Body Composition and Clinical Outcomes in Esophageal Cancer Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Obesity is associated with increased mortality in various cancers, but the relationship between obesity and clinical outcomes in unresectable or recurrent esophageal cancer who receive immune checkpoint inhibitors (ICIs) remains unknown. This study investigated the association between body composition and clinical outcomes in patients with unresectable or recurrent esophageal cancer who received ICIs. METHODS: Utilizing an unbiased database of 111 unresectable or recurrent esophageal cancers, we evaluated the relationships between body composition (body mass index, waist circumference, psoas major muscle volume, and subcutaneous and visceral fat areas) at the initiation of ICI treatment and clinical outcomes including the disease control rate and progression-free survival (PFS). RESULTS: Waist circumference was significantly associated with the disease control rate at the first assessment (P = 0.0008). A high waist circumference was significantly associated with favorable PFS in patients treated with nivolumab. In an univariable model, for 5-cm increase of waist circumference in the outcome category of PFS, univariable hazard ratio (HR) was 0.73 (95% confidence interval [CI], 0.61-0.87; P = 0.0002). A multivariable model controlling for potential confounders yielded a similar finding (multivariable HR, 0.56; 95% CI, 0.33-0.94; P = 0.027). We observed the similar finding in esophageal cancer patients treated with pembrolizumab+CDDP+5-FU (P = 0.048). In addition, waist circumference was significantly associated with the prognostic nutritional index (P = 0.0073). CONCLUSIONS: A high waist circumference was associated with favorable clinical outcomes in ICI-treated patients with unresectable or recurrent esophageal cancer, providing a platform for further investigations on the relationships among body composition, nutrition, and the immune status.

Intratumour Fusobacterium nucleatum and immune response to oesophageal cancer.

BACKGROUND: Experimental evidence suggests a role of intratumour Fusobacterium nucleatum in the aggressive behaviour of gastrointestinal cancer through downregulating anti-tumour immunity. We investigated the relationship between intratumour F. nucleatum and immune response to oesophageal cancer. METHODS: Utilising an unbiased database of 300 resected oesophageal cancers, we measured F. nucleatum DNA in tumour tissue using a quantitative polymerase chain reaction assay, and evaluated the relationship between the abundance of F. nucleatum and the densities of T cells (CD8 + , FOXP3 + and PDCD1 + ), as well as lymphocytic reaction patterns (follicle lymphocytic reaction, peritumoural lymphocytic reaction, stromal lymphocytic reaction and tumour-infiltrating lymphocytes) in oesophageal carcinoma tissue. RESULTS: F. nucleatum was significantly and inversely associated only with the peritumoural lymphocytic reaction (P = 0.0002). Compared with the F. nucleatum-absent group, the F. nucleatum-high group showed a much lower level of the peritumoural lymphocytic reaction (univariable odds ratio, 0.33; 95% confidence interval, 0.16-0.65; P = 0.0004). A multivariable model yielded a similar finding (multivariable odds ratio, 0.34; 95% confidence interval 0.16-0.69; P = 0.002). CONCLUSIONS: Intratumour F. nucleatum is associated with a diminished peritumoural lymphocytic reaction, providing a platform for further investigations on the potential interactive roles between intratumour F. nucleatum and host immunity.

Conversion Surgery After Atezolizumab Plus Bevacizumab for Primary and Peritoneal Metastasis After Hepatocellular Carcinoma Rupture.

BACKGROUND/AIM: Conversion surgery (CS) following atezolizumab plus bevacizumab (Atez+Bev) is a treatment strategy for unresectable hepatocellular carcinoma (UR-HCC). Herein, we report a case of CS after transcatheter arterial embolization (TAE) and Atez+Bev for primary HCC with peritoneal metastases and multiple liver metastasis after HCC rupture. CASE REPORT: A 75-year-old man with a suspected ruptured HCC in segment 4b was referred to the National Hospital Organization Kumamoto Medical Center. TAE was performed to stop the bleeding. Subsequently, 15 courses of Atez+Bev were administered for UR-HCC with primary tumor, peritoneal metastasis, and multiple liver metastases. Multiple liver metastases and peritoneal metastasis resolved 7 months after initiation of Atez+Bev. The primary HCC had shrunk, but the patient decided not to continue treatment because of severe numbness in his fingers. Six months after stopping Atez+Bev, CS was performed because no new lesions were observed, and the patient wished to become cancer-free by resection of the remaining tumor. HCC was successfully resected, and he was discharged without any complications. The pathological findings demonstrated that there was no remnant viable HCC. CONCLUSION: We herein present a case of CS following TAE and Atez+Bev for unresectable and ruptured HCC. The patient did not require chemotherapy after CS and is alive and recurrence-free for 7 months.

Gut microbiome in gastrointestinal cancer: a friend or foe?

The impact of the gut microbiome on host health is becoming increasingly recognized. To date, there is growing evidence that the complex characteristics of the microbial community play key roles as potential biomarkers and predictors of responses in cancer therapy. Many studies have shown that altered commensal bacteria lead to cancer susceptibility and progression in diverse pathways. In this review, we critically assess the data for gut microbiota related to gastrointestinal cancer, including esophageal, gastric, pancreatic, colorectal cancer, hepatocellular carcinoma and cholangiocarcinoma. Importantly, the underlying mechanisms of gut microbiota involved in cancer occurrence, prevention and treatment are elucidated. The purpose of this review is to provide novel insights for applying this understanding to the development of new therapeutic strategies in gastrointestinal cancer by targeting the microbial community.

Shanghai fever, a fatal enteric illness, in an adult patient with neutropenia caused by treatment-related myelodysplastic syndrome: a case report.

BACKGROUND: Shanghai fever is a rare community-acquired enteric illness with sepsis caused by Pseudomonas aeruginosa. Cases of Shanghai fever in pediatric patients have been reported; however, to the best of our knowledge, there are no reports of adult cases. CASE PRESENTATION: A 65-year-old man visited the emergency department with sudden onset of abdominal pain. He was diagnosed as treatment-related myelodysplastic syndrome after treatment of follicular lymphoma. Moderate tenderness in the middle right abdominal quadrants was noted. Computed tomography showed abdominal free air with a small amount of effusion to the surrounding edematous small intestine, and we performed emergency exploration. During operation, we found multiple bowel perforations with patchy necrotic lesions. The patient was admitted to an intensive care unit postoperatively. Blood culture showed Pseudomonas aeruginosa. His condition improved; however, on the 8th postoperative day, the abdominal drain tube showed turbid drainage. We performed re-operation and found anastomotic leakage with two new bowel perforations. After the re-operation, the patient showed signs of septic shock and his general condition got worse, and the patient died due to multiple organ failure on the 12th postoperative day. CONCLUSION: Shanghai fever may occur in an adult patient with neutropenia.

Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway.

Fusobacterium nucleatum, found in the oral cavity, influences the progression of gastrointestinal cancers. Additionally, our previous results suggested that F. nucleatum is associated with poor patient prognosis in esophageal squamous cell carcinoma (ESCC). However, the mechanism by which F. nucleatum affects aggressive tumor behavior has yet to be elucidated. We have conducted this clinical, in vitro, and in vivo study to clarify the mechanism of ESCC progression induced by F. nucleatum. Transmission electron microscopy revealed that F. nucleatum invaded and occupied ESCC cells and impacted gene and protein expression. Comprehensive mRNA expression and pathway enrichment analyses of F. nucleatum-treated ESCC cells identified the "NF-κB" and "NOD-like receptor" signaling pathways as enriched. We confirmed the relationship between the presence of F. nucleatum and NF-κB activation in resected ESCC tissues. Furthermore, F. nucleatum-treated ESCC cells demonstrated enhanced growth ability, and NF-κB activation, as well as overexpression of NOD1 and phosphorylated RIPK2. Furthermore, treated cells showed accelerated tumor growth, with NF-κB activation in xenograft models. F. nucleatum invaded ESCC cells and induced the NF-κB pathway through the NOD1/RIPK2 pathway, leading to tumor progression.

Prognostic Impact of PD-1 on Tumor-Infiltrating Lymphocytes in 433 Resected Esophageal Cancers.

BACKGROUND: Immune checkpoint inhibitors targeting the programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have demonstrated antitumor effects in patients with various malignancies, including esophageal cancer. Thus, a better understanding of local immunity in esophageal cancer is crucial for improving treatment and clinical outcomes. METHODS: We evaluated PD-1 expression on tumor-infiltrating lymphocytes (TILs), as well as PD-L1 expression on cancer cells, by immunohistochemistry and immunofluorescence using a nonbiased database of 433 curatively resected esophageal cancers. With the idea of application as liquid biopsy, PD-1 expression status on peripheral lymphocytes was evaluated by flow cytometry. RESULTS: The cutoff value of PD-1 expression was the median PD-1 count. Compared with cases of low PD-1 expression (n = 219), cases with high levels of PD-1 expression (n = 213) showed significantly worse overall survival (log-rank P = .0017). The prognostic effect of PD-1 differed according to the preoperative treatment status (P for interaction = .040); PD-1 expression was associated with high overall mortality among patients without preoperative therapy, while no such association was present among those with preoperative treatment. A stratification based on PD-1 and PD-L1 status was also significantly associated with overall survival (log-rank P = .0005). PD-1 expression on TILs was significantly associated with that on peripheral lymphocytes (P < .0001). CONCLUSIONS: PD-1 expression on TILs was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. The combination of PD-1 and PD-L1 expression enabled further classification of patients according to clinical outcome.

PD-L1 and PD-L2 expression status in relation to chemotherapy in primary and metastatic esophageal squamous cell carcinoma.

Immune checkpoint inhibitors have shown efficacy in various cancers. Although programmed death ligand 1/2 (PD-L1/L2) expressions have been demonstrated as predictive biomarkers of response to immune checkpoint inhibitors and prognostic markers, whether PD-L1/L2 expression is altered in esophageal squamous cell carcinoma during the therapeutic course is unclear. Whether PD-L1/L2 expression in metastatic or recurrent lesions is consistent with that in primary tumors is also unknown. This study included 561 surgically resected esophageal squamous cell carcinomas and PD-L1/L2 expression was evaluated by immunohistochemistry. We investigated the influence of chemotherapeutic drugs (cisplatin and fluorouracil) on PD-L1/L2 expression and PD-L1/L2-related pathways in vitro. We also examined PD-L1/L2 expression in 18 surgically resected lymph node metastases and 10 recurrent lesions compared with primary lesions. The positive rate of PD-L1 was significantly higher in patients with preoperative chemotherapy than in those without preoperative therapy. The positive rate of PD-L2 expression showed no significant difference between patient groups. Cisplatin increased PD-L1 expression in cancer cell lines in vitro, but decreased PD-L2 in some cell lines. The effects of cisplatin on phosphorylated signal transducer and activator of transcription 1/3 (pSTAT1/3) also differed depending on cell lines. Fluorouracil increased PD-L1 and PD-L2 expression. PD-L1/L2 expression in lymph node metastases and recurrent lesions did not always match expression in primary lesions. PD-L1/L2 expression may be altered by preoperative chemotherapy, and PD-L1 /L2 expression in primary lesions does not always match that of metastatic/recurrent lesions. Thus, one-time evaluation is not sufficient to evaluate PD-L1/L2 expression as a biomarker in esophageal cancer.

Adapted systemic inflammation score as a novel prognostic marker for esophageal squamous cell carcinoma patients.

BACKGROUND: The adapted systemic inflammation score (aSIS), calculated from serum albumin and the lymphocyte-to-monocyte ratio, has been reported to be a novel prognostic marker for some types of cancers. However, the prognostic impact of aSIS in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to examine the prognostic effects of aSIS in a large cohort of 509 ESCC patients. METHODS: Preoperative aSIS was retrospectively calculated for 509 ESCC patients who underwent curative resection. Time-dependent receiver operating characteristics (t-ROC) curves were used for comparing the prognostic impact. RESULTS: Patients with high aSIS showed significantly poorer overall survival (OS) than patients with low aSIS (log rank P < .001). The multivariate analysis revealed that aSIS was an independent prognostic factor for overall survival (multivariate hazard ratio 1.76; 95% confidence interval 1.13-2.75; P = .013). The t-ROC analysis showed that aSIS was more sensitive than other nutritional prognostic factors (controlling for nutritional status, systemic inflammation score, and the neutrophil-to-lymphocyte ratio). CONCLUSION: Preoperative aSIS may be a useful prognostic biomarker in ESCC patients who underwent curative resection.

Analysis of the survival and clinical characteristics of colorectal cancer patients with mental disorders.

AIM: Many studies have shown that patients with mental disorders are less likely than non-psychiatric patients to be diagnosed with or treated for various types of cancers because of their low awareness and understanding of the disease as well as reduced ability to cooperate with medical staff. We analyzed the clinical features of patients with colorectal cancer (CRC) and preexisting mental illness. METHODS: All patients underwent primary tumor resection for CRC. We reviewed the records of 68 patients who were diagnosed with mental disorders. The patients' clinicopathological information was compared with that of a control group of 893 CRC patients. RESULTS: There was no significant difference in the overall disease stage at the time of surgery between the groups. However, disease-free survival, cancer-specific survival, and overall survival were significantly worse in the mental disorder group than in the control group (P < .01). In particular, among those with stage III CRC, overall survival was significantly worse in the patients with mental disorders than in the non-psychiatric patients (P < .001). The frequency of complications of ≥grade 2 according to the Clavien-Dindo classification was higher in the SMI group because of postoperative paralytic ileus. CONCLUSIONS: Advanced CRC patients with mental disorders are less likely to receive postoperative adjuvant chemotherapy or treatment for recurrent cancer than CRC patients without mental disorders; therefore, they experience worse outcomes. Collaboration across multiple departments is necessary for managing CRC patients with mental disorders.

Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC). METHODS: We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance. RESULTS: ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens. CONCLUSIONS: F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.

Outcomes of esophageal bypass surgery and self-expanding metallic stent insertion in esophageal cancer: reevaluation of bypass surgery as an alternative treatment.

PURPOSE: Advanced esophageal cancer often results in esophageal stenosis or tracheoesophageal fistula. Esophageal bypass surgery and esophageal stent insertion are palliative treatments for esophageal cancer. With improvements in metallic stents and the stent insertion technique, esophageal stent insertion appears to be performed more frequently than bypass surgery, worldwide. The aim of this study was to evaluate the outcomes of bypass surgery and stent insertion in our hospital and reevaluate which patients would benefit from bypass surgery. METHODS: A total of 70 esophageal cancer patients who could not tolerate oral feeding due to esophageal stenosis or tracheoesophageal fistula underwent palliative treatment [esophageal bypass surgery (N = 34) and esophageal stent insertion (N = 36)] at Kumamoto University. We retrospectively investigated the clinicopathological factors, postoperative outcomes, and complications. RESULTS: Both treatments could significantly improve the amount of food intake and the dietary form (P < 0.01). The length of hospital stay was shorter (P < 0.01) and complications associated with treatment were reduced in the stent group (P = 0.03). The overall survival did not differ significantly between the groups (log rank P = 0.22). Importantly, in the bypass surgery group, the patients who received postoperative treatment had a better prognosis than those who did not receive postoperative treatment (log rank P < 0.01). CONCLUSION: Both bypass surgery and stent insertion allowed oral intake in patients who could not tolerate oral feeding because of esophageal stenosis or tracheoesophageal fistula. Considering that patients who undergo stent insertion have a shorter hospital stay and fewer complications, stent insertion may be a better first choice for treatment than bypass surgery. However, bypass surgery may be an option for patients who can tolerate postoperative treatment.

Fibrosis-4 Index, a Noninvasive Fibrosis Marker, Predicts Survival Outcomes After Hepatectomy for Colorectal Cancer Liver Metastases.

BACKGROUND: Liver fibrosis influences liver regeneration and surgical outcomes, and several noninvasive models based on laboratory data have been developed to predict liver fibrosis. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, a noninvasive fibrosis marker, can predict the prognosis in patients with colorectal liver metastases (CRLM) undergoing hepatectomy. METHODS: This retrospective study involved 193 consecutive patients with CRLM who underwent hepatectomy. The FIB-4 index was calculated by laboratory data and age before hepatectomy and before preoperative chemotherapy. The FIB-4 cut-off was determined using survival classification and regression tree analysis. Patients were divided into two groups (high and low FIB-4 index), and post-hepatectomy overall survival (OS) and recurrence-free survival (RFS) were investigated. RESULTS: In total, 193 patients were evaluated. Chemotherapy before hepatectomy was performed in 105 (54.4%) patients. A high FIB-4 index (> 2.736) was found in 39 (20.2%) patients. OS was significantly shorter in patients with a high FIB-4 index than those with a low FIB-4 index in the univariate (45.9 vs. 74.4 months, log-rank p = 0.007) and multivariate analysis (hazard ratio 2.28, 95% confidence interval 1.39-3.74; p = 0.001). Among patients who received chemotherapy before hepatectomy, those with a high FIB-4 index had significantly shorter RFS (6.9 vs. 45.3 months, log-rank p = 0.047) and OS (23.9 vs. 55.0 months, log-rank p = 0.003) than those with a low FIB-4 index. This association was also confirmed by multivariate analysis (hazard ratio 4.28, 95% confidence interval 1.46-12.6; p = 0.008). CONCLUSION: Both the preoperative and prechemotherapy FIB-4 index can predict long-term outcomes after hepatectomy in patients with CRLM.

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD-L1 expression on tumors, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.

Port site recurrence of esophageal adenocarcinoma after minimally invasive esophagectomy: a case report.

BACKGROUND: Port site recurrence has been observed after a variety of oncologic resection procedures. However, few have reported port site recurrence of esophageal cancer. CASE PRESENTATION: A 51-year-old man underwent minimally invasive esophagectomy for pT3(AD)N3M0 adenocarcinoma of the esophagus. One year after surgery, he presented with a rapidly growing tumor on the right thoracic wall. Contrast computed tomography demonstrated an enhancing tumor with uptake on positron emission tomography. We performed resection of the thoracic wall, including the skin and subcutis. The pathologic diagnosis was poorly differentiated adenocarcinoma, consistent with metastasis of esophageal origin. CONCLUSION: This was the first report on thoracic port site recurrence of esophageal adenocarcinoma. We recommend elimination of leakage around the thoracoscopic ports to prevent such recurrence. We should provide prudent postoperative clinical surveillance.

Prognostic and clinical impact of PD-L2 and PD-L1 expression in a cohort of 437 oesophageal cancers.

BACKGROUND: The PD-1/PD-L1 pathway plays critical roles in tumour immunology, and serves as an immune-based therapeutic target. Less is known regarding PD-L2, another ligand of PD-1, and its relation to clinical outcome in human cancers. METHODS: We used a database of 437 surgically and 100 endoscopically resected oesophageal cancers (squamous cell carcinoma, n = 483; adenocarcinoma, n = 36; others, n = 18) to evaluate PD-L2 and PD-L1 expression by immunohistochemistry. RESULTS: Compared with PD-L2-negative cases (n = 366, 83.8%), PD-L2-positive cases (n = 71, 16.2%) had worse overall survival (P = 0.011, log-rank test). There was not a significant correlation between PD-L2 and PD-L1 expression. Multiplex immunofluorescence revealed that there was variability in the expression pattern of PD-L2 and PD-L1. In early-stage tumours, PD-L2 expression was more frequently observed compared with PD-L1. CONCLUSIONS: PD-L2 as well as PD-L1 were associated with an unfavourable prognosis in oesophageal cancer, supporting the role of PD-L2 as a prognostic biomarker. Considering that PD-L2 and PD-L1 had different features in terms of expression timing and responses to chemotherapeutic drugs, evaluation of both PD-L2 and PD-L1 expression may be clinically important.

Laparoscopic dissection for pelvic lymph node recurrence of thymic carcinoma: A case report.

Thymic carcinoma, a rare mediastinal neoplasm, is characterized by extensive local invasion and distant metastasis. To our knowledge, this is the first case report demonstrating the efficacy of laparoscopic dissection for pelvic lymph node metastases from thymic carcinoma. A 64-year-old man was found to have a mediastinal mass by CT and underwent radical resection. Six months after resection of his thymic carcinoma, follow-up CT revealed a gluteal tumor and enlarged pelvic lymph nodes. The gluteal tumor was resected percutaneously. Two months after this procedure, PET showed that the three pelvic lymph nodes had abnormal uptake of 18 F-fluorodeoxyglucose and had enlarged further. The patient accordingly underwent laparoscopic dissection of these lymph nodes. Pathological examination of all resected specimens showed metastatic thymic carcinoma. We recommend laparoscopic dissection of pelvic lymph node metastases because it provides a clear intraoperative view and is minimally invasive.

Clinical significance of evaluating endoscopic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Clinical significance of endoscopic response (ER) after neoadjuvant chemotherapy (NAC) for esophageal cancer has not been fully understood. Thus, the present study aimed to investigate the association between ER to NAC and its clinicopathological outcomes in patients with esophageal squamous cell carcinoma (ESCC). METHODS: In total, 141 patients who underwent NAC and subsequent esophagectomy for ESCC were included. ER to NAC was retrospectively evaluated based on macroscopic findings of the primary tumor, which was classified into three categories: endoscopic no response (eNR), endoscopic partial response (ePR), and endoscopic good response (eGR). An endoscopic responder was defined as patients with eGR/ePR. RESULTS: Approximately 89.4% of patients had cStage II-III disease, and 7.1% had pathological complete response. Upon ER evaluation, eNR, ePR, and eGR were observed in 46 (32.6%), 54 (38.3%), and 41 (29.1%) patients, respectively. Pathological responders significantly increased as the ER grade became better. Among preoperative clinical factors, only ER significantly correlated with pathological response in univariate and multivariate analysis. Endoscopic responders showed a significantly better prognosis than did eNR patients (P < 0.001), although the overall survival (OS) of the patients with eGR and ePR was equivalent. Endoscopic responder, ypT, ypN, and pathological responder were significant predictors of OS in the univariate analysis, and endoscopic responder, ypN, and pathological responder were independent predictors in the multivariate analysis. CONCLUSION: This study suggests that ER can be a simple and important tool to predict the pathological response and survival of patients who undergo NAC for ESCC.

Lysyl oxidase impacts disease outcomes and correlates with global DNA hypomethylation in esophageal cancer.

Abnormal function of human body enzymes and epigenetic alterations such as DNA methylation have been shown to lead to human carcinogenesis. Lysyl oxidase (LOX) enzyme has attracted attention due to its involvement in tumor progression in various cancers. The purpose of this study was to clarify the clinical importance of LOX expression and its epigenetic regulation in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Using a database of 284 ESCCs, we examined LOX expression and its prognostic characteristics. The functional role of LOX was assessed by in vitro growth, migration, and invasion assays. The relationship between LOX expression, global DNA hypomethylation (ie, LINE-1 methylation), and LOX promoter methylation was evaluated by using mRNA expression arrays and pyrosequencing technology. High LOX expression cases had a significantly shorter overall survival and cancer-specific survival (log-rank, P < .001). The prognostic effect of LOX expression was not significantly modified by other clinical variables. Silencing and enzymatic inhibition of LOX suppressed growth and reduced the invasion and migration ability of ESCC cell lines along with the downregulation of AKT and MMP2. An integrated gene analysis in tissues and cell lines revealed that LOX was the most highly upregulated gene in LINE-1 hypomethylated tumors. In vitro, LOX expression was upregulated following DNA demethylation. LOX promoter methylation was not associated with LOX expression. Conclusively LOX expression was associated with poor prognosis in ESCC and was regulated epigenetically by genome-wide hypomethylation. It could serve as a prognostic biomarker in ESCC patients, and therapeutically targeting LOX could reverse the progression of esophageal cancer.

Thyroid metastasis from esophageal adenocarcinoma: a case report and literature review.

BACKGROUND: The incidence of metastatic spread of gastrointestinal malignancies to the thyroid gland is relatively low and most of these malignancies originate from the colorectum. Thyroid metastasis originating from the esophagus is poorly documented. CASE PRESENTATION: A 79-year-old man presented with hoarseness of voice and swallowing difficulty. Eighteen months earlier, he had undergone preoperative chemotherapy (S-1 and oxaliplatin [SOX] therapy) and subtotal esophagectomy with regional lymph nodes dissection and retrosternal narrow gastric tube reconstruction for advanced Barrett's esophageal adenocarcinoma. In the ultrasonographic examination, there was a hypoechoic, indistinct border and heterogeneous nodule in the left lobe of the thyroid gland. Pathological examination of an ultrasound-guided fine-needle aspiration showed adenocarcinoma, supporting a diagnosis of esophageal adenocarcinoma metastases in the thyroid. CONCLUSION: This is a first case of a patient with thyroid metastasis from Barrett's esophageal adenocarcinoma after subtotal esophagectomy.