Chondrosarcoma of the larynx: a report of two cases and a review of the literature.

Chondrosarcoma of the larynx: a report of two cases and a review of the literature. This paper describes two cases of low-grade laryngeal chondrosarcoma. In both cases, the tumours were located on the cricoid, and could be visualized with a CT scan and magnetic resonance imaging. The diagnosis was made by a deep wedge biopsy with a CO2 laser, and after subtotal supracricoid laryngectomy. Most of the reported cases have been successfully managed by voice-sparing surgery, but the two cases reported here, needed more radical treatment.

Testing health care professionals' communication skills: the usefulness of highly emotional standardized role-playing sessions with simulators.

Although standardized role-playing sessions (SRPS) with simulators are increasingly used to assess health care professionals' (HCPs) communication skills (CS) and the effectiveness of training workshops (TWs), nothing has been done to date to define the optimal emotional content of SRPS. Three emotionally different SRPS contexts-weakly emotional (WE-), moderately emotional (ME-), and highly emotional (HE-SRPS)-were, therefore, tested in order to assess induced CS and sensitivity to TW-related changes. The study included 25 HCPs. Tape-recorded SRPS, scheduled before and after the TW, were retranscribed, and assessed according to the Cancer Research Campaign Workshop Evaluation Manual (CRCWEM), which provides a rating of form, function and structure for each utterance. Results show that induced CS are different in WE-, ME-, and HE-SRPS, regarding form (HE-SRPS induced more 'directing', 'leading' or 'multiple' questions; WE: 20.7%; ME: 19.7%; HE: 33.7% (p<0.001)); function (HE-SRPS induced more 'inappropriate' information; WE: 6. 5%; ME: 8.2%; HE: 15.6% (p<0.001)); and blocking (HE-SRPS induced more 'blocking' utterances; WE: 7.2%; ME: 13.8%; HE: 30.2% (p<0. 0001)). Finally, CS changes induced by TWs are the highest in HE-SRPS (14.8% increase of 'open' questions for the HE- versus 1.0% for the WE-SRPS; 11.6% decrease of 'inappropriate' information for the HE- versus 3.3% for the WE-SRPS; and 17.5% decrease of 'blocking' for the HE- versus 2.6% for the WE-SRPS). In conclusion, SRPS, with a HE content, induce more inappropriate CS. Moreover, they are more sensitive to TW effects. SRPS with a HE content should, thus, be recommended for the assessment of TW effectiveness.

What are the immunologically active components of bacille Calmette-Guérin in therapy of superficial bladder cancer?

The subcomponents of bacille Calmette-Guérin (BCG) involved in the mechanism of action of intravesical BCG immunotherapy used for prophylaxis of superficial bladder cancer recurrences have been poorly investigated. We purified various BCG subcomponents and analyzed in vitro their ability to enhance a Th1 polarized immune response as well as to increase lymphocyte-mediated cytotoxicity against bladder tumors. Human peripheral blood mononuclear cells (PBMCs) from healthy purified protein derivative-positive subjects were incubated for 7 days with whole BCG and various fractions (BCG cell wall, plasma membrane, cytosol, purified polysaccharides as glucan or arabinomannan, purified native proteins from BCG culture filtrate, recombinant 22 kDa protein, phosphate transporter PstS-2 and -3 proteins). IFN-gamma, IL-12, IL-2, and IL-6 production by stimulated PBMCs was compared to unstimulated controls and the phenotype of expanded cells analyzed by flow cytometry (FACS analysis). A (51)Cr-release assay monitored the cytotoxicity of amplified effector cells against T24 bladder tumor cells. Live BCG and most of its subcomponents (with the exception of cytosol, PstS-2 and -3) significantly enhanced IFN-gamma and IL-12 secretion, expanded CD3(-)CD56(+) cells and the non-MHC-restricted cytotoxicity against bladder tumor cells compared to unstimulated controls (all P < 0.001, t-test). IL-2 receptor blockage resulted in a clear reduction in the cytotoxic activity of stimulated PBMCs. Numerous BCG subcomponents thus provide positive stimuli for Th1 cell differentiation and enhance in vitro, non-MHC-restricted cytotoxicity against bladder tumor cells. Our findings provide the basis for the therapeutic use of several of these subfractions in experimental animal models bearing bladder tumors.

Superficial bladder tumors and increased reactivity against mycobacterial antigens before bacillus Calmette-Guerin therapy.

PURPOSE: The precise mechanism of action of bacillus Calmette-Guerin (BCG) in bladder cancer treatment remains poorly understood. Whether bladder tumor cells are destroyed by nonspecific mechanisms or targeted by specifically activated lymphocytes recognizing cognate antigens is unclear. To investigate a possible cross-reactivity between BCG and bladder cell tumors, we tested before BCG treatment the lymphoproliferation of peripheral blood lymphocytes against several mycobacterial antigens, including the secreted fibronectin binding antigen 85 complex from BCG (AG 85) in patients with superficial bladder tumors compared to control matched patients. MATERIALS AND METHODS: Using a whole blood assay, T cell response against purified protein derivative, BCG extract, whole BCG, purified AG 85, and the nonspecific mitogens pokeweed and phytohemagglutinin was investigated in 79 patients with superficial bladder tumors before BCG and in 39 control subjects without malignancy matched for age and sex. Neither group had a history of tuberculosis. Lymphoproliferation was measured with a tritiated thymidine uptake assay on day 7 of culture. RESULTS: Of the 79 patients with superficial transitional cell carcinoma, a significant lymphoproliferative response before BCG against PPD, BCG extract, whole BCG and AG 85 was observed in 65 (82.2%), 67 (84.81%), 30 (37.97%) and 49 (62.02%) patients, respectively. Of the 39 controls only 26 (64.1%), 23 (58.9%), 3 (7.7%) and 3 (7.7%) patients, respectively, had a significant lymphoproliferation against PPD, BCG extract, BCG and AG 85 (p >0.05, p = 0.004, p = 0.00001 and p = 0.00001, respectively). In terms of lymphoproliferative levels, patients with superficial transitional cell carcinoma also showed a significantly higher response against PPD (p = 0.000012), BCG extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001) and pokeweed (p = 0.01) than controls but not against phytohemagglutinin. CONCLUSIONS: Patients with superficial transitional cell carcinoma demonstrate an increased lymphoproliferation against mycobacterial antigens before BCG compared to control subjects. Although a nonspecific activation of the immune system cannot be excluded at this stage, our data may suggest the possible existence of bladder cancer antigens cross-reactive with mycobacterial antigens responsible for boosting precursor cells witnessing previous contacts with mycobacteria. The implication of these findings in the antitumoral mechanism of action of BCG are under investigation.

Cross-reactive immune responses against Mycobacterium bovis BCG in mice infected with non-tuberculous mycobacteria belonging to the MAIS-Group.

Two bacillus Calmette-Guérin (BCG)-susceptible mouse strains, BALB/c and C57BL/6, were infected intravenously with Mycobacterium intracellulare, M. avium or M. scrofulaceum and monitored during 3 months for mycobacterial replication and antibody and Th1-type cytokine production in response to cytoplasmic and secreted antigens from M. bovis BCG. Whereas initial colony-forming unit (CFU) counts of M. intracellulare and M. avium were higher in lungs than in spleen, the opposite was observed for M. scrofulaceum. Mycobacterium intracellulare was the most virulent species and its replication could not be controlled in either mouse strain. It also induced the strongest antibody response. Mycobacterium avium was eliminated in both mouse strains and M. scrofulaceum finally was eliminated in C57BL/6 but multiplied in spleen from BALB/c mice. Significant sustained interleukin-2 and interferon-gamma production towards BCG antigens was only found in M. scrofulaceum infection. As in BCG-vaccination, M. scrofulaceum-infected C57BL/6 mice demonstrated a higher response towards whole BCG culture filtrate, BCG extract and purified antigen 85 complex (Ag85) from BCG than did BALB/c mice. The data suggest that the presence of M. scrofulaceum in the environment may possibly interfere in genetically predisposed subjects with BCG vaccine and its protective efficacy against M. tuberculosis.

[The need of prolonged BCG treatment in superficial bladder cancer is suggested by the development of a peripheral immune response induced by BCG]. / La nécessité d'un traitement prolongé par BCG dans les cancers superficiels de la vessie est suggérée par l'évolution de la réponse immunitaire périphérique induite par le BCG.

Optimal duration of immunotherapy treatment by BCG for the prevention of recurrences of superficial bladder cancer is still unknown. We have studied the evolution and duration of the cellular immunity response at the peripheral level after BCG intravesical instillations. Our results show that immunity activation after BCG is of short duration and don't take more than 6 months. Our results support, strengthen and partially allow to explain the utility of maintenance treatment by BCG following 6-weekly instillations.

Evolution and clinical significance of the T cell proliferative and cytokine response directed against the fibronectin binding antigen 85 complex of bacillus Calmette-Guerin during intravesical treatment of superficial bladder cancer.

PURPOSE: The antitumorigenic effect of intravesical bacillus Calmette-Guerin (BCG) in superficial bladder cancer was reported to be initiated by the attachment of BCG to the bladder wall via fibronectin. The antigen 85 complex secreted in BCG culture filtrate binds specifically to fibronectin and is a powerful T cell stimulus. Therefore, we investigated the evolution and clinical significance of the cellular proliferative response and cytokine production during intravesical BCG therapy against this purified antigen 85 complex. MATERIALS AND METHODS: Evolution of the lymphoproliferation, interleukin-2 and interferon-gamma production of peripheral blood lymphocytes against tuberculin (purified protein derivative), purified antigen 85, BCG culture filtrate, whole BCG bacilli and pokeweed mitogen was tested before and after 6 weekly intravesical BCG instillations in 29 patients with superficial bladder cancer at intermediate or high risk for recurrence. RESULTS: A major increase in the lymphoproliferative response against purified protein derivative, antigen 85, BCG culture filtrate, whole BCG and pokeweed mitogen was observed in 69.0, 65.5, 79.3, 48.3 and 65.3% of the patients, respectively, analyzed after BCG therapy. Reactivity returned to baseline values at 6 months of followup. Of the patients who received a second BCG course because of tumor recurrence 66% had a novel increase in lymphoproliferation against antigen 85. An increase in the production of interleukin-2 and interferon-gamma by peripheral lymphocytes against antigen 85 was noted in 42.1 and 50% of the treated patients, respectively, after a single BCG course. During a mean followup of 23.11 months 48.5% of the patients remained tumor-free. No correlation could be found between the immunological response against any of the BCG antigens and the clinical evolution of the response. CONCLUSIONS: Intravesical BCG instillations induce a transient (less than 6 months) peripheral immune activation against several purified BCG antigens and among them the fibronectin binding antigen 85 complex. Reactivation is observed in most cases after additional BCG courses. The absence of long lasting immune activation after a single 6-week course of BCG could be related to the increased clinical efficacy observed with BCG maintenance instillations.

Effects of chemotherapy on antibody levels directed against PGL-I and 85A and 85B protein antigens in lepromatous patients.

IgG antibodies against antigens 85A and 85B from Mycobacterium bovis BCG, IgM antibodies against phenolic glycolipid-I (PGL-I) and circulating PGL-I antigen were measured in the serum of 11 patients with lepromatous leprosy receiving multidrug therapy (MDT). Before treatment, 6 patients were reactive to antigen 85A, 10 patients to antigen 85B, and 11 patients to PGL-I; circulating PGL-I was detected in the sera of all of them. After 2 years of MDT PGL-I antigen could no longer be detected in all of the patients, except for two who were not compliant with treatment. IgG antibodies directed against the 85A and 85B antigens and IgM antibodies against the PGL-I antigen also decreased significantly during treatment but more slowly. The determination of circulating PGL-I antigen remains the most appropriate tool for monitoring lepromatous leprosy under MDT.

An isoelectric focusing method for the study of the humoral response against the antigen 85 complex of Mycobacterium bovis BCG in the different forms of leprosy.

Isoelectric focusing was used to separate the three components of the antigen 85 complex of Mycobacterium bovis BCG. Antibody responses of leprosy patients against each Mycobacterium bovis BCG. Antibody responses of leprosy patients against each component were quantitated by densitometric analysis of immunoblot assays. The 85A component was recognized by 40% (8/20) of the lepromin positive and negative healthy subjects, by 76% (19/25) of the tuberculoid and by 96% (24/25) of the lepromatous leprosy sera. In contrast, the 85B component was not stained by the control sera, nor by the tuberculoid leprosy sera but by 64% (16/25) of the lepromatous leprosy sera. The results suggest that antigen 85B contains one or several epitopes that are specifically recognized by sera of lepromatous leprosy patients only.

Humoral immune response of tuberculous patients against the three components of the Mycobacterium bovis BCG 85 complex separated by isoelectric focusing.

An isoelectric-focusing technique followed by Western blot (immunoblot) analysis was used to investigate the immunoglobulin G response of tuberculous patients against each of the three components of the Mycobacterium bovis BCG antigen 85 complex. The 85A component was stained by the tuberculous as well as the non-tuberculous sera. In contrast, the 85B and the 85C proteins of the complex were not stained by the control sera but were stained by 20 of 28 tuberculous serum samples.

Tympano-ossicular allografts following J. Marquet: the evaluation of a school.

The experience with 1.645 transplantation procedures by ENT surgeons, trained in tympano-ossicular allograft technique following J. Marquet, is reported. The grafts originated from different tissue banks. The anatomical and functional results one year postoperatively were analysed. There appeared to be no statistical differences between tissue banks, nor between surgeons. Contrary to the anatomical results, functional differences existed between allograft tympanoplasties and some types of allograft tympano-ossiculoplasties. It was concluded that the routine use of allograft tympano-ossiculoplasty offers a major tool in otological surgery and that it is the method of choice by the ENT surgeons trained by the School of J. Marquet.

A scanning electron-microscopic study of different tympanic grafts.

The surface architecture of dried temporalis fascia autografts and preserved tympanic allografts was investigated by scanning electronmicroscopy. During the storage in formaldehyde-cialit solutions the outer epithelial as well as the inner mucosal layer of tympanic allografts are progressively detached, and finally the lamina propria with outer radial and inner circular fiber arrangement remains. Due to dehydration phenomena irregular "crater-like" defects, surrounded by an amorphous structure, appear in dried fascia autografts. While a real lamina propria graft may induce migration and differentiation of the host's canal wall epithelium into a specific tympanic epithelium, one may imagine epithelial spreading toward the middle ear along the observed defects in dried fascia grafts. This latter observation gives new evidence for the immigration cholesteatoma theory.

[The Audiant Bone Conductor. Clinical experience in 2 patients]. / De Audiant bone conductor. Klinische ervaring bij twee patienten.

In this paper we present you our clinical experience of 2 cases in which we implanted the Audiant Bone Conductor (by J. Hough). Our conclusion is that we should be very careful in making the decision to do such an implant; indications and limitations should be known by every surgeon who intends to do an implant.

A scanning electron microscope study of preserved allograft tympanic membranes: a comparison with autogenous grafts, xenografts and the normal eardrum.

Scanning electron microscopy was used to investigate the surface architecture of the human tympanic membrane. The morphology of the eardrum was compared with the surface structures of preserved tympanic membranes (allografts), fresh air-dried temporalis fascia and preserved calf jugular veins (xenografts). The role of the physical structure and the composition of the extracellular matrix in the regeneration of a tympanic graft is discussed.

Congenital middle ear malformations.

After a profound review of normal embryology, a systematical and topographical classification of congenital middle ear malformations in general and of meatal atresia in particular is proposed; the classification of congenital aural atresia is essentially based on the recognition of two types according to the course of the facial nerve in its third segment: in type I, a normal topography of the facial nerve is found and consequently, the middle ear anomalies are rather minimal; in type II, an antero-superior displacement of the facial nerve in its third segment is recognized and the middle ear malformations are considerable worse. In this report, also attention is paid to syndromal nosology and its genetic aspects. In view of functional surgical; reconstruction, the technique of allograft canal surgery, similar to our combined approach tympanoplasty technique, is described in detail and compared with other classical techniques. Preoperative as well as postoperative problems and complications are extensively discussed. The excellent results of our technique are proposed even after 25 years of experience. An overview of cosmetic surgery techniques is given and also alternative techniques with implantable auditory prosthetic materials are summarized.

Tympanic grafts. An ultrastructural study.

Scanning electron microscopy (SEM) was used to investigate the surface architecture of human tympanic membranes. The morphology of the normal eardrum was compared with the surface structure of preserved tympanic membrane (allograft), fresh air-dried fascia temporalis and preserved calf jugular vein (xenograft). The role of the physical structure and composition of the extra-cellular matrix in the restoration of a tympanic graft is discussed.