External Biliary Drainage Research Articles

Experimental Study on Lipid and Bilirubin Metabolism after Biliary Drainage for Obstructive Jaundice

Background. The present experimental study was carried out to determine variations in bilirubin and lipid metabolism in obstructive jaundice after external biliary drainage alone and in combination with intraintestinal administration of the drained bile.Materials and methods. Variations in lipid and bilirubin metabolism were studied in adult mongrel dogs with obstructive jaundice treated by external biliary drainage (EBD) and EBD plus intraintestinal administration of autologous bile (IBD).Results. There was no difference between these two groups in regard to the volume of excreted bile after drainage. The biliary concentration and total daily excretion of bilirubin were higher in the IBD group (P < 0.0001), but there was no intergroup difference in the rate of decrease of serum bilirubin. In regard to lipid metabolism, the levels of total cholesterol, triglyceride, and low-density lipoprotein were decreased after biliary drainage; improvement in lipid metabolism was more rapid in the EBD group. Although the triglyceride level was lower after drainage, the activity of HMG-CoA reductase, the level of high-density lipoprotein 3-C, and the carrier protein apolipoprotein A-I were increased after drainage, with more rapid improvement in the EBD group.Conclusions. To improve lipid metabolism in obstructive jaundice, external biliary drainage is superior in the early stages of treatment, while replacement by EBD plus intraintestinal administration of autologous bile may be advantageous in cases of prolonged use.

External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice.

This study investigates the importance of intestinal bile flow in cellular immunity. Sprague-Dawley rats undergoing bile duct ligation (BDL) and sham ceiliotomy (Sham) for 14 and 21 days were investigated. Experimental animals following BDL were further divided into an external drainage (ED) group, an ED group with rat chow mixed with 2:2:1 cholic acid, chenodeoxycholic acid, and deoxycholic acid (ED + BF), and an internal drainage (ID) group. Fourteen days later, they were killed and analyzed for spleen lymphocytic [3H] thymidine uptake (LHU) under mitogen stimulation with phytohemagglutinin, blood biochemistry, hemogram, and liver pathology. In the 14-day BDL experiment, LHU and serum albumin level were decreased in the BDL group (P < 0.05). After drainage, they were not significantly different among sham, ED, ED + BF, and ID groups. In the 21-day BDL experiment, the red cell volume was decreased (P < 0.05). After drainage, the ED, ED + BF, and ID groups still had a significantly lower LHU than the sham group (P < 0.05). However, the ID group had higher LHU than the ED and ED + BF groups (P < 0.05). The ED + BF group had a slightly higher LHU than the ED group but not statistically significant. Liver pathology returned to normal after drainage in the 14-day BDL model. In contrast, the 21-day BDL group had prominent periportal necrosis and developed periportal fibrosis after drainage. The present study reveals the duration of BDL determines the severity of hepatic damage. In the 14-day BDL groups, all kinds of drainage completely reverse the impaired liver function and cellular immunity. In the 21-day BDL group, 14-day drainage is inadequate for recovery because irreversible pathological changes are found. The reversal of cellular immunity in ID is better and faster, because it provides a better hepatic functional, nutritional, and hematological recovery besides the presence of primarily secreted bile acids.

Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.

The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase: alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage.

Bacterial translocation in obstructive jaundice in rats: role of mucosal lacteals.

To study the ultrastructure of the ileal wall in rats with obstructive jaundice alone and after passive external biliary drainage to see if we could discover the reason for the increased risk of infective complications and multisystem failure in the presence of obstructive jaundice and after external biliary drainage. Histological examination of the wall of the terminal ileum using light microscopy, as well as scanning and transmission electron microscopy (EM). Experimental laboratory, Republic of Georgia. 56 adult male Wistar rats. Rats were divided into 7 groups: controls (not operated on, n = 6); sham-operated and studied after 6 and 12 days (n = 6 in each); bile duct ligation alone studied after 6 and 12 days (n = 10 in each); and bile duct ligation followed 6 and 12 days later by one-day of external biliary drainage (n = 9 in each). Percentage of destroyed villi. The extent of oedema of villi, necrosis of neurons, and disturbances in the secretory capacity of enterocytes correlated well with the duration of cholestasis. After 6 and 12 days ligation alone 7.2% and 17.3%, respectively, of villi were found to be destroyed; their connective tissue framework including lymphatics was in direct contact with the intestinal contents. The changes were not reversed by one day of external biliary drainage. The gaps in the ileal mucosa caused by obstructive jaundice (and not relieved by one day of external biliary drainage) may enable gut bacteria and their endotoxin to reach the systemic circulation through the lymphatic-system. This could increase the risk of infective complications.

Reconstruction of small and fragile bile ducts without mucosa-to-mucosa anastomosis.

We describe a simple and easy technique for performing choledochojejunostomy without the need to suture the full thickness of the ductal and intestinal walls for patients in whom standard choledochojejunostomy is difficult because the stumps of the residual bile ducts are small and fragile. This technique is useful in partial liver transplantation or after hepatectomy that includes removal of the extrahepatic bile ducts. The procedure involves the placing of external biliary drainage tubes through a Roux-en-Y jejunal loop, positioned transanastomotically, and the use of an external jejunostomy to decompress the loop. The tubes are fixed to the jejunal loop by a purse-string suture and to the duct by simple ligation or a purse-string suture. Anastomosis is performed by suturing the connective tissue and liver parenchyma around the ductal stump to the seromuscular layer of the intestine. Choledochojejunostomy according to this method was performed in 5 cases; the biliary drainage tubes were removed 1 to 4 months after surgery. The only complications were cerebellar infarction and cholangitis, both of which resolved with conservative treatment. We consider that this technique will be helpful as a last-ditch measure when standard choledochojejunostomy, with suturing of the full thickness of the walls of the duct and intestine to secure mucosa-to-mucosa apposition, is impossible because of small and fragile bile ducts.

Comparison of C-Arm CT Fluoroscopy and Conventional Fluoroscopy for Percutaneous Biliary Drainage Procedures

To conduct a prospective randomized evaluation of C-arm computed tomography (CT) fluoroscopy for external biliary drainage procedures in comparison with conventional fluoroscopic guidance to reduce the number of transhepatic punctures as a primary endpoint. In 18 patients with biliary obstructions, 20 external percutaneous biliary drainage procedures were prospectively performed with use of either C-arm CT fluoroscopy or conventional fluoroscopy alone. The number of hepatic punctures, procedure time, and fluoroscopy time, were analyzed separately for both methods. C-arm CT fluoroscopy resulted in a reduced number of transhepatic punctures, with decreased procedure and fluoroscopy times (P < .05; t test). When compared with conventional external biliary drainage procedures, a mean of 1.8+/-1 versus 4.8+/-2.8 hepatic punctures at a fluoroscopy time of 3.4+/-1.5 versus 11.4+/-7.4 minutes was required for C-arm CT fluoroscopy, while procedure times were 11+/-3.6 versus 16.2+/-9.3 minutes. C-arm CT fluoroscopy is associated with decreased procedure and fluoroscopy times, while fewer transhepatic punctures are required to establish external biliary drainage.

Choledochal cyst in infancy: a follow-up study.

From January 1980 to February 1997, 19 cases, 8 males and 11 females, of choledochal cyst were diagnosed before one year old. The majority of patients were diagnosed by ultrasonography before 6 months old (15/19; 79%), including two diagnosed prenatally. According to Todani's classification, type Ia was the most common (74%), followed by type Ic (26%). Fourteen patients underwent Roux-en-Y choledocho- or hepatico-jejunostomy and cyst excision, 3 patients underwent Kasai operation, and I patient underwent external biliary drainage only. The remaining one patient with Trisomy 18 anomaly refused operation. Four of the 10 patients in whom liver histologic examinations were performed, had liver cirrhosis. The follow-up period of these patients ranged from 6 months to 9 years, with a mean of 4.1 years. We divided these 19 cases into 2 groups, according to the presence or absence of biliary atresia. In the 7 infants with biliary atresia (37%), all presented with jaundice and alcoholic stool. Two patients died due to delayed presentation and surgery, both had liver cirrhosis. One patient is living with liver cirrhosis. Another patient was lost to follow-up, but frequent cholangitis was noted till 8 months old. The remaining 3 patients are living and well. In the 12 without biliary atresia, 9 patients are living and well. Two patients died, one due to Trisomy 18 anomaly and the other with delayed surgery and liver cirrhosis. One case was lost to follow-up. In summary: 1-) a possibility of the association of biliary atresia in infants with choledochal cyst should be carefully searched and considered as a unique group; 2) ultrasonography is a good diagnostic tool in choledochal cyst during prenatal or infancy period; 3) the mortality cases were characterized by prolonged bile stasis, biliary cirrhosis, delayed surgery, or multiple anomalies; 4) surgery should be performed as early as possible for those with persistent jaundice and light colored stools.

Aggressive surgery is unwarranted for biliary tract rhabdomyosarcoma

Background/Purpose: Rhabdomyosarcoma (RMS) of the biliary tract is rare, and, in addition to multiagent chemotherapy with or without radiotherapy (RT), some investigators recommend aggressive surgery. To assess the role of surgery, records of all 25 eligible patients with biliary RMS enrolled in IRSG studies I through IV from 1972 to 1998 were reviewed.Methods: Treatment included surgery with or without vincristine, dactinomycin, cyclophosphamide, doxorubicin, cisplatin, etoposide, ifosfamide, and with or without RT. Data evaluated included clinical presentation, treatment, complications, and outcome.Results: Diagnostic imaging identified the primary tumor but failed to identify regional metastases. Despite aggressive surgery, gross total resection at diagnosis was possible in only 6 cases, 2 of which had negative surgical margins. Although only 6 (29%) patients without distant metastases underwent gross total resection, estimated 5-year survival rate was 78% (95% CI 58%, 97%). Infectious complications were common and frequently associated with external biliary drains. Five (20%) died within the first 2 months, 3 of sepsis.Conclusions: Surgery is critical for establishing an accurate diagnosis and determining the extent of regional disease. Gross total resection is rarely possible despite aggressive surgery, and outcome is good despite residual disease after surgery. External biliary drains increase the risk of postoperative infectious complications.

Palliative decompression of obstructive hilar malignancies utilizing an extrahilar biliary approach.

Hilar cancers carry a dismal prognosis. Palliation of obstructive jaundice in patients with hilar cancer can be achieved by either surgical or nonsurgical means. Selection of the appropriate palliative measures is a challenging problem. Segmental bilioenteric anastomosis procedures were performed on 19 patients with hilar cancer. Seventeen of the bypasses were done to the segment III duct, known as the ligamentum teres approach, and two bypasses were to the segment V duct. Five patients, who had already been stented percutaneously or endoscopically, were operated on after the stents were clogged and a duodenal obstruction ensued. There were two postoperative deaths (10.5%) and four postoperative complications (21%). All of the 17 surviving patients experienced improvement in the level of jaundice postoperatively and the levels of serum total and direct bilirubin decreased by 78.9% and 84.2%, respectively. Two patients developed late cholangitis before death and were treated by external biliary drainage; one developed duodenal obstruction and was treated by gastrointestinal anastomosis. The mean length of hospital stay was 15.2 days. Mean survival was 8.2 months and the mean period of well-being was 7.8 months. Median survival was 7 months and median period of well being was 7 months. Three patients are still alive at 8, 8, and 24 months. These data suggest that the ligamentum teres approach offers effective palliation for patients with unresectable hilar cancer.

Drainage of the Common Bile Duct by the Axial Transomphalic Extraperitoneal Route

Aim: A retrospective analysis was made of results obtained in 169 patients with axial transomphalic external biliary drainage, operated between 1984 and 1998. However, the authors’ experience with this method covers a total of 773 cases in which this type of drainage was used between 1966 and 1998. Method: The technique is described in detail. The use of the omphalic ligament provides a completely extraperitoneal trajectory for biliary drainage tubing inserted between the two peritoneal layers of the ligament. Results: Postoperative mortality and morbidity in the patients presented here were not related to the drainage procedure, but were related to the background illness, associated disturbances and the surgical procedures applied. Axial transomphalic biliary drainage has many indisputable advantages in comparison with other types of external biliary drainage. Indications and counterindications of the method are summarized. Conclusion: The technique is especially valuable because it protects biliary-digestive anastomoses and common biliary duct sutures, facilitating implantation of prostheses and reconstruction of the main biliary pathway, as well as benign and malignant stenoses.

Hépatectomie dans la lithiase intrahépatique

Liver resection for hepatolithiasis. Study aim: The aim of this study was to report the immediate results of a series of 65 hepatic resections for hepatolithiasis performed in Vietnam. Patients and method: From 1986 to 1998, 44 men and 21 women (mean age: 40 years) underwent hepatic resection for hepatolithiasis. Fourty patients had previously undergone one or several operations for hepatolithiasis. The procedure was performed on emergency in 25 patients. Indications for hepatic resection were: angiocholitis and liver abscess in 22 cases, stones closely inserted in the biliary duct in 20 cases, hemobilia in 12 cases, stones located above a biliary stricture in 8 cases and stones associated with a postoperative biliary fistula in 3 cases. Liver resections (minor in 61 patients, including 55 left lobectomies, and major in 4 patients) were performed through transhepatic approach according to the Ton That Tung technique and followed by an external biliary drainage with a Kehr tube. Results: There were 6 postoperative deaths (9%), 3 due to septic shock, 2 to cachexia, and 1 to liver failure. The 15 patients with complications recovered with conservative therapy. Bile infection was present in 93%, mostly with Escherichia coli and Enterobacter. Pigmented stones were usually found. Conclusion: Vietnam is a country with high incidence of hepatolithiasis. Hepatic resection is an adequate treatment for localized intrahepatic bile duct stones when the involved segment including biliary strictures and calculi can be completely removed. The procedure may be performed on emergency for liver abscess, or hemobilia.

Hepatocyte Growth Factor Concentration in Rat Bile Is Affected by Hepatic Resection Volume and External Biliary Drainage

Background/aims. Hepatocyte growth factor (HGF) concentrations in bile have been shown to be useful in the early assessment of liver function after hepatectomy. The aim of the present study is to prove the hypothesis that the level of bile HGF is proportional to the regeneration capacity of the liver using a rat model.Methods. Blood and bile were sampled from rats who underwent 30 or 70% hepatectomy, with or without biliary drainage. HGF concentrations were determined using enzyme-linked immunosorbent assay.Results. Liver regeneration was significantly suppressed after hepatectomy in the rats that underwent external biliary drainage. The bile HGF concentration was positively correlated with the resected liver volume within 24 h of hepatectomy, and HGF levels were markedly increased by external biliary drainage. The postoperative changes in plasma HGF were less dramatic.Conclusions. HGF appears to play an important role in liver regeneration. Bile HGF concentrations, unlike plasma HGF levels, are a good reflection of the hepatic biosynthesis of this growth factor. Increased concentrations of HGF in bile after external biliary drainage may reflect a compensatory response to the continuous loss of hepatocyte growth factor-rich fluid.

Interleukin 6 in bile as an indicator of liver function after hepatectomy in patients with biliary tract carcinoma.

Interleukin (IL) 6 is one of the important components of the early signalling pathways leading to liver regeneration, and has been detected in the bile after liver transplantation. IL-6 concentrations in the bile were studied in an attempt to predict liver function after major hepatectomy for biliary tract carcinoma. This study involved 24 patients without cirrhosis who underwent major hepatectomy for biliary tract carcinoma. The bile was sampled regularly through external biliary drainage tubes. IL-6 concentrations in bile and serum were measured using an enzyme-linked immunosorbent assay. Bile IL-6 concentrations increased 37-fold (from mean(s.e.) 56(13) pg/ml before hepatectomy to 2071(398) pg/ml on day 1 after operation) in patients without liver failure after hepatectomy (n = 18) and increased sevenfold (from 71(24) to 530(76) pg/ml) in patients with liver failure after hepatectomy (n = 6). The values were significantly lower in patients with liver failure than in those without liver failure (P < 0.05). The bile IL-6 concentration on day 1 after operation exhibited a significant negative correlation with the maximum serum total bilirubin concentration after hepatectomy. Although serum IL-6 concentrations were also increased in both groups after hepatectomy, there was no significant correlation with postoperative liver function. Increased bile IL-6 concentrations after hepatectomy may reflect liver regenerative capacity. Measurement of bile IL-6 concentrations may be clinically useful for the early identification of liver failure after hepatectomy.

Traitement laparoscopique de la lithiase de la voie biliaire principale. Étude de 56 cas

Aim of the study The aim of this retrospective study was to report the results of the laparoscopic management of common bile duct stones in an unicentric series of 56 patients. Patients and method From January 1993 to April 1998, 56 patients, 38 women, 18 men (mean age: 59.2 years), underwent a common bile duct exploration for lithiasis through a laparoscopic approach. The patients were hospitalised for angiocholitis (n = 13), cholecystitis (n = 11), biliary pain (n = 29, nine with jaundice), pancreatitis (n = 3), abnormality of hepatic profile (n = 1). All the patients underwent an intraoperative cholangiography. Removal of the stones was tried in 50 cases through a choledochotomy, in four through the cystic duct, using Mirrizi forceps, or Dormia and Fogarty catheters in case of failure. External biliary drainage and postoperative cholangiography were done systematically. The average diameter of the common bile duct was 10.5 mm (6–20 mm). Results In 41 patients, removal of the stones was laparoscopically successful. In 11 patients, a conversion into laparotomy was necessary for several reasons. In three patients with common bile duct of small diameter, the stores were abandoned for a further endoscopic sphincterotomy. There was no mortality and the morbidity rate was 7%.The mean postoperative hospital stay was 8.6 days 14–20) for all the series and 7.8 days in case of successful laparoscopic management. Conclusion In 73% of the patients, the treatment of the common bile-duct lithiasis could be achieved laparoscopically but conventional) approach and endoscopic sphincterotomy are still useful in case of failure of the laparoscopic management.

Reduced acute rejection after liver transplantation with neoral-based double immunosuppression

CCYCLOSPORINE (CyA) is unequivocally a milestone in the development of organ transplantation. However, the wide interand intrapatient variability in gut absorption and the subsequent different bioavailability limited the exploitation of CyA in inducing immunosuppression without frequent blood monitoring. The clinical use of CyA in liver transplantation is further complicated by its bile-dependent absorption. These characteristics lead to fluctuations in the blood levels and to a potential higher incidence of acute rejection mainly in the early postoperative period. Recently, a new microemulsion formulation (Neoral) of CyA has been introduced in the clinical arena. The new formulation is better absorbed by the gastrointestinal tract, even in liver transplant patients with open external biliary drainage. Few open and randomized trials confirm the possibility of inducing immunosuppression by oral administration of CyA with a lower incidence of rejection in the Neoral arms. In this open, nonrandomized, retrospective study, we compare the incidence of acute rejection and nephrotoxicity during the first postoperative month and graft and patient survival rates at 1 year in 33 consecutive liver transplant adult patients: 17 patients treated with a Sandimmune-based double therapy and 16 patients treated with Neoral-based double therapy.

Towards T-tube free laparoscopic bile duct exploration: a methodologic evolution during 300 consecutive procedures.

To establish a simple, reproducible, and safe technique of laparoscopic common bile duct exploration (CBDE) with high clearance rates and low morbidity and mortality rates. For most general surgeons, laparoscopic CBDE appears an unduly complex and demanding procedure. Since the introduction of laparoscopic cholecystectomy, many surgeons use endoscopic cholangiography (ERC) and endoscopic sphincterotomy as their only option in treating bile duct stones. ERC is more specific if used after surgery, but it carries an appreciable morbidity rate and has the disadvantage of requiring a second procedure to deal with bile duct stones. To this end, various methods of laparoscopic CBDE have been developed. Between August 1991 and February 1997, 300 consecutive unselected patients underwent laparoscopic CBDE. Of 300 laparoscopic CBDE procedures, 173 (58%) were managed using a transcystic approach and 127 (42%) with choledochotomy. Successful laparoscopic stone clearance was achieved in 271 (90%). Of the 29 (10%) patients not cleared laparoscopically, 10 had an elective postsurgical ERC, 12 were converted to an open procedure early in the series, and 7 had unexpected retained stones. There was one death (mortality rate 0.3%) and major morbidity occurred in 22 patients (7%). The last 100 procedures were performed from July 1995 to February 1997, and stone clearance was unsuccessful in only two patients. Laparoscopic transcystic basket extraction of common duct stones under fluoroscopic guidance is a relatively quick, successful, and safe technique. Choledochotomy, when required, is associated with a higher morbidity rate, particularly with T-tube insertion, and the authors advocate primary bile duct closure with or without insertion of a biliary stent as a more satisfactory technique for both surgeon and patient. Most patients with gallbladder and common duct calculi should expect a curative one-stage laparoscopic procedure without the need for external biliary drainage or ERC.

Liver transplantation and bile analysis: a parallel evolution.

Liver transplantation and bile analysis: a parallel evolution.

PERCUTANEOUS DILATATION TECHNIQUE FOR POSTOPERATIVE BENIGN BILIARY STRICTURES

Effect of percutaneous dilatation technique using a stent tube obtainable internal and external biliary drainage indwelling for management of postoperative bengin biliary strictures was evaluated in this study. Among 24 cases of postoperative benign biliary stricture encountered in Teikyo university hospital at Mizonokuchi for the past 15 years, 19 cases treated with percutaneous dilatation technique were involved in this study. The route for percutaneous cholangioscopy were PTBD fistula in 15 cases (87.9%) and T-tube fistula in four cases (21.1%). In the patients with biliary fistula, the stent tube was in place after mechanical dilatation of the fistula under fluoroscopy. Dilatation of stricture site was also mechani-cally performed along a guidewire inserted under an endoscopic control. The size of the stent tube used ranged from 12 Fr to 18 Fr in diameter. The mean period of indwelling time of the stent tube was 125.1 days. Regarding complications, two patients had liver dysfunction and one patient had cholangitis, but the former two patients were treated conservatively. Two patients with re-stenosis and one patient of repeated cholangitis required surgical treatment. The remaining 16 patients (84.2%) had been leading a normal social life without any symptom of stenosis of the biliary duct. In conclusion, percutaneous biliary dilatation technique using a stent tube obtainable internal and external biliary drainage seemed to be an effective procedure for postoperative benign biliary strictures, because it can be treated without any foreign body left behind.

Neoral in de novo liver transplantation: Adequate immunosuppression without intravenous cyclosporine

Absorption of cyclosporine from the traditional oral formulation Sandimmune (Novartis Pharma, Basel, Switzerland) is particularly unpredictable in the early stages after liver transplantation. The absorption of cyclosporine is influenced by liver function, postoperative paralytic ileus, and graft dysfunction. Oral absorption of cyclosporine from Sandimmune is also bile dependent; cholestasis and external biliary drainage are associated with low cyclosporine absorption. Postoperative administration of intravenous Sandimmune is therefore often necessary to obtain adequate immunosuppression, despite the increased risk of renal and neurological toxicity. A microemulsion formulation of cyclosporine, Neoral (Novartis), has been developed to overcome the problems of poor and variable absorption of cyclosporine from Sandimmune. Uptake of cyclosporine from Neoral is rapid and less dependent on bile secretion so that higher peak concentrations are reached and absorption is less variable than with Sandimmune. A review of several open studies in which Neoral was administered to liver transplant patients immediately after transplantation is presented. The results suggest that the use of Neoral as a primary immunosuppressive therapy provides adequate cyclosporine trough levels, minimizing or obviating the need for intravenous cyclosporine administration. In addition, Neoral appears to reduce the risk of acute rejection episodes compared with immunosuppressive regimens involving intravenous cyclosporine. (Liver Transpl Surg 1997 Nov;3(6):571-7)

Neoral in de novo liver transplantation: adequate immunosuppression without intravenous cyclosporine.

Absorption of cyclosporine from the traditional oral formulation Sandimmune (Novartis Pharma, Basel, Switzerland) is particularly unpredictable in the early stages after liver transplantation. The absorption of cyclosporine is influenced by liver function, postoperative paralytic ileus, and graft dysfunction. Oral absorption of cyclosporine from Sandimmune is also bile dependent; cholestasis and external biliary drainage are associated with low cyclosporine absorption. Postoperative administration of intravenous Sandimmune is therefore often necessary to obtain adequate immunosuppression, despite the increased risk of renal and neurological toxicity. A microemulsion formulation of cyclosporine, Neoral (Novartis), has been developed to overcome the problems of poor and variable absorption of cyclosporine from Sandimmune. Uptake of cyclosporine from Neoral is rapid and less dependent on bile secretion so that higher peak concentrations are reached and absorption is less variable than with Sandimmune. A review of several open studies in which Neoral was administered to liver transplant patients immediately after transplantation is presented. The results suggest that the use of Neoral as a primary immunosuppressive therapy provides adequate cyclosporine trough levels, minimizing or obviating the need for intravenous cyclosporine administration. In addition, Neoral appears to reduce the risk of acute rejection episodes compared with immunosuppressive regimens involving intravenous cyclosporine.