Background/Aim: This study investigated the anti-inflammatory effect of apigenin in an experimental model of acute pancreatitis. Inflammatory response was reflected by tissue expression of the cytokine TNF-α coupled with histological examination. Materials and Methods: Wistar rats were divided into three groups: Sham-group animals underwent laparotomy only, without any other interventions. Control-group animals underwent laparotomy and bilio-pancreatic duct ligation to induce pancreatitis without apigenin administration. Apigenin group animals were further treated with apigenin. Euthanasia was performed at 6, 12, 24, 48 and 72 h post-operatively. Results: Over-expression of TNF-α in relation to postoperative time was observed in the control group (p<0.001). In the apigenin group, under-expression of TNF-α in relation to postoperative time was observed (p<0.013). At 72 h, apigenin reduced pancreatic TNF-α expression and prevented pancreatic necrosis. Conclusion: Apigenin slows progression and reduces severity of acute pancreatitis. Apigenin may serve as an adjunct to a more successful therapeutic strategy in acute pancreatitis.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is a leading cause of cancer-related death worldwide. Immunotherapy has emerged as the mainstay treatment option for unresectable HCC. Toll-like receptor 4 (TLR4) plays a crucial role in the innate immune response by recognizing and responding primarily to bacterial lipopolysaccharides. In addition to its role in the innate immune system, TLR4 has also been implicated in adaptive immunity, including specific anti-tumor immune responses. In particular, the TLR4 signaling pathway seems to be involved in the regulation of several cancer hallmarks, such as the continuous activation of cellular pathways that promote cell division and growth, the inhibition of programmed cell death, the promotion of several invasion and metastatic mechanisms, epithelial-to-mesenchymal transition, angiogenesis, drug resistance, and epigenetic modifications. Emerging evidence further suggests that TLR4 signaling holds promise as a potential immunotherapeutic target in HCC. The aim of this review was to explore the multilayer aspects of the TLR4 signaling pathway, regarding its role in liver diseases and HCC, as well as its potential utilization as an immunotherapy target for HCC.

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 has a dismal prognosis and necessitates a multimodal and multidisciplinary approach from diagnosis to treatment. High-definition white-light endoscopy and histopathological confirmation remain the gold standard for the definitive diagnosis of premalignant and malignant lesions. Artificial intelligence using deep learning (DL) methods for image analysis constitutes a promising adjunct for the clinical endoscopist that could effectively decrease BE overdiagnosis and unnecessary surveillance, while also assisting in the timely detection of dysplastic BE and esophageal cancer. A plethora of studies published during the last five years have consistently reported highly accurate DL algorithms with comparable or superior performance compared to endoscopists. Recent efforts aim to expand DL utilization into further aspects of esophageal neoplasia management including histologic diagnosis, segmentation of gross tumor volume, pretreatment prediction and post-treatment evaluation of patient response to systemic therapy and operative guidance during minimally invasive esophagectomy. Our manuscript serves as an introduction to the growing literature of DL applications for image analysis in the management of esophageal neoplasia, concisely presenting all currently published studies. We also aim to guide the clinician across basic functional principles, evaluation metrics and limitations of DL for image recognition to facilitate the comprehension and critical evaluation of the presented studies.

Pulmonary complications remain the most common problem following transthoracic esophagectomy. Minimally invasive approach has significantly improved clinical outcomes; however, respiratory distress is still significant. Minimally invasive transcervical esophagectomy with mediastinal lymphadenectomy avoids thoracic access, which may decrease pulmonary complications. Transcervical esophagectomy refers to transcervical esophageal mobilization and mediastinal lymphadenectomy followed by a transhiatal gastric and distal-esophageal mobilization, abdominal and lower mediastinal lymphadenectomy. Adoption of innovative minimally invasive techniques for the transcervical or transhiatal approach, such as laparoscopy or robotic-assisted mediastinoscopy have made possible transmediastinal approach for radical esophagectomy. This novel approach with avoidance of thoracotomy or thoracoscopy can omit one lung ventilation as in transthoracic esophagectomy. Patients with previous thoracic surgery, impaired respiratory system, and major comorbidities, who are unable to undergo transthoracic esophagectomy, become candidates for radical esophagectomy with promising results. Minimally invasive transcervical esophagectomy for esophageal cancer is a safe and feasible approach and may be a valuable alternative with promising clinical and oncological outcomes.