duct-type IPMNs by cell block cytology were identical to the results of histological typing in the surgical specimens in every case but one. However, the specificity of cell block cytology for grading IPMNs was 55.6%.ConclusionsThe cell block cytological findings were fairly consistent with the histopathological features of the surgical specimens, thereby indicating that cell block cytology may be useful for preoperative and typing of IPMNs, but only play a supplementary role in grading IPMNs.     

Simultaneous and sequential combination of genetic and epigenetic biomarkers for the presence of high-grade dysplasia in patients with pancreatic cyst: Discovery in cyst fluid and test in pancreatic juice

Background/ObjectivesScreening patients with intraductal papillary mucinous neoplasms (IPMN) has the primary goal of identifying potentially curable noninvasive precursors. We aimed to evaluate the diagnostic impact of genetic and epigenetic biomarkers in the presence of noninvasive precursors.MethodsMutated KRAS/GNAS and methylated SOX17/TBX15/BMP3/TFPI2 DNA were assessed by droplet digital PCR in a discovery cohort of 70 surgically aspirated cyst fluids, and diagnostic performances for differentiating high-grade dysplasia (HGD) from low-grade dysplasia (LGD) was evaluated. We then tested these markers using an independent test cohort consisting of 156 serially collected pancreatic juice samples from 30 patients with IPMN.ResultsMutated KRAS and GNAS are specific for IPMNs but are not helpful for the prediction of histological grades. Cyst fluids from IPMN with HGD showed higher methylation levels of SOX17 (median, 0.141 vs. 0.021; P = 0.086) and TBX15 (median, 0.030 vs. 0.003; P = 0.028) than those with LGD. The combination of all tested markers yielded a diagnostic performance with sensitivity of 69.6%, and specificity of 90.0%. Among the 30 pancreatic juice samples exhibiting the highest abundance of KRAS/GNAS mutations in each patient in the test cohort, patients with histologically proven HGD due to pancreatic resection had a significantly higher prevalence (100% vs. 31%, P = 0.018) and abundance (P = 0.037) of methylated TBX15 than those without cytohistological diagnosis undergoing surveillance.ConclusionsA simultaneous and sequential combination of mutated and methylated DNA markers in pancreatic cyst fluid and juice sample markers can help detect noninvasive pancreatic precursor neoplasms.     

Management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts. IPMNs have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. IPMNs are classified into main duct and branch duct types, based on the site of tumor involvement. IPMN patients have a favorable prognosis if appropriately treated. The postoperative 5-year survival rate is nearly 100% for benign tumors and noninvasive carcinoma, and approximately 60% for invasive carcinoma. A main duct type IPMN should be resected. Surgical treatment is indicated for a branch duct IPMN with suspected malignancy (tumor diameter ≥ 30 mm, mural nodules, dilated main pancreatic duct, or positive cytology) or positive symptoms. Malignant IPMNs necessitate lymph node dissection (D1). IPMNs are associated with a high incidence of extrapancreatic malignancies and pancreatic ductal carcinoma.     

Watchman Occlusion in Long-Standing Persistent Atrial Fibrillation: Larger Left Atrial Appendages With Greater Residual Leak

ObjectivesThis study sought to compare patients with and without long-standing persistent atrial fibrillation (LSPAF) undergoing Watchman left atrial appendage (LAA) occlusion.BackgroundAn increased burden of atrial fibrillation is associated with progressive left atrial remodeling and enlargement.MethodsTransesophageal echocardiography (TEE) measures of LAA ostial diameter and depth, device compression, and residual leak were evaluated in 101 consecutive Watchman cases. The patients were categorized into LSPAF (n = 48) or non-LSPAF (n = 53) groups and compared.ResultsThe average LAA ostial diameter for LSPAF versus non-LSPAF by TEE omniplane at 0° was 21.1 ± 4.1 mm versus 18.2 ± 3.6 mm (p = 0.0002); at 45° was 18.7 ± 3.4 mm versus 16.3 ± 3.1 mm (p = 0.0004); at 90° was 19.6 ± 3.8 mm versus 16.2 ± 3.4 mm (p = 0.00001); and at 135° was 21.0 ± 4.1 mm versus 18.0 ± 4.1 mm (p = 0.0005). The average LAA depth for LSPAF versus non-LSPAF by TEE at 0° was 28.1 ± 6.4 mm versus 25.2 ± 4.9 mm (p = 0.02); at 45° was 27.9 ± 5.8 mm versus 25.1 ± 4.3 mm (p = 0.007); at 90° was 27.2 ± 5.2 mm versus 22.8 ± 3.7 mm (p = 0.0001); and at 135° was 25.6 ± 5.4 mm versus 21.5 ± 3.8 mm (p = 0.0001). In successfully treated patients, 77% of the LSPAF group received larger device (27, 30, or 33 mm) implants versus only 46% in the non-LSPAF group (p = 0.003). While both groups had similar rates of moderate (3 to 5 mm) leaks at implant (2% vs. 0%; p = 0.14), 27% of the LSPAF vs. 4% of the non-LSPAF group had moderate leaks (p = 0.04) on 6-week follow-up TEE.ConclusionsPatients with LSPAF have significantly larger LAA sizes, require larger devices, and have more residual leak on follow-up TEE. LSPAF may represent a higher risk group that warrants more stringent long-term follow-up.     

Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy

BackgroundThe decision to perform surgery is complicated by the presence of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs), which are characterized by two or more cysts located in different areas of the pancreas.ObjectivesWe aimed to establish a suitable treatment strategy and surgical indications in patients with MF-IPMNs.MethodsThis single-center retrospective study included patients with IPMNs who underwent pancreatic resection from 2006 to 2020. Patients with distant metastasis and patients with IPMNs of the main pancreatic duct were excluded from the analysis.ResultsAfter excluding 22 patients, 194 patients were included. One hundred thirteen patients (58.2%) had unifocal IPMNs, while 81 patients (41.8%) had MF-IPMNs. There were no significant differences in the 5-year disease-specific survival (DSS) rate (92.3% vs. 92.4%, p = 0.976) and the 5-year disease-free survival rate (88.6% vs. 86.5%, p = 0.461). The multivariate analysis identified high-risk stigmata, invasive carcinoma, and lymph node metastasis as independent predictors of DSS. The presence of cystic lesions in the pancreatic remnant was not a predictor of survival. Even in the MF-IPMN group, there were no significant differences in DSS when stratified by procedure (total pancreatectomy vs. segmental pancreatectomy, p = 0.268) or presence of cystic lesions in the pancreatic remnant (p = 0.476). The multivariate analysis identified lymph node metastasis as an independent predictor of DSS in the MF-IPMN group.ConclusionsIn patients with MF-IPMNs, each cyst should be evaluated individually for the presence of features associated with malignancy.