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Biomedical subjects

P Monnier

Publications and source records attributed to P Monnier.

At least 55 records · Page 3Linked to original sources

[Impact of diagnosis and treatment of early stage secondary tumors on outcome for the oncologic ORL patient].

OBJECTIVE: To study the incidence, location and stage of second primary tumours in patients with head and neck cancer and analyse the survival and outcome of patients with early-stage second primary tumours. METHODS: Retrospective chart review of patients treated for head and neck cancer from 1989 to 1993. Survival analyses and statistical comparisons with the Kaplan-Meier method and log-rank test. RESULTS: 99 of the 311 patients had second primary tumours. 45 patients had synchronous second primary tumours and 54 metachronous second primary tumours, diagnosed at an early stage (stage 0 or I) in 78 and 63% of cases respectively. Patients with second primary tumours had a significantly (p = 0.03) lower survival rate than patients with single tumour. However, for patients with early stage second primary tumours survival was not significantly decreased (p = 0.3). DISCUSSION: This study confirms the high incidence of second primary tumours and their negative impact on the outcome of patients with head and neck cancer. Early diagnosis and treatment of second primary tumours results in a survival rate very similar to that of patients with a single head and neck cancer. This provides indirect evidence that in patients with curable initial head and neck cancer intensive screening for second primary tumours may result in an improved overall outcome.

Adult↗

Photodynamic therapy of early squamous cell cancers of the esophagus.

The conventional treatment for the cure of esophageal cancer is surgical resection. Esophageal cancer, when detected at an early stage, has a very good probability of being eradicated by less aggressive procedures, and photodynamic therapy has proven to be a safe and effective treatment modality in some carefully selected patients. The indications, outcomes, and future considerations regarding the use of photodynamic therapy for the treatment of superficial squamous cell carcinomas of the esophagus are discussed in this article.

Aminolevulinic Acid↗

Cricotracheal resection for pediatric subglottic stenosis.

Until recently, cricotracheal resection (CTR) has not been commonly accepted as a treatment modality for severe subglottic stenosis in the pediatric age group. The reasons have included the risk of a possible dehiscence at the site of the anastomosis, the likelihood of injury to the recurrent laryngeal nerves, and the interference with normal growth of the larynx. Thirty-eight infants and children with a severe subglottic stenosis underwent a partial cricoid resection with primary thyrotracheal anastomosis. Thirty-three patients were tracheotomy-dependent at the time of surgery and 34 were referred cases; 27 were classified as grade III, and 10 as grade IV stenoses according to new Cotton's classification. Nineteen patients were younger than 3 years of age at the time of surgery. The tracheotomy was resected during the surgical procedure in 21 cases. Decannulation was achieved in 36/38 cases after an open procedure. There is one complete restenosis and one good result awaiting decannulation after further surgery for a Pierre Robin syndrome. The authors experienced no lesion of the recurrent laryngeal nerves and no fatality. Thirty-one patients show no exertional dyspnea, three a slight stridor while exercising, and two patients are not decannulated. The postoperative follow-up in longer than 10 years in eight cases. All patients show a normal growth of the larynx and trachea. Compared to laryngotracheoplasties, CTR gives better results for severe subglottic stenosis. This operation should become the treatment of choice for severe (grade III and IV) subglottic stenosis in infants and children.

Child↗

Necrotizing otitis externa caused by Staphylococcus epidermidis.

We present a case of malignant necrotizing otitis externa (MNOE) caused by Staphylococcus epidermidis, which is usually a non-pathogenic microorganism. The patient is an otherwise healthy, nondiabetic 58-year-old white man. Contributory history began in 1994 after surgery for bilateral exostoses of the external auditory canals. Between April 1994 and May 1998 persistent otalgia occurred, with progressive mixed hearing losses, purulent discharge from both ears, spontaneous perforations of the tympanic membranes and ulceration of canal wall skin. From the beginning, Staph. epidermidis was isolated in all but one culture, but was not recognized as the pathological agent because of the presence of other more frequently involved bacteria and fungi. After multiple intravenous and oral antibiotics and antifungal treatments failed, further management involved frequent debridement of both external auditory canals and tympanic membranes, right tympanoplasty, bilateral mastoidectomy, revision tympanomastoidectomies and left modified radical mastoidectomy. Antistaphylococcal therapy including ceftazidime, vancomycin, teicoplanin, clindamycin and rifampicin was tried. Following the modified radical radical mastoidectomy, normalization of the status of his ears took approximately 2 months and has since remained stable to date. His left ear is deaf because of vancomycin administration, while magnetic resonance imaging and gallium scintigraphy have shown persistent inflammation of the skull base.

Aminoglycosides↗

Long-segment congenital tracheal stenosis: treatment by slide-tracheoplasty.

BACKGROUND/PURPOSE: The prognosis of long-segment funnel-shaped congenital tracheal stenosis improved with surgical management by enlargement-tracheoplasty with a pericardial patch. However, the final outcome is not always satisfying mainly because of the complications related to the pericardial graft and because of misdiagnosed associated cardiovascular malformations. The objective of the report is to show a further improvement of the prognosis by a thorough preoperative planning and the use of a slide-tracheoplasty for the cure of the stenosis, to avoid the major drawbacks of enlargement tracheoplasties. METHODS: Two children, 7 months and 3 years old, underwent a bronchoesophagoscopy, spiral computed tomography, an echocardiogram, and a heart catheterization. The tracheal stenosis and the associated severe cardiovascular malformations were cured during a single operative session under cardiopulmonary bypass; the tracheal stenosis was corrected by a slide-tracheoplasty. RESULTS: The postoperative period was remarkably uneventful and the recovery extremely quick (hospital stay of 18 and 17 days). The midterm results are excellent, and the tracheal growth is not impaired (follow-up of 3 1/2 and 3 years). CONCLUSIONS: According to the authors' experience and to the literature, the slide-tracheoplasty seems to be the most efficient surgical procedure for correction of long-segment funnel-shaped congenital tracheal stenosis. But the success of the treatment depends also on a complete preoperative diagnosis allowing a 1-stage surgical treatment of all associated thoracic malformations.

Child, Preschool↗

A photosensitising adenovirus for photodynamic therapy.

We have developed a new approach to photodynamic therapy based on adenoviral transduction of the rate-limiting enzyme in heme synthesis. Conventional phototherapy uses porphyrin-based chemical photosensitisers, including delta-aminolaevulinic acid (ALA) which is converted to protoporphyrin IX (PpIX) by the enzymes of the heme biosynthetic pathway. The lack of a specific mechanism for targeting chemical photosensitisers and PpIX to tumour cells means that therapeutic irradiation can damage normal tissue and exposure to sunlight following treatment can cause severe burns. The rate limiting enzyme in PpIX synthesis is ALA-synthase (ALA-S). We have developed a new yeast vector system for manipulation of the adeno- virus genome and used it to construct a virus expressing a mutant form of ALA-S lacking the iron response elements which regulate ALA-S translation and the heme regulatory motifs which regulate import of ALA-S into mitochondria. The virus induces a large increase in PpIX expression and confers photosensitivity on cultured cells. Unlike conventional photodynamic therapy, a viral approach makes it possible to restrict photosensitivity by biological rather than purely physical or chemical means. As with HSV thymidine kinase, ALA-S expression is a general mechanism for sensitisation to a therapeutic agent which can easily be adapted to whatever means of gene delivery is most effective.

5-Aminolevulinate Synthetase↗

Pulse oximeter as a cause of skin burn during photodynamic therapy.

Photodynamic therapy is increasingly being used for the treatment of various cancers. However, this technique has a major adverse effect, namely skin photosensitization. An unusual case of skin burn associated with pulse oximetry during photodynamic therapy in a patient treated for an early esophageal tumor is described. The patient, who was treated with mTHPC, suffered a second-degree burn on the index finger with subsequent loss of the nail. The only previously reported case of such a complication occurred with Photofrin, whereby no tissue other than skin was damaged.

Burns↗

Abrasive esophageal cytology for the oncological follow-up of patients with head and neck cancer.

OBJECTIVES: The occurrence of a second primary cancer in the esophagus in patients with head and neck squamous cell carcinoma is frequent and is associated with a poor prognosis. The aim of this study was to evaluate the yield of abrasive esophageal cytology as a means of screening for metachronous cancer of the upper aerodigestive tract. STUDY DESIGN: We retrospectively reviewed the results of abrasive esophageal cytology performed twice yearly for the screening of patients with prior head and neck cancer. METHODS: From 1987 to 1996, 320 patients treated for head and neck cancer underwent 1,673 abrasive cytology examinations of the esophagus during a mean follow-up period of 4 years. Cytological results were classified as negative, suspect, or positive for malignancy. RESULTS: Twenty-five patients without symptoms had one or more suspect or positive cytologic findings, leading to 29 endoscopic examinations. These revealed 20 premalignant or early malignant lesions of the esophagus (2 dysplasias, 18 squamous cell carcinomas), 2 glandular carcinomas, and 10 clinically unsuspected oral or pharyngeal carcinomas. In seven patients, positive cytological results were associated with clinically visible head and neck cancer. Of the 34 patients with suspect cytological results for malignancy, 10 had no evidence of tumor at endoscopy and 24 had no endoscopic examination because of refusal or because suspected cells were not found in additional examinations. Negative results on cytological examination were found for 254 patients throughout their follow-up, and none of them developed esophageal cancer during a mean follow-up period of 3 years. CONCLUSIONS: For patients with head and neck cancer, abrasive sponge cytology is useful for detecting esophageal cancer at an early stage. In addition, it may reveal unsuspected second primaries or recurrences in the head and neck region.

Carcinoma, Squamous Cell↗

Stability of the fluorescence measurement of Foscan in the normal human oral cavity as an indicator of its content in early cancers of the esophagus and the bronchi.

Photodynamic therapy (PDT) with Foscan (mTHPC) is used to cure early cancers of the esophagus or the tracheobronchial tree. However, fixed PDT parameters (drug dose, light dose, etc.) do not permit an accurate prediction of the tissue damage. Large interpatient fluctuations in tissue drug level, at the time of light application, suggest that the light dose must be adjusted to the drug dose shortly before the PDT. This drug dose can be measured endoscopically by light-induced fluorescence spectroscopy, but this measurement is inconvenient and somewhat difficult. A better test site, yielding comparable information, is needed. The oral cavity seems ideal. However, it first had to be established to what extent the estimation of the drug dose was dependent upon the location of the measurement and the pressure applied to the probe. These measurements prove to be not only correlated to similar measurements in the esophagus or the bronchi but also more consistent and less sensitive to the location and the applied pressure. The buccal mucosa is therefore recommended as a test site for measuring the Foscan fluorescence signal at the time of PDT in the esophagus or the bronchi. This measurement is accurate enough for use in light-dose adjustment.

Aged↗

Outpatient ENT surgery in an academic center: one and a half year's experience.

UNLABELLED: OBJECTIVE/PROBLEM: Evaluation of the early phase of an ENT outpatient surgery programme. STUDY DESIGN: Between May 1995 and December 1996, 452 ENT outpatient operations were carried out on 416 patients. In order to determine the patients' satisfaction as well as the types and frequency of complications associated with ambulatory procedures, an 18 item multiple choice questionnaire was sent to all patients. RESULTS: Replies were received from almost 80% of the patients. The great majority of patients were satisfied with their operation and would recommend it to friends and relatives. Ten percent of the patients had to be hospitalised for longer than originally expected. The reasons for these prolonged stays are described. CONCLUSIONS: Our results show that procedures performed on an outpatient basis do not differ from similar in patient procedures with regard to the types and frequency of complications. Medical expenses are reduced from 200-400% depending on the type of operation. In the present climate of tighter economic controls, the feasibility of lowering medical costs substantially without compromising patient care deserves our utmost attention.

Adolescent↗

Interstitial photodynamic therapy with tetra(m-hydroxyphenyl)chlorin: tumor versus striated muscle damage.

PURPOSE: The present study was initiated to determine the conditions under which a single photodynamic treatment would induce maximal damage to a tumor with no or at least minimal reversible damage to a normal striated muscle. METHODS AND MATERIALS: The technique of interstitial light delivery was used after prior 0.5 mg/kg tetra(m-hydroxyphenyl)chlorin administration in a hamster model. After having estimated the threshold light doses required for minimal muscle damage, the same light doses were applied to squamous cell carcinomas to evaluate the efficiency of interstitial photodynamic therapy. Sixteen and 96 h after the injection, irradiation at 650 nm was performed on the thigh muscle of the left hind leg. The applied light doses ranged between 0.3-15 J and were delivered at an intensity of 44 mW per cm of diffuser length. RESULTS: The threshold of muscle damage was obtained using light doses of 1.5-3 J at two drug-light intervals of 16 and 96 h, respectively. More than 85% of the tumor mass was destroyed when lesions were illuminated using these threshold conditions. In terms of immediate short-term tumor response, this means that for the given irradiation conditions, a relatively low threshold energy of only 1.5 or 3 J, depending on the drug-light interval, is sufficient to induce massive tumor destruction with minimal muscle damage. CONCLUSION: These results have implications for evaluating interstitial PDT for squamous cell cancers in unfavorable localization in the oral cavity or pharynx, such as at the base of the tongue.

Animals↗

Food groups and risk of oral and pharyngeal cancer.

The role of specific food groups and diet variety on the risk of oral and pharyngeal cancer has been considered using data from a case-control study conducted between 1992 and 1997 in the Swiss Canton of Vaud. Cases were 156 patients (126 males, 30 females) aged under 75 (median age 56) years with incident, histologically confirmed cancer of the oral cavity and pharynx, and controls were 284 subjects (246 males, 38 females, median age 57 years), admitted to the same university hospital for a wide spectrum of acute, non-neoplastic conditions unrelated to tobacco and alcohol consumption or to long-term modification of diet. After allowance for education, alcohol, tobacco and total energy intake, significant trends of increasing risk with more frequent intake emerged for eggs (OR = 2.3 for the highest tertile), red meat (OR = 2.1) and pork and processed meat (OR = 3.2). Inverse trends in risk were observed for milk (OR = 0.4 for the highest tertile), fish (OR = 0.5), raw vegetables (OR = 0.3), cooked vegetables (OR = 0.1), citrus fruit (OR = 0.4) and other fruits (OR = 0.2). The addition of a serving per day of fruit or vegetables was associated with an about 50% reduction in oral cancer risk. The most favourable diet for oral cancer risk is therefore given by infrequent consumption of red and processed meat and eggs and, most of all, frequent vegetable and fruit intake. Diet diversity was inversely related to oral and pharyngeal cancer: ORs were 0.35 for the highest tertile of total diversity, 0.24 for vegetable and 0.34 for fruit diversity. In terms of attributable risk, high meat intake accounted for 49% of oral and pharyngeal cancers in this population, low vegetable intake for 65% and low fruit intake for 54%.

Adult↗

Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma.

In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.

Animals↗

Use of transcription reporters with novel p53 binding sites to target tumour cells expressing endogenous or virally transduced p53 mutants with altered sequence-specificity.

p53 triple mutants (120N/121G/277H, 120H/121G/ 277H, 120S/121G/277H and 120H/121G/277Y) have altered sequence specificity in bandshift assays in vitro and transcription assays in vivo. These mutants activate transcription from the site TTT CATG AAA but not from wild type sites. The triple mutants activate more strongly than p53 with a single 277Y mutation. The TTT site matches the wild type p53 consensus at only 4/10 positions and is not recognised by wild type p53. 277Y mutations have been described in human tumours, and Ewing tumour cells expressing this mutant from the endogenous p53 locus selectively activate transcription from transfected luciferase reporters regulated by TTT-mutant p53 binding sites. p53 mutants with altered sequence specificity have potential advantages for cancer gene therapy: if used to activate transcription of conditionally toxic genes they would allow tumour-targeting by p53, which acts as a sensor for the malignant state, but place control over cell killing in the hands of the clinician. Rare tumours expressing such mutants from the endogenous p53 locus could be targeted directly with p53-regulated suicide vectors, but for most tumours both the p53 mutant and the reporter would need to be encoded by the virus.

Base Sequence↗

Clinical photodynamic therapy for superficial cancer in the oesophagus and the bronchi: 514 nm compared with 630 nm light irradiation after sensitization with Photofrin II.

Photodynamic therapy (PDT) for cancer in the oesophagus and bronchi with red (630 nm) light may occasionally lead to wall perforation and fistula. Therefore, we investigated the clinical use of a less penetrating wavelength (514 nm) for the curative treatment of nine superficial carcinomas in the oesophagus and bronchi after photosensitization with Photofrin II. Tumours without infiltration beyond the submucosa in the oesophagus and beyond the lamina propria in the bronchi were considered as superficial cancers. The outcome and complications were compared with those of 13 superficial cancers treated with PDT and 630 nm light. In addition, we evaluated histologically the extent of the long-term tissue damage and scarring following treatment of six oesophageal cancers with either green or red light. At first endoscopic control, 7-10 days after PDT, tissue necrosis simply matched the illuminated area, without evidence of selective tumour damage. Six of nine tumours treated with 514 nm light had a complete response compared with nine of 13 after 630 nm irradiation. No perforation or fistula occurred in either treatment group. However, severe chest pain and fever with or without pleural effusion, consistent with occult perforation, were observed in three patients after 630 nm illumination in the oesophagus. Histologically, fibrous scarring in the three distinct sites treated with green light was limited to the superficial layers of the oesophagus. After red light treatment, transmural fibrosis with marked thinning of the oesophageal wall was evident in two of the three specimens available for inspection. These results indicate that PDT with 514 nm light has the potential to cure superficial cancer in the oesophagus and bronchi with essentially the same probability of success as red light. In the oesophagus, green light prevents deep tissue damage, thus reducing the risk of perforation.

Aged↗