The place of downstaging for hepatocellular carcinoma

In the treatment of hepatocellular carcinomas, therapies such as trans-arterial chemo-embolisation, trans-arterial radioembolisation, percutaneous ethanol injection and radio-frequency ablation can decrease the size (and overall viability) of the tumours, thus potentially increasing the proportion of patients qualifying for resection and transplantation.While the use of such downstaging therapies is straightforward when resection is the aim, in a similar way to other neo-adjuvant treatments in the surgery of tumours that are too large or awkwardly placed to be primarily resected the issues related to transplantation are more complex. In the context of transplantation the word “downstaging” designates not only a neo-adjuvant treatment, but also a selection strategy to allow patients who are initially outside accepted listing criteria to benefit from transplantation should the neo-adjuvant therapy be successful in reducing tumour burden. The effectiveness of downstaging as a selection strategy, at first questioned because of methodological bias in the studies that described it, has been recently demonstrated by more solid prospective investigations. Several issues however remain open, such as inclusion criteria before the strategy is implemented (size/number, surrogate markers of differentiation/vascular invasion such as alpha-fetoprotein), the choice of which downstaging therapy, the end-points of treatment, and the need and duration of a period of observation proving disease response or stabilisation before the patient can be listed.The present review discusses which treatments and strategies are available for downstaging HCC on the basis of the published literature

Spontaneous Resolution of Brain Edema in Fulminant Hepatic Failure due to Hepatitis E

Fulminant hepatic failure is characterized by the presence of hepatic encephalopathy in the setting of acute liver injury that occurs in a noncirrhotic organ. Brain edema is the ultimate complication of advanced hepatic encephalopathy as it often leads to cerebral herniation and death. Thus, the presence of fulminant hepatic failure indicates the need for urgent liver transplantation to prevent death or irreversible brain damage. We report a very unusual evolution of fulminant hepatic failure complicated by brain edema and hepatic coma in a 45-year-old woman admitted with acute viral hepatitis E infection

Image-guided multipolar radiofrequency ablation of liver tumours: initial clinical results

The local effectiveness and clinical usefulness of multipolar radiofrequency (RF) ablation of liver tumours was evaluated. Sixty-eight image-guided RF sessions were performed using a multipolar device with bipolar electrodes in 53 patients. There were 45 hepatocellular carcinomas (HCC) and 42 metastases with a diameter ≤3cm (n = 55), 3.1-5cm (n = 29) and >5cm (n = 3); 26 nodules were within 5mm from large vessels. Local effectiveness and complications were evaluated after RF procedures. Mean follow-up was 17 ± 10months. Recurrence and survival rates were analysed by the Kaplan-Meier method. The primary and secondary technical effectiveness rate was 82% and 95%, respectively. The major and minor complication rate was 2.9%, respectively. The local tumour progression at 1- and 2-years was 5% and 9% for HCC nodules and 17% and 31% for metastases, respectively; four of 26 nodules (15%) close to vessels showed local progression. The survival at 1year and 2years was 97% and 90% for HCC and 84% and 68% for metastases, respectively. Multipolar RF technique creates ablation zones of adequate size and tailored shape and is effective to treat most liver tumours, including those close to major hepatic vessel

Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis

Biliary intraepithelial neoplasia (BilIN), a preneoplastic condition that may precede invasive intrahepatic cholangiocarcinoma (ICC), has been compared to pancreatic intraepithelial neoplasia (PanIN), a precursor lesion of pancreatic carcinoma. Biliary tract carcinoma development and progression is associated with several gene alterations, but BilIN lesions have yet to be studied in detail by molecular techniques. We describe a case of extensive intrahepatic biliary dysplasia, with lesions ranging from BilIN-1 to BilIN-3 lesions, and multifocal microscopic ICC in hepatitis C virus (HCV)- and alcohol-related cirrhosis. The small ICC foci had remained undetected prior to transplantation. Fluorescence in situ hybridization (FISH) analysis was performed on three foci of BilIN-3 lesions and on three microinvasive ICC foci with a combination of three FISH probes directed against genes frequently altered in pancreatic and biliary tract carcinomas. FISH analysis revealed a CDKNA2 heterozygous deletion in one BilIN-3 focus, and in one non-contiguous ICC focus, although the deletion was just above the chosen threshold. No deletions were detected in the genomic regions encoding TP53 and SMAD4. This report documents for the first time the development of multifocal ICC in the setting of extensive biliary dysplasia in a patient with three risk factors, HCV infection, alcohol abuse, and cirrhosis, and suggests heterogeneous carcinogenesis in ICC and possible involvement of the CDKNA2 gen

Neoadjuvant Chemotherapy in Patients with Stage IV Colorectal Cancer: A Comparison of Histological Response in Liver Metastases, Primary Tumors, and Regional Lymph Nodes

Background: We report the histopathological results of a novel "inversed” strategy designed to manage patients with colorectal cancer (CRC) who have synchronous liver metastases by using chemotherapy first, liver surgery second, and resection of the primary tumor as a final step. This study was designed to compare the response to chemotherapy in liver metastases, primary tumors, and locoregional lymph nodes. Methods: Twenty-nine patients with stage IV CRC received a combination of oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin (OCFL) for 3-4months. Histological response to chemotherapy was assessed by using a tumor regression grading (TRG) score based on presence of residual tumor cells and extent of fibrosis. Results: Median age of patients was 56 (range, 37-69) years. Primary tumor location was right colon (n=5), left colon (n=7), and rectum (n=17 patients). TRG scores correlated across disease sites (Spearman correlation coefficients for TRG in the primary tumor and lymph nodes was 0.59 [P=0.005]; for the primary tumor and metastases 0.44 [P=0.021]; and for lymph nodes and metastases 0.58 [P=0.006]). Complete absence or poor tumor response (TRG4/5) was significantly more frequent in primary tumors (35.7%) and locoregional lymph nodes (38%) than in liver metastases (6.9%; McNemar test, P=0.02). Two patients had a complete pathologic response (pT0N0M0). Conclusions: In patients with stage IV colorectal cancer, liver metastases exhibit a better histological response than primary tumors to OCFL neoadjuvant chemotherap

Radiofrequency ablation of small liver malignancies under magnetic resonance guidance: progress in targeting and preliminary observations with temperature monitoring

Objectives: To evaluate the feasibility and effectiveness of magnetic resonance (MR)-guided radiofrequency (RF) ablation for small liver tumours with poor conspicuity on both contrast-enhanced ultrasonography (US) and computed tomography (CT), using fast navigation and temperature monitoring. Methods: Sixteen malignant liver nodules (long-axis diameter, 0.6-2.4cm) were treated with multipolar RF ablation on a 1.5-T wide-bore MR system in ten patients. Targeting was performed interactively, using a fast steady-state free precession sequence. Real-time MR-based temperature mapping was performed, using gradient echo-echo planar imaging (GRE-EPI) and hardware filtering. MR-specific treatment data were recorded. The mean follow-up time was 19 ± 7months. Results: Correct placement of RF electrodes was obtained in all procedures (image update, <500ms; mean targeting time, 21 ± 11min). MR thermometry was available for 14 of 16 nodules (88%) with an accuracy of 1.6°C in a non-heated region. No correlation was found between the size of the lethal thermal dose and the ablation zone at follow-up imaging. The primary and secondary effectiveness rates were 100% and 91%, respectively. Conclusions: RF ablation of small liver tumours can be planned, targeted, monitored and controlled with MR imaging within acceptable procedure times. Temperature mapping is technically feasible, but the clinical benefit remains to be prove

Systematic review and meta-analysis of fibrin sealants for patients undergoing pancreatic resection

AbstractIntroductionPost-operative pancreatic fistula (POPF) is a common complication after partial pancreatic resection, and is associated with increased rates of sepsis, mortality and costs. The role of fibrin sealants in decreasing the risk of POPF remains debatable. The aim of this study was to evaluate the literature regarding the effectiveness of fibrin sealants in pancreatic surgery.MethodsA comprehensive database search was conducted. Only randomized controlled trials comparing fibrin sealants with standard care were included. A meta-analysis regarding POPF, intra-abdominal collections, post-operative haemorrhage, pancreatitis and wound infections was performed according to the recommendations of the Cochrane collaboration.ResultsSeven studies were included, accounting for 897 patients. Compared with controls, patients receiving fibrin sealants had a pooled odds ratio (OR) of developing a POPF of 0.83 [95% confidence interval (CI): 0.6–1.14], P = 0.245. There was a trend towards a reduction in post-operative haemorrhage (OR = 0.43 (95%CI: 0.18–1.0), P = 0.05) and intra-abdominal collections (OR = 0.52 (95%CI: 0.25–1.06), P = 0.073) in those patients receiving fibrin sealants. No difference was observed in terms of mortality, wound infections, re-interventions or hospital stay.ConclusionOn the basis of these results, fibrin sealants cannot be recommended for routine clinical use in the setting of pancreatic resection

Ablation of hepatocellular carcinoma by percutaneous ethanol injection: Imaging findings

Summary: Since PEI is a treatment based on imaging techniques, the radiologist should be familiar with the various findings that may be observed after PEI on US, CT, and MR images immediately after treatment and during later follow-up. Although US is well suited for performing PEI, contrast-enhanced CT currently is the most commonly used imaging method to evaluate the effect of PEI. Residual, nodular areas of contrast enhancement correlate well with residual tumor and warrant additional treatment. Although the findings on MR images obtained after PEI are more complex, MR imaging may be used as an alternative to C

Survival after Lung Metastasectomy in Colorectal Cancer Patients with Previously Resected Liver Metastases

Background: Resection of hepatic metastases is indicated in selected stage IV colorectal cancer (CRC) patients. A minority will eventually develop pulmonary metastases and may undergo lung surgery with curative intent. The aims of the present study were to assess clinical outcome and identify parameters predicting survival after pulmonary metastasectomy in patients who underwent prior resection of hepatic CRC metastases. Methods: We performed a retrospective analysis of 27 consecutive patients (median age 62years; range: 33-75years) who underwent resection of pulmonary metastases after previous hepatic metastasectomy from CRC in two institutions from 1996 to 2009. All patients underwent complete resection (R0) for both colorectal and hepatic metastases. Results: Median follow-up was 32months (range: 3-69months) after resection of lung metastases and 65months (range: 19-146months) after resection of primary CRC. Three- and 5-year overall survival rates after lung surgery were 56 and 39%, respectively, and median survival was 46months (95% CI 35-57). Median disease-free survival after pulmonary metastasectomy was 13months (95% CI 5-21). At the time of last follow-up, seven patients (26%) had no evidence of recurrent disease and 6 of these 7 patients presented initially with a single lung metastasis. Conclusions: Resection of lung metastases from CRC patients may result in prolonged survival, even after previous hepatic metastasectomy. Yet, prolonged disease-free survival remains the exception, and seems to occur only in patients with a single lung lesio

Impact of HLA matching on the outcome of simultaneous pancreas-kidney transplantation

Background. Simultaneous pancreas-kidney (SPK) transplantation has become the therapy of choice for type 1 diabetic patients with end-stage renal disease. The current analysis examined the impact of human leukocyte antigen (HLA) matching on graft outcome following SPK transplantation. The study population was obtained from patients enrolled in the Euro-SPK 001 study. Methods. The effect of HLA matching on graft function and survival was assessed in 180 SPK recipients in whom complete donor-recipient HLA data were available. A group of 45 patients with 0-3 HLA mismatches (MM) was compared with a group of 135 patients with 4-6 MM. Results. There were no differences in 3-year kidney, pancreas or patient survival between the 0-3 and 4-6 MM groups. Biological parameters of kidney and pancreas graft function were similar in both groups. Significantly more patients with 0-3 MM (66%) were rejection-free at 3 years than was the case among those with 4-6 MM (41%; P = 0.003). The relative risk of acute rejection was 2.6 times higher among patients with 4-6 MM than among those with 0-3 MM. Conclusions. There was no evidence that HLA matching was associated with improved kidney or pancreas survival. However, a higher rate of acute rejection was observed with poor HLA match, which may impact long-term surviva