The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposals for the N and the M Components for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: Stage classification is an important underpinning of management in patients with cancer and rests on a combination of three components-T for tumor extent, N for nodal involvement, and M for distant metastases. This article details the revision of the N and the M components of thymic epithelial tumors for the ninth edition of the TNM classification of malignant tumors proposed by the Thymic Domain of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee. METHODS: The N and M components of the eighth edition staging system were verified by a large international collaborative data source through a data-driven analysis. A total of 9147 cases were included for analysis, including 7662 thymomas, 1345 thymic carcinomas, and 140 neuroendocrine thymic tumors. RESULTS: Lymph node involvement rates were 1.5% in thymomas and 17.6% and 27.7% in thymic carcinomas and neuroendocrine thymic tumors, respectively. Rates of lymph node metastasis were increasingly higher in tumors with higher T stage and higher-grade histologic type. Survival analysis validated the differences in the N and M categories proposed in the eighth edition staging system. Good discrimination in overall survival was detected among pathologic (p)N and pM categories in patients with thymoma and thymic carcinoma. CONCLUSIONS: No changes are proposed from the eighth edition for the N and M components. The proposed stage classification will provide a useful tool for management of the disease among the global thymic community.

Reply to Perrella et al. Coming Back to the Basics. Comment on "Cangir et al. A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors. Diagnostics 2022, 12, 416".

We thank to Dr. Perrella and and his fellow authors for your kind letter and thoughtful comments [...].

Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group.

Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: A Re-Assessment of the International Thymic Malignancy Interest Group/International Association for the Study of Lung Cancer Lymph Node Map for Thymic Epithelial Tumors for the Forthcoming Ninth Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: A lymph node map is the pillar on which accurate assignment and documentation of nodal classification stands. The International Thymic Malignancy Interest Group created the first map for thymic epithelial malignancies in conjunction with the eighth edition of the TNM classification, representing the first official TNM classification of thymic epithelial malignancies. The map was based on clinical experience and published studies, but it was largely empirical because of limited available data. Dissemination of the map and implementation of a standard thymic stage classification across the world in 2017 have provided more consistent and granular data. METHODS: More than twice as many cases of node involvement are available for analysis in the current database compared with that of the eighth edition database, allowing validation of many aspects of the eighth edition map. This article details the process and considerations for refinement of the thymic map for the ninth TNM used by the Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer. The committee evaluated a large international collaborative data set, published anatomical and clinical studies pertaining to lymph node spread from thymic epithelial tumors, in conjunction with the analysis underlying refinements of the TNM components for the ninth edition TNM classification. RESULTS: The node map boundaries of the N1 and N2 categories remain unchanged. Visual clarifications have been added to the nomenclature of nodal stations within these regions. CONCLUSIONS: On the basis of the recommendation to keep the N component unchanged for the ninth edition TNM classification, the lymph node map remains unchanged as well; however, clarifications have been added to facilitate clinical use.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposal for a Stage Classification for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, composed of multispecialty international experts, was charged to develop proposals for the ninth edition. This article outlines the proposed definitions for the T, the N, and the M components and their combination into stage groups. METHODS: A large central database of 11,347 patients with thymic epithelial tumors was assembled thanks to the contribution of the major thymic organizations worldwide and analyses were carried out for the T, the N, and the M components and the stage groups. Overall survival was the outcome measure for patients with completely and incompletely resected tumors, and recurrence for those with complete resection. When the number of patients was sufficient, analyses were performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors. RESULTS: Tumor size is included in the T1 category as T1a (≤5cm) and T1b (>5 cm); the mediastinal pleura is dropped as a T descriptor; invasion of the lung or phrenic nerve is reclassified as T2 (instead of T3). No changes are proposed for the N and the M components from the eighth edition. The stage groups remain the same. CONCLUSIONS: The proposed changes for the ninth edition of the TNM classification set the stage for further progress in the future for these rare tumors.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: An Overview of the Central Database Informing Revision of the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: In 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group for the eighth edition of the American Joint Commission on Cancer and the Union for International Cancer Control stage classification system. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer received the mandate to make proposals for the ninth edition of the TNM stage classification. METHODS: A central thymic database was collected by the Cancer Research And Biostatistics with the contribution of the major thymic associations in the world. RESULTS: A total of 11,347 patients were collected. Submitting organizations were the following: Japanese Association for Research in the Thymus, European Society of Thoracic Surgeons, Chinese Alliance for Research in Thymoma, Korean Association for Research in the Thymus, International Thymic Malignancy Interest Group, and Réseau tumeurs THYMiques et Cancer. Additional contributions came from centers in the United States, United Kingdom, Turkey, Australia, Spain, and Italy. A total of 9147 cases were eligible for analysis. Eligible cases for analysis came from Asia and Australia (5628 cases, 61.5%), Europe (3113 cases, 34.0%), and North America (406 cases, 4.4%). CONCLUSIONS: This report provides an overview of the database that has informed the proposals for the updated T, N, and M components and the stage groups for the ninth TNM of malignant tumors.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain of the Staging and Prognostics Factor Committee of the International Association for the Study of Lung Cancer developed a new database with the purpose to make proposals for the ninth edition stage classification system. This article outlines the proposed definitions for the T categories for the ninth edition TNM stage classification of thymic malignancies. METHODS: A worldwide collective database of 11,347 patients with thymic epithelial tumors was assembled. Analysis was performed on 9147 patients with available survival data. Overall survival, freedom-from-recurrence, and cumulative incidence of recurrence were used as outcome measures. Analysis was performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors. RESULTS: Proposals for the T categories include the following: T1 category is divided into T1a (≤5 cm) and T1b (>5 cm), irrespective of mediastinal pleura invasion; T2 includes direct invasion of the pericardium, lung, or phrenic nerve; T3 denotes direct invasion of the brachiocephalic vein, superior vena cava, chest wall, or extrapericardial pulmonary arteries and veins; and T4 category remains the same as in the eighth edition classification, involving direct invasion of the aorta and arch vessels, intrapericardial pulmonary arteries and veins, myocardium, trachea, or esophagus. CONCLUSIONS: The proposed T categories for the ninth edition of the TNM classification provide good discrimination in outcome for the T component of the TNM-based stage system of thymic epithelial tumors.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Unresolved Issues to be Addressed for the Next Ninth Edition of the TNM Classification of Malignant Tumors.

Thymic epithelial tumors are presently staged using a consistent TNM classification developed by the International Association for the Study of Lung Cancer (IASLC) and approved by the Union for International Cancer Control and the American Joint Committee on Cancer. The stage classification is incorporated in the eight edition of the TNM classification of thoracic malignancies. The IASLC Staging and Prognostic Factors Committee (SPFC)-Thymic Domain (TD) is in charge for the next (ninth) edition expected in 2024. The present article represents the midterm report of the SPFC-TD: in particular, it describes the unresolved issues identified by the group in the current stage classification which are worth being addressed and discussed for the ninth edition of the TNM classification on the basis of the available data collected in the central thymic database which will be managed and analyzed by Cancer Research And Biostatistics. These issues are grouped into issues of general importance and those specifically related to T, N, and M categories. Each issue is described in reference to the most recent reports on the subject, and the priority assigned by the IASLC SPFC-TD for the discussion of the ninth edition is provided.

A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors.

Radiomics is a new image processing technology developed in recent years. In this study, CT radiomic features are evaluated to differentiate pulmonary hamartomas (PHs) from pulmonary carcinoid tumors (PCTs). A total of 138 patients (78 PCTs and 60 PHs) were evaluated. The Radcloud platform (Huiying Medical Technology Co., Ltd., Beijing, China) was used for managing the data, clinical data, and subsequent radiomics analysis. Two hand-crafted radiomics models are prepared in this study: the first model includes the data regarding all of the patients to differentiate between the groups; the second model includes 78 PCTs and 38 PHs without signs of fat tissue. The separation of the training and validation datasets was performed randomly using an (8:2) ratio and 620 random seeds. The results revealed that the MLP method (RF) was best for PH (AUC = 0.999) and PCT (AUC = 0.999) for the first model (AUC = 0.836), and PC (AUC = 0.836) in the test set for the second model. Radiomics tumor features derived from CT images are useful to differentiate the carcinoid tumors from hamartomas with high accuracy. Radiomics features may be used to differentiate PHs from PCTs with high levels of accuracy, even without the presence of fat on the CT. Advances in knowledge: CT-based radiomic holds great promise for a more accurate preoperative diagnosis of solitary pulmonary nodules (SPNs).

A New "Ice Globe" Method for Dilating Leaking Cervical Esophageal Strictures.

An esophageal stricture may develop during healing of a large esophageal perforation. When such a stricture occurs, mechanical dilatation is the treatment of choice. As in our case, if a cervical esophageal stricture and leakage are present together, the treatment becomes even more challenging. As a new treatment method, we made spherical ice globes of various sizes using molds created with a 3D printer to treat the esophageal stricture and prevent its progression. This method can be used to safely treat leaking cervical esophageal strictures. A step-by-step of how to do it has been described.

Different View on Tumor Size Dilemma in Tumor-Node-Metastasis Staging System for Thymoma.

BACKGROUND: Although tumor size is included in the definition of T descriptor in the tumor-node-metastasis (TNM) classification of many solid tumors, it is not considered for thymomas. This study aimed to assess the relationship of tumor diameters (the largest tumor diameter [LTD] and the mean tumor diameter [MTD]) with survival in thymoma patients undergoing surgical resection in a single center. METHODS: The study included 127 thymoma patients (age, 49.2 ± 15.2 years; 65 males), who were evaluated based on pathological tumor sizes according to the LTD and MTD ([largest diameter + shortest diameter] / 2) and divided into three subgroups for each parameter as: patients with an LTD of ≤5 cm, 5.1 to 10 cm, and >10 cm and patients with an MTD of ≤5, 5.1 to 10, and >10 cm. RESULTS: In thymoma patients, survival significantly differed according to the presence of myasthenia gravis (p = 0.018), resection status (R0 or R1; p = 0.001), T status (p = 0.015), and the Masaoka-Koga stage (p = 0.003). In the LTD subgroups, the overall survival of those with R0 resection was lower in those with an LTD of 5.1 to 10 cm than in those with an LTD of ≤5 cm (p = 0.051) and significantly lower in those with an MTD of 5.1 to 10 cm than in those with an MTD of ≤5 cm (p = 0.027). In the MTD subgroups, survival decreased as the tumor size increased. CONCLUSION: Both smaller tumor size and complete resection are associated with better survival in thymoma patients. Therefore, the largest or the mean tumor size might be considered as a criterion in the TNM staging for thymoma.

The International Association for the Study of Lung Cancer Thymic Tumors Staging Project: The Impact of the Eighth Edition of the Union for International Cancer Control and American Joint Committee on Cancer TNM Stage Classification of Thymic Tumors.

OBJECTIVES: The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee-Thymic Domain conducted a web-based cross-sectional survey to assess the acceptance of the TNM thymic staging system in the thoracic community. METHODS: A 50-item, web-based questionnaire was circulated among the members of the major thymic organizations worldwide from September to December 2018. The survey consisted of six sections (general information; overall perception of the TNM system; pretreatment staging; T category; N category; and perioperative treatments). RESULTS: In total, 217 responses were collected from 37 countries in four continents. The TNM classification was considered useful by 78% of the responders (N = 169); the Masaoka-Koga staging system was being used by 87% of the responders (N = 189). With regard to the T category, most responders (mostly surgeons) felt that the capsular and mediastinal pleural involvements should be considered separate T categories. As for the N category, 48% of the responders (N = 105) used the International Thymic Malignancies Interest Group/International Association for the Study of Lung Cancer thymic nodal map, and lymph node dissection (N1/N2) was performed for 50%/21% thymomas and 66%/41% thymic carcinomas. While analyzing the results by the three continents (Europe, Asia, and Americas), responders in Asia were found to report the largest use of the TNM system, the greatest attention to the N category, and the best participation in international thymic databases. CONCLUSIONS: The survey indicates that the Union for International Cancer Control/American Joint Committee on Cancer TNM stage classification of thymic tumors is gaining acceptance among the scientific community. The present results will guide the work of the Staging and Prognostic Factors Committee-Thymic Domain for the revision of the ninth edition of the TNM stage classification of thymic tumors.

Diffuse Neuroendocrine Cell Hyperplasia: Report of Two Cases.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder characterised by a proliferation of neuroendocrine cells within the lung. It is believed that a minority of the patients with DIPNECH can develop carcinoid tumors. Here, we report two new cases of DIPNECH with coexisting carcinoid tumors.

Association of cadmium but not arsenic levels in lung cancer tumor tissue with smoking, histopathological type and stage.

BACKGROUND: To evaluate association of lung cancer with arsenic and cadmium levels measured in tumor tissue. MATERIALS AND METHODS: Ninety-five patients with lung cancer tumor tissue obtained surgically were included in this study. Arsenic and cadmium levels were measured and levels of metals were compared among types of lung cancer and with reference to patient data. RESULTS: The histopathologic diagnoses of the 95 cases were SCC, 49, adenocarcinoma, 28, large cell, 11 and SCLC, 1. Mean tumor arsenic and cadmium levels were 149.3±129.1µg/kg and 276.3±219.3µg/kg, respectively. Cadmium levels were significantly associated with smoking (p=0.02), histopathologic type (p=0.005), and TNM staging (r=0.325; p=0.001), although arsenic was not related to any parameter (p>0.05). There was no relation between metal levels and mortality (p>0.05). CONCLUSIONS: We found a significant association between tumor cadmium levels of patients with lung cancer and smoking, histopathologic type and staging, although there was no relation with arsenic levels.

The outcome of bifocal surgical resection in non-small cell lung cancer with synchronous brain metastases: results of a single center retrospective study.

BACKGROUND: The reported median survival in patients with non-small cell lung cancer (NSCLC) metastases to the brain varies from 3 to 12 months with combined treatment modalities. Bifocal surgical resection of synchronous brain metastasis and primary NSCLC has not been reported widely, and there have been only a small number of articles published in the literature. The aim of this retrospective study was to evaluate the prognostic factors among patients undergoing bifocal surgical resection. MATERIALS AND METHODS: We retrospectively analyzed 28 patients who had a solitary metastatic brain lesion at the time of diagnosis, and underwent synchronous surgical resection of the brain metastasis and primary lung tumor. Survival time was measured in all the patients from the date of craniotomy until death or the most recent date of follow-up for those still surviving. RESULTS: Mean age was 53 years. The mean length of follow-up was 23.6 (4-69) months. The overall survival rates were 79, 42, and 8% at the 1st, 2nd, and 5th years, respectively. The median length of survival was 24 ± 3.8 months. The median survival was found to be statistically significantly lower for the stage T3 tumors when compared with both stage T1 and T2 tumors (p = 0.037). CONCLUSION: NSCLC patients with resectable solitary cranial metastasis, low locoregional stage (stages IA, IB, IIA) in which T3 status is counted out, with no mediastinal lymph node involvement or any other extrathoracic spread will mostly benefit from consecutive complete resection of both tumors and are supposed to have a better survival.

Association of ABO blood group and risk of lung cancer in a multicenter study in Turkey.

BACKGROUND: The ABO blood groups and Rh factor may affect the risk of lung cancer. MATERIALS AND METHODS: We analyzed 2,044 lung cancer patients with serologically confirmed ABO/Rh blood group. A group of 3,022,883 healthy blood donors of Turkish Red Crescent was identified as a control group. We compared the distributions of ABO/Rh blood group between them. RESULTS: The median age was 62 years (range: 17-90). There was a clear male predominance (84% vs. 16%). Overall distributions of ABO blood groups were significantly different between patients and controls (p=0.01). There were also significant differences between patients and controls with respect to Rh positive vs. Rh negative (p=0.04) and O vs. non-O (p=0.002). There were no statistically significant differences of blood groups with respect to sex, age, or histology. CONCLUSIONS: In the study population, ABO blood types were associated with the lung cancer. Having non-O blood type and Rh-negative feature increased the risk of lung cancer. However, further prospective studies are necessary to define the mechanisms by which ABO blood type may influence the lung cancer risk.

Clinicopathological features of patients with malignant mesothelioma in a multicenter, case-control study: no role for ABO-Rh blood groups.

BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. Previous studies have observed an association between ABO blood groups and risk of certain malignancies, including pancreatic and gastric cancer; however, no information on any association with MM risk is available. The aim of this study was to investigate possible associations amoong MM clinicopathological features and ABO blood groups and Rh factor. MATERIALS AND METHODS: In 252 patients with MM, the ABO blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with various clinicopathological features were also evaluated in the patient group. RESULTS: The median age was 55 (range: 27-86) and 61.5% of patients were male. While 82.8% of patients had a history of exposure to asbestos, 60.7% of patients had a smoking history. Epithelioid (65.1%) was the most common histology and 18.7% of patients had mixed histology. Overall, the ABO blood group distribution of the 252 patients with MM was comparable with the general population. The median overall survival (OS) was 14 months (95% confidence interval, 11.3-16.6 months). The median OS for A, B, AB, and O were 11, 15, 16, and 15 months respectively (p=0.396). First line chemotherapy was administered to 118 patients. The median OS of patients on pemetrexed or gemcitabine was longer than patient who was not administered chemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9-11.0); p<0.001]. CONCLUSIONS: The results of this study suggest that patients with MM can benefit from treatment with pemetrexed or gemcitabine in combination with cisplatin. We did not observe a statistically significant association between ABO blood group and risk of MM.

Parenchyma-preserving surgery in the management of pulmonary hydatid cysts.

Pulmonary hydatid cysts remain a significant health problem in endemic regions like Turkey. Here, we present our surgical experience in patients with pulmonary hydatid cysts. Between January 1985 and January 2001, 1118 operations were performed in 1032 patients (528 males, 504 females; mean age 32.7 years; range 1-87 years) with pulmonary hydatid cysts in our department. Posterolateral thoracotomy was performed in 1015 (98.3%), two-stage thoracotomy in 34 (3.3%), and median sternotomy in 17 (1.7%) patients. We preferred conservative surgical procedures. As a surgical procedure, cystotomy and capitonnage was performed in 626 (56%), cystotomy alone in 368 (33%), wedge resection in 81 (7%), enucleation in 29 (3%), and decortication in 11 (1%) patients. None of our patients were treated with anatomic resection. During surgery, 949 patients (92%) had unruptured and 83 patients (8%) had ruptured hydatid cyst. The morbidity ratio was 6.7%. Major complications were wound infection (2.3%), prolonged air leak (1.9%), atelectasis (1.2%), pleural effusion (0.8%), postoperative hemothorax (0.6%), and empyema (0.3%). Two patients (0.2%) died within the first month postoperatively. Mean follow-up was 31.2 months. Recurrence was detected in only 35 patients (3.3%). Treatment of pulmonary hydatid cyst is primarily surgical. Medical treatment is indicated for recurrent and multiple hydatid cysts postoperatively. Cystotomy alone, or cystotomy and capitonnage, as parenchyma-preserving surgery, is preferred. Radical surgery including pneumonectomy, lobectomy, and segmentectomy should be avoided.

Management of recurrent malignant pleural effusion with chemical pleurodesis.

PURPOSE: Malignant pleural effusion is a common complication of primary and metastatic pleural malignancies. It is usually managed by drainage and pleurodesis, but there is no consensus as to the best method of pleurodesis. We compared the effectiveness, side effects, and cost of different chemical pleurodesis agents used in patients with malignant pleural effusion. METHODS: Between January 1990 and December 2001, 108 patients with malignant pleural effusion underwent chemical pleurodesis in our department. Thoracoscopy was performed in 64 patients (59%), a minithoracotomy in 18 (17%), tube thoracostomy in 11 (10%), and a small-bore catheter was inserted in 15 (14%). Talc was used in 68 (63%) patients, tetracycline in 26 (24%), and bleomycin in 14 (13%). Talc was instilled by insufflation during surgery after drainage, whereas tetracycline and bleomycin were instilled via tube or catheter for pleural analgesia. RESULTS: Talc resulted in significantly earlier tube and catheter removal, after an average 4.1 days versus 5.1 days after tetracyline, and 6.3 days after bleomycin (P = 0.026, P = 0.001, respectively). A significantly lower reaccumulation ratio in 90 days was achieved by the talc group, with nine (13.2%) patients, representing an 86.8% success rate, than in the tetracyline and bleomycin groups, with seven (26.7%) and five (35.7%) patients, respectively, representing 73.8% and 64.3% success rates (P = 0.04). CONCLUSIONS: Talc resulted in the earliest expansion, minimal drainage, and the earliest tube and catheter removal.