Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases.

BACKGROUND: Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Non-alcoholic fatty liver disease (nafld) can decrease the liver's capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor ß, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration. METHODS: This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined. RESULTS: The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median disease-free survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate. CONCLUSIONS: This study reveals an important potential negative effect of hepatocyte ballooning on hepatic disease-free survival.

The MAP kinase phosphatase-1 MKP-1/DUSP1 is a regulator of human liver response to transplantation.

Orthotopic liver transplantation (OLT) continues to be the only remedy for end-stage liver disease. In an attempt to decrease the ever-widening gap between organ donor and recipient numbers, and ultimately make more livers amenable to transplantation, we characterized the healthy human liver's response to ischemia and reperfusion-induced injury during transplantation. This was carried out by transcriptional profiling using cDNA microarray to identify genes whose expression was modulated at the 1-h postreperfusion time point. We observed that the map kinase phosphatase-1/dual-specificity phosphatase-1 (MKP-1/DUSP1) mRNA was strongly and significantly upregulated. Validation of this observation was carried out using reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemistry. In addition, we characterized the signaling pathways regulating MKP-1 expression using the human hepatoma cell line HepG2. Finally, by combining MKP-1 silencing with reperfusion-associated stresses, we reveal the preferential role of this protein in attenuating the activity of the JNK and p38(MAPK) pathways, and the resulting apoptosis, making MKP-1 a potential target for therapeutic intervention.

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.

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.