The oral cavity is an important organ for nutrient intake, and nutritional status is affected by impaired oral function due to hypofunction of the temporomandibular joints, masticatory muscles, missing teeth, and impaired swallowing function [35–37]. In the present study, the examination of occlusal support zone status and nutritional biomarkers revealed significant differences in GPS and CONUT levels and PNI values. The Eichner C group without occlusal support had higher GPS levels than did Group A, and the CONUT levels revealed moderate or severe malnutrition; PNI values were low in this group. However, there was no significant difference in NLR between the three groups. Furthermore, nutritional evaluations using the protein levels of the blood revealed significant differences in the oral cavity function failure among the three groups; whereas, a significant difference was not found in nutritional evaluation using the blood cells. Therefore, the change in diet due to oral cavity function disorder reduced plasma proteins such as albumin and cholesterol, and was thought to result in undernutrition and poor immunocompetence. The results suggested that impaired oral function due to oral diseases and tooth loss reduces dietary intake and is associated with undernutrition. The correlation between the number of residual teeth and nutritional status has been reported in many studies, and the results of the present study are comparable with those of such studies. Meanwhile, the bite force varies depending on periodontal disease and stability of the remaining teeth, and it affects the food choice and nutritional status. Thus, even among patients with the same number of remaining teeth, their conditions may differ depending on the sites and arrangement of the remaining teeth.
Plasma proteins decrease due to undernutrition arising from poor caloric intake. The decrease in plasma proteins reduces immunocompetence, and the presence of inflammation worsens the situation. Although the Eichner classification is based on the assessment of the occlusal support zone status at the time of clinical examination, it may help make a diagnosis of oral frailty [37] after a certain period because the simultaneous loss of multiple teeth rarely occurs. Thus, this classification was used in the present study. A comparison among the 3 Eichner groups revealed significant differences in GPS, CONUT, and PNI among the groups, and multiple comparisons revealed a significant difference between groups A and C. It is rare to lose many teeth in a short period of time; the patients in group C might were likely undernourished before they were diagnosed with gastric cancer.
In patients with poor preoperative nutritional status, the relative risks of postoperative complications and in-hospital death are considered to be increased by 2–4 folds. Cell-mediated immunity is most affected by undernutrition. Undernourished people exhibit atrophy of the thymus, reduced peripheral T cell counts, reduced CD4/CD8 ratios (CD4 dominant), and atrophy of lymph nodes, spleen, and gut-associated lymphoid tissue (GALT), which is the immune tissue of the intestinal tract. Atrophy of GALT reduces the immunity of the intestinal mucosa and causes gastrointestinal infection. In addition, severe malnutrition reduces immunoglobulin levels. On the other hand, neither neutrophil nor peripheral B lymphocyte count decreases; but the phagocytic capacity, bactericidal capacity, and complement production are reduced [38–41].
Furthermore, systemic inflammatory responses are reported to reflect immune responses and are associated with prognosis. Systemic inflammatory responses are useful for predicting prognosis via a mechanism different from that of conventional tumor markers [41, 42]. Many tumor markers are tumor antigens and substances secreted by tumors that are measured directly and assessed. On the other hand, systemic inflammatory responses are an indirect measure of cancer progression. This is considered to be due to the following mechanism: host immunity is activated by tumor recognition, and proinflammatory cytokines are released in blood as intracellular mediators. Consequently, acute inflammatory proteins increase; thus, host immune responses are enhanced as tumors progress [43].
Biomarkers for assessing systemic inflammatory responses and the nutritional status include the Glasgow prognostic score [29, 30], neutrophil/lymphocyte ratio [31, 32], lymphocyte/monocyte ratio [44, 45], and CRP/ALB ratio [46]. These markers are calculated based on serum protein levels (e.g., CRP and ALB), cell counts (e.g., neutrophil, lymphocyte, and monocyte), and ratios of these values. Each nutrient rating system has its intrinsic characteristics. There are limitations to the use of a single index; thus, we chose appropriate nutritional indexes and evaluated them based on the disease stage and the therapeutic option employed.
The GPS was the index reported in non-small lung cell cancer by Macmillan, and the GPS combines CRP and ALB and evaluates blood protein moieties primarily. The GPS has been reported in various cancer studies to be a prognostic marker. The thing that comes to have a poor prognosis is reported in the systemic inflammatory reaction sthenia case like GPS Category 2, 3. The poor case shows systemic inflammatory such as the GPS Category 2 and 3 and undernutrition. The CRP level of patients with cancer reflects IL-6 levels in the blood, and a persistent increase in IL-6 levels suggests inflammation of the carcinoma tissue [47]. Whereas, the progression of periodontal disease and the presence of dental caries cause odontogenic infectious diseases and an increase in CRP.
However, between the three Eichner groups, a significant difference was not found in CRP levels. The effect on GPS had little impact on teeth and chronic odontogenic infectious diseases in this examination, while for effect on GPS category, ALB was thought to be more important. Systemic inflammatory responses are assessed as changes in biochemical data that result from activation of the immune system by the presence of tumors and secretion of IL-6 and other proinflammatory cytokines [47–49].
NLR is a nutrient rating system using blood cells (neutrophils and lymphocytes). Lymphocytes have been used as one of the nutritional evaluation indexes for a long time [50]. We are used for an index of the immunocompetence that the lymphocytes are related to tumor immunity and act for a tumor restrainingly. The lymphocytes are related to tumor immunity and act for a tumor restrainingly [51, 52]. Whereas neutrophils increase due to inflammation and induce the production of chemokines and cytokine, the produced chemokines and cytokines enhance the growth, invasion, and neovascularization of tumors. Therefore, tumor growth is closely associated with inflammation [53, 54]. NLR, which evaluates CRP and ALB ratios, is reported as an oncological prognostic marker similar to GPS. A significant difference was not found in this examination between the three Eichner groups. NLR is considered to mirror a balance between the innate and adaptive immune mechanisms [54]. The NLR can reflect the initial innate immune mechanisms (involving cells such as neutrophils and macrophages that provide a nonspecific response), which triggers the adaptive immune mechanisms (T-cell/B-cell mediated, and partly PLT stimulated) that result in periodontal destruction. In cases of high NLR values, periodontitis becomes more severe [52]. It is reported that NLR is useful for clinical evaluations of periodontitis. A mouth cleaning state is good in Eichiner A where many residual teeth are present in, and inflammatory reaction is poor. Additionally, there is no effect as we raise CRP because Eichner C has few residual teeth causing odontogenic infectious diseases. The difference was not found in such situation. Whereas there are many patients that a lot of residual teeth have good mouth cleaning state in Eichner A. Also, Eichner C has few residual teeth and does not reach it before we greatly change CRP even if periodontal disease is severe because there are few teeth causing inflammation. A difference was not found from such situation. PNI and CONUT are indexes that are dependent on the evaluation of lymphocyte counts, ALB, and cholesterol. It has been reported that it has a poor prognosis in low level of PNI and the extensive malnutrition category of CONUT. The lymphocytes have antitumor immunity eligibility. The lymphocytes commit a tumor restrainingly and have antitumor immunocompetence [53]. Cholesterol half-life in the blood is eight days, shorter than 21 days for ALB, and reflects malnutrition subtly [24–26, 55]. Significant differences were found between the three groups and PNI and CONUT proved to the more reflective of undernutrition in group C than in group A. Wakai et al. [55] reported that as the number of teeth decreases, people consume fewer vegetables but their total calorie intake increases with an increase in the consumption of carbohydrate such as rice, and other confectionaries. If the occlusion status is poor, carbohydrates and glucide play key dietary roles. Simultaneously, there is a reduced intake of neutral fat or proteins. As a result, these indexes are thought to worsen.
The present study has several limitations. Nutritional status is affected by many factors. In addition to oral findings such as prosthodontic treatment with dentures and conditions of the remaining teeth, other factors including socioeconomic strata, income levels, and acquired behavioral patterns are also very important [52]. It was impossible to control all of these potential variables in the present study. Furthermore, to determine whether dentures functioned well, factors that can influence outcomes such as the levels of technical skills of dentists, designs of dentures, the difficulty of cases, skills of dental technicians who fabricate dentures, perfection levels of dentures, and the actual use of dentures, should be assessed. However, there are no standardized methods to assess these factors, and only a few studies have reported the evaluation of these factors. These factors should be assessed in future studies. Because the present study is a cross-sectional study, no causal relationship could be determined. Thus, we cannot state that the number of teeth or occlusal status directly affects nutritional status.
An early transition to oral intake is essential in the treatment of gastric cancer. The reasons for this are not only that oral intake is the best enteral nutrition, but also that eating through the mouth is an important activity, which is associated with human dignity and affects QOL. In addition to the problems of undernutrition, prolonged lack of oral intake leads to a disuse hypofunction of the eating and swallowing muscles. Thus, a delayed start of oral intake due to complications, such as postoperative ruptured suture, should be avoided, and efforts should be made to precisely diagnose and improve preoperative undernutrition. Given the importance of the function of the remaining teeth for nutrient intake and the unduly significant effects of impaired masticatory function on nutritional status, dentists and dental hygienists in a nutrition support team play an important role in maintaining and improving oral function, which is important for nutrient intake. For example, the oral cavity should be kept clean, and the periodontal condition should be maintained. In addition, patients with occlusal disharmony may be undernourished, as an underlying condition, even if they are satisfied with denture use. Thus, occlusal disharmony is suggested to be a possible factor for the consideration of preoperative nutritional supplementation. Based on this study, there are two conclusions that can be drawn regarding malnutrition and inflammation in patients with gastric cancer patients with oral health conditions: 1) There are direct effects of occlusal abnormalities on dietary intake, and 2) There is indirect action of systemic inflammatory conditions such as odontogenic infectious diseases on acute protein synthesis.
Further studies on oral health and its role in malnutrition and inflammation are warranted. A long-term prospective study and intervention study are necessary to completely evaluate the association among systemic inflammation in oral health, malnutrition, and gastric cancer.