Alastair L. Young

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.

Repeat hepatic resection for colorectal liver metastases.

Some 75–80 per cent of patients undergoing liver resection for colorectal liver metastases develop intrahepatic recurrence. A significant number of these can be considered for repeat liver surgery. This study examined the outcomes of repeat liver resection for the treatment of recurrent colorectal metastases confined to the liver.

Variation in referral practice for patients with colorectal cancer liver metastases

Half of patients with colorectal cancer develop liver metastases. There remains great variability between hospitals in rates of liver resection for colorectal cancer liver metastases (CLM). This study aimed to determine how many patients with potentially resectable CLM are not seen by specialist liver surgeons.

Portal Vein Arterialization as a Salvage Procedure During Left Hepatic Trisectionectomy for Hilar Cholangiocarcinoma

d h c r s urgical resection for hilar cholangiocarcinoma (HCCA) emains a challenge for surgeons aiming to maximize paients’ chances for longterm survival. Since 1984, it has een accepted that standard bile duct resection should be ombined with an additional major hepatic resection to btain improved oncological clearance and increase quanity and quality of survival. This aggressive approach was nitially criticized, but today a consensus exists that perorming such extended resections is the treatment of choice or HCCA.There is strong evidence of better survival when 0 resection is performed. The extended resections that nable a better oncological clearance have become achievble as a result of the major advances in surgical techniques nd preoperative and postoperative care, which have reuced morbidity and mortality after major liver resection. Recent studies suggest that portal vein resection with econstruction can increase the chance for cure in some atients with advanced HCCA who were previously hought to have inoperable disease. Because perineual invasion correlates with poorer outcomes, theoretically, esection of the hepatic artery with its nerve sheath will uarantee an even better oncological result. Arterial resecion and reconstruction can be technically problematic and ometimes unachievable, with very few cases reported in he literature. To overcome this, a recent study rom Japan by Kondo and colleagues has reported 10 cases f portal vein arterialization (PVA) after hepatic artery reection for biliary cancers, with some accompanied by mall hepatic resections. We report a case where PVA was used with good result as salvage technique during left hepatic trisectionectomy nd a second case where the same technique was used to

The value of MELD and sodium in assessing potential liver transplant recipients in the United Kingdom

As the result of the widening gap between supply and demand of organs for liver transplantation, efforts to improve allocation have become an increasingly important yet controversial subject. The MELD score has been adopted in the USA but its usefulness has rarely been examined in Europe. We carried out an intention to treat analysis of 422 patients placed on our transplant waiting list over a 5‐year period. We examined multiple variables to investigate the value of MELD, sodium and other factors in predicting post‐transplant outcomes. MELD at transplant was the most important indicator of post‐transplant outcomes. In addition, delta‐MELD and hyponatreamia were significant at predicting, which patients placed on the waiting list would not proceed to transplant. While a move to allocating solely by MELD is not justified in the UK allocation system, there is value in using MELD, delta‐MELD and hyponatreamia in making decisions regarding the allocation of organs. This may subsequently help to improve overall outcomes.

Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors

Background: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience. Methods: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. Jamess University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared. Results: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90‐day mortality (2.5% vs 13.6%, respectively), disease‐specific 5‐year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival. Conclusion: Disease‐specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long‐term survival.

Index admission laparoscopic cholecystectomy for patients with acute biliary symptoms: results from a specialist centre

BACKGROUND Index admission laparoscopic cholecystectomy (ALC) is the treatment of choice for patients admitted with biliary symptoms but is performed in less than 15% of these admissions. We analysed our results for ALC within a tertiary hepatobiliary centre. METHODS Data from all cholecystectomies carried out under the care of the two senior authors from 1998 to 2008 were prospectively collected and interrogated. RESULTS 1710 patients underwent cholecystectomy of which 439 (26%) were ALC. Patients operated on acutely did not have a significantly different complication rate (P= 0.279; 4% vs.3%). Factors predicting complications were abnormal alkaline phosphatase (ALP) (P= 0.037), dilated common bile duct (CBD) (P= 0.026), cholangitis (P= 0.040) and absence of on table cholangiography (OTC) (P= 0.011). There were no bile duct injuries. Patients undergoing ALC had a higher rate of conversion to an open procedure (P < 0.001:10% vs.3%). The proportion of complicated disease was higher in the ALC group (P < 0.001; 70% vs.31%). Only complicated disease (P= 0.006), absence of OTC (P < 0.001) and age greater than 65 years (P < 0.001) were predictive of conversion on multivariate analysis. CONCLUSIONS Laparoscopic cholecystectomy can be performed safely in patients with acute biliary symptoms and should be considered the gold standard for management of these patients thus avoiding avoidable readmissions and life-threatening complications. A higher conversion rate to an open procedure must be accepted when treating more complicated disease. It is the severity of disease rather than timing of surgery which most probably predicts complications and conversions.

The effect of Liver Transplantation on the quality of life of the recipient's main caregiver - a systematic review.

Liver transplantation (LT) is a transformative, life‐saving procedure with life‐long sequale for patients and their caregivers. The impact of LT on the patients main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health‐Related Quality of Life (HRQL) of LT patients’ main caregivers. We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however, the other four showed caregivers levels of stress, anxiety and depression, remained similar or got worse post‐LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data were available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. The current information about LT caregivers’ needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients’ family and caregivers to understand the importance of caregiver support to maximize outcomes of LT for the patient and their caregivers.

Regional differences in prostaglandin E2 metabolism in human colorectal cancer liver metastases

BackgroundProstaglandin (PG) E2 plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE2 catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE2 content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE2 in human CRC cells in vitro.MethodsTissue from the periphery and centre of 20 human CRCLM was analysed for PGE2 levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) β.ResultsPGE2 levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE2. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo.ConclusionsThere is significant intra-tumoral heterogeneity in PGE2 content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE2 metabolism should be targeted for novel treatment of advanced CRC.

Posterior Superior Mesenteric Artery First Dissection Versus Classical Approach in Pancreaticoduodenectomy: Outcomes of a Case-Matched Study.

Objectives Posterior superior mesenteric artery (SMA) first dissection in pancreaticoduodenectomy (PD) may allow for early assessment of resectability and aberrant anatomy. Study objectives were to compare resection margins, perioperative outcomes, disease-free survival (DFS) and overall survival (OS) in patients undergoing a posterior SMA first dissection PD to a classical technique PD. Methods Patients (n = 77) who underwent a posterior SMA first PD for adenocarcinoma were case matched for patient and tumor characteristics with patients undergoing a classical approach PD from 2006 to 2014 (n = 177). Results The SMA first patients had an improved negative resection margin rate (27 [35.1%] vs 14 [18.2%], P = 0.042) and a higher lymph node yield (median 28 [22–34] vs 21 [17–27], P < 0.001) compared with the classical approach group. No difference was demonstrated in serious complications or 30-day mortality between the SMA first and classical approach patients (Clavien-Dindo 3/4 16 [20.8%] vs 11 [14.3%], P = 0.336; 30-day mortality 3 [3.9%] vs 3 [3.9%], P = 1.00 respectively). Median DFS and OS was similar in SMA first compared with classical approach patients (DFS, 1.6 vs 1.1 years, P = 0.122; OS, 2.5 vs 1.5 years, P = 0.220 respectively). Conclusions A posterior SMA first approach is a comparably safe technique that may improve oncological results in PD compared with classical approach dissection.