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P Monnier

Publications and source records attributed to P Monnier.

At least 91 records · Page 5Linked to original sources
PubMed1996

Measurements by fluorescence microscopy of the time-dependent distribution of meso-tetra-hydroxyphenylchlorin in healthy tissues and chemically induced "early" squamous cell carcinoma of the Syrian hamster cheek pouch.

The influence of the time interval between dye administration and detection by fluorescence microscopy was assessed in "early" squamous cell carcinomas of the cheek pouch mucosa and different healthy tissues of the Syrian hamster. Following intracardiac injection of 0.15 mg (kg bodyweight)-1 of meso-tetra-hydroxyphenylchlorin (m-THPC), groups of three animals were sacrificed at different time intervals up to 30 days. A group of three non-injected animals was used to detect the endogene fluorescence of the corresponding normal tissues for autofluorescence subtraction. The following excised organs (oesophagus, trachea, liver, spleen, kidney, skin, striated muscle, healthy and tumoral cheek pouch mucosae) were fast frozen in liquid nitrogen and stored at -70 degrees C for fluorescence microscopy. The results show significant differences in the detectable m-THPC levels in different tissue layers (for instance, the epithelia and muscle of the oesophagus, trachea and cheek pouch) at different time intervals. These data indicate that pharmacokinetic studies may be useful for selecting the optimal time for the photodetection and phototherapy of cancer.

Animals↗
PubMed1996

7,12-dimethylbenz[a]anthracene-induced 'early' squamous cell carcinoma in the Golden Syrian hamster: evaluation of an animal model and comparison with 'early' forms of human squamous cell carcinoma in the upper aero-digestive tract.

To test and optimize photodynamic therapy of early cancers in the upper aero-digestive tract and oesophagus, we sought an appropriate animal model, which was found in the 7,12-dimethylbenz[a]anthracene-induced early squamous cell carcinoma in the Golden Syrian hamster. This chemically induced neoplasm is shown, by histology and immunohistochemistry, to pass through similar stages of early cancer development as its human counterpart. Its time sequence is highly reproducible, leading to a well differentiated carcinoma in situ and microinvasive carcinoma in the hamster cheek pouch over a period of 10 weeks.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Photodynamic therapy for cancer of the upper aerodigestive tract using tetra(m-hydroxyphenyl)chlorin.

A major step in the development of photodynamic therapy (PDT) is the clinical optimization and evaluation of new photosensitizers (PS). Ideally, new compounds should be more effective and/or induce fewer side effects than the first generation PS such as hematoporphyrin derivative and Photofrin. We report the results of our study of PDT applied in the human upper aerodigestive tract, using tetra(m-hydroxyphenyl)chlorin (mTHPC) as the photosensitizing drug. Twenty-seven patients with early (i.e., in situ or microinvasive) squamous cell carcinomas and 4 patients with T1 or T2 cancers were studied. In most cases, illumination of the tumor was performed 4 days after i.v. injection of 0.15 mg/kg of mTHPC using 652 or 514 nm laser light. Of the 36 early tumors evaluated 30 (83%) showed no recurrence after a mean disease-free follow-up of 15.3 months (3-35 months). Of the T1 and T2 cancers, only one achieved a complete response. Major complications, all following red light illuminations, included 1 bronchial stenosis, 1 esophagotracheal fistula, and 2 probable occult perforations of the esophagus. PDT in the esophagus with green light renders such perforations essentially impossible, without, however, reducing the efficacy of the treatment. Skin photosensitization, never observed later than the first week after injection, was seen in 12 patients. In conclusion, photodynamic therapy with mTHPC is a safe and effective technique for the treatment of early carcinomas of the upper aerodigestive tract. Its efficacy is much lower for more advanced cancers.

Adult↗
PubMed1996

Risk of transmission of human immunodeficiency virus infection during tympano-ossicular homograft: an experimental study.

It is generally agreed that middle ear reconstructive surgery performed with tympano-ossicular homografts produces superior functional results compared with prosthetic material, especially with respect to extrusion rate. The use of homografts, though, has been seriously hampered recently by the fear of transmission of human immunodeficiency virus (HIV) infection. In HIV-infected patients, the virus is primarily found in the cells of the lymphoid and monocytic lineage. The nature of the tissues in the eardrum and ossicles, mostly fibrous tissue and compact bone without marrow, suggests that little virus load should be found in homografts. Indeed, culturing minced homograft tissue from two HIV-infected donors with acquired immune deficiency syndrome (AIDS) in a sensitive culture system with PHA-stimulated lymphoblasts produced no virus. Before use, homografts undergo a fixation procedure in 5% formaldehyde and then are kept in a solution containing Cialit as a preservative. The authors therefore examined the capacity of formaldehyde and Cialit to reduce the infectivity of HIV in models of infected tissue as measured in vitro. The reduction of in vitro infectivity due to these treatments was at least 10(5)-fold and 10(2)-fold, respectively. Coupled with the low virus burden in tympano-ossicular tissue, our data suggests that the fixation procedure affords such a reduction in infectivity that the risk of HIV transmission, even from an HIV-infected donor, is vanishingly low.

Culture Techniques↗
PubMed1996

In vivo fluence rate effect in photodynamic therapy of early cancers with tetra(m-hydroxyphenyl)chlorin.

Several parameters affect clinical trials in photodynamic therapy and influence the therapeutic outcome. Beside drug dose, light dose, drug-light interval and other variables, the fluence rate is a parameter that can influence the therapeutic results. In this study we have evaluated the fluence rate effect with a second-generation photosensitizer, tetra(m-hydroxyphenyl)chlorin (mTHPC) using a 7,12-dimethylbenz(a)anthracene induced early squamous cell carcinoma of the Syrian hamster cheek pouch as a tumor model. Following injection of 0.5 mg/kg of mTHPC, irradiation tests were performed at two drug-light intervals, 4 and 8 days. Wavelength and light dose were adapted from those applied routinely in clinical trials. Irradiations at 652 nm were carried out with fluences ranging from 8 to 20 J/cm2 delivered at fluence rates of 15 and 150 mW/cm2. Similar tests were also performed at 514 nm with a fluence of 80 J/cm2 delivered at fluence rates ranging from 25 to 125 mW/cm2. At both wavelengths and drug-light intervals for a given fluence, the higher fluence rates resulted in less tissue damage in tumor and healthy mucosae. However, the lower fluence rates yielded slightly less therapeutic selectivity. This study confirms that the fluence rate is of major importance in clinical PDT.

Animals↗
PubMed1996

The use of the covered Wallstent for the palliative treatment of inoperable tracheobronchial cancers. A prospective, multicenter study.

STUDY OBJECTIVE: To investigate the safety, efficacy, and tolerance of the covered Wallstent for the palliative treatment of inoperable tracheobronchial cancer. DESIGN: An 8-month prospective study employing either a rigid bronchoscope or a flexible delivery system for prosthesis insertion. SETTING: Multicentric setting involving four teaching hospitals in Switzerland and Germany. PATIENTS: Forty patients (29 men, 11 women), average age of 62 years, presenting with an inoperable tracheobronchial cancer. INTERVENTIONS: After partial airway recanalization with an Nd-YAG laser, the covered Wallstent was inserted 23 times using a rigid bronchoscope (Rigidstep device), and 27 times using a flexible delivery system (Telestep device) under fluoroscopic and endoscopic visualization. RESULTS: Clinical and endoscopic examination at 1, 30, and 90 days showed improvement in the bronchial lumen and in the dyspnea index. No serious complication (death, perforation, hemorrhage, inability to remove an improperly placed prosthesis) was observed during surgery. Late complications included migration (12%), inflammatory granulations or tumor regrowth at the tip of the prosthesis (36%), and symptomatic retention of secretion (38%). CONCLUSIONS: Compared with other tracheobronchial prostheses, notably the Dumon stent, the covered Wallstent presents the following advantages: insertion with visual guidance, treatment of extrinsic compressions and esophagobronchial fistulas, and little chance of migration when the prosthesis diameter is chosen correctly. The following disadvantages can be noted: high price; both repositioning and extraction of the released stent are more difficult, though certainly possible; and risk of granulations at the tips of the prosthesis and retention of secretions. Suggestions are made for potential improvements to the stent and insertion system that may result in a significant decrease in early and late complications.

Adult↗
PubMed1996

[Indications and complications of free micro-flaps in ORL oncology].

Eighty-three free flaps were used to repair head and neck cancer defects between 1993 and 1995. The flaps used were 37 (44%) radial forearm flaps, 29 (35%) iliac crest flaps, 8 (10%) free jejunum flaps, 4 (5%) fibula flaps, 3 (3%) latissimus dorsi flaps and 2 (2%) rectus abdomini flaps. The indications for each flap are discussed. The flap loss rate was 4.8%, which led to reoperation with a new free flap in 3.6% of the cases. The other complications are discussed. Pre and post operative radiotherapy had no influence on the outcome of the free flaps. The mean duration of hospitalisation was 36 days. 78% of the patients who underwent a mandibular reconstruction were fitted with a fixed dental prosthesis and had normal mastication. 66% of the patients with oropharyngeal reconstruction had normal deglutition and 30% had a mixed diet. The acceptable complication rate, the good esthetic and functional results obtained with free flaps indicate that they should be used as a first choice technique in the reconstruction of head and neck cancer defects.

Adenocarcinoma↗
PubMed1995

Clinical pharmacokinetic studies of tetra(meta-hydroxyphenyl)chlorin in squamous cell carcinoma by fluorescence spectroscopy at 2 wavelengths.

To optimize photodynamic therapy (PDT) and photodetection of cancer with second-generation photosensitizers, knowledge of important variables such as the uptake of the dye and the dye contrast between normal and tumoral tissue after injection is necessary. The pharmacokinetics of a second-generation photosensitizer, tetra(meta-hydroxyphenyl)chlorin (mTHPC), is presented. To study this in a clinical context, an apparatus based on fluorescence spectroscopy and a noninvasive optical fiber probe has been used. The mTHPC fluorescence is induced at 2 excitation wavelengths (420 and 520 nm) with different penetration depth. The pharmacokinetics of mTHPC in patients with a squamous-cell carcinoma in the oral cavity show a signal selectivity as high as 16 about 3 hr after i.v. injection for the more advanced carcinomas. The magnitude of this selectivity appears to correlate with the staging of the cancer, the more invasive tumors showing the highest selectivity. Results obtained at 420 and 520 nm show little difference. These pharmacokinetics can be used directly for optimizing photodetection with mTHPC. However, complementary information on the localization of the drug by fluorescence microscopy, and a correlation of this data with tumor necrosis efficacy, are needed to optimize PDT timing.

Aged↗
PubMed1995

Clinical pharmacokinetic studies of photofrin by fluorescence spectroscopy in the oral cavity, the esophagus, and the bronchi.

BACKGROUND: To optimize photodynamic therapy (PDT) and photodetection of cancer, two important variables that must be considered are the uptake of the dye and the dye contrast between normal and neoplastic tissue after injection. METHODS: To study these variables in a clinical context, an apparatus based on a noninvasive optical fiber that detects the dye by light-induced fluorescence (LIF) was constructed. RESULTS: Studies on the pharmacokinetics of the fluorescent fraction of Photofrin in patients with early squamous cell carcinoma in the oral cavity, esophagus or bronchi show a signal contrast ranging from 1.5 to 3.5 a short time after intravenous injection that rapidly decreases and tends to unity (one) about 12 hours later. The magnitude of this contrast appears to correlate with the staging of the cancer, the more invasive tumors showing the highest contrast. The more invasive tumors also show the highest uptake. The oral cavity pharmacokinetics are similar to those found in the esophagus and the bronchi. CONCLUSIONS: The oral cavity appears to be a good model, with easy access for optimizing photodetection and PDT in the esophagus and the bronchi. These pharmacokinetics can be used directly for optimizing photodetection. However, complementary information on the detailed localization of the drug by fluorescence microscopy and a correlation of these data with tumor necrosis efficacy are necessary to optimize PDT timing and therapeutic gain.

Adult↗
PubMed1995

Cricotracheal resection for pediatric subglottic stenosis: update of the Lausanne experience.

Controversy still exists concerning the best treatment modality for severe (Cotton's grade III and IV) subglottic stenosis in infants and children. Although laryngotracheoplasty procedures remain the operation of choice in most centres, this series of 26 partial cricoid resections with primary thyrotracheal anastomoses show a decannulation rate of 96% (25/26 cases) after a single open procedure. Twenty-three patients practice sport freely without dyspnea, 2 show a slight exertional stridor and one teenager experienced a complete restenosis. The postoperative voice is normal in 18 (70%) and a slight residual dysphonia is present in 7 (27%). We encountered no lesion to the recurrent laryngeal nerves and no fatalities. In 10 cases, the tracheostoma site was resected during the same operative session. In the future, cricotracheal resection should be considered as an important, if not the best, treatment option for severe subglottic stenosis in infants and children.

Adolescent↗
PubMed1994

Percutaneous transtracheal jet ventilation for paediatric endoscopic laser treatment of laryngeal and subglottic lesions.

Percutaneous transtracheal high frequency jet ventilation (TTJV) in adults is frequently used during anaesthesia for laryngeal microsurgery. It provides excellent surgical operating conditions and safety for the patient. The technique has not been evaluated in infants and children. Accordingly, we studied 16 infants and children (mean age 5.5 +/- 3.8 yr, range 6 wk-12 yr) who underwent 28 consecutive endoscopic procedures with laser microsurgery of the glottic or subglottic space under general anaesthesia using a TTJV technique. All patients had a severe obstructive lesion of the larynx and/or upper trachea. The mean duration of the procedure was 70 +/- 27 min (range 30-140 min). Indications for TTJV were: subglottic stenosis: 5, haemangioma: 4, laryngeal papillomatosis: 5, pharyngeal cyst: 1, laryngomalacia: 1. Adequate control of the airway and satisfactory gas exchange were obtained in all cases. Surgery was performed without being impeded by anaesthetic equipment. Three complications occurred: one extensive surgical emphysema; one bilateral pneumothorax; one severe vagus-induced cardiovascular depression. Prompt and complete recovery without sequelae followed appropriate treatment. In 32% of the cases, the children were outpatients and in about half of the procedures (13/28) they left the hospital between the first and the third day. We conclude that percutaneous transtracheal jet ventilation is effective in paediatric endoscopic surgery. Procedures that might otherwise require a tracheostomy can be performed safely with this minimally invasive technique. Adequate indications and appropriate understanding of the technique and its potential problems are required for its correct application and successful use.

Airway Obstruction↗
PubMed1994

Rapidly alternating chemotherapy and hyperfractionated radiotherapy in the management of locally advanced head and neck carcinoma: four-year results of a phase I/II study.

PURPOSE: Treatment of locally advanced head and neck carcinoma by surgery and/or radiotherapy is associated with a high recurrence rate, poor survival, and, often, limitation in speech and swallowing functions. Because prolonged time of treatment might be detrimental for tumor control, we designed a study to develop a schedule of alternating radiotherapy and chemotherapy that should be administered over the shortest period of time and with the highest dose of radiotherapy as possible. PATIENTS AND METHODS: Following four successive steps of schedule modifications, regimens alternating split hyperfractionated radiotherapy (2.0 Gy/d times three over 30 to 40 days, to a total of 48 Gy to 60 Gy) and chemotherapy (cisplatin 80 to 100 mg/m2 and fluorouracil 1,000 mg/m2 by continuous infusion for 3 to 4 days, +/- vindesine 8 mg/m2 for two cycles) were administered in 91 patients with advanced squamous cell carcinoma of the head and neck. Adenectomy was performed for residual nodes and major surgery for progression only. RESULTS: The overall response rate was 95.6% (95% confidence interval [CI], 89.1 to 98.8), with 69.2% complete and 26.4% partial responses. Among partial responders, two patients were converted into complete responders by resection of a residual node. With a median follow-up duration of 45 months, distant mestastases occurred in 18% and a second primary tumor in 7.7% of patients. The median overall survival (OS) and progression-free survival (PFS) durations were 24 months and 17 months, respectively. At 4 years, the survival rate was 40%. All of the locoregional recurrences occurred within the first 15 months, in 14% and 73% of the complete and partial responders, respectively. Mucositis was the dose-limiting toxicity, with a World Health Organization (WHO) grade III and IV rate of 81% at a 60-Gy dose of radiotherapy, compared with 65% at 48 Gy or 54 Gy, which precluded further dose escalation. Leukopenia was severe in the first two steps of treatment, with WHO grade IV toxicity occurring in 41% of patients; however, this decreased to 10% when vindesine was deleted from the chemotherapy regimen in the last two steps. Late toxicity in 29% of patients was not different from that expected with radiotherapy alone. Among patients with resectable tumors, a 64% rate of organ preservation was obtained. CONCLUSION: We demonstrated that a full dose of hyperfractionated radiotherapy alternated with chemotherapy over 40 days could produce high antitumor activity. Mucositis was the dose-limiting toxicity, but this resolved completely within a median period of 6 weeks.

Adult↗
PubMed1994

[Primary cardiac lymphoma with obstructive cardiac insufficiency].

A 80 year old man, in general good health, presented with a rapidly progressive congestive heart failure, without response to treatment. At echocardiography, there were masses in the right atrium and ventricle. The patient deceased two months after the first clinical manifestations. At autopsy, we found a massive right-sided atrio-ventricular infiltration by a malignant non-Hodgkin's lymphoma of centroblastic type, causing a subtotal obstruction of the tricuspid and pulmonary valves. We observed also four intestinal metastases without other manifestations of lymphoma.

Aged↗
PubMed1994

[Magnetic resonance imaging and x-ray computed tomography in advanced cancer of the oral cavity. A comparative clinical, radiological and morphological study].

The objective of this prospective study is to assess the impact of magnetic resonance imaging (MRI) and computed tomography (CT) as compared to physical examination in the choice of type of surgery for advanced intraoral cancers (with or without resection of the mandibula). From 1990 to 1993, we operated on 21 intraoral malignant tumors with segmental resection of the mandibula followed by a histological examination. The preoperative evaluation consisted of an MRI (n = 8), a CT (n = 8) or both (n = 5). MRI suspected an infiltration of the bone in 9 cases, CT in 4 and physical examination in 16. This was histologically confirmed in 6 of the 21 patients only. MRI and CT both have a high sensitivity, as does physical examination, but neither have a good specificity (physical examination: 5 true positive, 4 true negative, 11 false positive, 1 false negative; MRI: 4 true positive, 4 true negative, 5 false positive, 0 false negative; CT: 3 true positive, 7 true negative, 3 false positive, 0 false negative). In conclusion, the decision of a mandibular resection can only be taken after a careful physical examination, including palpation under general anesthesia in a fully relaxed patient. This is best accomplished during the pretherapy bronchoesophagoscopy, routinely performed for the detection of synchronous second primary tumors using toluidin blue as a vital staining method. If this initial evaluation gives a suspicion of a massive infiltration of the mandible, an MRI, rather than a CT, should be performed to determine the extent of the resection because of a high rate of artefacts with CT.

Adult↗
PubMed1993

[Precancerous conditions of the esophagus].

In the upper aerodigestive tract, carcinogenesis in squamous cell mucosa is characterized by a tendency to field carcinogenesis leading to multicentricity of lesions and synchronous or metachronous multiple tumoral lesions, namely multifocality. During pretherapy broncho-esophagoscopy carried out on ENT-cancer patients, the rate of synchronous second primary cancer is 24%. In 85% of the cases, these second primaries are detected at an early stage (in situ, microinvasive or submucosal carcinoma) and do not give rise to symptoms. Early diagnosis of cancer of the upper aerodigestive tract is possible provided that high risk patients are recognized and screening endoscopy of the whole mucosa is performed in every high risk patient. On the other hand, squamous cell carcinoma and adenocarcinoma may occur with increased frequency in patients with esophageal lesions such as achalasia, caustic stenosis and Barrett's esophagus. The premalignant potential of these three entities is discussed.

Barrett Esophagus↗
PubMed1993

Comparison of results of intravenous infusion of anistreplase versus streptokinase in acute myocardial infarction.

This randomized study compares the coronary perfusion rate in patients with acute myocardial infarction (AMI) treated with 2 different intravenous thrombolytic agents: streptokinase 1.5 million U given over 60 minutes and anisoylated human plasminogen streptokinase activator complex (anistreplase) administrated as a bolus of 30 U over 5 minutes. One hundred seventy-five patients (149 men and 26 women, mean age 54 years) have been included in this study. Eighty-nine patients were treated with anistreplase and 86 patients with streptokinase. AMI was inferior in 54 patients (61%) in the anistreplase group and in 54 patients (63%) in the streptokinase group. It was anterior in 35 (40%) and 32 (37%) patients, respectively. Coronary angiography and ventriculography were performed at a mean time (+/- SEM) of 207 +/- 11 minutes after the beginning of thrombolysis in 170 patients. A perfusion score grade of 2 or 3 according to the Thrombolysis in Myocardial Infarction trial was found in 63 patients (72%) in the anistreplase group and in 56 patients (68%) in the streptokinase group (p = NS). Severe bleeding occurred in 7 patients (8%) after anistreplase and in 6 patients (7%) after streptokinase. No cerebral hemorrhage occurred. Nine patients (5%) died during their hospital stay: 6 after anistreplase and 3 after streptokinase. It is concluded that intravenous administration of anistreplase or streptokinase is efficient and safe. Coronary patency 207 minutes after fibrinolysis, incidence of adverse events and mortality are similar in both groups.

Adult↗