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Ultra-remote robot-assisted right upper lobectomy between the Shanghai and Kashi Prefectures: a case report. 上海和喀什地区超远程机器人辅助右上肺叶切除术一例报告。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/jtd-24-1605
Yu Tian, Huibin Lv, Adilijiang Jumai, Tuersun Tuerhong, Lihong Zhuang, Jia Huang, Jiantao Li, Peiji Lu, Guorong Tao, Yoshikane Yamauchi, Raja M Flores, Haohua Teng, Tianxiang Chen, Qingquan Luo

Background: Robot-assisted thoracic surgery has been shown to have several advantages over conventional surgery. As mobile communication technology and surgical robotic devices in China continue to progress rapidly, the conditions for performing remote surgery have been optimized. Consequently, informatized and remote advanced medical cooperation is becoming a new direction for supporting the medical development of border regions and promoting the equitable distribution of medical resources in China.

Case description: In this case, a 53-year-old female patient in Kashi was admitted with a mixed ground-glass lesion in the right upper lobe. The size and density of the lesion were found to be increasing progressively. After a comprehensive multidisciplinary team consultation, the patient was clinically diagnosed with early stage lung cancer. The patient gave informed consent to undergo remote robot-assisted right upper lobectomy and lymph node dissection, which was performed on July 13, 2024 between Shanghai and Kashi using a dedicated network and 5G mobile communication. The procedure was successfully conducted with an average delay of 100 ms and no connection interruptions. Pathology and immunohistochemistry confirmed invasive mucinous adenocarcinoma (T1aN0M0). Postoperative imaging showed good lung re-expansion; the patient had an ideal recovery and was discharged smoothly.

Conclusions: We reported the first case in which a remote robot-assisted lobectomy was performed using a robotic surgical system, 5G technology, and corresponding procedures. More cohorts or clinical studies need to be conducted to further clarify the guidelines and promote the application of remote thoracic surgery.

背景:机器人辅助胸外科手术已被证明比传统手术有几个优点。随着中国移动通信技术和手术机器人设备的快速发展,远程手术的条件得到了优化。因此,信息化和远程先进医疗合作正成为支持边境地区医疗发展、促进中国医疗资源公平配置的新方向。病例描述:在本病例中,一名来自喀什的53岁女性患者因右上叶混合性磨玻璃病变而入院。病灶的大小和密度逐渐增大。经过综合多学科团队会诊,患者临床诊断为早期肺癌。患者知情同意于2024年7月13日在上海和喀什之间通过专用网络和5G移动通信进行远程机器人辅助右上肺叶切除和淋巴结清扫。该过程成功完成,平均延迟为100毫秒,没有连接中断。病理及免疫组化证实为浸润性粘液腺癌(T1aN0M0)。术后影像学显示肺再扩张良好;病人恢复良好,顺利出院。结论:我们报告了第一例使用机器人手术系统、5G技术和相应程序进行远程机器人辅助肺叶切除术的病例。需要更多的队列研究或临床研究来进一步明确指导方针,促进远程胸外科手术的应用。
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引用次数: 0
Case series on the use of the indocyanine green fluorescence real-time imaging technique for lymph node sorting in patients undergoing radical esophagectomy. 应用吲哚菁绿荧光实时成像技术进行根治性食管切除术患者淋巴结分选的病例系列。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-28 DOI: 10.21037/jtd-2024-1939
Xiao Wang, Weixin Liu, Xiaodan Hu, Yangle Zhao, Yun Zhao, Xingxing Xue, Xiaogang Liu, Lining Wang, Thomas Bauer, Jian Cui, Yong Li

Background: There is a clear correlation between accurate postoperative lymph node staging and the survival prognosis of patients. This study aimed to explore the application and value of indocyanine green (ICG) fluorescence real-time imaging technology in lymph node sorting during radical esophagectomy for esophageal cancer.

Methods: From August 2022 to June 2023, the specimens of 66 patients who underwent esophageal cancer resection with lymph node dissection were examined. Among them, 12 cases of ex vivo esophageal specimens underwent secondary lymph node sorting using ICG fluorescence real-time imaging technology after conventional lymph node sorting, while the remaining 54 cases underwent conventional lymph node sorting.

Results: A total of 329 lymph nodes were detected in the 12 patients with an average of 29.75±9.19 nodes per patient. Lymph node metastasis was detected in five patients, of whom, three were diagnosed as N1 (N refers to regional lymph nodes, N1: involves 1 to 2 regional lymph node metastases), and two were diagnosed as N2 (N refers to regional lymph nodes, N2: involves 3-6 regional lymph node metastases). Following the ICG injection of 12 patient specimens, lymph nodes were re-detected in 6 patients of them (above we stated 12 patients), yielding a detection rate of 50%. In total, 17 lymph nodes were detected. There was a statistically significant difference in the total number of lymph nodes detected before and after the injection of ICG (P=0.02). Among the other 54 patients, an average of 34.06±15.66 lymph nodes were detected. There was no statistically significant difference in the total number of lymph nodes detected between the two groups (P=0.21).

Conclusions: The use of ICG fluorescence real-time imaging technology facilitate lymph node identification in resected specimens and will become a powerful technique for precise staging in esophageal cancer treatment.

背景:准确的术后淋巴结分期与患者的生存预后有明显的相关性。本研究旨在探讨吲哚菁绿(ICG)荧光实时成像技术在食管癌根治性食管切除术中淋巴结分选中的应用及价值。方法:对2022年8月~ 2023年6月行食管癌切除术合并淋巴结清扫术的66例患者标本进行分析。其中12例离体食管标本在常规淋巴结分选后采用ICG荧光实时成像技术进行二次淋巴结分选,其余54例进行常规淋巴结分选。结果:12例患者共检出淋巴结329个,平均29.75±9.19个。5例患者检测到淋巴结转移,其中3例诊断为N1 (N指区域淋巴结,N1:涉及1 ~ 2个区域淋巴结转移),2例诊断为N2 (N指区域淋巴结,N2:涉及3 ~ 6个区域淋巴结转移)。12例患者标本注射ICG后,其中6例(上文所述12例)再次发现淋巴结,检出率为50%。共检出17个淋巴结。注射ICG前后淋巴结检出总数比较,差异有统计学意义(P=0.02)。其余54例患者平均检出34.06±15.66个淋巴结。两组患者淋巴结总数比较,差异无统计学意义(P=0.21)。结论:ICG荧光实时成像技术的应用有助于对切除标本进行淋巴结识别,将成为食管癌治疗中精确分期的有力技术。
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引用次数: 0
Use of the anatomical formulae for predicted postoperative (PPO) evaluation overestimates the loss of FEV1 and DLCO after minimally invasive lung resections. 使用解剖公式进行预测术后(PPO)评估高估了微创肺切除术后FEV1和DLCO的损失。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/jtd-24-447
Sara Degiovanni, Sara Parini, Guido Baietto, Fabio Massera, Esther Papalia, Giulia Bora, Daniela Ferrante, Piero Emilio Balbo, Ottavio Rena

Background: Pulmonary function assessment is mandatory before oncological lung resection surgery. To do so, subjects undergo a pulmonary function test (PFT) and the calculation of predicted postoperative (PPO) values to estimate the residual lung function after surgery. The aim of this study is to evaluate the use of anatomical formulae in estimating postoperative pulmonary function in patients undergoing minimally invasive surgery (MIS).

Methods: This is a retrospective study. Patients affected by lung cancer who underwent pulmonary lobectomy or segmentectomy with MIS or thoracotomy approach at our center from June 2020 to May 2021 were considered. Exclusion criteria were: subjects who underwent atypical pulmonary resection surgery or pneumonectomy; and patients who underwent adjuvant therapy (chemotherapy or immunotherapy). PFT data measured before and 1 year after surgery were collected. In particular, postoperative PFT data, especially forced expiratory volume in the first second (FEV1) and diffusing capacity for carbon monoxide (DLCO), and PPO values calculated by the anatomical formulae were compared. Secondary endpoints were: analysis of the postoperative pulmonary function in patients who underwent lung resection with the standard approach (thoracotomy) and evaluation of the anatomical formulae accuracy in subjects operated through thoracotomy.

Results: The sample consisted of 48 patients operated on MIS (video-assisted thoracoscopic surgery and robotic-assisted thoracoscopic surgery) and 20 subjects who underwent thoracotomy for stage I-IIA and I-IIB lung cancer in both groups. The anatomical formula seemed to underestimate the postoperative FEV1% by 8.65% [interquartile range (IQR), 0.5-17.28%; P<0.001]. Furthermore, when comparing postoperative PPODLCO% and post-operative DLCO%, a significant difference was shown with an underestimation of the actual postoperative value of 2.78% (IQR, -3.63% to 10.47%; P=0.045).

Conclusions: Our results confirmed that the anatomical formulae currently used to predict postoperative pulmonary function are reliable in the case of the standard approach (thoracotomy), while they tend to overestimate the loss of FEV1 and DLCO in the postoperative period in patients who were operated on MIS, thus excluding some subjects from the operation.

背景:肿瘤肺切除术前肺功能评估是强制性的。为此,受试者接受肺功能测试(PFT)和术后预测(PPO)值的计算,以估计术后残余肺功能。本研究的目的是评估在微创手术(MIS)患者术后肺功能评估中的解剖学公式的使用。方法:回顾性研究。本研究纳入了2020年6月至2021年5月在我中心行MIS或开胸入路肺叶切除术或肺节段切除术的肺癌患者。排除标准为:接受非典型肺切除术或全肺切除术的受试者;以及接受辅助治疗(化疗或免疫治疗)的患者。收集术前和术后1年的PFT数据。特别比较术后PFT数据,特别是第一秒用力呼气量(FEV1)和一氧化碳弥散量(DLCO),以及由解剖公式计算的PPO值。次要终点为:标准入路(开胸)肺切除术患者术后肺功能分析及开胸手术患者解剖公式准确性评价。结果:样本包括48例MIS(视频辅助胸腔镜手术和机器人辅助胸腔镜手术)患者和20例两组I-IIA期和I-IIB期肺癌患者行开胸手术。解剖公式似乎低估了术后FEV1%的8.65%[四分位数间距(IQR), 0.5-17.28%;PDLCO%和术后DLCO%,差异有统计学意义,低估了术后实际值2.78% (IQR, -3.63% ~ 10.47%;P = 0.045)。结论:我们的研究结果证实,目前用于预测术后肺功能的解剖公式在标准入路(开胸)情况下是可靠的,但它们往往高估了MIS手术患者术后FEV1和DLCO的损失,从而将部分受试者排除在手术之外。
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引用次数: 0
Who is at risk for tPA/DNase treatment failure in empyema?-protocol to identify key predictors for early surgical intervention from a retrospective study. 谁有tPA/DNase治疗脓胸失败的风险?-从回顾性研究中确定早期手术干预关键预测因素的方案。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-28 DOI: 10.21037/jtd-24-1256
Mena Louis, Deepak Dev Vivekanandan, Nathaniel Grabill, Gagan Kumar, Hardeep Singh, J Clifton Hastings, Vijaya Ramalingam

Background: Empyema, characterized by the accumulation of pus in the pleural cavity, poses significant treatment challenges. While intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy is effective for many patients, a substantial proportion require surgical intervention, such as video-assisted thoracoscopic surgery (VATS), following treatment failure. Identifying tPA/DNase treatment failure-associated predictors is crucial for optimizing patient management and improving outcomes. This study aims to identify clinical and biochemical predictors of tPA/DNase treatment failure in empyema patients, facilitating early and targeted interventions.

Methods: We conducted a retrospective analysis of 223 empyema patients treated with tPA/DNase at Northeast Georgia Medical Center between January 2018 and December 2023. Data were collected on demographics, comorbidities, pleural fluid analysis, radiological findings, and laboratory results. Multivariable logistic regression was used to identify predictors of treatment failure, with statistical significance set at a P value <0.05.

Results: Of the 223 patients, 28 (12.6%) experienced treatment failure and required VATS. Several predictors of treatment failure were identified. Younger age was associated with a higher likelihood of treatment failure [odds ratio (OR) =0.97; 95% confidence interval (CI): 0.94-0.99; P=0.03]. The presence of Staphylococcus aureus (S. aureus) infection significantly predicted treatment failure (OR =4.1; 95% CI: 1.2-14.5; P=0.03). Biochemical markers in pleural fluid, such as pH, lactate dehydrogenase (LDH), and protein levels, were not associated with tPA/DNase failure.

Conclusions: Key predictors of tPA/DNase treatment failure in empyema patients include younger age (median age of 60.5 vs. 67 years old) and S. aureus infection. Recognizing these predictors can guide clinicians in identifying high-risk patients and considering early surgical intervention. Future studies should aim to validate these findings in diverse populations to refine and confirm these predictive models.

背景:以胸膜腔积液为特征的脓胸给治疗带来了重大挑战。虽然胸膜内组织纤溶酶原激活剂(tPA)和脱氧核糖核酸酶(DNase)治疗对许多患者有效,但在治疗失败后,很大一部分患者需要手术干预,如视频辅助胸腔镜手术(VATS)。确定tPA/DNase治疗失败相关预测因子对于优化患者管理和改善预后至关重要。本研究旨在确定脓胸患者tPA/DNase治疗失败的临床和生化预测因素,促进早期和有针对性的干预。方法:回顾性分析2018年1月至2023年12月在东北乔治亚医学中心接受tPA/DNase治疗的223例脓胸患者。收集了人口统计学、合并症、胸膜液分析、放射学发现和实验室结果的数据。结果:223例患者中,有28例(12.6%)出现治疗失败并需要VATS治疗。确定了治疗失败的几个预测因素。年龄越小,治疗失败的可能性越大[优势比(OR) =0.97;95%置信区间(CI): 0.94-0.99;P = 0.03)。金黄色葡萄球菌(S. aureus)感染的存在显著预测治疗失败(OR =4.1;95% ci: 1.2-14.5;P = 0.03)。胸膜液中的生化指标,如pH值、乳酸脱氢酶(LDH)和蛋白水平,与tPA/DNase衰竭无关。结论:脓胸患者tPA/DNase治疗失败的关键预测因素包括年龄较小(中位年龄60.5 vs. 67岁)和金黄色葡萄球菌感染。认识到这些预测因素可以指导临床医生识别高危患者并考虑早期手术干预。未来的研究应该致力于在不同的人群中验证这些发现,以完善和确认这些预测模型。
{"title":"Who is at risk for tPA/DNase treatment failure in empyema?-protocol to identify key predictors for early surgical intervention from a retrospective study.","authors":"Mena Louis, Deepak Dev Vivekanandan, Nathaniel Grabill, Gagan Kumar, Hardeep Singh, J Clifton Hastings, Vijaya Ramalingam","doi":"10.21037/jtd-24-1256","DOIUrl":"10.21037/jtd-24-1256","url":null,"abstract":"<p><strong>Background: </strong>Empyema, characterized by the accumulation of pus in the pleural cavity, poses significant treatment challenges. While intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy is effective for many patients, a substantial proportion require surgical intervention, such as video-assisted thoracoscopic surgery (VATS), following treatment failure. Identifying tPA/DNase treatment failure-associated predictors is crucial for optimizing patient management and improving outcomes. This study aims to identify clinical and biochemical predictors of tPA/DNase treatment failure in empyema patients, facilitating early and targeted interventions.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 223 empyema patients treated with tPA/DNase at Northeast Georgia Medical Center between January 2018 and December 2023. Data were collected on demographics, comorbidities, pleural fluid analysis, radiological findings, and laboratory results. Multivariable logistic regression was used to identify predictors of treatment failure, with statistical significance set at a P value <0.05.</p><p><strong>Results: </strong>Of the 223 patients, 28 (12.6%) experienced treatment failure and required VATS. Several predictors of treatment failure were identified. Younger age was associated with a higher likelihood of treatment failure [odds ratio (OR) =0.97; 95% confidence interval (CI): 0.94-0.99; P=0.03]. The presence of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infection significantly predicted treatment failure (OR =4.1; 95% CI: 1.2-14.5; P=0.03). Biochemical markers in pleural fluid, such as pH, lactate dehydrogenase (LDH), and protein levels, were not associated with tPA/DNase failure.</p><p><strong>Conclusions: </strong>Key predictors of tPA/DNase treatment failure in empyema patients include younger age (median age of 60.5 <i>vs.</i> 67 years old) and <i>S. aureus</i> infection. Recognizing these predictors can guide clinicians in identifying high-risk patients and considering early surgical intervention. Future studies should aim to validate these findings in diverse populations to refine and confirm these predictive models.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 12","pages":"8602-8610"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circular RNA SPECC1 promoted tumorigenesis and osimertinib resistance in lung adenocarcinoma via a circular RNA-microRNA network. 环状RNA spec1通过环状RNA- microrna网络促进肺腺癌的肿瘤发生和奥希替尼耐药性。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-28 DOI: 10.21037/jtd-2024-2144
Zhexue Hao, Fenlan Feng, Qi Wang, Yucong Wang, Jin Li, Jinkun Huang

Background: Tyrosine kinase inhibitors (TKIs) are the first-line therapy for patients with non-small cell lung cancer (NSCLC) with sensitized mutations in the epidermal growth factor receptor (EGFR). However, resistance to TKIs is a major clinical issue that affects the survival and prognosis of the patients, with the mechanisms underlying this resistance remaining elusive. Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules, which are generated from pre-messenger RNAs (mRNAs) through back splicing. The aim of this study was to investigate the role of cRNA SPECC1 in promoting resistance to TKIs in NSCLC and to explore its potential involvement in tumorigenesis and metastasis of lung adenocarcinoma (LUAD).

Methods: In this study, we identified differentially expressed genes through RNA sequencing from three tumor samples obtained from patients with poor postoperative TKI treatment outcomes. Validation was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and cell function experiments. We further constructed a competing endogenous RNA (ceRNA) network and performed Gene Ontology (GO) analysis to explore the underlying mechanisms of circRNA.

Results: SPECC1 circular RNA (circSPECC1) was found to be significantly upregulated in tumors as compared to adjacent tissues. Knockdown of circSPECC1 in NSCLC cell lines resulted in decreased proliferation, migration, and invasion. Additionally, apoptosis was increased in cell lines with TKI-sensitive EGFR mutations when treated with osimertinib.

Conclusions: circSPECC1 may promote TKI resistance and contribute to the tumorigenesis and metastasis of NSCLC. This study offers a novel perspective on TKI resistance research at the RNA level.

背景:酪氨酸激酶抑制剂(TKIs)是表皮生长因子受体(EGFR)致敏突变的非小细胞肺癌(NSCLC)患者的一线治疗药物。然而,对TKIs的耐药是影响患者生存和预后的主要临床问题,其耐药机制尚不清楚。环状RNA (circRNAs)是一类由前信使RNA (mrna)通过反剪接产生的单链共价封闭RNA分子。本研究的目的是探讨cRNA SPECC1在促进非小细胞肺癌TKIs耐药中的作用,并探讨其在肺腺癌(LUAD)的发生和转移中的潜在作用。方法:在本研究中,我们通过RNA测序从术后TKI治疗效果较差的患者获得的三个肿瘤样本中鉴定出差异表达基因。采用实时定量聚合酶链反应(qRT-PCR)和细胞功能实验进行验证。我们进一步构建了竞争性内源性RNA (ceRNA)网络,并进行了基因本体(GO)分析,以探索circRNA的潜在机制。结果:肿瘤中SPECC1环状RNA (circSPECC1)的表达水平明显高于邻近组织。在非小细胞肺癌细胞系中敲低circspec1导致增殖、迁移和侵袭减少。此外,当奥西替尼处理tki敏感EGFR突变的细胞系时,细胞凋亡增加。结论:circspec1可能促进TKI耐药,参与非小细胞肺癌的发生转移。本研究为TKI在RNA水平上的耐药研究提供了新的视角。
{"title":"Circular RNA <i>SPECC1</i> promoted tumorigenesis and osimertinib resistance in lung adenocarcinoma via a circular RNA-microRNA network.","authors":"Zhexue Hao, Fenlan Feng, Qi Wang, Yucong Wang, Jin Li, Jinkun Huang","doi":"10.21037/jtd-2024-2144","DOIUrl":"https://doi.org/10.21037/jtd-2024-2144","url":null,"abstract":"<p><strong>Background: </strong>Tyrosine kinase inhibitors (TKIs) are the first-line therapy for patients with non-small cell lung cancer (NSCLC) with sensitized mutations in the epidermal growth factor receptor (<i>EGFR</i>). However, resistance to TKIs is a major clinical issue that affects the survival and prognosis of the patients, with the mechanisms underlying this resistance remaining elusive. Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules, which are generated from pre-messenger RNAs (mRNAs) through back splicing. The aim of this study was to investigate the role of cRNA SPECC1 in promoting resistance to TKIs in NSCLC and to explore its potential involvement in tumorigenesis and metastasis of lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>In this study, we identified differentially expressed genes through RNA sequencing from three tumor samples obtained from patients with poor postoperative TKI treatment outcomes. Validation was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and cell function experiments. We further constructed a competing endogenous RNA (ceRNA) network and performed Gene Ontology (GO) analysis to explore the underlying mechanisms of circRNA.</p><p><strong>Results: </strong><i>SPECC1</i> circular RNA (circ<i>SPECC1</i>) was found to be significantly upregulated in tumors as compared to adjacent tissues. Knockdown of circ<i>SPECC1</i> in NSCLC cell lines resulted in decreased proliferation, migration, and invasion. Additionally, apoptosis was increased in cell lines with TKI-sensitive <i>EGFR</i> mutations when treated with osimertinib.</p><p><strong>Conclusions: </strong>circ<i>SPECC1</i> may promote TKI resistance and contribute to the tumorigenesis and metastasis of NSCLC. This study offers a novel perspective on TKI resistance research at the RNA level.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 12","pages":"8754-8770"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Short-term and long-term outcomes of lung transplantation from marginal donors: a single-center retrospective study. 边缘供体肺移植的短期和长期结果:一项单中心回顾性研究。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/jtd-24-1699
Leyan Chen, Chaojian Chen, Yongqi Cheng, Jiaji Zhou, Feifan Ge, Huachi Jiang, Guibin Qiao, Feng Liu

Background: To expand the donor pool, medical centers worldwide are applying marginal donor lungs in clinical settings. We carried out this research to reveal the short-term and long-term outcomes of marginal lung donor transplantation.

Methods: We performed retrospective research using data from patients who underwent lung transplantation (LT) in The Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu Province, China, between 2018 and 2022 to compare the short-term and long-term outcomes of standard donors and marginal donors.

Results: A total of 553 cases were incorporated in this study. The perioperative mortality of recipients who received marginal donor lungs was around 20.8%, compared with 13.4% in the standard donor recipients (P=0.03). There were no significant differences between the two groups in terms of mechanical ventilation or extracorporeal membrane oxygenation (ECMO), length of intensive care unit and hospital stay, occurrence of primary graft dysfunction, and prevalence of acute rejection. The 1-year survival rate for recipients in the standard group and marginal group was 71.7% and 54.2% (P<0.001), respectively. There was a worse survival rate in the subgroups of age >55 years, smoking ≥20 pack-years, and abnormal chest radiographs; however, the 1-year survival rate in the subgroup analysis of donors with ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg and purulent secretions on bronchoscopy was not significantly different.

Conclusions: Our findings suggest that marginal donor recipients can expect to have a lower survival rate than standard donor recipients. However, marginal lung transplant recipients could also gain benefit equivalent to that provided by standard donor LTs in both the short- and long-term when proper assessment and management strategies are implemented.

背景:为了扩大供体池,世界各地的医疗中心在临床环境中应用边缘供体肺。我们开展这项研究是为了揭示边缘肺供体移植的短期和长期结果。方法:我们对2018年至2022年在中国江苏省南京医科大学附属无锡市人民医院接受肺移植(LT)患者的数据进行回顾性研究,比较标准供体和边缘供体的短期和长期结果。结果:本研究共纳入553例。边缘供肺组围手术期死亡率约为20.8%,而标准供肺组为13.4% (P=0.03)。两组患者在机械通气或体外膜氧合(ECMO)、重症监护病房和住院时间、原发性移植物功能障碍发生率和急性排斥发生率方面无显著差异。标准组和边缘组受者1年生存率分别为71.7%和54.2% (P55年,吸烟≥20包年,胸片异常;然而,对动脉氧分压与吸入氧分数(PaO2/FiO2)之比的供者的1年生存率进行亚组分析。结论:我们的研究结果表明,边缘供者的存活率可能低于标准供者。然而,当实施适当的评估和管理策略时,边缘肺移植受者在短期和长期内也可以获得与标准供体LTs相当的益处。
{"title":"Short-term and long-term outcomes of lung transplantation from marginal donors: a single-center retrospective study.","authors":"Leyan Chen, Chaojian Chen, Yongqi Cheng, Jiaji Zhou, Feifan Ge, Huachi Jiang, Guibin Qiao, Feng Liu","doi":"10.21037/jtd-24-1699","DOIUrl":"https://doi.org/10.21037/jtd-24-1699","url":null,"abstract":"<p><strong>Background: </strong>To expand the donor pool, medical centers worldwide are applying marginal donor lungs in clinical settings. We carried out this research to reveal the short-term and long-term outcomes of marginal lung donor transplantation.</p><p><strong>Methods: </strong>We performed retrospective research using data from patients who underwent lung transplantation (LT) in The Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu Province, China, between 2018 and 2022 to compare the short-term and long-term outcomes of standard donors and marginal donors.</p><p><strong>Results: </strong>A total of 553 cases were incorporated in this study. The perioperative mortality of recipients who received marginal donor lungs was around 20.8%, compared with 13.4% in the standard donor recipients (P=0.03). There were no significant differences between the two groups in terms of mechanical ventilation or extracorporeal membrane oxygenation (ECMO), length of intensive care unit and hospital stay, occurrence of primary graft dysfunction, and prevalence of acute rejection. The 1-year survival rate for recipients in the standard group and marginal group was 71.7% and 54.2% (P<0.001), respectively. There was a worse survival rate in the subgroups of age >55 years, smoking ≥20 pack-years, and abnormal chest radiographs; however, the 1-year survival rate in the subgroup analysis of donors with ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaO<sub>2</sub>/FiO<sub>2</sub>) <300 mmHg and purulent secretions on bronchoscopy was not significantly different.</p><p><strong>Conclusions: </strong>Our findings suggest that marginal donor recipients can expect to have a lower survival rate than standard donor recipients. However, marginal lung transplant recipients could also gain benefit equivalent to that provided by standard donor LTs in both the short- and long-term when proper assessment and management strategies are implemented.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 12","pages":"8656-8668"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incidence, mortality and survival of pleural mesothelioma in Zurich between 1981 and 2019, Switzerland. 1981年至2019年瑞士苏黎世胸膜间皮瘤的发病率、死亡率和生存率
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-19 DOI: 10.21037/jtd-24-766
Linda Vinci, Miriam Wanner, Nena Karavasiloglou, Holger Dressel, Fabio Barresi, Dimitri Korol, Sabine Rohrmann

Background: Pleural mesothelioma is mainly caused by (occupational) asbestos exposure. Since 1990, the import and use of asbestos is prohibited in Switzerland. However, due to the long latency time between exposure and the development of disease, incidence in Switzerland was expected to further increase for years after the ban. The aim of the present study was to analyse incidence, mortality, and survival of patients diagnosed with malignant pleural mesothelioma in the canton of Zurich in Switzerland.

Methods: Population-based cancer registry data and cause of death statistics of the canton of Zurich from 1981 to 2019 were used to calculate age-standardized incidence and mortality rates. Time trends were investigated with joinpoint regression and net survival was computed using the Pohar-Perme method.

Results: In men, the incidence rate increased from 1981 to 2002 {annual percentage change (APC) 4.7 [95% confidence interval (CI): 2.6 to 6.8]} and then decreased until 2019 [APC: -2.3 (95% CI: -4.2 to -0.3)], while in women it increased over the whole period [APC 6.2 (95% CI: -1.3 to 14.4)]. Mortality rates were stable in men and women. Three-year net survival was 9.7% (95% CI: 7.8% to 12.2%) for men and 22.1% (95% CI: 15.3% to 32.1%) for women. Men with stage I or II pleural mesothelioma had a net survival of 25.4% (95% CI: 17.2% to 37.5%) after three years whereas men with stage III or IV experienced a net survival of 7.4% (95% CI: 3.9% to 13.8%) after three years.

Conclusions: Malignant pleural mesothelioma incidence seems to have reached the peak in the canton of Zurich in men, but not yet in women. Mortality rates were stable in men and women, and net survival was poor for both sexes, particularly in men.

背景:胸膜间皮瘤主要由职业性石棉暴露引起。自1990年以来,瑞士禁止进口和使用石棉。然而,由于接触和疾病发展之间的潜伏期较长,预计瑞士的发病率将在禁令实施后的数年内进一步增加。本研究的目的是分析瑞士苏黎世州诊断为恶性胸膜间皮瘤患者的发病率、死亡率和生存率。方法:采用1981 - 2019年苏黎世州基于人群的癌症登记数据和死因统计数据,计算年龄标准化发病率和死亡率。用连接点回归研究时间趋势,用Pohar-Perme法计算净生存率。结果:1981年至2002年,男性的发病率增加{年变化百分比(APC)为4.7[95%可信区间(CI): 2.6至6.8]},然后下降到2019年[APC: -2.3 (95% CI: -4.2至-0.3)],而女性的发病率在整个时期都在增加[APC: 6.2 (95% CI: -1.3至14.4)]。男性和女性的死亡率保持稳定。男性的三年净生存率为9.7% (95% CI: 7.8%至12.2%),女性为22.1% (95% CI: 15.3%至32.1%)。I期或II期胸膜间皮瘤患者三年后的净生存率为25.4% (95% CI: 17.2%至37.5%),而III期或IV期患者三年后的净生存率为7.4% (95% CI: 3.9%至13.8%)。结论:恶性胸膜间皮瘤的发病率似乎在苏黎世州的男性中达到了顶峰,但在女性中尚未达到顶峰。男性和女性的死亡率都很稳定,两性的净存活率都很低,尤其是男性。
{"title":"Incidence, mortality and survival of pleural mesothelioma in Zurich between 1981 and 2019, Switzerland.","authors":"Linda Vinci, Miriam Wanner, Nena Karavasiloglou, Holger Dressel, Fabio Barresi, Dimitri Korol, Sabine Rohrmann","doi":"10.21037/jtd-24-766","DOIUrl":"https://doi.org/10.21037/jtd-24-766","url":null,"abstract":"<p><strong>Background: </strong>Pleural mesothelioma is mainly caused by (occupational) asbestos exposure. Since 1990, the import and use of asbestos is prohibited in Switzerland. However, due to the long latency time between exposure and the development of disease, incidence in Switzerland was expected to further increase for years after the ban. The aim of the present study was to analyse incidence, mortality, and survival of patients diagnosed with malignant pleural mesothelioma in the canton of Zurich in Switzerland.</p><p><strong>Methods: </strong>Population-based cancer registry data and cause of death statistics of the canton of Zurich from 1981 to 2019 were used to calculate age-standardized incidence and mortality rates. Time trends were investigated with joinpoint regression and net survival was computed using the Pohar-Perme method.</p><p><strong>Results: </strong>In men, the incidence rate increased from 1981 to 2002 {annual percentage change (APC) 4.7 [95% confidence interval (CI): 2.6 to 6.8]} and then decreased until 2019 [APC: -2.3 (95% CI: -4.2 to -0.3)], while in women it increased over the whole period [APC 6.2 (95% CI: -1.3 to 14.4)]. Mortality rates were stable in men and women. Three-year net survival was 9.7% (95% CI: 7.8% to 12.2%) for men and 22.1% (95% CI: 15.3% to 32.1%) for women. Men with stage I or II pleural mesothelioma had a net survival of 25.4% (95% CI: 17.2% to 37.5%) after three years whereas men with stage III or IV experienced a net survival of 7.4% (95% CI: 3.9% to 13.8%) after three years.</p><p><strong>Conclusions: </strong>Malignant pleural mesothelioma incidence seems to have reached the peak in the canton of Zurich in men, but not yet in women. Mortality rates were stable in men and women, and net survival was poor for both sexes, particularly in men.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 12","pages":"8240-8249"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predictive and prognostic value of ACSL4 and GPX4 in patients with esophageal squamous cell carcinoma receiving post-operative radiotherapy. ACSL4和GPX4在食管鳞状细胞癌术后放疗中的预测和预后价值。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-18 DOI: 10.21037/jtd-24-1193
Xiaohang Wang, Xin Xu, Yuhui Huang, Ling Rong, Lei Zhang, Yongrui Bai, Xiumei Ma

Background: Although multimodality treatment, including chemoradiotherapy and surgery has significantly improved the prognosis of patients with esophageal squamous cell carcinoma (ESCC), a valid predictor is crucial for individualized treatment. As acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) are key genes with radiation responses and constituents of the ferroptosis signaling pathway, the present study adopted ACSL4 and GPX4 protein expression to explore their predictive and prognostic value in patients with ESCC receiving adjuvant radiotherapy.

Methods: A total of 108 patients with thoracic ESCC who had undergone radical surgery and adjuvant radiotherapy were enrolled in the present retrospectively study. ACSL4 and GPX4 immunohistochemistry experiments were performed on paraffin-embedded tumor samples. The prognostic value of ACSL4 and GPX4 was examined using survival analysis, and the predictive value of ACSL4 and GPX4 for long-term survival was examined using univariate and multivariate Cox regression analyses, and verified by receiver operating characteristic (ROC) analysis.

Results: The survival analysis revealed that overall survival (OS) and disease-free survival (DFS) were significantly longer in the high ACSL4 expression group, and the DFS was significantly shorter in the high GPX4 expression group. The results of univariate and multivariate Cox regression analyses revealed that the ACSL4 expression level was an independent predictor for OS and DFS, and that the GPX4 expression level was an independent predictor for DFS. ROC analysis verified the predictive role of ACSL4 expression for DFS and OS, with an area under the curve (AUC) of 0.713 and 0.663.

Conclusions: The present study demonstrates that ACSL4 and GPX4 may serve as valuable prognostic biomarkers for long-term survival, and play a key translational role in individualized therapy for patients with ESCC.

背景:虽然包括放化疗和手术在内的多模式治疗显著改善了食管鳞状细胞癌(ESCC)患者的预后,但有效的预测因子对于个体化治疗至关重要。由于酰基辅酶a合成酶长链家族成员4 (ACSL4)和谷胱甘肽过氧化物酶4 (GPX4)是影响放射反应的关键基因,是铁死亡信号通路的组成部分,本研究通过ACSL4和GPX4蛋白表达,探讨其在ESCC辅助放疗患者中的预测和预后价值。方法:回顾性分析108例接受根治性手术和辅助放疗的胸椎ESCC患者。石蜡包埋肿瘤标本行ACSL4和GPX4免疫组化实验。采用生存分析检验ACSL4和GPX4的预后价值,采用单因素和多因素Cox回归分析检验ACSL4和GPX4对长期生存的预测价值,并采用受试者工作特征(ROC)分析进行验证。结果:生存分析显示,ACSL4高表达组的总生存期(OS)和无病生存期(DFS)明显延长,GPX4高表达组的DFS明显缩短。单因素和多因素Cox回归分析结果显示,ACSL4表达水平是OS和DFS的独立预测因子,GPX4表达水平是DFS的独立预测因子。ROC分析验证了ACSL4表达对DFS和OS的预测作用,曲线下面积(AUC)分别为0.713和0.663。结论:本研究表明,ACSL4和GPX4可能是ESCC患者长期生存的有价值的预后生物标志物,并在ESCC患者的个体化治疗中发挥关键作用。
{"title":"Predictive and prognostic value of ACSL4 and GPX4 in patients with esophageal squamous cell carcinoma receiving post-operative radiotherapy.","authors":"Xiaohang Wang, Xin Xu, Yuhui Huang, Ling Rong, Lei Zhang, Yongrui Bai, Xiumei Ma","doi":"10.21037/jtd-24-1193","DOIUrl":"https://doi.org/10.21037/jtd-24-1193","url":null,"abstract":"<p><strong>Background: </strong>Although multimodality treatment, including chemoradiotherapy and surgery has significantly improved the prognosis of patients with esophageal squamous cell carcinoma (ESCC), a valid predictor is crucial for individualized treatment. As acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) are key genes with radiation responses and constituents of the ferroptosis signaling pathway, the present study adopted ACSL4 and GPX4 protein expression to explore their predictive and prognostic value in patients with ESCC receiving adjuvant radiotherapy.</p><p><strong>Methods: </strong>A total of 108 patients with thoracic ESCC who had undergone radical surgery and adjuvant radiotherapy were enrolled in the present retrospectively study. ACSL4 and GPX4 immunohistochemistry experiments were performed on paraffin-embedded tumor samples. The prognostic value of ACSL4 and GPX4 was examined using survival analysis, and the predictive value of ACSL4 and GPX4 for long-term survival was examined using univariate and multivariate Cox regression analyses, and verified by receiver operating characteristic (ROC) analysis.</p><p><strong>Results: </strong>The survival analysis revealed that overall survival (OS) and disease-free survival (DFS) were significantly longer in the high ACSL4 expression group, and the DFS was significantly shorter in the high GPX4 expression group. The results of univariate and multivariate Cox regression analyses revealed that the ACSL4 expression level was an independent predictor for OS and DFS, and that the GPX4 expression level was an independent predictor for DFS. ROC analysis verified the predictive role of ACSL4 expression for DFS and OS, with an area under the curve (AUC) of 0.713 and 0.663.</p><p><strong>Conclusions: </strong>The present study demonstrates that ACSL4 and GPX4 may serve as valuable prognostic biomarkers for long-term survival, and play a key translational role in individualized therapy for patients with ESCC.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 12","pages":"8317-8326"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Specific risks and outcomes of octogenarians post-lung cancer resection: our 5-year experience. 80多岁老人肺癌切除术后的具体风险和结果:我们5年的经验。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-23 DOI: 10.21037/jtd-24-703
Hiral Jhala, Jennifer Whiteley, Mathew Thomas

Background: An increasingly large proportion of patients undergoing curative surgery for lung cancer, are octogenarians. We evaluated our short and long-term survival and adverse outcomes after oncological lung resections.

Methods: Octogenarians undergoing anatomical resection for confirmed or suspected lung cancer at a single-centre between January 2016 and December 2021 were included. Retrospective analysis of demographic, clinical, and operative data was performed and correlated with mortality and long-term outcomes.

Results: Out of 214 patients, 189 were included in the final analysis. Median age was 82 years (range, 80-89 years). Most patients had lobectomies and minimally invasive approach. Ninety-day mortality was 3.2% with no intraoperative deaths. Chronic obstructive pulmonary disease (COPD) primarily conferred a greater likelihood of persistent air leak (PAL), chest infection, reintubation and intensive care admission (all P<0.01). Complications occurred more in those with high white cell counts (WCCs) (P=0.03) and squamous cell carcinoma subtype (P<0.01). Wedge resections conferred fewer complications (P=0.049). Hospital length of stay (LOS) was reduced by 1 day in sublobar resections (P=0.01) and halved in minimally invasive approaches compared to thoracotomy (P=0.02). The median overall survival (OS) was 3.5 years (1-, 3-, and 5-year survival was 82.5%, 57.1%, and 38.2%, respectively). Pathological tumour stage (P<0.01) and incomplete resection (R1 or R2) (P=0.02) conferred a worse OS and disease-free survival (DFS). Median DFS was 2.4 years. No significant difference was seen in OS or DFS from extent of resection or tumour subtype (P=0.78, P=0.97 and P=0.40, P=0.91).

Conclusions: Curative surgery is safe and feasible with good long-term outcomes in appropriately selected octogenarians. Predictors of specific complications can be identified and optimised in order to better counsel patients pre-operatively and offer surgery at an early pathological stage.

背景:越来越多的接受根治性手术治疗肺癌的患者是80多岁的老人。我们评估了肿瘤肺切除术后的短期和长期生存以及不良后果。方法:纳入2016年1月至2021年12月在单中心接受解剖切除确诊或疑似肺癌的80多岁老人。回顾性分析了人口学、临床和手术资料,并将其与死亡率和长期预后相关联。结果:214例患者中,189例纳入最终分析。中位年龄为82岁(范围80-89岁)。大多数患者行肺叶切除术和微创入路。90天死亡率为3.2%,无术中死亡。慢性阻塞性肺疾病(COPD)主要导致持续性漏气(PAL)、胸部感染、再插管和重症监护住院的可能性更大。结论:在适当选择的80多岁老年人中,治疗性手术是安全可行的,具有良好的长期预后。可以识别和优化特定并发症的预测因素,以便在手术前更好地咨询患者并在早期病理阶段提供手术。
{"title":"Specific risks and outcomes of octogenarians post-lung cancer resection: our 5-year experience.","authors":"Hiral Jhala, Jennifer Whiteley, Mathew Thomas","doi":"10.21037/jtd-24-703","DOIUrl":"https://doi.org/10.21037/jtd-24-703","url":null,"abstract":"<p><strong>Background: </strong>An increasingly large proportion of patients undergoing curative surgery for lung cancer, are octogenarians. We evaluated our short and long-term survival and adverse outcomes after oncological lung resections.</p><p><strong>Methods: </strong>Octogenarians undergoing anatomical resection for confirmed or suspected lung cancer at a single-centre between January 2016 and December 2021 were included. Retrospective analysis of demographic, clinical, and operative data was performed and correlated with mortality and long-term outcomes.</p><p><strong>Results: </strong>Out of 214 patients, 189 were included in the final analysis. Median age was 82 years (range, 80-89 years). Most patients had lobectomies and minimally invasive approach. Ninety-day mortality was 3.2% with no intraoperative deaths. Chronic obstructive pulmonary disease (COPD) primarily conferred a greater likelihood of persistent air leak (PAL), chest infection, reintubation and intensive care admission (all P<0.01). Complications occurred more in those with high white cell counts (WCCs) (P=0.03) and squamous cell carcinoma subtype (P<0.01). Wedge resections conferred fewer complications (P=0.049). Hospital length of stay (LOS) was reduced by 1 day in sublobar resections (P=0.01) and halved in minimally invasive approaches compared to thoracotomy (P=0.02). The median overall survival (OS) was 3.5 years (1-, 3-, and 5-year survival was 82.5%, 57.1%, and 38.2%, respectively). Pathological tumour stage (P<0.01) and incomplete resection (R1 or R2) (P=0.02) conferred a worse OS and disease-free survival (DFS). Median DFS was 2.4 years. No significant difference was seen in OS or DFS from extent of resection or tumour subtype (P=0.78, P=0.97 and P=0.40, P=0.91).</p><p><strong>Conclusions: </strong>Curative surgery is safe and feasible with good long-term outcomes in appropriately selected octogenarians. Predictors of specific complications can be identified and optimised in order to better counsel patients pre-operatively and offer surgery at an early pathological stage.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 12","pages":"8192-8203"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elevated MCL1 expression drives esophageal squamous cell carcinoma stemness and induces resistance to radiotherapy. 升高的MCL1表达驱动食管鳞状细胞癌的干性并诱导对放疗的抵抗。
IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-31 Epub Date: 2024-12-28 DOI: 10.21037/jtd-2024-2027
Junjie Chen, Guoling Chen, Xinying Fang, Jie Sun, Jiahui Song, Zhiming Chen

Background: Esophageal squamous cell carcinoma (ESCC) stands as the sixth most common cause of cancer-related mortality on a global scale, with a strikingly high proportion-over half-of these fatalities occurring within China. The emergence of radiation resistance in ESCC patients significantly diminishes overall survival rates, complicating treatment regimens and reducing clinical outcomes. There is an urgent need to explore the molecular mechanisms that underpin radiation resistance in ESCC, which could lead to the identification of new therapeutic targets aimed at overcoming this resistance. This study aims to elucidate the role of myeloid cell leukemia-1 (MCL1) in ESCC and its association with radioresistance, thereby providing a novel strategy for enhancing the efficacy of radiotherapy.

Methods: We used The Cancer Genome Atlas (TCGA) database, Genotype-Tissue Expression (GTEx) project and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) of 10 pairs of fresh endoscopic biopsy samples from patients with ESCC to analyze the messenger RNA (mRNA) expression levels of MCL1 in esophageal cancer tissues as compared to normal tissues. Immunohistochemistry (IHC) staining and Western blotting were performed using an anti-MCL1 antibody to visualize protein expression. The mechanism of radioresistance of ESCC was examined by combining bioinformatics analysis, Western blotting, and clone formation and stemness sphere formation assays.

Results: The analysis of TCGA database and the results of RT-qPCR indicated that the mRNA level of MCL1 was overexpressed in esophageal cancer tissues. Subsequently, the results of IHC and Western blotting showed that the protein level of MCL1 expression in cancer tissues was significantly higher than that in adjacent normal tissues. Moreover, there was a significant upregulation of MCL1 in ESCC tissues and in radioresistant tissues and cells, with its overexpression correlating with the acquisition of stemness properties in ESCC. In terms of mechanism, MCL1 induced cell cycle arrest by regulating the expression of cyclin D3 and p21 through the JAK-STAT signaling pathway. G0/G1 phase arrest contributed to the stem cell-like phenotype. Blocking JAK-STAT signaling significantly improved the efficacy of radiotherapy for ESCC.

Conclusions: These findings indicate that MCL1 is a critical cell cycle regulator that drives the stemness and radioresistance of ESCC and may thus be a potential target in a combined therapeutic strategy aimed at overcoming radioresistance.

背景:食管鳞状细胞癌(ESCC)在全球范围内是癌症相关死亡的第六大常见原因,其比例高得惊人,其中一半以上的死亡发生在中国。ESCC患者放射耐药的出现显著降低了总生存率,使治疗方案复杂化并降低了临床结果。目前迫切需要探索ESCC中辐射耐药的分子机制,这可能导致确定新的治疗靶点,旨在克服这种耐药。本研究旨在阐明髓样细胞白血病-1 (MCL1)在ESCC中的作用及其与放疗耐药的关系,从而为提高放疗疗效提供一种新的策略。方法:利用癌症基因组图谱(TCGA)数据库、基因型-组织表达(GTEx)项目和实时荧光定量聚合酶链反应(RT-qPCR)对10对ESCC患者新鲜内镜活检标本进行分析,分析食管癌组织中MCL1 mRNA的表达水平与正常组织的差异。使用抗mcl1抗体进行免疫组织化学(IHC)染色和Western blotting观察蛋白表达。结合生物信息学分析、Western blotting、克隆形成和干球形成试验,探讨了ESCC的耐辐射机制。结果:TCGA数据库分析和RT-qPCR结果显示,MCL1 mRNA水平在食管癌组织中过表达。随后,免疫组化和Western blotting结果显示,MCL1蛋白在癌组织中的表达水平明显高于癌旁正常组织。此外,MCL1在ESCC组织和耐辐射组织和细胞中显著上调,其过表达与ESCC中干细胞特性的获得相关。在机制上,MCL1通过JAK-STAT信号通路调控cyclin D3和p21的表达,诱导细胞周期阻滞。G0/G1期阻滞有助于干细胞样表型。阻断JAK-STAT信号可显著提高ESCC的放疗疗效。结论:这些发现表明,MCL1是一个关键的细胞周期调节剂,可驱动ESCC的干性和放射耐药,因此可能是旨在克服放射耐药的联合治疗策略的潜在靶点。
{"title":"Elevated <i>MCL1</i> expression drives esophageal squamous cell carcinoma stemness and induces resistance to radiotherapy.","authors":"Junjie Chen, Guoling Chen, Xinying Fang, Jie Sun, Jiahui Song, Zhiming Chen","doi":"10.21037/jtd-2024-2027","DOIUrl":"10.21037/jtd-2024-2027","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) stands as the sixth most common cause of cancer-related mortality on a global scale, with a strikingly high proportion-over half-of these fatalities occurring within China. The emergence of radiation resistance in ESCC patients significantly diminishes overall survival rates, complicating treatment regimens and reducing clinical outcomes. There is an urgent need to explore the molecular mechanisms that underpin radiation resistance in ESCC, which could lead to the identification of new therapeutic targets aimed at overcoming this resistance. This study aims to elucidate the role of myeloid cell leukemia-1 (MCL1) in ESCC and its association with radioresistance, thereby providing a novel strategy for enhancing the efficacy of radiotherapy.</p><p><strong>Methods: </strong>We used The Cancer Genome Atlas (TCGA) database, Genotype-Tissue Expression (GTEx) project and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) of 10 pairs of fresh endoscopic biopsy samples from patients with ESCC to analyze the messenger RNA (mRNA) expression levels of <i>MCL1</i> in esophageal cancer tissues as compared to normal tissues. Immunohistochemistry (IHC) staining and Western blotting were performed using an anti-MCL1 antibody to visualize protein expression. The mechanism of radioresistance of ESCC was examined by combining bioinformatics analysis, Western blotting, and clone formation and stemness sphere formation assays.</p><p><strong>Results: </strong>The analysis of TCGA database and the results of RT-qPCR indicated that the mRNA level of <i>MCL1</i> was overexpressed in esophageal cancer tissues. Subsequently, the results of IHC and Western blotting showed that the protein level of MCL1 expression in cancer tissues was significantly higher than that in adjacent normal tissues. Moreover, there was a significant upregulation of <i>MCL1</i> in ESCC tissues and in radioresistant tissues and cells, with its overexpression correlating with the acquisition of stemness properties in ESCC. In terms of mechanism, <i>MCL1</i> induced cell cycle arrest by regulating the expression of <i>cyclin</i> <i>D3</i> and <i>p21</i> through the <i>JAK-STAT</i> signaling pathway. G0/G1 phase arrest contributed to the stem cell-like phenotype. Blocking <i>JAK-STAT</i> signaling significantly improved the efficacy of radiotherapy for ESCC.</p><p><strong>Conclusions: </strong>These findings indicate that <i>MCL1</i> is a critical cell cycle regulator that drives the stemness and radioresistance of ESCC and may thus be a potential target in a combined therapeutic strategy aimed at overcoming radioresistance.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 12","pages":"8684-8698"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of thoracic disease
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