Microbiota and Gut-Liver Axis: An Unbreakable Bond?

The gut microbiota, amounting to approximately 100 trillion (1014) microbes represents a genetic repertoire that is bigger than the human genome itself. Evidence on bidirectional interplay between human and microbial genes is mounting. Microbiota probably play vital roles in diverse aspects of normal human metabolism, such as digestion, immune modulation, and gut endocrine function, as well as in the genesis and progression of many human diseases. Indeed, the gut microbiota has been most closely linked to various chronic ailments affecting the liver, although concrete scientific data are sparse. In this narrative review, we initially discuss the basic epidemiology of gut microbiota and the factors influencing their initial formation in the gut. Subsequently, we delve into the gut-liver axis and the evidence regarding the link between gut microbiota and the genesis or progression of various liver diseases. Finally, we summarise the recent research on plausible ways to modulate the gut microbiota to alter the natural history of liver disease.

Liver transplantation for iatrogenic bile duct injury: a systematic review.

BACKGROUND: Bile duct injury (BDI) is an infrequent but serious complication of cholecystectomy, often with life-changing consequences. Liver transplantation (LT) may be required following severe BDI, however given the rarity, few large studies exist to guide management for complex BDI. METHODS: A systematic review was performed to assess post-operative complications, 30-day mortality, retransplant rate and 1-year and 5-year survival following LT for BDI in Medline, EMBASE, Web of Science or Cochrane Clinical Trials Database. RESULTS: Seven articles met inclusion criteria, describing 179 patients that underwent LT for BDI. Secondary biliary cirrhosis (SBC) was the main indication for LT (82.2% of patients). Median model for end-stage liver disease (MELD) scores at time of LT ranged from 16 to 20.5. Median 30-day mortality was 20.0%. The 1-year and 5-year survival ranges were 55.0-84.3% and 30.0-83.3% respectively, and the overall retransplant rate was 11.5%. CONCLUSION: BDI is rarely indicated for LT, predominantly for SBC following multiple prior interventions. MELD scores poorly reflect underlying morbidity, and exception criteria for waitlisting may avoid prolonged LT waiting times. 30-day mortality was higher than for non-BDI indications, with comparable long term survival, suggesting that LT remains a viable but high risk salvage option for severe BDI.

Heterogeneity of management practices surrounding operable gallbladder cancer - results of the OMEGA-S international HPB surgical survey.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive, uncommon malignancy, with variation in operative approaches adopted across centres and few large-scale studies to guide practice. We aimed to identify the extent of heterogeneity in GBC internationally to better inform the need for future multicentre studies. METHODS: A 34-question online survey was disseminated to members of the European-African Hepatopancreatobiliary Association (EAHPBA), American Hepatopancreatobiliary Association (AHPBA) and Asia-Pacific Hepatopancreatobiliary Association (A-PHPBA) regarding practices around diagnostic workup, operative approach, utilization of neoadjuvant and adjuvant therapies and surveillance strategies. RESULTS: Two hundred and three surgeons responded from 51 countries. High liver resection volume units (>50 resections/year) organised HPB multidisciplinary team discussion of GBCs more commonly than those with low volumes (p < 0.0001). Management practices exhibited areas of heterogeneity, particularly around operative extent. Contrary to consensus guidelines, anatomical liver resections were favoured over non-anatomical resections for T3 tumours and above, lymphadenectomy extent was lower than recommended, and a minority of respondents still routinely excised the common bile duct or port sites. CONCLUSION: Our findings suggest some similarities in the management of GBC internationally, but also specific areas of practice which differed from published guidelines. Transcontinental collaborative studies on GBC are necessary to establish evidence-based practice to minimise variation and optimise outcomes.

A Novel Method for the Prevention and Treatment of Small-for-Size Syndrome in Liver Transplantation.

BACKGROUND: Currently there is no consensus on the optimal management of small-for-size syndrome following liver transplantation. Here we describe a technique to alleviate portal hypertension and improve the hepatocyte reperfusion in small-for-size liver transplantation in a Lewis rat model. METHODS: The rats underwent trans-portal vein intra-hepatic portosystemic shunt using a self-developed porous conical tube (TPIPSS: Fig. 1) on small-for-size liver transplants (SFS) with right lobe graft. The treatment effect was evaluated by comparing hemodynamic parameters, morphological changes, serum parameters, ET-1 and eNOS expression, hepatocyte proliferation and apoptosis, CYP3A2 levels, postoperative complications, and survival between the two groups with SFS liver transplants. RESULTS: Porous conical prosthesis prolonged the filling time of small-for-size grafts. Moreover, grafts with TPIPSS showed a lower portal vein pressure, improved microcirculatory flow, alleviated histological changes, decreased ET-1 and increased eNOS expressions, and significantly less damage to liver function comparing to grafts without TPIPSS. Mean survival and overall 30-day survival were significantly higher in the TPIPSS group. CONCLUSIONS: These results demonstrate that porous conical tube as trans-portal vein intra-hepatic portosystemic shunt device is an effective way to alleviate portal vein hypertension and improve hepatocyte reperfusion after small-for-size liver transplantation.

Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study.

BACKGROUND: Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer. METHODS: This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13. FINDINGS: Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37-60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6-59·1) in the capecitabine group compared with 36·4 months (29·7-44·5) in the observation group (adjusted hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55-0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30-44) in the observation group (adjusted HR 0·75, 95% CI 0·58-0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6-35·9) in the capecitabine group and 17·5 months (12·0-23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8-46·3) in the capecitabine group and 17·4 months (12·0-23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (<1%) patient had grade 4 cardiac ischaemia or infarction. Serious adverse events were observed in 47 (21%) of 223 patients in the capecitabine group and 22 (10%) of 224 patients in the observation group. No deaths were deemed to be treatment related. INTERPRETATION: Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting. FUNDING: Cancer Research UK and Roche.

Negative predictive value of drain amylase concentration for development of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. METHODS: 405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.

Surgical intervention for mediastinal pancreatic pseudocysts. A case series and review of the literature.

CONTEXT: Development of mediastinal pancreatic pseudocysts is a rare complication of pancreatitis. There is currently no consensus on the optimal management of this condition, options for which include conservative management with somatostatin analogues, endoscopic drainage procedures and surgery. CASE REPORT: Here we present two patients with mediastinal pancreatic pseudocysts which were initially managed endoscopically. However, in both cases, this led to complications secondary to the endoscopic procedures, recurrence or non-resolution of symptoms, requiring surgical cystogastrostomy and/or cystojejunostomy. CONCLUSION: These cases suggest that surgery may be ultimately necessary for mediastinal pancreatic pseudocysts where endoscopic procedures might have a high likelihood of failure.

The discard of deceased donor kidneys in the UK.

It is essential to minimize the unnecessary discard of procured deceased donor kidneys, but information on discard rates and the extent to which discard can be avoided are limited. Analysis of the UK Transplant Registry revealed that the discard rate of procured deceased donor kidneys has increased from 5% in 2002-3 to 12% in 2011-12. A national offering system for hard-to-place kidneys was introduced in the UK in 2006 (the Declined Kidney Scheme), but just 13% of kidneys that were subsequently discarded until 2012 were offered through the scheme. In order to examine the appropriateness of discard, 20 consecutive discarded kidneys from 13 deceased donors were assessed to determine if surgeons agreed with the decision that they were not implantable. Donors had a median (range) age of 67 (31-80) yr. Kidneys had been offered to a median of 3 (1-12) centers before discard. Four (20%) of the discarded kidneys were thought to be usable, and nine (45%) were possibly usable. As a result of these findings, major changes to the UK deceased donor kidney offering system have been implemented, including simultaneous offering and broader entry criteria for hard-to-place kidneys. Organizational changes are necessary to improve utilization of deceased donor kidneys.

Improved long-term survival after resection of colorectal liver metastases following staging with FDG positron emission tomography.

BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal liver metastases staged by PET CT has not been reported. Objectives were to investigate whether PET CT staging results in actual improved long-term survival, to examine outcome in patients with 'equivocal' PET CT scans, and those excluded from hepatectomy by PET CT. METHODS: A retrospective analysis of patients undergoing hepatectomy for colorectal liver metastases between March 1998 and September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET CT staging resulted in management changes in 23% of patients. PET CT staged patients showed significantly better survival than those staged by CT alone at 3 years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of 6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT scans showed worse median survival than those with favourable PET CT (log rank P = 0.002), but may include a subpopulation whose prognosis trends towards a more favourable outcome than those excluded from liver resection by PET CT, whose median survival remains limited to 21 months. CONCLUSIONS: Staging of patients with colorectal liver metastases by PET CT is associated with significantly improved actual long-term survival, and provides valuable prognostic information which guides surgical and oncological treatments.

Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study.

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.

Direct histological processing of EUS biopsies enables rapid molecular biomarker analysis for interventional pancreatic cancer trials.

OBJECTIVE: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. METHODS: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing. RESULTS: We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p<0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts. CONCLUSIONS: Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients.

Laparoscopic adrenalectomy: auditing the 10 year experience of a single centre.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard for benign adrenal resection, and has been performed at our centre since 2000. We present a retrospective audit of our ten-year experience, and discuss the learning curve. METHODS: Creating a retrospective database, clinical and outcome data were collected for all resections performed over a ten-year period (2000-2010). Patients were chronologically divided into an 'early' (first 40 cases) and 'late' (subsequent cases) group to provide an insight into the learning curve. RESULTS: Over this period, 134 laparoscopic resections were performed, predominantly for benign adenomas (80.3%), with 48% of patients having primary hyperaldosteronism. There was almost equal sex distribution and mean age was 50.2 years, with a median BMI of 28.2. The mean operating time for left and right procedures were 127 and 124 min respectively, with 56.7% of resections being left sided. Our rate of conversion to open was 3.9%. Median length of stay was 4 days post-operatively. There was no mortality and 8.7% patients experienced a surgical complication. Analysis of the grouped data demonstrated a statistically significant reduction in open conversion rate (p = 0.017) and operative time (p = 0.011) in the 'late' group. Among the two groups there was no statistically significant difference in the length of stay and surgical complication rate. All results were comparable to published series in the literature. CONCLUSION: LA has proven to be a safe procedure with a low complication rate at our centre. Our data provide evidence that operative time and conversion rate improves with experience.

Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study.

PURPOSE: The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses. METHODS: This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13. RESULTS: Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex. CONCLUSION: This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care.

Impact of pancreatic leaks on survival following pancreaticoduodenectomy.

CONTEXT: Pancreatic leak following pancreaticoduodenectomy has a major impact on postoperative mortality. However, it is not clear whether pancreatic leaks affect long term survival in patients with pancreatic ductal adenocarcinoma. OBJECTIVE: The aim of this study is to compare the long term outcome in patients who underwent pancreaticoduodenectomy, with and without postoperative pancreatic leak. PATIENTS: All 133 patients who underwent a pancreaticoduodenectomy at the HepatoPancreatoBiliary Unit, Addenbrooke's Hospital, Cambridge, between June 2002 and June 2007 were identified from a prospectively held database. The study was restricted to 47 patients who had a confirmed diagnosis of pancreatic ductal adenocarcinoma. SETTING: Pancreatic leak was defined as drain fluid amylase more than three times the serum level for more than 3 days post operatively. MAIN OUTCOME MEASURE: Long term survival of patients with and without leaks were compared using Kaplan-Meier curves and significance was measured using the log-rank test. RESULTS: Median follow-up was 30.8 months. The median actuarial survival of all ductal adenocarcinoma patients was 19 months. Pancreatic leaks occurred in 9 patients (19.1%). There were no significant differences in the overall survival or presence of recurrence between the two groups. CONCLUSIONS: Pancreatic leak following pancreaticoduodenectomy does not appear to impact on long-term outcome of patients with pancreatic ductal adenocarcinoma.

Perioperative immunonutrition in hepatectomy: A systematic review and meta-analysis.

BACKGROUNDS/AIMS: The role of immunonutrition (IMN) after liver resections or hepatectomies remains unclear and controversial. We undertook a systematic review to evaluate the effects of IMN on clinical outcomes of patients undergoing hepatectomy. METHODS: Main electronic databases were searched for randomised trials reported clinical outcomes or effects of IMN. The systematic review was conducted in accordance with the PRISMA guideline and meta-analysis was analysed using fixed or random-effects models. RESULTS: Eleven RCTs were identified. A total of 1084 patients (529 IMN and 555 Control) were included in the final pooled analysis. Of these patients, 43% (440/1016) underwent major hepatectomies and the majority are for hepatocellular carcinoma (90%, 956/1055) with Child-Pugh A disease (89%, 793/894). IMN significantly reduced post-operative wound infection (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.43 to 0.96; p=0.03). IMN also had a shorter hospital stay (MD -4.97 days, 95% CI -8.23 to -1.72; p=0.003). There was no statistically significant in other post-operative morbidities and mortality. CONCLUSIONS: Wound infection rate was not significantly different between oral and parenteral IMN group. The length of hospital stay was significantly lower in parenteral IMN group than in oral IMN group. The mortality rates were not affected. Immunonutrition should be recommended routinely as part of the nutritional support in the Enhanced Recovery after Surgery (ERAS) protocol for hepatectomy.

Work-Based Assessments in Higher General Surgical Training Program: A Mixed Methods Study Exploring Trainers' and Trainees' Views and Experiences.

Introduction In the United Kingdom, work-based assessments (WBAs) including procedure-based assessments (PBAs), case-based discussions (CBDs), clinical evaluation exercises (CEXs), and direct observation of procedural skills (DOPS) have been used in Higher General Surgical Training Program (HGSTP) since the introduction of Modernising Medical Careers. Although the Intercollegiate Surgical Curriculum Project states that they should be used for the formative development of trainees using feedback and reflection, there is no study to look at the perception of their usefulness and barriers in using them, particularly in HGSTP. The aim of this study is to investigate trainer's and trainee's perception of their usefulness, barriers in using them, and way forward for their improvement in HGSTP. Methods This was a mixed method study. In phase I, after ethics committee approval, an online survey was sent to 83 trainers and 104 trainees, with a response rate of 33 and 37%, respectively, using Online Surveys (formerly Bristol Online Survey) from July 2018 to December 2018. After analysis of this result, in phase II, semistructured interviews were conducted with five trainees and five trainers who had volunteered to take part from phase I. Thematic analysis was performed to develop overarching themes. Results For professional formative development, 15% of the trainers and 53% of the trainees felt that WBAs had a low value. Among 4 WBAs-CEX, CBD, PBA, and DOPS-PBA was thought to be the most useful WBA by 52% trainers and 74% trainees. More trainers than trainees felt that it was being used as a formative tool (33 vs. 16%). The total number of WBAs thought to be required was between 20 and 40 per year, with 46% of the trainers and 53% of the trainees preferring these numbers. The thematic analysis generated four themes with subthemes in each: theme 1, "factors affecting usefulness," including the mode of validation, trainer/trainee engagement, and time spent in validating; theme 2, "doubt on utility" due to doubt on validity and being used as a tick-box exercise; theme 3, "pitfalls/difficulties" due to lack of time to validate, late validation, e-mail rather than face-to-face validation, trainer and trainee behavior, variability in feedback given, and emphasis on number than quality; and theme 4, "improvement strategies." Conclusions The WBAs are not being used in a way they are supposed to be used. The perception of educational impact (Kirkpatrick levels 1 and 2) by trainers was more optimistic than by trainees. Improvements can be made by giving/finding more time, trainer training, more face-to-face validation, and better trainer trainee interactions.

Colorectal liver metastases: Current management and future perspectives.

The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.

Radiation exposure during laparoscopic cholecystectomy with routine intraoperative cholangiography.

BACKGROUND: For many years, intraoperative cholangiography during cholecystectomy to aid definition of the biliary anatomy and to detect choledocholithiasis has been advocated. Although radiation exposure in fluoroscopic procedures is a concern, few available data exist regarding the radiation exposure incurred during intraoperative cholangiography. This study aimed to determine the average radiation exposure sustained during this procedure. METHODS: Radiation dose data were recorded between 5 September 2007 and 21 July 2008 for 108 consecutive patients undergoing laparoscopic cholecystectomy with intraoperative cholangiography. Dose area product values were used to calculate the entrance skin dose, an indicator of potential skin damage, and the effective dose, an indicator of long-term cancer risk, for each patient. RESULTS: The median age of the 108 patients (67% females) included in the data analysis was 51 years (range, 17-87 years). The mean entrance skin dose during intraoperative cholangiography was 0.0069 +/- 0.0066 Gy, and the mean effective dose was 0.18 +/- 0.17 mSv. No results exceeded the threshold of 2 Gy for skin damage, and the lifetime risk for the development of new cancer due to intraoperative cholangiography was less than 0.001%. CONCLUSION: Radiation doses administered during intraoperative cholangiography are safe and do not represent a contraindication to this procedure.

Current status of fast-track recovery pathways in pancreatic surgery.

CONTEXT: Pancreatic surgery is often associated with significant morbidity, thus requiring high level of peri-operative care and long hospital stay. Multi-modal "enhanced recovery" or "fast-track" pathways have recently been introduced, aiming to expedite patient recovery. OBJECTIVE: To evaluate the evidence underpinning the use of fast-track pathways in the peri-operative care of patients undergoing pancreatic cancer surgery. RESULTS: The available evidence is limited, consisting of three retrospective studies that report median length of hospital stay between 7 and 13 days. No significant difference has been noted in re-admission or 30-day mortality rates between fast-track patients and historical controls, but there is a trend for higher overall complication rate for the fast-track groups. CONCLUSION: Implementation of an enhanced recovery pathway is feasible and can achieve shorter hospital stay and reduced costs, with no increase in re-admission or peri-operative mortality rates. There is, however, conflicting evidence on the physiological mechanisms that contribute to accelerated patient recovery. Certain safety issues associated with post-operative morbidity warrant rigorous evaluation in further prospective studies.