Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy. METHODS: In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child-Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt. RESULTS: Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8-8.5 cm), which decreased with tace to 5.0 cm (range: 3.3-7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival. CONCLUSIONS: The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.

Regulation of membrane trafficking by a novel Cdc42-related protein in Caenorhabditis elegans epithelial cells.

Rho GTPases are mainly known for their implication in cytoskeleton remodeling. They have also been recently shown to regulate various aspects of membrane trafficking. Here, we report the identification and the characterization of a novel Caenorhabditis elegans Cdc42-related protein, CRP-1, that shows atypical enzymatic characteristics in vitro. Expression in mouse fibroblasts revealed that, in contrast with CDC-42, CRP-1 was unable to reorganize the actin cytoskeleton and mainly localized to trans-Golgi network and recycling endosomes. This subcellular localization, as well as its expression profile restricted to a subset of epithelial-like cells in C. elegans, suggested a potential function for this protein in polarized membrane trafficking. Consistent with this hypothesis, alteration of CRP-1 expression affected the apical trafficking of CHE-14 in vulval and rectal epithelial cells and sphingolipids (C(6)-NBD-ceramide) uptake and/or trafficking in intestinal cells. However, it did not affect basolateral trafficking of myotactin in the pharynx and the targeting of IFB-2 and AJM-1, two cytosolic apical markers of intestine epithelial cells. Hence, our data demonstrate a function for CRP-1 in the regulation of membrane trafficking in a subset of cells with epithelial characteristics.

Ureteral implantation technique and urologic complications in adult kidney transplantion.

AIM: To assess the incidence of urological complications and hematuria after adult kidney transplantation using the Lich-Gregoire (LG) versus the Taguchi (T) ureteral implantation technique. METHODS: We performed a retrospective analysis of 212 consecutive kidney transplants from our institution using an access database. RESULTS: Sixty four patients underwent ureteral implantation using the T technique, and the other 148, the LG implantation. Both groups were matched for donor/recipient characteristics and for cold/warm ischemia times. There were 23 urological complications in 17 patients. Twenty-seven patients developed complicated hematuria. The rates of urinary leak and ureteral stones were not different. There was a higher incidence of permanent ureteral strictures using the LG technique (P =.05). T technique was associated more frequently with hematuria, but there was no difference in the length of stay. CONCLUSIONS: We identified an increased incidence of permanent strictures with the LG technique. The rate of hematuria was higher in the T group. Both techniques can be used interchangeably with acceptable rates of urological complications. The simplicity of the T technique has made it the technique of choice in our institution.

Correlation of cell necrosis and tissue calcification with ischemia/reperfusion injury after liver transplantation.

BACKGROUND: The cellular events following liver ischemia/reperfusion (I/R) during transplantation are largely unknown. The spectrum of I/R damage to the liver can be clinically revealed by the development of primary graft dysfunction or nonfunction. Because viral-induced liver necrosis has been associated with the development of calcifications in an animal model, we investigated the spectrum of I/R changes identified at an ultrastructural level among livers after liver transplant (LT). MATERIALS AND METHODS: Random liver biopsies from five recipients with different degrees of liver dysfunction (LD) were processed for light (LM) and electron (EM) microscopic examination. The degree of calcification was estimated as mild-moderate or severe. The degree of cell vacuolization, used as a surrogate marker of cell necrosis, was reported as mild-moderate or severe. RESULTS: Two patients with severe LD had obvious calcifications by LM and EM examinations. Both showed significant vacuole formation, suggesting a severe degree of cell necrosis, and both succumbed to the sequelae of their LD. One patient showed evidence of mild calcifications at EM (but not LM) examination, with mild vacuole formation. The remaining two patients displayed no microcalcifications. Both presented only mild vacuole formation. Both patients recovered from LD and are currently alive. CONCLUSION: In this preliminary report, we conclude that the clinically observed degree of LD after orthotopic liver transplant (OLT)correlates well with ultrastructural modifications. These include calcification and vacuole formation. We believe that both findings can be used as surrogate markers of a clinically significant hepatic I/R injury.

The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients.

BACKGROUND: Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS: We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS: Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS: Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.

Leukoreduction and acute rejection in liver transplantation: an interim analysis.

BACKGROUND: Little is known about the effect of blood transfusions and leukoreduction on acute rejection in liver transplantation. The purpose of this study was to assess the impact of leukoreduction on the occurrence of early rejection episodes in liver transplantation. METHODS: In 1999, mandatory leukoreduction was implemented in our program. Data from 339 consecutive liver transplant recipients were analyzed with attention to the time period as a proxy for leukoreduction, the number of transfusions, the wait list status, the hepatitis B or C status, the recipient age, and the type of immunosuppression. RESULTS: Using an early (6-month) rejection-free graft survival model, we observed that introduction of leukoreduction was independently associated with fewer rejection episodes (P =.001). Despite the lower rejection rate, due to a regimen of tacrolimus and antithymocyte globulin, the effect of implementation of leukoreduction remained significant (P =.021). CONCLUSION: The use of leukoreduction is associated with fewer early rejections, irrespective of the type of immunosuppression. These data support an exploration of the immunomodulatory effect of leukoreduction.

Do biliary endoprostheses decrease biliary complications after liver transplantation?

AIM: Most technical complications after orthotopic liver transplantation (OLT) are related to the biliary tree. This report reviews the role of routine intraoperative placement of stents to reduce biliary complications. METHODS: We retrospectively analyzed 396 consecutive OLTs. We reviewed rates of biliary complications after hepaticojejunostomy (HJA) as well as following choledochocholedochostomy (CCA) groups: "experimental" group (routine intraoperative biliary stenting, last 10 months), "recent" control group (nonstented, previous 10 months), "historical" control group (prior to that period of time). RESULTS: All groups were matched for donor/recipient characteristics and for graft cold/warm ischemia time. The overall prevalence of biliary complications was 30.7% after CCA versus 35% after HJA. In the experimental group 21 patients had a 4.8% biliary complication rate compared to the recent control and historical groups, where biliary complication rates were 30% and 32.6%, respectively (P <.05). CONCLUSIONS: The intraoperative use of biliary stents is feasible and appears to decrease the rate of biliary complications. These results support the need for a prospective randomized trial.

Liver transplantation for metastases from a bile duct carcinoid.

BACKGROUND: A 29-year-old woman who presented with fatigue and jaundice was found to have an obstructing mass at the bifurcation of the bile duct. The patient underwent a successful left hepatectomy with resection of the bile duct bifurcation and a reconstruction with a right hepaticojejunostomy. Pathology revealed an atypical carcinoid tumour of the left extrahepatic bile duct, with perineural and lymphatic invasion. The patient subsequently developed multiple metastases in the remaining liver. METHODS: In the absence of extrahepatic disease, the patient underwent a successful liver transplant. RESULTS: Two years later she remains disease-free. DISCUSSION: To our knowledge this is the first report of a biliary carcinoid treated with hepatectomy and finally with liver transplantation, with excellent results. The biological behaviour of these rare tumours mandates aggressive surgical management.

Proliferating cell nuclear antigen and heat shock protein 70 immunolocalization in invasive ductal breast cancer not otherwise specified.

A series of 80 female patients undergoing surgery for primary breast ductal infiltrating carcinoma not otherwise specified (NOS) was immunohistochemically studied in order to verify any relationships between Proliferating Cell Nuclear Antigen (PCNA) immunostaining, Heat Shock Protein 70 (HSP70) immunoreactivity, and several clinicopathological predictors. Positive PCNA scores (> 20% of strongly immunopositive malignant nuclei) were observed in neoplastic cells' nuclei in 13 tumors (16.25%) and were intimately associated with axillary nodal involvement (p = 0.0131), relatively high tumor grades (p = 0.0016), increased tumor size (p = 0.0312), and low or negative levels of estrogen receptors (p = 0.0323). HSP70 positive immunoexpression in malignant cells' cytoplasm (percentage of HSP70 immunoreactive cells > 10%) was detected in 33 samples (41.25%). It correlated significantly with presence of axillary lymph nodal metastases (p = 0.0033) and rather poor tumor differentiation (p = 0.0014), whereas an association of borderline statistical significance emerged between HSP70 immunoreactivity and high progesterone receptor status (p = 0.0637). PCNA positive immunostaining demonstrates the tumors' proliferative fraction and might be used as an indicator of increased malignant potential in breast cancer since it was associated with four adverse prognosticators. HSP70 immunodetection is a probable marker of the biological stress experienced by breast cancer cells, since it was related to relatively high tumor grades. Since both proteins may potentially predict disease outcome, their prognostic significance must be validated by direct relation to survival. A multivariate statistical analysis including the variables with which both proteins were associated will reveal any possible independent prognostic value of PCNA and HSP70 immunostaining in local, ductal invasive breast cancer NOS.