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Management of liver metastases from uveal melanoma (LMUM) requires multimodal approach. This study describes evolution of liver resection for LMUM, reviewing current literature and institutional outcomes. Records of patients referred to the Melanoma Multi-Disciplinary Team between February 2005 and August 2018 were reviewed. All publications describing surgery for LMUM were identified from PubMed, Embase, and Google Scholar. Thirty-one of 147 patients with LMUM underwent laparoscopic liver biopsy, and 29 (14 females) had liver resections. Nineteen liver resections were performed locally [7 major (≥3 seg), 14 laparoscopic] without major complications or mortality. Overall survival positively correlated with the time from uveal melanoma to LMUM (Spearman's rho rs = 0.859, P 0.0001). Overall and recurrence-free survivals were comparable following R1 or R0 resections (OS 25 vs. 28 months, P = 0.404; RFS 13 vs. 6 months, P = 0.596). R1 resection cohort had longer lead-time (median 100 vs. 24 months, P = 0.0408). Eleven publications describing liver resection for LMUM were identified and included in the narrative review. Surgery for LMUM is safe and complements multidisciplinary management. Despite heterogeneity in literature, time from diagnosis of uveal melanoma to LMUM remains a key factor affecting survival after liver resection.

PDF file, 20K, Results of DAVID bioinformatic analysis.

PDF file, 4936K, MiRNA profiling concordance and summary DAVID data.

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PDF file, 3852K, Additional functional studies of miR-153 effect.

PDF file, 86K, Patient clinicopathological data.

PDF file, 4417K, Control experiments.

PDF file, 5326K, Copy number change in miR-153.

PDF file, 102K, Univariate analysis table.

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Aim Avoiding preoperative biliary drainage (PBD) can facilitate early curative surgery for patients with periampullary tumours. However, the evidence over PBD is conflicting. This prospective re-audit aimed to assess compliance to NICE guidelines (NG85) and surgical outcomes at a well-established HPB surgery unit after achieving additional theatre sessions following prior audit. Methods Prospective data collection and analysis for all patients undergoing pancreaticoduodenectomy with curative intent was performed as re-audit at a tertiary pancreatic centre between September 2020 to August 2021. Results 64 or 71 patients received curative pancreaticoduodenectomy (43 Kausch-Whipple & 23 pylorus-preserving pancreaticoduodenectomy, 7 inoperable). Of 29 patients without PBD, 10 were jaundiced with median bilirubin levels of 138 Micromole/L (range 27–357 Mmol/L). Median time (range) from diagnostic imaging to surgery with curative intent was 21 days (3–42) for patients without PBD compared to 62 days (22–305) for those with PBD (p=0.00028). No statistically significant difference in median HDU/ITU stay (4 Vs 3 days, p=0.849), postoperative complications (C-D>2) (30% Vs 27.8%, p=0.755), R0 resection rates (42.8% Vs 75%, p=0.364), and median hospital stay (17 Vs 10 days, p=0.076) was observed for patients without or with PBD respectively. Interestingly, inoperable patients had shorter time delay from diagnostic imaging to surgery (29 Vs 49 days, p=0.010) Conclusion Fast-track (expedited) pancreaticoduodenectomy is feasible and safe for selected group of jaundiced patients without PBD. The constraints and challenges posed by Covid-19 pandemic are likely reflected in higher number of patients receiving PBD (42/ 71) despite clear referral pathway established following prior work at our institute.

While microRNAs (miRNAs) have been broadly studied in cancer, comparatively less is understood about their role in progression. Here we report that miR-153 has a dual role during progression of colorectal cancer (CRC) by enhancing cellular invasiveness and platinum-based chemotherapy resistance. MiRNA profiling revealed that miR-153 was highly expressed in a cellular model of advanced stage CRC. Its upregulation was also noted in primary human CRC compared to normal colonic epithelium, and in more advanced CRC stages compared to early stage disease. In CRC patients followed for 50 months, 21/30 patients with high levels of miR-153 had disease progression compared to others in this group with low levels of miR-153. Functional studies revealed that miR-153 upregulation increased CRC invasiveness and resistance to Oxaliplatin and Cisplatin both in vitro and in vivo. Mechanistic investigations indicated that miR-153 promoted invasiveness indirectly by inducing MMP9 production, whereas drug resistance was mediated directly by inhibiting the Forkhead transcription factor FOXO3a. In support of the latter finding, we found that levels of miR-153 and FOXO3a were inversely correlated in matched human CRC specimens. Our findings establishes key roles for miR-153 overexpression in CRC progression, rationalizing therapeutic strategies to target expression of this miRNA for CRC treatment.

Objective: to reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method.Summary background data: textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking.Methods: this international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. Results from the Delphi rounds were used to establish an international definition of TOLS.Results: in total, 44 expert liver surgeons from 22 countries and all three major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%) and 41 (98%) of the experts participated in round 2, 3 and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality and the presence of R0 resection margin.Conclusions: this is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

Background Management of liver metastases from uveal melanoma (LMUM) requires a ‘multi-modal’ approach including surgical resection. This study aimed to evaluate the role, safety, and oncological effectiveness of liver surgery for patients with LMUM in the context multidisciplinary management. A comprehensive treatment pathway developed upon current published evidence, prevalent national guidelines and novel treatment options is presented (Figure 2) Methods Retrospective review of prospectively maintained database between February 2005 to August 2018 was performed using the institutional electronic patient record system from oncology and surgical department. Demographic data, MDT outcome letters, operative records, clinic letters, letters from referring hospitals, discharge summaries, radiology reports, and histology findings were reviewed. Focused literature review was conducted to identify all relevant publications. All advanced statistical analysis was performed using SPSS version 27.0 software (IBM Corp., Armonk, NY, USA). A p-value of Results 31 patients underwent diagnostic laparoscopy and 17 patients received 19 liver resections locally (Figure 1). 7 major (≥ 3 seg) and 12 minor liver resections (14 laparoscopic) were done without any mortality or major complications. 10/19 (52.6%) were R0 resections. Overall survival positively correlated with the time from UM to LMUM (rs = 0.859, p Conclusions Liver resection for LMUM is safe, effective and complements multimodal management. Lead time from development of UM to LMUM remains a key factor affecting survival outcomes. As novel treatment modalities for regional and systemic disease control for metastatic uveal melanoma continue to develop, surgical intervention will also continue to evolve as part of the multi-disciplinary management. We emphasise the need for developing a collaborative database at a national and international level. We present an evidence-based, multi-disciplinary management pathway for LMUM patients (Figure 2).

Background Isolated metastatic disease within the pancreas is an uncommon finding. The potentially higher perioperative risk and low incidence of resectable metastases has limited the development of evidence based guidelines for pancreatic metastectomy. However, reports in the literature suggest a considered approach to resecting patients with limited disease, favourable tumour type and a significant disease free interval. The aim of this study was to examine the indications and outcomes of pancreatic resection for metastatic disease and non-pancreatic, non-neuroendocrine malignancy at a high-volume pancreatic surgery centre. Methods This is a retrospective analysis of a prospectively managed database of pancreatic resections for metastatic disease or primary non-pancreatic, non-neuroendocrine tumours at a single institution. Data collected and analysed included patient demographics, operative details and peri-operative outcomes, subsequent survival and mode of recurrence. Results Records of 711 patients who underwent pancreatic resection were examined. 21 consecutive patients met the inclusion criteria, representing 3% of the unit’s throughput. The perioperative morbidity and mortality were 33% and 0% respectively. Overall survival was 86months (95%CI 63-107) for renal cell carcinoma and 64months for other tumours. Conclusions When coupled with the low morbidity and mortality rates of a high-volume pancreatic surgery centre using careful patient selection, pancreatic metastectomy has the potential to result in good long-term survival. Recent improvement in the efficacy of systemic therapies, particularly for renal cell carcinoma and melanoma contribute to the utility of resection and to the improved survival of patients.

Background The glycated haemoglobin (HbA1c) test is a venous blood test used as a diagnostic test for diabetes mellitus and to monitor glucose control in patients known to have diabetes. The test has been recommended by National Institute for Health Care Excellence (NICE) clinical guidelines in the pre-operative setting since 2016. The purpose of testing is to reduce perioperative morbidity and mortality by optimising management of blood glucose levels in the perioperative period. The aim of this study was to assess the prognostic value of HbA1c in pancreatic cancer patients treated with pancreaticoduodenectomy. Methods This is a retrospective analysis of a prospectively managed database of pancreatic resections at a single institution from January 2016 to December 2020. Included patients had confirmed pancreatic adenocarcinoma and underwent a pancreaticoduodenectomy with preoperative measurement of their HbA1c. Patients who were already prescribed insulin were excluded. Demographic data, survival, operative and perioperative details were collected. Included patient records were assessed for the incidence of postoperative complications in accordance with International Study Group of Pancreatic Surgery guidelines for pancreatic fistula, delayed gastric emptying and post pancreatectomy haemorrhage. An HbA1c greater than 41 was deemed elevated. Results There were 145 patients who met the inclusion criteria. The HbA1c level was normal in 101/145 (70%) and elevated in 44/45 (30%). The postoperative pancreatic fistula rate was 18% in the patients with a normal HbA1c and 23% in those with elevated HbA1c (p = 0.499). The rate of delayed gastric emptying was 21 and 23% in the patients with normal and elevated HbA1c respectively. There were five relaparotomies overall, one of these patients had an elevated preoperative HbA1c. There were no perioperative deaths. Overall survival was 31months (95%CI 27-35) with a normal preoperative HbAlc and 32months (95%CI 27-38) if elevated. Conclusions There is little doubt that the preoperative HbA1c is helpful in the package of preoperative assessment tests to optimise patients for surgery. However, the preoperative HbA1c level in patients planned for pancreaticoduodenectomy is not predictive of pancreaticoduodenectomy specific complications such as postoperative pancreatic fistula, delayed gastric emptying, relaparotomy or mortality. In addition, long-term overall survival is not influenced by an elevated preoperative HbAlc.

Background Portal vein resection (PVR) with pancreaticoduodenectomy (PD) is often performed to achieve clear margins for patients with vascular involvement in pancreatic ductal adenocarcinoma (PDAC). However, there is evidence to suggest that patients undergoing PVR often have more advanced cancers, therefore the impact of PVR on survival and recurrence remains unclear. The aim of this study is to assess overall (OS) and recurrence free (RFS) survival in patients who underwent PVR during PD, with particular attention to margin positivity. Methods A retrospective analysis was performed on 638 patients who underwent PD during a 12-year period. Exclusion criteria included PD for non-PDAC tumours, neoadjuvant chemotherapy or intra-operative radiotherapy. 374 patients were included in the study (90 PVR and 284 non-PVR). Patient characteristics and histopathological factors associated with OS and RFS were then evaluated using univariate and multivariate Cox regression analyses. 270 patients (90 PVR and 180 non-PVR), were matched by propensity score based on perineural invasion, pT and pN staging. The Kaplan-Meier method was used to calculate survival and log-rank tests. Results Resection margin positivity was associated with shorter OS and RFS (p Conclusions Positive resection margins are associated with shorter survival times, and the SMV margin is the most significant prognostic indicator for overall survival and recurrence compared to other margins. PVR is a relatively safe procedure, however, it does not achieve the intended survival benefits of complete margin clearance. The impact on survival for margin positivity, particularly the SMV margin, and nodal metastasis should be considered when making decisions with regards to vein resection and adjuvant treatments.

New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6. WGS was performed in tumour and leucocytes. RNAseq was performed in MFD-1, and two classic OAC cell lines FLO1 and OE33. Transposase-accessible chromatin sequencing (ATAC-seq) was performed in MFD-1, OE33, and non-neoplastic HET1A cells. Functional studies were performed. MFD-1 had a high SNP genotype concordance with matched germline/tumour. Parental tumour and MFD-1 carried four somatically acquired mutations in three recurrent mutated genes in OAC: TP53, ABCB1 and SEMA5A, not present in FLO-1 or OE33. MFD-1 displayed high expression of epithelial and glandular markers and a unique fingerprint of open chromatin. MFD-1 was tumorigenic in SCID mouse and proliferative and invasive in 3D cultures. The clinical utility of whole genome sequencing projects will be delivered using accurate model systems to develop molecular-phenotype therapeutics. We have described the first such system to arise from the oesophageal International Cancer Genome Consortium project.

A1 Effects of enhanced recovery pathways on renal function Charles R. Horres, Mohamed A. Adam, Zhifei Sun, Julie K. Thacker, Timothy J. Miller, Stuart A. Grant A2 Economic outcomes of enhanced recovery after surgery (ERAS) Jeffrey Huang A3 What does eating, drinking and mobilizing after enhanced recovery surgery really mean? Kirstie McPherson, Sanjiv Patel, Su Cheen Ng, Denise Veelo, Bart Geerts, Monty Mythen A4 Intra-operative fluid monitoring practices Su Cheen Ng, Mark Foulger, Tim Collins, Kirstie McPherson, Michael Mythen A5 Development of an integrated perioperative medicine care pathway Mark Edwards, Denny Levett, Tristan Chapman, Imogen Fecher – Jones, Julian Smith, John Knight, Michael Grocott A6 Cardiopulmonary exercise testing for collaborative decision making prior to major hepatobiliary surgery Mark Edwards, Thomas Sharp, Sandy Jack, Tom Armstrong, John Primrose, Michael Grocott, Denny Levett A7 Effect of an enhanced recovery program on length of stay for microvascular breast reconstruction patients Adam B. King, Kye Higdon, Melissa Bellomy, Sandy An, Paul St. Jacques, Jon Wanderer, Matthew McEvoy A8 Addressing readmissions associated with an enhanced recovery pathway for colorectal surgery Anne C. Fabrizio, Michael C. Grant, Deborah Hobson, Jonathan Efron, Susan Gearhart, Bashar Safar, Sandy Fang, Christopher Wu, Elizabeth Wick A9 The Manchester surgical outcomes project: prevalence of pre operative anaemia and peri operative red cell transfusion rates Leanne Darwin, John Moore A10 Preliminary results from a pilot study utilizing ears protocol in living donor nephrectomy Aparna Rege, Jayanth Reddy, William Irish, Ahmad Zaaroura, Elizabeth Flores Vera, Deepak Vikraman, Todd Brennan, Debra Sudan, Kadiyala Ravindra A11 Enhanced recovery after surgery: the role of the pathway coordinator Deborah Watson A12 Hospitalization costs for patients undergoing orthopedic surgery treated with intravenous acetaminophen (IV-APAP) + IV opioids or IV opioids alone for postoperative pain Manasee V. Shah, Brett A. Maiese, Michael T. Eaddy, Orsolya Lunacsek, An Pham, George J. Wan A13 Development of an app for quality improvement in enhanced recovery Kirstie McPherson, Thomas Keen, Monty Mythen A14 A clinical rotation in enhanced recovery pathways and evidence based perioperative medicine for medical students Alexander B Stone, Christopher L. Wu, Elizabeth C. Wick A15 Enhanced recovery after surgery (ERAS) implementation in abdominal based free flap breast reconstruction Rachel A. Anolik, Adam Glener, Thomas J. Hopkins, Scott T. Hollenbeck, Julie K. Marosky Thacker A16 How the implementation of an enhanced recovery after surgery (ERAS) protocol can improve outcomes for patients undergoing cystectomy Tracey Hong, Andrea Bisaillon, Peter Black, Alan So, Associate Professor, Kelly Mayson A17 Use of an app to improve patient engagement with enhanced recovery pathways Kirstie McPherson, Thomas Keen, Monty Mythen A18 Effect of an enhanced recovery after surgery pathway for living donor nephrectomy patients Adam B. King, Rachel Forbes, Brad Koss, Tracy McGrane, Warren S. Sandberg, Jonathan Wanderer, Matthew McEvoy A19 Introduction and implementation of an enhanced recovery program to a general surgery practice in a community hospital Patrick Shanahan, John Rohan, Desiree Chappell, Carrie Chesher A20 “Get fit” for surgery: benefits of a prehabilitation clinic for an enhanced recovery program for colorectal surgical patients Susan VanderBeek, Rebekah Kelly A21 Evaluation of gastrointestinal complications following radical cystectomy using enhanced recovery protocol Siamak Daneshmand, Soroush T. Bazargani, Hamed Ahmadi, Gus Miranda, Jie Cai, Anne K. Schuckman, Hooman Djaladat A22 Impact of a novel diabetic management protocol for carbohydrate loaded patients within an orthopedic ERAS protocol Volz L, Milby J A23 Institution of a patient blood management program to decrease blood transfusions in elective knee and hip arthroplasty Opeyemi Popoola, Tanisha Reid, Luciana Mullan, Mehrdad Rafizadeh, Richard Pitera

The commonest context in which pulmonary metastasectomy is performed is for recurrent colorectal cancer. With a more active policy of surveillance among cancer teams, ready access to ever faster CT scans and a willingness to perform further surgery to control recurrent cancer, the practice of pulmonary metastasectomy is increasing. In this pro/con debate the issues are explored. It is recognized by both sides that there is no randomized trial evidence on which to base the practice. The difference of opinion is whether there is sufficient evidence from very many case series of both pulmonary and hepatic metastasectomy on which to base current practice. The surgeon's view is that the weight of evidence from many follow-up studies is in favour of continuing this practice. The mathematician's view is that case selection could account for nearly all the observed results.

THE optic disc is an intriguingly small and intricate structure. Some of the pathological processes known or assumed in other conditions can be of help to us in elucidating the changes occurring in papilloedema. By papilloedema in this study I mean the non-inflammatory type found typically in cases of raised intracranial pressure, but also occurring, as we shall see, in some other conditions. The tissue of the disc derives its blood supply from the arterial circle of Haller (or Zinn) (Fig. 1). Each trabecula of the lamina cribrosa (nourishing the nerve fibre bundle within it) is essentially the result of the ingrowth of a vessel derived from the circle of Haller accompanied by glial and connective tissue (Wolff, 1954). The circle of Haller is formed by about three of the short ciliary arteries which also supply the anterior end of the optic nerve. There are connexions usually on a capillary level across the cribriform plate with the inconstant artery of the optic nerve (Fran9ois and Neetens, 1963), and with twigs from the central retinal artery arising just behind the cribriform plate. Although these are usually quite inadequate to maintain the vitality of the retina if there is a blockage of the central retinal artery, this may reflect