A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer.

BACKGROUND: The prognosis for patients with hepatocellular cancer (HCC) undergoing transarterial therapy (TACE/TAE) is variable. METHODS: We carried out Cox regression analysis of prognostic factors using a training dataset of 114 patients treated with TACE/TAE. A simple prognostic score (PS) was developed, validated using an independent dataset of 167 patients and compared with Child-Pugh, CLIP, Okuda, Barcelona Clinic Liver Cancer (BCLC) and MELD. RESULTS: Low albumin, high bilirubin or α-fetoprotein (AFP) and large tumour size were associated with a two- to threefold increase in the risk of death. Patients were assigned one point if albumin <36 g/dl, bilirubin >17 µmol/l, AFP >400 ng/ml or size of dominant tumour >7 cm. The Hepatoma arterial-embolisation prognostic (HAP) score was calculated by summing these points. Patients were divided into four risk groups based on their HAP scores; HAP A, B, C and D (scores 0, 1, 2 and >2, respectively). The median survival for the groups A, B, C and D was 27.6, 18.5, 9.0 and 3.6 months, respectively. The HAP score validated well with the independent dataset and performed better than other scoring systems in differentiating high- and low-risk groups. CONCLUSIONS: The HAP score predicts outcomes in patients with HCC undergoing TACE/TAE and may help guide treatment selection, allow stratification in clinical trials and facilitate meaningful comparisons across reported series.

Long-term results of patients with malignant carcinoid syndrome receiving octreotide LAR.

BACKGROUND: Octreotide LAR is an established treatment for malignant carcinoid syndrome. However, studies with large number of patients and long follow-up are lacking. AIM: To present long-terms results with octreotide LAR, assessing duration of clinical and objective response and treatment tolerance, in a large, homogeneous cohort of patients with malignant carcinoid syndrome. METHODS: A total of 108 patients with metastatic midgut neuroendocrine tumours were included in this 8-year study. Clinical evaluation was based on a symptom score. Radiological assessment was based on RECIST (Response Evaluation Criteria In Solid Tumours) criteria. RESULTS: Of the 108 patients, 24% had a sustained symptomatic response. In the remaining patients, loss of symptomatic response with the initial dose was noted within 3-60 months. In 17% of them, symptoms were controlled by just an increase of octreotide LAR dose, whilst the other patients required additional treatment. Overall, in 45.3% of patients, symptoms were well controlled during the study period with only octreotide LAR, and no additional treatment was required. No significant adverse effects were noted. CONCLUSIONS: Octreotide LAR treatment provides a sustained symptomatic response in about half of the patients with malignant carcinoid syndrome and contributes to disease stabilization for a longer period than previously described.

Expression of somatostatin and dopamine 2 receptors in neuroendocrine tumours and the potential role for new biotherapies.

INTRODUCTION: Somatostatin and dopamine receptors are both G-protein-coupled receptors. Somatostatin receptor (SSTR) expression in neuroendocrine tumours has been well characterised, and there is evidence of dopamine receptor expression in neuroendocrine tumours. In this study, we examined expression of D2R, SSTR-2 and SSTR-5 using immunohistochemistry in patients with neuroendocrine tumours. METHODS: Consecutive samples of formalin-fixed paraffin-embedded tumour tissue were available from 56 patients with a histologically confirmed diagnosis of neuroendocrine tumour (NET). The study population was divided into low-grade (n = 29), intermediate-grade (n = 18) and high-grade NET (n = 9). Immunohistochemical evaluation was performed for the expression of SSTR-2a, SSTR-5 and D2 receptors (D2R). RESULTS: Both SSTR-2 and SSTR-5 were expressed in 100% of low-grade, 94.4% of intermediate-grade and 66.7% of high-grade NET. D2R was expressed in 93.1% of low-grade, 77.8% of intermediate-grade and 44.4% of high-grade tumours. Co-expression of all 3 receptors was present in 93.1% of low-grade tumours. There was an inverse correlation of SSTR-2 (r = -0.380, p < 0.005) and SSTR-5 (r = -0.472, p < 0.0001) with tumour grade. D2R was positively correlated with SSTR-2 (r = 0.269, p = 0.041) and SSTR-5 (r = 0.267, p = 0.045). Also, D2R expression was inversely correlated with grade of tumour (r = 0.395, p = 0.006). Octreoscan correlated with SSTR-2, SSTR-5 and D2R expression. CONCLUSION: D2R is expressed in the majority of low and intermediate grade tumours. It is co-expressed with SSTR-2 and SSTR-5 in the majority of cases. The advent of new chimeric molecules that bind both somatostatin and dopamine receptors may provide a new therapeutic option in the management of neuroendocrine patients.

Surgical management and palliative treatment in bronchial neuroendocrine tumours: a clinical study of 45 patients.

Bronchial neuroendocrine tumours account for 1-2% of all lung cancers; they are thought to arise from the neuroendocrine cells located in the bronchial mucosa. The majority of the literature available comprises surgical series and there is a scarcity of data available for the management of patients with inoperable disease. We present a series of 45 patients referred to our institution from 1998 to 2006, with a mean follow-up of 54 months. Histological diagnosis from our department was available for 39 patients, with the remainder having had histological assessment performed previously. Typical carcinoid was present in 25 cases, atypical in 9 cases, large cell neuroendocrine carcinoma in 4 and 1 case of small cell lung carcinoma. All patients were staged at time of initial diagnosis with CT scan, in addition Octreoscans were performed when appropriate. Twenty-six of these 45 cases had unresectable disease, whilst the remainder were treated with surgical resection. Initial therapy with surgical resection was performed in 19 patients, 2 of whom had undergone neo-adjuvant chemotherapy. Recurrence occurred in 7 (36.8%), average duration of disease-free survival post-surgery was 61 months. Chemotherapy was first line therapy in five cases, four achieved disease stabilization and one case had progressive disease. Somatostatin analogues were used as first line therapy in six patients, for symptom control and anti-tumour effect. Peptide receptor radionuclide therapy, with Yttrium-90 DOTA-Octreotate, was given in two cases, both of whom achieved disease stabilization for 9-12 months respectively. There was a significant difference between Stage 4 and Stage 1 disease at presentation and survival. In conclusion curative surgical resection is treatment of choice, however, chemotherapy, somatostatin analogues and peptide receptor radionuclide therapy offers palliation improving both symptoms and mortality.

Tumour size and differentiation in predicting recurrence of hepatocellular carcinoma after liver transplantation: external validation of a new prognostic score.

BACKGROUND: A new prognostic score including tumour differentiation--establishing two groups of patients: group A with >3 points and group B with >4 points--improved the accuracy of the Milan criteria in predicting recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) in a large multicentre study (Decaens 2007). AIM: The aim of this study was to validate the new score in our HCC cohort. METHODS: The study involved 100 consecutive patients with mean age 55 years (range 31-68 years) (M/F: 88/22) transplanted for known HCC: 60 unifocal and 40 multifocal (2-3 nodules in 32 and >or=4 nodules in 8) at pre-LT imaging. Survival differences were analysed by log-rank test. Patient/tumour variables before LT and tumour differentiation at explant were assessed by univariate/multivariate analysis. RESULTS: Median follow-up was 29 months (range 1-145 months). HCC recurrence was recorded in 18 patients. Five-year recurrence-free survival rate was 67 +/- 7%. Patient survival at 3 months was 84 +/- 4% and at 5 years was 45 +/- 6%. Both recurrence-free survival and patient survival were not significantly different between groups A and B. Diameter of largest nodule was the sole pre-LT variable independently associated with recurrence [odd ratio (OR) 1.07; 95% confidence interval (CI) 1.01-1.12; P = 0.012]. Recurrence-free survival was significantly better in patients with diameter <30 mm compared with those with larger nodules (P = 0.0229). Number of nodules and tumour differentiation did not influence recurrence. There were three HCC recurrences with largest nodule size <30 mm, seven recurrences between 30-40 mm, and eight recurrences >40 mm. CONCLUSION: Tumour differentiation did not add significantly to prediction of HCC recurrence in our cohort. Conversely, diameter of the largest nodule remained a significant risk for recurrence.

Review article: renal function assessment in cirrhosis - difficulties and alternative measurements.

BACKGROUND: Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of serum creatinine in the model for end-stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA. AIM: To review the accuracy of the surrogate markers for the assessment of renal function, i.e. glomerular filtration rate, particularly in patients with cirrhosis. METHOD: We reviewed the available literature in PubMed regarding the markers for GFR evaluation and the factors which affect their accuracy in cirrhosis. RESULTS: Although creatinine is widely available, it is an unreliable marker of glomerular filtration rate, particularly in patients with cirrhosis. Clearance of exogenous markers is considered the 'gold standard', but this methodology has many drawbacks, particularly poor applicability. Several mathematical formulae for estimated glomerular filtration rate are used to overcome some of these limitations: Cockcroft-Gault and Modification of Diet in Renal Disease formulae are the most frequently applied, but they are based on serum creatinine. CONCLUSIONS: Due to the inaccuracy of serum creatinine and its derived formulae in estimating glomerular filtration rate, alternative serum markers, such as cystatin C, and new formulae are desirable. These need formal evaluation in patients with cirrhosis so as to have a reliable surrogate of glomerular filtration rate, and to obviate many problems that are associated with using creatinine and estimated glomerular filtration rate.

Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC.

BACKGROUND: Tumour biopsy is usually considered mandatory for patient management by oncologists. Currently percutaneous ablation is used therapeutically for cirrhotic patients with small hepatocellular carcinoma (HCC), not suitable for resection or waiting for liver transplantation. However malignant seeding is a recognized complication of both diagnostic and therapeutic procedures in patients with HCC. Although percutaneous therapy whether with or without biopsy of a suspected HCC nodule may minimize the risk of seeding, this has not been confirmed. AIM: To evaluate the risk of seeding, defined as new neoplastic disease occurring outside the liver capsule, either in the subcutaneous tissue or peritoneal cavity following needle biopsy and/or local ablation therapy (LAT). METHODS: A literature search resulted in 179 events in 99 articles between January 1983 and February 2007: 66 seedings followed liver biopsy, 26 percutaneous ethanol injection (PEI), 1 microwave, 22 radiofrequency ablation (RFA), and 64 after combined biopsy and percutaneous treatment (5 microwave; 33 PEI; 26 RFA). RESULTS: In 41 papers specifying the total number of patients biopsied and/or treated, the median risk of seeding was 2.29% (range 0-11%) for biopsy group; 1.4% (1.15-1.85%) for PEI when used with biopsy and 0.61% (0-5.56%) for RFA without biopsy, 0.95% (0-12.5%) for RFA with biopsy and 0.72% (0-10%) for liver nodules (including non-HCC nodules) biopsied and ablated. CONCLUSION: Risk of seeding with HCC is substantial and appears greater with using diagnostic biopsy alone compared to therapeutic percutaneous procedures. This risk is particularly relevant for patients being considered for liver transplantation.

The transjugular route: the key hole to the liver world.

Portal hypertensive complications are major causes of morbidity and mortality in patients with liver cirrhosis. The advent of the transjugular route with its minimal access allows non-surgical management of portal hypertension, therapy of venous complications of liver transplantation, monitoring of therapy for portal hypertension, hepatic venous pressure gradient and is also the major route to treat hepatic venous obstruction syndromes. In addition, the transjugular route is a safe route to perform a liver biopsy (transjugular liver biopsy) and allows retrograde evaluation of the portal vein. All these procedures can be combined in the same session. These hepatic interventional radiological skills should be incorporated into the expertise of the liver team in specialised hepatological centres, particularly in liver transplant centres as they are especially useful in improving outcomes of cirrhotic patients on the liver transplantation waiting list. A limitation in achieving this goal, could be the number of experienced radiologists, but hepatologists can be trained, at least for the most simple procedures (transjugular liver biopsy and hepatic venous pressure gradient). This would allow wider applicability and use of these diagnostic and therapeutic techniques, all through a 2 mm hole in the neck--the key hole to the liver world.

Female liver transplant recipients with the same GFR as male recipients have lower MELD scores--a systematic bias.

Women have lower glomerular filtration (GFR) than men for the same serum creatinine (Cr) value, not accounted for in model for end-stage liver disease (MELD). We compare male/female Cr, GFR (using MDRD formula) and respective MELD scores in 403 Cr measurements using standard (sCr), O'Leary modified (mCr) and Compensated (cCr) Jaffe and Enzymatic (eCr) in 158 liver disease patients, mCr in 208 liver transplantation (LT) candidates, and EDTA-Cr(51)-GFR in 38 other candidates for LT; considering each female as male, a 'corrected' Cr was derived. MELD scores were calculated for measured and "corrected" Cr in females. Median Cr and GFR in females were lower than males (p < 0.05). Both MDRD and EDTA-Cr(51) GFR were lower in females than males, despite lower Cr values. In females, each MELD score was lower than the corresponding MELD-corrected Cr (p < 0.001) with > or =three-point difference in liver disease patients: 25%[sCr]; 23%[mCr]; 11%[eCr]; and 14%[cCr]. In 65% of female LT candidates, two- or three-point difference was found. Females with liver disease have lower GFR than males for the same Cr value; correcting Cr increases MELD score by two or three points in 65% of female LT candidates. MELD score adjustment in females would ensure equal LT priority by gender.