Invasive IPMN Research Articles

Prognostic factors in resected high grade and invasive intraductal papillary mucinous neoplasm. Analysis of the national cancer database

Objective: Consensus guidelines for management of IPMN primarily address the combined risk of specific lesions developing high grade dypsplasia or an invasive component. Long term prognosis of resected high grade and invasive IPMN remains unclear. We sought to determine factors associated with survival in these cases. Methods: We queried the NCDB from 2001–2006 for patients who underwent curative resection for high grade and invasive IPMN using ICD-O 3 codes. We evaluated the impact of demographic, facility, surgical and pathologic features on overall survival using Cox regression, univariate and multivariate analysis. P<0.05 was considered significant. Results: Of 581 patients who underwent surgery for invasive (n=263) and high grade (n=318) IPMN, increasing age (HR=1.04/year) and medicare (HR=1.35) vs private insurance status were negative prognostic indicators. Tumor features including increasing size, node positive disease, invasiveness, and margin status all negatively impacted survival (p<0.05). Median survival for high-grade disease was 10.11 years. Median survival for invasive disease was 5.17 for node negative disease and 1.41 years for node positive (p<0.01). Considering all patients, at multivariate analysis, only age, nodal status (HR: 4.24, CI: 2.97–6.04), and invasive disease (HR: 1.73, CI: 1.262.37) were associated with a worse outcome. Conclusion: Based on our analysis of high grade and invasive IPMN in patients undergoing resection, age, nodal status and degree of invasiveness were the most important prognostic indicators. Overall survival for high grade lesions and invasive lesions without nodal disease is surprisingly similar. Nodal disease however is a significant predictor of poor outcome and similar to resected pancreas cancer in general.

A large multicenter study of recurrence after surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas.

Surgery for pancreatic branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) is indicated for therapy of symptomatic patients and to prevent development of invasive cancer. There is currently no consensus on management of BD-IPMN patients after surgical resection. The aim of this retrospective multicenter study was to determine the recurrence and long-term survival after surgical resection of BD-IPMN and to determine the predictive factors of recurrence. All patients who underwent surgery for BD-IPMN from 2005 to 2011 at 2 centers were identified. The diagnosis of BD-IPMN was based upon imaging and endosonographic analysis, and was confirmed by pathological analysis. The lesions were classified into 4 categories according to the WHO classification. Data on cyst characteristics, operative procedure, recurrence, and follow-up were evaluated. Recurrence was defined as the presence of BD-IPMN or mass in the remnant pancreas after surgery as seen on follow-up imaging. Recurrence suspected on imaging was confirmed via histological analysis when possible. A number of 271 patients (67% female; mean age 63.4 yrs) with BD-IPMN underwent surgical resection. The mean size of the cyst was 24.2mm (range, 12-80). There were 34 (12.5%) patients with an associated mass. 82 (30.3%) patients had worrisome features in the cyst on pre-operative EUS, included mural nodules (N.=25), solid component (N.=27), debris (N.=25), and a dilated major pancreatic duct (N.=5). 144(53%) patients had a pancreaticoduodenectomy for head lesions, 125 (46%) had distal pancreatectomy for tail/body lesions, and 1 (1%) underwent a total pancreatectomy. Histology showed 86% with noninvasive IPMN (adenoma 31%, moderate dysplasia 24%, severe dysplasia or carcinoma in situ 31%) and 14% with invasive IPMN. The mean patient follow-up was 28 months (range, 10-180 months). Recurrence in the remnant pancreas occurred in 34 (12.5%) patients. Of the patients with recurrence, 3/34 had invasive carcinoma and 31/34 had noninvasive cystic lesions; all patients with invasive carcinoma recurrence were those with a previous invasive IPMN. On MVA, risk factors for cyst recurrence were severe dysplasia/intraductal carcinoma in situ and invasive IPMN even after adjusting for elevated CEA (>193 ng/mL), type of surgery, and cyst size (OR 2.8, 95% CI=1.1-7.3; P=0.028). 3 patients who had invasive IPMN and 1 who had severe dysplasia patient with recurrence died, all because of recurrent cancer, with the mean time from recurrence to death being 36 months. The risk of BD-IPMN recurrence after resection depends upon the histological type, with the highest-risk groups being those with severe dysplasia/intraductal carcinoma in situ and invasive IPMN. Even after negative resection margins, the pancreatic remnant still harbors a risk of recurrence which requires long-term surveillance.

Technical and Biological Predictors of On-Site Accuracy and Histologic Core Acquisition in Pancreatic Cancer Biopsies

Introduction: There is an increasing need for high quality core biopsies in patients with suspected pancreatic adenocarcinoma. Although significant advances have been made in the EUS-guided sampling methods, the factors that predict acquisition of histologic cores with preserved architecture are not known. Our goal was to understand both procedural and tumor factors associated with sampling accuracy and the ability to obtain core biopsies. Methods: We identified patients who underwent EUS-guided sampling of pancreatic adenocarcinoma between 2011-15 who had immediate surgical resection without neoadjuvant therapy. We evaluated the rate and predictors of ROSE (rapid on-site evaluation) positivity, early ROSE positivity (first pass) and histologically preserved tissue (intact epithelial and stromal compartments), using imageJ. Data was collected on biopsy technique, needle type and tumor histology (grade, type, degree of necrosis, pancreatitis). Statistical analysis was performed with Pearson's Chi square and Fischer's exact tests for categorical variables and the Mann Whitney-U test for continuous variables. Results: We first evaluated the rate and predictors of ROSE positivity in 58 patients (FNA=36, FNB=22). ROSE was performed on 56 samples (96%) and was positive in 35 samples (62.5%) but did not correlate with needle type, gauge, technique, median size or histological grade of tissue obtained. However, early ROSE positivity, which we observed in 17 samples (30.3%), was associated with larger median tumor size (p=.018) while the presence of pancreatitis was associated with a higher rate of non-diagnostic biopsies (p=.004). We next assessed 41 samples for the presence of architecturally preserved core tissue, with a histological review by a pathologist. Larger median tumor size and invasive IPMN origin (vs. sporadic adenocarcinoma) were each associated with a larger core biopsy area (p=.002). In a univariate analysis, there were no technical factors or other tumor characteristics that were predictive of biopsy accuracy, core area or quantification of lymphocytes, stroma or tumor cells on histologic slide review. Conclusion: Median tumor size correlated with first pass ROSE positivity while biopsies of larger tumors and those associated with IPMN are more likely to provide quality core tissue. However, endoscopic technique and other tumor biology factors did not affect biopsy accuracy or the acquisition of quality core biopsies.

Precise pathological tracing of invasive IPMN lesions and related adenocarcinoma: Defining the molecular underpinnings of distinct routes to invasive carcinomas of the pancreas

Precise pathological tracing of invasive IPMN lesions and related adenocarcinoma: Defining the molecular underpinnings of distinct routes to invasive carcinomas of the pancreas

Management implications of resection margin histology in patientsundergoing resection for IPMN: A meta-analysis.

IPMN is a relatively new clinical entity and surgeons are continuing to develop their understanding of this complex pathology. Little is known of the natural disease process post-resection of an IPMN, particularly the impact of gland histology and margin status on the chance of recurrence and survival in benign and invasive IPMN. An online search was conducted to evaluate and include those studies which reported on gland histology, margin status and disease recurrence in resected benign and malignant IPMN. A Meta analysis was then performed using a random effects model. The chance of recurrence in non-invasive margin positive IPMN is similar to margin negative IPMN. The chance of recurrence is higher in invasive gland IPMN compared to non-invasive gland. The vast majority of recurrences occurred in patients with positive margins demonstrating invasion. All patients with intra- or post-operative evidence of invasive carcinoma at the resection margin should undergo further resection to achieve a negative margin. Patients with evidence of IPMN at the transaction margin (even with changes of high grade dysplasia/CIS) may not achieve any benefit from further resection. Patients with recurrence in benign/non-invasive IPMN should undergo re-resection, whereas patients with recurrence in invasive IPMN should not.

網羅的糖鎖解析によるIPMNの悪性度診断能の検討

網羅的糖鎖解析によるIPMNの悪性度診断能の検討

Branch duct intraductal papillary mucinous neoplasm of the pancreas: single-center experience with 324 patients who underwent surgical resection.

Backgrounds/AimsInternational treatment guidelines for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas have been proposed, for features associated with malignancy and invasiveness. We investigated the clinicopathological characteristics that are predictive of malignancy or invasiveness and disease recurrence.MethodsA review of 324 patients with resected and pathologically confirmed BD-IPMN, between March 1997 and December 2013, was conducted.ResultsThere were 144 (44.4%) low grade dysplasia (LGD), 138 (42.6%) intermediate grade dysplasia (IMGD), 17 (5.3%) high grade dysplasia (HGD), and 25 (7.7%) invasive carcinoma (invIPMC) cases. The 5-year survival rates were 98.1% for LGD, 95.3% for IMGD, 100% for HGD, and 71.8% for invIPMC. Through a univariate analysis, the male sex was associated with malignancy, and CA19-9 was related to both malignant and invasive IPMN. The high risk or worrisome features of the international guidelines were associated with both malignant and invasive IPMN: the total bilirubin of the head/uncinate lesion, tumor size, mural nodule, and the size of the main pancreatic duct (MPD). Through a multivariate analysis, the male sex, elevated CA19-9, mural nodule, and dilated MPD diameter were independently correlated with the malignant IPMN. The elevated CA19-9 and dilated MPD diameter were also correlated with invasive carcinoma. The patient age and the initial pathological diagnosis were strongly associated with disease recurrence following surgical resection.ConclusionsThe high risk or worrisome features in the current treatment guidelines for BD-IPMN are confined to the morphological characteristics of the disease. Patient factors and biological features should also be considered in order to develop optimal therapeutic or surveillance strategies.

Data analysis of 36 cases with intraductal papillary mucinous neoplasm of the pancreas for their clinicopathological features, diagnosis, and treatment

Background Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic cystic neoplasm, accounting for 1% of all exocrine pancreatic neoplasms. This study aimed to summarize the clinicopathological and biological behaviors, as well as the experience in diagnosis and treatment of IPMN. Methods Clinicopathological data were collected from 36 cases with IPMN who were treated in Department of General Surgery, Peking University Third Hospital from May 2001 to July 2011. Results The 36 cases of IPMN patients included 27 males and 9 females (M:F=3:1). The age of patients ranged from 52 to 78 years, with an average of 67.3 years. Regarding tumor location, 20 tumors were located in pancreatic head, 3 in pancreatic neck, 10 in pancreatic body and tail, and 3 in the whole pancreas. All the 36 cases underwent surgical treatment, with 13 cases of pancreaticoduodenectomy, 3 cases of middle pancreatectomy, 7 cases of tumor resection plus pancreaticojejunostomy, 3 cases of distal pancreatectomy, 7 cases of distal pancreatectomy plus spleen resection, and 3 cases of total pancreaticoduodenectomy. Of the 36 patients, 9 patients underwent the operations under laparoscopy. The 36 cases included main duct type (14 cases, 38.9%), branch duct type (10 cases, 27.7%), and mixed duct type (12 cases, 33.3%). Pathologically, of the 36 cases, there were 7 IPMN adenomas, 11 borderline IPMNs, 6 IPMN with carcinomas in situ, and 12 IPMNs with invasive carcinomas. All the 36 cases were followed up. During an average of 42 months follow-up period (26-129 months), no recurrence occurred. Conclusions IPMN, which primarily occurs in male, is a low-grade malignancy which may involve any part of the pancreas, with specific clinicopathological features. IPMN is a different malignancy type from pancreatic ductal carcinoma. Imaging and laboratory examination are helpful for the diagnosis and differential diagnosis. The prediction of invasive IPMN is still difficult. Surgical resection is recommended as the first choice of treatment. Aggressive and proper operation procedure produces better prognosis. Long-term follow-up is necessary for patients after operation. Laparoscopic distal pancreatectomy is a feasible and safe procedure for the indicated patients.

Predictors of early stages of histological progression of branch duct IPMN.

An appropriate timing for surgical resection of branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) to achieve sufficient postoperative survival is still unknown. Of 80 patients with histologically proven IPMNs, 61 patients who had BD-IPMN without pancreatic cancer concomitant with IPMN were enrolled in this study. We divided BD-IPMN into four groups according to disease progression: low to intermediate grade of dysplasia (LGD/IGD-IPMN), high grade of dysplasia (HGD-IPMN), minimally invasive IPMN (MI-IPMN: T1a), and invasive IPMN (IN-IPMN: ≥T1b). Indicators of surgical resection were investigated on the basis of pathological findings and postoperative prognosis. Postoperative survival was distinctly worse for patients with IN-IPMN than for patients with MI-IPMN, HGD-IPMN, and LGD/IGD-IPMN. Postoperative disease-specific 5-year survival rate was 100 % in patients with IN-IPMN, HGD-IPMN, and LGD/IGD-IPMN, by contrast, 40 % in patients with IN-IPMN. The presence of two of the three factors (pancreatitis, serum carbohydrate antigen [CA] 19-9 levels >13 U/mL, and mural nodules) could distinguish HGD-IPMN from LGD/IGD-IPMN with a sensitivity of 92.9 %, specificity of 90.2 %, positive predictive value of 76.5 %, negative predictive value of 97.4 %, and accuracy of 90.9 %. To manage patients with BD-IPMN and achieve a good postoperative prognosis, surgical resection should be performed before progression to IN-IPMN.

Su1495 Proteomic Studies on Aspirates From Cystic Neoplasms of the Pancreas Provide New Clues to Their Molecular Background and Reveal Novel Biomarker Candidates

G A A b st ra ct s papillary mucinous neoplasm and to assess the impact on the diagnosis of IPMN. Methods: We retrospectively analysed the clinicopathological factors of 177 patients (114 men, median age 63 yr) undergoing resection for branch duct type IPMNs at 15 tertiary hospitals in korea that had the diameter of main pancreatic duct less than 5 mm for identifying malignant predictors of this neoplasm. For the analysis, Br-IPMN with adenoma (n=72), borderline neoplasm (n=66) were grouped as benign and Br-IPMNs with carcinoma in situ(n=10), and invasive carcinoma (n=29) as malignant. Malignant IPMNs were defined as those with noninvasive (n=10 noninvasive carcinoma, and 29 invasive carcinoma). and invasive IPMN. Results: Among 177 patients with branch duct IPMN, we found significant predictors for malignancy in these patients in a univariate analysis; cyst size > 3cm, presence of a mural nodule in the cyst at abdominal CT, the history of acute pancreatitis, serum CA19-9. In a multivariate analysis among 177 patients, a mural nodule on CT imaging, cyst size>3cm, and serum CA19-9 were independent factors associated with malignancy. In patients (n= 110) who had endoscopic ultrasonography (EUS), cyst size > 3cm (odd ratio=10.6, CI= 2.812-40.199) and mural nodule larger than 5mm (odd ratio=14.9, CI=4.027-55.418) on EUS imaging is strongly associated with Malignant Br-IPMNs (p 5mm used instead of definitive mural nodule on EUS imaging in the 2012 international consensus guideline for IPMNs, the sensitivity and specificity was 84% and 85%. Conclusions: We identified useful predictive factors for malignancy in pure branch duct IPMN ; the presence of mural nodule and cyst size > 3cm on abdominal CT imaging, and the mural nodule larger than 5 mm on EUS imaging. In the worrisome features of 2012 international guideline for surgical indication of IPMNs, using the mural nodule larger than 5 mm instead of definitive mural nodule on EUS imaging may be reasonable.

Definition of a Standardized Pathway in Pathological Examination of Pancreaticoduodenectomy (PD) Surgical Specimen in a High Volume Surgical Centre: Improvement in Pathological Reporting Quality Indexes

Context Curative (R0) resection is considered a prognostic key factor among patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). Although guidelines for the processing of PD specimens have been established, there is currently no widely accepted standard protocol, resulting in large variation of reported R1 and lymph-nodes rates; it ultimately precludes meaningful comprehension of clinicopathological correlation usually leading to therapeutic decisions. Objective Definition of a standardized pathway in processing of surgical specimens after pancreatico­duodenectomy (PD) for PDAC in a referral centre for pancreatic disease and evaluation of its impact on pathological analysis quality indexes. Methods Between January 2010 and May 2013 we performed 206 PD, of which 108 for PDAC; invasive IPMN (n=12) and neoadjuvant CT patients (n=8) were excluded. On overall 88 patients were then included in the present study: we realized a comparison between a control group of patients, treated between 2010 and 2011 (n=39), and a group composed by patients who underwent surgery between 2012 and 2013 (n=49), when a standardized pathway for specimen processing was defined: setting up of a selected group of dedicated pathologists, highly interactive with surgical team and guided by a senior pathologist acting as a tutor on specimen sampling; creation of a standard report form comprising all resection margins; frequent re-sampling of surgical specimens; external tutoring if necessary. Results R1% in the whole group of patients (n=88) was 34.1%; in the first group, however, it was 17.9%, while in the later it increased to 46.9% (P=0.004); the improving detection of margin infiltration is further highlighted by the R1% observed in the last months (Jan-May 2013), equal to 73.3%. Median number of lymph-nodes derived from surgical specimen was 15 (range: 1-31) in the first group, while in the second group it increased to 21 (range: 7-47)(P<0.001 at Wilcoxon test). In a similar way N1% increased from 64.1% to 83.7% (P=0.035) between first and second period. Inadequate node sampling (less than 12, according to AJCC/TNM) decreased from 23.1% (n=9) to 2.0% (n=1) (P=0.001). Conclusions As several authors suggested, R1% in PDAC surgery should be considered a pathological examination quality index, instead of a parameter regarding pure surgical technique; N1% and total lymph-node number hold a similar value. A structured pathway regarding specimen analysis, able to guarantee an high quality output, is an essential facility in a pancreatic surgery referral centre.

Feasibility and Results of Radical Surgery and Adjuvant Therapy in Patients Older than 70 Years with Pancreatic Adenocarcinoma

Context High morbidity rates following pancreatic surgery and adverse effects of chemo-radiation treatments still make surgeons and oncologist reluctant to candidate elderly patients to these surgical or medical therapies. Objective Evaluation of postoperative outcomes and adjuvant chemo-radiation protocols adherence among over 70-year-old patients with pancreatic adenocarcinoma (PDAC) treated in a referral center for pancreatic disease. Methods Between January 2010 and May 2013 we performed 161 pancreatic resection for PDAC (including invasive IPMN): 106 pancreatico­duodenectomies (PD), 44 left spleno-pancreatectomies (LP), and 11 total pancreatectomies (TP). In the present study we focused on over 70-year-old patients treated with surgery and, successively, candidate or not to adjuvant therapy. We prospectively recorded data about perioperative outcomes as well as patient’s adherence to planned chemo-radiation schedules. Results In our series over 70-year-old patients were 75 (47.2%). Median age at surgery was 76 years (range: 70-85 years). Thirty-one patients (41.3%) had ASA ≥3. Mean BMI was 23.6 kg/m 2 . Forty-seven patients received PD, 21 had LP, 7 underwent TP. Overall morbidity was 48% (Clavien Dindo ≥3: 12%); POPF was 13.3% (ISGPF B-C: 4.4%); biliary fistula rate was 5.5%; DGE rate was nihil; PPH was 5.3% (4 cases, 2 of them requiring reintervention); medical complications were 14.5%; reintervention were 5.3% (4 cases); mortality was 1.3% (1 case). Median LOS was 10 days (range: 5-31 days). Patients candidate for adjuvant treatment were 39 (52.0%): 25 chemotherapy (64.1%), 6 radiotherapy (15.4%), 8 combined chemo-radiation (20.5%). Of the other patients, 27 (36.0%) were not enrolled in any adjuvant schedule after surgery, 8 (10.7%) resulted stage 0-I at histology and 1 (1.3%) died during surgical hospitalization. Among patient undergoing chemotherapy, 70% received gemcitabine, 9% PEX-G, and 6% GemOx. Thirty-three percent of the patients experienced low grade toxicity (G1-2), while 18% had high grade (G3-4). Twelve percent of the patients could not complete the schedule because of toxicity or disease progression during the treatment. Median survival after surgery was 25 months. Conclusions The morbidity and mortality rate we observed in elderly patients is acceptable and aligned with data reported in larger series. In a similar way, adjuvant treatments toxicity appeared limited, and patients adherence to scheduled therapy adequate. An accurate preoperative and postoperative asses­sment, referring to biological more than chronological age, is mandatory in evaluation of cases eligible to surgery and adjuvant treatments.

Disease spectrum of intraductal papillary mucinous neoplasm with an associated invasive carcinoma: Invasive IPMN versus pancreas ductal adenocarcinoma-associated IPMN

Disease spectrum of intraductal papillary mucinous neoplasm with an associated invasive carcinoma: Invasive IPMN versus pancreas ductal adenocarcinoma-associated IPMN

Pancreatic Cystic Neoplasms: Management and Unanswered Questions

Approximately 10% of persons 70 years old or older are now diagnosed with pancreatic cysts, but it is not clear which ones require additional analysis, interventions, or follow-up. Primary care doctors rely on gastroenterologists for direction because no one wants to miss a diagnosis of pancreatic cancer, but meanwhile there is pressure to limit use of diagnostic tests and limit costs. We review the different cystic neoplasms of the pancreas and diagnostic strategies based on clinical features and imaging data. We discuss surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines. Intraductal papillary mucinous neoplasm (particularly the branch duct variant) is the lesion most frequently identified incidentally. We report what is known about its pathology, its risk of developing into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk. We also review surgical treatment and strategies for surveillance of pancreatic cysts.

PTEN and MIR-21 Expression in IPMN and PDAC

Context The prognosis of invasive IPMN is better than for PDAC and many authors believe that IPMNs have distinct genetic and biological characteristics underlying this different clinical behavior. Objective Since previous studies correlated miR-21 expression with PTEN levels and worse prognosis in PDAC, we compared PTEN and miR-21 expression in invasive IPMNs and PDACs. Methods Ten invasive IPMN and 16 PDAC were evaluated for both PTEN expressions, with a validated immunohistochemistry method: 4 degrees of score (0 absent, 1 weak, 2 moderate, 3 strong). The miR-21 expression, as assessed by PCR in mRNA isolated from laser-microdissected samples. According to the miR21 quantification, all samples were identified as follow: (IPMN-L, IPMN-H, PDAC-L and PDAC-H). Statistical analysis was performed using ANOVA tests. Results IPMNs with high mi-R21 expression presented a negative/weak PTEN cytoplasmatic staining, with only few scattered positive cells, while IPMNs characterized by low mi-R21, had a moderate or strong cytoplasmic PTEN expression. This inverse correlation of miR-21 and PTEN expression was also observed in PDAC. However, we observed a significant difference comparing PTEN IPMN-L vs . PDAC-L (P=0.021), IPMN-L vs . IPMN-H (P=0.041) and all groups (P=0.037). Conclusion PTEN expression correlated with miR-21 in both invasive IPMNs and PDACs. Moreover, PDAC had significantly higher levels of miR-21 and lower levels of PTEN than IPMNs, suggesting that these biological characteristics might underline the better clinical outcome of IPMN compared to PDAC.

Cyst fluid carcinoembryonic antigen level is not predictive of invasive cancer in patients with intraductal papillary mucinous neoplasm of the pancreas.

Cyst fluid CEA concentration>192 ng/mL has proven accurate to differentiate mucinous from non-mucinous pancreatic cystic neoplasms. It is unclear whether the degree of cyst fluid CEA elevation is predictive of malignant behavior in IPMNs.To determine whether elevated cyst fluid CEA concentrations were predictive of invasive cancer.Cross sectional study.Single National Cancer Institute comprehensive cancer care center experience.47 patients underwent preoperative EUS-FNA with cyst fluid analysis and surgical resection of an IPMN over a 9 year period.Cyst fluid CEA concentrations among the four grades associated with IPMN (low grade dysplasia, moderate dysplasia, high grade dysplasia, and invasive cancer).The mean±standard deviation cyst fluid CEA concentration increased as the pathology progressed from low grade dysplasia (1,261±1,679 ng/mL) to moderate dysplasia (7,171±22,210 ng/mL) to high grade dysplasia (10,807±36,203 ng/mL). However, the mean CEA level decreased (462±631 ng/mL) once invasive cancer developed (P=0.869). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a cyst fluid CEA concentration greater than 200 ng/mL for the diagnosis of malignant IPMN (cases of high grade dysplasia and invasive IPMN) was 52.4%, 42.3%, 42.3%, 52.4% and 46.8%, respectively.Single center experience, small patient numbers, retrospective data collection.The degree of cyst fluid CEA elevation is a poor predictor of malignant degeneration within IPMNs. Clinical management decisions regarding surgical resection should not be based upon degree of cyst fluid CEA elevation.

Mo1201 Pancreatic Stellate Cells Express Inducible Nitric Oxide Synthase

BACKGROUND: IPMN is a precursor lesion to pancreatic ductal adenocarcinoma consisting of 4 epithelial subtypes with varying grades of dysplasia. Intestinal type (IPMN-I) often involves the main duct and has a higher risk of developing invasive carcinoma in comparison to gastric type (IPMN-G). Differentiation of high-risk/malignant IPMN from low-risk IPMN and other benign/low-grade cystic pancreatic lesions remains a challenge, especially in the preoperative setting. mAb Das-1 reacts specifically to a colonic epithelial phenotype. It is both sensitive and specific in identifying various pre-malignant and malignant lesions of the upper GI tract including Barrett's esophagus and incomplete gastrointestinal metaplasia associated with gastric cancer. We have previously demonstrated that it specifically detects high risk IPMN tissue histologically. AIM: To assess the ability of mAb Das-1 to identify cyst fluid of IPMN with a high risk of malignant transformation. METHODS: Cyst fluid was aspirated during surgical resection of IPMN (n=10), serous cystadenoma (n=1), and cystic low-grade neuroendocrine tumor (n=1). Cyst fluid was also aspirated during EUS-FNA of pancreatic pseudocysts (n=4). Sandwich ELISA was performed on each sample (utilizing mAb Das-1 IgM & IgG isotypes) and results were confirmed by Western Blot analysis. Statistical significance was calculated by T-test. RESULTS: Pancreatic cyst fluid from all benign/low-grade lesions (n=8) demonstrated very little reactivity with mAb Das-1 (OD 0.137±0.181). Specifically, reactivity was low among cyst fluid collected from low-grade IPMN-G (OD 0.088±0.003, n=2), pseudocyst (n=4) (OD 0.088±0.041), and non-pseudocyst, benign/low-grade lesions (n=4) (OD 0.187±0.251). In comparison, high-risk and malignant IPMN lesions (intermediate-grade IPMN-I & all high-grade/invasive IPMNs n=8) expressed a significantly higher amount of reactivity (OD 0.866±0.151) when compared to low-grade IPMN-G (p<0.001), pseudocyst (p<0.001), and all benign/low-grade lesions (p<0.002). When stratified by subtype, low-grade IPMN-G (n=2, OD 0.088±0.003), IPMN-G with highgrade dysplasia or invasive carcinoma (n=2, OD 0.402±0.313), intermediate-grade IPMN-I (n=2, OD 0.6339±0.100), IPMN-I with high-grade dysplasia or invasive carcinoma (n=3, OD 1.232±0.265) and high-grade Oncocytic IPMN (OD 1.161), demonstrated a progressive increase in reactivity to mAb Das-1 among each subtype. All results obtained by ELISA were confirmed by western blot analysis. CONCLUSION: mAb Das-1 demonstrates significantly higher reactivity in cyst fluid from high-risk and malignant IPMN compared to fluid from low-grade IPMN-G, pancreatic pseudocyts, and other low-grade pancreatic cystic lesions. The expression of this marker in preoperative cyst fluid may be a useful tool to identify high-risk IPMN lesions and stratify surgical management.

Outcome of the pancreatic remnant following segmental pancreatectomy for non-invasive intraductal papillary mucinous neoplasm

ObjectivesIntraductual papillary mucinous neoplasms (IPMNs) are often multifocal and involve the entire pancreas. Because of the morbidity associated with total pancreatectomy, surgeons will perform segmental pancreatectomy, resecting only the most ‘threatening’ IPMN lesion(s). We sought to determine whether the presence of residual IPMN following segmental pancreatectomy for non-invasive IPMN increases the risk for subsequent development of invasive pancreatic cancer and decreases survival. MethodsData on patients undergoing segmental resection of non-invasive IPMN during the period 1991–2010 at a high-volume academic institution were prospectively accrued. ResultsOf 243 patients who underwent segmental resection for IPMN, 191 (79%) demonstrated non-invasive pathology. Of these, 153 (80%) showed the absence and 38 (20%) the presence of residual IPMN at the initial operation. Of the 38 patients with residual IPMN, eight had positive IPMN margins, 23 had radiographic evidence of IPMN, and seven had both. During a mean follow-up of 73 months, 31 (20%) of 153 patients without residual IPMN developed a new radiographic lesion consistent with IPMN and, of these, three (10%) were found to represent invasive cancer. One (3%) of 38 patients with residual IPMN developed invasive cancer. In summary, in 191 initially non-invasive cases of IPMN, four invasive cancers (2%) developed during follow-up. The mean progression-free interval in these four patients was 54 months (range: 20–99 months). ConclusionsCompared with patients undergoing complete operative IPMN clearance, patients with residual IPMN after segmental pancreatectomy do not demonstrate increased risk for the development of invasive disease or reduced survival. In patients without residual IPMN who later develop new IPMN, the risk for invasive IPMN is increased.

Epithelial subtype influences the prognosis of invasive IPMN

Invasive intraductal mucinous papillary neoplasms (IPMNs) are a heterogenous group of neoplasms, but little is known about the epithelial subtypes of the precursor IPMNs from which these lesions arise and how they might influence prognosis. Mari Mino-Kenudson and colleagues constructed a multivariate, stage-matched Cox proportional hazard model to compare hazard ratio according to tumor type (both invasive carcinomas and intraductal components) in patients with invasive IPMNs.

Diffusion-weighted imaging in characterization of cystic pancreatic lesions

To evaluate whether apparent diffusion coefficient (ADC) measurements from diffusion-weighted imaging (DWI) can characterize or predict the malignant potential of cystic pancreatic lesions. Retrospective review of the magnetic resonance imaging (MRI) database over a 2-year period revealed 136 patients with cystic pancreatic lesions. Patients with DWI studies and histological confirmation of cystic mass were included. In patients with known pancreatitis, lesions with amylase content of >1000 IU/l that resolved on subsequent scans were included as pseudocysts. ADC of cystic lesions was measured by two independent reviewers. These values were then compared to categorize these lesions as benign or malignant using conventional MRI sequences. Seventy lesions were analysed: adenocarcinoma (n=4), intraductal papillary mucinous neoplasm (IPMN; n=28), mucinous cystic neoplasm (MCN; n=9), serous cystadenoma (n=16), and pseudocysts (n=13). There was no difference between ADC values of malignant and non-malignant lesions (p=0.06), between mucinous and serous tumours (p=0.12), or between IPMN and MCN (p=0.42). ADC values for low-grade IPMN were significantly higher than those for high-grade or invasive IPMN (p=0.03). ADC values may be helpful in deciding the malignant potential of IPMN. However, they are not useful in differentiating malignant from benign lesions or for characterizing cystic pancreatic lesions.