Preoperative endoscopic biliary drainage by metal versus plastic stents for resectable perihilar cholangiocarcinoma

Background and Aims: Adequate preoperative biliary drainage (PBD) is recommended in most patients with resectable perihilar cholangiocarcinoma (pCCA). Most expert centers use endoscopic plastic stents rather than self-expandable metal stents (SEMSs). In the palliative setting, however, use of SEMSs has shown longer patency and superior survival. The aim of this retrospective study was to compare stent dysfunction of SEMSs versus plastic stents for PBD in resectable pCCA patients. Methods:In this multicenter international retrospective cohort study, patients with potentially resectable pCCAs who underwent initial endoscopic PBD from 2010 to 2020 were included. Stent failure was a composite end point of cholangitis or reintervention due to adverse events or insufficient PBD. Other adverse events, surgical outcomes, and survival were recorded. Propensity score matching (PSM) was performed on several baseline characteristics. Results: A total of 474 patients had successful stent placement, of whom 61 received SEMSs and 413 plastic stents. PSM (1:1) resulted in 2 groups of 59 patients each. Stent failure occurred significantly less in the SEMSs group (31% vs 64%; P &lt; .001). Besides less cholangitis after SEMSs placement (15% vs 31%; P = .012), other PBD-related adverse events did not differ. The number of patients undergoing surgical resection was not significantly different (46% vs 49%; P = .71). Complete intraoperative SEMSs removal was successful and without adverse events in all patients. Conclusions: Stent failure was lower in patients with SEMSs as PBD compared with plastic stents in patients with resectable pCCA. Removal during surgery was quite feasible. Surgical outcomes were similar.</p

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients

Background: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. Methods: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. Results: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0&nbsp;mm. 61.0% were pT3 (n&nbsp;=&nbsp;36), nodal positivity rate was 37.3% (n&nbsp;=&nbsp;22), and synchronous distant metastases were present in 10.1% of the patients (n&nbsp;=&nbsp;6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n&nbsp;=&nbsp;18 only systemic, n&nbsp;=&nbsp;6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p&nbsp;=&nbsp;0.004, p&nbsp;=&nbsp;0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p&nbsp;=&nbsp;0.542) nor DFS (p&nbsp;=&nbsp;0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. Discussion: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting

International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors

Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com

A Preoperative Clinical Risk Score Including C-Reactive Protein Predicts Histological Tumor Characteristics and Patient Survival after Surgery for Sporadic Non-Functional Pancreatic Neuroendocrine Neoplasms:An International Multicenter Cohort Study

Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients >60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off >= 0.2 mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size >= 3.0 cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p <0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy

Background Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. Methods A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. Results Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2− to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. Conclusion These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.publishedVersio

A Preoperative Clinical Risk Score Including C-Reactive Protein Predicts Histological Tumor Characteristics and Patient Survival after Surgery for Sporadic Non-Functional Pancreatic Neuroendocrine Neoplasms: An International Multicenter Cohort Study

Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients &gt;60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off &ge;0.2 mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size &ge;3.0 cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p &lt; 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival

Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy

Background: Novel technology has enabled researchers to better characterize pancreatic cancers at the molecular level. We wanted to explore some of the emerging discoveries, such as molecular subclassification, use of liquid biopsy and use of organoids in cancer assessment. Methods: A literature review with a search specific to the topic, with recent reviews in major journals and a focus on the last 5 years (until December 2018), was done. Results: Pancreatic ductal adenocarcinoma (PDAC) may now be classified into clinical subgroups based on the predominant genomic profiles, but consensus on one classification system is lacking. Several subtypes have been suggested, including categories such as basal-like, stroma-activated, desmoplastic, pure classical and immune classical types. Further refinement may translate into clinically meaningful groups for therapeutic or prognostic purposes. Liquid biopsies (by means of circulating cancer cells, cell-free DNA, exosomes or other constituents of cancer cells in blood) may aid in earlier diagnosis, define prognostic groups and even predict therapy response and resistance. Organoids are increasingly used for the opportunity to investigate druggable and effective targets ex vivo and should facilitate personalized and precise, targeted therapy in the near future. While immunotherapy has not yet proved to be effective, a better understanding of molecular subgroups and specific immune profiles may help identify candidates for this approach in a more selective approach. Conclusion: Novel molecular techniques have the potential to accelerate the road to improved outcomes in patients with pancreatic cancer

Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy

Background: Novel technology has enabled researchers to better characterize pancreatic cancers at the molecular level. We wanted to explore some of the emerging discoveries, such as molecular subclassification, use of liquid biopsy and use of organoids in cancer assessment. Methods: A literature review with a search specific to the topic, with recent reviews in major journals and a focus on the last 5 years (until December 2018), was done. Results: Pancreatic ductal adenocarcinoma (PDAC) may now be classified into clinical subgroups based on the predominant genomic profiles, but consensus on one classification system is lacking. Several subtypes have been suggested, including categories such as basal-like, stroma-activated, desmoplastic, pure classical and immune classical types. Further refinement may translate into clinically meaningful groups for therapeutic or prognostic purposes. Liquid biopsies (by means of circulating cancer cells, cell-free DNA, exosomes or other constituents of cancer cells in blood) may aid in earlier diagnosis, define prognostic groups and even predict therapy response and resistance. Organoids are increasingly used for the opportunity to investigate druggable and effective targets ex vivo and should facilitate personalized and precise, targeted therapy in the near future. While immunotherapy has not yet proved to be effective, a better understanding of molecular subgroups and specific immune profiles may help identify candidates for this approach in a more selective approach. Conclusion: Novel molecular techniques have the potential to accelerate the road to improved outcomes in patients with pancreatic cancer

Minimally invasive pancreatic surgery-where are we going?

Background Introduced in the mid-1990s, minimally invasive pancreatic surgery (MIPS) developed slowly over the next two decades, and its real-life benefits remained unclear. Methods In this review, the current status and evidence on the most common types of MIPS, such as minimally invasive pancreatoduodenectomy (MIPD), distal pancreatectomy, enucleation, and central pancreatectomy are presented. Results Minimally invasive distal pancreatectomy (MIDP) is the most frequently used procedure among these, and its indications are nowadays expanding. MIDP for benign and low-grade malignant tumors is advantageous compared to the open approach, suggesting less intraoperative blood loss, shorter hospital stay, faster functional recovery, and better quality of life. The oncological adequacy of MIDP in pancreatic cancer is unclear, as no randomized trials have been published. In contrast, MIPD is a technically challenging procedure performed in a small number of centers and in a selected group of patients. Its use remains controversial, as conflicting data have been reported in the literature. Annual volume and learning curve seem to be the key determinants of safety in MIPD. Minimally invasive pancreatic enucleation and central pancreatectomy are less common. Although one randomized trial was published on minimally invasive vs. open central pancreatectomy, current evidence on these procedures is mostly based on retrospective, single-institution series clearly affected by selection bias and small sample size. Conclusion Well-designed prospective studies based on national registries are needed to expand knowledge on MIPS and determine its role in pancreatic surgery. To facilitate further development of MIPS, it has to integrate effectively with the outcome-improving effect of a dedicated pancreatic team