Race is associated with discontinuation of active surveillance of low-risk prostate cancer: results from the Duke Prostate Center.

BACKGROUND: Active surveillance (AS) is increasingly utilized in low-risk prostate cancer (PC) patients. Although black race has traditionally been associated with adverse PC characteristics, its prognostic value for patients managed with AS is unclear. METHODS: A retrospective review identified 145 patients managed with AS at the Duke Prostate Center from January 2005 to September 2011. Race was patient-reported and categorized as black, white or other. Inclusion criteria included PSA <10 ng ml(-1), Gleason sum ≤ 6, and ≤ 33% of cores with cancer on diagnostic biopsy. The primary outcome was discontinuation of AS for treatment due to PC progression. In men who proceeded to treatment after AS, the trigger for treatment, follow-up PSA and biopsy characteristics were analyzed. Time to treatment was analyzed with univariable and multivariable Cox proportional hazards models and also stratified by race. RESULTS: In our AS cohort, 105 (72%) were white, 32 (22%) black and 8 (6%) another race. Median follow-up was 23.0 months, during which 23% percent of men proceeded to treatment. The demographic, clinical and follow-up characteristics did not differ by race. There was a trend toward more uninsured black men (15.6% black, 3.8% white, 0% other, P = 0.06). Black race was associated with treatment (hazard ratio (HR) 2.93, P = 0.01) as compared with white. When the analysis was adjusted for socioeconomic and clinical parameters at the time of PC diagnosis, black race remained the sole predictor of treatment (HR 3.08, P = 0.01). Among men undergoing treatment, the trigger was less often patient driven in black men (8 black, 33 white, 67% other, P = 0.05). CONCLUSIONS: Black race was associated with discontinuation of AS for treatment. This relationship persisted when adjusted for socioeconomic and clinical parameters.

African-American men with low-grade prostate cancer have higher tumor burdens: results from the Duke Prostate Center.

BACKGROUND: To investigate racial differences in tumor burden (cancer volume, cancer percentage and cancer to PSA ratios) in a large cohort of men undergoing radical prostatectomy (RP). METHODS: Demographic, clinical and pathological data of patients undergoing RP between 1993-2010 were reviewed and compared between African-American (AA) and non African-American (nAA) men. Further assessments of pathological tumor burden (estimated tumor volume, percent of cancer involvement, and estimated tumor volume/PSA ratios) were performed across Gleason score categories. RESULTS: Of 4157 patients in the analysis, 604 (14.5%) were AA. Overall, AA patients were younger, had higher Gleason scores, PSA levels and incidence of palpable disease (all P < 0.001). Despite comparable prostate weights (39.4 vs. 39.6 g), AA men had higher percent cancer involvement and estimated tumor volume (all P < 0.001) but similar estimated tumor volume/PSA ratios ( P> 0.05). When stratified by Gleason scores, prostate weights were comparable; however, estimated tumor volume, percent cancer involvement and estimated tumor volume/PSA ratios were higher in AA men with low grade (≤ 6) prostate cancer (PCa), similar in intermediate grade (7-8) and lower in high grade (9-10) PCa compared to nAA men. CONCLUSIONS: In this large series, AA patients had higher disease burden (estimated tumor volume, percent cancer involvement, estimated tumor volume/PSA ratios) compared to nAA but this association was especially pronounced in low grade (Gleason ≤ 6) cancers. These data depict a complex picture of relations between race and tumor burden across the spectrum of PCa aggressiveness. Further investigation is warranted to understand the mechanisms of racial disparities in PCa.

Radiofrequency ablation for the treatment of small renal masses: safety and oncologic efficacy.

The successful introduction of radio frequency ablation (RFA) into various surgical fields has fueled the interest of the urological community to study its application in small renal masses (SRM). However, some controversies remain regarding its oncologic efficacy. In this paper, we review the complication rates and highlight local ablative success and long-term oncologic outcomes of recent, larger RFA series. Review of the recent literature (Medline from January 2003 through May 2011 with the terms ("radiofrequency ablation" OR "catheter ablation") AND ("renal cell carcinoma" OR "renal tumor" OR "renal mass" OR "renal cancer" OR "kidney cancer"). Twelve RFA studies including a minimum of 35 treated tumors, and representing 717 patients were identified and analyzed for local ablative success rates and complications. Reported complications were classified according to Dindo-Clavien. Another five studies representing 172 patients were identified to assess long-term oncologic outcomes. Final pathology revealed 82.3% biopsy-proven renal cell carcinomas (RCCs) in 8 of the 12 evaluable RFA studies. Local ablative success rates after a first RFA session ranged from 67% to 100%. However, accepting a 8.8% repeat ablation rate, final success rates were 89.7-100%, with 7 of 12 studies showing final ablative success in >95%. These results demonstrate RFA to achieve adequate local tumor control regardless of histology. Risk of complications was 13.2%. Of complications, 10% were minor (grade I or II), while only 3.2% were major complications (grade ≥III). Five papers were identified describing oncological outcome at a minimum follow-up of 53 months (range 53-61.2). Progression-free survival, cancer-specific survival and overall survival ranged from 79.9 to 93.8%, 98 to 100% and 58.3 to 85%, respectively. This literature review confirms that RFA can deliver durable local tumor control and excellent long-term oncological outcomes. However, in order to achieve this, a repeat ablation rate of 8.8% has to be accepted. Complication rates are low, with 10% grade I-II and only 3.2% grade >III. These observations render RFA an attractive alternative to surgery in an elderly or comorbid population.

On-demand use of erectile aids in men with preoperative erectile dysfunction treated by whole gland prostate cryoablation.

Prostate cryoablation is an established minimally invasive treatment for localized prostate cancer (PCa). However, the impairment of erectile function (EF) is considered a serious complication of the procedure. To investigate the efficacy of erectile aids following cryotherapy, 93 patients who underwent whole gland prostate cryoablation with required complete medical records were analyzed. The changes in postoperative EF were evaluated using the International Index of Erectile Function (IIEF-5) questionnaire. Additionally, independent factors that could have a correlation to the postoperative IIEF-5 score or postoperative Expanded Prostate Cancer Index Composite (EPIC) score were assessed. In the entire cohort, the mean preoperative IIEF-5 score was 7.0 ± 6.2. A total of 72 (77.4%) patients had moderate-to-severe preoperative erectile dysfunction. In longitudinal investigation, the patients using erectile aids showed the ability to recover to baseline after 24 months from cryoablation compared with the patients not using erectile aids. There were significant differences of IIEF-5 scores between these groups at 24 months (7.5 vs 3.0; P = 0.025) and 36 months (8.5 vs 3.5; P = 0.010). In multivariate analysis, the use of erectile aids correlated with restoration of IIEF-5 scores (odds ratio, 5.11; confidence interval (CI), 1.87-13.96; P < 0.001) and lower EPIC sexual bother (coef, 19.61; CI, 0.32-38.89; P = 0.046). Our data indicate that on-demand use of erectile aids could help restore EF and reduce sexual bother after whole gland prostate cryoablation. Although, erectile aids could not play a role as an adequate treatment for ED after whole gland prostate cryoablation, these results may aid in the decision-making process for PCa patients with preoperative and postoperative ED who have concern about sexual health-related quality of life.

Concordance in the perception of couples recovering from primary surgical treatment of prostate cancer.

Although prostate cancer affects men, research shows effects on both members of the couple. We analyzed concordance in couples recovering from primary surgical treatment of prostate cancer when surveyed on psychological domains including emotional status, relationship, self-image, partnership quality and support. Retrospective Sexual Surveys were utilized to survey physiological changes as well as psychological effects. In total, 28 heterosexual couples (56 people) were enrolled. Patients were treated between February 2002 and March 2007 with a median follow-up of 26 (range: 4-59) months. When polled on psychological aspects that may have been affected by treatment, overall concordance was 75.0%. Partnership had the highest concordance (92.2%) with treatment satisfaction questions following in second (90.7%). Subcategories focused on self-image (77.5%), relationship (67.3%), support (66.4%) and emotional status (55.6%), were less concordant. Although couples report relationships as strong and team-like, misconception between partners is widespread. Further research with regards to the effect of such disparities in couples might provide additional insight into improving recovery.

Urologic pelvic surgery following mesh hernia repair.

PURPOSE: Few and controversial reports have recently appeared on the role of previously performed surgery in the inguinal region using a prosthetic mesh and the ensuing difficulties encountered by urologists during radical retropubic prostatectomy. We analyzed our experience with various surgical urological procedures performed after prior low abdominal wall hernia repair with synthetic mesh. METHODS: We reviewed our database for all patients who underwent mesh repair of lower abdominal hernias and subsequent urologic surgery in our department between 2002 and 2008. Their perioperative parameters, complications, and postoperative outcomes were analyzed. RESULTS: Twenty-three patients (one female) underwent pelvic urologic surgery for benign and malignant disease after having undergone previous prosthetic hernia repair. The mean patient age was 75.3 years (range 58-91). The mean interval between hernia repair and pelvic urologic surgery was 3.8 years (range 1-7). Twenty-two patients underwent previous mesh inguinal hernia repair and one had prosthetic postoperative ventral hernia repair after a transabdominal hysterectomy. The urologic procedures included 16 open suprapubic prostatectomies, two radical cystoprostatectomies, one bladder augmentation, and four laparoscopic radical prostatectomies. Severe postoperative complications were abortion of surgery (n = 1), inability to perform lymph node dissection (n = 2), bleeding (n = 1), bladder injury (n = 2), and additional surgery (n = 3: mesh removal, transurethral prostatectomy, and transurethral fulguration of the prostatic fossa). CONCLUSIONS: Prior application of synthetic mesh during abdominal wall surgery creates difficulties during subsequent urological procedures and may dictate change in operative planning. Nevertheless, the surgery is feasible and should not be ruled out.

Hand-assisted laparoscopic donor nephrectomy: analysis of the learning curve in a training model in vivo.

INTRODUCTION: Hand-assisted laparoscopic donor nephrectomy (HALDN) outcomes are impaired mainly by the risks associated with the learning curve. Considering that practice by in vivo training may reduced this risk, we recently assessed a swine model of HALDN. The aim of this study was to analyze the learning curve of HALDN using an in vivo training model. MATERIALS AND METHODS: Ten female white pigs underwent a left and then a right HALDN in the same session for a total of 20 procedures by the same first operator. The HALDN were divided into 2 groups: group A, the first 10 nephrectomies and group B, the latter 10. For each group, we assessed operative times, intraoperative complications, estimated blood loss (EBL), warm ischemia time (WIT), and graft quality. RESULTS: We observed a significant decrease in operative times among group B. Two right HALDN of group A were converted to open procedures owing to bleeding. The EBL was consequently lower in group B (P < .05); the mean WIT was not significantly different between the 2 study groups. The graft quality was good in 5/8 kidneys evaluated in group A and 9/10 in group B. DISCUSSION: Standardization of analyzed parameters after a number of procedures, which were comparable to the clinical settings, confirmed the validity of this in vivo training model and its potential utility to allow many transplantation centers to adopt this technique by reducing the risk of the learning curve.

Urological complications after kidney transplantation: experience of more than 1,000 transplantations.

OBJECTIVE: Urinary fistulas and stenoses are the most common complications that may require surgical revision after kidney transplantation. The aim of this study was to retrospectively assess the incidence of and risk factors for early (within 30 days) or late major urological complications (stenoses and fistulas) after kidney transplantation. PATIENTS AND METHODS: The study population comprised 1142 consecutive patients who underwent kidney transplantation between January 1990 and September 2007. Endpoints were early and late urological complications (stenoses and fistulas). The variables considered upon multivariate and univariate analyses were: recipient age, sex, etiology of renal failure, number (first/second) and type (single/double/combined with other organs) of kidney transplantations, cold ischemia time, type of urinary reconstruction, stent positioning, as well as donor cause of death, sex, age, and serum creatinine and clearance. We also examined the presence of graft polar arteries, acute rejection episodes, and postoperative graft function. RESULTS: Among 1142 transplantation performed at our center, 100 patients (8.7%) experienced 107 urological complications: 85 (79.4%) were early (56 fistulas, 29 stenoses) and 22 (20.5%) late (7 fistulas and 15 stenoses). Multivariate analysis for all complications revealed significant associations with male recipient sex (P = .00, HR = 2), while first kidney transplantation was protective (P = .00, HR = .4). Male gender both of the recipient and of the donor was significantly associated with early fistulas (P = .01, HR = 2.5 and P = .02, HR = 2, respectively). First (versus second) kidney transplantation had a protective effect on early stenoses (P = .01, HR = .27). Late fistulas were associated with anastomotic stenting (P = .03) in univariate but not multivariate analysis. Multivariate analysis for late stenoses did not demonstrate any significant association with the considered variables; however, the late stenosis cases showed significantly higher recipient and donor ages (P < .05) and a lower donor creatinine clearance (P < .05). The type of urinary anastomosis, stenting, cold ischemia time, presence of polar arterial branches, and type of transplantation did not influence the incidence of urinary fistulas or stenoses. CONCLUSIONS: Our data confirmed that older recipients and organs from older donors, especially of male gender, and retransplantations are to be considered risk factors for urological complications. The present analysis cannot suggest any modification of the actual surgical strategy that would prevent urological complications in kidney transplantation.

Generation of a novel antibody probe to the apical sodium-dependent bile acid transporter that inhibits ileal bile acid absorption.

Intestinal bile acid absorption is mediated by a sodium-dependent transporter located in the brush border apical membrane of ileocytes. The transmembrane topology and the role of individual amino acid residues in the bile acid transport process have been investigated by means of various experimental approaches, leading to multiple hypotheses. We raised a monoclonal antibody against a segment of the transporter comprising vicinal cysteine residues, in order to evaluate its functional role. A 14 amino acid peptide, corresponding to amino acids 104-117 of the transporter, was synthesized, and a monoclonal anti-peptide antibody was raised. In vitro uptake-inhibition studies in the presence of the monoclonal anti-peptide antibody were performed using ileal brush border membrane vesicles. Rabbit ileum was perfused in vivo with 5 mM taurocholic acid in the presence of the monoclonal antibody, and bile acid absorption inhibition was evaluated. The anti-peptide monoclonal antibody significantly reduced the in vitro uptake and in vivo absorption of taurocholic acid. The present data demonstrate the functional relevance of the 104-117 peptide segment and report the generation of a novel antibody against the apical sodium-dependent bile acid transporter (ASBT) that may be used as a therapeutic agent in hypercholesterolemia and in cholestatic pruritus.

Kidney transplantation combined with other organs in Bologna: an update.

BACKGROUND: We retrospectively reviewed our experience in combined liver-kidney (L-KT) and heart-kidney (H-KT) transplantations. PATIENTS AND METHODS: Between January 1997 and April 2007, we performed 25 L-KT and 5 H-KT. Patient mean age was 51+/-8 years in L-KT and 43+/-11 years in H-KT. The main cause of liver failure was chronic viral hepatitis (14 cases). Etiology of heart failure was dilated cardiomyopathy and hypertrophic cardiomyopathy (4 and 1 patients, respectively). The main causes of renal failure in L-KT were chronic glomerulonephritis (n=8) and polycystic disease (n=7). Etiology of renal failure in H-KT was interstitial nephropathy (n=2), vascular nephropathy (n=2), and chronic glomerulonephritis (n=1). RESULTS: Mean follow-up was 32+/-26 months in L-KT and 24+/-17 months in H-KT. Immunosuppression was cyclosporine-based (n=4) or tacrolimus-based (n=21) in L-KT and cyclosporine-based in H-KT. Acute rejection rate was 8% for both liver and kidney in L-KT; 80% (mild) for heart and 40% for kidney in H-KT. In the L-KT group, there was no primary graft nonfunction (PGNF). Two patients experienced liver delayed graft function (DGF); 1 patient required postoperative dialysis. One-year graft and patient survivals were both 84% and overall graft and patient survival was 76%. In the H-KT group, 3 patients needed postoperative dialysis and 1 required a cardiac assistance device for 48 hours; overall graft and patient survival was 100% with good cardiac and renal functions. CONCLUSION: Our experience confirmed that H-KT and L-KT are safe procedures, offering good long-term results.

Endolymphatic immunotherapy in inoperable hepatocellular carcinoma.

INTRODUCTION: We report the preliminary results of endolymphatic immunotherapy in patients with inoperable hepatocellular carcinoma (HCC). METHODS: From 2003 to 2005 we enrolled 31 patients with inoperable HCC. The patients underwent monthly endolymphatic injections of 15-30 x 10(6) interleukin-2 (IL-2)-activated peripheral autologous lymphocytes (LAK) and 250 IU of IL-2. Follow-up included blood biochemistry every 3 months and imaging studies every 6 months. To assess therapy efficacy we considered 12 biochemical parameters, vascular invasion or thrombosis, Child-Pugh scoring system, histological grading, lymphadenopathy, viral state, and alpha-fetoprotein. RESULTS: Sixteen patients completed at least 3 cycles, and 10 patients completed more than 6. No clinically significant adverse reactions occurred. Imaging studies showed no significant decrease in tumor mass. However, the survival of patients who completed 12 therapy cycles was significantly higher than survival of patients with fewer than 12 cycles. Both are significantly higher than that of untreated patients. All patients with 12 completed cycles showed an improvement of 9 parameters or more. DISCUSSION: Endolymphatic immunotherapy is safe, easily performed, inexpensive, and effective in terms of survival. This study should encourage future large-scale investigations so as to reach a firmer conclusion and define uniform inclusion criteria.

Extracorporeal portal vein oxygenation improves outcome of acute liver failure in swine.

BACKGROUND: Portal vein arterialization (PVA) has shown efficacy to treat acute liver failure (ALF) in preclinical studies. The next step is to perform large animal studies that propose a clinically acceptable method of PVA. In this study, we assessed the efficacy of PVA using an extracorporeal device to treat 2 ALF models in swine. MATERIALS AND METHODS: The 2 ALF swine models were carbon tetrachloride toxic ALF and subtotal hepatectomy using 8 animals per group. PVA was performed with an extracorporeal device that may be suitable for future clinical studies. Arterial blood was drawn from the iliac artery and delivered into the portal vein for a 6-hour treatment. We analyzed biochemical, blood gas, and histological parameters as well as 1-week survival rates. RESULTS: In both models, ALF was successfully achieved. Control group animals deteriorated biochemically, dropping their prothrombin times and increasing the liver enzymes. In contrast, treated animals improved with a survival rate of 75% at 7 days compared with 0% for the former group. CONCLUSIONS: PVA using an extracorporeal device was feasible and effective to treat both toxic and resective ALF in swine.

A new swine training model of hand-assisted donor nephrectomy.

INTRODUCTION: Despite the described advantages of hand-assisted laparoscopic donor nephrectomy (HALDN), the learning curve risks discourage many transplant centers to switch from the traditional technique to the laparoscopic approach. Considering that the learning curve risk may be softened with practice on a training model the aim of this study was examine a low-cost, high-fidelity model of HALDN in pigs. METHODS: Ten female white pigs underwent a left and then a right HALDN in the same session for a total of 20 procedures. For each nephrectomy, we assessed operative times and intraoperative complications. All nephrectomies were performed by a single senior transplantation surgeon. RESULTS: All animals that survived bilateral nephrectomy were sacrificed. Two right HALDNs were converted to open procedures due to bleeding. One spleen lesion and one lumbar vein injury were treated laparoscopically. Considering only the 18 HALDN completed, we registered a mean total operative time of 75.4 min (range=52 to 120). DISCUSSION: The in vivo training model described herein made it possible to reproduce the positions and operative difficulties similar to those encountered in clinical practice. Moreover, the costs can be considerably reduced by performing two procedures in each animal employing reusable instruments. Our model represented a valid high-fidelity training procedure that was useful and convenient to achieve skills for HALDN that may help transplantation centers adopt this technique to reduce the learning curve risk.

Protective effect of an inhibitor of interleukin-8 (meraxin) from ischemia and reperfusion injury in a rat model of kidney transplantation.

INTRODUCTION: Since the ischemia and reperfusion injury is one of the main causes of delayed graft function after transplantation, research efforts have focused on studying the molecules involved in this inflammatory process. The chemokine interleukin-8 (IL-8) seems to be the main one responsible through a chemoattractive action toward neutropils. Therefore, one of the strategies adopted to prevent this process is blocking the binding between IL-8 and its receptors. The aim of our study was to test the effect of meraxin, a new derivative from repertaxin, to protect the renal graft from ischemia and reperfusion injury. MATERIALS AND METHODS: Eighty male syngenic rats were divided into four groups. The control group underwent only kidney transplantation, while the other groups were treated with meraxin at various dosages 2 hours before graft reperfusion. Blood and histological samples were taken at sacrifice 24 hours after transplantation. RESULTS: Creatinine was significantly lower in the group treated with the high dosage of meraxin. Histological observation of the grafted tissue showed instead only a mild and not significant neutrophilic infiltration, equal in each group. CONCLUSIONS: Graft function was improved by the administration of meraxin at high dosage, but this effect did not seem to be connected to a reduction in inflammatory infiltration in the parechymal tissue. Maybe the cause is in the mechanisms of clotting activation, due to alteration of adhesion molecules and endothelial cells.

Bologna transplant center results in double kidney transplantation: update.

INTRODUCTION: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of this study was to verify the results obtained with double-kidney transplantation in terms of graft/patient survivals and complications. PATIENTS AND METHODS: Between September 2001 and September 2006. 26 double-kidney transplantations were performed in our center. Indications for surgery were: chronic glomerulonephritis (n = 17), polycystic disease (n = 4), reflux nephropathy (n = 1), hypertensive nephroangiosclerosis (n = 4). The kidneys were all perfused with Celsior solution and mean cold ischemia time was 16.7 +/- 2.5 hours. In all cases, a pretransplant kidney biopsy was performed to evaluate the damage (mean score: 4.3). Immunosuppression was tacrolimus-based for all patients. RESULTS: Eighteen patients had good renal postoperative function, while the other eight displayed acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31%. There were two surgical reoperations for intestinal perforation. Graft and recipient survivals were 82.7% and 100%, and 78.9% and 94% at 3 and 36 months, respectively. CONCLUSIONS: Double-kidney transplantation is a safe strategy to face the organ shortage. The score used in this study is useful to determine whether a kidney should be refused or suitable for single- or dual-kidney transplantation. The results of our experience are encouraging, but the series is too small to allow a conclusion.

Portal vein arterialization in hepatobiliary surgery and liver transplantation.

We reviewed the literature reports and our personal experience on partial portal vein arterialization (PPVA) to prevent and treat acute liver failure (ALF) following major hepatobiliary surgery or another etiology. Experimental studies in rats have assessed the efficacy of PPVA in treatment of ALF induced by extended resections in normal or fatty livers or in toxic carbon-tetrachloride damage. The treated groups showed greater survival and faster recovery of liver function. Among 11 clinical cases reported in the literature, PPVA was performed in four cases to prevent and in seven cases to treat ALF. Eight patients survived, showing rapid recovery of liver function and resolution of the clinical condition. This relatively simple procedure has shown itself able to promote liver regeneration. The PPVA procedure has shown itself to be safe and simple as well as to offer a promising approach to the failing liver.

Protective effect of portal vein arterialization in acute liver failure induced by hepatectomy in normal and fatty liver rat.

AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.

Portal vein arterialization for the treatment of post resection acute liver failure in the rat.

INTRODUCTION: Hyperoxygenation of the liver has been suggested to improve its regenerative capacity. Thus, this study sought to determine whether an additional supply of oxygenated blood delivered by portal vein arterialization (PVA) was protective against acute liver failure induced by hepatectomy. METHODS: Sprague-Dawley rats (six per each group) were divided to either undergo PVA or be untreated after extended hepatectomy. Liver injury was evaluated by the serum alanine aminotransferase (ALT) levels. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. Serum ALT levels were significantly reduced in arterialized versus nonarterialized rats. PVA promotes liver regeneration. Finally, PVA significantly improved host survival compared to the controls: 90% versus 30%, respectively. CONCLUSION: These data suggested that an additional supply of arterial oxygenated blood through PVA promoted a rapid regeneration, leading to a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool to optimize hepatocyte regeneration.

Successful treatment of CCL4-induced acute liver failure with portal vein arterialization in the rat.

INTRODUCTION: Optimization of the conditions for regeneration of the native diseased liver is a major goal in patients with acute liver failure. This study sought to determine whether portal vein arterialization (PVA), which increases the oxygen supply to the liver, was protective in a rat model of liver failure. METHODS: At 24 hours after CCl(4) intoxication, Sprague-Dawley rats (six per group) were assigned to receive PVA or as controls. We determined blood tests, histology, and 10-day survivals. Hepatocyte regeneration was assessed by the mitotic index and bromodeoxyuridine (BrdU) incorporation. RESULTS: Serum transaminases were significantly lower in PVA-treated rats than in control animals: liver necrosis resolved rapidly after PVA. The BrdU staining and mitotic index were severalfold higher among PVA-treated than in untreated rats. Survival was 100% among rats with PVA and 40% in untreated animals (P < .01). CONCLUSIONS: PVA led to resolution of CCl(4)-induced massive liver necrosis in the rat. This effect was probably mediated by activation of rapid and extensive hepatocyte regeneration. PVA might provide a novel, alternative approach to treat acute liver failure.