Background:Despite intensive research and novel adjuvant therapies, there is currently no cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites such as the liver; however, the therapeutic blockade with the existing agents has proven difficult.Methods:AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for its ability to inhibit the migration of melanoma cells compared with the commonly described antagonist AMD3100.Results:AMD11070 abrogated melanoma cell migration and was significantly more effective than AMD3100. Importantly for the clinical context, the expression of B-RAF-V600E did not the affect the sensitivity of AMD11070.Conclusion:Liver-resident myofibroblasts excrete CXCL12, which is able to promote the migration of CXCR4-expressing tumour cells from the blood into the liver. Blockade of this axis by AMD11070 thus represents a novel therapeutic strategy for both B-RAF wild-type and mutated melanomas.

INTRODUCTIONBetween 4% and 13% of patients with operable pancreatic malignancy are found unresectable at the time of surgery. Double bypass is a good option for fit patients but it is associated with high risk of postoperative complications. The aim of this study was to identify pre-operatively which patients undergoing double bypass are at high risk of complications and to assess their long-term outcome.METHODSOf the 576 patients undergoing pancreatic resections between 2006 and 2011, 50 patients who underwent a laparotomy for a planned pancreaticoduodenectomy had a double bypass procedure for inoperable disease. Demographic data, risk factors for postoperative complications and pre-operative anaesthetic assessment data including the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) and cardiopulmonary exercise testing (CPET) were collected.RESULTSFifty patients (33 men and 17 women) were included in the study. The median patient age was 64 years (range: 39–79 years). The complication rate was 50% and the in-hospital mortality rate was 4%. The P-POSSUM physiology subscore and low anaerobic threshold at CPET were significantly associated with postoperative complications (p=0.005 and p=0.016 respectively) but they were unable to predict them. Overall long-term survival was significantly shorter in patients with postoperative complications (9 vs 18 months). Postoperative complications were independently associated with poorer long-term survival (p=0.003, odds ratio: 3.261).CONCLUSIONSP-POSSUM and CPET are associated with postoperative complications but the possibility of using them for risk prediction requires further research. However, postoperative complications following double bypass have a significant impact on long-term survival and this type of surgery should therefore only be performed in specialised centres.

INTRODUCTION Advanced (pT2/T3) incidental gallbladder cancer is often deemed unresectable after restaging. This study assesses the impact of the primary operation, tumour characteristics and timing of management on re-resection. METHODS The records of 60 consecutive referrals for incidental gallbladder cancer in a single tertiary centre from 2003 to 2011 were reviewed retrospectively. Decision on re-resection of incidental gallbladder cancer was based on delayed interval restaging at three months following cholecystectomy. Demographics, index cholecystectomy data, primary pathology, CA19-9 tumour marker levels at referral and time from cholecystectomy to referral as well as from referral to restaging were analysed. RESULTS Thirty-seven patients with pT2 and twelve patients with pT3 incidental gallbladder cancer were candidates for radical re-resection. Following interval restaging, 24 patients (49%) underwent radical resection and 25 (51%) were deemed inoperable. The inoperable group had significantly more patients with positive resection margins at cholecystectomy (p=0.002), significantly higher median CA19-9 levels at referral (p=0.018) and were referred significantly earlier (p=0.004) than the patients who had resectable tumours. On multivariate analysis, urgent referral (p=0.036) and incomplete cholecystectomy (p=0.048) were associated significantly with inoperable disease following restaging. CONCLUSIONS In patients with incidental, potentially resectable, pT2/T3 gallbladder cancer, inappropriate index cholecystectomy may have a significant impact on tumour dissemination. Early referral of breached tumours is not associated with resectability.

In the bariatric surgery literature, the optimum approach to the gallbladder is controversial. Recommendations range from concomitant cholecystectomy to selective screening and postoperative medical prophylaxis. At our institution, we have taken a highly selective approach where patients are not routinely screened for gallstones, nor are they medically treated postoperatively with bile salts. We have reviewed our experience with this approach. From January 2003 to January 2005, 407 laparoscopic Roux en Y gastric bypasses were performed at UCLA and postoperative outcomes were collected into a prospective database. Exclusion criteria included previous cholecystectomy, a follow-up period less than 6 months, or incomplete records. One hundred ninety-nine patients were included in the study. With a mean follow up period of 17.8 months, 12 (6%) patients required cholecystectomy for gallstone-induced pathology. Laparoscopic removal was performed in 11 (92%) patients. Indications for surgery included acute cholecystitis in five (2.5%) patients, gallstone pancreatitis in two (1%) patients, and biliary colic alone in another five (2.5%) patients. The incidence of symptomatic gallstones requiring cholecystectomy after laparoscopic Roux en Y gastric bypass is low. These results are similar to those from institutions where routine preoperative screening and prophylactic postoperative medical therapy is used. Routine preoperative screening or medical prophylaxis may not be necessary.

A laparoscopic approach is being used increasingly in specialist centres for the resection of hepatocellular carcinomas and compares favourably with the traditional open approach, in terms of perioperative morbidity and mortality as well as long-term survival. We present a case of port site recurrence in a patient who underwent a laparoscopic left lateral segmentectomy for a hepatocellular carcinoma diagnosed during investigation of symptomatic gallstones. Nearly three years following surgery, surveillance computed tomography demonstrated a suspicious lesion at the site of one of the laparoscopic ports. Further resection was carried out and the lesion was confirmed histologically to be an isolated recurrence of the primary hepatocellular carcinoma, involving peritoneum and adominal wall. This case demonstrates that it is possible to encounter port site metastasis following laparoscopic resection of primary liver tumours although the incidence is very rare. Over the last decade, laparoscopic liver resection has become broadly accepted as an alternative to open surgery in appropriately selected patients. The 2008 Louisville consensus statement on laparoscopic liver surgery concluded that small hepatocellular carcinomas (HCCs), either in the context of a normal background liver or compensated cirrhosis, could be safely resected laparoscopically provided that this was undertaken in experienced centres. 2 The authors found that laparoscopic liver resection was associated with less intraoperative blood loss and a reduced incidence of postoperative liver failure but had no impact on either margin positivity rates or tumour recurrence. To our knowledge, there are no published reports of isolated port site recurrence following laparoscopic liver resection for hepatocellular cancer. In this paper, we report one such case occurring nearly three years following liver resection. Case HistoryWe present the case of a 68-year-old woman who, while being investigated for symptomatic gallstone disease, was found on ultrasonography to have a mass lesion in the left lateral aspect of the liver. Subsequent triple phase computed tomography (CT) and liver protocol magnetic resonance imaging confirmed the lesion to have characteristic features of HCC.The patient's past medical history included hyperthyroidism, type 2 diabetes mellitus, hypertension and cerebrovascular disease. She had also received a recent diagnosis of a ductal carcinoma of the left breast and a decision was therefore made to proceed with a laparoscopic cholecystectomy with biopsy of the liver lesion in the first instance. This confirmed the presence of a well differentiated HCC and so she underwent a laparoscopic left lateral liver resection a few weeks later, without complication. The specimen was retrieved in an Endo Catch bag (Covidien, Dublin, Ireland). Histology confirmed the presence of a 45mm Edmondson grade 2 HCC over 3cm from the closest surgical resection margin. The breast cancer was treated subsequently with wide local excision and external beam r...