Arjun Takhar

Propensity score-based analysis of outcomes of laparoscopic versus open liver resection for colorectal metastases.

There is a need for high‐level evidence regarding the added value of laparoscopic (LLR) compared with open (OLR) liver resection. The aim of this study was to compare the surgical and oncological outcomes of patients with colorectal liver metastases (CRLM) undergoing LLR and OLR using propensity score matching to minimize bias.

Outcome and Learning Curve in 159 Consecutive Patients Undergoing Total Laparoscopic Hemihepatectomy

Importance Widespread implementation of laparoscopic hemihepatectomy is currently limited by its technical difficulty, paucity of training opportunities, and perceived long and harmful learning curve. Studies confirming the possibility of a short and safe learning curve for laparoscopic hemihepatectomy could potentially benefit the further implementation of the technique. Objective To evaluate the extent and safety of the learning curve for laparoscopic hemihepatectomy. Design, Setting, and Participants A prospectively collected single-center database containing all laparoscopic liver resections performed in our unit at the University Hospital Southampton National Health Service Foundation Trust between August 2003 and March 2015 was retrospectively reviewed; analyses were performed in December 2015. The study included 159 patients in whom a total laparoscopic right or left hemihepatectomy procedure was started (intention-to-treat analysis), including laparoscopic extended hemihepatectomies and hemihepatectomies with additional wedge resections, at a tertiary referral center specialized in laparoscopic hepato-pancreato-biliary surgery. Main Outcomes and Measures Primary end points were clinically relevant complications (Clavien-Dindo grade ≥III). The presence of a learning curve effect was assessed with a risk-adjusted cumulative sum analysis. Results Of a total of 531 consecutive laparoscopic liver resections, 159 patients underwent total laparoscopic hemihepatectomy (105 right and 54 left). In a cohort with 67 men (42%), median age of 64 years (interquartile range [IQR], 51-73 years), and 110 resections (69%) for malignant lesions, the overall median operation time was 330 minutes (IQR, 270-391 minutes) and the median blood loss was 500 mL (IQR, 250-925 mL). Conversion to an open procedure occurred in 17 patients (11%). Clinically relevant complications occurred in 17 patients (11%), with 1% mortality (death within 90 days of surgery, n = 2). Comparison of outcomes over time showed a nonsignificant decrease in conversions (right: 14 [13%] and left: 3 [6%]), blood loss (right: 550 mL [IQR, 350-1150 mL] and left: 300 mL [IQR, 200-638 mL]), complications (right: 15 [14%] and left: 4 [7%]), and hospital stay (right: 5 days [IQR, 4-7 days] and left: 4 days [IQR, 3-5 days]). Risk-adjusted cumulative sum analysis demonstrated a learning curve of 55 laparoscopic hemihepatectomies for conversions. Conclusions and Relevance Total laparoscopic hemihepatectomy is a feasible and safe procedure with an acceptable learning curve for conversions. Focus should now shift to providing adequate training opportunities for centers interested in implementing this technique.

Aetio-pathogenesis and the management of spontaneous liver bleeding in the West: a 16-year single-centre experience

BACKGROUND Spontaneous liver bleeding (SLB) is a rare but potentially fatal complication. In contrast to the East, various benign pathologies are the source of SLB in the West. An accurate diagnosis and a timely implementation of appropriate treatment are crucial in the management of these patients. The present study presents a large Western experience of SLB from a specialist liver centre. METHODS A retrospective analysis of patients presented with SLB between January 1995 and January 2011. RESULTS Sixty-seven patients had SLB, 44 (66%) were female and the median age at presentation was 47 years. Abrupt onset upper abdominal pain was the presenting symptom in 65 (97%) patients. The aetiology for SLB was hepatic adenoma in 27 (40%), hepatocellular carcinoma (HCC) in 17 (25%) and various other liver pathologies in the rest. Emergency treatment included a conservative approach in 42 (64%), DSA and embolization in 6 (9%), a laparotomy and packing in 6 (9%) and a liver resection in 11 (16%) patients. Eleven (16%) patients had further planned treatments. Seven (10%) died during the same admission but the mortality was highest in patients with HELLP syndrome. At a median follow-up of 54 months all patients with benign disease are alive. The 1-, 3- and 5-year survival of patients with HCC was 59%, 35% and 17%, respectively. CONCLUSION SLB is a life-threatening complication of various underlying conditions and may represent their first manifestation. The management should include initial haemostasis followed by appropriate staging investigations to provide a definitive treatment for each individual patient.

Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population

BACKGROUND Selected populations of murine natural killer (NK) cells possess memory features to haptens, cytokines, and viruses. Liver-specific adhesion molecules CXCR6 and CD49a have been identified as surface markers in mice. In people, expansion of long-lived terminally differentiated NKG2C+ populations occur in the blood after viral infection. We aimed to compare intrahepatic and blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+ NK cells in human liver and define the maturation status of NKG2C+ NK cells at this site. METHODS Tissue samples were taken from the liver margin of 39 patients with hepatic metastases and flushed with chelating buffer followed by collagenase or mechanical digestion. Paired peripheral blood samples were taken from 15 patients, the remainder being unpaired. Mononuclear cells were isolated by ficoll separation and cell surface staining performed for CD3, CD56, CD16, CD57, CD117, CD161, CD158a, CD158b, CD49a, CD49b, CXCR6, NKG2C, and NKp46. Statistical analysis to compare intrahepatic and blood NK cell receptor expression included the median, IQR, and Mann-Whitney U test. FINDINGS Frequencies of NK cell precursors were similar in the liver and the blood (0·91% [0·62-3·26] vs 0·87 [0·41-1·52]); however, expression of all later markers of maturity were reduced including CD16 (47% [40·4-61·4] vs 88·7 [82·2-93·2], p<0·0001), CD57 (30·7% [25·0-53·9] vs 73·4 [70·4-87·6], p=0·0003), and KIR (11·2% [7·5-14·5] vs 26·7 [17·3-30·8], p<0·0001). Expanded hepatic CD16- NK cells were particularly immature with reduced CD57 and increased CD161 compared with the blood. NKG2C+ NK cells were found in similar frequencies in liver and blood. The hepatic NKG2C+ population was terminally differentiated, as in the circulation, but demonstrated a three-fold increase in KIR expression compared with NKG2C- counterparts, which was not seen in the blood. As in previously published research in mice, CD49a+ and CXCR6+ NK cells were liver resident (6·5% [3·9-14·6] liver vs 2·1 [1·3-4·3] blood, p<0·0001, and 65·3 [48·1-75·2] vs 4·5 [1·43-12·12], p=0·0039, respectively). Both populations were immature, with reduced KIR expression. INTERPRETATION We have shown that the liver contains an expanded population of immature CD16- NK cells. These cells might traffic from the blood and then differentiate into hepatic-specific CD49a+ and CXCR6+ NK cells. The function of these subsets is unknown but their immaturity hints against memory. Terminally differentiated NKG2C+ cells show KIR expansion in the human liver and probably represent an antigen-experienced population, raising the question of whether the liver is a site of NK cell memory acquisition. FUNDING MRC Clinical Research Fellowship.

IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells: Tissue-homing natural killer cells

Murine hepatic NK cells exhibit adaptive features, with liver‐specific adhesion molecules CXCR6 and CD49a acting as surface markers.

Alternative Fistula Risk Score for Pancreatoduodenectomy (a-FRS): Design and International External Validation

Objective: The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor. Background: Blood loss, one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations. Methods: The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS. Results: For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture [odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80–3.69], small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61–0.76), and high body mass index (BMI) (per kg/m2 increase, OR: 1.07, 95% CI: 1.04–1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71–0.78) after internal validation, and 0.78 (0.74–0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05). Conclusion: The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.

Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease

Metastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M‐PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy.