[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.

Neuro-endocrine adenoma of the middle ear: a case study.

Neuroendocrine adenomas are rare tumors, which can appear in the middle ear. Approximately a hundred cases have been reported in the literature. We report the case of a 58-year-old man who consulted for an abnormal sensation of fullness in the right ear. The otoscopic examination showed a retrotympanic tumefaction. The CT scan and MRI of the middle ear demonstrated a well-defined tissue mass without any osteolysis. We performed surgical exeresis by transcanal procedure with a cartilage graft tympanoplasty. Microscopic examination and immunohistochemistry revealed an endocrine adenoma of the middle ear. Neuroendocrine adenomas can develop in a number of different sites. When they appear in the middle ear they usually produce hypoacousia. The otoscopic examination shows non-specific findings with only retrotympanic swelling. Surgical exeresis enables histologic and immunohistochemically analysis of the surgical specimen. The adenoma is composed of two cellular types: neuroendocrine (which closely resemble carcinoid tumors) and glandular. Regular clinical and radiologic follow-up is necessary since recurrence is possible. The formal diagnosis of neuroendocrine adenomas of the middle ear requires histologic and immunohistochemically confirmations since the clinical symptoms are non-specific. Surgical excision with removal of the ossicular chain is the treatment of choice in order to prevent recurrence.

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.

[In vivo assessment of corneal epithelial toxicity of timolol with benzalkonium chloride using very-high-frequency ultrasound imaging]. / Evaluation in vivo par échographie à très haute fréquence des modifications épithéliales cornéennes induites par un bêta-bloquant avec 0,01% de chlorure de benzalkonium.

PURPOSE: To assess in vivo the corneal epithelial damage caused by a topical toxic medication using a 60-MHz ultrasound device. MATERIAL: and methods: A solution of timolol with 0.01% benzalkonium chloride (BAC) was applied twice a day in the test eyes of ten rabbits, and a BAC-free solution of timolol in the control eyes, for 56 days. We used a 60-MHz ultrasound device to evaluate the epithelial damage in BAC-exposed eyes, compared to control eyes. The clinical and ultrasound examinations were performed every week, and the histological analysis at the end of the experiment. RESULTS: The clinical findings were conjunctival redness, corneal staining and instability of the tear film. In vivo VHF ultrasound revealed a thinning of the epithelium of test eyes (from 40.9+/-1,6 microm at D0 to 31.8+/-3.4 microm at D56; p=0.0006 for D0 vs D56), while the epithelium of control eyes remained unchanged. Ultrasound epithelial thickness was correlated with corneal staining (at D34 and D56; p=0.0025 and 0.0377, respectively) and histological epithelial pachymetry (p=0.0176 for control and 0.0505 for tested epithelium). Moreover, we report qualitative VHF ultrasound imaging of early epithelial damage. CONCLUSION: This new device could be very useful in ocular toxicity evaluation as a reproducible and reliable tool for multicentric clinical research.

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate.

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

Histologic multifocality is predictive of skin recurrences after conserving treatment of stage I and II breast cancers.

OBJECTIVE: To distinguish various types of local recurrence after conserving treatment of breast cancer and to evaluate their predictive value. MATERIALS AND METHODS: We first researched the pronostic factors after local recurrence and second evaluated the predictive factors of skin and inflammatory recurrences out of a series of 605 cases of stage I and stage II breast cancer of less than 4 cm in diameter that occurred after conserving treatment. RESULTS: Multivariate analysis revealed two major predictors of poor prognosis associated with recurrence: early appearance Hazard ratio 3.0 (1.28-7.00) (p = 0.011) and inflammatory or skin involvement Hazard ratio 3.38 (1.36-8.45) (p = 0.009). A local recurrence multiplied the relative risk for metastasis by 2.6. This result depended on the type of recurrence: when those with inflammatory and cutaneous types were excluded, local recurrence was no longer a poor prognostic factor. Patients who experienced primary invasive tumor with histologic multifocality have a 4.08 (1.44-11.59) (p < 0.004) times greater risk of developing cutaneous or inflammatory recurrences compared with patients who experienced breast cancer unique localization. CONCLUSION: As histologic multifocality is the only factor predictive of dark prognosis local breast cancer recurrences, aggressive therapy at the time of the primary treatment could be the therapeutic implications of such finding on the original tumor.

[Borderline tumors of the ovary: a multicenter study in 137 patients]. / Tumeurs borderline de l'ovaire: Etude multicentrique a propos de 137 patientes.

OBJECTIVES: Evaluate management of patients with a borderline ovarian tumor. MATERIALS AND METHODS: A multicentric retrospective survey was conducted in 137 patients with borderline ovarian tumor diagnosed between January 1, 19975 and December 31, 1995. RESULTS: Mean follow-up was 6.5 years, mean age was 50 years. Initial surgery was cystectomy, unilateral salpingo-oophorectomy and total hysterectomy with bilateral salpingo-oophorectomy in 22, 40 and 75 cases respectively. Eleven patients had residual disease. Serous, mucinous and Brenner tumors were observed in 67, 69 and 1 cases respectively. Staging was I, II, III in 117, 3, and 17 cases respectively with two pseudomyxomas. Adjuvant therapy was given in 15 patients. There was a recurrence in 15 patients and 14 died. The 5-year survival rate was 89.3%. Prognosis factors with an impact on survival rate were age, recurrence and type of surgery. Factors with a negative impact on recurrence were adjuvant therapy and residual disease after surgery. CONCLUSION: Careful staging followed by complete and radical surgery is essential. Unilateral salpingo-oophorectomy with omentectomy and multiple peritoneal biopsies may be indicated in younger patients undergoing radical surgery after pregnancy. Aduvant therapy is necessary for invasive implants.

A new serologic index for low-grade non-Hodgkin's lymphoma based on initial CA125 and LDH serum levels.

BACKGROUND: Serum CA125 (sCA125) was recently reported to be of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma (NHL). This report aims to investigate the prognostic value of a new serologic index combining sCA125 and LDH serum levels. PATIENTS AND METHODS: One hundred thirty-seven patients were studied, sixty-three with histologically proven low-grade NHL, and seventy-four with a high-grade subtype. RESULTS: sCA125 and LDH levels were elevated in more than one third of patients. sCA125 was more frequently increased than LDH in low-grade NHL. In this group, complete remission (CR) was achieved in 87, 45, and 0% (P = <2 x 10(-6)) of patients with normal sCA125 and LDH serum levels (Low-risk group), one parameter increased (Intermediate-risk group), and increased sCA125 and LDH serum levels (high-risk group), respectively. The estimated five-year overall survival was 97%, 67% and 22% for low, intermediate, and high-risk groups, respectively. This combination was the only parameter predictive of RFS and OS in multivariate analysis (P < 0.0001). CONCLUSIONS: In this study the combination of s-LDH and sCA125 levels (normal vs. abnormal) was found to be an important prognostic factor in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

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.

Herpetic salpingitis and fallopian tube prolapse.

AIM: We describe the unusual association of fallopian tubal prolapse and herpetic infection, an occurrence not previously reported to our knowledge. METHODS AND RESULTS: A 37-year-old woman presented with a small polypoid mass of the vaginal vault, 3 months after abdominal hysterectomy and abdominoplasty. The vaginal mass proved to be the fimbriated end of a fallopian tube, herniated into the vagina. Reintervention 3 months later with resection of a small vaginal 'polyp' revealed a residual portion of fallopian tube, with superimposed herpes simplex virus (HSV) infection and marked cytological atypia of surface epithelial cells. HSV-2 immunostaining of viral nuclear inclusions and of atypical cells confirmed the herpetic nature of the infection. CONCLUSION: Involvement of the genito-urinary tract by HSV may occur via an ascending infection from the cervix, but the fallopian tube, deeply located in the pelvis, is generally spared from herpetic infection. In the setting of fallopian tubal prolapse, direct exposure of the herniated fallopian tube to various pathogens in the vagina provides an unique clinical model for salpingitis. In herpetic tubal infections, special attention must be paid to cytological atypia of probable viral cytopathogenic origin, to avoid a misdiagnosis of malignancy.

[An unusual variant of urothelial carcinoma: the "nested variant of urothelial carcinoma." Report of two cases]. / Une variante particulière de carcinome urothélial: le "nested variant of urothelial carcinoma". A propos de deux cas.

We report two cases of a poorly known variant of transitional cell carcinoma, the "nested variant of urothelial carcinoma". This tumor is composed of small islands or nests of transitional cells, presenting little atypia and mimicking von Brünn's nests. This low grade tumoral variant seems to behave as a high grade tumor of the same stage. Deep biopsies are necessary to display tumoral invasion, which allows the diagnosis. Importance of the knowledge of this entity is highlighted in order to avoid misdiagnoses that could delay appropriate therapy.

[Adenoid basal carcinoma and adenoid cystic carcinoma of the uterine cervix]. / Carcinome adénoïde basal et carcinome adénoïde kystique du col utérin.

Adenoid basal carcinoma and adenoid cystic carcinoma are rare primary cervical neoplasms occurring in postmenopausal women. They are generally regarded as distinct entities on the basis of their distinctive morphology and a different biological behaviour. Although the separation of these two entities is still mandatory, some rare complex cases may show overlapping pathological features and are difficult to classify. We report a case of composite cervical tumor with both types of carcinoma, an in situ epidermoid carcinoma and a hitherto undescribed clear cell component, each with a different morphology and immunophenotype. The adenoid basal component is mainly immunoreactive for cytokeratin KL1. The adenoid cystic component is strongly stained for smooth muscle actin and is associated with a hyaline stroma immunostained for collagen IV.

[Retroperitoneal malignant fibrous histiocytoma]. / Histiocytome fibreux malin rétropéritonéal.

Malignant fibrous histiocytoma is the commonest soft tissue sarcoma of adults. The soft tissue of the extremities is the commonest primary site of malignant fibrous histiocytoma. It is much less common in the female retroperitoneum, leading to diagnostic errors. The clinical, radiographic and CT signs are non-specific. This tumor can only be diagnosed by histology. An initial complete resection is essential for successful treatment of the primary tumor. Radiation therapy is limited and chemotherapy has only been successful in a limited number of cases. This tumor has a poor prognosis. These lesions are relatively rare and consequently difficult to study. The authors report three cases and review the literature.

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.

Membrane fatty acids of breast carcinoma: contribution of host fatty acids and tumor properties.

To assess the part that host fatty-acid supply and tumor-specific fatty-acid utilization contribute to the membrane lipid composition of tumor tissue, intra-individual comparisons of membrane fatty acids were carried out between breast-carcinoma tissue and non-tumorous breast tissue adjacent to the tumor and taken as reference. Phospholipids were purified by thin-layer chromatography from tumor biopsies obtained from 59 patients with a localized presentation of breast cancer, and fatty acids analyzed by capillary gas chromatography. Elevated levels of palmitic, palmitoleic and arachidonic acids, along with a low level of linoleic acid, were observed in membrane phospholipids of tumors with poor histoprognostic grade. The level of mono-unsaturated fatty acids was higher, and the level of essential fatty acids was lower in the tumor than in the reference breast tissue. Fatty-acid-desaturating activity was not detectable in tumors. A positive relationship was observed among patients for most of the fatty acids between carcinoma and non-tumorous breast tissue, except for mono-unsaturated and essential fatty-acid levels, which were not correlated between both tissues. These data suggest that mechanisms specifically related to malignant transformation and tumor progression influence the membrane fatty-acid profile of breast carcinoma. Fatty acid supply to the tumor, possibly modified by metabolic conditions related to the host, also seems to play a decisive role in this composition.

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.