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Adoptive immunotherapy with antitumor effector cells is an attractive therapeutic approach in metastatic renal cell carcinoma (RCC). The aim of the work was to enhance in vitro activation of lymphocytes with optimal cytotoxic activity against tumor cells. We evaluated a procedure based on the use of dendritic cells (DCs) loaded with irradiated tumor cells (DC-Tu) to stimulate lymphocytes. Experimental conditions were established with cells from healthy donors and melanoma cell lines. Procedures were then applied to cells from RCC patients. A total of 30 tumor biopsies, 14 proximal lymph nodes, and 17 peripheral blood samples from 30 patients were used. When lymphocytes were stimulated in vitro with DC-Tu, they responded to tumor cells with an increased cytolytic activity for all the assays with donor cells (n=18). For RCC patients, DC-Tu stimulation improved the final cytotoxic activity in only half of the assays (16/31). When significantly enhanced (>10%, n=8), responder cells resulted in a final 43% cytotoxicity against autologous RCC cells. Mechanism of lysis was at least in part class I mediated. Effector cells have no lytic activity against normal renal cells. Percentage of cells with regulatory T-cell phenotype was not found to be enhanced in the DC-Tu stimulated lymphocytes. Individual differences were observed in the characteristics of DCs generated from RCC patients in contrast to that observed in donors and could explain why lymphocyte stimulation was not improved by DC-Tu in half of the RCC assays. T-cell spreading was suitable for a therapeutic use (>10(9) cells) irrespective of the procedure (with or without DC-Tu stimulation) or the tissular origin of lymphocytes from patients. Data show that precursors of selective antitumor effector cells are present in patients with RCC and can be amplified in vitro either with or without DC-Tu stimulation. One of these populations could be chosen for an adoptive transfer immunotherapy.

Introduction: The frequency of amyloidosis is not well known in France. We compiled a register of amyloidosis diagnosed from 1995 to 1999 in the University Hospital of Rennes., Patients and Methods: This retrospective study was performed between 01 January 1995 and 31 december 1999. Diagnosis was assessed on positivity of red Congo by anatomopathology. Immunohistochemistry allowed the definition the type of amyloidosis. Clinical data, staging and outcome of patients were analysed., Results: Forty-three amyloidosis were diagnosed (27 women, 16 men) with an incidence of 8,6 new cases per year. Mean age was 63.7 years. Five diagnosis were realised in 1995, six in 1996, six in 1997, 12 in 1998, 14 in 1999. Twenty amyloidosis were AL type (46.5%), seven AA (16.3%), 1 beta2 microglobulin type, 15 (35%) remained of undetermined type. Thirty-three amyloidosis (77%) were systemic, 10 were localized to one organ (23%). When diagnosis was made, biopsies concerned affected organs in 86% of the cases, accessory sites (labial salivary glands, bone marrow) in only 14% of the cases. Twenty-five patients died (58%). Two deaths were treatment-related, 16 to amyloidois, seven patients died of another complaint., Conclusion: Increased incidence of amyloidosis needs to be confirmed. We emphasize the importance of immunohistochemical typing on frozen samples, the value of accessory biopsies and the need for complete extension staging.

Chronic angiotensin I-converting enzyme inhibition can be associated with aldosterone escape. We investigated the effects of enalapril, spironolactone, and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters to determine whether these drugs could exert additive effects. Cardiomyopathic hamsters, Bio TO-2 dilated strain, were orally treated with enalapril (20 mg. kg. day ) and/or spironolactone (20 mg. kg. day ) according to a 2 x 2 factorial design from 120 days of age. Animals were investigated at 180 (10 animals per group) and 240 (16 animals per group) days of age. Compared with corresponding untreated groups, enalapril significantly decreased mean blood pressure (-18%); enalapril and spironolactone significantly increased cardiac output (+28%, +11%) and femoral blood flow (+10%, +12%) and significantly decreased systemic (-38%, -17%) and femoral (-26%, -13%) vascular resistances. Enalapril and spironolactone significantly decreased left ventricle cavity area (-21%, -26%) and left (-34%, -47%) and right (-37%, -48%) ventricle collagen density. Spironolactone significantly increased left ventricle wall thickness (+4%). There were significant enalapril x spironolactone interactions for most variables (compared with control group, +52%, +36%, +45% for cardiac output; +26%, +28%, +26% for femoral blood flow; -50%, -30%, -45% for systemic vascular resistance; -33%, -20%, -35% for femoral vascular resistance; -27%, -31%, -40% for left ventricle cavity area; and -46%, -58%, -60% for left and -39%, -50%, -66% for right ventricle collagen density in enalapril, spironolactone, and enalapril + spironolactone groups, respectively). In cardiomyopathic hamsters, enalapril and spironolactone in combination did not improve hemodynamics more than enalapril alone but induced stronger effects than each drug alone on cardiac remodeling.

The use of beta-blockers reduces angiotensin II levels, but could not adequately suppress aldosterone production. Thus, the combination of a beta-blocker with an aldosterone receptor antagonist could exert additive effects. The effects of metoprolol and spironolactone and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters (CMH) were investigated. The Bio TO-2 dilated strain of CMH was treated orally with metoprolol (10 mg/kg/day), spironolactone (20 mg/kg/day), or both according to a 2 x 2 factorial design (24 animals per group) from 120 days of age and during 120 days. As compared to corresponding untreated groups, metoprolol significantly decreased mean blood pressure (-7%), and metoprolol and spironolactone significantly increased cardiac output (18% and 19%, respectively), mesenteric blood flow (11% and 14%), and femoral blood flow (13% and 17%), and significantly decreased systemic (-24% and -15%), mesenteric (-14% and -13%) and femoral (-19% and -10%) vascular resistances. Metoprolol significantly increased renal blood flow (22%) and significantly decreased renal vascular resistance (-23%). Metoprolol and spironolactone significantly decreased the cavity area of the left ventricle (-21% and -32%, respectively) and the collagen density of the left (-36% and -39%) and right (-38% and -43%) ventricles. Although the combination did not induce stronger effects than each drug alone on the systemic and most regional hemodynamic variables, it did have a stronger effect on the cardiac remodeling (compared to control group: -24%, -34%, and -46% for the left ventricle cavity area, -33%, -35%, and -62% for collagen density in the left ventricle, and -52%, -57%, and -59% for collagen density in the right ventricle, respectively, in the metoprolol, spironolactone, and metoprolol + spironolactone groups). In CMH, metoprolol and spironolactone combined did not improve hemodynamics more than each drug alone, but did exert additive effects on cardiac remodeling.

The effects of the selective angiotensin II type 1 receptor antagonist candesartan on cardiac, systemic, and regional hemodynamics and on cardiac, pulmonary, and hepatic histomorphometry were investigated in cardiomyopathic hamsters (CMHs), Bio TO-2 dilated strain, with advanced congestive heart failure (CHF). Two groups were treated orally with candesartan cilexetil at 22 or 50 mg/kg/d from 190 days of age and compared with a control group (38 animals/group). Investigations were performed at 225, 255, and 285 days of age. Left ventricle (LV) and systemic blood pressures and cardiac output and mesenteric and femoral blood flows were measured in anesthetized animals. LV cavity area, LV and right ventricle (RV) wall thickness and collagen density, and pulmonary and hepatic congestion were assessed. Compared with the control group, candesartan did not modify cardiac hemodynamics but significantly and dose-dependently decreased systemic vascular resistances (on average: -23 and -32% after 22 and 50 mg/kg, respectively) and increased stroke volume (+32 and +42%) and cardiac output (+27 and +34%). Candesartan did not modify mesenteric vascular resistances and blood flow but significantly and dose-dependently decreased femoral vascular resistances (-19 and -33%) and increased femoral blood flow (+33 and +43%). Candesartan significantly decreased LV cavity area (-14 and -8%) and LV (-15 and -31%) and RV (-16 and -24%) collagen density but did not modify LV and RV wall thickness. Candesartan decreased pulmonary congestion at 255 and 285 days of age but did not modify hepatic congestion. In CMHs with advanced CHF, candesartan cilexetil improves systemic and femoral hemodynamics, partly reverses cardiac remodeling, and decreases pulmonary congestion.

We investigated the effects of the beta1-beta2-alpha1-blocker, labetalol, in the congestive heart failure (CHF) model induced by aortic constriction in the guinea pig. One hundred days after aortic constriction, 52 animals were given either placebo, labetalol 2 mg/kg/d, or labetalol 20 mg/kg/d for 60 days. Eighteen sham-operated animals were used as controls. Investigations were performed at the end of the treatment period. Compared with sham-operated animals, banded animals receiving placebo showed signs of overt CHF with cardiac, systemic and regional (mesenteric and femoral) hemodynamic dysfunction, and pulmonary and hepatic congestion. An increase in whole heart, atria, and left and right ventricle weights associated with left ventricular cavity enlargement and left and right ventricular wall thickening indicated a remodeling process. Compared with placebo, labetalol did not significantly modify cardiac, systemic, or regional hemodynamic variables but significantly decreased pulmonary and hepatic congestion. Labetalol significantly reduced left ventricular cavity area (-10 and -20% after 2 and 20 mg/kg, respectively) and left ventricular (-4 and -16%) and right ventricular (-4 and -19%) wall thickness. In conclusion, labetalol induced partial regression of cardiac remodeling before hemodynamic improvement. This early anti-remodeling effect could play a role in the favorable effects observed with beta1-beta2-alpha1-blockers in humans.

We report the second case of squamous cell carcinoma arising in a hepatic foregut cyst (CHFC) in a 40-year-old woman. Microscopically, the lining of the cyst was composed of ciliated columnar epithelium, gastric and squamous epithelium. The squamous epithelium showed areas with dysplastic changes and other areas with carcinomatous transformation. In this congenital lesion, it was not surprising to find squamous and gastric mucosa because oesophagus, stomach, and tracheobronchic tree derive from the embryologic foregut. Squamous carcinoma might develop in a context of inflammation as in biliary cyst. In agreement with the first case described in the literature, this report also suggests that a large-sized symptomatic hepatic cyst should be excised.

The natural history of the disease of the dilated strain Bio TO-2 of cardiomyopathic hamsters (CMH) is not totally characterized. We investigated its hemodynamic and histomorphometric characteristics at 140, 180, 220, 260, and 300 days of age. Forty CMH and 40 controls were investigated (8 at each stage). Mean arterial pressure (MAP, carotid artery catheter) and cardiac output and femoral blood flow (CO, FBF, transit time method) were measured in anesthetized animals. Systemic (SVR) and femoral (FVR) vascular resistances were calculated. Atria, left and right ventricles (LV, RV), lungs, and liver were weighed. LV cavity area, LV and RV wall thicknesses and collagen densities were determined (computer-assisted image analyzer). Pulmonary and hepatic congestion were assessed (arbitrary scales). Compared with controls, MAP, CO and FBF were significantly lower in CMH throughout the study (on average: -22%, -34%, -33%, respectively), FVR was significantly increased (+15%), but SVR was not significantly modified. Concerning histomorphometric characteristics, differences between groups significantly increased with age for most variables: at 300 days, atria (+292%), RV (+13%), lungs (+44%), and liver (+23%) weights, LV cavity area (+130%), LV (+364%) and RV (+181%) collagen densities were significantly increased in CMH vs controls, whereas LV (-40%) and RV (-23%) wall thicknesses were significantly decreased. At 260 and 300 days, CMH showed significant pulmonary congestion without hepatic alteration. Bio TO-2 CMH progressively develop an alteration of cardiac function leading to decreased MAP and musculo-cutaneous blood flow associated with cardiac remodeling including atria hypertrophy and LV dilation, wall thinning and a rise in collagen density.

We assessed the evolution with time of the responsiveness of three vascular beds in dilated cardiomyopathic hamsters of the Bio TO-2 strain. Eight cardiomyopathic hamsters and 8 control hamsters were investigated at 180 and 300 days of age. Thoracic aorta and mesenteric and renal artery rings were studied in isolated organ baths. Cumulative concentration-response relations to phenylephrine, acetylcholine, sodium nitroprusside, and angiotensin II were established for each ring. Maximum effect (Emax) and concentration inducing 50% of Emax (EC50) were determined from each concentration-response curve and pD2 was calculated as -log(EC50). Compared with control hamsters, in cardiomyopathic hamsters, Emax of phenylephrine was not modified in aorta, whereas it was significantly lower in mesenteric (-6% and -33% at 180 and 300 days, respectively) and renal (-17% and -24%) arteries. Emax of acetylcholine was significantly higher in aorta (+57% and +30%), mesenteric (+42% and +34%), and renal (+168% and +70%) arteries. Emax of sodium nitroprusside was significantly higher in aorta (+26% and +16%) and tended to be higher in mesenteric (+25% and +23%) and renal (+27% and +10%) arteries. Emax of angiotensin II was not modified in aorta and tended to be lower in mesenteric artery at 300 days. The pD2 of phenylephrine was significantly increased in aorta and the pD2 of sodium nitroprusside was significantly increased in aorta and renal artery. In conclusion, in dilated cardiomyopathic hamsters, endothelium-dependent and -independent vasodilations are enhanced early, demonstrating increased sensitivity of vascular smooth muscle to nitric oxide. This abnormality may be involved in the decreased responsiveness to phenylephrine and angiotensin II.

Specified galectins are known to play a role in regulating cell proliferation, differentiation, adhesion and migration. Po66, a mouse IgG1 monoclonal antibody produced by immunization against squamous cell cancer, reacts against a carbohydrate-binding protein (Po66-CBP), recently shown to be a member of the galectin family with a strong homology with galectin-8 (PCTA-1), identified as a human tumor-associated antigen. We studied Po66 in squamous metaplasia of the bronchi in order to determine whether it could be specifically involved in neoplastic conditions and if so, if it would be helpful in distinguishing metaplasia at risk of cancer. Twenty-eight formalin-fixed, paraffin-embedded archival tissues of 17 metaplasias with SCC, 3 metaplasia with distant neoplastic disease and 8 metaplasias with an inflammatory process, were immunostained using a streptavidin biotin peroxydase method. The squamous metaplasias were positively stained in non-neoplastic disease as well as in neoplastic processes. Expression was also observed in stromal and normal cells. Po66-CBP was not associated with a pre-neoplastic character. We discussed the expression of this intra-cellular component of galectin-8 according to the functions of galectins in cellular differentiation, host reaction against tumor, and inflammation.

Primary small cell carcinoma of the urinary bladder is an uncommon tumor, compared to the frequency of urothelial tumors. Fifty percent of cases are combined with a non endocrine carcinomatous component. We report six new cases of this tumor, three of pure, and three associated with an urothelial carcinoma. Diagnosis is easy established by the immunohistochemical study which show the neuro-endocrine differentiation of these aggressive tumors. Pathologist needs to look for a neuro-endocrine part in all bladder cancer, as its presence modify the treatment. Chemotherapy is used in these cancers, due to their high metastatic power. Places of radical surgery and radiotherapy need to be specified.

Objectives: Nuclear grade and tumor stage are important prognostic factors in renal cell carcinoma, but tumors of similar stage and grade can exhibit a wide variation in biologic behavior and clinical outcome. In this retrospective study, we evaluated the immunologic markers, Ki-67 (MIB1) and p53, in 73 cases of conventional (clear cell) renal cell carcinoma and compared these markers with the accepted prognostic features of grade, stage, and tumor size in predicting outcome., Methods: Specimens of 73 renal cell carcinomas of different nuclear grade (20 Furhman I/II, 32 Fuhrman III, and 21 Fuhrman IV) and different stage (10 pT1, 23 pT2, 36 pT3, and 4 pT4) were immunostained with monoclonal antibodies against Ki-67 and p53., Results: Univariate statistical analysis showed that tumor size (P <0. 001), nuclear grade (P <0.01), tumor stage (P <0.01), Ki-67 index (P <0.001), and p53 immunostaining (P <0.03) correlated significantly with a poor prognosis. A Ki-67 index of 20% was a powerful predictor of survival in all patients (P <0.00001), with strong predictive values. On multivariate analysis, the Ki-67 index and metastases were significant independent prognostic factors (P <0.02 and <0.01, respectively)., Conclusions: Ki-67 immunostaining appeared to be an additional prognostic indicator of biologic aggressiveness in renal cell carcinoma. Immunohistochemical assessment of tumor antigens could be used to identify patients at high risk of tumor progression in addition to conventional prognostic factors.

We report a case of light chain deposition disease associated with multiple myeloma revealed by congestive heart failure. Endomyocardial biopsy showed Congo red negative deposits and lambda light chain deposits by the immunofluorescence method. After chemotherapy with melphalan and prednisone, complete remission of multiple myeloma and major improvement in cardiac condition were observed.

We report a case of nested cell carcinoma, an uncommon transitional tumor. These tumors are composed of regular cuboidal transitional cells forming small nests with minimal cytologic atypia. Despite the benign course, this tumor resembling proliferation of Brunn's nests or inverted papilloma, must be considered as an aggressive transitional tumor. Thus, morphologic criteria are needed to make the diagnosis. Because of its aggressive behaviour, the surgical therapy depends on the tumor's infiltration.

In the 80s it was established that atherosclerotic renal artery stenosis (ARAS) is a leading cause of renal insufficiency and that this condition ranks among the rare etiologies of chronic renal failure amenable to improvement or stabilization particularly in the white. Nephroangiosclerosis (NAS) is an increasing cause of ESRD in the western countries, especially in blacks. Epidemiological data on the vascular nephropathies leading to ESRD are still rare. In this study, we compare annual incidence of ESRD due to ARAS and NAS during two five-year periods: period A = 1982-1986, period B = 1992-1996. The region of the survey comprised 410,664 inhabitants (99.6% of Caucasians), of whom 100,230 were aged over 60 years. Diagnosis of ARAS required arteriography and that of NAS a renal biopsy. Undetermined vascular nephropathy was diagnosed when ESRD patients had had previously no arteriography or no histological examination. Major results were as follow (A vs B, incidence = n/million inhabitants): 1) Increasing incidence of ESRD due to all causes: 76 vs 95 per million, mean age at ESRD 56 vs 62 yrs, percentage of patients over 65 yrs 28 to 59% (p < 0.001). 2) Increasing incidence of ESRD due to vascular nephropathies: 5.5 vs 27.5 per million (p < 0.0001) in general population and 22 vs 110 per million (p < 0.0001) in population aged over 60 years, mean age at ESRD 68 vs 73 yrs. 3) Increasing incidence of different types of ischemic renal diseases leading to ESRD: ARAS 2.5 vs 15 per million (p < 0.0001) in general population and 10 vs 60 per million (p < 0.001) in those aged over 60 yrs, mean age 69 vs 74 yrs, NAS: 1 vs 8 and 4 vs 32 per million (p < 0.001), mean age 67 vs 72 yrs, undetermined VN 0.5 vs 2.5 and 2 vs 10 per million, 65 vs 73 yrs. Our study demonstrates that ischemic renal diseases 1) have become the most frequent causes of ESRD (27% of all patients and 43% of those aged over 6C years) in the Caucasian elderly. 2) are the only cause of increasing incidence of ESRD in this French region.

Background/aims: Laminins, the major non-collagenous basement membrane components, are involved in various biological processes. Laminin isoforms have never been characterized in human livers. The expression of five laminin mRNA was investigated in livers with or without cancer and in hepatoma cells and, by comparison, in both rat hepatoma and hepatic stellate cells., Methods: Laminin alpha1, alpha2, beta1, beta2 and gamma1 mRNA was detected by northern blot and/or RT-PCR in livers without chronic disease (n=5), in both tumoral and non-tumoral areas of livers with hepatocellular carcinomas (n=13) or metastases (n=18), in human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic stellate cell cultures., Results: Laminin alpha1, alpha2 and beta1 mRNA were found in 25-33% and gamma1 mRNA in 58% of the livers, the signal for laminin beta2 mRNA being faint in all the samples. Laminin alpha2, beta1, beta2 and gamma1 mRNA were expressed in hepatoma and stellate cells. The laminin alpha2 cDNA probe recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells revealed 90% identity with the alpha2 chain sequence. Antibodies against peptide deduced from the conserved C-terminal domain of both alpha1 and alpha2 chains recognized polypeptides corresponding to the degradation products of alpha2 chain in liver extracts and both media and cell layers from hepatoma and stellate cells. In addition, a Mr=130000 polypeptide was revealed by these antibodies in liver extracts and cell layers, which was consistent with the expected size deduced from the 3.5 kb mRNA., Conclusions: This first report on laminin isoforms in human livers indicates that laminin 1 (alpha1-beta1-gamma1), 2 (alpha2-beta1-gamma1), 3 (alpha1-beta2-gamma1) and 4 (alpha2-beta2-gamma1) mRNA and a polypeptide homologous to the alpha2 isoform, which could correspond to a truncated form of this chain, are usually expressed in non-tumoral and/or tumoral livers.

We report a case of intravascular malignant lymphomatosis observed in a 71 year-old male and characterised by the presence of a proteinuria in relation to the specific intraglomerular localisation. This malignant lymphoma, usually of the B phenotype, is rare and affects predominantly the central nervous system and the skin. Neoplastic cells home selectively to endothelium. Histological renal infiltration is frequent but a glomerular localisation, with proteinuria, is rare. The mechanism whereby lymphocytes home to endothelium cells is unclear but it could be related to the expression of lymphocyte-endothelium adhesion molecules. When present the nephrotic syndrome is associated with minimal change disease.

Non hemochromatotic liver siderosis often present an heterogeneous iron distribution, but histological scoring of iron overload are validated only in case of genetic hemochromatosis, where iron is homogeneously distributed. The aim of this work was to study the improvement of histological scoring by introducing a coefficient of heterogeneity in cases of heterogeneous liver siderosis. Thus, on 254 liver biopsies with siderosis were determined: i) the histologic total iron score (TIS) as previously described; ii) the coefficient of heterogeneity, leading to corrected TIS (corTIS); iii) the liver iron content (LIC). Liver siderosis was homogeneously distributed in 160 biopsies and heterogeneously distributed in 94. Correlation between histological scoring and LIC, in the group with heterogeneous liver siderosis, was improved by the use of the coefficient of heterogeneity. This coefficient leads to accurately quantify all liver siderosis.

Background: Some adjuvant or neoadjuvant therapy could be important for patients operated on for tumours of the ampulla of Vater, especially for those having a higher risk of recurrence., Aim: To evaluate prognostic factors after curative surgery based on a series of 45 cases of malignant tumours of the Oddi sphincter., Patients: From 1970 to 1992, a curative resection was performed in 45 patients (age 62.8 (SD 10.1) years) with adenocarcinoma of the ampulla. Surgical procedures included pancreatoduodenectomy (n = 42) and resection of the ampulla (n = 3). Actuarial survival was 44 (SD 9)% at five years., Methods: Various prognostic variables were studied: clinical manifestations, macroscopic aspect, differentiation, noninvasive adenomatous component, mucin histochemistry, immunohistochemistry (CEA, CA19.9, p53, Ki67), and accepted classifications (Blumgart and Kennedy, Martin, Yamaguchi and Enjoji, Talbot et al, pTNM)., Results: Variables with prognostic power, in order of importance were: Classification of Talbot et al; CA19.9; pTNM; sialomucins; classification of Yamaguchi and Ejoji; Martin classification; sulphomucins; non-invasive adenomatous component (positive > negative); jaundice; tumour localisation., Conclusions: This series confirmed the prognostic power of former classifications and showed the prognostic power of other variables (mucin, non-invasive adenomatous component, CA19.9).

We present a case of a primary pericardic thymoma, revealed by a pericardic effusion. This ectopic localisation is very unusual; neoplastic pericarditis are usually due to metastasis of carcinomas or lymphomas. Sometimes, they are secondary to pericardic invasion by mediastinal malignant thymomas or a metastasis of thymomas. Our patient presented a single pericardic localisation of thymoma without any other site. We discuss ectopic localisations of thymic tissue and thymomas and the diagnostic usefulness of the MIC 2 antibody.

From March 1972 to 1st of January 1996, 804 kidney, liver and pancreas transplants were performed in 690 patients. 39 post transplant cancers occurred in 27 patients. 21 skin tumors (15 squamous cell carcinoma, 4 basocellular carcinomas, 1 squamous carcinoma, 1 melanoma), 4 squamous cancers (anus, esophagus, tongue, and parotid), 4 post-transplant lymphoproliferative disorders, 1 non-Hodgkin's lymphoma T, 4 gynecological tumors (breast, ovarian peritoneal carcinomatosis, 2 uterine cervix cancers), 4 miscellaneous tumors (larynx, right colon, brain, prostate, own kidney). 14 patients died (14/27: 52%). Post transplant de novo cancers are a major risk in transplant patients These cancers are mainly represented by skin tumors and lymphomas. Skin cancers are mainly spinocellular and occur in the areas which are exposed to the sun. Post transplant lymphoproliferative disorders are very close to Burkitt's lymphoma, they produced B lymphocyte proliferation due to the reduction of the control of T lymphocytes and induced by Epstein-Barr virus. They can disappear with the diminution of immunosuppression.

Three cases of necrotizing sarcoid granulomatosis (NSG) are reported. All 3 patients had pulmonary lesions; one of them had additional extrapulmonary lesions which were ophthalmologic (dacryoadenitis) and digestive (ulcerative colitis). This patient was followed for 5 years and developed several respiratory, ophthalmologic and digestive recurrences. In 2 cases the diagnosis of NSG had been initially overlooked and the authors emphasize the difficulties of this histologic diagnosis in terms of the differential diagnosis with other necrotic and granulomatous pulmonary diseases such as tuberculosis and Wegener's granulomatosis. They stress the possibility of extrapulmonary lesions in NSG and discuss the relationship between NSG and sarcoidosis.

Hyperplastic polyps are the most common type of colorectal polyps. They are usually multiple and localized in the rectosigmoid area. They are easily recognized by their small size (< 10 mm), sessile form, smooth-surface and translucid appearance. Typically, these polyps have no malignant potential. We report the case of a 68-year-old man who had multiple rectosigmoid polyps, some of them having macroscopic features of adenomatous polyps. Because of the occurrence of bleeding after endoscopic polypectomy of two polyps corresponding to adenomas at examination, because of the multiplicity of these polyps and their localization in diverticulosis, a left colectomy followed by coloanal anastomosis was performed. Histologic examination of the surgical specimen revealed the hyperplastic nature of all polyps with, in two of them, a focus of adenomatous tissue.

A case of hepatic mesenchymal hamartoma, found after sudden onset clinical and biological cholestasis, is reported in a 18-year-old man. Abdominal ultrasound examination and computed tomography showed a intrahepatic cystic tumor. The diagnosis of hepatic mesenchymal hamartoma was made by the pathological examination of the resected specimen. This rare tumor is found in most cases in children less than 2 years old. Thirteen cases in adulthood were already reported, five of them in Japanese patients. Our case is peculiar because no hepatic tumor was shown by ultrasound examination, 2 years before, the large size of cysts and presence of smooth muscle fibers in the wall.

This retrospective study reports the clinical results obtained in a series of 150 heart transplantations performed from October 1986 to January 1995. Overall actuarial survival rate, including operative mortality, was 71% and 57% at 1 and 5 years respectively. Despite a certain level of morbidity, the spectacular functional results in this series are emphasized.

Iron was systematically studied in the nontumorous liver of 24 patients with hepatocellular carcinoma (HCC) developed on a noncirrhotic liver compared with 4 control groups (cirrhosis with and without HCC, liver metastasis, and normal liver) matched according to age, sex, and presence of chronic alcoholism. Assessment of liver iron was made by (1) histology according to iron distribution and quantification (total iron score: 0 to 60), and (2) biochemistry (liver iron concentration-N < 36 mumol/g) with calculation of the hepatic iron index (liver iron concentration/age). Patients with hepatocellular carcinoma developed on a noncirrhotic liver presented with (1) histological iron in 83%; (2) parenchymal iron excess significantly more frequent (90%) than in controls; (3) total iron score (15 +/- 12) and liver iron concentration (81 +/- 96) significantly greater than in controls; and (4) hepatic iron index significantly increased (1.4 +/- 1.5) when compared with control groups, except for the hepatocellular carcinoma complicating cirrhosis group (0.9 +/- 1.1). This study (1) shows a mild but unquestionable parenchymal iron excess in the nontumorous liver of most patients presenting with hepatocellular carcinoma developed on a noncirrhotic liver and, at a lesser extent, on cirrhosis, (2) should incite others to study the putative role of iron in the development of liver cancer both in patients with cirrhosis and those without it, whatever the cause of the underlying liver disease, and (3) add argument to take into account and to treat any liver iron excess, even when mild.

Aims: To assess the value of histology in diagnosing inflammatory bowel disease (IBD) in colorectal biopsy specimens., Methods: Retrospective, double blind evaluation of colorectal biopsy specimens from 41 patients with colitis (28 with ischaemic colitis and 13 with acute self-limited colitis) and 84 patients with IBD (42 with Crohn's disease and 42 with ulcerative colitis)., Results: The features distinguishing IBD from other forms of colitis included distorted architecture, lymphocyte and plasma cell infiltrate, excess of polymorphonuclear leucocytes, polymorphonuclear cryptitis, crypt abscesses, and basal lymphoid aggregates. The features discriminating between Crohn's disease and ulcerative colitis included an irregular or villous surface, distorted architecture, decrease in mucus content, and polymorphonuclear cryptitis. Using multivariate analysis, 90% of patients with Crohn's disease and 71% of those with ulcerative colitis were correctly classified, the former being strongly defined by epithelioid granulomas, microgranulomas and isolated giant cells, and the latter best defined by an irregular or villous surface, decrease in mucus content and crypt atrophy., Conclusions: Examination of colorectal biopsy specimens is a reliable method for diagnosing IBD. In the absence of epithelioid granulomas, microgranulomas and isolated giant cells a diagnosis of Crohn's disease is based on the absence of histological criteria favouring ulcerative colitis. The histological spectrum of indeterminate colitis remains to be clarified.

Hemangiopericytoma is an uncommon vascular tumor with variable malignant potential. The origin, structure and function of pericytes remains controversial. Intra-abdominal hemangiopericytomas are highly aggressive soft tissue tumors with a great propensity for malignant transformation. We report on a case of hemangiopericytoma of the pancreas in a 53-year-old female presenting with abdominal pain. Ultrasonography and CT scan revealed a cystic tumor of the head of the pancreas. The patient underwent successful pancreaticoduodenal resection and is alive with no signs of recurrence 25 months following surgery. Ultrastructural studies are necessary to differentiate hemangiopericytomas from other sarcomas. Malignancy may be ascertained only in the presence of metastases or local recurrence. Routine surveillance is advocated.

The authors report a case of laryngeal ulceration due to cytomegalovirus occurring in a 60-year-old man one month after heart transplant. The recipient was initially CMV seronegative and the donor positive. No preventive treatment was administered. One month after the transplantation, search for CMV in blood and urine became positive and a seroconversion occurred. Laryngeal biopsy showed an inflammatory reaction with cells containing atypical inclusions and positivities with anti-CMV antibody. Usual intranuclear eosinophilic inclusions of classic CMV infection were absent. The authors stress the unusual site of the lesions in this primo-infection and the atypical aspect of the inclusions. Such atypical inclusions which have already been reported in immunosuppressed people make the diagnosis more difficult.

The authors report two cases of adenocarcinoma arising from Brünner's glands. The diagnosis was made on histological, histochemical and lectin-histochemical grounds. Brünner's glands carcinoma cells were alike and located very close to normal Brünner's glands. Brünner's glands carcinoma cells contained neutral glycoproteins and were positive for Concanavalin A.

Between January 1st, 1976 and December 31st, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years. The prevalence of PGD during a 70-year exposure to risk (10-80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3,8 in 1000 females). The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females). The annual incidence of the disease was evaluated separately for 3 consecutive 5-year periods: period A (1976-80), period B (1981-85), and period C (1986-90). Within each of these 3 periods the number of patients with PGD was 179, 170 and 131 respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000. The incidence of IgA nephropathy remained the same throughout the 3 periods: 2.6, 3.1 and 2.5 in 100,000. The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15/100,000). Acute streptococcal glomerulonephritis virtually disappeared during periods B and C. Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.3 and 0.6 in 100,000). There was no significant difference between the 3 periods regarding the incidence of other PGD. Incidence of IgA nephropathy was 3 to 4-fold higher in the adult aged from 20 to 60 years than in the elderly. In contrast, membranous nephropathy was 3 fold more frequent in the elderly than in the adult. Therefore only some histopathological forms have a different incidence according to age, but the major information furnished by this study is that the risk of occurrence of a PGD is similar in the population living in the area, whatever the age group (10-19 years: 6.4/10(5) inhabitants, 20-39: 7.1/10(5), 40-59: 8.4/10(5), 60-79: 8.4/10(5)). Finally, we confirm that the most common PGD going to end stage renal disease was IgA nephropathy, particularly under 60 years of age (0.8/10(5)). In contrast, membranous nephropathy was a less frequent cause of ESRD (0.2/10(5)).

Between January 1, 1976 and December 31, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France, comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years. The prevalence of PGD during a 70 year exposure to risk (10 to 80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3.8 in 1000 females). The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females). The annual incidence of the disease was evaluated separately for three consecutive five-year periods: period A (1976-80), period B (1981-85), and period C (1986-90). Within each of these three periods the number of patients with PGD was 179, 170 and 131, respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000. The incidence of IgA nephropathy remained the same throughout the three periods: 2.6, 3.1 and 2.5 in 100,000. The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15 in 100,000), while that of membranous nephropathy increased slightly (1.2, 1.6 and 1.7 in 100,000). Acute streptococcal glomerulonephritis virtually disappeared during periods B and C. Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.4 and 0.6 in 100,000). There was no significant difference between the three periods regarding the incidence of other PGD.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary intestinal lymphangiectasia is a rare congenital condition associated with protein-losing enteropathy. Hypogammaglobulinemia and lymphopenia secondary to this condition are frequent but infectious complications are not. So far few immunological studies have been made in these patients. We report here the results of such a study carried out in two adolescents. Both patients presented with a dramatic decrease in serum gammaglobulins, especially IgG and IgA, and in peripheral blood lymphocytes, especially CD4 T helper cells. From a functional standpoint, the proliferative response to certain mitogens was reduced. A decrease in in vitro production of immunoglobulins by B lymphocytes may be due to a faulty T/B cell cooperation. Histological examination of duodenal biopsy specimens revealed a decreased number of intraepithelial lymphocytes. Colonoscopy revealed nodular lymphoid hyperplasia in the terminal ileum, confirmed by endoscopic biopsy. The role of these abnormalities in the development of infectious complications and lymphoma is underscored.

Intraductal mucin-producing tumors of the pancreas are rare, recently described tumors; they have a better prognosis than usual ductal carcinomas of the pancreas. We report two cases of villous tumor of the main pancreatic duct and one case of mucinous ductal ectasia, with histochemical and immunohistochemical study.

The authors report a case of congenital epulis in the lower gum of a new born female. This rare benign tumor of the newborn is histologically characterized by the granular aspect of its cells. It occurs more frequently in females than in males. Differential diagnosis mainly concerns Abrikossoff tumor whose histogenesis and evolution are different. The distinctive features of epulis are the presence of a fusiform cell component and the negativity of the granular cells for PS100.