Raj Prasad

The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases

The nature of the invasive growth pattern and microvessel density (MVD) have been suggested to be predictors of prognosis in primary colorectal cancer (CRC) and colorectal liver metastases. The purpose of the present study was to determine whether these two histological features were interrelated and to assess their relative influence on disease recurrence and survival following surgical resection. Archival tissue was retrieved from 55 patients who had undergone surgical resection for primary CRC and matching liver metastases. The nature of the invasive margin was determined by haematoxylin and eosin (H&E) histochemistry. Microvessel density was visualised using immunohistochemical detection of CD31 antigen and quantified using image capture computer software. Clinical details and outcome data were retrieved by case note review and collated with invasive margin and MVD data in a statistical database. Primary CRCs with a pushing margin tended to form capsulated liver metastases (P<0.001) and had a significantly better disease-free survival than the infiltrative margin tumours (log rank P=0.01). Primary cancers with a high MVD tended to form high MVD liver metastases (P=0.007). Microvessel density was a significant predictor of disease recurrence in primary CRCs (P=0.006), but not liver metastases. These results suggest that primary CRCs and their liver metastases show common histological features. This may reflect common mechanisms underlying the tumour–host interaction.

Circulating markers of biliary malignancy: opportunities in proteomics?

Cholangiocarcinoma, a primary liver tumour that arises from biliary epithelial cells, is increasing in incidence and has poor prognosis. Diagnosis is difficult, particularly in patients with primary sclerosing cholangitis, who are at risk of developing the disease. Timely diagnosis is essential because surgical resection in early disease remains the only cure. The lack of a sensitive and specific early diagnostic marker and of alternative treatments are the main reasons why patients have limited survival. The use of proteomic-based approaches, which analyse the physiological or pathological complement of proteins (ie, the proteome) in cells, tissues, or biological fluids, has received substantial interest in biomarker discovery. Proteomics complements genomic studies and examines functional end-units quantitatively and qualitatively, including post-translational modifications which might vary with disease and might have key roles in protein function or localisation. Major advances in technology and bioinformatics have enhanced proteomic studies, resulting in increased understanding of the pathogenesis of many diseases and in biomarker discovery with effective use of tissues, cell lines, and biological fluids. We review the current status and promise of proteomic-based approaches in biomarker discovery for cholangiocarcinoma.

Quantitative Assessment of Hepatic Function and its Relevance to the Liver Surgeon

BackgroundStandard evaluation of patients undergoing hepatic surgery has been through radiological and quantitative determination of liver function. As more complex and extensive surgery is now being performed, often in the presence of cirrhosis/fibrosis or following administration of chemotherapy, it is questioned whether additional assessment may be required prior to embarking on such surgery. The aim of this review was to determine the current knowledge base in relation to the performance of quantitative assessment of hepatic function both pre- and post-operatively in patients undergoing hepatic resectional surgery and liver transplantation.MethodsAn electronic search was performed of the medical literature using the MEDLINE database to identify relevant articles with cross-referencing of all identified papers to ensure full literature capture.Results and ConclusionsThe review has identified a number of different methods of dynamically assessing hepatic function, the most frequently performed being through the use of indocyanine green clearance. With the recent and further anticipated developments in hepatic resectional surgery, it is likely that quantitative assessment will become more widely practiced in order to reduce post-operative hepatic failure and improve outcome.

Hepatic artery pseudoaneurysm after liver transplantation: treatment with percutaneous thrombin injection.

Pseudoaneurysms of the hepatic artery are a rare complication of liver transplantation. Early diagnosis and treatment are essential to avoid life-threatening hemorrhage. Conventional treatment consists of surgical resection and vascular reconstruction or transarterial coil embolization. More recently, percutaneous thrombin injection has been successfully used in the treatment of femoral artery pseudoaneurysms. We describe a 70-year-old woman who had a hepatic artery pseudoaneurysm after orthotopic liver transplantation, which was successfully treated by percutaneous thrombin injection.

Indication for treatment and long-term outcome of focal nodular hyperplasia

INTRODUCTION Unlike malignant liver tumours, the indications for hepatic resection for benign disease are not well defined. This is particularly true for focal nodular hyperplasia (FNH). Here we summarize a single-centre experience of the diagnosis and management of FNH. MATERIALS AND METHODS Using a prospectively collected database, a retrospective analysis of consecutive patients who were managed at our centre for FNH between January 1997 and December 2006 was performed. RESULTS The cohort was divided into two groups of patients: those who were managed surgically (n=15) and those managed conservatively (n=37). There was no correlation between tumour size and number of lesions with oral contraceptive use (p=0.07 and 0.90, respectively) and pregnancy (p=0.45 and 0.60, respectively). However, tumour size (p=0.006) and number of lesions (p=0.02) were associated with the occurrence of pain in these patients. Pain was the commonest symptom of patients (13/15) who were managed surgically. All patients underwent radiological imaging before diagnosis. The sensitivities of ultrasound, CT scanning and MRI scanning in characterizing these lesions were 30%, 70% and 87%, respectively. There were no postoperative deaths and three postoperative complications that were successfully managed non-operatively. With a median follow-up of 24 months in the surgically treated group, one patient has developed recurrent symptoms of pain. CONCLUSION. In this series, there was no mortality directly due to the surgical procedure and a modest morbidity, justifying surgical resections in selected patients.

Expression patterns of hypoxic markers at the invasive margin of colorectal cancers and liver metastases.

AIM To understand the role of hypoxia in cancer progression of primary colorectal cancer and colorectal liver metastases. To look at associations of hypoxia with more aggressive phenotypes. METHODS Archival tissue was retrieved from 55 patients and tissue micro arrays were constructed using tissue from the margin and the centre of the tumour. Hypoxia markers Hif-1alpha, Vegf, CA-9, VHL and Glut-1 were visualised using immunohistochemical detection and quantified using semi-quantitative analysis of the digitised images. Clinical details and outcome data were retrieved by case note review and collated with hypoxia markers data in a statistical database. RESULTS Significantly increased expression of all markers were found at the tumour margin compared to the tumour centre, both in primary colorectal cancer (CRC) and liver metastases. Pushing margin CRC was associated with increased Vegf expression. Positive correlations were observed between Hif-1alpha and Vegf (p<0.001), and Hif-1alpha and VHL (p<0.001) in primary CRC, but no relationship was seen between Hif-1alpha and either Glut-1 or CA-9. A significant trend to worse disease-free survival was also noted with increased margin expression of Hif-1alpha (p<0.001) and VHL (p=0.02) in primary CRC, but not for any of the other markers. CONCLUSION This study underlines the importance of the invasive margin in colorectal cancer biology. It is the area most responsive to hypoxic influences and its dependence on its ability to up-regulate Hif-1alpha has a significant impact on disease-free survival.

Intermittent Pringle manoeuvre is not associated with adverse long-term prognosis after resection for colorectal liver metastases.

Intermittent clamping of the porta hepatis, or the intermittent Pringle manoeuvre (IPM), is often used to control inflow during parenchymal liver transection. The aim of this study was to determine whether IPM is associated with an adverse long‐term outcome after liver resection for colorectal liver metastasis (CRLM).

Meta-analysis of self-gripping mesh (Progrip) versus sutured mesh in open inguinal hernia repair.

BACKGROUND This metaanalysis was designed to systematically analyse all published randomized controlled trials comparing self-gripping mesh (ProGrip) and sutured mesh to analyse early and long term outcomes for open inguinal hernia repair. METHODS A literature search was performed using the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase and Science Citation Index Expanded. Randomized trials comparing self-gripping mesh with sutured mesh were included. Statistical analysis was performed using Review Manager Version 5.2 software. The primary outcome measures were hernia recurrence and chronic pain after operation. Secondary outcome measures included surgical time, wound complications and perioperative complications. RESULTS Five randomized trials were identified as suitable, including 1170 patients. There was no significant difference between the two types of mesh repairs in perioperative complications, wound haematoma, chronic groin pain and hernia recurrence. Wound infection was lower in self gripping mesh group compared to sutured mesh but this was not statistically significant (risk ratio (RR) 0.57, 95% confidence interval 0.30-1.06, P = 0.08). The duration of operation was significantly shorter with self-gripping mesh compared to sutured mesh with a mean difference of -5.48 min [-9.31, -1.64] Z = 2.80 (P = 0.005). CONCLUSION Self-gripping mesh was associated with shorter operative time compared to sutured mesh. Both types of mesh repairs have comparable perioperative and long term outcomes.

Outcomes in right liver lobe transplantation: a matched pair analysis.

Split liver transplantation (SLT) has proven to be an effective technique of increasing the donor pool and thereby reducing adult and paediatric waiting list mortality. There remains concern regarding complications in adult recipients. Here, we compare SLT with matched whole liver grafts. Adult recipients of primary extended right lobe grafts (ERL) were matched to recipients of whole liver transplantations (WLTs) according to the following criteria: model of end‐stage liver disease (MELD) score, recipient age, indication for liver transplantation and year of transplantation. Twenty‐seven pairs of recipients were transplanted for chronic liver disease. The overall 30‐day patient survival rates after ERL and WLT were 88.9% and 92.5% and 3‐year survival rates after SLT and WLT were 77.8% and 85.2% respectively (log‐rank = 0.38). Two patients with SLTs had hepatic artery thromboses and were retransplanted with none from the WLT group. The prevalence of a biliary leak was higher among the SLT group (n = 4) compared with none in the WLT group (P = 0.05). Patients with preoperative hyponatraemia showed a trend towards poorer survival after SLT compared with WLT. Our data suggest that SLT with extended right liver lobes, although not significantly different, shows a trend towards a poorer outcome.

Renal function evaluated by measured GFR during follow‐up in pediatric liver transplant recipients

Abstract:  Calcineurin inhibitors form the mainstay of immunosuppression in pediatric liver transplantation, but may cause significant nephrotoxicity. We evaluated renal function in liver transplant recipients treated with a tacrolimus‐based immunosuppressive regimen. GFR was measured using 99 mTc‐DTPA in patients pretransplant and annually thereafter. GFR calculated by Schwartz formula was compared with the measured values. Sixty patients who underwent 69 transplants were followed for at least one yr post‐transplant (median three yr). In children over two yr of age at transplant GFR fell significantly from pretransplant (140 mL/min/1.73 m2) to one yr post‐transplant (112 mL/min/1.73 m2) (p = 0.01) but thereafter there was no significant decline. In younger children the picture was confounded by maturation of renal function, but again there was no significant fall to five yr post‐transplant. Although 13 (22%) patients developed renal dysfunction post‐transplant, none required renal replacement therapy. cGFR correlated poorly with measured values (r = 0.21). Use of a tacrolimus‐based immunosuppressive regimen is associated with an initial decline in GFR, though this picture is confounded in younger children by normal maturation of renal function. There is no further significant fall in GFR in the medium‐term. The Schwartz formula is inaccurate in determining GFR in this patient group.