Stage Classification System Research Articles

Evaluation of the presence and extension valvular-related cardiac damage in patients with moderate aortic stenosis and its impact on outcomes

Abstract Introduction and objective Echocardiographic measurements form the basis for diagnosing and determining the indication for therapy in aortic stenosis (AS). These measurements may vary depending on different patient-related and operator-related conditions. Recently, staging cardiac damage has emerged as a prognostic tool in asymptomatic and moderate to severe AS. We aim to evaluate the presence and severity of cardiac damage (1,2), and its impact on outcomes, in patients with a first diagnosis of moderate and severe AS. Methods A total of 119 patients undergoing transcatheter aortic valve replacement (TAVR) from November 2019 to January 2021 were included in a single-center retrospective registry. In each patient, the first echocardiogram establishing the diagnosis of moderate and severe AS was analysed. Results 119 patients with a mean age of 82.8±5.33 years (51% men) were included. At the first echo study with the diagnosis of moderate AS, mean pressure gradient was 23±9 mmHg, maximum pressure gradient was 42±15 mmHg, and mean aortic valve area was 1.13±0.41 cm2 (0.64±0.23 cm2/m2). Regarding cardiac damage, mean left ventricular ejection fraction was 65.4±10.4%, mean longitudinal global strain was -18.5±5.4%, and mean left atrial volume index was 41.6±31.2 mL/m2. 16% of patients have significant mitral regurgitation, and 10% right ventricular dysfunction. The mean progression time between moderate and severe diagnoses was 36 (2.4-175.2) months. Figure 1 shows the distribution of patients in different staging classification systems (1,2) at the time of diagnosis of moderate and severe AS. According to one of these staging classifications (1), 75.7% of patients had left-sided cardiac damage (Stages 1 and 2) and 16.8% had right-sided damage (Stages 3 and 4), without differences compared to the same patients when the stenosis became severe (p=0.194). On the contrary, following the most recent second classification (2), 63% had no significant cardiac damage (Stage 0), 31.1% of patients had left-sided cardiac damage (Stages 1 and 2) and 5.9% had right-sided damage (Stage 3), and this system showed better ability to discriminate between moderate and severe AS related-damage (p=0.002). The area under the ROC curve for one-year mortality after TAVR for the 2 staging systems applied at the moment of diagnosis of moderate and severe AS is presented in Figure 2. When used in moderate AS, it showed fair discrimination. However, the best model for predicting one-year mortality among those used, is the one used in the second classification (2) when the stenosis became severe. Conclusions AS-related cardiac damage may be present in early stages of AS and may help to guide the timing of intervention in selected patients. Staging classification of cardiac damage AUROC curve for one-year mortality

Automatic TNM staging of colorectal cancer radiology reports using pre-trained language models

Background and Objective:Colorectal cancer is one of the major causes of cancer death worldwide. Essential for prognosis and treatment planning, TNM staging offers critical insights into the advancement of colorectal cancer. However, manual TNM staging from colon magnetic resonance imaging (MRI) is a laborious and error prone process. This study introduces an automated text classification system for TNM staging of colon MRI images in Spanish. Methods:A dataset of 1319 Spanish colon MRI reports was collected and manually labeled with TNM staging. In order to automate the task of TNM staging, a multimodal system was proposed. The system is based on RoBERTa language model pre-trained on a combination of biomedical and clinical Spanish language corpora and uses Natural Language Processing (NLP) techniques to extract relevant categorical and numerical features from MRI reports. Results:The performance of the system was evaluated using different metrics and the results obtained are very promising: the best performance among the proposed systems reached 0.7464, 0.8792 and 0.6776 of macro F1-score for T, N and M respectively. Conclusions:This study demonstrates the feasibility of using a language model for automatic TNM staging based on Spanish clinical reports of colorectal cancer patients. The proposed system can be a useful tool to improve the efficiency and accuracy of colorectal cancer diagnosis.

Comparison of Alternative Mayo Staging Classification Systems USED in LIGHT-Chain Amyloidosis

Comparison of Alternative Mayo Staging Classification Systems USED in LIGHT-Chain Amyloidosis

Development of Novel Peripheral Blood Count-Based Prognostic Index for Multiple Myeloma

In multiple myeloma (MM), clonal plasma cells evade immune surveillance and proliferate within an inflammatory bone marrow microenvironment. During pathogenesis, monocyte-derived tumor-associated macrophages help myeloma cells to avoid apoptosis; effector T cell lymphocytes undergo senescence to enable preferential upregulation of their immunosuppressive regulatory T cell counterparts; and myeloma cells interact with hematopoietic stem cells to inhibit downstream megakaryocyte differentiation into platelets.1 Our prior research has suggested a prognostic role for the absolute monocyte count (AMC), absolute lymphocyte count (ALC), and platelet count as biomarkers. We have shown that abnormal AMC and decreased ALC and platelet count are associated with decreased overall survival (OS) among patients with MM at diagnosis and follow-up. Based on the easy accessibility of these peripheral blood markers and need for dynamic prognostication among patients with MM undergoing novel therapies, we created a categorical peripheral blood-based prognostic index for MM incorporating AMC, ALC and platelet count. We retrospectively evaluated this index in 10790 patients diagnosed with MM between 2000 and 2019 at Veterans Administration hospitals using cell counts obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into 3 levels based on a logarithmic risk score, where those with the lowest counts across all cell lines (AMC, ALC, and platelet count) were in level III and those with counts approaching normalcy were in level I. At diagnosis, 8% of patients were in level III and had the highest risk of death (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.85-2.24; P < .01) compared to those in levels I (HR 1.15; 95% CI, 1.08-1.23; P < .01) and II (HR 1.37; 95% CI, 1.28-1.46; P < .01). Moreover, the risk of inferior OS associated with level III status persisted during treatment and follow-up and existed independently of other known risk stratification tools (including Charlson comorbidity index, lactate dehydrogenase, International Staging System classification). With further validation, our findings support the use of our novel prognostic index, which potentially reflects the underlying tumor microenvironment, as an available tool for risk stratification during the MM disease course.

Prognostic Value of Adding Blood and Lymphatic Vessel Invasion to the 8th Classification of TNM in Lung Cancer in Stages I and II

ObjectivesExpanding TNM staging system for lung cancer with the addition of new prognostic factors could enhance patient stratification and survival prediction. The goal of this study is to assess if TNM prognosis capacity could be improved by incorporating other pathological characteristics of surgical specimen. MethodsWe retrospectively reviewed lung cancer resections, stages I–II, performed between January 1st 2010 and May 1st 2019. We collected clinical variables and pathological characteristics, including vascular, lymphovascular and perineural invasion, STAS, necrosis and stromal features. Mortality and recurrence-free survival were assessed with univariable and multivariable Cox analysis. We explored how these factors would modify the TNM Harrel's index. Results629 tumors were analyzed. Median overall survival was 53.9 months. Median recurrence-free survival was 47.6 months. Specific survival at 3, 5 and 10 years was 90, 83 and 74%. Recurrence-free survival at 3, 5 and 10 years was 76, 70 and 65%.The multivariable analysis showed that overall survival was significantly related to TNM classification (p<0.0002), vascular infiltration (HR 1.93, CI 1.42–2.64, p<0.0001), lymphovascular invasion (HR 1.88, CI 1.30–2.71, p<0.0015) and necrosis (HR 1.74, CI 1.24–2.45, p<0.0025). Harrell's index for TNM was 0.6139. Adding vascular, lymphovascular invasion and necrosis, it increased up to 0.6531.The multivariable analysis showed that specific survival was significantly related to TNM classification (p<0.001), vascular infiltration (HR 2.23, CI 1.44–3.46, p<0.001) and lymphovascular invasion (HR 1.85, CI 1.09–3.13, p<0.021). Harrell's index for TNM was 0.6645. Adding vascular and lymphovascular invasion, it increased up to 0.7103. Recurrence-free survival was related to TNM, vascular infiltration (HR 1.48, CI 1.05–2.09, p<0.023) and lymphovascular invasion (HR 2.40, CI 1.64–3.50, p<0.001). Harrell's index for TNM was 0.6264. Adding vascular and lymphovascular invasion, it increased up to 0.6794. ConclusionsIncluding vascular and angiolymphatic invasion in the staging system classification could better stratify patients at risk of recurrence and tumor-related death.

Primary and residual cardiometabolic risk factors among young adults in a Russian city

BackgroundCardiovascular diseases are a leading cause of mortality and a significant contributor to temporary and permanent disabilities worldwide. This study aimed to investigate the burden of primary and residual cardiometabolic risk factors in a sample of young adults in the Russian city of Kazan.MethodsThis case-control study used the Cardiometabolic Disease Staging (CMDS) classification system, which has been validated in several countries. The study included 191 individuals aged 25–44 years who met the inclusion criteria but did not meet any exclusion criteria. Data collection involved a patient card with questions from the World Health Organization’s STEPS instrument, face-to-face patient interviews, and a physical examination. Anthropometric assessments included height, weight, and waist circumference measurements. Body composition was evaluated using bioelectrical impedance measurements. Patients also underwent in-depth laboratory biochemical analyses.ResultsThe study cohort was comprised of 97 females (50.8%) and 94 males (49.2%). The median age of participants was 35.00 years [IQR: 30.00–39.00]. The study cohort showed an increase in all anthropometric parameters, with abdominal obesity and overweight reaching 100% in the CMDS 3. Apart from atherogenic lipids and raised blood pressure, other risk factors that precipitate residual risk and were not part of CMDS, such as insulin levels, insulin resistance, leptin values, and hyperuricemia, increased as CMDS levels increased.ConclusionsThe prevalence of cardiometabolic risk factors was high in young adults in Kazan. This study highlights the need for the early identification and management of cardiometabolic risk factors in young adults to prevent the development of cardiovascular diseases later in life.

Nomogram-based prognostic stratification for patients with large hepatocellular carcinoma: a population study of SEER database and a Chinese cohort.

Large hepatocellular carcinoma (HCC) with a diameter ≥5 cm remains a significant challenge of poor survival and raises the need for prognosis evaluation. This study aimed to develop and validate a nomogram-based prognostic stratification to assess overall survival (OS) of patients with large HCC. Data of patients with large HCC were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database and our hospital, and were divided into the training cohort, internal validation cohort and external validation cohort. Cox analysis was performed to identify independent prognostic factors for the construction of nomogram in training cohort. The predictive ability of the nomogram was validated compared with the tumor node metastasis (TNM) classification staging system. Furthermore, prognostic stratification system based on nomogram was developed. Independent prognostic factors including histological grade, T stage, M stage, alpha fetoprotein (AFP), fibrosis score and surgery, were incorporated to construct nomogram. C-indexes of nomogram were 0.730, 0.726 and 0.724 in the training, internal and external validation cohorts, respectively. Importantly, nomogram harbored a superior discrimination and clinical benefit than the TNM staging system. Nomogram-based prognostic stratification divided patients into three groups: 345-414 (low-risk group), 415-460 (medium-risk group) and 461-513 (high-risk group). As shown in Kaplan-Meier curves, there were significant differences in OS among low-, medium- and high-risk groups (P<0.01). Nomogram showed a superior prognostic predictive ability compared with the TNM staging system. The prognostic stratification serves as a valuable tool to assist clinicians on the selection of optimal treatment method and follow-up plan, particularly for the high-risk population.

Establishment of a clinical model based on vessels encapsulating tumour clusters that could efficiently predict recurrence of patients with hepatocellular carcinoma after curative hepatectomy

According to previous studies, vessels encapsulating tumour clusters (VETC) could promote metastasis of hepatocellular carcinoma (HCC) in a manner independent from epithelial–mesenchymal transition (EMT). However, the prognostic significance of VETC among patients undergoing curative hepatectomy has not been fully explored. This study was performed to assess the prognostic significance of VETC among patients undergoing curative hepatectomy. A total of 81 patients undergoing curative hepatectomy were included in this study. A predictive model based on VETC was established. Then this predictive model based on VETC was compared with the American Joint Committee on Cancer Tumor Nodal Metastasis (AJCC TNM) stage and Barcelona Clinic Liver Cancer (BCLC) system. It was revealed by multivariate Cox regression analysis that a high neutrophil-to-lymphocyte ratio (NLR) [p = 0.013, hazard ratio (HR) = 6.175, 95% confidence interval (CI): 1.468–25.977], number of tumours (p ＜ 0.001, HR = 4.119, 95% CI: 1.886–8.995) and VETC positivity (p = 0.010, HR = 2.440, 95% CI: 1.235–4.821) were independent predictive factors for disease-free survival (DFS). Additionally, by Kaplan–Meier analysis, we revealed that VETC positivity was associated with worse DFS (p = 0.018). Then the clinical predictive model combining the NLR, the number of tumours, and VETC was compared with AJCC TNM stage and BCLC classification system by performing time-dependent receiver operating curve (td-ROC) analysis, revealing that the clinical predictive model was superior to AJCC TNM stage and BCLC system at different timepoints. Additionally, we demonstrated that the clinical model could well predict DFS by plotting calibration curves. VETC could be utilised as an efficient prognostic factor for HCC and the clinical predictive model combining the NLR, the number of tumours, and VETC was superior to AJCC TNM stage and BCLC system in predicting cancer recurrence.

The morphology of epiretinal membranes in SS-OCT and SS-OCT angiography and its impact on surgical outcomes

The aim of this review is to revisit the current state of knowledge regarding epiretinal membranes, explore current methods of medical diagnosis, and assess the impact of Swept-source OCT (SS-OCT) and SS-OCT angiography (SS-OCT A) on therapeutic procedures. Several attempts have been made to establish a staging classification system for this well-known retinal pathology, yet not all of them proved to be clinically useful. This work intends to improve understanding of the pathophysiology of the disease, selecting the most important symptoms to aid classification according to the stage of advancement and correct recognition of the appropriate moment of surgical intervention to achieve a better postoperative effect. This article demonstrates the benefits of using SS-OCT and SS-OCT A in the treatment of epiretinal membrane, describing the morphological changes of the retina that can be observed.

An enzyme-inspired specificity in deep learning model for sleep stage classification using multi-channel PSG signals input: Separating training approach and its performance on cross-dataset validation for generalizability

Numerous automatic sleep stage classification systems have been developed, but none have become effective assistive tools for sleep technicians due to issues with generalization. Four key factors hinder the generalization of these models are instruments, montage of recording, subject type, and scoring manual factors. This study aimed to develop a deep learning model that addresses generalization problems by integrating enzyme-inspired specificity and employing separating training approaches. Subject type and scoring manual factors were controlled, while the focus was on instruments and montage of recording factors. The proposed model consists of three sets of signal-specific models including EEG-, EOG-, and EMG-specific model. The EEG-specific models further include three sets of channel-specific models. All signal-specific and channel-specific models were established with data manipulation and weighted loss strategies, resulting in three sets of data manipulation models and class-specific models, respectively. These models were CNNs. Additionally, BiLSTM models were applied to EEG- and EOG-specific models to obtain temporal information. Finally, classification task for sleep stage was handled by ‘the-last-dense’ layer. The optimal sampling frequency for each physiological signal was identified and used during the training process. The proposed model was trained on MGH dataset and evaluated using both within dataset and cross-dataset. For MGH dataset, overall accuracy of 81.05 %, MF1 of 79.05 %, Kappa of 0.7408, and per-class F1-scores: W (84.98 %), N1 (58.06 %), N2 (84.82 %), N3 (79.20 %), and REM (88.17 %) can be achieved. Performances on cross-datasets are as follows: SHHS1 200 records reached 79.54 %, 70.56 %, and 0.7078; SHHS2 200 records achieved 76.77 %, 66.30 %, and 0.6632; Sleep-EDF 153 records gained 78.52 %, 72.13 %, and 0.7031; and BCI-MU (local dataset) 94 records achieved 83.57 %, 82.17 %, and 0.7769 for overall accuracy, MF1, and Kappa respectively. Additionally, the proposed model has approximately 9.3 M trainable parameters and takes around 26 s to process one PSG record. The results indicate that the proposed model demonstrates generalizability in sleep stage classification and shows potential as a feasibility tool for real-world applications. Additionally, enzyme-inspired specificity effectively addresses the challenges posed by varying montage of recording, while the identified optimal frequencies mitigate instrument-related issues.

Inter-observer reproducibility of the 2021 AAGL Endometriosis Classification.

Inter-observer agreement for the American Association of Gynecologic Laparoscopists (AAGL) 2021 Endometriosis Classification staging system has not been described. Its predecessor staging system, the revised American Society for Reproductive Medicine (rASRM), has historically demonstrated poor inter-observer agreement. We aimed to determine the inter-observer agreement performance of the AAGL 2021 Endometriosis Classification staging system, and compare this with the rASRM staging system. A database of 317 patients with coded surgical data was retrospectively analysed. Three independent observers allocated AAGL surgical stages (1-4), twice. Observers made their own interpretation of how to apply the tool in the first staging allocation. Consensus rules were then developed for a second staging allocation. First staging allocation: odds ratio (OR) (and 95% CI) for observer 1 to score higher than observer 2 was 8.08 (5.12-12.76). Observer 1 to score higher than observer 3 was 12.98 (7.99-21.11) and observer 2 to score higher than observer 3 was 1.61 (1.03-2.51). This represents poor agreement. Second staging allocation (after consensus): OR for observer 1 to score higher than observer 2 was 1.14 (0.64-2.03), observer 1 to score higher than observer 3 was 1.81 (0.99-3.28) and observer 2 to score higher than observer 3 was 1.59 (0.87-2.89). This represents good agreement. These findings suggest that in its current format the AAGL 2021 Endometriosis Classification staging system has poor inter-observer agreement, not superior to the rASRM staging system. However, performance improved when additional measures were taken to simplify and clarify areas of ambiguity in interpreting the staging system.

Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case-Control Study.

A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC. Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes. In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation. The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification.

Serum cholesterol level as a predictive biomarker for prognosis of Neuroblastoma

BackgroundNeuroblastoma (NB), a type of solid tumor in children, has a poor prognosis. Few blood biomarkers can accurately predict the prognosis, including recurrence and survival, in children with NB. In this study, we found that the serum total cholesterol (Tchol) level was associated with the prognosis of patients through a retrospective study.MethodsMultivariate Cox regression model was used to identify the independent risk factors in the children with NB. Kaplan–Meier method was used to analyze the correlation between the common biomarkers, including the serum Tchol level, and the prognosis of the patients. ROC curves were used to predict the accuracy of the International Neuroblastoma Staging System (INSS) stage and Children’s Oncology Group (COG) risk stratification after adding the serum Tchol level.ResultsCompared with the other patients, serum Tchol level was significantly increased in the relapsed and died patients (P < 0.05). Subsequently, serum Tchol level was found as an independent risk factor to affect the outcome of patients (P < 0.05). Finally, we added serum Tchol level into traditional stage and risk classification system to form the new INSS stage and COG risk classification system. It was found that the areas under the ROC curve (AUC) of recurrence-free survival in the new INSS stage and COG risk classification system were increased to 0.691 (95%CI: 0.535–0.847) and 0.748 (95%CI: 0.622–0.874), respectively. Moreover, the AUC areas of overall survival in the new INSS stage and COG risk classification system were increased to 0.722 (95%CI: 0.561–0.883) and 0.668 (95%CI: 0.496–0.819), respectively.ConclusionWe found that serum Tchol level, a clinical biomarker, is a risk factor for recurrence and death among the children with NB. The serum Tchol level could significantly increase the accuracy of the prediction for NB prognosis.

The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Expanded Database to Inform Revisions in the Ninth Edition of the TNM Classification of Pleural Mesothelioma

The International Association for the Study of Lung Cancer collaborated with the International Mesothelioma Interest Group to propose the first TNM stage classification system for diffuse pleural mesothelioma in 1995, accepted by the Union for International Cancer Control and the American Joint Committee on Cancer for the sixth and seventh edition stage classification manuals. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Mesothelioma Domain developed and analyzed an international registry of patients with pleural mesothelioma and updated TNM descriptors for the eighth edition of the stage classification system. To inform revisions for the forthcoming ninth edition of the TNM stage classification system, data submission was solicited for patients diagnosed between 2013 and 2022 with expanded data elements on the basis of the first project’s exploratory analyses, including pleural thickness measurements, updated surgical nomenclature, and molecular markers. The resulting database consisted of a total of 3598 analyzable cases from Europe, Australia, Asia, North America, and South America, with a median age of 71 years (range: 18–99 y), 2775 (77.1%) of whom were men. With only 1310 patients (36.4%) undergoing curative-intent operations, this iteration of the database includes far more patients treated nonsurgically compared with prior. Four separate manuscripts on T, N, M, and stage groupings submitted to this journal will summarize analyses of these data and will serve collectively as the primary source of the proposed changes to the upcoming ninth edition of the pleural mesothelioma stage classification system.

#307 : Establishment of an Early Blastocyst Stage Classification System and Its Implications for Clinical Pregnancy and Live Birth Outcomes

Background and Aims: Sub-optimal embryo development on day 5 often leads to the transfer of an early blastocyst (EB) stage embryo, especially for women &gt;38 years of age. Yet there are few studies of reported outcomes, nor an industry-wide EB classification system to identify EBs for fresh transfer with the best outcomes. Hence, this study aimed to determine clinical outcomes and whether an EB-stage classification system could be beneficial. Method: A retrospective cohort study analysed 537 cycles undertaken between 2019 and 2022 at two large clinics, in which patients had on day-5 a single fresh EB stage embryo transferred. A novel EB classification system was developed and applied to determine clinical pregnancy rate (CPR) and live birth rate (LBR) outcomes, as well as the effects of maternal age ([Formula: see text] or &gt; 38 years of age). EB stage embryos were classified into four categories based on day-5 morphological features from highest (EB-A) to lowest (EB-D) quality. Data were analysed using Fisher’s exact and non-parametric analyses. Results: Transfer of a fresh EB embryo resulted in a 20.1% CPR and 14.7% LBR. Classification of EBs into four distinct sub-groups identified differences in CPR and LBR (LBR: EB-A 23.4%; EB-B 10.3%; EB-C 12.9%; EB-D 7.6%). Similar CPR and LBR trends were determined for patients [Formula: see text] 38 years of age (LBR:26.7%,14.2%,19.0%, 2.1%) and &gt;38 years of age (LBR:17.5%,4.3%,5.8%,2.7%), with an overall lower LBR for women &gt;38 years of age (8.0%) compared with [Formula: see text] 38 years old (19.5%; P&lt;0.05). Conclusion: Whilst pregnancies and live births can result from an EB transfer, LBR varied by &gt;15% between different morphological classifications. If required, transfer of a late-stage EB results in a higher LBR, especially for women [Formula: see text] 38 years of age. Use of an EB classification system would benefit clinical decisions around when to transfer an EB stage embryo.

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

IntroductionIn 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. MethodsA central thymic database was collected by the Cancer Research And Biostatistics with the contribution of the major thymic associations in the world. ResultsA 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%). ConclusionsThis 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

IntroductionA 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. MethodsA 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. ResultsProposals 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. ConclusionsThe 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.

Retrospective study evaluating the efficacy of stereotactic body radiation therapy for the treatment of confirmed or suspected primary pulmonary carcinomas in dogs.

Canine primary pulmonary carcinomas (PCCs) are commonly treated with surgery with overall median survival times (MST) around a year; however, due to extent of disease, prognosis, or client preference, alternative treatments have been considered. Stereotactic body radiation therapy (SBRT) has been utilized in human cancer patients for local control of lung tumours as a surgical alternative. Twenty-one PCCs in 19 dogs that received SBRT for local control were retrospectively evaluated. Dogs were staged according to the canine lung carcinoma stage classification (CLCSC) system with three as Stage 1, five as Stage 2, three as Stage 3, and eight as Stage 4. Overall MST was 343 days with 38% of patients alive at 1 year. Stage did not significantly impact survival time (p = .72). Five (26%) dogs had lymphadenopathy and MST was not significantly different from dogs without lymphadenopathy (343 vs. 353 days; p = .54). Five out of 18 evaluable dogs (28%) experienced acute lung VRTOG effects and 2 of 12 dogs (17%) experienced late lung VRTOG effects. Median lung dose, V5, V20, and D30 to the lung did not correlate significantly with the development of adverse radiation events. Twelve dogs had follow-up imaging and the best response included a complete response (17%), partial response (42%), and stable disease (42%). Progressive disease was noted in seven dogs a median of 229 days after SBRT. SBRT was documented to be a safe and effective alternative to surgery and may have survival advantages for Stage 3 or 4 dogs according to the CLCSC.

A review of liver fibrosis and cirrhosis regression.

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

A review of liver fibrosis and cirrhosis regression

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.