Background
Head and neck cancer (HNC) was the seventh most common cancer and the seventh leading cause of cancer deaths worldwide in 2020.1 In 2020, the global annual incidence of HNC was approximately 932,000, and >467,000 new deaths were reported.1 In Taiwan, HNC was the third most common cancer and the fifth leading cause of cancer deaths among men in 2020.2 Among patients reported to have HNC, most (>80%) have had the oral cavity squamous cell carcinoma (OCSCC) subtype.3–11 Although nationwide population-based oral cancer screening programs have been implemented and therapeutic advances have been made,9–11 room for improvement in the survival rate of patients with OCSCC in Taiwan remains considerable.2 Notably, the risk of postoperative pneumonia (POP), which is high in patients with OCSCC who receive curative surgery, contributed to the high mortality and morbidity of these patients.12–14 Consequently, identifying a modifiable risk factor for POP is crucial for improving OCSCC survival.
Pneumonia is a major noncancer cause of death; thus, understanding the risk factors for pneumonia is essential.15–18 Pulmonary complications are a major cause of morbidity and mortality during postoperative periods.16 The reported incidence of postoperative pulmonary complications ranges from 5% to 80%, depending on the patient population and the criteria used to define a complication.18 The incidence of postoperative complications also varies across hospitals; one study reported lower rates of postoperative complications after esophagectomy, pancreatectomy, and intact abdominal aortic aneurysm repair in hospitals with a higher patient volume than in those with a lower patient volume.17 However, no study has examined the prevalence of POP among patients with OCSCC who received curative surgery or has identified correctable preexisting risk factors for POP in patients with OCSCC who received curative surgery.
Sarcopenia is a condition that is characterized by loss of muscle mass, strength, and performance.19–22 In contrast to cancer cachexia, sarcopenia is not necessarily associated with cancer-related malnutrition.23 The pathogenesis of sarcopenia is multifactorial and involves muscle disuse, endocrine function alteration, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies.21 Preexisting sarcopenia is a key prognostic factor for overall survival, locoregional recurrence, and distant metastasis for patients with OCSCC who received curative surgery.24 Although studies have explored the association between sarcopenia and pneumonia, they have not distinguished between preexisting and cancer-related sarcopenia.15,25 Several studies have reported that sarcopenia (including unclear preexisting, cancer-related, and cancer treatment–related sarcopenia) is associated with increased POP risk in patients with various cancers.26–29 However, whether preexisting sarcopenia (a correctable condition) is an independent risk factor for POP in patients with OCSCC remains unclear. Therefore, we conducted head-to-head propensity score matching (PSM) to estimate the statistical correlation between preexisting sarcopenia and the POP risk in patients with OCSCC who underwent curative surgery.
Patients and Methods
Study Population
Patients with OCSCC who underwent curative surgery—tumor resection and neck dissection—between January 1, 2007, and December 31, 2017, were enrolled in the present study; their data were obtained from the Taiwan Cancer Registry Database (TCRD). The follow-up period was from the index date (ie, date of surgery) to December 31, 2018. The types of neck dissection and their indications were supraomohyoid neck dissection for clinical N0 tumors30; modified neck dissection for ipsilateral, clinically positive nodes31; and bilateral neck dissection for contralateral metastases or tumors that crossed the midline.32 Adjuvant treatments for patients with OCSCC were administered based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers and the patients’ tolerance.33 The TCRD contains detailed cancer-related patient data, including the clinical stage of cancer, cigarette smoking habits, treatment modalities, pathologic data, and grade of differentiation.6,9–11,34 The study protocols were reviewed and approved by the Institutional Review Board of Tzu-Chi Medical Foundation (IRB109-015-B).
Inclusion and Exclusion Criteria
Diagnoses of enrolled patients were confirmed after reviewing their pathologic data, and the patients who were newly diagnosed with OCSCC and confirmed to have no other cancers or distant metastasis were included in the present study. All patients with OCSCC underwent curative-intent surgery. Patients were included in the present study if they were aged ≥20 years, had a diagnosis of pathologic stage I–IVB OCSCC without metastasis (determined in accordance with the 7th edition of the AJCC Cancer Staging Manual), and underwent tumor resection and neck dissection. Patients were excluded if they had a history of other cancers before the index date, had an unknown pathologic stage, were missing data regarding their sex, had an unclear differentiation of tumor grade, or had a nonsquamous cell carcinoma pathologic type.
In the present study, sarcopenia was defined in accordance with the definition used in other studies that have used Taiwan’s National Health Insurance Research Database (NHIRD).24,35 To reduce the selection bias resulting from the definition of sarcopenia, we only included the patients with sarcopenia who were diagnosed by rehabilitation specialists, orthopedic physicians, or family physicians. In Taiwan, the diagnostic coding of sarcopenia is based on a Taiwan-based study36; specifically, individuals are regarded as having sarcopenia if their skeletal muscle mass index is 2 or more standard deviations less than the mean of a normal sex-specific young person.
Patients given a diagnosis of sarcopenia after an OCSCC diagnosis and those given a diagnosis of sarcopenia within 1 year of their OCSCC diagnosis (excluding cancer treatment–related and cancer cachexia–related sarcopenia) were excluded. The diagnosis of POP was defined in accordance with the coding used by Taiwan’s NHIRD, which involves imaging, treatments, and evidence of pneumonia after curative surgery for patients with OCSCC. We categorized the enrolled patients into 2 groups depending on whether they had preexisting sarcopenia before their OCSCC diagnosis (group 1 [nonsarcopenic OCSCC] and group 2 [preexisting sarcopenic OCSCC]). In addition, we estimated the postoperative incidence risk of POP that is associated with sarcopenia.
PSM and Covariates
To reduce the effects of potential confounders during the comparison of the risk of POP in the patients with and without preexisting sarcopenia, we performed 2:1 PSM with a caliper of 0.2 for the following variables: age, sex, years of diagnosis, OCSCC site, AJCC pathologic stage, pathologic tumor stage (pT), pathologic nodal stage (pN), differentiation grade, surgical margin, lymphovascular invasion, adjuvant treatments, Charlson comorbidity index (CCI) scores, prior comorbidities, a current smoking habit, excessive alcohol use, and use of preoperative sedation for sleep. These variables were potential risk factors for POP in patients with OCSCC who underwent curative surgery. A Cox proportional hazards model was used to regress the POP risk in the patients with OCSCC, and a robust sandwich estimator was used to account for clustering within the matched sets.37 Multivariate Cox regression analyses were performed to calculate hazard ratios (HRs) to determine whether preexisting sarcopenia was an independent predictor of POP, and the aforementioned variables were revealed to be potential independent prognostic factors for POP with residual imbalance.38,39 The potential confounding factors for POP in the patients with OCSCC were controlled for in the PSM (supplemental eTable 1, available with this article at JNCCN.org), and POP was the primary endpoint for both groups. After the completion of PSM, real-world data could be analyzed to determine the POP outcomes associated with preexisting sarcopenia in patients with OCSCC who underwent curative surgery.
Incidence Risk of POP During Various Time Periods
Multivariate logistic regression model analyses were performed to calculate odds ratios to determine whether preexisting sarcopenia was an independent predictor of POP during the following postoperative time periods: first to 30th day, 31st to 90th day, 91st day to first year, first to second year, second to third year, third to fourth year, and fourth to fifth year.
Statistical Analysis
Adjustments were made for confounders, and all statistical analyses were performed using SAS 9.4 (SAS Institute Inc.). For the 2-tailed Wald test, a P value of <.05 was regarded as significant. The POP risk was estimated using the Kaplan-Meier method, and between-group differences were compared by performing a stratified log-rank test (stratified according to matched sets).40
Results
Study Cohorts Before and After PSM
The PSM yielded 16,257 patients (10,822 without sarcopenia and 5,435 with sarcopenia) who were eligible for inclusion in further analyses; their characteristics are summarized in supplemental eTable 1. Age, sex, years of diagnosis, OCSCC site, AJCC pathologic stage, pT, pN, differentiation grade, surgical margin, lymphovascular invasion, adjuvant treatments, CCI scores, prior comorbidities, a current smoking habit, alcohol use, and use of preoperative sedation for sleep were balanced among the cohorts (all P>.05). After PSM was completed, the crude incidence of POP was significantly higher in the patients with versus without sarcopenia (supplemental eTable 1).
Cox Proportional Hazard Models for POP
A multivariate Cox regression analysis revealed that preexisting sarcopenia was a significant independent predictor of POP (Table 1). The results of both univariate and multivariate Cox regression analyses indicated that the POP risk was greater in the patients with preexisting sarcopenia than in those without. The HR for the univariate model was similar to that for the multivariate Cox regression model. Male sex, age ≥50 years, ≥pT3 cancer, ≥pN2 cancer, a positive surgical margin, adjuvant treatments, a CCI score of ≥1, chronic obstructive pulmonary disease (COPD), asthma, preoperative dysphagia, a current smoking habit, excessive alcohol consumption, and use of preoperative sedation for sleep were significant risk factors for POP in the patients with OCSCC who received curative surgery.
Cox Proportional Regression Analysis of POP Risk in Propensity Score–Matched Patients
Incidence Risk of POP During Various Time Periods
Table 2 compares the propensity score–matched sarcopenic and nonsarcopenic OCSCC groups in terms of their incidence risk of POP during various time periods. For both groups, the incidence risk of POP peaked between the 91st day and the first year after their surgery; specifically, it was 17.76% in patients in the sarcopenic OCSCC group and 15.91% in patients in the nonsarcopenic OCSCC group. For the patients with OCSCC and preexisting sarcopenia, the highest adjusted odds ratio of the incidence risk of POP was observed within the 30 days after curative surgery (1.526; 95% CI, 1.24–1.67; P<.0001) relative to patients in the nonsarcopenic OCSCC group. The statistical difference in POP risk between patients with sarcopenic and nonsarcopenic OCSCC who underwent curative surgery persisted over the following postoperative time periods: the 31st to 90th day, 91st day to first year, first to second year, second to third year, third to fourth year, and fourth to fifth year.
Incidence Risk of POP
Kaplan-Meier Cumulative Curves for POP
Figure 1 presents the Kaplan-Meier cumulative curves for the incidence risk of POP in patients in the propensity score–matched sarcopenic and nonsarcopenic OCSCC groups who underwent curative surgery. The POP risk curve for those in the sarcopenic OCSCC group was higher than that for those in the nonsarcopenic OCSCC group (Figure 1; P<.001).
Kaplan-Meier curves of cumulative incidence risk of POP in patients with sarcopenic or nonsarcopenic OCSCC who underwent curative surgery.
Abbreviations: OCSCC, oral cavity squamous cell carcinoma; POP, postoperative pneumonia.
Citation: Journal of the National Comprehensive Cancer Network 20, 12; 10.6004/jnccn.2022.7063
Kaplan-Meier curves of cumulative incidence risk of POP in patients with sarcopenic or nonsarcopenic OCSCC who underwent curative surgery.
Abbreviations: OCSCC, oral cavity squamous cell carcinoma; POP, postoperative pneumonia.
Citation: Journal of the National Comprehensive Cancer Network 20, 12; 10.6004/jnccn.2022.7063
Kaplan-Meier curves of cumulative incidence risk of POP in patients with sarcopenic or nonsarcopenic OCSCC who underwent curative surgery.
Abbreviations: OCSCC, oral cavity squamous cell carcinoma; POP, postoperative pneumonia.
Citation: Journal of the National Comprehensive Cancer Network 20, 12; 10.6004/jnccn.2022.7063
Discussion
Several studies have reported that patients with sarcopenia who underwent surgery were at a higher risk of POP compared with those without sarcopenia.27,41 Nevertheless, no study has focused on the risk of POP among patients with sarcopenic and nonsarcopenic OCSCC who underwent tumor resection and neck dissection. Our comparative study is the first to evaluate the risk of short-term and long-term POP among patients with sarcopenic and nonsarcopenic OCSCC who underwent curative surgery (Table 2). Our study examined homogeneous covariates through a PSM design, a large sample size, and a long-term follow-up period, and revealed that the risk of POP was higher not only within 30 days, 90 days, and 1 to 2 years after surgery but also at 5 years after surgery (Table 2 and Figure 1). These findings indicate that the risk of POP for patients with OCSCC who underwent curative surgery was both a short-term and long-term complication, especially in the sarcopenic OCSCC group. Studies have suggested that the acute and chronic complications of POP are associated with higher mortality,42,43 especially among patients with sarcopenic OCSCC who are compatible to those analyzed in our previous study.24 Because POP can become a long-term complication, the incorporation of swallowing training into preoperative and postoperative rehabilitation is crucial for patients with OCSCC who have received curative surgery, especially those with sarcopenia.44–46 Our results can serve as a valuable reference for the government to establish health policies involving the early correction of preexisting sarcopenia and the implementation of early rehabilitative intervention for preventing acute and chronic POP in patients with OCSCC; these measures can help increase the survival of such patients.
Table 1 reveals that the risk factors for POP in patients with OCSCC were male sex, age ≥50 years, ≥pT3 cancer, ≥pN2 cancer, a positive surgical margin, adjuvant treatments, a CCI score of ≥1, COPD, asthma, preoperative dysphagia, a current smoking habit, excessive alcohol consumption, and the use of preoperative sedation for sleep. Studies have also identified advanced age, male sex, smoking, tumor site, tumor stage, tumor recurrence, treatment modalities, preoperative serum albumin levels, duration of surgery, and postoperative hospital stay as independent risk factors for POP15,47,48; although most of these risk factors are consistent with those identified in the present study, they are mostly nonmodifiable risk factors.15,47,48 In contrast, preexisting sarcopenia is a modifiable risk factor that is related not only to a high POP risk but also to poor oncologic outcomes in patients with OCSCC who underwent curative surgery.24 In addition, our findings reveal various novel predictors of POP in patients with OCSCC who underwent curative surgery: sarcopenia, COPD, asthma, preoperative dysphagia, excessive alcohol consumption, and use of preoperative sedation for sleep (Table 1). Physicians should pay attention to patients with OCSCC with the aforementioned risk factors and aim to prevent POP by implementing deep breathing and coughing interventions involving the application of an incentive spirometer and early ambulation.49
The higher POP risk in patients with sarcopenic OCSCC compared with those with nonsarcopenic OCSCC could be the result of various factors. Studies have proposed that a loss of function in swallowing-related and respiratory muscles due to sarcopenia may increase POP risk in patients with esophageal or gastric cancer.27,41 Sarcopenic dysphagia due to the decreased strength of swallowing-related muscles is a possible reason.27,41 Among patients with OCSCC who underwent curative surgery, the risk of POP is higher in those with versus without sarcopenia; the swallowing function of patients with sarcopenic OCSCC may be affected by tumor involvement, anatomic alteration from surgical intervention, scarring or fibrosis resulting from surgery, definitive irradiation, or adjuvant irradiation.15,25,44,45 Poor effectiveness of coughing due to a decrease in respiratory muscle strength is another possible mechanism; ineffective clearance of the airways significantly increases the risk of POP.50 POP can result in prolonged hospital stays, higher costs, and increased morbidity and mortality in surgical patients, including those with OCSCC.42,43 The implementation of early intervention to correct preexisting sarcopenia is a key method for improving the outcomes of patients with OCSCC who are undergoing curative surgery.
A previous study suggested that preexisting sarcopenia is a significant poor prognostic factor for overall survival, locoregional recurrence, and distant metastasis for patients with OCSCC who underwent curative surgery.24 For susceptible patients who are at risk for OCSCC, sarcopenia prevention measures (eg, exercise and early nutrition intervention) should be encouraged. However, why preexisting sarcopenia contributes to poor oncologic outcomes in patients with OCSCC who underwent curative surgery is still unclear. The potential reason is found in the differences between patients with sarcopenic and nonsarcopenic OCSCC who have experienced curative surgery–related complications.
Pneumonia is a major noncancer cause of death in patients with HNC; thus, understanding the related risk factors is essential.15–18 The most common postoperative complications in patients with sarcopenia are postoperative pulmonary complications.41,51 However, no study involving a large sample size and a long-term follow-up period has been conducted to estimate the risk of pulmonary complications in patients with sarcopenic and nonsarcopenic OCSCC who underwent curative surgery. Our study is the first to provide evidence that acute and chronic POP risk are higher in patients with sarcopenic OCSCC than in those with nonsarcopenic OCSCC.
Studies have reported that sarcopenia is related to POP in surgical patients, including those with esophageal and gastric cancers.27–29 However, these studies did not differentiate between preexisting sarcopenia from cancer-related cachexia-induced sarcopenia and that from cancer treatment–related sarcopenia.27–29 Therefore, their results did not establish causality between sarcopenia and POP.27–29 The present study is the first head-to-head PSM, large-scale, and long-term follow-up study that evaluates the correlation between acute and chronic POP and preoperative sarcopenia. Our results indicate that preexisting sarcopenia is an independent risk factor for both acute and chronic POP. In the present study, the statistical difference in POP risk between patients with sarcopenic and nonsarcopenic OCSCC who underwent curative surgery was observed in the following postoperative time periods: the 31st to 90th day, 91st day to first year, first to second year, second to third year, third to fourth year, and fourth to fifth year (Table 2). The risk of POP can be attributed to anatomic alterations resulting from surgical intervention, surgery-related scarring or fibrosis, definitive irradiation, and adjuvant irradiation15,25,44,45; these are complications that can have both short-term and long-term effects on patients with OCSCC who underwent curative surgery, especially those with sarcopenic OCSCC. Because POP is a major cause of morbidity and mortality during short-term and long-term postoperative periods, the problems associated with POP must be resolved to improve the survival of patients with OCSCC who underwent surgery.
Our finding that preexisting sarcopenia is an independent risk factor for POP supports the implementation of early screening, prevention, and intervention for sarcopenia in populations with a high risk of developing oral cancer (eg, populations with betel nut chewing, alcohol use, or smoking habits)3; these measures should be implemented because the incidence of oral cancer is 123-fold higher in patients who smoke, consume alcohol, and chew betel quid than in abstainers.3 For the susceptible population with an OCSCC risk,3 the implementation of resistance exercise, high-protein diets, and vitamin D supplementation to correct sarcopenia can reduce the POP risk in individuals who develop oral cancer and undergo curative surgery.52–55 In addition, we suggest that patients with sarcopenic OCSCC who underwent curative surgery will benefit from preventive POP measures, including deep breathing and coughing exercise interventions involving the application of an incentive spirometer and early ambulation.49 Rehabilitative swallowing training is also crucial for patients with OCSCC who underwent surgery, especially those with sarcopenic OCSCC.
Our study has several limitations. First, the cohort was derived from an Asian population in Taiwan. Although no other study has highlighted the influence of race or ethnicity on the POP risk in patients with OCSCC who underwent curative surgery, the results of the present study should be applied to non-Asian populations with caution. Second, PSM cannot balance unmeasured characteristics and confounders; thus, the remaining unmeasured confounding variables could have led to biased results. Third, there may be selection bias in the use of the CCI as a variable with which the authors matched their patients and control patients, because the variables that make up the CCI are not necessarily homogeneous. Fourth, the diagnosis of comorbidities was based on the ICD-9-CM or ICD-10-CM codes of the Taiwan NHIRD. Taiwan’s National Health Insurance Administration reviews the charts and interviews of beneficiaries in the TCRD to verify the accuracy of diagnoses, and audits hospitals with outlier changes or practices and heavily penalizes them if it identifies any malpractice or discrepancies. Nevertheless, large-scale randomized controlled trials that compare patients with sarcopenic OCSCC against those with nonsarcopenic OCSCC are warranted to obtain precise population specificity, collect disease occurrence data, and minimize unmeasured confounding variables. However, such randomized controlled trials may be difficult to conduct.
Despite the limitations of the present study, its major strength is its use of a nationwide population-based registry with detailed baseline information. The TCRD is linked with Taiwan’s National Cause of Death Database; this linkage enabled us to perform a lifelong follow-up for most of the patients examined. Moreover, this study is the first and largest comparative cohort study in which a long-term follow-up period was used to estimate the POP risk in OCSCC populations with and without preexisting sarcopenia who underwent curative surgery. The covariates between the 2 groups were homogeneous, and any measured confounders between the 2 groups were balanced by PSM. Given the magnitude and statistical significance of the observed effects in the present study, its limitations are unlikely to have a substantial effect on our conclusions.
Conclusions
The high incidence of pneumonia persists for a long time in patients with OCSCC who underwent curative surgery, and this high incidence may even persist 5 years after surgery, especially in patients with sarcopenic OCSCC. Therefore, susceptible populations with a high risk of OCSCC should be screened for sarcopenia to facilitate the early correction of sarcopenia and improve their survival.
References
- 1.↑
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–249.
- 2.↑
Health Promotion Administration, Ministry of Health and Welfare. 2020 Health Promotion Administration annual report. Accessed December 28, 2020. Available at: https://www.hpa.gov.tw/EngPages/Detail.aspx? nodeid=1070&pid=13282
- 3.↑
Ko YC, Huang YL, Lee CH, et al. Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 1995;24:450–453.
- 4.↑
Chang JH, Wu CC, Yuan KS, et al. Locoregionally recurrent head and neck squamous cell carcinoma: incidence, survival, prognostic factors, and treatment outcomes. Oncotarget 2017;8:55600–55612.
- 5.↑
Chen JH, Yen YC, Chen TM, et al. Survival prognostic factors for metachronous second primary head and neck squamous cell carcinoma. Cancer Med 2017;6:142–153.
- 6.↑
Chang CL, Yuan KS, Wu SY. High-dose or low-dose cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer. Head Neck 2017;39:1364–1370.
- 7.↑
Chen JH, Yen YC, Yang HC, et al. Curative-intent aggressive treatment improves survival in elderly patients with locally advanced head and neck squamous cell carcinoma and high comorbidity index. Medicine (Baltimore) 2016;95:e3268.
- 8.↑
Wu SY, Wu AT, Liu SH. MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing. Oncotarget 2016;7:51482–51493.
- 9.↑
Liu WC, Liu HE, Kao YW, et al. Definitive intensity-modulated radiotherapy or surgery for early oral cavity squamous cell carcinoma. Head Neck 2021;43:1142–1152.
- 10.↑
Lin KC, Chen TM, Yuan KS, et al. Assessment of predictive scoring system for 90-day mortality among patients with locally advanced head and neck squamous cell carcinoma who have completed concurrent chemoradiotherapy. JAMA Netw Open 2020;3:e1920671.
- 11.↑
Liu WC, Liu HE, Kao YW, et al. Definitive radiotherapy or surgery for early oral squamous cell carcinoma in old and very old patients. Radiother Oncol 2020;151:214–221.
- 12.↑
Damian D, Esquenazi J, Duvvuri U, et al. Incidence, outcome, and risk factors for postoperative pulmonary complications in head and neck cancer surgery patients with free flap reconstructions. J Clin Anesth 2016;28:12–18.
- 13.↑
Ligh CA, Nelson JA, Wink JD, et al. An analysis of early oncologic head and neck free flap reoperations from the 2005-2012 ACS-NSQIP dataset. J Plast Surg Hand Surg 2016;50:85–92.
- 14.↑
Landis SH, El-Hariry IA, van Herk-Sukel MP, et al. Prevalence and incidence of acute and chronic comorbidity in patients with squamous cell carcinoma of the head and neck. Head Neck 2012;34:238–244.
- 15.↑
Ko CA, Fang TJ, Chi CC, et al. Pneumonia in patients with head and neck cancer. J Int J Head Neck Sci 2020;4:146–155.
- 16.↑
Lawrence VA, Cornell JE, Smetana GW. Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery. Ann Intern Med 2006;144:596–608.
- 17.↑
Dimick JB, Pronovost PJ, Cowan JA Jr, et al. Variation in postoperative complication rates after high-risk surgery in the United States. Surgery 2003;134:534–540; discussion 540–541.
- 18.↑
Fisher BW, Majumdar SR, McAlister FA. Predicting pulmonary complications after nonthoracic surgery: a systematic review of blinded studies. Am J Med 2002;112:219–225.
- 20.↑
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412–423.
- 22.↑
Lindle RS, Metter EJ, Lynch NA, et al. Age and gender comparisons of muscle strength in 654 women and men aged 20–93 yr. J Appl Physiol 1997;83:1581–1587.
- 23.↑
Muscaritoli M, Anker SD, Argilés J, et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by special interest groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics.” Clin Nutr 2010;29:154–159.
- 24.↑
Tsai YH, Chen WM, Chen MC, et al. Effect of pre-existing sarcopenia on oncological outcomes for oral cavity squamous cell carcinoma undergoing curative surgery. Cancers (Basel) 2022;14:3246.
- 25.↑
Okazaki T, Ebihara S, Mori T, et al. Association between sarcopenia and pneumonia in older people. Geriatr Gerontol Int 2020;20:7–13.
- 26.↑
Reddy PD, Yan F, Nguyen SA, et al. Factors influencing the development of pneumonia in patients with head and neck cancer: a meta-analysis. Otolaryngol Head Neck Surg 2021;164:234–243.
- 27.↑
Kamiya A, Hayashi T, Sakon R, et al. Long-term postoperative pneumonia in elderly patients with early gastric cancer. BMC Surg 2022;22:220.
- 28.↑
Kurita D, Oguma J, Ishiyama K, et al. Handgrip strength predicts postoperative pneumonia after thoracoscopic-laparoscopic esophagectomy for patients with esophageal cancer. Ann Surg Oncol 2020;27:3173–3181.
- 29.↑
Fukuda Y, Yamamoto K, Hirao M, et al. Sarcopenia is associated with severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy. Gastric Cancer 2016;19:986–993.
- 30.↑
Dias FL, Lima RA, Kligerman J, et al. Relevance of skip metastases for squamous cell carcinoma of the oral tongue and the floor of the mouth. Otolaryngol Head Neck Surg 2006;134:460–465.
- 31.↑
Byers RM, Weber RS, Andrews T, et al. Frequency and therapeutic implications of “skip metastases” in the neck from squamous carcinoma of the oral tongue. Head Neck 1997;19:14–19.
- 32.↑
Capote-Moreno A, Naval L, Muñoz-Guerra MF, et al. Prognostic factors influencing contralateral neck lymph node metastases in oral and oropharyngeal carcinoma. J Oral Maxillofac Surg 2010;68:268–275.
- 33.↑
Pfister DG, Spencer S, Adkins D, et al. NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancer. Version 2.2022. Accessed April 26, 2022. To view the most recent version, visit https://www.nccn.org
- 34.↑
Qin L, Chen TM, Kao YW, et al. Predicting 90-day mortality in locoregionally advanced head and neck squamous cell carcinoma after curative surgery. Cancers 2018;10:392.
- 35.↑
Sun MY, Chang CL, Lu CY, et al. Sarcopenia as an independent risk factor for specific cancers: a propensity score-matched Asian population-based cohort study. Nutrients 2022;14:1910.
- 36.↑
Chien MY, Huang TY, Wu YT. Prevalence of sarcopenia estimated using a bioelectrical impedance analysis prediction equation in community-dwelling elderly people in Taiwan. J Am Geriatr Soc 2008;56:1710–1715.
- 37.↑
Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med 2013;32:2837–2849.
- 38.↑
Nguyen TL, Collins GS, Spence J, et al. Double-adjustment in propensity score matching analysis: choosing a threshold for considering residual imbalance. BMC Med Res Methodol 2017;17:78.
- 39.↑
Zhang Z, Kim HJ, Lonjon G, et al. Balance diagnostics after propensity score matching. Ann Transl Med 2019;7:16.
- 40.↑
Austin PC. The use of propensity score methods with survival or time-to-event outcomes. Stat Med 2014;33:1242–1258.
- 41.↑
Xu J, Zheng B, Zhang S, et al. Effects of preoperative sarcopenia on postoperative complications of minimally invasive oesophagectomy for oesophageal squamous cell carcinoma. J Thorac Dis 2019;11:2535–2545.
- 42.↑
Sabaté S, Mazo V, Canet J. Predicting postoperative pulmonary complications. Curr Opin Anaesthesiol 2014;27:201–209.
- 43.↑
Sekiya H, Kurasawa Y, Maruoka Y, et al. Cost-effectiveness analysis of perioperative oral management after cancer surgery and an examination of the reduction in medical costs thereafter: a multicenter study. Int J Environ Res Public Health 2021;18:7453.
- 44.↑
Nguyen NP, Moltz CC, Frank C, et al. Impact of swallowing therapy on aspiration rate following treatment for locally advanced head and neck cancer. Oral Oncol 2007;43:352–357.
- 45.↑
Eisbruch A, Lyden T, Bradford CR, et al. Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2002;53:23–28.
- 46.↑
Miki Y, Makuuchi R, Honda S, et al. Prospective phase II study evaluating the efficacy of swallow ability screening tests and pneumonia prevention using a team approach for elderly patients with gastric cancer. Gastric Cancer 2018;21:353–359.
- 47.↑
Sood R, Paul J, Rajan S, et al. Predictors of postoperative pneumonia in patients undergoing oral cancer resections and its management. J Head Neck Phys Surg 2018;6:69–72.
- 48.↑
Xu J, Hu J, Yu P, et al. Perioperative risk factors for postoperative pneumonia after major oral cancer surgery. PLoS One 2017;12:e0188167.
- 49.↑
Cassidy MR, Rosenkranz P, McCabe K, et al. I COUGH: reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148:740–745.
- 50.↑
Laveneziana P, Albuquerque A, Aliverti A, et al. ERS statement on respiratory muscle testing at rest and during exercise. Eur Respir J 2019;53:1801214.
- 51.↑
Zhang C, Yu D, Hong L, et al. Prevalence of sarcopenia and its effect on postoperative complications in patients with Crohn’s disease. Gastroenterol Res Pract 2021;2021:3267201.
- 52.↑
Yamada M, Kimura Y, Ishiyama D, et al. Synergistic effect of bodyweight resistance exercise and protein supplementation on skeletal muscle in sarcopenic or dynapenic older adults. Geriatr Gerontol Int 2019;19:429–437.
- 53.↑
Morley JE, Argiles JM, Evans WJ, et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc 2010;11:391–396.
- 54.↑
Gkekas NK, Anagnostis P, Paraschou V, et al. The effect of vitamin D plus protein supplementation on sarcopenia. Maturitas 2021;145:56–63.
