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P Monnier

Publications and source records attributed to P Monnier.

At least 37 records · Page 2Linked to original sources

Localization of tetra(m-hydroxyphenyl)chlorin (Foscan) in human healthy tissues and squamous cell carcinomas of the upper aero-digestive tract, the esophagus and the bronchi: a fluorescence microscopy study.

To date, little is known about precise time-dependent distribution and histological localization of tetra(m-hydroxyphenyl)chlorin (mTHPC) in human healthy tissues and squamous cell malignancies in the upper aero-digestive tract. A fluorescence microscopy study was performed on 50 healthy tissue biopsies and on 13 tumors (graded from Tis to T1 SCC) from 30 patients. Tissue samples were taken between 4 h and 11 days following injection of 0.15 mg/kg mTHPC. A fairly comparable distribution pattern in various tissues was observed over time in different patients. Vascular localization of mTHPC fluorescence predominates at a short delay, whereas the dye is essentially located in the tumoral and healthy mucosa after longer delays. A much lower uptake and retention of mTHPC fluorescence was noted in striated muscle and cartilage as compared to neoplastic lesions. No significant selectivity was found between healthy and tumoral mucosa. The obtained data are important to confirm drug-light interval that have been selected for effective PDT for early SCC malignancies while minimizing the risks of over- or under-treatment. The low fluorescence level in striated muscle provides the opportunity to develop interstitial PDT as a treatment modality for invasive SCC of unfavorable locations in the oral cavity or pharynx, such as the base of the tongue.

Aged↗

Treatment of early stage squamous-cell carcinoma of the glottic larynx: endoscopic surgery or cricohyoidoepiglottopexy versus radiotherapy.

BACKGROUND: Both surgery and radiotherapy are recognized treatments of T1-T2 squamous cell carcinoma of the larynx. We retrospectively analyze and compare the oncological outcome of patients treated in a single institution, either by endoscopic surgery or partial supracricoid laryngectomy versus radiation therapy. METHODS: The medical records of 156 patients treated between 1983 and 1996 with either surgery (n = 75) or radiotherapy (n = 81) were reviewed. Male to female ratio, median age, and T-stage distribution were comparable. RESULTS: With a median follow-up time of 59 months, the 5-year cause-specific survival rate of 93% was identical for both groups. The actuarial incidence of metachronous second primaries was 7% at 5 years. Local control at 5 years remained 84% after surgery and 77% after radiotherapy. Anterior commissure infiltration was shown to represent a negative predictive factor of local control for radiotherapy (p =.01). Salvage treatment brought ultimate local control to 96% of patients after surgery and 94% after radiation therapy with long-term laryngeal preservation rate altered significantly (p =.05) in the group of patients who received radiotherapy (90.1% vs 97.4%). CONCLUSION: The treatment of laryngeal cancer is always a compromise between oncological efficiency and preservation of function. Our data suggest that, assuming proper selection of patients, radiation therapy and surgery yield similar local control and survival rates. The functional disadvantages after surgery are moderate and clearly counterbalanced by a significant decrease in long-term laryngeal preservation rate after radiotherapeutic treatment.

Carcinoma, Squamous Cell↗

2D and 3D CT imaging correlated to rigid endoscopy in complex laryngo-tracheal stenoses.

The aim of this study was to compare 2D and 3D CT imaging in the pre- and postoperative evaluation of complex benign larynges-tracheal airway stenoses with rigid endoscopy, considered as the gold standard. Six patients (aged 5-72 years) with a total of nine complex laryngo-tracheal stenoses underwent non-contrast helical CT scans (slice thickness 3 mm, pitch 1.3, reconstruction interval 1.5 mm) before and after surgical resection. With prototype software, virtual endoscopy (VE) post-processing algorithms were applied to the imaging data sets. The VE and multiplanar 2D findings were compared with rigid endoscopy, considered as standard of reference. All nine stenoses were correctly identified on 3D images and their anatomical locations correctly assessed on 2D reconstructions. Artifacts were met when patients were unable to suspend their breath, leading to one false-positive result. Two-dimensional images and 3D VE of tracheal stenoses proved to be efficient and complementary to the rigid endoscopy, permitting a reliable endoluminal 3D view and evaluation of the surrounding anatomical structures. Limitations of this technique relate to the maximal spatial resolution of 1.5 mm, the lack of color, and the inability to assess the mucosa. Virtual endoscopy is for complex laryngo-tracheal stenoses an excellent complement for rigid endoscopy, remaining the method of reference, and may be indicated with complicated pathological structures.

Adolescent↗

Uncertainty, attentional capacity and chromatic mechanisms in visual search.

Two general questions were investigated using a visual search task. First, we asked whether effects of target uncertainty on reaction time varied with the discriminability of the target and distractors. Second, a higher order chromatic mechanism model was tested against a flexible model in which the signals in cardinal color-opponent mechanisms are combined through an attentional process. The models were tested by measuring the effects of target uncertainty on search time. A regression analysis indicated that the magnitude of the uncertainty effect was approximately constant in logarithmic units as a function of the chromatic difference between the target and distractors. The constant magnitude of the uncertainty effect suggested that an attentional capacity limit was exceeded when observers were required to monitor several chromatic mechanisms at several locations. The results of experiments 3 and 4 suggested that search for chromatic targets among distractors was mediated by diagonally tuned higher order chromatic mechanisms, rather than by signals in cardinal color-opponent mechanisms that were combined through an attentional mechanism.

Adult↗

Set-size and chromatic uncertainty in an accuracy visual search task.

Thresholds for chromatic differences were measured in a simple visual search task in which the target differed from the distractors in chromaticity only. In Experiment 1, the spatial separation between stimulus elements was varied. Slopes of threshold versus set-size (2-16) for elements in close proximity were somewhat elevated, suggesting non-independence of the stimulus elements. In Experiment 2, chromatic uncertainty was introduced to increase the attentional load beyond that accomplished with the set-size manipulation. The results were accounted for by a model assuming no limit in attention capacity. Furthermore, chromatic uncertainty was successfully modeled as a simple increase in the number of monitored signals.

Adult↗

Evolution of DNA ploidy during squamous cell carcinogenesis in the esophagus.

Image and flow cytometry was used to study the nuclear DNA content (ploidy) during the squamous cell carcinogenesis in the esophagus. The present retrospective study comprised 26 surgical specimens of squamous cell carcinomas (SCC) in patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne, between January 1992 and December 1999. We analyzed 53 healthy tissues, 43 tumors, and six lymph node metastases. Diploid DNA histogram patterns were observed in all non-pathologic tissues analyzed, either distant or proximal to the lesion. Aneuploidy was observed in 30 (70%) of 43 lesions; 20 (62.5%) of 32 early squamous-cell carcinomas; and 10 (91%) of 11 advanced carcinomas. In patients with various tumor stages or with multicentric synchronous or metachronous tumors, DNA content was not different among different tumor stages. Four of six lymph node metastases had the same DNA content as the primary tumor. In four patients, discordance between image and flow cytometry analysis was observed for malignant lesions only. Ploidy status was not statistically associated with the differentiation of the tumor, but it was associated with the stage of tumor (P < 0.001). These findings suggest that early malignant changes in the esophagus are already associated with alteration in DNA content, and aneuploidy tends to correlate with progression to invasive SCC. This cell kinetic information could help clinicians in selecting the optimal treatment for the individual patient.

Aged↗

In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers.

We are developing an imaging system to detect pre-/early cancers in the tracheo-bronchial tree. Autofluorescence might be useful but many features remain suboptimal. We have studied the autofluorescence of human healthy, metaplastic and dysplastic/CIS bronchial tissue, covering excitation wavelengths from 350 to 480 nm. These measurements are performed with a spectrofluorometer whose distal end is designed to simulate the spectroscopic response of an imaging system using routine bronchoscopes. Our data provide information about the excitation and emission spectral ranges to be used in a dual range detection imaging system to maximize the tumor vs healthy and the tumor vs. inflammatory/metaplastic contrast in detecting pre-/early malignant lesions. We find that the excitation wavelengths yielding the highest contrasts are between 400 and 480 nm with a peak at 405 nm. We also find that the shape of the spectra of healthy tissue is similar to that of its inflammatory/metaplastic counterpart. Finally we find that, when the spectra are normalized, the region of divergence between the tumor and the nontumor spectra is consistently between 600 and 800 nm and that the transition wavelength between the two spectral regions is around 590 nm for all the spectra regardless of the excitation wavelength, thus suggesting that there might be one absorber or one fluorophore. The use of backscattered red light enhances the autofluorescence contrast.

Bronchi↗

Mitomycin C for control of recurrent bronchial stenosis: a case report.

A 27-year-old patient with cystic fibrosis underwent a bilateral lung transplantation despite the presence of multiresistant Burkholderia cepacia. Postoperatively, the patient presented with bilateral bronchial necrosis. During the 14th week, his FEV(1) dropped to 2.5 L from a baseline level of 3.4 L. A subtotal occlusion of the right mainstem bronchus below the suture was noted. Using argon electrocoagulation, the right upper lobe bronchus, the intermediate bronchus, and the right middle lobe bronchus were reopened. During the period between weeks 20 and 42 post-transplantation, a recurrent stenosis required eight endoscopic interventions combining dilatation and stenting. During the 42nd week, dilatation followed by mitomycin C application stabilized the right lung function. This case report is the first to describe the effectiveness of the local application of mitomycin C to stop recurring extensive bronchial stenosis following bronchial necrosis secondary to lung transplantation.

Administration, Topical↗

[Treatment of subglottis stenosis in children by cricotracheal resection].

Fifty-eight infants and children with a severe subglottic stenosis underwent a partial cricotracheal resection with primary thyrotracheal anastomosis. There were 2 grade II, 40 grade III, and 16 grade IV stenoses according to the Myer-Cotton classification. A 100% subglottic lumen was formed in 34 cases and a better than 80% lumen in 23 cases. Fifty-four of the 58 (93%) patients are presently decannulated; one patient sustained a complete restenosis and three patients with a better than 80% subglottic airway still await decannulation for the following reasons: severe tracheomalacia, bilateral cricoarytenoïd joint fixation and laryngeal malformation with fusion of the vocal cords in each case respectively. Forty-four patients have no exercise intolerance, 8 live fully normally but present a slight exertional dyspnea, one patient with a laryngeal malformation is decannulated but suffers from a severe exertional dyspnea, and 4 patients are still not decannulated. The voice is normal in 20 cases, a slight dysphonia is present in 17, a moderate to severe dysphonia in another 17 and 4 patients are still not decannulated.

Adolescent↗

Langerhans cell histiocytosis of the larynx.

A pediatric case of Langerhans cell histiocytosis leading to severe and recurrent subglottic stenosis, ultimately necessitating partial cricotracheal resection, is presented and the literature on this very rare disorder is briefly reviewed.

Biopsy, Needle↗

Esophageal cytology in the follow-up of patients with treated upper aerodigestive tract malignancies.

BACKGROUND: Patients with an history of carcinoma of the upper aerodigestive tract are at high risk for recurrence or the development of new tumors in this region. In the majority of follow-up protocols, these patients undergo radiologic and endoscopic evaluation as a means of surveillance for the early detection of recurrence. The brush biopsy-capsule technique represents a noninvasive and inexpensive screening device for this patient population. In the current study, the authors retrospectively assessed the sensitivity, specificity, and predictive value of esophageal brush-capsule cytology for the detection of malignant lesions of the upper aerodigestive tract in this high risk patient population. METHODS: Cytologic specimens from 334 patients with previously treated upper aerodigestive malignancies were available for review. The cytologic, endoscopic, and clinical follow-up of each case were studied over a follow-up period of 3 years. Gold standard was the clinical follow-up for the negative cases (who were not submitted to biopsy) and biopsy for the positive cases. Sensitivity, specificity, and predictive value were calculated. RESULTS: Using cytology 33 malignancies were detected in 25 patients during a 3-year follow-up period. The test was found to have a sensitivity of 88.7% and a specificity of 90.7%. In 66% of cases the malignancies were located in the oropharynx; the others were located in the esophagus. In 70% of cases the malignancies were detected at an early stage. CONCLUSIONS: Esophageal brush-capsule cytology is a simple noninvasive technique that has been proven to be useful in the early detection of metachronous and recurrent neoplasms in the follow-up of patients with previously treated carcinomas of the ear, nose, and throat.

Adult↗

Fluorescence pharmacokinetics of Lutetium Texaphyrin (PCI-0123, Lu-Tex) in the skin and in healthy and tumoral hamster cheek-pouch mucosa.

We have investigated the pharmacokinetics (PK) of Lutetium Texaphyrin (Lu-Tex), a second-generation photosensitizer, in the Syrian hamster cheek pouch early cancer model. Ten male hamsters, five with chemically induced early squamous cell cancer of the left cheek pouch, received an intracardiac injection of a 10 mg/ml Lu-Tex solution, resulting in a dose of 12 mg Lu-Tex per kg of bodyweight. The PK of the dye have been measured during the 24 h following the injection with an optical-fiber-based spectrofluorometer on the ventral skin, the healthy and the tumoral cheek-pouch mucosa. The Lu-Tex fluorescence is excited at 460 nm and detected around 740 nm. All the measurements yield very similar pharmacokinetic curves. The fluorescence intensity reaches a maximum between two and three hours after the injection and, at its maximum, it is consistently higher (up to 1.5 times) on the tumor than on the healthy mucosa. It remains smaller on the skin than on cheek-pouch mucosa. After 24 h, the Lu-Tex fluorescence is no longer detectable either on the skin, on the lesion or on the healthy mucosa. Moreover, Lu-Tex clearly displays a significant fluorescence selectivity between early carcinoma and healthy mucosa in this model. Furthermore, the inter-animal fluctuations of the fluorescence signal are small (+/-16% on the tumor-bearing mucosa). Eight-minute-long skin-irradiation tests have been performed 24 h after the injection of the Lu-Tex on the ventral skin of 16 additional animals with a solar simulator. No reaction is observed, either macroscopically or microscopically, which further demonstrates, as suggested by the fluorescence measurements, that this photosensitizer is significantly cleared from the skin after 24 h.

9,10-Dimethyl-1,2-benzanthracene↗

Pharmacokinetics and pharmacodynamics of tetra(m-hydroxyphenyl)chlorin in the hamster cheek pouch tumor model: comparison with clinical measurements.

The pharmacokinetics (PK) of the photosensitizer tetra(m-hydroxyphenyl)chlorin (mTHPC) was measured by optical fiber-based light-induced fluorescence spectroscopy (LIFS) in the normal and tumoral cheek pouch mucosa of 29 Golden Syrian hamsters with chemically induced squamous cell carcinoma. Similar measurements were carried out on the normal oral cavity mucosa of five patients up to 30 days after injection. The drug doses were between 0.15 and 0.3 mg per kg of body weight (mg/kg), and the mTHPC fluorescence in the tissue was excited at 420 nm. The PK in both human and hamster exhibited similar behavior although the PK in the hamster mucosa was slightly delayed in comparison with that of its human counterpart. The mTHPC fluorescence signal of the hamster mucosa was smaller than that of the human mucosa by a factor of about 3 for the same injected drug dose. A linear correlation was found between the fluorescence signal and the mTHPC dose in the range from 0.075 to 0.5 mg/kg at times between 8 and 96 h after injection. No significant selectivity in mTHPC fluorescence between the tumoral and normal mucosa of the hamsters was found at any of the applied conditions. The sensitivity of the normal and tumoral hamster cheek pouch mucosa to mTHPC photodynamic therapy as a function of the light dose was determined by light irradiation at 650 nm and 150 mW/cm2, 4 days after the injection of a drug dose of 0.15 mg/kg. These results were compared with irradiations of the normal oral and normal and tumoral bronchial mucosa of 37 patients under the same conditions. The reaction to PDT of both types of human mucosae was considerably stronger than that of the hamster cheek pouch mucosa. The sensitivity to PDT became comparable between hamster and human mucosa when the drug dose for the hamster was increased to 0.5 mg/kg. A significant therapeutic selectivity between the normal and neoplastic hamster cheek pouch was observed. Less selectivity was found following irradiations of normal mucosa and early carcinomas in the human bronchi. The pharmacodynamic behavior of mTHPC was determined by test irradiations of the normal mucosa of hamsters and patients between 6 h and 8 days after injection of 0.5 and 0.15 mg/kg in the hamsters and the patients, respectively. The normal hamster cheek pouch showed a maximum response to irradiation 6 h after injection and then decreased continuously to no observable reaction at 8 days after injection. The reaction of the normal human oral mucosa, however, showed an increasing sensitivity to the applied light between 6 h and 4 days after mTHPC injection and then decreased again at 8 days. The hamster model with the chemically induced early squamous cell cancer in the cheek pouch thus showed some similarity to the early squamous cell cancer of the human oral mucosa considering the PK. However, a quantitative difference in fluorescence signal for identical mTHPC doses as well as a significant difference in pharmacodynamic behavior were also observed. The suitability of this animal model for the optimization of PDT parameters in the clinic is therefore limited. Hence great care must be taken in screening new dyes for PDT of early squamous cell cancer of the upper aerodigestive tract based upon observables in the hamster cheek pouch model.

Animals↗

Supracricoid partial laryngectomy with cricohyoidoepiglottopexy and cricohyoidopexy for glottic and supraglottic carcinomas.

OBJECTIVES: To review the patients operated in our department with supracricoid partial laryngectomy with either cricohyoidoepiglottopexy (CHEP) (59 cases) or cricohyoidopexy (CHP) (10 cases) technique, for primary or recurrent glottosupraglottic squamous cell carcinoma and compare the technique with other surgical or conservative approaches for treatment of laryngeal carcinoma. METHODS: From hospital charts, we retrospectively reviewed 69 patients who had undergone supracricoid partial laryngectomy with the CHEP or CHP technique between 1983 and 1996 for primary or recurrent glottosupraglottic squamous cell carcinoma in our department. Statistical evaluation of oncological and functional results were conducted. Results were compared with other surgical and conservative treatment for glottosupraglottic carcinoma of the larynx that were published previously in the literature. RESULTS: Sixty-nine patients had CHEP or CHP for glottosupraglottic carcinoma of the larynx. Thirteen percent of the patients received adjuvant radiotherapy. Minimum follow-up was 2 years or until death. Five-year actuarial survival (Kaplan-Meier method) was 68%. Global local control was achieved in 84% of cases. Among previously untreated patients (n = 54), local control rate was 94.5%. After 1 year, 92.7% of patients achieved normal swallowing and respiration. Salvage total laryngectomy had to be performed in four patients (5.7%) for persistent aspiration and in five patients (7.2%), who were previously treated with radiotherapy, for local recurrence. No permanent tracheostomy or gastrostomy was required. CONCLUSIONS: Our experience with supracricoid partial laryngectomy with either CHP or CHEP suggests that this technique is a valuable alternative to radiotherapy for T2-T4 glottosupraglottic carcinomas, particularly those with extension and invasion of the anterior commissure. It allows for preservation of a good laryngeal function without altering the long-term survival, keeping total laryngectomy as a salvage procedure.

Adult↗

Food groups and oesophageal cancer risk in Vaud, Switzerland.

The influence of food groups on oesophageal cancer risk was analysed using data from a case-control study conducted between 1992 and 1999 in the Swiss Canton of Vaud on 101 incident, histologically confirmed cases (92 squamous cell, 9 adenocarcinomas) and 327 controls admitted to hospital for acute, non-neoplastic conditions. Multivariate odds ratios (OR) were computed after allowance for age, sex, tobacco, alcohol and non-alcohol energy. Significant increased risks emerged for red meat (OR = 1.7 for an increase of one serving per day), pork and processed meat (OR = 1.6), and eggs (OR = 1.5), whereas inverse associations were observed for milk (OR = 0.7), raw and cooked vegetables (OR = 0.5), citrus and other fruits (OR = 0.5), as well as for a more varied diet (OR = 0.5). Most associations were apparently stronger in heavy alcohol drinkers, suggesting an interaction between poor diet and alcohol drinking in oesophageal carcinogenesis.

Adult↗

Time-dependent biodistribution of tetra(m-hydroxyphenyl)chlorin and benzoporphyrin derivative monoacid ring A in the hamster model: comparative fluorescence microscopy study.

The pharmacokinetics of the photosensitizer used play a key role in the understanding of the mechanism of photodynamic therapy-induced damage. Fluorescence microscopy was used to compare time-dependent biodistribution of tetra(m-hydroxyphenyl)chlorin (mTHPC) and benzoporphyrin derivative monoacid ring A (BPD-MA) in different hamster tissues, including an early, chemically induced, squamous cell carcinoma. Following injection of 0.5 mg/kg body weight of mTHPC and 2.0 mg/kg BPD-MA, groups of three animals were sacrificed at different time points and a series of fluorescence micrographs from different excised organs were analyzed. The highest fluorescence intensities of mTHPC were observed at 96 h for squamous epithelia and skin and at 48 h for smooth muscle. There is no real peak of BPD-MA fluorescence between 30 min and 3 h in the basal epithelial layers, fibroconnective tissue, muscles or blood vessels. At 4 h after injection, the fluorescence level of BPD-MA decreased and at 24 h it had returned to background level in all observed tissues. The significantly faster clearance of BPD-MA is the principal advantage as compared to mTHPC. However, similar localization patterns in different tissues with essentially vascular affinity represent a possible disadvantage for treating early malignancies with BPD-MA as compared to mTHPC, which is mainly localized in various epithelia. For both photosensitizers no significant selectivity between early squamous cell carcinoma and healthy mucosae is seen. Pharmacokinetic studies of different photosensitizers in an appropriate animal model are essential for selecting new-generation photosensitizers with the most favorable localization for photodynamic therapy of early malignancies in hollow organs.

Animals↗

[Treatment of laryngeal cancer: cordectomy or crico-hyoido-epiglottopexy versus radiotherapy].

INTRODUCTION: Both radiotherapy and endoscopic or open functional surgery are recognised treatments for laryngeal cancer stage I and II. A comparison between two groups of patients treated with either modality may clarify the indications for both treatments. METHODS: Over a period of 13 years two separate series of patients were treated for laryngeal cancer (stage I and II) by either surgery (n = 72) or radiotherapy (n = 81). We have analysed and compared the two groups. RESULTS: Statistical analyses show a better local control among patients treated with surgery, when the anterior commissure was involved (p < 0.01) or with extension of the tumour (T2). However, long-term survivals were not significantly different in the two groups. As postradiation recurrence was diagnosed at an early stage, salvage (requiring total laryngectomy in many cases) was efficient but contributed to an appreciable difference in the long-term laryngeal preservation rate between the two groups (91% after radiotherapy and 99% after surgery). CONCLUSION: The treatment of laryngeal cancer must always compromise between oncological efficiency and functional preservation. With anterior commissure involvement (T1b) or more extensive disease (T2), surgery appears to be better. Therefore, preservation of perfect laryngeal function should be subordinate to oncological safety.

Carcinoma, Squamous Cell↗