Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy.

BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

The Role of Colour Segmented Fluorescence (CSF) Mode and Same-day Administration of Low-dose Indocyanine Green in Liver Surgery: Our Initial Experience : Indocyanine Green Fluorescence Guided Resection of Liver Tumours.

Indocyanine green (ICG) fluorescence image guidance (I-FIGS) is increasingly used in liver surgery. Several regimens have been described regarding the optimum timing and dose of administration. This study presents our early experience with utilising monochromatic Colour Segmented Fluorescence (CSF)-mode and same-day administration of low-dose-ICG in the resection of liver tumours. Between November 2020 and March 2022, I-FIGS was used in 15 patients with suspected liver tumours. ICG was administered intravenously at 0.02 to 0.05 mg/kg dose 2-3 h before surgery. ICG camera was switched to CSF-grey-scale mode to visualise the tumour and to avoid the interference of the green background liver. Using the SPY-CSF mode, the image was scaled to near-infra-red (NIR) fluorescence intensity to accurately identify the tumours and resection margins. Fifteen patients (eight males) with a median age of 71 years (range: 36-86) underwent I-FIGS. Of these, 67% underwent laparoscopic liver surgery, 78% had non-anatomical resections, and 33% underwent redo liver surgery. The mean tumour size was 40.6 mm (SD+/-41 mm). The median number of tumours was two (1-7). All colorectal liver metastases (CRLM) had a signet ring appearance. Hepatocellular carcinomas (HCC) showed partial fluorescence. Tumours were well/moderately differentiated, with CRLM in 86% and HCC in two patients. The R0 resection rate was 72%. In our experience, low-dose-ICG administered at least 2-3 h before surgery can identify liver tumours and their margins in CSF-grey-scale mode. Further research is needed to evaluate its role in reducing R1 resection rates and surgical outcomes.

The role of intraoperative pancreatoscopy in the surgical management of intraductal papillary mucinous neoplasms of the pancreas: a systematic scoping review.

BACKGROUND: The type and the extent of surgery is still debatable for intraductal papillary mucinous neoplasm (IPMN). Intraoperative pancreatoscopy (IOP) allows the visualization of the main pancreatic duct (MPD) in its entire length and could help determine the extent of MPD involvement and the type and extent of pancreatic resection. However, current guidelines do not advise its routine use as there is a lack of evidence supporting its safety and feasibility. The present study aims to perform a scoping review of published evidence on the safety and feasibility of IOP in IPMN surgical management. METHODS: We systematically searched PubMed, Cochrane, Medline and EMbase to identify studies reporting the use of IOP in IPMN surgical management. The research was completed in June 2023. Data extracted included patient selection criteria, demographics, safety of the procedure, intraoperative findings, impact on surgical strategy, histology results and postoperative outcomes. RESULTS: Four retrospective and one prospective study were included in this scoping review. A total of 142 patients had IOP. The selection criteria for inclusion were heterogenous, with one out of five studies including branch duct (BD), main duct (MD) and mixed type IPMN. Indications for IOP and surgical resection were only reported in two studies. A median of seven outcomes (range 5-8) was described, including the type of surgical resection, additional lesions and change of surgical plan, and complications after IOP. IOP showed additional lesions in 48 patients (34%) and a change of surgical plan in 48(34%). No IOP-related complications were reported. CONCLUSIONS: This scoping review suggests IOP is safe and identifies additional lesions impacting the surgical strategy for IPMN. However, the included studies were small and heterogeneous regarding IPMN definition and indications for surgery and IOP. There is a need for a large multi-centre prospective study to determine the role of IOP and its impact on surgical strategy for IPMN.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

A UK survey on variation in the practice of management of choledocholithiasis and laparoscopic common bile duct exploration (ALiCE Survey).

BACKGROUND: The practice of managing suspected/confirmed common bile duct stones (CBDS) can vary significantly in the UK. We aimed to assess this variability in practice and challenges to form a basis for future consensus. METHODS: An electronic survey containing 40 questions on various aspects of management of CBDS was sent to surgeons who perform cholecystectomies via five surgical associations. RESULTS: A total of 132 surgeons responded to the survey. The speciality of surgeons includes upper gastro-intestinal (68%), general (18%), colorectal (12%), and others (2%). For patients with suspected CBD stones, 80% would choose magnetic resonance cholangio-pancreatography, and 14.4% would proceed to intra-operative imaging. Most surgeons preferred intra-operative cholangiogram over intra-operative ultrasound (83% vs 17%). For the treatment, 62.1% preferred a two-stage approach [endoscopic retrograde cholangio-pancreatography (ERCP) followed by laparoscopic cholecystectomy (LC)] and 33.4% chose a single-stage approach [LC + laparoscopic common bile duct exploration (LCBDE)]. Eighty (60.6%) responders performed LCBDE, and 19 (23.8%) of them performed > 10 LCBDEs in a year. Two third of surgeons (62.5%) preferred a trans-choledochal approach to CBDS. Half of the surgeons that perform LCBDE use a T-tube selectively and 1.6% routinely. The "availability of very good ERCP service" and "lack of formal training" were the two main reasons for surgeons not performing LCBDE. Both surgeons' speciality and whether they perform other complex laparoscopic surgery were significantly associated with choosing a two-stage approach over a one-stage approach (χ2 test, speciality p = 0.033, complex surgery p = 0.011). CONCLUSION: Our survey confirms the significant variability in the diagnosis and management of CBDS. The two-stage approach is still the most common way of managing CBDS in the UK. The main reasons for the low uptake of the single-stage approach are the availability of good ERCP service, lack of equipment and lack of formal training in the technique of LCBDE.

Delayed cholecystectomy following endoscopic retrograde cholangio-pancreatography is not associated with worse surgical outcomes.

BACKGROUND: There is no universal consensus on the optimal timing of cholecystectomy following endoscopic retrograde cholangio-pancreatography (ERCP). This study aims to evaluate the effect of time delay and post-ERCP complications on cholecystectomy outcomes. MATERIALS AND METHODS: All patients who underwent pre-op ERCP for concurrent cholelithiasis and choledocholithiasis between January 2009 and August 2019 at University Hospitals Plymouth, UK, were included. Patients who underwent single-stage cholecystectomy and common bile duct exploration were excluded from the study. Based on the delay to cholecystectomy, the patients were divided into early (within 2 weeks), intermediate (2-6 weeks) and late (> 6 weeks) groups. The operative outcomes between the three groups were compared. RESULTS: We included 444 patients in the study, with 62 (14%), 90 (20%) and 292 (66%) patients in the early, intermediate and late groups, respectively. The median duration from ERCP to cholecystectomy was 75 days. There was no statistically significant difference in the conversion-to-open rate, bile leak rate or retained stones between the three groups. The median post-operative hospital stay (PHS) was 2, 2 and 1 day (P = 0.005) in the early, intermediate and late groups, respectively. The readmission rate was significantly more in the delayed group (3.2%, 11.1% and 13.7%; P = 0.05). Patients who suffered post-ERCP complications had a significantly longer PHS (4 vs 1 day, P = 0.001) and had higher conversion-to-open rate (16 vs 4.5%, P = 0.04). CONCLUSION: Delayed cholecystectomy following ERCP is not associated with worse peri-operative outcomes and can facilitate more day-case surgery. However, early cholecystectomy can significantly reduce readmissions with gallstone-related symptoms and its associated hospital stay. Post-ERCP complications lead to a difficult cholecystectomy.

Is there a role for preoperative liver reducing diet in hepatectomy? A systematic review.

PURPOSE: Preoperative very low-calorie diets (VLCDs) have been shown to reduce liver volume, reduce the risk of liver injury and improve safety during bariatric surgery. Hepatic steatosis (HS) has been associated with poorer outcomes in liver resection. VLCD can be used to improve HS. We aim to explore if preoperative VLCD could improve outcomes for patients with HS undergoing liver resection. METHODS: We performed a systematic review of MEDLINE, EMBASE, PubMed and Cochrane databases. Studies were included if they were full-text articles investigating the effect of a preoperative dietary intervention in patients undergoing liver resection on intra-operative and post-operative outcomes. The last search was performed on 11 Jun 2020. Evidence quality was assessed by "GRADE". A narrative review was undertaken. RESULTS: Five studies were found: one RCT and four cohort studies including 133 patients in intervention groups and 181 controls. Three used diet-only strategies and two diet and exercise strategies with varying time courses and monitoring. The quality of evidence assessed by GRADE was "high" for the RCT and "low" for the four cohort studies. Steatosis objectively improved in three studies, with evidence of reduced liver volume and increased attenuation on imaging in one. All studies showed a reduction in body weight and body mass index (BMI). Intra-operative blood loss was decreased following a diet-only intervention in two studies, and liver mobility improved in one. No difference was found in morbidity, mortality or hospital length of stay between intervention and control groups. CONCLUSIONS: There is evidence of poorer outcomes in liver resection patients with existing HS. There is an expected role for a preoperative VLCD to optimise these patients for surgery. Existing publications support this, but diet interventions and outcome measures are inconsistent, and patient numbers are small. There is scope for a well-designed, multi-centre randomised trial to investigate this further.

Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience.

INTRODUCTION: The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic. METHODS: A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved. RESULTS: Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic. CONCLUSION: The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

A systematic review and meta-analysis comparing the short- and long-term outcomes for laparoscopic and open liver resections for liver metastases from colorectal cancer.

BACKGROUND: The laparoscopic approach to liver resection has experienced exponential growth in recent years. However, evidence-based guidelines are needed for its safe future progression. The main aim of our study was to perform a systematic review and meta-analysis comparing the short- and long-term outcomes of laparoscopic and open liver resections for colorectal liver metastases (CRLM). METHODS: To identify all the comparative manuscripts between laparoscopic and open liver resections for CRLM, all published English language studies with more than ten cases were screened. In addition to the primary meta-analysis, 3 specific subgroup analyses were performed on patients undergoing minor-only, major-only and synchronous resections. The quality of the studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology and Newcastle-Ottawa Score. RESULTS: From the initial 194 manuscripts identified, 21 were meta-analysed, including results from the first randomized trial comparing open and laparoscopic resections of CRLM. Five of these were specific to patients undergoing a synchronous resection (399 cases), while six focused on minor (3 series including 226 cases) and major (3 series including 135 cases) resections, respectively. Thirteen manuscripts compared 2543 cases but could not be assigned to any of the above sub-analyses, so were analysed independently. The majority of short-term outcomes were favourable to the laparoscopic approach with equivalent rates of negative resection margins. No differences were observed between the approaches in overall or disease-free survival at 1, 3 or 5 years. CONCLUSION: Laparoscopic liver resection for CRLM offers improved short-term outcomes with comparable long-term outcomes when compared to open approach.

Splenic preservation versus splenectomy in laparoscopic distal pancreatectomy: a propensity score-matched study.

BACKGROUND: The laparoscopic approach in distal pancreatectomy is associated with higher rates of splenic preservation compared to open surgery. Although favorable postoperative short-term outcomes have been reported in open spleen-preserving distal pancreatectomy when compared to distal pancreatectomy with splenectomy, it is unclear whether this observation applies to the laparoscopic approach. The aim of this study is to compare laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with laparoscopic distal pancreatectomy with splenectomy (LDPS). STUDY DESIGN: This is a UK wide, propensity score-matched study, including patients who underwent LSPDP or LDPS between 2006 and 2016. Short-term outcomes were compared between LSPDP and LDPS according to intention to treat. Additionally, risk factors for unplanned splenectomy were explored. RESULTS: A total of 456 patients were included from eleven centers (229 LSPDP and 227 LDPS). We were able to match 173 LSPDP cases to 173 LDPS cases, according to intention to treat. No differences were seen in postoperative morbidity between the groups. The only identified risk factor for unplanned splenectomy was tumor size ≥ 30 mm. CONCLUSIONS: Preserving the spleen during laparoscopic distal pancreatectomy is not associated with a lower postoperative morbidity compared to sacrificing the spleen. Tumor size is a risk factor for unplanned splenectomy.

The Southampton Consensus Guidelines for Laparoscopic Liver Surgery: From Indication to Implementation.

OBJECTIVE: The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery. BACKGROUND: The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination. METHODS: A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements. RESULTS: Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee. CONCLUSION: The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards.

Differentiating Simple Hepatic Cysts from Mucinous Cystic Neoplasms: Radiological Features, Cyst Fluid Tumour Marker Analysis and Multidisciplinary Team Outcomes.

BACKGROUND: Differentiating hepatic mucinous cystic neoplasms (MCNs) from simple hepatic cysts (SCs) preoperatively is a challenging task. Our aim was to determine whether radiological features on ultrasound scan (USS), CT or MRI, cyst fluid tumour markers, or multidisciplinary team (MDT) outcomes could differentiate MCN from SC. METHODS: A retrospective review of radiological features, cyst fluid tumour marker levels and MDT outcomes in 52 patients was performed. RESULTS: There were 13 patients with MCN, 38 with SC and one ciliated foregut cyst. MCNs were more often solitary (p = 0.006). Although no other individual radiological characteristic on USS, CT or MRI was predictive of MCN, MDT outcomes stating that a cyst was complex in nature were highly predictive (p = 0.0007). Cyst fluid carbohydrate antigen 19-9, carcino-embryonic antigen and cancer antigen 125 were unable to differentiate MCN from SC (p = 0.45, p = 0.49, and p = 0.73, respectively). CONCLUSIONS: MDT outcomes are of greatest value when trying to differentiate MCN from SC, as well as having a solitary cyst on imaging. Conventional cyst fluid tumour markers are unhelpful. All suspicious cystic liver lesions should be discussed pre-operatively by a hepatobiliary MDT to determine the most appropriate surgical approach.

Variation in survival after surgery for peri-ampullary cancer in a regional cancer network.

BACKGROUND: Centralisation of specialist surgical services requires that patients are referred to a regional centre for surgery. This process may disadvantage patients who live far from the regional centre or are referred from other hospitals by making referral less likely and by delaying treatment, thereby allowing tumour progression. The aim of this study is to explore the outcome of surgery for peri-ampullary cancer (PC) with respect to referring hospital and travel distance for treatment within a network served by five hospitals. METHODS: Review of a unit database was undertaken of patients undergoing surgery for PC between January 2006 and May 2014. RESULTS: 394 patients were studied. Although both the median travel distance for patients from the five hospitals (10.8, 86, 78.8, 54.7 and 89.2 km) (p < 0.05), and the annual operation rate for PC (2.99, 3.29, 2.13, 3.32 and 3.07 per 100,000) (p = 0.044) were significantly different, no correlation was noted between patient travel distance and population operation rate at each hospital. No difference was noted between patients from each hospital in terms of resection completion rate or pathological stage of the resected tumours. The median survival after diagnosis for patients referred from different hospitals ranged from 1.2 to 1.7 years and regression analysis revealed that increased travel distance to the regional centre was associated with a small survival advantage. CONCLUSION: Although variation in the provision and outcome of surgery for PC between regional hospitals is noted, this is not adversely affected by geographical isolation from the regional centre. TRIAL REGISTRATION: This study is part of post-graduate research degree project. The study is registered with ClinicalTrials.gov (unique identifier NCT02296736 ) November 18, 2014.

Rebound growth of hepatic colorectal metastases after neo-adjuvant chemotherapy: effect on survival after resection.

BACKGROUND: A period of recovery is commonly allowed between completion of chemotherapy for colorectal liver metastases (CRLM) and resection, during which tumour progression may occur. The study-aim is to assess the growth of CRLM in this interval and association with outcome. METHOD: Data on 146 patients were analysed. Change in tumour size was assessed by comparing size determined by imaging performed on completion of chemotherapy with that determined by examination of the resected specimen, categorised by RECIST criteria. RESULTS: In the interval before surgery sixteen patients (11%) fulfilled criteria for partial response (PR), 48 (33%) had stable disease (SD) and 82 (56%) had progressive disease (PD). Among patients with PD following chemotherapy the median disease-free survival of patients who initially responded (26 months) was longer than in those who initially had stable disease (7 months) (P = 0.002). No association was noted between rate of tumour growth after completion of chemotherapy and disease-free survival. CONCLUSION: Change in tumour size after completion of chemotherapy is variable and can be rapid, especially in patients who initially respond to treatment. However, disease-free survival is determined by tumour behaviour during treatment and not by change in size after completion of chemotherapy.

Assessment of the effect of interval from presentation to surgery on outcome in patients with peri-ampullary malignancy.

BACKGROUND: Delay between diagnosis of peri-ampullary cancer (PC) and surgery may allow tumour progression and affect outcome. The aim of this study was to explore associations of interval to surgery (IS) with pathological outcomes and survival in patients with PC. METHOD: A database review of all patients undergoing surgery between 2006 and 2014 was undertaken. IS was measured from diagnosis by imaging. Potential association between IS and survival was measured using Cox regression analysis, and between IS and pathological outcome with multivariate logistic analysis. RESULTS: 388 patients underwent surgery. The median IS was 49 days (1-551 days), and was not associated with any of the evaluated outcomes in patients with pancreatic (149) or distal bile duct (46) cancer. For patients with ampullary cancer (71) longer IS was associated with improved survival, with median survival of 27.5 months for patients waiting ≤ median IS (35) and 38.3 months for patients waiting > median IS (36) for surgery (p = 0.041). A higher rate of margin positivity (31.4%) was also noted among patients who waited less than the median IS compared to those waiting longer than this interval (11.4%) (p = 0.032). CONCLUSION: For patients with ampullary cancer there is a paradoxical improvement in outcome among those with a longer IS, which may be explained by progression to inoperability of more aggressive lesions.