CLSSL-ResNet: Predicting malignancy of solitary pulmonary nodules from CT images by chimeric label with self-supervised learning.

BACKGROUND: Pulmonary granulomatous nodules (GN) with spiculation or lobulation have a similar morphological appearance to solid lung adenocarcinoma (SADC) under computed tomography (CT). However, these two kinds of solid pulmonary nodules (SPN) have different malignancies and are sometimes misdiagnosed. OBJECTIVE: This study aims to predict malignancies of SPNs by a deep learning model automatically. METHODS: A chimeric label with self-supervised learning (CLSSL) is proposed to pre-train a ResNet-based network (CLSSL-ResNet) for distinguishing isolated atypical GN from SADC in CT images. The malignancy, rotation, and morphology labels are integrated into a chimeric label and utilized to pre-train a ResNet50. The pre-trained ResNet50 is then transferred and fine-tuned to predict the malignancy of SPN. Two image datasets of 428 subjects (Dataset1, 307; Dataset2, 121) from different hospitals are collected. Dataset1 is divided into training, validation, and test data by a ratio of 7:1:2 to develop the model. Dataset2 is utilized as an external validation dataset. RESULTS: CLSSL-ResNet achieves an area under the ROC curve (AUC) of 0.944 and an accuracy (ACC) of 91.3%, which was much higher than that of the consensus of two experienced chest radiologists (77.3%). CLSSL-ResNet also outperforms other self-supervised learning models and many counterparts of other backbone networks. In Dataset2, AUC and ACC of CLSSL-ResNet are 0.923 and 89.3%, respectively. Additionally, the ablation experiment result indicates higher efficiency of the chimeric label. CONCLUSION: CLSSL with morphology labels can increase the ability of feature representation by deep networks. As a non-invasive method, CLSSL-ResNet can distinguish GN from SADC via CT images and may support clinical diagnoses after further validation.

Safety and efficacy of neoadjuvant treatment with immune checkpoint inhibitors in esophageal cancer: real-world multicenter retrospective study in China.

Immune checkpoint inhibitors (ICIs) have shown a powerful benefit in the neoadjuvant therapy for esophageal cancer, but evidence for its safety and efficacy is limited and may not reflect real-world practice. We retrospectively reviewed the database of treatment-naive patients from 15 esophageal cancer centers in China who received ICIs as neoadjuvant treatment for locally advanced esophageal cancer from May 2019 to December 2020. The primary endpoints were rate and severity of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs). Secondary endpoints included pathologically complete response (pCR) rate, R0 resection rate, mortality and morbidity. Among the 370 patients, 311 (84.1%) were male with a median age of 63 (range: 30-81) years and stage III or IVa disease accounted for 84.1% of these patients. A total of 299 (80.8%) patients were treated with ICIs and chemotherapy. TRAEs were observed in 199 (53.8%) patients with low severity (grade 1-2, 39.2%; grade 3-4, 13.2%; grade 5, 1.4%), and irAEs occurred in 24.3% of patients and were mostly of grade 1-2 severity (21.1%). A total of 341 (92.2%) patients had received surgery and R0 resection was achieved in 333 (97.7%) patients. The local pCR rate in primary tumor was 34.6%, including 25.8% of ypT0N0 and 8.8% of ypT0N+. The rate of postoperative complications was 41.4% and grade 3 or higher complications occurred in 35 (10.3%) patients. No death was observed within 30 days after surgery, and three patients (0.9%) died within 90 days postoperatively. This study shows acceptable toxicity of neoadjuvant immunotherapy for locally advanced esophageal cancer in real-world data. Long-term survival results are pending for further investigations.

Classification of Tea Leaves Based on Fluorescence Imaging and Convolutional Neural Networks.

The development of the smartphone and computer vision technique provides customers with a convenient approach to identify tea species, as well as qualities. However, the prediction model may not behave robustly due to changes in illumination conditions. Fluorescence imaging can induce the fluorescence signal from typical components, and thus may improve the prediction accuracy. In this paper, a tea classification method based on fluorescence imaging and convolutional neural networks (CNN) is proposed. Ultra-violet (UV) LEDs with a central wavelength of 370 nm were utilized to induce the fluorescence of tea samples so that the fluorescence images could be captured. Five kinds of tea were included and pre-processed. Two CNN-based classification models, e.g., the VGG16 and ResNet-34, were utilized for model training. Images captured under the conventional fluorescent lamp were also tested for comparison. The results show that the accuracy of the classification model based on fluorescence images is better than those based on the white-light illumination images, and the performance of the VGG16 model is better than the ResNet-34 model in our case. The classification accuracy of fluorescence images reached 97.5%, which proves that the LED-induced fluorescence imaging technique is promising to use in our daily life.

LncRNA GACAT3 promotes esophageal squamous cell carcinoma progression through regulation of miR-149/FOXM1.

BACKGROUND: The long noncoding RNA gastric cancer associated transcript 3 (GACAT3) has been demonstrated to be implicated in the carcinogenesis and progression of many malignancies. However, GACAT3's levels and role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. METHODS: GACAT3 amounts were investigated in ESCC tissues and cell lines by qPCR. Its biological functions were examined by CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, transwell assay, and xenograft model establishment. The relationship between GACAT3 and miR-149 was assessed by dual-luciferase reporter assay. RESULTS: GACAT3 amounts were elevated in ESCC tissue and cell specimens. Functional studies showed that GACAT3 silencing reduced the proliferation, migration and invasion of cultured ESCC cells, and decreased tumor growth in mice. Furthermore, GACAT could directly interact with miR-149. In addition, colony formation and invasion assays verified that GACAT3 promotes ESCC tumor progression through miR-149. Moreover, GACAT3 acted as a competing endogenous RNA (ceRNA) to modulate FOXM1 expression. CONCLUSIONS: These findings indicate that GACAT3 functions as an oncogene by acting as a ceRNA for miR-149 to modulate FOXM1 expression in ESCC, suggesting that GACAT3 might constitute a therapeutic target in ESCC.

Minimally invasive esophagectomy via Sweet approach in combination with cervical mediastinoscopy is a valuable approach for surgical treatment of esophageal cancer. / 治疗食管癌的一种有价值的方法­­Sweetå ¥è·¯è”åˆçºµéš”é•œé£Ÿç®¡åˆ‡é™¤æœ¯.

OBJECTIVES: To compare the short-, mid-, and long-term outcomes in patients with esophageal cancer between minimally invasive esophagectomy via Sweet approach in combination with cervical mediastinoscopy (MIE-SM) and minimally invasive esophagectomy via McKeown approach (MIE-MC), and to evaluate the value of MIE-SM in the surgical treatment of esophageal cancer. METHODS: A prospective, nonrandomized study was adopted. A total of 65 esophageal cancer patients after MIE-SM and MIE-MC from June 2014 to May 2016 were included. Among them, 33 patients underwent MIE-SM and 32 patients underwent MIE-MC. Short-term outcomes (including the duration of surgery, intraoperative blood loss volume, ICU stay time, postoperative complications, postoperative hospital stay, reoperation, open surgery, number of dissected lymph nodes, and 30-day mortality), mid-term outcomes, [including Quality of Life Core Questionnaire (QLQ-C30) and the esophageal site-specific module (QLQ-OES18)], long-term outcomes [including overall survival and disease-free survival] were compared between the 2 groups. RESULTS: Radical resection (R0) were achieved in all patients. There were no significant differences in the duration of surgery, intraoperative blood loss volume, ICU stay time, postoperative complications, and postoperative hospital stay between the 2 groups (all P>0.05). More lymph nodes were dissected in the MIE-SM group (24.1±7.3) than those in the MIE-MC group (17.8±5.0, P<0.001). The emotional function, global health status scale scores in QLQ-C30 scale in the MIE-SM group were significantly higher than those in the MIE-MC group (P=0.025, P<0.001, respectively), and the pain score in the MIE-SM group was significantly lower than that in the MIE-MC group (P=0.013). QLQ-OES18 results showed that the pain score in the MIE-SM group was significantly lower than that in the MIE-MC group (P=0.021). Survival analysis showed that the overall survival and disease-free survival were similar between the 2 groups. CONCLUSIONS: MIE-SM appears to be a safe surgical approach, which may get better quality of life, suffer less pain, and can achieve the same therapeutic effect as MIE-MC. Therefore, MIE-SM should be considered as a valuable approach for the treatment of middle and lower esophageal cancer.

Long noncoding RNA lnc-ABCA12-3 promotes cell migration, invasion, and proliferation by regulating fibronectin 1 in esophageal squamous cell carcinoma.

Long noncoding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). We previously demonstrated that a novel lncRNA, lnc-ABCA12-3, was overexpressed in ESCC tissues. However, the exact function of lnc-ABCA12-3 is unknown. In the current study, we aimed to evaluate the expression of lnc-ABCA12-3 in ESCC and to explore the potential mechanism of lnc-ABCA12-3 in cell migration, invasion, and proliferation. We showed that lnc-ABCA12-3 was upregulated in ESCC tumor tissues and cell lines. The increased expression of lnc-ABCA12-3 was positively associated with advanced tumor-node-metastasis stages and poor prognosis. The knockdown of lnc-ABCA12-3 inhibited the cell migration, invasion, and proliferation abilities of KYSE-510 and Eca-109 cells. We also found that fibronectin 1 (FN1) was upregulated in ESCC tumor tissues. The expression of FN1 messenger RNA was positively correlated with the expression of lnc-ABCA12-3 in ESCC tumor tissues. After lnc-ABCA12-3 knockdown, the expression of FN1 was downregulated. In addition, the overexpression of FN1 restored the abilities of cell migration, invasion and proliferation in Eca-109 cells. Further studies indicated that lnc-ABCA12-3 acted as a competing endogenous RNA for miR-200b-3p to regulate FN1 expression. In conclusion, these results suggest that lnc-ABCA12-3 is a novel oncogene in tumorigenesis and that its high expression is related to a poor prognosis for patients with ESCC. lnc-ABCA12-3 promotes cell migration, invasion, and proliferation via the regulation of FN1 in ESCC. Our data suggest that lnc-ABCA12-3 might serve as a potential prognostic biomarker and therapeutic target for ESCC.

Structural and functional alterations of the tracheobronchial tree after left upper pulmonary lobectomy for lung cancer.

BACKGROUND: Pulmonary lobectomy has been a well-established curative treatment method for localized lung cancer. After left upper pulmonary lobectomy, the upward displacement of remaining lower lobe causes the distortion or kink of bronchus, which is associated with intractable cough and breathless. However, the quantitative study on structural and functional alterations of the tracheobronchial tree after lobectomy has not been reported. We sought to investigate these alterations using CT imaging analysis and computational fluid dynamics (CFD) method. METHODS: Both preoperative and postoperative CT images of 18 patients who underwent left upper pulmonary lobectomy are collected. After the tracheobronchial tree models are extracted, the angles between trachea and bronchi, the surface area and volume of the tree, and the cross-sectional area of left lower lobar bronchus are investigated. CFD method is further used to describe the airflow characteristics by the wall pressure, airflow velocity, lobar flow rate, etc. RESULTS: It is found that the angle between the trachea and the right main bronchus increases after operation, but the angle with the left main bronchus decreases. No significant alteration is observed for the surface area or volume of the tree between pre-operation and post-operation. After left upper pulmonary lobectomy, the cross-sectional area of left lower lobar bronchus is reduced for most of the patients (15/18) by 15-75%, especially for 4 patients by more than 50%. The wall pressure, airflow velocity and pressure drop significantly increase after the operation. The flow rate to the right lung increases significantly by 2-30% (but there is no significant difference between each lobe), and the flow rate to the left lung drops accordingly. Many vortices are found in various places with severe distortions. CONCLUSIONS: The favorable and unfavorable adaptive alterations of tracheobronchial tree will occur after left upper pulmonary lobectomy, and these alterations can be clarified through CT imaging and CFD analysis. The severe distortions at left lower lobar bronchus might exacerbate postoperative shortness of breath.

Deep CNN models for pulmonary nodule classification: Model modification, model integration, and transfer learning.

BACKGROUND: Deep learning has made spectacular achievements in analysing natural images, but it faces challenges for medical applications partly due to inadequate images. OBJECTIVE: Aiming to classify malignant and benign pulmonary nodules using CT images, we explore different strategies to utilize the state-of-the-art deep convolutional neural networks (CNN). METHODS: Experiments are conducted using the Lung Image Database Consortium image collection (LIDC-IDRI), which is a public database containing 1018 cases. Three strategies are implemented including to 1) modify some state-of-the-art CNN architectures, 2) integrate different CNNs and 3) adopt transfer learning. Totally, 11 deep CNN models are compared using the same dataset. RESULTS: Study demonstrates that, for the model modification scheme, a concise CifarNet performs better than the other modified CNNs with more complex architectures, achieving an area under ROC curve of AUC = 0.90. Integrated CNN models do not significantly improve the classification performance, but the model complexity is reduced. Transfer learning outperforms the other two schemes and ResNet with fine-tuning leads to the best performance with an AUC = 0.94, as well as the sensitivity of 91% and an overall accuracy of 88%. CONCLUSIONS: Model modification, model integration, and transfer learning can play important roles to identify and generate optimal deep CNN models in classifying pulmonary nodules based on CT images efficiently. Transfer learning is preferred when applying deep learning to medical imaging applications.

Efficacy comparison of transcervical video-assisted mediastinoscopic lymphadenectomy combined with left transthoracic esophagectomy versus right transthoracic esophagectomy for esophageal cancer treatment.

BACKGROUND: This study aimed to propose a new surgical strategy, i.e., the transcervical video-assisted mediastinoscopic lymphadenectomy (VAMLA) with esophagectomy via the left transthoracic approach for patients with esophageal cancer (EC), and to compare the outcomes with those of esophagectomy via the right thoracic approach. METHODS: From December 2014 to March 2016, 49 cases were enrolled in this non-randomized concurrent control study. Twenty-eight patients with EC who underwent transcervical VAMLA with esophagectomy via the left transthoracic approach were assigned into the study group, while 21 EC patients undergoing esophagectomy via the right transthoracic approach during the same period were enrolled into the control group. Operative outcomes including operative time, the numbers of removed lymph nodes, intraoperative blood loss, the length of hospital stay, and postoperative complications in both groups were evaluated and compared. RESULTS: There were no significant differences in the baseline profiles between the two groups, and all patients in the two groups successfully underwent the surgery. There was a significant difference between transcervical VAMLA with esophagectomy via the left thoracic approach and esophagectomy via the right thoracic approach with regard to the number of all dissected lymph nodes [(29.0 ± 8.7) vs. (17.8 ± 8.1), p < 0.05], dissected superior mediastinal lymph nodes [(11.2 ± 5.0) vs. (3.7 ± 2.9), p < 0.05], and dissected in the recurrent laryngeal nerve lymph nodes [(5.6 ± 3.5) vs. (2.3 ± 2.1), p < 0.05]. No significant differences were observed in the operative time, intraoperative blood loss, length of postoperative hospital stay, number of dissected abdominal lymph nodes, postoperative pulmonary complications (pneumonia and atelectasis), anastomotic fistula, chylothorax, and vocal cord paralysis (p > 0.05). CONCLUSION: Transcervical VAMLA combined with esophagectomy via the left thoracic approach appears technically feasible and safe and shows advantages in the number of dissected superior mediastinal lymph nodes, suggesting that it may serve as a new treatment option for patients with esophageal carcinoma.

Airflow in Tracheobronchial Tree of Subjects with Tracheal Bronchus Simulated Using CT Image Based Models and CFD Method.

Tracheal Bronchus (TB) is a rare congenital anomaly characterized by the presence of an abnormal bronchus originating from the trachea or main bronchi and directed toward the upper lobe. The airflow pattern in tracheobronchial trees of TB subjects is critical, but has not been systemically studied. This study proposes to simulate the airflow using CT image based models and the computational fluid dynamics (CFD) method. Six TB subjects and three health controls (HC) are included. After the geometric model of tracheobronchial tree is extracted from CT images, the spatial distribution of velocity, wall pressure, wall shear stress (WSS) is obtained through CFD simulation, and the lobar distribution of air, flow pattern and global pressure drop are investigated. Compared with HC subjects, the main bronchus angle of TB subjects and the variation of volume are large, while the cross-sectional growth rate is small. High airflow velocity, wall pressure, and WSS are observed locally at the tracheal bronchus, but the global patterns of these measures are still similar to those of HC. The ratio of airflow into the tracheal bronchus accounts for 6.6-15.6% of the inhaled airflow, decreasing the ratio to the right upper lobe from 15.7-21.4% (HC) to 4.9-13.6%. The air into tracheal bronchus originates from the right dorsal near-wall region of the trachea. Tracheal bronchus does not change the global pressure drop which is dependent on multiple variables. Though the tracheobronchial trees of TB subjects present individualized features, several commonalities on the structural and airflow characteristics can be revealed. The observed local alternations might provide new insight into the reason of recurrent local infections, cough and acute respiratory distress related to TB.

[Clinical analyses of surgical treatment for lung metastatic tumors].

OBJECTIVE: To evaluate the distribution, diagnosis, indication and modus operandi of surgical treatment and prognostic factors for patients with lung metastatic tumors. METHODS: The clinical features were collected for 329 surgical patients with lung metastatic tumors during March 1998 and December 2013. Survival analysis was also performed by Log-rank test and Cox-regression analysis. RESULTS: The origins were epithelial tissue tumors (n = 278), sarcomas (n = 32), germ cell tumors (n = 3), malignant melanoma (n = 3) and miscellaneous tumors (n = 13). Their 1, 3 and 5-year survival rates were 85.1％, 50.9％ and 37.1％ respectively with a median survival time of 38 months. Log-rank survival analysis showed that resection extent (P = 0.004), lymph node dissection (P = 0.017) and radical operation (P < 0.01) were significantly associated with patient survival. And multi-variable Cox-regression analysis showed that lymph node dissection and radical operation were two independent prognostic factors. CONCLUSION: For lung metastatic tumor patients with well-controlled primary malignancy and non-metastasis of other organs, radical resection should be performed with minimal resection extent. And routine systematic lymph node dissection is not recommended. The necessity of lymph node dissection should be determined by radiological evaluations and surgical explorations.

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.

BACKGROUND: Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles. OBJECTIVE: To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs. METHOD: LncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis. RESULTS: LncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p<0.0001). The signature was applied to the test group (median survival 21.5 months vs >60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages. CONCLUSIONS: Our results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.

Multi-branch attention Raman network and surface-enhanced Raman spectroscopy for the classification of neurological disorders.

Surface-enhanced Raman spectroscopy (SERS), a rapid, low-cost, non-invasive, ultrasensitive, and label-free technique, has been widely used in-situ and ex-situ biomedical diagnostics questions. However, analyzing and interpreting the untargeted spectral data remains challenging due to the difficulty of designing an optimal data pre-processing and modelling procedure. In this paper, we propose a Multi-branch Attention Raman Network (MBA-RamanNet) with a multi-branch attention module, including the convolutional block attention module (CBAM) branch, deep convolution module (DCM) branch, and branch weights, to extract more global and local information of characteristic Raman peaks which are more distinctive for classification tasks. CBAM, including channel and spatial aspects, is adopted to enhance the distinctive global information on Raman peaks. DCM is used to supplement local information of Raman peaks. Autonomously trained branch weights are applied to fuse the features of each branch, thereby optimizing the global and local information of the characteristic Raman peaks for identifying diseases. Extensive experiments are performed for two different neurological disorders classification tasks via untargeted serum SERS data. The results demonstrate that MBA-RamanNet outperforms commonly used CNN methods with an accuracy of 88.24% for the classification of healthy controls, mild cognitive impairment, Alzheimer's disease, and Non-Alzheimer's dementia; an accuracy of 90% for the classification of healthy controls, elderly depression, and elderly anxiety.

A real-world comparison between neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable non-small cell lung cancer.

BACKGROUND: The impact of neoadjuvant chemoimmunotherapy on pulmonary resection and related outcomes had been poorly reported in previous studies. The present study aims to clarify the efficacy and safety of neoadjuvant chemoimmunotherapy, and intraoperative difficulty in the following surgery, in comparison with chemotherapy alone in non-small cell lung cancer (NSCLC). METHODS: Patients with newly diagnosed clinical stages IB-IIIB(T3-4N2) NSCLC, received neoadjuvant chemotherapy + PD-1 inhibitors (PD-1 + Chemo group) or chemotherapy alone (Chemo group) followed by surgery between December 2018 and December 2020 were included. The clinicopathological characteristics were retrospectively reviewed and analyzed. RESULTS: There were 69 NSCLC patients in the PD-1 + Chemo group and 121 in the Chemo group. The major pathological response (MPR) rate in the PD-1 + Chemo group was 49.3%, higher than that of 19.0% in the Chemo group (p < 0.001). The 2-year disease-free survival (DFS) rate was 79.3% and 60.2%, respectively, in the two groups (p = 0.048). Multivariate analysis identified surgical radicality (hazard ratio (HR), 2.954, 95% confidence interval (CI), 1.527-5.714, p = 0.001), and pathological response (MPR(CR) vs. SD(PD), HR, 0.248, 95% CI, 0.107-0.572, p = 0.001) to be independent prognostic factors for DFS. Lobectomy was performed in 73.9% and 66.1% of patients, respectively, and bronchial sleeve resection/bronchoplasty rate was also comparable (43.4% vs. 40.5%, p = 0.688). More patients in the PD-1 + Chemo group received vascular sleeve resection/angioplasty (15.9% vs. 6.6%, p = 0.039) and pericardial resection (10.1% vs. 2.5%, p = 0.038). After propensity score matching analysis, pericardial resection rate was still slightly higher in the PD-1 + Chemo group (9.4% vs. 1.6%, p = 0.05). Perioperative morbidities within 30 days and mortality in 90 days were comparable between groups (p > 0.05). CONCLUSIONS: Neoadjuvant chemoimmunotherapy for NSCLC is safe and feasible, with higher MPR rates, as well as favorable DFS than chemotherapy alone. Surgical complexity might be increased in certain patients, with comparable perioperative morbidity and mortality.

Surgical resection of a giant thymolipoma causing respiratory failure: A case report.

BACKGROUND: Thymolipoma is a rare benign tumor arising from the anterior mediastinal thymus and is composed of mature fatty tissue and interspersed nonneoplastic thymic tissue. This tumor accounts for only a small percentage of mediastinal masses, and the majority of them are asymptomatic and found incidentally. To date, fewer than 200 cases have been published in the world literature, of which most excised tumors weighed less than 0.5 kg and the largest weighed 6 kg. CASE SUMMARY: A 23-year-old man presented with a complaint of progressive breathlessness for 6 mo. His forced vital capacity was only 23.6% of the predicted capacity, and his arterial partial pressure of oxygen and carbon dioxide were 51 and 60 mmHg, respectively, without oxygen inhalation. Chest computed tomography revealed a large fat-containing mass in the anterior mediastinum that measured 26 cm × 20 cm × 30 cm in size and occupied most of the thoracic cavity. Percutaneous mass biopsy revealed only thymic tissue without signs of malignancy. A right posterolateral thoracotomy was successfully performed to remove the tumor along with the capsule, and the excised tumor weighed 7.5 kg, which to our knowledge, was the largest surgically removed tumor of thymic origin. Postoperatively, the patient's shortness of breath was resolved, and the histopathological diagnosis was thymolipoma. No signs of recurrence were observed at the 6-mo follow-up. CONCLUSION: Giant thymolipoma causing respiratory failure is rare and dangerous. Despite the high risks, surgical resection is feasible and effective.

Perioperative outcomes of neoadjuvant chemotherapy plus camrelizumab compared with chemotherapy alone and chemoradiotherapy for locally advanced esophageal squamous cell cancer.

Purpose: Neoadjuvant chemoimmunotherapy (nCIT) is becoming a new therapeutic frontier for resectable esophageal squamous cell carcinoma (ESCC); however, crucial details and technical know-how regarding surgical techniques and the perioperative challenges following nCIT remain poorly understood. The study investigated and compared the advantages and disadvantages of esophagectomy following nCIT with neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT). Methods: We retrospectively analyzed data of patients initially diagnosed with resectable ESCC at clinical stage T2-4N+ and received neoadjuvant therapy followed by esophagectomy at the Hunan Cancer Hospital between October 2014 and February 2021. Patients were divided into three groups according to neoadjuvant treatment: (i) nCIT; (ii) nCT; and (iii) nCRT. Results: There were 34 patients in the nCIT group, 97 in the nCT group, and 31 in the nCRT group. Compared with nCT, nCIT followed by esophagectomy achieved higher pathological complete response (pCR; 29.0% versus 4.1%, p<0.001) and major pathological response (MPR; 52.9% versus 16.5%, p<0.001) rates, more resected lymph nodes during surgery (25.06 ± 7.62 versus 20.64 ± 9.68, p=0.009), less intraoperative blood loss (200.00 ± 73.86 versus 266.49 ± 176.29 mL, p=0.035), and comparable results in other perioperative parameters. Compared with nCRT, nCIT achieved similar pCR (29.0% versus 25.8%) and MPR (52.9% versus 51.6%, p=0.862) rates, with significantly more lymph nodes resected during surgery (25.06 ± 7.62 versus 16.94 ± 7.24, p<0.001), shorter operation time (267.79 ± 50.67 versus 306.32 ± 79.92 min, p=0.022), less intraoperative blood loss (200.00 ± 73.86 versus 264.53 ± 139.76 mL, p=0.022), and fewer ICU admissions after surgery (29.4% versus 80.6%, p<0.001). Regarding perioperative adverse events and complications, no significant statistical differences were detected between the nCIT and the nCT or nCRT groups. The 3-year overall survival rate after nCIT was 73.3%, slightly higher than 46.1% after nCT and 39.7% after nCRT, with no statistically significant differences (p=0.883). Conclusions: This clinical analysis showed that nCIT is safe and feasible, with satisfactory pCR and MPR rates. Esophagectomy following nCIT has several perioperative advantages over nCT and nCRT, with comparable perioperative morbidity and mortality. The long-term survival benefits after nCIT still requires further investigation.

Neoadjuvant chemoimmunotherapy cycle number selection for non-small cell lung cancer and clinical outcomes: a real-world analysis.

Objectives: Neoadjuvant chemoimmunotherapy is the optimal choice in the treatment of NSCLC; however, the optimal number of therapeutic cycles remains unclear. The primary aim of this study was to determine the optimal number of neoadjuvant therapeutic cycles in NSCLC. Methods: This study was a real-world clinical analysis that included patients who received neoadjuvant chemoimmunotherapy followed by surgery from January 2020 to August 2022. Patients were divided into two groups based on the number of therapeutic cycles: 2-cycle group and 3-4-cycles group. The primary endpoint was the major pathological response (MPR) rate. Results: A total of 251 patients were included: 150 in the 2-cycle group and 101 in the 3-4-cycles group. Baseline characteristics were well-balanced between the groups. The MPR in the 2-cycle group was 57.3% and not significantly different from that of 57.4% in the 3-4-cycles group (p=0.529). Thirty-two patients (31.7%) in the 3-4-cycles group underwent surgery > 42 days after the final cycle of neoadjuvant therapy, significantly more than the 24 patients (16.0%) in the 2-cycle group (p=0.003). The incidence of adverse events related to neoadjuvant therapy was higher in the 3-4-cycles vs 2-cycle groups (72.3% versus 58.0%, respectively; p=0.021), while the 2-cycle group had a higher rate of postoperative morbidities (28.0% versus 12.9%, respectively; p=0.004). Additionally, for patients with ≤ 44.2% regression in diameter on computed tomography after two cycles of treatment, the MPR rate was higher in the 3-4-cycles vs 2-cycle group (47.3% versus 29.9%, respectively; p=0.048). For cases with programmed death-ligand 1 expression, regarding tumor proportion score ≤ 10%, 3-4 cycles of neoadjuvant treatment increased the MPR rate compared with 2 cycles (37.5% versus 9.5%, respectively; p=0.041). Conclusion: Our data support the positive role of chemoimmunotherapy in the neoadjuvant treatment of NSCLC. Extending to 3-4 cycles instead of 2 cycles of neoadjuvant chemoimmunotherapy may improve the safety of surgery and result in a lower incidence of postoperative morbidities; however, the MPR rate may not increase significantly. CT re-evaluation during treatment and PD-L1 expression at initial diagnosis are potential indicators to guide the choice of the number of therapeutic cycles.

Chronic pulmonary mucormycosis caused by rhizopus microsporus mimics lung carcinoma in an immunocompetent adult: A case report.

BACKGROUND: Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients. This disease usually develops acutely and progresses rapidly, often leading to a poor clinical prognosis. Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients. CASE SUMMARY: A 43-year-old man, who was a house improvement worker with a long history of occupational dust exposure, presented with an irritating cough that had lasted for two months. The patient was previously in good health, without dysglycemia or any known immunodeficiencies. Chest computed tomography revealed a mass in the left lower lobe, measuring approximately 6 cm in diameter, which was suspected to be primary lung carcinoma complicated with obstructive pneumonia. Thoracoscopic-assisted left lower lobectomy was performed, and metagenomic next-generation sequencing detection, along with special pathological staining of surgical specimens, suggested Rhizopus microsporus infection. Postoperatively, the patient's respiratory symptoms were relieved, and no signs of recurrence were found during the six-month follow-up. CONCLUSION: This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency. The patient's surgical outcome was excellent, reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.

Replication-driven HBV cccDNA loss in chimeric mice with humanized livers.

Hepatitis B virus (HBV) infection is largely noncytopathic and requires the establishment of covalently closed circular DNA (cccDNA), which is considered stable in the nuclei of infected cells. Although challenging, approaches to directly target cccDNA molecules or kill infected cells are recommended to eliminate cccDNA. Herein, cccDNA levels were investigated in HBV-infected chimeric mice with humanized livers. HBV-infected cells support robust replication, progressively retain viral products, and head for cytopathic destruction and cccDNA loss. It is difficult for infected cells to retain cccDNA and remain noncytopathic. Replication-driven cccDNA loss is observed at both phases of spread of and persistent infection. The cccDNA replenishment is required to compensate for cccDNA loss. Blocking cccDNA replenishment pathways reduces cccDNA levels by >100-fold. These results prove an unconventional cccDNA elimination strategy that does not directly target cccDNA but aims to transform spontaneous cccDNA loss into progressive cccDNA elimination by blocking cccDNA replenishment.

Copy number variations mediate major pathological response to induction chemo-immunotherapy in unresectable stage IIIA-IIIB lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Despite this, evidence supporting optimal management of certain stages remains a topic of debate. In this retrospective study we examine the efficacy and safety, as well as exploring the biomarkers of neoadjuvant induction immuno-chemotherapy, in Chinese patients with unresectable stage III NSCLC. METHODS: Patients with unresectable stage III NSCLC who were identified as driver mutation-negative and who received neoadjuvant chemo-immunotherapy were enrolled from three Chinese hospitals between Jan. 17, 2019, and Jan.17, 2022. Perioperative outcomes and survival data were collected. Retrospective biomarker exploration was performed in available baseline tumor samples and surgical specimens. RESULTS: 94 patients were enrolled and received chemo-immunotherapy as neoadjuvant treatment. 80 patients had squamous cell carcinoma, and 26 had stage IIIB disease. Surgery conversion rate was 74.4%, R0 resection rate was 98.4%. Of 64 patients who underwent surgery, major pathological response (MPR) rate was 65.6% and pathologic complete response (pCR) rate was 42.2%. 73% of patients with N2 disease demonstrated down-staging to N0. Treatment-related adverse events (TRAEs) occurred in 43 patients (45.7%) with anemia was the most common. The Grade ≥ 3 TRAEs rate was 3.2% (3/94). A significant association between copy number variation (CNV) ploidy was also found. CONCLUSION: The combination treatment of immuno-chemotherapy for unresectable stage III NSCLC is not only effective but also has a favourable safety profile. For the first time we provide evidence that CNV status may be a predictive biomarker of MPR.