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Background Machine learning (ML) is an application of artificial intelligence (AI) which enables automatic learning from large datasets. The advances in this computer science coupled with the increase in minimally invasive surgery (MIS) and availability of surgical videos, has resulted in ML algorithms designed to analyse intraoperative videos. This technology aims to improve surgical training and surgical assessment resulting in improved surgical safety. Methods A literature search of MEDLINE and EMBASE was conducted. The search terms included the following, individually or in combination: ‘machine learning, ‘video analysis’, ‘computer vision’, ‘neural networks’ and ‘surgery’. Results Relevant articles were scanned and included in the discussion. These include research developing ML algorithms for surgical phase recognition, instrument recognition, gestures recognition, and anatomical landmark recognition. The implications for the future of surgical training are discussed. Conclusions The next decade is likely to see a huge increase in MIS, particularly robotic surgery, and ML video analytics of these operations. This is likely to enhance surgical training and reduce surgical errors. However, there is a necessity for much bigger datasets for all operative procedures to allow increasing accuracy of the ML algorithms.

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.

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

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.

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.

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.

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.

A best evidence topic was written according to a structured protocol. The question addressed was whether the prophylactic administration of somatostatin or somatostatin analogues in patients undergoing pancreaticoduodenectomy (Whipple's procedure) is beneficial in terms of improved surgical outcomes, reduced morbidity or reduced mortality. A total of 118 papers were found using the reported searches of which 5 represented the best evidence (1 meta-analysis, 1 systematic review and 3 randomized control trials). The authors, date, journal, study type, population, main outcome measures and results were tabulated. There is evidence that the perioperative administration of somatostatin or somatostatin analogues reduces biochemical incidence of pancreatic fistula but, it is still unclear if there is a beneficial effect in the incidence of clinically significant pancreatic fistula. Further adequately powered trials with low risk of bias are necessary. From the available data, somatostatin or somatostatin analogues have no effect on mortality post Whipple's. Interestingly, there are only limited data available on the cost-benefit and financial constraints imposed by this treatment, an issue that has only been addressed in a few studies.

Objectives To evaluate the effectiveness of PET in differentiating malignant from benign pancreatic cystic tumors. Methods Between 2009 and 2010, all patients with pancreatic cystic tumors who had PET, triple phase contrast computed tomography (CT) and endoscopic ultrasound (EUS) were reviewed. Clinicopathological characteristics and final histology were correlated with preoperative PET, CT and EUS to assess the value of each modality in detecting malignant from benign lesions for clinical decision-making. Results Twenty of a total of 116 patients with pancreatic cystic tumors had 18F-FDG PET because of diagnostic difficulties after evaluation with conventional modalities. Sensitivity and specificity of PET in differentiating malignant from benign pancreatic cystic tumors were 100% and 93.75%, with an accuracy of 95%. PET had the best sensitivity, specificity and accuracy for detecting malignant cystic tumors compared with CT and EUS. In 5 cases, the PET results altered the treatment options completely to follow-up instead of surgery ( n = 2), limited resection instead of Whipple's resection ( n = 1), and surgery instead of follow-up ( n = 2). Conclusions PET is an accurate, non-invasive method to distinguish malignant from benign pancreatic cystic tumors and can be used as an adjunct to facilitate clinical decision making.

Background. In recent years the progress of laparoscopic procedures and the development of new and dedicated technologies have made laproscopic hepatic surgery feasible and safe. In spite of this laparoscopic liver resection remains a surgical procedure of great challenge because of the risk of massive bleeding during liver transection and the complicated biliary and vascular anatomy in the liver. A new laparoscopic device is reported here to assist liver resection laparoscopically. Methods. The laparoscopic Habib™ 4X is a bipolar radiofrequency device consisting of a 2x2 array of needles arranged in a rectangle. It is introduced perpendicularly into the liver, along the intended transection line. It produces coagulative necrosis of the liver parenchyma sealing biliary radicals and blood vessels and enables bloodless transection of the liver parenchyma. Results. Twenty-four Laparoscopic liver resections were performed with LH4X out of a total of 28 attempted resections over 12 months. Pringle manoeuvre was not used in any of the patients. None of the patients required intraoperative transfusion of red cells or blood products. Conclusion. Laparoscopic liver resection can be safely performed with laparoscopic Habib™ 4X with a significantly low risk of intraoperative bleeding or postoperative complications.

Introduction Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. Material and methods From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. Result Twenty-one patients (F = 11, M = 10; age range 40–75 years, mean = 58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary ( n = 10) and non-colorectal primaries ( n = 8), and primary liver tumours ( n = 3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2–2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks ( p = 0.01). The mean pre-treatment SUV was 12.2 ± 3.7 and the mean post-treatment SUV was 9.3 ± 3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127 ± 115 vs 75 ± 72 μ/l, p = 0.39). Complications were seen in 4 patients (19%) including radiation hepatitis ( n = 2), cholecystitis ( n = 1) and duodenal ulceration ( n = 1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). Conclusion SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.

Background Radiofrequency-assisted laparoscopic liver resection is reported. Methods Patients suitable for liver resection were carefully assessed for laparoscopic resection. Patient and intraoperative and postoperative data were prospectively collected and analyzed. Results Eighteen patients underwent laparoscopic liver resection. All operations were performed without vascular clamping and consisting of tumorectomy (n = 9), multiple tumoretcomies (n = 2), segmentectomy (n = 2), and bisegmentectomies (n = 2). Mean blood loss was 121 ± 68 mL, and mean resection was time 167 ± 45 minutes. There was no need for perioperative or postoperative transfusion of blood or blood products. One patient developed pneumothorax during surgery as a result of direct puncture of pleura with the radiofrequency probe, and 1 patient had transient liver failure and required supportive care after surgery. The mean length of hospital stay was 6.0 ±1.5 days. At follow-up, those with liver cancer had no recurrence. Conclusions Radiofrequency-assist laparoscopic liver resection can decrease the risk of intraoperative bleeding and blood transfusion.

Background Liver parenchyma transection technique using heat coagulative necrosis induced by radiofrequency (RF) energy is evaluated in this series. Methods Between January 2000 and October 2004, 156 consecutive patients underwent liver resection with the RF-assisted technique. Data were collected prospectively to assess the outcome, including intraoperative blood loss, blood transfusion requirement, and morbidity and mortality rates. Results There were 30 major hepatectomies and 126 minor resections. While total operative time was 241 ± 89 minutes, the actual resection time was 75 ± 51 minutes. Intraoperative blood loss was 139 ± 222 mL. Nine patients (5%) received blood transfusion, predominantly those receiving major hepatectomy ( P = .006). Thirty-six patients (23%) developed postoperative complications, and the mortality rate was 3.2%. Mean hospital stay was 12 ± 12 days. Conclusion The RF-assisted technique is associated with minimal blood loss, a low blood transfusion requirement, and reduced mortality and morbidity rates and can be used for both minor and major liver resections.

Although resection is currently the only curative approach for metastatic liver cancer, only a small number of cases are suitable for this procedure. In the past few years, gene therapy has emerged as an appealing treatment option for liver cancer. Phase I and II clinical trials have been conducted in patients with either primary or secondary liver cancer using a variety of genes including tumor-suppressor gene p53, suicide genes, immune genes, and replication-competent oncolytic adenoviruses. The results have shown that, although gene therapy has been well tolerated and toxicity has been low, the clinical benefit has so far been marginal. Gene therapy as a definitive treatment for liver metastases remains limited, at least for the time being, but it may be useful as an adjuvant treatment in combination with radiotherapy, chemotherapy, and/or surgery to achieve disease-free survival.

BACKGROUND: Radiofrequency ablation (RFA) is emerging as a new therapeutic method for management of solid tumors. We report here our experience in the use of this technique for management of primary and secondary unresectable liver cancers. METHODS: Thirty-five patients with liver cancers were considered not suitable for curative resection at presentation: 8 with primary hepatocellular carcinoma ([HCC] 6 HCC and 2 fibrolamellar); 27 with metastatic liver cancer (17 colorectal carcinoma and 10 others). They were treated either with radiofrequency heat ablation (Radionics Europe N.V., Wettdren, Belgium) alone percutaneously and/or intraoperatively or in conjunction with surgical resections. The quality of RFA was based on the subjective feeling of whether the tumor was completely destroyed or not. The effectiveness of RFA was assessed according to clinical findings, radiographic images, and tumor markers at follow-up. RESULTS: In 8 primary liver cases, 4 patients with a high level of α fetoprotein (AFP) benefited from the RFA with a 83.3% to 99.7% reduction of AFP. One with fibrolamellar hepatocellular carcinoma died 2 months after an incomplete percutaneous RFA from recurrence. The rest all had stable disease at the time of follow-up (mean 10.4 months). In patients with colorectal liver metastases, there were 4 deaths: 1 patient died postoperatively on the 30th day from a severe chest infection having shown a considerable reduction of carcinoembryonic antigen level (CEA, 8 versus 36 μg/L); 3 died from local and systemic disease, 1 at 12 months and 2 at 1 month, having had an incomplete RFA. The others had stable disease at follow-up (mean 7.6 months). Five patients underwent liver resections successfully with the application of RFA for residual lesions in the remaining contralateral lobe. In 10 patients with other liver tumors, 7 patients had stable disease at follow-up (mean 13.4 months); 1 patient had evidence of local and systemic recurrence 10 months after surgical resections with the intraoperative RFA and 2 patients died of systemic recurrence of disease 3 and 6 months after RFA alone. Two patients had liver resections in conjunction with the intraoperative RFA. The mean follow-up in our series was 8.5 months. CONCLUSION: Radiofrequency heat ablation is useful as a primary treatment for unresectable liver cancers. The procedure can be used to treat the small residual tumor load in the contralateral lobe following liver resection in those considered unresectable at the first presentation. This new therapeutic strategy seems to increase surgical resectability in patients judged unresectable.

Background MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of mRNAs and are aberrantly expressed in cancer with important roles in tumorigenesis. A broad analysis of the combined effects of altered activities of miRNAs in pancreatic ductal adenocarcinoma (PDAC) has not been done, and how miRNAs might affect tumour progression or patient outcomes is unclear. Methods We combined data from miRNA and mRNA expression profiles from PDAC and normal pancreas samples (each n=9) and used bioinformatic analyses to identify a miRNA–mRNA regulatory network in PDAC. We validated our findings in PDAC cell-lines (PANC-1, MIA PaCa-2, LPc006, and LPc167), subcutaneous PDAC xenografts in mice, and laser capture microdissected PDACs from patients (n=91). We used this information to identify miRNAs that contributed most to tumorigenesis. Findings We identified three miRNAs (miR-21, miR-23a, and miR-27a) that acted as cooperative repressors of a network of tumour suppressor genes that included PDCD4, BTG2 , and NEDD4L . Inhibition of miR-21, miR-23a, and miR-27a had synergistic effects in reducing proliferation of PDAC cells in culture and the growth of xenograft tumours. The level of inhibition was greater than that of silencing oncomiR-21 alone. In PDACs from patients, high levels of the combination of miR-21, miR-23a, and miR-27a was a strong independent predictor of short overall survival after surgical resection (hazard ratio 3·21, 95% CI 1·78–5·78). High expression of this combination was also associated with a more aggressive tumour phenotype: more microscopic tumour infiltration at resection margin and increased perineural invasion. Interpretation In an integrated data analysis, we identified functional miRNA–mRNA interactions that contribute to PDAC growth. These findings indicate that miRNAs act together to promote tumour progression and that future therapeutic strategies might require inhibition of several miRNAs. Furthermore, high tumour expression of the miR-21, miR-23a, and miR-27a combination could have potential use in the future as a prognostic signature for patients with PDAC. Funding Peel Medical Research Trust, Alliance Family Foundation, Action Against Cancer, National Institute for Health Research, Association for International Cancer Research, Jason Boas Fellowship, Imperial Biomedical Research Centre, Rosetrees Trust, Joseph Ettedgui Charitable Foundation.

s / Pancreatolog S84 Background: The circulating tumour cells (CTCs) responsible for metastasis in pancreatic cancer (PDAC) are heterogeneous; tailoring therapy based on their molecular profile could permit personalised therapy and improve survival. Aims: Optimise whole blood enrichment to allow next generation sequencing (NGS) of CTCs in PDAC. Materials & methods: An experimental sample, 10 Panc-1 cells spiked into 7.5mls of whole blood, and a clinical sample, 7.5mls of whole blood from a patient with advanced PDAC were used. Streptavidin coated magnetic beads were chemically bonded with CD45 antibodies specific to leucocytes and thoroughly mix with the samples. Leukocytes were removed with a magnet. DNA was isolated from the supernatant using Roche Magnupure. Libraries were diluted to 10 genomes and multiple independent barcoded assays were run per analysis. Barcoded primers for exons 5,6,7 and 8 of Tp53 were used for PCR amplification. Deep sequencing of Tp53 was performed with ion torrent NGS. 10% mutation sequence in one of 100 barcodes was taken as evidence of 0.1% mutation frequency. The limiting dilution removes the possibility of low level PCR error being confused with genuine mutation. Results: The known p.R273H mutation in Panc-1 cells was identified at a frequency 2% in the spiked sample. Amutation p.E271Vwas identified at a frequency 3.4% in the processed sample but was undetectable (