The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up.

OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

The role of IFN-γ-signalling in response to immune checkpoint blockade therapy.

Treatment with immune checkpoint inhibitors, widely known as immune checkpoint blockade therapy (ICBT), is now the fourth pillar in cancer treatment, offering the chance of durable remission for patients with advanced disease. However, ICBT fails to induce objective responses in most cancer patients with still others progressing after an initial response. It is necessary, therefore, to elucidate the primary and acquired resistance mechanisms to ICBT to improve its efficacy. Here, we highlight the paradoxical role of the cytokine interferon-γ (IFN-γ) in ICBT response: on the one hand induction of IFN-γ signalling in the tumour microenvironment correlates with good ICBT response as it drives the cellular immune responses required for tumour destruction; nonetheless, IFN-γ signalling is implicated in ICBT acquired resistance. We address the negative feedback and immunoregulatory effects of IFN-γ signalling that promote immune evasion and resistance to ICBT and discuss how these can be targeted pharmacologically to restore sensitivity or circumvent resistance.

Risk profiles and a concise prediction model for lymph node metastasis in patients with lung adenocarcinoma.

BACKGROUND: Lung cancer is the second most commonly diagnosed cancer and ranks the first in mortality. Pathological lymph node status(pN) of lung cancer affects the treatment strategy after surgery while systematic lymph node dissection(SLND) is always unsatisfied. METHODS: We reviewed the clinicopathological features of 2,696 patients with LUAD and one single lesion ≤ 5 cm who underwent SLND in addition to lung resection at the Sun Yat-Sen University Cancer Center. The relationship between the pN status and all other clinicopathological features was assessed. All participants were stochastically divided into development and validation cohorts; the former was used to establish a logistic regression model based on selected factors from stepwise backward algorithm to predict pN status. C-statistics, accuracy, sensitivity, and specificity were calculated for both cohorts to test the model performance. RESULTS: Nerve tract infiltration (NTI), visceral pleural infiltration (PI), lymphovascular infiltration (LVI), right upper lobe (RUL), low differentiated component, tumor size, micropapillary component, lepidic component, and micropapillary predominance were included in the final model. Model performance in the development and validation cohorts was as follows: 0.861 (95% CI: 0.842-0.883) and 0.840 (95% CI: 0.804-0.876) for the C-statistics and 0.803 (95% CI: 0.784-0.821) and 0.785 (95% CI: 0.755-0.814) for accuracy, and 0.754 (95% CI: 0.706-0.798) and 0.686 (95% CI: 0.607-0.757) for sensitivity and 0.814 (95% CI: 0.794-0.833) and 0.811 (95% CI: 0.778-0.841) for specificity, respectively. CONCLUSION: Our study showed an easy and credible tool with good performance in predicting pN in patients with LUAD with a single tumor ≤ 5.0 cm without SLND and it is valuable to adjust the treatment strategy.

AMG-510 and cisplatin combination increases antitumor effect in lung adenocarcinoma with mutation of KRAS G12C: a preclinical and translational research.

BACKGROUND: The efficacy of monotherapy of AMG-510 is limited. This study explored whether the AMG-510 and cisplatin combination increases the anti-tumor effect in lung adenocarcinoma with the mutation of Kirsten rat sarcoma viral oncogene (KRAS) G12C. METHODS: Patients' data were used to analyze the proportion of KRAS G12C mutation. Besides, the next-generation sequencing data was used to uncover information about co-mutations. The cell viability assay, the concentration inhibiting 50% of cell viability (IC50) determination, colony formation, and cell-derived xenografts were conducted to explore the anti-tumor effect of AMG-510, Cisplatin, and their combination in vivo. The bioinformatic analysis was conducted to reveal the potential mechanism of drug combination with improved anticancer effect. RESULTS: The proportion of KRAS mutation was 2.2% (11/495). In this cohort with KRAS mutation, the proportion of G12D was higher than others. Besides, KRAS G12A mutated tumors had the likelihood of concurrent serine/threonine kinase 11 (STK11) and kelch-like ECH-associated protein 1 (KEAP1) mutations. KRAS G12C and tumor protein p53 (TP53) mutations could appear at the same time. In addition, KRAS G12D mutations and C-Ros oncogene 1 (ROS1) rearrangement were likely to be present in one tumor simultaneously. When the two drugs were combined, the respective IC50 values were lower than when used alone. In addition, there was a minimum number of clones among all wells in the drug combination. In in vivo experiments, the tumor size reduction in the drug combination group was more than twice that of the single drug group (p < 0.05). The differential expression genes were enriched in the pathways of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling and extracellular matrix (ECM) proteoglycans compared the combination group to the control group. CONCLUSIONS: The anticancer effect of the drug combination was confirmed to be better than monotherapy in vitro and in vivo. The results of this study may provide some information for the plan of neoadjuvant therapy and the design of clinical trials for lung adenocarcinoma patients with KRAS G12C mutation.

Establishment and validation of a prognostic risk classification for patients with stage T1-3N0M0 esophageal squamous cell carcinoma.

INTRODUCTION: At present, clinical factors and hematological indicators have been proved to have great potential in predicting the prognosis of cancer patients, and no one has combined these two valuable indicators to establish a prognostic model for esophageal squamous cell carcinoma (ESCC) patients with stage T1-3N0M0 after R0 resection. To verify, we aimed to combine these potential indicators to establish a prognostic model. METHODS: Stage T1-3N0M0 ESCC patients from two cancer centers (including training cohort: N = 819, and an external validation cohort: N = 177)-who had undergone esophagectomy in 1995-2015 were included. We integrated significant risk factors for death events by multivariable logistic regression methods and applied them to the training cohort to build Esorisk. The parsimonious aggregate Esorisk score was calculated for each patient; the training set was divided into three prognostic risk classes according to the 33rd and 66th percentiles of the Esorisk score. The association of Esorisk with cancer-specific survival (CSS) was assessed using Cox regression analyses. RESULTS: The Esorisk model was: [10 + 0.023 × age + 0.517 × drinking history - 0.012 × hemoglobin-0.042 × albumin - 0.032 × lymph nodes]. Patients were grouped into three classes-Class A (5.14-7.26, low risk), Class B (7.27-7.70, middle risk), and Class C (7.71-9.29, high risk). In the training group, five-year CSS decreased across the categories (A: 63%; B: 52%; C: 30%, Log-rank P < 0.001). Similar findings were observed in the validation group. Additionally, Cox regression analysis showed that Esorisk aggregate score remained significantly associated with CSS in the training cohort and validation cohort after adjusting for other confounders. CONCLUSIONS: We combined the data of two large clinical centers, and comprehensively considered their valuable clinical factors and hematological indicators, established and verified a new prognostic risk classification that can predict CSS of stage T1-3N0M0 ESCC patients.

The postoperative prognosis of skip-N2 metastasis is favorable in small-cell lung carcinoma patients with pathological N2 classification: a propensity-score-adjusted retrospective multicenter study.

Background: The study on skip-N2 metastasis in small-cell lung cancer (SCLC) is lacking. Therefore, this study aimed to explore the prognostic significance of skip-N2 metastasis based on a multicenter cohort. Methods: We collected 176 SCLC patients with pathological categories T1-4N1-2M0 from four hospitals in China. Survival curves were drawn through the Kaplan-Meier method and compared by the log-rank test. The Cox regression method was used to calculate the hazard ratio (HR) and 95% confidence interval of the characteristics for cancer-specific survival (CSS). Two propensity-score methods were used to reduce the bias, including the inverse probability of treatment weighting (IPTW) and propensity-score matching (PSM). Results: This multicenter database included 64 pN1 patients, 63 non-skip-N2 cases, and 49 skip-N2 cases. Skip-N2 and the non-skip-N2 patients had gap CSS rates (skip-N2 no versus yes: 41.0% versus 62.0% for 1-year CSS, 32.0% versus 46.0% for 2-year CSS, and 20.0% versus 32.0% for 3-year CSS). After PSM, there were 32 pairs of patients to compare survival differences between N2 and skip-N2 diseases, and 34 pairs of patients to compare prognostic gaps between N1 and skip-N2 diseases, respectively. The results of IPTW and PSM both suggested that skip-N2 cases had better survival outcomes than the non-skip-N2 cases (IPTW-adjusted HR = 0.578; PSM-adjusted HR = 0.510; all log-rank p < 0.05). Besides, the above two analytic methods showed no difference in prognoses between pN1 and skip-N2 diseases (all log-rank p > 0.05). Conclusions: Skip-N2 patients were confirmed to have a better prognosis than non-skip-N2 patients. Besides, there was no survival difference between pN1 and skip-N2 cases. Therefore, we propose that the next tumor-node-metastasis staging system needs to consider the situation of skip metastasis with lymph nodes in SCLC.

Nomogram predicts the prognosis of patients with thymic carcinoma: A population-based study using SEER data.

BACKGROUND: Thymic carcinoma (TC) is a rare malignant tumor that can have a poor prognosis, and accurate prognostication prediction remains difficult. We aimed to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) based on a large cohort of patients. METHODS: The Surveillance Epidemiology and End Results (SEER) database was searched to identify TC patients (1975-2016). Univariate and multivariable Cox regression analyses were used to identify predictors of OS and CSS, which were used to construct nomograms. The nomograms were evaluated using the concordance index (C-index), calibration curve, receiver operating characteristic curve, and decision curve analysis (DCA). Subgroup analysis was performed to identify high-risk patients. RESULTS: The analysis identified six predictors of OS (Masaoka stage, surgical method, lymph node metastasis, liver metastasis, bone metastasis, and radiotherapy) and five predictors of CSS (Masaoka stage, surgical method, lymph node metastasis, tumor size, and brain metastasis), which were used to create nomograms for predicting three-year and five-year OS and CSS. The nomograms had reasonable C-index values (OS: 0.687 [training] and 0.674 [validation], CSS: 0.712 [training] and 0.739 [validation]). The DCA curve revealed that the nomograms were better for predicting OS and CSS, relative to the Masaoka staging system. CONCLUSION: We developed nomograms using eight clinicopathological factors that predicted OS and CSS among TC patients. The nomograms performed better than the traditional Masaoka staging system and could identify high-risk patients. Based on the nomograms' performance, we believe they will be useful prognostication tools for TC patients.

Prognostic value of preoperative C-reactive protein to albumin ratio in patients with thymic epithelial tumors: a retrospective study.

BACKGROUND: The C-reactive protein to albumin ratio (CAR) is associated with poor prognosis in various cancers. However, its value in thymic epithelial tumors remains to be elucidated, we aimed to evaluate the prognostic significance of preoperative CAR in patients with surgically resected thymic epithelial tumors (TETs). METHODS: We retrospectively collected data from 125 patients with TETs who underwent thymoma resection at our center. The best cutoff values ​​for the continuous variable, CAR, were obtained using X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate CAR as an independent predictor of overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis and log-rank tests were used to present risk stratification of patients based on CAR and the Glasgow-prognostic-score (GPS). The prognostic effect of CAR was assessed using a receiver operating characteristic curve. RESULTS: Patients were categorized into high (≥ 0.17) and low (< 0.17) CAR groups according to the optimal cutoff value of 0.17. Univariate and multivariate analyses showed that CAR was an independent predictor of prognosis. World health organization stage, CAR level, GPS score, and drinking history were important independent prognostic factors for OS (p < 0.05). T stage, CAR level, and drinking history were important independent prognostic factors for RFS (p < 0.05). The area under the curve value of CAR to predict prognosis was 0.734 for OS and 0.680 for RFS. CONCLUSIONS: Elevated preoperative CAR was independently associated with poor OS and RFS after thymectomy. Therefore, CAR may be a valuable biomarker for the postoperative prognosis of TETs.

The Prognostic Value of Preoperative Serum D-dimer Levels After Surgical Resection of Thymic Epithelial Tumors.

INTRODUCTION: Thymic epithelial tumors are the most common mediastinal tumors. Despite the high survival rate after surgery, some patients still require postoperative adjuvant therapy and closer follow-up. Hematological indicators such as biochemical routines and coagulation indicators have been reported to be independently associated with the prognosis of various malignancies. Therefore, we included hematological indicators in the analysis. METHODS: The data of 105 patients with thymic epithelial tumors were retrospectively collected from Sun Yat-sen University Cancer Center, and the patients with missing preoperative hematological indicators were excluded. X-tile software was used to obtain the best cutoff value of each preoperative hematological indicator, and COX regression analysis and Kaplan-Meier survival curves were used to demonstrate statistically significant results. RESULTS: COX univariate regression analysis of all patients showed that Masaoka stage, T stage, WHO histologic types, D-dimer, albumin-fibrinogen ratio (AFR), Fibrinogen (Fbg) were associated with postoperative overall survival (P < .05). T stage, WHO histologic types, D-dimer, and AFR were associated with postoperative recurrence-free survival (P < .05). Finally, multivariate regression analysis showed that T stage, D-dimer levels were independently associated with postoperative overall survival (OS) and recurrence-free survival (RFS) in patients with thymic epithelial tumors. CONCLUSIONS: For thymic epithelial tumors, higher preoperative D-dimer levels predict poorer survival and shorter recurrence-free survival. This may help guide postoperative adjuvant therapy and follow-up patterns in patients with thymic epithelial tumors.

Prognostic Value of Preoperative Serum Carcinoembryonic Antigen for Overall Survival and Recurrence-Free Survival in Resectable Thymic Epithelial Tumors.

Introduction: Tumor markers have been shown to be closely related to the long-term survival of patients with cancer and the recurrence of various malignant tumors. However, their role in thymic epithelial tumors (TETs) remains to be elucidated. We aimed to investigate whether the preoperative tumor biomarkers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) could serve as independent predictors of postoperative prognosis in patients with TETs. Materials and Methods: We retrospectively included a total of 111 patients with TETs who underwent thymectomy at our hospital. Cox regression analysis was used to evaluate the statistical significance of CEA and NSE as independent predictors of overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier curves were used to present the results of our survival analyses. Results: Cox regression analysis showed that T stage, World Health Organization (WHO) histologic type, tumor size, and CEA levels served as independent prognostic factors for OS (P < .05). Whereas for RFS, multivariate analysis showed that only T stage, WHO histologic type, and drinking history were independently associated with it (P < .05). Conclusion: Our study found that preoperative serum CEA levels and tumor size may be strong predictors of postoperative OS in patients with TETs.

Prognostic Value of Preoperative Nutritional Assessment and Neutrophil-to-Lymphocyte Ratio in Patients With Thymic Epithelial Tumors.

Introduction: Systemic nutrition and immune inflammation are the key factors in cancer development and metastasis. This study aimed to compare and assess four nutritional status and immune indicators: prognostic nutritional index (PNI), nutritional risk index (NRI), neutrophil-to-lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII) as prognostic indicators for patients with thymic epithelial tumors. Materials: We retrospectively reviewed 154 patients who underwent thymic epithelial tumor resection at our hospital between 2004 and 2015. The optimal cutoff value for each nutritional and immune index was obtained using the X-tile software. Kaplan-Meier curves and Cox proportional hazards models were used for survival analysis. Results: Univariate analysis showed that PNI, NRI, NLR, SII, albumin (ALB), the albumin/globulin ratio (A/G), WHO stage, T stage, and drinking history were associated with the overall survival (OS) of patients (P < 0.05). The NRI, NLR, A/G, ALB, T stage, and WHO stage were significant independent prognostic factors of OS in multivariate analysis (P < 0.05). Finally, we constructed a coNRI-NLR model to predict OS and recurrence-free survival (RFS). Conclusions: This study suggests that the preoperative NRI, NLR, and coNRI-NLR model may be important prognostic factors for patients with thymic epithelial tumors who undergo surgical resection.

Postoperative survival effect of the number of examined lymph nodes on esophageal squamous cell carcinoma with pathological stage T1-3N0M0.

BACKGROUND: The postoperative survival effect of the number of examined lymph nodes on patients of R0-resected esophageal squamous cell carcinoma with pathological stage T1-3N0M0 is still unclear. METHODS: Patients diagnosed with pathological stage T1-3N0M0 esophageal squamous cell carcinoma from two cancer databases-our cancer center (N = 707), and Surveillance Epidemiology and End Results (N = 151). The primary clinical endpoint was overall survival. The X-tile software was used to determine the optimal cutoff value of the number of examined lymph nodes, and propensity score matching was conducted to reduce selection bias according to the results of X-tile software. The cohort of 151 patients from another database was used for validation. RESULTS: X-tile software provided an optimal cutoff value of 15 examined lymph nodes based on 707 patients, and 231 pairs of matched patients were included. In the unmatched cohort, Cox proportional hazard regression analysis revealed better overall survival in patients with more than 15 examined lymph nodes (adjusted hazard ratio, 0.566, 95% confidence interval, 0.445-0.720; p < 0.001) compared with patients with 15 or fewer examined lymph nodes. In the validation cohort, patients with more than 15 examined lymph nodes also had better overall survival (adjusted hazard ratio 0.665, p = 0.047). CONCLUSIONS: The number of examined lymph nodes is a significant prognostic factor in esophageal squamous cell carcinoma patients with pathological stage T1-3N0M0, and more than 15 examined lymph nodes are associated with better overall survival. Although the difference is not significant, the survival curve of patients with examined lymph nodes > 30 is better than those with examined lymph nodes 15-30. We believe that the number of examined lymph nodes can provide prognostic guidance for those patients, and the more examined lymph nodes cause lesser occult lymph nodes metastasis and lead to a better prognosis. Therefore, surgeons and pathologists should try to examine as many lymph nodes as possible to evaluate the pathological stage precisely. However, we need more validation from other studies.

Nomogram predict relapse-free survival of patients with thymic epithelial tumors after surgery.

BACKGROUND: Hematological indicators and clinical characteristics play an important role in the evaluation of the progression and prognosis of thymic epithelial tumors. Therefore, we aimed to combine these potential indicators to establish a prognostic nomogram to determine the relapse-free survival (RFS) of patients with thymic epithelial tumors undergoing thymectomy. METHODS: This retrospective study was conducted on 156 patients who underwent thymectomy between May 2004 and August 2015. Cox regression analysis were performed to determine the potential indicators related to prognosis and combine these indicators to create a nomogram for visual prediction. The prognostic predictive ability of the nomogram was evaluated using the consistency index (C-index), receiver operating characteristic (ROC) curve, and risk stratification. Decision curve analysis was used to evaluate the net benefits of the model. RESULTS: Preoperative albumin levels, neutrophil-to-lymphocyte ratio (NLR), T stage, and WHO histologic types were included in the nomogram. In the training cohort, the nomogram showed well prognostic ability (C index: 0.902). Calibration curves for the relapse-free survival (RFS) were in good agreement with the standard lines in training and validation cohorts. CONCLUSIONS: Combining clinical and hematologic factors, the nomogram performed well in predicting the prognosis and the relapse-free survival of this patient population. And it has potential to identify high-risk patients at an early stage. This is a relatively novel approach for the prediction of RFS in this patient population.

Identification of TH Variants in Chinese Dopa-Responsive Dystonia Patients and Long-Term Outcomes.

Background: Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder. Methods: Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared). Results: A total of 20 DRD patients were included (11 with GCH1 variants, 9 with TH variants). During long-term levodopa treatment, three patients with TH variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG. Conclusions: Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with TH variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms.

A Nomogram to Predict Long-Term Survival Outcomes of Patients Who Undergo Pneumonectomy for Non-small Cell Lung Cancer With Stage I-IIIB.

Background: In this study, we aim to establish a nomogram to predict the prognosis of non-small cell lung cancer (NSCLC) patients with stage I-IIIB disease after pneumonectomy. Methods: Patients selected from the Surveillance, Epidemiology, and End Results (SEER, N = 2,373) database were divided into two cohorts, namely a training cohort (SEER-T, N = 1,196) and an internal validation cohort (SEER-V, N = 1,177). Two cohorts were dichotomized into low- and high-risk subgroups by the optimal risk prognostic score (PS). The model was validated by indices of concordance (C-index) and calibration plots. Kaplan-Meier analysis and the log-rank tests were used to compare survival curves between the groups. The primary observational endpoint was cancer-specific survival (CSS). Results: The nomogram comprised six factors as independent prognostic indictors; it significantly distinguished between low- and high-risk groups (all P < 0.05). The unadjusted 5-year CSS rates of high-risk and low-risk groups were 33 and 60% (SEER-T), 34 and 55% (SEER-V), respectively; the C-index of this nomogram in predicting CSS was higher than that in the 8th TNM staging system (SEER-T, 0.629 vs. 0.584, P < 0.001; SEER-V, 0.609 vs. 0.576, P < 0.001). In addition, the PS might be a significant negative indictor on CSS of patients with white patients [unadjusted hazard ration (HR) 1.008, P < 0.001], black patients (unadjusted HR 1.007, P < 0.001), and Asian or Pacific Islander (unadjusted HR 1.008, P = 0.008). In cases with squamous cell carcinoma (unadjusted HR 1.008, P < 0.001) or adenocarcinoma (unadjusted HR 1.008, P < 0.001), PS also might be a significant risk factor. Conclusions: For post-pneumonectomy NSCLC patients, the nomogram may predict their survival with acceptable accuracy and further distinguish high-risk patients from low-risk patients.

Prognostic Modeling of Patients Undergoing Surgery Alone for Esophageal Squamous Cell Carcinoma: A Histopathological and Computed Tomography Based Quantitative Analysis.

OBJECTIVE: To evaluate the effectiveness of a novel computerized quantitative analysis based on histopathological and computed tomography (CT) images for predicting the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients. METHODS: We retrospectively reviewed the medical records of 153 ESCC patients who underwent esophagectomy alone and quantitatively analyzed digital histological specimens and diagnostic CT images. We cut pathological images (6000 × 6000) into 50 × 50 patches; each patient had 14,400 patches. Cluster analysis was used to process these patches. We used the pathological clusters to all patches ratio (PCPR) of each case for pathological features and we obtained 20 PCPR quantitative features. Totally, 125 computerized quantitative (20 PCPR and 105 CT) features were extracted. We used a recursive feature elimination approach to select features. A Cox hazard model with L1 penalization was used for prognostic indexing. We compared the following prognostic models: Model A: clinical features; Model B: quantitative CT and clinical features; Model C: quantitative histopathological and clinical features; and Model D: combined information of clinical, CT, and histopathology. Indices of concordance (C-index) and leave-one-out cross-validation (LOOCV) were used to assess prognostic model accuracy. RESULTS: Five PCPR and eight CT features were treated as significant indicators in ESCC prognosis. C-indices adjusted for LOOCV were comparable among four models, 0.596 (Model A) vs. 0.658 (Model B) vs. 0.651 (Model C), and improved to 0.711with Model D combining information of clinical, CT, and histopathology (all p<0.05). Using Model D, we stratified patients into low- and high-risk groups. The 3-year overall survival rates of low- and high-risk patients were 38.0% and 25.0%, respectively (p<0.001). CONCLUSION: Quantitative prognostic modeling using a combination of clinical data, histopathological, and CT images can stratify ESCC patients with surgery alone into high-risk and low-risk groups.

Association between number of dissected lymph nodes and survival in stage IA non-small cell lung cancer: a propensity score matching analysis.

BACKGROUND: For patients with stage IA non-small cell lung cancer (NSCLC) with tumor size ≤ 2 cm, the prognostic significance of the number of removed lymph nodes (NLNs) through different surgical methods remains unclear. To determine the association of NLNs with cancer-specific survival (CSS) and overall survival (OS) in patients with stage IA NSCLC with tumor size ≤ 2 cm who underwent different lung surgeries. METHODS: We retrospectively enrolled 7293 patients from the Surveillance, Epidemiology and End Results database. Median NLNs was used to classify the patients into two groups: group A with NLNs ≤ 5 and group B with NLNs > 5. Propensity score matching (PSM) was performed to decrease selection bias. Kaplan-Meier analysis and Cox regression analysis were performed to identify the association between NLNs and survival outcomes. RESULTS: Group B had better survival than group A in the unmatched cohort and matched cohort (all P < 0.05). Multivariable analyses revealed that the NLNs significantly affected CSS and OS of eligible cases in the unmatched cohort and matched cohort. Additionally, we found that the NLNs was a protective prognostic predictor of OS for patients who underwent wedge resection, segmental resection, or lobectomy. CONCLUSION: The NLNs was a protective prognostic factor in NSCLC patients with tumor size ≤ 2 cm. We demonstrated that patients with > 5 NLNs in the cohort of wedge resection, segmental resection, or lobectomy exhibited a significantly better OS.

Correction: +mRNA expression of LRRC55 protein (leucine-rich repeat-containing protein 55) in the adult mouse brain.

[This corrects the article DOI: 10.1371/journal.pone.0191749.].

+mRNA expression of LRRC55 protein (leucine-rich repeat-containing protein 55) in the adult mouse brain.

LRRC55 (leucine-rich repeat-containing protein 55) protein is an auxiliary γ subunit of BK (Big conductance potassium channel) channels, which leftward shifts GVs of BK channels around 50 mV in the absence of cytosolic Ca2+. LRRC55 protein is also the only γ subunit of BK channels that is expressed in mammalian nervous system. However, the expression pattern of LRRC55 gene in adult mammalian brain remains elusive. In this study, we investigated the distribution of LRRC55 mRNA in the adult mouse brain by using in situ hybridization. We found that LRRC55 mRNA is richly expressed in the adult mouse medial habenula nucleus (MHb), cerebellum and pons. However, the potential role of LRRC55 in MHb and cerebellum could be different based on the function of BK channels in these brain regions.

A familial Cri-du-Chat/5p deletion syndrome resulted from rare maternal complex chromosomal rearrangements (CCRs) and/or possible chromosome 5p chromothripsis.

Cri-du-Chat syndrome (MIM 123450) is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs), diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5)(p13.3p15.33) spanning ≈ 26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5) (q23;p14.1p15.31),ins(21;5)(q21;p13.3p14.1),ins(21;5)(q21;p15.31p15.33),inv(7)(p22q32)dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5) identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5). Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.