Esophageal Malignancy Research Articles

S2819 Impressive Finding of Tracheoesophageal Finding Due to Esophageal Malignancy

S2819 Impressive Finding of Tracheoesophageal Finding Due to Esophageal Malignancy

Oxidative Damage as a Fundament of Systemic Toxicities Induced by Cisplatin-The Crucial Limitation or Potential Therapeutic Target?

Cisplatin, an inorganic complex of platinum, is a chemotherapeutic drug that has been used for 45 years. Despite the progress of pharmaceutical sciences and medicine and the successful application of other platinum complexes for the same purpose, cisplatin is still the therapy of choice in many cancers. Treatment for testicular, ovarian, head and neck, urothelial, cervical, esophageal, breast, and pulmonary malignancies is still unthinkable without the use of this drug. However, cisplatin is also known for many side effects, of which the most pronounced are nephrotoxicity leading to acute renal failure, neurotoxicity, and ototoxicity. Mechanistic studies have proven that one of the conditions that plays a major role in the development of cisplatin-induced toxicities is oxidative stress. Knowing the fact that numerous antioxidants can be used to reduce oxidative stress, thereby reducing tissue lesions, organ failure, and apoptosis at the cellular level, many studies have defined antioxidants as a priority for investigation as a cotreatment. To investigate the mechanism of antioxidant action in vivo, many animal models have been employed. In the last few years, studies have mostly used rodents and zebrafish models. In this article, some of the most recent investigations that used animal models are listed, and the advantages and disadvantages of such experimental studies are pointed out.

COVID-19 Effect on Surgery for Gastrointestinal Malignancies: Have Operative Volumes Recovered?

BackgroundCOVID-19 disrupted elective operations, cancer screening, and routine medical care while simultaneously overwhelming hospital staff and supplies. Operations for gastrointestinal (GI) malignancies rely on endoscopic screening, staging, and neoadjuvant therapy (NAT), each of which was disrupted by the pandemic. The aim was to evaluate the effect of the COVID-19 pandemic on the US national rates of gastrointestinal oncologic operations. MethodsThe Vizient Clinical Data Base® was queried for oncologic operations for esophageal, gastric, and colorectal malignancies with and without NAT from March 2019 to March 2022. Control chart analysis examined operative volume over time while Wilcoxon rank sum tests were used to compare mean monthly volume before and during the pandemic. ResultsA total of 95,912 patients were identified over 36 months; 5.8% esophageal, 6.3% gastric, 77.5% colonic, and 10.4% rectal operations. Esophageal operative volume decreased for 9 months during the pandemic and was significantly lower during than before the pandemic (p=0.002). Gastric operations decreased for 10 months early in the pandemic, but rebounded so that after 2 years volumes were unchanged (p=0.49). Colonic operations experienced a sharp decrease for 4 months at the beginning of the pandemic, but volumes quickly increased and overall were unchanged (p=0.29). Rectal operations decreased for 13 months and were significantly lower during than before the pandemic (p=0.018). Oncologic operations for patients receiving NAT varied. ConclusionCOVID-19 significantly disrupted the volume of gastrointestinal oncologic operations in the USA. Esophageal and rectal oncologic operations experienced prolonged and significant reductions while gastric and colonic oncologic operations transiently decreased but rebounded during the pandemic.

TP53 Mutations in Esophageal Squamous Cell Carcinoma.

The occurrence and development of esophageal cancer involve multiple genetic abnormalities that contribute to the malignant transformation of esophageal epithelial cells, followed by invasion and metastasis, leading to a poor outcome. Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal malignancy in East Asia, with approximately half of newly diagnosed ESCC cases occurring in China. The TP53 tumor suppressor gene mutation is one of the most common mutations in ESCC. TP53 mutations are observed even in the early phases of esophageal carcinogenesis. Normal functions of the p53 network are lost in cells of ESCC patients who harbor the mutant TP53 gene, inducing tumor development, radiation resistance, chemotherapy resistance, and immune suppression, promoting progression and metastasis, thereby resulting in an overall poor prognosis. Although clinical trials of several pharmacological compounds targeting mutational TP53 have been explored, novel approaches are still urgently required to improve the observed dismal survival. A better understanding of the role of the mutant TP53 gene in human ESCC might lead to the discovery of innovative targeted therapies to treat this malignancy.

Chinese clinical practice guidelines for the prevention and treatment of radiation‐induced esophagitis

AbstractAcute radiation‐induced esophagitis is a common complication of radiotherapy for esophageal, lung, and other malignancies. Therefore, understanding the diagnosis, grading, risk factors, prevention, and treatment of radiation‐induced esophagitis is essential. Currently, there are few consensuses and guidelines on radiation‐induced esophagitis worldwide, mainly the American College of Gastroenterology (ACG) clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE) and the Digestive Endoscopy Society of Chinese Medical Association's “Guidelines for the Diagnosis and Treatment of Reflux Esophagitis.” However, no consensus or guidelines specifically addressing radiation‐induced esophagitis have been established. Efforts have been made to organize experts to draft Chinese consensus or guidelines, but the recommendations in these guidelines also vary owing to differences in expert backgrounds. The clinical practice guidelines presented herein were developed for the first time with the joint participation of Chinese radiotherapy experts. Drugs and methods with clinical significance were selected by reviewing and summarizing the prevention and treatment of radiation‐induced esophagitis and combining them with China's national conditions. After multiple rounds of discussion and revision, clinical practice guidelines were established in line with the needs of Chinese clinicians, providing useful clinical guidance for the prevention and treatment of radiation‐induced esophagitis.

Associations between depression and cancer risk among patients with diabetes mellitus: A population-based cohort study.

The co-occurrence of depression and diabetes mellitus has been linked to an increased risk of developing cancer. This study aimed to investigate whether depression further amplifies the risk of cancer among individuals with diabetes. This population-based matched cohort study utilized Taiwan's National Health Insurance claims database. A total of 85,489 newly diagnosed diabetic patients with depressive disorders were selected, along with 427,445 comparison subjects. The matching process involved age, sex, and the calendar year of diabetes onset. The average follow-up duration for the two cohorts was 6.4 and 6.5 years, respectively. The primary outcome of interest was the occurrence of overall cancer or cancer at specific anatomical sites. The adjusted hazard ratios for overall cancer incidence were 1.08 (95% CI, 1.05-1.11). For site-specific cancers, depression exhibited significant associations with oropharyngeal, esophageal, liver, gynecological, prostate, kidney, and hematologic malignancies among patients with diabetes. Notably, a severity-response relationship was observed, indicating that patients with recurrent episodes of major depressive disorders exhibited a higher incidence of cancer compared to those diagnosed with dysthymia or depressive disorder not otherwise specified. Furthermore, the strength of the association between depression and cancer risk was more pronounced among younger patients with diabetes as opposed to older adults. However, no significant relationship was observed between adherence to antidepressant treatment and cancer risk. The findings of this study indicate a significant association between depression and an elevated risk of cancer among individuals diagnosed with diabetes. Future investigations should replicate our findings, explore the effects of pharmacological and non-pharmacological treatments on cancer risk, and identify the underlying mechanisms.

259. ROBOTIC ESOPHAGECTOMY AND THREE FIELD LYMPHADENECTOMY WITH INTRA-OPERATIVE RECURRENT LARYNGEAL NERVE MONITORING

Abstract https://www.dropbox.com/s/uu8gju382tkch29/3FTTE_ISDE_SJ_0423.mp4?dl=0. Background Surgery for esophageal malignancy is associated with significant morbidity and mortality, especially in cases requiring extensive lymphadenectomy. Recurrent laryngeal nerve (RLN) injury can result in hoarseness, aspiration, pneumonia, tracheostomy, and could even be life-threatening. A 33 year old lady with a lower thoracic esophageal squamous carcinoma with left trachea-esophageal groove nodes in the superior mediastinum underwent a Xi robotic esophagectomy and three field lymphadenectomy with intra-operative recurrent laryngeal nerve monitoring after neoadjuvant chemotherapy. Methods We used a bronchial blocker (COOPDECH bronchial blocker, Daiken-Iki Corporation, Japan) with a single-lumen electromyographic (EMG) endotracheal tube) (NIM EMG endotracheal tube, Medtronic Xomed, Jacksonville, FL, USA) for lung isolation along with capnothorax. Semiprone position with 3 robotic ports and an assistant port was utilised. Nerve monitoring provided an audiovisual waveform when either the vagus or the RLN was stimulated and transformed the laryngeal muscle activity into EMG signals. Grounding electrodes were placed on the patient’s shoulder or near the sternum. A prerequisite for adequate and effective nerve monitoring is the avoidance of neuromuscular blockers during anesthesia. Results Esophageal mobilisation was done in the standard fashion. The lymphadenectomy along the recurrent laryngeal nerves in the mediastinum and neck was guided by the nerve identification and stimulation utilising the long intra-thoracic nerve monitoring probes. In the mediastinum, the right recurrent laryngeal nerve was identified taking off from the right vagus along the lateral border of the trachea and looping around the right subclavian artery. The thoracic left recurrent nerve was identified in the aorto-pulmonary window as well along the left lateral border of the trachea in the trachea-esophageal groove where the metastatic lymph nodes were identified on radiology. Conclusion Minimally invasive esophagectomy is now the preferred modality for surgical extirpation of esophageal malignancies, with extensive lymphadenectomy used in appropriate cases. Interventions to reduce postoperative morbidity resulting from the dissection of nodes around the RLN need to be used. The use of IONM is associated with lower RLN palsy rates and superior lymph nodal yield and needs to be investigated with large-scale randomized studies for beneficial clinical outcomes.

190. PROGNOSTIC VALUE OF COMBINATION OF LYMPHOCYTE-TO-MONOCYTE-RATIO AND CYFRA 21-1 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Previous studies have shown that serum tumor markers and systematic inflammatory and nutritional indicators, including Cytokeratin fragments (CYFRA) 21–1 and the lymphocyte-to-monocyte ratio (LMR), are associated with the prognosis of esophageal malignancies. However, their individual prognostic sensitivity and specificity are not yet sufficient. This study aims to investigate the potential of a combined score (CA-LMR) based on CYFRA 21-1 levels and LMR as a novel prognostic predictor for patients with esophageal squamous cell carcinoma (ESCC). Methods A total of 460 consecutive patients underwent oesophagectomy were enrolled, and three groups were established based on CA-LMR score. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan–Meier analysis, and associated factors were analyzed by multivariate Cox analysis. Additionally, modified-pStage (mpStage) was developed based on CA-LMR score, the discriminatory ability, monotonicity, homogeneity and prognosis prediction ability were measured by log-rank χ2, linear-trend χ2, likelihood-ratio χ2 test and Akaike Information Criterion. Results The allocation of CA-LMR score of 0, 1 and 2 were 107 (23.3%), 280 (60.9%), and 73 (15.9%). There was a significant association between CA-LMR and male gender (P = 0.001), smaller BMI (P = 0.035), longer tumor lesions (P = 0.002), and high pT, pN, pStage (P < 0.001, P = 0.011, P = 0.001). The 5-year OS for CA-LMR scores of 0, 1, and 2 were 75.4%, 60.2%, and 32.8%, respectively (P < 0.001) (Fig. 1A,B). Multivariate analysis indicated CA-LMR score (P = 0.011) was an independent prognostic factor for OS (Fig. 1C-E). Furthermore, the proposed mpStage system demonstrated superior discriminatory ability, monotonicity, homogeneity and prognosis prediction ability over AJCC 8th pStage system. Conclusions The CA-LMR score, combined with tumor marker and inflammatory index, could use as a potential prognostic indicator, moreover, our modified pStage system exhibited superior stratification and prognostic accuracy for patients with ESCC, making it possible to serve as novel reference for clinical management.

406. A SYSTEMATIC REVIEW AND META-ANALYSIS ON THE USE OF ARTIFICIAL INTELLIGENCE IN THE ENDOSCOPIC DIAGNOSIS OF ESOPHAGEAL CANCER

Abstract Introduction Endoscopy plays a key role in the surveillance of patients with Barrett’s esophagus and the diagnosis of esophageal cancer. The subtleties of endoscopic interpretation are subject to clinical expertise, diagnostic skill, and thus human error. Therefore, artificial intelligence (AI) is increasingly being incorporated into endoscopy in order to improve diagnostic accuracy and early detection. This systematic review and meta-analysis consolidates the evidence on the use of AI in the endoscopic diagnosis of esophageal cancer. Methods The systematic review was carried out using Pubmed, MEDLINE and Ovid EMBASE databases as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies which described the role of AI in supporting endoscopic video or image diagnosis of esophageal cancer were included. A meta-analysis was also performed. Results 45 studies formed the qualitative and quantitative review. 14 studies with 1590 patients in total assessed the use of AI in endoscopic diagnosis of esophageal squamous cell carcinoma (ESCC)- the pooled sensitivity and specificity were 91.2% (84.3–95.2%) and 80% (64.3–89.9%). A further, 9 studies consisting of 478 patients overall explored the capabilities of AI in supporting the endoscopic diagnosis of esophageal adenocarcinoma (EAC), with a pooled sensitivity and specificity of 93.1% (86.8–96.4%) and 86.9% (81.7–90.7%). AI was often superior to endoscopists when diagnosing ESCC and improved the overall accuracy of both novice and expert endoscopists. Conclusion AI technology, as an adjunct to endoscopy has proven to be beneficial in early, accurate detection of esophageal malignancy. Multiple studies have shown superior diagnostic capabilities when comparing AI technology to endoscopists alone. Despite promising results, the application in real-time endoscopy is limited, and further multicenter trials are required to accurately assess its use in routine practice.

436. USEFULNESS OF INTRAOPERATIVE CONTINUOUS NERVE MONITORING IN TRANSMEDIASTINAL MINIMALLY INVASIVE ESOPHAGECTOMY

Abstract Introduction We have previously reported that continuous intraoperative nerve monitoring (CIONM) is useful in reducing postoperative left recurrent laryngeal nerve paralysis (RLNP) in transmediastinal esophagectomy (TME). In this study, we investigated the relationship between the paralysis risk types on CIONM and postoperative RLNP. Methods A total of 161 patients who underwent TME for esophageal malignancies and esophagogastric junctional cancer with CIONM between October 2017 and July 2022. The relationship between clinical background factors, changes in amplitude during surgery, and left RLNP (endoscopic vocal cord findings on postoperative day 7) was retrospectively investigated. Furthermore, the relationship between LOS types (segmental or diffuse) and left RLNP was examined. Results The median age was 70 years, with 127 male and 34 female patients. At the end of transcervical procedure, 46 patients had amplitude less than 100 μV (LOS: loss of signal) and 78 patients had amplitude ≤50% of baseline. Postoperatively, 76.1% of LOS cases and 46.2% of cases with amplitudes ≤50% of baseline had left RLNP. The amplitude reduction types (LOS, baseline≤50%), primary tumor in the cervical/upper thoracic/middle thoracic esophagus, and males were significantly associated with left RLNP (p < 0.001). When examined by LOS type, RLNP was more common in segmental LOS than in diffuse LOS. Conclusion The pattern of amplitude reduction on CIONM is useful in predicting postoperative left RLNP. We will continue to increase the number of cases and verify the further effectiveness of CIONM for TME.

A resected case of malignant peripheral nerve sheath tumor arising in the cervical esophagus

We report herein a case of malignant peripheral nerve sheath tumor (MPNST), an extremely rare, esophageal malignancy. A 67-year-old, female patient presented with a nodular lesion in the cervical esophagus which was detected on follow-up computed tomography (CT) after surgery for bilateral breast cancer and gastric cancer. Upper gastrointestinal endoscopy revealed a hemispheric, submucosal lesion in the cervicothoracic esophagus. Endoscopic ultrasound-guided fine needle aspiration cytology revealed spindle-shaped cells with nuclear atypia and positive staining for the S100 protein, a neurogenic marker. Based on clear CT findings of lesion growth over two years, MPNST was diagnosed, and treatment for sarcoma was begun. After one course of preoperative chemotherapy, open resection of the esophagus was performed, revealing a solid, white tumor with a maximum diameter of 1.8 cm. The tumor was histopathologically found to be located within the intrinsic muscularis propria. Based on this finding, low-grade MPNST with a schwannoma-like component at its margins was diagnosed. Approximately 50% of MPNST cases occur against a background of neurofibromatosis type 1 (NF1) while about 40% occur sporadically, and 10% occur after irradiation. The patient’s history of radiotherapy for left breast cancer may have contributed to the development of the MPNST.

The role of artificial intelligence in the endoscopic diagnosis of esophageal cancer: a systematic review and meta-analysis.

Early detection of esophageal cancer is limited by accurate endoscopic diagnosis of subtle macroscopic lesions. Endoscopic interpretation is subject to expertise, diagnostic skill, and thus human error. Artificial intelligence (AI) in endoscopy is increasingly bridging this gap. This systematic review and meta-analysis consolidate the evidence on the use of AI in the endoscopic diagnosis of esophageal cancer. The systematic review was carried out using Pubmed, MEDLINE and Ovid EMBASE databases and articles on the role of AI in the endoscopic diagnosis of esophageal cancer management were included. A meta-analysis was also performed. Fourteen studies (1590 patients) assessed the use of AI in endoscopic diagnosis of esophageal squamous cell carcinoma-the pooled sensitivity and specificity were 91.2% (84.3-95.2%) and 80% (64.3-89.9%). Nine studies (478 patients) assessed AI capabilities of diagnosing esophageal adenocarcinoma with the pooled sensitivity and specificity of 93.1% (86.8-96.4) and 86.9% (81.7-90.7). The remaining studies formed the qualitative summary. AI technology, as an adjunct to endoscopy, can assist in accurate, early detection of esophageal malignancy. It has shown superior results to endoscopists alone in identifying early cancer and assessing depth of tumor invasion, with the added benefit of not requiring a specialized skill set. Despite promising results, the application in real-time endoscopy is limited, and further multicenter trials are required to accurately assess its use in routine practice.

Interpretation of Tumor Response Grade following Preoperative Therapy for Gastric Cancer: An Overview.

Gastric cancer is among the top five causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. A pathologic response to preoperative therapies, called the Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, the literature has demonstrated inconsistent results for TRG systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic responses to preoperative therapies using RECIST 1.1 criteria and endoscopically assessed tumor response have demonstrated association with survival; however, their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy, where treatment-related changes can obscure the gastric wall layers. While the response to preoperative therapies with positron emission tomography (PET) has shown promising results in esophageal and esophagogastric junction (EGJ) malignancies, its role in gastric cancer is still under investigation. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview of the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis.

#6612 ACUTE KIDNEY INJURY ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITOR THERAPY: REPORT OF 4 CASES

Abstract Background and Aims Immunotherapy using immune check point inhibitors (ICIs) is the cornerstone of modern cancer therapy. Despite significant clinical benefits, ICIs are associated with remarkable adverse events of autoimmune nature involving various organs. Acute Kidney Injury (AKI) occurs more rarely, mainly with the appearance of acute interstitial nephritis. We present a series of patients with AKI after administration of immunotherapy with ICIs. Method Patient 1 with metastatic small cell lung cancer on immunotherapy with atezolizumab presented with purpura on the trunk and lower extremities, AKI, microscopic glomerular hematuria, and proteinuria. Patient 2 with esophageal malignancy on immunotherapy with pembrolizumab and worsening renal function. Patient 3 with endometrial malignancy on immunotherapy with pembrolizumab developed AKI, nephrotic syndrome and microscopic hematuria. Patient 4 with melanoma on immunotherapy with pembrolizumab presented with microscopic hematuria and rash. Results A kidney biopsy was performed in all 4 patients unreavealling the following; Patient 1: pauci-immune necrotizing glomerulonephritis with fibrinoid necrosis and inflammation in the wall of a vessel. Patient 2: acute interstitial nephritis with intense inflammation. Patient 3: findings consistent with focal segmental glomerulosclerosis (FSGS, NOS), without evidence of immune complex disease. Patient 4: focal segmental glomerulosclerosis, moderate interstitial fibrosis and interstitial nephritis in remission. The patient had already been treated with glucocorticoid. In all 4 patients immunotherapy was temporarily discontinued and they were treated with intravenous pulses of methyl-prednisolone followed by oral glucocorticoids, with significant improvement of kidney function and resolution of all extra renal manifestation i.e skin rash etc. Escalation of immunosuppressive therapy with the addition of another agent was avoided in order not to cause relapse of the malignancy. Conclusion AKI is a rare but potentially serious complication of ICIs. Temporal discontinuation of the implicated agent is of major importance while treatment with glucocorticoids may be critical for kindey function. Yet, constant vigilance and sustained collaboration among medical specialists are becoming essential in the increasing use of immunotherapy.

M1A and m7G modification-related genes are potential biomarkers for survival prognosis and for deciphering the tumor immune microenvironment in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is the most common esophageal malignancy, and RNA methylation has been reported to be involved in the tumorigenesis of ESCC. However, no study has explored methylation modifications in m1A and m7G as prognostic markers for survival prediction in ESCC.MethodsPublic gene-expression data and clinical annotation of 254 patients obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases were analyzed to identify potential consensus clusters of m1A and m7G modification-related genes. The RNA-seq of 20 patients in Sun Yat-Sen University Cancer Center was used as the validation set. Following screening for relevant differentially expressed genes (DEGs) and enrichment pathways were elucidated. DEGs were used to construct risk models using the randomForest algorithm, and the prognostic role of the models was assessed by applying Kaplan–Meier analysis. Extent of immune cell infiltration, drug resistance, and response to cancer treatment among different clusters and risk groups were also evaluated.ResultsConsensus clustering analysis based on m1A and m7G modification patterns revealed three potential clusters. In total, 212 RNA methylation-related DEGs were identified. The methylation-associated signature consisting of 6 genes was then constructed to calculate methylation-related score (MRScore) and patients were dived into MRScore-high and MRScore-low groups. This signature has satisfied prognostic value for survival of ESCC (AUC = 0.66, 0.67, 0.64 for 2-, 3-, 4- year OS), and has satisfied performance in the validation SYSUCC cohort (AUC = 0.66 for 2- and 3-year OS). Significant correlation between m1A and m7G modification-related genes and immune cell infiltration, and drug resistance was also observed.ConclusionsTranscriptomic prognostic signatures based on m1A and m7G modification-related genes are closely associated with immune cell infiltration in ESCC patients and have important correlations with the therapeutic sensitivity of multiple chemotherapeutic agents.

Abstract 363: Modelling cancer cachexia using a comprehensive panel of heterogeneous esophageal squamous cell carcinoma xenografts for therapeutic application

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is one of deadliest esophageal malignancies in Asia. Cancer cachexia is a multifactorial body wasting syndrome and is one of the major causes of death in late-stage patients (1). It is characterized by skeletal muscle loss and atrophy, adipose and body wasting, and metabolic dysregulations and stress (1). ESCC is one of the cancer types with the highest morbidity and mortality rates due to cancer cachexia (2). However, there are few effective and approved treatments targeting cancer cachexia. Currently, cancer cachexia animal models are highly limited with few cancer types available as a pre-clinical drug testing platform, with none related to esophageal carcinoma (3). Results: Here we have developed a panel of ESCC patient-derived organoid xenograft (PDOX) mouse model based on our latest patient-derived organoid cultures originating from Hong Kong patients. Our immunodeficient mouse-based PDOX model resembles different cachexic phenotypes that cell line-derived xenograft lacks, including body (skeletal muscle and adipose tissue) wasting and functional signs (e.g. lack of body movement, reduced muscle strength, and loss of appetite). The slow-proliferating characteristic of the ESCC PDOX allows development of a cachexic condition before humane endpoint. Furthermore, our full panel of PDOX lines allowed us to identify the full spectrum, differential cachexia severity across mice bearing different PDOXs, indicating a heterogenous nature. We have comprehensively characterized the cachexia phenotypes and performed proof-of-concept preclinical drug tests using established anti-cachexic drugs; treated PDOX-bearing mice have improved body condition and function compared to the control, which were further verified by histological examinations of tissue samples. Molecular analysis showed that several classic cachexia related gene expressions were down-regulated in isolated liver (Il1b) and inguinal adipose tissues (adipose triglyceride lipase). Conclusions: Our ESCC PDOX model potentially serves as a great pre-clinical cachexia-targeted drug testing platform, providing more treatment options for ESCC patients for better disease management. Acknowledgement: We acknowledge the Research Grants Council (TRS T12-701/17-R to MLL) and the Food and Health Bureau (HMRF 06171566 to VZY) of Hong Kong Special Administrative Region for funding supports. We acknowledge DSMZ for the KYSE cell lines. We acknowledge the HKUMed-CPOS for providing imaging facilities.

Clinicopathological correlation of aspartate aminotransferase-to-platelet ratio (APRI) and aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) with survival in esophageal carcinoma patients: a retrospective cohort analysis of 951 patients.

The objectives of the current study were to associate novel markers, including aspartate aminotransferase-to-platelet ratio (APRI) and aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) with survival in esophageal malignancy. A retrospective study in a tertiary care hospital (single-center) included 951 patients having diagnosed esophageal carcinoma of any age group. The median (interquartile range) age of study participants were 50 (38-60) years, including 43% males and 57% female patients, while the median (interquartile range) levels of AAR and APRI were 0.97 (0.81-1.25) and 0.19 (0.13-0.29), respectively. AAR was found to be higher in dysphagia for solids only and dysphagia for both liquids and solids rather than liquids only (P=0.002), while other associations included well-differentiated tumor grade (P=0.011), finding of esophageal stricture on esophagogastroduodenoscopy (P=0.015), and characteristic of mass on computerized tomography scan being both circumferential and mural (P=0.005). APRI was found to be higher in adenocarcinoma (P=0.038), and finding of circumferential±ulcerated mass on esophagogastroduodenoscopy (P<0.001). On survival analysis, adenocarcinoma (P<0.001), luminal narrowing (P=0.002), AAR greater than 1.0 (P=0.006), and APRI greater than 0.2 (P=0.007) were found to be poor survival predictors. On Cox proportional hazards regression, APRI was found to be more associated with poor survival than AAR (Hazard ratio: 1.682, 1.208-2.340, P=0.002). This study correlated clinical and pathological features of esophageal malignancy with noninvasive markers of hepatic function.

Escherichia fergusonii bacteremia after esophagectomy: a case report and literature review

We report the case of a 68-year-old man who experienced Escherichia fergusonii bacteremia after esophageal cancer surgery. The patient presented with complaints of abdominal pain persisting for 1 week. The patient was diagnosed with esophageal malignancy, which was confirmed by surgical exploration and pathological biopsy. The patient developed septic shock on postoperative day 12, and blood culture suggested the growth of E. fergusonii. After treatment with meropenem, the patient's clinical symptoms improved significantly, and the second culture was negative. In this paper, we discuss the characteristics, diagnosis, and treatment of E. fergusonii. E. fergusonii is rarely reported, and its pathogenesis, drug resistance, and potential effects have not been completely confirmed. Thus, this case report adds valuable knowledge to the literature on E. fergusonii.

Robotic assisted laryngopharyngoesophagectomy in an advanced carcinoma of hypopharynx- assistance of newer surgical armamentarium in an advanced malignancy

Still in today's advanced era to reconstruct surgical abnormalities following removal of upper airway and proximal esophageal malignancies is regarded a herculean task which does require tremendous surgical experience and expertise and multidisciplinary team work. In this short communication we are presenting a case of advanced carcinoma hypopharynx which was surgically managed with laryngopharyngoesophagectomy with Robotic assistance.

TACH101, a first-in-class pan-inhibitor of KDM4 histone demethylase.

Histone lysine demethylase 4 (KDM4) is an epigenetic regulator that facilitates the transition between transcriptionally silent and active chromatin states by catalyzing the removal of methyl groups on histones H3K9, H3K36, and H1.4K26. KDM4 overamplification or dysregulation has been reported in various cancers and has been shown to drive key processes linked to tumorigenesis, such as replicative immortality, evasion of apoptosis, metastasis, DNA repair deficiency, and genomic instability. KDM4 also plays a role in epigenetic regulation of cancer stem cell renewal and has been linked to more aggressive disease and poorer clinical outcomes. The KDM4 family is composed of four main isoforms (KDM4A-D) that demonstrate functional redundancy and cross-activity; thus, selective inhibition of one isoform appears to be ineffective and pan-inhibition targeting multiple KDM4 isoforms is required. Here, we describe TACH101, a novel, small-molecule pan-inhibitor of KDM4 that selectively targets KDM4A-D with no effect on other KDM families. TACH101 demonstrated potent antiproliferative activity in cancer cell lines and organoid models derived from various histologies, including colorectal, esophageal, gastric, breast, pancreatic, and hematological malignancies. In vivo , potent inhibition of KDM4 led to efficient tumor growth inhibition and regression in several xenograft models. A reduction in the population of tumor-initiating cells was observed following TACH101 treatment. Overall, these observations demonstrate the broad applicability of TACH101 as a potential anticancer agent and support its advancement into clinical trials.