Spatiotemporal distribution of mediastinal neoplasms: A comprehensive multi-center study.

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.

Second Hematologic Malignancies Associated With Primary Mediastinal Germ Cell Tumors: A Population-based Study.

BACKGROUND: Studies addressing second hematologic malignancies (SHMs) in patients with primary mediastinal germ cell tumors (PMGCTs) are scarce. To better describe this phenomenon, we analyzed a large case series from a population-based registry. METHODS: The Surveillance, Epidemiology, and End Results database was used to report the clinical characteristics and incidence of SHMs in patients with PMGCT. RESULTS: Among 1297 PMGCTs, 27 cases (2.08%) of SHM were found, with a median latency period of 12 months (95% CI: 5-41). All SHM occurred in males, 20 of whom (74.1%) had a previous nonseminomatous tumor. Acute myeloid leukemia was the most frequent SHM, accounting for 13 cases, 4 of which were acute megakaryoblastic leukemia that occurred within 5 months of diagnosis. The median survival after the diagnosis of SHM was 6 months (95% CI: 2-41). The risk of SHM was significantly higher than expected for the reference population, with a standardized incidence ratio of 6.21 (95% CI: 3.31-10.62) and an absolute excess risk of 19.19 per 10,000 person-years. CONCLUSIONS: Patients with PMGCT are at a higher risk of developing SHMs than the general population, particularly acute myeloid leukemia. This risk ranges from synchronous diagnosis of acute megakaryoblastic leukemia to the later onset of other hematological disorders that might be related to PMGCT therapies. Our findings may help create follow-up schedules for patients with PMGCT and raise the level of suspicion surrounding this association.

Clinical Features and Survival Outcomes in Children and Adolescents With Malignant Mediastinal Germ Cell Tumors Based on Surveillance, Epidemiology, and End Results Database Analysis.

INTRODUCTION: The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant mediastinal germ cell tumors (MMGCT). METHODS: Data on the demographics, treatment, and survival outcomes of children and adolescents with MMGCT from January 1, 2000 to December 31, 2018 were obtained. To compare survival curves, the log-rank test was employed. The generation of survival curves based on different parameters was done using Kaplan-Meier estimations. Cox proportional hazards regression was performed to determine the variables linked to disease-specific survival. RESULTS: The selection criteria were met by 152 MMGCT patients, 130 of whom were male. Fifty three cases of mixed germ cell tumors (GCTs), 41 cases of malignant teratomas, 26 cases of yolk sac tumors, 14 cases of seminoma, 13 cases of choriocarcinomas, and five cases of embryonal carcinoma were reported. Overall survival at 3 and 5 y for all patients was 63.1% and 61.2%, respectively. Malignant teratoma, yolk sac tumors, and mixed GCTs in children and adolescents had comparable survival rates, while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Embryonal carcinoma, malignant teratoma, mixed GCTs, and choriocarcinoma were found as risk factors by multivariate Cox proportional hazards analysis. In contrast, surgery and younger age were protective factors. However, chemotherapy alone showed no survival benefits. CONCLUSIONS: Our population-based evidence showed that MMGCT had worse prognosis in older children and adolescents. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery can prolong survival time. Chemotherapy and radiotherapy were not associated with improved prognosis.

Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: A Surveillance, Epidemiology, and End Results-based Study.

OBJECTIVES: Extragonadal germ cell tumors (EGCT) are a rare entity, most of them being located in the mediastinum and retroperitoneum. Information on these tumors is scarce, requiring carrying out large population-based studies to better understand these diseases. We aimed to determine the clinical features and prognosis of patients with EGCT of the mediastinum and retroperitoneum. MATERIALS AND METHODS: Demographic and clinicopathological features of patients diagnosed with EGCT of the mediastinum and retroperitoneum from 1975 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 1674 patients were included, 1297 (77.5%) of mediastinal origin and 377 (22.5%) of retroperitoneum. Nonseminomatous tumors (56.3%) were slightly more frequent than seminomas (43.7%) with similar distribution between mediastinum and retroperitoneum. After a median follow-up of 137 months, the median overall survival was 263 months (95% CI, 220-296) whereas the median cause-specific survival (CSS) has still not been reached. The 10-year overall survival and CSS were 57.4% (95% CI, 55-59.7) and 63% (95% CI, 60.6-65.2) respectively. Multivariate analysis showed that older age, mediastinal location, nonseminomatous histology, and distant disease at diagnosis were independent prognostic factors correlated with a worse prognosis. Patients with mediastinal choriocarcinoma and embryonal carcinoma have the worst prognosis, both with a median CSS of only 12 months. CONCLUSIONS: Despite a decreasing incidence observed in recent decades, EGCT continues to represent a challenge for oncologists. The prognosis of choriocarcinoma and embryonal carcinoma of the mediastinum remains poor and treatment strategies need to be improved urgently.

Current thoracoscopic approach for mediastinal neuroblastoma in Japan-results from nationwide multicenter survey.

BACKGROUND: Minimally invasive surgery (MIS) is appropriate for the treatment of some neuroblastomas (NBs); however, the indications and technical issues are unclear. This study aimed to clarify the current status of MIS for mediastinal NB in Japan. METHODS: Preliminary questionnaires requesting the numbers of neuroblastoma cases in which MIS was performed from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. Secondary questionnaires were sent to institutions with MIS cases to collect detailed data. RESULTS: One hundred thirty-four (84.2%) institutions returned the preliminary questionnaire and 83 institutions (52.2%) reported a total of 1496 operative cases. MIS was performed for 175 (11.6%) cases. Among the 175 cases, completed forms of 140 patients were returned and 40 (male, n = 28; female, n = 12) cases had mediastinal NB. Fourteen patients received thoracoscopic biopsy, none were converted to thoracotomy. Twenty-eight patients received MIS for radical resection, none were converted to thoracotomy. Perioperative complications (Horner's syndrome) were recognized after radical resection in one (2.5%) case. CONCLUSIONS: MIS was performed in a limited number of mediastinal NB cases. A thoracoscopic approach would be feasible for mediastinal NB.

Survival among patients with composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma and classical Hodgkin lymphoma: A population-based study.

BACKGROUND: Data on composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma (LBCL) and classical Hodgkin lymphoma (cHL) are rare. METHODS: We identified 25 cases with composite lymphoma (CL), 116 cases developing LBCL as a second primary cancer after cHL (cHL-LBCL), and 74 cases developing cHL as a second primary cancer after LBCL (LBCL-cHL) from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Comparisons of overall survival (OS) and lymphoma cause-specific survival (CSS) between patients with cHL-LBCL or cHL-LBCL and their de novo counterparts were performed. RESULTS: The 5-year OS of patients with CL was 74.8 %. No significant difference in unadjusted OS and lymphoma CSS were observed between patients with de novo LBCL (LBCL-1 group) and patients with cHL-LBCL. However, the age- and stage-adjusted cHL-LBCL group had inferior OS and lymphoma CSS compared with that in the LBCL-1 group. The unadjusted and adjusted OS and lymphoma CSS in the LBCL-cHL group were significantly worse than patients with de novo cHL. CONCLUSIONS: CL between LBCL and cHL may have good outcomes. cHL survivors had poorer outcomes after a LBCL diagnosis versus patients with LBCL-1. Significantly poor outcomes were observed in patients with LBCL-cHL compared with patients with de novo cHL.

Primary mediastinal germ cell tumors - A retrospective analysis of >30 years of experience in a single institution.

BACKGROUND: This study was performed to clarify the treatment outcome of patients with primary mediastinal germ cell tumors (PMGCTs), focusing on the clinical manifestations and management during definitive therapy and long-term follow-up. METHODS: In this study, we retrospectively reviewed the medical records of patients with PMGCTs treated at Shinshu University School of Medicine, and examined the clinical profiles and treatment outcomes of 22 patients (mean age of 29 years) with primary mediastinal GCTs treated at our hospital between 1983 and 2019. RESULTS: Five patients were diagnosed with pure seminoma and 17 had nonseminomatous GCT. A total of 21 patients were treated with cisplatin-based chemotherapy and 15 patients (68.2%) underwent thoracic surgery after chemotherapy. Although all cases of nonseminomatous GCT were negative for tumor markers after cisplatin-based chemotherapy, two cases showed variable GCT cells and two had somatic components (angiosarcoma and rhabdomyosarcoma) in resected specimens. Three relapsed soon after surgery. Growing teratoma syndrome developed during chemotherapy in four cases. Urgent thoracic surgery was performed in three patients, but one case was inoperable. The calculated 10-year overall survival rates were 100% in mediastinal seminoma and 64.7% in NSGCT. During follow-up, second non-GCT malignancies developed in three patients (colon cancer, 190 months; thyroid cancer, 260 months; non-small cell lung cancer, 250 months after the initial chemotherapy) and one patient with primary mediastinal seminoma was associated with multiple type I endocrine tumors. CONCLUSIONS: Our experiences demonstrated that long-term survival and/or cure can be achieved with adequate chemotherapy followed by local surgical treatment even in patients with mediastinal GCTs. However, the clinical manifestations and biological behaviors during and/or after chemotherapy were complex and varied. In addition, the development of secondary malignancies should be taken into consideration for long-term follow-up. Clinicians should be aware of the various clinical features and secondary malignancies in primary mediastinal GCTs.

Incidental mediastinal masses detected at low-dose CT screening: prevalence and radiological characteristics.

PURPOSE: The primary and secondary aims were to investigate the prevalence of incidental mediastinal masses on low-dose chest CT examinations during health check-ups, and to review the radiological characteristics of prevascular mediastinal masses, respectively. MATERIALS AND METHODS: This retrospective study included 38,861 participants (mean age: 57.1 years; range: 21-99 years; men: 51.3%; never-smokers: 57.4%) who underwent low-dose chest CT examinations between January 2011 and December 2016. All images with incidental mediastinal masses were reviewed, and prevascular mediastinal masses were assessed for qualitative and quantitative imaging characteristics by two radiologists. Univariate and multivariate analyses were performed in clinical and CT features between some combinations of participants. RESULTS: Overall, 653 participants (1.68%, 653 of 38,861) had incidental mediastinal masses; 578 in prevascular mediastinum, including 93 intrathymic cysts and 24 thymic epithelial tumors. Presence of mediastinal mass was not significantly associated with sex (p = 0.089) and smoking history (p = 0.098) but with age (p < 0.001). Significant differences were found between intrathymic cysts and thymic epithelial tumors in terms of shapes (p = 0.049), contours (p = 0.018), and CT values (p = 0.012). CONCLUSION: The prevalence of asymptomatic mediastinal masses on low-dose chest CT was 1.68%. CT values, shapes, and contours may effectively distinguish intrathymic cysts from thymic epithelial tumors.

Lobe-Specific Lymph Node Dissection for Clinical Early-Stage (cIA) Peripheral Non-small Cell Lung Cancer Patients: What and How?

OBJECTIVE: We investigated the possible lobe-specific lymph node (LN) metastasis pattern of early-stage peripheral non-small cell lung cancers (NSCLC) and define the extent of lobe-specific LN dissection for them. METHODS: We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy for clinical T1N0M0 peripheral NSCLC from January 2015 to December 2018. The LN metastasis pattern was analyzed by tumor lobe location. RESULTS: A total of 590 patients were included for analysis. The mean number of total dissected LNs was 12.3 ± 5.8 and 8.2 ± 4.1 for total dissected mediastinal LNs. The rate of mediastinal LN metastasis was 9.5%. For cases of upper lobe tumor and lower lobe tumor, 8.8% and 6.0% of them respectively metastasized to the upper LN zone (P = 0.274). However, upper lobe tumors hardly metastasized to the subcarinal (0.3%) and lower (0.3%) LN zones while for lower lobe tumors, the rate of LN metastasis was 10.2% and 5.4% respectively (both P < 0.001). However, all cases (100%) metastasizing from lower lobes to the upper LN zone had a tumor size of 2-3 cm, whereas cases with a tumor size ≤ 2 cm had no metastasis (0%). None of the tumors in the right middle lobe metastasized to the lower LN zone (0%). CONCLUSIONS: A lobe-specific LN metastasis pattern was observed in clinical stage IA peripheral NSCLC. For tumors in upper lobes (≤ 3 cm), there may be no need to dissect lower mediastinal LNs and for tumors in lower lobes (≤ 2 cm), dissecting upper mediastinal LNs may not be required.

Distribution of Mediastinal Lesions Across Multi-Institutional, International, Radiology Databases.

INTRODUCTION: Mediastinal lesions are uncommon; studies on their distribution are, in general, small and from a single institution. Furthermore, these studies are usually based on pathology or surgical databases and, therefore, miss many lesions that did not undergo biopsy or resection. Our aim was to identify the distribution of lesions in the mediastinum in a large international, multi-institutional cohort. METHODS: At each participating institution, a standardized retrospective radiology database search was performed for interpretations of computed tomography, positron emission tomography-computed tomography, and magnetic resonance imaging scans including any of the following terms: "mediastinal nodule," "mediastinal lesion," "mediastinal mass," or "mediastinal abnormality" (2011-2014). Standardized data were collected. Statistical analysis was performed. RESULTS: Among 3308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%), and lymphomas (16.1%) were most common. The distribution of lesions varied among mediastinal compartments; thymomas (38.3%), benign cysts (16.8%), and neurogenic tumors (53.9%) were the most common lesions in the prevascular, visceral, and paravertebral mediastinum, respectively (p < 0.001). Mediastinal compartment was associated with age; patients with paravertebral lesions were the youngest (p < 0.0001). Mediastinal lesions differed by continent or country, with benign cysts being the most common mediastinal lesions in the People's Republic of China, thymomas in Europe, and lymphomas in North America and Israel (p < 0.001). Benign cysts, thymic carcinomas, and metastases were more often seen in larger hospitals, whereas lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p < 0.01). CONCLUSIONS: Our study confirmed that the spectrum and frequency of mediastinal lesions depend on mediastinal compartment and age. This information provides helpful demographic data and is important when considering the differential diagnosis of a mediastinal lesion.

Clinical manifestation of pediatric mediastinal tumors, a single center experience.

Medical decisions should be well-planned to improve prognosis and reduce complications of mediastinal tumors. In this study, we analyzed the clinical presentations of pediatric mediastinal tumors and their correlation with long-term clinical outcome.Forty patients under 18 years of age diagnosed with mediastinal tumors at China Medical University Children's Hospital between 2001 and 2016 were enrolled. The patients' sex, age of onset, initial clinical symptoms, and treatment outcomes were analyzed.75% of the patients with mediastinal tumors in this study were men, and the median age of onset was 13 years old (age range: 0-17 years). The overall mortality rate was 40%. The most common tumors were lymphoma (47.5%), followed by germ cell tumors (12.5%), neuroblastoma (12.5%), and thymoma (7.5%). Neuroblastoma was more prevalent in girls younger than 5 years old. The initial presentations of these patients included breathing difficulty (65%), productive cough (47.5%), pleural effusion (54.5%), superior vena cava (SVC) syndrome (35%), neck mass (35%), airway compression (32.5%), fever (30%), chest pain (27.5%), and pericardial effusion (25%). Lymphomas were more likely to be accompanied by neck mass (52.6% vs19.0%, P = .04) and SVC syndrome (52.6% vs 19.0%, P = .026), yet also had a better 1-year-survival rate (68.4% vs 52.4%, P = .02).Overall, lymphoma should be suspected when children present with neck mass and SVC syndrome. Neuroblastoma with a posterior mediastinal origin should be suspected among children younger than 5 years old. Tumor-related airway obstruction, pleural effusion, and pericardial effusion were leading cause of cardiopulmonary instability during sedation for invasive procedures, which should be managed cautiously.

Impact of Teratoma on the Cumulative Incidence of Disease-Related Death in Patients With Advanced Germ Cell Tumors.

PURPOSE: In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT. METHODS: Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed. RESULTS: Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status (P < .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status (P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01). CONCLUSION: The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.

Pediatric Malignant Mediastinal Masses.

OBJECTIVE: To describe the clinical spectrum and outcome-associated variables of pediatric malignant mediastinal masses in a resource-limited setting. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatric Hematology-Oncology, The Children's Hospital, Lahore, from October 2016 to November 2017. METHODOLOGY: Children with malignant mediastinal masses were enrolled. The variables studied were median age at presentation, gender distribution, immunisation status, socio-economic background, causes of delayed presentation, presenting complaints, complications of disease, methods for mass biopsy, final diagnosis, staging, and outcome of the disease. Results were described in terms of descriptive statistics. RESULTS: The median age at diagnosis was 7.5 years with male-to-female ratio of 2:1. The commonest presenting complaint was fever (82%), respiratory distress (58%), and lymphadenopathy (51%). Seventy-eight percent patients belonged to lower socio-economic class. Eighty-six percent of patients had delayed presentation to the tertiary care hospital and the most common reason was delayed diagnosis by the medical professionals (49%). Fifty-one percent patients had weight-for-age less than 5th percentile. Common complications were airway obstruction (35%), pericardial effusion (19.6%), superior vena cava syndrome and gross pleural effusion (13.7% each). Commonest diagnosis was T-cell acute lymphoblastic leukemia (35%) followed by lymphoblastic lymphoma and Hodgkin's lymphoma (15.7% each). Fourtyfive percent patients expired, 2% defaulted treatment and 5.9% completed treatment; 25% patients were under treatment, 3.9% patients had progressive disease while outcome of 17.6% of patients could not be known. The most significant factor associated with the outcome primary diagnosis (p<0.001), delayed presentation (p=0.007) and educational status of the family. CONCLUSION: The pattern of clinical presentation, complications and diagnoses of pediatric malignant mediastinal masses showed some variation from the already reported. Low literacy rate and delay in presentation are common and contribute significantly to the poor outcome.

Klinefelter syndrome in males with germ cell tumors: A report from the Children's Oncology Group.

BACKGROUND: Males with Klinefelter syndrome (KS) (47,XXY) may be more likely to develop germ cell tumors (GCTs), particularly mediastinal GCTs. To date, there are no reports characterizing the prevalence of KS among male GCT cases. METHODS: The authors used array genotyping data from a Children's Oncology Group epidemiology study to estimate the prevalence of KS in males with GCTs (433 males aged birth-19 years). Using Fisher's exact tests, the authors examined differences in age at diagnosis, race/ethnicity, tumor location and histology, and several birth characteristics between cases of KS-GCT and GCT cases without chromosomal abnormalities. Using publicly available data, the authors estimated the 1-year risk, risk ratio, and corresponding 95% confidence interval of GCTs among KS cases. RESULTS: Based on analysis of array genotyping data, 3% of male GCT cases (13 cases) had KS. The additional X chromosome was of maternal origin in 7 of the 13 cases. Of these 13 KS cases, 5 of 9 KS-GCT cases with parental questionnaire data (56%) reported a diagnosis of KS. No significant differences were observed with regard to patient or birth characteristics between KS-GCT and non-KS-GCT cases. KS-GCT cases were significantly more likely to be diagnosed with mediastinal tumors than non-KS-GCT cases (P<.01). The authors estimated the risk of developing a GCT among males with KS to be 0.00025, or 1 per 4000 males (risk ratio, 18.8; 95% confidence interval, 11.7-30.0). CONCLUSIONS: Compared with males without chromosomal abnormalities, males with KS are more likely to be diagnosed with a mediastinal GCT. The presence of KS should be considered in males with a diagnosis of mediastinal GCT. In the current study, the authors report that approximately one-third of males with mediastinal germ cell tumors have Klinefelter syndrome, and therefore screening of these individuals for the syndrome may be warranted. Males with Klinefelter syndrome are 19 times as likely as males without Klinefelter syndrome to develop germ cell tumors.

Utilizing multiple pathway cross-talk networks reveals hub pathways in primary mediastinal B-cell lymphoma.

OBJECTIVE: The objective of this paper was to reveal hub pathways in primary mediastinal B-cell lymphoma (PMBL) based on multiple pathway crosstalk networks (PCNs) and give insight for its pathological mechanism. MATERIALS AND METHODS: Based on gene expression data, pathway data and protein-protein interaction data, background PCN (BPCN) and tumor PCN (TPCN) of PMBL were constructed. The rank product algorithm was implemented to identify hub pathways of BPCN and TPCN. Finally, topological properties (degree, closeness, betweenness, and transitivity) of hub pathways were analyzed. RESULTS: For BPCN, there were three hundred nodes and 42,239 edges, and the pathway pairs had great overlaps. TPCN was composed of 281 nodes and 12,700 cross-talks. A total of five hub pathways were identified, nonalcoholic fatty liver disease (NAFLD), tuberculosis, human T-lymphotropic virus type-I (HTLV-I) infection, hepatitis B, and Epstein-Barr virus infection. The topological properties for them were different from each other, further between PMBL and normal controls. CONCLUSION: We have identified five hub pathways for PMBL, such as NAFLD, HTLV-I infection, and Hepatitis B, which might be potential biomarkers for target therapy for PMBL.

Incidence and Distribution of Lobe-Specific Mediastinal Lymph Node Metastasis in Non-small Cell Lung Cancer: Data from 4511 Resected Cases.

OBJECTIVE: We aimed to investigate the incidence and distribution of mediastinal lymph node metastases (MLNM) in operable non-small cell lung cancer (NSCLC) with the purpose of guiding mediastinal lymph node dissection (MLND). METHODS: A total of 4511 NSCLC patients who underwent resection between January 2001 and December 2014 were included. These patients were preoperatively untreated and grouped according to the primary tumor lobes. The incidence and distribution of pathologic MLNM were compared among groups, and multivariate analysis was conducted to find the independent factors impacting MLNM. RESULTS: Lymph node involvement was observed in 1784 patients (39.5%). A total of 628 cases (13.9%) were N1-positive only, 752 cases (16.7%) were both N1- and N2-positive, and 404 cases (9.0%) were N2-positive only. The most common sites of mediastinal metastasis for different primary tumor lobes were the right upper lobe, station 4R (21.5%, 192/893); right middle lobe, station 7 (21.1%, 69/327); right lower lobe, station 7 (24.1%, 212/878); left upper lobe, station 5 (22.2%, 224/1008); and left lower lobe, station 7 (21.7%, 136/628). However, when only N2 cases were considered, each mediastinal lymph node zone can be involved with metastasis to a high proportion (> 5%). Multivariable analyses showed that poor cell differentiation, adenocarcinoma, larger tumor size, central type, and younger age were independent factors favoring MLNM. CONCLUSIONS: Different primary tumor locations have a different propensity to be sites of MLNM; however, once MLNM occurs, each zone can be involved and should not be neglected. Systematic MLND is the preferred procedure for operable NSCLC.

Variability in invasive mediastinal staging for lung cancer: A multicenter regional study.

OBJECTIVE: Prior studies have reported underuse of-but not variability in-invasive mediastinal staging in the pretreatment evaluation of patients with lung cancer. We sought to compare rates of invasive mediastinal staging for lung cancer across hospitals participating in a regional quality improvement and research collaborative. METHODS: We conducted a retrospective study (2011-2013) of patients undergoing resected lung cancer from the Surgical Clinical Outcomes and Assessment Program in Washington State. Invasive mediastinal staging included mediastinoscopy and/or endobronchial/esophageal ultrasound-guided nodal aspiration. We used a mixed-effects model to mitigate the influence of small sample sizes at any 1 hospital on rates of invasive staging and to adjust for hospital-level differences in the frequency of clinical stage IA disease. RESULTS: A total of 406 patients (mean age, 68 years; 69% clinical stage IA; and 67% lobectomy) underwent resection at 5 hospitals (4 community and 1 academic). Invasive staging occurred in 66% of patients (95% confidence interval [CI], 61%-71%). CI inspection revealed that 2 hospitals performed invasive staging significantly more often than the overall average (94%, [95% CI, 89%-96%] and 84% [95% CI, 78%-88%]), whereas 2 hospitals performed invasive staging significantly less often than overall average (31% [95% CI, 21%-44%] and 17% [95% CI, 7%-36%]). CONCLUSIONS: Rates of invasive mediastinal staging varied significantly across hospitals providing surgical care for patients with lung cancer. Future studies that aim to understand the reasons underlying variability in care may inform quality improvement initiatives or lead to the development of novel staging algorithms.

Tumor histology predicts mediastinal nodal status and may be used to guide limited lymphadenectomy in patients with clinical stage I non-small cell lung cancer.

OBJECTIVE: Methods to minimize surgical trauma from mediastinal lymphadenectomy in patients with early-stage lung cancer are still immature. This study aimed to identify predictors of negative pathologic N2, which may be used to select patients for limited mediastinal lymphadenectomy. METHODS: Clinicopathologic features of 1430 patients with resected clinical stage I non-small cell lung cancer and complete mediastinal lymphadenectomy were retrospectively analyzed for variables associated with negative N2 nodal metastasis (2008-2015). Overall and recurrence-free survival in patients after complete or limited mediastinal lymphadenectomy were assessed via Kaplan-Meier survival analysis and log-rank testing. The accuracy of frozen section diagnosis for predicting final pathology was retrospectively assessed in 126 randomly selected patients after the surgery. RESULTS: Multivariable analysis revealed that tumor size ≤2 cm, negative pN1, lymphovascular invasion, and lepidic adenocarcinoma were associated with negative mediastinal nodal metastasis. Notably, none of the patients with histology of adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic pattern-predominant adenocarcinoma on final pathology had pN2 disease, and the 5-year overall and recurrence free-survival of these patients (99.3% and 99.3%, respectively) was not different from those after limited mediastinal lymphadenectomy (98.7% and 100%, P = .582 and .511, respectively). If these subtypes were classified together as the low-risk group, the concordance rate between frozen section and final pathology diagnosis was 88.9% in the retrospective test cohort. CONCLUSIONS: Tumor histology may predict negative mediastinal metastasis in patients with early-stage lung cancer. Future prospective studies are merited to validate the feasibility of using frozen section to select patients for limited mediastinal lymphadenectomy.

Evaluation of the new TNM-staging system for thymic malignancies: impact on indication and survival.

BACKGROUND: The objective of this study is the evaluation of the Masaoka-Koga and the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system on clinical implementation and prognosis of thymic malignancies. METHODS: A retrospective study of 76 patients who underwent surgery between January 2005 and December 2015 for thymoma. Kaplan-Meier survival analysis was used to determine overall and recurrence-free survival rates. RESULTS: Indication for surgery was primary mediastinal tumor (n = 55), pleural manifestation (n = 17), or mediastinal recurrence (n = 4) after surgery for thymoma. Early Masaoka-Koga stages I (n = 9) and II (n = 14) shifted to the new stage I (n = 23). Advanced stages III (Masaoka-Koga: n = 20; ITMIG/IASLC: n = 17) and IV (Masaoka-Koga: n = 33; ITMIG/IASLC: n = 35) remained nearly similar and were associated with higher levels of WHO stages. Within each staging system, the survival curves differed significantly with the best 5-year survival in early stages I and II (91%). Survival for stage IV (70 to 77%) was significantly better compared to stage III (49 to 54%). Early stages had a significant longer recurrence-free survival (86 to 90%) than advanced stages III and IV (55 to 56%). CONCLUSIONS: The proportion of patients with IASLC/ITMIG stage I increased remarkably, whereas the distribution in advanced stages III and IV was nearly similar. The new TNM-staging system presents a clinically useful and applicable system, which can be used for indication, stage-adapted therapy, and prediction of prognosis for overall and recurrence-free survival.