Biomedical subjects

F Blanchet

Publications and source records attributed to F Blanchet.

At least 19 recordsLinked to original sources

PubMed2000

Control by GABA and tachykinins of the evoked release of acetylcholine in striatal compartments under different modalities of NMDA receptor stimulation.

The contribution of endogenously released dopamine, GABA and its co-transmitters, substance P (SP) and neurokinin A (NKA), to the control of the evoked release of acetylcholine was investigated in vitro in the striosomes and the matrix of the rat striatum under various modalities of NMDA receptor stimulation (NMDA 50 microM or 1 mM without or with 10 microM D-serine). Sulpiride, bicuculline, SR140333 and SR48968, the antagonists of D(2), GABA A, NK(1) and NK(2) tachykinin receptors, respectively, were used for this purpose. (1) In both striatal compartments, the dopamine-mediated inhibitory regulation of the evoked release of acetylcholine only occurred when D-serine was co-applied with 50 microM or 1 mM NMDA. (2) In striosomes, the dopamine-dependent inhibitory effects of SP and NKA on the evoked release of acetylcholine only occurred when D-serine was co-applied with 50 microM or 1 mM NMDA. (3) A similar inhibitory regulation by NKA, but not SP, was found in the matrix when 1 mM NMDA was co-applied with D-serine. (4) In contrast, the dopamine-dependent facilitatory effect of GABA on the evoked release of acetylcholine did not require added D-serine and was more important with 1 mM than 50 microM NMDA. In the presence of D-serine, and depending on the NMDA concentration, the facilitatory regulation of GABA was reduced (matrix) or suppressed (striosomes). This latter effect was partially restored in the presence of SR48968. Therefore, the dopamine-dependent inhibitory effects of tachykinins on the evoked release of acetylcholine only occurred when NMDA receptors were stimulated in the presence of saturating concentrations of D-serine.

Acetylcholine↗

PubMed2000

[Renal function during long-term cyclosporin treatment of psoriasis].

INTRODUCTION: The goal of this retrospective study was to evaluate the effects of cyclosporin A on renal function in patients treated for five years or more. PATIENTS AND METHODS: Two hundred twenty-four psoriasis patients were treated with cyclosporin at St. Louis Hospital, in Paris, from 1988 to 1997. Eleven patients (5 p. 100 of the total) took cyclosporin for at least five years. Nine case histories were available for the analysis. RESULTS: The group studied consisted of eight men and one woman, ranging in age from 28 to 48 with an average age of 38 years. The average cyclosporin dosage was 3.6 mg/kg/day (2.0-5.0 mg/kg/day). The changes in renal function were not significant as compared to the baseline level. The patients did not show persistent increases of serum creatinine more than 30 p. 100 of the pre-treatment value. Two patients had to discontinue treatment after 6 years because of a 20 p. 100 decrease in glomerular filtration rate. DISCUSSION: Previous studies have shown that cyclosporin A is not a suitable long-term continuous monotherapy for psoriasis. However, with precise and regular monitoring of kidney function, a minority of patients can benefit from prolonged treatment without experiencing side effects.

Adult↗

PubMed1999

Role of arachidonic acid in the regulation of the NMDA-evoked release of acetylcholine in striatal compartments.

The role of endogenously released arachidonic acid in the control of the NMDA (50 microM)-evoked release of [3H]-acetylcholine previously formed from [3H]-choline was investigated in striosome-enriched areas and in the matrix of the rat striatum using a microsuperfusion procedure in vitro. Experiments were performed with either mepacrine (0.2 microM) or bovine serum albumin (BSA, 0.02%) which inhibits phospholipase A2 activity or binds endogenously released arachidonic acid, respectively. Both treatments similarly reduce the NMDA-evoked release of [3H]-acetylcholine, this effect being more pronounced in striosomes than in the matrix. These reductions result from a facilitation of dopamine release, since they were not observed in the presence of (-)sulpiride, the D2 dopamine receptor antagonist. Moreover, the superfusion with BSA was shown to enhance the release of [3H]-dopamine (formed from [3H]-tyrosine), this effect being of larger amplitude in striosomes than in the matrix. In control conditions, due to the blockade of the presynaptic inhibitory effect of GABA on dopamine release, bicuculline (GABA(A) receptor antagonist) reduces the NMDA-evoked release of [3H]-acetylcholine in both striatal compartments. Bicuculline was no longer effective following superfusions with either mepacrine or BSA, suggesting that these treatments eliminate the GABAergic presynaptic inhibitory control on dopamine transmission and thus lead to the dopamine-mediated inhibition of [3H]-acetylcholine release. These results indicate that arachidonic acid endogenously formed under weak stimulation of NMDA receptors contributes to the regulation of the evoked release of [3H]-acetylcholine by facilitating GABAergic transmission and that this process is more important in striosomes than in the matrix.

Acetylcholine↗

PubMed1998

Distinct modifications by neurokinin1 (SR140333) and neurokinin2 (SR48968) tachykinin receptor antagonists of the N-methyl-D-aspartate-evoked release of acetylcholine in striosomes and matrix of the rat striatum.

The effects of SR140333 and SR48968 (neurokinin1 and neurokinin2 tachykinin receptor antagonists, respectively) on the N-methyl-D-aspartate-evoked release of [3H]acetylcholine (previously formed from [3H]choline) were investigated in striosome-enriched areas and in the matrix of the rat striatum using an in vitro microsuperfusion method. In both striatal compartments, SR140333 and SR48968 did not modify the 50 microM N-methyl-D-aspartate-evoked release of [3H]acetylcholine. However, in low concentrations, both SR140333 (0.1 microM to 1 pM) and SR48968 (0.1 microM to 0.1 nM) markedly enhanced the 1 mM N-methyl-D-aspartate (+10 microM D-serine)-evoked release of [3H]acetylcholine in striosome-enriched areas. These responses were dopamine-dependent since they were not observed any more following the local blockade of D2 receptors by sulpiride or of dopamine synthesis by alpha-methyl-p-tyrosine. A dopamine-dependent disinhibitory effect (of lower amplitude) on the 1 mM N-methyl-D-aspartate (+10 microM D-serine)-evoked release of [3H]acetylcholine was also induced by SR48968 (0.1 microM to 0.1 nM) (but not by SR140333) in the matrix. In addition, in the matrix, as shown only in the presence of alpha-methyl-p-tyrosine, both SR140333 and SR48968 reduced the 1 mM N-methyl-D-aspartate (+10 microM D-serine)-evoked response and these non-dopamine-mediated inhibitory effects only occurred at the highest tested concentration (0.1 microM) of the antagonists. Indicating the specificity of these responses, the effects of SR140333 were reproduced by RP67580, another neurokinin1 receptor antagonist and, as expected from previous binding studies, corresponding SR140333 and SR48968 enantiomers were without effect. These results suggest that under potent stimulation of N-methyl-D-aspartate receptors, endogenously released substance P and neurokinin A (or related tachykinins) regulate differently the N-methyl-D-aspartate-evoked release of [3H]acetylcholine in striosomes and in the matrix. The inhibitory effects of these tachykinins on the evoked release of [3H]acetylcholine are mediated by dopamine. On the contrary, their facilitatory responses are only observed in the matrix under blockade of dopamine transmission.

Acetylcholine↗

PubMed1997

N-methyl-D-aspartate-evoked release of [3H]acetylcholine in striatal compartments of the rat: regulatory roles of dopamine and GABA.

The N-methyl-D-aspartate-evoked release of [3H]acetylcholine previously formed from [3H]choline was estimated in striosome- (identified by [3H]naloxone binding) or matrix-enriched areas of the rat striatum using an in vitro microsuperfusion procedure. Experiments were performed in either the absence or the presence of dopaminergic and/or GABAergic receptor antagonists. Although the cell bodies of the cholinergic interneurons were mainly found in the matrix, in the absence of magnesium, N-methyl-D-aspartate (50 microM) stimulated the release of [3H]acetylcholine in both striatal compartments. These responses were blocked by either magnesium, dizocilpine maleate, 7-chlorokynurenate or tetrodotoxin. N-Methyl-D-aspartate responses were concentration-dependent, but the 1 mM N-methyl-D-aspartate response was higher in striosomes than in the matrix. The co-application of D-serine (10 microM) enhanced the 10 microM N-methyl-D-aspartate response in both compartments, but reduced those induced by 1 mM N-methyl-D-aspartate, this reduction being higher in striosomes. The blockade of dopaminergic transmission with the D2 and D1 dopaminergic receptor antagonists, (-)-sulpiride (1 microM) and SCH23390 (1 microM), was without effect on the 50 microM N-methyl-D-aspartate-evoked release of [3H]acetylcholine, but markedly enhanced the 1 mM N-methyl-D-aspartate+D-serine-evoked response in striosomes and to a lesser extent in the matrix. Disinhibitory responses of similar amplitude were observed not only in striosomes but also in the matrix when (-)-sulpiride was used alone, while SCH23390 alone enhanced the 1 mM N-methyl-D-aspartate+D-serine response only in striosomes and to a lower extent than (-)-sulpiride. These results indicate that D2 receptors are mainly involved in the inhibitory effect of dopamine on the 1 mM N-methyl-D-aspartate+D-serine-evoked release of [3H]acetylcholine. They also show that the stimulation of D1 receptors can either reduce (striosomes) or enhance (matrix) this response, since in the latter case the effect induced by the combined application of the D1 and D2 receptor antagonists was smaller than that observed with the D2 receptor antagonist alone. Indicating that released GABA facilitates N-methyl-D-aspartate responses, the blockade of GABAA receptors with bicuculline (5 microM) reduced the 50 microM N-methyl-D-aspartate-evoked release of [3H]acetylcholine in both striatal compartments and the 1 mM N-methyl-D-aspartate+D-serine response in the matrix. These effects result from an inhibition by GABA of the evoked release of dopamine, since the reducing effects of bicuculline on N-methyl-D-aspartate responses were not observed under the complete blockade of dopaminergic transmission by the D1 and D2 receptor antagonists. Further demonstrating a facilitatory role of GABA in the control of N-methyl-D-aspartate-evoked release of [3H]acetylcholine, in the presence of bicuculline, (-)-sulpiride and SCH23390 alone or in combination enhanced, in both compartments, the responses induced not only by 1 mM N-methyl-D-aspartate+D-serine, but also by 50 microM N-methyl-D-aspartate.

Acetylcholine↗

PubMed1997

Pressure-heart rate responses to alpha-adrenergic stimulation and hormonal regulation in normotensive patients with obstructive sleep apnea.

Seven normotensive untreated patients with obstructive sleep apnea (OSA) and five control subjects without OSA were compared. Patients with cardiac dilation, chronic airflow limitation, liver and kidney disease, or diabetes mellitus were excluded. Change in pressure-heart rate relation to alpha-adrenergic stimulation (P-HRR), extracellular volume (ECV), and plasma volume (Vp) were measured during daytime. Plasma atrial natriuretic peptide (ANP), plasma renin and aldosterone concentrations were obtained at 1 hour intervals during the night. A mean apnea/hypopnea index (AHI) of 52.2 +/- 23.9/h and a mean lowest arterial oxygen saturation (SaO2) of 61.2 +/- 19.3% (mean +/- SD) were determined from polysomnographic monitoring in the patient group. Release of ANP was significantly higher during sleep in OSA patients than in control subjects (P < .01), with a maximum concentration between 4 and 6 AM in the former. Daytime ECV was significantly higher (P < .05) and Vp significantly lower (P < .05) in OSA patients. Night maximum concentration of ANP (max ANP) was negatively related to AHI (P < .05). P-HRR was negatively related to AHI (P < .05) and positively related to max ANP (P < .05). In conclusion, OSA syndrome alters hormonal system control of body fluid compartment regulation. The decreased response in night max ANP secretion in the most severe OSA patients could be explained by the smaller Vp observed in these patients, decreasing atrial and ventricular pressure loading. Furthermore, alteration of P-HRR, correlated to AHI and max ANP, strengthens the hypothesis that patients who develop hypertension are those in whom the protective mechanism of ANP release failed.

Adrenergic alpha-Agonists↗

PubMed1997

Evaluation of renal acidification in HIV-infected patients with hypergammaglobulinemia.

Distal renal tubular acidosis has been reported in several diseases associated with hypergammaglobulinemia, particularly Sjögren's syndrome. Since HIV infection is now a common cause of hypergammaglobulinemia, we evaluated renal acidification under basal and dynamic conditions in 8 asymptomatic HIV-seropositive subjects. Basal acid-base status was normal in all except 1 patient who had respiratory acidosis subsequent to recent pneumonia. Acid-loading tests showed normal acid excretion except for 1 patient who had low acid excretion attributed to non-ingestion of the ammonium chloride capsules. Bicarbonate-loading tests showed normal distal acidification indexes in 7 patients. The only patient with a low acidification defect was diagnosed 2 weeks later as having tuberculosis. Our results suggest that hypergammaglobulinemia per se is not a sufficient condition to induce renal tubular acidosis.

Acidosis, Renal Tubular↗

PubMed1996

Diet and cancers of the larynx and hypopharynx: the IARC multi-center study in southwestern Europe.

The main causes of cancer of the larynx and hypopharynx are smoking cigarettes and drinking alcohol. However, for these as well as for other cancers of the upper aerodigestive tract, some dietary components, mainly low consumption of fruit and vegetables, have been observed to be associated with increased cancer risk. We report results from a multicenter case-control study carried out in six regions of Europe located in northern Spain, northern Italy, Switzerland, and France. A total of 1,147 males with cancer (cases) and 3,057 population controls were interviewed on usual diet, lifelong drinking and smoking habits, and occupational history. Cancer cases had histologically verified epidermoid carcinomas. The cancers were classified in two anatomic sub-entities: the epilarynx (hypopharynx and upper part of the larynx), which enters into contact with the bolus and the air; and the endolarynx, through which air and tobacco smoke pass, but not the bolus. A previous report from this study found that alcohol drinking presents a greater risk factor for cancer of the epilarynx than for cancer of the endolarynx. The main results regarding diet indicate that high intake of fruit, vegetables, vegetable oil, fish, and low intake of butter and preserved meats were associated with reduced risk of both epilaryngeal and endolaryngeal cancers, after adjustment for alcohol, tobacco, socioeconomic status, and non-alcohol energy intake. Among nutrients, a reduced risk was found for high intake of vitamins C and E and for a high polyunsaturated/saturated fatty acids (P/S) ratio. While these variables are relevant in scoring nutritional behaviour, it remains unresolved whether the biologic properties of these nutrients play a role in the apparent protective effect.

Alcohol Drinking↗

PubMed1996

Long-term safety of cyclosporine in the treatment of psoriasis.

BACKGROUND AND DESIGN: Cyclosporine has proved to be highly effective in the treatment of psoriasis. However, cyclosporine is potentially toxic. Side effects include renal toxic effects, hypertension, and an increased risk of malignant neoplasm. The toxicity of cyclosporine is dose-related, yet the safe duration of treatment is undefined. We studied the hospital records of all patients with psoriasis treated with cyclosporine at Saint Louis Hospital, Paris, France, between January 1, 1987, and December 31, 1993. In total, 122 patients treated for 3 to 76 months were evaluated. RESULTS: The percentage of patients who discontinued treatment because of side effects rose from a mean +/- SD of 14% +/- 2.4% at 12 months to 41% +/- 6.7% at 48 months. An increase in serum creatinine levels to more than 30% above the baseline value occurred in 53 patients after a median treatment time of 23 months. Hypertension developed in 29 patients after a median treatment time of 53 months. Three initial patient characteristics--age older than 50 years (P = .04), initial diastolic pressure higher than 75 mm Hg (P = 0.5), and serum creatinine levels more than 100 mumol/L (1.1 mg/dL) (P = .02, log rank test)--predicted discontinuation of cyclosporine because of side effects. CONCLUSIONS: The risk of cyclosporine-induced toxic effects increases with age of the patient and with preexisting hypertension or high serum creatinine levels. The data suggest that the incidence of side effects increases with time. Thus, cyclosporine is not an acceptable long-term monotherapy for psoriasis.

Adolescent↗

PubMed1994

Effect of the platelet activating factor antagonist BN52021 in rabbits: role in gentamicin nephrotoxicity.

Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including drug nephrotoxicity. Aminoglycosides are potent antibiotics but their use is limited by their nephrotoxic potential. We assumed that PAF could participate in inducing gentamicin nephrotoxicity, and we used the PAF antagonist BN52021 to test this hypothesis. We studied renal glomerular and tubular function by clearance techniques and renal histology in four groups of New Zealand male rabbits treated for 7 days with isotonic saline, BN52021, gentamicin, or gentamicin + BN52021. BN52021 alone reduced only fractional excretions (FE) of sodium and chloride, without modifying the other parameters studied. Renal histology was not altered. Gentamicin reduced glomerular filtration rate and renal plasma flow. Free water clearance was not modified. Sodium, potassium, chloride, calcium, and magnesium FEs were raised. Renal histology showed a massive and diffuse tubular necrosis. BN52021 did not modify gentamicin glomerular, tubular, or histopathological alterations. These data suggest that PAF might physiologically affect tubular function in New Zealand male rabbits, increasing sodium and chloride excretions, and in a minute manner, potassium, calcium, and magnesium excretions. Under our experimental conditions, there was no evidence for a role of PAF in gentamicin nephrotoxicity.

Animals↗

PubMed1993

Effects of diltiazem on netilmicin-induced nephrotoxicity in rabbits.

Aminoglycoside nephrotoxicity remains a common clinical problem and is the major cause of acute toxic renal failure in hospitalized patients. In recent studies, calcium channel blockers gave controversial results in the prevention of acute ischemic or toxic renal failure. The aims of the study were (i) to describe a rabbit model of mild renal failure (50% reduction in glomerular filtration rate with a mean value of 1.78 +/- 0.46 ml/kg/min) induced by netilmicin given intramuscularly at 20 mg/kg of body weight every 8 h for 5 days, (ii) to investigate the protective effect of diltiazem given at a therapeutic dose (1 mg/kg given intramuscularly every 8 h for 5 days), and (iii) to investigate the mechanisms of this protection through evaluation of function tests, optic histology, and glomerular morphometry. Animals treated with netilmicin and diltiazem exhibited an unchanged glomerular filtration rate compared with controls (3.39 +/- 0.58 versus 3.68 +/- 0.78 ml/kg/min, respectively). This protective effect was not associated with any change in systemic or renal hemodynamics (i.e., no change in renal plasma flow) or changes in the pharmacokinetics of netilmicin, as assessed by fractional excretion and cortical uptake. Netilmicin-induced tubular toxicity was unchanged by diltiazem. Our results suggest that (i) netilmicin exhibits a toxic effect at both the glomerular and the tubular levels, (ii) diltiazem, a calcium channel blocker, when given at low therapeutic doses, is able to prevent the aminoglycoside-induced renal failure through a potential glomerular mechanism. The precise mechanisms of the protection remain to be elucidated. These results deserve clinical evaluation in high-risk patients.

Aldosterone↗

PubMed1993

Pilot study of cardiopulmonary risk from pentoxifylline in adult respiratory distress syndrome.

Neutrophils and cytokines are directly involved in the pathophysiology of adult respiratory distress syndrome (ARDS). Pentoxifylline (PTX) has been shown in vitro to protect against the inflammatory effects of neutrophils and cytokines. The same protective effects have been demonstrated on animal models of lung injury. These results suggested that PTX might be useful in patients with ARDS. The cardiopulmonary effects of large doses of PTX were evaluated in a pilot study performed in six patients with severe ARDS. PTX was administered with an initial 1-mg/kg bolus, followed by infusion of 1.5 mg/kg/h over 6 h. No significant change was observed in the gas exchange and hemodynamic parameters, except for a 10 percent increase in the heart rate during the infusion period. Our results demonstrate that large doses of PTX induced only minor hemodynamic changes without worsening in pulmonary gas exchange. Further studies are warranted to evaluate human safety and ultimately the effectiveness of PTX in the treatment of ARDS.

Aged↗

PubMed1993

Cardiopulmonary effects of bronchoalveolar lavage in critically ill patients.

Bronchoalveolar lavage (BAL) has been proposed as a useful procedure for bacteriologic diagnosis of lower respiratory tract infection in mechanically ventilated patients. To determine the cardiopulmonary effects of this procedure and to identify the patients at risk of poor tolerance, 30 critically ill ventilated patients suspected of having pneumonia were studied. Hemodynamic and gas exchange parameters were continuously recorded using an arterial catheter, a Swan-Ganz catheter with SvO2 display, and a pulse oximeter. In addition to the basal sedation required by these patients, midazolam, 0.1 mg/kg intravenously, was administered 5 min prior to bronchoscopy. A moderate increase (10 percent from basal values) in heart rate, mean arterial pressure, and cardiac index was recorded at each measurement during the procedure. A marked decrease in PaO2 was observed during bronchoscopy associated with an increase in oxygen consumption. Maximal changes in SaO2 and SvO2 were recorded at the end of BAL. Two hours after the end of BAL, PaO2 values were still 20 percent lower than pre-BAL values in 40 percent of the patients. We conclude that BAL can be performed safely in most critically ill ventilated patients who have stable hemodynamic and ventilatory parameters. However, none of the recorded parameters allows identification of the patients at risk of poor tolerance of the procedure.

Analysis of Variance↗

PubMed1992

[Renal functional reserve].

The term "renal functional reserve" (RFR) refers commonly to the reserve of glomerular filtration rate (GFR) and renal blood flow. RFR can be elicited by an oral protein load or by infusion of aminoacids, glucagon, or dopamine. The increase in GFR which follows aminoacid administration results from a cascade of events including at least pancreatic release of glucagon, involvement of an hepatic step yet unidentified, and renal synthesis of vasodilatory prostaglandins. RFR represents a constant fraction of baseline GRF as long as the latter is above 40-50 l/min. It has been suggested tha permanent challenge of RFR, which occurs in protein-rich diet or during the hyperfiltration phase of diabetic nephropathy, might lead to and accelerate impairment of renal function. The relevance of RFR measurement as a tool to predict the evolution of renal function in various types of renal diseases remains to be evaluated.

Female↗

PubMed1991

Randomised EORTC head and neck cooperative group trial of preoperative intra-arterial chemotherapy in oral cavity and oropharynx carcinoma.

Between February 1978 and January 1984, 222 eligible patients were randomised in a multicentre trial of preoperative intra-arterial chemotherapy in the treatment of oral cavity and oropharynx carcinoma. Patients were randomised between either surgery or preoperative chemotherapy. This latter group received vincristine and bleomycin for 12 days. Patients were stratified according to the primary site: floor of the mouth (FM) versus posterior oral cavity or oropharynx (POC) and institution. The FM group received postoperative radiotherapy depending upon quality of the margins and lymph-node pathological involvement, when it was systematically applied in the POC group. Tumour regression after chemotherapy either complete (CR) or partial (PR greater than 50%) was observed in 48% in the FM group and 41% in the POC group, and lymph-node regression (CR + PR) was respectively 15% and 23%. Some discrepancies appeared between clinical regression and pathological response, and the number of cases without histological response was clearly higher than the number of cases without clinical response. The overall survival showed a statistically significant difference (P = 0.048) between FM and POC groups. In the FM group, median survival in the chemotherapy arm was estimated at 7 years compared with 3 years in the surgery arm. In the POC group, median survival was estimated at 3 years in both treatment arms. Chemotherapy lowered the uncontrolled disease and local recurrence in the FM group. These differences do not exist in the POC group, which may be due to the systematically postoperative radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Cancer of the endolarynx, epilarynx and hypopharynx in south-western Europe: assessment of tumoral origin and risk factors.

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Adult↗

PubMed1991

[The functional renal reserve].

The term "renal functional reserve" (RFR) refers commonly to the reserve of glomerular filtration rate (GFR) and renal blood flow. RFR can be elicited by an oral protein load or by infusion of amino acids, glucagon, or dopamine. The increase in GFR which follows amino acid administration results from a cascade of events including pancreatic release of glucagon, involvement of an hepatic step, and renal synthesis of vasodilatory prostaglandins. RFR represents a constant fraction of baseline GFR as long as the latter is above 40-50 ml/min. RFR becomes virtual for lower values of GFR. It has been suggested that permanent challenge of RFR, which occurs in protein-rich diet or during the hyperfiltration phase of diabetic nephropathy, might lead to and accelerate impairment of renal function. The relevance of RFR measurement as a tool to predict the evolution of renal function in various types of renal diseases remains to be evaluated.

Amino Acids↗

PubMed1991

[The value of extemporaneous study of the surgical margins of cancers of the upper aero-digestive tract. Apropos of 129 cases of oral and oropharyngeal tumors].

129 patients, who had oral cavity or oropharyngeal carcinoma underwent excision with intraoperative histopathologic examination. Thanks to this method, the number of satisfying resections has increased from 25% to 75%. Whatever the quality of the surgical excision may be, postoperative radiotherapy improves the prognosis.

Carcinoma in Situ↗