Branch-duct Intraductal Papillary Mucinous Neoplasms Research Articles

Sa1510 Impact of Positive MUC 1 Expression in Cell Block Cytology Specimen for the Progression of Branch-Duct Type Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Sa1510 Impact of Positive MUC 1 Expression in Cell Block Cytology Specimen for the Progression of Branch-Duct Type Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Sendai criteria is safe for follow up of patients with branch duct IPMN

Introduction: Branch duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas can exhibit various degrees of dysplasia, and pancreatic cancer may develop in up to 20%. The Sendai Criteria recommend that patients with ‘high-risk stigmata' (jaundice, enhanced solid component, and main pancreatic duct size ≥10 mm) should undergo resection. Patients with ‘worrisome features' (cyst size ≥3 cm, thickened enhanced cyst walls, non-enhanced mural nodules, main pancreatic duct size 5–9 mm, abrupt change in main pancreatic duct caliber with distal pancreatic atrophy, lymphadenopathy, and clinical acute pancreatitis) should be evaluated by endoscopic ultrasonography. The objective of this study is to analyze our population of patients with BD-IPMN. Methods: We perform a retrospective analysis of a prospective database including population of with type II IPMNs. Patients were selected for follow up according to 2006 Sendai criteria. All the patients completed the follow up at our institution exclusively. Results: 118 BD-IPMN were diagnosed. Mean age of 66 (31–91). Most were incidentally diagnosed. Only 10% required surgery. The reason to indicate surgery were: pain (8), the presence of mural nodules (1) and increase in size (3). No patient presented invasive cancer on pathology examination. Coexistence of oncological disease was found in 15% of these patients. Conclusion: The management of small BD-IPMNs remains controversial. The 2012 guidelines should be considered to indicate surgery and patients who do not undergo resection should undergo careful surveillance. Sendai criteria is a safe strategy for follow up of patients with type II IPMN.

Su1375 A Large Multicenter Study of Recurrence After Surgical Resection of Branch-Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas

Su1375 A Large Multicenter Study of Recurrence After Surgical Resection of Branch-Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas

International multicenter study to characterize the individual risk of malignancy in branch duct IPMN and proposal of nomogram to predict malignancy

International multicenter study to characterize the individual risk of malignancy in branch duct IPMN and proposal of nomogram to predict malignancy

Su1369 Association of Diabetes Mellitus for Progression of Branch Duct IPMN

Su1369 Association of Diabetes Mellitus for Progression of Branch Duct IPMN

Endoscopic ultrasound-guided ablation of branch-duct intraductal papillary mucinous neoplasms: Feasibility and safety tests using porcine gallbladders.

Radiofrequency ablation (RFA) and ethanol ablation are accepted methods of tissue destruction for treating cystic tumors. The aim of the present study was to evaluate the feasibility, efficacy, and safety of endoscopic ultrasound (EUS)-guided ablation using normal porcine gallbladders as a substitute model for branch-duct intraductal papillary mucinous neoplasms (BD-IPMN). Six adult mini pigs were included in this prospective study. EUS-guided RFA with or without ethanol ablation of the gallbladder was carried out using a prototype 18-gauge endoscopic RFA electrode, and RFA and ethanol ablation were done in a single session. Outcomes were assessed in terms of macroscopic and microscopic evaluations of the treated gallbladders. The prototype RFA electrode was used for ablation of the mucosa, aspiration of the internal contents of the gallbladder, and ethanol injection. RFA plus ethanol lavage resulted in a greater mean percentage of denuded gallbladder mucosa (97.5%) than RFA alone (55.8%). Effects of ablation extending to the cystic duct and partially denuded cystic duct mucosae were detected in five of the six pigs. There were no major procedure-related adverse events. EUS-guided ablation of the gallbladder mucosa was feasible and effective in the porcine model. Additional studies will be required to fully assess the risk of procedure-related damage to the main pancreatic duct before using this technique in a clinical setting.

Management of branch-duct intraductal papillary mucinous neoplasms: a large single-center study to assess predictors of malignancy and long-term outcomes

Management of branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging. We determined factors associated with malignancy in BD-IPMNs and long-term outcomes. This retrospective cohort study included all patients with established BD-IPMNs by the International Consensus Guidelines (ICG) 2012 and/or pathologically confirmed BD-IPMNs in a tertiary care referral center between 2001 and 2013. Main outcome measures were the association between high-risk stigmata (HRS)/worrisome features (WFs) of the ICG 2012 and malignant BD-IPMNs, performance characteristics of EUS-FNA for the diagnosis of malignant BD-IPMNs, and recurrence and long-term outcomes of BD-IPMN patients undergoing surgery or imaging surveillance. Of 364 BD-IPMN patients, 229 underwent imaging surveillance and 135 underwent surgery. Among the 135 resected BD-IPMNs, HRS/WFs on CT/magnetic resonance imaging (MRI) were similar between the benign and malignant groups, but main pancreatic duct (MPD) dilation (5-9mm) was more frequently identified in malignant lesions. On EUS-FNA, mural nodules, MPD features suspicious for involvement, and suspicious/positive malignant cytology were more frequently detected in the malignant group with a sensitivity, specificity, and accuracy of 33%, 94%, and 86%; 42%, 91%, and 83%; and 33% 91%, and 82%, respectively. Mural nodules identified by EUS were missed by CT/MRI in 28% in the malignant group. Patients with malignant lesions had a higher risk of any IPMN recurrence during a mean follow-up period of 131 months (P= .01). Among HRS and WFs of the ICG 2012, an MPD size of 5 to 9mm on CT/MRI was associated withmalignant BD-IPMNs. EUS features including mural nodules, MPD features suspicious for involvement, and suspicious/malignant cytology were accurate and highly specific for malignant BD-IPMNs. Our study highlights the incremental value of EUS-FNA over imaging in identifying malignant BD-IPMNs, particularly in patients without WFs and those with smaller cysts. Benign IPMN recurrence was observed in some patients up to 8 years after resection.

Evolution of incidental branch-duct intraductal papillary mucinous neoplasms of the pancreas: A study with magnetic resonance imaging cholangiopancreatography.

AIMTo investigate the type and timing of evolution of incidentally found branch-duct intraductal papillary mucinous neoplasms (bd-IPMN) of the pancreas addressed to magnetic resonance imaging cholangiopancreatography (MRCP) follow-up.METHODSWe retrospectively evaluated 72 patients who underwent, over the period 2006-2016, a total of 318 MRCPs (mean 4.4) to follow-up incidental, presumed bd-IPMN without signs of malignancy, found or confirmed at a baseline MRCP examination. Median follow-up time was 48.5 mo (range 13-95 mo). MRCPs were acquired on 1.5T and/or 3.0T systems using 2D and/or 3D technique. Image analysis assessed the rates of occurrence over the follow-up of the following outcomes: (1) imaging evolution, defined as any change in cysts number and/or size and/or appearance; and (2) alert findings, defined as worrisome features and/or high risk stigmata (e.g., thick septa, parietal thickening, mural nodules and involvement of the main pancreatic duct). Time to outcomes was described with the Kaplan-Meir approach. Cox regression model was used to investigate clinical or initial MRCP findings predicting cysts changes.RESULTSWe found a total of 343 cysts (per-patient mean 5.1) with average size of 8.5 mm (range 5-25 mm). Imaging evolution was observed in 32/72 patients (44.4%; 95%CI: 32-9-56.6), involving 47/343 cysts (13.7%). There was a main trend towards small (< 10 mm) increase and/or decrease of cysts size at a median time of 22.5 mo. Alert findings developed in 6/72 patients (8.3%; 95%CI: 3.4-17.9) over a wide interval of time (13-63 mo). No malignancy was found on endoscopic ultrasound with fine-needle aspiration (5/6 cases) or surgery (1/6 cases). No clinical or initial MRCP features were significantly associated with changes in bd-IPMN appearance (P > 0.01).CONCLUSIONChanges in MRCP appearance of incidental bd-IPNM were frequent over the follow-up (44.4%), with relatively rare (8.3%) occurrence of non-malignant alert findings that prompted further diagnostic steps. Changes occurred at a wide interval of time and were unpredictable, suggesting that imaging follow-up should be not discontinued, though MRCPs might be considerably delayed without a significant risk of missing malignancy.

A comparative study of EUS, CT, and MRCP to predict malignancy of branch-duct type intraductal papillary mucinous neoplasm

A comparative study of EUS, CT, and MRCP to predict malignancy of branch-duct type intraductal papillary mucinous neoplasm

ダンベル状の形態を呈し，分枝型IPMNを疑った嚢胞性膵神経内分泌腫瘍の1例

63歳，男性．他院にて以前より膵体部に11mm大の嚢胞性病変を指摘されており，経過観察となっていた．2014年6月病変の増大を認めたため精査加療目的に当院紹介となった．当院で施行した造影CTでは膵体部に新たに13mm大の嚢胞性病変が出現しており，以前より指摘されていた嚢胞との間には造影効果を有する充実成分が介在していた．ERCPにて嚢胞性病変と主膵管に交通は確認できなかったが，膵管擦過細胞診ではIPMNの所見として矛盾しないと判断され，分枝型IPMNの術前診断で腹腔鏡下脾温存膵体尾部切除を施行した．切除標本では結節を伴う多房性嚢胞を認め，免疫染色を含む病理組織所見で膵神経内分泌腫瘍と診断された．嚢胞成分は腫瘍の嚢胞変性と考えられたが，一部では嚢胞内面を膵管上皮が覆い，腫瘍増生に伴った膵管拡張が疑われた．非典型的な画像所見を呈し診断に難渋した膵神経内分泌腫瘍の1例を経験したので報告する．

Validity of the management strategy for intraductal papillary mucinous neoplasm advocated by the international consensus guidelines 2012: a retrospective review.

The aim of this study was to investigate the validity of the management strategy for intraductal papillary mucinous neoplasms (IPMNs) advocated by the international consensus guidelines 2012 (ICG2012). The medical records of 49 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. According to preoperative imaging, 10 patients (20%) had main-duct IPMNs, 20 (41%) had mixed IPMNs, and 19 (39%) had branch-duct IPMNs, with malignancy frequencies of 80, 15, and 37%, respectively. Twenty-seven patients had high-risk stigmata and 21 had worrisome features, with malignancy frequencies of 59 and 10%, respectively. The sensitivity, specificity, and positive and negative predictive values of high-risk stigmata for malignancy were 88, 65, 59, and 91%, respectively. Lesions were malignant in 88% of patients with an enhanced solid component, which was significantly correlated with the prevalence of malignancy (P<0.01). However, of the 10 patients who underwent pancreatectomy solely due to a main pancreatic dilation of ≥10mm, 9 (90%) had benign IPMNs. Many mixed IPMNs defined according to ICG2012 are benign. Although the management strategy advocated by ICG2012 has been improved relative to the Sendai criteria, the different high-risk stigmata carry unequal weights. Consequently, ICG2012 remains suboptimal for predicting malignant IPMN.

Risk of misdiagnosis and overtreatment in patients with main pancreatic duct dilatation and suspected combined/main-duct intraductal papillary mucinous neoplasms

Segmental/diffuse dilatation of the main pancreatic duct (MPD) is the typical feature of combined/main-duct intraductal papillary mucinous neoplasms (CMD-IPMNs). MPD dilation in IPMNs may be also expression of mucus hypersecretion/obstructive chronic pancreatitis (OCP). The aim of this study was to evaluate the presence and extension of MPD involvement by tumor/OCP and assess the risk of overtreatment. Retrospective analysis of suspected CMD-IPMNs resected between January 2009 and October 2014 were included. Pathologic correlations among MPD dilatation, IPMN, and OCP was searched. Overall, 93 patients were resected for suspected CMD-IPMNs. At pathology, CMD-IPMNs were found in 69 patients (74%). Branch-duct IPMNs (BD-IPMNs) were found in 8 cases (9%), pancreatic ductal adenocarcinoma (PDAC) in absence of IPMN in 9 (10%), cystic neuroendocrine tumor (NET G2) in 1 (1%), serous cystadenoma in 2 (2%), and OCP alone/mucinous metaplasia in 4 patients (4%). Overall, 18 patients (19%) underwent an overtreatment because unnecessary (2 BD-IPMNs, 2 serous cystadenomas, and 4 OCPs only) or too extensive resections (9 CMD-IPMNs and 1 PDAC with associated OCP). In these, total pancreatectomy was the most common procedure (67%). Median size of MPD in IPMN-involved area was 12 mm compared with 7 mm when only OCP was found (P < .05). There is a considerable risk of overtreatment in patients with a preoperative morphologic diagnosis of CMD-IPMNs. Partial pancreatectomy with margin examination should be performed instead of upfront total pancreatectomy. Radiologic observation can be considered in asymptomatic patients with "worrisome" MPD dilatation (5-9 mm) and lacking other high-risk stigmata.

Total Laparoscopic Central Pancreatectomy with Pancreaticogastrostomy for High-Risk Cystic Neoplasm

Organ-sparing pancreatic resection is important in prophylactic surgery for cystic neoplasms. There is controversy regarding the optimal surgical approach for pancreatic lesions in the neck or proximal body of the pancreas. Central compared with distal pancreatectomy is technically more challenging, but preserves more functional pancreatic tissue. Because of the prophylactic nature of the surgery and long survival of patients with benign and borderline malignant lesions, surgeons need to stratify greater importance to surgical morbidity and sparing pancreatic parenchyma. The patient is a 59-year-old active woman with a symptomatic cystic neoplasm of the pancreas exhibiting high-risk imaging features. The cyst of 2.2×1.8cm in the body of the pancreas was impinging on the portal venous confluence. The patient was positioned in the French Position, the lesser sac was opened, and the pancreatic body exposed. A retropancreatic tunnel was created with staple division of the neck. The body was mobilized off the portal vein and splenic vessels transected. A retrogastric pancreaticogastrostomy was sewn through an anterior gastrotomy. The stent was delivered past the pylorus to decrease pancreatic enzymatic activation. Pathology demonstrated a mixed predominantly branch duct IPMN with multifocal high grade dysplasia and PanIN3. Laparoscopic ultrasound helps in defining cyst borders, and minimal blood loss optimizes visualization during the dissection. A minimally invasive pancreaticogastrostomy created through an anterior gastrotomy is technically feasible and safe. This approach can minimize the morbidity of prophylactic pancreatic surgery for patients with cystic neoplasms. Nevertheless, it should not compromise safety, oncologic completeness, or an organ-sparing approach.

Grave Clinical Course of Pancreatic Invasive Cancer Developed in the Patients with Branch Duct IPMN: A Report of Three Cases

Grave Clinical Course of Pancreatic Invasive Cancer Developed in the Patients with Branch Duct IPMN: A Report of Three Cases

Cystic Lesions of the Pancreas: Observe or Operate.

Cystic Lesions of the Pancreas: Observe or Operate.

A Case of Pancreaticobiliary Adenocarcinoma Secondary to Malignant Transformation of Remnant Tissue From a Type I Choledochal Cyst

Introduction: Surgical resection of the choledochal cyst reduces but does not eliminate the risk of malignant transformation, suggesting the important role of continued surveillance. Case presentation: A 38-year-old man with a history of cadaveric liver allograft and a peripancreatic cystic mass presented with right upper quadrant abdominal pain, nausea, and involuntary weight loss. Eight years prior, the patient suffered from acute cholangitis and hepatic failure. He was diagnosed with a type I choledochal cyst. He underwent liver transplantation with cyst resection. Hepatic fibrosis and cholangitis were identified. A surveillance abdominal CT later revealed a 12-mm hypodense cystic lesion at the head of the pancreas. Differential diagnoses considered were intraductal papillary mucinous neoplasm (IPMN) and pancreatic pseudocyst. Abdominal MRCP later demonstrated a larger cystic mass with a tubular connection to the main pancreatic duct, suspicious for branch duct IPMN. Fine needle aspiration (FNA) of the cyst was not diagnostic. The physical exam revealed a tender abdomen at the right upper quadrant, without a palpable mass or jaundice. Laboratory studies revealed an elevated serum alkaline phosphate level and otherwise normal liver function tests. Serum CEA and CA-19-9 levels were elevated. The abdominal CT demonstrated a heterogeneous hypodense solid mass at the pancreatic head with surrounding desmoplastic reaction, portal vein invasion, regional adenopathy, and multiple liver lesions. Deep FNA was performed on one liver lesion: Metastatic pancreaticobiliary adenocarcinoma was diagnosed. The patient was initiated on chemotherapy, but the disease continued to progress. Discussion: We report a case of adenocarcinoma of pancreaticobiliary origin, secondary to malignant transformation of presumed remnant tissue from a type I choledochal cyst, despite efforts in surveillance. The choledochal cyst, a congenital abnormality from embryological development, is usually a pediatric diagnosis. The Todani classification delineates different anatomical features of a choledochal cyst. Complications include acute cholangitis and hepatic injury with fibrosis. While the management is generally early surgical resection due to the risk of malignant transformation to cholangiocarcinoma, removal does not eliminate the risk entirely, as remnant tissue could transform. Therefore, close surveillance remains a priority after resection of a choledochal cyst.Figure 1Figure 2Figure 3

Imaging morphological changes of intraductal papillary mucinous neoplasm of the pancreas was associated with its malignant transformation but not with development of pancreatic ductal adenocarcinoma

A considerable number of branch duct intraductal papillary mucinous neoplasm (BD-IPMN) developed not infrequently pancreatic malignancy, either as part of IPMN (malignant IPMN) or as concomitant pancreatic ductal adenocarcinoma (PDAC). To date, imaging morphological changes predicting occurrence of malignancy in BD-IPMN are not well-investigated. This study aimed to evaluate the relationships between occurrence of malignancy in BD-IPMN and imaging morphological changes of the tumors observed during follow-up. 515 BD-IPMN patients with mural nodule <10 mm and negative cytology were included. 19 patients developed malignant IPMN and 8 patients developed concomitant PDAC during mean follow-up of 4.7 years. The following imaging morphological features were assessed: cyst/main pancreatic duct (MPD) diameter, occurrence of additional cyst/mural nodule. Growth rate of cyst/MPD diameter were significantly larger in patients who developed malignant IPMN compared to those in patients whose IPMN remained benign (p = 0.013, p = 0.01). Occurrence of additional cyst/mural nodule were more frequently observed in patients who developed malignant IPMN (p = 0.009, p = 0.04). In contrast, none of the factors associated with imaging morphological changes of IPMN were shown to be significantly different between patients who developed concomitant PDAC and patients whose IPMN remained benign. Growth rate of MPD diameter and occurrence of additional cyst were independent factors associated with development of malignant IPMN (odds ratio 21.5, and 5.62, respectively). Imaging morphological changes of IPMN, such as growth rate of MPD diameter and occurrence of additional cyst, could be indicators for development of malignant IPMN, but not for development of concomitant PDAC.

Abstract 4253: A vascular endothelial growth factor gene polymorphism predicts malignant potential in intraductal papillary mucinous neoplasm

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) are well known to be premalignant lesions that sequentially progress from adenoma to carcinoma. Radiological type, size of cystic mass, and the presence of mural nodules are widely accepted as predictive malignant factors; however, its underlying mechanism is still unclear. Angiogenesis plays an important role in the progression and metastasis of various tumor types, and vascular endothelial growth factor (VEGF) is a critical component. In previous studies, at least 30 single-nucleotide polymorphisms (SNP) of the VEGF gene have been reported. VEGF +405G/C SNP (rs2010963) is located within the 5′-untranslated region and may affect transcription factor binding affinity. In contrast, VEGF -460C/T SNP (rs833061) is located in the promoter region and may influence promoter activity. Recent studies reported that serum VEGF levels were significantly higher in pancreatic ductal adenocarcinoma (PDAC) patients compared with control subjects, and VEGF +405G/C SNP was strongly associated with the carcinogenesis of PDAC patients. Objective The aim of this study was to investigate the distribution of VEGF SNPs with regard to malignant transformation in IPMN patients. Furthermore, correlations between VEGF SNPs and clinicopathological parameters including the morphological subtypes were statistically analyzed. Methods A total of 169 IPMN and 108 PDAC patients who underwent curative resection were enrolled. Low grade and moderate dysplasia were defined as benign IPMNs, on the other hand, high grade dysplasia and invasive carcinoma were defined as malignant IPMNs. The intraductal components were classified into four distinct epithelial subtypes, gastric, intestinal, pancreatobiliary, and oncocytic, based on their epithelial morphology on hematoxylin and eosin staining. VEGF +405G/C and -460C/T polymorphisms were examined by TaqMan Allele Discrimination. Results VEGF +405C/C was found more frequently in malignant IPMNs compared with +405G/G (odds ratio: 2.7, P = 0.04), and +405C allele was associated with malignant IPMNs compared with +405G (P = 0.055). In branch duct IPMNs, VEGF +405C/C was significantly associated with malignant transformation (CC vs GG; odds ratio: 4.0, P = 0.03, CC vs CG+GG; odds ratio: 3.3, P = 0.04), and there was a trend of VEGF +405C/C associated with malignant transformation of gastric type IPMNs (CC vs GG; odds ratio: 3.0, P = 0.07). When the survival outcomes were analyzed based on VEGF +405G/C SNPs, however, there was no relationship between VEGF SNPs and overall survival in patients with both IPMNs and PDAC. Conclusion VEGF +405G/C SNP was significantly associated with malignant transformation in IPMNs, especially branch duct and gastric type IPMNs. VEGF +405G/C SNP might be helpful in predicting clinical course in pancreatic disease with potential for malignant transformation. Citation Format: Suguru Yamada, Norimitsu Yabusaki, Tsutomu Fujii, Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera. A vascular endothelial growth factor gene polymorphism predicts malignant potential in intraductal papillary mucinous neoplasm. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4253. doi:10.1158/1538-7445.AM2015-4253

Sendai Consensus Guidelines for Branch-duct IPMN

Sendai Consensus Guidelines for Branch-duct IPMN

Reappraisal of pancreatic enucleations: A single-center experience of 126 procedures

Parenchyma-sparing pancreatectomies, especially enucleations, could avoid disappointing functional results associated with standard resections for benign/low-grade pancreatic neoplasms. This study aimed to assess short- and long-term outcomes in a large, single-center series of enucleations. All 126 patients who underwent enucleation for benign/low-grade neoplasms between 1996 and 2011 were included retrospectively. Lesions were mainly incidentally diagnosed (71%), most often located in the head (46%), and with a median size of 20mm. Enucleations were mainly performed for branch-duct intraductal papillary mucinous neoplasm (30%), nonfunctioning pancreatic neuroendocrine tumors (29%), and mucinous cystadenoma (21%). Overall mortality was 0.8% and morbidity 63%, mainly owing to pancreatic fistula (57%). Most were significant clinically, that is, grade B or C (41%), but managed conservatively (85%). Reoperation rate was 3%, mainly owing to hemorrhage. Postoperative de novo diabetes was 0.8%, and exocrine insufficiency never observed. The 1-, 3-, and 5-year recurrence-free survival were 100%, 98%, and 93%, respectively. Enucleation is associated with substantial morbidity, especially pancreatic fistula. Enucleations as an alternative to standard resection are best indicated for small, benign, and low-grade lesions located far from the main pancreatic duct. Enucleations should be proposed to young and fit patients able to tolerate postoperative morbidity and who could benefit from the excellent long-term results.