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BACKGROUND: Inflammatory biomarkers in the peripheral blood have been established as predictors for immunotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC). Whether they can also predict major pathological response (MPR) in neoadjuvant setting remains unclear. METHODS: In this multi-center retrospective study, 122 and 92 stage I-IIIB NSCLC patients from six hospitals who received neoadjuvant chemoimmunotherapy followed by surgery were included in the discovery and external validation cohort, respectively. Baseline and on-treatment neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) were calculated and associated with MPR. Furthermore, resected tumor samples from 37 patients were collected for RNA-sequencing to investigate the immune-related tumor microenvironment. RESULTS: In both the discovery and validation cohorts, the on-treatment NLR, dNLR, PLR, and SII levels were significantly lower in the patients with MPR versus non-MPR. On-treatment SII remained an independent predictor of MPR in multivariate logistic regression analysis. The area under the curve (AUC) of on-treatment SII for predicting MPR was 0.75 (95%CI, 0.67-0.84) in the discovery cohort. Moreover, the predictive value was further improved by combining the on-treatment SII and radiological tumor regression data, demonstrating an AUC of 0.82 (95%CI, 0.74-0.90). The predictive accuracy was validated in the external cohort. Compared with the SII-high group, patients with SII-Low were associated with the activated B cell receptor signaling pathway and a higher intratumoral immune cell infiltration level. CONCLUSIONS: On-treatment SII was independently associated with MPR in NSCLC patients receiving neoadjuvant chemoimmunotherapy. Further prospective studies are warranted.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Terapia Neoadjuvante , Biomarcadores , Inflamação , Neutrófilos/patologia , Prognóstico , Microambiente TumoralRESUMO
OBJECTIVE: To compare perioperative and long-term outcomes of robot-assisted minimally invasive esophagectomy (RAMIE) and conventional minimally invasive esophagectomy (MIE) in the treatment for patients with esophageal squamous cell carcinoma (ESCC). SUMMARY BACKGROUND DATA: RAMIE has emerged as an alternative to traditional open or thoracoscopic approaches. Efficacy and safety of RAMIE and MIE in the surgical treatment for ESCC remains uncertain given the lack of high-level clinical evidence. METHODS: The RAMIE trial was designed as a prospective, multicenter, randomized, controlled clinical trial that compares the efficacy and safety of RAMIE and MIE in the treatment of resectable ESCC. From August 2017 to December 2019, eligible patients were randomly assigned to receive either RAMIE or MIE performed by experienced thoracic surgeons from 6 high-volume centers in China. Intent-to-treat analysis was performed. RESULTS: Significantly shorter operation time was taken in RAMIE (203.8 vs 244.9 min, P<0.001). Compared with MIE, RAMIE showed improved efficiency of thoracic lymph node dissection in patients who received neoadjuvant therapy (15 vs 12, P = 0.016), as well as higher achievement rate of lymph node dissection along the left recurrent laryngeal nerve (79.5% vs 67.6%, P = 0.001). No difference was found in blood loss, conversion rate, and R0 resection. The 90-day mortality was 0.6% in each group. Overall complications were similar in RAMIE (48.6%) compared with MIE (41.8%) (RR, 1.16; 95% CI, 0.92-1.46; P = 0.196). Besides, the rate of major complications (Clavien-Dindo classification ≥ III) was also comparable (12.2% vs 10.2%, P = 0.551). RAMIE showed similar incidences of pulmonary complications (13.8% vs 14.7%; P = 0.812), anastomotic leakage (12.2% vs 11.3%; P = 0.801), and vocal cord paralysis (32.6% vs 27.1%, P = 0.258) to MIE. CONCLUSIONS: Early results demonstrate that both RAMIE and MIE are safe and feasible for the treatment of ESCC. RAMIE can achieve shorter operative duration and better lymph node dissection in patients who received neoadjuvant therapy. Long-term results are pending for further follow-up investigations. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03094351.
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Boehmeria , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Robótica , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240). METHODS: The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events. DISCUSSION: This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021. TRIAL REGISTRATION: ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Terapia Neoadjuvante , Estudos ProspectivosRESUMO
Esophagogastric anastomosis stricture is one of the most common postoperative complications after esophagectomy; yet, its pathogenesis is still not fully understood, and the treatment and prevention of anastomotic stricture are limited due to the lack of a proper animal model. The insufficient blood supply in the gastric tube is considered a risk factor for postoperative anastomotic strictures. In this study, we used thermal imaging to develop a stable rodent model with esophagogastric anastomotic stricture caused by ischemia. Briefly, 30 male Sprague-Dawley rats have been divided into the control group and the ischemia group. The esophagogastric ischemia anastomosis was performed with the help of intraoperative thermal imaging to identify the poor perfusion area. An unpaired t test with Welch's correction was used to analyze the difference between the two groups. On postoperative day 84, in the control group, no anastomosis stricture was observed, while in the ischemia group, 12 out of 15 animals (80%) developed obvious anastomosis stricture which could not let a 2.7-mm endoscope pass through. The diameter of the anastomosis in the control group and the ischemia group were 2.80 ± 0.15 mm and 1.73 ± 0.44 mm (p < 0.01), respectively (evaluated by endoscopy examination and barium radiography). H&E stain and Masson's trichrome showed that the anastomosis in the ischemia group had more connective tissue hyperplasia and collagen deposition than control group. Thus, this new rat model can be used as a platform to further investigate the potential interventions for prevention of esophagogastric anastomotic stricture.
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Neoplasias Esofágicas , Masculino , Ratos , Animais , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Neoplasias Esofágicas/cirurgia , Ratos Sprague-Dawley , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Isquemia/etiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controleRESUMO
BACKGROUND: Hexokinase domain component 1 (HKDC1) plays an oncogenic role in certain types of cancer, such as lymphoma, liver cancer, and breast cancer. Previous bioinformatics study revealed that HKDC1 was significantly upregulated in lung adenocarcinoma (LUAD). However, its biological functions and potential mechanism in LUAD have not been studied. METHODS: We performed bioinformatics analysis, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and a series of functional assays in vitro and in vivo to investigate the roles of HKDC1 in LUAD. RESULTS: We discovered that HKDC1 was highly expressed in LUAD tissues and cell lines, and the positive expression of HKDC1 was correlated with aberrant clinicopathological characteristics in LUAD patients. Furthermore, HKDC1 could serve as a prognostic predictor for LUAD patients. Overexpression of HKDC1 promoted proliferation, migration, invasion, glycolysis, EMT and tumorigenicity, whereas knockdown of HKDC1 produced the opposite functional effects. Mechanistically, HKDC1 could regulate the AMPK/mTOR signaling pathway to perform its biological function. CONCLUSIONS: Our findings suggest that HKDC1 plays an oncogenic role in LUAD. Targeting this gene may provide a promising therapeutic target to delay LUAD progression.
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BACKGROUND: Currently, there are three main surgical approaches for resectable esophageal cancer: open transthoracic esophagectomy (OTE), conventional minimally invasive esophagectomy (MIE) and robot-assisted esophagectomy (RAE). Previous studies had demonstrated the better short-term outcomes in MIE or RAE when compared to OTE, respectively. However, to date, no prospective study was designed to compare these two minimally invasive approaches (MIE and RAE). The primary objective of this study is to compare the outcomes on survival, safety and efficacy, quality of life between RAE and MIE in the treatment for resectable esophageal squamous cell carcinoma (ESCC). METHODS: This study is designed as a multicenter, prospective, randomized, non-inferiority phase III clinical trial, investigating the safety and efficacy of RAE compared with MIE in the treatment of resectable ESCC. Eligible patients are randomly assigned to either RAE (n = 180) or MIE (n = 180) group. The follow-up visits will be scheduled at 3, 6, 9, and 12 months in the first two years, and then every 6 months until the end of the study. During the follow-up period, clinical data and quality of life questionnaires will be examined. The primary endpoint is the 5-year overall survival (OS). The secondary endpoints are 3-year OS, 5-year disease-free survival (DFS), short-term outcomes as well as quality of life. DISCUSSION: This is the first prospectively randomized controlled trial designed to compare RAE with MIE as surgical treatment for resectable ESCC. According to our hypothesis, RAE will result in at least similar oncologic outcomes and long-term quality of life, but with a shorter operation time, lower percentage of perioperative complications, lower blood loss, and shorter hospital stay when compared with MIE. This study started in July 2017. Follow-up will terminate after 5 years from the time when the last patient was enrolled. TRIAL REGISTRATION: ClinicalTrial.gov: NCT03094351 (March 29, 2017). The trial was prospectively registered.
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Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Dysregulation of protein arginine methyltransferase 1 (PRMT1) has been reported in several cancer types. However, its expression pattern and biological functions in esophageal squamous cell carcinoma (ESCC) remained unknown. Here, we have found that the expression of PRMT1 was up-regulated in ESCC samples. In the biological function studies, forced expression of PRMT1 promoted the growth and migration of ESCC cells. However, knocking down the expression of PRMT1 inhibited the growth, migration, and metastasis of ESCC cells. Moreover, PRMT1 activated Hedgehog signaling and up-regulated the expression of target genes downstream of Hedgehog signaling. Taken together, our study revealed the oncogenic roles of PRMT1 in the progression of ESCC, and PRMT1 might be a promising therapeutic target for the treatment of ESCC.
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Carcinoma de Células Escamosas/patologia , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Proteína-Arginina N-Metiltransferases/genética , Proteínas Repressoras/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Hedgehog/genética , Humanos , Transdução de Sinais/genética , Regulação para Cima/genéticaRESUMO
Currently, long non-coding RNAs (lncRNAs) have been shown to have critical regulatory roles in various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Here, we focused on lncRNA BC032469, one of the lncRNAs involved in the development of ESCC. The levels of a specific differentially expressed lncRNA (termed lncRNA-BC032469) were measured in 45 paired esophageal squamous cell carcinoma tissue samples by quantitative real-time RT-PCR and then subjected to correlation analysis with clinical parameters and prognosis. The functions of lncRNA-BC032469 were evaluated by silencing and overexpressing the lncRNA in vitro and in vivo. The expression level of BC032469 in esophageal squamous cell carcinoma tissues was higher than that in the corresponding non-cancerous tissues. High BC032469 levels were correlated with lymph node metastasis, TNM stage, and tumor size and lower overall survival. Knockdown of BC032469 in TE13 and Eca109 cells inhibited cell proliferation, migration, and invasion; induced cell cycle arrest in the G0/G1 phase; and promoted apoptosis. Western blot analysis revealed that BC032469 regulated the expression of human telomerase reverse transcriptase (hTERT), which is important for cell proliferation and metastasis. Moreover, the restored expression of hTERT protein in BC032469-knockdown cells attenuated the suppressive effects of BC032469 on ESCC cells. Collectively, these results indicated that lncRNA-BC032469 is an oncogenic lncRNA that promotes tumor progression and leads us to propose that lncRNAs may serve as key regulatory hubs in ESCC development.
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Protein arginine methylation, which is mediated by the protein arginine methyltransferases (PRMTs), is associated with numerous fundamental cellular processes. Our previous studies have shown that PRMT1 activated Hedgehog signaling in the esophageal squamous cell carcinoma (ESCC) cells and promoted the growth and migration of cancer cells. However, the detailed mechanisms are unknown. In this study, it was found that PRMT1 interacted with the transcriptional factor Gli1 (glioma-associated oncogene homolog 1) in ESCC cells. The DNA-binding domain (DBD) of Gli1 is responsible for its interaction with PRMT1. Moreover, PRMT1 promoted the methylation of Gli1, and knocking down the expression of PRMT1 impaired the transcriptional activity as well as the biological functions of Gli1. Taken together, our study demonstrated that PRMT1 is a positive regulator of Hedgehog signaling, and PRMT1 might be a therapeutic target for ESCC.
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Proteína-Arginina N-Metiltransferases/genética , Proteínas Repressoras/genética , Transcrição Gênica/genética , Proteína GLI1 em Dedos de Zinco/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Proteínas Hedgehog/genética , Humanos , Transdução de Sinais/genética , Fatores de Transcrição/genética , Ativação Transcricional/genéticaRESUMO
Previous studies verified that miR-214 is of great significance in the invasion and migration of a variety of cancers. It has been demonstrated that UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) is a putative target of miR-214. We performed this study to figure out how miR-214 and GALNT7 play their roles in the invasion and migration of esophageal squamous cell carcinoma (ESCC). The expression of miR-214 was significantly downregulated in tumors compared to the corresponding non-tumor tissues while GALNT7 showed an opposite tendency. The low expression of miR-214 and the high expression of GALNT7 were found positively correlated with poor tumor differentiation (P = 0.004), tumor invasion (P = 0.013), and lymph node metastasis (P = 0.012) in ESCC patients. Functional study demonstrated that overexpression of miR-214 or knockdown of GALNT7 could weaken invasive and migratory ability in Eca109, TE1, and KYSE150. Moreover, tumorigenicity assay showed us mice injected with cells containing miR-214 mimic or GALNT7 small interfering RNA formed substantially smaller tumors than that in miR-214 inhibitor group. Consequently, we concluded that miR-214 shows potential to be a diagnostic marker and therapeutic target in ESCC.
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Carcinoma de Células Escamosas/secundário , Movimento Celular , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , N-Acetilgalactosaminiltransferases/metabolismo , Idoso , Animais , Apoptose , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Regulação para Baixo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , N-Acetilgalactosaminiltransferases/antagonistas & inibidores , N-Acetilgalactosaminiltransferases/genética , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
Reconstruction for patients with advanced squamous cell carcinoma of the hypopharynx (SCCHP) after radical surgery is a challenge for head and neck surgeons, especially when one flap alone cannot entirely cover the defects. In this report, we describe the successful use of gastric pull-up combined with pectoralis major flaps for single-stage reconstruction after total laryngopharyngoesophagectomy in patients with SCCHP. We retrospectively reviewed the records of 23 patients with stage IV SCCHP who underwent this reconstructive procedure. Surgical details and perioperative morbidity were described, and functional and oncologic outcomes were evaluated. We used the gastric pull-up and pectoralis major flap procedure to reconstruct the defects for all 23 patients. In 13 patients the combined flaps were used to restore intestinal continuity, and in 10 patients the defects were repaired using gastric pull-up alone and covered by the pectoralis major flap. All the combined flaps worked well, and patients recovered normal swallowing function a mean 19.6 days after surgery. After an overall mean follow-up time of 25.3 months, six patients were still alive at the time of this analysis with no evidence of disease. Our results indicate that for patients with advanced SCCHP after total laryngopharyngoesophagectomy, using a pectoralis major flap combined with gastric pull-up enables one-stage reconstruction even when gastric pull-up alone cannot restore intestinal continuity. Furthermore, the functional and oncologic outcomes from this study suggest that this reconstructive procedure is safe and reliable, and more patients with advanced disease could be considered.
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Carcinoma de Células Escamosas/cirurgia , Esofagectomia/efeitos adversos , Neoplasias Hipofaríngeas/cirurgia , Laringectomia/efeitos adversos , Faringectomia/efeitos adversos , Estômago/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the efficacy of MSCs autografting with fibrin sealant could for the closure of cervical anastomotic fistula. METHODS: Twenty-one healthy New Zealand rabbits were involved and randomly assigned to treatment group (n = 12) or control group (n = 9). After the bone marrow were aspirated, the MSCs were isolated, purified and labelled by transfection of Lenti. GFP. The rabbit models of cervical esophageal anastomotic fistula were established by leaving a caliber rubber tube inside esophageal lumen. One week later, a 0.2 ml FS with 2 x 10(6) GFP+ MSCs was employed to close the fistula for each animal in the treatment group, while the same procedure was performed without MSCs in the control group. MRI examination was performed to evaluate the closure of fistula after 5 weeks. All animals were killed and the esophageal tissues were collected 7 weeks later. Histology and immunohistochemistry study were performed. RESULTS: The rabbit models of cervical anastomotic fistula were successfully established. There was no significant difference of fisutla caliber between both groups ( (2.30 ± 0.15) mm vs (2.20 ± 0.17) mm, P < 0.05), MRI exam revealed that there was only inflammation sign in the treatment group, by contrast, most of the rabbits were showed purulent infection sign which induced by persistent fistula in the control group. At the end of the study, the mortality of the treatment group and the control group were 3/12 and 5/9 (P = 0.20). However, the closure rates of the fistula were 10/12 and 1/9, respectively, with significant difference between two groups (P = 0.02). Histological study indicated that there was mild inflammation response and less collagen deposition for treatment group, compared to control group. Immunohistochemistry study further demonstrated that the autografted MSCs colonized to the fistula and differentiated into myofibroblasts. CONCLUSION: Auto-transplantation of MSCs and FS can increase the closure rate of the cervical anastomotic fistula through the mechanisms of immunomodulatory, extracellular matrix reconstruction and anti-immigration effect of FS.
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Fístula Esofágica/terapia , Adesivo Tecidual de Fibrina , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular , Colágeno/metabolismo , Miofibroblastos/citologia , Coelhos , Distribuição Aleatória , Transplante AutólogoRESUMO
OBJECTIVE: This study aims to report the 2-year outcomes of patients with clinical stage N2-3 esophageal squamous cell carcinoma who received neoadjuvant chemotherapy and immunotherapy followed by surgery from a phase 2 NICE trial. METHODS: Eligible patients with clinical stage N2-3 esophageal squamous cell carcinoma were screened and enrolled, then treated with regimen of nab-paclitaxel (100 mg/m2, days 1, 8, 15), carboplatin (area under the curve = 5, day 1), camrelizumab (200 mg, day 1) of two 21-day cycles and esophagectomy 4 to 6 weeks after the last chemotherapy. Oncologic outcomes, recurrence patterns, overall survival (OS), and recurrence-free survival (RFS) were explored. RESULTS: From November 20, 2019, to December 22, 2020, 60 patients were recruited. After a median follow-up of 27.4 months, disease recurrence was observed in 19 (37.3%) patients, with 5 (9.8%) locoregional recurrence, 9 (17.6%) distant metastasis, and 5 (9.8%) combined recurrence. Lung was the most commonly involved metastatic site. The median time to recurrence was 10.8 months (interquartile range, 7.5-12.7 months). The 2-year OS and RFS rates were 78.1% and 67.9%, respectively. Patients who achieved major pathologic response (MPR) had a significantly greater 2-year OS rate (91.4% vs 47.7%; P < .001) and RFS rate (77.1% vs 45.9%; P = .003). On multivariable analysis, MPR was indicated as an independent prognostic factor for disease recurrence (hazard ratio, 0.39; 95% confidence interval, 0.21-0.82; P = .029). CONCLUSIONS: In patients receiving neoadjuvant chemotherapy and immunotherapy, distant metastasis remains the predominant recurrence pattern. MPR is associated with lower recurrence and better survival. Long-term results derived from randomized controlled trials are further required. TRIAL REGISTRATION NUMBER: ChiCTR1900026240.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Cisplatino , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/patologia , ImunoterapiaRESUMO
Introduction: Congenital bronchial atresia (CBA), as a rare developmental abnormality of the lung, is usually asymptomatic and is accidently discovered in most cases. Currently, no standardized guidelines for the treatment or management of CBA have been established. Case presentation: A 22-year-old male soldier was referred to Shanghai Changhai Hospital, The First Affiliated Hospital of Naval Medical University due to chest tightness and shortness of breath after repeated strenuous activities. Contrast-enhanced computed tomography (CT) revealed an 18mm × 11mm solitary, well-circumscribed, and solid nodule with no enhancement in the right upper lobe (RUL), and emphysematous changes distributed throughout the RUL. A flexible bronchoscopic examination showed extrinsic compression stenosis in the bronchial opening of the right middle lobe (RML). After three-dimensional (3D) reconstruction CT and a multidisciplinary consultation, a diagnosis of CBA in the anterior segment (B3) of RUL was established. Subsequently, thoracoscopic right upper lobectomy was performed and resulted in an improved respiratory capacity 6 months after surgery. To date, the patient has good quality of life without any complication. Conclusion: This study underscores the role of bronchoscopy, 3D reconstruction CT, and a multidisciplinary consultation in the diagnosis of CBA, and highlights that a thoracoscopic intervention should be considered in such case.
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BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.
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Metilação de DNA , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/sangue , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Método Duplo-Cego , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , AdultoRESUMO
BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.
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This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia Neoadjuvante , Piridinas , Humanos , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Adulto , Estadiamento de Neoplasias , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
Background: Esophageal cancer is one of the deadliest malignancies in the world, and 5-year overall survival (OS) of esophageal cancer ranges from 12% to 20%. Surgical resection remains the principal treatment. The American Joint Commission on Cancer (AJCC) TNM (tumor, node, and metastasis) staging system is a key guideline for prognosis and treatment decisions, but it cannot fully predict outcomes. Therefore, targeting the molecular and biological features of each patient's tumor, and identifying key prognostic biomarkers as effective survival predictors and therapeutic targets are highly important to clinicians and patients. Methods: In this study, three different methods, including Univariate Cox regression, Lasso regression, and Randomforest regression were used to screen the independent factors affecting the prognosis of esophageal squamous cell carcinoma and construct a nomogram prognostic model. The accuracy of the model was verified by comparing with TNM staging system and the reliability of the model was verified by internal cross validation. Results: Preoperative neutrophil lymphocyte ratio(preNLR), N-stage, p53 level and tumor diameter were selected to construct the new prognostic model. Patients with higher preNLR level, higher N-stage, lower p53 level and larger tumor diameter had worse OS. The results of C-index, Decision Curve Analysis (DCA), and integrated discrimination improvement (IDI) showed that the new prognostic model has a better prediction than the TNM staging system. Conclusion: The accuracy and reliability of the nomogram prognostic model were higher than that of TNM staging system. It can effectively predict individual OS and provide theoretical basis for clinical decision making.
RESUMO
BACKGROUND: Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC. METHODS: We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. RESULTS: The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85-0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83-0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I-II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III-IV ESCC. CONCLUSIONS: The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.