A malignant tracheoesophageal/bronchoesophageal fistula (TEF) is a life-threatening complication of esophageal squamous cell carcinoma. A feeding gastrostomy/jejunostomy had been the most common treatment method for patients with TEF before the era of stenting. The aim of this retrospective study is to compare the prognosis of esophageal squamous cell carcinoma patients with TEF treated with an esophageal metallic stent to those treated with a feeding gastrostomy/jejunostomy. We retrospectively reviewed a total of 1011 patients with esophageal squamous cell carcinoma between 1996 and 2011 at Kaohsiung Chang Gung Memorial Hospital, and 86 patients with TEF (8.5%) were identified. The overall survival and other clinical data were compared between 30 patients treated with an esophageal metallic stent and 35 patients treated with a feeding gastrostomy/jejunostomy. Among the 65 patients receiving either an esophageal metallic stent or a feeding gastrostomy/jejunostomy, univariate analysis showed that treatment modality with an esophageal metallic stent (P = 0.007) and radiotherapy treatment after fistula diagnosis (P = 0.04) were predictive of superior overall survival. In the multivariate comparison, treatment modality with an esophageal metallic stent (P = 0.026, odds ratio: 1.859) represented the independent predictive factor of superior overall survival. There were no significant differences between groups in mean decrease in serum albumin or mean body weight loss. Compared to the feeding gastrostomy/jejunostomy group, a significantly higher proportion of patients in the stenting group (53% versus 14%, P = 0.001) were able to receive chemotherapy within 30 days after fistula diagnosis, indicating better infection control in the stenting group. Compared with a feeding gastrostomy/jejunostomy, an esophageal metallic stent significantly improves overall survival in patients with malignant TEF in our retrospective analysis. Esophageal metallic stent placement may be considered the first-line of treatment for patients with malignant TEF.

The global KEYNOTE-590 trial was the first to show a significant improvement in survival with immunotherapy plus chemotherapy in the first-line treatment of esophageal cancer (EC) and supported the approval of pembrolizumab plus chemotherapy in this setting. After a median follow-up of 22.6 months, pembrolizumab plus chemotherapy compared with placebo plus chemotherapy had a manageable safety profile and significantly improved survival of participants with previously untreated advanced EC. Results of a median follow-up of 58.8 months (range 49.2-70.6 months) are reported. Adults with previously untreated advanced EC or Siewert type 1 gastroesophageal junction cancer were randomly assigned 1 : 1 to receive chemotherapy with or without pembrolizumab. Study outcomes were efficacy and safety. Overall, 749 participants received pembrolizumab plus chemotherapy (n = 373) or placebo plus chemotherapy (n = 376). Median overall survival was 12.3 months versus 9.8 months [hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.62-0.84] with pembrolizumab plus chemotherapy versus placebo plus chemotherapy; 5-year survival rates were 10.6% and 3.0%. Median progression-free survival (PFS) was 6.3 months versus 5.8 months (HR 0.64, 95% CI 0.54-0.75); 5-year PFS rates were 5.5% and not reached. Grade ≥3 treatment-related adverse events occurred in 71.9% and 67.6% of participants in the pembrolizumab plus chemotherapy and placebo plus chemotherapy groups, respectively. Data from KEYNOTE-590 continue to show durable efficacy after 5 years, and pembrolizumab plus chemotherapy more than tripled the 5-year overall survival rate compared with placebo plus chemotherapy, with no new safety signals. These results support first-line therapy with pembrolizumab plus chemotherapy as standard for previously untreated patients with advanced EC with programmed death-ligand 1 combined positive score ≥1.

The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3–4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3–4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival.

The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma. A total of 141 esophageal squamous cell carcinoma patients receiving esophagectomy were identified, and were divided into two groups: an ACEI/ARB group (n=20), and a non-ACEI/ARB group (n=121). The effect of ACEIs or ARBs on cell proliferation and vascular endothelial growth factor (VEGF) secretion of esophageal squamous cell carcinoma cell lines, CE81T/VGH and TE2, were investigated by 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Enzyme-linked immunosorbent assay (ELISA), respectively. Use of ACEI/ARB (p=0.032), pathologic T stage (p<0.001), pathologic N stage (p=0.012), tumor stage (p=0.006), and tumor location (p=0.032) were significantly associated with superior overall survival. In multivariate comparison, use of ACEI/ARB (p=0.006), tumor stage (p=0.002), and tumor location (p=0.014) represented the independent prognosticators of superior overall survival. In cell lines, ACEIs/ARBs inhibit cell proliferation and VEGF secretion in a dose-dependent manner. ACEIs/ARBs administration is independently associated with superior overall survival in patients with esophageal squamous cell carcinoma receiving esophagectomy. Our data support further investigation of the role of RAS inhibitors as a potential therapy in esophageal squamous cell carcinoma.

Sirtuin 1 (SIRT1) regulates DNA repair and metabolism by deacetylating target proteins. SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the prognostic role of SIRT1 in patients with esophageal squamous cell carcinoma (ESCC) and evaluate the effect of SIRT1 inhibitor in vitro. The expression of SIRT1 was evaluated immunohistochemically in 155 surgically resected ESCC and the staining results were evaluated semiquantitatively by the Immunoreactive Scoring System. The clinical features and treatment outcome were analyzed. The effect of SIRT1 inhibitor, SIRT 1 inhibitor IV, (S)-35, was investigated in vitro on ESCC cell lines. The expression of SIRT1 on ESCC did not correlate with age, gender, tumor location, stage, T classification, N classification, surgical margin or histology. Univariate analysis showed that SIRT1 overexpression was associated with inferior overall survival (P = 0.004) and disease-free survival (P = 0.004). In multivariate comparison, SIRT1 overexpression remained independently associated with worse overall survival (P = 0.009, hazard ratio = 1.776) and disease-free survival (P = 0.017, hazard ratio = 1.642). In cell lines, SIRT1 inhibitor inhibited ESCC growth. Our study suggests that SIRT1 overexpression is an independent prognosticator for patients with ESCC and the SIRT1 inhibitor suppressed cell proliferation of ESCC cell lines. Our findings suggest that inhibition of SIRT1 signaling may be a promising novel target for ESCC.