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 < .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.

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.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

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 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 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.

Long-Term Outcomes of Perioperative Versus Neoadjuvant Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-Score Matched Analysis with Stratification by Contemporary Risk-Scoring.

BACKGROUND: There is still debate regarding the principal role and ideal timing of perioperative chemotherapy (CTx) for patients with upfront resectable colorectal liver metastases (CRLM). This study assesses long-term oncological outcomes in patients receiving neoadjuvant CTx only versus those receiving neoadjuvant combined with adjuvant therapy (perioperative CTx). METHODS: International multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010 and 2015. Characteristics and outcomes were compared before and after propensity score matching (PSM). Primary endpoints were long-term oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS). Furthermore, stratification by the tumour burden score (TBS) was applied. RESULTS: Of 967 patients undergoing hepatectomy, 252 were analysed, with a median follow-up of 45 months. The unmatched comparison revealed a bias towards patients with neoadjuvant CTx presenting with more high-risk patients (p = 0.045) and experiencing increased postoperative complications ≥Clavien-Dindo III (20.9% vs. 8%, p = 0.003). Multivariable analysis showed that perioperative CTx was associated with significantly improved RFS (hazard ratio [HR] 0.579, 95% confidence interval [CI] 0.420-0.800, p = 0.001) and OS (HR 0.579, 95% CI 0.403-0.834, p = 0.003). After PSM (n = 180 patients), the two groups were comparable regarding baseline characteristics. The perioperative CTx group presented with a significantly prolonged RFS (HR 0.53, 95% CI 0.37-0.76, p = 0.007) and OS (HR 0.58, 95% CI 0.38-0.87, p = 0.010) in both low and high TBS patients. CONCLUSIONS: When patients after resection of CRLM are able to tolerate additional postoperative CTx, a perioperative strategy demonstrates increased RFS and OS in comparison with neoadjuvant CTx only in both low and high-risk situations.

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.

Early postoperative arterial lactate concentrations to stratify risk of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) represents the major determinant for death after liver resection. Early recognition is essential. Perioperative lactate dynamics for risk assessment of PHLF and associated morbidity were evaluated. METHODS: This was a multicentre observational study of patients undergoing hepatectomy with validation in international high-volume units. Receiver operating characteristics analysis and cut-off calculation for the predictive value of lactate for clinically relevant International Study Group of Liver Surgery grade B/C PHLF (clinically relevant PHLF (CR-PHLF)) were performed. Lactate and other perioperative factors were assessed in a multivariable CR-PHLF regression model. RESULTS: The exploratory cohort comprised 509 patients. CR-PHLF, death, overall morbidity and severe morbidity occurred in 7.7, 3.3, 40.9 and 29.3 per cent of patients respectively. The areas under the curve (AUCs) regarding CR-PHLF were 0.829 (95 per cent c.i. 0.770 to 0.888) for maximum lactate within 24 h (Lactate_Max) and 0.870 (95 per cent c.i. 0.818 to 0.922) for postoperative day 1 levels (Lactate_POD1). The respective AUCs in the validation cohort (482 patients) were 0.812 and 0.751 and optimal Lactate_Max cut-offs were identical in both cohorts. Exploration cohort patients with Lactate_Max 50 mg/dl or greater more often developed CR-PHLF (50.0 per cent) than those with Lactate_Max between 20 and 49.9 mg/dl (7.4 per cent) or less than 20 mg/dl (0.5 per cent; P < 0.001). This also applied to death (18.4, 2.7 and 1.4 per cent), severe morbidity (71.1, 35.7 and 14.1 per cent) and associated complications such as acute kidney injury (26.3, 3.1 and 2.3 per cent) and haemorrhage (15.8, 3.1 and 1.4 per cent). These results were confirmed in the validation group. Combining Lactate_Max with Lactate_POD1 further increased AUC (ΔAUC = 0.053) utilizing lactate dynamics for risk assessment. Lactate_Max, major resections, age, cirrhosis and chronic kidney disease were independent risk factors for CR-PHLF. A freely available calculator facilitates clinical risk stratification (www.liver-calculator.com). CONCLUSION: Early postoperative lactate values are powerful, readily available markers for CR-PHLF and associated complications after hepatectomy with potential for guiding postoperative care.Presented in part as an oral video abstract at the 2020 online Congress of the European Society for Surgical Research and the 2021 Congress of the Austrian Surgical Society.

Liver failure represents a major complication after liver resection and determines the risk of postoperative death, therefore early anticipation and risk stratification are highly relevant. This study, of 991 patients in three international centres, shows that the maximum lactate blood level within 24 h after surgery is a very strong factor predicting the further course after liver operations. Lactate could potentially aid in clinical decision making such as prophylactic treatment, intensified observation or early discharge of patients.

Perioperative chemotherapy versus surgery alone for resectable colorectal liver metastases: an international multicentre propensity score matched analysis on long-term outcomes according to established prognostic risk scores.

BACKGROUND: There is still uncertainty regarding the role of perioperative chemotherapy (CTx) in patients with resectable colorectal liver metastases (CRLM), especially in those with a low-risk of recurrence. METHODS: Multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010-2015. Patients were divided into two groups according to whether they received perioperative CTx or not and were compared using propensity score matching (PSM) analysis. Then, they were stratified according to prognostic risk scores, including: Clinical Risk Score (CRS), Tumour Burden Score (TBS) and Genetic And Morphological Evaluation (GAME) score. RESULTS: The study included 967 patients with a median follow-up of 68 months. After PSM analysis, patients with perioperative CTx presented prolonged overall survival (OS) in comparison with the surgery alone group (82.8 vs 52.5 months, p = 0.017). On multivariable analysis perioperative CTx was an independent predictor of increased OS (HR 0.705, 95%CI 0.705-0.516, p = 0.029). The benefits of perioperative CTx on survival were confirmed in patients with CRS and TBS scores ≤2 (p = 0.022 and p = 0.020, respectively) and in patients with a GAME score ≤1 (p = 0.006). CONCLUSION: Perioperative CTx demonstrated an increase in OS in patients with CRLM. Patients with a low-risk of recurrence seem to benefit from systemic treatment.

Validation of the revised 2018 AAST-OIS classification and the CT severity index for prediction of operative management and survival in patients with blunt spleen and liver injuries.

OBJECTIVES: Non-operative management (NOM) is increasingly utilised in blunt abdominal trauma. The 1994 American Association of Surgery of Trauma grading (1994-AAST) is applied for clinical decision-making in many institutions. Recently, classifications incorporating contrast extravasation such as the CT severity index (CTSI) and 2018 update of the liver and spleen AAST were proposed to predict outcome and guide treatment, but validation is pending. METHODS: CT images of patients admitted 2000-2016 with blunt splenic and hepatic injury were systematically re-evaluated for 1994/2018-AAST and CTSI grading. Diagnostic accuracy, diagnostic odds ratio (DOR), and positive and negative predictive values were calculated for prediction of in-hospital mortality. Correlation with treatment strategy was assessed by Cramer V statistics. RESULTS: Seven hundred and three patients were analysed, 271 with splenic, 352 with hepatic and 80 with hepatosplenic injury. Primary NOM was applied in 83% of patients; mortality was 4.8%. Comparing prediction of mortality in mild and severe splenic injuries, the CTSI (3.1% vs. 10.3%; diagnostic accuracy = 75.4%; DOR = 3.66; p = 0.006) and 1994-AAST (3.3% vs. 10.5%; diagnostic accuracy = 77.9%; DOR = 3.45; p = 0.010) were more accurate compared with the 2018-AAST (3.4% vs. 8%; diagnostic accuracy = 68.2%; DOR = 2.50; p = 0.059). In hepatic injuries, the CTSI was superior to both AAST classifications in terms of diagnostic accuracy (88.7% vs. 77.1% and 77.3%, respectively). CTSI and 2018-AAST correlated better with the need for surgery in severe vs. mild hepatic (Cramer V = 0.464 and 0.498) and splenic injuries (Cramer V = 0.273 and 0.293) compared with 1994-AAST (Cramer V = 0.389 and 0.255; all p < 0.001). CONCLUSIONS: The 2018-AAST and CTSI are superior to the 1994-AAST in correlation with operative treatment in splenic and hepatic trauma. The CTSI outperforms the 2018-AAST in mortality prediction. KEY POINTS: • Non-operative management of blunt abdominal trauma is increasingly applied and correct patient stratification is crucial. • CT-based scoring systems are used to assess injury severity and guide clinical decision-making, whereby the 1994 version of the American Association of Surgery of Trauma Organ Injury Scale (AAST-OIS) is currently most commonly utilised. • Including contrast media extravasation in CT-based grading improves management and outcome prediction. While the 2018-AAST classification and the CT-severity-index (CTSI) better correlate with need for surgery compared to the 1994-AAST, the CTSI is superior in outcome-prediction to the 2018-AAST.

Early response evaluation during preoperative chemotherapy for colorectal liver metastases: Combined size and morphology-based criteria predict pathological response and survival after resection.

BACKGROUND: Short treatment-duration with early restaging is crucial to avoid liver injury after preoperative chemotherapy (preopCTX) for colorectal liver metastases (CRLM). Response evaluation according to response evaluation criteria in solid tumors (RECIST) criteria implies several limitations. Early tumor shrinkage (ETS; ≥20% size reduction <6-12 weeks) or morphological criteria (MC) may better predict oncological outcome. METHODS: In patients undergoing resection after preopCTX between 2003-2017 pathological and radiological response was reassessed according to Blazer classification, ETS, MC, and RECIST within 90 days and correlated with survival. RESULTS: Seventy-two patients were included, with a median of two (1-10) liver lesions, 53% bilobar involvement, and 7% extrahepatic disease. PreopCTX was applied for 3 months in median (1-6). During restaging after a median of 62 days, presence of ETS was associated with improved median overall survival (OS; 57.1 vs 33.7 months; P = .010) and disease-free survival (16 vs 7.2 months; P = .025). MC significantly correlated with major pathological response (P = .021). When combining ETS with optimal MC, presence of one or both factors was associated with pathological response (61.5% and 92.3%; P = .044) and OS in log-rank (P = .011), and multivariable analysis (hazard ratio [HR] 0.41; 95% confidence interval [CI], 0.19-0.90 and HR 0.32; 95%CI, 0.11-0.97). CONCLUSION: Response-grading by combined ETS/MC criteria less than 90 days after preopCTX initiation predicts pathological response and postoperative survival in CRLM.

Perioperative von Willebrand factor dynamics are associated with liver regeneration and predict outcome after liver resection.

von Willebrand Factor (vWF) was found to mediate platelet influx during the early phase of liver regeneration in mice. Furthermore, increased vWF-antigen (vWF-Ag) levels were shown to be predictive for outcome of patients with chronic liver disease. Accordingly, we aimed to assess the relevance of perioperative vWF-Ag dynamics in terms of liver regeneration and clinical outcome in patients undergoing liver resection (LR). Accordingly, we observed that vWF-Ag and its activity-estimated by ristocetin cofactor measurement-increased immediately after induction of liver regeneration and was associated with platelet accumulation within the liver. However, a significant vWF-Ag burst was only observed in patients with unaffected postoperative liver regeneration. E-selectin, as an established marker for endothelial cell activation, was found to correlate with vWF-Ag in the liver vein after induction of liver regeneration (R = 0.535, P = 0.022). Preoperative vWF-Ag levels significantly predicted postoperative liver dysfunction (LD; N = 95; area under the curve, 0.725; P = 0.009). Furthermore, a cutoff of vWF-Ag ≥182% was defined to identify patients with a higher risk for postoperative LD or morbidity. This was confirmed within an independent mulitcenter validation cohort (N = 133). Ultimately, multivariable analysis revealed that vWF-Ag was an independent predictor of postoperative LD and morbidity. CONCLUSION: Within this study, we were able to provide evidence that an initial vWF burst is required to allow for adequate platelet accumulation and concomitant liver regeneration post-LR and might be abolished as a consequence of intrahepatic endothelial cell dysfunction. We were further able to reveal and validate the potential of preoperative vWF-antigen levels to predict poor postoperative outcome in patients undergoing LR. Despite the pathophysiological relevance of our findings, vWF-Ag seems to be a valuable tool for preoperative risk assessment in patients undergoing LR. (Hepatology 2018;67:1516-1530).

Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells.

Histone deacetylases (HDACs) play a key role in epigenetic mechanisms in health and disease and their dysfunction is implied in several cancer entities. Analysis of expression patterns in pancreatic neuroendocrine tumors (pNETs) indicated HDAC5 to be a potential target for future therapies. As a first step towards a possible treatment, the aim of this study was to evaluate the in vitro cellular and molecular effects of HDAC5 inhibition in pNET cells. Two pNET cell lines, BON-1 and QGP-1, were incubated with different concentrations of the selective class IIA HDAC inhibitor, LMK-235. Effects on cell viability were determined using the resazurin-assay, the caspase-assay, and Annexin-V staining. Western Blot and immunofluorescence microscopy were performed to assess the effects on HDAC5 functionality. LMK-235 lowered overall cell viability by inducing apoptosis in a dose- and time-dependent manner. Furthermore, acetylation of histone-H3 increased with higher LMK-235 concentrations, indicating functional inhibition of HDAC4/5. Immunocytochemical analysis showed that proliferative activity (phosphohistone H3 and Ki-67) decreased at highest concentrations of LMK-235 while chromogranin and somatostatin receptor 2 (SSTR2) expression increased in a dose-dependent manner. HDAC5 expression was found to be largely unaffected by LMK-235. These findings indicate LMK-235 to be a potential therapeutic approach for the development of an effective and selective pNET treatment.

HDAC-Linked "Proliferative" miRNA Expression Pattern in Pancreatic Neuroendocrine Tumors.

Epigenetic factors are essentially involved in carcinogenesis, tumor promotion, and chemoresistance. Two epigenetic key players are miRNAs and histone deacetylases (HDACs). As previously shown by own theoretical databank analysis, the crosstalk between miRNAs and HDACs is relevant in different human chronic diseases and cancerogenic pathways. We aimed to investigate a potential connection between the expression of a well-defined subset of "proliferation-associated" miRNAs and the expression of HDACs as well as clinical parameters in pancreatic neuroendocrine tumors (pNETs). MATERIALS AND METHODS: Expression levels of miRNA132-3p, miRNA145-5p, miRNA183-5p, miRNA34a-5p, and miRNA449a in 57 pNETs resected between 1997 and 2015 were measured and linked to the immunohistochemical expression pattern of members of the four HDAC classes on human tissue microarrays. All pNET cases were clinically and pathologically characterized according to published guidelines. Correlation analysis revealed a significant association between expression of specific miRNAs and two members of the HDAC family (HDAC3 and HDAC4). Additionally, a linkage between miRNA expression and clinico-pathological parameters like grading, TNM-staging, and hormone activity was found. Moreover, overall and disease-free survival is statistically correlated with the expression of the investigated miRNAs. Overall, we demonstrated that specific miRNAs could be linked to HDAC expression in pNETs. Especially miRNA449a (associated with HDAC3/4) seems to play an important role in pNET proliferation and could be a potential prognostic factor for poor survival. These first data could help, to improve our knowledge of the complex interactions of the epigenetic drivers in pNETs for further therapeutic approaches.

First Episode of Spontaneous Pneumothorax: CT-based Scoring to Select Patients for Early Surgery.

BACKGROUND: Although recurrence of primary spontaneous pneumothorax (PSP) is frequent, guidelines do not routinely recommend surgery after first presentation. A CT-based lung dystrophy severity score (DSS) has recently been proposed to predict recurrence following conservative therapy. This study compares the DSS in surgically and conservatively treated patients. METHODS: This is a retrospective analysis of first episode PSP patients, comparing video-assisted thoracic surgery (VATS; group A) to conservative treatment with or without chest drainage (group B). CT scans were reviewed for blebs or bullae, and patients were assigned DSS values and stratified into risk groups (low and high-grade). Primary end point was ipsilateral or contralateral recurrence. RESULTS: Fifty-six patients were included, 33 received VATS and 23 conservative treatment. In total, 37.5 % experienced recurrence, with a 5-year estimated recurrence rate of 40.7 % (group A: 13.3 %; group B: 73.9 %; p < 0.001). In group B, detection of any dystrophic lesions resulted in significantly higher 5-year recurrence rates (86.7 vs. 50.0 %; p = 0.03), there was no significant difference in group A (17.7 vs. 7.7 %; p = 0.50). Greater DSS values correlated with higher 5-year recurrence rates in group B (p = 0.02), but not in group A (p = 0.90). Comparing low- and high-grade patients in group B resulted in a significant 5-year recurrence rate of 53.8 versus 100 % (p = 0.023). CONCLUSIONS: The DSS is useful to indicate VATS after the first episode. For routine application, assigning patients to low- and high-grade groups seems most practical. We recommend CT-evaluation for every PSP patient and early surgery for those with lesions exceeding one bleb. After VATS, the preoperative DSS is not beneficial in predicting recurrence.

Relevance of MicroRNA200 Family and MicroRNA205 for Epithelial to Mesenchymal Transition and Clinical Outcome in Biliary Tract Cancer Patients.

Extensive stromal interaction is one reason for the dismal outcome of biliary tract cancer (BTC) patients. Epithelial to mesenchymal transition (EMT) is involved in tumor invasion and metastasis and is partly regulated by microRNAs (miRs). This study explores the expression of anti-EMT miR200 family (miR141, -200a/b/c, -429) and miR205 as well as the EMT-related proteins E-cadherin and vimentin in a panel of BTC cell lines and clinical specimens by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry, respectively. MicroRNA expression was correlated to (i) the expression patterns of E-cadherin and vimentin; (ii) clinicopathological characteristics; and (iii) survival data. MicroRNA-200 family and miR205 were expressed in all BTC cells and clinical specimens. E-cadherin and vimentin showed a mutually exclusive expression pattern in both, in vitro and in vivo. Expression of miR200 family members positively correlated with E-cadherin and negatively with vimentin expression in BTC cells and specimens. High expression of miR200 family members (but not miR205) and E-cadherin was associated with longer survival, while low miR200 family and high vimentin expression was a predictor of unfavorable survival. Overall, the current study demonstrates the relevance of the miR200 family in EMT of BTC tumors and suggests these miRs as predictors for positive outcome.

Evolution of surgical microwave ablation for the treatment of colorectal cancer liver metastasis: review of the literature and a single centre experience.

Surgical resection is the gold standard treatment for colorectal liver metastasis, with reported five-year survival rates of 40 %. Unfortunately, despite progress in systemic therapies and surgical techniques, only 20-30 % of patients can be offered this potentially curative treatment modality. Ablative therapies have recently been suggested to treat unresectable lesions or to extend the margins of resectability. Additionally, cases of local recurrence after hepatic surgery might require alternative strategies and options for re-intervention. Microwave ablation (MWA) has recently become a matter of particular interest for such indications. We, herein, present a review of the literature published between January 1999 and June 2013 from a database search with the following keywords: microwave, ablation, liver metastases, colorectal neoplasm, resection, hepatectomy, colonic neoplasm, cancer. Furthermore, we provide insight based on our own data for 28 consecutive patients who underwent hepatic resection combined with MWA from 2005 to 2012 in a single centre.

Preparing for prospective clinical trials: a national initiative of an excellence registry for consecutive pancreatic cancer resections.

BACKGROUND: Despite significant improvements in perioperative mortality as well as response rates to multimodality treatment, results after surgical resection of pancreatic adenocarcinoma with respect to long-term outcomes remain disappointing. Patient recruitment for prospective international trials on adjuvant and neoadjuvant regimens is challenging for various reasons. We set out to assess the preconditions and potential to perform perioperative trials for pancreatic cancer within a well-established Austrian nationwide network of surgical and medical oncologists (Austrian Breast & Colorectal Cancer Study Group). METHODS: From 2005 to 2010 five high-volume centers and one medium-volume center completed standardized data entry forms with 33 parameters (history and patient related data, preoperative clinical staging and work-up, surgical details and intraoperative findings, postoperative complications, reinterventions, reoperations, 30-day mortality, histology, and timing of multimodality treatment). Outside of the study group, in Austria pancreatic resections are performed in three "high-volume" centers (>10 pancreatic resections per year), three "medium-volume" centers (5­10 pancreatic resections per year), and the rest in various low-volume centers (<5 pancreatic resections per year) in Austria. Nationwide data for prevalence of and surgical resections for pancreatic adenocarcinoma were contributed by the National Cancer Registry of Statistics of Austria and the Austrian Health Institute. RESULTS: In total, 492 consecutive patients underwent pancreatic resection for ductal adenocarcinoma. All postoperative complications leading to hospital readmission were treated at the primary surgical department and documented in the database. Overall morbidity and pancreatic fistula rate were 45.5 % and 10.1 %, respectively. Within the entire cohort there were 9.8 % radiological reinterventions and 10.4 % reoperations. Length of stay was 16 days in median (0­209); 12 of 492 patients died within 30 days after operation, resulting in a 30-day mortality rate of 2.4 %. Seven of the total 19 deaths (36.8 %) occurred after 30 days, during hospitalization at the surgical department, resulting in a hospital mortality rate of 3.9 % (19/492). With a standardized histopathological protocol, there were 70 % (21/30) R0 resections, 30 % (9/30) R1 resections, and no R2 resections in Vienna and 62.7 % (32/51) R0 resections, 35.3 % (18/51) R1 resections, and 2 % (1/51) R2 resections in Salzburg. Resection margin status with nonstandardized protocols was classified as R0 in 82 % (339/411), R1 in 16 % (16/411), and R2 in 1.2 % (5/411). Perioperative chemotherapy was administered in 81.1 % of patients (8.3 % neoadjuvant; 68.5 % adjuvant; 4.3 % palliative); chemoradiotherapy (1.6 % neoadjuvant; 3 % adjuvant; 0.2 % palliative), in 4.9 % of patients. The six centers that contributed to this registry initiative provided surgical treatment to 40 % of all Austrian patients, resulting in a median annual recruitment of 85 (51­104) patients for the entire ABCSG-group and a median of 11.8 (0­38) surgeries for each individual department. CONCLUSIONS: Surgical quality data of the ABCSG core pancreatic group are in line with international standards. With continuing centralization the essential potential to perform prospective clinical trials for pancreatic adenocarcinoma is given in Austria. Several protocol proposals aiming at surgical and multimodality research questions are currently being discussed

Hepatocellular carcinoma.

An update on the management of Hepatocellular carcinoma (HCC) is provided in the present article for those interested in the UEMS/EBSQ exam in Surgical Oncology. The most recent publications in HCC, including surveillance, guidelines, and indications for liver resection, liver transplantation, and locoregional or systemic therapies, are summarised. The objective is to yield a set of main points regarding HCC that are required in the core curriculum of hepatobiliary oncological surgery.