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Background: The grim (<10% 5-year) survival rates for pancreatic ductal adenocarcinoma (PDAC) are attributed to its complex intrinsic biology and most often late-stage detection. The overlap of symptoms with benign gastrointestinal conditions in early stage further complicates timely detection. The suboptimal diagnostic performance of carbohydrate antigen (CA) 19-9 and elevation in benign hyperbilirubinaemia undermine its reliability, leaving a notable absence of accurate diagnostic biomarkers. Using a selected patient cohort with benign pancreatic and biliary tract conditions we aimed to develop a data analysis protocol leading to a biomarker signature capable of distinguishing patients with non-specific yet concerning clinical presentations, from those with PDAC., Methods: 539 patient serum samples collected under the Accelerated Diagnosis of neuro Endocrine and Pancreatic TumourS (ADEPTS) study (benign disease controls and PDACs) and the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, healthy controls) were screened using the Olink Oncology II panel, supplemented with five in-house markers. 16 specialized base-learner classifiers were stacked to select and enhance biomarker performances and robustness in blinded samples. Each base-learner was constructed through cross-validation and recursive feature elimination in a discovery set comprising approximately two thirds of the ADEPTS and UKCTOCS samples and contrasted specific diagnosis with PDAC., Results: The signature which was developed using diagnosis-specific ensemble learning demonstrated predictive capabilities outperforming CA19-9, the only biomarker currently accepted by the FDA and the National Comprehensive Cancer Network guidelines for pancreatic cancer, and other individual biomarkers and combinations in both discovery and held-out validation sets. An AUC of 0.98 (95% CI 0.98-0.99) and sensitivity of 0.99 (95% CI 0.98-1) at 90% specificity was achieved with the ensemble method, which was significantly larger than the AUC of 0.79 (95% CI 0.66-0.91) and sensitivity 0.67 (95% CI 0.50-0.83), also at 90% specificity, for CA19-9, in the discovery set (p = 0.0016 and p = 0.00050, respectively). During ensemble signature validation in the held-out set, an AUC of 0.95 (95% CI 0.91-0.99), sensitivity 0.86 (95% CI 0.68-1), was attained compared to an AUC of 0.80 (95% CI 0.66-0.93), sensitivity 0.65 (95% CI 0.48-0.56) at 90% specificity for CA19-9 alone (p = 0.0082 and p = 0.024, respectively). When validated only on the benign disease controls and PDACs collected from ADEPTS, the diagnostic-specific signature achieved an AUC of 0.96 (95% CI 0.92-0.99), sensitivity 0.82 (95% CI 0.64-0.95) at 90% specificity, which was still significantly higher than the performance for CA19-9 taken as a single predictor, AUC of 0.79 (95% CI 0.64-0.93) and sensitivity of 0.18 (95% CI 0.03-0.69) (p = 0.013 and p = 0.0055, respectively)., Conclusion: Our ensemble modelling technique outperformed CA19-9, individual biomarkers and indices developed with prevailing algorithms in distinguishing patients with non-specific but concerning symptoms from those with PDAC, with implications for improving its early detection in individuals at risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: UM reports stock ownership in Abcodia UK between 2011 and 2021; UM has received grants from the Medical Research Council (MRC), Cancer Research UK, the National Institute for Health Research (NIHR), the India Alliance, NIHR Biomedical Research Centre at University College London Hospital, and The Eve Appeal; UM currently has research collaborations with iLOF, RNA Guardian and Micronoma, with funding paid to UCL; UM holds patent number EP10178345.4 for Breast Cancer Diagnostics; AG currently has research collaborations with Micronoma and iLoF, with the research funding awarded to UCL. The other authors have declared that no competing interests exist., (Copyright: © 2024 Ney et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB., Patients and Methods: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS)., Results: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively)., Discussion: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

A literature search of MEDLINE/PUBMED was conducted with the aim to highlight current endoscopic management of localised gastro-entero-pancreatic NETs. Relevant articles were identified through a manual search, and reference lists were reviewed for additional articles. The results of the research have been displayed in a narrative fashion to illustrate the actual state-of-the-art of endoscopic techniques in the treatment of NETs. Localised NETs of the stomach, duodenum and rectum can benefit from advanced endoscopic resection techniques (e.g., modified endoscopic mucosal resection, endoscopic full thickness resection, endoscopic submucosal dissection) according to centre expertise. Radiofrequency thermal ablation can be proposed as an alternative to surgery in selected patients with localised pancreatic NETs.

Background: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe., Methods: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application., Results: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification., Conclusion: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes., Competing Interests: Conflict of interest None to declare., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

To mitigate COVID-19-related shortage of treatment capacity, the hepatopancreatobiliary (HPB) unit of the Royal Free Hospital London (RFHL) transferred its practice to independent hospitals in Central London through the North Central London Cancer Alliance. The aim of this study was to critically assess this strategy and evaluate perioperative outcomes. Prospectively collected data were reviewed on all patients who were treated under the RFHL HPB unit in six hospitals between November 2020 and October 2021. A total of 1541 patients were included, as follows: 1246 (81%) at the RFHL, 41 (3%) at the Chase Farm Hospital, 23 (2%) at the Whittington Hospital, 207 (13%) at the Princess Grace Hospital, 12 (1%) at the Wellington Hospital and 12 (1%) at the Lister Hospital, Chelsea. Across all institutions, overall complication rate were 40%, major complication (Clavien-Dindo grade ≥ 3a) rate were 11% and mortality rates were 1.4%, respectively. In COVID-19-positive patients (n = 28), compared with negative patients, complication rate and mortality rates were increased tenfold. Outsourcing HPB patients, including their specialist care, to surrounding institutions was safe and ensured ongoing treatment with comparable outcomes among the institutions during the COVID-19 pandemic. Due to the lack of direct comparison with a non-pandemic cohort, these results can strictly only be applied within a pandemic setting., (© 2023. Springer Nature Limited.)

Background: Pancreatic cystic lesions (PCL) represent an increasingly diagnosed condition with significant burden to patients' lives and medical resources. Endoscopic ultrasound (EUS) ablation techniques have been utilized to treat focal pancreatic lesions. This systematic review with meta-analysis aims to assess the efficacy of EUS ablation on PCL in terms of complete or partial response and safety., Methods: A systematic search in Medline, Cochrane and Scopus databases was performed in April 2023 for studies assessing the performance of the various EUS ablation techniques. The primary outcome was complete cyst resolution, defined as cyst disappearance in follow-up imaging. Secondary outcomes included partial resolution (reduction in PCL size), and adverse events rate. A subgroup analysis was planned to evaluate the impact of the available ablation techniques (ethanol, ethanol/paclitaxel, radiofrequency ablation (RFA), and lauromacrogol) on the results. Meta-analyses using a random effects model were conducted and the results were reported as percentages with 95% confidence intervals (95%CI)., Results: Fifteen studies (840 patients) were eligible for analysis. Complete cyst resolution after EUS ablation was achieved in 44% of cases (95%CI: 31-57; 352/767; I 2 = 93.7%), and the respective partial response rate was 30% (95%CI: 20-39; 206/767; I 2 = 86.1%). Adverse events were recorded in 14% (95%CI: 8-20; 164/840; I 2 = 87.2%) of cases, rated as mild in 10% (95%CI: 5-15; 128/840; I 2 = 86.7%), and severe in 4% (95%CI: 3-5; 36/840; I 2 = 0%). The subgroup analysis for the primary outcome revealed rates of 70% (95%CI: 64-76; I 2 = 42.3%) for ethanol/paclitaxel, 44% (95%CI: 33-54; I 2 = 0%) for lauromacrogol, 32% (95%CI: 27-36; I 2 = 88.4%) for ethanol, and 13% (95%CI: 4-22; I 2 = 95.8%) for RFA. Considering adverse events, the ethanol-based subgroup rated the highest percentage (16%; 95%CI: 13-20; I 2 = 91.0%)., Conclusion: EUS ablation of pancreatic cysts provides acceptable rates of complete resolution and a low incidence of severe adverse events, with chemoablative agents yielding higher performance rates.

Background: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions., Methods: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases., Results: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001)., Conclusion: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: New biomarkers have the potential to facilitate early diagnosis of pancreatic cancer (PC). Circulating exosomes are cell-derived protein complexes containing RNA that can be used as indicators of cancer development. The aim of this review is to evaluate the current literature involving PC patient groups for highly accurate exosomal biomarkers., Methods: The literature search followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight-hundred and seventy-five studies were identified across various databases (Ovid MEDLINE, Embase, and Cochrane) published between 2009 and 2020. Nine studies fulfilled the inclusion criteria: human PC patients, diagnosis as outcome of interest, serum biomarker of exosomal content, reporting of diagnostic values, and disease progress. Area under the curve (AUC) of the exosomal biomarker was compared against that of CA19-9., Results: Nine papers were reviewed for relevant outcomes based on the inclusion criteria. These studies involved 565 participants (331 PC, 234 controls; male/female ratio 1.21; mean age 64.1). Tumor staging was reported in all studies, with 45.6% of PC patients diagnosed with early-stage PC (T1-2). The mRNA panel (ARG1, CD63, CK18, Erbb3, GAPDH, H3F3A, KRAS, ODC1) and GPC 1 reported the highest performing sensitivity and specificity at 100% each. The microRNA panel (miR-10b, miR-21, miR-30c, miR-181a, and miR-let7a), mRNA panel (ARG1, CD63, CK18, Erbb3, GAPDH, H3F3A, KRAS, ODC1), and GPC 1 showed a perfect AUC of 1.0. Five studies compared the AUC of the exosomal biomarker against CA19-9, each being superior to that of CA19-9., Conclusion: The potential of exosomal biomarkers remains promising in PC diagnosis. Standardization of future studies will allow for larger comparative analyses and overcoming contrasting findings., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background/aim: Postoperative complications have a tremendous impact on in-hospital costs. The novel Comprehensive Complication Index ® (CCI ® ) summarizes all complications together and is more sensitive than existing morbidity endpoints. The purpose of this study was to assess the correlation of CCI ® with in-hospital costs and externally validate a novel cost prediction calculator., Patients and Methods: This was a prospective study including consecutive patients undergoing elective major hepatopancreaticobiliary (HPB) surgery for malignancy at a London tertiary referral hospital. A priori sample size and post-hoc power calculations were performed., Results: Thirty patients were included in the analysis, 14 were female, and the median age was 67 [interquartile range (IQR)=54-74] years. The median Charlson Comorbidity Index was 6 (IQR=5-8). Eighteen patients underwent liver, 9 pancreatic surgery and three a palliative bypass; 11 patients had a major complication (≥grade 3a) according to the Clavien-Dindo classification. The median CCI ® was 30.2 (IQR=12.18-39.5). The mean cost per case was 13,908 (SD=4,600) GBP. There was no correlation between the Charlson Comorbidity Index or age with actual cost. However, there was very good correlation of actual cost with the CCI ® (r=0.77, 95% confidence interval=0.57-0.89, p<0.001) as well as with the predicted cost (Clavien Cost Prediction Calculator) (r=0.70, 95% confidence interval=0.44-0.85, p<0.001)., Conclusion: These findings support the hypothesis that complications are the most important predictor of overall cost in the setting of elective major HPB surgery for malignancy. Furthermore, CCI ® and the novel Cost Prediction Calculator can be used in this setting to accurately predict costs using no additional resources., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH., Methods: Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan-Meier approach. All analyses were adjusted for age, gender, and side of primary tumour., Results: One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19-89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months [95% Confidence Interval (CI) 21.5-29.0], and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12-0.29, p < 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival-with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank p < 0.0001). After exclusion of those who received systemic chemotherapy only ( n = 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20-0.63, p < 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival., Conclusion: Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness.

Background: Pancreatic cystic lesions (PCL) are being detected with increasing frequency. Current methods of stratifying risk of malignant transformation are imperfect. This study aimed to determine the frequency of pancreatic malignancy in patients with PCL and define clinical and radiological features that predict malignant transformation in patients managed by surgery and/or surveillance. Methods: A retrospective cohort of adults who were evaluated in a tertiary hepatopancreaticobiliary centre between January 2000 - December 2013 with a confirmed PCL and followed up for at least 5 years. All cystic lesions were discussed at a weekly multidisciplinary meeting. Results: Of the 1,090 patients diagnosed with a PCL, 768 patients were included in the study: 141 patients were referred for immediate pancreatic resection, 570 entered surveillance while 57 had a malignant PCL which was unresectable at diagnosis (n=47) or were unfit for surgery (n=10). In those who were resected following presentation, malignancy was present in 38%. During follow-up 2% of those entering a surveillance programme underwent malignant transformation. Clinical and radiological features associated with a high-risk PCL included older age, symptoms, associated solid component or dilated main pancreatic duct. In intraductal papillary mucinous neoplasms, larger size was not a feature of malignant transformation (benign vs. malignant 30mm vs. 23mm; P= 0.012). Conclusion: The sensitivity of standard diagnostic tests leading to immediate surgery for high-risk PCL (malignant or mucinous) was 92% but with a specificity of just 5%. Surveillance of PCL without high-risk features within a multidisciplinary meeting was associated with a low incidence of cancer development, supporting the use of worrisome clinical and radiological features in the initial stratification of PCL., Competing Interests: No competing interests were disclosed.

Background and study aims  Pancreatic cystic lesions (PCL) are common. While some harbor malignant potential, accurate preoperative diagnosis remains challenging. Needle-based confocal laser endomicroscopy (nCLE) via a 19G FNA needle enables real-time imaging of the cyst wall. This study evaluated the safety and utility of nCLE in patients with an indeterminate PCL undergoing EUS-FNA. Patients and methods  The CONCYST study prospectively recruited patients with indeterminate PCL attending three hepatopancreaticobiliary (HPB) referral centers in the UK, with indeterminate PCL, who required EUS-FNA between July 2014 and October 2016. Following the procedure, all patients were followed up in telephone clinic for at least 12 months. Ethical approval for the study was granted by the National Research Ethics Service (14/LO/0040). Results  Sixty-seven patient were recruited, 11 excluded and 56 included in the final analysis: 35 male, 21 female; median age 68 (range 28 - 80). Recognizable confocal images were obtained in 48 of 56 cases. Median nCLE scanning time was 5 minutes and did not exceed 10 minutes in any case. EUS-nCLE findings correlated with final diagnosis (based on imaging, cytology and multidisciplinary team review) in 43/56 (77 %) of cases, compared with 37/56 (66 %) for cytology alone ( P  = 0.12). One patient experienced mild pruritus following the procedure and another developed an infected pseudocyst, which resolved with antibiotics. Conclusions  EUS-nCLE under conscious sedation in the day case setting is safe and provides additional information to standard EUS-FNA for diagnosing indeterminate PCL.

Aim: To study the published evidence on the impact of colectomy in preventing recurrent primary sclerosing cholangitis (rPSC)., Methods: An unrestricted systematic literature search in PubMed, EMBASE, Medline OvidSP, ISI Web of Science, Lista (EBSCO) and the Cochrane library was performed on clinical studies investigating colectomy in liver transplantation (LT) recipients with and without rPSC in the liver allograft. Study quality was evaluated according to a modification of the methodological index for non-randomized studies (MINORS) criteria. Primary endpoints were the impact of presence, timing and type of colectomy on rPSC. Overall presence of inflammatory bowel disease (IBD), time of IBD diagnosis, posttransplant IBD and immunosuppressive regimen were investigated as secondary outcome., Results: The literature search yielded a total of 180 publications. No randomized controlled trial was identified. Six retrospective studies met the inclusion criteria of which 5 studies were graded as high quality articles. Reporting of IBD was heterogenous but in four publications, either inflammatory bowel disease, ulcerative colitis or in particular active colitis post-LT significantly increased the risk of rPSC. The presence of an intact ( i.e ., retained) colon at LT was identified as risk factor for rPSC in two of the high quality studies while four studies found no effect. Type of colectomy was not associated with rPSC but this endpoint was underreported (only in 33% of included studies). Neither tacrolimus nor cyclosporine A yielded a significant benefit in disease recurrence of primary sclerosing cholangitis (PSC)., Conclusion: The data favours a protective role of pre-/peri-LT colectomy in rPSC but the current evidence is not strong enough to recommend routine colectomy for rPSC prevention.

Background: There is dire need for discovery of novel pancreatic cancer biomarkers and of agents with the potential for simultaneous diagnostic and therapeutic capacity. This study demonstrates calreticulin expression on hamster pancreatic adenocarcinoma via bio-conjugated gold quantum dots (AuQDs)., Materials and Methods: Hamster pancreatic adenocarcinoma cells were cultured, fixed and incubated with fluorescent AuQDs, bio-conjugated to anti-calreticulin antibodies. Anti-calreticulin and AuQDs were produced in-house. AuQDs were manufactured to emit in the near-infrared. Cells were further characterized under confocal fluorescence., Results: AuQDs were confirmed to emit in the near-infrared. AuQD bio-conjugation to calreticulin was confirmed via dot-blotting. Upon laser excitation and post-incubation with bio-conjugated AuQDs, pancreatic cancer cell lines emitted fluorescence in near-infrared., Conclusion: Hamster pancreatic cancer cells express calreticulin, which may be labelled with AuQDs. This study demonstrates the application of nanoparticle-based theranostics in pancreatic cancer. Such biomarker-targeting nanosystems are anticipated to play a significant role in the management of pancreatic cancer., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The aim of this prospective observational study was to compare peri/post-operative outcomes of thoracic epidural analgesia (TEA) versus intrathecal morphine and fentanyl patient-controlled analgesia (ITM+fPCA) for patients undergoing a hepatic resection (HR)., Method: Patients undergoing elective, one-stage, open HR for benign and malignant liver lesions, receiving central neuraxial block as part of the anaesthetic, in a high-volume hepato-pancreato-biliary unit, were included in the study. The primary outcome measure was post-operative length of stay (LoS)., Results: A total of 73 patients (36 TEA and 37 ITM+fPCA) were included in the study. The median (IQR) post-operative LoS was 13 (11-15) and 11 (9-13) days in the TEA and ITM+fPCA groups, respectively (P = 0.011). There was significantly lower median intra-operative central venous pressure (P < 0.001) and blood loss (P = 0.017) in the TEA group, and a significant reduction in the time until mobilization (P < 0.001), post-operative intra-venous fluid/vasopressor requirement (P < 0.001/P = 0.004) in the ITM+fPCA group. Pain scores were lower at a clinically significant level 12 h post-operatively in the TEA group (P < 0.001); otherwise there were no differences out to day five. There were no differences in quality of recovery or postoperative morbidity/mortality between the two groups., Conclusion: ITM+fPCA provides acceptable post-operative outcomes for HR, but may also increase the incidence of intra-operative blood loss in comparison to TEA., (© 2014 International Hepato-Pancreato-Biliary Association.)

Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis. Current standard therapy is limited to chemotherapy or chemoradiotherapy. Few regimens have been shown to have a substantial survival advantage and novel treatment strategies are urgently needed. Thermal and laser based ablative techniques are widely used in many solid organ malignancies. Initial studies in the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high quality imaging such as computed tomography and intraoperative or endoscopic ultrasound has enabled real time treatment monitoring and significant improvements in safety. We conducted a systematic review of the literature up to October 2013. Initial studies suggest that ablative therapies may confer an additional survival benefit over best supportive care but randomised studies are required to validate these findings.

The field of liver transplantation is limited by the availability of donor organs. The use of living donor and split cadaveric grafts is one potential method of expanding the donor pool. However, primary graft dysfunction can result from the use of partial livers despite the absence of other causes such as vascular obstruction or sepsis. This increasingly recognised phenomenon is termed "Small-for-size syndrome" (SFSS). Studies in animal models and humans have suggested portal hyperperfusion of the graft combined with poor venous outflow and reduced arterial flow might cause sinusoidal congestion and endothelial dysfunction. Graft related factors such as graft to recipient body weight ratio < 0.8, impaired venous outflow, steatosis > 30% and prolonged warm/cold ischemia time are positively predictive of SFSS. Donor related factors include deranged liver function tests and prolonged intensive care unit stay greater than five days. Child-Pugh grade C recipients are at relatively greater risk of developing SFSS. Surgical approaches to prevent SFSS fall into two categories: those targeting portal hyperperfusion by reducing inflow to the graft, including splenic artery modulation and portacaval shunts; and those aiming to relieve parenchymal congestion. This review aims to examine the controversial diagnosis of SFSS, including current strategies to predict and prevent its occurrence. We will also consider whether such interventions could jeopardize the graft by compromising regeneration.