[T1 bladder carcinoma: prognostic value of the muscularis mucosae invasion (T1a/T1b). A multicenter study by the French Urological Association (CCAFU)]. / Tumeur urothéliale de vessie T1 : valeur pronostique du franchissement de la muscularis mucosae (T1a/T1b). Etude multicentrique du Comité de cancérologie de l'Association française d'urologie (CCAFU).

OBJECTIVE: The aim of this multicenter study was to determine the prognostic value of the depth of invasion of lamina propria and more specifically the influence of the invasion of the muscularis mucosae on survival parameters in T1 bladder carcinoma. PATIENTS: Six urological centers included patients between 1994 and 2004 who had an initial T1 bladder tumor. All T1 tumors were substaged according to the muscularis mucosae (MM) invasion into T1a (no invasion beyond the MM) and T1b (invasion beyond MM but preserving the muscle). Among the 387 patients included, 269 (69.5%) were found T1a and 118 (30.5%) T1b. Mean follow-up was 45.4 months. T1a and T1b groups were comparable except for tumor grade that was higher in T1b (p<0.001). RESULTS: Survival without recurrence was not significantly different between T1a and T1b groups (p<0.3) but T1a stage was found as an independent factor for survival without progression (RR=0.49; IC 95%=[0.71-0.90]), specific survival (RR=0.33; IC 95%=[0.16-0.67]) and global survival (RR=0.52; IC 95%=[0.32-0.85]). CONCLUSION: This study, the largest on the subject to our knowledge, have shown that muscularis mucosae invasion was a prognostic factor for survival without progression, specific survival, and global survival. We support that routine pathological assessment of the level of MM invasion in patients with stage T1 bladder cancer should be included in the histopathological report.

The utility of a nebulised intra-tracheal rat model of invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis (IPA) is of particular concern to immunodeficient patients, whose mortality rates may exceed 80%. The development of an animal model that faithfully reproduces the pathophysiology of IPA would improve the studies on diagnostic and therapeutic modes, and the use of rats as a possible model for IPA seems to have been largely overlooked. Such a model could be established with the MicroSprayer IA-1B. Male Sprague-Dawley rats (6-8 weeks old) were rendered immunodeficient by cyclophosphamide injections and a protein-deficient diet. On day D0, they were anaesthetised by inhalation of 5% isoflurane and infected by the intra-tracheal aerosolization of 100 microl of an Aspergillus fumigatus spore suspension through a MicroSprayer IA-1B. This inoculation process was simple and rapid, with no deaths observed during or immediately after the procedure. The rats regained consciousness within 1 min. Follow-up data including those for clinical factors (weight changes, mortality rate), biological factors (Aspergillus antigens) and histological factors were consistent with previous studies. The advantages of this model include the ease of animal manipulation, the reproducibility of infection and the potential for repeated blood sampling.

Transient global amnesia caused by painless aortic dissection.

Neurological syndromes secondary to acute aortic dissection (AAD) are uncommon and usually consist of focal deficits after an embolic cerebral infarction. This article reports the observation of an AAD with the chief complaint of transient acute memory impairment-that is, a non-usual stroke-like symptom.

Quantitative magnetic resonance and isotopic imaging: early evaluation of radiation injury to the brain.

PURPOSE: Using magnetic resonance (MR) and isotopic imaging to investigate the cerebral alterations after highdose single-fraction irradiation on a pig model. We assessed the nuclear magnetic resonance (NMR) relaxation times as early markers of radiation injury to the healthy brain. METHODS AND MATERIALS: A total of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T1-weighted scans, T2-weighted scans, and scintigrams were performed on all animals to study neurological abnormalities, cerebral blood flow, and blood-brain barrier (BBB) integrity. T1 and T2 relaxation times were measured in selected regions of interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T1 after irradiation/T1 before irradiation, and a ratio T2 after irradiation/T2 before irradiation, were calculated, pooled for each dose group, and followed as a function of time after irradiation. RESULTS: Scintigraphy visualized the brain perfusion defect and BBB disruption in all irradiated brains. The ratio T2 after irradiation/T2 before irradiation was proportional to the effective dose received. The T2 ratio kinetics could be analyzed in three phases:an immediate and transient phase, two long-lasting phases, which preceded compression of the irradiated lateral ventricle, and edema and necrosis at later stages of radiation injury, respectively. The magnetic resonance imaging (MRI) observations correlated well with histological analysis. CONCLUSION: The results show that quantitative imaging is a sensitive in vivo method for early detection of cerebral radiation injury. The reliability and dose dependence of T2 relaxation time may offer new opportunities to detect and understand brain pathophysiology after high-dose single-fraction irradiation.

Calcitonin-secreting carcinomas of the prostate. An immunohistochemical and ultrastructural analysis.

Two cases of calcitonin-producing carcinomas of the prostate are reported. Light microscopical, immunohistochemical, and ultrastructural investigations have been performed. These tumors displayed a remarkable dual, endocrine and common epithelial (exocrine), differentiation. However, they presented two different architectural growth patterns. Of particular interest, numerous calcitonin cells were immunocharacterized. In addition, the endocrine component could harbour carcinoembryonic antigen, serotonin, human chorionic gonadotrophin, and prostate-specific acid phosphatase immunoreactive cells. Ultrastructural analysis confirmed the presence of numerous endocrine cells. These findings are not unexpected, since calcitonin, serotonin, and human chorionic gonadotrophin immunoreactive cells are normal and constitutive inhabitants of prostate gland. In the current cases, calcitonin cells showed a strong carcinoembryonic antigen immunoreactivity, as observed also in thyroidal C-cells. This peculiar kind of prostatic carcinoma might be compared to certain thyroidal tumors of intermediate type coupling parafollicular and follicular differentiation.

Argyrophilic cells in mammary carcinoma.

Breast tumor tissues were treated by the Grimelius procedure and examined for the presence of argyrophilic cells. Carcinomas found to contain argyrophilic cells did not include classic carcinoid tumors; the group was, in fact, heterogeneous, comprising poorly differentiated ductal carcinomas, lobular carcinomas, carcinomas of uncertain origin, and colloid carcinomas. Colloid tumors were the most frequently encountered. The prominence of argyrophilic cells in colloid carcinomas raises the possibility that development into mucin-producing cells is propitious for endocrine differentiation.

Experimental MR study of cerebral radiation injury: quantitative T2 changes over time and histopathologic correlation.

PURPOSE: To use the pig brain as a large-animal model to examine the effects of high-dose single-fraction irradiation on MR images, T2 relaxation time, and histologic integrity. METHODS: A total of 24 Meishan pigs were studied: 20 irradiated animals and 4 unirradiated controls. A high dose was delivered to the right hemisphere of the animals, using a 12-MeV electron beam. Ten animals received 40 Gy at the 90% isodose, and 10 animals received 60 Gy. Quantitative measurement of T2 relaxation time was compared with qualitative analysis of T2-weighted images and histologic studies. RESULTS: Quantitative analysis revealed a reproducible increase of the T2 parameter within the irradiated areas. The T2 kinetic could be analyzed in two phases, which appeared before the visualization of ventricle compression, necrosis, and edema. The first is characterized by vascular inflammation and the latter by radiation necrosis and edema. Both are dose dependent. CONCLUSION: These results underline the ability of quantitative MR for early diagnosis of brain radiation lesions in vivo.

Potential of T2 relaxation time measurements for early detection of radiation injury to the brain: experimental study in pigs.

PURPOSE: To investigate the MR T2 relaxation time and histologic changes after a single-fraction 25-Gy dose of radiation to the brain of pigs. METHODS: The right hemisphere of 10 Meishan pigs was irradiated with a single dose of 25 GY at the 90% isodose, using a 12-MeV electron beam. T2 relaxation time was measured within three regions of interest in the brain: those that had received 90%, 70%, and 40% of the total dose, respectively. T2 kinetics over time was compared with histologic studies. RESULTS: Brain T2 values were noted to increase within the irradiated areas. T2 kinetics were analyzed in three phases: an immediate transient phase and two long-lasting phases. These two long-lasting phases were correlated with the detection of ventricular compression and necrosis, respectively. The T2 increase within the 90% region of interest was 19%, 22%, and 26% for phases I, II, and III, respectively. T2 measurements within other regions of interest were not significant. CONCLUSION: Although our results suggest a dose threshold for T2 variations, brain T2 values increased after irradiation at a level at which disease could not be seen on conventional MR images. This illustrates the value of using conventional MR imaging in a quantitative manner to assess molecular tissue abnormalities at earlier stages of developing diseases.

Granular cell tumor of the pituitary stalk. Case report.

The case is described of a granular cell tumor of the pituitary stalk in a 40-year-old woman with secondary amenorrhea. A computerized tomography scan showed a large contrast-enhancing mass, and T1-weighted magnetic resonance images demonstrated a tumor isointense to the brain parenchyma with nonhomogeneous enhancement after intravenous administration of gadolinium diethylenetriamine penta-acetic acid. Histopathological examination, especially immunocytochemical and electron microscopic studies, showed elements supporting an astrocytic origin for this type of tumor, a hypothesis advanced by many authors but still controversial.

Endocrine cells in the excurrent duct system of the testis. An immunohistochemical analysis.

A systematic search for endocrine cells in the excurrent duct system of the testis was carried out by means of histochemical and immunohistochemical techniques. A panel of antibodies against amine and polypeptide hormones was used. 80 specimens comprising representative areas of rete testis, ductuli efferentes, ductus epididymis and 30 examples of ductus deferens were investigated. Cells immunoreactive for serotonin were detected in four out of 110 specimens. They were invariably in normal-appearing ductuli efferentes. A salient feature was their rarity and focal distribution. We failed to detect any endocrine cells in other segments of the excurrent duct system and notably not among epididymal epithelium. It seems of interest that serotonin cells are specifically distributed throughout remnants of excretory mesonephric tubules in both males and females.

Unusual endocervical lesions with endocrine cells.

Four cases of unusual lesions of endocervix are presented. They were all incidental findings, showing no obvious infiltrative and metastatic properties to attest their malignant nature. Two lesions were entirely confined to the endocervical mucosa. The main characteristics of these proliferative processes thus were an abnormal architecture with branched or small glands, a hypermucinous benign-appearing epithelium of endocervical type, and stromal smooth-muscle. In contrast with normal endocervical mucosa, all lesions contained prominent and variegated endocrine cells. These 4 cases were quite comparable to 3 other observations previously reported. This homogeneous group of endocervical lesions does not correspond to a well-defined type of endocervical neoplasia. It shares morphological analogies with adenoma malignum. The relationship with adenoma malignum as well as with some other gynaecological neoplasms is discussed. The recognition of these small-sized and highly differentiated lesions is largely facilitated by the use of the Grimelius reaction to detect argyrophilic cells.

Papillary tumour of the vagina resembling transitional cell carcinoma.

A case of a peculiar papillary neoplasia of the vagina resembling a urothelial tumour is presented. Four vaginal tumours were excised from a 76-year-old woman. Five years before this patient had undergone a uretero-nephrectomy for a non-invasive papillary transitional cell carcinoma of the renal pelvis. The four vaginal tumours demonstrated gross and microscopic similarities to low-grade papillary transitional cell carcinoma of the urinary tract. This observation indicates that multicentric, non-invasive, papillary tumours may affect the whole uro-genital area. The vaginal wall was not overlaid by a normal squamous epithelium, but by a peculiar "transitional-like" epithelium. Variegated endocrine cells were documented within this lining, using immunohistochemical and ultrastructural techniques. The eventuality of a histogenetic link between the tumour and the adjacent epithelial lining remains unresolved.

Endocrine cells in median raphe cysts of the penis.

Serotonin-storing cells are distributed in all tissues derived from cloaca. They were observed in the cavernous portion of penile urethra whereas they were absent from the glans portion. Serotonin cells were detected in several morphologic varieties of median raphe cysts. It is suggested that these cysts arise from the endodermal part of urethra.

Glycoprotein hormone alpha-chain-immunoreactive endocrine cells in prostate and cloacal-derived tissues.

All cloacal-derived tissues contain a similar endocrine cell population. Human chorionic gonadotropin (hCG)-like immunoreactivity has been reported in some prostatic endocrine cells. On the other hand, immunoreactivity to alpha-hCG is well known to occur in a variety of extraprostatic endocrine elements. Most cloacal-derived tissues were tested with a panel of monoclonal antibodies against hCG and subunits. The previously described hCG-like positivity was found to be exclusively related to the free alpha-subunit of hCG. Moreover, alpha-chain immunoreactivity was more broadly distributed in most cloacal-derived tissues, including those from the anal canal. In the anal canal, alpha-chain was an excellent marker of the anal transitional zone. alpha-Chain-immunoreactive endocrine cells were normal and nonneoplastic constituents of these tissues; they corresponded to a subpopulation of serotonin cells. In addition, certain prostatic argyrophil cell carcinomas might be exclusively alpha-subunit producing.

Prognostic factors in ductal carcinoma in situ of the breast: results of a retrospective study of 575 cases. The Association for Research in Oncologic Gynecology.

OBJECTIVE: Conservative treatment for ductal carcinoma in situ of the breast exposes patients to the risk of infiltrating recurrence which can lead to metastasis. The primary purposes of this retrospective study were to evaluate diagnostic and therapeutic methods over a 10-year period and to validate prognostic factors. This information should greatly improve patient selection for conservative treatment or mastectomy. STUDY DESIGN: A multi-institutional data base including 575 patients treated between 1983 and 1993 was established by combining data from 16 French institutions. Survival at 5 and 7 years was studied as a function of various prognostic factors. RESULTS: Recurrence-free survival at 7 years was 0.96 after modified radical mastectomy and 0.83 after breast-conserving treatment and radiotherapy (P=0.003). Metastasis-free survival at 7 years was 0.99 after modified radical mastectomy and 0.94 after breast-conserving treatment and radiotherapy (not significant). No factor was predictive of local recurrence after mastectomy. Clinical stage was the only factor significantly correlated with metastasis after mastectomy. Recurrence-free survival after breast-conserving treatment with radiotherapy was significantly lower for patients with comedo carcinoma, multifocal lesions, or unclear resection margins, regardless of whether the histological type was comedo or non-comedo carcinoma. Metastasis-free survival was significantly lower for patients with multifocal lesions and for patients with unclear margins after excision of comedo carcinoma. CONCLUSIONS: Breast-conserving treatment with radiotherapy is a valid alternative to mastectomy. Patients must be selected carefully on the basis of morphological criteria. Swift gains in therapeutic outcome can be obtained by stressing quality control at each stage of diagnosis and treatment.

Abdomino pelvic irradiation after second-look laparotomy for stage III ovarian carcinoma.

OBJECTIVE: The purpose of this retrospective analysis of 34 patients with stage III ovarian carcinoma was to review results and morbidity of whole abdominal irradiation after surgery and chemotherapy. METHODS AND MATERIALS: All of the 34 patients had reached a complete clinical remission after first cytoreductive surgery and chemotherapy. After second-look laparotomy each patient underwent whole abdominal irradiation. Except for two patients with chronic myelosuppression, the dose administered was of 22.5 Gy to the abdominal cavity with a boost of 22.5 Gy added to the pelvis. RESULTS: Three and 5-year overall survival rates were 62% and 43%, respectively. Three and 5-year disease-free survival rates were 53% and 38%. Twenty-three patients (68%) developed local relapse or local disease progression. Metastasis occurred in five cases and were always associated with an abdominal cavity recurrence. Residual disease after first cytoreductive surgery appeared as a prognostic factor in univariate analysis. Patients with unresected residuum had a 5-year survival probability of 35% versus 83% for patients without residual disease. We observed 12% grade-3 intestinal toxicities and one fatal case of radiation enteritis. CONCLUSION: Despite its curative potential, the long term benefit of whole abdominal irradiation in the multimodality treatment of advanced ovarian carcinoma must be evaluated in well designed controlled trials.

[Primary non-Hodgkin's high grade malignant lymphoma of the digestive system. A prospective study of the combination of surgery-chemotherapy-radiotherapy]. / Lymphomes malins non hodgkiniens primitifs du tube digestif de haut grade de malignité. Etude prospective de l'association chirurgie-chimiothérapie-radiothérapie.

We report a prospective study concerning the association of surgery-chemotherapy and radiotherapy in the treatment of primary high grade digestive non-Hodgkin's lymphomas in 19 patients. The analysis of 11 stages IE, 5 stages II1E and 3 stages II2E allowed us to evaluate the efficacy and the tolerance of this triple therapeutic association. Fifteen patients are alive and well with a median follow-up of 54 months. One of these patients relapsed, but after autologous bone marrow transplantation is in second unmaintained complete remission. Four patients died of intercurrent aetiology although one death was related to treatment morbidity. Our results and the analysis of literature data lead us to recommend the triple association in the treatment of stage II2E high grade primary digestive lymphomas (PDL) and for PDL without complete resection. However, surgery and chemotherapy appear to be sufficient in the treatment of stages IE and II1E with complete resection.

[The glucagonoma syndrome. 3 new cases]. / Le syndrome du glucagonome: trois nouveaux cas.

We report three new cases of glucagonoma revealed, 6 to 12 months after its onset, by non-specific and misleading skin lesions associated in all 3 cases with diabetes mellitus, severe deterioration of the general condition and hyperglucagonaemia. Non-invasive methods, such as ultrasonography and computerized tomography (CT), are most helpful to locate the pancreatic tumour. Phlebography with tiered venous blood sampling is useful in difficult cases. A false positive result has been recorded with arteriography. Ultrasonography and CT have yielded two false negative results. The alpha-chain of the chorionic gonadotrophin hormone has limited value in the diagnosis of malignant glucagonoma. Treatment is surgical, but despite it, the prognosis is severe (two of our three patients died), due to the risk of thromboembolism, to cachexia and to metastases that are frequent at the time of diagnosis.

[Endocrine cells in Walthard's cell rests]. / Cellules endocrines dans les restes de Walthard.

Walthard cell nests have been systematically examined for the presence of some endocrine cell types using histochemical and immunohistochemical techniques. Serotonin immunoreactive cells were the only endocrine cells demonstrated in this site. These cells were immunocharacterized using a peroxidase-antiperoxidase technique. This finding reinforces the homology with transitional epithelium (urothelium) of urinary tract and Brenner tumors. In all these structures, the abundance of endocrine cells seems to be related to the intensity of the proliferative process affecting the transitional epithelium.

[Malignant mesodermal mixed tumor of the ovary with neuro-ectodermic differentiation]. / Tumeur mixte mésodermique maligne de l'ovaire avec contingent neuro-ectodermique.

A striking ovarian tumour was observed in a post-menopausal, 54-year-old woman. Most of the tumour shows histologic features of a malignant mesodermal (müllerian) mixed tumour. However, this tumour harbours a peculiar component suggesting neuroectodermal neoplasia. Histochemical and immunohistochemical studies demonstrate focal pheochromocytomatous (or paraganglionic) and ganglionic differentiations. Several types of cells could be identified: ganglion cells (NSE +, neurofilaments +), pheochromocytes or paraganglion cells (chromogranin +), Schwann cells (S 100 protein +), and neuroblastomatous elements (NSE +). This neoplastic component could be compared with compound tumours such as pheochromocytomaganglioneuroblastoma or gangliocytic paraganglioma. This type of tumour has not been reported in ovary, notably in association with a mesodermal mixed tumour. Such observation prompts us to consider tumours of somatic origin containing germ cell-type elements, with a review of the literature.