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Simple Summary: Early detection of kidney diseases in dogs is crucial. While many studies focus on urine biomarkers, this study explored the potential of plasma biomarkers. We investigated plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1) in small-breed dogs for detecting chronic kidney disease (CKD). Our findings suggest that pNGAL and pKIM-1 can identify CKD stages and risk groups effectively. These biomarkers showed better diagnostic accuracy than traditional indicators like serum creatinine. Therefore, pNGAL and pKIM-1 could be valuable tools for early CKD detection in veterinary practice. Multiple diagnostic modalities are urgently needed to identify early-stage kidney diseases. Various molecules have been investigated; however, most studies have focused on identifying specific biomarkers in urine. Considering that assessing the symmetrical dimethylarginine (SDMA) plasma concentration is more suitable as an early diagnostic test for chronic kidney disease (CKD) in routine veterinary practice, we aimed to investigate the clinical usefulness of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1) concentrations for CKD detection in small-breed dogs. Through a retrospective analysis, we found that numerous clinicopathological data showed a log-normal distribution, even when they satisfied normality tests. Moreover, the log-transformed pNGAL and pKIM-1 concentrations successfully identified CKD International Renal Interest Society (IRIS) stages 1–4 and the risk group with underlying CKD risk factors. Correlation analysis and group comparison of other factors confirmed the possibility of using these two biomarkers for detecting the CKD risk group and IRIS stage 1. Receiver operating characteristic curve analysis revealed that the diagnostic accuracy for discriminating the risk group was superior in the order of pKIM-1, pNGAL, SDMA, and serum creatinine levels. In conclusion, these results suggest that pKIM-1 and pNGAL are possible early or quantifiable markers of insignificant CKD or can be at least used as an adjunct with traditional indicators. [ABSTRACT FROM AUTHOR]

Background: Several magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed. Objective: Comparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials. Methods: Progressive supranuclear palsy‐Richardson's syndrome (PSP‐RS) patients with one‐year‐follow‐up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age‐matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas‐based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data. Results: Of 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems. Conclusions: This evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas‐based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Mitral annular calcification (MAC) is a progressive degenerative process associated with comorbidities and increased mortality. A staging system that considers extramitral cardiac damage in MAC may help improve patient selection for mitral valve interventions. This study sought to develop a transthoracic echocardiogram (TTE)-based cardiac staging system in patients with MAC and significant mitral valve dysfunction and assess its prognostic utility. We retrospectively evaluated all adults who underwent TTE over 1 year at Mayo Clinic with MAC and significant mitral valve dysfunction defined as mitral stenosis and/or at least moderate mitral regurgitation. Patients were categorized into 5 stages according to extramitral cardiac damage by TTE. All-cause mortality and heart failure hospitalization were assessed. For the 953 included patients, the mean age was 76.2 ± 10.7 years, and 54.0% were women. Twenty-eight (2.9%) patients were classified in stages 0 to 1, 499 (52.4%) in stage 2, 115 (12.1%) in stage 3, and 311 (32.6%) in stage 4. At the 3.8-year follow-up, mortality was significantly higher in patients in stages 2 to 4 compared to stages 0 to 1 and increased with each stage. Survival differences were maintained after adjustment for age, diabetes mellitus, and glomerular filtration rate. The rate of heart failure hospitalization was significantly higher in stages 3 and 4 compared to stages 0 to 1. Similar results were observed in subgroup analysis in patients with moderate or severe MAC, predominant mitral stenosis, or predominant mitral regurgitation. Using the proposed extramitral cardiac damage staging system in patients with MAC and significant mitral valve dysfunction, more advanced stages are associated with higher mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early‐onset MCC (EOMCC) and the differences between EOMCC and late‐onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer‐specific survival (CSS) of EOMCC.Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome.The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002–5.456], P < 0.001), advanced T stage (HR 1.430 [1.139–1.797], P = 0.002), advanced N stage (HR 1.522 [1.221–1.897], P < 0.001), M1 stage (HR 2.587 [1.480–4.521], P < 0.001), and radiation (HR 0.586 [0.410–0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog‐rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone.We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone. [ABSTRACT FROM AUTHOR]

An interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma (ES-HHCC) after hepatectomy is still lacking. This study was aimed at exploring the independent risk parameters and developing an interactive model for predicting the cancer-specific survival (CSS) of ES-HHCC. Data from patients with ES-HHCC who underwent hepatectomy were collected. The dimensionality of the clinical features was reduced by least absolute shrinkage and selection operator regression and further screened as predictors of CSS by Cox regression. Then, an interactive prediction model was developed and validated. Among the 514 screened patients, 311 and 203 of them were assigned into the training and validation cohort, respectively. Six independent variables, including alpha-fetoprotein, cirrhosis, microvascular invasion, satellite, tumor morphology, and tumor diameter, were identified and incorporated into the prediction model for CSS. The model achieved C-indices of 0.724 and 0.711 in the training and validation cohorts, respectively. Calibration curves showed general consistency in both cohorts. Compared with single predictor, the model had a better performance and greater benefit according to the time-independent receiver operating characteristic curve and decision curve analysis (P < 0.05). The calculator owned satisfactory accuracy and flexible operability for predicting the CSS of ES-HHCC, which could serve as a practical tool to stratify patients with different risks, and guide decision-making. [ABSTRACT FROM AUTHOR]

Olfactory neuroblastomas are uncommon malignancies that arise from olfactory receptor cells located high in the nasal cavity. Accurate diagnosis plays a crucial role in determining clinical results and guiding treatment decisions. Diagnosis can be a major challenge for pathologists, especially when dealing with tumours with poor differentiation. The discovery of several molecular and immunohistochemical markers would help to overcome classification difficulties. Due to the paucity of large-scale studies, standardisation of diagnosis, treatment and prediction of outcome remains a challenge. Surgical resection by endoscopic techniques with the addition of postoperative irradiation is the treatment of choice. In addition, it is advisable to consider elective neck irradiation to minimise the risk of nodal recurrence. Molecular characterisation will help not only to make more accurate diagnoses but also to identify specific molecular targets that can be used to develop personalised treatment options tailored to each patient. The present review aims to summarise the current state of knowledge on histopathological diagnosis, the molecular biology and management of this disease. [ABSTRACT FROM AUTHOR]

Due to the scarcity of large‐sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44–88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non‐surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non‐surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma. [ABSTRACT FROM AUTHOR]

Abstract Background The current gastric cancer staging system relies on the number of metastatic lymph nodes (MLNs) for nodal stage determination. However, incorporating additional information such as topographic status may help address uncertainties. This study evaluated the appropriateness of the current staging system and relative significance of MLNs based on their anatomical location. Methods Patients who underwent curative gastrectomy for gastric cancer between 2000 and 2019 at six Catholic Medical Center-affiliated hospitals were included. Lymph node-positive patients were classified into the perigastric (stations 1–6, group P) or extragastric (stations 7–12) groups. The extragastric group was further subdivided into the near-extragastric (stations 7–9, group NE) and far-extragastric (stations 10–12, group FE) groups. Results We analyzed the data of 3,591 patients with positive lymph node metastases. No significant survival differences were found between group P and the extragastric group in each N stage. However, in N1 and N2, group FE showed significantly worse survival than the other groups (p = 0.013 for N1, p

Abstract Objectives To validate an appropriate evaluation method of liver fibrosis assessment based on the unique pathological features of biliary atresia (BA) that could well predict its prognosis. Methods A total of 68 patients with BA who underwent Kasai procedure (KP) and an intraoperative liver biopsy, followed up from January 2019 to December 2021, were recruited in a retrospective analysis. Ishak, Metavir, and BA-specific staging systems in relation to outcomes were analyzed using logistic regression, COX proportional hazard regression, Kaplan-Meier analysis, etc. Results Kaplan-Meier analysis determined a significant difference in native liver survival according to the BA-specific stage (p = 0.002). The ROC curve analysis for predicting prognosis showed that the AUC of BA-specific staging combined with iBALF and severe bile duct proliferation (BDP) (0.811, 95% CI: 0.710–0.913, p

Multiple diagnostic modalities are urgently needed to identify early-stage kidney diseases. Various molecules have been investigated; however, most studies have focused on identifying specific biomarkers in urine. Considering that assessing the symmetrical dimethylarginine (SDMA) plasma concentration is more suitable as an early diagnostic test for chronic kidney disease (CKD) in routine veterinary practice, we aimed to investigate the clinical usefulness of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1) concentrations for CKD detection in small-breed dogs. Through a retrospective analysis, we found that numerous clinicopathological data showed a log-normal distribution, even when they satisfied normality tests. Moreover, the log-transformed pNGAL and pKIM-1 concentrations successfully identified CKD International Renal Interest Society (IRIS) stages 1–4 and the risk group with underlying CKD risk factors. Correlation analysis and group comparison of other factors confirmed the possibility of using these two biomarkers for detecting the CKD risk group and IRIS stage 1. Receiver operating characteristic curve analysis revealed that the diagnostic accuracy for discriminating the risk group was superior in the order of pKIM-1, pNGAL, SDMA, and serum creatinine levels. In conclusion, these results suggest that pKIM-1 and pNGAL are possible early or quantifiable markers of insignificant CKD or can be at least used as an adjunct with traditional indicators.

Background: The current gastric cancer staging system relies on the number of metastatic lymph nodes (MLNs) for nodal stage determination. However, incorporating additional information such as topographic status may help address uncertainties. This study evaluated the appropriateness of the current staging system and relative significance of MLNs based on their anatomical location. Methods: Patients who underwent curative gastrectomy for gastric cancer between 2000 and 2019 at six Catholic Medical Center-affiliated hospitals were included. Lymph node-positive patients were classified into the perigastric (stations 1–6, group P) or extragastric (stations 7–12) groups. The extragastric group was further subdivided into the near-extragastric (stations 7–9, group NE) and far-extragastric (stations 10–12, group FE) groups. Results: We analyzed the data of 3,591 patients with positive lymph node metastases. No significant survival differences were found between group P and the extragastric group in each N stage. However, in N1 and N2, group FE showed significantly worse survival than the other groups (p = 0.013 for N1, p < 0.001 for N2), but not in N3. In the subgroup analysis, group FE had a significantly lower overall survival in N2, regardless of the cancer location. Conclusions: Our large-scale multi-institutional big data analysis confirmed the superiority of the current numerical nodal staging system for gastric cancer. Nonetheless, in N1 and N2 in which there is an upper limit on metastatic nodes, attention should be paid to the potential significance of topographic information for specific nodal stations. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. METHODS: The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. RESULTS: Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1-99.7), 72.7% (95% CI 63.4-83.4), 48.0% (95% CI 41.2-56.0), and 16% (95% CI 11-23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0-2.8), III (HR 3.32; 95% CI 2.07-5.31), and IV (HR 7.44; 95% CI 4.61-12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant. DISCUSSION: The proposed independently validated staging system uses nonhistopathologic data to successfully stratify patients into 4 stages. This staging system has better prognostic accuracy compared with the TNM staging and can assist physicians and patients in treatment of iCCA. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether a specific tooth or teeth provide the most accurate estimation of chronological age (CA), and determine which of the three staging systems studied represents dental development for an individual tooth. Method: Data were collected from 400 digital panoramic radiographs of healthy Saudi children aged 6.00-15.99 years. Each permanent tooth on the left side was evaluated to determine its developmental stage and dental age using the methods by Moorrees, Fanning, and Hunt (MFH) (1963), as adapted by Smith (1991), Gleiser and Hunt (1955), and Nicodemo et al. (1974). The accuracy (bias) of each tooth type and stage was assessed in relation to the CA, the teeth and the methods were compared, and the accuracy of age estimation using all teeth and the most accurate tooth in each method were compared. Results: Regarding staging systems, comparatively, Gleiser and Hunt's method had the lowest bias for the lower first molar (-0.50 ± 1.05 years). Nicodemo et al.'s method had a lower bias for all other mandibular teeth compared to the MFH method. For individual teeth using the MFH method, the most and least accurate teeth for the combined sexes were the lower central incisor (-0.59 ± 0.77 years) and the lower first molar (-1.54 ± 0.93 years), respectively. No significant difference was found between the biases when using the lower central incisor alone and when using all teeth for the combined sexes. For individual teeth using Nicodemo et al.'s method, the most and least accurate teeth for combined sexes were the upper central incisor (-0.03 ± 1.01 years) and the lower first molar (-1.08 ± 1.59 years), respectively. A significant difference was found between the biases using the upper central incisor alone and all teeth for the combined sexes, with the upper central incisor exhibiting the lowest bias (P=0.028). Conclusions: Comparatively, Nicodemo et al.'s method had the lowest bias for all teeth except for the lower first molar, where Gleiser and Hunt's method had the lowest bias. This, however, should not be confused with precision. MFH's staging system was more representative of dental development for an individual tooth. For combined sexes, the lower central and lateral incisors were the most accurate teeth using the MFH method. The upper central incisor and lower first premolar were the most accurate teeth using Nicodemo et al.'s method. The lower first molar was the least accurate tooth using both methods. [ABSTRACT FROM AUTHOR]

Objectives: To validate an appropriate evaluation method of liver fibrosis assessment based on the unique pathological features of biliary atresia (BA) that could well predict its prognosis. Methods: A total of 68 patients with BA who underwent Kasai procedure (KP) and an intraoperative liver biopsy, followed up from January 2019 to December 2021, were recruited in a retrospective analysis. Ishak, Metavir, and BA-specific staging systems in relation to outcomes were analyzed using logistic regression, COX proportional hazard regression, Kaplan-Meier analysis, etc. Results: Kaplan-Meier analysis determined a significant difference in native liver survival according to the BA-specific stage (p = 0.002). The ROC curve analysis for predicting prognosis showed that the AUC of BA-specific staging combined with iBALF and severe bile duct proliferation (BDP) (0.811, 95% CI: 0.710–0.913, p < 0.0001) was higher than BA-specific staging alone (0.755, 95% CI: 0.639–0.872, p < 0.001). Conclusions: The BA-specific staging system reflects the condition of the liver fibrosis, and its combination with iBALF and severe BDP helps to better evaluate the prognosis of patients with BA. [ABSTRACT FROM AUTHOR]

According to the different classifications now in use, thymic tumours are staged by the extent of local invasiveness, and tumour size is not included as a major determinant for the T category. The aim of this double-site retrospective study is to analyse the correlation between tumour dimension and overall survival (OS) in patients who underwent surgical treatment. From January 2000 to December 2020, patients with thymic epithelial tumours who underwent surgical resection were included in this study. Data from a total of 332 patients were analysed. Five- and ten-year overall survival (5–10 YOS) was 89.26% and 87.08%, respectively, while five- and ten-year disease-free survival (DFS) was 88.12% and 84.2%, respectively. Univariate analysis showed a significant correlation between male sex (p-value 0.02), older age (p-value < 0.01), absence of myasthenia gravis (p-value < 0.01), increase in pTNM (pathological Tumor Node Metastasis) (p-value 0.03) and increase in the number of infiltrated organs (p-value 0.02) with an increase in tumour dimension. Tumour dimension alone was not effective in the prediction of DFS and OS, both when considered as a continuous variable and when considered with a cut-off of 3 and 5 cm. However, with multivariate analysis, it was effective in predicting OS in the aforementioned conditions (p-value < 0.01). Moreover, multivariate analysis was also used in the thymoma and Masaoka I subgroups. In our experience, the role of tumour dimension as a descriptor of the T parameter of the TNM (Tumor Node Metastasis) staging system seemed to be useful in improving this system. [ABSTRACT FROM AUTHOR]

Purpose: We developed DeepSurv, a deep learning approach for predicting overall survival (OS) in patients with esophageal squamous cell carcinoma (ESCC). We validated and visualized the novel staging system based on DeepSurv using data from multiple cohorts. Methods: Totally 6020 ESCC patients diagnosed from January 2010 to December 2018 were included in the present study from the Surveillance, Epidemiology, and End Results database (SEER), randomly assigned to the training and test cohorts. We developed, validated and visualized a deep learning model that included 16 prognostic factors; then a novel staging system was further constructed based on the total risk score derived from the deep learning model. The classification performance at 3-year and 5-year OS was assessed by the receiver-operating characteristic (ROC) curve. Calibration curve and the Harrell's concordance index (C-index) were also used to comprehensively assess the predictive performance of the deep learning model. Decision curve analysis (DCA) was utilized to assess the clinical utility of the novel staging system. Results: A more applicable and accurate deep learning model was established, which outperformed the traditional nomogram in predicting OS in the test cohort (C-index: 0.732 [95% CI 0.714–0.750] versus 0.671 [95% CI 0.647–0.695]). The ROC curves at 3-year and 5-year OS for the model also showed good discrimination ability in the test cohort (Area Under the Curve [AUC] at 3-/5-year OS = 0.805/0.825). Moreover, using our novel staging system, we observed a clear survival difference among different risk groups (P < 0.001) and a significant positive net benefit in the DCA. Conclusions: A novel deep learning-based staging system was constructed for patients with ESCC, which performed a significant discriminability for survival probability. Moreover, an easy-to-use web-based tool based on the deep learning model was also implemented, offering convenience for personalized survival prediction. We developed a deep learning-based system that stages patients with ESCC according to their survival probability. We also created a web-based tool that uses this system to predict individual survival outcomes. [ABSTRACT FROM AUTHOR]

Background: This study developed the first comprehensive nomogram for predicting the cancer-specific survival (CSS) of patients with Kaposi's sarcoma (KS). Methods: Data on the demographic and clinical characteristics of 4143 patients with KS were collected from the Surveillance, Epidemiology, and End Results (SEER) database and used for the prognostic analysis. The patients were randomly divided into two groups: training cohort (n = 2900) and validation cohort (n = 1243). Multivariate Cox regression analysis was used to identify the predictive variables for developing the first nomogram for the survival prediction of patients with KS. The new survival nomogram was further evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision curve analysis (DCA). Results: A nomogram was developed for determining the 3-, 5-, 8-, and 10-year CSS probabilities for patients with KS. The nomogram showed that tumor stage had the greatest influence on the CSS of patients with KS, followed by demographic variables (race, marital status, and age at diagnosis) and other clinical characteristics (surgery status, chemotherapy status, tumor risk classification, and radiotherapy status). The nomogram exhibited excellent performance based on the values of the C-index, AUC, NRI, and IDI as well as calibration plots. DCA further confirmed that the nomogram had good net benefits for 3-, 5-, 8-, and 10-year survival analyses. Conclusions: In this study, by using data from the SEER database, we developed the first comprehensive nomogram for analyzing the survival of patients with KS. This nomogram could serve as a convenient and reliable tool for clinicians to predict CSS probabilities for individual patients with KS. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose of this study is to report the clinical characteristics of macular telangiectasia type 2 (MacTel 2) in Taiwan. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with MacTel 2 over a 7-year period in Changhua Christian Hospital. Best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography (OCTA) images were reviewed. Differences in BCVA and central macular thickness (CMT) were compared between the initial/baseline and final visits. The staging was performed according to the Gass and Blodi classification and OCTA. RESULTS: There were 38 eyes in 19 patients were collected (Male: Female = 5:14). The mean age at diagnosis was 65.90 ± 8.26 years and the follow-up duration was 39.26 ± 28.31 months. All patients had both eyes affected, and eight of the 19 patients had a history of diabetes mellitus (DM). The mean initial logarithm of the minimum angle of resolution (logMAR) BCVA was 0.40 ± 0.31 and the mean final logMAR BCVA was 0.61 ± 0.53. Difference of BCVA equal or more than two lines between both eyes was noted in 63.1% (12 of 19) of patients at the initial visit and in 78.9% (15 of 19) of patients at the final follow-up. The mean CMT was 224.42 ± 38.50 µm at baseline and 222.05 ± 40.27 µm at the final visit. OCT illustrated macular hole in three eyes of three patients. At the final follow-up, retinal--choroidal anastomosis was noted in 17 eyes. Subretinal neovascularization (SRNV) was not present in any eye. CONCLUSION: Bilateral involvement, asymmetrical BCVA in both eyes, low incidence of SRNV, and high prevalence of DM were characteristics of patients of MacTel 2 in Taiwan. [ABSTRACT FROM AUTHOR]

Kévin Jean,1,2 Ahmed Tawheed,3 Liem Binh Luong Nguyen,4 Tarek Heikal,5 Usama Eldaly,5 Neveen Elhadidy,6 Ahmed Elghaieb,7 Ahmed Aboudonia,7 Laura Tondeur,1 Amélie Dublineau,4 Arnaud Fontanet,2,4 Mohamed El-Kassas3 1Laboratoire MESuRS, Conservatoire national des arts et métiers, Paris, France; 2Unité PACRI, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France; 3Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt; 4Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris-Cité, Paris, France; 5Medical Oncology Department, Damietta Oncology Center, Damietta, Egypt; 6Pharmaceutical Services Department, Damietta Oncology Center, Damietta, Egypt; 7Radiology Department, Damietta Oncology Center, Damietta, EgyptCorrespondence: Kévin Jean, Laboratoire MESuRS, Conservatoire national des arts et métiers, 292 rue Saint Martin, Paris, 75003, France, Email kevin.jean@lecnam.netIntroduction: We aimed to assess temporal changes in the presentation and survival of patients with hepatocellular carcinoma (HCC) in the northern Egypt region, one of the regions reporting the highest incidence of the disease globally.Methods: We conducted a monocentric retrospective study. Patients presenting at the Damietta Oncology referral center between 2007 and 2019 with a diagnosed HCC were eligible. Individual, clinical and tumor characteristics at HCC diagnosis, including the Barcelona Clinic Liver Cancer (BCLC) staging, were retrieved from medical files and patients’ final vital status was ascertained by combining various data sources. Patients were divided into 2 groups based on diagnosis period: pre- and post-2014. Survival was analysed based on Kaplan–Meier curves and differences in restricted mean survival time (RMST).Results: Data from 5097 patients (among 5210 eligible, 97.8%) were analyzed. We observed a significant trend toward HCC diagnosed at earlier stage in the post- vs pre-2014 period (BCLC stage 0/A or B: 37.2% vs 27.1%, p< 10− 3). Overall patient’s survival after the HCC diagnosis was poor, with a median of 8.1 months. The BCLC staging system performed well in predicting survival. Despite a trend toward HCC diagnosed at earlier stages, we did not observe a significant improvement in survival over time. Overall, treatments offered in this medical center were in line with international guidelines, and 16.1% of the patients who received a curative treatment had an improved survival (30.7 months in median). However, HCC recurrence was frequent among patients cured for HCC, with a median time to recurrence of 22 months.Discussion: Overall survival after HCC diagnosis in Egypt remains poor but is significantly improved by curative therapy. Despite a trend toward earlier diagnosis of HCC, we did not observe a general improvement in survival over time, which remains to be clearly understood.Keywords: hepatocellular carcinoma, liver cancer, Egypt, staging system, survival, epidemiology

Intraoral examinations are essential in the evaluation of the upper airway in patients with obstructive sleep apnea (OSA). The morphology of the anatomic structures of the soft palate, the tonsillar fossae, and the palatoglossus and palatopharyngeal muscles is an important determinant of the size and collapsibility of the velum and oropharynx. The Palatopharyngeal Arch Staging System (PASS) is a systematic way to explore the oropharynx and report anatomic variations in the visible part of the palatopharyngeal muscle. In this prospective study, 30 sleep surgeons evaluated the reliability of the PASS using a selection of 23 videos of oropharyngeal examinations of healthy patients. The corresponding score on the PASS scale was graded for each examination. For internal structure and internal agreement, the Cronbach and Krippendorff alpha values were 0.96 and 0.46, which corresponded to a nearly perfect interrelationship and a moderate agreement, respectively. These findings suggest that the PASS is a valuable tool for evaluating the position of the palatopharyngeus muscle during oropharyngeal examinations and may be useful for creating a common language for sleep surgeons when evaluating the palatopharyngeal muscle. [ABSTRACT FROM AUTHOR]

According to the different classifications now in use, thymic tumours are staged by the extent of local invasiveness, and tumour size is not included as a major determinant for the T category. The aim of this double-site retrospective study is to analyse the correlation between tumour dimension and overall survival (OS) in patients who underwent surgical treatment. From January 2000 to December 2020, patients with thymic epithelial tumours who underwent surgical resection were included in this study. Data from a total of 332 patients were analysed. Five- and ten-year overall survival (5–10 YOS) was 89.26% and 87.08%, respectively, while five- and ten-year disease-free survival (DFS) was 88.12% and 84.2%, respectively. Univariate analysis showed a significant correlation between male sex (p-value 0.02), older age (p-value < 0.01), absence of myasthenia gravis (p-value < 0.01), increase in pTNM (pathological Tumor Node Metastasis) (p-value 0.03) and increase in the number of infiltrated organs (p-value 0.02) with an increase in tumour dimension. Tumour dimension alone was not effective in the prediction of DFS and OS, both when considered as a continuous variable and when considered with a cut-off of 3 and 5 cm. However, with multivariate analysis, it was effective in predicting OS in the aforementioned conditions (p-value < 0.01). Moreover, multivariate analysis was also used in the thymoma and Masaoka I subgroups. In our experience, the role of tumour dimension as a descriptor of the T parameter of the TNM (Tumor Node Metastasis) staging system seemed to be useful in improving this system.

Rationale & objectiveChronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.Study designCross-sectional individual participant-level analyses in a global consortium.Setting & study populations17 CKD and 38 general population and high-risk cohorts.Selection criteria for studiesCohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.Data extractionData were obtained and analyzed between July 2015 and January 2018.Analytical approachWe modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.ResultsThe CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g).LimitationsVariations in study era, health care delivery system, typical diet, and laboratory assays.ConclusionsLower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients.Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients.Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets.Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.

Jinhua Ding,1,2,&ast; Li Jiang,3,&ast; Zheng Xu,4 Yong Chen,4 Weizhu Wu,2 Jian Huang1,5 1Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 3Department of General Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 4Ningbo University School of Medicine, Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China; 5Key Laboratory of Tumour Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Huang, Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, People’s Republic of China, Tel +86-13958123068, Email drhuangjian@zju.edu.cnPurpose: The 8th edition American Joint Committee on Cancer (AJCC) prognostic staging system (PS) has been validated numerous times; however, the prognostic value of PS for breast cancer based on molecular subtype has rarely been explored. This study aimed to investigate the prognostic value of PS in Chinese patients with luminal B-like human epidermal growth factor receptor 2 (HER2)-negative breast cancer.Methods: A total of 407 eligible cases were included in the study. All of the cases were restaged using the 8th edition AJCC Anatomic Staging System (AS) and PS. The Kaplan–Meier method was used to calculate estimated survival and the Log rank test was used to compare the survival differences between groups.Results: The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 90.3% and 93.5%, respectively, and there were statistically significant differences in the 5-year DSS and 5-year OS rates among the different anatomic and prognostic stage groups. The application of the PS resulted in the assignment of 215 (52.8%) patients to a different group. Different prognostic stage groups restaged from anatomic Stage III had significant differences in both DSS (χ2 = 4.366, p = 0.037) and OS (χ2 = 7.549, p = 0.006); additionally, different prognostic stage groups from the anatomic Stage II group had significant differences in DSS (χ2 = 7.724, p = 0.021) but no significant differences in OS (χ2 = 5.182, p = 0.075). However, different prognostic stage groups from anatomic Stage I had no significant differences in either DSS (χ2= 0.159, p = 0.690) or OS (χ2 = 0.099, p = 0.753).Conclusion: The 8th edition AJCC PS refined the anatomic stage grouping in luminal B-like HER2-negative breast cancer and could lead to a more personalized approach to breast cancer treatment.Keywords: breast cancer, staging system, prognosis, survival outcome, human epidermal growth factor receptor 2

Objective: To establish a new classification of biliary tumor thrombus (BTT). Methods: Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging systems. Univariate and multivariate analyses were used to determine factors affecting the overall survival (OS) to form the basis of our new classification for BTT. Results: All 6 international staging systems showed overlapping survival curves. Univariate followed by multivariate analyses showed that total bilirubin and intrahepatic/extrahepatic BTT were significant risk factors of OS. Based on these data, a new BTT classification was defined as: Type I: intrahepatic BTT; and Type II: extrahepatic BTT involving a common bile duct or common hepatic duct. Type I was further subdivided into type Ia: BTT involving a second-order intrahepatic duct or above, and type Ib: BTT involving a first-order intrahepatic duct. Type II was further subdivided into type IIa and type IIb using a cut-off total bilirubin (TB) > 300 μmol/L. The numbers (percentages) of patients with types I and II BTT were 69 (34.2%) and 133 (65.8%), respectively. The median OS of type I patients was significantly higher than that of type II patients (37.5 months vs. 23.2 months; P = 0.002). Using subgroup analyses, OS outcomes were significantly different between the subgroups of type IIb and type IIa, although there was no significant difference between the type Ia and type Ib subgroups (P = 0.07). Conclusions: A new BTT classification was established to predict prognoses of HCC patients with BTT who underwent liver resection.

Microvascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). The current classification of MVI is not refined enough to prognosticate long-term survival of these patients, and a new MVI classification is needed. Patients with HCC who underwent R0 LR at the Eastern Hepatobiliary Surgery Hospital from January 2013 to December 2013 and with resected specimens showing MVI were included in this study with an aim to establish a novel MVI classification. The classification which was developed using multivariate cox regression analysis was externally validated. There were 180 patients in the derivation cohort and 131 patients in the external validation cohort. The following factors were used for scoring: α-fetoprotein level (AFP), liver cirrhosis, tumor number, tumor diameter, MVI number, and distance between MVI and HCC. Three classes of patients could be distinguished by using the total score: class A, ≤3 points; class B, 3.5–5 points and class C, >5 points with distinct long-term survival outcomes (median recurrence free survival (mRFS), 22.6, 10.2, and 1.9 months, P < 0.001). The predictive accuracy of this classification was more accurate than the other commonly used classifications for HCC patients with MVI. In addition, the mRFS of class C patients was significantly prolonged (1.9 months vs. 6.2 months, P < 0.001) after adjuvant transcatheter arterial chemoembolization (TACE). A novel MVI classification was established in predicting prognosis of HCC patients with MVI after R0 LR. Adjuvant TACE was useful for class C patients. [ABSTRACT FROM AUTHOR]

Purposes: The lymph node ratio (LNR) has been considered a better prognostic factor than traditional N staging in patients with gastric cancer (GC), but its accuracy is unclear for those who receive neoadjuvant therapy (NAT). We aimed to compare the node ratio (Nr) staging with the ypN staging and to thereby develop a modified staging system incorporating Nr staging. Methods: A total of 1791 patients who underwent gastrectomy after NAT in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. ypTNrM staging was established based on the overall survival (OS). Results: The Nr staging was generated using 0.2 and 0.5 as the cutoff values of LNR and represented patients with more homogeneous OS compared with ypN staging. The 5-year OS rates for ypTNrM stages IA, IB, II, IIIA, and IIIB were 70.2%, 54.2%, 36.0%, 21.2%, and 6.6%, respectively, compared with 58.8%, 39.1%, and 21.6% for ypTNM stages I, II, and III, respectively. Compared with the ypTNM staging system, the ypTNrM staging system had a lower misclassification rate (3.0% vs. 50.9%) and better prognostic predictive power (C-index: 0.645 vs. 0.589, P < 0.001). Conclusions: The ypTNrM staging system incorporating Nr staging may provide a more accurate assessment in the clinical decision-making process for GC after NAT. [ABSTRACT FROM AUTHOR]

Nasal-type extranodal NK-T-cell lymphoma (ENKTL) is a rare non-Hodgkin lymphoma. The optimal staging system for it remains undefined. In this study, we evaluated different staging systems in 205 patients with nasal-type ENKTL based on a consistent LVDP (L-asparaginase, etoposide, dexamethasone, cisplatin) regimen. All patients were staged by Ann Arbor staging system (AASS) and CA staging system (CASS). Their characteristics, treatment responses, survival outcomes, prognostic factors, and prognostic values of AASS and CASS were analyzed. The median follow-up time was 78 months. All patients received a median 4 cycles of the LVDP chemotherapy. Based on CASS, patients with stages I through IV were more evenly distributed than with AASS, and numbered at 56 (27.3%), 70 (33.2%), 45 (21.9%), and 34 (17.6%), respectively. At the end of therapy, the objective response rate (ORR) was 81.2% for all patients. For all patients, the 5-year progression-free survival (PFS) and overall survival (OS) were 61.6% and 67.8%. According to AASS, the 5-year OS of patients with stages Ⅰ through Ⅳ were 77.9%, 61.2%, 60.0%, and 38.7%, respectively (χ²=20.578, p

Yong-Fa Zhang,1,2,* Ming Shi,3,* Liang-He Lu,3 Lu Wang,1,2 Rong-Ping Guo3 1Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3The Department of Hepatobiliary Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu WangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of ChinaTel/Fax +8620-64175590Email cms024mm@163.comRong-Ping GuoDepartment of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of ChinaTel/Fax +8620-87342266Email guorp@sysucc.org.cnPurpose: It remains unknown which staging system is best in predicting the survival of patients with intermediate stage hepatocellular carcinoma (HCC). We aimed to investigate the performance of nine currently used HCC staging systems.Patients and Methods: Between 2005 and 2014, a large cohort of 880 consecutive patients with intermediate stage HCC and sufficient data for utilization in all staging systems were enrolled. The prognostic performance of each staging system was compared. Independent prognostic variables were also identified.Results: Multivariate analysis revealed that alkaline phosphatase (ALP), aspartate aminotransferase (AST), etiology, alpha-fetoprotein (AFP), Child-Pugh stage, tumor size, and tumor number were independent prognostic factors for survival. In the entire cohort, the Hong Kong Liver Cancer (HKLC) staging system was associated with the highest Harrell’s c-index and lowest Akaike information criterion value in comparison with other systems. In subgroup analysis according to treatment strategy, the HKLC staging system remained the best prognostic model in patients undergoing hepatic resection (n=222) or transarterial chemoembolization (n=658). Additional prognostic factors of AST, ALP, etiology, and AFP improved the discriminatory ability of HKLC.Conclusion: The HKLC staging system is stable and consistently the best prognostic model in all patients with intermediate-stage HCC and in patients subjected to different treatment strategies. Selecting an optimal staging system is helpful in improving the design of future clinical trials in intermediate stage HCC.Keywords: hepatocellular carcinoma, intermediate-stage, staging system, prognosis, overall survival, hepatic resection, transarterial chemoembolization

Non-small Cell Lung Cancer (NSCLC) with intralobar satellite nodule are defined as T3 (T3SN). We investigated the main features of these tumors and analyzed their impact on Overall Survival (OS). This was a retrospective multicentric study including all pT3SN NSCLC operated on between 2005 and 2020, excluding patients with multifocal ground-glass opacities; who received induction therapies; N3 or stage IV. The diameter of largest (LgN) and smallest nodule (SmN), the total diameter (sum of diameter of all nodules, TS), and the number of SN were measured. Among 102 patients, 64.7 % were male. 84.3 % of patients had one SN (84.3 %), 9.8 % two SN while 5.9 % more than 2 SN. 63 patients were pN0. LgN (p = 0.001), SN (p = 0.005) and TS (p = 0.014) were significantly related to lymph-node metastasis; the LgN and TS were related to visceral pleural invasion (p < 0.001). Five-year OS was 65.1 %; at univariable analysis more than 2 satellite nodules, LgN and TS were significantly related to worse OS; at multivariable analysis, TS (Hazard Ratio [HR] 1.116 95 % Confidence Interval [CI] 1.008–1.235, p = 0.034) was an independent prognostic factors for OS. No significant prognostic factors were found for DFS at multivariable analysis. In pN0 patients, LgN (HR 1.051, 95 % CI 1.066–1.099, p = 0.027) and non-adenocarcinoma (HR 5.315 CI 95 % 1.494–18.910, p = 0.010) influenced OS. Tumor size is related to tumor's local invasiveness. TS is an independent prognostic factor for OS. Patients with more than 2 SN seem to be at higher risk for death and recurrence. [ABSTRACT FROM AUTHOR]

Intraoral examinations are essential in the evaluation of the upper airway in patients with obstructive sleep apnea (OSA). The morphology of the anatomic structures of the soft palate, the tonsillar fossae, and the palatoglossus and palatopharyngeal muscles is an important determinant of the size and collapsibility of the velum and oropharynx. The Palatopharyngeal Arch Staging System (PASS) is a systematic way to explore the oropharynx and report anatomic variations in the visible part of the palatopharyngeal muscle. In this prospective study, 30 sleep surgeons evaluated the reliability of the PASS using a selection of 23 videos of oropharyngeal examinations of healthy patients. The corresponding score on the PASS scale was graded for each examination. For internal structure and internal agreement, the Cronbach and Krippendorff alpha values were 0.96 and 0.46, which corresponded to a nearly perfect interrelationship and a moderate agreement, respectively. These findings suggest that the PASS is a valuable tool for evaluating the position of the palatopharyngeus muscle during oropharyngeal examinations and may be useful for creating a common language for sleep surgeons when evaluating the palatopharyngeal muscle.

Background: The clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed. Methods: Data were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy. Results: This retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively. Conclusion: We developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with < 16 retrieved lymph nodes (rLNs). Here, this study aimed to validate a practical lymph node (LN) staging strategy to homogenize the nodal classification of GC cohorts comprising of both < 16 (Limited set) and ≥ 16 (Adequate set) rLNs. Methods: All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N') resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases. Results: Significant difference in OS between the Limited and Adequate set (corresponding N0–N3a) using the 8th AJCC system was observed but the OS of N0limited vs. N1adequate, N1limited vs. N2adequate, N2limited vs. N3aadequate, and N3alimited vs. N3badequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N' classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N'0 = N0adequate + pT1N0M0limited, N'1 = N1adequate + N0limited (excluding pT1N0M0limited), N'2 = N2adequate + N1limited, N'3a = N3aadequate + N2limited, and N'3b = N3badequate + N3alimited). This N' classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN'M system over the 8th AJCC edition and was successfully validated using the SEER dataset. Conclusion: The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with < 16 and ≥ 16 rLNs. [ABSTRACT FROM AUTHOR]

BackgroundThe clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed.MethodsData were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy.ResultsThis retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively.ConclusionWe developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma.

Background: Lymph node metastasis (LNM) is closely associated with the prognosis of ampullary carcinoma (AC). The purpose of this study is to explore the relationship between lymph node ratio (LNR) and the prognosis of patients with AC after curative pancreaticoduodenectomy and to establish a new LNR-based staging system. Methods: AC patients in the Cancer Hospital, Chinese Academy of Medical Sciences, between 1998 and 2020 were retrospectively reviewed as the training cohort; and AC patients in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018 were obtained as the validation cohort. Within the training group, Kaplan–Meier survival analyses and Cox proportional hazards regression were conducted to assess the prognostic value of LNR and establish a new LNR-based staging system. Then, the new staging system was compared with the 8th American Joint Committee on Cancer (AJCC) TNM staging system in both the training and validation cohorts. Results: A total of 264 patients in the training cohort and 199 patients in the validation cohort were enrolled. Significant overall survival (OS) difference was observed between LNR-low stage and LNR-high stage in both training (p = 0.001) and validation cohorts (p < 0.001). Then a new LNR-based staging system was developed. Under the new system, the number of patients in the training cohort and validation cohort of stage I, stage II, and stage III was 30 (11%) vs. 18 (9%), 190 (72%) vs. 96 (48%), and 44 (17%) vs. 85 (43%), respectively. The new staging system classified patients with respect to survival better than did the 8th AJCC TNM staging system. Conclusions: The new LNR-based staging system had better discriminability for predicting survival in AC patients after curative pancreaticoduodenectomy. More data are needed for further validation. [ABSTRACT FROM AUTHOR]

Background: Microvascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). However, whether the existing staging systems of hepatocellular carcinoma can distinguish the prognosis of patients with MVI and the prognostic value of MVI in different subtypes of hepatocellular carcinoma remains to be clarified. Methods: A dual-center retrospective data set of 1,198 HCC patients who underwent R0 LR was included in the study between 2014 and 2016. Baseline characteristics and staging information were collected. Homogeneity and modified Akaike information criterion (AICc) were compared between each system. And the prognostic significance of MVI for overall survival (OS) was studied in each subgroup. Results: In the entire cohort, there were no significant survival differences between Cancer of the Liver Italian Program (CLIP) score 2 and 3 (p = 0.441), and between Taipei Integrated Scoring System (TIS) score 3 and 4 (p = 0.135). In the MVI cohort, there were no significant survival differences between Barcelona Clinic Liver Cancer stages B and C (p=0.161), CLIP scores 2 and 3 (p = 0.083), TIS scores 0 and 1 (p = 0.227), TIS scores 2 and 3 (p =0.794), Tokyo scores 3 and 4 (p=0.353), and American Joint Committee on Cancer Tumor-Node-Metastasis 7th stage I and II (p=0.151). Among the eight commonly used HCC staging systems, the Hong Kong Liver Cancer (HKLC) staging system showed the highest homogeneity and the lowest AICc value in both the entire cohort and MVI cohort. In each subgroup of the staging systems, MVI generally exhibited poor survival outcomes. Conclusions: The HKLC staging system was the most accurate model for discriminating the prognosis of MVI patients, among the eight staging systems. Meanwhile, our findings suggest that MVI may be needed to be incorporated into the current HCC staging systems as one of the grading criteria. [ABSTRACT FROM AUTHOR]

BackgroundLymph node metastasis (LNM) is closely associated with the prognosis of ampullary carcinoma (AC). The purpose of this study is to explore the relationship between lymph node ratio (LNR) and the prognosis of patients with AC after curative pancreaticoduodenectomy and to establish a new LNR-based staging system.MethodsAC patients in the Cancer Hospital, Chinese Academy of Medical Sciences, between 1998 and 2020 were retrospectively reviewed as the training cohort; and AC patients in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018 were obtained as the validation cohort. Within the training group, Kaplan–Meier survival analyses and Cox proportional hazards regression were conducted to assess the prognostic value of LNR and establish a new LNR-based staging system. Then, the new staging system was compared with the 8th American Joint Committee on Cancer (AJCC) TNM staging system in both the training and validation cohorts.ResultsA total of 264 patients in the training cohort and 199 patients in the validation cohort were enrolled. Significant overall survival (OS) difference was observed between LNR-low stage and LNR-high stage in both training (p = 0.001) and validation cohorts (p < 0.001). Then a new LNR-based staging system was developed. Under the new system, the number of patients in the training cohort and validation cohort of stage I, stage II, and stage III was 30 (11%) vs. 18 (9%), 190 (72%) vs. 96 (48%), and 44 (17%) vs. 85 (43%), respectively. The new staging system classified patients with respect to survival better than did the 8th AJCC TNM staging system.ConclusionsThe new LNR-based staging system had better discriminability for predicting survival in AC patients after curative pancreaticoduodenectomy. More data are needed for further validation.

BackgroundMicrovascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). However, whether the existing staging systems of hepatocellular carcinoma can distinguish the prognosis of patients with MVI and the prognostic value of MVI in different subtypes of hepatocellular carcinoma remains to be clarified.MethodsA dual-center retrospective data set of 1,198 HCC patients who underwent R0 LR was included in the study between 2014 and 2016. Baseline characteristics and staging information were collected. Homogeneity and modified Akaike information criterion (AICc) were compared between each system. And the prognostic significance of MVI for overall survival (OS) was studied in each subgroup.ResultsIn the entire cohort, there were no significant survival differences between Cancer of the Liver Italian Program (CLIP) score 2 and 3 (p = 0.441), and between Taipei Integrated Scoring System (TIS) score 3 and 4 (p = 0.135). In the MVI cohort, there were no significant survival differences between Barcelona Clinic Liver Cancer stages B and C (p=0.161), CLIP scores 2 and 3 (p = 0.083), TIS scores 0 and 1 (p = 0.227), TIS scores 2 and 3 (p =0.794), Tokyo scores 3 and 4 (p=0.353), and American Joint Committee on Cancer Tumor-Node-Metastasis 7th stage I and II (p=0.151). Among the eight commonly used HCC staging systems, the Hong Kong Liver Cancer (HKLC) staging system showed the highest homogeneity and the lowest AICc value in both the entire cohort and MVI cohort. In each subgroup of the staging systems, MVI generally exhibited poor survival outcomes.ConclusionsThe HKLC staging system was the most accurate model for discriminating the prognosis of MVI patients, among the eight staging systems. Meanwhile, our findings suggest that MVI may be needed to be incorporated into the current HCC staging systems as one of the grading criteria.

Background and Aims: The prognostic value of bile duct invasion (BDI) remains controversial. We aimed to investigate the prognostic value of BDI and the stage of BDI in different staging systems. Methods: Patients with hepatocellular carcinoma (HCC) from nine hepatobiliary medical centers who underwent R0 resection were included. Overall survival (OS) was assessed using the Kaplan–Meier method and tested using the log-rank test. The prognostic effect of BDI was analyzed using univariate and multivariate Cox proportional hazard regression analyses. The predictive performance of these models was evaluated using the concordance index and time-dependent receiver operating characteristic curve (tdAUC). Results: Of 1021 patients with HCC, 177 had BDI. OS was worse in the HCC with BDI group than in the HCC without BDI group (p<0.001); multivariate analysis identified BDI as an independent risk factor for OS. After adjustment for interference of confounding factors using the Cox proportional hazard regression model, HCC with BDI and without macrovascular invasion was classified as Barcelona Clinic Liver Cancer (BCLC) B, eighth edition American Joint Committee on Cancer (AJCC) IIIA, and China Liver Cancer (CNLC) IIb, respectively, whereas HCC with BDI and macrovascular was classified as BCLC C, AJCC IIIB, and CNLC IIIA, respectively. C-indexes and tdAUCs of the adjusted staging systems were superior to those of the corresponding current staging systems. Conclusion: We constructed adjusted staging systems with the BDI status, improved their predictive performance and facilitate clinical use. [ABSTRACT FROM AUTHOR]

The topic of pulmonary metastases has long been of high interest and ongoing controversy. There is a group of patients with pulmonary metastases who may benefit from curative resection. It remains unclear which among them will benefit from surgery in terms of survival. This work updates a previously proposed classification system for pulmonary metastases, similar in its essence to the tumor, nodes, metastasis (TNM) classification used for primary tumors and named pmTNM classification, where 'pm' stands for 'pulmonary metastasis'. The objective is to allow future studies to explore predictive and survival prognostic factors for pulmonary metastases and separate patients who will benefit from lung metastasectomy from those who will not. The secondary aim is to provide a classification system that will allow physicians, oncologists and surgeons to speak the same language in comparing their data and assessing the results of treatment of lung metastases. [ABSTRACT FROM AUTHOR]

Objective: To compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using prospective data from a multi-ethnic cohort of ALS patients. Methods: The stages of disease were determined prospectively based on existing definitions. The two systems were compared for timing of stages using box plots, correspondence using chi-square tests and association using Spearman's rank correlation. Results: The distribution of stages differed between the two systems. The proportions of disease stages of the King's staging system were more evenly distributed whereas in MiToS, there was greater weight seen at the later stages of disease. At the early stages, patients moved consecutively in the MiToS staging system but not in the King's staging system where patients tended to skip stages to reach later stages. Both systems had good correlation (Spearman's rho = 0.869) and the King's stage 4 most frequently corresponded to MiToS stage 2. Conclusion: We found the King's staging was helpful in determining the stages of disease burden, whereas both were helpful in determining the time to functional dependence with MiToS further refining the levels of dependence. [ABSTRACT FROM AUTHOR]

Background and AimsThe prognostic value of bile duct invasion (BDI) remains controversial. We aimed to investigate the prognostic value of BDI and the stage of BDI in different staging systems.MethodsPatients with hepatocellular carcinoma (HCC) from nine hepatobiliary medical centers who underwent R0 resection were included. Overall survival (OS) was assessed using the Kaplan–Meier method and tested using the log-rank test. The prognostic effect of BDI was analyzed using univariate and multivariate Cox proportional hazard regression analyses. The predictive performance of these models was evaluated using the concordance index and time-dependent receiver operating characteristic curve (tdAUC).ResultsOf 1021 patients with HCC, 177 had BDI. OS was worse in the HCC with BDI group than in the HCC without BDI group (p

BackgroundThe staging system for patients with anaplastic thyroid cancer (ATC) was updated in the 8th edition of the American Joint Committee on Cancer Staging Manual. A cut-off age of 55 years was stipulated as a prognostic factor for differentiated thyroid cancer; however, age was not considered for ATC patients. To this end, this study investigated the relationship between age at diagnosis and prognosis of ATC patients.MethodsThe clinical information on ATC patients was acquired from the Surveillance, Epidemiology, and End Results Program public database. Youden’s index and X-tile analyses were used to calculate the high-point age at diagnosis associated with prognosis. Cox proportional hazards models, Kaplan-Meier curves, and 1000-person-year were then used for verifying the accuracy of the high-point age.ResultsAfter inclusion/exclusion criteria was applied, 586 patients were included in this study. The high-point age was determined to be 70 years by both the Youden’s index and X-tile plot methods. The hazard ratio was 1.662 (95% confidence interval [CI]: 1.321-2.092), indicating that there was an increased risk of poor prognosis for patients > 70 years of age. The cancer-specific mortality rates per 1000-person-years for patients ≤ and > 70 years-old were 949.980 (95% CI: 827.323-1090.822) and 1546.667 (95% CI: 1333.114-1794.428), respectively. P-values were < 0.001 for the results shown above.ConclusionOur study found that age influenced the prognosis of ATC patients. Furthermore, we determined that the high-point age at diagnosis was 70 years and that > 70 years of age was associated with a poor prognosis. These results provide a useful addition to the staging manual and can improve the diagnosis, treatment strategies and prognosis of ATC patients.

Background: The staging system for patients with anaplastic thyroid cancer (ATC) was updated in the 8th edition of the American Joint Committee on Cancer Staging Manual. A cut-off age of 55 years was stipulated as a prognostic factor for differentiated thyroid cancer; however, age was not considered for ATC patients. To this end, this study investigated the relationship between age at diagnosis and prognosis of ATC patients. Methods: The clinical information on ATC patients was acquired from the Surveillance, Epidemiology, and End Results Program public database. Youden's index and X-tile analyses were used to calculate the high-point age at diagnosis associated with prognosis. Cox proportional hazards models, Kaplan-Meier curves, and 1000-person-year were then used for verifying the accuracy of the high-point age. Results: After inclusion/exclusion criteria was applied, 586 patients were included in this study. The high-point age was determined to be 70 years by both the Youden's index and X-tile plot methods. The hazard ratio was 1.662 (95% confidence interval [CI]: 1.321-2.092), indicating that there was an increased risk of poor prognosis for patients > 70 years of age. The cancer-specific mortality rates per 1000-person-years for patients ≤ and > 70 years-old were 949.980 (95% CI: 827.323-1090.822) and 1546.667 (95% CI: 1333.114-1794.428), respectively. P-values were < 0.001 for the results shown above. Conclusion: Our study found that age influenced the prognosis of ATC patients. Furthermore, we determined that the high-point age at diagnosis was 70 years and that > 70 years of age was associated with a poor prognosis. These results provide a useful addition to the staging manual and can improve the diagnosis, treatment strategies and prognosis of ATC patients. [ABSTRACT FROM AUTHOR]

In previous studies, it's recommended that the lymph node involvement should be evaluated with enough examined lymph nodes (eLNs) in the 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer. This study aims to put forward a rescue staging system for pancreatic ductal adenocarcinoma (PDAC) patients with inadequate eLNs after pancreatoduodenectomy (PD). 11,224 PDAC patients undergoing PD in The Surveillance, Epidemiology, and End Results (SEER) database were included. Another Ruijin Pancreatic Disease Center (RJPDC) database consisted of 821 patients was utilized for external validation. The proportions of patients with eLNs≥15 were 44.7% and 32.8% in SEER and RJPDC database separately. The rescue staging system was put forward relying on LNR (HR = 1.83, 95% CI 1.74–1.92, P < 0.001) for N staging of eLNs<15 population and pLNs for the rest. The TNM modalities were also rearranged in the rescue system for better survival coordination. The C-index of rescue staging system was 0.638 while that of AJCC 8th staging system was 0.613 in SEER database. Similar phenomena were observed in RJPDC database. Kaplan-Meier analyses revealed reliable internal coherences (SEER: Ib: P = 0.26; IIa: P = 0.063; IIb: P = 0.53; IIIa: P = 0.11. RJPDC: Ib: P = 0.32; IIa: P = 0.66; IIb: P = 0.76; IIIa: P = 0.66) and significant staging efficiency (SEER: P < 0.001; RJPDC: P = 0.002). A rescue staging system was put forward regardless of the eLNs number. And the novel system manifested better predictive capacity than 8th AJCC staging system. [ABSTRACT FROM AUTHOR]