Sharing of split livers between centers is easily feasible.
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Europe↗
Biomedical subjects
X Rogiers
Publications and source records attributed to X Rogiers.
Effects of an educational segment concerning organ donation and transplantation.
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Adolescent↗
Predictors of the intention to donate organs: an empirical model.
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Adolescent↗
[Colorectal liver metastases: does the number of metastases determine of resection is oncologically indicated?].
Complete surgical removal of colorectal liver metastases offers the patient the only curative option as long as there is no extrahepatic spread. Apparently the number of parameters of prognostic significance is unlimited. Consequently their importance for the individual prognosis remains questionable. One of the most frequently discussed parameters is the number of lesions in the liver. The aim of this study was therefore to review the literature and to analyze our own patients with colorectal liver metastases. For 302 patients a complete follow-up was available. The patients were grouped according to the number of lesions and the status of resection (R0, R1, R2, Exploration). The groups were compared by Kaplan Meier Analyses with log rank tests. The literature was reviewed until December 1998. The number of metastases was confirmed to be of prognostic value. Three or more metastases made a resection without residual tumor more unlikely than if there were only two or less (17.8% versus 67.2%). 5-year survival after curative resection was reduced in the group with more metastases from 36% to 9% and 10-year survival was reduced from 18% to 0% without reaching statistical significance (p < 0.07). The number of liver metastases may have some prognostic impact for patients after colorectal cancer. However, even if more than four metastases were resected with clear margins some patients did survive for a long time. The most important parameter to predict an oncological benefit is resection without residual tumor. If this is technically and functionally possible the patient should not be denied surgery, his only chance for cure.
Colorectal Neoplasms↗
Long-term results of pre-emptive liver transplantation in primary hyperoxaluria type 1.
In primary hyperoxaluria type 1 (PH 1), deficiency or mistargeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow-up 3-5.7 yr after performing successful PLTx in four children (at the age of 3-9 yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27-98 mL/min/1.73 m2). There was no mortality or long-term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27 mL/min/1.73 m2) who showed a stable course for more than 5.7 yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis.
Acute Kidney Injury↗
Intensive care management after pediatric liver transplantation: a single-center experience.
A retrospective study was conducted to determine the significance of intensive care management on outcome after liver transplantation (LTx) in children. Of 195 transplants performed in 162 children, factors affecting morbidity and mortality were documented during the post-operative intensive care unit (ICU) stay. To assess the gain in experience of ICU management, we compared mean ventilation time and stay in the ICU as well as mortality, incidence of surgical complications, infections, and rejection episodes, during three different time-periods (October 1991-August 1994, September 1994-July 1996, and August 1996-February 1998). The time spent by patients in the ICU (9.7 days vs. 7.9 days vs. 4.7 days, p < 0.001) and time on ventilation (5.2 days vs. 3.1 days vs. 1.2 days, p < 0.001) were significantly reduced over the duration of the study. The overall mortality was 18.0% (n = 30) and 76.7% (n = 23) of these deaths occurred during the early post-operative period in the ICU. The incidence of severe surgical complications decreased significantly over time, and the application of intra-operative Doppler ultrasound since 1994 led to detection of 27 correctable vascular complications. The overall incidence of acute cellular rejection episodes in our center was 64.1%: 43.5% of the infectious episodes occurred in the ICU (bacterial 70.2%, viral 12.3%, and fungal 17.5%). The main side-effect from immunosuppressive drugs was arterial hypertension in 29% of the patients. We conclude that our efforts to improve intensive care management and monitoring were the key elements in reducing morbidity and mortality after pediatric LTx.
Adolescent↗
Interleukin-1 receptor antagonist in ascites indicates acute graft rejection after pediatric liver transplantation.
Acute graft rejection is one of the most frequent complications after pediatric liver transplantation (LTx). In clinical practice, it is sometimes difficult to differentiate acute cellular graft rejection from other complications because clinical and chemical findings are often nonspecific. We therefore investigated the value of cytokine quantification in drained ascites, in addition to quantification of cytokine concentrations of serum, in 30 children in the first 2 weeks after orthotopic liver transplantation (OLT). Six of 30 patients showed acute graft rejection, with rising levels of alanine aminotransferase (ALT) and alpha-glutathione-S-transferase (alpha-GST) in serum up to 24 h prior to biopsy-proven rejection. There were no significant elevations of interleukin-2 receptor (IL-2r) and interleukin-6 (IL-6) in serum and ascites. In contrast to these findings, the concentration in ascites of the interleukin-1 receptor antagonist (IL-1ra) increased 48 h before rejection was proven by liver biopsy (p < 0.01, in comparison with the non-rejecting group, n = 24). The IL-1ra concentration in ascites was up to 11-fold higher than in serum during rejection (15.43 vs. 1.38 ng/mL). Two children with early infectious complication showed no significant increase in ascitic IL-1ra concentration. We conclude from these data that quantification of IL-1ra in ascites indicates the start of graft rejection after LTx. As long as abdominal drainage is performed, this non-invasive procedure may be of additional value in differential diagnoses and early diagnosis of rejection.
Acute Disease↗
Split-cava technique: liver splitting for two adult recipients.
Split-liver transplantation for 2 adult recipients is a challenging procedure because of the need to split through the midplane of the donor liver. In applied techniques, usually the middle hepatic vein is retained with the left split and the vena cava retained with the right split graft, particularly to avoid serious venous congestion of the right graft after reperfusion. The indispensable division of the caudate lobe veins lead to uncertain viability of liver segment I, and resection might be necessary. To provide optimal venous drainage of both hemiliver grafts, we developed the split-cava technique. This article describes our new technique of liver splitting, which has been successfully used in 2 in situ harvesting procedures.
Adult↗
Priming of hepatocytes for cell culture by partial hepatectomy prior to cell isolation.
The combination of ex vivo gene transfer and a sufficient transplant model for hepatocytes may permit treatment of single enzyme-based metabolic liver diseases. Induction of replicative potential (priming) in hepatocyte cultures may enhance the efficiency of gene transfer under stable in vitro conditions. It is known that hepatocyte replication is increased in vivo after partial hepatectomy. We investigated the effect of partial hepatectomy prior to cell isolation on hepatocytes in vitro. Male Lewis rats served as donors. Hepatocytes were isolated by collagenase digestion from either intact livers or from livers 48 h after 70% hepatectomy (PH). Cells were seeded on collagen-coated culture dishes with hormone-supplemented culture media. Hepatocyte morphology, number, albumin secretion rate, and mono-ethyl-glycin-xylidid (MEGX)-biotransformation capacity were assessed on days 1, 3, and 5 in culture. PH significantly increased hepatocyte number and albumin secretion of cultured hepatocytes over the whole observation period. In contrast, MEGX-biotransformation capacity was significantly decreased. Morphology of cultured hepatocytes was not affected by PH prior to hepatocyte isolation. These results suggest a prolonged and complex response of hepatocytes to PH in vitro. Hepatocyte priming by PH is a promising approach toward stable cultures of proliferating hepatocytes and may provide a model for in vitro studies of hepatic regeneration mechanisms. Further research on hepatocyte priming toward an application in ex vivo gene transfer and hepatic tissue engineering seems justified.
Animals↗
Boerhaave-mimicking esophageal perforation with subsequent esophagobronchial fistula formation as the primary manifestation of Crohn's disease.
BACKGROUND: Spontaneous ruptures of the esophagus are rare, but may lead to deleterious courses, even if diagnosed early. CASE REPORT: We report a case of Boerhaave's syndrome-mimicking esophageal perforation due to a stricture of the distal esophagus as the primary manifestation of Crohn's disease. Diagnosis was delayed resulting in a complicated clinical course. The presented patient is the first case in the literature with esophageal perforation related to a previously undiagnosed Crohn's disease that lead to stenosis of the distal esophagus before becoming clinically apparent. CONCLUSION: Difficulties in differential diagnosis, problems related to initial misdiagnosis and consecutive mismanagment of spontaneous esophageal perforation, and treatment options including nonsurgical approaches are discussed.
Aged↗
Split liver transplantation (SLT).
OBJECTIVES: In the last three decades liver transplantation (LT) has become a standard procedure for terminal liver failure. Anyway the procedure is highly limited by the availability of donor organs. The use of segmental liver grafts from living or cadaver donors are an attractive way to increase the donor pool for LT in adults and children. METHODS: Between 1991 and April 1999 we performed 647 liver transplantations in 416 adults and 231 children. 431 OLT, 124 SLT and 92 LRLT. Commonly used segmental liver grafts are the full right graft, the full left graft, the left lateral lobe graft and the right extended graft from living or cadaver donors respectively. RESULTS: The 1-year survival of elective SLT in adults is 80.5% and in children 84.3% (SLT + LRLT). CONCLUSIONS: Splitting procedures in liver transplantation are a promising completion to whole organ transplantations. The results of split liver (SLT) and living related liver transplantations (LRLT) are comparable to whole organ transplantations. These methods are able to increase the organ pool and thus decrease the pretransplant mortality both in children and adults.
Adult↗
Mycophenolate mofetil for prevention of liver allograft rejection: initial results of a controlled clinical trial.
UNLABELLED: Mycophenolate Mofetil (M MF) is a new immunosuppressive agent with proven efficacy for the prevention of kidney allograft rejection. However, only little experience is available with the use of MMF in liver transplant recipients. OBJECTIVES: In this prospective, controlled trial the efficacy and safety of MMF and Azathioprine (AZA) were compared in a Neoral based quadruple immunosuppressive regimen after orthotopic liver transplantation. METHODS: Between 12/96 and 12/98 57 adult patients were enrolled in the study at the University of Hamburg. 28 patients were randomised to MMF, 29 patients to AZA in combination with equivalent doses of lymphocyte antibodies, Neoral and methylprednisolone. RESULTS: After a median follow-up of 10+/-3.2 months patient or graft survival did not differ significantly between the MMF and AZA group. However, MMF treated patients experienced less frequently acute rejection episodes (MMF: 6/28; 21.4% versus AZA: 13/29; 44.8%) (p=0.06). Furthermore, thrombocytopenia (MMF: 6/28; 21.4% versus AZA: 14/29; 48.3%) (p<0.05) and leukopenia (MMF: 2/28; 7.1% versus AZA: 6/29; 20%) (p=0.14) were less often observed under MMF compared to AZA. The incidence of serious bacterial infections and cytomegalovirus infections was almost identical in both groups. These preliminary data suggest that after liver transplantation primary immunosuppression with MMF is advantageous over AZA with regard to safety and efficacy.
Adult↗
Surgical management of hepatic metastatic disease.
In Europe, liver metastases are the most common malignomas of the liver. The majority of metastases are due to colorectal cancer. Radical surgical resection, if possible, is the treatment of choice. Radical resection of metastases from wilms-tumor, carcinoids, carcinoma of the breast, hypernephroma, adrenal tumors, malignant melanoma, leiomyosarcoma and gastric cancer may improve long time survival, however knowledge is too small for giving general directions. Local destructive therapies are only beneficial when a total necrosis of the tumor is reached. Indications for this treatment are quite rare. Both, systemic and local chemotherapy offers only palliation with little influence on long time survival. Adjuvant and neo-adjuvant chemotherapy is applicated under study conditions with encouraging results. Chemoembolisation of metastases might be useful in individual cases.
Antineoplastic Combined Chemotherapy Protocols↗
Long-term differentiated function of heterotopically transplanted hepatocytes on three-dimensional polymer matrices.
Hepatocyte transplantation using porous matrices is under investigation as an alternative therapy for certain liver diseases. For this purpose, long-term function of transplanted hepatocytes is mandatory. This problem has not been sufficiently investigated yet. In this study Lewis rats were used as donors and recipients. Stimulated (group A, portocaval shunt) or unstimulated (group B) hepatocytes were transplanted into prevascularized polyvinyl-alcohol matrices. Cell-free matrices served as controls (group C). Matrices were harvested between 1 h and 1 year after implantation and analyzed by morphometry; albumin RNA in situ hybridization; and cytokeratin-, actin-, desmin-, and macrophage-specific antigen immunohistology. The hepatocyte number significantly decreased within the first week following implantation. Between 1 month and 1 year after transplantation a significant increase in hepatocyte number was noted in groups A and B. Albumin transcripts of transplanted hepatocytes were at normal levels at all times except for group B after 1 year. The immunohistology suggested engraftment of nonparenchymal liver cells. We conclude that 3-dimensional matrices provide a sufficient environment for long-term engraftment of transplanted liver cells. The hepatocytes are able, despite suboptimal initial engraftment, to repopulate the scaffold for at least half of the recipient's life span and maintain cell-specific function after sufficient stimulation.
Animals↗
Is there an optimal concentration of cotransplanted islets of Langerhans for stimulation of hepatocytes in three dimensional matrices?
BACKGROUND: Hepatocyte transplantation using three-dimensional matrices is under investigation as an alternative therapy for several liver diseases. For sufficient transplantation results hepatotrophic stimulation is necessary. We investigated the stimulatory effect of cotransplanted pancreatic islets in different ratios. METHODS: Lewis rats were used as donors and recipients. A portocaval shunt (group A) or sham operation (groups B-G) was performed 1 week before hepatocyte transplantation. Four polyvinyl-alcohol matrices each containing 1.25 x 10(7) hepatocytes (groups A and B) or 1.25 x 10(7) hepatocytes and 125 (C), 250 (D), 500 (E), or 750 (F) islets were implanted between small bowel mesenteric leaves. In group G, medium soaked matrices were implanted. One month after implantation, specimens were harvested and investigated using albumin-RNA in situ hybridization, and insulin, glucagon, and bromodesoxy uridine immunohistochemistry. The hepatocyte area was assessed using image analysis. RESULTS: Hepatocyte area and proliferation ratio increased depending on the number of cotransplanted islets with a peak at 40 islets per 1 million hepatocytes (group E). Cotransplantation of islets in higher concentrations did not further increase hepatocyte area or proliferation ratio. Hepatocytes in all groups expressed albumin RNA at normal transcription levels as compared to standard liver sections. Islets displayed insulin and glucagon in physiological distribution. DISCUSSION: Three-dimensional matrices provide a sufficient environment for transplanted hepatocytes and islets. The hepatotrophic effect of cotransplanted islets is comparable to portocaval shunting and has a saturation limit at 40 islets per 1 million hepatocytes. For further application of islet cotransplantation, this ratio seems to be preferable.
Albumins↗
Standard liver volume in the Caucasian population.
Living donor and split-liver transplantation techniques require the calculation of a standard liver volume (SLV) as a reference point for the minimal volume necessary for the recipient. We therefore examined whether a widely used formula developed on the basis of a Japanese population sample was also adequate for the Caucasian population. The documentation of volumes of 1332 autopsy livers from a German Forensic Medicine Department was used to create a formula for an SLV for the Caucasian population. The Japanese formula estimated the Caucasian liver volume to be on average 322.6 +/- 335. 8 g (SD) less than they actually were. The following new formula for the calculation of SLV for Caucasians was established by linear regression analysis: Liver volume (mL) = 1072.8 * body surface area(m2)-345.7.
Anthropometry↗
Liver transplantation in children: long-term outcome and quality of life.
UNLABELLED: Liver transplantation has become a standard therapy in acute and chronic liver failure. Since 1968, 2554 paediatric patients receiving a liver transplant have been registered in the European Liver Transplant Registry (ELTR). Compared with 22,600 total transplants registered in the ELTR over the same period of time this means that about 10% of all liver transplants performed in Europe concern paediatric recipients, aged from 0 to 15 years. The indications in the paediatric population differ significantly from those of adult patients: More than 50% of patients suffer from cholestatic disorders, followed by hepatic based metabolic disorders, acute liver failure, non-cholestatic cirrhosis and liver tumours. The results of liver transplantation in paediatric patients have improved remarkably since the early 1980s. In 1997 a survival rate of 80% is almost the international standard. This improvement is due to the use of better immunosuppressive agents such as cyclosporin A and tacrolimus, followed by improvement in surgical techniques and finally by improvement in intensive care, better diagnostic tools for viral, bacterial and fungal infections and corresponding appropriate therapies. Quality of life as a measure of transplant results has not been sufficiently studied. The majority of paediatric liver transplant recipients has a good quality of life; only 10% suffer from significant morbidity. The impact of pretransplant damage to other organs such as brain, kidneys, bone and lungs and the influence of immunosuppression on somatic growth, neurological development, infection and metabolic balance are subjects of increasing concern. CONCLUSION: The results available today show convincing evidence that liver transplantation is a therapeutic option in otherwise fatal hepatic disorders. Much effort, however, has to be made in order to achieve further improvements by increasing our knowledge of the pathophysiology of both pre- and posttransplant conditions.
Adolescent↗
[Mesentericoportal Rex-shunt as a treatment for extrahepatic portal vein thrombosis].
The most common cause of portal hypertension in children with healthy livers is the prehepatic block. A 7-year-old girl had presented with portal vein thrombosis after umbilical vein catheterization in the newborn period. She suffered from collateral circulation with recurrent bleeding episodes due to esophageal varices (stage III-IV) and developed hypersplenism. Ultrasound demonstrated an open branch of the left portal vein. Direct splenoportography showed an open and communicating superior mesenteric vein. Liver biopsy was normal. An autologous left jugular vein graft was used to create a bypass from the superior mesenteric vein to the umbilical portion of the left intrahepatic portal vein (mesentericoportal Rex-shunt). Postoperatively, normal intrahepatic portal vein flow was demonstrated by ultrasound. After 2 years of follow-up, the patient is asymptomatic with no signs of portal hypertension. In contrast to classic portosystemic shunt operations, this bypass restores physiological portal vein flow, thus avoiding the possible consequences of longterm portosystemic shunting and low-grade encephalopathy.
Child↗