Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia: A pilot study.

OBJECTIVES: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs. METHODS: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis. RESULTS: In total, 46 patients, 48% females, mean age (range) 67 years (45-82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas. CONCLUSION: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.

Is surgical resection justified for pancreatic ductal adenocarcinoma with distant abdominal organ metastasis? A position paper by experts in pancreatic surgery at the Joint Meeting of the International Association of Pancreatology (IAP) & the Japan Pancreas Society (JPS) 2022 in Kyoto.

Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.

The use of ace inhibitors influences the risk of progression of BD-IPMNs under follow-up.

BACKGROUND: Chemoprevention's ability to slow down or prevent the progression of BD-IPMNs is extremely appealing. Aspirin (ASA), Ace Inhibitors/Angiotensin Receptor Blockers (ACEIs/ARBs) and Statins (STATs) are frequently prescribed drugs with a possible beneficial effect on different cancer types. Their effect on IPMNs is largely unknown. AIM: To evaluate the association between the use of ASA, ACEIs/ARBs and STATs and the risk of progression of BD-IPMNs in follow-up. MATERIALS AND METHODS: multicenter, retrospective cohort study on patients with presumed BD-IPMNs without relative or absolute indication for surgery. Pharmacological exposures and risk factors were collected. We identified clinically relevant progression (occurrence of radiological absolute or relative indication for surgery) and any progression (occurrence of clinically relevant progression OR any dimension increase OR the occurrence of new cysts). RESULTS: Overall 594 patients were included. ACEIs were associated with a lower occurrence of any progression (HR = 0.70; 95% CI 0.49-0.98, p = 0.04) and clinically relevant progression, HR = 0.42 (95% CI 0.20-0.88; p = 0.02). No significant effect was shown for factors associated with the occurrence of pancreas cancer such as smoking, alcohol consumption and 1st degree family history of pancreas cancer. Among pharmacological exposures, no convincing effect was shown for the chronic use of ASA, ARB and STAT. CONCLUSIONS: ACEIs might have an effect in slowing the progression of BD-IPMNs. ASA, STAT and ARBs show no convincing effect on the progression of BD-IPMNs. Further, prospective, and long-term multicenter studies are needed to verify such association and to define the potential underlying mechanisms.

Branch-duct intraductal papillary mucinous neoplasm (IPMN): Are cyst volumetry and other novel imaging features able to improve malignancy prediction compared to well-established resection criteria?

OBJECTIVES: Current guidelines base the management of intraductal papillary mucinous neoplasms (IPMN) on several well-established resection criteria (RC), including cyst size. However, malignancy may occur in small cysts. Since branch-duct (BD) IPMN are not perfect spheres, volumetric and morphologic analysis might better correlate with mucin production and grade of dysplasia. Nonetheless, their role in malignancy (high-grade dysplasia/invasive cancer) prediction has been poorly investigated. Previous studies evaluating RC also included patients with solid-mass-forming pancreatic cancer (PC), which may affect the RC yield. This study aimed to assess the role of volume, morphology, and other well-established RC in malignancy prediction in patients with BD- and mixed-type IPMN after excluding solid masses. METHODS: Retrospective ethical review-board-approved study of 106 patients (2008-2019) with histopathological diagnosis of BD- and mixed-type IPMN (without solid masses) and preoperative MRI available. Standard imaging and clinical features were collected, and the novel imaging features cyst-volume and elongation value [EV = 1 - (width/length)] calculated on T2-weighted images. Logistic regression analysis was performed. Statistical significance set at two-tails, p < 0.05. RESULTS: Neither volume (odds ratio (OR) = 1.01, 95% CI: 0.99-1.02, p = 0.12) nor EV (OR = 0.38, 95% CI: 0.02-5.93, p = 0.49) was associated with malignancy. Contrast-enhancing mural nodules (MN), main pancreatic duct (MPD) ≥ 5 mm, and elevated carbohydrate antigen (CA) 19-9 serum levels (> 37 µmol/L) were associated with malignancy (MN OR: 4.32, 95% CI: 1.18-15.76, p = 0.02; MPD ≥ 5 mm OR: 4.2, 95% CI: 1.34-13.1, p = 0.01; CA19-9 OR: 6.72; 95% CI: 1.89 - 23.89, p = 0.003). CONCLUSIONS: Volume and elongation value cannot predict malignancy in BD- and/or mixed-type IPMN. Mural nodules, MPD ≥ 5 mm and elevated CA19-9 serum levels are associated with higher malignancy risk even after the exclusion of solid masses. KEY POINTS: • Novel and well-established resection criteria for IPMN have been evaluated after excluding solid masses. • BD-IPMN volume and elongation value cannot predict malignancy. • Main pancreatic duct ≥ 5 mm, mural nodules, and elevated carbohydrate antigen 19-9 levels are associated with malignancy.

Adenomatous neoplasia in the papilla of Vater endoscopic and/or surgical resection?

BACKGROUND: Adenomatous neoplasia in the papilla of Vater needs to be resected in order not to progress. It can be challenging to distinguish between early ampullary malignant lesions and non-invasive adenomas, due to the overlap in symptoms and radiological findings. This retrospective study describes the different findings and treatment decisions taken prior to endoscopic and/or surgical resection of ampullary adenomatous lesions. MATERIALS AND METHODS: Patients treated with endoscopic and/or surgical resection for suspected or verified ampullary adenomatous neoplasia, between January 2006 and July 2018, where pre-interventional cross-sectional imaging could not discern an obvious invasive, malignant tumor, were included. Findings were compared against the final diagnosis of the histopathological analysis on the resected specimen. RESULTS: In total, 172 met the inclusion criteria. Patients were treated with either surgical resection (n = 96), endoscopic papillectomy (EP) (n = 55) or both (n = 21). The final diagnosis was in 48% ampullary adenocarcinoma, and the remaining had either ampullary adenoma (38%) or non-neoplastic lesions (14%). In patients where symptoms and cross-sectional imaging were suspicious for malignancy, but with no tissue samples that confirmed neoplasia prior to surgical resection, only 47% had adenocarcinoma. The remaining had either adenoma (9%) or non-neoplastic lesions (44%). Adenocarcinoma was revealed in 27% of the patients where endoscopic biopsies had shown adenoma. Patients with adenoma, treated with EP, were cured in 59%. However, 28% were after EP sent for further surgery due to ductal invasion or a finding of adenocarcinoma. CONCLUSIONS: In patients with a suspicion of ampullary neoplasia on imaging, attempts should be made to get endoscopic tissue samples before deciding on a treatment strategy. If biopsies show ampullary adenoma, patients should be considered for EP, unless there are clear radiologic or endoscopic signs of malignancy. Patients with adenocarcinoma on endoscopic biopsies should undergo surgical resection.

Single-operator peroral pancreatoscopy in the preoperative diagnostics of suspected main duct intraductal papillary mucinous neoplasms: efficacy and novel insights on complications.

BACKGROUND: Distinguishing intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic lesions is essential since IPMNs carry the risk of becoming malignant. Differentiating the main pancreatic duct involving IPMNs (MD-IPMNs) through conventional imaging is deficient. Single-operator peroral pancreatoscopy (SOPP) represents a promising method offering additional information on suspected lesions in the pancreatic main duct (MD). We aimed to determine the role of SOPP in the preoperative diagnostics of suspected MD-IPMNs and identify factors contributing to SOPP-related complications. MATERIALS AND METHODS: In this primarily retrospective study, SOPPs were performed at three high-volume centers on suspected MD-IPMNs. Primary outcome was the clinical impact of SOPP to subsequent patient care. Additionally, we documented post-SOPP complications and analyzed several assumed patient- and procedure-related risk factors. RESULTS: One hundred and one (101) SOPPs were performed. Subsequent clinical management was affected due to the findings in 86 (85%) cases. Surgery was planned for 29 (29%) patients. A condition other than IPMN explaining MD dilatation was found in 28 (28%) cases. In 35 (35%) cases, follow-up with MRI was continued. Post-SOPP pancreatitis occurred in 20 (20%) patients and one of them was fatal. A decrease in odds of post-SOPP pancreatitis was seen as the MD diameter increases (OR 0.714 for 1.0 mm increase in MD diameter, CI 95% 0.514-0.993, p = 0.045). Furthermore, a correlation between lower MD diameter values and higher severity post-SOPP pancreatitis was seen (TJT = 599, SE = 116.6, z = - 2.31; p = 0.020). History of pancreatitis after endoscopic retrograde cholangiopancreatography was a confirmed risk factor for post-SOPP pancreatitis. Conclusions between complications and other risk factors could not be drawn. CONCLUSION: SOPP aids clinical decision-making in suspected MD-IPMNs. Risk for post-SOPP pancreatitis is not negligible compared to non-invasive imaging methods. The risk for pancreatitis decreases as the diameter of the MD increases.

Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection.

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here, we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labeled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression-including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products, and trimethylamine-oxide. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer).

Surgery Improves Survival After Neoadjuvant Therapy for Borderline and Locally Advanced Pancreatic Cancer: A Single Institution Experience.

OBJECTIVE: Neoadjuvant therapy (NAT) has become part of the multimodality treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). SUMMARY BACKGROUND DATA: It is currently uncertain which are the preferable NAT regimens, who benefits from surgery, and whether more aggressive surgical strategy is motivated. METHODS: A retrospective cohort analysis was performed for all patients with BRPC/LAPC discussed and planned for NAT at multidisciplinary conference at Karolinska University Hospital from 2010 to 2017. RESULTS: Of 233 patients eligible, 168 (72%) received NAT and were reevaluated for possibility of resection. A total of 156 (67%) patients (mean 64 yrs, 53% male) had pancreatic adenocarcinoma, comprising the study group for survival analysis. LAPC was diagnosed in 132 patients (85%), BRPC in 22 (14%), and resectable tumor in 2 (1.3%). Fifty patients (40.3%) received full-dose NAT. Only 54 (34.6%) had FOLFIRINOX. The overall survival among resected patients was similar for BRPC and LAPC (median survival 15.0 vs 14.5 mo, P = 0.4; and 31.9 vs 21.8 mo, P = 0.7, respectively). Resected patients had better survival than nonresected, irrespective of the type or whether full-dose NAT was given (median survival 22.4 vs 12.7 mo; 1-, 3-, and 5-yr survival: 86.4%, 38.9%, 26.9% vs 52.2%, 1.5%, 0%, respectively (P < 0001). For all preoperative values of Ca 19-9, surgical resection had positive impact on survival. CONCLUSIONS: All patients with BRPC/LAPC who do not progress during NAT should be considered for surgical resection, irrespective of the type or dose of NAT given. Higher levels of Ca 19-9 should not be considered an absolute contraindication for resection.

Chronic use of statins and acetylsalicylic acid and incidence of post-endoscopic retrograde cholangiopancreatography acute pancreatitis: A multicenter, prospective, cohort study.

OBJECTIVES: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP. METHODS: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated. RESULTS: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P = 0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94-2.99, P = 0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P = 0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49-2.13), P = 0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20 minutes, were risk factors. CONCLUSIONS: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.

Main Duct Dilatation Is the Best Predictor of High-grade Dysplasia or Invasion in Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: The purpose of this study is to determine preoperative factors that are predictive of malignancy in patients undergoing pancreatic resection for intraductal papillary mucinous neoplasms (IPMN). SUMMARY BACKGROUND DATA: IPMN of the pancreas may be precursor lesions to pancreatic cancer (PC) and represent a target for early diagnosis or prevention. While there has been much effort to define preoperative risk factors for malignant pathology, guidelines are ever-changing and controversy remains surrounding which patients would benefit most from resection. METHODS: We performed a retrospective analysis of 901 consecutive patients obtained from two tertiary referral centers who underwent pancreatic resection for histologically proven IPMN between 2004 and 2017. Collected data included patient demographic characteristics, preoperative symptoms, radiological findings, and laboratory data. RESULTS: Main pancreatic duct (MPD) dilatation was the only variable that was significantly associated with increased probability of malignancy (defined high-dysplasia or invasion) on both univariate and multivariate analysis. Even middle-range MPD dilatation from 5 mm to 9.9 mm (n = 286) was associated with increased odds of HG-IPMN (OR = 2.74; 95% CI = 1.80-4.16) and invasion (OR = 4.42; 95% CI = 2.55-7.66). MPD dilatation >10 mm (n = 150) had even greater odds of HG-IPMN (OR = 6.57; 95% CI = 3.94-10.98) and invasion (OR = 15.07; 95% CI = 8.21-27.65). A cutoff of 5 to 7 mm MPD diameter was determined to be the best predictor to discriminate between malignant and benign lesions. CONCLUSIONS: In agreement with current IPMN management guidelines, we found MPD dilatation, even low levels from 5 mm to 9.9 mm, to be the single best predictor of HG-IPMN or invasion, highlighting the critical role that MPD plays in the selection of surgical candidates.

Gynecological and reproductive factors and the risk of pancreatic cancer: A case-control study.

BACKGROUND: /Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence in men compared to women, although the difference in known risk factors cannot explain this disparity completely. Reproductive and hormonal factors have been demonstrated in pre-clinical studies to influence pancreatic carcinogenesis, but the few published data on the topic are inconsistent. The aim was to investigate the role of reproductive and hormonal factors on PDAC occurrence in women. METHODS: We conducted a unicenter case-control study; PDAC cases were matched to controls by age with a 1:2 ratio. Risk factors were screened through questionnaires about gynecologic and medical history. Comparisons were made using Chi-square and Fisher's exact tests where appropriate for categorical variables and Student's t-test for continuous variables. Logistic regression was used to calculate Odds Ratios (ORs) and their 95% confidence intervals (CI). Multivariable logistic regression models were adjusted for potential confounders. RESULTS: 253 PDAC and 506 matched controls were enrolled. At logistic regression multivariable analysis adjusted for confounding factors, older age at menopause (OR:0.95 per year; 95% CI:0.91-0.98; p = 0.007), use of Oral Contraceptives (OR:0.52; 95% CI:0.30-0.89; p = 0.018), use of Hormonal Replacement Therapy (OR:0.31; 95% CI:0.15-0.64; p = 0.001), and having had two children (OR:0.57; 95% CI:0.38-0.84; p = 0.005) were significant, independent protective factors for the onset of PDAC. CONCLUSIONS: These data confirm some previous findings on menopause age and number of births while, to our knowledge, this is the first study to show a protective effect of HRT and OC use. The results collectively support the hypothesis that exposure to estrogens plays a protective role towards PDAC.

Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can progress to invasive pancreatic cancer. Associations between oncogenesis and oral microbiome alterations have been reported. This study aims to investigate a potential intracystic pancreatic microbiome in a pancreatic cystic neoplasm (PCN) surgery patient cohort. DESIGN: Paired cyst fluid and plasma were collected at pancreatic surgery from patients with suspected PCN (n=105). Quantitative and qualitative assessment of bacterial DNA by qPCR, PacBio sequencing (n=35), and interleukin (IL)-1ß quantification was performed. The data were correlated to diagnosis, lesion severity and clinical and laboratory profile, including proton-pump inhibitor (PPI) usage and history of invasive endoscopy procedures. RESULTS: Intracystic bacterial 16S DNA copy number and IL-1ß protein quantity were significantly higher in IPMN with high-grade dysplasia and IPMN with cancer compared with non-IPMN PCNs. Despite high interpersonal variation of intracystic microbiota composition, bacterial network and linear discriminant analysis effect size analyses demonstrated co-occurrence and enrichment of oral bacterial taxa including Fusobacterium nucleatum and Granulicatella adiacens in cyst fluid from IPMN with high-grade dysplasia. The elevated intracystic bacterial DNA is associated with, but not limited to, prior exposure to invasive endoscopic procedures, and is independent from use of PPI and antibiotics. CONCLUSIONS: Collectively, these findings warrant further investigation into the role of oral bacteria in cystic precursors to pancreatic cancer and have added values on the aetiopathology as well as the management of pancreatic cysts.

Surgical treatment of metastatic pancreatic ductal adenocarcinoma: A review of current literature.

BACKGROUND: There is no international consensus concerning the role of surgical treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), but favorable prognoses can be expected for highly selected patients. METHODS: A comprehensive literature search of the PubMed and Cochrane databases was conducted using combinations of keywords to 4 July 2018. Eligible studies were those reporting on patients with histologically confirmed mPDAC undergoing surgery with curative intent. We excluded case reports with fewer than five patients, insufficient descriptions of survival data, and palliative or cytoreductive surgery as well as studies that assessed para-aortic lymph node metastasis or peritoneal washing cytology. RESULTS: Thirteen studies were deemed eligible, and six studies were identified from their references. The studies involved 428 patients who underwent surgical resection for liver metastases (n = 343), lung metastases (n = 57), and peritoneal dissemination (n = 28). Median overall survival (OS) in patients with synchronous liver metastases who underwent conversion surgery following favorable response to initial chemotherapy was 27 or 34 months, and peritoneum metastases was 28 months. Median OS after the initial treatment was varied from 51 to 121 months in metachronous lung metastasis and from 24 to 40 months in metachronous liver metastasis, respectively. CONCLUSION: Encouraging OS was indicated in patients with synchronous mPDAC of liver and peritoneum who underwent conversion surgery. Metastasectomy for metachronous lung and liver oligometastases could be considered a practical treatment option.

Main pancreatic duct dilation greater than 6 mm is associated with an increased risk of high-grade dysplasia and cancer in IPMN patients.

INTRODUCTION: IPMNs, considered precursor lesions of pancreatic adenocarcinoma (PDAC), might display histological alteration varying from low-grade dysplasia (LGD) to cancer. Nevertheless, the prevalence of PDAC is far below the prevalence of IPMN; therefore, not all of these precursor lesions finally progress to cancer. Preoperative features consistent with and finding at final histology of high-grade dysplasia (HGD) or cancer are currently lacking. The aim of this study is to correlate the presence of preoperative clinical features with the finding of advance lesions at final histology. METHODS: This is retrospective cohort analysis of patients who underwent surgery for histologically confirmed IPMNs at Karolinska University Hospital, from 2008 to 2015. RESULTS: MPD 6-9.9 mm and ≥ 10 mm were associated with an increased risk of HGD/cancer (respectively, OR 2.92, CI 1.38-6.20, p = 0.005 and OR 2.65, CI 1.12-6.25, p = 0.02). Preoperative high CA19.9 and jaundice were both associated with a higher risk of HGD/cancer at final histology (respectively, OR 4.15, CI 1.90-9.05, p = 0.0003 and OR 15.36, CI 1.94-121.22, p = 0.009). At sex- and age-adjusted multivariable logistic regression analysis, MPD between 6 and 9.9 mm (OR 2.64, CI 1.15-6.06, p = 0.02), jaundice (OR 12.43, CI 1.44-106.93, p = 0.02), and elevated CA19.9 (OR 3.71, CI 1.63-8.46, p = 0.001) remained associated with the occurrence of HGD/cancer. DISCUSSION: The presence of MPD dilation ≥ 6 mm, jaundice, and elevated CA19.9 in IPMN patients are consistent with the finding for HGD/cancer at final histology, thus representing possible markers of advanced lesions suitable for earlier or preventive curative surgical treatment.

Pancreatectomy with arterial resection is superior to palliation in patients with borderline resectable or locally advanced pancreatic cancer.

BACKGROUND: Few studies have investigated the outcome of pancreatectomy associated with artery resection (PAR). METHODS: Retrospective analysis of a cohort of operated borderline or locally advanced pancreatic cancer patients with surgically confirmed arterial involvement. Short and long-term outcome were analyzed and compared in patients who underwent PAR (Group 1) and palliative surgery (Group 2). RESULTS: Of 73 patients who underwent surgical exploration with intent of resection, 34 underwent PAR (±venous resection) (Group 1) and 39 underwent palliation (Group 2). 23 patients (67.7%) in Group 1 underwent combined artery-vein resection (AVR). Operation time was longer and blood loss higher in group 1 compared to group 2. There were no differences in post-operative mortality (2.9% vs 2.6%, p = 0.9) and post-operative surgical complications (38.2% vs 25.6%, p = 0.2). The 1, 3 and 5 years survival in Group 1 was superior to Group 2 (63.7%, 23.4% and Q3 23.4% vs 41.7%, 3.2% and 0, p = 0.003). CONCLUSION: PAR seems to be safe and feasible in well selected patients and associated with an advantage of survival compared to palliation, in patients affected by locally advanced pancreatic cancer.

Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Validation of artificial neural networks as a methodology for donor-recipient matching for liver transplantation.

In 2014, we reported a model for donor-recipient (D-R) matching in liver transplantation (LT) based on artificial neural networks (ANNs) from a Spanish multicenter study (Model for Allocation of Donor and Recipient in España [MADR-E]). The aim is to test the ANN-based methodology in a different European health care system in order to validate it. An ANN model was designed using a cohort of patients from King's College Hospital (KCH; n = 822). The ANN was trained and tested using KCH pairs for both 3- and 12-month survival models. End points were probability of graft survival (correct classification rate [CCR]) and nonsurvival (minimum sensitivity [MS]). The final model is a rule-based system for facilitating the decision about the most appropriate D-R matching. Models designed for KCH had excellent prediction capabilities for both 3 months (CCR-area under the curve [AUC] = 0.94; MS-AUC = 0.94) and 12 months (CCR-AUC = 0.78; MS-AUC = 0.82), almost 15% higher than the best obtained by other known scores such as Model for End-Stage Liver Disease and balance of risk. Moreover, these results improve the previously reported ones in the multicentric MADR-E database. In conclusion, the use of ANN for D-R matching in LT in other health care systems achieved excellent prediction capabilities supporting the validation of these tools. It should be considered as the most advanced, objective, and useful tool to date for the management of waiting lists. Liver Transplantation 24 192-203 2018 AASLD.

Pancreatectomies for pancreatic neoplasms in pediatric and adolescent age: A single institution experience.

BACKGROUND: There are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth. METHODS: This is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017. RESULTS: Overall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3-15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection. CONCLUSIONS: In our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant.

Diagnosis, treatment and long-term outcome of autoimmune pancreatitis in Sweden.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a pancreatic inflammatory process characterized by a strong inflammatory cell infiltration and two histopathologically distinct subtypes: type 1 and type 2. Diagnosis is often challenging and requires a combination of clinical, laboratory and imaging data. AIP can mimic pancreatic tumours leading to unnecessary resections if not correctly diagnosed. Short- and long-term outcomes of AIP have been poorly investigated so far and no large series have been previously reported from Sweden. METHODS: A single-centre, retrospective, cohort study of patients with histologically confirmed or highly probable diagnosis of AIP according to ICDC criteria. Demographic, clinical and radiological characteristics, type of treatment and its outcomes were collected and analysed. RESULTS: Seventy-one patients with AIP (87% with type 1), were evaluated at Karolinska University Hospital between 2004 and 2018; 49% males, mean age 49 years (range 44-53). Among them, 28% were histologically confirmed, 35% presented with jaundice, 22% with acute pancreatitis, 39% had non-specific symptoms such as weight loss or abdominal pain, 84% showed other organ involvement (OOI). Radiologically, 76% showed a focal pancreatic enlargement, 27% diffuse enlargement, 27% signs of acute pancreatitis and 10% of chronic pancreatitis. Overall, 58 patients (81%) underwent treatment with different medications: 46 (79%) cortisone, 7 (12%) azathioprine, 5 (8%) other immunosuppressive drugs. Twenty-six (36%) underwent biliary stenting and 12 (16%) were given surgery. In total, 47% of patients developed pancreatic exocrine insufficiency (PEI), of whom 76% had a severe form (faecal elastase-1 < 100 µg/g) and 21% of patients developed diabetes mellitus (pancreatic endocrine insufficiency), of whom 73% required insulin. CONCLUSIONS: AIP is a challenging disease for diagnosis and treatment. Cortisone treatment is generally successful and provides clinical remission in the large majority of patients (>90%). In the further course of the disease, a considerable number of patients develop PEI and diabetes. Only one-quarter of patients exhibit on imaging the characteristic "sausage-like" pancreas (diffuse enlargement), approximately three-quarters had a focal mass that could be misdiagnosed as pancreatic malignancy.