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1.
BMC Cancer ; 24(1): 596, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755542

ABSTRACT

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Neoplasm Recurrence, Local , Humans , Male , Female , Middle Aged , Esophageal Neoplasms/pathology , Esophageal Neoplasms/radiotherapy , Esophageal Neoplasms/surgery , Retrospective Studies , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Aged , Lymph Nodes/pathology , Lymph Nodes/surgery , Esophageal Squamous Cell Carcinoma/surgery , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/radiotherapy , Esophagectomy , Adult , Prognosis , China/epidemiology , Neoplasm Staging
3.
Pol Przegl Chir ; 96(2): 21-25, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38629277

ABSTRACT

<b><br>Indroduction:</b> Significant dysphagia, aspiration pneumonia, and impossible oral nutrition in patients with unresectable or recurrent gastroesophageal malignancy or bronchial cancer invading the oesophagus with a tracheoesophageal fistula lead to cachexia. Dehiscence of the esophago-jejunal or gastroesophageal anastomosis may cause severe oesophageal haemorrhage. We believe that X-ray-guided oesophageal stent implantation (SEMS) is an alternative palliative method for microjejunostomy or full parenteral nutrition.</br> <b><br>Aim:</b> The aim of this paper was to assess the safety and efficacy of a novel X-ray-guided oesophageal stent implantation technique.</br> <b><br>Materials and methods:</b> This retrospective analysis included 54 patients (35 men and 19 women) treated for malignant dysphagia, gastroesophageal/gastrointestinal anastomotic fistula or bronchoesophageal fistula in two Surgical Units between 2010 and 2019, using a modified intravascular approach to oesophageal stent implantation.</br> <b><br>Results:</b> The presented modified intravascular method of oesophageal stent implantation was successfully performed in all described patients requiring oral nutrition restoration immediately following oesophageal stent implantation. Two patients with oesophageal anastomotic dehiscence died on postoperative days 7 and 9 due to circulatory and respiratory failure. One patient was reimplanted due to a recurrent fistula. Two patients with ruptured thoracic aneurysm and thoracic stent graft implantation due to oesophageal haemorrhage, who were implanted with an oesophageal stent, died on postoperative days 4 and 14.</br> <b><br>Conclusions:</b> The modified intravascular X-ray-guided SEMS technique may be a palliative treatment for patients with unresectable oesophageal malignancies.</br>.


Subject(s)
Carcinoma , Deglutition Disorders , Esophageal Neoplasms , Tracheoesophageal Fistula , Male , Humans , Female , Deglutition Disorders/etiology , Deglutition Disorders/surgery , X-Rays , Retrospective Studies , Neoplasm Recurrence, Local , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgery , Carcinoma/etiology , Stents/adverse effects , Hemorrhage/etiology
4.
J Cell Mol Med ; 28(6): e18195, 2024 03.
Article in English | MEDLINE | ID: mdl-38429907

ABSTRACT

METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.


Subject(s)
Carcinoma , Esophageal Neoplasms , Methyltransferases , Humans , Biomarkers , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Glycolysis/genetics , Lactic Acid , Methyltransferases/genetics , RNA, Competitive Endogenous
5.
BMC Genomics ; 25(1): 135, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38308202

ABSTRACT

INTRODUCTION: Pseudogenes have been implicated for their role in regulating cellular differentiation and organismal development. However, their role in promoting cancer-associated differentiation has not been well-studied. This study explores the tumour landscape of oesophageal carcinoma to identify pseudogenes that may regulate events of differentiation to promote oncogenic transformation. MATERIALS AND METHOD: De-regulated differentiation-associated pseudogenes were identified using DeSeq2 followed by 'InteractiVenn' analysis to identify their expression pattern. Gene expression dependent and independent enrichment analyses were performed with GSEA and ShinyGO, respectively, followed by quantification of cellular reprogramming, extent of differentiation and pleiotropy using three unique metrics. Stage-specific gene regulatory networks using Bayesian Network Splitting Average were generated, followed by network topology analysis. MEME, STREME and Tomtom were employed to identify transcription factors and miRNAs that play a regulatory role downstream of pseudogenes to initiate cellular reprogramming and further promote oncogenic transformation. The patient samples were stratified based on the expression pattern of pseudogenes, followed by GSEA, mutation analysis and survival analysis using GSEA, MAF and 'survminer', respectively. RESULTS: Pseudogenes display a unique stage-wise expression pattern that characterizes stage II (SII) ESCA with a high rate of cellular reprogramming, degree of differentiation and pleiotropy. Gene regulatory network and associated topology indicate high robustness, thus validating high pleiotropy observed for SII. Pseudogene-regulated expression of SOX2, FEV, PRRX1 and TFAP2A in SII may modulate cellular reprogramming and promote oncogenesis. Additionally, patient stratification-based mutational analysis in SII signifies APOBEC3A (A3A) as a potential hallmark of homeostatic mutational events of reprogrammed cells which in addition to de-regulated APOBEC3G leads to distinct events of hypermutations. Further enrichment analysis for both cohorts revealed the critical role of combinatorial expression of pseudogenes in cellular reprogramming. Finally, survival analysis reveals distinct genes that promote poor prognosis in SII ESCA and patient-stratified cohorts, thus providing valuable prognostic bio-markers along with markers of differentiation and oncogenesis for distinct landscapes of pseudogene expression. CONCLUSION: Pseudogenes associated with the events of differentiation potentially aid in the initiation of cellular reprogramming to facilitate oncogenic transformation, especially during SII ESCA. Despite a better overall survival of SII, patient stratification reveals combinatorial de-regulation of pseudogenes as a notable marker for a high degree of cellular differentiation with a unique mutational landscape.


Subject(s)
Carcinoma , Cytidine Deaminase , Esophageal Neoplasms , Proteins , Humans , Pseudogenes , Bayes Theorem , Carcinogenesis/genetics , Esophageal Neoplasms/genetics , Cellular Reprogramming , Carcinoma/genetics , Homeodomain Proteins/genetics
6.
BMC Cancer ; 23(1): 505, 2023 Jun 04.
Article in English | MEDLINE | ID: mdl-37270496

ABSTRACT

BACKGROUND: The systemic inflammation score (SIS), based on serum albumin (Alb) and lymphocyte-to-monocyte ratio (LMR), is a novel prognostic tool for some tumours. Studies indicate that the SIS can be used as a postoperative prognostic marker. However, its predictive value in elderly oesophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is unclear. METHODS: In total, 166 elderly ESCC patients who received radiotherapy with or without chemotherapy were included. Based on different combinations of Alb and LMR levels, the SIS was divided into 3 groups, SIS = 0 (n = 79), SIS = 1 (n = 71) and SIS = 2 (n = 16). The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to assess prognosis. Time-dependent receiver operating characteristic (t-ROC) curves were used to compare the prognostic accuracy of the SIS with that of Alb, LMR, neutrophil-to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). RESULTS: Decreased Alb and LMR were both associated with shorter OS, whereas a lower SIS was significantly associated with better outcomes. The OS of SIS = 0, SIS = 1 and SIS = 2 was 28.0 ± 2.9, 16.0 ± 2.8 and 10.0 ± 7.0 months, respectively (p = 0.000). Similar results were also observed for PFS. Multivariate analysis of the model with SIS revealed that the SIS was a significant independent biomarker for predicting OS and PFS. The nomogram showed that the C-index was improved to 0.677 when the SIS factor was incorporated. Furthermore, the 3-year OS rates for patients in the SIS-high group (SIS = 1 and SIS = 2) undergoing concurrent radiotherapy with a single agent (CCRT-1) and concurrent radiotherapy with two agents (CCRT-2) were 42% and 15%, respectively (p = 0.039). The t-ROC curve showed that the SIS was more sensitive than other prognostic factors for predicting overall survival. CONCLUSION: The SIS may be a useful prognostic marker in elderly patients with ESCC receiving radiotherapy alone or chemoradiotherapy. The SIS showed a better predictive ability for OS than the continuous variable Alb and could stratify patient prognosis in different therapeutic regimens. CCRT-1 may be the best treatment for SIS-high patients.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Aged , Prognosis , Case-Control Studies , Retrospective Studies , Inflammation/pathology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Lymphocytes/pathology , Neutrophils/pathology
7.
Cancer Med ; 12(13): 14037-14051, 2023 07.
Article in English | MEDLINE | ID: mdl-37306615

ABSTRACT

OBJECTIVES: To statistically study the 3D shape of oesophageal cancer (EC) and its spatial relationships based on computed tomography angiography (CTA) 3D reconstruction, to determine its relationship with T-stages, and to create an optimal T-stage diagnosis protocol based on CTA calculation. METHODS: Pre-operative CTA images of 155 patients with EC were retrospectively collected and divided into four groups: T1-T4. We used Amira software to segment and 3D reconstruct the EC, oesophagus, aorta, pericardium and peripheral lymph nodes and measured their surface area, volume, major axis, minor axis, longitudinal length, roughness and relationship to the aorta of the EC. One-way ANOVA, independent sample t-test, ROC, etc., were performed and critical values between different T-stages were calculated. We also invited two radiologists to evaluate the measurements. RESULTS: There were no significant differences in EC longitudinal length, roughness score and relationship with the aorta between the different T-stages of EC. There were significant differences in EC surface area, EC volume and mean major and minor axis among the different T-stages. The volumes of the T1-T4 tumours were 12,934.36 ± 7739.25, 23,095.27 ± 14,975.67, 37,577.98 ± 36,085.64 and 58,579.25 ± 41,073.96 mm3 separately (p < 0.05), and the T1-T4 volume cut-off values were 11,712.00, 19,809.00 and 44,103.50 mm3 separately. For comparison with radiologists, the AUC value of our measurements was 0.704, which was higher than the radiologists of AUC = 0.630. CONCLUSIONS: EC volume, major and minor axis can be used as important factors for surgeons in the T-stage diagnosis of EC, which helps to improve prognosis and treatment decisions after CTA.


Subject(s)
Computed Tomography Angiography , Esophageal Neoplasms , Humans , Tumor Burden , Retrospective Studies , Tomography, X-Ray Computed/methods , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery
8.
BMC Cancer ; 23(1): 293, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37004010

ABSTRACT

BACKGROUND: This cross-sectional cohort study assessed the inequalities in oesophageal carcinoma risk by age, sex and nativity in Kuwait: 1980-2019. METHODS: Using oesophageal cancer incidence data from the Kuwait National Cancer Registry, relevant Kuwaiti population data and World Standard Population as a reference, age-standardized incidence rates (ASIR) (per 100,000 person-years) overall and by subcohorts were computed. The incident oesophageal cancer cases count was overdispersed with excessive structural zeros, therefore, it was analyzed using multivariable zero-inflated negative binomial (ZINB) model. RESULTS: Overall ASIR of oesophageal cancer was 10.51 (95% CI:  6.62-14.41). The multivariable ZINB model showed that compared with the younger age category (< 30 years), the individuals in higher age groups showed a significant (p < 0.001) increasing tendency to develop the oesophageal cancer.  Furthermore, compared with the non-Kuwaiti residents, the Kuwaiti nationals were significantly (p < 0.001) more likely to develop oesophageal cancer during the study period. Moreover, compared with 1980-84 period, ASIRs steadily and significantly  (p < 0.005) declined in subsequent periods till 2015-19. CONCLUSIONS: A high incidence of oesophageal cancer was recorded in Kuwait, which consistently declined from 1980 to 2019. Older adults (aged ≥ 60 years) and, Kuwaiti nationals were at high risk of oesophageal cancer. Focused educational intervention may minimize oesophageal cancer incidence in high-risk groups in this and other similar settings. Future studies may contemplate to evaluate such an intervention.


Subject(s)
Carcinoma , Esophageal Neoplasms , Humans , Aged , Cross-Sectional Studies , Incidence , Kuwait/epidemiology , Esophageal Neoplasms/epidemiology
9.
Eur J Clin Invest ; 53(4): e13929, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36453878

ABSTRACT

BACKGROUND: Oesophageal carcinoma (EC) is one of the types of prevalent malignant cancer in the globe. Many researchers reported the vital role played by long-coding RNAs in EC. In the current research, we investigated the mechanisms of the action of lncRNA BBOX1-AS1 in EC progression. METHODS: In EC tissues and EC cells, the expression levels of miR-361-3p along with COL1A1 and BBOX1-AS1 were detected through RT-qPCR or western blotting. MiR-361-3p interactions with BBOX1-AS1 or COL1A1 were verified through Luciferase reporter and RIP tests. Loss of function combined with caspase-3 activity, CCK-8 and Transwell assays was performed to investigate cell apoptosis, proliferation and migration, respectively. Knockdown of BBOX1-AS1 was used for evaluating BBOX1-AS1 effects on tumour development in vivo. RESULTS: BBOX1-AS1 was remarkably elevated in EC tissues and cells. In addition, the silencing of BBOX1-AS1 attenuated the cell viability, cell migration and enhanced cell apoptosis of EC, as well as suppressed EC tumour formation in vivo. Moreover, BBOX1-AS1 was found to be a sponge of miR-361-3p, which downregulated miR-361-3p expression. MiR-361-3p inhibitor rescued the anti-tumour effect of BBOX1-AS1 knockdown on the progression of EC. Furthermore, we discovered that miR-361-3p specially bound to COL1A1 3'UTR and downregulated COL1A1 and COL1A1 reduction declined the promoting effect of silencing miR-361-3p on EC cell malignant phenotypes. CONCLUSION: BBOX1-AS1 facilitated the EC development and malignancy via miR-361-3p/COL1A1 axis, indicating BBOX1-AS1 could be a novel therapy target for the diagnostic of EC.


Subject(s)
Esophageal Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Apoptosis , Blotting, Western , Cell Movement , Cell Proliferation , Cell Line, Tumor , Gene Expression Regulation, Neoplastic
10.
BMC Cancer ; 22(1): 1329, 2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36536299

ABSTRACT

BACKGROUND: Lymphovascular invasion (LVI) is a factor correlated with a poor prognosis in oesophageal squamous cell carcinoma (ESCC). Lymphatic invasion (LI) and vascular invasion (VI) should be reported separately because they may indicate a difference in prognosis. The prognostic role of LI and VI in ESCC patients remains controversial. A meta-analysis was conducted to resolve this question. METHODS: We searched the PubMed, EMBASE, Web of Science, Scopus and Cochrane Library databases for studies on the association between LI and VI and the prognosis of patients with ESCC. The PICOs (Participant, Intervention, Comparison, Outcome) strategy were selected for the systematic review and meta-analysis. The effect size (ES) was the hazard ratio (HR) or relative ratio (RR) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS). RESULTS: A total of 27 studies with 5740 patients were included. We calculated the pooled results from univariate and multivariate analysis using the Cox proportional hazards method. The heterogeneity was acceptable in OS and RFS. According to the pooled results of multivariate analysis, both LI and VI were correlated with a worse OS. VI was a negative indicator for RFS, while the p value of VI was greater than 0.05. The prognostic role was weakened in subgroup analysis with studies using haematoxylin-eosin staining method. CONCLUSIONS: Both LI and VI were indicators of a worse OS outcome. LI was a more significant indicator in predicting a worse RFS. More larger sample studies with immunohistochemical staining and good designs are required to detect the prognostic value of separate LI and VI in ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Neoplasms/pathology , Prognosis , Proportional Hazards Models
11.
BMC Surg ; 22(1): 225, 2022 Jun 11.
Article in English | MEDLINE | ID: mdl-35690775

ABSTRACT

BACKGROUND: The gastric conduit is the best replacement organ for oesophageal reconstruction, but a reversed gastric conduit (RGC) is rare. Oesophageal reconstruction for oesophageal cancer patients with a previous history of complicated gastrointestinal surgery is rather difficult. Here, we report a case in which oesophageal reconstruction was successfully managed using RGC based solely on the left gastroepiploic artery supply. CASE PRESENTATION: A 69-year-old man with oesophageal cancer had a history of endoscopic intestinal polypectomy and pylorus-preserving pancreaticoduodenectomy (PPPD). The right gastroepiploic artery and right gastric artery had been completely severed. The only supply artery that could be used for the gastric conduit was just the left gastroepiploic artery. Because of the complex history of abdominal surgery, we had no choice but to use the RGC to complete the oesophageal reconstruction, in which the gastric conduit was passed reversely through the hiatus to the oesophageal bed and layered end-to-side manual intrathoracic anastomosis with the esophagus. The patient had transient feeding problems with postoperative delayed thoracic stomach emptying but no anastomotic stenosis or thoracic stomach fistula. He was satisfied with his life and had no long-term complications. There was no significant effect on gut physiological function, and RGC could work normally. CONCLUSIONS: Oesophageal reconstruction with RGC is a feasible procedure for complex oesophageal carcinoma that can simplify complicated surgical procedures, has less influence on gut function, is less invasive, and is safe.


Subject(s)
Esophageal Neoplasms , Gastric Emptying , Aged , Anastomosis, Surgical , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgery , Humans , Male , Pancreaticoduodenectomy/methods , Postoperative Complications/surgery , Pylorus/surgery , Stomach/blood supply , Stomach/surgery
12.
Surg Endosc ; 36(11): 8364-8370, 2022 11.
Article in English | MEDLINE | ID: mdl-35534732

ABSTRACT

BACKGROUND: Stenting is the management of choice for many benign and malignant oesophageal conditions and in the interest of safety stent insertion has traditionally been performed under fluoroscopic guidance. But this incurs additional expense, time, radiation risk and for the foreseeable future, an increased risk of Covid infection to patients and healthcare personnel. We describe a protocol that obviates the need for fluoroscopic guidance, relying instead on a systematic checklist to ensure safe positioning of the guidewire and the accurate positioning of the stent. The aim of this retrospective study was to review our experience of stent insertion employing a checklist system and compare our outcomes with outcomes using fluoroscopy in the literature. METHODS: We performed a retrospective review of a prospectively collected dataset of all patients undergoing oesophageal stent insertion between December 2007 and October 2019. The primary end points were patient safety parameters and complications of stent insertion. RESULTS: Total of 163 stents were deployed of which 93 (57%) were in males and the median age was 67.9 years (25-92 years). Partially covered self-expanding metallic stents (SEMS) were used in 80% of procedures (130/163). One hundred nineteen stents (73%) were for malignant strictures and 127 (78%) were deployed for strictures in the lower third of the oesophagus. There was no stent misplacement, injury, perforation or death associated with the procedure. Vomiting was the main post-operative complication (14%). Severe odynophagia necessitated stent removal in 3 patients. Stent migration occurred in 17 (10%) procedures with a mean time to stent migration of 6.4 weeks (range 1-20 weeks). CONCLUSIONS: Oesophageal stent placement without fluoroscopy is safe provided that a strict checklist is adhered to. The outcomes are comparable to the results of fluoroscopic stent placement in the literature, with considerable saving in time, cost, personnel, and risks of radiation and Covid exposure.


Subject(s)
COVID-19 , Esophageal Neoplasms , Male , Humans , Aged , Retrospective Studies , Checklist , Constriction, Pathologic/etiology , Treatment Outcome , Stents/adverse effects , Fluoroscopy , Esophagus , Palliative Care/methods , Esophageal Neoplasms/surgery
13.
J Med Ultrasound ; 30(1): 47-49, 2022.
Article in English | MEDLINE | ID: mdl-35465584

ABSTRACT

Intramural gastric metastasis of the esophageal carcinoma, excluding the direct extension of primary neoplasm, is rare. However, intramural metastasis to the esophagus is commoner than this. These are more common in squamous cell carcinoma variant. This signifies a poor prognosis. It is due to the spread of pathology through the intramural lymphatic channels. Sometimes the metastatic lesion is more extensive in volume than the primary. This is more often diagnosed on histopathology in postoperative specimens. We share our imaging experience with surface esophageal squamous cell carcinoma with giant intramural gastric metastasis infiltrating the liver in a 39-year-old male. Due to its rarity, and secondary lesion being more extensive than the primary leads to misinterpretation and wrong diagnosis. Knowledge of this rare phenomenon can prevent misdiagnosis, fasten the imaging workup, and ultimately improve the patient's survival.

14.
Cell Mol Life Sci ; 79(5): 243, 2022 Apr 16.
Article in English | MEDLINE | ID: mdl-35429253

ABSTRACT

Bile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array of metabolites. The bulk of bile acid synthesis takes place in the liver yielding primary bile acids; however, other tissues have also the capacity to generate bile acids (e.g. ovaries). Hepatic bile acids are then transported to bile and are subsequently released into the intestines. In the large intestine, a fraction of primary bile acids is converted to secondary bile acids by gut bacteria. The majority of the intestinal bile acids undergo reuptake and return to the liver. A small fraction of secondary and primary bile acids remains in the circulation and exert receptor-mediated and pure chemical effects (e.g. acidic bile in oesophageal cancer) on cancer cells. In this review, we assess how changes to bile acid biosynthesis, bile acid flux and local bile acid concentration modulate the behavior of different cancers. Here, we present in-depth the involvement of bile acids in oesophageal, gastric, hepatocellular, pancreatic, colorectal, breast, prostate, ovarian cancer. Previous studies often used bile acids in supraphysiological concentration, sometimes in concentrations 1000 times higher than the highest reported tissue or serum concentrations likely eliciting unspecific effects, a practice that we advocate against in this review. Furthermore, we show that, although bile acids were classically considered as pro-carcinogenic agents (e.g. oesophageal cancer), the dogma that switch, as lower concentrations of bile acids that correspond to their serum or tissue reference concentration possess anticancer activity in a subset of cancers. Differences in the response of cancers to bile acids lie in the differential expression of bile acid receptors between cancers (e.g. FXR vs. TGR5). UDCA, a bile acid that is sold as a generic medication against cholestasis or biliary surge, and its conjugates were identified with almost purely anticancer features suggesting a possibility for drug repurposing. Taken together, bile acids were considered as tumor inducers or tumor promoter molecules; nevertheless, in certain cancers, like breast cancer, bile acids in their reference concentrations may act as tumor suppressors suggesting a Janus-faced nature of bile acids in carcinogenesis.


Subject(s)
Bile Acids and Salts , Esophageal Neoplasms , Bile Acids and Salts/metabolism , Carcinogenesis/pathology , Esophageal Neoplasms/metabolism , Humans , Liver/metabolism , Male
15.
Front Oncol ; 12: 839516, 2022.
Article in English | MEDLINE | ID: mdl-35280748

ABSTRACT

Background: The oesophageal carcinoma patients show high incidence of malnutrition, which negatively affects their therapy outcome. Moreover, benefits of enteral nutrition remain to be studied in details in these patients. Therefore, we set to assess the effects of enteral nutrition on the nutritional status, treatment toxicities and survival in the oesophageal carcinoma patients treated with concurrent chemoradiotherapy (CCRT). Materials and Methods: Eligible patients were randomly assigned to either the experimental or control group. The patients in the experimental group were treated with a whole-course enteral nutrition management, while the control group were provided a unsystematic nutrition without setting intake goals for energy and protein. The primary endpoint was a change in body weight, while the secondary endpoints included nutrition-related haematological indicators, toxicities, completion rate of treatment and survival. Results: A total of 222 patients were randomised to either the experimental (n=148) or control (n=74) group. Patients in the experimental group showed significantly less decrease in body weight, serum albumin and haemoglobin levels, a lower incidence rates of grade ≥3 myelosuppression and infection, and a higher completion rate of CCRT than those in the control group. While analyses of the 2 and 3 year overall survival (OS) and progression-free survival (PFS) did not reveal differences between these groups, we observed a significantly higher OS at 1 year (83.6% vs. 70.0%). In the subgroup analysis, patients with patient-generated subjective global assessment (PG-SGA)=C were likely to have better OS and PFS with enteral nutrition. Conclusions: In EC patients treated with CCRT, enteral nutrition conferred positive effects on the nutritional status, treatment toxicities and prognosis, which mandate its inclusion in clinical practice. Clinical Trial Registration: This prospective trial has been registered with www.clinicaltrials.gov as NCT02399306.

16.
Int J Surg Case Rep ; 90: 106749, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34999470

ABSTRACT

INTRODUCTION AND IMPORTANCE: This case report describes postoperative complications in a patient after hybrid oesophagectomy for oesophageal carcinoma after COVID pneumonia. The global COVID-19 pandemic affected cancer patients indicated for surgery. Covid 19 may worsen the results of oesophageal cancer surgery. More similar studies are needed. CASE PRESENTATION: A 69-year-old male was diagnosed with squamous cell carcinoma of the middle oesophagus based on PET/CT without disease generalisation. His stenotic tumour required a nutritive jejunostomy, with subsequent neoadjuvant radiochemotherapy indicated according to the CROSS protocol. The patient developed COVID pneumonia during the cancer therapy. After managing the COVID pneumonia, oncological therapy was completed and a hybrid oesophagectomy was performed 8 weeks later. Serious complications (respiratory failure, septic shock, anastomosis dehiscence) developed during the postoperative period. All complications were managed therapeutically. The patient was type IVb according to the Clavien-Dindo classification. CLINICAL DISCUSSION: Postoperative complications may develop in any patient operated for oesophageal carcinoma, especially if high-risk predictive factors are present. The question arises as to how much the post-COVID condition affected the onset of these serious complications. CONCLUSION: Post-COVID patients are at a risk of developing post-COVID syndrome, which may lead to a wide range of symptoms in the affected organs. Further studies on the relationship between COVID-19 and oesophagectomy for oesophageal carcinoma will be necessary to clarify the relationship between the complications during the postoperative period in patients with oesophageal malignancy.

17.
Tumour Virus Res ; 13: 200231, 2022 06.
Article in English | MEDLINE | ID: mdl-34920177

ABSTRACT

Oesophageal carcinoma ranks the sixth leading cause of cancer death and affected 544,000 - 604,000 people in 2020. Patients often presented with a poor cancer prognosis with a low survival rate of 15-25%. Depending upon the cell type, oesophageal carcinoma is categorised into oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC). ESCC is predominantly reported in developing countries, while EAC is more common in developed countries. Aside from the presence of exogenous co-factors, such as cigarette smoking, alcohol consumption, obesity, gastroesophageal reflux disease (GERD); infection with oncogenic viruses is suspected to be one of the major factors contributing to EC development. Oncogenic viruses, including human papillomavirus (HPV), Epstein Barr virus (EBV), Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) have been detected in various proportions of EC samples. Nonetheless, their aetiological roles in EC remain debatable. In this review, we garnered previous studies that focus on the association between oncogenic viruses and EC. Among these oncogenic viruses, HPV appears to have a stronger association with EC than the others. In addition, we also discuss the pros and cons of the treatment regimens to treat EC patients, including immunotherapy, chemo- and chemoradiotherapy, and their efficacy.


Subject(s)
Alphapapillomavirus , Carcinoma , Epstein-Barr Virus Infections , Papillomavirus Infections , Carcinoma/complications , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/genetics , Humans , Papillomaviridae/genetics , Papillomavirus Infections/complications , Prevalence
18.
J Clin Orthop Trauma ; 24: 101725, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34926153

ABSTRACT

Muscle metastasis is uncommon. We present second reported case of ossifying metastasis from oesophageal carcinoma and review the literature. Our case highlights the different patterns of ossification in muscle, which is essential to make the diagnosis of myositis ossificans, a "don't touch lesion" in contrast to muscle metastasis or tumour, that needs oncological management.

19.
J Med Imaging Radiat Oncol ; 65(7): 925-930, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34405578

ABSTRACT

INTRODUCTION: Definitive chemoradiotherapy (dCRT) and radical radiotherapy are central to the management of distal oesophageal carcinoma. This study sought to establish whether the spleen receives a significant incidental radiation dose when treating distal oesophageal carcinoma with the standardised dCRT or radical radiotherapy doses. METHODS: In this single-centre retrospective study, all patients (n = 34) with distal oesophageal cancer, treated with either dCRT or radical radiotherapy over an 18-month period using a volumetric modulated arc therapy (VMAT) planning technique, were included. The median age was 74 years old: 56% were male; 50% (n = 17) had adenocarcinoma and 41% (n = 14) had squamous carcinoma. The majority (79%) received dCRT with a prescribed dose of 50 Gy in 25 fractions while the other 21% of patients were treated with radical radiotherapy alone (55 Gy in 20 fractions). The spleen was retrospectively contoured by one physician, and the V10 Gy and mean splenic dose (MSD) were calculated using Eclipse planning software. RESULTS: The median MSD was 14.4 Gy with a range of 0.75-28.3 Gy. The median V10 Gy was 62.7%. Of the cohort, 67.6% received an MSD of more than 10 Gy. CONCLUSIONS: Two-thirds of the patients received a dose of more than the 10 Gy. A review of the literature suggests that higher splenic radiation doses may increase the long-term risk of infection and impact on other outcomes. This study provides important evidence that the spleen receives a significant dose of radiation when treating distal oesophageal cancer and should be considered as an organ at risk.


Subject(s)
Esophageal Neoplasms , Radiotherapy, Intensity-Modulated , Aged , Chemoradiotherapy , Esophageal Neoplasms/radiotherapy , Humans , Male , Organs at Risk , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Retrospective Studies , Spleen
20.
Front Genet ; 12: 607238, 2021.
Article in English | MEDLINE | ID: mdl-34234806

ABSTRACT

TP53 mutation (TP53MUT) is one of the most common gene mutations and frequently occurs in many cancers, especially esophageal carcinoma (ESCA), and it correlates with clinical prognostic outcomes. Nevertheless, the mechanisms by which TP53MUT regulates the correlation between ESCA and prognosis have not been sufficiently studied. Here, in the current research, we constructed a TP53MUT-related signature to predict the prognosis of patients with esophageal cancer and successfully verified this model in patients in the TP53 mutant group, esophageal squamous cell carcinoma group, and adenocarcinoma group. The risk scores proved to be better independent prognostic factors than clinical features, and prognostic features were combined with other clinical features to establish a convincing nomogram to predict overall survival from 1 to 3 years. In addition, we further predicted the tumor immune cell infiltration, chemical drugs, and immunotherapy responses between the high-risk group and low risk group. Finally, the gene expression of the seven-gene signature (AP002478.1, BHLHA15, FFAR2, IGFBP1, KCTD8, PHYHD1, and SLC26A9) can provide personalized prognosis prediction and insights into new treatments.

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