Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis.

BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

How to Handle Arterial Conduits in Liver Transplantation? Evidence From the First Multicenter Risk Analysis.

OBJECTIVE: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective. BACKGROUND: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature. STUDY DESIGN: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival. RESULTS: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT. CONCLUSION: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC.

Hepatopancreatoduodenectomy -a controversial treatment for bile duct and gallbladder cancer from a European perspective.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

Variation in the Use of Resection for Colorectal Cancer Liver Metastases.

OBJECTIVE: The aim of this study was to investigate variation in the frequency of resections for colorectal cancer liver metastases across the English NHS. BACKGROUND: Previous research has shown significant variation in access to liver resection surgery across the English NHS. This study uses more recent data to identify whether inequalities in access to liver resection still persist. METHODS: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2012 were identified in the COloRECTal cancer data Repository (CORECT-R). All episodes of care, occurring within 3 years of the initial bowel operation, corresponding to liver resection were identified. RESULT: During the study period 157,383 patients were identified as undergoing major resection for a colorectal tumor, of whom 7423 (4.7%) underwent ≥1 liver resections. The resection rate increased from 4.1% in 2005, reaching a plateau around 5% by 2012. There was significant variation in the rate of liver resection across hospitals (2.1%-12.2%). Patients with synchronous metastases who have their primary colorectal resection in a hospital with an onsite specialist hepatobiliary team were more likely to receive a liver resection (odds ratio 1.22; 95% confidence interval, 1.10-1.35) than those treated in one without. This effect was absent in resection for metachronous metastases. CONCLUSIONS: This study presents the largest reported population-based analysis of liver resection rates in colorectal cancer patients. Significant variation has been observed in patient and hospital characteristics and the likelihood of patients receiving a liver resection, with the data showing that proximity to a liver resection service is as important a factor as deprivation.

Primary liver resection for patients with cirrhosis and hepatocellular carcinoma: the role of surgery in BCLC early (A) and intermediate stages (B).

AIM: This study aims to report the outcomes following primary liver resection (PLR) in patients with cirrhosis including stratification according to the Barcelona Clinic Liver Cancer (BCLC) classification. METHODS: Patients with cirrhosis and hepatocellular carcinoma (HCC) who had PLR between 2000 and 2013 were examined. Overall survival (OS), disease-free survival (DFS) and recurrence rate (RR) were analysed. Management after recurrence was reviewed as well as comparison to a series of 116 patients listed directly for liver transplant. RESULTS: Seventy-one patients underwent PLR. Median follow-up was 40 months. The 1-, 3- and 5-year OS and DFS for the series were 77, 69 and 61 % and 69, 39 and 28 % respectively. Overall recurrence was 59 % (44/71) and only 36 % (15/44) of those patients had a further potentially curative procedure. The 1-3-5-year OS and DFS in the BCLC-A (44 patients) were 86, 78 and 68 % and 78, 48 and 44 % respectively. The RR in BCLC-A was 45 % (20 patients) with half (11 patients) suitable for further treatment with curative intent. The 1-3-5-year OS and DFS in the BCLC-B (17 patients) were 81, 74 and 60 % and 58, 29 and 7 % respectively. The overall RR in BCLC-B was 76 % (13 patients). CONCLUSION: Recurrence following PLR for HCC in patients with cirrhosis is high with only a third of patients suitable for further potentially curative procedures. For patients with BCLC-A (or within Milan criteria), PLR provided a 68 % 5-year OS with 44 % of them free of disease. Surgery can offer satisfactory OS in carefully selected patients in the BCLC-B stage.

Contemporary management and classification of hepatic leiomyosarcoma.

BACKGROUND: Hepatic leiomyosarcomas are rare soft-tissue tumours. The majority of lesions previously considered as leiomyosarcomas have been identified as gastrointestinal stromal tumours (GISTs). Consequently, understanding of the role of liver resection for true leiomyosarcoma is limited, a fact that is exacerbated by the increasing recognition of leiomyosarcoma subtypes. This study presents data on the outcomes of liver resection for leiomyosarcoma and suggests an algorithm for its pathological assessment and treatment. METHODS: Patients were identified from a prospectively collected departmental database. All tumours were negative for c-kit expression. Immunohistochemistry was performed to identify the presence of oestrogen or progesterone receptor (OR/PR) expression or Epstein-Barr virus (EBV) and patients were stratified according to this profile. RESULTS: Eight patients (of whom seven were female) underwent a total of 11 liver resections over a 12-year period. One patient had a primary hepatic leiomyosarcoma. Of those with metastatic leiomyosarcomas, the primary tumours were located in the mesentery, gynaecological organs and retroperitoneum in four, two and one patient, respectively. Both leiomyosarcomas of gynaecological origin stained positive for OR/PR expression. One patient had previously undergone renal transplantation; this leiomyosarcoma was associated with EBV expression. Median survival was 56 months (range: 22-132 months) and eight, six and four patients remained alive at 1, 3 and 5 years, respectively. CONCLUSIONS: Hepatic resection for leiomyosarcoma is associated with encouraging rates of 5-year overall and disease-free survival. The worse outcome that had been expected based on data derived from historical cohorts (partly comprising subjects with GIST) was not observed. An algorithm for pathological classification and treatment is suggested.

A cost effective analysis of a laparoscopic versus an open left lateral sectionectomy in a liver transplant unit.

INTRODUCTION: This study aimed to assess the cost effectiveness of a laparoscopic left lateral sectionectomy (LLLS) compared with an open (OLLS) procedure and its role as a training operation as well as the learning curve associated with a laparoscopic approach. METHOD: Between 2004 and 2013, a prospectively maintained database was reviewed. LLLS were compared with age- and sex-matched OLLS. In addition, the outcomes of LLLS with a consultant as the primary surgeon were compared with those performed by trainees. RESULTS: Forty-three LLLS were performed during the study period. LLLS was a significantly cheaper operation compared with OLLS (P = 0.001, £3594.14 versus £5593.41). The median hospital stay was shorter in the laparoscopic group (P = 0.002, 3 versus 7 days). No difference was found in outcomes between a LLLS performed by a trainee or consultant (operating time, morbidity or R1 resection rate). The procedure length was significantly shorter during the later half of the study period [120 versus 129 min (P = 0.045)]. CONCLUSION: LLLS is a significantly cost effective operation compared with an open approach with a reduction in hospital stay. In addition, it is suitable to use as a training operation.

One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.

OBJECTIVE: To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. BACKGROUND: There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. METHODS: Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. RESULTS: A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). CONCLUSION: One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.

Minimally invasive surgery training using multiple port sites to improve performance.

BACKGROUND: Structural learning theory suggests that experiencing motor task variation enables the central nervous system to extract general rules regarding tasks with a similar structure - rules that can subsequently be applied to novel situations. Complex minimally invasive surgery (MIS) requires different port sites, but switching ports alters the limb movements required to produce the same endpoint control of the surgical instrument. The purpose of the present study was to determine if structural learning theory can be applied to MIS to inform training methods. METHODS: A tablet laptop running bespoke software was placed within a laparoscopic box trainer and connected to a monitor situated at eye level. Participants (right-handed, non-surgeons, mean age = 23.2 years) used a standard laparoscopic grasper to move between locations on the screen. There were two training groups: the M group (n = 10) who trained using multiple port sites, and the S group (n = 10) who trained using a single port site. A novel port site was used as a test of generalization. Performance metrics were a composite of speed and accuracy (SACF) and normalized jerk (NJ; a measure of movement 'smoothness'). RESULTS: The M group showed a statistically significant performance advantage over the S group at test, as indexed by improved SACF (p < 0.05) and NJ (p < 0.05). CONCLUSIONS: This study has demonstrated the potential benefits of incorporating a structural learning approach within MIS training. This may have practical applications when training junior surgeons and developing surgical simulation devices.

Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis.

OBJECTIVE: A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM). METHODS: A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival. RESULTS: Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified. CONCLUSION: A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.

Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure.

BACKGROUND: An acetominophen overdose (AOD) is the leading cause of acute liver failure (ALF) in the UK and USA. For patients who meet the King's College Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver transplantation (OLT) is conventionally performed with subsequent life-long immunosuppression. A new technique was developed in 1998 for AOD-induced ALF where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft auxiliary liver transplant (WGALT) was performed with complete withdrawal of immunosupression during the first year post-operatively. RESULTS: During 1998-2010, 68 patients were listed for an emergency transplantation for AOD ALF at our institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5 years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off immunosuppression. Poor prognostic factors in the WGALT group included higher donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54 kg, P = 0.036). CONCLUSION: Although OLT remains standard practice for AOD-induced ALF, life-long immunosuppression is required. A favourable survival rate using a subtotal hepatectomy and WGALT has been demonstrated, and importantly, all successful patients have undergone complete immunosuppression withdrawal. This technique is advocated for patients who have acetominophen hepatotoxicity requiring liver transplantation.

Liver transplantation for neuroendocrine tumors in Europe-results and trends in patient selection: a 213-case European liver transplant registry study.

OBJECTIVE: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. BACKGROUND: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. METHODS: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. RESULTS: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. CONCLUSIONS: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

Kinetics of liver function tests after a hepatectomy for colorectal liver metastases predict post-operative liver failure as defined by the International Study Group for Liver Surgery.

BACKGROUND: Post-hepatectomy liver failure (PHLF) has been defined by the International Study Group for Liver Surgery (ISGLS). The purpose of the present study was to examine the kinetics of conventional liver function tests (LFT) after a major liver resection and is the first to examine their utility in predicting PHLF in groups defined by the ISGLS. METHODS: Consecutive patients undergoing a major liver resection for colorectal liver metastases were stratified into ISGLS groups and their LFT up to 1 year after surgery compared. Receiving-operating characteristic (ROC) analysis of LFT identified optimal thresholds in predicting category C liver failure. RESULTS: In total, 32, 22 and 19 patients belonged to ISGLS groups A, B and C, respectively. The median international normalized ratio (INR) and bilirubin values on post-operative days 1, 3, 5 and 7 were significantly different among the groups (all P-values <0.05). ROC analysis of day 1 INR (AUC 0.813) and day 5 bilirubin (AUC 0.798) revealed thresholds of 1.35 and 52 µmol/l to have sensitivities of 85% and 81% and specificities of 63% and 73%, respectively, to predict group C liver failure. DISCUSSION: Post-operative LFT after a major liver resection differs significantly among the three ISGLS groups. Thresholds of bilirubin and INR can be used to identify patients who are at a maximum risk of complications.

Abdominal Organ Preservation Solutions in the Age of Machine Perfusion.

The past decade has been the foreground for a radical revolution in the field of preservation in abdominal organ transplantation. Perfusion has increasingly replaced static cold storage as the preferred and even gold standard preservation method for marginal-quality organs. Perfusion is dynamic and offers several advantages in comparison with static cold storage. These include the ability to provide a continuous supply of new metabolic substrates, clear metabolic waste products, and perform some degree of organ viability assessment before actual transplantation in the recipient. At the same time, the ongoing importance of static cold storage cannot be overlooked, in particular when it comes to logistical and technical convenience and cost, not to mention the fact that it continues to work well for the majority of transplant allografts. The present review article provides an overview of the fundamental concepts of organ preservation, providing a brief history of static cold preservation and description of the principles behind and basic components of cold preservation solutions. An evaluation of current evidence supporting the use of different preservation solutions in abdominal organ transplantation is provided. As well, the range of solutions used for machine perfusion of abdominal organs is described, as are variations in their compositions related to changing metabolic needs paralleling the raising of the temperature of the perfusate from hypothermic to normothermic range. Finally, appraisal of new preservation solutions that are on the horizon is provided.

Treatment and surveillance of polypoid lesions of the gallbladder in the United Kingdom.

OBJECTIVES: The increase in the routine use of abdominal imaging has led to a parallel surge in the identification of polypoid lesions in the gallbladder. True gallbladder polyps (GBP) have malignant potential and surgery can prevent or treat early gallbladder cancer. In an era of constraint on health care resources, it is important to ensure that surgery is offered only to patients who have appropriate indications. The aim of this study was to assess treatment and surveillance policies for GBP among hepatobiliary and upper gastrointestinal tract surgeons in the UK in the light of published evidence. METHODS: A questionnaire on the management of GBP was devised and sent to consultant surgeon members of the Association of Upper Gastrointestinal Surgeons (AUGIS) of Great Britain and Ireland with the approval of the AUGIS Committee. It included eight questions on indications for laparoscopic cholecystectomy and surveillance based on GBP (size, number, growth rate) and patient (age, comorbidities, ethnicity) characteristics. RESULTS: A total of 79 completed questionnaires were returned. The vast majority of surgeons (>75%) stated that they would perform surgery when a single GBP reached 10 mm in size. However, there was a lack of uniformity in the management of multiple polyps and polyp growth rate, with different surveillance protocols for patients treated conservatively. CONCLUSIONS: Gallbladder polyps are a relatively common finding on abdominal ultrasound scans. The survey showed considerable heterogeneity among surgeons regarding treatment and surveillance protocols. Although no randomized controlled trials exist, national guidelines would facilitate standardization, the formulation of an appropriate algorithm and appropriate use of resources.

Role of quantification of hepatic steatosis and future remnant volume in predicting hepatic dysfunction and complications after liver resection for colorectal metastases: a pilot study.

OBJECTIVES: Accurate prediction of safe remnant liver volume to minimize complications following liver resection remains challenging. The aim of this study was to assess whether quantification of steatosis improved the predictive value of preoperative volumetric analysis. METHODS: Thirty patients undergoing planned right or extended right hemi-hepatectomy for colorectal metastases were recruited prospectively. Magnetic resonance imaging was used to assess the level of hepatic steatosis and future remnant liver volume. These data were correlated with data on postoperative hepatic insufficiency, complications and hospital stay. Correlations of remnant percentage, remnant mass to patient mass and remnant mass to body surface area with and without steatosis measurements were assessed. RESULTS: In 10 of the 30 patients the planned liver resection was altered. Moderate-severe postoperative hepatic dysfunction was seen in 17 patients. Complications arose in 14 patients. The median level of steatosis was 3.8% (range: 1.2-17.6%), but was higher in patients (n= 10) who received preoperative chemotherapy (P= 0.124), in whom the median level was 4.8% (range: 1.5-17.6%). The strongest correlation was that of remnant liver mass to patient mass (r= 0.77, P < 0.001). However, the addition of steatosis quantification did not improve this correlation (r= 0.76, P < 0.001). CONCLUSIONS: This is the first study to combine volumetric with steatosis quantifications. No significant benefit was seen in this small pilot. However, these techniques may be useful in operative planning, particularly in patients receiving preoperative chemotherapy.

Inferior vena cava resection with hepatectomy: challenging but justified.

OBJECTIVE: The aim of this study was to evaluate the clinical outcome of hepatectomy combined with inferior vena cava (IVC) resection and reconstruction for treatment of invasive liver tumours. METHODS: From February 1995 to September 2010, 2146 patients underwent liver resections in our hospital's hepatopancreatobiliary unit. Of these, 35 (1.6%) patients underwent hepatectomy with IVC resection. These patients were included in this study. Data were analysed from a prospectively collected database. RESULTS: Resections were carried out for colorectal liver metastasis (CRLM) (n= 21), hepatocellular carcinoma (n= 6), cholangiocarcinoma (n= 3) and other conditions (n= 5). Resections were carried out with total vascular occlusion in 34 patients and without in one patient. In situ hypothermic perfusion was performed in 13 patients; the ante situm technique was used in three patients, and ex vivo resection was used in six patients. There were four early deaths from multiple organ failure. Postoperative complications occurred in 14 patients, three of whom required re-operation. Median overall survival was 29 months and cumulative 5-year survival was 37.7%. Rates of 1-, 2- and 5-year survival were 75.9%, 58.7% and 19.6%, respectively, in CRLM patients. CONCLUSIONS: Aggressive surgical management of liver tumours with IVC involvement offers the only hope for cure in selected patients. Resection by specialist teams affords acceptable perioperative morbidity and mortality rates.

Evolution of the surgical management of perihilar cholangiocarcinoma in a Western centre demonstrates improved survival with endoscopic biliary drainage and reduced use of blood transfusion.

BACKGROUND: Perihilar cholangiocarcinoma (PHCCA) remains a surgical challenge for which few large Western series have been reported. The aims of this study were to investigate the results of surgical resection for PHCCA and assess how practice has evolved over the past 15 years. METHODS: A prospectively maintained database was interrogated to identify all resections. Clinicopathological data were analysed for impact on survival. Subsequently, data for resections carried out during the periods 1994-1998, 1999-2003 and 2004-2008 were compared. RESULTS: Eighty-three patients underwent resection. Trisectionectomy was required in 67% of resections. Overall survival was 70%, 36% and 20% at 1, 3 and 5 years, respectively. Size of tumour, margin (R0) status, lymph node status, distant metastasis, tumour grade, portal vein resection, microscopic direct vascular invasion, T-stage and blood transfusion requirement significantly affected outcome on univariate analysis. Distant metastasis (P = 0.040), percutaneous biliary drainage (P = 0.015) and blood transfusion requirement (P = 0.026) were significant factors on multivariate analysis. Survival outcomes improved and blood transfusion requirement was significantly reduced in the most recent time period. DISCUSSION: Blood transfusion requirement and preoperative percutaneous biliary drainage were identified as independent indicators of a poor prognosis following resection of PHCCA. Longterm survival can be achieved following the aggressive surgical resection of this tumour, but the emergence of a clear learning curve in our analyses indicates that these patients should be managed in high-volume centres in order to achieve improved outcomes.

Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus.

BACKGROUND: Human growth factors are potential therapeutic agents for various inflammatory disorders affecting the gastrointestinal tract. However, they are unstable when administered orally and systemic administration requires high doses increasing the risk of unwanted side effects. Live microorganism-based delivery systems can overcome these problems although they suffer from the inability to control heterologous protein production and there are concerns regarding biosafety and environmental contamination. METHODS: To overcome these limitations we have developed a new live bacteria drug-delivery system using the human commensal gut bacterium Bacteroides ovatus engineered to secrete human growth factors in response to dietary xylan. The anaerobic nature of B ovatus provides an inherent biosafety feature. B ovatus strains expressing human keratinocyte growth factor-2, which plays a central role in intestinal epithelial homeostasis and repair (BO-KGF), were generated by homologous recombination and evaluated using the dextran sodium sulfate (DSS)-induced model of intestinal epithelial injury and colitis. RESULTS: In response to xylan BO-KGF produced biologically active KGF both in vitro and in vivo. In DSS treated mice administration of xylan and BO-KGF had a significant therapeutic effect in reducing weight loss, improving stool consistency, reducing rectal bleeding, accelerating healing of damaged epithelium, reducing inflammation and neutrophil infiltration, reducing expression of pro-inflammatory cytokines, and accelerating production of goblet cells. BO-KGF and xylan treatment also had a marked prophylactic effect limiting the development of inflammation and disruption of the epithelial barrier. CONCLUSION: This novel, diet-regulated, live bacterial drug delivery system may be applicable to treating various bowel disorders.