Gut Microbiota Characteristics Are Associated With Severity of Acute Radiation-Induced Esophagitis.

Background: Acute radiation-induced esophagitis (ARIE) is one of the most debilitating complications in patients who receive thoracic radiotherapy, especially those with esophageal cancer (EC). There is little known about the impact of the characteristics of gut microbiota on the initiation and severity of ARIE. Materials and Methods: Gut microbiota samples of EC patients undergoing radiotherapy (n = 7) or concurrent chemoradiotherapy (n = 42) were collected at the start, middle, and end of the radiotherapy regimen. Assessment of patient-reported ARIE was also performed. Based on 16S rRNA gene sequencing, changes of the gut microbial community during the treatment regimen and correlations of the gut microbiota characteristics with the severity of ARIE were investigated. Results: There were significant associations of several properties of the gut microbiota with the severity of ARIE. The relative abundance of several genera in the phylum Proteobacteria increased significantly as mucositis severity increased. The predominant genera had characteristic changes during the treatment regimen, such as an increase of opportunistic pathogenic bacteria including Streptococcus. Patients with severe ARIE had significantly lower alpha diversity and a higher abundance of Fusobacterium before radiotherapy, but patients with mild ARIE were enriched in Klebsiella, Roseburia, Veillonella, Prevotella_9, Megasphaera, and Ruminococcus_2. A model combining these genera had the best performance in prediction of severe ARIE (area under the curve: 0.907). Conclusion: The characteristics of gut microbiota before radiotherapy were associated with subsequent ARIE severity. Microbiota-based strategies have potential use for the early prediction of subsequent ARIE and for the selection of interventions that may prevent severe ARIE.

Clinical significance of risk stratification of esophageal squamous cell carcinoma after neoadjuvant chemoradiation and surgery.

OBJECTIVE: Nowadays, there were few studies reporting the risk stratification of patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiation (NCRT) and surgery. We aimed to establish a simple risk stratification to help postoperative detection and adjuvant treatment. METHODS: We included 146 patients with locally advanced ESCC who received NCRT followed by esophagectomy. The impacts of clinicopathological factors on overall survival (OS) and disease-free survival (DFS) were analyzed. The recurrence site, time, and frequency were recorded as well. RESULTS: The median follow-up was 53 months. The pathological complete respond (pCR) group demonstrated better 5-year OS and DFS (78.6% and 77.0%) than the non-pCR group (44.8% and 35.2%, all P < 0.005). Multivariate analysis for the non-pCR group revealed perineural invasion (PNI) (HR:2.296, P = 0.013) and ypTNM stage (I/II vs III/IV) (HR:1.972, P = 0.046) were considered as independent unfavorable factors affecting OS, while PNI (HR:1.866, P = 0.045) and lymph vessel invasion (LVI) (HR:3.370, P < 0.001) were considered as independent adverse factors for DFS. Based on clinicopathological factors (including pCR, ypTNM stage, PNI, LVI), patients were divided into the low-risk (pCR), mediate-risk (non-pCR without PNI, LVI, stage III/IV), high-risk (non-pCR with one factor of PNI, LVI or stage III/IV (n = 45)), highest risk (non-pCR with two or more factors of PNI, LVI or stage III/IV) groups. The corresponding 5-year OS rates were 78.6%, 60.4%, 49.6%, 18.6%, respectively (P < 0.005) and 5-year DFS rates were 77.0%, 46.9%, 41.1%, 12.1%, respectively (P < 0.005). Adjuvant chemotherapy may improve survival in high or highest risk groups of patients with low prognostic nutritional index (< 49). CONCLUSIONS: A novel risk stratification based on clinicopathological factors may be conducive to postoperative surveillance and guide adjuvant chemotherapy.

Delayed postoperative radiotherapy might improve the long-term prognosis of locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: There is no consensus on the optimal timing of postoperative radiotherapy (PORT) for locally advanced esophageal squamous cell carcinoma (ESCC). We aimed to determine whether the timing of PORT affects the long-term prognosis of ESCC, and plotted nomograms to predict survival. METHODS: We retrospectively analyzed 351 ESCC patients who underwent radical surgery and PORT. Receiver operating characteristic curves were used to estimate the optimal cutoff point of the time interval between surgery and PORT. Cox proportional hazards regression was used to identify prognostic predictors. Overall survival (OS) and progression-free survival (PFS) were predicted using nomograms. RESULTS: The median follow-up was 53 months (range: 3-179 months). Compared to early PORT, PORT at >48 days after surgery was associated with better OS (adjusted hazard ratio [HR]: 1.406, p = 0.037) and PFS (adjusted HR: 1.475, p = 0.018). In the chemotherapy subgroup, incorporation of chemotherapy timing into the analysis suggested that 2-4 chemotherapy cycles followed by PORT was the optimal treatment schedule as compared to 0-1 chemotherapy cycle followed by PORT and concurrent chemoradiotherapy (5-year PFS: 65.9% vs. 51.0% vs. 50.1%; p = 0.049). The nomograms for OS and PFS were superior to the TNM classification (concordance indices: 0.721 vs. 0.626 and 0.716 vs. 0.610, respectively). CONCLUSIONS: Delayed PORT (>48 days) provides better survival benefit than early PORT among ESCC patients. PORT following 2-4 chemotherapy cycles might lead to the best survival rate. The nomogram plotted in this study effectively predicted survival and may help guide treatment.

Direct Detection of Vibrio vulnificus, Vibrio parahaemolyticus, and Vibrio alginolyticus from Clinical and Environmental Samples by a Multiplex Touchdown Polymerase Chain Reaction Assay.

BACKGROUND: Vibrio vulnificus, V. alginolyticus, and V. parahaemolyticus are commonly and opportunistically pathogenic to humans. METHODS: In this study, a novel multiple touchdown polymerase chain reaction method (MT-PCR) was developed to benefit rapid and simultaneous detection of the presence of the three Vibrio species from the enriched clinical and environmental samples. RESULTS: The method showed a sensitivity of 104 colony forming units (CFU)/mL for V. vulnificus, 103 CFU/mL for V. parahaemolyticus and V. alginolyticus, and a specificity of 100% for all the three Vibrio species. All strains of the three Vibrio species were detected in the spiked samples artificially contaminated with reference strains and were identified directly from the enriched clinical and environmental samples within three hours by this MT-PCR assay. All the corresponding bacteria were isolated from these enriched samples in 48 hours by standard microbiologic procedures. CONCLUSIONS: This MT-PCR method, which can detect V. vulnificus, V. parahaemolyticus, and V. alginolyticus directly and simultaneously, was rapid, sensitive, specific, and can be used in clinical diagnostics, food industry studies, and risk assessment of environment.