Mediastinal Nodes Research Articles

Thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection after definitive chemoradiotherapy for patients with esophageal cancer.

Salvage esophagectomy for residual tumor and localized relapses after definitive chemoradiotherapy (dCRT) for patients with esophageal cancer is associated with a high rate of postoperative complications and in-hospital mortality. In addition, there are many controversial issues associated with salvage esophagectomy, such as the acceptability of minimally invasive surgery and the need for prophylactic dissection of mediastinal lymph nodes. The aim of this study was to evaluate the safety and usefulness of thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection. The study included 31 patients who underwent thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection after dCRT between 2013 and 2022 (salvage patients) and 610 nonsalvage patients who underwent conventional thoracoscopic esophagectomy during the same time period. Differences between the median ages and sexes of the 2 patient groups were not significant. The dominant location of tumors in the salvage patients was the upper thoracic esophagus. More salvage patients had clinical T4 disease. The salvage patients had a lower median number of retrieved mediastinal lymph nodes than the nonsalvage patients. The differences between the rates of R0, postoperative complications, and in-hospital deaths in the 2 patient groups were not significant. The 3-year overall survival (OS) rates for the salvage patients were 73%, with 3-year OS rates for R0 vs non-R0 of 81% vs 0%, p < 0.01 and pN0 vs pN1-3 of 89% vs 49%, p < 0.01. Regarding short-term outcomes, prophylactic mediastinal lymph node dissection for patients undergoing thoracoscopic salvage esophagectomy was as safe as prophylactic dissection for patients undergoing conventional thoracoscopic esophagectomy. R0 surgery and pN0 are important factors for long-term survival in patients undergoing thoracoscopic salvage esophagectomy.

A Case of Ocular Sarcoidosis with an Atypical Presentation of Subretinal Mass

Purpose: To describe a case of ocular sarcoidosis manifesting as an atypical subretinal mass.Case summary: A 59-year-old woman reported reduced visual acuity in her left eye lasting for 1 month. Her best corrected visual acuity in the left eye had diminished to 0.3. A fundus examination revealed a whitish elevated lesion, approximately one disc diameter in size, in the perimacular area of the left eye. Optical coherence tomography identified a hyporeflective oval-shaped mass in the choriocapillaris region accompanied by subretinal fluid. Initial assessment suggested choroidal osteoma with choroidal neovascularization. Consequently, the patient underwent two intravitreal bevacizumab injections, which did not lead to improvement. To rule out systemic diseases, including syphilis, tuberculosis, and sarcoidosis, further radiologic and laboratory tests were conducted. A chest computed tomography highlighted mediastinal lymph node enlargement and pervasive nodules in both lung parenchymata, and serum angiotensin-converting enzyme levels were elevated to 77 U/L. Based on these findings, a diagnosis of sarcoidosis was confirmed, and the patient commenced treatment with oral prednisolone. Eight weeks after treatment, the subretinal lesion and fluid had resolved, and the best corrected visual acuity in the patient’s left eye had improved to 0.9.Conclusions: Ocular sarcoidosis can manifest as a subretinal mass. This presentation should be differentiated from other subretinal lesions.

Unforeseen Complication in a Patient with Recurrent Papillary Carcinoma Thyroid.

The incidence of thyroid papillary cancer is approximately 13.5 per 100,000.Papillary thyroid carcinoma (PTC) is usually associated with favorable survival and low recurrence rate.The mortality rate is estimated to be between 11% and 17%. Common metastatic sites include lung, bone, mediastinal lymph nodes, pelvic area, brain, and liver and rarely the trachea.

SLAM-family receptors promote resolution of ILC2-mediated inflammation

Type 2 innate lymphoid cells (ILC2) initiate early allergic inflammation in the lung, but the factors that promote subsequent resolution of type 2 inflammation and prevent prolonged ILC2 activation are not fully known. Here we show that SLAM-family receptors (SFR) play essential roles in this process. We demonstrate dynamic expression of several SFRs on ILC2s during papain-induced type 2 immunity in mice. SFR deficiency exacerbates ILC2-driven eosinophil infiltration in the lung, and results in a significant increase in IL-13 production by ILC2s exclusively in mediastinal lymph nodes (MLN), leading to increased dendritic cell (DC) and TH2 cell numbers. In MLNs, we observe more frequent interaction between ILC2s and bystander T cells, with T cell-expressed SFRs (especially SLAMF3 and SLAMF5) acting as self-ligands to suppress IL-13 production by ILC2s. Mechanistically, homotypic engagement of SFRs at the interface between ILC2s and T cells delivers inhibitory signaling primarily mediated by SHIP-1. This prevents activation of NF-κB, driven by IL-7 and IL-33, two major drivers of ILC2-mediated type 2 immunity. Thus, our study shows that an ILC2-DC-TH2 regulatory axis may promote the resolution of pulmonary type 2 immune responses, and highlights SLAMF3/SLAMF5 as potential therapeutic targets for ameliorating type 2 immunity.

Disease relapse in relation to lymph node sampling in lung carcinoid patients.

The predictive value of the extent of peri-operative lymph node (LN) sampling in relation to disease relapse in patients with pulmonary carcinoid (PC) is unknown. Furthermore, post-surgery follow-up recommendations rely on institutional retrospective studies with short follow-ups. We aimed to address these shortcomings by examining the relation between LN sampling and relapse in a population-based cohort with long-term follow-up. By combining the Dutch nationwide pathology and cancer registries, all patients with surgically resected PC (2003-2012) were included in this analysis (last update 2020). The extent of surgical LN dissection was scored for the number of LN samples, location (hilar/mediastinal), and completeness of resection according to European Society of Thoracic Surgeons (ESTS) guidelines. Relapse-free interval (RFI) was evaluated using Kaplan Meier and multivariate regression analysis. 662 patients were included. The median follow-up was 87.5 months. Relapse occurred in 10% of patients, mostly liver (51.8%) and locoregional sites (45%). The median RFI was 48.1 months (95% CI 36.8-59.4). Poor prognostic factors were atypical carcinoid, pN1/2, and R1/R2 resection. In 546 patients LN dissection data could be retrieved; at least one N2 LN was examined in 44% and completeness according to ESTS in merely 7%. In 477 cN0 patients, 5.9% had pN1 and 2.5% had pN2 disease. In conclusion, relapse occurred in 10% of PC patients with a median RFI of 48.1 months thereby underscoring the necessity of long-term follow-up. Extended mediastinal LN sampling was rarely performed but systematic nodal evaluation is recommended as it provides prognostic information on distant relapse.

Endobronchial ultrasound-guided transbronchial fine needle aspiration of mediastinal lymphadenopathy: Diagnostic performance and clinical implications of the World Health Organization reporting system.

Lymph node fine-needle aspiration cytology (LN-FNAC) is a common, rapid, minimally invasive and cost-effective diagnostic method. For mediastinal lymph nodes, endobronchial ultrasound (EBUS) guided LN-FNAC is a first-line investigation and has an indispensable role in the diagnosis and staging of patients with suspected lung cancer. Recently, a new WHO system has been proposed for classification of LN-FNAC heralding five different diagnostic categories; insufficient, benign, atypical, suspicious for malignancy and malignant. The aim of this study was to evaluate the diagnostic accuracy and risk of malignancy (ROM) of these categories in EBUS-guided LN-FNAC from mediastinal lymph nodes. We evaluated 2110 consecutive mediastinal lymph nodes during this one-year retrospective study. Corresponding radiological images and histologic material were used as ground truth to calculate accuracy, sensitivity, specificity and ROM. The WHO system showed an overall accuracy of 93.7% with a sensitivity of 83.0% and a specificity of 97.5%. The positive predictive value was 92.3% and the negative predictive value 94.2%. The overall ROM for each category in the WHO classification system was 12.8% for the inadequate, 2.4% for the benign, 47.4% for the atypical, 81.0% for the suspicious for malignancy and 93.6% for the malignant category. The results of the present study indicate that the new WHO system entails a high diagnostic accuracy regarding EBUS-guided LN-FNAC assessment of mediastinal lymph nodes and supports its integration into clinical practice. Application of the WHO system standardizes risk assessment thus facilitating communication between cytopathologists and clinicians and minimizes the need for histopathological analysis.

Correlation between chest DW-MRI and 18F-FDG PET/CT in newly diagnosed non-small cell lung cancer (NSCLC)

BackgroundPET/CT is currently the gold standard for lung cancer staging, and it is also used to identify distant and nodal metastases. High-resolution MRI can also be used to diagnose and provide morphological details about lung cancer. Standardized uptake value ‘SUV’ calculated from PET/CT gives information about tumor behavior where the SUV reflects metabolic tumor activity. Apparent diffusion coefficient ‘ADC’ calculated from DW-MRI is a quantitative imaging marker aiming to assess tumor cellularity which reflects tumor behavior. The study aimed to correlate ADC assessed by DW-MRI and metabolic activity determined by SUV max in PET/CT in local and nodal staging of newly diagnosed NSCLC.ResultsOur study involved twenty-one patients who were pathologically proven to be NSCLC, 19 males (90.5%) and 2 females (9.5%), with a median age of 61 years (ranging from 37 to 84 years). Among all NSCLC primary mass lesions, we observed a statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR (r = − 0.509 and p = 0.019, r = − 0.472 and p = 0.031 and r = − 0.434 and p = 0.049 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively). Additionally, we observed another statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR in NSCLC mediastinal lymph nodes (r = − 0.699 and p = 0.011, r = − 0.58 and p = 0.048 and r = − 0.629 and p = 0.028 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively).ConclusionsADC values calculated from DW-MRI might act as a new prognostic tool owing to its significant inverse correlation with SUV max achieved from PET/CT in NSCLC primary mass lesions as well as mediastinal lymph nodes.

Patterns of recurrence after esophagectomy following neoadjuvant Immunochemotherapy for esophageal squamous cell carcinoma.

e16101 Background: To explore the recurrence pattern and risk factors of the initial relapse for esophageal squamous cell carcinoma (ESCC) who received radical surgery following neoadjuvant Immunochemotherapy (NICT). Methods: We reviewed 191 ESCC patients who underwent radical surgery following NICT from 2020 to 2022. The pattern of the first postoperative failure and simple lymph node (LN) recurrence were analyzed. Risk factors for failure were analyzed using logistic multivariate regression. Postoperative recurrence-free survival (RFS) was determined using the Kaplan-Meier method, and the log-rank test was applied to assess differences. Results: Until November 26, 2023, 66 of 191 patients experienced postoperative failure. The failure rates at 6 months, 1 year and 2 years were 7.3%, 21.0% and 37.4%, respectively. The overall recurrence pattern included single-pattern recurrence (84.8%) and multiple-pattern recurrence (15.2%). Among the single-pattern recurrence, simple LN recurrence (77%) was the most common. In total, 112 recurrent areas were observed in 43 patients with simple LN recurrence, and the failure rates of cervical, mediastinal and abdominal LNs were 15%, 70% and 15%, respectively. In patients with mediastinal LN failure, superior mediastinal LN recurrence accounted for the highest proportion (54%,60/112), of which 2R (16%,18/112) and 4R (14%,16/112) were the most frequent. The highest proportion (71.4%) of LN failure was located outside the scope of surgical dissection, and the highest incidence was in the supraclavicular area (21%) and the mediastinal 4R area (20%). According to the number of dissected LN areas, patients were divided into three groups: 1-6≤, 6-9≤, and 9-14≤. The 2-year RFS rates for three groups were 50.5%, 72.3%, and 63.5%, respectively (P = 0.04). According to the number of dissected LNs, patients were divided into three groups: 15 &lt; , 15-30 &lt; , and ≥30. The 2-year RFS rates of the three groups were 49.7%, 61.6%, and 71.6%, respectively (P = 0.28). Subgroup analysis showed that the 2-year RFS rates in ypT0-1N0 patients were 80%, 90% and 78.4% (P = 0.56), respectively, and ypT0-1N0 patients with more than 30 LNs did not show significant advantage. Multivariate analysis showed that tumor length &gt; 5 cm, preoperative efficacy evaluation of stable disease (SD), number of dissected LN areas≤6, and ypN2-3 stage were unfavorable factors for postoperative failure in patients. Conclusions: LN recurrence is a common failure mode after radical surgery following NICT for ESCC, and the LN recurrence in the mediastinal 4R and 2R regions is the most common. Tumor length &gt; 5cm, preoperative efficacy evaluation of SD, number of dissected LN areas≤6, and ypN2-3 stage were unfavorable factors for postoperative failure in patients. The suitability of extensive and multiple LN dissection after NICT in ESCC remains to be further investigated.

Management of chylothorax after retrocrural lymphadectomy in a patient with ovarian cancer: a case report

Introduction and importance: With the widespread use of positron emission tomography and computed tomography (PET/CT), a significantly greater proportion of patients with advanced ovarian cancer (OC) are now diagnosed with superior renal-vein lymph node metastases involving retrocrural and mediastinal nodes. To the authors’ knowledge, retrocrural lymphadenectomy has not yet been reported in patients with OC. The authors performed retrocrural lymph node resection in a patient with ovarian cancer. Case presentation: A 64-year-old woman with ovarian cancer who had not undergone surgery upon initial diagnosis was admitted to the authors’ hospital because tumour markers increased during bevacizumab maintenance therapy. PET/CT imaging revealed adnexal masses and multiple metastases in pelvic, para-aortic, retrocrural, and mediastinal lymph nodes. Reduction surgery was performed, and retrocrural lymph nodes were excised. However, the patient’s postoperative course was complicated by a chylothorax. Because of the failure of conservative treatment, interventional embolization was performed, but failed to obstruct lymphatic vessels. The patient underwent reoperation. A fistula was located where Hem-o-lock clips penetrated the pleura, clearly indicating the injury site, which was then sutured and embedded in the surrounding diaphragmatic tissue and filled with gel sponge. The patient recovered from chylous leakage postoperatively. She later underwent chemotherapy and targeted maintenance therapy. Clinical discussion: The authors may have injured the communicating branch of the thoracic duct posterior to the diaphragm during the first operation and did not ligate it. The accumulated chylous fluid finally penetrated through the weak point on the pleura and led to chylothorax 3 days later. If conservative treatment or interventional embolization are unsuccessful, surgical treatment should be selected in time. Conclusion: The location of the retrocrural lymph node at the anastomosis of the chylous cistern and the thoracic duct may pose a significant risk of chylous leakage as a complication of lymphadenectomy. Full exposure of the surgical field and thorough ligation of the lymphatic vessels may lead to successful superior renal-vein lymphadenectomy.

Combining machine and deep transfer learning for mediastinal lymph node evaluation in patients with lung cancer

BackgroundThe prognosis and survival of patients with lung cancer are likely to deteriorate with metastasis. Using deep-learning in the detection of lymph node metastasis can facilitate the noninvasive calculation of the likelihood of such metastasis, thereby providing clinicians with crucial information to enhance diagnostic precision and ultimately improve patient survival and prognosis MethodsIn total, 623 eligible patients were recruited from two medical institutions. Seven deep learning models, namely Alex, GoogLeNet, Resnet18, Resnet101, Vgg16, Vgg19, and MobileNetv3 (small), were utilized to extract deep image histological features. The dimensionality of the extracted features was then reduced using the Spearman correlation coefficient (r ≥ 0.9) and Least Absolute Shrinkage and Selection Operator. Eleven machine learning methods, namely Support Vector Machine, K-nearest neighbor, Random Forest, Extra Trees, XGBoost, LightGBM, Naive Bayes, AdaBoost, Gradient Boosting Decision Tree, Linear Regression, and Multilayer Perceptron, were employed to construct classification prediction models for the filtered final features. The diagnostic performances of the models were assessed using various metrics, including accuracy, area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value. Calibration and decision-curve analyses were also performed. ResultsThe present study demonstrated that using deep radiomic features extracted from Vgg16, in conjunction with a prediction model constructed via a linear regression algorithm, effectively distinguished the status of mediastinal lymph nodes in patients with lung cancer. The performance of the model was evaluated based on various metrics, including accuracy, area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value, which yielded values of 0.808, 0.834, 0.851, 0.745, 0.829, and 0.776, respectively. The validation set of the model was assessed using clinical decision curves, calibration curves, and confusion matrices, which collectively demonstrated the model's stability and accuracy ConclusionIn this study, information on the deep radiomics of Vgg16 was obtained from computed tomography images, and the linear regression method was able to accurately diagnose mediastinal lymph node metastases in patients with lung cancer.

Roginolisib, an oral, highly selective and allosteric modulator of phosphoinositide 3-kinase inhibitor delta (PI3Kδ) in patients with uveal melanoma and advanced cancers.

9597 Background: The highly selective, oral allosteric modulator of PI3Kδ, roginolisib (IOA-244), blocks the activity of PI3Kδ-dependent signaling, in both tumor cells and Tregs. Methods: Continuous daily dosing of roginolisib at 10, 20, 40 and 80 mg in patients (pts) with pretreated solid tumours and Follicular Lymphoma (FL) were evaluated (Part A). Part B consists of a dose confirmation cohort in uveal melanoma (UM) pts of 2 parts, B.1 and B.2. Primary objective: safety of the anticipated biologically effective dose (BED). Secondary objectives: PK; PD (e.g., inhibition of CD63 expression on basophils, changes in immune cell subsets in peripheral blood); RECIST 1.1 or Lugano-based responses; PFS and OS. Exploratory studies: phenotypic changes in circulating immune cells by mass cytometry (i.e., CyTOF); response assessments by radiomics; analysis of circulating protein signatures via Olink proteomics. Results: Part A Solid Tumour (completed): Sixteen pts were treated in 4 cohorts of 4 pts each. Pts characteristics: uveal melanoma (9/16; 56%), cutaneous melanoma (5/16; 31%) and pleural mesothelioma (2/16; 13%). Only Grade 1 and 2 AEs by CTCAE v.5 were observed, including 2 cases of transient (lasting &lt; 24 hrs) diarrhoea and 2 of AST/ALT elevation. Part A FL Cohort (completed): 8 pts were treated at 20 mg (n=4) and 80 mg (n=4). Grade 3 toxicities were transient and observed in 2/8 (25%) pts. 2/4 pts (50%) at the 80 mg had PR as per Lugano criteria. Treatment-emergent adverse events (TEAEs) did not result in study drug discontinuation, immune-related toxicity, or dose-limiting toxicity in either the solid tumor or hematological patients. UM pts (Part A and Part B)&gt;: 29 pts (Part A: 9 pts; Part B.1: 7 pts, Part B.2: 13 pts), of which 23 were treated at 80 mg QD (RP2D). Mean time on treatment: 10.7 mo (range: 1.5-39.6 mo). ORR (RECIST 1.1): PR: 1/29 (3%); SD: 21/29 (72%). Median OS for Part A: 20.8 mo (5/9 with 4 pts alive); Part B.1 20.1 (4/7 with 3 pts alive); Part B.2 not determined; 1-year OS rate: Part A 66.7%; Part B.1 71%; Part B.2 immature. Exploratory Investigations: At 3.7 mo (Cycle 5), there were 2 groups: one with SD (13/29; 45%) and the other with PD (16/29; 55%). At 6 mo, this split continued with 38% (11/29) showing SD and 62% having PD (18/29). Volumetric changes matched durable SDs while having higher sensitivity in the 15 analyzed patients. Interestingly, tumor burden reduction in mediastinal lymph nodes was indicative of SD and 70% of pts had volumetric spleen size reduction. Volumetric and radiomic changes were matched with peripheral changes in plasma proteins and immune cell changes. Conclusions: Roginolisib is well tolerated at 80 mg, demonstrates efficacy, and induces phenotypic changes in circulating immune cells. At the RP2D, the most robust anti-tumour activity was observed in FL (50% PR) and UM pts (3% PR; 72% SD). Clinical trial information: NCT04328844 .

Five-year survival outcomes from the PIT-1 trial: Pemetrexed-cisplatin plus bevacizumab or concurrent thoracic radiation therapy followed by surgery in stage IIIA (N2) nonsquamous non-small cell lung cancer.

8064 Background: Personized Induction Therapy-1 (PIT-1) is a multicenter, randomized phase II selection design trial of pemetrexed-cisplatin plus bevacizumab (BEV arm) or concurrent thoracic radiation therapy (TRT arm) followed by surgery in patients with stage IIIA (N2) nonsquamous non-small cell lung cancer (NSCLC). The TRT arm was chosen as the investigational induction treatment strategy for a future phase III study based on the results of a numerically higher 2-year progression-free survival (PFS, primary endpoint) in the TRT arm and fatal postoperative complications observed only in the BEV arm. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned. Methods: Patients with stage IIIA (N2) nonsquamous NSCLC were randomly assigned (1:1) induction therapy consisting of pemetrexed and cisplatin plus bevacizumab (n = 44) or concurrent TRT (n = 44) followed by surgery. Among them, 38 patients in the BEV arm and 37 patients in the TRT arm underwent surgery. Five-year overall survival (OS), 5-year PFS, and patterns of postoperative recurrence were compared between arms. Prognostic factors of OS were analyzed in surgically resected patients using Cox’s proportional hazard model. Results: The median follow-up was 66.4 months. In 82 treated patients, the 5-year OS and PFS rates were 63.5% (95% CI: 46.9-76.1) and 26.2% (95% CI: 14.1-40.0) in the BEV arm (n = 42), and 57.2% (95% CI: 40.5-70.8) and 27.5% (95% CI: 14.9-41.7) in the TRT arm (n = 40), respectively. There were no statistical differences in OS ( P = 0.572) and PFS ( P = 0.356). In 75 surgically resected patients, pathological nodal down stage was the only significant prognostic factor of OS ( P = 0.014). Age, sex, smoking status, clinical T stage, clinical N stage based on a computed tomography scan, preoperative serum CEA and CYFRA level, EGFR mutation status, pathological complete response, and major pathological response did not have a significant prognostic impact on OS. The patterns of postoperative recurrence were different between arms: locoregional only, in four (11%) and one (3%); distant metastasis only, in 16 (42%) and 21 (57%); and both, in five (13%) and four (11%) in the BEV and TRT arms, respectively. The recurrence rate of ipsilateral hilar or mediastinal lymph nodes (the irradiation field) was significantly lower in the TRT arm (3%) than in the BEV arm (21%, P= 0.01). Conclusions: Five-year survival outcomes were not different between the BEV and TRT arms. The TRT arm demonstrated sufficient local control, but insufficient control of distant metastasis so this is an important issue that requires improvement in the future. Clinical trial information: s031180402.

A prospective phase II randomized clinical study of folic acid in the intervention of radiation esophagitis induced by concurrent chemoradiotherapy in lung cancer.

e20004 Background: To investigate the efficacy and safety of folic acid intervention in lung cancer patients with radiation esophagitis caused by concurrent chemoradiotherapy. Methods: It was a randomized, controlled, single-center clinical trial of 82 patients with stage N2~N3 lung cancer including SCLC and NSCLC were prospectively included. All patients were randomly divided into experimental and control group according to 1:1, and patients were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes (More than 2 cycles of chemotherapy were completed during the same period of radiotherapy or take targeted drugs at the same time, the cumulative radiation dose of chest lesions should exceed 40Gy). The experimental group took folic acid tablets 30mg/day orally at the beginning of radiotherapy until the end of radiotherapy, while the control group did not receive any drug intervention.When two groups appeared radiation esophagitis, the grading criteria for RTOG should be evaluated first, then according to the guidelines of symptomatic treatment.Esophageal toxicity was evaluated during radiotherapy, and improved RTOG and NCI-CTC ratings were performed weekly at the onset of radiation esophagitis and thereafter until 1 week after the end of radiotherapy. Results: The incidence of radiation esophagitis in the experimental group was low during the observation period, and the occurrence time of radiation esophagitis could be delayed in the experimental group, but there was no statistical significance between the two groups ( P=0.456). After folic acid intervention, the symptoms of pain and dysphagia of radiation esophagitis in the experimental group were significantly decreased, especially the RTOG grade and NCI-CTC improvement grade decreased significantly 2 weeks after the occurrence of radiation esophagitis( P=0.007, P=0.009). In the experimental group, it was found that the greater the change of hemoglobin before and after radiotherapy, the occurrence time of radiation esophagitis was about delayed, which was statistically significant(r=0.348, P=0.040).The correlation analysis of the control group showed that the change of body mass index was positively correlated with the onset time of radiation esophagitis(r=0.372, P=0.020);The lower the hemoglobin content after radiotherapy and the larger the hemoglobin difference before and after radiotherapy, the higher the highest incidence of radiation esophagitis(r= -0.454, P=0.004;r= -0.343, P=0.032). Conclusions: Oral folic acid can delay the onset of radiation esophagitis due to concurrent chemoradiotherapy and promote the recovery of radiation esophagitis to a certain extent,but can not interfere with the occurrence of radiation esophagitis.This trial is registered in Clinical Trials(NCT0529636). Clinical trial information: NCT0529636 .

China Anti-Cancer Association Guidelines for the diagnosis, treatment, and follow-up of thymic epithelial tumors (2023).

Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumors with higher incidence in Asians. The diagnosis and treatment pattern has long been based mainly on clinical experience and expert consensus. In recent years, with an increasing number of TETs detected in physical examinations, there is an urgent need to develop the guidelines that apply to the Chinese population. Thus, we intend to develop a holistic integrative guideline for TETs. Under the leadership of the Chinese Anti-Cancer Association (CACA) Mediastinal Tumor Committee, a multidisciplinary guideline development group was established. Systemic literature review and two rounds of questionnaires regarding key clinical issues were carried out. The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations. The CACA guideline provides recommendations for the clinical differential diagnosis of anterior mediastinal lesions, management of asymptomatic small anterior mediastinal nodules, pathological classification and staging systems of TETs, as well as principles of surgery, neoadjuvant and adjuvant therapies, systemic therapies for advanced TETs, and follow-up strategies after surgical resection. This guideline provides holistic integrative management strategies for TETs and would be a useful tool for clinicians on decision-making.

Systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus)

Systemic amyloid light-chain (AL) amyloidosis is an infrequent disease in which amyloid fibrils derived from the immunoglobulin light chain are deposited in systemic organs, resulting in functional impairment. This disease has been notably uncommon in animals, and nonhuman primates have not been reported to develop it. In this study, we identified the systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus) and analyzed its pathogenesis. Amyloid deposits were found severely in the submucosa of the large intestine, lung, mandibular lymph nodes, and mediastinal lymph nodes, with milder lesions in the liver and kidney. Mass spectrometry-based proteomic analysis revealed an abundant constant domain of the immunoglobulin kappa chain in the amyloid deposits. Immunohistochemistry further confirmed that the amyloid deposits were positive for immunoglobulin kappa chains. In this animal, AL amyloidosis resulted in severe involvement of the gastrointestinal submucosa and lymph nodes, which is consistent with the characteristics of AL amyloidosis in humans, suggesting that AL amyloid may have a similar deposition mechanism across species. This report enhances the pathological understanding of systemic AL amyloidosis in animals by providing a detailed characterization of this disease based on proteomic analysis.

Analysis of related factors and treatment effect of chylothorax after lung surgery.

Chylothorax is a seldom encountered complication following lung surgery. However, due to the widespread practice of lung surgery, postoperative complications have inevitably arisen. Chylothorax significantly affects a patient's discharge and recovery. This study investigates the risk factors for postoperative chylothorax at our center and analyzes various treatment modalities and prognostic outcomes. A retrospective analysis was conducted on all postoperative lung resections performed between January 2018 to August 2021 that met the inclusion criteria. Inclusion criteria covered patients undergoing various thoracic surgeries for lung conditions, while exclusion criteria included postoperative referrals for surgeries unrelated to lung tumors. Postoperative chylothorax occurred in 42 of 5,706 patients after lung surgery. General information and disease-related data of the chylothorax and control group were analyzed by univariate and multivariate analyses. Multivariate analysis showed that serum albumin before surgery [odds ratio (OR) =0.86, 95% confidence interval (CI): 0.81-0.91, P<0.001], γ-glutamyl transferase level before surgery (after logarithmic transformation, OR =1.01, 95% CI: 1.00-1.01, P=0.01), squamous cell carcinoma (OR =2.77, 95% CI: 1.37-5.6, P=0.008), right mediastinal lymph node dissection (OR =3.15, 95% CI: 1.62-6.14, P<0.001) were independent risk factors for postoperative chylothorax. Among the 42 cases of postoperative chylothorax, 26 patients were improved with conservative treatments, and 6 patients were improved with chemical pleurodesis. Eight patients with postoperative chylothorax underwent thoracoscopic thoracic duct ligation. Three patients experienced severe postoperative complications: one was discharged after prolonged treatment, while the remaining two either succumbed or were discharged against medical advice. The incidence of chylothorax after lung surgery closely correlates with the intraoperative trauma and nutritional status of patients during the perioperative period. The majority of patients with postoperative chylothorax experienced relief through conservative measures, somatostatin administration, and chemical pleurodesis. Nevertheless, substantial postoperative chylothorax necessitated surgical intervention, involving thoracic duct ligation or drug pleurodesis.

Rapamycin reduces atherosclerotic plaque inflammation in aged mice

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 1. ERA-CVD. Beat ATHERO consortium. 2. Dutch Heart Foundation Aims Aging is the most dominant risk factor of atherosclerotic cardiovascular disease (CVD), the main underlying cause of death worldwide. Both aging and atherosclerosis are associated with changes in the composition and function of the immune system, such as an enlarged T cell effector memory pool and elevated pro-inflammatory cytokine secretion. Since the accumulation of these pro-inflammatory factors contribute to atherosclerosis progression, halting inflammation might be a promising strategy to combat CVD. Rapamycin is an immunosuppressant that was recently discovered to increase lifespan due to the inhibition of senescent cells and effector T cells. We therefore hypothesized that rapamycin treatment can attenuate pro-atherogenic immunity in aged mice. Methods To explore the effects of rapamycin treatment, we administrated 1 mg/kg rapamycin or control solvent to aged (22 months old) male atherosclerotic Ldlr-/- mice (n=16 per group) three times a week intraperitoneally. After eight weeks, mice were sacrificed and their organs were collected for flow cytometry, single-cell RNA sequencing and histological analysis. Results Using flow cytometry, we revealed that rapamycin treatment decreased total T cell numbers in the atherosclerotic aorta and spleen compared to control treatment and attributed to a 24% increase in the relative frequency of immunosuppressive regulatory T cells in the aorta (rapa: 70.6±3.0% vs. ctrl: 57.1±3.8%, p&amp;lt;0.05), indicating skewing towards anti-atherogenic immunity. Within the reduced effector T cell pool of rapamycin-treated mice, we observed increased percentages of IL-10 and IFN-γ-expressing CD4+ and CD8+ T cells. In addition, rapamycin diminished the percentage of pro-atherogenic age-associated B cells (rapa: 7.5±1.8% vs. ctrl: 9.2±1.5%, p&amp;lt;0.05) in the mediastinal lymph nodes, and the percentage of pro-atherogenic age-associated B cells in the mediastinal lymph nodes, and reduced the expression of the senescent markers p19 and BTG2 in the spleen. In line with attenuated inflammation we observed a 36% reduction in relative plaque macrophage content in rapamycin-treated mice (rapa: 14.0±3.6% vs. ctrl: 21.8±5.5%, p&amp;lt;0.05). Conclusions Collectively, our study demonstrates that rapamycin treatment in aged atherosclerotic mice promotes regulatory T cells and reduces systemic and plaque accumulation of T cells, ABCs and macrophages. This provides a new understanding of rapamycin in regulating age-associated atherogenic immunity, indicating rapamycin could be a potential therapeutic to halt CVD.

Anti-interleukin-18 as therapy against atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Established Investigator of the Dutch Heart Foundation Background Interleukin-18 (IL-18) is a pro-inflammatory cytokine and is secreted by macrophages after NLRP3-inflammasome activation. IL-18 is important for the induction of the Th1 response and overexpression of IL-18 aggravates atherosclerosis, suggesting that inhibition of IL-18 may act atheroprotective. In this study, we investigated the therapeutic potential of an IL-18 neutralizing antibody (anti-IL18) on atherosclerosis development. Methods and results Female ApoE-/- mice were fed a Western-type diet for 8 weeks and simultaneously received an antibody against IL-18 (100 µg/mouse; n=15) or a rat IgG2a control (100 µg/mouse; n=15) 3x per week intraperitoneally, after which the mice were sacrificed. First, we assessed macrophage phenotype in the peritoneal cavity. Expression of the proinflammatory markers CD80 (control: 46.3±1.4 *103; p&amp;lt;0.05 vs. anti-IL18: 40.4 ±1.7 *103) and iNOS (control: 15.5±1.8 *102 vs. anti-IL18: 8.0±1.9 *102; p&amp;lt;0.01) were reduced. In the aorta, MFIs of anti-inflammatory macrophage markers Arginase-1 (control: 389±99 vs. anti-IL18: 654±85; p=0.06) and CD206 (control: 55.2±2.4 *103 vs. anti-IL18: 62.8±3.7 *103; p=0.1) tended to be increased expression in the ascending aorta of anti-IL18 mice compared to controls. In addition, anti-IL18 treatment promoted the number of CD4 T cells (control: 20±1% vs. anti-IL18: 28±1%; p&amp;lt;0.0001) in the mediastinal lymph node and increased it’s regulatory phenotype (Tregs; Foxp3+) of CD4 (control: 23±1% vs. anti-IL18: 26±1%; p=0.07) and CD8 T cells (control: 0.4±0.02% vs. anti-IL18: 0.9±0.09%; p&amp;lt;0.0001). These effects however, did not translate into an effect on plaque size in the aortic root, as measured using an Oil-Red-O staining, which did not differ between the control and anti-IL18 treatment group (control: 47.1±2.4 *104 µm2 vs. anti-IL18: 43.4±2.3 *104 µm2). Conclusions Anti-IL18 treatment reduced the proinflammatory phenotype of peritoneal macrophages and promoted Tregs in the mediastinal lymph node. Further analyses on plaque stability and intraplaque macrophage subsets are currently being performed.

Utility of SHOX2 and RASSF1A gene methylation detection on the residual cytology material from endobronchial ultrasound-guided transbronchial needle aspiration.

This study aims to assess the effectiveness of Short Stature Homeobox 2 (SHOX2) and RAS Association Domain Family 1 Isoform A (RASSF1A) gene methylation detection in residual liquid-based cytology (LBC) materials from Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) and investigate the diagnostic accuracy of a comprehensive diagnostic approach. Between June 2022 and May 2023, a total of 110 cases that underwent EBUS-TBNA were enrolled in the study. SHOX2 and RASSF1A genes methylation detection using the residual cytological material, LBC, and cell block (CB) were conducted for each EBUS-TBNA case. The sensitivity and specificity of cytology, CB histopathology, SHOX2, and RASSF1A methylation in diagnosing EBUS-TBNA samples were determined based on follow-up data. Among the 72 cases confirmed as pulmonary carcinomas, the methylation test yielded positive results in 24 adenocarcinoma cases, 10 squamous cell carcinoma cases, and 14 small cell carcinoma cases. The sensitivity of the comprehensive diagnosis (combining LBC, CB, and methylation detection) in distinguishing metastatic pulmonary epithelial malignancies in mediastinal and hilar lymph nodes or masses from benign lesions was higher (97.22%, 70/72) than that of morphological diagnosis alone (LBC and CB) (88.89%, 64/72; P < 0.05). SHOX2 and RASSF1A methylation detection demonstrates a high sensitivity and negative predictive value in the identification of pulmonary epithelial malignancies and holds promise as a valuable ancillary approach to enhance morphological diagnosis of EBUS-TBNA.

Comparison of diagnostic value of quantitative parameters from FAPI and FDG PET/CT in the detection of mediastinal lymph node metastasis in non-small cell lung cancer

Comparison of diagnostic value of quantitative parameters from FAPI and FDG PET/CT in the detection of mediastinal lymph node metastasis in non-small cell lung cancer