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Background Minimally invasive surgery is the standard technique for many operations. Laparoscopic training has a long learning curve. Robotic solutions may shorten the training pathway. The aim of this study was to compare laparoscopic with robotic training in surgical trainees and medical students. Methods Surgical trainees (ST group) were randomized to receive 6 h of robotic or laparoscopic simulation training. They then performed three surgical tasks in cadaveric specimens. Medical students (MS group) had 2 h of robotic or laparoscopic simulation training followed by one surgical task. The Global Rating Scale (GRS) score (maximum 30), number of suture errors, and time to complete each procedure were recorded. Results The median GRS score for the ST group was better for each procedure after robotic training compared with laparoscopic training (total GRS score: 27·00 (i.q.r. 22·25–28·33) versus 18·00 (16·50–19·04) respectively, P, Medical students and surgical trainees were randomized to robotic or laparoscopic simulator training followed by cadaveric surgical tasks. The robotic groups had a shorter learning curve with better task performance. Another advantage for robotic surgery

Background There is an ongoing debate on the feasibility, safety, and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique. The aim of this study was to compare ALPPS, two-staged hepatectomy (TSH), and portal vein embolization (PVE)/ligation (PVL) using updated traditional meta-analysis and network meta-analysis (NMA). Data sources Electronic databases were used in a systematic literature search. Updated traditional meta-analysis and NMA were performed and compared. Mortality and major morbidity were selected as primary outcomes. Results Nineteen studies including 1200 patients were selected from the pool of 436 studies. Of these patients, 315 (31%) and 702 (69%) underwent ALPPS and portal vein occlusion (PVO), respectively. Ninety-day mortality based on updated traditional meta-analysis, subgroup analysis of the randomized controlled trials (RCTs), and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE, PVL, and TSH cohorts. Moreover, analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts. The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters, time to operation, definitive hepatectomy, and R0 margins rates compared with the PVO cohort. In contrast, 1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort. Conclusions This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches. Furthermore, two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts.

Background: Theoretical advantages of robotic surgery compared to conventional laparoscopic surgery include improved instrument dexterity, 3D visualization, and better ergonomics. This systematic review and meta-analysis aimed to determine advantages of robotic surgery over laparoscopic surgery in patients undergoing liver resections. Method: A systematic literature search was conducted for studies comparing robotic assisted or totally laparoscopic liver resection. Meta-analysis of intraoperative (operative time, blood loss, transfusion rate, conversion rate), oncological (R0 resection rates), and postoperative (bile leak, surgical site infection, pulmonary complications, 30-day and 90-day mortality, length of stay, 90-day readmission and reoperation rates) outcomes was performed using a random effects model. Result: Twenty-six non-randomized studies including 2630 patients (950 robotic and 1680 laparoscopic) were included, of which 20% had major robotic liver resection and 14% had major laparoscopic liver resection. Intraoperatively, robotic liver resection was associated with significantly less blood loss (mean: 286 vs 301 mL, p Conclusions: Robotic liver resection appears to offer some advantages compared to conventional laparoscopic surgery, although both techniques appear equivalent. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomized trial comparing both techniques is needed.

Advances in surgery, peri-operative care and systemic chemotherapy have not significantly improved the prognosis of pancreatic cancer for several decades. Early clinical trials of immunotherapy have yielded disappointing results proposing other means by which the tumour microenvironment serves to decrease the immune response. Additionally, the emergence of various subtypes of pancreatic cancer has emerged as a factor for treatment responses with immunogenic subtypes carrying a better prognosis. Herein we discuss the reasons for the poor response to checkpoint inhibitors and outline a rationale why combination treatments are likely to be most effective. We review the therapies which could provide optimal synergistic effects to immunotherapy including chemotherapy, agents targeting the stroma, co-stimulatory molecules, vaccinations and methods of immunogenic tumour priming including radiofrequency ablation. Finally, we discuss reasons why peri-operative and in particular neoadjuvant combination treatments are likely to be most effective and should be considered for early clinical trials.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has gained interest, as the potential alternative to portal vein embolisation for inducing future liver remnant hypertrophy in patients at risk of post-hepatectomy liver failure but is associated with high morbidity and mortality. As a result, several variant ALPPS have been reported to reduce ALPPS related morbidity and mortality. ALPPS is able to induce more extensive hypertrophy in a shorter time-period than portal vein embolisation. Minimally-invasive surgery, which has known benefits with regards to morbidity and mortality, has also been applied to ALPPS, with promising results regarding safety and feasibility and patient outcomes. Evidence suggests that both laparoscopic and robot-assisted ALPPS present technically feasible and safe options for patients. Minimally-invasive ALPPS offers a clear benefit to patients, including reduction of fibrous adhesions, shorter length of hospital stay, and lower morbidity. However, the technical difficulty of the procedure still limits its wide application, even to experienced hepato-pancreato-biliary centres. Keywords: ALPPS, Robotic hepatectomy, Laparoscopic hepatectomy, Staged liver resection

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Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality worldwide. Despite significant advancements in detection and treatment of HCC, its management remains a challenge. Artificial intelligence (AI) has played a role in medicine for several decades, however, clinically applicable AI-driven solutions have only started to emerge, due to gradual improvement in sensitivity and specificity of AI, and implementation of convoluted neural networks. A review of the existing literature has been conducted to determine the role of AI in HCC, and three main domains were identified in the search: detection, characterisation and prediction. Implementation of AI models into detection of HCC has immense potential, as AI excels at analysis and integration of large datasets. The use of biomarkers, with the rise of '-omics', can revolutionise the detection of HCC. Tumour characterisation (differentiation between benign masses, HCC, and other malignant tumours, as well as staging and grading) using AI was shown to be superior to classical statistical methods, based on radiological and pathological images. Finally, AI solutions for predicting treatment outcomes and survival emerged in recent years with the potential to shape future HCC guidelines. These AI algorithms based on a combination of clinical data and imaging-extracted features can also support clinical decision making, especially treatment choice. However, AI research on HCC has several limitations, hindering its clinical adoption; small sample size, single-centre data collection, lack of collaboration and transparency, lack of external validation, and model overfitting all results in low generalisability of the results that currently exist. AI has potential to revolutionise detection, characterisation and prediction of HCC, however, for AI solutions to reach widespread clinical adoption, interdisciplinary collaboration is needed, to foster an environment in which AI solutions can be further improved, validated and included in treatment algorithms. In conclusion, AI has a multifaceted role in HCC across all aspects of the disease and its importance can increase in the near future, as more sophisticated technologies emerge.

INTRODUCTION Recurrence is the driving factor for reduced long-term survival in patients following resected hepatocellular carcinoma (HCC). Extensive research efforts have been conducted to understand the molecular processes precipitating disease recurrence. Modern genomic techniques have identified two distinct mechanisms for recurrent HCC (RHCC): Intrahepatic metastasis (IM-HCC); and multicentric origin (MO-HCC). Medline, EMBASE and Cochrane library were methodically searched for primary research articles in English with the aim of appraising existing literature on the identification of clonal origin of RHCC and its potential clinical utility. AREAS COVERED Molecular and next-generation sequencing techniques, when applied to clonal origin identification, yield superior accuracy than traditional clinicopathological criteria. Despite various treatment modalities, no optimal therapy has yet been identified for treating clonally differentiated RHCC. Patients with MO-HCC appear to experience improved long-term survival following re-treatment compared to their IM-HCC counterparts (91.7% vs 22.9% 5-year survival, p

Hepatic epithelioid hemangio-endothelioma (EHE) is a rare, often misdiagnosed malignancy of vascular origin. We describe a case of a 36-year-old, who presented with a burning sensation in his chest on exercise and was believed to have bilobar intrahepatic cholangiocarcinoma. After receiving chemotherapy with partial response, the patient underwent staged resection modified ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) procedure – laparoscopic radiofrequency assisted ALPPS (RALPPS). Histological examination of the stage 1 specimen revealed EHE deposits in the left lobe of the liver. The patient proceeded to have stage 2 open right hepatectomy with concurring histology. 90-days follow-up CT scan showed almost complete resolution of EHE lesions. Low incidence, non-specific clinical and radiological characteristics all contribute to high EHE misdiagnosis rate. Histological analysis can be used for confirmation of the diagnosis; however, specialist staining is required, which is not routinely performed. Multiple treatments are available against EHE, but only liver resection and liver transplantation are potentially curative. ALPPS and its modifications (such as RALPPS) offer an alternative for conventional two-stage hepatectomy for patients with extensive bilobar EHE, who are at risk of developing post-hepatectomy liver failure or patients with anomalous hepatic vasculature anatomy, which makes PVE challenging.

Introduction Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality worldwide. Despite significant advancements, the diagnosis and management of HCC remain a challenge. This review aims at exploring artificial intelligence (AI) solutions applied to HCC. Method A review of the literature from Embase, MEDLINE and Cochrane Library was conducted to determine the role of AI in HCC, across three domains: detection, characterisation, and prediction. 56 relevant original research studies were identified and included in a qualitative synthesis. Results AI models can be implemented into detection of HCC, as they excel at analysis and integration of large datasets. Moreover, AI outclasses traditional statistical models at tumour characterisation based on radiological and pathological images. Predicting treatment outcomes and survival using AI can shape future HCC guidelines and support clinical decision making, especially treatment choice. AI in HCC has limitations, hindering its clinical adoption. Small sample size, single-centre data, non-transparent reporting, lack of external validation, and overfitting all results in low generalisability of findings. Conclusions AI has immense potential; however, interdisciplinary collaboration is needed to improve, validate, and implement it across all aspects of HCC. AI has a multifaceted role in HCC and its importance can increase in the future, as more sophisticated technologies emerge.

Background Staple line reinforcement during surgery may decrease morbidity or reduce the risk of staple line leaks and bleeding. There is debate regarding the benefit, safety, and best form of reinforcement. This case series characterizes the safety of a stapler with a pre-attached buttress in bariatric surgeries. Methods This prospective, multicenter, post-market study examined the use of stapler reloads with built in reinforcement material. The primary endpoint is the incidence of reported device-related adverse events up to 30 days after laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (SG) surgeries. Specific outcomes included bleeding (≥50 mL), leaks, and 30-day readmissions. Outcomes A total of 51 patients (19 RYGB, 32 SG) were assessed after exclusion criteria were applied. Intraoperatively, no leaks or bleeding related to the staple line occurred. Four patients (8% overall, 3 RYGB, 1 SG) experienced bleeding unrelated to the staple line and staple line intervention, in these cases, was not required. Four subjects (8%, all SG) required readmission and each were attributed as unrelated to the investigational device. No unanticipated device-related events were observed. Two adverse events (bleeding) occurred post-operatively that were attributed as possibly related to the device; both were endoscopically managed. Conclusions This study demonstrates that there were no serious safety concerns from the AEs observed related to reinforced reload use during or in the 30-day course after 51 common bariatric procedures in a multicenter setting. Trial registration The study was registered with clinicaltrials.gov (NCT02500537). Thoracic subjects from this study are described in a separate manuscript.

Pancreaticoduodenectomy is performed using an open technique (OPD) as the gold standard. However, an increase in those performed laparoscopically (LPD) and robotically (RPD) are now reported with the known benefits of minimally invasive surgery seen. RPD is safe to perform with comparable morbidity, mortality and equivocal histopathological outcomes to LPD and OPD in cancer cases. Operating time is longer for RPD compared with open PD. Length of stay, blood loss and transfusion requirement is significantly improved compared to OPD and less cases require conversion than LPD.

Three-dimensional (3D) visualization involves feature extraction and 3D reconstruction of CT images using a computer processing technology. It is a tool for displaying, describing, and interpreting 3D anatomy and morphological features of organs, thus providing intuitive, stereoscopic, and accurate methods for clinical decision-making. It has played an increasingly significant role in the diagnosis and management of liver diseases. Over the last decade, it has been proven safe and effective to use 3D simulation software for pre-hepatectomy assessment, virtual hepatectomy, and measurement of liver volumes in blood flow areas of the portal vein; meanwhile, the use of 3D models in combination with hydrodynamic analysis has become a novel non-invasive method for diagnosis and detection of portal hypertension. We herein describe the progress of research on 3D visualization, its workflow, current situation, challenges, opportunities, and its capacity to improve clinical decision-making, emphasizing its utility for patients with liver diseases. Current advances in modern imaging technologies have promised a further increase in diagnostic efficacy of liver diseases. For example, complex internal anatomy of the liver and detailed morphological features of liver lesions can be reflected from CT-based 3D models. A meta-analysis reported that the application of 3D visualization technology in the diagnosis and management of primary hepatocellular carcinoma has significant or extremely significant differences over the control group in terms of intraoperative blood loss, postoperative complications, recovery of postoperative liver function, operation time, hospitalization time, and tumor recurrence on short-term follow-up. However, the acquisition of high-quality CT images and the use of these images for 3D visualization processing lack a unified standard, quality control system, and homogeneity, which might hinder the evaluation of application efficacy in different clinical centers, causing enormous inconvenience to clinical practice and scientific research. Therefore, rigorous operating guidelines and quality control systems need to be established for 3D visualization of liver to develop it to become a mature technology. Herein, we provide recommendations for the research on diagnosis and management of 3D visualization in liver diseases to meet this urgent need in this research field.

Pancreatic cancer is detected late in the disease process and has an extremely poor prognosis. A blood-based biomarker that can enable early detection of disease, monitor response to treatment, and potentially allow for personalized treatment would be of great benefit. This review analyzes the literature regarding two potential biomarkers, circulating tumor cells (CTCs) and cell-free DNA (cfDNA), with regard to pancreatic ductal adenocarcinoma. The origin of CTCs and the methods of detection are discussed and a decade of research examining CTCs in pancreatic cancer is summarized, including both levels of CTCs and analyzing their molecular characteristics and how they may affect survival in both advanced and early disease and allow for treatment monitoring. The origin of cfDNA is discussed, and the literature over the past 15 years is summarized. This includes analyzing cfDNA for genetic mutations and methylation abnormalities, which have the potential to be used for the detection and prognosis of pancreatic ductal adenocarcinoma. However, the research certainly remains in the experimental stage, warranting future large trials in these areas.

Background Randomized controlled trials (RCTs) inform clinical practice and have provided the evidence base for introducing minimally invasive surgery (MIS) in surgical oncology. Crossover (unplanned intraoperative conversion of MIS to open surgery) may affect clinical outcomes and the effect size generated from RCTs with homogenization of randomized groups. Objectives Our aims were to identify modifiable factors associated with crossover and assess the impact of crossover on clinical endpoints. Methods A systematic review was performed to identify all RCTs comparing MIS with open surgery for gastrointestinal cancer (1990–2017). Meta-regression analysis was performed to analyze factors associated with crossover and the influence of crossover on endpoints, including 30-day mortality, anastomotic leak rate, and early complications. Results Forty RCTs were included, reporting on 11,625 patients from 320 centers. Crossover was shown to affect one in eight patients (mean 12.6%, range 0–45%) and increased with American Society of Anesthesiologists score (β = + 0.895; p = 0.050). Pretrial surgeon volume (β = − 2.344; p = 0.037), composite RCT quality score (β = − 7.594; p = 0.014), and site of tumor (β = − 12.031; p = 0.021, favoring lower over upper gastrointestinal tumors) showed an inverse relationship with crossover. Importantly, multivariate weighted linear regression revealed a statistically significant positive correlation between crossover and 30-day mortality (β = + 0.125; p = 0.033), anastomotic leak rate (β = + 0.550; p = 0.004), and early complications (β = + 1.255; p = 0.001), based on intention-to-treat analysis. Conclusions Crossover in trials was associated with an increase in 30-day mortality, anastomotic leak rate, and early complications within the MIS group based on intention-to-treat analysis, although our analysis did not assess causation. Credentialing surgeons by procedural volume and excluding high comorbidity patients from initial trials are important in minimizing crossover and optimizing RCT validity. Electronic supplementary material The online version of this article (10.1245/s10434-017-6210-y) contains supplementary material, which is available to authorized users.

Plasmonic gold (Au) nanotriangular arrays, functionalized with a near infrared (NIR) fluorophore-conjugated immunoassay to Carbohydrate Antigen 19-9 (CA 19-9), a pancreatic cancer biomarker, produce optically tunable substrates with two orders of magnitude fluorescence enhancement. Through nanoscale morphological control, the sensitivities of the plasmonic nanotriangular arrays are controllable, paving the way of such optical platforms for multiplexing. Here, we report a limit of detection (LOD) of 7.7 × 10−7 U.mL−1 for CA 19–9 by using such tunable Au nanotriangular arrays, a great improvement compared to commercially available CA 19–9 immunoassays. The linear dynamic range was from 1 × 10−6 U.mL−1 to 1 U.mL−1, i.e. up to six orders of magnitude. Moreover, high specificity was demonstrated, together with successful validation in serum samples. Their superior tunable sensitivity, along with efforts to combine CA 19–9 with other biomarkers for improved accuracy, open up the possibility for multiplexed NIR-fluorescence enhancement microarrays, for early cancer diagnosis and therapeutic monitoring.

BACKGROUND: Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less-specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay. METHODS: Euadrenal patients undergoing elective surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical day, induction and 1 hour, 2 hour, 4 hour and 8 hour after. Subsequent samples were taken daily at 8 am until postoperative day 5 or hospital discharge. Total cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding globulin (CBG) using a radioimmunoassay. Surgical severity was classified by POSSUM operative severity score. RESULTS: Ninety-three patients underwent surgery: Major/Major+ (n = 37), Moderate (n = 33) and Minor (n = 23). Peak cortisol positively correlated to severity: Major/Major+ median 680 [range 375-1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis test, P = .0031). CBG fell by 23%; the magnitude of the drop positively correlated to severity. CONCLUSIONS: The range in baseline and peak cortisol response to surgery is wide, and peak cortisol levels are lower than previously appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays might explain our observed lower peak cortisols. The criteria for the dynamic testing of cortisol response may need to be reduced to take account of these factors. Our data also support a lower-dose, stratified approach to dosing of steroid replacement in hypoadrenal patients, to minimize the deleterious effects of over-replacement.

Background Intrahepatic recurrence of hepatocellular carcinoma (HCC) following resection is common. However, no current consensus guidelines exist to inform management decisions in these patients. Systematic review and meta-analysis of survival following different treatment modalities may allow improved treatment selection. This review aimed to identify the optimum treatment strategies for HCC recurrence. Methods A systematic review, up to September 2016, was conducted in accordance with MOOSE guidelines. The primary outcome was the hazard ratio for overall survival of different treatment modalities. Meta-analysis of different treatment modalities was carried out using a random-effects model, with further assessment of additional prognostic factors for survival. Results Nineteen cohort studies (2764 patients) were included in final data analysis. The median 5-year survival rates after repeat hepatectomy (525 patients), ablation (658) and transarterial chemoembolization (TACE) (855) were 35·2, 48·3 and 15·5 per cent respectively. Pooled analysis of ten studies demonstrated no significant difference between overall survival after ablation versus repeat hepatectomy (hazard ratio 1·03, 95 per cent c.i. 0·68 to 1·55; P = 0·897). Pooled analysis of seven studies comparing TACE with repeat hepatectomy showed no statistically significant difference in survival (hazard ratio 1·61, 0·99 to 2·63; P = 0·056). Conclusion Based on these limited data, there does not appear to be a significant difference in survival between patients undergoing repeat hepatectomy or ablation for recurrent HCC. The results also identify important negative prognostic factors (short disease-free interval, multiple hepatic metastases and large hepatic metastases), which may influence choice of treatment.

Controversy related to endoscopic or surgical management of pain in patients with chronic pancreatitis remains. Despite improvement in endoscopic treatments, surgery remains the best option for pain management in these patients.

Resume Objectifs L’extension de l’ evidence-based medicine a la chirurgie est confrontee a divers obstacles. Nous tentons de les identifier afin d’evaluer la legitimite de l’ evidence-based surgery (EBS). Patients et methode Etude qualitative menee sur une periode d’un mois dans un centre academique de chirurgie hepatobiliaire a l’aide de questionnaires remis aux patients, aux chirurgiens et des informations medicales necessaires. Resultats Treize patients accepterent de participer. Cent pour cent des patients ont beneficie d’un traitement repondant a la definition de l’EBS, dont 38,5 % justifies par un essai controle randomise (ECR), et 76,9 % justifies par une etude retrospective ou plus. De plus, 23,1 % de divergence ont ete observees entre le sentiment d’avoir transmis l’information scientifique par le chirurgien et celui de l’avoir recue par le patient. Conclusion L’EBS est un progres necessaire dont l’application est limitee par les outils d’evaluation inadaptes a la chirurgie. L’aspect situationnel semble denature. Il convient donc de ne pas accorder une valeur superieure a celle d’une analyse retrospective a l’EBS.

Injuries occurring during laparoscopic bile duct exploration in the course of laparoscopic cholecystectomy may represent threatening complications and lead to inappropriate management. We present a case of patient with biliary colic who underwent laparoscopic cholecystectomy. During the procedure, a common bile duct injury occurred, compelling conversion to open approach, and the patient was treated using a manually inserted biliary stent. She was referred with severe right upper quadrant pain six weeks after the surgery. Investigation with endoscopic retrograde cholangiopancreatography showed a malpositioned biliary stent with completely extra-biliary trajectory. This is thought to be the first description of a malpositioned common bile duct stent through the common biliary duct as a complication of the commonly performed surgical procedure of bile duct exploration.

Although a recognized condition, growing teratoma syndrome (GTS) has no guidelines for management, and patients diagnosed with the condition are managed empirically by the most appropriate teams. We report a case of GTS in a 33-year-old patient who was initially treated with unilateral salpingo-oophorectomy and subsequent chemotherapy for a germ cell ovarian tumor. GTS was subsequently diagnosed with massive pelvic and upper abdominal masses as well as lung tumors. We also conducted a literature review on cases of GTS presenting with large tumors. Based on this, we suggest a management plan to guide the care of women with GTS. The condition is best managed in a multidisciplinary team involving the relevant surgeons, including gynecologist, abdominal and thoracic surgeons., Lay abstract Growing teratoma syndrome (GTS) is a rare but recognized condition presenting with an abdominal mass in a woman with history of malignant ovarian tumor treated with chemotherapy. There are no established guidelines for the management of women diagnosed with GTS. We report a case of GTS in a 33-year-old patient requiring major abdominal and thoracic surgery. We also review the literature on previously published cases of GTS and propose a management plan to guide clinicians looking after women with GTS. Collaboration between different surgeons including gynecologists, abdominal and thoracic surgeons as well as radiologists and oncologist should be sought.

Pancreaticoduodenectomy is performed using an open technique (OPD) as the gold standard. An increase in those performed laparoscopically (LPD) and robotically (RPD) are now reported. We compared the short-term outcomes of RPD cases with LPD and OPD.A retrospective review of a prospectively collected database was undertaken of our first consecutive RPD, our first LPD and consecutive OPD cases. Those requiring venous and/or arterial resection were excluded.RPD (n = 25) had longer median operating times (461 (IQR 358-564) mins) than LPD (n = 41) (330 (IQR 262.5-397.5) mins) and OPD (n = 37) (330 (IQR 257-403) mins, p 0.0001). Estimated blood loss and transfusion requirement was less after RPD and LPD compared to OPD (p = 0.012 and p 0.0001 respectively). No RPD cases required conversion to open operation compared to 24.4% of LPD. Morbidity was comparable with a Clavien Dindo score ≥3 in 20.00%, 24.39% and 18.92% for RPD, LPD and OPD respectively (p = 0.83). Post-operative pancreatic fistula rates were seen in 16.00%, 29.27% and 21.62% of our RPD, LPD and OPD cohorts respectively (p = 0.81). 90-day mortality was seen in 0.97% of the total cohort. Length of hospital stay (LOS) was shorter for RPD compared to both LPD (p = 0.030) and OPD (p = 0.002).RPD is safe to perform with comparable outcomes to LPD and OPD. Further evidence is provided that a randomised controlled trial for PD techniques is required.

Background Minimally invasive pancreaticoduodenectomy (MIPD) is a demanding surgical procedure, thus explaining its slow expansion and limited popularity amongst Hepato-Pancreatico-Biliary (HPB) surgeons. However, three main advantages of robotic assisted pancreaticoduodenectomy (PD) including improved dexterity, 3D vision less surgical fatigue, may overcome some of the hurdles and ultimately lead to a wider adoption. This systematic review and network meta-analysis aims to evaluate the current literature on open and MIPD. Methods A systematic literature search was conducted for studies reporting robotic, laparoscopic and open surgery for PD. Network meta-analysis of intraoperative (operating time, blood loss, transfusion rate), postoperative (overall and major complications, pancreatic fistula, delayed gastric emptying, length of hospital stay) and oncological outcomes (R0 resection, lymphadenectomy) were performed. Results Sixty-one studies including 62,529 patients were included in the network meta-analysis, of which 3% (n = 2131) were totally robotic (TR) and 10% (n = 6514) were totally laparoscopic (TL). There were no significant differences between surgical techniques for major complications, overall and grade B/C fistula, biliary leak, mortality and R0 resections. Transfusion rates were significantly lower in TR compared to TL and open. Operative time for TR was longer compared with open and TL. Both TL and TR were associated with significantly lower rates of wound infections, pulmonary complications, shorter length of stay and higher lymph nodes examined when compared to open. TR was associated with significantly lower conversion rates than TL. Conclusion In summary, this network meta-analysis highlights the variability in techniques within MIPD and compares other variations to the conventional open PD. Current evidence appears to demonstrate MIPD, both laparoscopic and robotic techniques are associated with improved rates of surgical site infections, pulmonary complications, and a shorter hospital stay, with no compromise in oncological outcomes for cancer resections.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with an extremely poor prognosis (5-year survival rate ~ 6%). Identifying biomarkers able to prognosticate and stratify patients will all...

Robotic pancreaticoduodenectomy (RPD) offers theoretical advantages to conventional laparoscopic surgery including improved instrument dexterity, 3D visualization and better ergonomics. This review aimed to determine if these theoretical advantages translate into improved patient outcomes comparing patients having either robotic pancreaticoduodenectomy or laparoscopic (LPD) equivalent.A systematic literature search was conducted for studies reporting minimally invasive surgery for pancreaticoduodenectomy either robotic assisted or totally laparoscopic. Meta-analysis of intra-operative (blood loss, operating times, conversion and R0 resections) and postoperative outcomes (overall complications, pancreatic fistula, length of hospital stay) was performed using a random effects model.This review identified 44 studies, of which six were non-randomised comparative studies including 3462 patients (1025 robotic and 2437 laparoscopic). Intraoperatively, RPD was associated with significantly lower conversion rates (OR 0.45, p 0.001) and transfusion rates (OR: 0.60, p = 0.002) compared to LPD. However, no significant difference in blood loss (mean: 220 vs 287 mL, p = 0.1), operating time (mean: 405 vs 418 min, p = 0.3) was noted. Postoperatively RPD was associated with a shorter hospital stay (mean: 12 vs 11 days, p 0.001) but no significant difference was noted in postoperative complications, incidence of pancreatic fistulae and R0 resection rates.RPD appears to offer some advantages compared to conventional laparoscopic surgery, although both approaches appear to offer equivalent clinical outcomes. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomised trial comparing both techniques is needed.

Purpose To evaluate the technical feasibility and therapeutic outcomes of percutaneous US/MRI fusion-guided radiofrequency ablation (RFA) of recurrent subcentimeter-sized hepatocellular carcinomas (HCCs). Materials and Methods For this retrospective study, between January 2012 and December 2014 a total of 194 planning US examinations were performed in 186 patients (159 men and 27 women; mean age, 61.1 years ± 10.0 [standard deviation]) for newly developed subcentimeter recurrent HCCs. These recurrent HCCs were defined as hypervascular nodules (5.5 mm and10 mm) with typical MRI findings of HCC. The study assessed how often US/MRI fusion-guided percutaneous RFA was deemed technically feasible at planning US examination (the feasibility rate) and the therapeutic outcomes after RFA, including the rates of technical success, technique efficacy, local tumor progression (LTP), and major complications. Cumulative LTP rates were estimated with the Kaplan-Meier method. Results The feasibility rate of percutaneous RFA at planning US examination was 65.7% (138 of 210 HCCs). The most common reason for RFA infeasibility was that an index tumor was inconspicuous at US. Among 138 subcentimeter HCCs feasible for RFA, 125 lesions underwent percutaneous RFA. The rates of both technical success and technique efficacy were 98.4% (123 of 125). The cumulative LTP rates at 1, 2, and 3 years were 3.6%, 5.4%, and 7.4%, respectively. The major complication rate was 2.5% (three of 119). Conclusion Percutaneous US/MRI fusion-guided radiofrequency ablation (RFA) was feasible in approximately two-thirds of subcentimeter recurrent hepatocellular carcinomas (HCCs). Percutaneous US/MRI fusion-guided RFA is a safe and effective treatment modality for patients with subcentimeter recurrent HCCs.

In order to induce liver hypertrophy to enable liver resection in patients with a small future liver remnant (FLR), various methods have been proposed in addition to portal vein embolisation (PVE). Most recently, the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique has gained significant international interest. This technique is limited by the high morbidity associated with an in situ liver splitting and the patient undergoing two open operations. We present the case of a variant ALPPS technique performed entirely laparoscopically with no major morbidity or mortality. An increased liver volume of 57.9% was seen after 14 days. This technique is feasible to perform and compares favourably to other ALPPS methods whilst gaining the advantages of laparoscopic surgery.

The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) remains dismal despite current chemotherapeutic agents and inhibitors of molecular targets. As the incidence of PDAC constantly increases, more effective multidrug approaches must be made. Here, we report a novel method of delivering antitumorigenic therapy in PDAC by upregulating the transcriptional factor CCAAT/enhancer-binding protein-α (C/EBPα), recognized for its antiproliferative effects. Small activating RNA (saRNA) duplexes designed to increase C/EBPα expression were linked onto PDAC-specific 2'-Fluropyrimidine RNA aptamers (2'F-RNA) - P19 and P1 for construction of a cell type-specific delivery vehicle. Both P19- and P1-C/EBPα-saRNA conjugates increased expression of C/EBPα and significantly suppressed cell proliferation. Tail vein injection of the saRNA/aptamer conjugates in PANC-1 and in gemcitabine-resistant AsPC-1 mouse-xenografts led to reduced tumor size with no observed toxicity. To exploit the specificity of the P19/P1 aptamers for PDAC cells, we also assessed if conjugation with Cy3 would allow it to be used as a diagnostic tool on archival human pancreatic duodenectomy tissue sections. Scoring pattern from 72 patients suggested a positive correlation between high fluorescent signal in the high mortality patient groups. We propose a novel aptamer-based strategy for delivery of targeted molecular therapy in advanced PDAC where current modalities fail.

© 2016 Springer-Verlag Berlin HeidelbergObjective: To assess surgical morbidity and mortality of maximal effort cytoreductive surgery for disseminated epithelial ovarian cancer (EOC) in a UK tertiary center. Methods/materials: A monocentric prospective analysis of surgical morbidity and mortality was performed for all consecutive EOC patients who underwent extensive cytoreductive surgery between 01/2013 and 12/2014. Surgical complexity was assessed by the Mayo clinic surgical complexity score (SCS). Only patients with high SCS ≥5 were included in the analysis. Results: We evaluated 118 stage IIIC/IV patients, with a median age of 63 years (range 19–91); 47.5 % had ascites and 29 % a pleural effusion. Median duration of surgery was 247 min (range 100–540 min). Median surgical complexity score was 10 (range 5–15) consisting of bowel resection (71 %), stoma formation (13.6 %), diaphragmatic stripping/resection (67 %), liver/liver capsule resection (39 %), splenectomy (20 %), resection stomach/lesser sac (26.3 %), pleurectomy (17 %), coeliac trunk/subdiaphragmatic lymphadenectomy (8 %). Total macroscopic tumor clearance rate was 89 %. Major surgical complication rate was 18.6 % (n = 22), with a 28-day and 3-month mortality of 1.7 and 3.4 %, respectively. The anastomotic leak rate was 0.8 %; fistula/bowel perforation 3.4 %; thromboembolism 3.4 % and reoperation 4.2 %. Median intensive care unit and hospital stay were 1.7 (range 0–104) and 8 days (range 4–118), respectively. Four patients (3.3 %) failed to receive chemotherapy within the first 8 postoperative weeks. Conclusions: Maximal effort cytoreductive surgery for EOC is feasible within a UK setting with acceptable morbidity, low intestinal stoma rates and without clinically relevant delays to postoperative chemotherapy. Careful patient selection, and coordinated multidisciplinary effort appear to be the key for good outcome. Future evaluations should include quality of life analyses.

Paragangliomas (or ‘extra-adrenal phaeochromocytomas’) are rare tumours arising from neural crest cells. They occur most commonly in the abdomen along the paraspinal sympathetic ganglion. The malignancy rate can be up to 35% and surgical resection is the recommended treatment. While laparoscopic excision of phaeochromocytomas is now well established, the overall number of cases of paragangliomas reported is much smaller owing to their rarity (even more so for giant paragangliomas of ≥8cm) and controversy remains over the completeness of excision. Furthermore, the risk of malignancy and recurrence rate are higher in paragangliomas, with incomplete excision giving rise to recurrent endocrinopathy and carcinomatosis. We report the case of a 26-year-old woman who underwent laparoscopic excision of an 8.2cm functioning paraganglioma. Complete resection of the tumour was achieved and the patient’s symptoms resolved. Twelve months later, she remains well with no evidence of recurrence.

4505 Background: Patients with borderline resectable pancreatic cancer have poor survival and low resection rates. Neoadjuvant therapy may improve the outcome for these patients. The aim of this trial was to determine the feasibility and efficacy of a comparison of immediate surgery versus neoadjuvant GEMCAP or FOLFIRINOX or CRT. Methods: Eligible patients with NCCN defined borderline resectable (following central review of the baseline CT scan) and biopsy proven pancreatic cancer were randomised (stratified by centre) to receive immediate surgery, or neoadjuvant therapy of either 2 cycles of GEMCAP, or 4 cycles of FOLFIRINOX or 50.4Gy capecitabine-based CRT in 28 daily fractions over 5 ½ weeks. Patients were restaged at 4-6 weeks and underwent surgical exploration if still borderline resectable. Resected patients received adjuvant therapy. Follow up was 12 months. There was quality assurance of surgery and CRT. Primary endpoints were recruitment rate and resection rate (R1/R0). Secondary endpoints included overall survival and toxicity. A target of 90 patients was set to determine feasibility and resection rates. Rates will be presented as point estimates and survival compared across treatment arms using a log-rank test. Analyses will be on an ITT basis. Results: Between August 2014 and December 2018, 90 patients were randomised with 88 included in the full analysis set (32 immediate surgery, 20 GEMCAP, 20 FOLFIRINOX, 16 CRT). Median age was 63 years, 44% were men. WHO performance status was 0 and 1 in 45% and 55% respectively. Median CA19-9 was 603 kU/L at baseline. 44 (79%) patients completed neoadjuvant therapy. Recruitment rate was 21 patients per year. Resection rate was 62% for immediate surgery and 55% for neoadjuvant therapy (p=0.668). R0 resection rate on resected patients was 15% and 23% respectively (p=0.721). One year survival rate was 40% [95% CI, 26% – 62%] for immediate surgery and 77% [95%CI, 66% - 89%] for neoadjuvant therapy. Log-rank analysis showed an HR=0.27 [95% CI, 0.13 – 0.55]; χ2 (1) = 14.91, P

// Tamara M.H. Gall 1 , Gareth Gerrard 2, 3 , Adam E. Frampton 1 , Leandro Castellano 1 , Raida Ahmad 4 , Nagy Habib 1 , Duncan Spalding 1 , Madhava Pai 1 , Letizia Foroni 4 and Long R. Jiao 1 1 Department of Surgery and Cancer, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom 2 Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom 3 Current address: Sarah Cannon Molecular Diagnostics, HCA Healthcare UK, London WC1E 6JA, United Kingdom 4 Department of Histopathology, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom Correspondence to: Long R. Jiao, email: l.jiao@imperial.ac.uk Keywords: PDAC; ion torrent; next-generation sequencing; nanostring; cell-free DNA Received: December 02, 2018 Accepted: December 12, 2018 Published: January 22, 2019 ABSTRACT Objective: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumour associated with poor 5-year survival. We aimed to determine factors which differentiate short and long-term survivors and identify a prognostic biomarker. Methods: Over a ten-year period, patients with resected PDAC who developed disease recurrence within 12 months (Group I) and those who had no disease recurrence for 24 months (Group II) were identified. Clinicopathological data was analysed. Ion Torrent high-throughput sequencing on DNA extracted from FFPE tumour samples was used to identify mutations. Additionally, peripheral blood samples were analysed for variants in cell-free DNA, circulating tumour cells (CTCs), and microRNAs. Results: Multivariable analysis of clinicopathological factors showed that a positive medial resection margin was significantly associated with short disease-free survival ( p = 0.007). Group I patients ( n = 21) had a higher frequency of the KRAS mutant mean variant allele (16.93% ± 11.04) compared to those in Group II ( n = 13; 7.55% ± 5.76, p = 0.0078). Group I patients also trended towards having a KRAS c.35G>A p.Gly12Asp mutation in addition to variants in other genes, such as TP53 , CDKN2A , and SMAD4 . Mutational status of cell-free DNA, and number of CTCs, was not found to be useful in this study. A circulating miRNA (hsa-miR-548ah-5p) was found to be significantly differentially expressed. Conclusions: Medial resection margin status and the frequency of KRAS mutation in the tumour tissue are independent prognostic indicators for resectable PDAC. Circulating miRNA hsa-miR-548ah-5p has the potential to be used as a prognostic biomarker.

Liver cancer is the sixth most common cancer and third most common cause of cancer-related mortality. Presently, indications for liver resections for liver cancers are widening, but the response is varied owing to the multitude of factors including excess intraoperative bleeding, increased blood transfusion requirement, post-hepatectomy liver failure and morbidity. The advent of the radiofrequency energy-based bipolar device Habib™-4X has made bloodless hepatic resection possible. The radiofrequency-generated coagulative necrosis on normal liver parenchyma provides a firm underpinning for the bloodless liver resection. This meta-analysis was undertaken to analyse the available data on the clinical effectiveness or outcomes of liver resection with Habib™-4X in comparison to the clamp-crush technique. The RF-assisted device Habib™-4X is considered a safe and feasible modality for liver resection compared to the clamp-crush technique owing to the multitude of benefits and mounting clinical evidence supporting its role as a superior liver resection device. The most intriguing advantage of the RF-device is its ability to induce systemic and local immunomodulatory changes that further expand the boundaries of survival outcomes following liver resection.

Objective Evaluate postoperative hepatic-function in patients with advanced ovarian cancer (OC) who underwent extensive right upper-quadrant (RUQ) cytoreduction in primary, relapsed or interval settings. Methods We retrospectively reviewed all patients with OC who underwent liver resection, mobilization and/or diaphragmatic-stripping between 01/2013 and 12/2016. Postoperative liver enzyme function (LFTs), assessed by alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (Bil), was correlated with postoperative complications. Results 132 patients were identified. 81 patients (61%) underwent upfront, 25(19%) interval and 26(20%) secondary cytoreduction. The surgical procedures were right diaphragmatic peritoneal stripping (81/132;61%), full-thickness resection (42/132;32%), liver-capsule resection (85/132;64%), porta-hepatis tumor resection (11/132;8%) and partial hepatectomy (5/132;4%). 74%(98/132) of patients increased their LFTs postoperatively with a peak at 24-hours. Highest ALT median was 1.7-fold of upper normal limit (UNL), with the highest ALT value rising up to 28-fold UNL on the 1st postoperative day (PoD)(range 6–1792 IU/L). Median value of highest ALP was within normal, with the highest ALP value rising up to 4-fold UNL on PoD 5(range 22–512 IU/L). Median value of highest Bilirubin level was also within normal, with highest Bilirubin level rising up to 6-fold UNL on PoD 5(range: 2–120 μmol/L). Mean LFT-normalization time was 7 days (range: 3–14 days). No significant morbidity was directly linked to LFT deterioration, apart from one case (0.8%) of fatal fulminant hepatic-failure. Conclusion RUQ-cytoreduction is almost always associated with a transient LFT-increase, with no significant clinical implications and spontaneous normalization within the first postoperative week. Due to the existing risk of fulminant liver failure, albeit rare and difficult to predict, postoperatively elevated LFTs should be monitored, until normalization. Large prospective studies are required to assess the predictive value of LFTs and other risk factors for postoperative hepatic failure in patients with OC undergoing extensive RUQ-cytoreduction.

To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis.A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function).Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure. In total, 323 patients underwent surgical procedures for chronic pancreatitis, including Beger (n = 138) and Frey (n = 99), minimal Frey (n = 32), modified Frey (n = 25) and Berne's modification (n = 29). Two studies comparing the Beger and Frey procedure were entered into a meta-analysis and showed no difference in post-operative pain (RD = -0.06; CI -0.21 to 0.09), mortality (RD = 0.01; CI -0.03 to 0.05), morbidity (RD = 0.12; CI -0.00 to 0.24), exocrine insufficiency (RD = 0.04; CI -0.10 to 0.18) and endocrine insufficiency (RD = -0.14 CI -0.28 to 0.01).All procedures are equally effective for the management of pain for chronic pancreatitis. The choice of procedure should be determined by other factors including the presence of secondary complications of pancreatitis and intra-operative findings. Registration number CRD42015019275. Centre for Reviews and Dissemination, University of York, 2009.

Reports have described the prognostic relevance of microRNAs (miRNAs) in patients treated for pancreatic ductal adenocarcinoma (PDAC). However, many of these include small numbers of patients. To increase statistical power and improve translation, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of miRNAs on overall survival (OS) and disease-free survival (DFS) in PDAC.Eligible studies were identified and quality assessed using multiple search strategies (last search December 2014). Data were collected from studies correlating clinical outcomes with dysregulated tumoural or blood miRNAs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.Twenty studies involving 1525 patients treated for PDAC were included. After correcting for publication bias, OS was significantly shortened in patients with high tumoural miR-21 (adjusted HR = 2.48; 1.96-3.14). This result persisted when only studies adjusting for adjuvant chemotherapy were combined (adjusted HR = 2.72; 1.91-3.89). High miR-21 also predicted reduced DFS (adjusted HR = 3.08; 1.78-5.33). Similarly, we found significant adjusted HRs for poor OS for high miR-155, high miR-203, and low miR-34a; and unadjusted HRs for high miR-222 and high miR-10b. The small number of studies, limited number of miRNAs and paucity of multivariate analyses are the limitations of our study.This is the first rigorous pooled analysis assessing miRNAs as prognostic biomarkers in PDAC. Tumoural miR-21 overexpression emerged as an important predictor of poor prognosis after PDAC resection independent of other clinicopathologic factors, including adjuvant chemotherapy use.

Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancers where prognosis has not improved over the past few decades. However, there have been several advances in our understanding of the disease leading to earlier detection and targeted therapeutic treatment. It is now understood that specific somatic and germline mutations lead to the development of the disease, and the risk factors associated with this are clearer. Further, several precursor lesions have been identified which, with early detection and surveillance, allows treatment before the development of carcinoma. PDAC can now be diagnosed with a high sensitivity and specificity following advances in radiology, and treatment can be commenced at an earlier stage of the disease. With continued research we are hopeful that the next decade will see an improved survival rate for all patients with pancreatic cancer.

Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of global liver disease that is associated with the rising prevalence of obesity worldwide. There is now increasing clinical and mechanistic evidence reporting on the metabolic and weight loss effects of bariatric surgery on improving NAFLD in obese patients. The aim of this paper was to quantify the effects of bariatric surgery on NAFLD by appraising the modulation between pre- and post-operative liver enzyme levels (as markers of liver injury) and liver histology. A systematic review of studies reporting pre-operative and post-operative liver enzymes or liver histology was done in obese patients with NAFLD undergoing bariatric surgery. Data were meta-analysed using random-effects modelling. Subgroup analysis, quality scoring and risk of bias were assessed. Bariatric surgery is associated with a significant reduction in the weighted incidence of a number of histological features of NAFLD including steatosis (50.2 and 95 %CI of 35.5–65.0), fibrosis (11.9 and 95 %CI of 7.4–16.3 %), hepatocyte ballooning (67.7 and 95 %CI 56.9–78.5) and lobular inflammation (50.7 and 95 %CI 26.6–74.8 %). Surgery is also associated with a reduction in liver enzyme levels, with statistically significant reductions in ALT (11.36 u/l, 95 %CI 8.36–14.39), AST (3.91 u/l, 95 %CI 2.23–5.59), ALP (10.55 u/l, 95 %CI 4.40–16.70) and gamma-GT (18.39 u/l, 95 %CI 12.62–24.16). Heterogeneity in results was high. Bariatric surgery is associated with a significant improvement in both histological and biochemical markers of NAFLD. Future studies must focus on higher levels of evidence to better identify the benefits of bariatric surgery on liver disease in order to enhance future treatment strategies in the management of NAFLD.

TGF-β/Activin induces epithelial-to-mesenchymal transition and stemness in pancreatic ductal adenocarcinoma (PDAC). However, the microRNAs (miRNAs) regulated during this response have remained yet undetermined. Here, we show that TGF-β transcriptionally induces MIR100HG lncRNA, containing miR-100, miR-125b and let-7a in its intron, via SMAD2/3. Interestingly, we find that although the pro-tumourigenic miR-100 and miR-125b accordingly increase, the amount of anti-tumourigenic let-7a is unchanged, as TGF-β also induces LIN28B inhibiting its maturation. Notably, we demonstrate that inactivation of miR-125b or miR-100 affects the TGF-β-mediated response indicating that these miRNAs are important TGF-β effectors. We integrate AGO2-RIP-seq with RNA-seq to identify the global regulation exerted by these miRNAs in PDAC cells. Transcripts targeted by miR-125b and miR-100 significantly overlap and mainly inhibit p53 and cell–cell junctions’ pathways. Together, we uncover that TGF-β induces an lncRNA, whose encoded miRNAs, miR-100, let-7a and miR-125b play opposing roles in controlling PDAC tumourigenesis., In pancreatic ductal adenocarcinoma, TGF-β/Activin induce epithelial-to-mesenchymal transition (EMT) and stemness. Here, the authors show that TGF-β induces pro-tumourigenic miR-100 and miR-125b, but blocks anti-tumourigenic let-7a maturation via LIN28B, regulating pathways to promote stemness, EMT and tumourigenesis.

// Adam E. Frampton 1, 2, * , Mireia Mato Prado 2, * , Elena Lopez-Jimenez 2 , Ana Belen Fajardo-Puerta 1 , Zaynab A.R. Jawad 1 , Phillip Lawton 2 , Elisa Giovannetti 3, 4 , Nagy A. Habib 1 , Leandro Castellano 2, 5 , Justin Stebbing 2, # , Jonathan Krell 2, # and Long R. Jiao 1, # 1 HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, London, UK 2 Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK 3 Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands 4 Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy 5 University of Sussex, School of Life Sciences, John Maynard Smith Building, Falmer, Brighton, UK * These authors share co-first authorship # These authors share co-senior authorship Correspondence to: Long R. Jiao, email: l.jiao@imperial.ac.uk Keywords: Glypican-1 (GPC1); pancreatic ductal adenocarcinoma (PDAC); exosome; biomarker; tumor size Received: October 28, 2017 Accepted: March 02, 2018 Published: April 10, 2018 ABSTRACT Background: Glypican-1 (GPC1) is expressed in pancreatic ductal adenocarcinoma (PDAC) cells and adjacent stromal fibroblasts. Recently, GPC1 circulating exosomes (crExos) have been shown to be able to detect early stages of PDAC. In this study, we investigated the usefulness of crExos GPC1 as a biomarker for PDAC. Methods: Plasma was obtained from patients with benign pancreatic disease ( n = 16) and PDAC ( n = 27) prior to pancreatectomy, and crExos were isolated by ultra-centrifugation. Protein was extracted from surgical specimens (adjacent normal pancreas, n = 13; and PDAC, n = 17). GPC1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: There was no significant difference in GPC1 levels between normal pancreas and PDAC tissues. This was also true when comparing matched pairs. However, GPC1 levels were enriched in PDAC crExos ( n = 11), compared to the source tumors ( n = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; P 4 cm; P = 0.012). Conclusions: High GPC1 crExos may be able to determine PDAC tumor size and disease burden. However, further efforts are needed to elucidate its role as a diagnostic and/or prognostic biomarker using larger cohorts of PDAC patients.

Background Radiofrequency (RF)-assisted liver resection allows non-anatomical liver resection with reduced blood loss and offers the opportunity for a combination of resection and ablation. However, there are still concerns with regard to postoperative complications related to this technique. In the present study, we discuss the technical aspects of RF-assisted liver resections and analyse the rate of perioperative complications, focusing on post-hepatectomy liver failure (PLF), bile leak and abscess, and mortality. Methods Between 2001 and 2015, 857 consecutive open and laparoscopic elective RF-assisted liver resections for benign and malignant liver tumours were reviewed retrospectively to assess perioperative outcomes. Results Median intraoperative blood loss was 130 mL, with 9.8% of patients requiring blood transfusion. Intra-abdominal collections requiring percutaneous drainage developed in 8.7% of all patients, while bile leak at resection margin developed in 2.8% of the cases. Major liver resection was performed in 34% of patients and the incidence of PLF was 1.5% with one directly related mortality (0.1%). Conclusion RF-assisted liver resection has evolved into a feasible and safe technique of liver resection with an acceptable incidence of perioperative morbidity and a low incidence of PLF and related mortality.