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.

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.

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.

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.

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.

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.

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.

Human primary liver cancer-derived organoid cultures for disease modeling and drug screening.

Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer.

OBJECTIVES: The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS: Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS: Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.

Surgical management of hepato-pancreatic metastasis from renal cell carcinoma.

AIM: To investigate the outcomes of liver and pancreatic resections for renal cell carcinoma (RCC) metastatic disease. METHODS: This is a retrospective, single centre review of liver and/or pancreatic resections for RCC metastases between January 2003 and December 2015. Descriptive statistical analysis and survival analysis using the Kaplan-Meier estimation were performed. RESULTS: Thirteen patients had 7 pancreatic and 7 liver resections, with median follow-up 33 mo (range: 3-98). Postoperative complications were recorded in 5 cases, with no postoperative mortality. Three patients after hepatic and 5 after pancreatic resection developed recurrent disease. Median overall survival was 94 mo (range: 23-94) after liver and 98 mo (range: 3-98) after pancreatic resection. Disease-free survival was 10 mo (range 3-55) after liver and 28 mo (range 3-53) after pancreatic resection. CONCLUSION: Our study shows that despite the high incidence of recurrence, long term survival can be achieved with resection of hepatic and pancreatic RCC metastases in selected cases and should be considered as a management option in patients with oligometastatic disease.

The role of arterial conduits for revascularisation in adult orthotopic liver transplantation.

The successful outcome in orthotopic liver transplantation (OLT) is critically dependent on the uncompromised hepatic graft blood inflow. Arterial conduits represent a good solution in cases where conventional revascularisation is not possible. The purpose of this systematic review is to analyse the published evidence on the use of arterial conduits in adult OLT. After review of the Pubmed and EMBASE databases, 19 relevant studies were identified and analysed. Even though patient survival was comparable, most large studies reported worse 1-, 3- and 5-year graft survival rates compared to grafts with standard arterial revascularisation. Primary grafts were more commonly affected than re-grafts. Early and late hepatic artery thrombosis occurred more commonly, while the use of an arterial conduit was identified as an independent risk factor. The overall biliary complications were comparable, however, ischaemic cholangiopathy was encountered about 3 times more in patients with arterial conduits and strongly correlated with the occurrence of late HAT. In conclusion, the use of arterial conduit is a useful option in adult OLT in cases that the conventional revascularisation technique cannot be used or results in suboptimal arterial inflow. More studies directly addressing issues such as pre-operative evaluation regarding the need for arterial conduit, the types of vessels used, positioning of the conduit and post-operative management are required.

Incidental non-benign gallbladder histopathology after cholecystectomy in an United Kingdom population: Need for routine histological analysis?

AIM: To analyse the range of histopathology detected in the largest published United Kingdom series of cholecystectomy specimens and to evaluate the rational for selective histopathological analysis. METHODS: Incidental gallbladder malignancy is rare in the United Kingdom with recent literature supporting selective histological assessment of gallbladders after routine cholecystectomy. All cholecystectomy gallbladder specimens examined by the histopathology department at our hospital during a five year period between March 2008 and March 2013 were retrospectively analysed. Further data was collected on all specimens demonstrating carcinoma, dysplasia and polypoid growths. RESULTS: The study included 4027 patients. The majority (97%) of specimens exhibited gallstone or cholecystitis related disease. Polyps were demonstrated in 44 (1.09%), the majority of which were cholesterol based (41/44). Dysplasia, ranging from low to multifocal high-grade was demonstrated in 55 (1.37%). Incidental primary gallbladder adenocarcinoma was detected in 6 specimens (0.15%, 5 female and 1 male), and a single gallbladder revealed carcinoma in situ (0.02%). This large single centre study demonstrated a full range of gallbladder disease from cholecystectomy specimens, including more than 1% neoplastic histology and two cases of macroscopically occult gallbladder malignancies. CONCLUSION: Routine histological evaluation of all elective and emergency cholecystectomies is justified in a United Kingdom population as selective analysis has potential to miss potentially curable life threatening pathology.

Time spent in hospital after liver transplantation: Effects of primary liver disease and comorbidity.

AIM: To explore the effect of primary liver disease and comorbidities on transplant length of stay (TLOS) and LOS in later admissions in the first two years after liver transplantation (LLOS). METHODS: A linked United Kingdom Liver Transplant Audit - Hospital Episode Statistics database of patients who received a first adult liver transplant between 1997 and 2010 in England was analysed. Patients who died within the first two years were excluded from the primary analysis, but a sensitivity analysis was also performed including all patients. Multivariable linear regression was used to evaluate the impact of primary liver disease and comorbidities on TLOS and LLOS. RESULTS: In 3772 patients, the mean (95%CI) TLOS was 24.8 (24.2 to 25.5) d, and the mean LLOS was 24.2 (22.9 to 25.5) d. Compared to patients with cancer, we found that the largest difference in TLOS was seen for acute hepatic failure group (6.1 d; 2.8 to 9.4) and the largest increase in LLOS was seen for other liver disease group (14.8 d; 8.1 to 21.5). Patients with cardiovascular disease had 8.5 d (5.7 to 11.3) longer TLOS and 6.0 d (0.2 to 11.9) longer LLOS, compare to those without. Patients with congestive cardiac failure had 7.6 d longer TLOS than those without. Other comorbidities did not significantly increase TLOS nor LLOS. CONCLUSION: The time patients spent in hospital varied according to their primary liver disease and some comorbidities. Time spent in hospital of patients with cancer was relatively short compared to most other indications. Cardiovascular disease and congestive cardiac failure were the comorbidities with a strong impact on increased LOS.

Time-varying impact of comorbidities on mortality after liver transplantation: a national cohort study using linked clinical and administrative data.

OBJECTIVE: We assessed the impact of comorbidity on mortality in three periods after liver transplantation (first 90 days, 90 days-5 years and 5-10 years). DESIGN: Prospective cohort study using records from the UK Liver Transplant Audit (UKLTA) linked to Hospital Episode Statistics (HES), an administrative database of hospital admissions in the English National Health Service (NHS). Comorbidities relevant for liver transplantation were identified from the 10th revision of the International Classification of Diseases (ICD-10) codes in HES records of admissions in the year preceding their operation. Multivariable Cox regression was used to estimate HRs for three different time periods after liver transplantation. SETTING: All liver transplant centres in the NHS hospitals in England. PARTICIPANTS: Adults who received a first elective liver transplant between April 1997 and March 2010 in the linked UKLTA-HES database. OUTCOMES: Patient mortality in three different time periods after transplantation. RESULTS: Among 3837 recipients, 45.1% had comorbidities. Recipients with cardiovascular disease had statistically significantly higher mortality in all three periods after transplantation (first 90 days: HR=2.0; 95% CI 1.4 to 2.9, 90 days-5 years: 1.6; 1.2 to 2.2, beyond 5 years: 2.8; 1.7 to 4.4). Prior congestive cardiac failure (3.2; 2.1 to 4.9) significantly increased mortality only in the first 90 days. History of non-hepatic malignancy appeared to increase risk over all periods, but significantly only in the first 90 days (1.9; 1.0 to 3.6). A diagnosis of connective tissue disease, dementia, diabetes, chronic pulmonary and renal disease did not have a significant impact on mortality in any period. CONCLUSIONS: The impact of comorbidities present at the time of transplantation changes with time after transplantation. Renal disease, pulmonary disease and diabetes had no impact on mortality in contrast to previous reports.

Salvage pancreaticoduodenectomy after complete response to chemoradiotherapy for a previously unresectable pancreatic adenosquamous carcinoma: a case report.

Pancreatic cancer is known for its typically late presentation and poor survival rates, with overall 5-year survival of less than 5%. The role of chemotherapy alone or with radiotherapy in the management of locally advanced tumors continues to be an area of debate.We report a case of locally advanced, pancreatic adenosquamous carcinoma that was initially deemed unresectable intraoperatively. Nonetheless, the tumor was resected after radiological response to gemcitabine-capecitabine chemoradiotherapy regimen similar to the Selective Chemoradiation in Advanced LOcalised Pancreatic cancer trial. Histological examination revealed complete pathological response with extensive fibrosis (ypT0 N0). On 12-month follow-up CT, a single liver lesion in the left lateral segment was identified and confirmed to be a metastasis with cytological diagnosis via EUS and FNA. The disease remained stable and confined to the solitary hepatic metastasis after further gemcitabine chemotherapy. Therefore, a further successful resection was performed.The 2 main strategies for the management of locally advanced unresectable pancreatic cancer are chemotherapy induction followed by consolidation chemoradiotherapy or chemotherapy alone, with conflicting published evidence. Evidence for the optimal management of the rare histological type of adenosquamous carcinoma is scant. We present a case of such tumor with a complete pathological response to chemoradiotherapy. The results of future studies in the area are eagerly awaited.

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.

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.

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.