A Retrospective Cross-Sectional Analyses of Swallowing and Tongue Functions in Maxillectomy Patients

Purpose To investigate the pro�les of swallowing and tongue functions, and to identify factors in�uencing swallowing in maxillectomy patients. Methods Maxillectomy patients whose swallowing function de�ned by Eating Assessment Tool (EAT-10) score and tongue functions (oral diadochokinesis: ODK, maximum tongue pressure: MTP) with or without maxillofacial prostheses had been evaluated were enrolled in this study. The effects of the history of radiotherapy or soft palate resection on swallowing function were evaluated. The effect of radiotherapy on oral dryness was also evaluated. To examine correlations of swallowing function with continuous variables, Spearman correlation coe�cients were calculated.


Introduction
Maxillectomy following head and neck, or oral cancers may cause maxillary defect and subsequent aesthetic and functional impairments, resulting in deterioration in quality of life (QoL) and oral healthrelated QoL (OHRQoL) [1][2][3][4].It is de nitely important to restore oral functions, including mastication and swallowing, with surgical and/or prosthetic (including an obturator or a maxillofacial prosthesis) rehabilitation after the resection.Aesthetic and functional outcomes of maxillectomy depend on intraand extra-oral conditions and the method of rehabilitation.Although primary closure is a predictable method for better oral functions, patients who got greater extent of resections generally need surgical reconstructions with grafts and/or rehabilitation with maxillofacial prostheses [4].Furthermore, most of these patients also lose their teeth and need to replace the teeth with maxillofacial dentures to restore oral functions.
Swallowing is equally important for well-nutrition, whereas it must be an extremely complex neuromuscular process [11,12].In maxillectomy patients, swallowing is often impaired by resection and radiotherapy [13][14][15][16] and previous studies evaluated the effect of maxillofacial prostheses on swallowing after maxillectomy [16][17][18][19][20][21][22], although functional impacts of maxillofacial prostheses remain controversial because multiple variables are related to swallowing.However, it is obvious that tongue functions play a crucial role in swallowing, especially during oral and pharyngeal phase [23][24][25][26].Contact of tongue against the hard palate or a prosthesis and tongue dynamics are representative assessment factors and it is reasonable to suppose that these are in uenced by surgical and prosthetic interventions in maxillectomy patients.
The purpose of this study was to evaluate tongue functions and swallowing function in maxillectomy patients and to identify predictable factors for estimating swallowing function in maxillectomy patients.The null hypothesis in this study was that no factors were signi cantly correlated with swallowing function in maxillectomy patients.

Materials And Methods
This cross-sectional retrospective study was conducted in the Department of Prosthodontics, Kyushu University Hospital.The study protocol was approved by the ethics committee of Kyushu University,

Study population
Maxillectomy patients who had prosthetic rehabilitation from April, 2016 to January 2019 were included in this study.The inclusion criteria were as follows: 1) age: 20 years old or older, 2) the history of maxillectomy due to cancer and maxillofacial prosthetic rehabilitation with or without surgical reconstruction, 3) patients who had been evaluated their swallowing function and tongue functions.The exclusion criteria were as follows: 1) patients with ongoing cancer therapy such as chemotherapy and radiotherapy, 2) the history of additional head and neck cancers other than original cancer attributed to maxillectomy.The following patient pro les were extracted from patient charts: age, number of remaining teeth and, the history of radiotherapy and soft palate resection.

Assessment of swallowing function
Swallowing function was assessed using Eating Assessment Tool (EAT-10) score.This self-administered, symptom-speci c outcome instrument has been utilized for diagnosis of dysphagia [27][28][29].

Assessment of tongue functions
In this study, tongue functions included tongue motor function and maximum tongue pressure.Tongue motor function was determined by oral diadochokinesis (ODK) [28,29].Patients were asked to utter /ta/ repeatedly as quickly as possible for 5 seconds.This method is useful to assess the elevation of anterior region of the tongue, which is observed during initial swallowing.The number of the syllables uttered per second was determined using an automatic counter (Kenkokun Handy, Takei Scienti c Instruments Co., Ltd., Niigata, Japan).Maximum tongue pressure (MTP) was recorded using a tongue pressure measuring instrument equipped with a balloon probe (JMS tongue pressure measuring instrument TPM-01, JMS Co., Ltd., Hiroshima, Japan) [26,28].Patients were instructed to compress the in ated balloon between tongue and anterior part of palate (including denture base) by elevating tongue.The measurements were conducted in triplicate and the average values were calculated.These functions were evaluated in patients with or without their maxillofacial prostheses.

Assessment of oral dryness
Saliva is known to form a bolus which is ready for swallowing, implying that saliva secretion can be a trigger of swallowing.Additionally, oral dryness, known as xerostomia, is one of the major radiationinduced side effects.In this study, oral dryness was also measured using an oral moisture checker (Mucus, Life Co., Ltd., Saitama, Japan) as a previous study showed [28].

Statistical analyses
The data including patient pro les (age and number of remaining teeth) were presented descriptively using medians with interquartile ranges (IQRs).For comparative analyses, data distribution was displayed in a box plot.The scores of EAT-10 and oral dryness in patients with or without the history of radiotherapy were compared using Wilcoxon rank sum test.The effect of soft palatal resection on the scores of EAT-10 was also examined in the same way.The results of ODK and MTP with or without a maxillofacial prosthesis were compared using Wilcoxon signed rank test.Correlations between EAT-10 scores and patient-related continuous variables including age, number of remaining teeth, tongue functions, and oral dryness examined with Spearman correlation coe cients.Statistical signi cance was set at P < 0.05.All statistical analyses were performed using JMP ® Pro (SAS Institute Inc., Cary, NC, USA)

Effect of radiotherapy and soft palate resection on the scores of EAT-10
The median value of EAT-10 scores in all patients was 3 [IQR: 0-14].The distribution of EAT-10 scores in patients with or without the history of radiotherapy are shown in Fig. 1.The scores in patients who had experienced radiotherapy were signi cantly worse than patients who had not (P<0.05),resulting in the rejection of our null hypothesis.The effect of soft palate resection on EAT-10 scores was also evaluated and our analysis did not demonstrate a signi cant difference in EAT-10 scores when comparing patients with or without soft palate resection (Fig. 2).

Effects of maxillofacial prostheses on tongue functions
The median values of ODK and MTP in all patients in this study was 3.8 [IQR:2.8-5.4] and 23.3 [IQR:17.0-27.4],respectively.Both tongue functions, ODK and MTP, were also measured with or without their maxillofacial prostheses.Both ODK and MTP scores were signi cantly improved by wearing their maxillofacial prostheses (P<0.0001,Fig. 3 and 4, respectively).

Effects of radiotherapy on oral dryness
The median values of oral dryness in all patients was 28.2 [IQR:26.6-29.4].The effect of radiotherapy on oral dryness was evaluated with an oral moisture checker.Our statistical analysis revealed no signi cant differences in oral dryness between the patients with and without radiotherapy (Fig. 5).

Correlations between EAT-10 scores and continuous variables
Correlations of EAT-10 scores with continuous variables were analyzed by Spearman's correlation coe cient.Our analyses demonstrated that there was a signi cant correlation between EAT-10 score and MTP (ρ=-0.30,P=0.04).This means that the null hypothesis in this study was rejected including the comparative result of EAT-10 scores between the patients with and without radiotherapy.The detailed results of the analyses are shown in Table 1.

Discussion
Swallowing procedure is known to be a complex activity and be conducted by several factors.In maxillectomy patients, poor swallowing function has been supposed to be caused by their speci c conditions such as maxillary defects including soft palate and other cancer therapy-related factors such as radiotherapy [1,4,14,16].In addition, it has been reported that tongue functions play a critical role in swallowing function in maxillectomy patients [23][24][25][26].However, the analyses that focused on the association between swallowing function and tongue functions in maxillectomey patients are still lacking.This study was conducted to examine the effects of maxillectomy patients-speci c factors including radiotherapy, and tongue functions on swallowing function using EAT-10 scores.
Our study showed that swallowing function is relatively poor in maxillectomy patients according to the reference value in the previous studies (poor swallowing function: EAT-10 score = 3 or higher) [27,28].The present study also found that swallowing function was signi cantly impaired by the history of radiotherapy, meaning that the radiotherapy does not guarantee normal swallowing function as the previous studies demonstrated [1,2,4,14,16] Radiotherapy is one of well-known causes of xerostomia identically to age and some medications [30].Saliva plays an important role in the preparing the food for swallowing by moistening, lubricating and facilitating bolus formation in addition to food bolus ow.
However, the present study demonstrated that we found no signi cant difference between oral dryness with and without the radiotherapy.We reason that the patients in the present study were maxilletomy patients and targeted radiation for maxillary cancer might reduce the damage and hypofunction of major salivary glands.In our institutional hospital, stereotactic radiotherapy or intensity modulated radiation therapy is often adopted for head and neck, or oral cancers to decrease the risk of surrounding tissue damage [31,32].As a result, the median values of oral dryness in this study might be 28.0 in the patients without the radiotherapy and 28.4 in the patients with the radiotherapy (the threshold value (27.0) de ned by Minakuchi et al. [28], which was approved as threshold value by Ministry of Health, Labour and Welfare in Japan, and Japanese Association for Dental Science).These ndings imply that poor swallowing function in patients with the history of radiotherapy is attributed to radiation-induced injury in neuromuscular system [14], although some detailed analyses will be required.On the other hand, there was no difference between patients with and without partial soft palate resection.Soft palate plays an important role in swallowing and it is very di cult to replace the soft palate with the prosthesis compared to hard palate [33,34].There have been previous studies that showed impaired swallowing function by soft palate resection [22,35].In this study, the distribution of EAT-10 scores in patients without soft palate resection was wide range and several patients without soft palate resection also had radiotherapy, which may be a confounding factor in them.Further studies with more patients are required to circumvent this problem.
Tongue functions were signi cantly improved with maxillofacial prostheses.A removable dental prosthesis with thicker denture base might be sometimes used to improve tongue functions like a palatal augmentation prosthesis (PAP) [36].However, it is also important to note that, in maxillectomy patients with a wide range of maxillofacial defects, larger maxillofacial prostheses are inevitably delivered to cover or ll the defects.In many cases, these prostheses tend to be unstable due to larger defects and poor support, resulting in poor functions including tongue functions which was assessed in this measurement method.The results of the present study might imply that functionally proper maxillofacial prostheses had been delivered.Improved tongue functions with maxillofacial prostheses might contribute to rehabilitation of swallowing functions as the previous studies showed [16,17,20].Fabrication and delivery of PAP would be determined after the assessment of MTP.However, future studies to investigate the association between defect size and con guration, and quality of maxillofacial prostheses including assessment of their functional contributions will be required.
Several comparative studies have revealed that prosthetic intervention with maxillofacial prostheses or obturators [17,18], and surgical reconstruction with or without prostheses [13][14][15][16] had positive effects on swallowing function.On the other hand, the evidence for an association between swallowing function and several factors in maxillectomy patients including tongue functions with maxillofacial prostheses and cancer treatment-related factors has been lacking.In the present study, a signi cant correlation of EAT-10 scores with MTP was identi ed, meaning lower MTP may result in impaired swallowing function in addition to the negative effect of radiotherapy on swallowing function shown in Fig. 1.Based on these ndings, the null hypothesis in this study was rejected.Whereas MTP and ODK were enhanced by wearing a prosthesis, only MTP, not ODK, was positively associated with swallowing function.
Interestingly, a previous study investigated the association between masticatory performance and both tongue functions, and demonstrated that motor functions of tongue which included both ODK and MTP were signi cant factor [37].Furthermore, it has also been reported that ODK was signi cantly associated with MTP [38].These ndings suggested that both tongue functions play a crucial role in the overall eating process and support our results.
Taken in the light of these ndings, following clinical managements will be recommended: 1) If maxillectomy patients showed weak and poor MTP, tongue muscle training and/or PAP might be recommended to improve swallowing function as the previous studies showed [36, 39-41], 2) In addition to tongue muscle training and/or PAP, food management such as the usage of thickener might be considered for maxillectomy patients who had radiotherapy and/or cannot improve tongue functions [16].Yet, few studies have investigated these impacts on swallowing or nutrition assessment in maxillectomy patients.Future research should focus more speci cally on these issues.
Considering the variables in this study and features in maxillectomy patients, we need to discuss the limitation of this study.This study was conducted as a cross-sectional retrospective study and this means that the number of our patients were limited.The defect size and con guration according to some classi cation might be considered [42,43].Furthermore, the duration of maxillofacial prostheses usage was not considered.Although the patients in this study could be classi ed into several groups according to these classi cations, it was unfavorable to analyze statistically due to the limited number of patients.The duration of prostheses usage is also associated with the habituation to prostheses and aging in patients.So far, there have been no longitudinal studies that evaluated oral functions in maxillectomy patients, to our knowledge.The impact of the duration of prostheses usage on oral functions with the consideration of the habituation to prostheses and aging in patients must be important in the future longitudinal study.These factors, including defect size, con guration and prosthesis design in maxillectomy patients, could be considered as confounding factors in swallowing function.To investigate the effect of these factors on swallowing function, more sophisticated research with a great number of patients will be required in the future.

Conclusions
Realizing that there are some limitations of this study, the authors conclude that swallowing function de ned by EAT-10 scores is relatively impaired in maxillectomy patients, especially in patients with the history of radiotherapy.Tongue functions can be restored with maxillofacial prostheses.More importantly, swallowing function is signi cantly in uenced by radiotherapy and MTF in the setting of the present study. Tables Comparative analysis of oral dryness between the subjects without and with the history of radiotherapy (Rad (-) and (+): without and with the history of radiotherapy, respectively).Wilcoxon rank sum test, no signi cant difference.

Faculty
of Dental Science (2019-144).The investigation in the present study was carried out in compliance with Helsinki declaration and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

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