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P Monnier

Publications and source records attributed to P Monnier.

At least 73 records · Page 4Linked to original sources
PubMed1998

Photodynamic therapy of early squamous cell carcinomas of the esophagus: a review of 31 cases.

BACKGROUND AND STUDY AIMS: Patients with cancers of the head and neck have a strong tendency to develop early synchronous and metachronous carcinomas of the esophagus. In many of these patients, whose general condition is poor as a result of alcohol and tobacco abuse, the second primary cancers require minimally invasive treatment. The aims of this study were to evaluate the efficacy of photodynamic therapy for the treatment of early esophageal carcinomas and to compare the results obtained with three different photosensitizers (hematoporphyrin derivative), porfimer sodium (Photofrin II), and meta-(tetrahydroxyphenyl)chlorin (m-THPC). PATIENTS AND METHODS: Thirty-one early squamous cell carcinomas (Tis or T1a) of the esophagus were treated by photodynamic therapy in 24 patients. Nine tumors were treated with hematoporphyrin derivative, eight with Photofrin II and 14 with m-THPC. RESULTS: The early cancers were cured in 84% of patients after a mean follow-up period of 2 years. Because the number of cases included in each group was small, the differences in recurrence rates for the different photosensitizers could not be evaluated statistically, but m-THPC was more phototoxic, induced a shorter period of photosensitization of the skin, and had better selectivity than either of the other photosensitizers. There were four major complications: two stenoses and two esophagotracheal fistulas. CONCLUSIONS: Photodynamic therapy eradicates early squamous cell carcinomas (Tis and T1a) of the esophagus efficiently. Transmural necroses leading to fistulas can be avoided by using a low-penetrating wavelength of laser light (green light at 514.5 m instead of red light at 630 or 652 nm). Stenoses always result from circumferential irradiation of the esophageal wall, and this can be avoided by using a 180 degrees or 240 degrees windowed cylindrical light distributor.

Adult↗
PubMed1998

Partial cricotracheal resection for severe pediatric subglottic stenosis: update of the Lausanne experience.

Until recently, severe pediatric subglottic stenosis (SGS) has been treated almost exclusively by laryngotracheoplasty procedures. Even in the most experienced centers, the results of single-stage operations for Cotton's grade III and IV stenoses have been disappointing. This paper reports our experience on 31 partial cricotracheal resections for severe SGS in infants and children. The stenosis was congenital in 6 cases and acquired after prolonged intubation in 25 cases. Twenty-seven patients were tracheotomy-dependent at the time of surgery. Twenty-two cases were classified as grade III and 9 cases as grade IV stenoses according to Cotton. The decannulation rate was 97% (30 of 31 cases) after an open procedure. There were no fatalities and no lesions to the recurrent laryngeal nerves, but there was 1 complete restenosis. Twenty-seven patients show no exertional dyspnea, 3 have a slight stridor with some dyspnea while exercising, and 1 patient is not decannulated. The voice is normal in 21 cases, a dysphonia is present in 9 cases, and the patient with complete restenosis acquired an esophageal voice. Postoperative follow-up is longer than 10 years in 8 cases and longer than 5 years in an additional 6 cases. All patients who reached adulthood show normal growth of the larynx and trachea. Considering the excellent results obtained in this consecutive series of 31 cases, partial cricoid resection with primary thyrotracheal anastomosis should be considered an important treatment option for severe SGS in infants and children.

Anastomosis, Surgical↗
PubMed1998

Pharmacokinetics of tetra(m-hydroxyphenyl)chlorin in human plasma and individualized light dosimetry in photodynamic therapy.

The pharmacokinetics of the photosensitizer 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC) was investigated in the plasma of 20 patients by absorption and fluorescence spectroscopy. The temporal behavior was characterized by a rapid decrease in concentration during the first minutes after intravenous injection of 0.15 mg/kg mTHPC. A minimum concentration in the plasma was reached after about 45 min. The drug concentration then increased again, attaining a maximum after about 10 h, after which it decreased again with a halflife of about 30 h. Irradiation tests in the oral cavity at different time intervals after the injection revealed that the tissue reaction was only partially correlated with the mTHPC plasma level. The tissue response was stronger at later drug-light intervals (1-4 days) than during the first hours after injection even though the mTHPC plasma concentration was higher at the shorter times. Relative mTHPC concentrations were also measured in the mucosae of the oral cavity, the esophagus and the bronchi of 27 patients by light-induced fluorescence spectroscopy using an optical fiber-based spectrometer. These measurements were performed prior to photodynamic therapy (PDT), 4 days after injection of the photosensitizer. Highly significant linear correlations were found between the relative mTHPC concentrations in the mucosae of these three organs. Likewise, the plasma levels of mTHPC measured just before PDT were significantly correlated with the mTHPC concentrations in the three types of mucosae mentioned above. These results indicate that mTHPC plasma levels measured just before PDT can be used for PDT light dosimetry.

Dose-Response Relationship, Radiation↗
PubMed1998

Clinical evaluation of the cutaneous phototoxicity of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin.

The cutaneous phototoxic reaction induced by intravenous injection of 5,-10,-15,-20-tetra(m-hydroxyphenyl)chlorin (mTHPC) has been clinically evaluated in patients undergoing photodynamic therapy. These tests were performed on the backs of 23 patients with a solar simulator at various times after drug administration ranging from 5 h to 57 days. The mTHPC doses ranged from 0.1 to 0.3 mg/kg, and the illuminations lasted from 30 s up to 8 min. These tests have shown that the duration of the skin photosensitization induced after a typical therapeutic dose of mTHPC (0.15 mg/kg) is less important than with Photofrin (2 mg/kg). The level of mTHPC in the skin was also assessed in vivo and at times corresponding to the irradiations using an optical fiber-based spectrofluorometer. This study indicates that the light-induced fluorescence spectroscopy of mTHPC enables prediction of the degree of photosensitivity of the skin.

Dose-Response Relationship, Drug↗
PubMed1998

[Endonasal sequelae after hypophysectomy].

Each year, 15 transvestibular transseptal transsphenoidal hypophysectomies are performed in Lausanne. The aim of the study was to determine the complications rate of our procedure and their influence on the life quality of patients. Questionnaires were sent to 178 patients, operated between 1984 and 1995. 125 questionnaires were returned. Out of those, 73 patients accepted to undergo a control rhinoscopy. The most frequent complains were nasal obstruction and crusting (38% each), whistling while breathing through the nose (12%), and stuffiness of the upper lip or teeth (7%). Endoscopically, we detected an anterior septal perforation in 10 cases (13.7%), 8 (80%) of which were symptomatic and a posterior septal perforation in 6 cases, all of them being asymptomatic. Finally, 36% of the patients had no complains and 19% of them had an improvement of respiration after the operation. Of the whole series of 178 patients, only 5% had complications requiring an ENT follow-up for longer than 6 months after having been operated.

Adolescent↗
PubMed1998

The role of acoustic rhinometry in the pre- and postoperative evaluation of surgery for nasal obstruction.

This is a prospective study evaluating the role of acoustic rhinometry (AR) in the measurement of nasal patency before and after surgery for nasal obstruction. We examined 27 patients before and 2 to 6 months after septoplasty associated with turbinoplasty, cauterisation of the inferior turbinates, rhinoplasty or uvulopalatopharyngoplasty in some cases. Surgery was performed for subjective nasal obstruction and indication based on symptoms and clinical findings. AR was performed after indication was made. Patients were evaluated for this study by marking subjective global nasal obstruction on a visual analogue scale and by AR before and after decongestion. All patients noted an improvement of subjective nasal patency after surgery. Mean unilateral minimal cross-sectional area (MCA) of the preoperatively narrower side and total MCA both increased but showed wide ranges with also negative results. The total volume of the nasal fossae did not increase. The volume of the preoperatively narrower nasal fossa increased with surgery, but there are enormous ranges. We could not find any correlation between the MCA of the preoperatively narrower side or the total MCA and subjective nasal patency, neither before nor after surgery. The same was the case for the volume of the nasal fossae. In our opinion AR is not a valuable method for the indication or evaluation of surgery for nasal obstruction.

Acoustics↗
PubMed1997

Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract.

Field cancerisation of the aerodigestive tract is caused by chronic exposure to alcohol and tobacco, but the nature of the genetic alterations preceding overt malignancy is unknown. To identify potential field changes we have used a functional assay which tests the transcriptional competence of human p53 expressed in yeast. To increase the sensitivity and reliability of the technique for samples containing under 20% mutant p53, the 5' and 3'-ends of the p53 cDNA were examined separately. With this split form of the assay the tissue p53 mRNA acts as its own control for RNA quality. Mutations were detected in 87% (46/53) of tumours, reflecting the high sensitivity of the technique. Multiple biopsies of histologically normal tissue from the upper aero-digestive tract were tested and clonal p53 mutations were identified in 76% (38/50) of biopsies from patients presenting with multiple tumours compared with 32% (38/117) of biopsies from patients presenting with single tumours (P<0.000001). All patients (16/16) presenting with multiple tumours had at least one positive biopsy, compared with only 53% (19/36) of patients presenting with single tumours (P <0.001). This defines expansion of multiple clones of mutant p53-containing cells as an important biological mechanism of field cancerisation, and provides a means to identify patients likely to benefit from intensive screening for the development of new head and neck tumours.

Adult↗
PubMed1997

Photodynamic therapy for early squamous cell carcinomas of the esophagus, bronchi, and mouth with m-tetra (hydroxyphenyl) chlorin.

OBJECTIVE: To clinically evaluate a new photosensitizer, m-tetra(hydroxyphenyl) chlorin (m-THPC), for the photodynamic therapy of early squamous cell carcinomas of the upper aerodigestive tract. DESIGN: Phase 1 included evaluation of the innocuousness of the compound after intravenous injection (control of vital parameters and blood analysis before and after injection) and evaluation of the duration of skin photosensitization. Phase 2 included assessment of optimal conditions for treatment (injected dose, drug-light interval, light dose, wavelength, etc), on 33 early squamous cell carcinomas of the mouth, esophagus, and bronchi, with a mean follow-up of 14 months; irradiation tests on healthy and neoplastic mucosae to determine the irradiation conditions that lead to tumor eradication with minimal damage to the surrounding normal mucosa and muscle layers; and localization of the dye in various tissue compartments and cells at different time intervals after the injection of the photosensitizer, by using a fluorescence microscope to analyze 46 biopsy specimens taken during the treatment sessions and 8 resected specimens of early cancers, excised with the carbon dioxide laser. SETTING: Endoscopic medical center of an otolaryngology-head and neck surgery department. PATIENTS: Twenty-five patients treated previously for a head and neck cancer with a synchronous or metachronous early second primary cancer. Patients with porphyria were excluded from the trial. RESULTS: The best results in the bronchi and mouth were obtained with an injected dose of 0.15 mg of m-THPC per kilogram of body weight 4 days before irradiation. The fluence was 7 to 16 J/cm2, and the fluence rate was between 100 and 150 mW/cm2 using red light at 652 nm. In the esophagus, green light at 514 nm is preferred to the red light to avoid fistulas. Optimal irradiation conditions at this wavelength, which was also used in the trachea, were found at a fluence of 75 to 100 J/cm2 and a fluence rate between 70 and 100 mW/cm2. Of 33 lesions treated thus far by photodynamic therapy with m-THPC, 28 show no recurrence with a mean follow-up of 14 months. Photosensitivity to sunlight does not exceed 6 weeks. CONCLUSIONS: m-Tetra(hydroxyphenyl) chlorin is a second-generation photosensitizer that has several significant advantages as compared with the first-generation porphyrin mixtures hematoporphyrin derivative and porfimer sodium (Photofrin II). It is a pure compound that is 100 times more phototoxic at 652 nm and 10 times more photoxic at 514 nm, has better selectivity for early carcinomas, and a shorter duration of skin photosensitivity. The therapeutic results indicate a recurrence rate that is similar to that obtained with Photofrin II, ie, about 15%.

Antineoplastic Agents↗
PubMed1997

Light dosimetry for photodynamic therapy in the esophagus.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is an efficient technique to treat superficial early cancers in the pharynx, esophagus, and tracheo-bronchial tree. However, the lack of selectivity of some of the clinically used photosensitizers can result in significant damage to the healthy tissue during the treatment. In the esophagus, this may lead to medical complications such as stenosis and fistula. Insufficient selectivity may be compensated to some extent by accurate light dosimetry. Here, we present an approach to safer and more efficient PDT by improved light dosimetry in the esophagus. STUDY DESIGN/MATERIALS AND METHODS: This includes the utilization of a suitable light distributor, the estimation of the radiant energy density in the tissue, and the knowledge of the esophagus morphology. The light distributor presently used in the clinic is described and several techniques to study light propagation in the esophageal wall have been investigated and are discussed. Thickness of different histological layers of the esophageal wall have been measured ex vivo and are presented. RESULTS: Under these conditions and based on a simple model of the light distribution in the tissue, some basic and clinically useful notions of light dosimetry can be drawn. These notions, associated with measured value of tissue optical properties at the wavelengths of interest with the presently used photosensitizers, are discussed regarding the particular morphology of the esophageal wall. In particular, the importance of the illumination wavelength from the safety point of view is shown. CONCLUSION: The proposed approach allows for improved safety and efficacy of PDT in the esophagus, particularly in the clinical tests of new photosensitizers.

Esophagus↗
PubMed1997

Three-dimensional optical phantom and its application in photodynamic therapy.

BACKGROUND AND OBJECTIVE: A technique to manufacture a stable, reproducible three-dimensional optical phantom is presented. This phantom reproduces the tissue's optical properties as well as the geometry and, to some extent, the mechanical properties of the organ concerned. Easy to make and to handle, this phantom is a useful tool for numerous medical applications involving light interaction with biological tissues. STUDY DESIGN/MATERIALS AND METHODS: The phantom is based on a transparent two-component silicone, which is molded into the desired shape and cured at room temperature. Specific optical properties are obtained by adding scatterers (Al2O3 particles or polystyrene microspheres) and absorbers (dyes or pigments). A method to measure the radiant energy fluence rate in the phantom is described. This method is based on a small isotropic optical detector. RESULTS: A three-dimensional phantom of the bronchial tree is presented. This phantom is used for testing new light distributors designed for photodynamic therapy of the bronchi. CONCLUSION: The proposed technique allows one to produce a stable three-dimensional phantom with accurately predictable optical properties.

Equipment Design↗
PubMed1997

Anaesthesia for tracheal resection: report of 17 cases.

PURPOSE: Laryngo-tracheal stenosis remains a major complication after prolonged intubation or tracheostomy. Surgical resection with end-to-end anastomosis carries the best long term prognosis. For the anaesthetist, however, this procedure represents a most challenging situation. METHODS: Since 1993, we have used high frequency jet ventilation (HFJV) for tracheal resection. This paper describes the technique and the results of our series including 7 adults and 10 children. RESULTS: There were no adverse haemodynamic or ventilatory consequences due to HFJV. Oxygenation was well maintained during the HFJV period. Sixteen of the 17 patients had a good outcome. Despite the good result of the resection-anastomosis, one child still suffers from an associated posterior glottic stenosis. CONCLUSION: Since the introduction of HFJV for surgery of tracheal stenosis in our institution no complication of this ventilatory technique has occurred. It reduces the manipulation of the ventilation system and the period of apnea, thus decreasing the risk of hypoxaemia. The good access to the surgical field contributes to the success of resection-anastomoses in laryngo-tracheal stenosis.

Adult↗
PubMed1997

Production of the free radicals O2.- and .OH by irradiation of the photosensitizer zinc(II) phthalocyanine.

Zinc(II) phthalocyanine (ZnPC) is a new photosensitizer currently undergoing phase I and II clinical trials at Lausanne's CHUV hospital for the photodynamic therapy (PDT) of early cancer in the upper aerodigestive tract. Activated oxygen species other than singlet oxygen produced during the photosensitization of ZnPC in liposomes have been examined by electron paramagnetic resonance (EPR) spin trapping and by the cytochrome c reduction method. Visible light irradiation of ZnPC associated with liposomes in the presence of the spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) gives an EPR spectrum characteristic of the DMPO-hydroperoxyl radical spin adduct (DMPO-.OOH). Superoxide anion attains a level of 1 microM min-1 20 min after the start of irradiation as determined by the superoxide dismutase (SOD)-inhibitable reduction of cytochrome c. The yield of O2.- is strongly enhanced by physiological electron donors. An EPR spectrum characteristic of the DMPO-hydroxyl radical spin adduct (DMPO-.OH) is also observed. The addition of dimethyl sulphoxide or ethanol produces additional hyperfine splittings due to the respective hydroxyalkyl radical products, indicating the presence of free .OH. DMPO-.OH is significantly inhibited by desferrioxamine or catalase. Conversely, this adduct is enhanced by hydrogen peroxide. These data demonstrate the ability of ZnPC in liposomes to photoreact effectively by an electron transfer mechanism. Such type I processes may add to the effects of singlet oxygen in ZnPC-mediated PDT.

Cyclic N-Oxides↗
PubMed1997

Photodynamic therapy of early squamous cell carcinoma with tetra(m-hydroxyphenyl)chlorin: optimal drug-light interval.

The optimal drug-light interval for effective photodynamic therapy (PDT) of early squamous cell carcinomas was evaluated with tetra(m-hydroxyphenyl)chlorin (mTHPC) by means of two complementary modalities: irradiation tests and ex vivo fluorescence microscopy. A Syrian hamster cheek pouch tumour model was used in these experiments. Photodynamic therapy on both tumour-bearing and contralateral healthy cheek pouch mucosae was performed at 650 nm and 514 nm. Light doses of 12 J cm(-2) were delivered at a light dose rate of 150 mW cm(-2) and light doses of 80 J cm(-2) were delivered at a light dose rate of 100 mW cm(-2) respectively, at these two wavelengths, between 6 h and 12 days after the injection of 0.5 mg kg(-1) body weight mTHPC. Two histologically different types of tissue damage were observed: first, a non-selective and non-specific ischaemic vascular necrosis for the cases in which PDT took place during the first 48 h after the injection of the dye and, second, tissue-specific PDT damage, as a coagulation necrosis, when PDT took place more than 72 h after injection of the dye. The time-dependent biodistribution of mTHPC investigated by fluorescence microscopy shows a weak and non-significant difference in relative fluorescence intensities between early SCC and healthy mucosae. Up to 2 days after the injection, the drug is mainly localized in the endothelial cells of the blood vessels. After this period, the dye accumulates in the squamous epithelia with a concentration peaking at 4 days. At all time points, a weak fluorescence intensity is observed in the underlying lamina propria and striated muscle. The information obtained from these studies could well be relevant to clinical trials as it suggests that time delays between 4 and 8 days after i.v. injection should be optimal for PDT of early malignancies in hollow organs.

Animals↗
PubMed1997

[The current status of broncho-esophagoscopy in otorhinolaryngology].

Most bronchoscopies and esophagoscopies are currently performed with flexible instruments by the respective specialist. Thus the field of bronchoesophagology is in danger of being fragmented; neither the pneumologist nor the gastroenterologist have the complete overview of the upper respiratory and digestive tract. This review shows that number of pathologic conditions in the ENT area and the mediastinum involve the upper respiratory as well as the digestive tract, and thus underscore the need for combined tracheobronchial and esophageal endoscopy. Mastering of rigid and flexible endoscopy is mandatory to be efficient in diagnostic and therapeutic broncho-esophagoscopy. The ENT specialist is in the best position to maintain an overview of this whole field. New developments in broncho-esophagoscopy are presented and discussed in terms of cost effectiveness.

Anesthesia↗
PubMed1997

Evaluation of the bone resistance of the sphenoid and ethmoid sinuses.

Functional endoscopic sinus surgery can be associated with iatrogenic complications. Some anatomical structures have been identified this clinically as specific danger sites. The aim of this study was to confirm and to compare these clinical data with measurements of the bone resistance of the sphenoid and ethmoid walls and to point out regions that have increased bony fragility. Critical dynamometric evaluation of the resistance to breakage of these bony structures was made on 21 anatomic specimens. This study allowed the authors to localization of surgical complications, to demonstrate that other regions renowned for their fragility can be relatively robust, and to point out that robust sites can be dangerously fragile as a result of individual morphological variations. Results from this study provide a supplement to the guidelines for novice surgeons to use in identifying dangerous areas.

Endoscopy↗
PubMed1996

Improvement of a polymerase chain reaction assay for the detection of Echinococcus multilocularis DNA in faecal samples of foxes.

A polymerase chain reaction (PCR) method was developed in order to permit a sensitive and specific identification of Echinococcus multilocularis DNA from fox faecal specimens. In an attempt to overcome problems related to the presence of endogenous PCR inhibitors in faecal extracts, we investigated a DNA extraction technique using an anion binding resin (Gene-Fizz). This simple and rapid procedure was applied to 61 faecal samples. Compared with the traditional microscopic examination, the sensitivity of PCR using Gene-Fizz was 82.3% and the specificity was 95.5%. No PCR signal was obtained for 20 Echinococcus granulosus isolates, showing that this method allowed discrimination between E. multilocularis and E. granulosus. Large-scale epidemiological surveys of fox excrements may be possible by using Gene-Fizz treatment prior to PCR amplification reactions.

Animals↗
PubMed1996

Optimizing light dosimetry in photodynamic therapy of early stage carcinomas of the esophagus using fluorescence spectroscopy.

BACKGROUND AND OBJECTIVE: Under standardized conditions (drug and light dose, timing), the result of the photodynamic therapy (PDT) of carcinomas of the esophagus with tetra(meta-hydroxyphenyl)chlorin (mTHPC) shows large variations between patients. STUDY DESIGN/MATERIALS AND METHODS: Before patients underwent PDT treatment, the mTHPC level was measured in the lesion, the normal surrounding tissue, and the oral cavity, with an apparatus based on fluorescence spectroscopy. RESULTS: The fluctuations in degree of tumor destruction between patients can be explained by individual variations in the mTHPC level in the mucosa of the esophagus. The patients showing the highest mTHPC fluorescence signal had also the highest response to PDT. Also, a correlation between the mTHPC level in the oral cavity and esophagus mucosa has been found. CONCLUSION: PDT can be improved by measuring the mTHPC level in the esophagus or the oral cavity before treatment by fluorescence spectroscopy, and then by adjusting the light dose to be applied to the observed mTHPC level.

Antineoplastic Agents↗