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V Costes

Publications and source records attributed to V Costes.

At least 19 recordsLinked to original sources

[Aggressive T cytotoxic CD8+ epidermotropic cutaneous lymphoma: a case in a patient with Steinert's myotonic dystrophy].

INTRODUCTION: Primary cutaneous "aggressive" CD8-positive epidermotropic cytotoxic T-cell lymphoma is a rare subset of cutaneous cytotoxic T/NK lymphomas that clearly differs from mycosis fungoides, whether CD4+ or CD8+, by the presence of rapidly evolving tumoral cutaneous lesions, foci of keratinocytes necrosis, a cytotoxic T phenotype and a poor prognosis. CASE REPORT: A 33-year-old man with Steinert's myotonic dystrophy was referred for evaluation of rapidly worsening cutaneous tumors along with marked deterioration of general status. Clinical, histological and immunohistological data led to the diagnosis of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma. CHOP chemotherapy was effective despite cardiac toxicity in the setting of Steinert's dystrophy, but the patient relapsed and died of pulmonary sepsis after chemotherapy was resumed. DISCUSSION: The treatment of primary cutaneous epidermotropic CD8+ cytotoxic T-cell lymphoma is not codified. CHOP chemotherapy is usually the first-line therapy but relapses are frequent with median survival of no more than 34 months. In our patient, an additional difficulty was the cardiac toxicity of cytostatic drugs linked to the myopathy which prevented the use of high dosages, requiring a change of therapeutic regimen.

Adult↗

The Mi15 monoclonal antibody (anti-syndecan-1) is a reliable marker for quantifying plasma cells in paraffin-embedded bone marrow biopsy specimens.

Plasmocyte selective monoclonal antibodies (MAb) recognizing syndecan-1 have recently been described. They belong to a new cluster, CD138. Using the MAb MI15, we investigated the expression of syndecan-1 in routinely paraffin-embedded tissues. Nontumoral lymph nodes (25 cases) and bone marrow biopsy specimens (63 cases) showed strong membrane staining of plasma cells only, allowing accurate analysis of the nuclear structure. The MI15 positivity correlated with kappa and lambda light chain expression in the cytoplasm. The percentages of plasma cells calculated in bone marrow biopsy specimens after MI15 staining were, respectively, 2.1% (range, 1% to 4%) in normal bone marrows, 8.5% (range, 5 to 17) in reactive plasmocytosis, and 4.66% in monoclonal gammapathy of undetermined significance (MGUS) patients (range, 1 to 13), in the same range but slightly higher than those obtained on smears or on hematoxylin and eosin (H&E)-stained sections. In multiple myeloma (40 cases), all plasma cell types were marked, and Mi15 MAb gave additional information in 8 of 40 (20%) patients. In lymph nodes, Mi15 MAb reacted with Reed-Sternberg cells of classical Hodgkin's disease in 23 of 31 cases (74%) with variable intensity. In contrast, nodular lymphocyte predominance Hodgkin's disease (10 cases), most B cell lymphomas (88 of 107 cases) and all T cell lymphomas (30 cases) were negative. In B cell lymphomas, plasmocytomas (8 cases), plasmocytic lymphomas (2 cases), and 5 of 13 cases of immunoblastic lymphoma with plasmocytoid differentiation were stained. In lymphoplasmocytoid lymphomas (4 lymph nodes and 20 bone marrow biopsy specimens), only mature plasma cells were positive. Moreover, a wide distribution of syndecan-1 was observed in normal and tumoral epithelial tissues. Finally, Mi15 MAb appears to be a reliable marker for identifying and quantifying normal and tumoral plasma cells in paraffin-embedded bone marrow and lymph node samples.

Antibodies, Monoclonal↗

Hepatitis C virus genotypes and quantification of serum hepatitis C RNA in liver transplant recipients. Relationship with histologic outcome of recurrent hepatitis C.

The reasons for wide variations in the severity of recurrent hepatitis C after liver transplantation are unclear. We studied liver transplant recipients to assess the effect of hepatitis C virus (HCV) genotype and HCV RNA quantification on histologic progression of recurrent hepatitis C after transplantation. Twenty-five patients underwent transplantation for HCV cirrhosis and were followed up with virologic and histologic assessments for a mean of 51 months. HCV genotype was determined by line probe assay. HCV RNA was quantitated in serum samples by nested polymerase chain reaction. The HCV genotype 1 was detected in 17 patients and other genotypes in 8. Acute lobular hepatitis developed in 17 patients 162 days posttransplantation on average. Long-term biopsy specimens (mean, 51 months after the date of liver transplantation; range, 24-86 months) showed chronic hepatitis in 19 patients (mild, 5; moderate, 9; and severe, 5, 2 with extensive scarring). The serum alanine aminotransferase level was correlated with hepatocyte necrosis (piecemeal and lobular) but not with portal inflammation or fibrosis. Patients infected with genotype 1 had a higher Knodell score, and the 5 patients with severe hepatitis C all were infected with genotype 1. HCV RNA levels were significantly higher in patients with genotype 1 than in patients with other genotypes, as were the severity of histologic recurrence and levels of viral replication.

Adult↗

Interleukin-10 and Gp130 cytokines in human multiple myeloma.

Interleukin (IL)-10 is a critical cytokine involved in the terminal differentiation of B cells into plasma cells. IL-10 is also involved in multiple myeloma, a malignant plasma cell disorder. IL-6 and, more generally the cytokines activating the gp130 IL-6 transducer, are major survival and proliferation factors of myeloma cells. IL-10 is also a growth factor of malignant plasma cells, produced by myeloma cells from about half the patients and is detected in the plasma of patients with plasma cell leukemia or solitary plasmacytoma. The myeloma cell growth activity of IL-10 is mediated through a gp130 cytokine, oncostatin M (OSM), that is frequently produced by myeloma cells. Myeloma cells fail to express OSM receptors but IL-10, by inducing it, confers on them the sensitivity to OSM.

Animals↗

[Urogenital amyloidosis: clinico-pathological study of 8 cases].

Amyloidosis of the genito-urinary tract is uncommon. We report 8 cases, often misdiagnosed as a neoplastic process (6/8). Amyloidosis was localized in the bladder (3 cases), in the ureter (1 case) and in the prostate and/or seminal vesicles (4 cases). The amyloid protein was characterized in 7 cases by immunohistochemistry. Among the bladder and ureter amyloidosis, 2 cases were classified as AL lambda amyloidosis and one case as AA amyloidosis in a patient with long history of chronic arthritis. In the fourth case, the deposits could not be identified. Nevertheless an AL amyloidosis might be suggested. Two cases of prostate and/or seminal vesicles amyloidosis were stained with an anti-B2M antibody, in hemodialyzed patients. The 2 others, positive with the anti-Transthyretina antibody, were classified as senile amyloidosis. This small series illustrated the heterogeneous pathogenic types of amyloidosis in the urogenital tract and emphasized the interest of immunohistochemistry to identify the chemical composition of these deposits.

Adult↗

A gp130 interleukin-6 transducer-dependent SCID model of human multiple myeloma.

Agonist antihuman gp130 transducer monoclonal antibodies (MoAbs) were used in SCID mice to grow myeloma cells whose survival and proliferation is dependent on gp130 transducer activation. The agonist anti-gp130 MoAbs neither bound to murine gp130 nor activated murine cells and, as a consequence, did not induce interleukin-6 (IL-6)-related toxicities in mice. They have a 2-week half-life in vivo when injected in the peritoneum. The agonist antibodies made possible the in vivo growth of exogenous IL-6-dependent human myeloma cells as well as that of freshly explanted myeloma cells from 1 patient with secondary plasma cell leukemia. Tumors occurred 4 to 10 weeks after myeloma cell graft and weighed 3 to 5 g. They grew as solid tumors in the peritoneal cavity and metastasized to the different peritoneal organs: liver, pancreas, spleen, and intestine. Tumoral cells were detected in blood and bone marrow of mice grafted with the XG-2 myeloma cells. Tumoral cells grown in SCID mice had kept the phenotypic characteristics of the original tumoral cells and their in vitro growth required the presence of IL-6 or agonist anti-gp130 MoAbs. Myeloma cells from 4 patients with medullary involvement persisted for more than 1 year as judged by detectable circulating human Ig. However, no tumors were detected, suggesting a long-term survival of human myeloma cells without major proliferation. These observations paralleled those made in in vitro cultures as well as the tumor growth pattern in these patients. This gp130 transducer-dependent SCID model of multiple myeloma should be useful to study various therapeutical approaches in multiple myeloma in vivo.

Animals↗

Interleukin-1 in multiple myeloma: producer cells and their role in the control of IL-6 production.

We studied the role of interleukin (IL)-1beta in patients with multiple myeloma. By in situ hybridization and immunochemistry, myeloid and megakaryocytic cells expressed high levels of the IL-1beta gene and produced IL-1beta. Myeloma cells less potently expressed the IL-1beta gene and IL-1beta protein. IL-1beta gene expression was not constitutive since it was detected in the bone marrow myeloma cells of two patients, unlike circulating tumoural cells. In addition, nine myeloma cell lines failed to express the IL-1beta gene and this expression could not be induced by 12 different cytokines. We demonstrated that IL-1 was mainly responsible for IL-6 production in the tumoural environment through a PGE2 loop. In fact, an IL-1 receptor antagonist (IL-1RA) blocked PGE2 synthesis and IL-6 production by 80%; this blockage could be reversed by adding synthetic PGE2. Similar findings were found with indomethacin, an inhibitor of cyclooxygenase that blocks PGE2 synthesis. Taken together, these data emphasize the possibility of blocking IL-1 by using IL-1RA or other antagonists in order to block IL-6 production, which is a major tumoural survival and proliferation factor.

Adult↗

Hepatitis C virus genotypes and quantitation of serum hepatitis C virus RNA in liver transplant recipients: relationship with severity of histological recurrence and implications in the pathogenesis of HCV infection.

The reasons for the wide variation of incidence and severity of recurrent hepatitis C after liver transplantation are not clear. We have studied liver transplant recipients to assess the impact of hepatitis C virus (HCV) genotype and HCV RNA quantification on HCV recurrence after transplantation. Twenty-two patients received transplants for HCV cirrhosis and were followed up with virological and histological assessments. Mean follow-up was 39 months. HCV genotype was determined with line probe assay (Inno-Lipa). HCV RNA quantity was determined in serum samples by use of polymerase chain reaction nested assay. HCV genotype 1 was detected in 13 patients and other genotypes in 9. Histological recurrence rates were 69% in patients with genotype 1 and 66% in patients with other genotypes. All cases of severe histological injury (chronic active hepatitis or cirrhosis) were observed in patients with genotype 1. HCV RNA quantity was significantly higher in patients with genotype 1 (mean, 2.023 x 10(3) copies/mL) than in patients with other genotypes (mean, 27,403 copies/mL). In conclusion, the severity of histological recurrence after liver transplantation for HCV disease was higher in patients infected by HCV genotype 1 than in those infected with other genotypes. The levels of viral replication were higher in patients with HCV genotype 1 than in those with other genotypes.

Adult↗

Expression of the interleukin 6 receptor in primary renal cell carcinoma.

AIMS: Interleukin 6 (IL-6) is expressed in the majority of renal cell carcinomas and has an important role in the proliferation of some renal cell carcinoma cell lines. This action is mediated by two membrane proteins, gp80 (the IL-6 receptor; IL-6R), which binds IL-6, and gp130, which transduces the signal. The soluble form of gp80 (sIL-6R) is able to activate gp130 when complexed to the IL-6 molecule. These considerations prompted an investigation of IL-6R expression in this malignancy. IL-6, C reactive protein (CRP), and sIL-6R were also measured in serum and correlated to clinical and pathological features. METHODS: Immunostaining was performed on cryostat sections from renal cell carcinoma tumours with M91, an anti-IL-6R monoclonal antibody, using the alkaline phosphatase antialkaline phosphatase technique. The proliferation index was measured using the KI-67 monoclonal antibody. CRP, IL-6, and sIL-6R were measured in serum before nephrectomy, using an immunoenzymatic or immunoradiometric assay. RESULTS: There were significant differences in survival in patients with tumours larger than 8 cm, metastasis at diagnosis, high nuclear grade tumours, detectable serum concentrations of IL-6 (correlated to CRP serum concentration), more than 4% proliferating cells, and the presence of the IL-6R in situ. Furthermore, the serum IL-6 concentration correlated with tumour size and stage. The mean serum sIL-6R concentration was not significantly different from that observed in 40 normal subjects. Tumour IL-6R expression was present in 10 samples. There was a significant association between the presence of the IL-6 receptor in tumours and tumour stage, nuclear grade, proliferation index, and serum IL-6. CONCLUSIONS: This study revealed the importance of IL-6/CRP and IL-6R expression in situ as potential new prognostic factors and opens the way to new therapeutic strategies in renal cell carcinoma.

Adult↗

[Undifferentiated soft tissue tumor with rhabdoid phenotype (extra-renal rhabdoid tumor). Report of a congenital case associated with medulloblastoma in a brother].

We report a case of congenital cervical rhabdoid tumor with association of a medulloblastoma in a brother. The immunohistochemical features of this tumor are compatible with a neuroectodermal differentiation (MIC 2+, Leu 7+). Extrarenal rhabdoid tumors share a common morphology but do not represent a single entity with only one histogenesis. Most of them are now considered to be of neuroectodermal origin. In our case, the association with a medulloblastoma in a brother seems to confirm this concept.

Cell Differentiation↗

Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop.

We have a previously reported that interleukin-10 (IL-10) is a potent but IL-6-unrelated growth factor for freshly explanted myeloma cells (Lu et al, Blood 85:2521, 1995). We have also shown that exogenous IL-10 supported the growth of XG-1 and XG-2 human myeloma cell lines (HMCL) through an IL-6-independent mechanism. (Lu et al, Blood 85:2521, 1995). Because the IL-10 receptor does not involve the gp 130 IL-6 transducer, we have attempted to elucidate the mechanisms of IL-10 action on myeloma cells. Our results indicate that the myeloma cell growth factor activity of IL-10 was abrogated by an antibody to the gp 130 IL-6 transducer, indicating that it was mediated through one of the gp 130-activating cytokines. We found that myeloma cells from XG-1 and XG-2 HMCL and from 5 of 6 patients' tumoral samples produced oncostatin M (OM) constitutively but failed to produce IL-6, IL-11 and leukemia-inhibitory factor (LIF). The autocrine OM was inactive in the absence of IL-10 due to lack of a functional OM receptor on myeloma cells. IL-10, by inducing the receptor for LIF (LIFR), produced a functional autocrine OM loop in XG-1 and XG-2 cells and in primary myeloma cells from 2 patients. We also found that some myeloma cell lines (XG-4, XG-6, and XG-7) an fresh myeloma cells from 3 of 6 patients produced an autocrine IL-10 and that these cells constitutively expressed LIFR. One HMCL (XG-7) produced IL-10, OM, and IL-6 an expressed LIFR. The XG-7 cells used OM and IL-6 as autocrine growth factors. We have previously shown that IL-10 could induce IL-11 receptor in myeloma cells and confer on them sensitivity to IL-11 (Lu et al, FEBS Lett 377:515, 1995). Taken together, these results show that IL-10 is a key cytokine for inducing the expression of LIFR and IL-11R and possibly another uncharacterized OM coreceptor on myeloma cells and that OM and IL-10 might be produced by myeloma cells. They also emphasize that all myeloma cell growth factors reported to data involve an activation of the gp130 IL-6 transducer.

Antigens, CD↗

Auxiliary liver transplantation: regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure--a multicenter European study.

Auxiliary liver transplantation (LT) is a special procedure of LT which could be proposed to patients with fulminant hepatic failure (FHF) and has for aim that complete regeneration of the native liver (NL) left in place will allow the graft recipient to resume normal liver function after allograft withdrawal. We report 30 cases of auxiliary LT performed for FHF in 12 European centers. Twenty-five of 30 patients were younger than 50 years. The cause of FHF was hepatitis A virus (HAV) in 4 patients, hepatitis B virus (HBV) in 7, paracetamol overdose in 5, ecstasy in 2, hepatotoxic drugs in 4, autoimmune hepatitis in 2, liver lesions of preeclampsia in 1 and unknown in 5. A postoperative, both clinical and histological follow-up of more than 3 weeks was obtained in 22 patients, enabling us to look for indicators predictive of NL regeneration and outcome. Histological changes observed in the NL included complete regeneration in 68%, incomplete regeneration with obvious fibrous sequelae in 14% and severe liver fibrosis or cirrhosis in 18%, of the 22 patients studied. The percentage and distribution of necrosis observed in tissue samples of the NL at the time of transplantation was not related to the final outcome. Complete NL regeneration was observed in 15 patients, out of whom 14 were younger than 40 years. Patients with complete regeneration were mainly affected by FHF due to HAV, HBV, or paracetamol overdose. After a follow-up of 18/11 (mean/median) months (range, 3 to 67 months), 19 of the 30 patients (63%) survived and 13 of them (68%), i.e., 43% of the 30 patients, had resumed normal NL function, with interrupted immunosuppression, the ultimate goal of emergency auxiliary LT. We conclude that, in patients with FHF, auxiliary LT is a procedure feasible in a number of centers and is associated with a complete regeneration capability of the NL in a majority of survivors, especially in those younger than 40 years. Confirmation of these encouraging preliminary results by large-scale prospective studies is required.

Adolescent↗

[Angiosarcoma arising from an arterio-venous fistula in a renal transplant recipient. An unusual complication].

An angiosarcoma arising at the site of an arteriovenous fistula in a renal transplant recipient is reported. Only two similar cases have yet been described. This report is documented with an immunohistochemical study and etiopathogenesis is discussed. Immunosuppressive therapy and the arterio-venous fistula might both be involved in the occurrence of this neoplasm. We focus attention on this uncommon complication which should always be entertained when a renal transplant recipient complains about a painful arterio-venous fistula.

Arteriovenous Fistula↗

Carcinoid tumors of the lung: do atypical features require aggressive management?

Atypical carcinoids are an intermediate form of tumor between low-grade malignant typical carcinoid and high-grade malignant small cell carcinoma, which represent the two ends of the spectrum of neuroendocrine bronchopulmonary tumors. Between 1983 and 1993, 27 patients with atypical carcinoids underwent surgical treatment. The histologic diagnosis of an atypical carcinoid was established if the criteria proposed by Arrigoni and associates were fulfilled. Seven pneumonectomies, 16 lobectomies, 2 segmentectomies, and 2 wedge resections were performed. Thirteen patients (48.1%) had regional nodal metastases and 6 patients (22%) had N2 disease at the time of surgical therapy. Distant metastases developed in 5 patients (18.5%) after initial treatment. The 10-year survival in patients with an atypical carcinoid was 49%, versus the 84% 10-year survival rate observed in patients with a typical carcinoid. We conclude that the aggressive behavior of atypical carcinoids precludes the use of limited surgical resection and requires a more aggressive approach, with lobectomy and mediastinal lymph node dissection constituting a minimal procedure. The same criteria used for well-differentiated lung carcinoma should apply to this form of neuroendocrine lung tumor. Adjuvant chemotherapy is recommended for patients with stage III or distant metastases.

Adult↗

Typical and atypical bronchopulmonary carcinoid tumors: a clinicopathologic and KI-67-labeling study.

Expression of a proliferating antigen by KI-67 immunohistochemistry was analyzed with a SAMBA 2005 computer-assisted image processor (Traitement de l'Information for des Techniques Nouvelles, Grenoble, France) in 47 surgically resected bronchopulmonary carcinoids embedded in paraffin. The clinicopathologic characteristics and KI-67 labeling, expressed in percentage of stained nuclear surface relative to the total nuclear surface, of 31 typical carcinoids and 16 atypical carcinoids were compared and assessed with respect to patient survival. The proliferation status was significantly higher in histologically atypical than in typical carcinoids. Moreover, using a 4% cutoff, we observed a significant difference for the 4-year overall survival rate. Semiquantitative analysis of the proliferation index by KI-67 immunostaining seemed to be an effective means of identifying high risk subsets among patients with histologically atypical carcinoids and for whom adjuvant chemotherapy could be proposed.

Biomarkers, Tumor↗

Hepatic artery thrombosis after liver transplantation: diagnosis with spiral CT.

OBJECTIVE: The purpose of this study was to prospectively evaluate spiral CT with maximum-intensity projection in the diagnosis of hepatic artery thrombosis in patients with liver transplants. SUBJECTS AND METHODS: Thirty liver transplant recipients (19 men, 11 women; mean age, 49 years) underwent Doppler sonography and spiral CT with maximum-intensity projection to evaluate both hepatic parenchyma and hepatic vessels. In five cases, these examinations were followed by angiography for suspected hepatic artery thrombosis. RESULTS: Among the 30 patients, results of both Doppler sonography and spiral CT were abnormal in five patients. In all five patients, Doppler sonography revealed an absence of intrahepatic arterial signal (sensitivity, 100%). Spiral CT showed the hepatic artery to be patent from its origin to the anastomosis and then occluded distally in four patients and showed occlusion of the entire hepatic artery in one patient (sensitivity, 100%). Aortography and/or selective arteriography of the celiac axis confirmed the diagnosis of hepatic artery thrombosis in all five cases. The other 25 patients had a normal clinical outcome, 24 with normal findings on Doppler sonograms (specificity, 96%), and 23 with normal findings on spiral CT. Two patients had false-positive CT studies because of technical failures (specificity, 92%). CONCLUSION: Spiral CT with maximum-intensity projection is highly accurate in identifying hepatic artery thrombosis after liver transplantation.

Adult↗