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1.
J Cardiothorac Surg ; 19(1): 214, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616255

RESUMO

BACKGROUND: Pseudoachalasia is a rare disease that behaves similarly to achalasia (AC), making it sometimes difficult to differentiate. CASE PRESENTATION: We report a case of 49-year-old male with adenocarcinoma of the gastroesophageal junction misdiagnosed as achalasia. No obvious abnormalities were found in his initial examinations including upper digestive endoscopy, upper gastrointestinal imaging and chest computed tomography (CT). During the subsequent introduced-peroral endoscopic myotomy (POEM), it was found that the mucosal layer and the muscular layer had severe adhesion, which did not receive much attention, delayed the clear diagnosis and effect treatment, and ultimately led to a poor prognosis for the patient. CONCLUSIONS: This case suggests that when patients with AC found mucosal and muscular adhesions during POEM surgery, the possibility should be considered that the lesion may be caused by a malignant lesion.


Assuntos
Acalasia Esofágica , Miotomia , Masculino , Humanos , Pessoa de Meia-Idade , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/cirurgia , Cárdia/cirurgia , Junção Esofagogástrica/cirurgia , Erros de Diagnóstico
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(3): 541-552, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38597446

RESUMO

OBJECTIVE: To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma. METHODS: We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP. qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines (OE-19, TE-7, Bic-1, Flo-1, SK-GT-4, and BE-3) and a normal esophageal epithelial cell line (HET-1A). OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection, and the changes in proliferation, migration and invasion of the cells were evaluated using Cell Counting Kit-8 (CCK-8) assay and Transwell migration/invasion assay. The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting. The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice. RESULTS: The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells. LINC00626 knockdown obviously inhibited the proliferation, migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice, while overexpression of LINC00626 produced the opposite effects. In esophageal adenocarcinoma cells, LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3. CONCLUSION: High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Janus Quinase 1 , Neoplasias Pulmonares , Proteínas de Ligação a RNA , Animais , Camundongos , Humanos , Camundongos Nus , Janus Quinases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Junção Esofagogástrica/metabolismo , Junção Esofagogástrica/patologia , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição STAT3/metabolismo , Transativadores
3.
Nat Commun ; 15(1): 3064, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594232

RESUMO

The gastroesophageal squamocolumnar junction (GE-SCJ) is a critical tissue interface between the esophagus and stomach, with significant relevance in the pathophysiology of gastrointestinal diseases. Despite this, the molecular mechanisms underlying GE-SCJ development remain unclear. Using single-cell transcriptomics, organoids, and spatial analysis, we examine the cellular heterogeneity and spatiotemporal dynamics of GE-SCJ development from embryonic to adult mice. We identify distinct transcriptional states and signaling pathways in the epithelial and mesenchymal compartments of the esophagus and stomach during development. Fibroblast-epithelial interactions are mediated by various signaling pathways, including WNT, BMP, TGF-ß, FGF, EGF, and PDGF. Our results suggest that fibroblasts predominantly send FGF and TGF-ß signals to the epithelia, while epithelial cells mainly send PDGF and EGF signals to fibroblasts. We observe differences in the ligands and receptors involved in cell-cell communication between the esophagus and stomach. Our findings provide insights into the molecular mechanisms underlying GE-SCJ development and fibroblast-epithelial crosstalk involved, paving the way to elucidate mechanisms during adaptive metaplasia development and carcinogenesis.


Assuntos
Fator de Crescimento Epidérmico , Junção Esofagogástrica , Animais , Camundongos , Fator de Crescimento Epidérmico/metabolismo , Junção Esofagogástrica/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fibroblastos/metabolismo , Análise de Célula Única
4.
Front Immunol ; 15: 1372272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638445

RESUMO

Background: Tumors in the distal esophagus (EAC), gastro-esophageal junction including cardia (GEJAC), and stomach (GAC) develop in close proximity and show strong similarities on a molecular and cellular level. However, recent clinical data showed that the effectiveness of chemo-immunotherapy is limited to a subset of GEAC patients and that EACs and GEJACs generally benefit less from checkpoint inhibition compared to GACs. As the composition of the tumor immune microenvironment drives response to (immuno)therapy we here performed a detailed immune analysis of a large series of GEACs to facilitate the development of a more individualized immunomodulatory strategy. Methods: Extensive immunophenotyping was performed by 14-color flow cytometry in a prospective study to detail the immune composition of untreated gastro-esophageal cancers (n=104) using fresh tumor biopsies of 35 EACs, 38 GEJACs and 31 GACs. The immune cell composition of GEACs was characterized and correlated with clinicopathologic features such as tumor location, MSI and HER2 status. The spatial immune architecture of a subset of tumors (n=30) was evaluated using multiplex immunohistochemistry (mIHC) which allowed us to determine the tumor infiltration status of CD3+, CD8+, FoxP3+, CD163+ and Ki67+ cells. Results: Immunophenotyping revealed that the tumor immune microenvironment of GEACs is heterogeneous and that immune suppressive cell populations such as monocytic myeloid-derived suppressor cells (mMDSC) are more abundant in EACs compared to GACs (p<0.001). In contrast, GACs indicated a proinflammatory microenvironment with elevated frequencies of proliferating (Ki67+) CD4 Th cells (p<0.001), Ki67+ CD8 T cells (p=0.002), and CD8 effector memory-T cells (p=0.024). Differences between EACs and GACs were confirmed by mIHC analyses showing lower densities of tumor- and stroma-infiltrating Ki67+ CD8 T cells in EAC compared to GAC (both p=0.021). Discussions: This comprehensive immune phenotype study of a large series of untreated GEACs, identified that tumors with an esophageal tumor location have more immune suppressive features compared to tumors in the gastro-esophageal junction or stomach which might explain the location-specific responses to checkpoint inhibitors in this disease. These findings provide an important rationale for stratification according to tumor location in clinical studies and the development of location-dependent immunomodulatory treatment approaches.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Humanos , Antígeno Ki-67/genética , Estudos Prospectivos , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Fenótipo , Microambiente Tumoral
6.
Zentralbl Chir ; 149(2): 202-208, 2024 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-38565166

RESUMO

Adenocarcinoma of the esophagogastric junction (AEG) still represent a certain surgical challenge. In contrary to the trend of thoracoabdominal surgery for AEG I and AEG II cancer, the proximal gastrectomy is regaining popularity through new reconstruction methods such as the double tract reconstruction. Proximal gastrectomy followed by double tract reconstruction represents an alternative for the thoracoabdominal approach for suitable AEG II cancer and an alternative to the total gastrectomy for AEG III cancers. Latest studies suggest a functional benefit of proximal gastrectomy and double tract reconstruction in comparison to total gastrectomy. The accurate indication for proximal gastrectomy for locally advanced cancers has to be established in the near future as well as the influence of the size of the remnant stomach on the outcome, as Asian techniques for early lesions sometimes significantly differ from European. The following article reflects the present evidence on proximal gastrectomy and double tract reconstruction as well as technical aspects in the context of cancer of the esophagogastric junction.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Gastrectomia/métodos , Adenocarcinoma/cirurgia , Estudos Retrospectivos , Neoplasias Esofágicas/cirurgia
7.
Gastric Cancer ; 27(3): 571-579, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38457083

RESUMO

BACKGROUND: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. METHODS: Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). RESULTS: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. CONCLUSIONS: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Pessoa de Meia-Idade , Idoso , Docetaxel/uso terapêutico , Oxaliplatina , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia
8.
Sci Rep ; 14(1): 7522, 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553594

RESUMO

To investigate the safety and efficacy of the neoadjuvant chemoradiotherapy (NCRT) followed by neoadjuvant consolidation chemotherapy (NCCT) and surgery for locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma. Patients diagnosed as locally advanced GC or Siewert II/III GEJ adenocarcinoma with clinical stage T3-4 and/or N positive were prospectively enrolled. Patients underwent NCRT (45 Gy/25 fractions) with concurrent S-1, followed by NCCT (4 to 6 cycles of the SOX regimen) 2 to 4 weeks after NCRT. Gastric cancer radical resection with D2 lymph node dissection was performed 4 to 6 weeks after the total neoadjuvant therapy. The study was conducted from November 2019 to January 2023, enrolling a total of 46 patients. During the NCRT, all patients completed the treatment without dose reduction or delay. During the NCCT, 32 patients (69.6%) completed at least 4 cycles of chemotherapy. Grade 3 or higher adverse events in NCRT (5 cases) were non-hematological. During the course of NCCT, a notable occurrence of hematological toxicities was observed, with grade 3 or higher leukopenia (9.7%) and thrombocytopenia (12.2%) being experienced. A total of 28 patients (60.9%) underwent surgery, achieving R0 resection in all cases. A significant proportion of cases (71.4%) exhibited pathological downstaging to ypT0-2, while 10 patients (35.7%) demonstrated a pathologic complete response (pCR). The total neoadjuvant therapy comprising NCRT followed by NCCT and surgery demonstrates a low severe adverse reactions and promising efficacy, which could be considered as a viable treatment for locally advanced GC or GEJ adenocarcinoma.Trial registration: Clinicaltrials.gov (registration number: NCT04062058); the full date of first trial registration was 20/08/2019.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Terapia Neoadjuvante , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patologia , Estudos Prospectivos , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Junção Esofagogástrica/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento
9.
J Cancer Res Clin Oncol ; 150(3): 145, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507110

RESUMO

OBJECTIVE: To investigate the superiority of preoperative ultrasound-guided titanium clip and nanocarbon dual localization over traditional methods for determining the surgical approach and guiding resection of Siewert type II adenocarcinoma of the esophagogastric junction (AEG). METHOD: This study included 66 patients with Siewert type II AEG who were treated at the PLA Joint Logistics Support Force 900th Hospital between September 1, 2021, and September 1, 2023. They were randomly divided into an experimental group (n = 33), in which resection was guided by the dual localization technique, and the routine group (n = 33), in which the localization technique was not used. Surgical approach predictions, proximal esophageal resection lengths, pathological features, and the occurrence of complications were compared between the groups. RESULT: The use of the dual localization technique resulted in higher accuracy in predicting the surgical approach (96.8% vs. 75.9%, P = 0.02) and shorter proximal esophageal resection lengths (2.39 ± 0.28 cm vs. 2.86 ± 0.39 cm, P < 0.001) in the experimental group as compared to the routine group, while there was no significant difference in the incidence of postoperative complications (22.59% vs. 24.14%, P = 0.88). CONCLUSION: Preoperative dual localization with titanium clips and carbon nanoparticles is significantly superior to traditional methods and can reliably delineate the actual infiltration boundaries of Siewert type II AEG, guide the surgical approach, and avoid excessive esophageal resection.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Nanopartículas , Neoplasias Gástricas , Humanos , Titânio , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Gastrectomia/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/diagnóstico por imagem , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Instrumentos Cirúrgicos , Ultrassonografia de Intervenção , Carbono
10.
Int J Cancer ; 154(12): 2142-2150, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447003

RESUMO

FOLFOX plus nivolumab represents a standard of care for first-line therapy of advanced gastroesophageal cancer (aGEC) with positive PD-L1 expression. The efficacy of second-line VEGFR-2 inhibition with ramucirumab (RAM) plus chemotherapy after progression to immunochemotherapy remains unclear. Medical records of patients with aGEC enrolled in the randomized phase II AIO-STO-0417 trial after treatment failure to first-line FOLFOX plus nivolumab and ipilimumab were retrospectively analyzed. Patients were divided into two groups based on second-line therapy: RAM plus chemotherapy (RAM group) or treatment without RAM (control group). Eighty three patients were included. In the overall population, progression-free survival (PFS) in the RAM group was superior to the control (4.5 vs 2.9 months). Responders (CR/PR) to first-line immunochemotherapy receiving RAM containing second-line therapy had prolonged OS from start of first-line therapy (28.9 vs 16.5 months), as well as second-line OS (9.6 vs 7.5 months), PFS (5.6 vs 2.9 months) and DCR (53% vs 29%) compared to the control. PD-L1 CPS ≥1 was 42% and 44% for the RAM and the control, respectively. Patients with CPS ≥1 in the RAM group showed better tumor control (ORR 25% vs 10%) and improved survival (total OS 11.5 vs 8.0 months; second-line OS 6.5 vs 3.9 months; PFS 4.5 vs 1.6 months) compared to the control. Prior exposure to first-line FOLFOX plus dual checkpoint inhibition followed by RAM plus chemotherapy shows favorable response and survival rates especially in patients with initial response and positive PD-L1 expression and has the potential to advance the treatment paradigm in aGEC.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , 60500 , Antígeno B7-H1 , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/patologia , Junção Esofagogástrica/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia
11.
Chin Clin Oncol ; 13(1): 8, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38453658

RESUMO

The survival outcome of patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer remains unsatisfactory, and improvements in survival and recurrence remain urgent issues for clinicians worldwide. Prior to the 2000s, locally advanced G/GEJ was a different disease between the West and the East regarding diagnosis, surgery, and prognosis. However, recent advances in medical oncology have set the stage for harmonization. Herein, this review highlights clinical trials of perioperative or neoadjuvant chemotherapy conducted during the past two decades to provide insights into future directions. We focused on pivotal clinical trials of perioperative or neoadjuvant chemotherapy for patients with locally advanced G/GEJ cancer. We paid special attention to the indication and oncological outcomes of perioperative or neoadjuvant chemotherapy. The attempts to investigate the optimal treatment strategy for locally advanced G/GEJ cancer over the past 20 years have resulted in a global consensus on the necessity of perioperative or neoadjuvant chemotherapy, although there have been different circumstances regarding treatment for G/GEJ cancer among the West, the East other than Japan, and Japan. Two randomized global phase III trials, the KEYNOTE-585 and MATTHERHORN, were successfully accomplished for a common indication. Furthermore, perioperative immunotherapy suggested a new indication with molecular biomarkers such as microsatellite status or PD-L1 status beyond the conventional tumor-lymph node-metastasis (TNM) staging system. Global studies provide the stage for discussing the future optimal indication of neoadjuvant chemotherapy, opening the door for future global collaborations to better treat patients with locally advanced G/GEJ cancer.


Assuntos
Neoplasias Esofágicas , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Japão , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
13.
Korean J Gastroenterol ; 83(3): 119-122, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38522855

RESUMO

Dieulafoy's lesion is a rare cause of gastrointestinal bleeding, accounting for approximately 1-2% of all cases of gastrointestinal bleeding. Dieulafoy's lesion usually occurs in the lesser curvature of the stomach within six centimeters of the gastroesophageal junction. On the other hand, extragastric Dieulafoy's lesions are uncommon. Diagnosing an extragastric Dieulafoy's lesion by endoscopy can be challenging because of its small size and obscure location. The key elements for an accurate diagnosis include heightened awareness and a careful early endoscopic evaluation following a bleeding episode. Various endoscopic hemostatic techniques can be used for treatment. This paper presents a case of successful hemostasis using argon plasma coagulation for a life-threatening duodenal Dieulafoy's lesion.


Assuntos
Hemorragia Gastrointestinal , Hemostase Endoscópica , Humanos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Duodeno/patologia , Hemostase Endoscópica/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Junção Esofagogástrica
15.
Radiat Oncol ; 19(1): 28, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433231

RESUMO

BACKGROUND: To assess the tolerability and oncological results of chemoradiation in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction. METHODS: This multi-center retrospective analysis included 86 elderly patients (≥ 65 years) with esophageal or gastroesophageal junction adenocarcinoma (median age 73 years; range 65-92 years) treated with definitive or neoadjuvant (chemo)radiotherapy. The treatment was performed at 3 large comprehensive cancer centers in Germany from 2006 to 2020. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities according to CTCAE criteria v5.0 were analyzed, and parameters potentially relevant to patient outcomes were evaluated. RESULTS: Thirty-three patients (38%) were treated with neoadjuvant chemoradiation followed by surgery, while the remaining patients received definitive (chemo)radiation. The delivery of radiotherapy without dose reduction was possible in 80 patients (93%). In 66 patients (77%), concomitant chemotherapy was initially prescribed; however, during the course of therapy, 48% of patients (n = 32) required chemotherapy de-escalation due to treatment-related toxicities and comorbidities. Twenty-nine patients (34%) experienced higher-grade acute toxicities and 14 patients (16%) higher-grade late toxicities. The 2-year LRC, DMFS, PFS, and OS amounted to 72%, 49%, 46%, and 52%, respectively. In multivariate analysis, neoadjuvant chemoradiation followed by surgery was shown to be associated with significantly better PFS (p = 0.006), DMFS (p = 0.006), and OS (p = 0.004) compared with all non-surgical treatments (pooled definitive radiotherapy and chemoradiation). No such advantage was seen over definitive chemoradiation. The majority of patients with neoadjuvant therapy received standard chemoradiotherapy without dose reduction (n = 24/33, 73%). In contrast, concurrent chemotherapy was only possible in 62% of patients undergoing definitive radiotherapy (n = 33/53), and most of these patients required dose-reduction or modification of chemotherapy (n = 23/33, 70%). CONCLUSIONS: In our analysis, omission of chemotherapy or adjustment of chemotherapy dose during definitive radiotherapy was necessary for the overwhelming majority of elderly esophageal cancer patients not eligible for surgery, and hence resulted in reduced PFS and OS. Therefore, optimization of non-surgical approaches and the identification of potential predictive factors for safe administration of concurrent chemotherapy in elderly patients with (gastro)esophageal adenocarcinoma is required.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Idoso , Humanos , Estudos Retrospectivos , Junção Esofagogástrica , Neoplasias Esofágicas/terapia , Adenocarcinoma/terapia
16.
Medicine (Baltimore) ; 103(9): e37289, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428860

RESUMO

Adenocarcinoma of the esophagogastric junction (AEG) has a high incidence, and the extent of lymph node dissection (LND) and its impact on prognosis remain controversial. This study aimed to explore the risk factors for lymph node metastasis (LNM) and prognosis in Siewert II/III AEG patients. A retrospective review of 239 Siewert II/III AEG patients surgically treated at Beijing Friendship Hospital from July 2013 to December 2022 was conducted. Preoperative staging was conducted via endoscopy, ultrasound gastroscopy, CT, and biopsy. Depending on the stage, patients received radical gastrectomy with LND and chemotherapy. Clinicopathological data were collected, and survival was monitored semiannually until November 2023. Utilizing logistic regression for data analysis and Cox regression for survival studies, multivariate analysis identified infiltration depth (OR = 0.038, 95% CI: 0.011-0.139, P < .001), tumor deposit (OR = 0.101, 95% CI: 0.011-0.904, P = .040), and intravascular cancer embolus (OR = 0.234, 95% CI: 0.108-0.507, P < .001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert III AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert II. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert II AEG, with rates of 5.45% and 3.64%, respectively. A 3-year survival analysis underscored LNM as a significant prognostic factor (P = .001). Siewert II AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert III AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No. 5 and No. 6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/patologia , Prognóstico , Excisão de Linfonodo , Adenocarcinoma/patologia , Junção Esofagogástrica/patologia , Fatores de Risco
17.
Nat Med ; 30(4): 1023-1034, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38504015

RESUMO

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1 , Terapia Neoadjuvante , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Junção Esofagogástrica , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
18.
Turk J Gastroenterol ; 35(1): 11-16, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454273

RESUMO

BACKGROUND/AIMS: Early-stage gastroesophageal junction (GEJ) adenocarcinoma can be challenging to diagnose and treat promptly using endoscopy. This study aims to summarize the endoscopic characteristics of early GEJ adenocarcinoma and investigate their correlation with pathological grade and invasion depth. MATERIALS AND METHODS: This retrospective case series study evaluated patients with early GEJ adenocarcinoma who underwent endoscopic or surgical resection at First Affiliated Hospital of Dalian Medical University between January 2016 and December 2022. RESULTS: A total of 71 patients were included in the analysis, with 59 males and a median age of 67 years. The majority of the lesions were located on the posterior side of the GEJ (40.8%) or the lesser curvature side (29.6%). Siewert II lesions accounted for 71.8% of cases, with most occurring on the posterior side (49.0%) and Siewert III lesions mostly occurring on the lesser curvature side (42.9%). Siewert I lesions accounted for only 7.0%, and all originated from Barrett mucosa. Paris classification of Is (P = .015) or IIc (P = .015), lesion size ≥12 mm (P = .017), red color with subsquamous extension (P = .038), and disordered microsurface with local fusion (P < .001) were independently and positively correlated with pathological grade and invasion depth by multivariable ordinal logistic regression. CONCLUSION: The posterior side and lesser curvature of the GEJ are the high-incidence sites of GEJ adenocarcinoma. Both forward and backward views during endoscopy should be combined to detect the lesion. Endoscopic characteristics such as Is or IIc morphology, larger size, red color with subsquamous extension, and disordered microsurface with local fusion may indicate a higher pathological grade and deeper invasion.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Masculino , Humanos , Idoso , Estudos Retrospectivos , Junção Esofagogástrica/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Adenocarcinoma/patologia , Endoscopia Gastrointestinal , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia
20.
Support Care Cancer ; 32(3): 189, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400905

RESUMO

PURPOSE: Many cancer patients and caregivers experience financial hardship, leading to poor outcomes. Gastric and gastroesophageal junction (GEJ) cancer patients are particularly at risk for financial hardship given the intensity of treatment. This pilot randomized study among gastric/GEJ cancer patients and caregivers tested a proactive financial navigation (FN) intervention to obtain a signal of efficacy to inform a larger, more rigorous randomized study. METHODS: We tested a 3-month proactive FN intervention among gastric/GEJ cancer patients and caregivers compared to usual care. Caregiver participation was optional. The primary endpoint was incidence of financial hardship, defined as follows: accrual of debt, income decline of ≥ 20%, or taking loans to pay for treatment. Data from participant surveys and documentation by partner organizations delivering the FN intervention was analyzed and outcomes were compared between study arms. RESULTS: Nineteen patients and 12 caregivers consented. Primary FN resources provided included insurance navigation, budget planning, and help with out-of-pocket medical expenses. Usual care patients were more likely to experience financial hardship (50% vs 40%) and declines in quality of life (37.5% vs 0%) compared to intervention patients. Caregivers in both arms reported increased financial stress and poorer quality of life over the study period. CONCLUSIONS: Proactive financial navigation has potentially positive impacts on financial hardship and quality of life for cancer patients and more large-scale randomized interventions should be conducted to rigorously explore the impact of similar interventions. Interventions that have the potential to lessen caregiver financial stress and burden need further exploration. TRIAL REGISTRATION: TRN: NCT03986502, June 14, 2019.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Qualidade de Vida , Humanos , Renda , Junção Esofagogástrica
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