Number and tumor size are not sufficient criteria to select patients for liver transplantation for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI). METHODS: From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded. RESULTS: HCC was confirmed in 168 patients (85.7%). The median follow-up was 74 months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria (P = NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival (P < 0.001). Two factors were significantly associated with VI: alfa-fetoprotein level of >400 ng/ml and tumor grade G3. CONCLUSIONS: Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.

The POU factor Oct-6 and Schwann cell differentiation.

The POU transcription factor Oct-6, also known as SCIP or Tst-1, has been implicated as a major transcriptional regulator in Schwann cell differentiation. Microscopic and immunochemical analysis of sciatic nerves of Oct-6(-/-) mice at different stages of postnatal development reveals a delay in Schwann cell differentiation, with a transient arrest at the promyelination stage. Thus, Oct-6 appears to be required for the transition of promyelin cells to myelinating cells. Once these cells progress past this point, Oct-6 is no longer required, and myelination occurs normally.

The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA.

The translocation (6;9) is associated with a specific subtype of acute myeloid leukemia (AML). Previously, it was found that breakpoints on chromosome 9 are clustered in one of the introns of a large gene named Cain (can). cDNA probes derived from the 3' part of can detect an aberrant, leukemia-specific 5.5-kb transcript in bone marrow cells from t(6;9) AML patients. cDNA cloning of this mRNA revealed that it is a fusion of sequences encoded on chromosome 6 and 3' can. A novel gene on chromosome 6 which was named dek was isolated. In dek the t(6;9) breakpoints also occur in one intron. As a result the dek-can fusion gene, present in t(6;9) AML, encodes an invariable dek-can transcript. Sequence analysis of the dek-can cDNA showed that dek and can are merged without disruption of the original open reading frames and therefore the fusion mRNA encodes a chimeric DEK-CAN protein of 165 kDa. The predicted DEK and CAN proteins have molecular masses of 43 and 220 kDa, respectively. Sequence comparison with the EMBL data base failed to show consistent homology with any known protein sequences.

Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements.

Fusion genes encoding the 3' part of the can gene are implicated in two types of leukemia. The dek-can fusion gene is present in t(6;9) acute myeloid leukemia and the set-can fusion gene is present in one case of acute undifferentiated leukemia. In order to obtain leads towards the molecular basis of these diseases, we have studied the cellular localization of the DEK-CAN and SET-CAN fusion proteins and their normal counterparts. DEK-CAN and SET-CAN were localized exclusively in the nucleus, and also DEK and SET were found to be nuclear proteins. However, CAN was mainly located at the nuclear and cytoplasmic face of the nuclear envelope. This observation is in accordance with the presence of an amino acid repeat in the C-terminal part of CAN, common to the family of nucleoporins. The C-terminal part also contains a nuclear location domain as shown by deletion analysis. This domain may be important for the presence of CAN at the nucleoplasmic side of the nuclear envelope. The relocation of the carboxyterminal part of CAN due to DEK-CAN and SET-CAN may reinforce a nuclear function of the CAN protein.

Is sirolimus responsible for proteinuria?

Sirolimus (SRL) is suspected to induce proteinuria. We retrospectively studied proteinuria in a population of liver (n = 29) and kidney transplant (n = 30) recipients switched to SRL with progressive diminution or withdrawal of calcineurin inhibitors (CNI). We also observed estimated glomerular filtration rate (GFR), modification of treatment with antiproteinuric drugs, and changes in concentration of SRL. Collection of data started 3 months before SRL introduction at a mean follow-up of 21 months. Following SRL introduction, proteinuria was not detected in the 28 liver transplant patients, and was stable in the two others. In the kidney transplant group, proteinuria did not occur in 12 patients, remained stable in three, and was slightly increased in 14 (0.57 +/- 0.93 g/d vs 1.83 +/- 1.26 g/d). For all patients, eGFR remained stable; there was no difference in management of antiproteinuric drugs. As suspected, cyclosporin (CsA) and tacrolimus (FK) serum concentrations were decreased. We observed a significant correlation between the variation of proteinuria and the variation of serum concentration of CsA or FK (respectively, P = .001 and P = .007). On the other hand, we did not find any correlation between variation in proteinuria and concentration of SRL. This retrospective study suggests that in our cohort of liver transplant patients without previous renal damage, SRL did not provoke proteinuria. On the other hand, the slight aggravation of proteinuria in a subgroup of kidney transplant patients seems to be linked to the hemodynamic renal effects due to CNI withdrawal.

[Diffuse sebaceous hyperplasia of the face induced by cyclosporine]. / Hyperplasies sébacées profuses du visage induites par la ciclosporine.

INTRODUCTION: Many cutaneous complications have been reported in patients treated with cyclosporine. Alterations of the pilosebaceous follicle are particularly frequent. Hypertrichosis, follicular keratosis, acne and folliculitis are very common. Nevertheless, the occurrence of sebaceous hyperplasia is exceptional. OBSERVATION: A 27 year-old man consulted in February 2003 for a papulous eruption of the face. He was treated by cyclosporine and prednisone since his renal transplantation in 1993. The lesions flowed together on the cheeks, forehead and temples. The histological analysis confirmed the diagnosis of sebaceous hyperplasia. There was a perceptible improvement of the cutaneous state after one month of isotretinoin treatment. DISCUSSION: Sebaceous hyperplasia appears in about 10 p. 100 of patients treated with cyclosporine. This side effect occurs only in men of a mean age of 40 years. An increase in sebaceous gland size is often described, but profuse forms are uncommon. Our case report is exceptional because of the young age of the patient, and the occurrence of diffuse sebaceous hyperplasia that appeared a long time after the introduction of cyclosporine.

Thermoelectric efficiency of (1 - x)(GeTe) x(Bi2Se0.2Te2.8) and implementation into highly performing thermoelectric power generators.

Here we report for the first time on a complete simulation assisted "material to module" development of a high performance thermoelectric generator (TEG) based on the combination of a phase change material and established thermoelectrics yielding the compositions (1 - x)(GeTe) x(Bi(2)Se(0.2)Te(2.8)). For the generator design our approach for benchmarking thermoelectric materials is demonstrated which is not restricted to the determination of the intrinsically imprecise ZT value but includes the implementation of the material into a TEG. This approach is enabling a much more reliable benchmarking of thermoelectric materials for TEG application. Furthermore we analyzed the microstructure and performance close to in-operandi conditions for two different compositions in order to demonstrate the sensitivity of the material against processing and thermal cycling. For x = 0.038 the microstructure of the as-prepared material remains unchanged, consequently, excellent and stable thermoelectric performance as prerequisites for TEG production was obtained. For x = 0.063 we observed strain phenomena for the pristine state which are released by the formation of planar defects after thermal cycling. Consequently the thermoelectric performance degrades significantly. These findings highlight a complication for deriving the correlation of microstructure and properties of thermoelectric materials in general.

Role of Oct-6 in Schwann cell differentiation.

Research into the POU transcription factor Oct-6 has been the focus of much current attention, in particular its role in Schwann cell development and differentiation. Based on published data and data presented here, we propose a model for Oct-6 function at two distinct stages of Schwann cell maturation. First, Oct-6 function is required in promyelin cells for their timely differentiation into myelinating cells. Second, Oct-6 functions during myelination and is required for the proper downregulation of its own gene. While the first function of Oct-6 is firmly established, the second function is still highly hypothetical. Experiments to establish a distinct role for Oct-6 in late Schwann cell differentiation are discussed.

Use of ELISA for measuring the extent of serological cross-reactivity between plant viruses.

The degree of antigenic relatedness between two plant viruses is commonly expressed by a serological differentiation index (SDI) which corresponds to the average number of two-fold dilution steps separating homologous from heterologous precipitin titers. Results obtained with several tobamo- and tombusviruses indicated that the indirect form of the enzyme-linked immunosorbent assay (ELISA) can also be used for calculating SDI values. This was achieved by comparing the antiserum dilutions that lead to the same absorbance measurements (for instance 1.0) when homologous and heterologous viruses are assayed by ELISA. SDI values calculated from ELISA were similar to those obtained from precipitin tests. Because of its greater sensitivity, ELISA is able to quantify weak cross-reactions that are not detectable by precipitin tests.

[Pregnancy after renal transplantation. Obstetrical follow up and long term outcome of the renal graft]. / La grossesse après transplantation rénale. Suivi obstétrical et retentissement à long terme sur le greffon rénal.

OBJECTIVES: To study the course of pregnancy after renal transplantation and to assess the impact of the pregnancy on the renal graft. MATERIAL AND METHODS: [corrected] Retrospective study of 20 pregnancies from 16 renal transplant recipients between January 1987 and December 1998. Mean patient age was 30.3 +/- 4 years. Mean time between transplantation and the onset of pregnancy was 56.4 +/- 34.8 months. RESULTS: The main maternal complications were hypertensive disorders (7 cases) of which 3 preeclampsia. The mean gestational age at delivery was 36 +/- 3.1 weeks. Ten patients delivered prematurely of which 9 were induced prematurity. Nine cesarean sections were carried out either for obstetrical reasons or for causes not directly related to the transplantation. The mean neonatal weight was 2386 +/- 644 g with five small for gestational age. We did not observe any acute rejection. The follow up revealed six cases of chronic rejection. None of them seemed directly related to the pregnancy. CONCLUSIONS: The course of pregnancy after renal transplantation is generally uncomplicated without increased risk of graft lose. However, a stable renal function and an interval of two years or more after the transplantation are requested before allowing a pregnancy. Hypertension, diabetes mellitus or impaired renal function (creatininemia > 150 mumol/l) are contraindications for pregnancy.

[Renal transplantation in thrombosis of the inferior vena cava. Implantation of the graft vein in the portal vein]. / Transplantation rénale en cas de thrombose de la veine cave inférieure. Implantation de la veine du greffon dans la veine porte.

An 8-year old girl with chronic renal failure underwent allogeneic renal transplantation with implantation of the renal vein of the graft on the portal vein, as the inferior vena cava was obstructed by thrombosis. The possible technical obstacles to renal transplantation are reviewed on that occasion, and solutions are suggested. In the presence of thrombosis of the inferior vena cava it seems necessary to determine its level and to look for a patent venous segment all the way up to the diaphragm. If no such segment is found, then the renal vein can be implanted on the portal vein.

Continuous infusion of local anesthesia after living donor nephrectomy: a comparative analysis.

INTRODUCTION: Today local anesthetic wound infiltration is widely recognized as a useful adjunct in a multimodality approach to postoperative pain management. The effectiveness of continuous wound infusion of ropivacaine for postoperative pain relief after laparoscopic living donor nephrectomy was analyzed in this retrospective, comparative analysis. METHODS: Twenty patients undergoing living donor nephrectomy were divided into two groups: standard analgesic therapy (n=10) and ropivacaine continuous infusion group (n = 10). RESULTS: We observed a significant difference in term of visual analogue scale scores, use of morphine, hospital stay, and bowel recovery in favor of the ropivacaine group. The cost analysis demonstrated an overall savings of 985 Euros/patient. DISCUSSION: Surgical wound infusion with ropivacaine was safe and seemed to improve pain relief and accelerate recovery and discharge, reducing the overall costs of care. Postoperative pain control in the donor is of primary importance for better patient compliance and greater perceived quality of health care service.

Laparoscopic ultrasound-guided radiofrequency ablation as a bridge to liver transplantation for hepatocellular carcinoma: preliminary results.

INTRODUCTION: The aim of this study was to assess the impact of laparoscopic thermoablation (LTA) as a neoadjuvant therapy prior to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). METHODS: Between January 2008 and January 2009, 12 consecutive patients, including 10 males and 2 females with unresectable HCC within liver cirrhosis, were treated with LTA under ultrasound (US) guidance. Most patients were in Child-Pugh class B (54.1%) with a mean age of 60.7 +/- 7.74 years (range, 45-69; median, 60). RESULTS: The LTA procedure was completed in all patients with thermoablation of 23 HCC nodules. LTA identified 4 new malignant lesions (20%) undetected by preoperative imaging (<0.5 cm). The mean length of surgery was 96 minutes (range, 45-118). Six procedures were performed in 4 patients. No postoperative hepatic insufficiency was reported. The mean hospital stay was 4.5 days; no postoperative morbidity was reported. Complete tumor necrosis was achieved in 19/23 thermoablated nodules (82.6%) as evidenced computed tomography (CT) scan by at 3 weeks after the treatment. All patients underwent OLT without complications. The histology of the native liver showed complete necrosis in 17/23 (74%) treated nodules. DISCUSSION: There is currently no convincing evidence that LTA allows one to expand the current selection criteria for OLT, nor that LTA decreases dropout rates on the waiting list. However, LTA does not increase the risk of postoperative complications. There is insufficient evidence that LTA offers any benefit when used prior to OLT either for early or for advanced HCC.