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benefits of minimally invasive surgery and equivalent oncological outcomes compared with conventional open PD (OPD). When LPD and RPD are compared, RPD offers better precision with 3D vision and advanced instrumentation. Although the learning curve for RPD is long with a longer operating time compared with OPD, this can be reduced to a duration similar to that for OPD through standardization of techniques and case numbers.Perioperative outcomes such as length of stay, blood loss, and transfusion requirement are significantly improved compared to OPD and fewer cases require conversion to open than LPD. In this article, we describe our approach to RPD through standardizing PD techniques along with tips and tricks for the benefit of surgeons interested in learning robotic pancreatic surgery.

Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK.A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed.Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P 0.05).En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.

Background An increasing number of robotic pancreatoduodenectomies (RPD) are reported, however, questions remain on the number of procedures needed for gaining technical proficiency in RPD. Therefore, we aimed to assess the influence of procedure volume on short-term RPD outcomes and assess the learning curve effect. Methods A retrospective review of consecutive RPD cases was undertaken. Non-adjusted cumulative sum (CUSUM) analysis was performed to identify the procedure volume threshold, following which before-threshold and after-threshold outcomes were compared. Results Since May 2017, 60 patients had undergone an RPD at our institution. The median operative time was 360 min (IQR 302.25–442 min). CUSUM analysis of operative time identified 21 cases as proficiency threshold, indicated by curve inflexion. Median operative time was significantly shorter after the threshold of 21 cases (470 vs 320 min, p p = 0.876). Conclusions A decrease in operative time after 21 RPD cases suggests a threshold of technical proficiency potentially associated with an initial adjustment to new instrumentation, port placement and standardisation of operative step sequence. RPD can be safely performed by surgeons with prior laparoscopic surgery experience.

Graphene field-effect transistor (GFET) biosensors exhibit high sensitivity due to a large surface-to-volume ratio and the high sensitivity of the Fermi level to the presence of charged biomolecules near the surface. For most reported GFET biosensors, bulky external reference electrodes are used which prevent their full-scale chip integration and contribute to higher costs per test. In this study, GFET arrays with on-chip integrated liquid electrodes were employed for COVID-19 detection and functionalized with either antibody or aptamer to selectively bind the spike proteins of SARS-CoV-2. In the case of the aptamer-functionalized GFET (aptasensor, Apt-GFET), the limit-of-detection (LOD) achieved was about 10

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent malignant pancreatic tumor. Few studies have shown how often PDACs arise from cystic precursor lesions. This special report aims to summarize the evidence on the progression of precancerous lesions to PDAC. A review of the literature found four studies that discussed pancreatic intraepithelial lesions (PanINs), three that discussed mucinous cystic neoplasms (MCN) and five that discussed intraductal papillary neoplasms (IPMNs). PanINs were the most common precursors lesion, with approximately 80% of PDACs originating from this lesion. The lack of evidence characterizing the features of PDAC precursor cystic lesions potentially leads to a subset of patients undergoing surgery unnecessarily. Advancements in molecular techniques could allow the study of cystic lesions at a genetic level, leading to more personalized management.Cancer arising from the ducts within the pancreas is the most common type of pancreatic cancer. Some cancers develop from precancerous changes, but these are not currently well described. Therefore, we have summarized the existing knowledge on the precancerous changes causing pancreatic cancer. We found three main precancerous changes: pancreatic intraepithelial lesions; mucinous cystic neoplasms; and intraductal papillary neoplasms. Pancreatic intraepithelial lesions were the most common pancreatic precancerous lesion, leading to 80% of cancers of the pancreatic ducts. A few studies indicate that patients would benefit from surgery to remove precancerous lesions. We believe that, due to advances in genetic studies, personalized strategies for treating pancreatic cancers will emerge in the future.

Graphene field-effect transistors (GFETs) are suitable building blocks for high-performance electrical biosensors, because graphene inherently exhibits a strong response to charged biomolecules on its surface. However, achieving ultralow limit-of-detection (LoD) is limited by sensor response time and screening effect. Herein, we demonstrate that the detection limit of GFET biosensors can be improved significantly by decorating the uncovered graphene sensor area with carbon dots (CDs). The developed CDs-GFET biosensors used for exosome detection exhibited higher sensitivity, faster response, and three orders of magnitude improvements in the LoD compared with nondecorated GFET biosensors. A LoD down to 100 particles/μL was achieved with CDs-GFET sensor for exosome detection with the capability for further improvements. The results were further supported by atomic force microscopy (AFM) and fluorescent microscopy measurements. The high-performance CDs-GFET biosensors will aid the development of an ultrahigh sensitivity biosensing platform based on graphene for rapid and early diagnosis of diseases.

The uptake of robotic surgery is rapidly increasing worldwide across surgical specialties. However, there is currently a much higher use of robotic surgery in the United States of America (USA) compared to the United Kingdom (UK) and Ireland. Reduced exposure to robotic surgery in training may lead to longer learning curves and worse patient outcomes. We aimed to identify whether any difference exists in exposure to robotic surgery during general surgical training between trainees in the USA, UK and Ireland. Over a 15-week period from September 2021, a survey was distributed through the professional networks of the research team. Participants were USA, UK or Irish trainees who were part of a formal general surgical training curriculum. 116 survey responses were received. US trainees (n = 34) had all had robotic simulator experience, compared to only 37.93% of UK (n = 58) and 75.00% of Irish (n = 24) trainees (p 0.00001). 91.18% of US trainees had performed 15 or more cases as the console surgeon, compared to only 3.44% of UK and 16.67% of Irish trainees (p 0.00001). Fifty UK trainees (86.21%) and 22 Irish trainees (91.67%) compared to 12 US trainees (35.29%) do not think they have had adequate robotics training (p 0.00001). Surgical trainees in the USA have had significantly more exposure to training in robotic surgery than their UK and Irish counterparts.

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.

Is the corresponding author a member of a Strategic Partner Society (50% discount on article publication charge)

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

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.

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.

Simple Summary Extracellular vesicles (EVs) are small particles that are released by cancer cells, and they may hold vital information for researchers looking for early markers for diagnosis. Size-exclusion chromatography (SEC) is a classical technique that has become increasingly popular and can be used for rapid isolation and investigation of both their cargo and functionality. This systematic review highlights its main technical aspects, the type of materials involved and by covering the findings of the identified papers hopes to demonstrate the utility of this method in cancer research to date. Abstract Cancer cells release extracellular vesicles, which are a rich target for biomarker discovery and provide a promising mechanism for liquid biopsy. Size-exclusion chromatography (SEC) is an increasingly popular technique, which has been rediscovered for the purposes of extracellular vesicle (EV) isolation and purification from diverse biofluids. A systematic review was undertaken to identify all papers that described size exclusion as their primary EV isolation method in cancer research. In all, 37 papers were identified and discussed, which showcases the breadth of applications in which EVs can be utilised, from proteomics, to RNA, and through to functionality. A range of different methods are highlighted, with Sepharose-based techniques predominating. EVs isolated using SEC are able to identify cancer cells, highlight active pathways in tumourigenesis, clinically distinguish cohorts, and remain functionally active for further experiments.

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.

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.

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.

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...