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Biomedical subjects

C Hennequin

Publications and source records attributed to C Hennequin.

At least 19 recordsLinked to original sources

Postoperative radiation therapy in 26 patients with invasive transitional cell carcinoma of the upper urinary tract: no impact on survival?

PURPOSE: To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus postoperative prophylactic irradiation for such a tumor. MATERIALS AND METHODS: Between February 1980 and October 1993, 18 men and 8 women (mean age 65 +/- 9 years, standard deviation) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 (58%). Tumor grade was 2 in 10 patients, 3 in 15 and unknown in 1. One patient had epidermoid metaplasia of urothelial cancer and 9 had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy. to the tumor bed (23) and/or regional nodes (18). RESULTS: After a mean followup of 45 months 13 patients (50%) were alive and 11 were disease-free at analysis. Local tumor relapse, nodal recurrence and metastasis were noted in 1, 4 (15%) and 14 (54%) patients, respectively. All patients with nodal recurrence had metastasis. A secondary location was noted frequently (6 bladder, 1 contralateral renal pelvis and 1 urethral tumors). Overall 5-year survival rate and 5-year survival rate with no evidence of disease were 49% and 30%, respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (p = 0.07), 49% for node-negative versus 15% for node-positive cancer (p = 0.04), and 90% for grade 2 and 0% for grade 3 tumors (p < 0.01). CONCLUSIONS: In our trial using a radio-surgical approach, local control of disease and survival rates were similar to those reported previously in surgical series. Prophylactic postoperative radiation therapy is not recommended except in prospective randomized studies.

Aged

Outbreak of Pneumocystis carinii pneumonia in a renal transplant unit.

The charts for seven renal transplant recipients who developed Pneumocystis carinii pneumonia were reviewed. They included six men and one woman transplanted a mean of 150 days before the diagnosis of this infection. Six presented at least one episode of acute graft rejection. Cytomegalovirus pneumonia was diagnosed in six of the patients. All patients were treated with cotrimoxazole. Global mortality was 43%. In additional to the classic hypothesis of latent Pneumocystis carinii reactivation in immunocompromised hosts, this and previous reports of outbreaks strongly suggest either a person-to-person transmission or acquisition from the environment. Molecular typing of isolates could be of value in identifying the source of such outbreaks. Chemoprophylaxis should be more systematically administered to renal transplant patients, co-trimoxazole being the drug of choice.

AIDS-Related Opportunistic Infections

Effect of radiation therapy after radical prostatectomy on serum prostate-specific antigen measured by an ultrasensitive assay.

OBJECTIVES: To study prospectively the impact of adjuvant radiation therapy on the serum level of prostate-specific antigen (PSA), as measured by an ultrasensitive Yang Proscheck assay in patients with detectable serum PSA and a negative metastatic survey after radical prostatectomy for T1 or T2 prostate cancer. METHODS: Seventeen patients had a detectable serum PSA (2.40 +/- 2.1 ng/mL; range, 0.5 to 10) by the Yang polyclonal assay 2 to 71 months after radical prostatectomy for P2N0 (2 patients) or P3N0 (15 patients) prostate cancer. Metastatic workup (bone and computed tomography scan) was negative; 9 of 17 patients had a local recurrence documented by a positive biopsy of the vesicourethral anastomosis. All patients were treated by external radiotherapy, receiving 65 Gy on the prostate fossa over 5 weeks for an assumed low volume residual disease. Patients were followed up by determination of serum PSA every 3 months, using the Yang ultrasensitive assay for a mean duration of 14.4 months. RESULTS: In 17.6% of the patients (3 of 17) PSA became undetectable (less than 0.05 ng/mL) after radiotherapy. Radiotherapy had no impact on PSA in 35.3% (6 of 17). PSA decreased after radiation therapy within 6 months in 47.1% (8 of 17) and for up to 12 months in 2 patients, with a nadir of 0.28 ng/mL. All patients in this group experienced a secondary rise in PSA a mean of 10.6 months (range, 6 to 18 months) after radiotherapy. CONCLUSIONS: External radiotherapy has a limited impact on residual disease after radical prostatectomy, as assessed by its impact on PSA.

Follow-Up Studies

S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells.

Cell viability following short (1 h) contact with paclitaxel or docetaxel was assayed using synchronised HeLa cells. Docetaxel proved almost totally lethal against S-phase cells. Its toxicity was only partial against cells in mitosis, and declined to a minimum with progression to G1. For paclitaxel, cytotoxicity increased with progression through S and G2, peaked at the time of mitosis, and decreased thereafter. Maximum resistance to paclitaxel was in early S. Although lethal, brief exposure to docetaxel in S-phase did not delay progression through S and G2. Gross damage was detectable immediately after mitosis, with dysfunction in cytokinesis and accumulation of multinucleated, non-viable cells. Arrest of cells at prometaphase required continuous contact with lethal amounts of docetaxel or reintroduction of drug shortly before mitosis following pulse-chase treatment in mid-S-phase. Paclitaxel at moderate doses presumably acts mostly via damage to the mitotic spindle. In contrast, the available data suggest that docetaxel primarily targets centrosome organisation, leading to abortive mitosis and cell death.

Antineoplastic Agents, Phytogenic

Congenital cholesteatoma of the temporal bone: MR findings and comparison with CT.

PURPOSE: To describe the MR findings of temporal bone congenital cholesteatoma and MR usefulness in preoperative diagnosis and follow-up, in comparison with CT. METHODS: Seven patients underwent CT and MR studies for facial palsy (n = 3), deafness (n = 3), vertigo (n = 1), tinnitus (n = 1), and otalgia (n = 1). Three patients had for congenital cholesteatoma previously undergone surgery. One of them was free of symptoms and referred for follow-up. Final diagnosis was obtained from surgical data in all the cases but one. RESULTS: Congenital cholesteatoma signal intensity was low or intermediate on T1-weighted images and high on T2-weighted images in all the cases. MR was useful in diagnosis in six cases, helping to differentiate congenital cholesteatoma from other nonenhancing tumors. When temporal bone wall erosion was observed with CT (n = 6), MR ruled out intracranial extension in five cases; in one case, MR found an associated epidermoid cyst of the cerebellopontine angle not identified with CT. However, CT assessed relationships with labyrinthine structures more easily. CONCLUSION: MR and CT are complementary in initial diagnosis and follow-up.

Adolescent

[Inflammatory cancer of the breast: review and experience at Saint-Louis hospital].

Inflammatory breast cancer represents about 1 to 6% of all breast cancers. It has a sudden onset and affects women of the same age as other breast cancers. Its particular feature is the almost constant development of metastases. The 5-year survival after surgery or surgery and radiotherapy varies between 0 and 28% with a median survival of 18 months. The use of anthracycline-based chemotherapy has doubled the median survival, but has not achieved cure. Clinical research is directed towards therapeutic intensification with or without autologous bone marrow transplantation. The authors report their experience at Hôpital Saint-Louis.

Adolescent

Severe psychiatric side effects observed during prophylaxis and treatment with mefloquine.

Mefloquine hydrochloride is now one of the major antimalarial drugs used both in prophylactic and therapeutic regimens. Large-scale studies have shown that it is efficacious and relatively well tolerated. However, some severe side effects, particularly neuropsychiatric reactions, have been described. We describe two young men with no previous medical history who experienced severe psychiatric reactions during prophylactic and curative mefloquine therapy. In both cases, full recovery was rapid after cessation of the therapy. There is no explanation for these reactions. Serum levels of mefloquine were within the normal range. The absence of contraindications and minor side effects during an initial course of mefloquine should be confirmed before another course is prescribed.

Adult

Interaction of ionizing radiation with the topoisomerase I poison camptothecin in growing V-79 and HeLa cells.

Interaction between gamma-rays and camptothecin (CPT) was investigated in vitro, using log phase HeLa-S3 cells and Chinese hamster V-79 fibroblasts. A plateau of toxicity was rapidly reached for both cell lines upon exposure to CPT alone, consistent with S-phase specificity of CPT. With synchronized HeLa cells, however, CPT proved cytotoxic after the middle of G1 phase. This effect was abolished by cotreatment with the DNA polymerase alpha inhibitor aphidicolin. CPT enhanced the initial slope of the radiation survival curves for asynchronous cells by a factor of 1.1 (HeLa) to 2.3 (V-79). This apparent radiation sensitization correlated with the intrinsic radiosensitivities of the drug-surviving fractions within the different compartments of the cell cycle. There was no evidence of mutual potentiation of CPT and radiation in terms of survival as well as with regard to the formation and rejoining of DNA double-strand breaks. V-79 cells exhibited pronounced postirradiation recovery. In contrast, the response of HeLa cells to drug did not vary appreciably for over 8-h following radiation. This difference proceeded from differential cell cycle redistribution. In both cell lines, acute irradiation produced depletion of the G1 compartment, accumulation at the S-G2 junction, and G2 arrest in proportion to the gamma-ray dose. However, while radiation brought about rapid depletion of the S-phase compartment in V-79 cells, it induced accumulation of HeLa cells into S phase. As a result, the CPT-sensitive HeLa cell population, consisting of the early-S, mid-S, and late G1 fractions, did not vary very much after irradiation. Exposure to CPT under conditions of low dose rate irradiation (1 Gy/h) selectively reversed the radiation effect on S-phase progression in V-79 cells; i.e., it induced accumulation of cells in S phase in the same way as found with HeLa cells. Isobolic analysis of survival data consistently showed supraadditivity of cell killing in both cell lines upon concomitant exposure to CPT and low dose rate irradiation. Cytokinetic cooperation appears to be the major determinant of cell survival in treatments associating CPT and radiation in growing cells. Attempts to predict the outcome of such a combined modality thus should take into consideration the response of the growing fraction of each cell line in terms of cell cycle-regulatory processes and redistribution.

Animals

Influence of various calcium intakes on calcium-oxalate crystalluria in rats on sodium-oxalate diet.

Forty adult male Wistar rats were placed in metabolic cages on a Ca-deficient diet (0.1%) for 7 days and then on a Ca-deficient, Na-oxalate (NaOx) enriched diet (20 mg/100 g) for another 14 days. The animals were subdivided into three groups receiving three different types of mineral water: group I (n = 13), Badoit (Ca 222 mg/l); group II (n = 14), Contrexéville (Ca 467 mg/l); and group III (n = 13), Evian (Ca 78 mg/l). Another series of 25 rats (group I, n = 9; group II, n = 8; group III, n = 8) underwent the same study protocol, except that they received a normal Ca diet (1%). On the low-Ca diet, urinary Ca-Ox monohydrate (COM) crystals were observed only under the Na-Ox diet, with a mean crystal number significantly greater in group III (16.7 +/- 4.5 crystals/mm3) than in group I or II rats (2.5 +/- 1.5 or 4.1 +/- 1.5 crystals/mm3, respectively). Urinary Ca concentrations decreased in all groups (P < 0.001) under the Na-Ox diet, while urinary oxalate concentrations increased in all groups (P < 0.001). On the normal Ca diet, COM crystal excretion was observed only with the Na-Ox-enriched diet, but in this case feeding the Na-Ox diet did not modify urinary oxalate excretion. Ca/Ox ratio was significantly lower under 0.1% Ca diet than under normal Ca diet, related with the type and the number of crystals observed, demonstrating that assessment of crystalluria can provide an index of disease severity. Moreover, the hardness of the drinking water influences urinary COM crystal excretion only under a low-Ca, oxalate-rich diet, suggesting that the total calcium intake rather than the water calcium content is an important factor in the occurrence of Ca-Ox nephrolithiasis.

Animals

Prolonged survival after high-dose rate endobronchial radiation for malignant airway obstruction.

STUDY OBJECTIVE: To show that prolonged survival can be observed after high-dose rate (HDR) endobronchial brachytherapy as the sole treatment for some selected patients presenting with an endobronchial malignant obstruction. PATIENTS: Twenty-nine patients (group 1) who presented with an endoluminal localized tumor without metastatic extension were treated by HDR endobronchial brachytherapy and are compared with 22 subjects who presented with extraluminal dissemination and were palliatively treated (group 2). TREATMENT PROTOCOL: Treatment consisted of sessions of two exposures, delivering 7 Grays at a 10-mm radius from the center of the applicator each, and repeated every 15 days, to a maximum of six exposures. Endoscopic response and survival are the main criteria of assessment. RESULTS: Follow-up bronchoscopies, performed 2 months after the end of the procedure, showed tumor regressions: macroscopic complete responses (CR) were observed in 21 of 25 patients evaluable in group 1, and 6 of 22 in group 2, with histologic CR in 18 and 2 patients, respectively. Median overall survival was not reached in group 1 after 23 months of follow-up; it was 5 months for group 2. CONCLUSIONS: These results confirm that HDR brachytherapy can be used as a monotherapy for carefully selected patients who have small tumors to all appearances limited to the bronchial lumen and bronchial wall without adjacent parenchymal extension or metastatic disease.

Airway Obstruction

Methodological aspects of spontaneous crystalluria studies in calcium stone formers.

Despite nearly a half-century of study, the clinical value of spontaneous crystalluria (Cx) examinations in calcium stone formers (CaSF) is still uncertain. The analytical complexity of urine particle study is largely responsible for this situation. As a result, there is no consensus regarding technical methods in Cx with several techniques for urine sampling and three different instruments currently used for particle study, namely, particle counting (PC), light microscopy (LM) and petrographic microscopy (PM). In this work, we first examined urine sampling and instrument methods regarding their appropriateness for Cx studies. Then we performed a comparative analysis of Cx studies in CaSF. Despite many technical and clinical discrepancies, several studies agree that the frequency of "all particles" and of the weddellite and whewellite calcium oxalate (CaOx) crystalline phases are increased in CaSF as compared to normal subjects (NS). Particle sizes and aggregation ratio are also often increased. Altogether, these results reinforce the need for an efficient method for Cx studies in these patients. Examining each technique leads us to conclude that most particle parameters can be studied by "direct LM" observation of freshly voided urine samples, i.e., urine samples without any separation steps. For clinical applications, several examinations should be performed, first to define the specific Cx characteristics in a patient, then for the study of treatment efficiency on Cx control, and finally, during the patient follow-up. Due to Cx variability in each patient, the frequency of Cx examinations during each phase needs to be determined in longterm comparative prospective studies of CaSF.

Calcium

[Radio-chemotherapy combinations: from biology to clinics].

Combination of radiotherapy and chemotherapy (CRC) is actually one important way of research in oncology. Theoretical advantages are: 1) Spatial cooperation; 2) Additivity, which is only obtained if the toxicity of each modality are different; 3) Supra-additivity, which needs a rigorous in vitro definition; the only way to prove it is to make an isobologram analysis. This model has however, some limitations: qualitative variable could not be used, results could be different, depending on the cell line and isoeffect chosen... In fact, a supra-additivity was only demonstrated for cisplatinum and etoposide. Interactions mechanisms were: 1) at the molecular level, creation of new lesions or inhibition of radiation lesions repair; 2) At the cellular level, either cytokinetic cooperation with S-phase dependent drugs, or synchronisation for the drugs which blocked the cells in M-phase; 3) At the tissular level, reoxygenation, cycle redistribution... In clinical practice, three mains schedules have been described: sequential, alternating and concomitant. Only the latter try to use the supra-additivity phenomena. Aims of CRC could be: improvement or in survival or in local control, preservation of an functional organ... Depending on the tumor site and aim of the CRC, some schedules had to be preferred. For head and neck cancers, alternating or concomitant schedules offer a better local control. In bronchial carcinomas, sequential administration of the two modalities reduce the metastatic rate, but not the local control. Concomitant schedule improve the local control rate only. In some conservative protocol of bladder cancers, sequential and concomitant administration were used. In conclusion, CRC begins to be the usual clinical practice. The present schedules could be improved with the help of laboratory findings, which are now more and more precise.

Antineoplastic Agents

[Scopulariopsis brevicaulis otomycosis after tympanoplasty].

We report a case of otomycosis due to Scopulariopsis brevicaulis in a patient who has undergone tympanoplasty 3 months before. Mycological finding led us to consider this fungus as the causative agent. Whereas in vitro studies show a better efficiency of azole derivatives, cure was obtained with nystatine after two treatment failures in our patient.

Administration, Topical