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Biomedical subjects

V McAlister

Publications and source records attributed to V McAlister.

At least 19 recordsLinked to original sources
PubMed2003

Survival after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Selection criteria for patients with hepatocellular carcinoma (HCC) suitable for liver transplantation (LT) include tumor size and number and vascular invasion. There has been a recent trend to expand the transplant criteria for HCC. We reviewed our experience to determine survival following LT based on tumor characteristics. METHODS: A retrospective analysis was performed on 72 patients with HCC who underwent LT between 1985 and July 2002. The Milan criteria were applied for LT candidacy for HCCs that were deemed unresectable from anatomical considerations and/or the severity of underlying cirrhosis. Patients were divided into four groups: group 1: patients with known HCC who satisfied the selection criteria (n = 22); group 2: patients with known HCC that exceeded the criteria (n = 17); group 3: patients with incidental HCC found at pathological examination of the explant (n = 33); group 4: contemporary LT recipients without HCC (n = 935). RESULTS: In the known HCC group, the interval between listing as status 2 and transplantation was 72.2 +/- 133.6 days (median 23 days). Three-year patient survival was 80.2% in group 1, 35.8% in group 2, 63.2% in group 3, and 81.5% in group 4. In group 2 patients, the tumors were significantly larger, had more nodules, and were more often bilobar. In group 3, five (15%) exceeded the criteria mainly because of tumor size and four patients died within 3 years post-LT (three from tumor recurrence). CONCLUSION: Liver transplantation for HCC yields acceptable survival in early-stage tumors, particularly if transplanted soon after listing. Long-term survival was inferior in patients with multiple tumors and tumors that were greater than 5 cm in diameter.

Carcinoma, Hepatocellular↗
PubMed2003

Liver transplantation for primary sclerosing cholangitis.

UNLABELLED: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. This report is a retrospective analysis of a Canadian centre experience with liver transplantation (LT) for PSC. Of 1107 LTs performed between 1984 and 2002, 132 were performed on 111 patients with PSC. Patient survival at 1, 3, 5, and 10 years was 84.5%, 84.5%, 83.4%, and 68.9%, respectively. Graft survival at 1, 3, 5, and 10 years was 80.8%, 79.8%, 72.7%, and 55.3%. These were not significantly different from overall patient survival (P =.91) or graft survival (P =.28) in non-PSC patients transplanted over the same time period. Early mortality was predominantly related to primary nonfunction and multi-organ failure; late mortality was predominantly related to malignancy. No patient with known cholangiocarcinoma (CCA) underwent LT, but three patients had an incidental CCA noted on explant pathology. All three died of widespread metastatic disease (10.8, 38.0, and 39.8 months after LT). Nineteen patients lost their primary grafts requiring retransplantation, and two of these patients required a third transplant. Recurrent PSC was detected in six patients and suspected in another six. Four patients have been retransplanted for recurrent PSC. Chronic rejection was detected in nine patients. Eight have required retransplantation. The incidence of biliary complications was 16.2%. CONCLUSIONS: LT is effective therapy for PSC. Patient and graft survival is comparable to that seen in patients transplanted for indications other than PSC, but long-term graft survival may be lower. Recurrent PSC and chronic rejection are the major determinants of graft loss.

Actuarial Analysis↗
PubMed2000

Prolongation of allograft survival by Nippostrongylus brasiliensis is associated with decreased allospecific cytotoxic T lymphocyte activity and development of T cytotoxic cell type 2 cells.

BACKGROUND: We have demonstrated that infection with Nippostrongylus brasiliensis (Nb), which induces strong type 2 responses, prolongs kidney allograft survival in rats. Here, we confirm that this effect is not species-specific and address immune modulation in allospecific T-cell responses mediated by nematode infection. METHODS: C57BL/6 mice were injected with Nb or phosphate-buffered saline. Four days later, mice were transplanted with BALB/c hearts and graft survival was assessed. In other experiments, Nb-infected mice were immunized with BALB/c spleen cells and allospecific T-cell responses were determined in vitro. RESULTS: In this study, we show that Nb prolongs cardiac allograft survival in mice. Further, spleen T cells from Nb-infected, allo-immunized mice exhibit reduced allospecific cytotoxic T-lymphocyte activity. In contrast, allospecific proliferation of T cells in the mixed lymphocyte reaction was not reduced by Nb, ruling out immunosuppression as the mechanism of Nb-induced allograft survival. Nb infection induced IL-4 and IL-6 and inhibited IFN-gamma production by T cells in response to allo-antigen. Furthermore, anti-IL-4 treatment reduced allospecific T-cell proliferation from Nb-infected but not control mice, indicating that type 2 allospecific T cells develop in the presence of Nb. We also double-stained T cells for CD8 and IL-4 and showed that Nb induces an 8-fold increase in Tc2 cell numbers. CONCLUSIONS: These results are consistent with a hypothesis that Nb mediates prolongation of allograft survival through induction of type 2 immunity, including the development of regulatory Tc2 cells, and subsequent inhibition of allospecific cytotoxic T-lymphocyte activity.

Animals↗
PubMed2000

Effect of recipient sensitization (peak PRA) on graft outcome in haploidentical living related kidney transplants.

OBJECTIVE: To evaluate the influence of pre-transplant recipient sensitization on the outcome of 1-haploidentical live related donor (LRD) kidney transplants. METHOD: We reviewed 141 consecutive cyclosporine-treated adult haploidentical first transplants for which panel reactive antibody (PRA) levels were available. Patients were divided into three groups according to their peak PRA levels: group I, PRA = 0 (n = 97); group II, PRA = 1-50% (n = 24); and group III, PRA = 51-100% (n = 20). RESULTS: Differences in PRA were associated with significant differences in short- and longer-term graft survival, unrelated to patient survival. Graft survival at 1, 3, and 5 yr was only 74, 40, and 27% in group III, compared to 92, 87, and 52% in group II, and 96, 91, and 85% in group I (p < 0.001). Increasing PRA was associated with shorter time-to-graft failure. In group III, 20% lost their transplant from acute rejection in the first 6 months, versus 4% in group II and 3% in group I (p < 0.01). Graft survival in group II diverged from that of group I only after 3 yr, due to an increase in loss from chronic rejection. Hospitalization was longer in group III, in association with a significantly higher incidence of acute rejection during the first 3 months after transplantation (p < 0.02). Serum creatinine was higher in sensitized than nonsensitized patients at all time points. CONCLUSIONS: Sensitization has a significant negative impact on the outcome of haploidentical LRD kidney transplants. Sensitized potential recipients and their potential donors should be aware of this in arriving at informed decision-making for transplantation. These patients may benefit from more sensitive cross-match testing, more intense or more novel immunosuppression, or immunomodulation to modify their immune responsiveness.

Adult↗
PubMed1999

Potential for improved therapeutic index of FK506 in liposomal formulation demonstrated in a mouse cardiac allograft model.

BACKGROUND: FK506 is a potent immunosuppressant that has improved clinical outcomes in kidney and liver transplantation both as a primary and as a rescue immunosuppressive agent. Despite these benefits, the potential value of FK506 is limited by toxic side effects that result in a narrow therapeutic index. By encapsulating the active drug within liposomes (LipoFK506), a new formulation has been developed that might improve this therapeutic index. METHODS: The biodistribution of tritiated-FK506 administered i.v. showed that the drug remained associated with the liposomal carrier in vivo, and that its tissue distribution was increased in heart and spleen compared to nonliposomal FK506. The immunosuppressive efficacy of lipoFK506 compared with conventional FK506 formulation was tested in vivo. CBA (H2k) mice were engrafted with BALB/c (H2d) mouse hearts with daily immunosuppression using either 1 mg/kg FK506, or 1 mg/kg LipoFK506, from day 0 to 14. RESULTS: At day 7 the blood trough level of FK506 in the FK506 group was 10-fold higher (25 microg/L) than that in the LipoFK506 group. In both groups the median heart allograft survival was similar at around 26 days. The possibility that FK506, or LipoFK506, might influence antibody-mediated tolerogenesis was addressed in the same model: neither formulation prevented tolerance induction by CD4 and CD8 blockade. CONCLUSION: LipoFK506 is a novel formulation of FK506 that is efficacious at low blood trough FK506 levels. This property has a direct potential benefit for clinical organ transplantation.

Animals↗
PubMed1999

The morbidity of prolonged wound drainage after kidney transplantation.

PURPOSE: The consequences of prolonged wound drainage, defined as extravasation of more than 50 ml. fluid daily for more than 1 week through a drain or wound after renal transplantation, have not been well described in the literature. We examine the association of prolonged wound drainage with other clinical events, and its impact on hospitalization, and patient and graft survival. MATERIALS AND METHODS: We prospectively documented prolonged wound drainage in 392 recipients of cadaver and live renal transplants from July 1993 to December 1997. Potential risk factors, associated outcomes within the first 6 months and effect on length of hospital stay due to prolonged wound drainage were determined. RESULTS: Prolonged wound drainage was significantly associated with pre-transplantation weight, weight gain by post-transplantation day 3, delayed graft function and continuous ambulatory peritoneal dialysis on univariate analysis but only with delayed graft function (odds ratio 2.8, 95% confidence intervals 1.4 to 5.6) on multivariate analysis. Post-transplantation lymphoceles (5.2, 9 to 14), wound infection (27, 5.7 to 130) and wound dehiscence (5.8, 1.7 to 20) were associated with prolonged wound drainage. Patients with prolonged wound drainage stayed 8.7 additional days during the first hospitalization and overall 11.3 additional days during the first 6 months after transplantation independent of other co-morbid events, such as delayed graft function, rejection or cytomegalovirus disease. CONCLUSIONS: Prolonged wound drainage is an important post-renal transplantation event that impacts patient outcomes and hospital resource use. Efforts to prevent this complication should be considered.

Adult↗
PubMed1996

Kidney transplantation, the Halifax experience.

In the absence of a national kidney sharing system in Canada, virtually all the cadaver kidneys we transplant come from donors within the 4 provinces we serve. Currently the only criteria we use for recipient selection of cadaver kidneys, apart from ABO blood group matching and a negative anti-T-cell crossmatch, are good HLA match and transplant wait-list seniority. All transplant recipients receive CsA-based immunosuppression. Antibody induction is used only for repeat transplants and pediatric transplants. Recipients of first cadaver kidney transplants with zero HLA-DR mismatches have significantly better graft survival than those with mismatches. Graft and patient survival rates for first cadaver transplants continue to improve within the CsA era, and are comparable to those seen in centers routinely using antibody induction and routine sequential quadruple immunosuppression. Chronic graft nephropathy continues to be the most important cause of graft loss after the first year, unchanged over the past 2 decades, followed closely by death with a functioning kidney. The latter is a more important cause of loss in recipients older than age 60, and in recipients of HLA-identical live donor transplants. Repeat cadaver transplant recipients have a 5-year graft survival rate today equivalent to that seen with first cadaver transplants. Graft loss from acute rejection is modest, but kidneys requiring rescue therapy for steroid-resistant rejection have significantly poorer one- and 5-year graft survival and ultimately are lost from rejection. Patients with HLA-identical live-related donor transplants have better long-term survival with CsA than with azathioprine due to a decrease in graft loss from chronic rejection. Pre-transplant sensitization has an adverse effect on graft survival for haploidentical but not HLA identical live-related transplants. Patients over age 60 have equivalent graft survival to younger recipients for at least 7 years, and should not be precluded from receiving transplants by age alone. Prolonged CIT > 24 hours is associated with a significantly increased incidence and duration of ATN and need for dialysis, significantly increased early and late graft loss from acute and chronic rejection respectively, significantly reduced QALY's, and significantly higher early and late costs of transplantation.

Adult↗
PubMed1993

[Right diaphragmatic paralysis after liver transplantation].

Right hemidiaphragm paralysis has been previously documented in patients after orthotopic liver transplantation (OLT) and it may contribute to the development of postoperative pulmonary problems. It has been postulated that a crush injury to the right phrenic nerve during OLT is the cause of dysfunction of the right hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury after OLT, we prospectively studied 51 adult liver recipients that we compared with twelve patients who underwent liver resection (LR) without suprahepatic vena cava clamping. We studied the diaphragm excursion by ultrasound, the pulmonary function tests and the transcutaneous phrenic nerve conduction. Righ phrenic nerve injury and hemidiaphragm paralysis occurred respectively in 79% and 38% of the liver recipients but not after LR. Conduction along the right phrenic nerve was absent in 53% of the patients and reduced in another 26%. Left phrenic nerve conduction and left hemidiaphragm excursion were normal in both groups. Liver recipients with no conduction in the right phrenic nerve had a significantly greater decrease in vital capacity in the supine position compared to those with some conduction (29% vs 14%; P < 0.001). However, neither the time on the ventilator or the hospital stay were significantly different between the two groups. Complete recovery of phrenic nerve conduction and diaphragm function may take up to nine months. Right phrenic nerve injury is common after OLT and causes right hemidiaphragm dysfunction.

Adolescent↗
PubMed1993

[Technique to minimize the incidence of hepatic artery thrombosis in pediatric liver transplantation].

Hepatic artery thrombosis is a life-threatening complication after pediatric liver transplantation. We reviewed our experience in 62 children who received 72 liver transplant (69 whole grafts and 3 reduced-size grafts) between January 1984 and December 1991. They ranged in age from 6 months to 16 years (mean 5.8 years). Fifteen children (22%) were under 2 years and 10 patients (14%) were between 2 and 5 years. Forty-eight grafts in older children (age: 1-16 years, x = 7 years had an anastomosis between the donor hepatic/celiac artery and the recipient hepatic of splenic artery (A-A). Three thromboses occurred in this group for an incidence of 6.2%. Two others types of arterial reconstruction were used in 24 children who were significantly younger (6-120 months, x = 47 months, p < 0.01). Eight grafts had an anastomosis between the donor celiac artery and the recipient aorta (A-Ao). No thromboses occurred in this group. Sixteen grafts were revascularized using a donor aortic conduit anastomosed to the recipient aorta (AC) with a 12.5% (2 to 16) incidence of thrombosis. The incidence of arterial thrombosis for the entire group was 6.9%. In conclusion, by using the recipient aorta for arterial reconstruction, a low incidence of hepatic artery thrombosis can be achieved even in the group of younger patients who are the highest risk for this complication.

Adolescent↗
PubMed1993

Endoscopic retrograde cholangiopancreatography in the management of choledocholithiasis with laparoscopic cholecystectomy.

With the advent of laparoscopic cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) has an increasing role in perioperative management. To assess this role, the authors studied, retrospectively, 12 patients who underwent ERCP out of a series of 475 who had laparoscopic cholecystectomy. ERCP was indicated preoperatively for biliary colic in four patients, gallstone pancreatitis in two and common bile duct stone on ultrasonography in one. ERCP was performed postoperatively for jaundice in three patients, for cholangitis in one and for a positive intraoperative laparoscopic cholangiogram in one. Choledocholithiasis was diagnosed in six patients preoperatively and in three postoperatively. Only one patient had an unsuspected residual bile duct stone postoperatively. Of nine patients with stones, endoscopic sphincterotomy was performed in eight and stones were cleared in all with no complications; a stone passed spontaneously in the other patient. ERCP is indicated before laparoscopic cholecystectomy in cases of jaundice, gallstone pancreatitis, cholangitis, abnormal liver biochemistry suggesting cholestasis and ultrasonographic demonstration of either a common bile duct stone or a common bile duct greater than 8 mm in diameter. Operative laparoscopic cholangiography is indicated when the anatomy is unclear or the bile duct appears dilated. If choledocholithiasis is founded, the options include open or laparoscopic common bile duct exploration and intra- or postoperative endoscopic sphincterotomy.

Adult↗