Periprandial changes of the sympathetic -- parasympathetic balance related to perceived satiety in humans Food intake regulation involves various central and peripheral mechanisms . In this study the relevance of physiological responses reflecting the autonomic nervous system were evaluated in relation to perceived satiety . Subjects were exposed to a lunch-induced hunger-satiety shift , while profiling diverse sensory , physiological , and biochemical characteristics at 15 min intervals . Sensory ratings comprised questionnaires with visual analogues scales about their feeling of satiety , desire to eat , fullness , and hunger . Physiological characteristics included heart rate , heart rate variability , and blood pressure , while biochemical markers such as cortisol levels and α-amylase activity were monitored in saliva . The four sensory ratings correlated with heart rate and salivary α-amylase suggesting a higher sympathetic tone during satiety . Furthermore , heart rate variability was associated with age and waist-to-hip ratio and cortisol levels negatively correlated with body mass index . Finally , neither chewing nor swallowing contributed to a heart rate increase at food consumption , but orosensory stimulation , as tested with modified sham feeding , caused a partial increase of heart rate . In conclusion , after meal ingestion critical physiological alterations reveal a elevated sympathetic tone , which is a potential measure of satiety . Introduction Regulation of food intake comprises both homeostatic and hedonic components controlled by hunger and satiety signals in both peripheral and central pathways . Afferent and most peripheral signals provide information about the body 's nutritional state and the central nervous system mediates and integrates episodic hunger and satiety signalling towards a functional output that controls metabolism with accompanying behaviour -LRB- Schwartz et al. 2000 -RRB- . While communication between periphery and brain is crucial in coordinating integrative processes for metabolism , such signals can also be anticipatory as they can rise even before food is ingested through visual , auditory , and olfactory stimuli -LRB- Mattes 1997 -RRB- , or even appear , like insulin secretion , when no food was presented to naïve subjects -LRB- Bellisle et al. 1985 -RRB- . In hunger and satiety signalling , endocrine systems and the autonomic nervous system -LRB- ANS -RRB- , play crucial roles . The sympathetic -LRB- SNS -RRB- and parasympathetic nervous system -LRB- PNS -RRB- , support distinct and opposite functions in alertness and physiology . They respond to changes in both the external and internal environments and are also important in regulation of metabolism and energy homeostasis -LRB- Tempel and Leibowitz 1994 ; Bray 2000 -RRB- . In relation to a hunger-satiety shift after food intake in humans , changes of the SNS and PNS activity can occur before those in nutritional hormone levels , as demonstrated by instant changes in the states of alertness -LRB- Craig and Richardson 1989 ; Geisler and Polich 1992 ; Holt et al. 1999 -RRB- , muscle sympathetic nerve activity -LRB- Fagius and Berne 1994 -RRB- , and cardiac output -LRB- Waaler et al. 1991 ; Waaler and Eriksen 1992 -RRB- , which may be part of cephalic phase responses -LRB- Mattes 1997 ; Nederkoorn et al. 2000 -RRB- . An inverse relationship of SNS activity and body fat emphasize the importance of the SNS in food intake , suggesting a role of β-adrenergic receptors in peripheral and central control of eating -LRB- Bray 2000 -RRB- . Tracking of ANS characteristics and how they are changing in relation to appetite and satiety helps to understand the role of the ANS in the context of food intake regulation , overweight and obesity . The present study assessed whether time course and patterns of physiological responses in humans may serve as consistent characteristics of the SNS -- PNS balance and indicate perceived satiety . We hypothesised that ANS characteristics are affected by satiety . Subjectively rated satiety , desire to eat , fullness , and hunger were evaluated over a session of 4.75 h , including a lunch-induced hunger-satiety shift , while heart rate -LRB- HR -RRB- , heart rate variability -LRB- HRV -RRB- and blood pressure were monitored . Cortisol levels and α-amylase activity were also measured from the subject 's saliva as two other determinants reflecting the SNS -- PNS balance . Related to food intake , cortisol , as the end product of the hypothalamic -- pituitary -- adrenal-axis , has a primary function in controlling nutrient ingestion and metabolism over the circadian cycle -LRB- Tempel and Leibowitz 1994 -RRB- , the hypothalamus is a key target for cortisol -LRB- Stricker-Krongrad and Beck 2002 ; Harthoorn et al. 2005 -RRB- , and adrenalectomy causes a reduction of food intake -LRB- Drazen et al. 2003 , 2004 -RRB- . Salivary α-amylase is a biomarker for SNS activity because it serves as a correlate of adrenergic activity under stress , and is predictive of plasma catecholamine levels -LRB- Chatterton et al. 1996 ; Rohleder et al. 2004 -RRB- . Finally , chewing , swallowing , and orosensory stimulation by food in a modified sham-feeding model were examined for a possible contribution to HR alterations . Methods Healthy subjects , 9 males and 9 females , aged between 23 and 63 years -LRB- average 42.9 years -RRB- participated in this study . Smokers and subjects with prescribed medication , except for contraceptives , and excessive weight loss during the last 3 months were excluded from participating in this study . The subjects were paid for their involvement and informed consent was obtained according to the guidelines of the Ethical Committee of Wageningen UR . Weight , height , and waist and hip circumferences , were measured while subjects wore light indoor clothing with emptied pockets and no shoes . To estimate body weight , 1 kg was subtracted from clothed body weight . Body mass index -LRB- BMI -RRB- was the weight divided by height squared . Waist circumference was measured at the level midway between the lower rib margin and the iliac crest , with participants in a standing position and breathing out gently . Hip circumference was measured at the level of the widest circumference over the greater trochanters . The waist-to-hip ratio -LRB- WHR -RRB- was calculated as waist circumference divided by hip circumference . Design and procedure Each subject was tested alone in a quiet furnished room with appropriate ventilation and lighting from 11:45 a.m. to 16:30 p.m. All subjects had their breakfast as usual at least 3 h before starting the test session . Subjects chose their lunch from a standard menu , which was served at exactly 12:30 p.m. , and was finished within 20 min . The lunch was ad libitum , and the left-over of each meal was weighed and calculated into energy content to calculate total intake . The meals eaten were between 2.5 and 3.3 MJ , which is about 30 % of the recommended regular daily intake , and contained 15 -- 20 % -LRB- energy -RRB- protein , 35 -- 40 % -LRB- energy -RRB- fat , and 40 -- 45 % -LRB- energy -RRB- carbohydrates . The meals did not contain caffeine or capsaicin . During the session a Polar S810 device -LRB- Polar Electro Oy , Kempele , Finland -RRB- recorded beat-by-beat periods -LRB- R -- R intervals -RRB- continuously . Every 15 min systolic and diastolic blood pressure were measured by an OMRON M4-I fully automatic monitor -LRB- OMRON Healthcare Europe , Hoofddorp , The Netherlands -RRB- , saliva was donated , and subjects were asked to rate `` how satiated are you '' , `` how is your desire to eat '' , `` how full are you '' , and `` how hungry are you '' , using 100-mm non-structured visual analogue line scales -LRB- VAS -RRB- all on one page and anchored at their ends by the descriptors `` very little '' and `` very much '' -LRB- Flint et al. 2000 -RRB- . HR and HRV For determination of HR and HRV , individual datasets were obtained from the Polar S810 device . Data processing and analysis were performed by Polar Precision Performance software -LRB- version 4.00.020 -RRB- , based on the consecutive numbers of successive R -- R intervals -LRB- ms -RRB- during the test session . HR was derived and expressed as beats/min of each successive 15 min . Determining R -- R interval over 15 min allowed HR and HRV measurement with high -LRB- < 3 ms -RRB- timing accuracy -LRB- Ruha et al. 1997 -RRB- . Power spectral analysis of HRV was computed from the R -- R formats over data segments of 15 min each , with cubic interpolation for the R -- R series at 4 Hz and spectrum estimation based on fast Fourier transformation . The two main rhythmic oscillations in the R -- R intervals were a high frequency -LRB- HF -RRB- component between 0.15 and 0.40 Hz synchronous to respiratory activity , and a low frequency -LRB- LF -RRB- component between 0.04 and 0.15 Hz related to vasomotor waves . For both LF and HF components , the centre frequency and associated power , i.e. area under the curves of individual components -LRB- ms2 -RRB- , were calculated . The power in the HF band represents PNS activity , while the power in the LF band characterises SNS activity and part of the PNS activity -LRB- Berger et al. 1986 ; Pagani et al. 1986 ; Malliani et al. 1994 ; Perini and Veicsteinas , 2003 -RRB- . A reciprocal relation exists between the HF and LF rhythms from which an index characterising the SNS -- PNS balance can be derived . The LF-to-HF ratio -LRB- % -RRB- was determined for every 15 min . Saliva biochemistry Every 15 min subjects chewed on a rolled 25-cm2 sheet of parafilm -LRB- Parafilm ® M -RRB- for up to 1 min and spat into a 12 ml polystyrene tube -LRB- Greiner Bio-One , Kremsmünster , Austria -RRB- . The saliva was immediately placed into a freezer at − 40 °C . For further biochemical analyses , saliva samples were centrifuged at 1,000 g for 2 min . The salivary cortisol level was determined on 25 μl of thawed saliva using a Cortisol Enzyme Immunoassay -LRB- EIA -RRB- Kit -LRB- DSL-10-67100 -RRB- -LRB- Diagnostic Systems Laboratories DSL , Sinsheim , Germany -RRB- with an intra-assay variation between 1.9 and 4.8 % and an inter-assay variation between 3.8 and 7.2 % . Determination of in vitro salivary α-amylase activity was performed on 10 μl of saliva by means of an α-Amylase Kinetic Reaction Kit -LRB- Salimetrics LLC , State College , PA , USA -RRB- using 2-chloro-p-nitrophenol linked with maltotriose as chromagenic substrate and measured at 405 nm . The intra-assay variation was between 2.5 and 7.2 % , and the inter-assay variation between 3.6 and 5.8 % . Oral activities and orosensory stimulation Of the 18 subjects , 6 men and 6 women -LRB- BMI between 21.5 and 28.4 -RRB- , were exposed to distinct sessions of 15 min in which different oral activities and processing were examined for their influence on HR . Baseline of HR was measured for 15 min . Sessions consisted of either chewing on parafilm for 15 min , drinking 200 ml of water during the first 5 min of the 15 min session , consuming 200 ml of yoghurt-drink -LRB- Friesland Foods , The Netherlands , 1.0 MJ , containing : 3.0 % -LRB- w/w -RRB- protein , 17 % -LRB- w/w -RRB- carbohydrates , 16 % -LRB- w/w -RRB- sugars , and 3.0 % -LRB- w/w -RRB- fat -RRB- during the first 5 min of a 15 min session , or modified sham feeding of this yoghurt-drink , a `` chew and spit '' technique in which foods are smelled , chewed , and tasted , but not swallowed -LRB- Robertson et al. 2001 -RRB- , during 5 min of the 15 min session . HR was monitored over data segments for resting and chewing periods and of 5 min periods for drinking and sham feeding . Data analyses Data are expressed as the mean ± SEM , unless otherwise specified . Of each measure and per time point , values were averaged over 18 subjects . Correlations were calculated between each of the four VAS ratings and HR , LF-to-HF ratio , blood pressure , cortisol , and α-amylase across the 20 time points of the session . Across subject correlations were done between age , BMI , WHR and both preprandial and postprandial levels of HR , LF-to-HF ratio , blood pressure , cortisol , and α-amylase per individual . For statistical assessment , postprandial values were compared to preprandial level and differences were established with repeated measures analysis of variance -LRB- ANOVA -RRB- . Differences with P values of 0.05 or less were considered to be statistically significant . All data were analysed by using Statistica -LRB- version 6.0 ; StatSoft , Tulsa , OK , USA -RRB- . Results Mean BMI was 25.0 ± 3.5 kg/m2 and mean WHR was 0.89 ± 0.07 -LRB- Table 1 -RRB- . As shown in Fig. 1 , prior to lunch , desire to eat and hunger ratings increased from about 35 to 70 mm . Satiety ratings decreased from 50 to 35 mm , whilst fullness scores did not change markedly during the preprandial period . Lunch induced changes in all four sensory ratings followed by a steady reduction of these shifts over time . Average ratings of satiety and fullness were increased over 30 min by about 40 mm , while desire to eat and hunger ratings decreased to about 10 mm . After these shifts , ratings gradually declined to about preprandial scores over the next 4 h. Table 1Anthropometric values for 18 subjects and session means of physiological characteristicsAverage ± SDRangeAge -LRB- years -RRB- 42.9 ± 13.023 -- 63Body mass index -LRB- kg/m2 -RRB- 25.0 ± 3.521.5 -- 36.1Waist-to-hip ratio0 .89 ± 0.070.77 -- 1.00 Heart rate -LRB- beats/min -RRB- 75.3 ± 7.863.3 -- 89.3LF-to-HF ratio -LRB- % -RRB- 409 ± 282103 -- 1,182 Blood pressure -LRB- mmHg -RRB- Systolic126 ± 13107 -- 150 Diastolic78 ± 1056 -- 95Salivary cortisol -LRB- nmol/l -RRB- 14.2 ± 6.16.0 -- 30.3 Salivary α-amylase -LRB- U/ml -RRB- 139 ± 6914 -- 263Fig . 1Satiety -LRB- a -RRB- , desire to eat -LRB- b -RRB- , fullness -LRB- c -RRB- , and hunger -LRB- d -RRB- rated on VAS for 18 subjects . Bars are SEM . Grey-shaded bar represents lunch HR , HRV , and blood pressure Shortly after starting the lunch , HR increased by 10 ± 2.5 % -LRB- P < 0.02 -RRB- for about 20 min , and then decreased for a following 30 min -LRB- Fig. 2a -RRB- . Forty-five to 50 min after starting the lunch , a second and more prolonged increase of HR was found -LRB- P < 0.02 -RRB- that lasted at least 1 h. Fig. 2 HR -LRB- a -RRB- , LF-to-HF ratio -LRB- b -RRB- , and blood pressure -LRB- c -RRB- for 18 subjects . Bars are SEM . Grey-shaded bar represents lunch . * Different from preprandial level -LRB- P < 0.02 -RRB- In the HRV a bi-phasic trend of postprandial fluctuations for LF-to-HF ratio was found , but these were not significantly different from the preprandial level -LRB- Fig. 2b -RRB- . Systolic pressure demonstrated minor fluctuations during the session , which were not significantly different from before lunch , however , diastolic pressure showed a postprandial decrease -LRB- P < 0.02 -RRB- -LRB- Fig. 2c -RRB- . Saliva biochemistry Salivary cortisol levels were high at the beginning of the session , followed by a gradual decrease during the day -LRB- Fig. 3a -RRB- without any significant influences of the lunch . Similar to the bi-phasic increase of HR , in vitro salivary α-amylase activity displayed a similar pattern over the session -LRB- Fig. 3b -RRB- . An increase of 60 ± 15 % as compared to preprandial level in α-amylase activity was observed -LRB- P < 0.01 -RRB- early after starting the lunch meal . A second and more lengthened increase of α-amylase activity was demonstrated between 1 and 3 h after starting the lunch -LRB- P < 0.01 -RRB- . Fig. 3Salivary cortisol levels -LRB- a -RRB- and in vitro α-amylase activity -LRB- b -RRB- for 18 subjects . Bars are SEM . Grey-shaded bar represents lunch . * Different from preprandial level -LRB- P < 0.01 -RRB- Sensory ratings and ANS characteristics Correlations were found between VAS satiety , desire to eat , fullness , and hunger . Variations in satiety rating across time correlated with fullness -LRB- r = 0.99 , P < 0.001 -RRB- , desire to eat -LRB- r = − 0.97 , P < 0.001 -RRB- , and hunger -LRB- r = 0.96 , P < 0.001 -RRB- . Desire to eat was correlated to fullness -LRB- r = − 0.96 , P < 0.001 -RRB- and hunger rating -LRB- r = 0.99 , P < 0.001 -RRB- , and fullness rating was correlated with hunger -LRB- r = − 0.95 , P < 0.001 -RRB- . HR showed correlations to satiety -LRB- r = 0.74 , P < 0.001 -RRB- , desire to eat -LRB- r = − 0.74 , P < 0.001 -RRB- , fullness -LRB- r = 0.74 , P < 0.001 -RRB- , and hunger -LRB- r = − 0.66 , P < 0.01 -RRB- . LF-to-HF ratio was not significantly correlated to the four sensory ratings . Although systolic pressure was not associated to any of the sensory ratings , diastolic pressure showed correlations to satiety -LRB- r = − 0.48 , P < 0.05 -RRB- , desire to eat -LRB- r = 0.53 , P < 0.05 -RRB- , fullness -LRB- r = − 0.50 , P < 0.05 -RRB- , and hunger -LRB- r = 0.58 , P < 0.01 -RRB- . Salivary cortisol levels were not significantly correlated with any of the sensory ratings , whereas salivary α-amylase was correlated to satiety -LRB- r = 0.78 , P < 0.001 -RRB- , desire to eat -LRB- r = − 0.83 , P < 0.001 -RRB- , fullness -LRB- r = 0.80 , P < 0.001 -RRB- , and hunger -LRB- r = − 0.83 , P < 0.001 -RRB- . Anthropometrics and physiological responses A correlation was found between age and both preprandial and postprandial LF-to-HF ratio -LRB- r = 0.55 , P < 0.02 and r = 0.52 , P < 0.05 , respectively -RRB- and age and postprandial HR -LRB- r = 0.49 , P < 0.05 -RRB- . WHR and postprandial LF-to-HF ratio appeared to be correlated -LRB- r = 0.55 , P < 0.02 -RRB- , but this relation was also found to be mediated by age . Preprandial cortisol levels were associated to BMI -LRB- r = − 0.47 , P < 0.05 -RRB- . Oral activities and orosensory stimulation Chewing , swallowing and orosensory stimulation by food in a modified sham-feeding model were examined for their possible effect on instant increases of HR . Neither chewing on parafilm nor drinking of water showed any increase of HR in comparison to baseline -LRB- Fig. 4 -RRB- . Drinking 200 ml of yoghurt , which was without chewing , increased HR about 10 % -LRB- P < 0.01 -RRB- . This was a similar increase as under the lunch fed conditions . Finally , orosensory stimulation by the same type of yoghurt in sham feeding way increased HR about 5 % -LRB- P < 0.01 -RRB- . Fig. 4 HR during chewing on parafilm , drinking water or yoghurt , and modified sham feeding with the same yoghurt-drink , expressed as stimulus-to-control ratio in relation to baseline for HR . Both consumption of yoghurt-drink and modified sham feeding of the yoghurt caused an increase in HR -LRB- P < 0.01 -RRB- . Bars represent SEM for 12 subjects Discussion Sensory ratings scales for satiety , desire to eat , fullness , and hunger were used in combination with measures to assess the relevance and temporal pattern of responses reflecting the sympathetic -- parasympathetic -LRB- SNS -- PNS -RRB- balance in relation to perceived satiety in humans . Satiety and hunger are often interpreted as being reciprocal , although they are mediated and signalled by different mechanisms , in which leptin , insulin , and cholecystokinin are important -LRB- Schwartz et al. 2000 -RRB- . For this reason several rating scales were used about feelings of satiety and hunger . Over a 4.75-h test session , including a lunch-induced hunger-satiety shift , all four VAS ratings showed consistent changes . The temporal profile of satiety rating was paralleled by fullness and inversely related to desire to eat and hunger ratings . Preprandially , increases of desire to eat and hunger ratings were larger than decreases of satiety and fullness ratings . Ingestion of a standard meal of 2.5 -- 3.3 MJ changed all four VAS ratings 40 -- 60 mm , but with regard to the lunch-induced hunger-satiety shift , changes in desire to eat and hunger ratings were found to be larger than the changes of ratings of satiety and fullness . This suggests that ratings of `` desire to eat '' and `` hunger '' are more sensitive to the evaluation of appetite periprandially than ratings of `` satiety '' and `` fullness '' . Sensory ratings tracked over time and combined with food intake demonstrated a gradual recovery to preprandial rating scores over about 4 h after meal consumption . This might reflect the gastrointestinal changes and processes over the same time that affect appetite . Although , differences may result from different types of food intake or different types of satiety measurements , recovery time also depends on sensory attributes -LRB- De Graaf 1993 -RRB- . The finding of a similar 4-h recovery time for all four sensory descriptors used , appears to be consistent following different types of meals -LRB- Green et al. 1997 ; Erdmann et al. 2004 -RRB- , and different rating techniques -LRB- Stubbs et al. 2001 -RRB- . Physiological responses reflecting the SNS -- PNS balance were simultaneous to altered patterns of perceived satiety . In this food-related context , these ANS characteristics not only provide additional insights into the integration of central and peripheral regulatory processes for metabolism , but also render a potential measure of satiety in humans . Both the SNS and PNS are segmented multifunctional systems , which can be evaluated in several ways -LRB- Morrison 2001 -RRB- . Changes in HR , HRV , and blood pressure are some of the variables that can be used to assess the SNS -- PNS balance , in which a higher HR and cardiovascular load and output is typified by a higher SNS -- PNS ratio . High salivary α-amylase levels are indicating a higher sympathetic tone , are predictive of high plasma catecholamine levels , and are reduced by adrenergic beta-blockers -LRB- Speirs et al. 1974 ; Chatterton et al. 1996 -RRB- . The SNS and PNS regulate processes and metabolic pathways important for recovery and energy homeostasis -LRB- Bray 2000 ; Szekely 2000 -RRB- . The changes of the SNS -- PNS balance , therefore , are relevant to satiety and may occur before those in circulating hormones that stimulate or inhibit food intake . With regard to the effects of food intake on appetite , two distinct phases have been considered within the postulated `` satiety cascade '' , called `` satiation '' and `` satiety '' , the first defined as the process which develops during eating and which brings eating to end , and the second defined as the state of inhibition over further eating -LRB- Green et al. 1997 -RRB- . This satiety cascade takes into account properties of food , physiological processing of nutrients that contribute to overall control of food intake , and also conceptualises differences between immediate postingestive effects and those produced later . The digestive period is divided into three to four phases depending on the site at which food acts to stimulate neural and endocrine organs , i.e. the cephalic and orosensory , gastric , and intestinal phases , which are sequential and follow on the progression of a meal . Both short - and long-term autonomic alterations occur towards a high sympathetic tone after a meal based on increases of HR and salivary α-amylase . The short-term increases may belong to cephalic and orosensory phase responses , whereas the long-term increases cohere to the gastrointestinal mechanisms . While the importance of α-amylase is on starch digestion , the association of both HR and α-amylase with the VAS ratings show the possibility of measures for perceived satiety . Moreover , HR and α-amylase have a recovery over about 4 h after a meal . Further , a diastolic blood pressure decline might characterize satiety , however , with weaker correlations . The haemodynamic changes illustrate that eating places demand on the cardiovascular system , most presumably specifically on the visceral compartment of the body . A postprandial increase in HR points to enhanced cardiac output , while a lower blood pressure during a high feeling of satiety may indicate a lower systemic resistance especially to visceral parts of the body , which results in a higher mesenteric blood flow -LRB- Jager et al. 1986 -RRB- , and may influence postprandial behaviour . The LF-to-HF ratio showed a similar bi-phasic trend as HR and salivary α-amylase , however , it was a less consistent measure of SNS -- PNS balance . In addition , a postprandial bi-phasic SNS predominance indicates immediate triggering of cephalic or orosensory responses and the more gradual activation of metabolic mechanisms within time frames coherent to the putative distinction between `` satiety '' and `` satiation '' -LRB- Green et al. 1997 -RRB- . The instant increase of HR with food intake can be part of a cephalic phase response triggered by oral physical activity , non-metabolic food cues , or sensory perception . Neither chewing , swallowing , nor water intake were responsible for a changed sympathetic tone as indicated by HR , however , orosensory stimulation with modified sham feeding enhanced HR to about half of the increase that was reached after intake of a meal . An instant increase in HR is , thus , induced in the oral cavity most presumably initiated by perception of taste , flavour , or energy-rich substrates . An alternative explanation for the bi-phasic effect on a higher SNS -- PNS balance is that the decrease in HR for about 30 min after finishing food intake is caused by inhibition of autonomic functioning . The satiety hormones cholecystokinin , glucagon-like peptide 1 , and gastric inhibitory peptide could be involved as their release from the gastrointestinal tract in response to eating -LRB- Matzinger et al. 2000 ; Burcelin 2005 -RRB- inhibit autonomic functioning at the central level as demonstrated in rodents , where cholecystokinin inhibites brainstem presympathetic neurons and reduces HR -LRB- Sartor and Verberne 2002 ; Fan et al. 2004 -RRB- . Aside from the close correlation between SNS and PNS balance and perceived satiety in a periprandial period , there is an inverse relationship between SNS activity and obesity , consistent with that most types of obesity are associated with low sympathetic activity -LRB- Bray 1991 -RRB- . Further personal characteristics like age , BMI , and WHR , were associated with the ANS characteristics . In addition to BMI as a marker of overweight , WHR serves as indicator of fat storage in abdominal depots . A negative correlation between salivary cortisol and BMI was found . The role of cortisol in obesity is complex with both high and low cortisol secretion patterns -LRB- Björntorp and Rosmond 2000 -RRB- . Cortisol is higher in subjects with the night-eating syndrome -LRB- Birketvedt et al. 1999 -RRB- and binge eating disorder and bulimia nervosa -LRB- Gluck et al. 2004 -RRB- . In overweight subjects , a hypoactive hypothalamic -- pituitary -- adrenal-axis , not knowing whether it is cause or consequence of a dysregulated SNS , may contribute to greater hunger and over-consumption . A mechanism of hypothalamic -- pituitary -- adrenal-axis inhibition is described in rats , showing a negative feedback of visceral fat on the hypothalamus that lowers cortisol levels -LRB- Dallman et al. 2003 , 2004 ; La Fleur et al. 2005 -RRB- . In conclusion , within a periprandial context a high sympathetic tone is a potential measure of satiety in humans , and activation of the SNS might be a satiety system , which may also help regulation of food intake and energy expenditure from body fuel stores . HR and salivary α-amylase may be implemented to measure satiety in eating disorders and overweight .

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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O


Voice quality after endoscopic laser surgery and radiotherapy for early glottic cancer : objective measurements emphasizing the Voice Handicap Index We analyzed the functional outcome and self-evaluation of the voice of patients with T1 glottic carcinoma treated with endoscopic laser surgery and radiotherapy . We performed an objective voice evaluation , as well as a physical , emotional and functional well being assessment of 19 patients treated with laser surgery and 18 patients treated with radiotherapy . Voice quality is affected both by surgery and radiotherapy . Voice parameters only show differences in the maximum phonation time between both treatments . Results in the Voice Handicap Index show that radiotherapy has less effect on patient voice quality perception . There is a reduced impact on the patient 's perception of voice quality after radiotherapy , despite there being no significant differences in vocal quality between radiotherapy and laser cordectomy . Introduction Surgery and radiotherapy offer the same results in the treatment of early glottic carcinoma , with a cure rate of approximately 90 % -LSB- 1 -RSB- . The introduction of endoscopic CO2 laser surgery in early glottic carcinoma -LRB- epidermoid carcinoma confined to the true vocal cords with normal mobility -RRB- has added controversy to the standard treatment choice . Laser surgery is quicker , which reduces cost considerably . However many institutions prefer to use radiotherapy in the belief that the voice will be better preserved after treatment -LSB- 2 -RSB- . Although the principal objective of oncology treatment is the complete eradication of the illness , normal voice preservation is another important consideration in the treatment choice of early glottic carcinoma . For this reason , post-treatment voice quality is a relevant factor to take into account when evaluating the results . Quantitative acoustic measurements are more regularly studied . These are obtained from tools that digitize and analyze the voice being investigated and quantify the characteristics that deviate from normality , understanding normality to mean when the voice is uniform in both amplitude and tone periodicity . The addition of noise to the voice signal is also a defect that affects voice quality , and this is the third acoustic characteristic that is studied using spectrography . Another of the factors to take into account is the auditive perception that is generated in the listener and is evaluated by ways of perceived voice quality , making use of semi-objective scales such as the GRBAS scale , as described by Hirano -LSB- 3 -RSB- . It is recommended that these measurements are made by two experts , although the parameters have shown sufficient reliability -LRB- inter - and intra-observer reproducibility -RRB- when used in a clinical setting -LSB- 4 -RSB- . Although all these measurements are important parameters in defining voice quality , they fail to provide information on the patient 's perceived voice quality . For this there is a method available that permits the patient to describe the sensations their voice gives : the Voice Handicap Index -LSB- 5 -RSB- . It is a questionnaire that reviews situations grouped into three areas -LRB- functional , physiological and emotional -RRB- and gives an idea of the subjective impact that a vocal problem produces in a specific individual . In this study , we present the objective and subjective analysis of voice quality following treatment of an early epidermoid glottic carcinoma . Results from the objective evaluation of the voice , along with the self-evaluation of voice quality quantified using the Voice Handicap Index of a group of patients treated with endoscopic laser surgery are compared with patients treated with radiotherapy . Materials and methods Voice analysis and quality of life studies of 19 patients treated with laser surgery and 18 with radiotherapy , suffering from early glottic carcinoma , were evaluated . Lesions were classified according to the American Joint Committee on Cancer -LSB- 6 -RSB- . In patients who received radiotherapy as the primary treatment , this was performed using a 6 mv linear accelerator to bilateral ports and one in front , with field sizes ranging from 5 × 5 to 6 × 6 cm . Wedges were used to establish dose homogeneity . In the case of patients treated with surgery , the treatment consisted of direct laryngoscopy for the complete resection -LRB- partial transmuscular cordectomy -RRB- of the lesion with CO2 laser . Objective voice analysis and voice quality studies , performed by both patients and examiners by means of an examination protocol including : perceptual analysis of dysphonia , acoustic analysis , aerodynamic efficiency and patient perception , were applied to both groups . In all patients , this protocol was undertaken at least 6 months after completing treatment . Perceptual analysis of dysphonia -LRB- GRBAS -RRB- Perceptual analysis of dysphonia was performed using the GRBAS scale -LSB- 3 -RSB- . Two experienced professionals evaluated the recorded voice samples simultaneously , classifying each sample from 0 to 3 -LRB- 0 = normal , 1 = mild , 2 = moderate , 3 = severe -RRB- . The severity of hoarseness is quantified under the parameter G -LRB- grade -RRB- , which represents overall voice quality . B -LRB- breathiness -RRB- : audible impression of turbulent air leakage through an insufficient glottic closure , which may include short aphonic moments -LRB- unvoiced segments -RRB- . R -LRB- roughness or harshness -RRB- : audible impression of irregular glottic pulses , abnormal fluctuations in F0 , separately perceived acoustic impulses -LRB- as in vocal fry -RRB- , includes diplophonia and register breaks . A -LRB- asthenicity -RRB- : impression of weakness in the spontaneous phonation , hypokinetic or hypofunctional voice . S -LRB- strain , vocal tension -RRB- : auditive impression of excessive force or tension associated with spontaneous phonation . Acoustic and spectrographic analysis The acoustic analysis was performed using Doctor Speech V3 software for Windows 95 . The acoustic signal was recorded using the Voice Assessment application . The computer used was a Pentium II at 100 MHz and with 16 Mb of RAM and a Sound Blaster 16 sound card . The sampling frequency was 44,100 Hz and a high frequency range microphone was used . The microphone was located 10 cm from the patient 's mouth while they emitted the `` e '' sound at comfortable intensity and pitch levels in a soundproof chamber . The computer captured 3 s of sound . Once the signal was digitized , the computer calculated the following acoustic parameters : fundamental frequency -LRB- F0 -RRB- , jitter or frequency variation -LRB- % -RRB- , shimmer or amplitude variation -LRB- % -RRB- and NNE or normalized noise energy , which measures the degree of noise produced by turbulent air escaping through the glottis during vocal emission . Using the same digitized voice sample , a narrow band spectrogram was generated -LRB- 45 Hz -RRB- using the Speech Analysis application . The spectrograms obtained were grouped into four types according to the Yanagihara criteria -LSB- 7 -RSB- . Aerodynamic efficiency analysis This consisted in measuring the maximum phonation time -LRB- TMF -RRB- for the `` a '' vocal after instructing the patient to sustain this vocal for the longest time possible at a comfortable pitch and intensity . The patients were asked to repeat the test at least three times and the highest value was retained . Patient self-perception analysis -LRB- Voice Handicap Index -RRB- The patients completed the `` Voice Handicap Index '' via a self-evaluation form comprising 30 questions covering three domains -LSB- 5 -RSB- : functional , physical and emotional , translated from the original work in English by one of the authors . Each question was assigned a score of 0 -- 4 -LRB- from least disability to most -RRB- . In each item , the maximum score was 40 points and we classified them as mild disability -LRB- less than 20 -RRB- , moderate -LRB- 21 -- 30 -RRB- and severe -LRB- more that 30 -RRB- . Adding the three scores together , the maximum possible was 120 , and we classified the vocal disability as mild -LRB- less than 30 -RRB- , moderate -LRB- 31 -- 60 -RRB- , severe -LRB- 61 -- 90 -RRB- and very severe -LRB- 91 -- 120 -RRB- . Statistical analysis The data obtained was gathered in the statistical database SPSS 12.0 . The statistical analysis used was the Student 's t test in order to compare averages and the Chi-squared test for comparing proportions . The statistical differences were considered significant when P was lower than 0.05 . Results In the patient group treated with CO2 laser , the ages were in the range 44 -- 86 years , with an average age of 64 and a mean follow-up of 30 months -LRB- 12 -- 48 -RRB- . In the patient group treated with radiotherapy , the ages were in the range 55 -- 81 years , with an average age of 67 and a mean follow-up of 43 months -LRB- 6 -- 81 -RRB- . All patients in both groups were males . In both groups , all lesions corresponded to stage I of the TNM classification . In the group of 19 patients treated with surgery , all the lesions were qualified as T1a and in the case of the 18 radiotherapy patients , 13 were classified as T1a and 5 as T1b . No metastases in the neck , or distant , were detected . At the time of the study , all patients were free from illness . In the group of patients treated with radiotherapy , the nominal total dose was 6,525 cGy , with 225 cGy daily doses for a total of 29 days . Of the PTV volume , 100 % received minimum doses of approximately 5,700 cGy , a maximum dose of approximately 6,720 cGy and an average dose of 6,520 cGy . Aerodynamic efficiency and spectrographic analysis In Table 1 , the maximum phonation times are presented for the `` a '' vocal along with the quantitative voice analysis of the vocal `` e '' obtained in the groups treated with laser and with radiotherapy . There was no significant difference between the parameters : fundamental frequency , -LRB- F0 -RRB- , jitter , shimmer and NNE on comparing both groups . However , there were significant differences in the maximum phonation time . Table 1MPT and acoustic analysis of the vocal / e / after treatment : laser -LRB- n = 19 -RRB- or radiotherapy -LRB- n = 18 -RRB- VariableLaserRadiotherapyMPT11 .83 ± 5.288.63 ± 3.23 P < 0.05 F0 -LRB- Hz -RRB- 173.39 ± 47.41199.04 ± 51.46 NSJitter -LRB- % -RRB- 0.44 ± 0.240.72 ± 0.91 NSShimmer -LRB- % -RRB- 5.08 ± 4.724.07 ± 4.04 NSNNE -LRB- dB -RRB- − 5.82 ± 2.98 − 5.02 ± 4.44 NSMPT maximum phonation time , F0 -LRB- Hz -RRB- fundamental frequency , NNE normalized noise energy In spectrographic terms , the 19 voice samples of patients treated with laser were classified as Grade I 4 -LRB- 21 % -RRB- , Grade II 5 -LRB- 25 % -RRB- , Grade III 7 -LRB- 37 % -RRB- and Grade IV 3 -LRB- 15 % -RRB- . In the group of patients treated with radiotherapy , the 18 voice samples were classified as Grade I 1 -LRB- 5 % -RRB- , Grade II 7 -LRB- 39 % -RRB- , Grade III 5 -LRB- 28 % -RRB- and Grade IV 5 -LRB- 28 % -RRB- . On comparing the spectrograms obtained in both groups , there were no statistically significant differences -LRB- P = 0.401 -RRB- . Perceptual dysphonia analysis -LRB- GRBAS -RRB- Table 2 shows the results obtained using GRBAS scale on patients treated with CO2 laser surgery . Mild dysphonia was found in 31.5 % of the cases , moderate dysphonia in 37 % and severe dysphonias in the remaining 31.5 % . Table 3 shows the GRABS results of the patients treated with radiotherapy . Normal voices were observed in 11 % , mild dysphonias in 44.4 % , moderate dysphonia in 27.8 % and severe dysphonia in 16.7 % of the cases . On comparing the results obtained in the G domain of the GRABS scale , which corresponds with the degree of dysphonia , no significant difference was found between each group -LRB- P = 0.309 -RRB- . Table 2Results obtained using GRBAS scale on the patients treated with CO2 laser surgery -LRB- n = 19 -RRB- 0123TotalG0 % 31.5 % -LRB- 6 -RRB- 37 % -LRB- 7 -RRB- 31.5 -LRB- 6 -RRB- 100 % -LRB- 19 -RRB- R10 .5 % -LRB- 2 -RRB- 58 % -LRB- 11 -RRB- 26 % -LRB- 5 -RRB- 5.5 % -LRB- 1 -RRB- 100 % -LRB- 19 -RRB- A21 % -LRB- 4 -RRB- 42 % -LRB- 8 -RRB- 21 % -LRB- 4 -RRB- 16 % -LRB- 3 -RRB- 100 % -LRB- 19 -RRB- B84 % -LRB- 16 -RRB- 16 % -LRB- 3 -RRB- 0 % 0 % 100 % -LRB- 19 -RRB- S31 .5 % -LRB- 6 -RRB- 31.5 % -LRB- 6 -RRB- 21 % -LRB- 4 -RRB- 16 % -LRB- 3 -RRB- 100 % -LRB- 19 -RRB- G grade , R roughness , A asthenicity , B breathiness , S strainTable 3GRABS results of patients treated with radiotherapy -LRB- n = 18 -RRB- 0123TotalG11 .1 % -LRB- 2 -RRB- 44.4 % -LRB- 8 -RRB- 27.8 % -LRB- 5 -RRB- 16.7 % -LRB- 3 -RRB- 100 % -LRB- 18 -RRB- R55 .6 % -LRB- 10 -RRB- 33.3 % -LRB- 6 -RRB- 5.6 % -LRB- 1 -RRB- 5.6 % -LRB- 1 -RRB- 100 % -LRB- 18 -RRB- A55 .6 % -LRB- 10 -RRB- 33.3 % -LRB- 6 -RRB- 11.1 % -LRB- 2 -RRB- 0 % 100 % -LRB- 18 -RRB- B44 .4 % -LRB- 8 -RRB- 27.8 % -LRB- 5 -RRB- 22.2 % -LRB- 4 -RRB- 5.6 % -LRB- 1 -RRB- 100 % -LRB- 18 -RRB- S77 .8 % -LRB- 14 -RRB- 16.7 % -LRB- 3 -RRB- 5.6 % -LRB- 1 -RRB- 0 % 100 % -LRB- 18 -RRB- G grade , R roughness , A asthenicity , B breathiness , S strain Patients self-perception analysis -LRB- Voice Handicap Index -RRB- Table 4 shows the averages obtained from the `` Voice Handicap Index '' questionnaire in the functional , physical and emotional scales , as well as the scores obtained in both groups . Upon completing the comparison between the two groups , the statistical difference is significant , in favor of the radiotherapy patients in the functional and emotional ratings as well as the global scores . No significant differences were found in the physical scales . Table 4Averages obtained from the `` Voice Handicap Index '' questionnaire in the functional , physical and emotional scales , as well as the scores obtained in both groupsLaser RadiotherapyFunctional11 .47 -LRB- 0 -- 32 -RRB- 2.83 -LRB- 0 -- 17 -RRB- P < 0.05 Physical12 .68 -LRB- 0 -- 31 -RRB- 6.22 -LRB- 0 -- 18 -RRB- NSEmotional4 .63 -LRB- 0 -- 20 -RRB- 0.61 -LRB- 0 -- 5 -RRB- P < 0.05 Global28 .79 -LRB- 0 -- 77 -RRB- 9.67 -LRB- 0 -- 29 -RRB- P < 0.05 Discussion Early glottic carcinoma can be treated using endoscopic surgery , radiotherapy or partial open surgery . Lesions limited to the vocal fold are normally treated with endoscopic surgery or partial open surgery , with local control results of between 80 and 90 % -LSB- 8 -RSB- . In choosing one treatment or another , one should contemplate the cure rate , larynx preservation rate , post-treatment voice quality , morbidity and treatment cost -LSB- 9 -RSB- . In recent years , endoscopic CO2 laser surgery has made headway compared to radiotherapy , based on its good oncology results and reduced morbidity . CO2 laser treatment in early glottic carcinoma has greatly improved voice quality compared to that obtained following cordectomy via laryngofissure . as documented by some authors such as Keilmann et al. -LSB- 10 -RSB- . However in other published studies , such as Schindler -LSB- 11 -RSB- , this improvement is not as evident . One of the advantages of laser surgery is its low cost when compared to radiotherapy , as well as the additional benefit of being able to opt for radiotherapy at a later stage to treat a relapse or second primary malignancy . In many institutions , these tumours are treated with external radiotherapy because of the supposedly better functional and quality of life results obtained compared to patients treated with surgery -LSB- 12 -RSB- . Various studies have been published comparing voice quality after both treatments -LSB- 13 -- 15 -RSB- . In some studies , voice quality is similar , while other authors maintain that the voice is better after radiotherapy than after laser surgery -LSB- 16 -- 18 -RSB- . However , there are fewer published works that include patient opinions with regard to the impact the illness and the treatment has had on their quality of life -LSB- 19 -- 21 -RSB- . In our work , no significant differences in fundamental frequency -LRB- F0 -RRB- , jitter , shimmer and NNE were found between the two groups . There were , however , significant differences in maximum phonation time , favoring the patients treated with CO2 laser cordectomy . Other authors do not find significant differences in the maximum phonation time between the groups -LSB- 22 -- 24 -RSB- . In the study by Tamura et al. -LSB- 13 -RSB- the fundamental frequency is higher for patients treated with CO2 laser surgery , which suggests that this surgery has a greater impact on the vocal fold function than radiotherapy . Krengli et al. -LSB- 18 -RSB- found statistically significant differences in the vocal acoustic parameters and fundamental frequency , favoring radiotherapy patients . In terms of the spectrograms obtained in both groups , no statistically significant differences were found . According to our results , 48 % of patients treated with laser , and 44 % of radiotherapy patients have an aesthetically acceptable voice -LRB- type I and II dysphonia -RRB- . There were no significant differences found between the two groups on comparing the scores obtained using the G parameter of the GRABS scale , which corresponds to the degree of dysphonia . Other studies such as Loughran et al. -LSB- 20 -RSB- failed to find statistically significant differences on comparing GRABS between patients treated with each technique . In our work , there is an elevated percentage of patients treated with CO2 laser -LRB- 84 % -RRB- who obtained low scores in the breathy voice domain -LRB- B -RRB- , which shows that apart from individual healing patterns , or treatment-induced secondary glottic defects , post-cordectomy phonetic compensating mechanisms are important in determining new voice quality . According to Sittel et al. -LSB- 25 -RSB- , glottic phonation voice quality is better than that obtained by the non-glottic phonation . Although one could believe that these patients had benefited from voice therapy , there are contradictory opinions on this -LSB- 26 -RSB- . While acoustic , physiological and perceptual measurements are important parameters in assessing vocal function , they do not provide information about the patient 's perception of their own voice quality . Given that voice quality , because of its potential impact on quality of life , can be an important factor in the choice of treatment , it is important to include this information when evaluating results . Not only should dysphonia as a by-product of laryngeal physiology be considered , but also the effects on patient quality of life must be considered as well . In our study , in order to quantify patient opinion as to the impact caused by treatment , the Voice Handicap Index has been employed . This is an instrument developed to help the professional in deciding the therapy , taking into account the patient 's subjective sensations with respect to their problem . It is a post-treatment global result evaluation method , from the point of view of the patient 's perceived global well being -LRB- physical , mental and social -RRB- . Although it is a subjective evaluation based on the patient 's own perception , it can provide valuable data as to the reasons why patients with similar dysphonia characteristics can have different handicap severity indices -LSB- 27 -RSB- . VHI allows investigators to obtain information regarding the patient 's subjective perception as well as providing the physician with important information pre and post treatment . Given that the preservation of adequate phonation is an important consideration in early glottic carcinoma treatment selection and given equal oncologic results between the two treatments , the VHI proves to be a very important tool in the therapeutic decision-making process . In our study , low scores were obtained for both groups in the three scales , functional , physical and emotional . This could imply reduced impact in the quality of life of patients treated either with laser surgery or radiotherapy . The statistically significant differences are in favor of radiotherapy patients in the functional and emotional scales , as well as the global scores . Although acoustic and perceptual voice analysis in both groups showed no significant differences , the radiotherapy group scored less in the VHI than the surgical group . Loughran et al. -LSB- 20 -RSB- performed a study where they compared the results between both therapies in terms of the Voice Handicap Index as well as two other questionnaires aimed at evaluating the patient 's subjective voice quality -LRB- Vocal Performance Questionnaire , VPQ , and Voice Symptom Score , VoiSS -RRB- . In this work , no significant differences were discovered between radiotherapy and CO2 laser surgery patients in any of the questionnaires , except for the emotional sub-scale inVoiSS . However , in other studies the average global score in the Voice Handicap Index questionnaire is lower for patients treated with endoscopic laser resection than in patients treated with radiotherapy . Peeters et al. -LSB- 21 -RSB- compared the results of both the Voice Handicap Index and a quality of life questionnaire -LRB- COOP/WOONCA -RRB- following both treatments . In their results , they found statistically significant differences in favor of laser surgery for the VHI and none in the quality of life results . They found higher scores for global VHI results in 40 % of patients treated using surgery , and 58 % for those treated with radiotherapy . Their conclusions reveal that the treatment for T1 glottic carcinoma frequently generates vocal problems in day-to-day life , influencing negatively certain social activities . This data contradicts the results of our study where VHI scores of both groups were low and the differences found favored the radiotherapy patient group . Recently , Cohen et al. -LSB- 28 -RSB- published a meta-analysis in order to classify the quality of life related to voice in patients with TI glottic carcinomas treated with radiotherapy compared with CO2 laser resection . Six studies with a total of 208 patients treated with surgery and 91 with radiotherapy had similar scores for VHI , from which they concluded that both treatments result in comparable vocal handicap levels for patients with T1 glottic carcinomas -LSB- 28 -RSB- . In other works such as that by Stoeckli -LSB- 19 -RSB- , which value long-term results with regard to quality of life -LRB- QOL -RRB- of early glottic carcinoma patients , no differences were found between the two treatments and they conclude that both therapies provide good results in terms of quality of life . They show in addition , differences in the relative scores for questions such as swallowing , xerostomy and dental problems , favoring patients treated surgically , and show no differences with regard to perceived voice quality . These results could be related to the fact that xerostomy , edema , mucositis and fibrosis increase the sensation of handicap to such an extent that these effects on patient quality of life could be greater than those coming from the dysphonia itself in laser surgery patients . Few are the patients that have a so-called `` normal '' voice upon completing radiotherapy , above all taking into account that the larynx of these patients has undergone a surgical procedure in order to get a biopsy , has been intensely exposed to tobacco smoke and belongs generally to aged patients . All these factors negatively affect voice quality -LSB- 29 -RSB- . Despite this , the results of our work reveal that radiotherapy treatment for T1 glottic carcinoma generates lower repercussions in the subjective perception of residual dysphonia , as much in functional as in emotional aspects , when compared with CO2 laser surgery . The scores obtained in the VHI were low in the three domains for both groups , from which we can infer a scarce impact on the quality of life for laser surgery and radiotherapy for this type of patient . Conclusions Both CO2 laser resection and external radiotherapy as treatment for T1 vocal carcinoma offer similar objective measurement results -LRB- acoustic and spectrographic analysis -RRB- and subjective measurement results -LRB- GRABS scoring -RRB- . However , in our series , the self-evaluation of the quality of voice , quantified by the VHI , shows a lower impact for radiotherapy patients .

O O O O B O O B O O O O O O O O O B I I O O O O O O O O O O O O O O B I O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O B I I O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O B B O O O O B O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O B O O O O B O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O B O O O B I O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O B O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O

glottic carcinoma
laser
voice handicap index
cordectomy
radiotherapy