Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma.

Renal cell carcinoma (RCC) is known to have a wide variation in clinical outcome despite the use of conventional prognostic factors, such as staging or grading. A better knowledge of the biologic aggressiveness of RCC could facilitate the selection of patients at high risk of tumor progression. The aim of this study was to determine if use of measurements of vascular density, cell proliferation, and cell adhesion could better predict the biologic behavior of RCC. We immunohistochemically analyzed CD34, Ki-67, and CD44H expression on formalin-fixed, paraffin-embedded tissues from 73 RCCs for quantifying microvessel density (MVD), Ki-67 labeling index (LI), and CD44H LI, respectively. Univariate cancer-specific survival analysis showed that tumor stage (P < .01), tumor size (P < .001), nuclear grade (P < .01), metastasis (P < .001), MVD (P < .03), Ki-67 LI (P < .001), and CD44H LI (P < .0001) were predictors of tumor-related death. There was a statistical correlation between CD44H LI and both Ki-67 LI (r' = .3) and MVD (r' = -44). Ki-67 LI (P < .04) and CD44H LI (P < .02), as well as metastasis (P < .008), emerged as independent predictors of cancer-specific survival in multivariate analysis in patients with metastases (P < .04 and P < .02, respectively) and in patients without metastases (P < .006 and P < .00001, respectively). Our study suggests that vascular density, cell proliferation, and cell adhesion represent a complex tumor-host interaction that may favor progression of RCC. Cell proliferation and CD44H expression appear to be powerful markers to identify patients with an adverse prognosis.

Proton magnetic resonance spectroscopy of blood plasma in heart transplant recipients treated with cyclosporine: an early prognosis test of long-term graft tolerance.

BACKGROUND: Previous results have established the potential interest of proton magnetic resonance spectroscopy (MRS) of plasma lipoproteins in the detection of rejection processes after heart transplantation. The aim of this study was to determine whether MRS can provide a relevant long-term prognosis factor as early as 1 week after transplantation. METHODS: Eighteen patients were monitored for a mean period of 16 months after transplantation. The ratio of the sum of the MRS total line widths (TLW) for lipoprotein moieties, obtained 1 week after transplantation and cyclosporine administration, over the same sum obtained on the day of transplantation (TLW(8/0)), as well as the ratio between the corresponding intensities of methyl and methylene moieties (IR) were used to quantify the lipoprotein spectral profile. RESULTS: TLW(8/0), with a cutoff value of 0.8, seemed to have the most value in predicting rejection processes (RP) several months later. All six patients with no RP (good prognosis) and all five patients with three or more RPs (poor prognosis) during the entire 16-month follow-up period were correctly detected as early as 8 days after transplantation. The seven patients with only one or two RPs, mainly occurring during the first months after transplantation, were usually classified by MRS as having good prognosis. CONCLUSIONS: The magnetic resonance spectrum depends on both qualitative and quantitative variations in the different lipoprotein fractions, known to be carriers of cyclosporine. The magnetic resonance spectrum could thus be an early expression of the ability of these lipoproteins to modulate the cyclosporine-mediated immunosuppression.

Meningioma in long-term survivors after allogeneic bone marrow transplantation.

Late complications occurring after allogeneic bone marrow transplant (BMT) are increasingly reported, since more patients survive. Among these late complications, solid tumors are of particular clinical concern. Only malignant brain tumors have been reported (astrocytoma, glioblastoma). We describe two cases of meningiomas developing 13 and 15 years after the graft. Occurrence of such benign tumors has been described after treatment of ALL, but not following allogeneic BMT. It is important to consider the diagnosis of meningioma in long-term survivors presenting with neurological symptoms.

Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis.

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.

Acute renal failure following collective intoxication by Cortinarius orellanus.

Twenty-six young men with no previous medical history all ingested mushroom soup, exclusively made with Cortinarius orellanus. They were hospitalized 10-12 days after the incident. On admission, 12 patients presented with acute tubulointerstitial nephritis with acute renal failure; 8 required haemodialysis. In addition to symptomatic treatment, 9 patients were given corticosteroids. In this group of 12 patients, 8 recovered rapidly, and the other 4 suffered from chronic renal failure for several months. In the other group of 14 patients, initial leukocyturia was observed in 12 cases, although renal function remained normal during a one-year follow-up. Hepatic acetylation and hydroxylation tests performed after 6 months in 22 patients did not provide any explanation for the strong individual sensitivity to the renal toxicity of this fungus.

Analysis of Ki-67, p53 and Bcl-2 expression in the dysplasia-carcinoma sequence of Barrett's esophagus.

The grading of dysplasia in Barrett's esophagus has prognostic importance, however observer variation limits the reliability of simple histological analysis alone. We investigated Ki-67, p53 and Bcl-2 expression in Barrett's esophagus, in the sequence from Barrett's low-grade dysplasia to high-grade dysplasia and infiltrating adenocarcinoma. Forty-four esophagectomy specimens were utilized: 39 specimens with esophageal dysplasia and adenocarcinoma and 5 specimens with esophageal dysplasia only. This gave 83 sections (2 sections for specimens with dyplasia and carcinoma) examined from 44 patients. The sections were examined for Ki-67, p53 and Bcl-2 reactivity by immunohistochemistry. Low-grade dysplasia was present in 14 sections, high-grade dysplasia in 30 sections and carcinoma in 39 sections. Ki-67 expression occurred in 2 out of 14 (14%) sections with low-grade dysplasia, in 22 out of 30 (73%) sections with high-grade dysplasia and in 34 out of 39 (87%) sections with carcinoma (p<0.001). p53 protein expression was found in 1 of 14 (7%) sections with low-grade dysplasia, in 18 of 30 (60%) sections with high-grade dysplasia and in 33 of 39 (85%) sections with carcinoma (p<0.001). Expression of Bcl-2 was found in 11 of 14 (84%) sections with low-grade dysplasia but immunoreactivity was not seen in any section with high-grade dysplasia or Barrett's carcinoma. Our results indicate that overexpression of Ki-67, Bcl-2 protein and p53 mutations can be identified as early events during neoplastic progression in Barrett's esophagus. These data support the hypothesis that, in the progression of Barrett's metaplasia to adenocarcinoma, the balance of proliferation/apoptosis plays an important role.

Expression of Po66-CBP, a galectin-8, in different types of primary and secondary broncho-pulmonary tumors.

The monoclonal antibody Po66 is an IgG1 immunoglobulin isolated from a human bronchial squamous carcinoma and directed against a carbohydrate binding protein, Po66-CBP, belonging to the galectin family involved in neoplastic processes. This Po66 antibody has been shown to be useful for immunoscintigraphic detection of squamous cell carcinoma metastasis. We examined the expression of Po66-CBP in a wider range of primary or secondary malignant tumors of the lung of various histological types. We studied 52 specimens of broncho-pulmonary tumors including 41 primary squamous, glandular or neuro-endocrine tumors and 11 secondary tumors of glandular, connective tissue, melanocytic or germinal origin as well as 9 extra-pulmonary primary tumors with histological types similar to lung metastases. An immunohistochemical study was performed using an amplification system on paraffin-embedded sections. All histological types were positive for Po66 antibody, the cell origin giving no influence on the expression of Po66-CBP. There was however a relation between Po66-CBP expression and the degree of differentiation notably for squamous cell cancer and neuro-endocrine tumors. The metastatic character of the tumor tissue did not affect Po66-CBP expression.

Red blood cell polyamine level changes following heart transplantation in man.

Follow-up of orthotopic heart transplanted patients has revealed the existence of abnormally high red blood cell (RBC) spermidine (Spd) levels during the first two months after surgical procedure (A-period). From the third month after heart transplantation (B-period), RBC Spd concentrations went back to normal values in early cardiac rejection (ECR) patients. During A- and B-periods, significantly higher Spd levels and Spd/Spm ratios were observed in late cardiac rejecting (LCR) patients than in ECR ones. The lack of a direct relationship between the histological grade of rejection and RBC Spd levels leads us to consider these polyamine blood levels as a new biological instrument in the diagnosis of heart rejection.

Detection of early gamma-postirradiation effects in murine spleen by proton NMR relaxation times.

BACKGROUND: It was our aim to evaluate the potential of proton relaxation times for the early detection of radiation-induced spleen changes. MATERIALS AND METHODS: Female Swiss mice were irradiated with doses ranging from 0.05 Gy to 4 Gy. The body weight, the spleen weight and the spleen water content of single animals were determined. Measurements of longitudinal (T1) and transversal (T2) proton relaxation times of the spleen samples were performed in a 0.47 T spectrometer. Histological examinations of the control and irradiated organs were performed. RESULTS: NMR measurements during the first five days after irradiation showed that total body gamma-irradiation with doses from 1.5 Gy to 4 Gy results in decreasing T1 of the murine spleen. Significant shortening in T2 was observed for the spleen of animals irradiated with a dose of 4 Gy. Histological examinations demonstrated subnormal architecture in slices derived from animals irradiated with 2 Gy and 4 Gy. CONCLUSION: The fluctuations of the spleen T1 and T2 of irradiated mice are correlated with relative spleen weight and can be used to estimate radiation induced changes in this organ.

Uptake and release of radiolabelled monoclonal antibody Po66 by multicellular aggregates obtained from a lung squamous carcinoma cell line.

Po66, a monoclonal antibody (MAb) directed against lung squamous cell carcinoma, has been shown, when injected intravenously, to be retained for a long time in tumors. This property encouraged trials to use Po66 as an agent of metabolic radiotherapy. The suitability of multicellular spheroids to reproduce the in vivo conditions of irradiation of tumors by Po66 was investigated in the present work. Spheroids were formed from the lung carcinoma cell line SK-MES-1. They resembled morphologically small carcinoma nodules with desmosome-like intercellular junctions at the periphery and a central necrotic core. The cells expressing the antigen recognized by Po66 had a heterogeneous distribution and were predominant in the outer layers of the cell aggregates. Spheroids were exposed to radiolabelled Po66. The MAb diffused slowly and reached a maximal incorporation after 4-12 hours incubation. A control unrelated antibody did not penetrate appreciably. Autohistoradiographic experiments suggested that the antibody accumulated in most cells expressing the antigen. The rate of MAb release from the spheroids was very low (T 1/2 = 163 h). Taken together, the data indicate that spheroids might be a relevant model to investigate the parameters controlling Po66-mediated immunoradiotherapy.

Serum and tissue distribution of a fragment of cytokeratin 19 (cyfra 21-1) in lung cancer patients.

A sensitive and relatively specific tumoral marker for lung epidermoid carcinomas could be used to identify patients likely to benefit from new therapeutic protocols. The cyfra 21-1 fragment of cytokeratin 19 has raised much hope in this regard amongst both technologists and clinicians. In a study of 195 subjects, we have shown by means of a serum assay that the usual cut-off value for this marker (3.3 ng/ml) can be lowered to 1.5 ng/ml without loss of specificity, and with an increase in sensitivity. There was a good correlation between serum marker level and tumor extension, but though cyfra 21-1 was not predictive of the suitability of a patient for surgery. A decrease of cyfra-21-1 was observed after complete resection of the tumor. There was no relation between serum assay results and immunohistochemical findings.

Immunohistochemical study of secretogranin II in 62 neuroendocrine tumours of the digestive tract and of the pancreas in comparison with other granins.

An immunohistochemical study on 62 cases of gastrointestinal and pancreatic neuroendocrine tumours was performed in order to test the interest and specificity of a new anti-human secretogranin II antibody and compared to the other granin markers (chromogranin A and chromogranin B). Specific immunoglobulins were purified by affinity chromatography from an antiserum raised against a recombinant secretogranin II. Gastric tumours did not express secretogranin II, and ileal and appendiceal tumours only rarely expressed it (1/10 and 1/7 respectively), unlike the other classic neuroendocrine members of the granin family. In duodenal and pancreatic tumours, secretogranin II was detected when the other granins were also expressed. On the other hand, all rectal tumours expressed secretogranin II (7/7), frequently in the absence of chromogranin A. Though the granins expressed in tumoral tissue and in adjoining non tumoral tissue are mostly related, strong secretogranin II positivity occurred in 4 tumours while mucosa was secretogranin II negative. These observations highlight the interest for associating another antigranin such as secretogranin II to the classical markers of neuroendocrine tumours.

A case of myospherulosis occurring in the perirenal adipose tissue.

The authors report a case of spontaneous myospherulosis that developed in the right perirenal adipose tissue, presented like an abscess, in an 82-year old man of the A, Rh+ blood group. The patient had a history of chronic lymphocytic leukaemia. Fine needle aspiration and histological examination of the renal cyst allowed the observation of 4- to 7-micron spherules (or endobodies) enclosed in saccular structures (or parent bodies) and accompanied by a foreign body-type response. The walls of the parent bodies were negative for PAS, Gomori's methenamine silver and Giemsa's stain. Immunohistochemical study was positive with anti A antibody specific of A1/A2 blood group and with anti glycophorin A antibody. The authors reviewed the literature concerning this rare lesion: it usually occurs in subcutaneous fat or in the paranasal sinuses, nose and middle ear but, up to now, no previous case has ever been reported in the urinary tract. The only case of visceral myospherulosis previously reported occurred in a cystic teratoma of the ovary. The reported case is also peculiar by the unusual thickness of the parent bodies. The authors also discuss the mechanism of the disease and suggest that, in the present observation, myospherulosis could have been induced by the rupture of a preexisting cyst in the perirenal adipose tissue.

Necrotizing sarcoid granulomatosis with and without extrapulmonary involvement.

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.

Immunohistochemical expression of the intracellular component of galectin-8 in squamous cell metaplasia of the bronchial epithelium in neoplastic and benign processes.

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.

Malignant lymphoma of mucosa associated lymphoid tissue: a new etiology of amyloidosis.

Non Hodgkin Malignant lymphomas (NHML) of mucosa associated lymphoid tissue (MALT) are known to have multiple involvement of the digestive tract. We report one case, presenting with an infiltrative process of the jejuno-ileum, associating lymphoplasmacytoid proliferating cells and amyloidosis. The plasmacytoid cells expressed Alpha and scarce Mu heavy chains, and lambda light chain. Lympho-epithelial lesions were more obvious at the second site of involvement, in the gastric mucosa. The amyloid substance was negative with the Amyloid A component antibody and gave a background noise with Alpha, Mu and lambda chains. No similar report of amyloidosis associated with MALT NHML has been found in the literature.

Malignant melanoma of the hepatic and common bile ducts. A case report and review of the literature.

We report a case of malignant melanotic melanoma involving the extrahepatic biliary tract in a 34-year-old white woman. The diagnosis was established using conventional light microscopic examination and immunohistochemical stains. The clinical absence of any primary cutaneous or visceral melanoma suggests that the tumor arose primarily from the biliary tract. To our knowledge, only two previous cases of malignant melanoma of the common bile duct have been reported in the literature.

Hemangiopericytoma of the pancreas: report of a case and review of the literature.

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.

Primary liver hemangiopericytoma associated with hypoglycemia: report of a second case.

Hemangiopericytoma is an uncommon vascular tumor which usually develops in soft tissues. It has been exceptionally described in the liver and only one case associated with hypoglycemia has been reported in this organ. A giant hemangiopericytoma which was revealed by life-threatening hypoglycemia is described. Imaging and pathological features are presented. The patient, a 73 year-old woman, was treated by hepatectomy. She is perfectly well after a 3-year follow-up, without any evidence of recurrence.

[Vitamin A status and the carcinogenic action of N-nitrosobenzyl methylamine on the esophagus in the rat]. / Statut vitaminique A et action cancérigène oesophagienne de la N-nitrosobenzylméthylamine chez le rat.

A state of pure vitamin A deficiency, without any clinical manifestations, rapidly induces a stimulation of ornithine decarboxylase (ODC) activity and some oesophageal mucosal abnormalities (hyperkeratosis, dyskeratosis, cytonuclear abnormalities) in rats treated with N-nitrosobenzylmethylamine (NBMA). Retinol deficient rats fed with retinoïc acid (all-trans) show a mucosal ODC induction, but no morphological lesion. The association of retinoïc acid + retinol, as does retinol alone, prevents simultaneously histological lesions and enzymatic induction. In the liver of vitamin A deficient rats treated with NBMA, a stimulation of the ODC system, without any macroscopical lesions, has been observed.