RESUMEN
BACKGROUND: Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal cancer. Several studies have investigated short-term outcomes after esophagectomy and the impact of periodontal disease, but few have examined the impact of periodontal disease on long-term outcomes. The purpose of this study was to investigate the rate of periodontitis among esophagectomy patients and the prognostic value of periodontitis and its effect on prognosis after esophagectomy. METHODS: A total of 508 patients who underwent esophagectomy received oral health care from a dentist before cancer treatment at Akita University Hospital between January 2009 and December 2021. We assessed the presence and severity of the patients' periodontitis and divided them into no-periodontitis, mild periodontitis, severe periodontitis and edentulous jaw groups. We then assessed 10-year overall survival (OS) and disease-specific survival (DSS) and determined whether periodontitis was an independent prognostic factor affecting OS and DSS. RESULTS: We found that 101 (19.9%) patients had no periodontitis, 207 (40.8%) had mild periodontitis, 176 (34.6%) had severe periodontitis requiring tooth extraction, and 24 (4.7%) had edentulous jaw. Both OS and DSS were significantly poorer in the periodontitis than no-periodontitis group (p < 0.001). In detail, the edentulous jaw group had the poorest prognosis (p < 0.001). Multivariate analysis showed that periodontitis was an independent risk factor affecting OS and DSS. CONCLUSION: Esophageal cancer patients had a high prevalence of periodontitis. Moreover, the presence of periodontitis and severity of periodontitis are independent risk factors contributing to a poorer prognosis after esophagectomy.
Asunto(s)
Neoplasias Esofágicas , Arcada Edéntula , Periodontitis , Humanos , Esofagectomía/efectos adversos , Estadificación de Neoplasias , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/cirugía , Pronóstico , Periodontitis/complicaciones , Periodontitis/epidemiología , Periodontitis/cirugía , Arcada Edéntula/cirugíaRESUMEN
Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC). Our previous findings suggest that high expression of toll-like receptor (TLR) 4, which recognizes lipopolysaccharide (LPS) released from periodontal pathogens, correlates with a poor prognosis after esophagectomy for ESCC. We therefore hypothesized that LPS influences cancer cell proliferation and disease progression in ESCC. We used 8 ESCC cell lines to investigate how LPS affects ESCC cell proliferation and migration activity. We also assessed mRNA and protein expression to determine how LPS affects cytokine production and whether blocking TLR4 signaling attenuates that effect. We also used a mouse xenograft model to investigate whether LPS upregulates ESCC tumor progression in vivo. We then determined whether C-C motif chemokine ligand 2 (CCL2) expression in clinical samples correlates with 5-year overall survival (OS) and disease-specific survival (DSS) in ESCC patients after esophagectomy. LPS significantly upregulated cell proliferation and migration in all ESCC lines. It also upregulated CCL2 production. In vivo, subcutaneous LPS administration significantly increased ESCC tumor volume in mice. In clinical samples, high CCL2 expression significantly correlated with 5-year OS and DSS. There was also a significant correlation between CCL2 and TLR4 expression status, suggesting the involvement of an LPS-TLR4-CCL2 cascade in clinical settings. LPS significantly upregulates cell proliferation and tumor progression through an LPS-TLR4-CCL2 cascade and influences prognosis after esophagectomy for ESCC. This suggests improving the oral environment has the potential to improve the prognosis of ESCC patients after esophagectomy.
RESUMEN
Objective: To test the hypothesis that neoadjuvant chemoradiotherapy (NACRT) is more effective against hot esophageal squamous cell carcinoma (ESCC) and that it may upregulate tumor immunogenicity. Background: There have been several recent reports showing the efficacy of immune check-point inhibitors (ICIs) against esophageal cancer, especially immunologically hot tumors. In addition, several studies have suggested that chemotherapy and radiotherapy may convert cold tumors to hot tumors. Methods: Of 105 ESCC patients who underwent surgery after NACRT between 2010 and 2018 at our hospital, 99 whose biopsy tissue samples were obtained were enrolled. Based on immunohistochemical analysis, tumors that were FOXA1 (+) and/or EYA2 (+) were defined as hot tumors, others were cold tumors. We then investigated the association between tumor immunogenicity and clinicopathological features. Results: The 29 patients with hot tumors before NACRT had a significantly better 5-year disease-specific survival (DSS) rate than the remaining 70 patients with cold tumors (85% vs 64%; P = 0.036). In a multivariate analysis, tumor immunogenicity was a significant independent predictor of DSS. Of 68 patients without a pathological complete response (non-pCR) in their primary tumor, 51 (75%) had hot tumors after NACRT. Moreover, 75% (36/48) of tumors that were cold before NACRT were converted to hot tumors after NACRT. Conclusions: Patients with hot ESCC tumors treated with NACRT plus esophagectomy had a better prognosis than those with cold tumors. NACRT upregulated cold tumor immunogenicity to hot tumors, suggesting NACRT may increase the sensitivity of ESCC to adjuvant ICIs.
RESUMEN
Most so-called "beneficial bacteria" in gut microbiota are Gram-positive, and TLR6 recognizes the peptidoglycan (PGN) present in their cell walls. We hypothesized that a high TLR6 expression status predicts a more favorable prognosis after esophagectomy. We used an ESCC tissue microarray (TMA) to examine TLR6 expression status in ESCC patients and to determine whether TLR6 expression status correlates with prognosis after curative esophagectomy. We also examined whether PGN influences the cell proliferation activity of ESCC lines. Clinical ESCC samples from 177 patients tested for the expression of TLR6 were categorized as 3+ (n = 17), 2+ (n = 48), 1+ (n = 68), or 0 (n = 44). High TLR6 expression (3+ and 2+) correlated with significantly more favorable 5-year overall survival (OS) and disease-specific survival (DSS) after esophagectomy than a lower TLR6 expression (1+ and 0). Univariate and multivariate analyses showed that TLR6 expression status is an independent prognostic factor that affects 5-year OS. PGN significantly inhibited the cell proliferation activity of ESCC lines. This is the first study to show that high TLR6 expression status predicts a more favorable prognosis in locally advanced thoracic ESCC patients after curative esophagectomy. PGN released from "beneficial bacteria" seems to have potential to inhibit the cell proliferation activity of ESCC.