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1.
Oncol Lett ; 28(2): 386, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38966579

RESUMEN

In the present study, the outcomes of elective neck dissection in patients with intrathoracic esophageal squamous cell carcinoma were investigated. From January 2016 to December 2022, 21 patients who underwent esophagectomy and elective neck dissection (both neck level IV) for intrathoracic esophageal squamous cell carcinoma were enrolled. Of these 21 patients, 19 patients were male and 2 were female. A total of 11 patients received concurrent chemoradiotherapy (CCRT) as preoperative treatment. As a result of elective neck dissection at both neck level IV, occult neck metastasis of esophageal squamous cell carcinoma was diagnosed in 3 cases, all of which involved left neck lymph nodes. The incidence of occult neck metastasis was statistically significant in patients with preoperative CCRT, high T stage and high N stage (P<0.05). In addition, 16 out of 21 patients had been under follow-up without disease recurrence after the completion of treatment. However, 3 out of 21 patients succumbed to esophageal squamous cell carcinoma and 2 out of 21 patients were alive with stable disease of esophageal carcinoma. The follow-up period was 19.2±18.4 months. In conclusion, three-field lymph node dissection for intrathoracic esophageal squamous cell carcinoma may be necessary in patients with certain phenotypes, such that collaboration between thoracic surgeons and otolaryngologists may help reduce surgical complications.

2.
Int J Pharm ; 661: 124413, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960342

RESUMEN

Local drug delivery to the esophagus is hampered by rapid transit time and poor permeability of the mucosa. If some strategies aimed to improve the residence time have been proposed, non-invasive approaches to increase the drug penetration in the mucosa have not been described so far. Herein, we designed mucosa-penetrating liposomes to favor the penetration and retention of curcumin (CURC) in the esophagus. A novel mucosa penetrating peptide (MPP), SLENKGP, was selected by Phage Display and conjugated to pegylated liposomes at different PEG and MPP's surface densities. Pegylation assured a long residence time of liposomes (at least 30 min) in the esophagus in vivo, but it did not favor the penetration of CURC in the mucosa. MPP-decorated liposomes instead delivered a significant higher amount of CURC in the mucosa compared to naked pegylated liposomes. Confocal microscopy studies showed that naked pegylated liposomes remain confined in the superficial layers of the mucosa whereas MPP-decorated liposomes penetrate the whole epithelium. In vitro, MPP reduced the interaction of PEG with mucin, meanwhile favoring the paracellular penetration of liposomes across epithelial cell multilayers. In conclusion, pegylated liposomes represent a valid approach to target the esophagus and the surface functionalization with MPP enhances their penetration in the mucosa.

3.
Microb Pathog ; : 106784, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38971508

RESUMEN

BACKGROUND: Esophageal cancer (EC) possesses a high degree of malignancy and exhibits poor therapeutic outcomes and prognosis. However, its pathogenesis remains unclear. With the development of macrogene sequencing technology, changes in the intestinal flora have been found to be highly related to the development of EC, although discrepancies and controversies remain in this research area. MATERIALS AND METHODS: We comprehensively searched the PubMed, EMBASE, and Cochrane's Central Controlled Trials Register and the Scientific Network's database search projects based on systematically reviewed preferred reporting projects and meta-analyses. We used Engauge Digitizer for data extraction and Stata 15.1 for data analysis. In addition, we used the Newcastle-Ottawa Scale for grade grading and forest and funnel plots, sensitivity, and Egger and Beggar tests to evaluate the risk of bias. RESULTS: This study included 10 studies that assessed stool, tumor, and nontumor esophageal mucosa (gastroscopy and surgical resection) samples from 527 individuals, including 273 patients with EC and 254 healthy control group. We observed remarkable differences in microbial diversity in EC patients compared to healthy controls. The Chao1 index (46.01 vs. 42.67) was significantly increased in EC patients, whereas the Shannon index (14.90 vs. 19.05), ACE (39.24 vs. 58.47), and OTUs(28.93 vs. 70.10) were significantly lower. At the phylum level, the abundance of Bacteroidetes (37.89 vs. 32.77) increased significantly, whereas that of Firmicutes (37.63 vs. 38.72) decreased significantly; the abundance of Clostridium and Verruciformis increased, while that of Actinobacteria and Proteobacteria decreased to varying degrees. The abundance of Bacteroides (8.60 vs. 15.10) and Streptococcaceae (15.08 vs. 27.05) significantly reduced in EC. CONCLUSIONS: According to our meta-analysis, in patients with EC, the Chao1 index increased, whereas the Shannon and the OTUs decreased. At the phylum level, the abundance of Firmicutes decreased significantly, whereas that of Bacteroidetes and Proteobacteria increased significantly. At the genus/family level, the abundance of Bacteroidaceae, Prevotellaceae and Streptococcaceae decreased significantly, whereas that of Veillonellaceae increased. This meta-analysis identified changes in gut microbiota in patients with EC; however, its conclusions were inconsistent.

4.
Eur J Med Res ; 29(1): 352, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951825

RESUMEN

OBJECTIVES: Esophageal perforations are a complex clinical scenario that have been poorly studied. To date, there is no grading of esophageal perforations, the reason being that the outcome is very heterogeneous, because the perforation is very heterogeneous. A grading of the severity of the perforation may guide treatment, and could ultimately affect morbidity and mortality. METHODS: The observation period of the study was four years. All patients with a perforation of the esophagus aged 18 to 90 years were included. All anastomotic insufficiencies or fistulas after surgery of the esophagus were excluded. The cause of the injury and the time interval between the event and the start of therapy were analyzed. The severity of each perforation was classified based on the results of a diagnostic CT scan, gastroscopy as well as clinical and laboratory findings. Therapy and signs of infection were evaluated. Endpoints of the study were patient recovery or death. The study was conducted as a retrospective single-center study at a university hospital of Düsseldorf. The study has been approved by the review board. Patients gave their informed consent before data collection. All data were analyzed using SPSS 29 (IBM SPSS Statistics software). RESULTS: Age, gender and cause of the esophageal perforation did not impact significantly on overall survival. The duration of injury > 24 h (p = 0.01), presence of mediastinitis (p = 0.01) and necrosis of the esophagus (p = 0.02) were associated with an unfavorable outcome. The correlation of the clinical grading of the severity of the perforation based on the endoscopic, radiological and clinical findings with the overall survival of patients was significant. Patients categorized into the four grades of severity (I-IV) had an overall survival of 100%, 100%, 70% and 50%, respectively. CONCLUSION: The severity of esophageal perforations can be systematically rated grades I to IV based on the radiological, endoscopic and clinical findings at diagnosis. Due to the grading and its correlation to the overall survival, a comparison of patients, their treatment and outcome becomes possible. In future, the grade of a perforation may guide treatment, and therefore affect morbidity and mortality.


Asunto(s)
Perforación del Esófago , Humanos , Perforación del Esófago/diagnóstico , Perforación del Esófago/etiología , Perforación del Esófago/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Adolescente , Estudios Retrospectivos , Adulto Joven
5.
World J Clin Oncol ; 15(6): 677-683, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38946837

RESUMEN

Sleep problems have become a significant public health concern, affecting a large portion of the global population and have been linked to increased morbidity and mortality. The incidence of gastrointestinal (GI) cancers continues to rise, posing a substantial burden on healthcare systems worldwide. This editorial aims to delve into the impact of sleep on GI cancers, including esophageal, gastric, colorectal, hepatobiliary, and pancreatic cancer. Recent literature investigating the potential connections between GI cancers and sleep was reviewed. We considered aspects such as sleep duration, sleep disorders, and circadian rhythmicity, in order to explore the underlying mechanisms that can contribute to the development of GI cancers and propose avenues for future research.

6.
Dig Liver Dis ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38972789

RESUMEN

BACKGROUND: Identifying children needing endoscopic evaluation for suspected eosinophilic esophagitis (EoE) is crucial for prompt diagnosis and management. AIMS: We aimed to develop a clinical prediction tool to distinguish children with EoE from children without the disease before endoscopy. METHODS: We conducted a retrospective case-control study of children undergoing upper endoscopy at a tertiary care center. Clinical characteristics before endoscopy were extracted from 380 EoE cases and 380 controls without EoE. We built a predictive model for case-control status and performed age-stratified analyses. RESULTS: After multivariable analysis, history of adaptive eating behaviors, food allergy, food impaction, male sex, and regurgitation were independently associated with EoE, and abdominal pain and failure to thrive with control status (AUC 0.81). Food allergy and male sex were predictors of EoE across all ages. Regurgitation and adaptive eating behaviors were specific to EoE in early (0-5 years) (AUC 0.74) and middle childhood (6-11 years) (AUC 0.82), while dysphagia and food impaction were specific to EoE in the adolescence (12-17 years) (AUC 0.87). CONCLUSION: We determined age-specific clinical features that predict EoE with good discrimination in a pediatric population before endoscopy. Validation of this model in an independent population can confirm the utility of this tool.

7.
Laryngoscope ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984434

RESUMEN

Fish bone foreign bodies (FFBs) are relatively common but can present diagnostic challenges. Herein, we report a case of a 43-year-old female who initially presented to the Emergency Department with fever and throat discomfort after a choking incident, which led to a misdiagnosis of a viral infection after negative chest X-ray findings. Persistent symptoms, including new-onset vocal cord paralysis, prompted further investigation and an otolaryngology - head and neck surgery referral one month later. During the otolaryngology visit eight months after the initial incident, laryngoscopy revealed left true vocal cord paralysis and a subsequent CT scan revealed a 2.3 cm fishbone in the esophagus. Surgical removal involved flexible esophagoscopy and open neck exploration with careful dissection to avoid vascular injury. This case highlights the limitations of initial diagnostic methods, such as X-rays, and the necessity for heightened clinical vigilance and advanced imaging modalities like CT scans for persistent or evolving symptoms, particularly vocal cord paralysis. This case also supports multidisciplinary surgical management in cases of suspected esophageal FFBs involving the internal jugular vein and common carotid artery to prevent serious complications. Laryngoscope, 2024.

8.
World J Surg ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956401

RESUMEN

BACKGROUND: Emergency presentations make up a large proportion of a general surgeon's workload. Patients who have emergency surgery carry a higher rate of mortality and complications. We aim to review the impact of surgical subspecialization on patients following upper gastrointestinal (UGI) emergency surgery. METHODS: A systematic search of Ovid Embase, Ovid MEDLINE, and Cochrane databases using a predefined search strategy was completed reviewing studies published from 1st of January 1990 to August 27, 2023. The study was prospectively registered with PROSPERO (CRD42022359326). Studies were reviewed for the following outcomes: 30-day mortality, in-hospital mortality, conversion to open, length of stay, return to theater, and readmission. RESULTS: Of 5181 studies, 24 articles were selected for full text review. Of these, seven were eligible and included in this study. There was a statistically significant improvement in 30-day mortality favoring UGI specialists (OR 0.71 [95% CI 0.55-0.92 and p = 0.009]) and in-hospital mortality (OR 0.29 [95% CI 0.14-0.60 and p = 0009]). There was a high degree of study heterogeneity in 30-day mortality; however, a low degree of heterogeneity within in-hospital mortality. There was no statistical significance when considering conversion to open and insufficient data to allow meta-analysis for return to theater or readmission rates. CONCLUSION: In emergency UGI surgery, there was improved 30-day and in-hospital mortality for UGI specialists. Therefore, surgeons should consider early involvement of a subspecialist team to improve patient outcomes.

9.
J Thorac Dis ; 16(6): 3535-3539, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38983140
10.
Hum Vaccin Immunother ; 20(1): 2370085, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38967227

RESUMEN

Small cell carcinoma of the esophagus (SCCE) is a rare and highly malignant type of esophageal cancer with no standard treatment, facing challenges of resistance to conventional therapies. This study presents the cases of one extensive-stage and two limited-stage SCCE patients treated with chemoimmunotherapy. The two limited-stage patients underwent surgery post-treatment and experienced notable and enduring positive responses. This represents the first documented application of neoadjuvant chemoimmunotherapy in limited-stage SCCE patients. Additionally, comprehensive immunohistochemical analysis and whole exome sequencing were performed on the case patients. The findings revealed that infiltration of CD8+ T cells and PD-L1 expression in the SCCE tumor were key factors for favorable responses in SCCE patients receiving chemoimmunotherapy.


Asunto(s)
Carcinoma de Células Pequeñas , Neoplasias Esofágicas , Inmunoterapia , Terapia Neoadyuvante , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Carcinoma de Células Pequeñas/terapia , Carcinoma de Células Pequeñas/tratamiento farmacológico , Masculino , Inmunoterapia/métodos , Persona de Mediana Edad , Antígeno B7-H1/metabolismo , Resultado del Tratamiento , Anciano , Biomarcadores de Tumor , Linfocitos T CD8-positivos/inmunología , Femenino , Secuenciación del Exoma
11.
Int J Surg Case Rep ; 120: 109868, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38852572

RESUMEN

INTRODUCTION: Esophageal cancer, notably rare in the proximal esophagus, demonstrates poor outcomes despite advanced treatments. This case underscores the successful management of proximal esophageal adenocarcinoma using chemoradiotherapy alone. CASE PRESENTATION: A 65-year-old Mediterranean woman presented with severe dysphagia and was diagnosed with stage IVA T4b N0M0 esophageal adenocarcinoma. She achieved complete remission after chemoradiotherapy, evidenced by PET CT scans, without surgical intervention. DISCUSSION: This case highlights the rarity of proximal esophageal adenocarcinoma and challenges the conventional treatment paradigm, emphasizing the potential of chemoradiotherapy as a standalone treatment in selected advanced cases. CONCLUSION: The complete response to chemoradiotherapy in this case of proximal esophageal adenocarcinoma illustrates the need for personalized treatment strategies and further research into non-surgical options for esophageal cancer management.

12.
J Clin Med ; 13(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38929948

RESUMEN

Background: Esophageal self-expandable metal stents (SEMS) are an important endoscopic tool. These stents have now been adapted successfully to manage post-bariatric surgery complications such as anastomotic leaks and strictures. In centers of expertise, this has become the primary standard-of-care treatment given its minimally invasive nature, and that it results in early oral feeding, decreased hospitalization, and overall favorable outcomes. Self-expandable metal stents (SEMS) fractures are a rare complication of unknown etiology. We aimed to investigate possible causes of SEMS fractures and highlight a unique endoscopic approach utilized to manage a fractured and impaled SEMS. Methods: This is a retrospective study of consecutive patients who underwent esophageal SEMS placement between 2015-2021 at a tertiary referral center to identify fractured SEMS. Patient demographics, stent characteristics, and possible etiologies of fractured SEMS were identified. A comprehensive literature review was also conducted to evaluate all prior cases of fractured SEMS and to hypothesize fracture theories. Results: There were seven fractured esophageal SEMS, of which six were used to manage post-bariatric surgery complications. Five SEMS were deployed with their distal ends in the gastric antrum and proximal ends in the distal esophagus. All stents fractured within 9 weeks of deployment. Most stents (5/7) were at least 10 cm in length with fractures commonly occurring in the distal third of the stents (6/7). The wires of a fractured SEMS were embedded within the esophagogastric junction in one case, prompting the use of an overtube that was synchronously advanced while steadily extracting the stent. Discussion: We suggest the following four etiologies of SEMS fractures: anatomical, physiological, mechanical, and chemical. Stent curvature at the stomach incisura can lead to strain- and stress-related fatigue due to mechanical bending with exacerbation from respiratory movements. Physiologic factors (gastric body contractions) can result in repetitive squeezing of the stent, adding to metal fatigue. Intrinsic properties (long length and low axial force) may be contributing factors. Lastly, the stomach acidic environment may cause nitinol-induced chemical weakness. Despite the aforementioned theories, SEMS fracture etiology remains unclear. Until more data become available, it may be advisable to remove these stents within 6 weeks.

13.
bioRxiv ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38915718

RESUMEN

Background: The incidence of Barrett esophagus (BE) and Gastroesophageal Adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BA) support fat digestion and undergo microbial metabolization in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis. The capacity of inhibiting cancer-related processes when activated, make FXR an appealing therapeutic target. In this work, we assess the role of diet on the microbiota-BA axis and evaluate the role of FXR in disease progression. Results: Here we show that high fat diet (HFD) accelerated tumorigenesis in L2-IL1B mice (BE- and GEAC- mouse model) while increasing BA levels and enriching gut microbiota that convert primary to secondary BA. While upregulated in BE, expression of FXR was downregulated in GEAC in mice and humans. In L2-IL1B mice, FXR knockout enhanced the dysplastic phenotype and increased Lgr5 progenitor cell numbers. Treatment of murine organoids and L2-IL1B mice with the FXR agonist obeticholic acid (OCA) deacelerated GEAC progression. Conclusion: We provide a novel concept of GEAC carcinogenesis being accelerated via the diet-microbiome-metabolome axis and FXR inhibition on progenitor cells. Further, FXR activation protected with OCA ameliorated the phenotype in vitro and in vivo, suggesting that FXR agonists have potential as differentiation therapy in GEAC prevention.

14.
Radiother Oncol ; 198: 110409, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38917884

RESUMEN

BACKGROUND AND PURPOSE: In this study, we assessed the robustness of intensity modulated proton therapy (IMPT) in esophageal cancer for anatomical variations during treatment. METHODS: The first sixty esophageal cancer patients, treated clinically with chemoradiotherapy were included. The treatment planning strategy was based on an internal target volume (ITV) approach, where the ITV was created from the clinical target volumes (CTVs) delineated on all phases of a 4DCT. For optimization, a 3 mm isotropic margin was added to the ITV, combined with robust optimization using 5 mm setup and 3 % range uncertainty. Each patient received weekly repeat CTs (reCTs). Robust plan re-evaluation on all reCTs, and a robust dose summation was performed. To assess the factors influencing ITV coverage, a multivariate linear regression analysis was performed. Additionally, clinical adaptations were evaluated. RESULTS: The target coverage was adequate (ITV V94%>98 % on the robust voxel-wise minimum dose) on most reCTs (91 %), and on the summed dose in 92 % of patients. Significant predictors for ITV coverage in the multivariate analysis were diaphragm baseline shift and water equivalent depth (WED) of the ITV in the beam direction. Underdosage of the ITV mainly occurred in week 1 and 4, leading to treatment adaptation of eight patients, all on the first reCT. CONCLUSION: Our IMPT treatment of esophageal cancer is robust for anatomical variations. Adaptation appears to be most effective in the first week of treatment. Diaphragm baseline shifts and WED are predictive factors for ITV underdosage, and should be incorporated in an adaptation protocol.

15.
Expert Rev Gastroenterol Hepatol ; : 1-11, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38940016

RESUMEN

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory, disabling disorder characterized by prominent eosinophilic inflammation of the esophagus, leading to troublesome symptoms including dysphagia and food impaction. The natural history of EoE is poorly known, but it may lead to esophageal strictures. The therapeutic armamentarium is expected to grow in the near future, especially due to the availability of novel biological therapies targeting crucial inflammatory pathways of EoE. AREAS COVERED: In this review, we discuss the main clinical features and natural history of EoE, focusing on the current therapeutic strategies, as well as past and current trials investigating biologics for its treatment. EXPERT OPINION: Dupilumab has been the first approved biologic drug for the treatment of EoE; long-term studies assessing how it could change the natural history of EoE are awaited. Novel biological drugs or other molecules are currently under study and could change the current treatment algorithms in the near future. Proper drug positioning and long term 'exit strategies' are yet to be defined.

16.
Cancer Invest ; : 1-9, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913915

RESUMEN

We examined Fusobacterium nucreatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) in non-neoplastic Barrett's esophagus (BE) from patients without cancer (n = 67; N group), with esophageal adenocarcinoma (EAC) (n = 27) and EAC tissue (n = 22). F. nucleatum was only detectable in 22.7% of EAC tissue. Pan-fusobacterium was enriched in EAC tissue and associated with aggressive clinicopathological features. Amount of Pan-fusobacterium in non-neoplastic BE was correlated with presence of hital hernia and telomere shortening. The result suggested potential association of Fusobacterium species in EAC and BE, featuring clinicpathological and molecular features.

17.
Biochem Biophys Res Commun ; 726: 150280, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38909534

RESUMEN

Esophageal epithelium is one of the most proliferative and regenerative epithelia in our body, indicating robust stem cell activity. However, the underlying mechanisms regulating the self-renewal and differentiation of esophageal stem cells need to be more elucidated. Here, we identify the role of YAP1 in esophageal stem cells. YAP1 is differentially expressed in the nuclei of esophageal basal cells. Furthermore, the treatment of verteporfin, a YAP1 inhibitor, interfered with esophageal organoid formation. Consistently, YAP1 deletion decreased esophageal organoid formation and the expression of basal genes while increasing the expression of suprabasal genes. Finally, global transcriptomic analysis revealed that YAP1 inhibition induced a significant enrichment of gene sets related to keratinization and cornification, while depleting gene sets related to DNA repair and chromosome maintenance. Our data uncover a novel regulatory mechanism for esophageal stem cells, which could provide a potential strategy for esophageal regenerative medicine.

18.
Int Immunopharmacol ; 137: 112364, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38865752

RESUMEN

BACKGROUND: Despite the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment, disease progression remains common in the majority of patients and subsequent therapeutic options for this population are limited. ICI rechallenge has been validated favorably in terms of efficacy and safety in many cancer types, while data in esophageal squamous cell carcinoma (ESCC) are still lacking. METHODS: Clinical and pathological characteristics of advanced ESCC patients who received ICI rechallenge were collected retrospectively. The primary outcomes of interest were the disease control rate (DCR) and progression-free survival (PFS). Treatment-related adverse events were also recorded. We categorized patients into primary resistance and secondary resistance based on a 6-month disease control duration following the initial immunotherapy and further conducted exploratory analyses. RESULTS: A retrospective cohort study spanning January 2018 and October 2023, at Peking University Cancer Hospital, scrutinized 45 advanced ESCC patients undergoing two lines of ICI-based therapies (ICI-1 and ICI-2). The initial therapeutic approach involved combining ICIs with chemotherapy, and the ICI rechallenge primarily comprised ICIs and angiogenesis inhibitors. The median PFS for ICI-1 was 6.7 months with a disease control rate of 88.9 %. Following the ICI rechallenge, the median PFS and disease control rate remained at 3.2 months and 73.3 %, respectively. It is noteworthy that patients with secondary resistance to ICI-1 exhibited a higher 6-month PFS rate (29.6 % v.s. 11.1 %) in the ICI-2 stage. Any grade of treatment-related adverse events was observed in 29 (64.4 %) and 18 (40.0 %) patients at ICI-1 and ICI-2. The incidence of treatment-related adverse events in grades 3-4 was 9.1 % at ICI-1 and 9.1 % at ICI-2. CONCLUSION: ICI rechallenge may offer a potential survival benefit and a favorable safety profile for patients with ESCC who have progressed after initial immunotherapy. Patients exhibiting acquired resistance during initial immunotherapy are more likely to achieve prolonged disease control after undergoing rechallenge therapy. Prospective studies are required to further explore the optimal combined therapy and select targeted population.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Inhibidores de Puntos de Control Inmunológico , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Masculino , Femenino , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/inmunología , Persona de Mediana Edad , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Estudios Retrospectivos , Anciano , Adulto , Resistencia a Antineoplásicos , Supervivencia sin Progresión
19.
Int Immunopharmacol ; 137: 112362, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38901248

RESUMEN

Oroxylin A (OA), a naturally active O-methylated flavone derived from Scutellaria baicalensis, is regarded as a potential drug with strong anticancer effects. Unfortunately, our understanding of the antineoplastic mechanism of oral exposure to such flavonoids is inadequate. Growing evidence has confirmed the important role of OA in the regulation of oxidative stress- and inflammatory-response-induced tissue injury. However, it remains unknown whether OA is capable of mitigating esophagus cancer (EC) progression and its potential molecular mechanism. Furthermore, the tripartite motif containing 40 (TRIM40) is a ubiquitin ligase that mediates the immune response. The potential molecular function of TRIM40 in regulating EC is largely unknown. We confirmed that OA-triggered oxidative stress markedly upregulates TRIM40. During the OA challenge, increased TRIM40 reduced oxidative stress and promoted the ER stress response. Inversely, deletion of TRIM40 facilitated oxidative stress and blocked cancer cell growth in vivo and in vitro. Mechanistically, in response to OA treatment, TRIM40 directly interacts with Keap1 and promotes ubiquitin-proteasome degradation, thus leading to the promotion of Nrf2 nuclear translocation and its downstream cascade activation, which increases antioxidant defense and cell survival. TRIM40 expression was positively correlated with Nrf2 expression and negatively associated with Keap1 expression in EC xenografts and human specimens. In addition, high TRIM40 expression correlates with poor patient survival in EC. The findings suggested that oral exposure to OA significantly mitigates EC development by targeting TRIM40 activity. These findings further elucidated the potential role of TRIM40 in EC progression by mediating Keap1 degradation, which could be considered a therapeutic target for the treatment of such a disease.


Asunto(s)
Neoplasias Esofágicas , Flavonoides , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Transducción de Señal , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Humanos , Animales , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Flavonoides/farmacología , Flavonoides/uso terapéutico , Ratones , Estrés Oxidativo/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Línea Celular Tumoral , Masculino , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Ratones Desnudos , Ratones Noqueados
20.
J Gastrointest Surg ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38876290

RESUMEN

BACKGROUND: Narrowing, trauma, tumors, and systemic diseases can cause esophageal dysfunction. Severe cases resist traditional surgery, leading to long-term gastrostomy or jejunostomy tubes, affecting patients negatively. No established surgery ensures both airway and oral function with proper speech. This article introduces the oral-vestibule-enteral anastomosis (OVEA) technique, targeting patients with compromised epiglottic closure competence and loss of cervical esophagus, where conventional methods fall short. METHODS: Technique description study evaluated in 13 patients in a single tertiary referral center in Mexico City treated with OVEA from January 1990 to July 2023. RESULTS: Of the 13 patients (69% male; mean age, 37.14 ± 12.907 years), preoperative conditions included a mean body mass index of 17.78 ± 2.66 kg/m2, 46% with previous abdominal surgeries, and 31% with a smoking history. After OVEA, complications affected 46%, primarily pneumonia (23%), abscess formations (15%), intestinal necrosis (8%), and airway fistula (8%). Reoperation was needed in 38%, addressing functionality loss, necrosis, stenosis, and jawbone remodeling. No fatalities occurred within the first 6 months after surgery; 84% had successful gastrostomy tube removal, and 8% retained a tracheostomy tube. Currently 13 patients (92%) use the OVEA as their main enteral route of feeding. CONCLUSION: The OVEA technique seems promising for cases involving esophageal loss or impaired epiglottic function, enhancing patients' quality of life by enabling oral feeding and restoring regular eating habits. Further research should focus on long-term results and identifying optimal candidates for this innovative surgical method.

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