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Biomedical subjects

J O Colonna

Publications and source records attributed to J O Colonna.

At least 19 recordsLinked to original sources
PubMed1993

Differences in oral FK506 dose requirements between adult and pediatric liver transplant patients.

The oral dose recommendation for FK506 (Fujisawa Pharmaceutical, Deerfield, IL) after liver transplantation has, to date, made no distinction between adult and pediatric patients. Sixteen pediatric and 33 adult liver transplant patients treated long term with oral FK506 were studied. Initial FK506 doses were 0.3 mg/kg/day p.o. or 0.15 mg/kg/day i.v. Thereafter, doses were adjusted to achieve therapeutic FK506 serum levels (0.5-3.0 ng/ml, ELISA liquid/liquid separation) and to maintain an acceptable serum creatinine. FK506 (in mg/kg/day), FK506 levels, and liver function were assessed at monthly intervals on outpatient visits. The mean age of 16 pediatric patients was 5.3 +/- 3.5 years and of 33 adult patients was 49 +/- 12 years. Mean days of FK506 therapy were 284 +/- 136 for pediatric patients and 239 +/- 112 for adult patients. For each time period, pediatric patients required a significantly higher dose of FK506 compared to adult patients (P < 0.001). The overall mean pediatric dose for the first year was 0.46 +/- 0.4 mg/kg/day compared to the mean adult dose of 0.13 +/- 0.01 mg/kg/day. The ratio of pediatric to adult oral FK506 dose requirements ranged from 2.7 to 4.4 over the 1 year of followup. FK506 levels monitored at the same time points showed no significant differences at any month between pediatric and adult patients. We conclude that the oral dose per kilogram per day of FK506 required to maintain similar FK506 levels is significantly greater in pediatric patients compared to adult recipients during the first year of follow-up. Pediatric recipients require substantially more, and adult recipients substantially less, than the recommended oral FK506 dose to achieve a therapeutic effect.

Administration, Oral↗
PubMed1993

A comparison of renal function in cyclosporine- and FK-506-treated patients after primary orthotopic liver transplantation.

In this randomized controlled trial comparing FK-506 to CsA, we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant (OLT). Patients randomized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day. Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml. CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels. A pre-OLT glomerular filtration rate (GFR) of > or = 30 ml/min/1.73/m2 and/or serum creatinine < or = 2.0 mg/dl were required for inclusion in the study. GFRs were obtained at post OLT days 28, 180, and 360. Other parameters of renal function evaluated were creatinine, magnesium, serum electrolytes, blood pressure, use of antihypertensives, and magnesium supplements. There were 38 patients in the FK-506 group and 34 in the CsA group. The mean days of follow up for each group was similar: 456 +/- 135 days for the FK-506 group and 451 +/- 112 days for the CsA group. The mean oral dose for the FK-506 group ranged from 0.13-0.16 mg/kg/day with mean FK-506 levels of 0.6-0.8 ng/ml. In the FK-506 group, there was a significant fall in the pre-transplant GFR from 89 +/- 31 ml/min/173 m2 to 43 +/- 15 ml/min/173 m2 at day 360. Similarly, for the CsA group, the pre-transplant GFR of 75 +/- 31 ml/min/1.73 m2 fell to 49 +/- 17 ml/min/1.73 m2 at day 360. At each time point studied, there was no significant difference in mean GFR between the two groups. There were no significant differences in the monthly mean values for creatinine, electrolytes, magnesium, or blood pressure between the two groups. Magnesium levels were in the low normal range (1.4-1.6 mEq/L), and the mean potassium levels in the high normal range (4.4-4.7 mEq/L). In both groups, a similar number of patients required magnesium supplementation or hypertensive medications. The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension.

Adult↗
PubMed1993

Radical resection combined with liver transplantation for foregut tumors.

Between February 1984 and July 1992, six adults with advanced pancreatic adenocarcinoma (n = 1), pancreatic neuroendocrine tumor (n = 2), and cholangiocarcinoma (n = 3) underwent radical foregut resections (n = 3) or radical pancreaticoduodenectomy (n = 3) combined with liver transplantation. The major postoperative complications included diarrhea (n = 4), pancreaticojejunostomy leak (n = 3), infection (n = 7), malnutrition (n = 3), refractory ascites (n = 2), and late hepatic artery thrombosis (n = 1). Tumor recurrence occurred in one patient. The actuarial survival for the group is 82 per cent at 1 year and 55 per cent at 2 years. The results demonstrate that radical pancreaticoduodenectomy/foregut resections combined with liver transplantation offer potential surgical cure of malignancies involving these organs. However, the procedure is formidable, with frequent complications.

Adenocarcinoma↗
PubMed1993

Resection of the caudate lobe through "bloody gultch".

Isolated resection of the caudate lobe for primary or metastatic neoplasms is an uncommon operation. Our experience with mobilization of the liver in more than 700 hepatic transplants has led us to a simplified technique for caudate lobe resection. Herein we describe our technique and report our experience with three patients.

Adult↗
PubMed1992

The interrelation between sclerosing cholangitis and ulcerative colitis in patients undergoing liver transplantation.

Thirty-six patients underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis under cyclosporine, azathioprine, and steroid immunosuppression. Of these patients, 29 suffered from chronic ulcerative colitis. The purpose of this study is to determine (1) whether replacement of the diseased liver and the altered immunocompetence suppresses the manifestation of chronic ulcerative colitis, and (2) if active colonic disease alters allograft function. Thirty of 36 patients survived OLT. After OLT, seven of 14 patients with symptomatic colon disease at the time of transplantation continue to suffer from active chronic ulcerative colitis, and three of 13 who were asymptomatic developed clinically active disease. Intractable colonic disease was the indication for post-OLT proctocolectomy in three patients, and one refused an indicated colectomy. Despite the long duration of the disease, none developed colonic malignancy. Long-term graft assessment showed good hepatocyte synthetic function in patients suffering from either active or inactive disease. Liver alkaline phosphatase, however, was significantly higher in patients suffering from active colonic disease. Furthermore, the alkaline phosphatase in symptomatic patients was higher than that seen in a matched cohort undergoing OLT for chronic active hepatitis or primary biliary cirrhosis. These results suggest that (1) liver replacement and immunosuppression in patients suffering from sclerosing cholangitis and ulcerative colitis do not alter the course of the colon disease, and (2) active chronic ulcerative colitis does not adversely affect allograft function, although elevation of alkaline phosphatase may be the harbinger of recurrence over the long term.

Adult↗
PubMed1992

Biliary strictures complicating liver transplantation. Incidence, pathogenesis, management, and outcome.

Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.

Adult↗
PubMed1992

Liver resection for primary neoplasms.

Resection is the treatment of choice for almost all hepatic neoplasms. Improvements in operative techniques and perioperative patient management have resulted in low morbidity and mortality. Patients with underlying chronic liver disease in association with hepatic malignancy now can be offered either subsegmental resection or liver transplantation in selected cases. The role of cryosurgery and alcohol injection in patients who are not candidates for resection should become clearer once longer follow-up data are available.

Adenoma, Bile Duct↗
PubMed1992

Hepatic artery thrombosis resulting in gas gangrene of the transplanted liver.

Early hepatic artery thrombosis after orthotopic liver transplantation results in massive injury to hepatocytes and the bile duct epithelium. In the fulminate form, impaired liver synthetic function is expressed by encephalopathy and coagulopathy. Ischemic bile duct injury is associated with the disruption of the biliary anastomosis, bile duct strictures, and intrahepatic bilomas. The inability of the liver macrophages to clear translocated portal blood intestinal pathogens results in persistent bacteremia and sepsis. The major radiologic finding is the radiographic evidence of gas gangrene of the liver graft. Early recognition and correct interpretation of the radiologic findings, immediate removal of the liver graft, and placement of the patient on venous-venous bypass or total hepatic devascularization while a new liver is being procured and retransplantation are the only hope for survival.

Adult↗
PubMed1991

Liver transplantation at UCLA: report of clinical activities.

Liver transplantation remains the treatment of choice for many forms of end-stage liver disease. In most large series, 5-year actuarial survival is greater than 70%. The majority of the morbidity and mortality occurs in the first 6 months posttransplant; as these figures have improved, so have overall survival rates. Infants under 1 year of age have a survival rate below that of older patients; in addition, a severe organ shortage for these patients continues. The use of reduced grafts has ameliorated the problem to a certain extent; however, further expansion of the donor pool is still necessary. Progress has also been made in the postoperative management of transplant patients. We currently follow AKBR and TNF levels in all patients to aid in the diagnosis of primary nonfunction and acute rejection, respectively. The introduction of additional immunosuppressive agents has instigated several large clinical trials. CsA, however, remains the gold standard to which these drugs must be compared.

Actuarial Analysis↗
PubMed1990

One-stage repair of colovaginal fistula complicating acute diverticulitis.

Fourteen patients with colovaginal fistula secondary to sigmoid diverticulitis were seen between 1964 and 1988. Thirteen had undergone prior hysterectomy. Three different operative approaches were used. Three patients were treated with colostomy alone; one died and the fistula persisted in one. Five patients underwent staged procedures. One patient died of complications after the second stage of a planned three-stage procedure. Four patients underwent a two-stage procedure (fistula takedown, colectomy with colostomy and colostomy closure), all with good results. Six patients were treated with one-stage fistula takedown, colectomy and primary anastomosis, without major complication. We advocate this as the procedure of choice and emphasize the following principles of epidemiology and management: 1) colovaginal fistula complicates diverticulitis in elderly women usually following hysterectomy; this association may be a factor in etiology; 2) vaginography is useful in diagnosis; and 3) planned one-stage repair is the best surgical approach.

Aged↗
PubMed1989

Effect of a prior portasystemic shunt on subsequent liver transplantation.

Fifteen patients who had a prior portasystemic shunt underwent orthotopic liver transplantation. Shunt types were portacaval in six patients, H-graft mesocaval in six, distal splenorenal in two, and proximal splenorenal in one. Mean blood loss and hospital stay were highest in the portacaval group. Retransplants (two patients) and deaths (two patients) also were limited to this group. In this report, technical considerations, advantages, and disadvantages of the various shunt types are described. Management of patients with late stages of portal hypertension must include estimation of the effects of a portasystemic shunt on subsequent liver transplantation. It is concluded that portacaval shunts should be avoided in patients who may be considered for transplantation. Distal splenorenal shunts are best performed in younger patients with intractable variceal bleeding who are not expected to require transplantation in the near future. A mesocaval H-graft is the shunt of choice in patients who are current liver transplant candidates.

Adult↗
PubMed1989

Randomized prospective trial of OKT3 for early prophylaxis of rejection after liver transplantation.

A group of 52 liver transplant patients was prospectively randomized to receive prophylactic immunosuppressive therapy consisting of either Orthoclone OKT3 for 14 days, azathioprine, and steroids (25 patients); or cyclosporine, azathioprine, and steroids (27 patients). The groups were similarly matched for age, diagnosis, and Child's classification. The patients were studied to determine the effect of these two regimens on the incidence of rejection, infection, renal dysfunction, and mortality. Seven rejection episodes, as determined by clinical and histological criteria, occurred in seven of 25 patients (28%) receiving OKT3 compared with 18 episodes in 27 patients (67%) receiving cyclosporine during the first 14 days after transplantation (P less than 0.02). In 20% of the OKT3 patients, CD3+ levels of greater than 10% developed during therapy, and 16% of the patients developed anti-OKT3 antibodies during OKT3 treatment. Five patients were retreated with OKT3 for steroid-resistant acute rejection episodes; all had resolution of the rejection episode. Infectious complications were similar in each group. Renal function, as measured by serum creatinine, was significantly better with OKT3 than with cyclosporine (P less than 0.003) at 14 days. We conclude that prophylactic OKT3 is effective in reducing the number of early rejection episodes after liver transplantation; after 14 days the incidence of rejection is similar; reuse of OKT3 has been successful in liver transplant patients; infectious complications are similar between OKT3 and cyclosporine; and OKT3 preserves renal function better than cyclosporine and is thus indicated in patients with compromised preoperative renal function.

Antibodies, Anti-Idiotypic↗