Biomedical subjects

D Azoulay

Publications and source records attributed to D Azoulay.

At least 37 records · Page 2Linked to original sources

PubMed2001

Split-liver transplantation for two adult recipients: feasibility and long-term outcomes.

OBJECTIVE: To identify the outcomes and risks of split-liver transplantation (SLT) for two adult recipients to determine the feasibility of more widespread use of this procedure to increase the graft pool for adults. SUMMARY BACKGROUND DATA: The shortage of cadaver liver grafts for adults is increasing. Using livers from donors defined as optimal, the authors have been developing techniques for SLT for two adult recipients at their center. METHODS: From July 1993 to December 1999, 34 adults have undergone SLT with grafts from optimal donors prepared by ex situ split (n = 30) or in situ split (n = 4), and 88 adults received optimal whole-liver grafts that were not split. Four split-grafts were transplanted at other centers. The outcomes of transplantation with right and left split-liver grafts were compared with those of whole-liver transplants. The main end points were patient and graft survival at 1 and 2 years and the incidence and types of complications. RESULTS: For whole-liver, right and left split-liver grafts, respectively, patient survival rates were 88%, 74%, and 88% at 1 year and 85%, 74%, and 64% at 2 years. Graft survival rates were 88%, 74%, and 75% at 1 year and 85%, 74%, and 43% at 2 years. Patient survival was adversely affected by graft steatosis and recipients inpatient status before transplantation. Graft survival was adversely affected by steatosis and a graft-to-recipient body weight ratio of less than 1%. Primary nonfunction occurred in three left split-liver grafts. The rates of arterial (6%) and biliary (22%) complications were similar to published data from conventional transplantation for an adult and a child. SLT for two adults increased the number of recipients by 62% compared with whole-liver transplantation and was logistically possible in 16 of the 104 (15%) optimal cadaver donors. CONCLUSIONS: Split-liver transplantation for two adults is technically feasible. Outcomes and complication rates can be improved by rigid selection criteria for donors and recipients, particularly for the smaller left graft, and possibly also by in situ splitting in cadaver donors. Wider use will require changes in the procedures for graft allocation and coordination between centers experienced in the techniques.

Adult↗

PubMed2001

Auxiliary partial orthotopic versus standard orthotopic whole liver transplantation for acute liver failure: a reappraisal from a single center by a case-control study.

OBJECTIVE: To reappraise the results of auxiliary partial orthotopic liver transplantation (APOLT) compared with those of standard whole-liver transplantation (OLT) in terms of postoperative death and complications, including neurologic sequelae. SUMMARY BACKGROUND DATA: Compared with OLT, APOLT preserves the possibility for the native liver to recover, and to stop immunosuppression. METHODS: In a consecutive series of 49 patients transplanted for fulminant or subfulminant hepatitis, 37 received OLT and 12 received APOLT. APOLT was done when logistics allowed simultaneous performance of graft preparation and the native liver partial hepatectomy to revascularize the graft as soon as possible. Each patient undergoing APOLT (12 patients) was matched to two patients undergoing OLT (24 patients) according to age, grade of coma, etiology, and fulminant or subfulminant type of hepatitis. All grafts in the study population were retrieved from optimal donors. RESULTS: Before surgery, both groups were comparable in all aspects. In-hospital death occurred in 4 of 12 patients undergoing APOLT compared with 6 of 24 patients undergoing OLT. Patients receiving APOLT had 1 +/- 1.3 technical complications compared with 0.3 +/- 0.5 for OLT patients. Bacteriemia was significantly more frequent after APOLT than after OLT. The need for retransplantation was significantly higher in the APOLT patients (3/12 vs. 0/24). Brain death from brain edema or neurologic sequelae was significantly more frequent after APOLT (4/12 vs. 2/24). One-year patient survival was comparable in both groups (66% vs. 66%), and there was a trend toward lower 1-year retransplantation-free survival rates in the APOLT group (39% vs. 66%). Only 2 of 12 (17%) patients had full success with APOLT (i.e., patient survival, liver regeneration, withdrawal of immunosuppression, and graft removal). One of these two patients had neurologic sequelae. CONCLUSIONS: Using optimal grafts, APOLT and OLT have similar patient survival rates. However, the complication rate is higher with APOLT. On an intent-to-treat basis, the efficacy of the APOLT procedure is low. This analysis suggests that the indications for an APOLT procedure should be reconsidered in the light of the risks of technical complications and neurologic sequelae.

Adolescent↗

PubMed2000

Transplantation of three adult patients with one cadaveric graft: wait or innovate.

Graft shortage continues to prolong waiting times for adults requiring liver transplantation. Living related donor transplantation is possible for only a small minority of adults. The techniques for in situ splitting of the liver used for right and left hepatectomies in living donors were adapted to a combined split-liver-domino procedure to obtain right and left hemiliver grafts from a patient undergoing total hepatectomy with liver transplantation for a metabolic disorder. The two grafts were adequate in size and function for transplantation to two adults with low priority for regular cadaver grafts. More frequent use of split-liver techniques in cadaver donors could considerably reduce the graft shortage and waiting time for adult liver recipients.

Adult↗

PubMed2000

Caval inflow to the graft: a successful way to overcome diffuse portal system thrombosis in liver transplantation.

Portal vein thrombosis was considered to be a major contraindication to liver transplantation before the introduction of vessel grafts from the recipient's area of confluence of the splenic and superior mesenteric veins, behind the neck of the pancreas, to the graft's portal vein. Refinement in surgical technique has given rise to a large number of possibilities to overcome portal vein thrombosis in OLT recipients, ranging from portal vein thrombectomy to several different venous graft jump reconstructions. All these reconstructions require the presence of a patent vein of the portal system. When neither splanchnic veins nor sufficiently large venous collaterals are available, liver transplantation has been considered impossible. Salvage solutions include arterialization of the portal vein with the associated risk of liver damage in the longterm, a combined liver and bowel transplantation has been proposed but not yet reported (and in any case the results of combined liver and bowel transplants are not as good as those of liver transplantation alone) and finally the use of blood inflow from the inferior vena cava as first reported by Tzakis and coworkers. Portal flow from the inferior vena cava may be performed as a last resort. Although the consequences of severe pretransplantation portal hypertension remain and should be treated before, during, and after transplantation, liver function is normal in the short and midterm. With this new procedure, diffuse portal vein thrombosis is no longer an absolute contraindication to liver transplantation. But this needs to be confirmed in light of further experience and longterm followup.

Anastomosis, Surgical↗

PubMed2000

Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation.

Severe veno-occlusive disease (VOD) of the liver is a leading cause of mortality after bone marrow transplantation (BMT). Vascular and parenchymal injuries account for acute portal hypertension and liver failure is frequently present. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT. TIPS was performed in 10 patients with histologically proven severe VOD. Portal hypertension was controlled by TIPS in all patients (mean hepatic venous pressure gradient before, 20 +/- 11 vs 6 +/- 5 mm Hg after TIPS, P < 0.01) without technical complications. Five patients with rapidly worsening VOD died within 10 days of TIPS without any improvement. The five remaining patients with less advanced disease showed improvement in various clinical and biological parameters. Four patients subsequently died. The lone survivor continues to do well with resolution of VOD 6 months after TIPS. TIPS can be performed safely and controls portal hypertension in VOD after BMT. Arguments from the present series and from eight previously reported cases favour earlier application of TIPS to obtain improved overall survival. Bone Marrow Transplantation (2000) 25, 987-992.

Adolescent↗

PubMed2000

Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization.

OBJECTIVE: To assess the influence of preoperative portal vein embolization (PVE) on the long-term outcome of liver resection for colorectal metastases. SUMMARY BACKGROUND DATA: Preoperative PVE of the liver induces hypertrophy of the remnant liver and increases the safety of hepatectomy. METHODS: Thirty patients underwent preoperative PVE and 88 patients did not before resection of four or more liver segments. PVE was performed when the estimated rate of remnant functional liver parenchyma (ERRFLP) assessed by CT scan volumetry was less than 40%. RESULTS: PVE was feasible in all patients. There were no deaths. The complication rate was 3%. The post-PVE ERRFLP was significantly increased compared with the pre-PVE value. Liver resection was performed after PVE in 19 patients (63%), with surgical death and complication rates of 4% and 7% respectively. PVE increased the number of resections of more than four segments by 19% (17/88). Actuarial survival rates after hepatectomy with or without previous PVE were comparable: 81%, 67%, and 40% versus 88%, 61%, and 38% at 1, 3, and 5 years respectively. CONCLUSIONS: PVE allows more patients with previously unresectable liver tumors to benefit from resection. Long-term survival is comparable to that after resection without PVE.

Aged↗

PubMed2000

Percutaneous portal vein embolization increases the feasibility and safety of major liver resection for hepatocellular carcinoma in injured liver.

OBJECTIVE: To assess the influence of preoperative portal vein embolization (PVE) on the long-term outcome of liver resection for hepatocellular carcinoma (HCC) in injured liver. SUMMARY BACKGROUND DATA: On an healthy liver, PVE of the liver to be resected induces hypertrophy of the remnant liver and increases the safety of hepatectomy. On injured liver, this effect is still debated. METHODS: During the study period, 10 patients underwent preoperative PVE and 19 patients did not before resection of three or more liver segments for HCC in injured liver (cirrhosis or fibrosis). PVE was performed when the estimated rate of remnant functional liver parenchyma (ERRFLP) assessed by computed tomographic scan volumetry was less than 40%. RESULTS: In all patients, PVE was feasible. There were no deaths or complications. The ERRFLP after PVE was significantly increased compared with the pre-PVE value. Liver resection was performed after PVE in 9 of 10 patients, with surgical death and complication rates of 0% and 45%, respectively. PVE increased the number of resections of three or more segments by 47% (9/19). Overall actuarial survival rates with or without previous PVE (89%, 67%, and 44% vs. 80%, 53%, and 53% at 1, 3 and 5 years, respectively) and disease-free actuarial survival rates (86%, 64%, and 21% vs. 55%, 17%, and 17% at 1, 3, and 5 years respectively) after hepatectomy were comparable. CONCLUSION: With the use of PVE, more patients with previously unresectable HCC in injured liver can benefit from resection. Long-term survival rates are comparable to those after resection without PVE.

Carcinoma, Hepatocellular↗

PubMed2000

Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors.

OBJECTIVE: To assess feasibility, risks, and patient outcomes in the treatment of colorectal metastases with two-stage hepatectomy. SUMMARY BACKGROUND DATA: Some patients with multiple hepatic colorectal metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization, or combined with a locally destructive technique. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. In selected patients with irresectable multiple metastases not amenable to a single hepatectomy procedure, two-stage hepatectomy might offer a chance of long-term remission. METHODS: Of consecutive patients with conventionally irresectable colorectal metastases treated by chemotherapy, 16 of 398 (4%) became eligible for curative two-stage hepatectomy combined with chemotherapy and adjuvant nonsurgical interventions as indicated. RESULTS: Two-stage hepatectomy was feasible in 13 of 16 patients (81%). There were no surgical deaths. The postoperative death rate (2 months or less) was 0% for the first-stage procedure and 15% for the second-stage one. Postoperative complication rates were 31% and 45%, respectively, with only one complication leading to reoperation. The 3-year survival rate was 35%, with four patients (31%) disease-free at 7, 22, 36, and 54 months. Median survival was 31 months from the second hepatectomy and 44 months from the diagnosis of metastases. CONCLUSIONS: Two-stage hepatectomy combined with chemotherapy may allow a long-term remission in selected patients with irresectable multiple metastases and increases the proportion of patients with resectable disease.

Aged↗

PubMed2000

Dramatic tumor response of bulky liver metastases following treatment with CPT-11 and a chronomodulated 4-day infusion of 5-fluorouracil, folinic acid and oxaliplatin every 2 weeks in a colorectal cancer patient.

Three active antitumor agents, i.e. 5-fluorouracil (5-FU), oxaliplatin and CPT-11, are available for the treatment of advanced colorectal cancer (CRC) patients and have been successfully combined in two-drug regimens. Hence, CRC has become a chemosensitive disease, but the optimal combination of these agents in first-line treatment remains to be determined. We report the first case of the combination of CPT-11 with oxaliplatin, 5-FU and folinic acid (FA) as first-line chemotherapy for a patient with a pre-occlusive sigmoid adenocarcinoma and synchronous bulky liver metastases. CPT-11 was given at 125 mg/m2, prior to the start of a chronomodulated 4-day infusion of oxaliplatin 25 mg/m2/day, 5-FU 800 mg/m2/day and FA 300 mg/m2/day repeated every 2 weeks. The doses could be escalated to 150 mg/m2 for CPT-11 and 900 mg/m2/day for 5-FU. After six cycles of chemotherapy 70% reduction in tumor size was documented in the liver. The primary tumor was no longer detectable by barium enema. The toxicity included three episodes of grade 4 neutropenic fever, and two episodes of severe diarrhea and vomiting with dehydration. A cumulative grade 2 neurosensory toxicity was observed after six cycles. Following surgery of the primary tumor, because of the major hepatic tumor response and of the absence of extra-hepatic metastases, the patient might be registered for a liver transplantation program. This first report of combining the three active agents in CRC every 2 weeks led to a high dose intensity of each agent and was associated with a dramatic tumor response of a very advanced disease in a patient with already altered performance status. The antitumor activity in this patient suggests that a three-drug intensified regimen might be feasible and active. A prospective study appears warranted to further examine the efficacy and toxicity of this therapeutic approach, and to determine whether it may increase the fraction of advanced CRC patients becoming resectable. This aggressive chemotherapy program may contribute to a re-examination of the usefulness of liver transplantation in patients with metastatic CRC confined to the liver.

Adenocarcinoma↗

PubMed2000

Complete remission of unresectable hepatocellular carcinoma on healthy liver by the combination of aggressive surgery and high-dose-intensity chemotherapy by CPT-11.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers. The only curative treatment is liver transplantation or complete surgical resection; however, most patients have inoperable disease at diagnosis. To date, no cytotoxic agent has demonstrated a clinical impact on time-related parameters, especially survival. The development of new treatments of inoperable HCC patients is highly desirable. Among the new cytotoxic agents, DNA topoisomerase I poisons are those with the widest spectrum of antitumor activity. However, few data are available in HCC patients. One of the main obstacles to the use of irinotecan in HCC is the frequent alterations of liver function at diagnosis. A 48-year-old patient with a HCC that had developed within a normal liver but of very poor prognosis because of a multifocal primary tumor with a large nodule measuring 10 cm of diameter, associated with a portal thrombosis, could tolerate very intensive treatment with irinotecan using doses up to 700 mg/m2 every 2 weeks and was responsive to treatment as measured by alpha-fetoprotein levels. Despite initial criteria of inoperability, the absence of disease progression under therapy with a follow-up of 1 year invited us to propose a liver transplant. The patient is still in post-surgical complete remission and has consolidation chemotherapy with irinotecan. This result invites us to consider the evaluation of the efficacy of topoisomerase I poisons in HCC patients and to escalate the dose of irinotecan in patients with less than grade 4 neutropenia.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Association of transjugular intrahepatic portosystemic shunt with embolization in the treatment of bleeding duodenal varix refractory to sclerotherapy.

BACKGROUND: Bleeding from duodenal varices are often severe (mortality as high as 40%), and more difficult to sclerose than esophageal varices. We report a patient with a bleeding duodenal varix, refractory to sclerotherapy, successfully treated by the association of portosystemic shunt placement and varix embolization, via the same transjugular intrahepatic route. METHODS: A 40-year-old Black male underwent emergency TIPS and duodenal varix embolization after failure of endoscopic sclerotherapy. The portosystemic pressure gradient droped from 16 to 9 mm Hg following TIPS. At 5 months from TIPS, the patient is well, with a patent shunt at Doppler ultrasound. CONCLUSION: The present report of successful control of duodenal varix, actively bleeding and refractory to sclerotherapy, by means of combined TIPS and embolization, supports the role of TIPS and suggests that its association to embolization can be valuably considered in the difficult setting of portal hypertension with bleeding duodenal varices.

Adult↗

PubMed2000

Paul Brousse Liver Transplantation: the first 1,500 cases.

During the past 16 years, more than 1,500 liver transplants were performed at Paul Brousse Hospital. The overall patient survival rates were 83% at one year and 65% at 10 years. Our group has pioneered a variety of new approaches to liver transplantation, including: 1. Anti-HBs (HBIG) prophylaxis for the prevention of HBV recurrence. To date more than 270 patients have received long-term treatment and the overall 10-year recurrence rate was 27%. 2. Transplantation for hepatocellular carcinoma of the cirrhotic liver in patients with uni- or binodular HCC (< 3 cm). Survival for transplanted patients was 83% compared with 18% if the liver was resected. 3. Transplantation for familial amyloidotic polyneuropathy (FAP). More than 60 patients had 5- and 10-year survival rates of 85% and 83%, respectively. Ten livers obtained after hepatectomy from these FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with satisfactory short-term results. 4. Reduced-size liver grafts have been used successfully to reduce pretransplant mortality and posttransplant morbidity and mortality by shortening the wait for our pediatric patients. 5. Split-liver transplantation has increased the number of transplantable livers by 28%. 6. Split-liver transplantation for 2 adults. Using optimal livers we have transplanted 34 adults with grafts prepared by ex-vivo or in-situ splitting with good survival rates. 7. Adult-to-adult living-related donor liver transplantation. In 2000, 7 adult-to-adult living donor transplants were performed with no complications from the donor surgeries. One recipient was retransplanted for arterial thrombosis, but all 7 recipients are alive at home. The Paul Brousse Hospital is committed to exploring new technologies to improve the outcome of and expand the indications for liver transplantation. We have taken a surgical approach to the organ shortage, finding new ways to serve the most patients with the limited number of livers available.

Adult↗

PubMed1999

Microsatellite instability in European hepatocellular carcinoma.

Genetic instability has been detected in many types of cancers but poorly investigated in hepatocellular carcinoma (HCC). We have studied the incidence of microsatellite instability (MI) at eight highly polymorphic microsatellite markers and the poly A tract BAT26 and tested for mutations at two sites of repetitive sequence (poly-A nucleotides 709-718 and GT repeat-nucleotides 1931-1936) in the Transforming Growth Factor beta (TGFbeta) type II receptor (RII) gene, in a group of 46 European HCCs and the surrounding nontumour tissue. This analysis showed that 63% of HCCs exhibit MI in at least one chromosome locus and 41% in two or more loci. No mutations of the TGFbetaRII gene were found in the MI positive tumours. No correlation was found with clinicopathological characteristics of the tumours such as cirrhosis, etiology, number of nodules, Edmondson's grade and vascular invasion. However, in patients who had a rearranged D16S402 microsatellite in their tumour, the recurrent disease and the number of nodules were significantly higher than in the others (P<0.005 and P<0.02, respectively). We propose to consider D16S402 rearrangement in HCC as a prognostic factor to identify patients presenting a higher risk of recurrence.

Adolescent↗

PubMed1999

[Percutaneous treatment of common bile duct lithiasis].

STUDY AIM: Biliary lithiasis in the main bile duct (particularly retained stones) may be treated percutaneously obviating reoperation or endoscopic sphincterotomy. The aim of this study was to determine risks and pitfalls of this approach. PATIENTS AND METHODS: Forty-two cases of biliary stones treated percutaneously between 1980 and 1998 were reported. Among them, 28 patients had already a biliary drainage and in 14, a drain was placed into the bile duct by transhepatic way or by punction of the intestinal loop of a bilio-jejunal anastomosis. The means to clear the bile ducts included percutaneous endoscopy and contact lithotripsy. Thirty patients had residual lithiasis (after a surgical intervention), 11 a new lithiasis above a bile duct stenosis and in 1 a bile duct lithiasis with a gallbladder lithiasis. RESULTS: Morbidity included four complications (9.5%--one severe) and no mortality. After 2.3 +/- 1 courses, desobstruction was complete in 33 cases (78.5%) and partial in one case (2.5%) allowing to optimize the patient for endoscopic sphincterotomy. Desobstruction failed in eight cases (19%), six patients were successfully treated by surgery and 2 by endoscopic sphincterotomy. CONCLUSIONS: Percutaneous desobstruction of the bile ducts may be proposed as a priority in patients with a biliary drain in place and when endoscopic sphincterotomy is impossible or contraindicated. These manoeuvres have a definitive place in hepato-biliary surgery.

Adult↗

PubMed1999

Domino liver transplants for metabolic disorders: experience with familial amyloidotic polyneuropathy.

BACKGROUND: Shortage of liver donors means that new methods of liver procurement must be explored. In domino transplantation, organs explanted during transplantation in one patient are transplanted into a second patient. Domino procedures can be performed with livers from patients having transplantation for hepatic metabolic disorders that cause systemic disease without affecting other liver functions. Familial amyloidotic polyneuropathy (FAP) type I is one of these. STUDY DESIGN: We reviewed the Paul Brousse experience with a domino liver transplant program for FAP, hoping to extend the approach to other metabolic disorders. RESULTS: Livers from 10 patients transplanted for FAP type 1 were used for domino transplants to patients with unresectable primary or metastatic liver cancers. There was no perioperative mortality. Neuropathy or cardiomyopathy did not increase the morbidity of the domino liver explant and transplant procedures. Morbidity for the domino recipients did not appear to be increased. Variant transthyretin was detected in the serum in FAP liver recipients, with no immediate clinical consequences. CONCLUSIONS: The domino approach is feasible and requires careful planning of the surgical procedures for liver explantation, particularly for the nature and site of vascular anastomoses. Domino transplantation of metabolically dysfunctional livers creates new categories of potential donors and potential recipients. It raises new ethical, technical, and societal issues. The domino approach could be used in several genetic or biochemical disorders now treated by liver transplantation. It has the potential to increase the number of liver grafts available for transplantation.

Adult↗

PubMed1999

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma.

p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12-30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of the p53 gene nor the serum alpha-fetoprotein levels and clinicopathological characteristics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P<0.03 and P<0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative 'good prognosis' in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis.

Adolescent↗

PubMed1999

[Hepatocellular carcinoma].

Hepatocellular carcinoma is a rapidly fatal tumor that usually becomes symptomatic only at a stage beyond the reach of currently available treatments. The only hope for a cure lies in early diagnosis. It follows that an effective screening strategy should be used in high-risk populations, including patients with cirrhosis due to any cause, patients with chronic hepatitis B or C, and asymptomatic carriers of the B virus genome (and probably the C virus genome). Screening currently relies on physical examination and on two investigations, ultrasound scanning and the alpha-fetoprotein (AFP) assay, whose sensitivity and specificity vary with tumor size. The optimal interval between evaluations seems to be four to six months, although large prospective studies confirming this are not yet available. Because the AFP assay lacks sensitivity and specificity in patients with small tumors, other serum markers are being evaluated. In parallel, hepatitis B immunization and alpha interferon therapy of chronic hepatitis C are expected to decrease the incidence of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed1998

Occurrence of gammopathies and lymphoproliferative disorders in liver transplant recipients randomized to tacrolimus (FK506)- or cyclosporine-based immunosuppression.

Lymphoproliferative disorders (LPDs) are a serious side effect of immunosuppression after liver transplantation, and the introduction on the market of a new immunosuppressive drug has been associated with an increased risk of these disorders. To compare the effect of cyclosporine A (CSA) and FK506 in a clinical setting, the incidence of monoclonal or oligoclonal gammopathies known to often precede the appearance of LPDs was evaluated. A total of 88 adult patients was analyzed, 46 were prospectively randomized to CSA and 42 to FK506 for immunosuppression. None of these patients had gammopathy before transplantation. All the patients were tested for immunoglobulin abnormalities five to nine times during a period of 1 year and then two to four times per year thereafter from December 1990 until March 1997. The same incidence of serum immunoglobulin (Ig) abnormalities was observed in both groups (13%) with a mean delay of appearance of 11.1 +/- 5.9 versus 7.6 +/- 3.6 months for CSA and FK506, respectively (P > .05). In each group, the gammopathies were transient in 3 patients and persisted in 2. The class of Ig involved was IgG, and a monoclonal component was documented in 2 patients treated with CSA and in 3 patients with FK506. One patient treated with FK506 developed an LPD localized to the lymph nodes 8 months after the occurrence of serum protein abnormalities. The lymphoproliferative lesions subsequently disappeared with the reduction of immunosuppression. In this study, an immunosuppressive regimen of FK506 has not shown an increased incidence of lymphoproliferation compared with CSA in adult liver transplant patients.

Adrenal Cortex Hormones↗