Clinical and Oncological Impact of the Toll-like Receptor-3 and -4 in Esophageal and Gastro-esophageal Junction Adenocarcinoma.

BACKGROUND/AIM: Esophageal and gastro-esophageal junction cancer is a major cause of cancer-related mortality, with poor prognosis. Toll-like receptors (TLRs) play a significant role in the innate immune system; their increased expression has been associated with esophageal adenocarcinoma. This study aimed to determine the association between TLR-3 and TLR-4 expression with clinical and oncological outcomes of patients that underwent esophagectomy for cancer. PATIENTS AND METHODS: This is a retrospective analysis of prospectively collected data from consecutive patients within a 2-year period. Primary endpoints of the study were the assessment of the expression of TLR-3 and TLR-4 in primary tumors as well as in metastatic lymph nodes. Secondary endpoints were the correlation of TLR-3 and TLR-4 values with the clinical, pathological, and oncological outcomes. RESULTS: A significantly higher expression of TLR-3 and TLR-4 in primary tumors and metastatic-lymph nodes was observed. There was a significant association between TLR-3 expression and T-stage, as well as TLR-4 expression and grade of differentiation in the primary site. Additionally, metastatic-lymph node TLR-4 expression was significantly correlated with N-stage. A strong correlation between TLR-4 expression and overall or progression-free survival rates was detected. CONCLUSION: This study found a significantly increased TLR expression in malignant tissue/metastatic lymph nodes, as well as a significant positive correlation between TLRs and worse clinical outcomes. TLRs have a pivotal role in the inflammation pathway in the esophagus and during esophageal carcinogenesis. This study highlights the need for further investigation into TLR-mediated signaling pathways and their potential role as diagnostic and therapeutic targets.

Gastrectomy for Cancer: A 15-Year Analysis of Real-World Data from the University of Athens.

Background and Objectives: Encouraging data have been reported from referral centers following gastrointestinal cancer surgery. Our goal was to retrospectively review patient outcomes following gastrectomy for gastric or gastroesophageal junction (GEJ) cancer at a high-volume unit of the University of Athens. Methods: The enrollment period was from June 2003 to September 2018. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were constructed to identify variables independently associated with time-to-event outcomes. Results: A total of 205 patients were analyzed. R0 resection was achieved in 183 (89.3%) patients and was more likely to occur following neoadjuvant chemotherapy (p = 0.008). Recurrence developed in 46.6% of our cohort and the median disease-free survival was 31.2 months. On multivariate analysis, only staging (HR = 2.15; 95% CI: 1.06-4.36) was independently associated with increased risk of recurrence. All-cause mortality was 57.2% and the median time of death was 40.9 months. On multivariate regression, staging (HR: 1.35; 95% CI: 1.11-1.65) and recurrence (HR: 2.87; 95% CI: 1.32-6.22) predicted inferior prognosis. Conclusions: Gastrectomy at the University of Athens has yielded favorable outcomes for patients with GEJ cancer.

The Role of Toll-like Receptors in Esophageal Cancer.

Esophageal adenocarcinoma (AC) develops through Barrett's esophagus (BE) and columnar dysplasia, preceded by gastro-esophageal reflux disease (GERD). Incidence of esophageal squamous cell carcinoma (SCC) is increased with tobacco smoking and alcohol abuse. Toll-like receptors (TLRs) can act as prognostic factors and potential therapeutic targets of esophageal cancer. TLRs, an important family of pattern recognition receptors, allow immune cells to recognize pathogens triggering inflammation. TLR-signaling pathway activates signaling-elements, regulating inflammatory response, possibly correlating to carcinogenesis. In the normal esophagus, TLRs recognize molecular patterns on microorganisms and inflammatory response produced by tissue-damage. TLR3, TLR4, TLR5, and TLR9 are expressed at increasing levels from GERD to AC. TLR4 is a mediator of proliferation in AC, while TRL1 and TLR4 over-expression in AC is related to poor prognosis and metastasis. Additionally, TLR3, TLR4, and TLR9 expression in SCC has been associated with lymphatic metastasis, whereas increased expression of TLR7 and TLR9 has been also associated with advanced disease. It seems that TLR expression can indicate esophageal metaplasia, dysplasia, and cancer. Herein, we aimed to present all available data regarding the relation of TLRs and esophageal cancer. They may represent significant and valuable diagnostic or prognostic factors for esophageal cancer.

Esophageal cancer surgery in Greece during the era of the financial crisis.

The aim of this study is to describe outcomes of esophageal cancer surgery in a quaternary upper gastrointestinal (GI) center in Athens during the era of the Greek financial crisis. We performed a retrospective analysis of patients that underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) cancer at an upper GI unit of the University of Athens, during the period January 2004-June 2019. Time-to-event analyses were performed to explore trends in survival and recurrence. A total of 146 patients were identified. Nearly half of the patients (49.3%) underwent surgery during the last 4 years of the financial crisis (2015-2018). Mean age at the time of surgery was 62.3 ± 10.3 years, and patients did not present at older ages during the recession (P = 0.50). Most patients were stage III at the time of surgery both prior to the recession (35%) and during the financial crisis (39.8%, P = 0.17). Ivor-Lewis was the most commonly performed procedure (67.1%) across all eras (P = 0.06). Gastric conduit was the most common form of GI reconstruction (95.9%) following all types of surgery (P < 0.001). Pre-recession anastomoses were usually performed using a circular stapler (65%). Both during (88.1%) and following the recession (100%), the vast majority of anastomoses were hand-sewn. R0 resection was achieved in 142 (97.9%) patients. Anastomosis technique did not affect postoperative leak (P = 0.3) or morbidity rates (P = 0.1). Morbidity rates were not significantly different prior to (25%), during (46.9%), and after (62.5%) the financial crisis, P = 0.16. Utilization of neoadjuvant chemotherapy (26.9%, P = 0.90) or radiation (8.4%, P = 0.44) as well as adjuvant chemotherapy (54.8%, P = 0.85) and irradiation (13.7%, P = 0.49) was the same across all eras. Disease-free survival (DFS) and all-cause mortality rates were 41.2 and 47.3%, respectively. Median DFS and observed survival (OS) were 11.3 and 22.7 months, respectively. The financial crisis did not influence relapse (P = 0.17) and survival rates (P = 0.91). The establishment of capital controls also had no impact on recurrence (P = 0.18) and survival (P = 0.94). Austerity measures during the Greek financial crisis did not influence long-term esophageal cancer outcomes. Therefore, achieving international standards in esophagectomy may be possible in resource-limited countries when centralizing care.

A complex modality of achalasia, diverticulum and paraesophageal hernia treated through three-dimensional left thoracoscopy.

Herein, we report a case of a patient with recurrent dysphagia after an open transabdominal hernia repair for a Type IV paraesophageal hernia performed elsewhere. Subsequent work-up and medical records' review revealed the coexistence of a large left epiphrenic diverticulum in combination with achalasia synchronous to the recently repaired paraesophageal hernia. A three-dimensional left thoracoscopic diverticulectomy with a long esophagomyotomy was conducted under endoscopic guidance intraoperatively, with no perioperative complications. At 12 months' follow-up evaluation, the patient presents well with no documented recurrence. Cumulative experience from various medical specialties regarding esophageal motility disorders and endoscopic state-of-the-art techniques, when combined with minimally invasive surgical techniques, provide an effective management of esophageal motility syndromes, overall.