Newly Diagnosed IDH-Wildtype Glioblastoma and Temporal Muscle Thickness: A Multicenter Analysis

Background: Reduced temporal muscle thickness (TMT) has been discussed as a prognostic marker in IDH-wildtype glioblastoma. This retrospective multicenter study was designed to investigate whether TMT is an independent prognostic marker in newly diagnosed glioblastoma. Methods: TMT was retrospectively measured in 335 patients with newly diagnosed glioblastoma between 1 January 2014 and 31 December 2019 at the University Hospitals of Leipzig and Rostock. The cohort was dichotomized by TMT and tested for association with overall survival (OS) after 12 months by multivariate proportional hazard calculation. Results: TMT of 7.0 mm or more was associated with increased OS (46.3 ± 3.9% versus 36.6 ± 3.9%, p > 0.001). However, the sub-groups showed significant epidemiological differences. In multivariate proportional hazard calculation, patient age (HR 1.01; p = 0.004), MGMT promoter status (HR 0.76; p = 0.002), EOR (HR 0.61), adjuvant irradiation (HR 0.24) and adjuvant chemotherapy (HR 0.40; all p < 0.001) were independent prognostic markers for OS. However, KPS (HR 1.00, p = 0.31), BMI (HR 0.98, p = 0.11) and TMT (HR 1.06; p = 0.07) were not significantly associated with OS. Conclusion: TMT has not appeared as a statistically independent prognostic marker in this cohort of patients with newly diagnosed IDH-wildtype glioblastoma.

Co-expression of Mesothelin and CA125/MUC16 Is a Prognostic Factor for Breast Cancer

Background: The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the clinicopathological significance and prognostic implications of the co-expression of mesothelin and CA125 in breast cancer. Methods: The expression of mesothelin and CA125 was immunohistochemically examined in tissue samples collected from 478 breast cancer patients. The expression of these two molecules in more than 1% of tumor cells was defined as positive. The relationships between the co-expression of mesothelin and CA125, clinicopathological parameters, and clinical outcomes were analyzed by the chi-squared test and Cox’s univariate and multivariate proportional hazard model analyses. Results: Among 478 patients, mesothelin and CA125 were co-expressed in 48 (10%), mesothelin only in 75 (16%), CA125 only in 217 (45%), and neither in 234 (49%). A strong correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with unfavorable patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox’s multivariate analysis. Conclusion: This is the first study to demonstrate the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of these two molecules may play a significant role in the acquisition of aggressive clinical behavior.

SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma

Immunoreactions regulated by TAMs (Tumor-associated macrophages) play a pivotal role in tumorigenesis and metastasis. In recent decades, treatments based on immune regulation have achieved revolutionary breakthroughs in cancer targeted therapies. The phenotypes of TAMs in gliomas are more heterogeneous and inherently complex than can be simply defined by classification into the M1 and M2 polarized states. The detailed mechanisms surrounding infiltrating macrophage phenotype and glioma characteristics remain undefined. SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) was found to be highly expressed in glioma and closely related to histological and genetic features in CGGA and TCGA databases. Simultaneously, we present evidence to show that there was a positive association between SAMD9 and malignancy characters in LGG. Univariable and Multivariate proportional hazard Cox analysis showed that SAMD9 was an independent prognostic factor for LGG. Surprisingly, Gene Ontology (GO) analysis showed SAMD9 expression level was remarkably well correlated with immunological responses and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis supported the connection with immune responses and tumorigenesis. Immune infiltration analysis demonstrated that high SAMD9 expression resulted in an accumulation of macrophages by CIBERSORT and TIMER databases, especially positively related to macrophage total marker gene AIF1 and Macrophage M2 marker gene CD163. IHC staining further indicated a high correlation of SAMD9 with those specific macrophage markers in the immune response. Human THP-1 cells were induced into M2 macrophages, which were then co-cultured with LN229 cells. Silencing of SAMD9 by shRNA in LN229 cells attenuated the infiltration abilities of M2 macrophage. SAMD9 explored immune response via relating of M2 macrophage in vitro. Our results revealed SAMD9 acted as the malignancy characters in LGG, enrichment with M2 macrophage.

Risk factors for tumor recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma after esophagectomy

Objective To analyze the factors contributing to recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC). Methods Patients with pT3N0M0 thoracic ESCC who underwent esophagectomy from January 2008 to December 2012 were included retrospectively. The last date of follow-up was 1 December 2016. Multivariate proportional hazard Cox models were used to identify factors associated with total (i.e., any) recurrence (TR), locoregional recurrence (LR), and distant metastasis (DM). Results A total of 692 patients were included. The median follow-up was 53 months (range: 3–107). The 3- and 5-year TR, LR, and DM rates were 35.8% and 41.0%, 28.7% and 32.1%, and 16.8% and 21.1%, respectively. The Cox analyses showed that the tumor location, number of dissected lymph nodes, and postoperative therapies were significantly associated with LR. The subgroup analysis showed that postoperative therapies could significantly decrease LR in the mediastinum but not in the neck and upper abdomen regions. Conclusions The recurrence rate of pT3N0M0 thoracic ESCC patients was high, especially for LR in the mediastinum. Postoperative therapies can significantly reduce the incidence of mediastinal recurrence.

The Value of Cervical Node Features in Predicting Long-Term Survival of Nasopharyngeal Carcinoma in Intensity-Modulated Radiotherapy Era

The prognostic value of cervical node features in nasopharyngeal carcinoma(NPC) patients treated with intensity-modulated radiotherapy (IMRT) was controversial. In this study, about 1752 patients after IMRT from 2008 to 2011 were recruited. The nodal features including the nodal number, maximize dimension diameter, extranodal extension(ENE)and cervical node necrosis(CNN) were retrospective analyzed. Univariate Cox and multivariate proportional hazard regression models were used to test the prognostic value of nodal features. Prognostic nomograms were built to predict the survival. The 10-year distant metastases free survival (DMFS) and disease-specific survival(DSS) rates were 86.5% and 80.8%. By multivariate analysis, the independent factors for the DSS were gender, age, lactate dehydrogenase (LDH), CNN, ENE, T stage and N stage. Nomogram A (without nodal features ) and nomogram B (with nodal features) were built. The calibration curve for the probability of DSS showed good agreement between prediction by nomogram and actual observation.The C-index of nomogram B was higher than for nomogram A in predicting DSS ( 0.708 vs 0.676,P <.01). These results demonstrated the nodal features including the ENE and CNN were negative prognostic factors in patients with NPC, and the prognostic nomogram incorporating the nodal features was more accurate.

Prognostic factors of pulmonary hypertension associated with connective tissue disease: pulmonary artery size measured by chest CT

Objective Pulmonary artery enlargement is a common manifestation of chest CT in patients with pulmonary arterial hypertension (PAH). The exact clinical significance of this phenomenon has not been clarified in connective tissue disease (CTD)-associated PAH (CTD-PAH). We aimed to explore the association between the dilatation of pulmonary artery and prognosis of CTD-PAH patients. Methods We retrospectively investigated 140 CTD-PAH patients diagnosed by echocardiography from 2009 to 2018. A chest multi-slice CT was performed on all the patients. Main pulmonary artery (MPA), right pulmonary artery (RPA), left pulmonary artery (LPA), ascending aorta (AAo) and descending aorta (DAo) diameters were measured. The ratios MPA/AAo and MPA/DAo were also calculated. The primary end point was all-cause mortality. Results During the observational period of 3.44 (0.23) years, 36 patients were followed to death. Cox univariate proportional hazard analysis showed that age, gender, MPA diameter, LPA diameter and RPA diameter were related to the risk of 5-year all-cause mortality in patients with CTD-PAH. In Cox multivariate proportional hazard analysis, MPA diameter and gender were predictors of all-cause mortality in CTD-PAH patients. An all-cause mortality risk prediction model revealed that baseline MPA diameter has the ability to predict 5-year all-cause mortality in CTD-PAH patients. Kaplan–Meier analysis showed that the 5-year survival rate was significantly lower in patients with MPA ≥37.70 mm (P ≤ 0.00012) compared with MPA ≤ 37.70 mm. Conclusion MPA diameter ≥37.70 mm measured by chest multi-slice CT was a potential independent risk factor of the poor long-term prognosis in Chinese CTD-PAH patients.

Potential Parenthood and Career Progression of Men and Women – A Simultaneous Hazards Approach

We analyze individual career transitions of men and women in Germany. Our particular focus is on the association of upward, downward and horizontal job changes with individual fertility. In contrast to most of the literature, we focus onpotentialrather thanrealizedfertility. Based on mixed multivariate proportional hazard models with competing risks, we find a significant negative relationship between the contemporaneous probability of having a child and horizontal career transitions for women and a positive significant association of the hazard of parenthood with upward career transitions for men. These effects persist when we apply fixed-effects panel data models allowing for correlation of individual parenthood hazards with unobserved individual characteristics. Our results suggest clear gender differences in the relationship between career patterns and potential fertility.

The Use of Antidepressant Medication before and after the Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Cohort Study

Background: The prevalent use of antidepressants (ATDs) in patients with Amyotrophic Lateral Sclerosis (ALS) varies across cross-sectional and clinic-based published studies. This population-based cohort study assesses the real-world prevalence of the use of ATDs, its trajectory and the association of incident use with clinical characteristics. Methods: All patients with incident ALS in the Friuli Venezia Giulia region, Italy, from 2002 to 2009, were identified through multiple sources including health databases. Diagnosis was validated through clinical documentation review. ATDs prescriptions from 2000 to 2011 were obtained from regional database. The trajectory was estimated through generalized estimating equations for repeated measures logistic regression and the Hazard ratio (HR) of initiating ATDs through multivariate proportional hazard Cox regression. Results: In this cohort of 261 ALS cases, age-, sex-adjusted prevalence of the use of ATDs was 37.3%, higher than in general population. The trajectory increased by 16% in 1-year period across diagnosis. Age ≤67 years at diagnosis (HR 1.28, 95% CI 0.84-1.95) and bulbar onset (1.43, 95% CI 0.90-2.26) were positively associated with initiating ATDs after diagnosis. Conclusions: More than one-third of patients used ATDs. Depression may occur more frequently than previously reported. Depression may precede motor alterations and be related to both ALS diagnosis and progression.

Survival outcomes of schirrhus gastric cancer treated by multidisciplinary treatments: Putative impact on prognosis by DCS NAC.

128 Background: Among gastric cancer, schirrhus exhibited the poorest prognosis, and many patients die even after curative resection due to recurrence. Although progress of multidisciplinary treatments of advanced gastric cancer is outstanding, recent clinical outcome is obscure by such intensive treatments. Methods: Among the 5,664 gastric cancer patients who underwent gastrectomy between 1971 and 2013 in the Kitasato University Hospital, 287 of shirrhus gastric cancer were included (5%). We divided the total periods into early (1971-2004) and late period (2005-2013), and compared their prognosis. Multivariate proportional hazard model was applied to the significant univariate prognostic factors (p<0.05), and identified independent prognostic factors (IPFs). Finally we compared the IPFs in terms of periods, and discuss the most appropriate treatments. Results: (1) Five-year survival rate was 13% and 31% in the early and late periods, respectively (p=0.0010). Between the periods, there were significant differences of pT (p=0.013), CY (p<0.0001), and Margin status (p=0.041). (2) Univariate prognostic factors were age (p=0.032), pT (p=0.0009), pN (p<0.0001), P (p=0.0033), CY (p=0.0002), and Margin status (p<0.0001). Multivariate proportional hazard model elucidated IPFs of pN (pN0-2 vs pN3a-X, p<0.0001) and Margin status (positive vs negative, p=0.0003). If the 2 factors were combined, patients with pN0-2 plus margin negative showed much better survival (about 40% of 5-year OS) than otherwise cases (below 10%)(p<0.0001). (3) Comparison of the IPFs between early and late periods, margin positive cases were significantly less infrequent in the late period. This may be aggressive application of neoadjuvant chemotherapy of DCS (Docetaxel/CDDP/S1). Conclusions: Due to recent progress of multidisciplinary treatments of preoperative aggressive chemotherapy and surgery with curative intent for negative margin for schirrhus gastric cancer, its 5-year survival was dramatically improved. pN0-2 patients were promising for reasonable prognosis if negative margin is secured, so intraoperative diagnosis must be urgently developed.