Esophagus最新文献

Background

High-resolution manometry (HRM) tools, like esophagogastric junction contractile integral (EGJ-CI), assess EGJ barrier function.

Goals

This study aimed to evaluate the relationships between manometric EGJ metrics with esophageal acid exposure.

Study

We conducted a retrospective review of 284 patients who underwent HRM and ambulatory reflux testing between 11/2017–1/2020. EGJ-CI and total-EGJ-CI were manually calculated. Pathologic acid exposure was defined as pH < 4 with esophageal acid exposure time (EAET) exceeding 6.0%. Pearson’s correlation, univariable and multivariable regression models were utilized to assess the relationships between pathologic acid exposure and EGJ parameters. Sensitivity and specificity thresholds for EGJ-CI and total EGJ-CI were optimized with ROC analyses.

Results

On univariable analysis, patients with pathologic acid exposure had increased odds of having lower mean basal LES pressures, EGJ-CI, and total EGJ-CI than patients without pathologic acid exposure. On multivariable analysis, age, EGJ-CI and mean DCI were significant predictors of pathologic acid exposure. There were significant, though weak, correlations between EAET and EGJ-CI and total EGJ-CI (r = − 0.18, − 0.19, p < 0.01, respectively). An EGJ-CI cutoff of 44.16 as a predictor for pathologic acid exposure had a sensitivity of 46% and specificity of 42% (AUC 0.60). Total EGJ-CI cutoff of 11,461.3 for pathologic acid exposure had a sensitivity of 44% and a specificity of 43% (AUC 0.62).

Conclusion

EGJ-CI can independently predict pathologic acid exposure. However, the poor correlation between EGJ-CI and acid exposure, as well as the low sensitivity and specificity of calculated thresholds, indicate that mechanisms other than EGJ barrier function may impact acid exposure.

Background

After radical resection for esophageal cancer, death within 1 year of surgery can occur due both to recurrence and to other diseases, even after postoperative complications have been overcome. This study identified risk factors for early death within 1 year of esophagectomy for reasons other than death in hospital in patients undergoing esophagectomy for esophageal cancer or esophagogastric junction cancer.

Methods

We reviewed 366 patients who underwent esophagectomy without adjuvant treatment between January 2009 and July 2022 for thoracic esophageal cancer or esophagogastric junction cancer. Patients who died within 1 year excluding in-hospital death were compared with those who did not. Multivariable logistic regression analysis was used to identify predictors of death within 1 year after surgery.

Results

Death within 1 year occurred in 32 of 366 patients, 24 from primary disease and 8 from other diseases. Deaths within 1 year were significantly older than the other cases, had significantly lower % vital capacity (%VC), and occurred significantly more often in cases in advanced stages of disease. In a multivariable analysis, a systemic inflammation score (SIS) based on serum albumin level and lymphocyte-to-monocyte ratio was identified as an independent predictor of death within 1 year. As SIS increased, %VC decreased significantly, and CRP level and neutrophil–lymphocyte ratio increased significantly. There was no relationship between SIS and pN. Death within 1 year increased as SIS increased (p = 0.001 for trend).

Conclusion

SIS assessment undertaken before beginning esophageal cancer treatment is a useful predictor of death within 1 year of surgery.

Background

First-line pembrolizumab plus chemotherapy (pembrolizumab–chemotherapy) demonstrated improved efficacy and a manageable safety profile versus placebo plus chemotherapy (placebo–chemotherapy) in the subgroup analysis of Japanese patients with advanced/metastatic esophageal cancer in KEYNOTE-590 at a median follow-up of 24.4 months. Longer-term data from the Japanese subgroup analysis of KEYNOTE-590 are reported.

Methods

Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for ≤ 35 cycles plus chemotherapy (cisplatin 80 mg/m² and 5-fluorouracil 800 mg/m²/day). Endpoints included overall survival (OS) and progression-free survival (PFS; investigator-assessed per RECIST v1.1; dual primary) and safety (secondary). Early tumor shrinkage (ETS) and depth of response (DpR) were assessed post hoc.

Results

Overall, 141 patients were enrolled in Japan. As of July 9, 2021, median follow-up was 36.6 months (range, 29.8–45.7). Pembrolizumab–chemotherapy showed a trend toward favorable OS (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.47–1.03) and PFS (0.57; 0.39–0.83) versus placebo–chemotherapy. In the pembrolizumab–chemotherapy group, patients with ETS ≥ 20% (55/74; 74.3%) versus < 20% (19/74; 25.7%) had favorable OS (HR, 0.23; 95% CI 0.12–0.42) and PFS (0.24; 0.13–0.43). Patients with DpR ≥ 60% (31/74; 41.9%) versus < 60% (43/74; 58.1%) had favorable OS (HR, 0.37; 95% CI 0.20–0.68) and PFS (0.24; 0.13–0.43). Grade 3–5 treatment-related adverse events occurred in 55/74 patients (74.3%) with pembrolizumab–chemotherapy and 41/67 patients (61.2%) with placebo–chemotherapy.

Conclusions

With longer-term follow-up of Japanese patients with advanced/metastatic esophageal cancer, efficacy continued to favor pembrolizumab–chemotherapy compared with placebo–chemotherapy, with no new safety signals observed.

Clinical trial registration: ClinicalTrials.gov, NCT03189719.

Background

In Japan, the standard management of Barrett’s esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett’s esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett’s esophagus.

Methods

We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett’s esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences.

Results

The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett’s esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively).

Conclusions

Risk stratification of multifocal cancer using length of Barrett’s esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Background: Venous thrombosis (VT) after esophagectomy for esophageal cancer is an important complication, potentially leading to pulmonary embolism. However, there are few available information about the risk for the postsurgical VT.

Methods: This study included 271 patients who underwent esophagectomy for esophageal cancer between 2006 and 2019. Contrast-enhanced computed tomography (CT) was performed for all patients on the seventh postoperative day to survey complications, including VT.

Results: VT was radiologically visualized in 48 patients (17.7%), 8 of whom (16.7%) had pulmonary embolism. The thrombus disappeared in 42 patients, the thrombus size was unchanged in 5 patients, and 1 patient died. Multivariate analysis was performed on factors clinically considered to have a significant influence on thrombus formation. The analysis showed that CVC insertion via the femoral vein (odds ratio, 7.67; 95% CI, 2.64-22.27; P < 0.001), retrosternal reconstruction route (odds ratio, 3.94; 95% CI, 1.90-8.17; P < 0.001) and intraoperative fluid balance < 5 ml/kg/hr (odds ratio, 0.38; 95% CI, 0.17-0.85; P = 0.019) were independently related to VT.

Conclusions: Intraoperative fluid balance < 5 ml/kg/hr, along with CVC insertion via the femoral vein and retrosternal reconstruction may be potential risk factors for VT after esophagectomy.

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.

Background: Chemotherapy has the potential to induce CD8⁺ T-cell infiltration in the tumor microenvironment (TME) and activate the anti-tumor immune response in several cancers including esophageal squamous cell carcinoma (ESCC). The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been known as a critical component for regulating immune cell activation in the TME. However, its effect on the infiltration of immune cells induced by chemotherapy in the ESCC TME has not been investigated.

Methods: We examined the effect of the tumor-cell intrinsic cGAS-STING pathway on the infiltration of CD8⁺ T cells induced by chemotherapy in ESCC using ESCC cell lines and surgically resected ESCC specimens from patients who received neoadjuvant chemotherapy (NAC).

Results: We found that chemotherapeutic agents, including 5-fluorouracil (5-FU) and cisplatin (CDDP), activated the cGAS-STING pathway, consequently inducing the expression of type I interferon and T-cell-attracting chemokines in ESCC cells. Moreover, the tumor cell-intrinsic expression of cGAS-STING was significantly and positively associated with the density of CD8⁺ T cells in ESCC after NAC. However, the tumor cell-intrinsic expression of cGAS-STING did not significantly impact clinical outcomes in patients with ESCC after NAC.

Conclusion: Our findings suggest that the tumor cell-intrinsic cGAS-STING pathway might contribute to chemotherapy-induced immune cell activation in the ESCC TME.

Background: Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy.

Methods: From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed.

Results: A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs.

Conclusions: IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality.