Search

Background:. Intraductal papillary mucinous neoplasm (IPMN) with involvement of the main pancreatic duct usually requires surgical resection. Consensus is lacking whether to partially or completely resect the pancreatic portion with a dilated main pancreatic duct. Intraoperative pancreatoscopy may be useful to determine the extent of IPMN to tailor surgical resection and was recently studied in a large prospective international study. IPMN is increasingly utilized using a robotic approach. Studies describing the technical approach to intraoperative pancreatoscopy in robotic pancreatoduodenectomy and robotic distal pancreatectomy are lacking. Methods:. During robotic pancreatoduodenectomy, pancreatoscopy is performed once the pancreas neck is transected. The scope is advanced via a laparoscopic port into the left and right-sided pancreatic duct, guided by robotic graspers. During robotic distal pancreatectomy, pancreatoscopy is performed before complete parenchymal transection. The scope is advanced through an anterior ductotomy to examine the duct and guide the pancreatic transection line. Tips and tricks how to perform the procedure efficiently without complications are detailed. Results:. In total, 28 robot-assisted pancreatoscopies were performed during robotic pancreatoduodenectomy and robotic distal pancreatectomy. No intraoperative complications resulting from the intraoperative pancreatoscopy were noted. In the 2 described procedures, the added time required to perform the pancreatoscopy was 6 and 17 minutes, respectively. Both patients recovered without complication and were discharged on postoperative day 5 for the robotic pancreatoduodenectomy and day 6 for the robotic distal pancreatectomy. Conclusions:. Intraoperative pancreatoscopy can be safely performed during both robotic pancreatoduodenectomy and robotic distal pancreatectomy for IPMN with the involvement of the main pancreatic duct. An international prospective study has recently been completed with this technique.

Abstract Background Single-operator, per-oral cholangiopancreatoscopy (SOPCP) enables direct biliopancreatic ductal visualization, targeted tissue sampling, and therapeutic intervention. At Karolinska University Hospital, SOPCP was introduced early and has since been extensively utilized according to a standardized protocol. We analysed the clinical value of SOPCP in the diagnosis and treatment of biliopancreatic diseases in a single high volume center. Methods All SOPCP procedures performed between March 2007 and December 2014 were retrospectively reviewed. Each procedure’s diagnostic yield and therapeutic value was evaluated using a predefined 4 grade scale; 1 - no diagnostic or therapeutic value, 2 - information gained did not impact clinical decision-making and in case of a therapeutic intervention, did not alter the clinical course of the patient, 3 - information gained had an impact on clinical decision-making and in the case of a therapeutic intervention, assisted subsequent disease management, and finally, 4 - information gained was essential and critical for clinical decision-making and in case of a therapeutic intervention, solved the clinical problem requiring no further therapeutic actions. Descriptive statistics were used to analyse results, with uni- and multivariate analyses completed to assess risk of adverse events. Results During the study period, 365 SOPCP procedures were performed. We found SOPCP of pivotal importance (grade 4) in 19% of cases, and of great clinical significance (grade 3) in 44% of cases. SOPCP did not affect clinical decision-making or alter clinical course (grade 1 and 2) in 37% of cases. Conclusion SOPCP offers direct access to the biliopancreatic ducts for both diagnostic and therapeutic purposes, adding significant clinical value in 64% of cases. Trial registration As this is a purely observational and retrospectively registered study in which the assignment of the medical intervention was not at the discretion of the investigator, it has not been registered in a registry.

Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.

ObjectivesIntraductal papillary mucinous neoplasms (IPMNs) are cystic precursor lesions to pancreatic cancer. The presence of oral microbes in pancreatic tissue or cyst fluid has been associated with high-grade dysplasia (HGD) and cancer. The present study aims at investigating if humoral immunity to pancreas-associated oral microbes reflects IPMN severity.DesignPaired plasma (n = 109) and saliva (n = 65) samples were obtained from IPMN pancreatic cystic tumor cases and controls, for anti-bacterial antibody analysis and DNA quantification by enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. Tumor severity was graded by histopathology, laboratory, and clinical data. Circulating plasma and salivary antibody reactivity to a pancreas-associated oral microbe panel were measured by ELISA and correlated to tumor severity.ResultsThe patient group with high-risk cystic tumors (HGD and/or associated invasive cancer) shows ample circulating IgG reactivity to Fusobacterium nucleatum (F. nucleatum) but not to Granulicatella adiacens (G. adiacens), which is independent of the salivary bacteria DNA levels. This group also shows higher salivary IgA reactivity to F. nucleatum, Fap2 of F. nucleatum, and Streptococcus gordonii (S. gordonii) compared to low-risk IPMN and controls. The salivary antibody reactivity to F. nucleatum and Fap2 are found to be highly correlated, and cross-competition assays further confirm that these antibodies appear cross-reactive.ConclusionOur findings indicate that humoral reactivity against pancreas-associated oral microbes may reflect IPMN severity. These findings are beneficial for biomarker development.

Background and study aims Conventional endoscopic retrograde cholangiopancreatography (ERCP) is hampered by two-dimensional visualization, post-procedural adverse events (AEs), and exposure to ionizing radiation. Bimodal ERCP might mitigate these challenges, but no reports of its use are available to date. The aim of this study was to explore the feasibility of bimodal ERCP, while investigating its potential clinical yield. Patients and methods This was a retrospective observational study of patients that underwent bimodal ERCP in a single tertiary academic referral center. Thirteen patients undergoing conventional ERCP had a previously T2-weighted isotropic 3 D TSE MRCP sequence aligned and fused with the two-dimensional image generated from the fluoroscopy c-arm unit in real time. Results Over a 2-month period, 13 patients with a mean age of 54 underwent bimodal ERCP for bile duct stricture (61.5 %), complex cholelithiasis (7.7 %) and ductal leakage (30.1 %). Bimodal ERCP was feasible in all 13 cases, and image quality was assessed as “good” in 11 patients (84.6 %). Bimodal ERCP aided in visualizing the lesion of interest (76.9 %), assisted in understanding the 3 D anatomy of the biliopancreatic ductal system (61.5 %), and aided in finding a favorable position for the c-arm (38.4 %) for subsequent therapeutic intervention. Conclusions This first report on bimodal ERCP proves its feasibility and suggests that it may assist in increasing both the diagnostic and therapeutic yield of ERCP, while at the same time decreasing AEs during and after ERCP. Its main application might lie in treatment of complex intrahepatic disease.

Thanks to the development of modern chemotherapeutic regimens, survival after surgery for pancreatic ductal adenocarcinoma (PDAC) has improved and pancreatologists worldwide agree that the treatment of PDAC demands a multidisciplinary approach. Neoadjuvant treatment (NAT) plays a major role in the treatment of PDAC since only about 20% of patients are considered resectable at the time of diagnosis. Moreover, increasing data demonstrating the benefits of NAT for borderline resectable/locally advanced PDAC are driving a shift from up-front surgery to NAT in the multidisciplinary treatment of even resectable PDAC. Our understanding of the role of NAT in PDAC has evolved from tumor shrinkage to controlling potential micrometastases and selecting patients who may benefit from radical resection. The present review gives an overview on the current literature of NAT concepts for BR/LA PDAC and resectable PDAC.

Objectives: To compare two Gaussian diffusion-weighted MRI (DWI) models including mono-exponential and bi-exponential, with the non-Gaussian kurtosis model in patients with pancreatic ductal adenocarcinoma. Materials and methods: After written informed consent, 15 consecutive patients with pancreatic ductal adenocarcinoma underwent free-breathing DWI (1.5T, b-values: 0, 50, 150, 200, 300, 600 and 1000 s/mm2). Mean values of DWI-derived metrics ADC, D, D*, f, K and DK were calculated from multiple regions of interest in all tumours and non-tumorous parenchyma and compared. Area under the curve was determined for all metrics. Results: Mean ADC and DK showed significant differences between tumours and non-tumorous parenchyma (both P

Background and study aims Preoperative biliary drainage in patients with periampullary tumors and jaundice has been popularized to improve the quality of life and minimize the risks associated with subsequent radical surgery. The aim of this study was to investigate the possible superiority of self-expandable metal stents (SEMS) over plastic stents, by comparing the amount of bacteria in intraoperatively collected bile and using this variable as a proxy for the efficacy of the respective biliary drainage modalities. Patients and methods In this randomized clinical trial, 92 patients with obstructive jaundice were enrolled; 45 were allocated to the plastic stent group and 47 to the SEMS group. The primary outcome was the extent and magnitude of biliary bacterial growth at the time of surgical exploration. Secondary outcomes were: macroscopic grading of inflammation of the stented bile ducts, occurrence of adverse events after stenting, stent dysfunction, recognized surgical complexities, and incidence of postoperative complications. Results The patients were well matched regarding clinical and disease-specific characteristics. At surgery, there were no group differences in the bacterial amount and composition of the bile cultures or the perceived difficulty of surgical dissection. During the preoperative biliary drainage period, more instances of stent dysfunction requiring stent replacement were recorded in the plastic stent group (19 % vs. 0 %; P = 0.03). Postoperative complications in patients who underwent curative surgery were more common in patients with plastic stents (72 % vs. 52 %), among which clinically significant leakage from the pancreatic anastomoses seemed to predominate (12 % vs. 3.7 %); however, none of these differences in postoperative adverse events reached statistical significance. Conclusion This randomized clinical study was unable to demonstrate any superiority of SEMS in the efficacy of preoperative bile drainage, as assessed by the amount of bacteria in the intraoperatively collected bile. However, some data in favor of SEMS were observed among the clinical secondary outcomes variables (preoperative stent exchange rates) without increases in local inflammatory reactions. Trial registered at ClinicalTrials.gov (NCT00501176).

[This corrects the article DOI: 10.1371/journal.pone.0166067.].

Adenocarcinomas of the pancreatobiliary system are currently classified by their primary anatomical location. In particular, the pathological diagnosis of intrahepatic cholangiocarcinoma is still considered as a diagnosis of exclusion of metastatic adenocarcinoma. Periampullary cancers have been previously classified according to the histological type of differentiation (pancreatobiliary, intestinal), but overlapping morphological features hinder their differential diagnosis. We performed an integrative immunohistochemical analysis of pancreato-biliary tumors to improve their diagnosis and prediction of outcome.This was a retrospective observational cohort study on patients with adenocarcinoma of the pancreatobiliary system who underwent diagnostic core needle biopsy or surgical resection at a tertiary referral center. 409 tumor samples were analyzed with up to 27 conventional antibodies used in diagnostic pathology. Immunohistochemical scoring system was the percentage of stained tumor cells. Bioinformatic analysis, internal validation, and survival analysis were performed.Hierarchical clustering and differential expression analysis identified three immunohistochemical tumor types (extrahepatic pancreatobiliary, intestinal, and intrahepatic cholangiocarcinoma) and the discriminant markers between them. Among patients who underwent surgical resection of their primary tumor with curative intent, the intestinal type showed an adjusted hazard ratio of 0.19 for overall survival (95% confidence interval 0.05-0.72; p value = 0.014) compared to the extrahepatic pancreatobiliary type.Integrative immunohistochemical classification of adenocarcinomas of the pancreatobiliary system results in a characteristic immunohistochemical profile for intrahepatic cholangiocarcinoma and intestinal type adenocarcinoma, which helps in distinguishing them from metastatic and pancreatobiliary type adenocarcinoma, respectively. A diagnostic immunohistochemical panel and additional extended panels of discriminant markers are proposed as guidance for their pathological diagnosis.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166-0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280-0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.