Prediction of long-term survival in patients with invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas may aid in patient assessment, risk stratification and personalization of treatment. This study aimed to investigate the predictive ability of artificial neural networks (ANN) and LASSO regression in terms of 5-year disease-specific survival. ANN work in a non-linear fashion, having a potential advantage in analysis of variables with complex correlations compared to regression models. LASSO is a type of regression analysis facilitating variable selection and regularization. A total of 440 patients undergoing surgical treatment for invasive IPMN of the pancreas registered in the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2016 were analyzed. The dataset was prior to analysis randomly split into a modelling and test set (7:3). The accuracy, precision and F1 score for predicting mortality were 0.82, 0.83 and 0.89, respectively for ANN with variable selection compared to 0.79, 0.85 and 0.87, respectively for the LASSO-model. ANN using all variables showed similar accuracy, precision and F1 score of 0.81, 0.85 and 0.88, respectively compared to a logistic regression analysis. McNemar´s test showed no statistical difference between the models. The models showed high and similar performance with regard to accuracy and precision for predicting 5-year survival status.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor lesion to pancreatic adenocarcinoma. It covers a broad histological spectrum, ranging from low grade dysplasia to invas...

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.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic tumor with a disease spectrum ranging from low-grade dysplasia to invasive carcinoma. The evidence for adjuvant treatment in invasive IPMN is limited and mostly derived from studies in conventional pancreatic ductal adenocarcinoma (PDAC). We performed a systematic review focusing on all clinical studies concerning the efficacy of adjuvant therapy in patients with invasive IPMN. We identified 8 retrospective cohort studies, using either adjuvant chemotherapy alone (n=1), adjuvant radiotherapy alone (n=1) or adjuvant chemotherapy in combination with radiation (n=6). Adjuvant therapy was associated with a survival benefit in 7 out of the 8 studies. Specific survival benefit was noted for patients with node-positive disease, higher TNM stage, positive resection margins, poor differentiation and tubular subtype. We conclude that adjuvant therapy may be beneficial in invasive IPMN, but current data suggest that it should be given selectively based on individual tumor characteristics. Further prospective, randomized studies are warranted.

Background: Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection. Methods: Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model. Results: A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09-0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05-0.25 and OR 0.38, 95% CI 0.26-0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12-23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71-7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32-0.57). Conclusion: Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC.

Background: Branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) presents a clinical conundrum. Rigorous long-term surveillance or surgical resection is recommended. The economic consequences of the management have not been fully investigated. Methods: A Markov decision model compared 4 strategies for low-risk BD-IPMN: I = upfront total pancreatectomy, II = upfront partial pancreatectomy, III = initial surveillance, IV = watchful waiting. Surveillance was based on the Swedish Guidelines for Pancreatic Cancer. Probabilities and costs were obtained from the participating unit and from the scientific literature. The incremental cost-effectiveness ratios (ICERs) were calculated and sensitivity analyses were performed by varying relevant parameters. Survival was reported in quality-adjusted life-years (QALYs). Results: Strategy III was the most cost-effective strategy with an ICER of ss31 682 compared to strategy IV. Strategy I was the most expensive but yielded the best QALY (9.32). Total number of years, annual risk of pancreatic cancer and annual risk of a low-risk BD-IPMN turning into a high-risk lesion had the greatest impact in the model. Conclusions: Initial surveillance seems to be the most cost-effective strategy in the management of low-risk asymptomatic BD-IPMN. However, the possibility of personalized approaches remains to be investigated.

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.

Background and Aims: To investigate the paraclinical and pathological features of surgically resected intraductal papillary mucinous neoplasms in Sweden. Materials and Methods: 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. Results: 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). Conclusion: 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.

Intraductal papillary mucinous neoplasm (IPMN) is one of the most common cystic neoplasms of the pancreas. It is a heterogeneous disease and can be divided into ductal types and morphological subtypes. The incidence of IPMN is increasing, likely due to the widespread use of cross-sectional imaging and a growing elderly population. IPMN poses an increasing demand on the health care system. Current guidelines provide indications for surgery and recommendations for surveillance, but management of IPMN is still challenging in routine clinical practice. In this article, we review current knowledge about IPMN and provide future directions for improving diagnosis and management.

Pancreatic cystic lesions represent a heterogeneous group of diseases ranging from benign to malignant lesions. They are increasingly being detected due to the widespread use of cross-sectional imaging. Their management is a challenge because it is often not possible to reliably discriminate between malignant and nonmalignant lesions using current imaging technology. Next-generation sequencing (NGS) has the ability of both whole genome and targeted sequencing at a low cost and from a limited amount of DNA. NGS of cyst fluid aspired by endoscopic ultrasonography-guided fine-needle aspiration provides a valuable tool in biomarker research and may in the future help improve diagnosis and management of pancreatic cystic lesions.

Background: Overweight, defined by body mass index (BMI), is correlated to complications following pan-creaticoduodenectomy (PD). The aim of this study was to evaluate the impact of body constitution, measured with different anthropometric measures, and diabetes on complications following PD. Materials and methods: Patients who underwent PD between 2000 and 2015 at Skane University Hospital were retrospectively included. Body mass index (BMI), body surface area (BSA) and body fat percentage (BF%) were calculated. Overweight and obesity were defined by BMI according to the WHO classification (overweight >= 25 and obesity >= 30). Values equal to or above the median value were considered as large by BSA (>= 1.87) and overweight by BF% (>= 29.6% (male) and >= 38.9% (female)). Main endpoints were events of postoperative pancreatic fistula (POPF), post pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE) and complications classified according to the Clavien-Dindo classification. Multivariable analysis was performed using logistic regression and a subgroup analysis on diabetic patients was performed. Results: In total 328 patients were included. The incidence of POPF grades B and C was increased among overweight and large patients defined by BMI (OR 4.16; p = 0.001), BSA (OR 2.88; p = 0.018) and BF% (OR 3.94; p = 0.001). However, the risk was not increased among diabetic patients with BMI >= 25 and BMI >= 30. DGE and complications classified as Clavien grade >= 3 were more common in patients defined as overweight by both BMI (OR 1.72; p = 0.024 and OR 2.63; p = 0.003, respectively) and BF% (OR 2.13; p = 0.001 and OR 2.31; p = 0.009, respectively). PPH was not more frequent in overweight or large patients. Conclusion: Body constitution has an impact on the risk of severe complications following PD. BMI, BSA and BF% can all be used to identify risk groups. The risk of developing POPF grades B and C was significantly increased in overweight and large patients, but not in patients with coexisting diabetes.

Future OncologyVol. 13, No. 20 EditorialBiomarkers, imaging and multifocality in intraductal papillary mucinous neoplasms: relevant for decision making?Daniel Ansari, Linus Aronsson & Roland AnderssonDaniel Ansari Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden, Linus Aronsson Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden & Roland Andersson*Author for correspondence: Tel.: +46 46 17 23 59; E-mail Address: roland.andersson@med.lu.se Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, SwedenPublished Online:23 Aug 2017https://doi.org/10.2217/fon-2017-0244AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: biomarkersgastrointestinalmolecular oncologyoncogenespancreatic biliarysurgeryReferences1 Aronsson L, Andersson R, Ansari D. 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Surg. 143(7), 639–646 (2008).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Vol. 13, No. 20 eToC Sign up Follow us on social media for the latest updates Metrics Downloaded 34 times History Published online 23 August 2017 Published in print August 2017 Information© 2017 Future Medicine LtdKeywordsbiomarkersgastrointestinalmolecular oncologyoncogenespancreatic biliarysurgeryFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Introduction: Intraductal papillary mucinous neoplasms (IPMN) are considered precursor lesions to pancreatic adenocarcinoma. The risk of malignancy is increased in main duct/mixed type IPMNs but even with modern imaging it may be challenging to accurately diagnose main pancreatic duct involvement. The objective of this study was to determine how well radiological findings correlate with pathological features of IPMNs. Methods: Consecutive cases of IPMN undergoing pancreatic resection at our unit were reviewed. All patients' radiological images and histological slides were retrieved and re-evaluated. Radiologists and pathologists performed independent blinded assessments of the tumors. Results: Twenty-two cases of IPMN were identified with a median age was 65 years. Male to female ratio was 10:12. The diagnosis of IPMN was preoperatively suspected in 82% of cases based on radiological evaluation. The surgical procedures performed included pancreaticoduodenectomy (n = 20), total pancreatectomy (n = 1) and distal pancreatectomy (n = 1). An invasive IPMN component was seen in 55% of the specimens on histopathological evaluation. Radiological accuracy was 45% for detecting involvement of the main pancreatic duct. Seven of the patients (32%) had a second malignancy within the tumor specimen, including ampullary adenocarcinoma in 3 patients, duodenal adenocarcinoma in 2 patients, cholangiocarcinoma in 1 patient and anaplastic pancreatic cancer in 1 patient. Conclusion: Preoperative radiological assessment is fairly accurate in diagnosing IPMN, however it frequently underestimates main pancreatic duct involvement, which may question the validity of basing surgical decisions on radiological assessment of duct engagement. IPMN is often associated with a secondary periampullary malignancy.

Background The safety of pancreatic resection for elderly patients is still controversial. We examined the postoperative morbidity and mortality in patients aged 75 years or more undergoing pancreatic resection. Methods Patients undergoing pancreatic resection were studied retrospectively and the outcomes were compared between patients aged <75 and ≥75 years. Results Of the 556 patients enrolled, 78 (14%) were ≥75 years old. Elderly patients had significantly more co-morbidities, especially cardiovascular pathology (P=0.005). Also, elderly patients had significantly lower body mass index prior to surgery (P=0.005). There were no significant differences in terms of surgical procedures and tumor types between age groups. The incidence of postoperative pancreatic fistula grade A was significantly lower in the elderly group (P=0.022), but no significant differences were noted in the overall morbidity or the incidence of postpancreatectomy hemorrhage, delayed gastric emptying, bile leakage, cardiac complications, pulmonary complications or septic complications. The 30-day mortality rate was similar between groups (0.8% vs. 1.3%; P=0.532). Conclusion Pancreatic resection is a safe option for selected elderly patients. Our study confirms that age alone should not preclude potentially curative surgical therapy.

In the post-genomic era, it has become evident that genetic changes alone are not sufficient to understand most disease processes including pancreatic cancer. Genome sequencing has revealed a complex set of genetic alterations in pancreatic cancer such as point mutations, chromosomal losses, gene amplifications and telomere shortening that drive cancerous growth through specific signaling pathways. Proteome-based approaches are important complements to genomic data and provide crucial information of the target driver molecules and their post-translational modifications. By applying quantitative mass spectrometry, this is an alternative way to identify biomarkers for early diagnosis and personalized medicine. We review the current quantitative mass spectrometric technologies and analyses that have been developed and applied in the last decade in the context of pancreatic cancer. Examples of candidate biomarkers that have been identified from these pancreas studies include among others, asporin, CD9, CXC chemokine ligand 7, fibronectin 1, galectin-1, gelsolin, intercellular adhesion molecule 1, insulin-like growth factor binding protein 2, metalloproteinase inhibitor 1, stromal cell derived factor 4, and transforming growth factor beta-induced protein. Many of these proteins are involved in various steps in pancreatic tumor progression including cell proliferation, adhesion, migration, invasion, metastasis, immune response and angiogenesis. These new protein candidates may provide essential information for the development of protein diagnostics and targeted therapies. We further argue that new strategies must be advanced and established for the integration of proteomic, transcriptomic and genomic data, in order to enhance biomarker translation. Large scale studies with meta data processing will pave the way for novel and unexpected correlations within pancreatic cancer, that will benefit the patient, with targeted treatment.