OBJECTIVE: To explore the independent predictors of pathological mediastinal lymph node (pN2) metastasis in clinical stage IA (cIA) pure-solid non-small cell lung cancer (NSCLC) patients, and to find an appropriate method of mediastinal lymph node dissection.
METHODS: This study retrospectively evaluated 533 cIA pure-solid NSCLC patients who underwent radical resection of lung cancer (lobectomy combined with systematic lymph node dissection) from January 2014 to December 2016. The relationship between clinicopathological characteristics and pN2 metastasis was analyzed, and the independent predictors of pN2 metastasis were determined by univariate and multivariate logistic regression analysis. We defined the new factor Y as composed of preoperative cT, CEA, and NSE.
RESULTS: There were 72 cases (13.5%) of pN2 metastasis in cIA pure-solid NSCLC patients. Preoperative clinical tumor diameter (cT), serum CEA level, serum NSE level, and pathological status of station 10 lymph nodes were independent predictors of pN2 metastasis. Patients with cT ≤ 21.5 mm, CEA ≤ 3.85 ng/mL, NSE ≤ 13.40 ng/mL and negative station 10 lymph node group showed lower rates of pN2 metastasis. The new factor Y was an independent predictor of pN2 metastasis. Only 3 (2.1%) of 143 patients in the Y low-risk group showed pN2 metastasis.
CONCLUSIONS: For patients with low risk of pN2 metastasis, it might be feasible to take lobe-specific lymph node sampling or systematic lymph node sampling. As for those with high risk of pN2 metastasis, systematic lymph node dissection would be recommended.

OBJECTIVE: To explore whether the upper and/or middle mediastinal nodes (UMMN) should be dissected in Siewert type II adenocarcinoma (AC) according to the incidence of lymph node metastasis. Additionally, to investigate the association between the length of esophageal involvement (LEI) and the UMMN metastases.
METHODS: A cohort with Siewert type II AC who were operated on by a surgical team that routinely treated esophagogastric junction (EGJ) tumors with esophagectomy and extended lymphadenectomy were assessed retrospectively. The primary endpoint of the research was the metastasis rate of UMMN.
RESULTS: A total of 94 patients with EGJ tumor from July 2018 to September 2022 were enrolled. Station 106recR (6.4%, 6/94) was the only station among upper mediastinal nodes (UMN) that presented positive nodes. Middle mediastinal nodes (MMN) metastases of station 107, 109 and station 108 were 2.1% (2/94) and 5.0% (4/80), respectively. Among the 11 patients with MMN or UMN metastases, 63.6% (7/11) had lesser than seven metastatic nodes, and 54.5% (6/11) had a pathological N stage ≤2. LEI >3 cm (p = 0.042) showed a higher risk for MMN metastases in univariable logistic analysis. However, no independent risk factor for mediastinal node metastases was detected.
CONCLUSIONS: This study demonstrated that the incidence of positive MMN and UMN is relatively low in resectable Siewert type II AC, which indicated that it is not necessary to perform a routine dissection upon these stations. LEI >3 cm might be associated with higher risk for mediastinal node metastasis. Certain patients could benefit from extended lymphadenectomy since most of the patients with positive MMN or UMN have a limited number of metastatic nodes.

We investigated the clinical therapeutic effects and prognosis of video-assisted thoracoscopic surgery (VATS) in mediastinal lymph node dissection of lung carcinoma. A total of 312 patients were divided into high-risk and conventional risk groups according to the severity of the disease. High-risk group (n=137) received thoracoscope-guided anatomical pulmonary segmentectomy and systematic lymph node dissection as well as conventional risk group (n=175) received thoracoscope-guided pulmonary lobectomy and systematic lymph node dissection. The results revealed that there are significant differences in age, gender, location, lymph node resection methods, and histological classification in the two groups (P<0.05). Moreover, in comparison with the high-risk group, T stage was higher in the conventional group and showed significant statistical significance (P<0.01). The analysis of independent risk factors of the above differences showed that T staging and histological classification showed high-risk coefficients for lymph node dissection. The risk coefficient was increased with patients\' age. The 5-year survival rate, disease-free survival, and postoperative recurrence rate of the patients in the two groups all indicated no obvious statistical differences. Consequently, thoracoscope-guided lymph node dissection could enhance the detection rate of lymph node metastasis. For the adenocarcinoma (AD) patients with T staging greater than T1, lymph node dissection could provide more accurate pathological staging. Anatomical pulmonary segmentectomy combined with systematic lymph node dissection should be applied in the treatment of elderly, high-risk, and advanced stage (prothrombin time (PT) state >2 cm, ≤3 cm) patients with non-small cell lung carcinoma (NSCLC). Taken together,thoracoscope-guided lymph node dissection could improve the detection rate of lymph node metastasis. In this case, the complete resection of lesions could be ensured. Besides, normal pulmonary tissues were preserved to the maximum extent with minimal trauma, safety, fast postoperative recovery, and definite long-term therapeutic effects.

T. marneffei is opportunistic and dimorphic fungus, which can cause systemic mycosis in human beings. It\'s being difficult to obtain histopathological or microbiological evidence in T. marneffei infection. We reported a rare non-HIV case of T. marneffei infection of bronchopulmonary and mediastinal lymph nodes which was diagnosed by EBUS-TBNA combined with mNGS. The high titer of anti-IFN-γ autoantibodies in serum was probably the cause of T. marneffei infection,which has yet to be fully known.
A 56-year-old Chinese man presented with a 5-month history of intermittent low or high fever and dry cough, followed by fatigue, night sweating, and chest pain when coughing. A large hilar lesion in the left lung and multiple mediastinal lymph node enlargements were found on his chest CT scan.
The patient received EBUS-TBNA of hilar tissue and lymph node biopsy for mNGS at the second Ultrasonic bronchoscopy. No fungal hyphae or spores were found in the histopathology. There were high sequencing reads of T. marneffei in samples of lymph node fluid and bronchogenesis tissue detected by mNGS. His plasma anti-IFN-γ autoantibodies level was positive with a high titer at 1:2500↑.
The patient went through atrial fibrillation at the first dose of amphotericin B liposomes and treated with voriconazole later.
His fever, cough and dyspnea quickly disappeared since the fourth day of treatment. After six months, there was not any focus in his chest CT scans. But his plasma anti-IFN-γ autoantibodies remained unchanged.
Complementing the traditional laboratory and bronchoscopy, mNGS combined with EBUS-TBNA facilitate rapid and precise diagnosis of bronchopulmonary mediastinal lymph nodes T. marneffei infection. Clinicians should be aware of anti-INF-γ autoantibodies in opportunistic infections of non-HIV patients.

UNASSIGNED: Toll-like receptors (TLRs) play a vital role as a first defense mechanism linking the innate with the adaptive immune system. Prior studies showed that TLR2 participated in immune responses of sarcoidosis. However, the role of TLR2 in the progression of mediastinal lymph nodes associated with sarcoidosis is still unknown. The current study aims to investigate the expression of Toll-like receptors 2 (TLR2) in mediastinal lymph nodes of patients with sarcoidosis.
UNASSIGNED: Mediastinal lymph nodes biopsy specimens were collected from 10 patients with sarcoidosis and 11 normal controls. The expression of TLR2 in mediastinal lymph nodes was detected by immunohistochemistry.
UNASSIGNED: In mediastinal lymph nodes specimens, immunohistochemical examination revealed that expression of TLR2 could be detected in sarcoidosis patients, while it was scarcely detected in the mediastinal lymph nodes of control. The mean optical density of TLR2 in mediastinal lymph nodes of sarcoidosis was significantly higher than controls (124.9±24.3 vs. 92.6±35.2, P=0.026). Among patients with sarcoidosis, correlation analysis showed that the mean optical density of TLR2 in mediastinal lymph nodes positively correlated with the level of 24-hour urinary calcium (R=0.781, P=0.038).
UNASSIGNED: The expression of TLR2 was upregulated in mediastinal lymph nodes of sarcoidosis patients. The expression of TLR2 in mediastinal lymph nodes was associated with the level of 24-hour urinary calcium, suggesting that TLR2 might become another predictor of disease activity.

To investigate the short-term outcomes and long-term oncological efficacy of video-assisted thoracic surgery (VATS) for surgical treatment of pN2 non-small cell lung cancer (NSCLC) compared with open thoracotomy (OT).
We retrospectively collected data from 1034 patients who underwent pulmonary resection and systemic lymph node dissection for pathological N2 NSCLC from September 2005 to December 2017 (536 patients in VATS group and 498 patients in OT group). Propensity score matching was applied to reduce the confounding effects. Factors affecting survival were assessed by Kaplan-Meier estimates and Cox regression analysis.
The VATS procedure was associated with shorter operative time compared with the OT procedure (147.96 ± 58.91 min vs. 165.34 ± 58.91 min, P < 0.001). No significant difference was identified between the two groups in the number of dissected mediastinal lymph nodes (MLNs) and number of dissected MLNs stations. More patients after VATS procedure received postoperative adjuvant therapy (83.4% vs. 75.5%, P = 0.002). At a median follow-up of 36 (range 4-150) months, comparing VATS procedure and OT procedure, no significant differences were noted in 5-year DFS (20.7% vs. 22.5%, P = 0.89) and 5-year OS (30.7% vs. 34.5%, P = 0.821). The VATS procedure was not found to be an independent predictor of DFS (hazard ratio, 0.986; 95% CI, 0.809 to 1.202) or OS (hazard ratio, 0.977; 95% CI 0.802 to 1.191).
In this large propensity-matched comparison, the VATS procedure offered comparable short-term outcomes and long-term oncological efficacy for patients with pN2 NSCLC when compared with OT procedure.

The aim of this study was to investigate predictive factors of occult mediastinal lymph node metastasis (MLNM) in preoperative 18 F-fluorodeoxy-glucose PET/CT node-negative lung adenocarcinoma patients.
We reviewed the clinical data and PET/CT parameters of 360 consecutive pulmonary adenocarcinoma patients who were scheduled to undergo anatomical pulmonary resection and systemic mediastinal node dissection. The nodal metastasis was pathologically defined and all resected tumors were classified according to the 2011 IASLC/ATS/ERS classification. Univariate and multivariate analysis were conducted to evaluate the associations between clinicopathological variables and MLNM.
Of all 360 patients, 54 (15.0%) had pathological N2 diseases. The serum CEA level, nodule type, hilar nodal SUVmax, tumor SUVmax, size, location and histologic subtype were associated with MLNM significantly on univariate analysis. On multivariate analysis, CEA ≥ 5.0 ng/mL (P < 0.001), solid nodule (P = 0.012), tumor SUVmax ≥ 3.7 (P < 0.027), hilar nodal SUVmax ≥ 2.0 (P < 0.001) and centrally located tumor (P = 0.035) were independent risk factors for MLNM. The area under the ROC curve (AUC) for tumor SUVmax and hilar nodal SUVmax in predicting MLNM was 0.764 and 0.730, respectively, and the combined use of five factors yielded a higher AUC of 0.885.
Increased primary tumor and hilar lymph node SUVmax, solid nodule, centrally located tumor and increased CEA level predicted the increased risk of mediastinal lymph node metastasis. Combined use of these factors improved the diagnostic capacity for predicting N2 disease preoperatively. Invasive mediastinal staging should be considered for patients with these risk factors, even those with a negative mediastinum on PET/CT.

OBJECTIVE: Our goal was to investigate the incidence and distribution of mediastinal lymph node metastases (MLNM) in non-small-cell lung cancers (NSCLC) 3 cm or less, with the purpose of guiding mediastinal lymph node dissection.
METHODS: A total of 2292 cases seen between January 2001 and December 2014 were included. These patients were grouped according to the lobes with the primary tumours. The incidence and distribution of pathological MLNM were compared among the groups. The impact of MLNM on overall survival was also compared.
RESULTS: The most common mediastinal metastatic sites for different primary tumour lobes were as follows: right upper lobe, 17.7% (87/492) for level 4R; right middle lobe, 14.9% (28/188) for level 7; right lower lobe, 19.8% (82/414) for level 7; left upper lobe, 18.2% (96/528) for level 5; and left lower lobe, 16.6% (42/253) for level 7. For patients with tumours in the upper lobe, the median survival time was 32 months for those with MLNM in the subcarinal zone or lower zone compared with 83 months for those with MLNM only in the upper zone (P < 0.01). When the tumours were 1 cm or less, the incidence of MLNM to the lower zone for upper lobe tumours and of MLNM to the upper zone for lower lobe tumours was zero.
CONCLUSIONS: Different primary NSCLC lobe locations have a different propensity to be sites of MLNM for those tumours that are 3 cm or less. For tumours no larger than 1 cm, a lower zone mediastinal lymph node dissection might be unnecessary for upper lobe tumours and an upper zone mediastinal lymph node dissection might be unnecessary for lower lobe tumours.

OBJECTIVE: This study evaluated the safety and efficacy of stereotactic radiation therapy (SRT) for the treatment of patients with oligometastases or oligorecurrence within mediastinal lymph nodes (MLNs) originating from different tumors.
METHODS: Between October 2006 and May 2015, patients with MLN oligometastases or oligorecurrence were enrolled and treated with SRT at our hospital. The primary endpoint was MLN local control (LC). Secondary endpoints were time to symptom alleviation, overall survival (OS) after SRT, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).
RESULTS: Eighty-five patients with 98 MLN oligometastases or oligorecurrences were treated with SRT. For the entire cohort, the 1-year and 5-year actuarial LC rates were 97% and 77%, respectively. Of 53 symptomatic patients, symptom alleviation was observed in 47 (89%) after a median of 5 days (range, 3-30 days). The median OS was 27.2 months for all patients. For patients with non-small cell lung cancer, univariate and multivariate analyses revealed that a shorter interval between diagnosis of primary tumors and SRT and larger MLN SRT volume were associated with worse OS. CTCAE v4.0 ≥ Grade 3 toxicities occurred in six patients (7%), with Grade 5 in three patients (all with RT history to MLN station 7).
CONCLUSIONS: SRT is a safe and efficacious treatment modality for patients with oligometastases or oligorecurrence to MLNs originating from different tumors, except for patients who received radiotherapy to MLN station 7. Further investigation is warranted to identify the patients who benefit most from this treatment modality.

BACKGROUND: Tumor recurrence is the most common cause of treatment failure, especially after complete resection of pathological stage N2 non-small cell lung cancer (NSCLC). In this study, we investigated the clinicopathological characteristics in order to identify independent risk factors for postoperative recurrence.
METHODS: Between January 2001 and December 2013, 96 patients who underwent surgical resection for pathological N2 NSCLC were retrospectively reviewed. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method to explore risk factors, while the Cox proportional hazard model was used to assess independent predictors.
RESULTS: The median and five-year RFS rates were 15 months and 27.4%, respectively. Univariate analysis showed a significantly poorer prognosis for non-regional N2 metastasis, more than three metastatic N2 lymph nodes, multiple N2 station, and multiple N2 zone involvement. Multivariate analysis demonstrated that non-regional N2 metastasis (hazard ratio [HR] 1.857, 95% confidence interval [CI] 1.061-3.249, P = 0.030) and more than three metastatic N2 lymph nodes (HR 2.555, 95% CI 1.164-5.606, P = 0.019) were independent risk factors for RFS. Additionally, the incidence of non-regional N2 metastasis was higher in patients with a primary tumor in the left lower (57.1%) or right lower lobe (48.1%), followed by left upper (31.8%), right middle (14.3%) and right upper lobe (7.7%).
CONCLUSIONS: The combination of the distribution and number of metastatic N2 lymph nodes provides a more accurate prediction for N2 NSCLC regarding recurrence. Non-regional N2 metastasis could occur with a primary tumor in any lobe, but occurs more frequently in the lower lobe.