Preoperative concurrent chemoradiotherapy for stages II-IV oral squamous cell carcinoma: a retrospective analysis and the future possibility of this treatment strategy

This study evaluated survival in 154 patients with stages II-IV oral squamous cell carcinoma (OSCC) treated with preoperative concurrent chemoradiotherapy and assessed the future use of this treatment strategy. 14 patients exhibited advanced stage II, 73 exhibited stage III and 67 exhibited stage IV. All patients received 40Gy irradiation and concurrent cisplatin-based chemotherapy in two courses. Radical surgery was undertaken after 2-6 weeks. The clinical tumour response, histopathologic regression grade, residual tumour grade (RGrade) in the primary tumour and the level of residual pN+ were associated with prognosis. 90% of patients with complete response and 73% of patients with good partial response in the primary tumour were RGrade 0 (no residual tumour cells) or RGrade 1 (viable tumour cells remained within central superficial portion). In patients with complete response in the neck, residual pN+ was only seen in levels IB (8%) and IIA (8%); the higher the level of residual pN+, the lower the survival rate (p<0.0001). This treatment strategy was excellent for stages II-IV OSCC. It may be possible to perform minimally invasive surgery in which the extent of resection in primary tumour and neck is reduced in patients who achieve good response following preoperative chemoradiotherapy.     

Neoadjuvant and adjuvant chemotherapy in the multidisciplinary treatment of oral cancer stage III or IV

We performed a retrospective analysis on the effect of initial induction chemotherapy with two courses of cisplatin (each course 120 mg/m² cisplatin on day 1, then 20 mg/m² bleomycin (alone) per day for 5 days with 4 weeks between courses) in 75 consecutive patients with advanced cancer of the oral cavity or lip. Further local therapy consisted of surgery or radiation, depending on tumour location. In 18 resected patients adjuvant chemotherapy was added. This consisted of carboplatin, 400 mg/m² on day 1 then ftorafur alone, 500 mg/m²/day for 30 consecutive days, repeated every month for 4 consecutive months.Among the patients treated in the neoadjuvant setting, complete response was observed in 10 out of 75 patients (13%), and partial response in a further 50 patients (67%) (partial plus complete rate 80%). Of all the patients, 43% in stage III and 26% in stage IV were long-term survivors. Improved survival was observed in surgical patients where adjuvant postoperative chemotherapy was added (P < 0.025).The main toxic effect was vomiting, observed in 71 patients. We noted a low rate of stomatitis (4%) and an important hearing loss (12%).Neoadjuvant and adjuvant cisplatin-based chemotherapy as part of a multidisciplinary approach have a high overall response rate and low toxicity, and should increase survival in cancer of the oral cavity or lip.     

三联化疗在口腔鳞癌综合治疗中的应用及其疗效评价

目的　评价术前三联化疗(PYM+5-Fu+DDP)配合手术治疗口腔鳞癌的临床疗效及与多药耐药性的关系。方法　采用术前三联化疗合并手术综合方案治疗口腔鳞癌患者102例,全部患者均经活检确诊。对所有患者的化疗效果进行评价,并对综合治疗的效果进行随访观察。结果　102例患者化疗有效率为82·4%。有完整随访资料者92例,存活69例,3年生存率为67·6%。结论　本三联化疗方案在口腔鳞癌综合治疗中具有用药剂量小、疗效确切等优点,可作为口腔鳞癌患者术前化疗方案之一。     

晚期口腔鳞癌患者独立预后因素及生存预测模型的建立

目的 探讨晚期口腔鳞癌患者的独立预后因素并构建生存预测模型。方法 收集117例晚期口腔鳞癌患者的一般资料及既往病史,所有患者均行口腔鳞癌切除术并联合放疗,根据患者情况进行羟基喜树碱及平阳霉素化疗。所有患者随访时间为手术结束至术后5年,记录患者生存情况,分析晚期口腔鳞癌患者预后的独立危险因素。采用SPSS 20.0软件包对数据进行统计学分析。结果 随访期间,2例因其他原因死亡,4例因失访而剔除。剩余111例患者中, 42例死亡,69例存活,生存率为62.16%;年龄、T分期及M分期不同的晚期口腔鳞癌患者生存情况无显著差异（P>0.05）;性别、组织分化程度、N分期及化疗情况不同的晚期口腔鳞癌患者生存情况差异显著（P<0.05）;性别、N分期及是否联合羟基喜树碱与平阳霉素化疗是晚期口腔鳞癌患者生存情况的独立危险因素（P<0.05）;组织分化程度不是晚期口腔鳞癌患者生存情况的独立危险因素（P>0.05）;性别、N分期及是否联合羟基喜树碱与平阳霉素化疗的生存曲线对晚期口腔鳞癌患者生存情况具有一定预测作用。结论 性别、N分期及是否联合羟基喜树碱与平阳霉素化疗是晚期口腔鳞癌患者生存情况的独立危险因素;性别、N分期及是否联合羟基喜树碱与平阳霉素化疗的生存曲线,可作为晚期口腔鳞癌患者的生存预测模型。     

Prognostic value of response to preoperative chemoradiotherapy and residual tumor grades in tongue carcinoma

OBJECTIVE: The purposes of the present study were to analyze our experience with preoperative chemoradiotherapy followed by surgery for advanced tongue carcinoma and to assess the prognostic value of response to preoperative therapy in these tumors.Study Design: Between May 1988 and December 1999, a total of 43 patients with advanced but potentially resectable squamous cell carcinoma of the tongue were candidates for this study. A minimum tumor size of 3 cm was required. The mean age was 59.8 years (range, 26-85 years); 13 cases were advanced stage II, 23 cases were stage III, and 7 cases were stage IV. All patients were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy; 2-6 weeks later, they underwent curative surgery. Tumor regression rate, residual tumor grade, and histologic regression grade to the preoperative therapy were analyzed to determine their influence on the prognosis. RESULTS: With a median follow-up of 60.5 months, overall survival rates were 86.0% for all cases, 92.3% for stage II cases, 77.3% for stage III cases, and 100% for stage IV cases. The progression-free survival rates according to tumor regression rate were 33.3% for group 1 (< 50% tumor regression), 66.7% for group 2 (> or = 50% and < 75% regression), 100% for group 3 (> or = 75% and < 100% regression), and 96.0% for group 4 (complete regression). The higher the tumor regression rates, the higher the survival rates. When patients who achieved a regression rate of 75% or higher were compared with those who did not, there was a significant difference in survival (P < .0001). The factors of residual tumor grade and histologic regression grade also had good correlations with the prognosis (residual tumor grade, P =.0324; histologic regression grade, P < .0001). CONCLUSIONS: The findings of the present study suggest that response to preoperative chemoradiotherapy, such as tumor regression rate, residual tumor grade, and histologic regression grade, could be of prognostic value in patients with tongue carcinoma.     

Nrf2对口腔鳞癌患者TPF诱导化疗效果的影响

目的: 检测核转录相关因子2（Nrf2）在口腔鳞癌组织中的表达,探讨其对TPF诱导化疗效果的影响。方法: 选择65例接受TPF诱导化疗的口腔鳞癌患者,采用免疫组织化学方法检测患者活检肿瘤标本中Nrf2的表达,分析Nrf2表达与患者基线资料及预后的关系。采用SPSS 23.0软件包对数据进行统计学分析。结果: 生存分析发现,口腔鳞癌患者Nrf2表达与TPF诱导化疗预后显著相关,Nrf2低表达者较高表达者具有更好的总生存率、无疾病生存率、局部无复发生存率、无远处转移生存率。单因素及多因素Cox风险模型分析发现,Nrf2是口腔鳞癌患者TPF化疗的独立预后风险因素。结论: Nrf2表达与口鳞癌患者TPF诱导化疗疗效相关,Nrf2低表达患者预后更好,Nrf2可作为预测口腔鳞癌患者TPF诱导化疗效果的生物标志物。     

Prognostic value of Ki67 from clinically and histologically ‘normal’ distant mucosa in patients surgically treated for oral squamous cell carcinoma: a prospective study

The frequent spread of oral squamous cell carcinoma (OSCC) has been explained by the persistence of genetically altered mucosa after surgery. This study examined whether clinically and histologically ‘normal’ mucosa distant from the primary tumour (from the opposite cheek) has an abnormal proliferative status, and whether this is associated with poor prognosis in terms of local recurrence or lymph node metastasis. The prospective study included 47 consecutive patients with OSCC. Disease-free survival endpoints were defined as the duration between surgical resection and the diagnosis of recurrence, lymph node metastasis, death or last follow-up. Proliferative status was evaluated by Ki67 expression. The mean Ki67 value (16.5 ± 8.9) in the distant mucosa was statistically higher than that in controls (8.8 ± 2.9). Abnormally high Ki67 values (>20%) were detected in 11 OSCC patients (23%). Multivariate analysis showed that Ki67 value in distant mucosa was a powerful independent prognostic factor, greater than tumour differentiation or clinical stage for the disease-free survival rate; it was statistically negative regarding local recurrence. Some patients surgically treated for OSCC have an abnormal proliferative status in areas distant from the primary tumour. The Ki67 value in these areas is a promising prognostic factor.     

Detection of serum Cyfra 21-1 in patients with primary oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region, and has a poor prognosis. Cyfra 21-1 is a useful tumour marker for squamous cell carcinoma, but the clinical value of Cyfra 21-1 in OSCC has not been confirmed. In order to investigate the diagnostic and prognostic value of serum Cyfra 21-1 in primary OSCC patients, the preoperative serum Cyfra 21-1 concentration of 100 OSCC patients and 56 healthy subjects was detected by enzyme-linked immunosorbent assay (ELISA). The cut-off value was calculated with a receiver operating characteristic (ROC) curve, and prognostic analysis was performed using the Kaplan-Meier method and Cox regression models. The preoperative serum Cyfra 21-1 concentration in OSCC patients (1.18+/-1.20 microg/L) was significantly higher (t=6.585, P<0.001) than that in healthy subjects (0.40+/-0.16 microg/L). With a cut-off value of 0.65 microg/L, the diagnostic sensitivity and specificity was 0.570 and 0.964, respectively. There was significant correlation with tumour recurrence and survival rate: the higher the serum Cyfra 21-1; the higher the tumour recurrence rate and lower the survival rate. Serum Cyfra 21-1 was an independent prognostic factor for OSCC using univariate and multivariate Cox models.     

Oral squamous sell carcinoma in North-Eastern Hungary I. Epidemiology

The purpose of this study was to characterize the epidemiological data of oral squamous cell carcinoma (OSCC) patients in North-Eastern Hungary. The medical records of 119 randomly selected patients with OSCC admitted to the Department of Maxillofacial Surgery of the Faculty of Dentistry, University of Debrecen were reviewed. Cases were identified according to the epidemiological data, as to site, tumor size, lymph node involvement, clinical stage, histological differentiation, treatment obtained, recurrence of disease and survival rate. There was an obvious male predominance (male:female = 5.2:1). The median age at diagnosis was 57.4 years. The most common sites of OSCC were the floor of the mouth (27.7%), the lip (26.9%) and the tongue (22.7%). The majority of the patients (58,8%) presented with early-stage (I-II) disease at the time of diagnosis, and 48.6% had moderately differentiated tumors. The most frequent therapeutic modality used was surgery with or with out of radiotherapy. Roughly one fifth of the cases (20.7%) experienced a recurrence of disease during the follow-up period. The overall 5-year survival rate was 38.7% (stage I: 68.3%, stage II: 31.0%, stage III: 22.6%, stage IV: 11.1%). There was a correlation between survival and tumor size, lymph node metastasis, clinical stage and surgical treatment (p < or = 0.05, respectively). We found no significant correlation between histological differentiation and survival. Clinical stage exerts the most strongly significant impact on survival. Therefore, early detection and proper surgical intervention enhance patients' survival most effectively.     

Outcomes of oral squamous cell carcinoma in Taiwan after surgical therapy: factors affecting survival.

PURPOSE: The study goal was to determine which clinical features correlated with 5-year survival in patients surgically treated for oral squamous cell carcinoma (OSCC) in Taiwan. Patients and Methods: The records of 378 OSCC patients surgically treated with or without chemotherapy and radiotherapy were reviewed retrospectively. Their 5-year survival in relation to age, gender, tumor site, lymph node involvement, presence of distant metastasis, staging, differentiation, and risk factors, including betel quid (BQ) chewing, cigarette smoking, and alcohol consumption, was analyzed. RESULTS: The majority of the patients were men (male-to-female ratio, 5.87:1) with the mean age of 57.1 +/-11.7 years. Tumors occurred mainly at the buccal mucosa (BM) (100 of 378, 26.5%), gingiva (105 of 378, 27.8%), and tongue (103 of 378, 27.2%). Neck nodal metastasis occurred frequently at the floor of the mouth (in >60% of cases), followed by the gingiva (45.7%), buccal mucosa (34%), and tongue (20.4%), whereas early distant metastasis was rare (5.3%). There were 104 (27.5%) stage 1, 96 (25.4%) stage 2, 98 (25.9%) stage 3, and 80 (21.2%) stage 4 patients. OSCC at the BM and gingiva was most (and at the tongue least) associated with risk factors of BQ use and smoking. The 5-year survival was 75%, 65.6%, 49%, and 30% for patients with stage I, II, III, and IV, respectively. The size, nodal involvement, distant metastasis, staging, differentiation, and BQ use significantly affected the survival (P <.05, Kaplan-Meier analysis). BQ use also correlated most significantly with the younger age of occurrence of OSCC patients. CONCLUSIONS: Our data suggest that early treatment is the key to increasing the survival of OSCC patients. Periodic screening of high-risk populations for OSCC represents an urgent need in Taiwan.     

Nuclear fractal dimension in oral squamous cell carcinoma: a novel method for the evaluation of grading,staging, and survival

Fractal dimension (FD) in tissue specimens from patients with oral squamous cell carcinoma (OSCC) was evaluated. FD values in different stages of OSCC, and the correlations with clinicopathological variables and patient survival were investigated. Histological sections from OSCC and control non‐neoplastic mucosa specimens were stained with hematoxylin–eosin for pathological analysis and with Feulgen for nuclear evaluation. FD in OSCC groups vs. controls revealed statistically significant differences (P < 0.001). In addition, a progressive increase of FD from stage I and II lesions and stage III and IV lesions was observed, with statistically significant differences (P = 0.003). Moreover, different degrees of tumor differentiation showed a significant difference in the average nuclear FD values (P = 0.001). A relationship between FD and patients' survival was also detected with lower FD values associated to longer survival time and higher FD values with shorter survival time (P = 0.034). These data showed that FD significantly increased during OSCC progression. Thus, FD could represent a novel prognostic tool for OSCC, as FD values significantly correlated with patient survival. Fractal geometry could give insights into tumor morphology and could become an useful tool for analyzing irregular tumor growth patterns.     

替尼泊甙对口腔鳞癌化疗敏感性的体外研究

目的　探讨替尼泊甙 (teniposide ,VM 2 6 )这一鬼臼毒植物碱类化疗药物对口腔鳞癌的体外抗瘤效果 ,为其治疗口腔鳞癌提供实验依据。方法　有 81例纳入研究的患者 ,切取经病理证实的口腔鳞癌术后标本或活检标本行体外药敏检测。检测VM 2 6时以顺铂 (cisplatin ,CDDP)作对照 ,药物应用 5倍的峰血浆浓度。VM 2 6终浓度为 6 0mg/L ,CDDP为 15mg/L。结果　 81例标本完成药敏检测 75例 ,药敏检测成功率为 92 .6 %。 75例患者按UICC标准的TNM分期结果为 :I期 2例 ,II期 11例 ,III期 34例 ,IV2 8例。这组患者病理分级结果为I级 18例 ,I～II级 37例 ,III级 2 0例。VM 2 6和CDDP对口腔鳞癌细胞的生长抑制率分别为 6 3.34%和 2 4 .0 8%,前者生长抑制率明显高于后者 (P <0 .0 1)。结论　VM 2 6对口腔鳞癌的抗瘤敏感性明显高于CDDP ,VM 2 6有望成为治疗口腔鳞癌的首选化疗药物。     

Prognostic factors of survival in a cohort of head and neck cancer patients in Oslo

A cohort of 433 Oslo patients with head and neck (H/N) carcinomas was analysed for prognostic factors of survival. Mean observation time was 635 days, the distribution of men and women was 2:1 and the mean age was 64.5 years. Tumour localisations were: oral cavity 32.1%, oro/hypopharynx 19.3%, larynx 22.6% and others 25.2%. Stage distribution was: stage I: 21.0%, stage II: 22.6%, stage III: 18.7% and stage IV: 37.4%. Pragmatic strategy showed independent prognostic factors of survival to be gender, age, tumour localisation and stage. A model of predicting 3 year survival was generated. An explanatory approach showed that female patients had a 38% lower risk of mortality compared to male patients after controlling for age, stage and tumour localisation. Comparing observed to expected mortality of the age and gender matched Norwegian population, showed excess risk of death among male compared to female patients when also adjusted for demographic confounders.     

Combined surgery and postoperative radiotherapy for oropharyngeal squamous cell carcinoma in Korea: analysis of 110 cases

The treatment of oropharyngeal squamous cell carcinoma (OSCC) remains controversial. This study reviews the authors' experience of treating OSCC, evaluates the oncologic outcome and assesses the factors affecting local/regional recurrence. A retrospective analysis of 110 consecutive OSCC patients treated primarily by surgery and/or postoperative radiotherapy was carried out. 82% of patients had advanced disease (stage III or IV). The 5-year overall survival and disease specific survival rates (DSSR) were 58% and 65%, respectively. The DSSR of the soft palate or posterior pharyngeal wall, tonsillar area, and base of tongue were 80%, 62%, and 51%, respectively (P<0.05). The 5-year DSSR according to the American Joint Committee on Cancer stages was 94% for early stage and 56% for advanced stage (P<0.05). The overall recurrence rate was 38% (42 patients). The most frequent site of recurrence was the neck (46%). Only 14% of patients with recurrences were treated successfully. Positive resection margins and the presence of pathologic lymph nodes influenced the recurrence at the primary lesion and in the neck, respectively, in a statistically significant manner. Surgery and postoperative radiotherapy provided a superior outcome in patients with advanced OSCC. A randomized study is required to assess the oncologic and functional superiority of surgery or chemoradiation.     

Prognostic significance of dysplasia associated with oral squamous cell carcinoma in patients undergoing surgery with curative intent

The aim of this study was to evaluate the prognostic significance of dysplasia in patients undergoing primary surgery with curative intent in the treatment of oral squamous cell carcinoma (OSCC). This study specifically aimed to demonstrate the effect of dysplasia on local recurrence, disease specific survival (DSS) and overall survival (OS). Data collection for 833 patients with OSCC undergoing treatment for curative intent was undertaken retrospectively for the period of February 2006 to May 2020. Analysis of any association between known clinicopathological prognostic categorical variables with respect to dysplasia was undertaken using the chi squared test. A Kaplan-Meier analysis was performed to demonstrate the impact of dysplasia on DSS and OS, and Cox’s proportional-hazards model deployed to obtain hazard ratios associated with dysplasia and the outcomes of interest. Dysplasia was statistically significant in predicting disease specific and overall survival in patients undergoing primary surgery for OSCC (DSS p<0.001, HR 0.577; 95%CI 0.428 to 0.777), OS p<0.001 HR 0.691; 95%CI 0.562 to 0.850) with the absence of dysplasia predicting poorer outcomes. The absence of dysplasia correlated with pathological higher T and N stage, increased categorised depth of tumour invasion, non-cohesive invasive front, lymphovascular invasion, perineural invasion, extranodal extension and increased modified Glasgow Prognostic Score. No significant prognostic relationship was attributable to the presence of dysplasia at a surgical margin. The absence of dysplasia appeared to be a significant independent prognostic indicator for patients with OSCC. The presence or absence of dysplasia may provide a heuristic means of stratifying OSCC primary lesions in terms of disease hostility.     

Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients

The purposes of this study were to examine the correlations between proliferation markers and survival rate in oral squamous cell carcinoma (OSCC) patients, and to evaluate the efficacy of proliferation markers in predicting lymph node metastasis. The patients' age, gender, T score, clinical stage, PCNA and Ki-67 index were analysed. Univariate analysis showed that T score had a significant influence on survival, and stage 4 group had a significantly lower survival rate. Lymph node metastasis was also a significant predictor of survival. Using a cut-off point of 25%, those patients with lower Ki-67 scores had survival advantage over those with higher Ki-67 scores. PCNA did not show any differences in survival with a cut-off point of 50%. Ki-67 and PCNA were significantly higher in the primary tumours associated with lymph node metastasis (pN+) than in those without lymph node metastasis (pN0). Multivariate analysis showed that clinical stage and Ki-67 were independent prognostic factors for survival in OSCC patients. From this result, it can be postulated that the cancer staging based on the TNM stage was a powerful prognostic variable and Ki-67 had a significant effect on the cumulative survival rate.     

Treatment outcomes of sinonasal adenoid cystic carcinoma: 30 cases from a single institution

ObjectiveTo establish the clinical features and prognostic factors of sinonasal adenoid cystic carcinoma (ACC).Material and methodsThirty patients with histopathological diagnosis of sinonasal ACC who were treated at Severance Hospital between 1990 and 2010 were included in this retrospective chart review study.ResultsThe 5-year disease-specific survival and disease-free survival rates were 75.3% and 37.2%, respectively. The maxillary sinus (63.3%) and nasal cavity (23.3%) were the most common sites of primary tumour. Most patients were diagnosed with advanced-stage (III/IV) disease (80.0%) and had undergone surgery and postoperative radiotherapy (70.0%). The most common histopathological subtype was cribriform type (40.9%). Local recurrence rate and distant metastasis rates were 26.7% and 23.3%, respectively. The mean time from primary treatment to recurrence was 44.5 months. Sinonasal ACC patients with stage IV and T4 disease had significantly worse survival than those with low stage and T disease. Patients with local recurrence had worse disease-specific survival than those with distant recurrence. Distant metastasis was associated with disease-free survival but not disease-specific survival.ConclusionDespite the frequent occurrence of distant metastasis, early diagnosis and effective local control seemed to be the most important factors influencing the survival of sinonasal ACC.     

头颈部肿瘤调强放疗联合手术和化疗的回顾性分析

目的:回顾性分析头颈部肿瘤调强放疗(IMRT)的长期随访结果和影响预后的因素。方法:136例初治头颈部肿瘤接受全程IMRT,48例(35.3%)联合化疗。手术联合放疗平均剂量62.14 Gy(50～73 Gy),根治性放疗平均剂量68.99 Gy(56.4～77 Gy)。结果:中位随访时间19个月,3年局控率、区域控制率、无远处转移生存率、无瘤生存率和总生存率分别为83.2%、93.2%、75.8%、66.4%、67.6%。多因素分析显示临床分期、治疗模式、放疗前有无贫血是影响患者生存率的独立预后因素。急性0、1、2、3级皮肤反应发生率分别为3.7%,71.3%,24.3%,0.7%;0、1、2、3、4级黏膜反应发生率分别为4.4%,22.8%,57.4%,14.7%,0.7%。治疗结束1年后1、2、3度口干发生率分别为21.3%、16.2%、0.7%。结论:IMRT联合手术和化疗治疗头颈部肿瘤可取得较好疗效,不良反应可以耐受。临床分期、治疗模式、放疗前有无贫血是影响生存的主要因素。     

Malignant tumours of the maxilla. Management and follow-up results of treatment of 128 patients

The authors present their own experience in the management, methods of treatment and follow-up results of 128 patients with malignant tumours of the maxilla. There were 77 males and 53 females (sex ratio 1.5: 1). Patients ages ranged from 3 to 83 years with an average of 53 years. Epithelial tumours were diagnosed in 69.5% and nonepithelial in 30.5%. In most cases the maxillary sinus was the primary focus of the tumour (40.3%). 94.4% of patients had epithelial tumours in stages III and IV (UICC classification, 1973). Radical treatment was carried out in 94 patients in 4 radiotherapy only (lymphatic tumours), in 90 patients surgery with adjuvant radio- and/or chemotherapy mainly in the postoperative stage. During the follow-up local recurrence was diagnosed in 36.5% of radically treated patients, who subsequently underwent reoperation. A five-year survival rate was obtained in 45.1% of patients with epithelial tumours and in 14.3% of patients with nonepithelial tumours. The authors carried out their own method of prosthetic rehabilitation, mainly immediate, in 82 patients operated on. Immediate prosthetic rehabilitation is a final step in the surgical procedure. This method significantly diminishes functional disturbances, mainly in speech and mastication and remarkably improves the aesthetic result.