Noninvasive Intraductal Papillary Mucinous Neoplasms Research Articles

Intraductal papillary mucinous neoplasm A Swedish nationwide register-based study on 238 patients

Background: Intraductal papillary mucinous neoplasms (IPMN) have an adenoma-carcinoma sequence but to date the impact of the different dysplastic grades on survival is not thoroughly explored. Studies often tend to classify high-grade dysplastic lesions as malignant together with invasive lesions when performing comparative subgroup analyses. Methods: A retrospective review of prospectively collected data was performed using a nationwide register on histologically diagnosed IPMNs resected in Sweden during 2011 - 2016. Patients with a histological staging of the dysplastic grade, from low-grade to invasive carcinoma were included. Results: A total of 238 patients were included (211 noninvasive and 27 invasive). There was no difference in survival between low-grade, intermediate-grade and high-grade dysplastic lesions (p=0.722) and they had similar 3-year survival 83%, 89% and 92%, respectively. However, once invasive the prognosis was severely impacted (p<0.001). One-year survival was 41% for invasive IPMN and 94% for noninvasive IPMN. Survival was slightly better but still worse in lymph node negative invasive IPMNs compared to noninvasive lesions (p=0.026). There was no age difference between the different dysplastic grades. Diabetes mellitus and a CA19-9 ≥37 U/ml were more often seen in patients with invasive IPMN. Conclusion: High-grade dysplastic IPMN should not be considered a malignant disease, a finding that is consisting with previous work. Invasive IPMN has a poor prognosis even when lymph node negative.

High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm

Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN).Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were evaluated in a cohort consisting of 109 serum samples, including 49 patients with resectable pancreatic cancer, 13 patients with resectable noninvasive IPMN and 47 healthy controls, using a targeted assay.Results: Multivariable analysis defined sets of panels comprising CA19-9 and distinctively glycosylated proteins for discrimination between pancreatic cancer, IPMN and healthy controls. A panel including CA 19-9, IL.17E, B7.1 and DR6 gave an AUC of 0.988 at 100% sensitivity at 90% specificity for the discrimination of stage 1 pancreatic cancer and healthy controls. B7.1 was found to be a valuable biomarker for differentiating between IPMN and healthy controls, with better performance alone than CA 19-9.Conclusions: Measurement of protein glycosylation profiles in serum may aid in the early detection of pancreatic cancer and precursor lesions.

ASO Author Reflections: Progression after Resection of Noninvasive or Microinvasive Intraductal Papillary Mucinous Neoplasms.

ASO Author Reflections: Progression after Resection of Noninvasive or Microinvasive Intraductal Papillary Mucinous Neoplasms.

Identification of nonalcoholic fatty liver disease following pancreatectomy for noninvasive intraductal papillary mucinous neoplasm

BackgroundNonalcoholic fatty liver disease (NAFLD) following pancreatectomy is a potential cause of long term morbidity in patients undergoing pancreatic resection with curative intent. Prior studies have reported an incidence of NAFLD up to 30% following pancreatectomy but the investigated cohorts were typically a mix of benign and malignant disease. Here we examined the incidence of NAFLD in a homogenous cohort of patients following pancreatectomy for benign intraductal papillary mucinous neoplasm (IPMN). MethodsA retrospective review of patients who underwent pancreatic resection for IPMN from 2000 to 2016 was performed. Post pancreatectomy CT/MRI scans were obtained as standard surveillance. We investigated changes in the liver parenchymal density on post surgical imaging to estimate the frequency with which NAFLD occurred. Radiographic criteria for NAFLD included Hounsfield units less than 40 on CT or liver:spleen ratio <0.9 on CT or MRI. Fischer's exact test, Kruskal-Wallis test, and logistic regression were performed. ResultsOur study cohort included 109 patients who underwent pancreatectomy for nonmalignant intraductal papillary mucinous neoplasm with no evidence of NAFLD preoperatively and at least 6 months follow-up. Mean follow-up was 52 months (range 8–130/months). The incidence of postoperative NAFLD was 17/109 (15.6%). Most cases occurred within 12 months of pancreatectomy. On multivariate analysis, proximal pancreatectomy (pancreaticoduodenectomy) and development of atrophy of the pancreas remnant were significant risk factors for development of hepatic steatosis (p < 0.05). ConclusionPatients undergoing pancreatectomy for benign disease have a significant risk of developing NAFLD but the frequency is lower than previously reported in cohorts that included individuals with malignant disease. Highest risk was observed in individuals who underwent pancreaticoduodenectomy or developed pancreatic atrophy. Further investigations to define the mechanisms that promote steatosis and interventions to prevent subsequent morbidity from NAFLD are warranted.

Does Surgical Margin Impact Recurrence in Noninvasive Intraductal Papillary Mucinous Neoplasms?: A Multi-institutional Study.

The relevance of margin positivity on recurrence after resection of intraductal papillary mucinous neoplasms (IPMNs) is poorly defined and represents one reason controversy remains regarding optimal surveillance recommendations. Patients undergoing surgery for noninvasive IPMN at 8 academic medical centers from the Central Pancreas Consortium were analyzed. A positive margin was defined as presence of IPMN or pancreatic intraepithelial neoplasia. Five hundred two patients underwent surgery for IPMN; 330 (66%) did not have invasive cancer on final pathology and form the study cohort. Of these, 20% harbored high grade dysplasia. A positive margin was found in 20% of cases and was associated with multifocal disease (P = 0.02). The majority of positive margins were associated with low grade dysplasia. At a median follow-up of 36 months, 34 (10.3%) patients recurred, with 6.7% developing recurrent cystic disease and 3.6% developing invasive cancer. On multivariate analysis, margin positivity was not associated with recurrence of either IPMN or invasive cancer (P > 0.05). No association between margin status and development of recurrence at the margin was found. Only 6% of recurrences developed at the resection margin and median time to recurrence was 22 months. Of note, 18% of recurrences occurred > 5 years following surgery. Margin positivity after resection for noninvasive IPMNs is primarily due to low grade dysplasia and is not associated with developing recurrence in the remnant pancreas or at the resection margin. Long-term surveillance is required for all patients, as a significant number of recurrences developed over 5 years after the index operation.

Multifocal cysts and incidence of pancreatic cancer concomitant with intraductal papillary mucinous neoplasm

ObjectivesThe present study was conducted in order to elucidate the relationship between the number of cyst-existing regions and incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN), which currently remains unclear. MethodsSubjects comprised 141 patients undergoing resection for IPMN (Non-invasive IPMN (IPMN with low-to high-grade dysplasia): N = 94, invasive IPMN: N = 31, and PDAC concomitant with IPMN: N = 16) between November 2000 and February 2017. A logistic regression analysis was performed to assess the relationship between the number of cyst-existing regions (one region/two or more regions) and incidence of PDAC concomitant with IPMN, adjusted by clinical characteristics. Cyst-existing regions were defined by the number of anatomical parts of the pancreas: the head/body/tail of the pancreas. ResultsMultiple cyst-existing regions (two or more regions) correlated with the incidence of PDAC concomitant with IPMN (PDAC concomitant with IPMN in one region vs. two or more regions: 3/66 vs. 13/75, multivariable odds ratio [OR] = 4.11, 95% confidence interval [CI] = 1.22 to 18.8, P = 0.02). In contrast, multiple cyst-existing regions did not correlate with the incidence of IPMN (invasive IPMN in one region vs. two or more regions: 13/66 vs. 18/75, OR = 1.19, 95% CI = 0.52 to 2.76, P = 0.67). ConclusionsMultifocal cysts correlated with the incidence of PDAC concomitant with IPMN, and may be a high-risk factor for PDAC concomitant with IPMN.

Intraductal Papillary Mucinous Neoplasms of The Pancreas: A Nationwide Registry-Based Study.

To investigate the paraclinical and pathological features of surgically resected intraductal papillary mucinous neoplasms in Sweden. A review of prospectively collected data on patients undergoing pancreatic resection for a histopathologically verified intraductal papillary mucinous neoplasm between 2010 and 2016 was performed using the Swedish National Registry for Pancreatic and Periampullary Cancer. A total of 3038 pancreatic resections were performed during the study period, of which 251 (8.3%) were due to intraductal papillary mucinous neoplasms. The intraductal papillary mucinous neoplasm cases comprised 227 noninvasive and 24 invasive lesions. There was an annual increase in the number of resected intraductal papillary mucinous neoplasms, from 13 in 2010 to 56 in 2016, and an increase in the proportion of intraductal papillary mucinous neoplasm to the total number of pancreatic resections (4.7%-11%). Biliary obstruction was the only independent predictor of invasive disease, with odds ratio 3.106 (p = 0.030). There was no difference in survival between low-, intermediate-, and high-grade dysplastic lesions (p = 0.417). However, once invasive, the prognosis was severely impacted (p < 0.001). Three-year survival was 90% for noninvasive intraductal papillary mucinous neoplasm and 39% for invasive intraductal papillary mucinous neoplasm. Survival was better in lymph node negative invasive intraductal papillary mucinous neoplasm (p = 0.021), but still dismal compared to noninvasive lesions (p < 0.001). The number of surgically resected intraductal papillary mucinous neoplasms is increasing in Sweden. Biliary obstruction is associated with invasive disease. Low-to-high-grade dysplastic intraductal papillary mucinous neoplasm has an excellent prognosis, while invasive intraductal papillary mucinous neoplasm has a poor survival rate.

Progression Patterns in the Remnant Pancreas after Resection of Non-Invasive or Micro-Invasive Intraductal Papillary Mucinous Neoplasms (IPMN).

Although IPMN are thought to represent a whole-gland disease, segmental resection remains the most frequently performed treatment. We sought to determine the rates, patterns, and predictors of IPMN progression in the pancreatic remnant following segmental resection of noninvasive or microinvasive IPMN. A prospectively maintained database was queried to identify all patients who underwent resection of noninvasive or microinvasive IPMN (≤ 10mm of invasive component) between 1989 and 2015. Progression (recurrence) was defined as either the development of cancer, a new IPMN cystic lesion > 1cm or ≥ 50% increase in the diameter of residual IPMN lesions in the remnant. Univariate and multivariate cox regression models were created to determine predictors of progression. A total of 319 patients underwent resection for noninvasive and microinvasive IPMN. The median age was 68, 53% had branch-duct (BD) IPMN, and 6% had microinvasive disease. After a median follow-up of 42months, 71 patients (22%) experienced IPMN progression. Within this group of 71 patients, 11 (16% of recurrence) developed invasive cancer in the pancreatic remnant after a median of 28months. Twelve patients (17%) experienced progression > 5years following initial resection. On multivariate analysis, a distal location of the initial lesion was associated with an increased risk of progression (multivariate hazards ratio = 2.43, confidence interval 1.47-4.0, p < 0.001). In this study, 22% of patients had disease progression following resection of noninvasive or microinvasive IPMN; 16% of these progressions represented invasive disease. These patients represent a high-risk group and should undergo long-term radiographic surveillance.

Major complications following pancreatectomy for small pancreatic neuroendocrine and cystic neoplasms less than 2-cm: an argument for selective observation or resection

Background: Increased utilization of high-quality cross-sectional imaging has resulted in more patients with incidental pancreatic lesions. However, the decision to observe or to operate on asymptomatic small lesions has remained controversial. We aim to identify factors associated with major complications following resection for small pancreatic neuroendocrine and cystic neoplasms. Methods: ACS-NSQIP Pancreatectomy database was used to identify patients who underwent pancreatectomy for benign pancreatic neoplasms <2 cm, including non-invasive intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), neuroendocrine tumors (PNET), and serous cystadenomas (SCA). Logistic regression was used to identify predictors of major complications. Results: A total of 414 patients with benign pancreatic lesions <2 cm were identified (48% IPMN, 25% PNET, 15% MCN, and 12% SCA). Operations include distal pancreatectomy (54%), pancreaticoduodenectomy (28%), and enucleation (9%). Overall morbidity and major complications were 27% and 20%, respectively, while the 90day mortality was 0.7%. These were similar whether lesions were greater or less than 2cm. Readmission rate was 19%, most often for abscesses or venous thromboembolism. Pancreatic morbidities include 22% fistula (14% required percutaneous drainage) and 9% delayed gastric emptying. On multivariate analysis, postoperative drain amylase >10,000 U/L and extent of pancreatectomy were independent predictors of major complications. Conclusion: Patients with benign lesions undergoing pancreatectomy are subject to considerable morbidity with difficult to measure oncologic benefit. In patients with asymptomatic, benign pancreatic neuroendocrine and cystic neoplasms, the risk of major complications may exceed the risk of malignancy. Patient counseling and radiographic surveillance may be appropriate in select patients.Tabled 1Multivariate logistic regression predicting major complications for patients undergoing pancreatectomy for benign pancreatic endocrine and cystic neoplasms less than 2-cm.OR95% ClP valueAge (per year)1.120.605–2.060.724ASA class >30.8410.472–1.4990.558BMI1.0160.971–1.0630.484Female0.4920.292–0.8310.008Type of pancreatectomy EnucleationReference Distal pancreatectomy5.5130.187–25.5960.029 Pancreaticoduodenectomy11.572.433–55.0510.002 Pancreatectomy NOS4.1090.721–23.4090.111Drain amaylase <10,000 U/LReference >10,000 U/L5 5512.120–14.538<0.001 Not reported1.1800.5855–2.3790.643 Open table in a new tab

Identification of a pyruvate-to-lactate signature in pancreatic intraductal papillary mucinous neoplasms

ObjectiveWe used transcriptomic profiling and immunohistochemistry (IHC) to search for a functional imaging strategy to resolve common problems with morphological imaging of cystic neoplasms and benign cystic lesions of the pancreas. MethodsResected pancreatic cancer (n = 21) and normal pancreas were laser-capture micro-dissected, and transcripts were quantified by RNAseq. Functional imaging targets were validated at the protein level by IHC on a pancreatic adenocarcinoma tissue microarray and a newly created tissue microarray of resected intraductal papillary mucinous neoplasms (IPMNs) and IPMN-associated adenocarcinomas. ResultsGenes encoding proteins responsible for cellular import of pyruvate, export of lactate, and conversion of pyruvate to lactate were highly upregulated in pancreatic adenocarcinoma compared to normal pancreas. Strong expression of MCT4 and LDHA was observed by IHC in >90% of adenocarcinoma specimens. In IPMNs, the pyruvate-to-lactate signature was significantly elevated in high grade dysplasia (HGD) and IPMN-associated adenocarcinoma. Additionally, cores containing HGD and/or adenocarcinoma exhibited a higher number of peri-lesional stromal cells and a significant increase in peri-lesional stromal cell staining of LDHA and MCT4. Interestingly, the pyruvate-to-lactate signature was significantly upregulated in cores containing only low grade dysplasia (LGD) from patients with histologically confirmed IPMN-associated adenocarcinoma versus LGD cores from patients with non-invasive IPMNs. ConclusionOur results suggest prospective studies with hyperpolarized [1–13C]-pyruvate magnetic resonance spectroscopic imaging are warranted. If these IHC results translate to functional imaging findings, a positive pyruvate-to-lactate imaging signature might be a risk factor for invasion that would warrant resection of IPMNs in the absence of other worrisome features.

Binding pancreaticogastrostomy anastomosis in central pancreatectomy: A single center experience.

A growing number of central pancreatectomies are performed. However, reconstruction of pancreaticoenteral digestive continuity after central pancreatectomy remains debated. This study evaluates the short-term outcomes of binding pancreaticogastrostomy anastomosis in central pancreatectomy.We have reviewed our experience with 52 patients who underwent binding pancreaticogastrostomy following central pancreatectomy from February 2009 to March 2015. Indication includes 6 noninvasive intraductal papillary mucinous neoplasms, 11 neuroendocrine tumors, 12 solid pseudopapillary tumor, 9 serous cystadenoma, 6 mucinous cystadenoma, and 8 focal pancreatic traumas.The mortality rate was nil while the morbidity rate was 34.6%. Eighteen patients experienced complications including 6 pancreatic fistulas, 2 postpancreatectomy hemorrhages, 4 delayed gastric emptying, 1 hypostatic pneumonia, and 5 pancreatitis. The median postoperative length of hospital stay was 12 days (10 days for patients without fistula). None of the 52 patients were found to have pancreatic endocrine or exocrine insufficiency or recurrence of tumors.Central pancreatectomy with binding pancreaticogastrostomy is a useful and practicable surgical procedure for benign or borderline lesions of the pancreatic neck or proximal body.

Factors Associated With Invasive Intraductal Papillary Mucinous Carcinoma of the Pancreas

Invasive intraductal papillary mucinous carcinoma has aggressive malignant behavior, including lymph node metastasis. It is important to identify factors associated with invasive intraductal papillary mucinous carcinoma to determine operative procedures, but they remain unclear. To identify the specific factors associated with invasive intraductal papillary mucinous neoplasms for branch duct, main duct, and mixed type carcinomas. Retrospective cohort study of 286 consecutive patients who underwent surgical resection for intraductal papillary mucinous neoplasm from July 1999 to December 2015 at a tertiary institute. We compared clinical features between 96 patients (33.6%) with invasive intraductal papillary mucinous carcinoma and 190 patients (66.4%) with noninvasive intraductal papillary mucinous neoplasm for each morphological type. Factors associated with invasive intraductal papillary mucinous carcinoma. Mural nodule size was measured by endoscopic ultrasonography. Of the 286 patients included in the cohort, the median (range) age was 71 (28-86) years, and 162 (56.6%) were male. High mural nodule size was independently associated with invasive intraductal papillary mucinous carcinoma in all types (branch duct: odds ratio [OR], 1.992; 95% CI, 1.177-3.367; P = .01; main duct: OR, 1.443; 95% CI, 1.094-1.905; P = .01; and mixed: OR, 1.178; 95% CI, 1.057-1.312; P = .04). The cutoff values for intraductal papillary mucinous neoplasms, determined by a receiver operating characteristic, were 9 mm for branch duct and 6 mm for mixed and main duct carcinoma. A high carcinoembryonic antigen level in the pancreatic juice was independently associated with mixed (OR, 1.002; 95% CI, 1.000-1.003; P = .01) and main duct (OR, 1.002; 95% CI, 1.000-1.003; P = .048) carcinomas, and the cutoff values were determined to be 150 and 300 ng/mL, respectively (to convert to micrograms per liter, multiply by 1). In addition, both being female and having an elevated serum carbohydrate antigen 19-9 level were also found to be independently associated with mixed type invasive intraductal papillary mucinous carcinoma, and using any 2 among 4 identified factors yielded the highest accuracy (79.0%) for mixed type carcinomas. For all types, the accuracy for these factors was 86.0% for differentiating between invasive and noninvasive intraductal papillary mucinous neoplasms, which was superior to the accuracies using the "high-risk stigmata" factors or "worrisome features" suggested by the international consensus guideline in 2012 (66.1% and 39.9%, respectively). The measurement of mural nodule size in all types of carcinomas and carcinoembryonic antigen level in the pancreatic juice in mixed and main duct carcinomas might play important roles in predicting invasive intraductal papillary mucinous carcinoma, but further large studies are needed to confirm these results.

Pancreatic resection for intraductal papillary mucinous neoplasm- a thirteen-year single center experience.

BackgroundThe purpose of this study is to review our results for pancreatic resection in patients with intraductal papillary mucinous neoplasm (IPMN) with and without associated carcinoma.MethodsA total of 54 patients undergoing pancreatic resection for IPMN in a single university surgical center (Medical University of Graz) were reviewed retrospectively. Their survival rates were compared to those of patients with pancreatic ductal adenocarcinoma.ResultsTwenty-four patients exhibit non-invasive IPMN and thirty patients invasive IPMN with associated carcinoma. The mean age is 67 (+/-11) years, 43 % female. Surgical strategies include classical or pylorus-preserving Whipple procedure (n = 30), distal (n = 13) or total pancreatectomy (n = 11), and additional portal venous resection in three patients (n = 3). Median intensive care stay is three days (range 1 – 87), median in hospital stay is 23 days (range 7 – 87). Thirty-day mortality is 3.7 %. Median follow up is 42 months (range 0 – 127). One-, five- and ten-year overall actuarial survival is 87 %; 84 % and 51 % respectively. Median overall survival is 120 months. Patients with non-invasive IPMN have significantly better survival than patients with invasive IPMN and IPMN-associated carcinoma (p < 0.008). In the subgroup of invasive IPMN with associated carcinoma, a positive nodal state, perineural invasion as well as lymphovascular infiltration are associated with poor outcome (p < 0.0001; <0.0001 and =0.001, respectively). Elevated CA 19-9(>37 U/l) as well as elevated lipase (>60 U/l) serum levels are associated with unfavorable outcome (p = 0.009 and 0.018; respectively). Patients operated for pancreatic ductal adenocarcinoma show significantly shorter long-term survival than patients with IPMN associated carcinoma (p = 0.001).ConclusionsLong-term outcome after pancreatic resection for non-invasive IPMN is excellent. Outcome after resection for invasive IPMN with invasive carcinoma is significantly better than for pancreatic ductal adenocarcinoma. In low- and intermediate risk IPMN with no clear indication for immediate surgical resection, a watchful waiting strategy should be evaluated carefully against surgical treatment individually for each patient.

Targeted DNA Sequencing Reveals Patterns of Local Progression in the Pancreatic Remnant Following Resection of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas.

The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS). Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm. Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression. We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas. Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas.

Plectin-1 as a Biomarker of Malignant Progression in Intraductal Papillary Mucinous Neoplasms: A Multicenter Study.

This study aimed to evaluate Plectin-1 expression as a biomarker of malignant risk for intraductal papillary mucinous neoplasms (IPMNs). Plectin-1 immunohistochemistry (IHC) was performed retrospectively on surgical (n = 71) and cytological (n = 33) specimens from Mayo Clinic Jacksonville and UCLA Medical Center, including IPMNs with low-grade dysplasia, high-grade dysplasia (HGD), or an associated invasive adenocarcinoma. Plectin-1 expression was increased in invasive adenocarcinoma compared with adjacent in situ IPMN (P = 0.005), as well as the in situ HGD component of IPMNs with invasive cancer compared with HGD of IPMNs without invasive cancer (P = 0.02). Plectin IHC discriminated IPMNs with invasive adenocarcinoma from noninvasive IPMN (area under the curve [AUC] of 0.79, 75% sensitivity, and 85% specificity) but was insufficient for discriminating HGD IPMN from low-grade dysplasia IPMNs in surgical resections (AUC of 0.67, 56% sensitivity, and 64% specificity) or fine-needle aspiration specimens (AUC of 0.45). Although Plectin-1 IHC has insufficient accuracy to be used as a definitive biomarker for malignant risk in the evaluation of IPMN biopsy or cytological specimens, increased Plectin-1 expression observed in both invasive cancer and in situ HGD of malignant IPMNs suggests that it might be successfully leveraged as a cyst fluid biomarker or molecular imaging target.

MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm.

Despite strict criteria for the observation of intraductal papillary mucinous neoplasm (IPMN), it remains difficult to distinguish invasive IPMN from non-invasive IPMN. The aim of the present study was to identify an indicator of invasive IPMN. The present study retrospectively evaluated 53 patients (28 with non-invasive and 25 with invasive IPMN) who underwent resection of IPMN, and examined the usefulness of the MIB-1 labeling index as an indicator of invasive IPMN. The MIB-1 labeling indexes in patients with invasive IPMN were significantly higher compared with those with non-invasive IPMN (P<0.001). A receiver operating characteristic curve revealed that the area under the curve was 0.822. These results suggested that a cut-off level for the MIB-1 labeling index should be set to 15.5% to distinguish invasive from non-invasive IPMN. A multivariate analysis using a logistic regression model revealed the MIB-1 labeling index (hazard ratio, 18.692; 95% confidential interval, 4.171-83.760; P<0.001) and the existence of mural nodules (hazard ratio, 6.187, 95% confidential interval, 1.039-36.861; P=0.045) were predictive factors for invasive IPMN. However, no statistically significant differences were observed between patients with a lower MIB-1 labeling index and patients with a higher MIB-1 labeling index (P=0.798). The MIB-1 labeling index must be considered as a candidate for the classification of IPMN.

Intraductal papillary mucinous neoplasm (IPMN): outcome of surgical resection

Introduction: The increased use of routine cross sectional imaging has resulted in an increasing number of incidentally detected IPMN of the pancreas. Our aim was to examine our experience with these lesions, in particular to review outcomes after resection. Methods: We utilised a prospectively maintained database of all patients with a diagnosis of IPMN on post-operative histology in the time period from Jan 2005 to Jan 2015. Data were analysed using Statview Ltd programme. Results: 90 patients underwent pancreatic resections for IPMN/T in the time period assessed. The median age was 63 years, 52 (58%) were females and the median follow up was 28 months, of the 25 (28%) patients found to have an invasive tumour on subsequent histology, 11 had a T1/2 tumour and 13 had a T3 tumour. Only 6 (24%) were identified as having a mass on pre-operative imaging (CT and EUS). A further 10 patients had suspicion of a mass at pre-operative EUS, none of whom were found to have invasion after resection. Pre-operative cyst fluid amylase and CEA were not predictive of malignant transformation. The overall survival for those with invasive disease was significantly lower than for those with non-invasive disease (Log Rank 0.005). However, there was no significant difference in overall survival between those patients with T1 tumour compared to non-invasive IPMN. Conclusion: The prognosis from IPMN is significantly reduced by the presence of more advanced invasive disease. Hence, early surgical intervention is recommended until more accurate preoperative diagnostic modalities are available.

Cystic Lesions of the Pancreas: Observe or Operate.

Cystic Lesions of the Pancreas: Observe or Operate.

Intraductal papillary mucinous neoplasm in an annular pancreas: a case report

Annular pancreas is a rare anomaly in which a ring of pancreatic tissue encircles the second portion of the duodenum. We herein report a case involving a 79-year-old Japanese man with an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Imaging studies showed that the pancreatic tissue encircled the descending part of the duodenum and that a 30-mm-diameter cystic tumor was present in the annular segment, leading to the diagnosis of pancreatic IPMN. Limited pancreatic resection was successfully performed by careful division of the annular segment from the second portion of the duodenum. The postoperative course was uneventful, and the patient’s pancreatic function was retained without the need for supplementation. To the best of our knowledge, this is the first report of IPMN occurring in the annular segment of the pancreas. Limited resection of the pancreatic annular segment is a feasible surgical treatment for noninvasive IPMN of the annular pancreas.

Serum N-glycan profiles in patients with intraductal papillary mucinous neoplasms of the pancreas.

Diagnosing the invasiveness of intraductal papillary mucinous neoplasms (IPMNs) is difficult, especially by blood test. Alterations in serum glycan profiles have been reported for several cancers, but changes in serum glycan profiles have not been investigated in patients with IPMNs. The objectives of this study were to determine the serum N-glycan profile and to investigate its clinical utility in patients with IPMNs. We measured serum N-glycan profiles in 79 patients with IPMNs, including 13 invasive IPMNs, by performing comprehensive glycome analysis and assessed the relationship between N-glycan changes and clinical parameters. Seventy glycans were identified and their expression profiles were significantly different depending on the cyst size, the presence of an enhancing solid component, and the histological grade of the IPMN. Nine glycans were highly expressed in patients with invasive IPMNs. The glycan m/z 3195, which is a fucosylated tri-antennary glycan, had the highest diagnostic value for distinguishing invasive IPMNs from non-invasive IPMNs (area under the receiver operating characteristic curve=0.803). Multivariate analyses revealed high levels of m/z 3195 [odds ratio (OR), 20.5; 95% confidence interval (CI) 2.60-486.4] and the presence of enhancing solid components (OR, 35.8; 95% CI, 5.39-409.6) were significant risk factors for invasive IPMNs. We performed a comprehensive evaluation of the changes in serum N-glycan profiles in patients with IPMNs for the first time. We determined that increased expression of fucosylated complex-type glycans, especially m/z 3195, is a potential marker for invasive IPMNs.