Safety and outcome of combined liver and pancreatic resections.

BACKGROUND: In Western countries, combined liver and pancreatic resections (CLPR) are performed rarely because of the perceived high morbidity and mortality rates. This study evaluated the safety and outcomes of CLPR at a tertiary European centre for hepatopancreatobiliary surgery. METHODS: A review of two prospectively maintained databases for pancreatic and liver resections was undertaken to identify patients undergoing CLPR between January 1994 and January 2012. Clinicopathological and surgical outcomes were analysed. Univariable and multivariable analyses for postoperative morbidity were performed. RESULTS: Fifty consecutive patients with a median age of 58 (range 20-81) years underwent CLPR. Indications for surgery were neuroendocrine carcinoma (16 patients), biliary cancer (15), colonic cancer (5), duodenal cancer (1) and others (13). The type of pancreatic resection included pancreaticoduodenectomy (30), distal pancreatectomy (17), spleen-preserving distal pancreatectomy (2) and total pancreatectomy (1). Twenty-three patients had associated major hepatectomies, 27 underwent minor liver resections and 11 had associated vascular resections. Mortality and morbidity rates were 4 and 46 per cent respectively. Univariable and multivariable analysis showed no differences in postoperative morbidity in relation to extent of liver resection or type of pancreatic resection. Use of preoperative chemotherapy was the only independent risk factor associated with postoperative morbidity (P = 0.021). CONCLUSION: CLPR can be performed with fairly low morbidity and mortality rates. Postoperative outcomes were not affected by the extent of liver resection or the type of pancreatic resection. Patients receiving chemotherapy should be evaluated carefully before surgery is considered.

Two-stage hepatectomy for multiple bilobar colorectal liver metastases.

BACKGROUND: As surgical resection of colorectal liver metastases (CLM) remains the only treatment for cure, efforts to extend the surgical indications to include patients with multiple bilobar CLM have been made. This study evaluated the long-term outcome, safety and efficacy of two-stage hepatectomy (TSH) for CLM in a large cohort of patients. METHODS: Patients undergoing surgery between December 1996 and December 2009 were reviewed. The early postoperative and long-term outcomes as well as the patterns of failure to complete TSH and its clinical implications were analysed. RESULTS: Eighty patients were scheduled to undergo TSH. Sixty-one patients had completion of TSH combined with (58 patients), or without (3) portal vein embolization/ligation (PVE/PVL). Five patients were excluded after first-stage hepatectomy and 14 after PVE/PVL. The 5-year overall survival rate and median survival in patients who completed TSH were 32 per cent and 39·6 months respectively, and corresponding recurrence-free values were 11 per cent and 9·4 months respectively. Six patients were alive beyond 5 years after TSH. Multivariable logistic regression analysis showed that failure to complete TSH was driven by two independent prognostic scenarios: three or more CLM in the future remnant liver (FRL) combined with age over 70 years predicted tumour progression after first-stage hepatectomy, and three or more CLM in the FRL combined with carcinomatosis at the time of first-stage hepatectomy predicted the development of additional FRL metastases after PVE/PVL. CONCLUSION: A therapeutic strategy using TSH provided acceptable long-term survival with no postoperative mortality. Further efforts are needed to increase the number of patients who undergo TSH successfully.

Liver transplantation in recipients over 65 yr old: a single center experience.

INTRODUCTION: The advanced age of the recipient is considered a "relative contraindication" to liver transplantation (LT). However, recently some studies reported a morbidity rate and an overall survival comparable with those of younger patients. Here, we reported the outcome after LT in recipients aged >65 yr. METHODS: Between January 2000 and December 2006, 565 LT was performed in 502 recipients in our institution. Of these, 34 were recipients of >65 yr old (aged group). We focused our study comparing: donor age, co-morbidities, model for end-stage liver disease (MELD) and American Society of Anesthesiologists (ASA) score, duration of operation, transfusions and outcome between the two groups (young/aged). RESULTS: For the group aged >65: the mean donor age was 52.5 (range 16-75) yr and the graft weight 1339 g (890-1880 g). Co-morbidity was recorded in 25 (73.5%), coronary artery disease (CAD) in 17 (50%), diabetes mellitus (DM) and chronic renal insufficiency in four (11.7%) and chronic obstructive pulmonary disease (COPD) in three patients (8.8%). Mean MELD score was 14.9 (range 12-29) and ASA score was two in 15 (44.1%); and three in 19 (55.8%) recipients. Mean operation time was four h 45 min, three patients also received combined kidney transplantation. Twenty-five (73.5%) recipients received blood transfusions (mean 3.2). Morbidity was observed in 20 patients (58.8%); of these two had hepatic artery thrombosis requiring re-LT. Overall survival was 80% (40 months of follow-up), in particularly, at 30-d, one yr, three yr was 91%, 84%, 80%, respectively. The only two statistical differences reported (p = 0.02) are: the lower rate of CAD in the younger group of recipients (12%), compared with the aged group (50%) and the subsequently lower mortality rate secondary to cardiac causes in the younger group (1.4%) compared with aged group (8.8%). CONCLUSION: Our results suggest that the recipient age should not be considered an absolute contraindication for LT when the graft/recipient matching is optimal and when an adequate cardiac assessment is performed.

Twenty seven years of experience in pediatric liver transplantation in Strasbourg: focus on the ex situ split techniques.

INTRODUCTION: Despite the well-known controversies about split-liver procedures, since 1979 we have utilized an ex situ instead of an in situ technique because of its feasibility. However, we sought to prove the equality of the results of these two procedures. Herein, we have presented our experience after 27 years' follow-up. MATERIALS AND METHODS: Between March 1979 and June 2006, we transplanted 84 livers in 67 pediatric recipients including 37 ex situ split livers implanted into 28 patients. RESULTS: We recorded demographic characteristics, transplantation, and retransplantation indications, age difference between donors and recipients, comorbidities, cold ischemia times, surgical times and complications, graft/recipient body weight ratios, organ recovery times, and overall survivals after 1, 5, and 15 years follow-up. We have herein reported 1, 5, and 15 years of patient versus organ survivals of 88.9.1%, 84.5%, 62.1% versus 78.6%, 74.2%, 57.4%, respectively. CONCLUSION: We have concluded that an ex situ split liver may be a valid alternative to in situ techniques to achieve good grafts for pediatric transplantation.

[Pancreaticoduodenectomy for cancer of the head of the pancreas]. / Duodénopancréatectomie céphalique pour cancer.

Many modifications of the original technique have been proposed to try to improve the results of the pancreaticoduodenectomy described by Whipple. To evaluate these modifications, we have reviewed randomized controlled trials, meta-analyses, and well-conducted retrospective series. Neither total pancreatectomy nor extended lymph node dissections have shown an improve of survival in retrospective studies. Preoperative evidence of mesenteric or portal vein involvement does not contraindicate pancreatic resection and survival rates are similar to those of patients with no venous involvement. Prospective trials and one meta-analysis have shown neither advantage nor disadvantage of pylorus-preserving pancreaticoduodenectomy or of pancreatico-gastric anastomosis. Three trials and one meta-analysis of pancreatico-gastric anastomosis have failed to demonstrate a decrease in the risk of pancreatic fistula. Two trials suggest that the risk of fistula formation is decreased by implantation of the pancreatic remnant into the jejunum or by trans-jejunal stenting of the pancreatico-jejunal anastomosis with external drainage; but these findings are not supported by a third trial. The results of the antisecretory use of somatostatin are contradictory. Leak and fistula formation were decreased when the criteria for leakage was based on laboratory findings; but in 4 out of 5 trials, somatostatin did not decrease the incidence of clinical fistula. The use of fibrin glue to occlude the pancreatic duct or seal the cut surface of the pancreas did not decrease the rate of intra-abdominal complications. In conclusion, the pancreaticoduodenal resection described by Whipple may still be considered the gold standard for resection of pancreatic cancer. The technical experience of surgeons and their institutional support staff resulted in lower perioperative morbidity and mortality and in higher survival rates.

Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases. Association Francaise de Chirurgie.

PURPOSE: Resection is the only chance for cure in patients with colorectal liver metastases (LM). Five-year survival rates are close to 25%. Unfortunately, recurrences occur in most patients. Some recurrent LM are technically resectable. The aim of this study was to determine the risks and benefits of repeat resections for recurrent LM. PATIENTS AND METHODS: Data from 130 patients who received 143 repeat liver resections for recurrent LM were collected. In 116 patients, only the liver was involved, while 14 had both liver and extrahepatic recurrences. RESULTS: In the first group, the operative mortality and morbidity rates were 0.9% and 24.7%, respectively. Two- and 3-year survival rates were 57% and 33%, respectively. Recurrences were observed in 66% of patients. Twelve patients underwent a third hepatectomy for recurrence. The mortality rate was nil, and the mean survival time was 12.5 months. In the group with liver and extrahepatic metastases, the operative mortality and morbidity rates were 0% and 25%. The mean survival time was 16 months. Eleven patients died and 13 had recurrences during the follow-up period. CONCLUSION: Some hepatic recurrences after surgical excision of colorectal metastases can be resected with a low operative risk and with a long-term survival rate similar to that obtained after first resections. This emphasizes the need for a careful follow-up after hepatectomy for colorectal metastases to detect resectable recurrences.

[Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients with solid organ transplantation: a clinical, neurophysiological and neuropathological study of 4 cases]. / Polyradiculonévrite chronique chez des patients avec une greffe d'organe solide: une étude clinique, neurophysiologique et neuropathologique de 4 cas.

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) rarely develops in patients with solid organ transplantation. PATIENTS AND METHOD: We describe the clinical, biological, electrophysiological and neuropathological features of 4 patients with solid organ transplantation who developed CIDP. Two patients had liver transplantation, one had kidney transplantation and one had lung transplantation. RESULTS: All 4 patients developed in the months following transplantation a syndrome that fulfilled criteria for definite CIDP. All patients had immunosuppressive therapy, with ciclosporin + prednisolone in 2 cases, tacrolimus in 1 case and azathioprine + prednisolone + ciclosporin in one case. One patient had chronic HCV and HBV infection. Treatment with intravenous immune globulin (IVIG) and/or a change in immunosuppressive therapy improved the neuropathy in all cases. CONCLUSION: CIDP is a rare and potentially treatable condition that should be considered in all patients with solid organ transplantation who develop a rapidly disabling sensorimotor polyneuropathy.

HIV-1 infection induces functional alterations in human liver endothelial cells in primary culture.

OBJECTIVES: Since human liver endothelial cells allow HIV-1 multiplication in vitro, we investigated whether HIV induced functional alterations in these cells in primary culture. DESIGN: Direct evidence of the replication of HIV in endothelial cells is sparse, but clotting abnormalities and thrombi, which suggest the existence of an endothelial dysfunction, have been observed in HIV-infected patients. We therefore studied the storage and release of endothelial-specific factors in primary cultures of liver endothelial cells infected with HIV, as well as their cytoskeleton, pinocytic and phagocytic properties. METHODS: Intracellular storage of von Willebrand's factor (vWF) was determined by immunofluorescence and computer image analysis. Excretion of vWF, protein S and endothelin-1 was measured using an enzyme-linked immunosorbent assay and radioimmunoassay. Cytoskeletal constituents were studied by light microscopy. The pinocytosis of acetylated low-density lipoproteins and the phagocytosis of latex beads were analysed under light and electron microscopy. RESULTS: The synthesis of vWF is markedly decreased in HIV-infected liver endothelial cells, as is the excretion of endothelin-1. In contrast, the excretion of protein S remains unaffected and the cytoskeletal network appears to be unaltered. Pinocytosis and phagocytosis are preserved. CONCLUSIONS: HIV infection triggers non-lethal functional alterations in cultured human liver sinusoidal endothelial cells, with a selective impairment in the storage and/or the excretion of endothelial-specific factors such as vWF. This functional modulation could play a role in the pathophysiology of HIV-induced disease.

Ultrastructural observations in hepatitis C virus-infected lymphoid cells.

It is currently unclear whether the hepatocellular damage in chronic hepatitis C virus (HCV) infection is produced through the intrahepatic action of the anti-HCV immune response or through a direct cytopathic effect. In order to investigate the features of HCV replication (morphogenesis and cytopathic effect), we studied the infection of a permissive lymphocytic B cell line, Daudi cells, which were infected with sera of HCV-positive patients, and were examined after various time points under electron microscope. Viral genomic RNA was detected by in situ hybridization, and apoptosis with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The amount of viral genomic RNA was observed to increase during infection. HCV replicated rapidly, since characteristics of viral morphogenesis resembling those of yellow fever virus in a hepatoma cell line could be found 2 days after infection. These included the following: a) several viral particles identical in size (about 42 nm) and structure (a spherical 30-nm-sized electron-dense nucleocapsid surrounded by a membrane) to yellow fever virus were present in the cytoplasm of cells displaying already typical signs of the early stage of apoptosis; b) numerous membrane-bound organelles and in particular the endoplasmic reticulum and vacuoles were observed; c) proliferation of membranes was apparent; and d) intracytoplasmic electron-dense inclusion bodies which have been demonstrated to correspond to nucleocapsids for other flaviviruses were detected. Several cells presented electron-dense areas in the endoplasmic reticulum displaying 30-nm circular structures lying among an amorphous material. Striking cytopathic features with ballooning, extremely enlarged vacuoles and signs of apoptosis were found in cells often containing sequestered aggregates of virus-like particles. By in situ hybridization we found that such enlarged cells contained HCV RNA. Our results thus indicate that the ultrastructural features of HCV viral particles and their morphogenesis resemble that of yellow fever virus and dengue virus. In Daudi cells, HCV infection seems to rapidly trigger apoptotic cell death, and efficient release of viral particles does not seem to take place.

'Dosimetric breast size': a new and useful parameter for the prediction of local recurrence after breast conservative treatment.

To evaluate the risk of local recurrence following breast-conserving therapy for breast cancer, we measured the distance between each entry point of the irradiation on the surface of the breast in line with the axis of the external and internal tangential fields (dosimetric breast size). 652 breast cancer patients were retrospectively analysed, with a median age of 51 years and a median follow-up of 99 months (range 84-192). There were 50 local recurrences, 44 isolated and 6 associated with nodal recurrence or metastases. The global rates of local recurrences at 5 and 10 years were 5.3% and 9%, respectively (Kaplan-Meier analysis). Following a Cox's multivariate analysis, the only significant and independent parameters related to local recurrence were quality of excision, age at diagnosis and dosimetric breast size. For a small dosimetric breast size (< or = 10 cm), the rate of local recurrence was 14.1 compared with 11.8 for medium dosimetric breast size (> 10 cm-< or = 12 cm) and 5.2 for large dosimetric breast size (> 12 cm). If the analysis was restricted to only those with complete excision, then the relative risk for a patient with a small dosimetric breast size was three times that for a large breast size.

Comparative evaluation of Celsior solution versus Viaspan in a pig liver transplantation model.

BACKGROUND: In a pig liver transplantation model, we compared the effects of Celsior solution (CS), an extracellular preservation solution, with Viaspan (University of Wisconsin solution, UW) on graft function and animal survival. METHODS: Pig livers were flushed with either CS or UW solution and cold-stored for 12 hr (group 1) or for 8 to 10 hr (group 2). Grafts were transplanted orthotopically. Intrahepatic reduced and oxidized glutathione and adenine nucleotides were evaluated 1 hr after reperfusion. Liver function of transplanted animals was monitored for up to 6 days by serum transaminases, total bilirubin, purine nucleoside phosphorylase, and prothrombin levels. RESULTS: In group 1, all animals died within 24 hr after reperfusion regardless of the preservation solution used. In group 2, no significant difference was seen in survival between the CS (72%) and the UW (67%) groups 6 days after transplantation, and there were no statistically significant differences in the biochemical data. There were no differences in histological evaluation of the livers at the time of death or killing of the animals between the CS and UW groups. CONCLUSION: Within the limits of this pilot study, CS is equivalent to UW in terms of graft function and animal survival.

Effects of platelet-activating factor antagonist on preservation/reperfusion injury of the graft in porcine orthotopic liver transplantation.

To investigate the role of platelet-activating factor (PAF) in the preservation/reperfusion injury of the liver graft, the effect of treatment with a potent PAF antagonist (E5880) was evaluated in a pig orthotopic liver transplantation model. The graft liver was flushed out and preserved for 8 hr at 4 degrees C using a simplified University of Wisconsin solution. The PAF antagonist was administered into the University of Wisconsin solution (1 mg/L), into the rinsing solution (1 mg/L), and to a recipient pig (0.3 mg/kg d.i.v.) in group 1. The PAF antagonist was not given in the control group (group 2). Postoperative survival of more than 12 hr was 100% (9/9) in group 1 and 56% (5/9) in group 2 (P < 0.05). At 12 hr after reperfusion of the graft (RPF), the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate) increased to 1.54 +/- 0.15 (mean +/- SEM) in group 1, compared with 0.95 +/- 0.09 (P < 0.05) in group 2. In group 2, blood leukocyte count decreased to 8.3 +/- 0.9 (x 10(3)/microliters) at 2 hr after RPF, in contrast to a slight increase in group 1 (14.3 +/- 1.8 x 10(3)/microliter, P < 0.01). At 4 hr after RPF, glutamic oxaloacetic transaminase (461 +/- 59 vs. 712 +/- 97 U/L, P < 0.05), glutamic pyruvic transaminase (65 +/- 4 vs. 82 +/- 5 U/L, P < 0.05), and the lactate level (6.2 +/- 1.1 vs. 9.4 +/- 1.0 mmol/L, P < 0.05) in arterial blood were significantly lower in group 1 than in group 2. Light and electron microscopic study at 1 hr after RPF showed neutrophil sludging in the sinusoids and sinusoidal endothelial cell damage in group 2, while these findings were attenuated in group 1. It is suggested that PAF plays a key role in microcirculatory disturbance of the liver graft manifested on reperfusion, and that the treatment with E5880 has a protective effect against preservation/reperfusion injury of the graft in liver transplantation.

Auxiliary liver transplantation for fulminant and subfulminant hepatic failure.

We report the first series of 9 auxiliary liver transplantations performed as a bridge to recovery in 8 patients with fulminant and subfulminant hepatic failure. Hepatic failure was due to hepatitis A virus (n = 3), hepatitis B virus (n = 1), hepatotoxic drugs (n = 2), autoimmune disease (n = 1), or it was of unknown origin (n = 1). The donor liver was reduced to a left lobe (n = 2), a left liver (n = 4), or a right liver (n = 3), and was implanted in an orthotopic position beside the native liver after it was resected by a left or a right hepatectomy. Conventional immunosuppression was used to prevent rejection. Six patients regained normal consciousness within 2 weeks, without any sequelae. Two patients had persisting encephalopathy due to graft initial dysfunction, one of whom showed portal vein thrombosis, which was successfully cleared. The other one showed hepatic vein stenosis and was retransplanted at day 15. Five of eight patients had to be reoperated because of a surgical complication. Five patients showed rapid regeneration of their native liver, but one died at day 45 from severe herpes virus broncholitis. The auxiliary grafts were removed (n = 3) or left to atrophy by tapering immunosuppression (n = 1). One patient developed cirrhosis of the native liver and died of infectious complications at day 42. The native livers of the two remaining patients are still atrophic, one at 4 months and one at 1 month posttransplant. Finally, 6 of 8 patients are alive with a follow-up of 1 to 17 months. Four of them have permanently stopped their immunosuppressive therapy. Our experience demonstrates that auxiliary orthotopic liver transplantation (1) is feasible in children and adults, using either a left or a right liver graft, (2) is efficient in providing adequate liver function, and (3) gives a real chance to the native liver to regenerate, offering these patients a future free of immunosuppression.

Permissivity of primary cultures of human Kupffer cells for HIV-1.

Kupffer cells (liver macrophages) represent the largest reservoir of fixed macrophages in the body. Accordingly, we have undertaken a study to evaluate their susceptibility to human immunodeficiency virus type 1 (HIV-1). Five-day-old primary cultures of Kupffer cells (KC) were infected with HIV-1, and as the infection progressed, syncytia appeared. Within the cells, viral proteins were detected by immunofluorescence using monoclonal antibodies directed against gp120 and p24. Electron microscopic examinations revealed the presence of typical Lentivirinae particles. The particles released from KC in the extracellular medium showed reverse transcriptase activity and p24 antigen; they could infect lymphocytic cells and were neutralized by a HIV+ patient's serum or an anti-gp120 monoclonal antibody. Our results thus demonstrate that the interaction of HIV-1 with KC in vitro leads to a productive infection. They suggest that the KC may be involved in the pathogenesis of HIV-1 infection and may (i) participate in the transmission of the infection to the peripheral blood cells, (ii) play a role in the depletion of uninfected CD4+ cells.

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Comparative phenotype and immunogenicity of freshly isolated and immortalized rat hepatocytes.

Immortalized hepatocytes are an attractive cell source for hepatocyte transplantation and gene transfer. We compared the phenotype and immunogenicity of freshly isolated (FIH) and immortalized (IMH) rat hepatocytes. Effect of culture and proinflammatory cytokines (TNF-alpha, IFN-gamma) was studied on phenotype. FIH were isolated by collagenase digestion. Two SV40 immortalized hepatocyte cell lines were tested (RH1 and P9). Immunophenotyping was performed by FACS analysis using anti-rat-specific antibodies. Immunogenicity was evaluated by a mixed lymphocyte hepatocyte reaction (MLHR). FIH suspension was an almost homogeneous parenchymal cell population with few (1-2%) CD8+ cells. FIH showed a positive staining for ICAM-1 (20-35%) and for Class I (RT1A, 30-60%) but no staining for Class II (RT1B). After 48 h of culture, the already ICAM-1-positive cells were more strongly stained and additionally 3.6% of the cells (possibly endothelial cells) were Class II positive. IMH showed a consistent expression of Class I (93-97%) and ICAM-1 (95-97%) but no expression of Class II. Culture of IMH for 48 h had no effect on Class II expression but increased ICAM-1 expression. Addition of TNF-alpha at 1000 UI/ml to cultures of FIH or IMH increased Class I and ICAM-1 expression whereas IFN-gamma (50 or 1000 UI/ml) had no evident effect. Hepatocyte immunogenicity, assessed in MLHR and appreciated by the stimulation index (SI) test/SI syngeneic control, was similar for IMH (RH1: 2.68+/-0.89; P9: 2.37+/-0.78) and FIH (2.52+/-0.18). In conclusion, despite some quantitative immunophenotypic differences, FIH and IMH induced the same proliferation rate of allogeneic T lymphocytes. Thus, immortalized hepatocytes may constitute an appropriate cellular model to study the prevention of hepatocyte rejection by gene transfer.

Engraftment and albumin production of intrasplenically transplanted rat hepatocytes (Sprague-Dawley), freshly isolated versus cryopreserved, into Nagase analbuminemic rats (NAR).

Banking of cryopreserved hepatocytes is a prerequisite for large-scale hepatocyte transplantation in the clinic. We compared the efficacy of intrasplenic transplantation into Nagase analbuminemic rats (NAR) of freshly isolated (FIH) and cryopreserved (CH) hepatocytes. Hepatocytes were cryopreserved using a controlled rate freezing protocol. Albumin production of thawed CH and FIH was measured in vitro in culture by ELISA and by Western blot. After in vivo intrasplenic transplantation of NAR with either FIH or CH we assessed 1) albumin in the serum of recipients by ELISA and by Western blotting analysis at different time intervals, and 2) hepatocyte engraftment by albumin immunohistochemical staining into spleens and livers at euthanasia. In vitro, albumin was produced up to day 4 of culture in both CH and FIH. In vivo, no intrasplenic engraftment of hepatocytes occurred. Intrahepatic engraftment of CH (cell number/mm2) was significantly (twofold) lower than that of FIH and appeared only as isolated cells and small (<10 cells) clusters, while bigger clusters (>10 cells) were observed with FIH. In the FIH group, serum albumin production was observed up to 32-49 days posttransplantation while in the CH group no serum albumin production was detected. Our results emphasize the need to improve 1) hepatocyte transplantation procedures either by repeated hepatocytes injections and/or by transplantation under a regeneration response, and 2) the freeze/thaw protocols of hepatocytes.

Relapse of Graves' disease after subacute thyroiditis.

We report the case of a 46-year-old man whose Graves' disease relapsed 5 years after its first appearance. At the time of relapse thyrotropin (TSH) receptor antibodies were very high, as was radioactive uptake in the left lobe of the thyroid. After thyroidectomy, histological analysis of the specimen showed evidence of treated Graves' disease, and there were signs of subacute thyroiditis in the right lobe. The clinical and immunologic characteristics of this observation are discussed as well as the hypothesis explaining the succession of an inflammatory and autoimmune thyroid disease.

Lobular carcinoma in situ of the breast: results of a radiosurgical conservative treatment.

From 1980 to 1992, 17 women underwent lumpectomy (13) or quadrantectomy (4) and whole breast irradiation (median dose: 52 Gy) for pure lobular carcinoma in situ (LCIS). Three cases correspond to palpable lesions and 14 were discovered only by mammography. Twelve women also received tamoxifen at 20 mg/day for two years. With a median follow-up of 88 months, no local or regional recurrences have been recorded. The global rate of bilateral carcinoma was 17.6% (2 synchronous and one metachronous). In the literature, only eight other cases of LCIS were treated by lumpectomy and radiation therapy, but without details and data on long-term results. After biopsy alone for LCIS subsequent infiltrating carcinoma occurred in about 15% of the cases. Thus, the classical radiosurgical association should represent an interesting alternative both for biopsy alone and radical surgery until now only proposed to treat LCIS.

Liver scintigraphy is useful for selecting candidates for preoperative transarterial chemoembolization among patients with hepatocellular carcinoma and chronic liver disease.

BACKGROUND: The indications for preoperative hepatic transarterial chemoembolization (TACE) have not been clarified by recent studies in patients with hepatocellular carcinoma (HCC) complicated by chronic liver diseases. The aim of the present study was to investigate which patients benefit most from preoperative TACE on the basis of hepatic functional reserve. Technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) liver scintigraphy was used to assess hepatic functional reserve before and after TACE. PATIENTS AND METHODS: Liver scintigraphy was performed before and several weeks after TACE in 64 patients with HCC complicated by chronic hepatitis or cirrhosis. The ratio of liver to heart-plus-liver radioactivity of Tc-GSA 15 minutes after injection (LHL15) was calculated. Conventional hepatic functional tests were also performed. Whether to perform hepatectomy after TACE was decided mainly on the basis of the previously reported value of LHL15 > or =0.91. RESULTS: LHL15, prothrombin time, and serum concentration of cholinesterase significantly decreased after TACE in patients with LHL15 > or =20.91 (P <0.01, P <0.05, and P <0.05, respectively). In patients with LHL15 <0.91, LHL15 and functional liver volume significantly increased after TACE (both P <0.05). Eight patients with LHL15 > or =0.91 did not undergo hepatectomy because LHL15 decreased to less than 0.91 after TACE, whereas 7 patients with LHL15 <0.91 underwent hepatectomy because LHL15 increased to more than 0.91 after TACE. Three major postoperative complications occurred in patients with LHL15 > or =0.91, and no major complications occurred in patients with LHL15 <0.91. CONCLUSIONS: The results suggest that preoperative TACE should be performed in HCC patients only when LHL15 is less than 0.91, and that preoperative TACE is not an appropriate treatment for patients with LHL15 > or =0.91 when HCC is resectable.