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Paolo R O Salvalaggio

Publications and source records attributed to Paolo R O Salvalaggio.

12 recordsLinked to original sources

Antigen exposure during enhanced CTLA-4 expression promotes allograft tolerance in vivo.

The role of CTLA-4 in tolerance is primarily inferred from knockout and blocking studies. Anti-CD45RB mediates allograft tolerance in mice by inducing CTLA-4 expression on CD4 cells, providing a novel opportunity to determine how therapeutic enhancement of CTLA-4 promotes tolerance. We now show that induced CTLA-4 expression normally resolves by day 17. Although thymectomy prolongs enhanced CTLA-4 expression, long-term engraftment is unaffected. To address the temporal relationship between increased CTLA-4 expression and engraftment, transplantation was delayed for various times after anti-CD45RB treatment. Delaying transplantation for 7 days (when CTLA-4 expression had peaked but treatment mAb was no longer detectable), resulted in long-term engraftment comparable to transplantation with no delay (day 0). Delaying transplantation from 10 to 18 days led to a progressively poorer outcome as CTLA-4 expression returned to baseline. This suggested that Ag exposure while CTLA-4 expression is enhanced is sufficient to induce long-term engraftment. To substantiate this, on day 0, anti-CD45RB-treated mice received BALB/c vs unrelated alloantigen, followed by transplantation of BALB/c islets 10 days later. Whereas recipients exposed to unrelated Ag experienced acute rejection, recipients exposed to donor Ag achieved long-term engraftment. Anti-CD45RB-treated mice exposed to alloantigen exhibited anergic CD4(+)CD25(-) effector cells and regulatory CD4(+)CD25(+) cells. Moreover, CD25 depletion in the peritransplant period prevented anti-CD45RB-mediated engraftment. Thus, exposure of CD4 cells expressing CTLA-4 to donor Ag is necessary and sufficient to induce long-term engraftment which appears to be mediated by both regulation and anergy.

Animals↗

Outcomes and risk factors for failure of radiologic treatment of biliary strictures in pediatric liver transplantation recipients.

Posttransplantation biliary strictures occur in 5-34% of the pediatric liver transplant patients and are conventionally managed by interventional radiological techniques. The aim of this manuscript is to assess the outcomes of patients with biliary strictures treated by percutaneous dilatation at our institution. Included in the study were 35 children with posttransplant biliary strictures that were treated with percutaneous dilatation and stenting. Initial dilation and biliary stent placement was accomplished in all patients without complications requiring surgical intervention. Recurrent strictures developed in 23 (66%) of 35 patients. The recurrence rate was 45% for anastomotic strictures, 90% for intrahepatic strictures, and 100% for those with both an anastomotic and intrahepatic component. Seven patients required revision of the choledochojejunostomy, 5 of them with a successful outcome and 2 requiring retransplant. Five patients were treated with retransplantation without surgical revision. Patients with an intrahepatic or a "combined" stricture were less likely to have a successful outcome after radiologic treatment. In conclusion, the radiological treatment of biliary strictures with balloon dilation and stenting can be performed successfully with minimal complications avoiding the need for surgical correction in many cases.

Adolescent↗

Proposed classification of complications after live donor nephrectomy.

OBJECTIVES: A standardized classification for the potential complications of living donor nephrectomy is an essential step in establishing a construct for monitoring and reporting the outcomes of this procedure. It is also helpful in informing potential donors about the inherent risks of the donor operation as part of the informed choice process. METHODS: We reviewed 600 laparoscopic live donor nephrectomies performed at our center. A modification of the Clavien classification system describing procedure-related complications was developed and used to grade the severity of all complications. RESULTS: We observed 43 complications (7.2%) in our series of 600 patients. Grade 1 defines all events that, if left untreated, would have a spontaneous resolution or needed a simple bedside procedure (39.5%). Grade 2 complications differ from grade 1 in that they are potentially life-threatening and usually require some form of intervention, but do not result in ongoing disability. We subdivided grade 2 complications (55.8% in our study) into 2a, 2b, and 2c. The latter describes complications requiring open conversion of laparoscopic donor nephrectomy for patient treatment. Grade 3 complications are events with residual or lasting disability (4.7% in our review). Grade 4 events are those resulting in renal failure or death because of any complication (none occurred in our series). CONCLUSIONS: A graded classification scheme for reporting the complications of donor nephrectomy may be useful for maintaining registry information on donor outcomes and when informing potential donors about the risks and benefits of this procedure.

Humans↗

Liver graft volume estimation in 100 living donors: measure twice, cut once.

Estimation of graft volume (GV) is critical in living donor liver transplantation. This study examines the accuracy of formula-derived GV estimates and compares them to both radiogically-derived estimates and actual measurements. We first compared formula-derived estimates of GV and compared them to actual volumes to provide estimates for both right lobe (RL) and left lateral segment (LLS) GV. We then applied these formulae to a validation cohort. Finally, we evaluated both formula-derived and radiologically-derived estimates by comparing them to actual GV measurements. There is a marginal concordance between formula-derived calculation and GV for RL donors, but the error ratio was lower than for radiologic estimates. In contrast, MRI measurements for LLS grafts demonstrated a lower error ratio than formula-derived estimation. Formula-derived estimates of GV should be routinely used in the initial screening of potential living donors as long as their limitations are appreciated.

Biometry↗

Presence of multiple bile ducts in the liver graft increases the incidence of biliary complications in pediatric liver transplantation.

We studied the impact of multiple bile duct anastomosis on the development of biliary complications after liver transplantation in children. A total of 101 patients received a primary liver transplant and were divided into 2 groups: those with a single bile duct (n = 77) and those with multiple bile ducts (n = 24). Mean follow-up was 39.8 +/- 20.8 months. A total of 27 patients presented with biliary complications (26.7%), 18 patients (18.7%) presented with early complications (12 leaks and 6 strictures), and 9 patients (8.9%) had late strictures. Hepatic artery thrombosis (HAT) and multiple bile ducts were significant risk factors for the development of biliary complications, and the presence of multiple bile ducts was an independent risk factor. Patients with multiple bile ducts had a significantly greater incidence of total biliary complications compared to those with single ducts. Patients with multiple ducts had a higher incidence of leaks when compared to those in the single duct group, but the incidence of strictures, both early and late, was similar in both groups. One-year patient and graft survivals were not statistically different in the 2 groups. In conclusion, the presence of more than one bile duct in the graft is an independent risk factor for the development of biliary complications after pediatric liver transplantation.

Anastomosis, Surgical↗

Liver transplantation with simultaneous removal of an intracardiac transjugular intrahepatic portosystemic shunt and a vena cava filter without the utilization of cardiopulmonary bypass.

Transjugular intrahepatic shunts (TIPSs) are widely used in the management of portal hypertension complications including variceal bleeding, refractory ascites, and hepatic hydrothorax. Vena cava filters (VCFs) are an important therapeutic modality in the prevention of pulmonary emboli in patients suffering deep venous thrombosis and clinical contraindications for anticoagulation. Stent and filter misplacement or migration may occur, complicating liver transplantation (LT) surgery. We describe the intraoperative management of a patient with cirrhosis, who had a TIPS extending into the right atrium (RA) and a retrohepatic VCF. Stent and filter removals were deferred until the time of LT. Both procedures were performed successfully by complete cava and portal reconstruction. In conclusion, careful assessment and surgical management of patients with stent and filters permits successful LT.

Adult↗

Comparative analysis of live liver donation risk using a comprehensive grading system for severity.

We investigated whether right lobe (RL) liver donation is associated with a higher incidence or severity of donor complications than left lobe (LL) liver and left lateral segment (LLS) liver donations. We studied 80 living donors: 35 RL liver donors and 45 LL/LLS liver donors. A modification of the Clavien classification was used to grade the severity of complications. RL and LL/LLS liver donations had equivalent blood loss, readmission and reoperation rates, use of blood products, and lengths of stay in the intensive care unit and hospital. RL liver donors underwent longer surgeries and experienced more postoperative pain than LL/LLS liver donors. The overall rate of complications was 33%. There was a higher rate of complications in RL liver donors (51%) than LL/LLS liver donors (20%). When graded by severity, there were more grade 2 complications in RL liver donors than in LL/LLS liver donors. Our report confirms that RL liver donation is associated with higher morbidity than LL/LLS liver donation. When the complications are systematically graded by severity, there is a significant difference in Clavien grade 2 complications in RL liver donors.

Adult↗

Laparoscopic donor nephrectomy 1997 to 2003: lessons learned with 500 cases at a single institution.

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to traditional open nephrectomy that has several potential advantages. However, there have been few large series reports describing the complications of LDN and the details of their management. METHODS: We performed a retrospective review of 500 LDNs performed at our center between October 1997 and September 2003. We evaluated preoperative donor characteristics, intraoperative parameters and complications, and postoperative recovery and complications. A modification of the Clavien classification was developed and used to grade the severity of all complications. RESULTS: The overall rate of intraoperative complications was 2.8%. There were 9 open conversions (1.8%), of which 6 were in the first 100 cases. Six of the 9 open conversions were for management of complications; 3 were elective. Seven renovascular incidents (1.4%) all required open conversion except one. The overall rate of postoperative complications was 3.4%. Thirty of 500 patients in our LDN series experienced an intraoperative or procedure-related complication (6.0%). When graded by severity, 18 of 31 (58.1%) of all complications were grade 1, 11 of 31 (35.4%) grade 2, and 2 of 31 (6.5%) grade 3. Only 1 recipient experienced delayed graft function, and only 1 recipient had a urologic complication. CONCLUSIONS: Our series supports the safety and efficacy of LDN with very low intraoperative complication and conversion rates. Most of the intraoperative complications can be managed laparoscopically. Readmissions are extremely rare (1.5%). Aberrant vascular anatomy and obesity are not contraindications to LDN, but they require experience. With careful surgical technique, delayed graft function and urologic complications in recipients can be avoided. A graded classification scheme for reporting complications of donor nephrectomy might be useful for maintaining registry information on donor outcomes and when informing potential donors about the risks and benefits of this procedure.

Adolescent↗

Simultaneous surgical and interventional radiological approach to treat complicated biliary strictures after pediatric liver transplantation.

Post-transplantation biliary strictures occur in 5-15% of the pediatric liver transplant patients and are conventionally managed by interventional radiological techniques. Failure of this treatment leads to reoperation and sometimes to retransplantation. Herein, we describe a surgical approach and interventional radiologic approach to manage biliary strictures that failed the conventional radiologic treatment, in order to avoid retransplantation. Included in the study were eight children who underwent liver transplantation at our center or referred to our institution for evaluation of the biliary strictures that failed radiological treatment. Biliary strictures were confirmed by a narrowing of the biliary anastomosis on the percutaneous transhepatic cholangiogram. At surgery, a guide wire was introduced into the distal bile system through the use of an enterotomy in Roux limb. Over the guide wire, the stricture was ballooned and the diameter of the biliary tree was determined. A pigtail catheter was introduced on the biliary tree across the abdominal wall, the liver, the stricture and the anastomosis into the enterotomy. A final cholangiogram confirmed the positioning of the catheter. Mean follow-up was 39.8 +/- 20.8 months. All patients had their strictures successfully treated and survived the procedure. Three patients were readmitted to the hospital with fever. It was necessary to revise the hepaticojejunostomy in three patients because of cholangitis and/or recurrence of biliary stricture. Of the eight patients of this study, two required retransplantation and one died. We conclude that an aggressive combined surgical and radiologic approach can avoid retransplantation in patients with complicated post-transplant biliary strictures.

Bile Ducts↗

Islet filtration: a simple and rapid new purification procedure that avoids ficoll and improves islet mass and function.

Islet isolation is a time-consuming process. Islet yields vary, and previous in vitro studies suggest that Ficoll may be an islet toxin. Here, we describe an alternative, Ficoll-free method to purify murine islets by filtration through a cell strainer. Collagenase digestion of pancreata was carried out using standard procedures. The pancreatic digest was divided into aliquots and purified either by Ficoll or by filtration. Following filtration, islets were intact and separated from nondigested tissue. Purity was similar to that achieved using Ficoll. However, purification by filtration was faster, increased islet yield, and resulted in higher insulin secretion in vitro. Moreover, when syngeneic diabetic hosts were transplanted with a marginal islet mass, islets purified by filtration restored normoglycemia significantly faster than those isolated by Ficoll. This suggests that Ficoll exposure negatively impacts islet function. In conclusion, islet filtration is a simple and rapid procedure for purification of islets that demonstrate improved functional mass.

Animals↗

Oral glutamine does not prevent bacterial translocation in rats subjected to intestinal obstruction and Escherichia coli challenge but reduces systemic bacteria spread.

OBJECTIVE: We investigated whether oral glutamine prevents bacterial translocation. METHODS: Male Wistar rats were fed with isocaloric and isoproteic standard rat chow and randomly assigned to receive glutamine (GLN) or glycine administered through an orogastric tube at 1.5 g.kg(-1).d(-1) for 7 d. On day 8 of the study, the animals were anesthetized and intestinal obstruction was produced by ligature of the terminal ileum. A suspension containing 10(9) colony-forming units per milliliter of Escherichia coli ATCC 25992 was injected into the lumen of the ileum. Twenty-four hours later, blood was withdrawn, and mesenteric lymph nodes and fragments of spleen, liver, and lung were sent for microbiological analysis. Cultures were done on blood agar and MacConkey agar. Student's t test and analysis of variance between two proportions were used. P < 0.05 was considered significant. RESULTS: Rats in both groups lost body weight during the experiment (not significant). Mesenteric lymph node cultures were positive in both groups. The GLN group had a smaller percentage of E. coli in blood and organ cultures (65.45% versus 82.67% in the glycine group; P = 0.027). Positive cultures of blood, spleen, liver and lung also were higher on glycine group, although not significantly. CONCLUSIONS: Oral GLN does not prevent bacterial translocation in rats after intestinal obstruction and E. coli challenge. No specific organ was protected by GLN. Nevertheless, its use was associated with a reduced number of positive E. coli cultures in blood and remote organs, and thus diminished bacteria spread. This association suggests a role for GLN in gut barrier protection, possibly by immune system enhancement.

Administration, Oral↗