Is biliopancreatic diversion with duodenal switch a solution for patients after laparoscopic gastric banding failure?

BACKGROUND: Weight loss failure after laparoscopic gastric banding (LAGB) can occur in ≤ 25% of patients. Conversion to a malabsorptive procedure might provide more durable weight loss. The present study evaluated biliopancreatic diversion with duodenal switch (BPD/DS) after LAGB failure with a 3-year follow-up period. METHODS: A total of 35 patients underwent BPD/DS after LAGB failure and were prospectively analyzed using a multidisciplinary approach. Weight indexes, co-morbidities, complications, morbidity/mortality, and nutritional status were analyzed. RESULTS: Excess weight decreased from 91% (134 kg, body mass index 48 kg/m(2)) to 75% (124 kg, body mass index 44 kg/m(2)) after LAGB failure and decreased further to 40% (100 kg, body mass index 35 kg/m(2)) after BPD/DS. The mean percentage of excess weight loss was 55% after LAGB and BPD/DS together and 48% after BPD/DS alone. The incidence of co-morbidities, such as diabetes, sleep apnea, hypertension, hyperlipidemia, joint problems, and chronic obstructive pulmonary disease was reduced after BPD/DS. Nutritional deficiencies were already present after LAGB failure (e.g., iron, ferritin, vitamins B(12), B(6), A, D, and E, albumin, and calcium) and either increased (folic acid, potassium, and vitamin B(12)), remained stable (iron, ferritin, vitamin A), or decreased after BPD/DS (albumin and vitamins B(6) and E). CONCLUSION: BPD/DS provided substantial weight loss after LAGB failure and reduced the incidence of obesity-related co-morbidities during a 3-year period. Long-term nutritional follow-up is advocated for all patients after malabsorptive BPD/DS.

Outcome of 232 morbidly obese patients treated with laparoscopic adjustable gastric banding between 1995-2003.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is widely used for the treatment of morbidly obese patients. We prospectively evaluated the effect of LAGB since 1995. METHODS: Between March 1995 and August 2003, 232 morbidly obese patients underwent LAGB. The pars flaccida technique was used in the majority of the patients. Data were prospectively collected. RESULTS: The median age was 35 years and 93% were female. Initial median body weight was 129 kg with a median BMI of 46. After 5 years of follow-up, median BMI decreased to 36 and the median body weight decreased to 98 kg. Median excess weight loss was 37% after 1 year, 42% after 3 years and 42% after 5 years of follow-up. Late postoperative complications were pouch dilatation (n = 33), port revision (n = 19), erosion (n = 4) and necrosis (n = 1). CONCLUSION: LAGB is a safe and successful treatment for patients with morbid obesity. Maximal weight reduction is achieved within 12 months and remains stable up to at least 5 years. These results suggest that LAGB could have a positive outcome on morbid obesity-associated morbidity and overall life expectancy.

In vitro comparison of two bioartificial liver support systems: MELS CellModule and AMC-BAL.

Clinically applied bioartificial liver (BAL) support systems are difficult to compare with regard to overall hepatocyte-specific function and clinical outcome. We compared two clinically applied BAL systems, the Modular Extracorporeal Liver Support (MELS) CellModule and the AMC-bioartificial liver (AMC-BAL) in an in vitro set-up. Both BAL systems were loaded with 10 billion freshly isolated porcine hepatocytes, cultured for 7 days and tested on days 1, 2, 4 and 7. Average decrease in hepatocyte-specific functions over 7 days was 9.7%. Three parameters differed between both bioreactors: lidocaine elimination at days 1 and 2 was significantly higher in the AMCBAL, ammonia elimination showed a significantly higher trend for the AMC-BAL over 7 days and LDH release was significantly lower at day 7 for the MELS CellModule. In conclusion, this first in vitro comparison of two clinically applied BAL systems shows comparable functional capacity over a period of 7 days.

Subnormothermic preservation maintains viability and function in a porcine hepatocyte culture model simulating bioreactor transport.

Bioartificial liver (BAL) systems have been developed to bridge patients with acute liver failure (ALF) to liver transplantation or liver regeneration. Clinical application of BAL systems is dependent on the supportive quality of cells used and direct availability of the whole system. Reliable transport of BAL systems from the laboratory to remote treatment centers is therefore inevitable. Subsequently, preservation conditions play a crucial role during transport of a BAL, with temperature being one of the most determining factors. In this study, we assessed the effect of subnormothermic preservation on freshly isolated porcine hepatocytes cultured in monolayer under oxygenation. Additionally, the effect of the University of Wisconsin (UW) preservation solution was compared with Williams' E (WE) culture medium at 4 degrees C. The control group was cultured for 3 days at 37 degrees C, whereas the transport groups were cultured at 4 degrees C, 15 degrees C, 21 degrees C, or 28 degrees C for 24 h at day 2. All groups were tested each day for cell damage and hepatic functions. Subnormothermic culture (i.e., 15 degrees C to 28 degrees C) for a period of 24 h did not reduce any hepatic function and did not increase cellular damage. In contrast, culture of hepatocytes in WE medium and preservation in UW solution at 4 degrees C significantly reduced hepatic function. In conclusion, freshly isolated porcine hepatocytes can be preserved for 24 h at subnormothermic temperatures as low as 15 degrees C. Future research will focus on the implementation of the AMC-BAL in an oxygenated culture medium perfusion system for transport between the laboratory and the hospital.

Liver support therapy: an overview of the AMC-bioartificial liver research.

Acute liver failure (ALF) is a disease with a mortality of 60-90% depending on the cause. Only high-urgency liver transplantation is able to increase survival compared to standard intensive care therapy. Liver transplantation is hampered by the increasing shortage of organ donors, resulting in a high incidence of patients with ALF dying on the transplantation waiting list. Amongst a variety of liver assist therapies, bioartificial liver (BAL) therapy is marked as the most promising solution to bridge ALF patients to liver transplantation or to liver regeneration, since several BAL systems showed significant improvement of survival time in experimental animals with irreversible ALF. One of these systems has been developed at the Academic Medical Center in Amsterdam, The Netherlands - the AMC-BAL. This overview describes the development of the AMC-BAL based on porcine hepatocytes which was started 10 years ago. Positive results of in-vitro functionality and in vivo safety and efficacy led to a successful phase I study in 12 ALF patients in Italy. However, xenotransplantation legislation in many European countries prohibits the use of porcine hepatocytes in clinically applied BAL systems. The future of the BAL, therefore, resides in the development of a human-derived hepatocyte cell line as biocomponent of BAL systems.

Extra-hepatic factor VIII expression in porcine fulminant hepatic failure.

In humans, fulminant hepatic failure (FHF) is frequently associated with increased factor VIII (FVIII) levels, despite widespread liver cell death. The mechanisms leading to increased FVIII levels and cellular sites of this enhanced FVIII production are poorly understood. We studied the effect of total hepatectomy in pigs, a large-animal model of FHF, on the expression of plasma and tissue FVIII during 24-hour follow-up. Tissue FVIII expression was determined before and 24 h after hepatectomy, both at the mRNA level and immunohistochemically. The expression of plasma and tissue von Willebrand factor (VWF), the natural stabilizing carrier protein of FVIII, was also measured. Total hepatectomy elicited a gradual and sustained twofold elevation of circulating FVIII, whereas FVIII mRNA levels in various organs did not increase after hepatectomy. The half-life of FVIII increased from 7.7 to 10.3 h and VWF levels were also elevated in anhepatic pigs. The increase in the half-life of FVIII and increased levels of VWF were not sufficient to explain the rise in plasma FVIII levels. At the protein level, prominent changes in the cellular distribution of FVIII were seen in spleen and kidney. These observations suggest that in this model of FHF the lack of hepatic FVIII synthesis is adequately compensated by other organs, notably spleen and kidneys.

Assessment and improvement of liver specific function of the AMC-bioartificial liver.

UNLABELLED: The variety of methods for measuring bioactive mass and functionality of bioartificial livers (BAL) is confusing and prevents accurate comparison of reported data. Here we present a comparison of different hepatocyte quantification methods and propose that estimation of cell pellet volume after centrifugation generates a reliable, useful and fast method. In addition a correlation is made between several function tests performed in 26 bioreactors to assess their predictive value. The ammonia eliminating capacity was found to be most predictive for other liver functions, except for lidocaine elimination as a measure of mixed function oxidase activity, which should therefore be determined separately. The oxygen consumption test proved to be an easy and predictive parameter as well. The first generation of our BAL system needed further development to assure optimal treatment of acute liver failure (ALF) patients. Changes in the porcine hepatocyte isolation method and bioreactor loading as well as changes in bioreactor configuration, including use of different materials, resulted in a significantly improved level and maintenance of in vitro BAL function. A fourfold increase in ammonia eliminating capacity, which is only reduced to 75% after seven days of culturing, offers promising prospects for further clinical application. CONCLUSION: The current second generation of our BAL and improvement of hepatocyte isolation and testing protocols have led to a significant increase in the level as well as the maintenance of hepatocyte specific function in our BAL. Finally, consensus on definition of the bioactive mass to be loaded in the bioreactor and insight in the variation and reliability of the functional and metabolic parameters enhances comparison of the different types of bioartificial livers presented in literature.