E Didiot

I Illina
email: illina@loria.fr

D Fohr
email: fohr@loria.fr

O Mella
email: mella@loria.fr

A Wavelet-Based Parameterization for Speech/Music Discrimination

Keywords: Speech/music discrimination, segmentation, wavelets, static parameters, dynamic parameters, long-term parameters

This paper addresses the problem of parameterization for speech/music discrimination. The current successful parameterization based on cepstral coefficients uses the Fourier transformation (FT), which is well adapted for stationary signals. In order to take into account the non stationarity of music/speech signals, this work proposes to study wavelet-based signal decomposition instead of FT. Three wavelet families and several numbers of vanishing moments have been evaluated. Different types of energy, calculated for each frequency band obtained from wavelet decomposition, are studied. Static, dynamic and long-term parameters were evaluated. The proposed parameterization are integrated into two class/non-class classifiers: one for speech/non-speech, one for music/non-music. Different experiments on realistic corpora, including different styles of speech and music (Broadcast News, Entertainment, Scheirer), illustrate the performance of the proposed parameterization, especially for music/non-music discrimination. Our parameterization yielded a significant reduction of the error rate. More than 30% relative improvement was obtained for the envisaged tasks compared to MFCC parameterization.

Introduction

This paper addresses the problem of parameterization for speech/music discrimination. We propose to take into account the difference between music and

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speech at the parameter level: a combination of time and frequency features that deal with non-stationary signals will be used. The proposed approaches were evaluated on several real-world corpora extracted from radio programs. These corpora contain a lot of superimposed segments, such as speech with music or songs with a "fade-in fade-out" effect.

In real world applications, automatic speech recognition systems (ASRs) are faced with a large diversity of audio signals: speech, music, noise as well as their superimpositions. The performance of standard ASRs usually decreases drastically when they are confronted with this kind of mixed condition. During the automatic speech recognition step, a wide variety of environment adaptation and compensation approaches can be used to treat the differences between training and testing conditions [START_REF] Junqua | Robustness in Automatic Speech Recognition: Problems, Issues, and Solutions[END_REF]. On the other hand, these techniques are not powerful enough in the case of mixed speech/music, because they only take into account the specificity of speech and are not appropriate for music. In these situations a preprocessing step is necessary before recognition. The basic principle of speech/music discrimination consists in segmenting the signal into homogeneous parts and in classifying each part in predefined categories like speech, music, speech superimposed on music (called speech over music). Sometimes more precise categories can be used for music, such as instrumental music, songs, etc. [START_REF] Ezzaidi | Automatic Music Genre Classification Using Second-Order Statistical Measures for the Prescriptive Approach[END_REF], [START_REF] Tzanetakis | Musical Genre Classification of Audio Signals[END_REF]. The music segments are then discarded, to avoid recognition mistakes and the speech over music segments can be used to perform powerful compensation or adaptation. For example, speech/music detection could speed up the process of automatic captioning of TV transmissions by skipping the non-speech segments and avoiding incorrect transcriptions during music, songs or jingle segments. Another realistic application of speech/music discrimination is its ability to give interesting information about the type of music for indexing and retrieval of audio documents. Thus, the development of speech/music discrimination methods has become an important research area. Speech/music discrimination differs from Voice Activity Detection (VAD). VAD aims to discriminate between noise and speech and not between speech and music. More particularly, VAD is not able to discriminate speech from songs.

Figure 1 illustrates the differences between speech and music signals. A wide variety of parameterization techniques has been used for speech/music discrimination. They can be divided into three classes according to the domain in which they are computed: the time, frequency or mixed (time and frequency) domain.

Time-domain features represent the temporal characteristics of the signal. For example, the zero crossing rate (ZCR) [START_REF] Saunders | Real-Time Discrimination of Broadcast Speech/Music[END_REF], [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], [START_REF] Panagiotakis | A Speech/Music Discriminator Based on RMS and Zero-Crossings[END_REF] can detect unvoiced parts of the audio signal. During speech there is an alternation of voiced and unvoiced segments. ZCR is greater during unvoiced segments than voiced segments. So, peaks occur in the evolution of the ZCR during speech. For music, the variations of the ZCR are smoother.

Frequency-domain features characterize the spectral envelope of the signal. Some examples are spectral centroid [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], harmonic coefficients [START_REF] Chou | Robust Singing Detection in Speech/Music Discriminator Design[END_REF], [START_REF] Wold | Classification, Search and Retireval of Audio[END_REF] and spectral peak track [START_REF] Zhang | Audio Content Analysis for Online Audiovisual Data Segmentation and Classification[END_REF], [START_REF] Taniguchi | Detection of Speech and Music Based on Spectral Tracking[END_REF]. The Mel Frequency Cepstral Coefficients parameters (MFCC), which could be classified in this category, are considered as one of the best parameterizations for speech/music discrimination [START_REF] Brun | ANTS : le système de transcription automatique du LORIA[END_REF], [START_REF] Carey | A Comparison of Features for Speech, Music Discrimination[END_REF], [START_REF] Alexandre-Cortizo | Application of Fisher Linear Discriminant Analysis to Speech/Music Classification[END_REF], [START_REF] Fredouille | Segmentation en macroclasses acoustiques d'émissions radiophoniques dans le cadre d'ESTER[END_REF], , [START_REF] Gauvain | The LIMSI 1998 Hub-4E Transcription System[END_REF], [START_REF] Gauvain | The LIMSI Broadcast News Transcription System[END_REF], [START_REF] Gravier | ESTER, une campagne d'évaluation des systèmes d'indexation automatique d'émissions radiophoniques en francais[END_REF], [START_REF] Hain | Segment Generation and Clustering in the HTK Broadcast News Transcription System[END_REF], [START_REF] Hain | Segmentation and Classification of Broadcast News Audio[END_REF], [START_REF] Logan | Mel Frequency Cepstral Coefficients for Music Modeling[END_REF], [START_REF] Razik | Segmentation Parole/Musique pour la transcription automatique[END_REF], [START_REF] Razik | Comparison of Two Speech/Music Segmentation Systems For Audio Indexing on the Web[END_REF].

Combinations of time and frequency features are for instance the spectral flux [START_REF] Lu | Content Analysis for Audio Classification and Segmentation[END_REF], [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF] or the 4Hz modulation energy [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], [START_REF] Pinquier | Speech and Music Classification in Audio Documents[END_REF]. The spectral flux detects the harmonic continuity in music. The high variations of spectral flux are specific for speech. This is due to the alternation of consonants and vowels. The 4Hz modulation energy is more specific for speech than for music, because it corresponds to the syllabic rate.

Concerning the classification step, most systems are based on Gaussian Mixtures Models (GMM) or Hidden Markov Models (HMM). Nevertheless, some systems use other speech/music classifiers, such as Multi-Layer Perceptron [START_REF] Kahn | Automatic Classification of Speech and Music using Neural Networks[END_REF], [START_REF] Keum | Speech/Music Discrimination Based on Spectral Peak Analysis and Multi-Layer Perceptron[END_REF], Maximum A Posteriori classifier [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], k-Nearest Neighbors [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], and different hybrid systems: MLP/SVM (Support Vector Machine) [START_REF] Ganapathiraju | Hybrid SVM/HMM Architectures for Speech Recognition[END_REF], MLP/HMM [START_REF] Ajmera | Speech/Music Discrimination using Entropy and Dynamism Features in a HMM Classification Framework[END_REF].

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This article presents a new parameterization approach for speech/music discrimination based on the wavelet decomposition of the signal. Our goal is not to propose a new wavelet type but to apply the wavelet formalism for speech/music discrimination. Our motivation to apply wavelets to speech/music discriňmination is due to their ability to extract time-frequency features and to deal with non-stationary signals. Kahn and al. Earlier,[START_REF] Kahn | Automatic Classification of Speech and Music using Neural Networks[END_REF] proposed the wavelet parameterization for speech/music detection. But he used only two values per frame to perform speech/music classification: the mean and the variance of the discrete wavelet transform coefficients. In our work, we use the wavelet coefficients in each frequency band of every frame, so a more accurate analysis can be performed. We study several features based on wavelet decomposition and test them on some broadcast programs. Furthermore, we compare their performance with MFCC because studies [START_REF] Carey | A Comparison of Features for Speech, Music Discrimination[END_REF], [START_REF] Alexandre-Cortizo | Application of Fisher Linear Discriminant Analysis to Speech/Music Classification[END_REF], [START_REF] Logan | Mel Frequency Cepstral Coefficients for Music Modeling[END_REF] have showed that the latter achieve state-of-the-art results in speech/music discrimination. Besides, many automatic news transcription systems use MFCC-based parameterization for speech/music segmentation in different evaluation campaigns, like the DARPA evaluation (1997)(1998)(1999)(2000) or the recent ESTER campaign (2003-2005) [START_REF] Gravier | ESTER, une campagne d'évaluation des systèmes d'indexation automatique d'émissions radiophoniques en francais[END_REF]. We refer to the systems designed by Cambridge (HTK) [START_REF] Hain | Segment Generation and Clustering in the HTK Broadcast News Transcription System[END_REF], LIA [START_REF] Fredouille | Segmentation en macroclasses acoustiques d'émissions radiophoniques dans le cadre d'ESTER[END_REF], LIMSI [START_REF] Gauvain | The LIMSI 1998 Hub-4E Transcription System[END_REF] and LORIA (ANTS, Automatic News Transcription System) [START_REF] Brun | ANTS : le système de transcription automatique du LORIA[END_REF].

To perform the classification we chose a "class/non-class" approach: a speech/nonspeech segmentation and a music/non-music segmentation [START_REF] Pinquier | Speech and Music Classification in Audio Documents[END_REF]. This approach allows us to determine the best parameters for each task and to increase the accuracy. The classification method is based on the Viterbi algorithm which uses HMM models (HTK toolkit [START_REF] Young | The HTK Book[END_REF]), because it simultaneously performs classification and segmentation.

The paper is organized as follows. First, the wavelet decomposition and the wavelet-based parameters are briefly introduced in section 2. Then, our speech/music discrimination system is presented in section 3. Next, experimental results obtained for speech/music discrimination on various corpora are discussed in section 4, followed by a conclusion in section 5.

Wavelet-based Parameters for Speech/Music Discrimination

In this section, we introduce our parameterization method based on wavelet transforms. The signal is first analyzed using the wavelet transform, then different energy parameters are calculated. As the purpose of this article is not wavelet signal analysis but only its use for speech/music discrimination, we shortly introduce the wavelet transforms.

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Wavelet Transforms

For speech/music discrimination, it is essential to deal with non-stationary signals and to achieve variable time and frequency localization of acoustic cues. Multi-resolution Analysis (MRA) is a signal analysis, which provides a time-frequency representation of the signal, well suited for non-stationary signals [START_REF] Mallat | A Theory for Multiresolution Signal Decomposition: The Wavelet Representation[END_REF], [START_REF] Mallat | A Wavelet Tour of Signal Processing[END_REF]. MRA analysis offers an alternative to the more traditional Short-Time Fourier Transform (STFT). The problem with STFT is that the shorter the analysis window is, the better the time resolution, but the poorer the frequency resolution. This means that STFT is facing the resolution problem, e.g. which window size to use. The solution of this problem is often application dependent. In contrast, MRA analyses the signal at different frequencies with different resolutions and is well adapted for non-stationary signals. Indeed, MRA makes sense especially when the signal has many high frequency components for short durations and low frequency components for long durations, which is often the case for speech and music signals.

In our work, we chose a specific case of MRA: Discrete Wavelet Transform (DWT). DWT provides a compact representation of the signal, has a rich set of basis functions and can be implemented very efficiently. Wavelet-based signal analysis has been successfully applied to various problems, such as image size reduction [START_REF] Saha | Image Compression from DCT to Wavelets: a Review[END_REF], speech denoising [START_REF] Kim | Speech Enhancement using Adaptive Wavelet Shrinkage[END_REF], automatic speech recognition [START_REF] Deviren | Revisiting speech recognition systems : dynamic Bayesian networks and new computational paradigms[END_REF], [START_REF] Sarikaya | High Resolution Speech Feature Parameterization for Monophone-based Stressed Speech Recognition[END_REF] and audio classification [START_REF] Lin | Audio Classification and Categorization Based on Wavelets and Support Vector Machine[END_REF], [START_REF] Tzanetakis | Musical Genre Classification of Audio Signals[END_REF].

A DWT can be derived from a Continuous Wavelet Transform (CWT). Given a time signal x(t), the continuous wavelet transform is given by:

CW T (r,s) = 1 |s| x(t)Ψ * ( t -r s )dt (1)
where * is the conjugate operator. Ψ(t) is a time function called "mother wavelet", r (r ≥ 0) is related to the time location of the analyzing window and s corresponds to scale (scale s < 1 dilates the analysis function, scale s > 1 compresses the analysis function. By varying r and s, the "mother wavelet" is scaled and shifted. Several "mother wavelets", called wavelet families, have been proposed. Using the dyadic decomposition (s = 2 j , cf. Figure 2), and a discrete signal

x[m],m = 0,..,N -1, a CWT is transformed into a DWT: DW T [n,2 j ] = N -1 m=0 x[m]Ψ * 2 j [m -n] (2)
where The DWT provides a rough approximation of the Mel scale and can be computed efficiently using a fast, pyramidal algorithm related to a multi-rate filterbank: S. Mallat [START_REF] Mallat | A Wavelet Tour of Signal Processing[END_REF] has shown that frequency band decomposition can be obtained by successive low-pass (L) and high-pass (H) filterings of the signal in the time domain. Figure 3 illustrates a decomposition with two levels. The symbol "↓ 2" denotes a down-sampling by 2. This figure illustrates that at each level j, the signal is decomposed into approximation coefficients a j (r) (output of low-pass filter) and detail coefficients w j (r) (output of high-pass filter). Approximation coefficients correspond to local averages of the signal. Detail coefficients, named also wavelet coefficients, can be viewed as the differences between two successive local averages, ie. between two successive approximations of the signal [START_REF] Misiti | Les ondelettes et leurs applications[END_REF]. The index j corresponds to the frequency band.

Ψ 2 j [n] = 1 √ 2 j Ψ( n 2 j ) (3)

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Our work on DWT is based on the Daubechie, Symlet and Coiflet families because these wavelets are some of the best known wavelets and have been successfully used for speech recognition [START_REF] Deviren | Frequency Filtering or Wavelet Filtering? ICANN/ICONIP[END_REF], [START_REF] Gemello | Integration of Fixed and Multiple Resolution Analysis in a Speech Recognition System[END_REF]. Daubechie and Symlet wavelet families correspond to FIR filters (L,H). Daubechie and Symlet wavelet families have an interesting property: they have a minimum support1 for a given number of vanishing moments. Small support size allows better singularity detection. The definition of vanishing moments will be provided in section 4.3.1.

For speech/music discrimination, we propose to use only wavelet coefficients w j (r) to analyze the acoustic signal, because they can capture the sudden modifications of the signal.

Energy-based Parameters

The energy distribution in each frequency band is a very relevant acoustic cue. For this reason we employ energy, calculated from DWT, as a speech/music discrimination feature.

Let, as below, w j (r) denote the wavelet coefficient at time position r and frequency band j. We underline that the frequency band decomposition and time decomposition correspond to the dyadic scale (see Figure 2): time resolution halves while the frequency resolution doubles. If N is the length of the analysis window, w j (r) has N j = N/2 j samples2 and three methods are investigated for extracting the wavelet energies:

-Instantaneous Energy (labelled E in Tables) gives the energy distribution in each band:

f E j = log 10   1 N j N j r=1 (w j (r)) 2   (4)
-Teager Energy (labelled T_E in Tables) was recently applied for speech recognition [START_REF] Potamianos | Time-Frequency Distributions for Automatic Speech Recognition[END_REF], [START_REF] Dimitriadis | Auditory Teager Energy Cepstrum Coefficients for Robust Speech Recognition[END_REF]:

f T _E j = log 10   1 N j N j -1 r=1 |(w j (r)) 2 -w j (r -1) * w j (r + 1)|   (5)
The discrete Teager Energy Operator (TEO), introduced by Kaiser [START_REF] Kaiser | On a Simple Algorithm to Calculate the 'Energy'of a Signal[END_REF], allows modulation energy tracking and gives a better representation of the formant information in the feature vector compared to MFCC. The Teager energy is a noise robust parameter for speech recognition because the effect of additive noise is attenuated: good results are obtained in presence of car

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engine noise [START_REF] Jabloun | The Teager Energy based Feature Parameters for Robust Speech Recognition in Car Noise[END_REF]. The Instantaneous energy reflects only the amplitude of the signal whereas the Teager energy operator reflects the variations in both amplitude and frequency of the signal [START_REF] Tolba | Automatic Speech Recognition Based on Ceptral Coefficients and a Mel-Based Discrete Energy Operator[END_REF]. Figure 4 is an example of two spectrograms: one based on wavelet coefficients (Coiflet, 5 bands, Teager energy) and the other based on STFT coefficients for the same signal. The variations of energy in each frequency band are greater for speech than for music. This can be observed for STFT parameters as well as for wavelet parameters.

-Hierarchical Energy (labelled H_E in Tables), used in automatic speech recognition to parameterize the signal [START_REF] Gemello | Integration of Fixed and Multiple Resolution Analysis in a Speech Recognition System[END_REF], [START_REF] Kryze | A New Noise-Robust Subband Front-End and its Comparison to PLP[END_REF]. We wanted to assess the idea presented by Kryze [START_REF] Kryze | A New Noise-Robust Subband Front-End and its Comparison to PLP[END_REF]. It provides a hierarchical time resolution and gives more importance to the center of the analysis window:

f H_E j = log 10   1 N J (N j +N J )/2 r=(N j -N J )/2 (w j (r)) 2   (6)
J corresponds to the lowest band.

After energy calculation, we decided not to perform a DCT (Discrete Cosinus Transform), like for MFCC, because we want to keep the interpretation of coefficients as frequency band energies.

3 Speech/Music Discrimination System

System Description

The chosen classification approach is a "class/non-class" one. In other words, class detection is performed by comparing a class model and a non-class model estimated on the same representation space. Two classification systems are implemented: speech/non-speech and music/non-music. By taking the "class/non-class" approach, we will be able to optimize the parameterization separately for each classification system. The decisions of both classification systems are merged and the audio signal is segmented into four categories: speech (S), music (M), speech over music (SM) and silence/noise (N) (cf. Table 1). Figure 5 shows the architecture of our speech/music discrimination system.

According to [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], the choice of classifier (GMM, HMM, NN, etc.) is not important for this kind of discrimination task. Therefore, we decided to choose a stochastic classifier. A GMM model containing between 8 and 64 Gaussians per state is trained to model each class. A frame by frame decision would lead

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Evaluation

To evaluate our different features, three error rates are computed:

-Music/Non-Music classification error rate (labelled M/NM in the Tables). Music/non-music segmentation could be useful for audio indexing. -Speech/Non-Speech classification error rate (labelled S/NS in the Tables).

Speech/non-speech detection is useful for discarding the non-speech segments when performing the automatic transcription of broadcast programs. -Global classification error rate (labelled GR in the Tables). Global rate can evaluate the quality of the segmentation system, because this measure takes into account all kinds of segmentation errors. The global error rate corresponds to a more difficult task: we have to segment the audio signal into 4 classes: speech, music, speech over music, other. For S/NS and M/NM tasks there are only 2 kinds of segments, so discrimination is easier and the error rate is smaller. Let n y z be the number of frames recognized as z having label y, and T the total number of frames. The global error rate is computed as follow:

100

* (1 -(n SM SM + n M M + n S S + n N N )/T )
4 Experiments and Results

Parameterization

The signal is sampled at 16kHz. After pre-emphasis, the following parameters are computed on a 32ms Hamming window with a 10ms shift. 32ms is a commonly used window duration in many ASR systems. We used two types of features:

-Baseline MFCC features. 12 MFCC coefficients including C 0 (computed from 24 triangular filters) with their first and second derivatives are computed. This parameterization is the most usual in speech recognition. Finally,

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a vector of 36 components is obtained. These parameters were chosen as baseline because they have achieved very good performance for speech/music discrimination (cf. section 1). -Wavelet-based features. The energy features, described in section 2.2, are calculated on wavelet coefficients obtained with different wavelet families: Daubechie, Coiflet and Symlet. As previously mentioned, these wavelet families are the most popular ones and have been utilized for speech recognition. Let us point out that we use only detail coefficients. Multi-resolution parameters are computed for different decomposition levels, i.e. for different numbers of frequency bands.

Database Description

All the following corpora are manually segmented into speech/non-speech and music/non-music. Silence and background noise segments are labelled as nonspeech and non-music.

Training Corpus

The training corpus is composed of two parts: "Audio CDs" and "Broadcast programs". The "Audio CDs" corpus (2 hours) is made up of several tracks of instrumental music (jazz, electronic music and classical music) and songs (rock and pop) extracted from CDs. The "Broadcast programs" corpus (4 hours 20mn) contains programs from the French radio: broadcast news as well as interviews and musical programs.

Test Corpora

We carried out test experiments on three entirely different corpora:

-We use only the test part of Scheirer corpus built by E. Scheirer and M. Slaney [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF]. All audio files are homogeneous and have the same duration of 15 seconds: 20 files of broadband or telephone speech, 21 files of music and 20 files of vocals. Note that this test part does not contain speech with music in background. The audio is recorded from an FM tuner in San Francisco Bay Area using a variety of stations, styles and noise levels.

The music styles are more various (jazz, pop, country, etc.) than in the Entertainment corpus (see below). Vocals (singing) are labeled as music. This corpus is composed of 32% speech frames and 68% music frames. This corpus allows us to evaluate our new parameterizations on a corpus which has been used in previous studies [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], [START_REF] Williams | Speech/Music Dscrimination Based on Posterior Probability Features[END_REF], [START_REF] Berenzweig | Locating Singing Voice Segments Within Music Signals[END_REF]. We don't exploit the file

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homogeneity information and our discrimination system can split a file into different segments.

Let us note that compared to [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], the cross-validation testing framework is not used here: only the test part of Scheirer data is used to build this test corpus and our models are trained as explained in 4.2.1. The confidence interval is ±1% at a 0.05 signifiance level for about 5% error rate.

-The News corpus consists of three 1-hour files of French radio stations

France-Inter and Radio France International and contains mainly speech or speech over jingles (86% speech, 11% speech over music and 3% music). This corpus is interesting in the way that our speech/music discrimination system can be evaluated on a broadcast news transcription task. The confidence interval is ±0.5% for about 10% error rate.

-The Entertainment corpus is composed of three 20-minutes shows (interviews and musical programs). It was recorded and given to us by a French radio station. This corpus is considered as quite difficult. Indeed, there are a lot of superimposed segments, such as speech with music or songs with an effect of "fade-in fade-out". Moreover, it contains an alternation of broadband speech and telephone speech and some interviews are very noisy. It is made up of 52% speech frames, 18% speech over music frames and 30% music frames. The confidence interval is ±1% for about 20% error rate.

As the three test corpora are very different (different kind of radio programs), more often than not, experimental results will be presented corpus by corpus.

Experimental Results and Discussion

As our goal was to study the relevance of wavelet parameterization for speech/music discrimination, we began our experiments by determining the best wavelets: wavelet type, number of vanishing moments and number of decomposition bands.

We then assessed the performance of the three energy parameters computed from the wavelet coefficients for each segmentation task and we compared these results with the ones obtained by the MFCC baseline segmentation system. Besides, we compared our parameters with 4Hz modulation energy, because according to Scheirer [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF] and Pinquier [START_REF] Pinquier | Speech and Music Classification in Audio Documents[END_REF] the 4Hz modulation was one of the best parameters for speech/music discrimination. After evaluating static wavelet parameters, we tested dynamic parameters [START_REF] Didiot | Speech/Music Discrimination Based on Wavelets for Broadcast Programs[END_REF]. Indeed, several studies [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], [START_REF] Umapathy | Multigroup Classification of Audio Signals Using Time-Frequency Parameters[END_REF] demonstrated that dynamic features allow to efficiently take into account the specificity of the speech and music structure.

The main conclusion of Scheirer's study was that the variance of the parameters give better results than the parameters themselves. [START_REF] Khan | Machine Learning-Based Classification of Speech and Music[END_REF] also concluded

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that variance of MFCC parameters is a relevant feature. Indeed, this kind of long-term parameter should capture the rhythm differences between speech and music. For these reasons, we studied the variance of wavelet parameters [START_REF] Didiot | A Wavelet-based Parametrization for Speech/Music Segmentation[END_REF].

Effect of Wavelet Type and the Number of Vanishing Moments

The goal of our first experiment was to study the influence of different families of wavelets (Daubechie, noted as db in the Tables, Coiflet, noted as coif, Symlet, noted as sym) and the number of vanishing moments of the mother wavelets that generated these families. The mother wavelet has p vanishing moments if:

+∞ -∞ t k Ψ(t) dt = 0, for 0 ≤ k < p (7)
This means that Ψ(t) is orthogonal to any polynomial of degree p -1. So, if the signal is well approximated by a Taylor polynomial of degree k, and k < p then the wavelet coefficients at fine scales have a small amplitude [START_REF] Mallat | A Wavelet Tour of Signal Processing[END_REF]. This property is useful to detect abrupt transitions: wavelet coefficients will be larger during a transition.

For this preliminary experiment, we chose to limit our study to static parameters: instantaneous energy and 5 bands. The corresponding frequency limits are [8000-4000], [4000-2000], [2000-1000], [1000-500], [500-250] Hz. To simplify their interpretation, the results are presented on all test corpora together in terms of speech/non-speech and music/non-music error rates.

Table 2 indicates that the best results were obtained with the smallest number of vanishing moments, especially for the music/non-music discrimination task. With a small number of vanishing moments, abrupt transitions give large wavelet coefficients. So the alternation vowel/fricative or vowel/plosive can be better detected and speech/music discrimination is more accurate.

Another conclusion that can be drawn from this Table is that the different wavelet families (Daubechie, Coiflet, Symlet) achieved similar performance when there is a low number of vanishing moments.

As the three wavelet families gave similar performance and in order to reduce the experimental part, we chose to only use Daubechie (db-2 ) and Coiflet (coif-1 ) wavelets in the following experiments.

Static Parameters

In this experiment, static features based on wavelets were studied. More precisely, we evaluated different decomposition levels (number of bands) and

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Wavelet different energies: instantaneous (labelled E in the Tables), Teager (labelled T_E ) and hierarchical (labelled H_E ) energies. As said in the previous section, we used only Daubechie and Coiflet wavelets. Two decomposition levels were evaluated: 5 and 7 because a preliminary study showed that best classification results were achieved with 5 and 7 decomposition bands.

The experimental results for speech/non-speech and music/non-music discrimination for each test corpus are presented in Tables 3 and4. Several conclusions can be drawn:

-Wavelets/MFCC For speech/non-speech discrimination, the performance of static wavelet features proposed in this paper is comparable to the performance of baseline MFCC features for Scheirer and News corpora (cf. Table 3). But, wavelet features outperform MFCC features for the most difficult corpus (Entertainment) which contains a lot of superimposed segments (speech over music).

For the music/non-music discrimination task, wavelet-based parameters are significantly better than MFCC ones (cf. Table 4) for all three corpora. This confirms our hypothesis that wavelet coefficients are better than MFCC for dealing with non-stationary signals.

We can notice that wavelet features have a more compact representation. Indeed, similar or better results are obtained with a 5-or 7-component vector for wavelet parameterization and with 36-component vector for MFCC.

-Coiflet/Daubechie

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Because it is difficult to predict which wavelet family is more suitable for a given task, we evaluated Coiflet and Daubechie for the two tasks. The two wavelet families obtained similar performance.

-Energies

For speech/non-speech, Teager Energy features provided slightly better discrimination for all corpora. This can be explained by the fact that Teager Energy has the ability to compensate additive noise [START_REF] Jabloun | The Teager Energy based Feature Parameters for Robust Speech Recognition in Car Noise[END_REF]. So, speech over music segments can be better classified. On the other hand, for music/nonmusic, no clear conclusion can be drawn.

-Number of bands

For corpora containing a lot of music (Scheirer ) or speech over music (Entertainment) it is better to use 7 bands for the music/non-music discrimination. In the low frequency (7th) band, on average less energy can be found for pure speech compared to music. So, using 7 bands is useful for music/non-music discrimination. restricted the studied parameters to one wavelet family (Coiflet) and to one number of decomposition bands for each task (5 bands for speech/non-speech, 7 bands for music/non-music).

Comparison between the Wavelet-based Parameters and the 4Hz Modulation Parameter

The goal of this section is to compare the performance of the 4Hz modulation parameter and the wavelet-based parameters because 4Hz modulation yielded a good speech/music discrimination. In our work, the 4Hz modulation parameter was computed as follows:

-Speech signal is segmented into 16ms windows without overlapping; -Mel filter bands are extracted with FFT; -Each frequency band is filtered with a band-pass filter centered at 4 Hz; -After this, all filter channels are added and the variance is computed on a 1-second window.

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Table 5 shows that:

-For speech/non-speech discrimination, wavelet parameters obtain better results than 4Hz modulation parameter; -For music/non-music task, 4Hz energy works well on the Scheirer and News corpora but does not obtain good results on Entertainment corpus. In this last case the errors are due to the fact that speech over music segments or speech with background noise are misclassified as music segments. An unique parameter (like 4Hz modulation) cannot capture the variability of speech over music or speech with background noise. Tab. 5 -Speech/non-speech and music/non-music discrimination results using wavelet-based (coif-1 E with 5 or 7 bands) and 4Hz modulation parameters. Frame error rate in percentages. Relative improvement rates compared to 4Hz modulation are presented in parentheses.

Dynamic Parameters

In order to study how the discrimination rates depend on the dynamic features, the first (∆) and second (∆∆) derivatives of the wavelet-based parameters were computed. Tables 6 and7 present the frame error rate for each corpus separately for dynamic parameters only and for static and dynamic parameters.

Table 6 shows that, for speech/non-speech discrimination, the dynamic coefficients alone are better than the static ones for all corpora and all energy types (except in one case: with Teager energy on the News corpus). This means that dynamic parameters are more discriminant than static ones. This is perhaps due to the fact that the variations of speech parameters are specific, for instance, to the alternation vowel-consonant. According to Table 7, for the music/non-music task, the dynamic parameters seem to be more discriminant than static ones on Scheirer and News corpora. This is not the case for the Entertainment corpus. One reason could be the fact that there are more music and speech over music in this corpus than in the other corpora.

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Tables 6 and 7 also show that the addition of first derivatives (∆) improves the results compared to static parameters. For instance, using Teager energy (coif-1 with 5 bands) for speech/non-speech discrimination, a relative significant gain of 48% for the Scheirer corpus, 16% for the News corpus and 31% for Entertainment corpus is obtained compared to the static features. For music/non-music discrimination, using Teager energy (coif-1 with 7 bands), a relative significant gain of 51% for the Scheirer corpus and 29% for the News corpus is obtained compared to the static features. For the Entertainment corpus no improvement is observed.

On the contrary, addition of the second derivatives (∆∆) does not improve the results compared to the addition of the first derivatives. We can even see a decrease in the performance for the music/non-music task. We attribute this slight decrease to the nature of ∆∆ coefficients. One possible explanation could be that ∆∆ coefficients have a high variability and depend on the type of music. So, if the type of music occuring in the test files has not been encountered in the training files, the ∆∆ coefficients are not useful and will add "noise" to the models.

In conclusion, the important result of this section is that combining the derivatives with the static wavelet parameters outperforms MFCC results for all corpora and for both segmentation tasks.

Long-Term Parameters

The study of long-term parameters such as variance on a large window (between 1 and 2.5 second duration) seems interesting [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], [START_REF] Umapathy | Multigroup Classification of Audio Signals Using Time-Frequency Parameters[END_REF], [START_REF] Williams | Speech/Music Dscrimination Based on Posterior Probability Features[END_REF], [START_REF] Khan | Machine Learning-Based Classification of Speech and Music[END_REF]. We conducted experiments in order to optimize the window duration for the computation of the variance. The best result was obtained for a 1-second window size. We applied this 1-second variance to static coefficients: MFCC and energy features based on the coif-1 wavelet family.

To study the behavior of wavelet variance parameter, we computed the histogram of the variance of the Teager energy computed in the third band, using wavelet coif-1 with 5 bands on the training corpus (cf. Figure 6). For the other bands, the shapes are similar. As expected the variance for speech segments is greater than the variance for music segments because of the alternation of vowel-consonant. The curve corresponding to speech over music segments overlaps the speech and music curves. This explains why it is difficult to discriminate speech over music segments.

Tables 8 and9 present the discrimination error rates provided only by variance of the parameters and by combining the variance with static parameters. For speech/non-speech discrimination, short term dynamic parameters ∆ (cf. Table 6). are better than the long term parameters (cf. Tab. 6 -Speech/non-speech discrimination results using wavelets coif-1 with 5 bands and dynamic parameters (∆, ∆∆). Frame error rate in percentages. Relative improvement rates compared to static parameters are presented in parentheses. music/non-music task, according to Table 9, the variance parameters give similar results than ∆ parameters (cf. Table 7) on the Scheirer and News corpora, and better results on the Entertainment corpus. Tables 8 and9 show that static plus variance parameters do not give any improvement compared to variance parameters. Moreover, for Entertainment corpus, a small degradation is observed.

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All these results point out that generally ∆ parameters are better than long term parameters.

Global Discrimination

This experiment aims to discriminate speech, music, speech over music and silence/noise. As we said previously (see section 3.2) global discrimination is a difficult task and allows to evaluate the quality of the segmentation system, because this measure takes into account all kinds of segmentation errors. This is obtained by performing speech/non-speech discrimination, then music/nonmusic discrimination, and finally taking into account these results to calculate a global discrimination rate (see section 3.2). For each discrimination task, we used the features giving the best discrimination results in the previous experiments, i.e. coif-1 with 5 bands for speech/non-speech discrimination and coif-1 with 7 bands for music/non-music discrimination. In the previous experiments, the three energy types reached almost the same performance. Tab. 9 -Music/non-music discrimination results using variance on a 1 second window and static with variance coefficients for wavelet coif-1 and 7 bands. Frame error rate in percentages. Relative improvement rates compared to MFCC are presented in parentheses.

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Consequently, we only take into account the Teager energy. We chose to test static parameters plus delta.

Table 10 shows that wavelet-based parameterization gives much better performance than MFCC parameterization for this more difficult task. This improvement is statistically significant and is 58% for Scheirer corpus, 40% for News corpus and 30% for Entertainment corpus compared to MFCC baseline system.

Param

Conclusion

In this paper we have proposed a new parameterization based on the wavelets for speech/music discrimination. Our goal was not to propose a new wavelet type but to apply the wavelet formalism for speech/music discrimination task.

Compared to MFCC parameters, widely used for this task, wavelet parameters are more compact, allow the extraction of time-frequency features and deal with non-stationary signal. Our discrimination system is based on the GMM class/non-class approach and the Viterbi algorithm performs the classification.

In the experiments, the proposed wavelet features have been compared to MFCC parameters on three various corpora: Scheirer, News, Entertainment. Scheirer corpus has been frequently used in previous studies, News corpus is a broadcast news corpus. Entertainment is considered as quite difficult because it contains a lot of superimposed segments: speech over music. As expected, the classification error rates on this last corpus are higher than on the two other corpora.

The following conclusions have been drawn from these experiments:

-The wavelet parameterization gives better results that MFCC features for all studied discrimination tasks (speech/non-speech, music/non-music and global discrimination) for all three corpora. For instance, compared to MFCC

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parameters, the wavelet parameterization led to a significant improvement in the error rate for global speech/music discrimination: 58% for Scheirer, 40% for News and 30% for Entertainment corpora. -The smaller the number of vanishing moments, the better the discrimination results are. -The choice of the wavelet family has a small effect on the discrimination results. -As it has been shown in the different studies for other parameterizations [START_REF] Scheirer | Construction and Evaluation of a Robust Multifeature Speech/Music Discriminator[END_REF], dynamic parameters give solid results. Long term parameters achieve slightly worse results. -Finally, the best results were obtained using wavelet coif-1 Teager energy and ∆: with 7 bands for music/non-music discrimination and 5 bands for speech/non-speech discrimination.

In conclusion, wavelet parameters are well suited for speech/music discrimination, especially when a corpus containing speech over music segments is being used.

Acknowledgements

We would like to thank Eric Scheirer and Malcolm Slaney for making their speech/music corpus available for us. We also thank the evaluation project Technolangue EVALDA-ESTER and the CNRS for its support of the RAIVES project.

Références

Fig. 1 -

 1 Fig. 1 -. Example of signals: music signal (Vivaldi excerpt, above) and speech signal (below).

Fig. 2 -Fig. 3 -

 23 Fig. 2 -. Example of a dyadic time-frequency decomposition.

Fig. 4 -Fig. 5 -

 45 Fig. 4 -. Above: spectrogram based on STFT (128 frequency bands, frame size 32ms), below: spectrogram based on Coiflet, (5 bands, Teager energy), for a 2s signal containing speech during the first part and music during the last one.

Fig. 6 -

 6 Fig. 6 -. Histogram of 1s variance of the Teager energy of the third band using wavelet coif-1 with 5 bands.

  Discrimination results with varying wavelet types and number of vanishing moments. Wavelets with 5 bands and instantaneous energy. Frame error rate in percentages. Scheirer, News and Entertainment corpora.

	Type NbVanishMom M/NM S/NS
	db-2	2	11.6	4.9
	db-4	4	15.8	4.6
	db-8	8	16.8	5.0
	db-12	12	19.0	5.6
	coif-1	2	11.5	4.8
	coif-3	6	16.3	4.9
	coif-5	10	19.0	5.6
	sym-2	2	11.6	4.9
	sym-4	4	16.0	4.6
	sym-8	8	16.7	5.2
	Tab. 2 -

Table 8

 8

	). For

  Speech/non-speech discrimination results using variance on a 1-second window and static with variance coefficients for wavelet coif-1 and 5 bands. Frame error rate in percentages. Relative improvement rates compared to MFCC are presented in parentheses.

				5	2.9	5.8
	Var	of	12	2.2 (12%) 4.1 (-41%) 8.1 (-40%)
	MFCC
	MFCC+(Var	24	3.4 (-36%) 4.3 (-48%) 10.4 (-79%)
	of MFCC)
	Var of E	5	1.7 (32%) 3.9 (-34%) 3.7 (36%)
	Var of T_E	5	1.7 (32%) 4.0 (-38%) 3.7 (36%)
	Var of H_E	5	1.7 (32%) 4.2 (-45%)	4.1 (29%)
	E+(Var of E)	10	2.1 (16%) 4.2 (-44%)	4.2 (28%)
	T_E+(Var of T_E)	10	1.7 (32%) 4.1 (-41%)	4.1 (29%)
	H_E+ (Var of H_E)	10	2.1 (16%) 4.5 (-55%)	5.1 (12%)
	Tab. 8 -
	Parameters	NbPar	Scheirer	News	Enter
	MFCC+∆+∆∆	36	6.5	13.1	23.1
	Var	of	12	3.1 (52%)	7.7 (41%)	25.1 (-9%)
	MFCC
	MFCC+(Var	24	4.7 (28%)	9.4 (28%)	22.5 (3%)
	of MFCC)
	Var of E	7	1.7 (74%) 7.5 (43%) 16.3 (29%)
	Var of T_E	7	1.8 (72%) 7.1 (46%) 16.4 (29%)
	Var of H_E	7	1.8 (72%)	7.3 (44%)	16.7 (28%)
	E + (Var of E)	14	1.8 (72%)	8.3 (37%)	18.4 (20%)
	T_E + (Var of T_E)	14	1.8 (72%)	9.2 (30%)	19.2 (17%)
	H_E + (Var of H_E)	14	1.8 (72%)	8.6 (34%)	19.1 (17%)

  Global discrimination with best features: wavelet coif-1 with 7 bands and ∆ for music/non-music discrimination and wavelet coif-1 with 5 bands and ∆ for speech/non-speech discrimination. Frame error rate in percentages. Relative improvement rates compared to MFCC are presented in parentheses.

	.M/NM	Param.S/NS	NbPar Scheirer	News	Enter
	MFCC+∆+∆∆	MFCC+∆+∆∆	36-36	8.1	15.0	26.3
	T_E(7bands)+∆ T_E(5bands)+∆	10-14	3.4(58%) 9.0(40%) 18.4(30%)
	Tab. 10 -

The scaling function is compactly supported if and only if the filter L has a finite support.

For instance, using 5 bands on 512 samples window, N 1 = 256, N 2 = 128, N 3 = 64, N 4 = 32 and N 5 = 16.

A duration of 0.5 seconds is chosen because we assume that a speech segment contains at least one word and consequently, lasts at least 0.5 seconds.


E Serrano

Ph Caron

Dr Sebastien Vergez

J Sarini

J Percodani

Lymph node management in clinically node-negative patients with papillary thyroid carcinoma

Keywords: papillary thyroid carcinoma, lymph node metastases, central neck dissection, selected neck dissection

Lymph node management in clinically node-negative patients with papillary thyroid carcinoma

Introduction

Systematic lymph node dissection in patients with papillary thyroid carcinoma (PTC) is controversial. Cervical areas are the first sites of the recurrence of PTC [START_REF] Noguchi | The value of lymph-node dissection in patients with differentiated thyroid cancer[END_REF]. The impact of lymph node metastasis (LNM) on the prognosis of papillary disease regarding survival without recurrence and overall survival determines the extent of surgery. Without preoperatively diagnosed LNM, the indications and the appropriate extents of central neck dissection (CND, compartment VI) and/or lateral neck dissections with their respective morbidity are debated and attitudes vary according to authors.

In patients with differentiated thyroid carcinoma, Hughes et al in a matched-pair analysis (n = 200), and Lin et al, in a retrospective study (n = 1013), have reported a correlation between node invasion and an increased rate of local recurrence [START_REF] Hughes | Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis[END_REF][START_REF] Lin | Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases[END_REF]. However, in these studies LNM did not influence the survival rate [START_REF] Hughes | Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis[END_REF][START_REF] Lin | Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases[END_REF]. Lundgren et al, in a nested case-control study of 5123 patients with differentiated thyroid carcinoma, reported a higher mortality in the pN1 group [START_REF] Lundgren | Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study[END_REF]. Therefore the impact of neck node dissection on the prognosis is controversial.

For some authors, the prognosis is not influenced by node surgery [START_REF] Steinmuller | Prognostic factors in patients with differentiated thyroid carcinoma[END_REF] whereas for others, neck node dissection significantly improves overall survival [START_REF] Tisell | Improved survival of patients with papillary thyroid cancer after surgical microdissection[END_REF][START_REF] Noguchi | Papillary thyroid carcinoma: modified radical neck dissection improves prognosis[END_REF].

The heterogeneity of these results assessing the prognostic impact of the LNM as well as dissection, combined with a lack of prospective analysis, explains the lack of consensus concerning the nodal management of PTC. In the case of cervical LNM, either suspected or proven by fine needle aspiration, it is commonly accepted that the surgery may not be limited to a Berry-Picking procedure [START_REF] Noguchi | The value of lymph-node dissection in patients with differentiated thyroid cancer[END_REF][START_REF] Tisell | Improved survival of patients with papillary thyroid cancer after surgical microdissection[END_REF][START_REF] Uchino | Modified radical neck dissection for differentiated thyroid cancer: operative technique[END_REF][START_REF] Palazzo | Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades[END_REF]. A dissection is systematically performed, but the limits differ from one centre to another. Noguchi and Murakami, as well as Uchino et al., performed a modified radical neck dissection (MRND) at the central and lateral levels (II, III, IV, and V), respecting the internal jugular vein, the spinal accessory nerve and the sternomastoid [START_REF] Noguchi | The value of lymph-node dissection in patients with differentiated thyroid cancer[END_REF][START_REF] Uchino | Modified radical neck dissection for differentiated thyroid cancer: operative technique[END_REF]. For the past forty years, Palazzo et al. has described a move away from the Picking and MRND towards a selective lateral neck dissection (SLND) adapted to the invasion, and most of the time concerning levels VI, III and IV [START_REF] Palazzo | Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades[END_REF]. Caron et al. also opted for selective dissections, systematically taking levels III and IV, and extended to other areas according to preoperative clinical and radiological assessment [START_REF] Caron | Selective modified radical neck dissection for papillary thyroid canceris level I, II and V dissection always necessary?[END_REF].

Our work was focused on the lymph node management in patients with PTC, exclusively in the absence of LNM diagnosed at the initial clinical and ultrasonographic (US) assessment. In our medical teams, before the European consensus [START_REF] Pacini | European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium[END_REF], we chose to routinely do bilateral CND and ipsilateral lateral neck dissection if there was no suspicious lymph nodes (cN0 patients). A bilateral lateral neck dissection was done in the presence of multiple, bilateral or isthmic tumors. The objective of our work was to evaluate the pattern of lymph node invasions in the central and lateral cervical compartments in patients with PTC and then to propose a lymph node management strategy.

Patients and methods

Selection of patients.

This retrospective study was carried out in Toulouse, France, in the Head and Neck surgery department of the Rangueil-Larrey University Hospital and the Claudius Regaud Institute. From 2000 to 2006, and before the European consensus [START_REF] Pacini | European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium[END_REF], the files from all patients who had a neck node dissection for a PTC were compiled.

From this exhaustive collection of 230 patients, those who had had a central and a lateral cervical dissection, without any preoperative diagnosis of LNM, were collected, resulting in 90 patients being included.

The selected criteria of inclusion gathered the histopathological diagnosis of the PTC (greater than 10 mm in size), whatever the stage and differentiation, with a clinically negative neck (cN0). There were no clinical or US signs suggesting LNM in the preoperative assessment. A precessive LNM (cN1) or a metastasis was considered as exclusion criteria in our study. Moreover, when the time between definitive thyroid histological diagnosis and complementary node surgery exceeded six months, we excluded the subjects. Some patients underwent a total thyroidectomy with a bilateral central and a uni-or bilateral lateral neck dissection at the same time in the case of a preoperative or intraoperative diagnosis of PTC (n = 28). A bilateral lateral neck dissection was done in the presence of multiple, bilateral or isthmic tumours. For the other patients (n = 62), the diagnosis of PTC was done secondarily and the average time between the lobectomy or thyroidectomy and the cervical dissection was 42 days.

All the surgical reports were analyzed, alongside all the pathology reports. The TNM stage was set for each patient, according to the AJCC 2002 classification. The number, the size and the localization of the tumours were detailed, and compared with the presence of cervical LNM. The number of LNM, with or without extracapsular spread, as well as their size was related to the number of lymph nodes dissected in each cervical area. The complications were also noted and hypoparathyroidism was considered definitive when requiring vitamin D supplementation for more than 6 months. Permanent laryngeal nerve palsy was considered definitive when persisting for more than 6 months.

Surgical procedures.

All the patients routinely underwent bilateral CND (compartment VI). After having identified and preserved the recurrent laryngeal nerve and the parathyroid glands, the node clearance was performed laterally to the carotid sheaths, caudally to the innominate artery, dorsally to the prevertebral fascia and cranially to the hyoid bone. Thus, the paratracheal, pretracheal, prelaryngeal and superior mediastinal node sites were dissected. In cases of reoperation of the central compartment, the recurrent nerve was found below the sclerosis of the previous surgery (near the innominate artery on the right side and adjacent to the trachea and the oesophagus on the left side).

The selective lateral neck dissection (SLND) systematically preserved the internal jugular vein, the sternomastoid muscle and the spinal accessory nerve. It systematically covered levels II, III and IV respectively, the upper, mid and lower jugular groups. Forty-five of the 90 patients operated on by one of the surgical teams also had a level V node dissection. We accessed these areas by two routes: a J incision along the medial edge of the sternomastoid, or a prolonged Kocher incision, that could be supplemented if necessary by a second high cervical parallel incision (Mac Fee modified). The statistical analysis included an ANOVA test with the StatView© software version 4.55. Differences were considered significant when p <0.05.

Results

Clinical characteristics

The patient population consisted of 71 women and 19 men, with a mean age of 45 +/-16 [range 13 -89] (Table -1). According to the TNM classification AJCC 2002 our population was composed of 30 pT1, 30 pT2 and 29 pT3. There was no tumour classified pT4 in our cohort. However, the detailed pathological description was missing for one patient (Table 1).

The CND was bilateral in 86 patients. In 4 patients, the surgical exploration could not be bilateral because of a

Pathological characteristics

Forty-one patients (i.e. 45.5%) had lymph node invasion (pN1) whereas neck palpation and ultrasound examination were negative at the assessment preceding the thyroid surgery. Among them, 28 (i.e. 31%) had metastatic invasion of the central compartment and the lateral compartment. For 13 patients (i.e. 14.5%), only the central compartment was the location of LNM. No patient presented a lateral lymph node invasion without a central invasion. Statistical analyses revealed that the patient's age, gender, tumour size and stage of TNM did not influence the risk of node invasion.

Among 28 patients pN1 in the lateral compartment, LNM were found in level II, III, and IV respectively for 15, 16 and 16 patients (54%, 57% and 57% of cases). For five patients, the lateral compartment invasion was limited to the upper jugular compartment (Level II). Among patients with at least one metastasis in the lateral compartment, 18 patients had an exploration at the posterior triangular level (V) and 9 of them had LNM in this area. A bilateral invasion of the central compartment was found in 18 patients (44% of pN1 patients). Six patients had bilateral invasion of the lateral compartments. Four patients had contralateral LNM in regard to the thyroid tumour. For one of them, a bilateral multifocal tumour with clear left predominance led to a left central and right lateral invasion. Unilateral tumours of three other patients were associated with contralateral central metastases and ipsilateral cervicolateral ones.

A total of 213 LNM were identified in the central compartment [average 5.2 +/-0.8 per patient]. The average size of central LNM was 4.7 mm +/-0.9 [range 0.5-30 mm]. Eighty one percent of invaded LNM were smaller than or equal to 5 mm, 16% were between 5 and 10 mm and 3% greater than 10 mm. We concentrated on the comparison of the maximum size of the removed LNM for each patient. While the exact size of each LNM was not always mentioned, the minimum and maximum sizes of the invaded lymph nodes were regularly recorded.

The proportion of LNM (in the central compartment) less than or equal to 5 mm was 66% while those strictly above 10 mm remained low at 5% (Table 2). The average size of LNM with extracapsular spread was 4.9 mm +/-1.9 [range 1-15 mm].

A total of 136 LNM were counted with an average number of lateral neck dissections of 4.9 +/-0.9. The average size of invaded lateral LNM was 7.9 mm +/-2.1 [range 0.5-40 mm]. The analysis of the maximal size of invaded lateral lymph nodes gave 7% of LNM inferior or equal to 5 mm, 93% of LNM superior to 5 mm (Table 2).

Complications

One patient presented a definitive laryngeal nerve palsy (i.e. 1%). This patient needed a reoperation for a contralateral lobectomy with lymph node dissections and was pN0. Six patients had a definitive hypoparathyroidism (i.e. 6.7%). Three of them had had a single operation and three others had been reoperated.

There was no significant difference between the morbidity of pN0 and pN1 patients (Table 1).

Follow-up

The median follow-up was 62 months . Ten patients who presented LNM (or a tumor, n=1) with a large extracapsular spread had had an external radiation therapy. Each patient received a radio-iodine treatment (90/90). This treatment needed to be repeated for six patients (initially pN1 with a detectable thyroglobulin blood levels during the follow-up without any radiological target for five of them). They are actually disease-free.

Three patients died (death unrelated to the disease). Seven patients were lost after the first year of follow-up.

Two patients with LNM in central compartment had had another dissection for a node recurrence and are disease-free at the last evaluation. Another patient who was initially pN0 developed recently a small and unique lateral LNM eight years after the treatment. The seventy-one other patients are disease-free since the first treatment.

Discussion

LNM staging

Preoperative node invasion is often underestimated in papillary disease. In our study, 41/90 cN0 patients actually had LNM. According to data from the literature, 38 to 90% of nodal metastases are not clinically diagnosed [START_REF] Mirallie | Localization of cervical node metastasis of papillary thyroid carcinoma[END_REF].

The proportion of non-diagnosed LNM in our study could have been explained by the size of nodal metastases, often less than 5 mm. On the contrary, few non-diagnosed LNM were above 10 mm but the US examination was done before the initial consultation and some patients had the node dissection a few weeks after the definitive pathological diagnosis of PTC. In this context, careful cervical palpation and a detailed cervical ultrasound examination are carried out preoperatively to search for central, jugular and spinal lymph nodes. A fine needle aspiration of lymphadenopathy for cytology can be done, possibly ultrasound-guided, combined with a measure of thyroglobulin concentration. Cystic appearance, hyperechoic punctuations, loss of hilum, and peripheral vascularization can be considered as major US criteria of LNM [START_REF] Leboulleux | Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer[END_REF]. It is interesting to note that in our results, central LNM were clearly smaller than lateral LNM, with most of the central LNM measuring less than 5 mm.

The sensitivity of the US diagnosis of central LNM described in literature varies from 10.5% to 29% [START_REF] Ito | Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid[END_REF][START_REF] Sugitani | Prospective outcomes of selective lymph node dissection for papillary thyroid carcinoma based on preoperative ultrasonography[END_REF]. Sugitani et al. found a positive predictive value of 98% for the lateral compartment (n = 130) [START_REF] Sugitani | Prospective outcomes of selective lymph node dissection for papillary thyroid carcinoma based on preoperative ultrasonography[END_REF]. Therefore a preoperative clinical or ultrasonographic diagnosis of LNM is particularly difficult in the central compartment, reinforcing the rationale of a systematic CND.

Central compartment LNM

In our patients, central node invasion was present in 45.5% of the patients. The central compartment is the first lymph node site in thyroid cancer [START_REF] Noguchi | The value of lymph-node dissection in patients with differentiated thyroid cancer[END_REF][START_REF] Palazzo | Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades[END_REF], except in rare cases of superior polar tumours in which a jugular chain drainage is first described [START_REF] Attie | Modified neck dissection in treatment of thyroid cancer: a safe procedure[END_REF]. This drainage frequently crosses at the central compartment [START_REF] Attie | Modified neck dissection in treatment of thyroid cancer: a safe procedure[END_REF]. In our study, a bilateral central nodal invasion was observed in 18 patients (i.e. 44% of pN1 patients), and 3 patients had a unilateral central invasion, contralateral to a unique tumour. Central invasion is frequent, precocious and non-lateralized, leading to the suggestion that a bilateral CND should be combined with a total thyroidectomy after the diagnosis of PTC [START_REF] Gimm | Pattern of lymph node metastases in papillary thyroid carcinoma[END_REF][START_REF] Koo | Predictive factors for ipsilateral or contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma[END_REF][START_REF] Lee | Predictive factors for central compartment lymph node metastasis in thyroid papillary microcarcinoma[END_REF]. In a retrospective analysis, with an average follow-up of 13.3 +/-6.2 years (n = 195), Tisell et al. highlighted an improvement of survival, brought about by a prophylactic central dissection [START_REF] Tisell | Improved survival of patients with papillary thyroid cancer after surgical microdissection[END_REF].

However, the CND procedure increases the morbidity observed after a thyroidectomy alone [START_REF] White | Central Lymph Node Dissection in Differentiated Thyroid Cancer[END_REF][START_REF] Filho | Surgical complications after thyroid surgery performed in a cancer hospital[END_REF]. Permanent laryngeal nerve palsy occurs with a higher incidence: 0 to 4.8% [START_REF] Koo | Predictive factors for ipsilateral or contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma[END_REF][START_REF] Filho | Surgical complications after thyroid surgery performed in a cancer hospital[END_REF][START_REF] Roh | Total Thyroidectomy Plus Neck Dissection in Differentiated Papillary Thyroid Carcinoma Patients: Pattern of Nodal Metastasis, Morbidity, Recurrence, and Postoperative Levels of Serum Parathyroid Hormone[END_REF]. CND significantly reduces serum parathyroid hormone levels [START_REF] Roh | Total Thyroidectomy Plus Neck Dissection in Differentiated Papillary Thyroid Carcinoma Patients: Pattern of Nodal Metastasis, Morbidity, Recurrence, and Postoperative Levels of Serum Parathyroid Hormone[END_REF]. Our hypoparathyroidism rates are in the upper range of the published rates.

Definitive hypoparathyroidism after CND has been described as being from 0.9% to 11.3% [START_REF] Ito | Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid[END_REF][START_REF] Koo | Predictive factors for ipsilateral or contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma[END_REF][START_REF] Filho | Surgical complications after thyroid surgery performed in a cancer hospital[END_REF][START_REF] Roh | Total Thyroidectomy Plus Neck Dissection in Differentiated Papillary Thyroid Carcinoma Patients: Pattern of Nodal Metastasis, Morbidity, Recurrence, and Postoperative Levels of Serum Parathyroid Hormone[END_REF][START_REF] Bonnet | Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment[END_REF]. In our study there was no significant difference seen when this dissection was done at a later date, but many authors report that this increases complications related to this surgery [START_REF] Filho | Surgical complications after thyroid surgery performed in a cancer hospital[END_REF][START_REF] Roh | Total Thyroidectomy Plus Neck Dissection in Differentiated Papillary Thyroid Carcinoma Patients: Pattern of Nodal Metastasis, Morbidity, Recurrence, and Postoperative Levels of Serum Parathyroid Hormone[END_REF][START_REF] Bonnet | Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment[END_REF][START_REF] Ito | Lateral and mediastinal lymph node dissection in differentiated thyroid carcinoma: dications, benefits and risks[END_REF]. And our unique definitive laryngeal nerve palsy was observed after a reoperation.

The European consensus acknowledges that a prophylactic CND allows an accurate staging of the disease and may guide subsequent treatment and follow-up, but it also specifies that its benefits remain controversial [START_REF] Pacini | European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium[END_REF].

On the other hand, the American Thyroid Association recent guidelines argue that a prophylactic CND should be considered for patients with PTC especially for advanced primary tumors (T3 or T4) [START_REF] Cooper | Revised american thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer[END_REF]. Evidence-based recommendations support CND for PTC in patients under the care of experienced endocrine surgeons [START_REF] White | Central Lymph Node Dissection in Differentiated Thyroid Cancer[END_REF].

Therefore we opted for a systematic bilateral CND, allowing an objective LNM staging.

Lateral compartment LNM

Bonnet et al. purposed a prophylactic neck dissection including central and ipsilateral III and IV (eventually extended to II and V) for PTC less than 2 cm. This LNM staging modified the indication for radioiodine ablation for 30% of patients [START_REF] Bonnet | Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment[END_REF]. Pereira et al. reported the lack of central recurrence in a group of patients who underwent a prophylactic central dissection, and described a correlation between an involvement in the lateral compartment (group of patients without prophylactic lateral dissection) and an initial central invasion including more than five LNM. No lateral disease in their series occurred in pN0 or pN1 patients who had less than five LNM [START_REF] Pereira | Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma[END_REF]. Goropoulos et al. decided to extend the node dissection into the lateral neck compartments depending on the histological results of the central compartment. Without a preoperative diagnosis of central invasion, the decision is made on the basis of the results of the analysis of frozen sections from CND [START_REF] Goropoulos | Value of the cervical compartments in the surgical treatment of papillary thyroid carcinoma[END_REF].

We found no lateral nodal involvement without a central involvement, but in the literature, the presence of lateral LNM without combined central invasion (skip metastases) has been regularly reported: Noguchi and Murakami 7%, Chung et al. 7.7%, Bonnet et al. 12.5%, Ito et al. 12.9% and Mirallie et al. [START_REF] Sugitani | Prospective outcomes of selective lymph node dissection for papillary thyroid carcinoma based on preoperative ultrasonography[END_REF].3% [START_REF] Noguchi | The value of lymph-node dissection in patients with differentiated thyroid cancer[END_REF][START_REF] Mirallie | Localization of cervical node metastasis of papillary thyroid carcinoma[END_REF][START_REF] Ito | Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid[END_REF][START_REF] Bonnet | Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment[END_REF][START_REF] Chung | Lateral lymph node metastasis in papillary thyroid carcinoma: results of a therapeutic lymph node disssection[END_REF].

A study conducted in a cohort of 2966 patients helped to highlight the gain in terms of survival provided by an MRND in the context of extrathyroid tumour invasion or large node invasions [START_REF] Noguchi | Papillary thyroid carcinoma: modified radical neck dissection improves prognosis[END_REF]. Ohshima et al. even suggested that a systematic prophylactic bilateral MRND should be carried out in the presence of risk factors, such as bulky, bilateral or isthmic tumours. In their series they decreased the proportion of distant metastases, the number of cancer deaths and improved the rate of survival at 10 years [START_REF] Ohshima | Is a bilateral modified radical neck dissection beneficial for patients with papillary thyroid cancer?[END_REF]. However, in the absence of LNM diagnosed during initial assessment, many authors do not perform any prophylactic node surgery [START_REF] Palazzo | Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades[END_REF][START_REF] Caron | Selective modified radical neck dissection for papillary thyroid canceris level I, II and V dissection always necessary?[END_REF]. In our study 62/90 patients had had an SLND without involvement in the lateral compartment and therefore we have now decided not to perform systematic SLND because the lateral compartment can easily be followed by ultrasound [START_REF] Sugitani | Prospective outcomes of selective lymph node dissection for papillary thyroid carcinoma based on preoperative ultrasonography[END_REF] and a SLND can be performed subsequently without the increased morbidity if an LNM (skipmetastasis or not) appears. Based on these results, we do not then expose every patient with PTC to the morbidity and the scar of a systematic SLND. But, in the cases of large extrathyroid invasion or large LNM in the central compartment, we perform an ipsilateral SLND.

In Sivanandan and Soo's studies, the proportion of invaded node levels in cN1 patients, confirmed the preferential invasion of middle and low jugular areas (levels III and IV, in 50 to 72%) [START_REF] Sivanandan | Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid[END_REF]. Nevertheless, they also recorded a non-negligible proportion of posterior triangular nodes (level V in 24 to 44%), and upper jugular (level II in 45 to 56%) involvement. In our study, this upper jugular and posterior triangular invasion were found in 54% and 50% respectively of pN1 patients laterally. Therefore, when a therapeutic SLND is indicated, we systematically pick out levels II to V.

Conclusion

This clinical study suggests that systematic bilateral central node dissection is indicated in patients with PTC (more than 1 cm in size). In case of preoperative or intraoperative diagnosis of PTC, this CND is performed at the time of the total thyroidectomy and enables an objective evaluation of the lymph node status to be made. The small diameter of the LNM of the central compartment explains the lack of sensitivity of the preoperative ultrasonographic assessment.

On the other hand, SLND is unnecessary without a clinical and/or US diagnosis of lymph node involvement at the initial assessment. This suggestion is based upon an initial cervical US which precisely evaluates the lateral cervical compartments (II-V).

These results reinforce the European consensus, but further prospective studies are necessary in order to analyse the impact on the quality of life and survival without recurrence in patients with PTC treated by total thyroidectomy and CND.

  major local sclerosis. An average of 4.7 +/-0.4 [range 0-21] lymph nodes on the right side and 4.4 +/-0.37 [range 0-22] on the left side had been removed. The proportion of right or left dissections without lymph nodes did not exceed 3 patients and systematically occurred during a second surgical intervention. The SLND was composed of about 25 lymph nodes +/-1.1 [range 6-54]. Nineteen patients had bilateral SLND due to the median nature of a single location or the bilateral nature of multiple locations. Sixty-three right dissections and 46 left dissections were done.

Table 1 .

 1 Pathological data of the patient population.

	Number of	Lateral and	Central pN1 pN0
	Patients	central pN1

Table 2 .

 2 Diameters of the largest LNM by compartment.

	5 mm < D
	D ≤ 5mm	D > 10mm
	D ≤ 10 mm

Acknowledgements. The authors thank Dr Delphine Berchery for the statistical analyses, Dr Adil Benlyazid and John Woodley for the English corrections.

Funding. This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Declaration of interest.

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.


Michael Kontos
email: michalis_kontos@yahoo.com

R S Lewis

M Lüchtenborg

L Holmberg

Does Immediate Breast Reconstruction using Free Flaps Lead to Delay in the Administration of Adjuvant Chemotherapy for Breast Cancer?

Keywords: Breast cancer, immediate reconstruction, delay, adjuvant treatment, free flaps, TRAM flaps

BACKGROUND: Immediate breast reconstruction (IBR) using Free flaps is becoming increasingly popular. However, these are complex surgical procedures with more complications and longer recovery time, which can potentially delay adjuvant treatment.

Our aim is to investigate the impact of free flap IBR on the timing of adjuvant treatment.

METHODS: Details of all breast cancer patients undergoing mastectomy with (study group) and without (control group) free flap IBR, followed by adjuvant treatment between 2002 and 2007 were obtained. The time lapse between surgery and adjuvant therapy was calculated and the causes of delay were recorded. The results were compared between the two groups and with local and international guidelines. RESULTS: Twenty-seven and 139 patients were included in the study and control group, respectively. The mean time period between surgery and commencement of adjuvant treatment for the study group was 55 days compared with 40 days for the controls. Furthermore, significantly less IBR patients received their adjuvant treatment within 6, 8 or 10 weeks after surgery in comparison to the control group. Groups appeared similar however at 12-week point. The reason for the delays was reconstruction-related surgical complications. CONCLUSION: There is a significant delay in the commencement of adjuvant treatment after mastectomy and free flap IBR in comparison to mastectomy alone patients due to reconstruction related surgical complications. The effects of this delay on survival have not been fully investigated yet and may be significant for at least some of the patients.

Introduction

Over the past few decades, there has been a surge in the popularity of immediate breast reconstruction (IBR). Restoring body image has been shown to have an important effect on the psychological recovery of breast cancer patients [START_REF] Dean | Effects of immediate breast reconstruction on psychological morbidity after mastectomy[END_REF][START_REF] Rosenqvist | Patients psychological and cosmetic experience after immediate breast reconstruction[END_REF] and there is evidence that there is greater psychological advantage in those who have immediate rather than delayed reconstruction [START_REF] Sk | The psychological impact of immediate rather than delayed breast reconstruction[END_REF].

Many of the patients who require a mastectomy, and therefore will be considered for IBR, will have high-risk cancers that require post-operative chemotherapy and/or radiotherapy [START_REF] Taylor | The effect of immediate breast reconstruction on adjuvant chemotherapy[END_REF]. According to current guidelines, chemotherapy should be given within 4-12 weeks of surgery [START_REF] Wilson | Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy[END_REF][START_REF]Early and locally advanced breast cancer: diagnosis and treatment[END_REF][START_REF] Lohrisch | Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer[END_REF][START_REF] Mortenson | Immediate Breast Reconstruction after Mastectomy Increases Wound Complications[END_REF] amid fears that a further delay could adversely affect systemic recurrence and survival [START_REF] Shannon | Does Timing of Adjuvant Chemotherapy for Early Breast Cancer Influence Survival?[END_REF]. It is also current practice to wait until wound healing is complete before starting chemotherapy, which in itself has its own complications.

Free flap reconstructions and especially TRAM (transverse rectus abdominis myocutaneous) and DIEP (deep inferior epigastric perforator) flaps have become the most commonly used techniques [START_REF] Schusterman | Immediate Breast Reconstruction: Why the Free TRAM Over the Conventional TRAM Flap?[END_REF][START_REF] Elliott | Immediate TRAM Flap Breast Reconstruction: 128 Consecutive Cases[END_REF]. Free flap reconstruction provides good cosmetic result but is an intricate surgical procedure with more complications and a longer recovery period than a mastectomy alone. There are several publications on the potential delay of adjuvant treatment due to IBR complications. However, they all share a common limitation in that they consider all types of reconstruction as one uniform group and differences between reconstruction techniques are not taken into account.

Our aim is to investigate the impact of immediate free flaps, namely TRAM flap related and S-Gap (superior Gluteus artery perforator) reconstructions for breast cancer on the timing of adjuvant treatment. The delay of adjuvant treatment among patients who received immediate reconstruction and those who had mastectomy alone is compared and possible causes of delay are identified. Eligible patients were those who had mastectomy for breast cancer and immediate free flap reconstruction followed by either adjuvant chemotherapy, radiotherapy or both.

Patients and Methods

M

Patients who did not receive their treatment at Guy's, had at least a part of their chemotherapy prior to surgery, private patients, patients who had delayed reconstructions and patients who delayed their own adjuvant therapy were excluded. Patients for whom exact dates of surgery and adjuvant therapy were not known were also excluded.

All patients were treated with cancer therapy as high priority. Irrespective of history of immediate reconstruction, adjuvant treatment was delivered to all patients as soon as possible after surgery and with the same chemotherapy protocols. Organisational issues could possibly delay chemotherapy by a matter of a few days and they apply equally to both reconstructed and not reconstructed patients.

Patients were followed postoperatively with regular clinic visits by the surgical and medical teams. Adjuvant treatment was commenced when healing was satisfactory and any surgical complications had been successfully treated. The time lapse between surgery and adjuvant therapy was calculated and the and full detail of causes of delay were recorded whenever possible.

Two sets of guidelines were used to determine the cut-offs for the delay of primary interest: the Guy's Hospital guidelines which state that adjuvant treatment should start within 6 weeks from surgery and Lohrisch's et al recommendations which are 12 weeks after surgery [START_REF] Lohrisch | Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer[END_REF]. The reason the latter was used is that the period of 12 weeks

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recommended is the longest reported in the literature and after which further delay is likely to have negative impact on survival.

Chi-square test was used to determine the differences between the number of patients who started their adjuvant treatment before the 6, 8, 10 and 12-week points between the two groups. Students' t-test was used to determine the difference of the mean time period between surgery and commencement of adjuvant treatment between the groups.

Results

Forty-eight patients underwent mastectomy, free TRAM, DIEP or S-GAP flap reconstruction and adjuvant chemotherapy and/or radiotherapy for breast cancer between 2002 and 2007 at Guy's and St. Thomas' NHS Foundation Trust. Nine of these patients had a delayed reconstruction, one was a private patient for whom details could not be obtained and ten patients had their adjuvant therapy outside the Trust, or incomplete data were available for them. One patient delayed her own adjuvant therapy. Therefore, 27 patients received immediate free flap reconstruction followed by adjuvant chemotherapy and/or radiotherapy and were included in the study group. Of them 1 had an S-GAP reconstruction and 26 TRAM/DIEP flaps.

The control group contained 139 patients all of them were treated in the Trust between 2002 and 2007. The characteristics of the two groups are summarised in Table 1.

The groups were of the same age (p=0.077) but reconstructed patients were more likely to have more advanced stage of the disease (p=0.0001).

Nine of the 27 patients in the study group received their adjuvant treatment within 6 weeks or less from surgery, 5 patients received their adjuvant treatment within 6.1 to 8 weeks from surgery, 6 patients 8.1-10 weeks, 5 patients 10.1-12 weeks and 2 patients after more than 12 weeks from surgery (Table 2). The causes for delay were mainly flap failure and abdominal wound complications as shown in Table 3.

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Eighteen patients (67%) were delayed for more than 6 weeks, not complying with local recommendations; and 2 patients (7%) were delayed for more than 12 weeks, not complying with Lohrisch's recommendations [START_REF] Lohrisch | Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer[END_REF].

Of the 139 patients in the control group, 99 received their adjuvant treatment within 6 weeks from surgery, 17 patients between 6.1 to 8 weeks, 11 patients between 8.1 to 10 weeks, 7 patients between 10.1 to 12 weeks and 5 patients more than 12 weeks from surgery. The two groups are graphically compared in fig 1 .   Forty patients (28.8%) in the control group were delayed for more than 6 weeks, not complying with local recommendations; and 5 patients (3.6%) were delayed for more than 12 weeks not complying with Lohrisch's recommendations [START_REF] Lohrisch | Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer[END_REF].

The number of patients whose commencement of adjuvant therapy exceeded the 6week point was different between the two groups (chi-square=15.28, p=0.0001), with the reconstruction group suffering the longest delay. The statistically significant difference was maintained for the 8 (chi-square=14.51, p=0.0002) and 10-week point (chi-square=6.67, p=0.0098). There was no statistically significant difference for the 12 week point (chi-square=0.81, p=0.37) although twice as many in the study group had their treatment delayed, the lack of statistical difference may have been due to the small number of patients at this point in time, although the % cumulative curves (fig 1) clearly start overlapping at about this point. The mean time period between surgery and commencement of adjuvant treatment for the study group was 55 days (95% confidence interval 46.6-64.3) and for the control group was 40 days (95% confidence interval 36.5-44.0). This difference is also statistically significant (t=3.08, p=0.0025).

Discussion

Since IBR enhances psychological recovery from breast cancer [START_REF] Dean | Effects of immediate breast reconstruction on psychological morbidity after mastectomy[END_REF][START_REF] Rosenqvist | Patients psychological and cosmetic experience after immediate breast reconstruction[END_REF][START_REF] Sk | The psychological impact of immediate rather than delayed breast reconstruction[END_REF] and seems to be oncologically safe. [START_REF] Zakhireh | Application of Screening Principles to the Reconstructed Breast[END_REF]13], it is not surprising that the IBR procedures are widely implemented into oncoplastic surgical practice [START_REF]Early and locally advanced breast cancer: diagnosis and treatment[END_REF][START_REF] Pennington | Breast reconstruction after Mastectomy: Current State of the Art[END_REF][START_REF] Heneghan | Evolution of breast cancer management in Ireland: a decade of change[END_REF][START_REF] Malycha | Oncoplastic breast surgery: a global perspective on practice, availability, and training[END_REF][START_REF] Recht | American Society of Clinical Oncology. Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology[END_REF][START_REF]Association of Breast Surgery at BASO 2009. Surgical guidelines for the management of breast cancer[END_REF]. Accumulated experience in Plastic There has been some research on the effect of the immediate reconstruction on the time interval between surgery and adjuvant therapy because of suggested risk that undue delay will compromise cancer treatment and consequently, survival. However, not only was the optimal time lag never determined through a large number of studies, but often in these reports all types of reconstruction are examined as if they were comparable and uniform groups, ignoring the fact that the "modern" option for free flaps is technically challenging with different types of complications which possibly lead to longer recovery times and delay of the commencement of adjuvant therapy.

The present study is the first report that specifically reviewed the effect of the "modern" reconstruction methods -free TRAM and DIEP flaps -on the time of commencement of adjuvant treatment. In this study we were able to demonstrate a delay in the administration of adjuvant treatment in the IBR free flap group compared to patients who did not undergo reconstruction. Patients receiving IBR free flap treatment received their chemotherapy with a significant 2-week delay on average compared to the control group and a significant proportion of them breached the local guidelines (chemotherapy within 6 weeks). Similarly, significantly less reconstructed patients received their adjuvant treatment within 8 or 10 weeks in comparison to the controls and only at the 12 week point the two groups appeared similar. The clinical significance of this remains to be determined as, despite published evidence [START_REF] Lohrisch | Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer[END_REF], current clinical practice recommends starting chemotherapy on a basis of "the sooner the better". Furthermore, there is a possibility that this interval may not have the same effect on every patient and tumours with worst prognosis or ER (-) may be affected most by a delay [START_REF] Buzdar | Effect of timing of initiation of adjuvant chemotherapy on disease-free survival in breast cancer[END_REF][START_REF] Colleoni | The International Breast Cancer Study Group. Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors[END_REF].

In the literature conclusions on the effect of TRAM/DIEP flap IBR on the timing of chemotherapy can only be indirectly extirpated from studies where autologous tissue reconstruction IBR patients are included in the study groups [START_REF] Lewis | Autologous tissue immediate breast reconstruction: desired but oncologically safe?[END_REF]: Wilson et al [START_REF] Wilson | Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy[END_REF] report that

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half of the patients who underwent IBR with free tissue transfer had their adjuvant therapy delayed by more than 40 days. Although there was no statistically significant difference between all methods of IBR and mastectomy alone patients, the free tissue transfer subgroup did seem to have a statistically significant 36% increase in the delay. Schusterman et al [START_REF] Schusterman | Immediate Breast Reconstruction: Why the Free TRAM Over the Conventional TRAM Flap?[END_REF] found that seven of the 28 TRAM IBR patients had their postoperative chemotherapy delayed due to surgical complications. Taylor and Kumar [START_REF] Taylor | The effect of immediate breast reconstruction on adjuvant chemotherapy[END_REF] report that 72% of IBR TRAM patients were delayed beyond 39 days vs. 41% in the mastectomy only group.

In contrast, published data by Elliot et al [START_REF] Elliott | Immediate TRAM Flap Breast Reconstruction: 128 Consecutive Cases[END_REF] showed that only 1 of 36 patients had a delay caused by flap complications after TRAM IBR.

Regarding the difference in the stage of the disease between the two groups, it is a frequent observation in relevant articles [START_REF] Mortenson | Immediate Breast Reconstruction after Mastectomy Increases Wound Complications[END_REF][START_REF] Allweis | Immediate reconstruction after mastectomy for breast cancer does not prolong the time to starting adjuvant chemotherapy[END_REF]. Allewis et al report that stage of disease does not affect time to chemotherapy in either group.

In order to determine what constitutes a delay, two cut off time points were used in the present study: local guidelines -6 weeks -and conclusions reported by Lohrisch et al [START_REF] Lohrisch | Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer[END_REF].

The latter permits a 12-week-long delay between surgery and commencement of chemotherapy and is in accordance with Hershman et al [25] who also conclude that delay beyond 3 months is associated with increased disease specific mortality. Other authors found no difference among groups which received chemotherapy in different times within the first 3 months [26-28].

Finally, as for the actual reason for the delay, reconstruction related surgical complications are the culprit. Surgical infections, cellulitis, skin breakdown, delayed wound healing, complete or partial flap failure and prolonged recovery period are reported in the literature [START_REF] Taylor | The effect of immediate breast reconstruction on adjuvant chemotherapy[END_REF][START_REF] Wilson | Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy[END_REF][START_REF] Mortenson | Immediate Breast Reconstruction after Mastectomy Increases Wound Complications[END_REF][START_REF] Schusterman | Immediate Breast Reconstruction: Why the Free TRAM Over the Conventional TRAM Flap?[END_REF][START_REF] Elliott | Immediate TRAM Flap Breast Reconstruction: 128 Consecutive Cases[END_REF]. This study agreed with published data showing that flap failure constituted the commonest factor (Table 3). This highlights the need for these complex procedures to take place in high-volume centres with experienced teams, where complications can be minimised, identified and treated quickly.

In conclusion, this study demonstrates that there is a significant delay in the commencement of adjuvant treatment after mastectomy and free flap IBR in comparison to mastectomy alone patients due to reconstruction related surgical complications. However,

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the effects of this delay on survival have not been fully investigated yet and may be significant for at least some of the patients. Further studies of this group of patients in correlation to relapse and survival could provide valuable information and may influence clinical practice and management.

  A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Details of all breast cancer patients treated with mastectomy with (study group) and without (control group) free flap reconstruction who received adjuvant therapy in the Breast Unit at Guy's and St. Thomas' NHS Foundation Trust between July 2002 and July 2007 were obtained. Patients were identified through the Hospital electronic patient database and further information was subsequently obtained from their detailed written hospital notes. Details included age at diagnosis, histopathological staging, date of immediate reconstruction, date of start of adjuvant treatment, co-morbidities and complications.

  in instrumentation and techniques paved the way for cosmetically superior but more complex breast reconstructive techniques. Many Breast Units nowadays prefer free TRAM and DIEP flaps over the conventional simple silicone implants or LD (Latissimus Dorsi) flaps[START_REF] Schusterman | Immediate Breast Reconstruction: Why the Free TRAM Over the Conventional TRAM Flap?[END_REF][START_REF] Massey | Group for the Advancement of Breast Reconstruction. Perforator flaps: recent experience, current trends, and future directions based on 3974 microsurgical breast reconstructions[END_REF][START_REF] Losken | Oncoplastic breast surgery: past, present, and future directions in the United States[END_REF].

Fig 1 .

 1 Figure captions

  Figures and schemes

Table 1 .

 1 Patients' characteristics

	Tables
		Study group	Control group
	No of patients included	27	139
	Gender	Female	Female
	Age	Range 34-62, mean 44.9y	Range 30-63, mean 47.9y
	Year of surgical treatment	07/2002-07/2007	07/2002-07/2007
	Type of surgical procedure	Modified radical mastectomy	Modified radical mastectomy
		with immediate free flap
		reconstruction: 1 SGAP, 26
		TRAM/DIEP
	Stage of disease	I: 4	I: 30
		II: 11	II: 106
		III: 9	III: 0
		Unknown: 3	Unknown: 3
	Adjuvant treatment	27	139
	Date of commencement of	Yes	Yes
	adjuvant treatment known
	Neoadjuvant chemotherapy None	None

Table 2 .

 2 Time between mastectomy with (study group) or without (control group) immediate breast reconstruction and commencement of adjuvant treatment.

	Time between surgery and commencement of	Study group	Control group
	adjuvant treatment	No of patients	No of patients
	Less than or equal to six weeks	9	99
	6.1 to 8 weeks	5	17
	8.1 to 10 weeks	6	11
	10.1 to 12 weeks	5	7
	Greater than 12 weeks	2	5