Search

Survival analyses of populations and the establishment of prognoses for individual patients are important activities in the practice of medicine. Standard survival models, such as the Cox proportional hazards model, require extensive feature engineering or prior knowledge to model at an individual level. Some survival analysis models can avoid these problems by using machine learning extended the CPH model, and higher performance has been reported. In this paper, we propose an innovative loss function that is defined as the sum of an extended mean squared error loss and a pairwise ranking loss based on ranking information on survival data. We apply this loss function to optimize a deep feed-forward neural network (RankDeepSurv), which can be used to model survival data. We demonstrate that the performance of our model, RankDeepSurv, is superior to that of other state-of-the-art survival models based on an analysis of 4 public medical clinical datasets. When modelling the prognosis of nasopharyngeal carcinoma (NPC), RankDeepSurv achieved better prognostic accuracy than the CPH established by clinical experts. The difference between high and low risk groups in the RankDeepSurv model is greater than the difference in the CPH. The results show that our method has considerable potential to model survival data in medical settings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The simplified thrombo-inflammatory score (sTIPS) has recently emerged as a novel prognostic score. Hence, we investigated the prognostic value of sTIPS for predicting long-term mortality in patients with heart failure (HF). Methods: A total of 3741 patients were analyzed in this study. The sTIPS was calculated based on the white blood cell count (WBC) and the mean platelet volume to platelet count (MPV/PC) ratio at admission. The mean follow-up time was 22.75 months. Multivariable Cox regression analyses were used to investigate the associations between the sTIPS and all-cause mortality (ACM). Results: In the whole study population, multivariate Cox regression analysis showed that patients in both the sTIPS 2 and sTIPS 1 groups had significantly increased risk of ACM as compared with patients in the sTIPS 0 group (hazard ratio [HR]=1.706, 95% confidence interval [CI]: 1.405– 2.072, P< 0.001 and HR = 1.431, 95% CI 1.270– 1.612, P< 0.001). The same significant trend was observed in heart failure with preserved ejection fraction (HFpEF) patients (sTIPS1 vs sTIPS0: HR = 1.366, 95% CI 1.100– 1.697, P = 0.005; sTIPS2 vs sTIPS0: HR = 1.995, 95% CI 1.460– 2.725, P< 0.001). However, only sTIPS 1 group had a significantly increased the risk of ACM compared to the sTIPS 0 group among patients with HFmrEF (sTIPS1 vs sTIPS0: HR = 1.648, 95% CI 1.238– 2.194, P = 0.001) and HFrEF (sTIPS1 vs sTIPS0: HR = 1.322, 95% CI 1.021– 1.712, P = 0.035). Conclusion: sTIPS is useful in predicting risk for long-term mortality in patients with HF. [ABSTRACT FROM AUTHOR]

Zinc finger protein 384 (ZNF384) rearrangement defined a novel subtype of B‐cell acute lymphoblastic leukemia (B‐ALL). The prognostic significance of ZNF384 fusion transcript levels represented measurable residual disease remains to be explored. ZNF384 fusions were screened out in 57 adult B‐ALL patients at diagnosis by real‐time quantitative polymerase chain reaction and their transcript levels were serially monitored during treatment. The reduction of ZNF384 fusion transcript levels at the time of achieving complete remission had no significant impact on survival, whereas its ≥2.5‐log reduction were significantly associated with higher relapse free survival (RFS) and overall survival (OS) rates after course 1 consolidation (p = 0.022 and = 0.0083) and course 2 consolidation (p = 0.0025 and = 0.0008). Compared with chemotherapy alone, allogeneic hematopoietic stem cell transplantation (allo‐HSCT) significantly improved RFS and OS of patients with <2.5‐log reduction after course 1 consolidation (p < 0.0001 and = 0.0002) and course 2 consolidation (p = 0.0003 and = 0.019), whereas exerted no significant effects in patients with ≥2.5‐log reduction (all p > 0.05). ZNF384 fusion transcript levels after course 1 and course 2 consolidation strongly predict relapse and survival and may guide whether receiving allo‐HSCT in adult B‐ALL. [ABSTRACT FROM AUTHOR]

Background: The prevalence of malnutrition is very high in patients with cancer. The purpose of this study was to investigate whether or not a nutrition support team (NST) could benefit esophageal cancer patients undergoing chemoradiotherapy (CRT). Methods: Between June 2012 and April 2014, 50 esophageal cancer patients undergoing concurrent CRT were randomly assigned into two groups: The NST group and the control group. The nutritional statuses of 25 patients in the NST group were managed by the NST. The other 25 patients in the control group underwent the supervision of radiotherapy practitioners. At the end of the CRT, nutritional status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay (LOS) and the in-patient cost were also compared between these two groups. Results: At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin (ALB), transferrin, and ALB parameters (P = 0.001, 0.000, and 0.000, respectively). The complication incidences, including bone marrow suppression (20% vs. 48%, P = 0.037) and complications related infections (12% vs. 44%, P = 0.012), in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy (96% vs. 76%, P = 0.103). Furthermore, the average LOS was decreased by 4.5 days (P = 0.001) and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times (P > 0.05) in the NST group. Conclusions: A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs.

To generate robust patient-derived xenograft (PDX) models for epithelial ovarian cancer (EOC), analyze the resemblance of PDX models to the original tumors, and explore factors affecting engraftment rates, fresh cancer tissues from a consecutive cohort of 158 patients with EOC were collected to construct subcutaneous PDX models. Paired samples of original tumors and PDX tumors were compared at the genome, transcriptome, protein levels, and the platinum-based chemotherapy response was evaluated to ensure the reliability of the PDXs. Univariate and multivariate analyses were used to determine the factors affecting the engraftment rates. The engraftment success rate was 58.23% (92/158) over 3–6 months. The Ki-67 index and receiving neoadjuvant chemotherapy can affect the engraftment rate in primary patients. The PDX models generated in this study were found to retain the histomorphology, protein expression, and genetic alteration patterns of the original tumors, despite the transcriptomic differences observed. Clinically, the PDX models demonstrated a high degree of similarity with patients in terms of the chemotherapy response and could predict prognosis. Thus, the PDX model can be considered a promising and reliable preclinical tool for personalized and precise treatment. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical characteristics, treatment and prognosis of fetal intracranial hemorrhage in pregnancy and to improve the level of diagnosis and treatment. Methods: We retrospectively analyzed the clinical data of eight cases of fetal intracranial hemorrhage in our hospital from 2014 to 2017, including the clinical manifestations, etiology, imaging features, treatment and prognosis. Results: All the cases were diagnosed by prenatal color ultrasound or magnetic resonance imaging (MRI); one of the cases had decreased fetal movements and abnormal fetal heart rate monitoring, and the remaining seven cases had no special clinical symptoms. No clear cause was found in all the cases. Two patients with grade I fetal intracranial hemorrhage and 1 patient with grade II had a cesarean delivery, and no neurological sequelae were found in these neonates after 6months of follow-up. There was one patient with grade III and four patients with grade IV fetal intracranial hemorrhage; one of the patients with grade IV was stillborn at the time of the discovery, and cesarean section was selected due to scarring of the uterus; intraamniotic injection of ethacridine lactate was selected to induce labor in three cases, and vaginal delivery was selected; one of the patients with grade IV chose vaginal delivery, and the neonatal cranial brain magnetic resonance imaging after delivery showed no increase in intracranial lesions but showed incomplete development of the remaining nervous system. Conclusion: Fetal intracranial hemorrhage can be diagnosed by prenatal color ultrasound and MRI, yet it is often impossible to determine the cause. The prognosis of fetal intracranial hemorrhage is related to grade, and the prognosis of cerebral hemorrhage in patients with grades III-IV is poor. [ABSTRACT FROM AUTHOR]

Background: Monocyte count and serum albumin (Alb) have been proven to be involved in the process of systemic inflammation. Therefore, we investigated the prognostic value of monocyte-to-albumin ratio (MAR) in patients who underwent percutaneous coronary intervention (PCI). Methods: We enrolled a total of 3561 patients in the present study from January 2013 to December 2017. They were divided into two groups according to MAR cut-off value (MAR < 0.014, n=2220; MAR = 0.014, n=1119) as evaluated by receiver operating characteristic (ROC) curve. The average follow-up time was 37.59 +- 22.24 months. Results: The two groups differed significantly in the incidences of all-cause mortality (ACM; P<0.001), cardiac mortality (CM; P<0.001), major adverse cardiovascular events (MACEs; P=0.038), and major adverse cardiovascular and cerebrovascular events (MACCEs; P=0.037). Multivariate Cox regression analyses revealed MAR as an independent prognostic factor for ACM and CM. The incidence of ACM increased by 56.5% (hazard ratio [HR] = 1.565; 95% confidence interval [CI], 1.086-2.256; P=0.016) and that of CM increased by 76.3% (HR = 1.763; 95% CI, 1.106-2.810; P=0.017) in patients in the higher-MAR group. Kaplan-Meier survival analysis suggested that patients with higher MAR tended to have an increased accumulated risk of ACM (Log-rank P<0.001) and CM (Log-rank P<0.001). Conclusion: The findings of the present study suggested that MAR was a novel independent predictor of long-term mortality in patients who underwent PCI. [ABSTRACT FROM AUTHOR]

aims to investigate whether the serum levels of brain natriuretic peptide (BNP), troponin I (TnI), and D-dimer, in addition to the neutrophil-to-lymphocyte ratio (NLR), can be used to determine the prognosis of patients with acute pulmonary embolism (APE). Methods: Data were collected from 72 patients that were diagnosed with APE in our hospital from January 2015 to December 2018. These patients were divided into three groups: a high-risk group (n = 10), a moderate-risk group (n = 33), and a low-risk group (n = 29). The serum levels of BNP, TnI, and D-dimer were determined, and the NLR was measured. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of the single and combined detection of BNP, TnI, and D-dimer, and the NLR was used to determine the prognosis of patients with APE. Results: The serum levels of BNP, TnI, and D-dimer were significantly higher in the high-risk group than they were in the moderate-risk and low-risk groups (P < 0.05). The serum levels of BNP, TnI, and D-dimer were also significantly higher in the moderate-risk group than they were in the low-risk group (P < 0.05). The serum levels of BNP, TnI, and D-dimer, as well as the NLR, were all significantly higher in the death group than they were in the survival group (P < 0.05). For the combined detection of the four indices, the area under the ROC curve was 0.92, the sensitivity was 0.889, and the specificity was 0.904; each of these values was higher than the corresponding values of single detection. Conclusion: In patients with APE, higher serum levels of BNP, TnI, D-dimer and NLR are associated with a higher risk stratification, greater severity of disease, and an increased risk of death. [ABSTRACT FROM AUTHOR]

Background: BRAF V600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients. The aim of this study is to evaluate the clinical and pathological features, prognostic value of BRAF mutations in CRC. Methods: We conducted a retrospective study to characterize the clinical and pathological features and survival of patients with BRAF mutated CRC. Patients were classified according to BRAF status as BRAF V600E mutation and non-V600E mutations. Difference of characteristics and survival between the two groups was analyzed. Results: There was no significant difference in gender, family history, location of primary tumor, metastatic sites between patients with BRAF -V600E mutation and non-V600E mutations. Patients with V600E mutation were younger than those with non-V600E mutations (p = 0.002). Patients with BRAF V600E mutation showed a poorer outcome than those with non-V600E mutations (23.1 vs. 49.9 months, respectively, p = 0.0024). Lack of CDX2 expression was associated with worse prognosis (mOS: 9.4 m vs. not reached, respectively, p = 0.016). Status of V600E mutation did not affect the mPFS and ORR of first-line or second-line treatment. Conclusion: BRAF V600E mutation defines a distinct subgroup of CRC with worse prognosis. Lack of CDX2 expression is associated with poor OS. Status of V600E mutation did not affect the mPFS of first-line or second-line treatment. [ABSTRACT FROM AUTHOR]

Purpose: To identify how Epstein‐Barr virus (EBV) status combined with molecular profiling predicts the prognosis of gastric cancer patients and their associated clinical actionable biomarkers. Experimental Design: A next‐generation sequencing assay targeting 295 cancer‐related genes was performed in 73 EBV‐associated gastric cancer (EBVaGC) and 75 EBV‐negative gastric cancer (EBVnGC) specimens and these results were compared with overall survival (OS). Results: PIK3CA, ARID1A, SMAD4, and PIK3R1 mutated significantly more frequently in EBVaGC compared with their corresponding mutation rate in EBVnGC. As the most frequently mutated gene in EBVnGC (62.7%), TP53 also displayed a mutation rate of 15.1% in EBVaGC. PIK3R1 was revealed as a novel mutated gene (11.0%) associated almost exclusively with EBVaGC. PIK3CA, SMAD4, PIK3R1, and BCOR were revealed to be unique driver genes in EBVaGC. ARID1A displayed a significantly large proportion of inactivated variants in EBVaGC. A notable finding was that integrating the EBV status with tumor mutation burden (TMB) and large genomic instability (LGI) categorized the tumors into four distinct molecular subtypes and optimally predicted patient prognosis. The corresponding median OSs for the EBV+/TMB‐high, EBV+/TMB‐low, EBV‐/LGI‐, and EBV‐/LGI+ subtypes were 96.2, 75.3, 44.4, and 20.2 months, respectively. The different subtypes were significantly segregated according to distinct mutational profiles and pathways. Conclusions: Novel mutations in PIK3R1 and TP53 genes, driver genes such as PIK3CA, SMAD4, PIK3R1, BCOR, and ARID1A, and distinguished genomic profiles from EBVnGC were identified in EBVaGC tumors. The classification of gastric cancer by EBV, TMB, and LGI could be a good prognostic indicator, and provides distinguishing, targetable markers for treatment. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Epstein–Barr virus (EBV)‐associated gastric carcinomas (EBVaGCs) may account for 8–9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV‐DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat‐sen University Cancer Center for EBER examination. We detected EBV‐DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV‐DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV‐negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3‐year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV‐DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV‐DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV‐DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients. What's new? Epstein–Barr Virus (EBV)‐associated gastric carcinomas (EBVaGC) may account for 8–9% of all gastric cancers (GC). The exact role of EBV status in predicting the prognosis of GC remains to be clarified, however. Here, the authors report a prevalence of EBVaGC in GC in China of 5.1%, as defined by EBER staining in cancerous tissue. EBVaGC patients had a better overall survival than EBV‐negative patients. Though only half of EBVaGC patients gained detectable plasma EBV‐DNA levels, elevated plasma EBV‐DNA predicted relapse and poor response to chemotherapy. Dynamic detection of plasma EBV‐DNA load may offer an easily accessible biomarker to monitor EBVaGC. [ABSTRACT FROM AUTHOR]

The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan–Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD. [ABSTRACT FROM AUTHOR]

Background: About 75% of newly diagnosed bladder cancer cases suffer from non-muscle invasive bladder cancer (NMIBC), which used to recur and progress despite transurethral resection of bladder tumor (TURBT). This meta-analysis was conducted to examine if combined application of intravesical bacille Calmette-Guérin (BCG) with chemotherapy is associated with better prognosis. Methods: Systematic searches of randomized controlled trials (RCTs) concerning NMIBC were performed in PubMed, EMbase, CENTRAL, CNKI, WanFang, VIP, CBM databases, and some specialized websites. Two researchers independently implemented study selection, quality assessment and data extraction. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for treatment effects on recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS) were directly extracted, if available, or estimated using relevant data from included studies. Side effects, such as fever, gastrointestinal reaction, cystitis, irritative bladder symptoms and hematuria, were also extracted as outcome measurements, and associated relative risks (RRs) were calculated to assess treatment safety. RevMan 5.3 software was used to perform statistical analyses. Results: Thirteen RCTs containing 1,754 patients with NMIBC were included in this meta-analysis. Compared with BCG alone, the combination therapy significantly improved RFS (HR = 0.53, 95% CI: 0.43–0.66, P < 0.01), OS (HR = 0.66, 95%CI: 0.50–0.86, P = 0.002), and DSS (HR = 0.48, 95%CI: 0.29–0.80, P = 0.005). While PFS showed no obvious difference between combination therapy and BCG alone (HR = 0.65, 95%CI: 0.25–1.68, P = 0.38). The rate of fever (RR = 0.50, 95%CI: 0.27–0.91, P = 0.02), irritative bladder symptoms (RR = 0.69, 95%CI: 0.52–0.90, P = 0.007) and hematuria (RR = 0.50, 95%CI: 0.28–0.89, P = 0.02) were significantly decreased in patients treated with combination therapy compared to those with BCG alone. There were no statistically significant differences between combination therapy and BCG alone in toxicity (RR = 0.69, 95%CI: 0.34–1.40, P = 0.30), gastrointestinal reaction (RR = 2.54, 95%CI: 0.61–10.60, P = 0.20) or cystitis (RR = 0.67, 95%CI: 0.29–1.54, P = 0.34). Conclusions: Combined application of intravesical BCG and chemotherapy appears to be an effective treatment for patients with intermediate- to high-risk NMIBC, but not for those with tumor in situ alone or recurrent bladder cancer. [ABSTRACT FROM AUTHOR]

Background: The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach.Patients and Methods: A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics.Results: The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3-4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3-4 AEs. High AUC0-24h of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS.Conclusions: Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. CLINICALTRIALS.Gov Identifier: NCT02090153. [ABSTRACT FROM AUTHOR]

Background X-linked lymphoproliferative disease (XLP) is a rare life-threatening syndrome. Rapid recognition and definitive diagnosis are critical to improve the prognosis and survival of patients with XLP. Nowadays, little is known about patients with XLP in China. Methods We report the characterization of five Chinese XLP patients with three novel mutations and review the literature related to this syndrome. Male patients with fulminant infectious mononucleosis (FIM), Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) or persistent EBV viraemia were enrolled in this study. The patients’ clinical features were assessed by retrieval of data from medical records. Immunological function included analysis of lymphocyte subsets and the detection of immunoglobulins G, A, M and/or E were evaluated by flow cytometry and nephelometry. Direct sequencing was used to detect SH2D1A/XIAP gene mutations. Results Twenty-two male patients with FIM, EBV-associated HLH or persistent EBV viraemia were evaluated among 421 PID patients in our centre. Four patients had SH2D1A mutations, and one patient had an XIAP mutation. The onset age of the 5 patients range from 1 month to 4 years which was earlier than that in the western world. The diagnosis age was between 16 months and 9 years with a long diagnosis lag (1–97 months). Two of them had positive family history. The clinical phenotypes varied in different patients among which two patients with FHLH and hypogammaglobulinaemia, one with hypogammaglobulinaemia, lymphoma and aplastic anaemia (AA) which is the first case with AA in China, one with hypogammaglobulinaemia only and the other one with FHLH. For immunological function, three exhibited reduced CD4/CD8 ratios. Arg55stop mutations as well as splice mutation in intron 1 were most frequently found and exon 2 was the hottest exon in China. Two patients died at the time of diagnosis for severe infection or hepatic coma. Three were alive and waiting for haematopoietic stem cell transplantation (HSCT). Conclusion For patients with severe EBV-associated HLH, hypogammaglobulinaemia, lymphoma and aplastic anaemia, possibility of XLP should be considered and if confirmed, HSCT should be performed as soon as possible. [ABSTRACT FROM AUTHOR]

The elevation of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) has been demonstrated to predict worse prognosis in various malignancies; however, their prognostic value in esophageal squamous cell carcinoma has not been well studied. We conducted a retrospective study of 906 patients with esophageal squamous cell carcinoma to explore their prognostic value for overall survival. The optimal cutoff points for ALP and LDH were determined. We analyzed the association between the levels of ALP and LDH and clinicopathological characteristics. Their prognostic value for overall survival was explored by univariate and multivariate analysis. We also proposed the ALP and LDH classification and examined its prognostic value in the general population and subgroups. The optimal cutoff points of ALP and LDH to predict overall survival were 90.7 and 361.5 U/L respectively. Higher levels of ALP and LDH were both associated with more advanced TNM stage ( P = 0.003 and 0.002, respectively) and more distant metastasis ( P = 0.001 and P < 0.001, respectively). Both ALP (≤90.7/>90.7 U/L) and LDH (≤361.5/>361.5 U/L) were independent prognostic factors for overall survival in esophageal squamous cell carcinoma ( P = 0.004 and P < 0.001 by multivariate analysis). The ALP and LDH classification categorized patients into three subgroups with distinct prognosis ( P < 0.001 by multivariate analysis) and identified a small group of patients who had extremely poor overall survival with a median of 4.2 months. In conclusion, ALP and LDH were both independent prognostic factors for overall survival. A combination of the two indexes might contribute to further identification of survival differences in esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the oncologic and reproductive outcomes after progestin treatment of complex endometrial hyperplasia (CEH) and grade 1 endometrial carcinoma (EC).Methods: In a retrospective study, data were obtained for patients aged 20-42years with CEH or grade 1 EC at presumed stage IA (without myometrial invasion) who wished to preserve fertility and were treated at the Peking Union Medical College Hospital, China, between January 1, 2000, and December 31, 2011. Patients had received oral medroxyprogesterone acetate (250-500mg/day) or megestrol acetate (160-480mg/day) for at least 6months. Response to progestin treatment was assessed histologically.Results: Among 53 included patients, 39 (74%) achieved complete response after a median period of 6 (3-24) months. Complete response was less frequent among obese than nonobese patients (4/12 [33%] vs 35/41 [85%]; P=0.001). Disease recurrence was recorded in 10 (26%) patients with complete response; the 5-year recurrence-free survival rate was 71%. Among the 33 patients who retained a desire to conceive, 17 (52%) became pregnant.Conclusion: Fertility-sparing management with oral progestin is effective. Obesity is associated with a lower probability of long-term success. [ABSTRACT FROM AUTHOR]

The monoclonal antibody trastuzumab has brought survival benefit to patients with advanced gastric cancer (AGC) that have human epidermal growth factor receptor 2 (HER2) over expression or amplification. This study was designed to compare the clinical outcomes of HER2-negative and HER2-positive AGC patients with or without trastuzumab treatment. There were three groups of patients enrolled for analysis. Group A was 51 HER2-positive AGC patients treated with trastuzumab and chemotherapy; group B was a matched control group of 47 HER2-positive patients who received chemotherapy only; group C was a matched group of 251 HER2-negative patients who received chemotherapy. All the patients were enrolled at Sun Yat-sen University Cancer Center or Zhongshan Hospital, Fudan University between January 2010 and December 2012. The primary endpoint was overall survival (OS). The Kaplan-Meier method and log-rank test were used for survival analysis. The median duration of follow-up was 13.5 months (range 5-18.6 months). The median OS of these three groups of patients was 14.8 months, 11.3 months and 14.4 months respectively ( p < 0.001). The survival difference between group A and B was significant, p < 0.001. Similarly, there was significant difference between group B and C, p < 0.001. Moreover the survival between group A and C was comparable, p = 0.281. The median progression-free survival for these three groups was 7.4, 6.0 and 7.2 months. Multivariate analysis confirmed that trastuzumab treatment was an independent prognostic factor in group A and B patients ( p = 0.017). HER2 positive was an independent adverse prognostic factor in group B and C patients ( p = 0.013). [ABSTRACT FROM AUTHOR]

Abstract: Background: This study was designed to evaluate the value of plasma cystatin C in predicting adverse cardiac events after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Methods: A total of 605 patients (404 male, mean age 60.4 ± 10.6 years) with ACS underwent successful PCI. Patients were divided into 4 groups according to the level of cystatin C, which was measured before the PCI: Q1 (<1.02 mg/L), Q2 (1.02-1.16 mg/L), Q3 (1.17-1.34 mg/L), and Q4 (≥1.35 mg/L). Results: After a follow-up of 14.3 ± 1.7 months, the incidence of mortality, nonfatal myocardial infarction, and target lesion revascularization in the Q2, Q3, and Q4 groups was higher than in the Q1 group (P < .001). The incidence of heart failure in the Q3 and Q4 groups was higher than in the Q1 group (P < .05). Multivariate Cox regression analysis showed that cystatin C elevation was an independent predictor of major adverse cardiac events. The cumulative survival rate of the Q3 and Q4 groups was lower than in the Q1 group (P < .001). Conclusion: High plasma cystatin C concentration is an independent predictor of major adverse cardiac events in patients with ACS treated with PCI. [Copyright &y& Elsevier]

Summary: Early-stage oral cancer patients may have distinct clinical outcomes and respond differently to the same treatment. Up to now, there is still no individual marker to identify such patients with poor outcome. Down-regulation of a tumor suppressor gene, S100A2, in oral cancer cells was identified by mRNA profiling analysis then confirmed by RT-PCR and Southern blotting. The expression of nuclear S100A2 protein examined by immunohistochemistry was not significantly associated with any patient characteristic among the 70 early-stage oral squamous cell carcinoma (SCC) patients. Intriguingly, the loss of nuclear S100A2 positivity was significantly associated with shorter disease-free survival (p =0.019) while having no effect on the overall survival of these patients. Cox regression analysis with backward elimination identified S100A2 (p =0.006), tobacco smoking (p =0.013), and betel quid chewing (p =0.019) as independent predictors of disease-free survival. This is a first study to demonstrate that loss of nuclear S100A2 may serve as an independent prognostic marker for early-stage oral cancer patients at high risk of recurrence. A more aggressive treatment modality and intensive follow-up may be recommended for the patients with reduced expression of S100A2 in tumor cell nuclei. [Copyright &y& Elsevier]

The prognostic heterogeneity in patients with BRAF V600E metastatic colorectal cancer (mCRC) remains poorly defined. Real-world data of 93 BRAF V600E mCRC patients from Sun Yat-sen University Cancer Center were evaluated using the prognostic factors affecting overall survival (OS). Treatment of metastases served as an independent prognosticator, where curative locoregional interventions (LRIs) were associated with superior clinical outcomes (adjusted hazard ratio (HR): 0.46, 95% confidence interval (CI): 0.22–0.98; p = 0.044). The LRIs group showed an improved median OS of 49.4 months versus 18.3 months for the palliative treatments (PTs) group. The median OS of patients with colorectal liver metastasis (CRLM) was significantly prolonged after undergoing LRIs (42.4 vs. 23.7 months; HR: 0.11, 95% CI: 0.01–1.22; p = 0.030), and patients in the LRIs plus liver-limited or lung-limited metastasis (LLM) group benefited more than those in the LRIs plus non-LLM group when compared to the PTs group (LLM from LRIs vs. PTs, HR: 0.16, 95% CI: 0.04–0.68; p = 0.006. Non-LLM from LRIs vs. PTs, HR: 0.47, 95% CI: 0.21–1.05; p = 0.074). In conclusion, we confirmed the positive prognostic value of LRIs in BRAF V600E mCRC, particularly in patients with CRLM or LLM. [ABSTRACT FROM AUTHOR]

Abstract Background Aberrant DNA methylation is significantly associated with breast cancer. Methods In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis. Results In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994–1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976–1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival. Conclusions Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

Summary: Gelsolin has important cellular functions, including cell motility, proliferation and apoptosis. Altered gelsolin expression has been reported in several types of human malignancies, but has not been evaluated in oral carcinogenesis. In this study, all normal oral mucosa (n =12) had high gelsolin expression, whereas only 7.7% of oral precancerous lesions (n =26) had positive gelsolin expression. A significant increased positive staining was found in primary (n =51; 37.3%) and metastatic (n =26; 30.8%) oral squamous cell carcinoma lesions. Tumors with high gelsolin expression were associated with greater tumour size (P =0.007), invasive growth (P =0.02), and younger age (P =0.006). High gelsolin expression conferred a poor clinical outcome in patients with metastatic disease (P =0.005). In conclusion, a biphasic profile in gelsolin expression was observed during the progression of oral carcinogenesis. This may be due to a balance of its multiple cellular functions in tumour invasion and cell growth. The underlying mechanisms, however, remain to be elucidated. [Copyright &y& Elsevier]