Reliable Predictive Markers Research Articles

Tumor contour irregularity on preoperative imaging: a practical and useful prognostic parameter for papillary renal cell carcinoma.

To illustrate tumor contour irregularity on preoperative imaging with a practical method and further determine its value in predicting disease-free survival (DFS) in patients with pRCC (papillary renal cell carcinoma). We performed a retrospective single-institution review of 267 Chinese pRCC patients between March 2009 and May 2019. Contour irregularity on cross-section was classified into smooth but distorted margin, unsmooth and sharply nodular margin, and blurred margin. Then, the ratio of the cross-section numbers of irregularity and the total tumor was defined as the contour irregular degree (CID). Cox regression and Kaplan-Meier analysis were performed to analyze the impact of CID on DFS. Then, the prognostic performance of CID was compared with pRCC risk stratification published by Leibovich et al. RESULTS: The median follow-up was 45 months (IQR: 23-69), in which 27 (10%) patients had metastasis or recurrence. Observed DFS rates were 95%, 90%, and 88% at 1, 3, and 5 years. The CID was an independent prognostic factor of DFS (HR = 1.048, 95% CI = 1.029-1.068, p < 0.001). The Kaplan-Meier plot showed that high-risk patients (CID ≥ 50%) tended to have a significantly shorter DFS (p < 0.001). The CID and Leibovich's pRCC model for DFS prediction had a C-index of 0.934 (95% CI = 0.907-0.961) and 0.833 (95% CI = 0.739-0.927) respectively. With our standard and practical method, the CID can be a reliable imaging marker for DFS prediction in patients with pRCC. • The updated contour irregularity was an independent parameter for predicting disease-free survival in patients with pRCC. • High-risk pRCC patients (contour irregular degree ≥ 50%) tended to have a shorter disease-free survival. • Tumor contour irregularity in pRCC risk stratification outperformed Leibovich's model from our cohort.

Neopterin Predicts Disease Severity in Hospitalized Patients With COVID-19.

This study evaluates the predictive value of circulating inflammatory markers, especially neopterin, in patients with coronavirus disease 2019 (COVID-19). Within this retrospective analysis of 115 hospitalized COVID-19 patients, elevated neopterin levels upon admission were significantly associated with disease severity, risk for intensive care unit admission, need for mechanical ventilation, and death. Therefore, neopterin is a reliable predictive marker in patients with COVID-19 and may help to improve the clinical management of patients.

GENECHOC study: genetic markers of arrhythmic risk in heart failure

Abstract Background Ventricular arrhythmic events are responsible for 50% of death in heart failure but no reliable predictive marker is known to discriminate patients at risk of fatal arrhythmia. Interestingly, familial predisposition has been reported suggesting a role of genetic factors. Purpose Identify genetic markers increasing the arrhythmic risk in heart failure population. Method We prospectively included heart failure patients with left ventricular ejection fraction (LVEF) under 35% and a cardioverter defibrillator in primary prevention in 22 French centres between 2009 and 2017. Patients were followed for 72 months and divided into two groups: cases with an arrhythmic event during follow-up and controls. A Genome Wide Association Study (GWAS) was done. Single Nucleotide Polymorphisms (SNPs) genotyping was performed on Affymetrix Axiom Precision Medicine Research Array plates. To complement the directly genotyped SNPs we performed large-scale imputation based on the Haplotype Reference Consortium European ancestry panel leading to a dataset of 7,5 million of SNPs. Results 332 cases and 567 controls were included (86% men, mean age at implantation 52±11 years). 78% of patients had ischaemic cardiopathy, 20% had dilated cardiomyopathy. Mean LVEF was 27±5%. No statistical difference was found between cases and controls on clinical parameters, biological results, electrocardiographic measures. No locus shows genome-wide significant association (p&amp;lt;5.10–8) on the GWAS analysis. However, 16 signals with a p-value between 5.10–8 and 5.10–5 were investigated. eQTL and chromatin conformation point to 35 genes with cardiac expression previously associated with heart failure, cardiomyopathies, cardiogenesis, arrhythmias and inflammation. Variants identified point to regulatory regions of the genome and may then propose a molecular mechanism predisposing patients to arrhythmias. Conclusion No locus raises genome-wide significance, but several signals with a nominal p-value point to relevant genes and pathways. Replication of the GWAS is ongoing on a cohort of 156 new patients with a less severe cardiopathy implanted with a cardioverter defibrillator in secondary prevention. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Nantes University Hospital

Precision medicine for adjuvant chemotherapy of resected colorectal cancer.

Colorectal cancer (CRC) is the most common cancer and the second leading cause of cancer death in Japan. Surgical resection is the only curative option for localized disease. However, undetectable micrometastases remaining after curative surgery may cause disease recurrence. Adjuvant chemotherapy aims to eradicate these micrometastases to improve the cure rate. Unfortunately, few reliable prognostic and predictive markers are available that identify patients at high risk for CRC during early‐stage disease. However, promising biomarkers may become available in the near future. Such biomarkers provide information for stratifying a patient's risk and for selecting the optimal treatment. Here, we provide an overview of current relevant prognostic and predictive biomarkers applicable to adjuvant treatment of early‐stage CRC and focus on the future of this field.

Is urinary β2-microglobulin a reliable marker for assessment of renal tubular dysfunction in chronic hepatitis B patients receiving tenofovir therapy?

Urinary β2-microglobulin (β2-M) is a marker for renal tubular dysfunction. The current study aimed to assess urinary β2-M as a reliable marker for early prediction of tenofovir disoproxil fumarate (TDF)-related nephrotoxicity among hepatitis B virus (HBV) patients. Forty-two HBV patients who were a candidate for TDF therapy or have recently started it (for less than 6 months) were enrolled and subjected to demographic, clinical, laboratory assessment, abdominal ultrasound and transient elastography. The glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Also, urinary β2-M was measured by the ELISA method within 6 months after the introduction of TDF treatment and 6 months later. Mean age was 41.8 (9.55) years, 27 were males and 59.5% of patients have elevated urinary β2-M after 6 months follow-up of TDF therapy. Urinary β2-M was 0.07 ± 0.07 μg/ml at baseline and insignificantly increased up to 0.09 ± 0.08 μg/ml after 6 months follow-up. Despite the insignificant increase in serum creatinine from 0.85 ± 0.23 mg/dl at baseline to 0.9 ± 0.21 mg/dl after 6 months and the insignificant decrease in eGFR from 126.2 ± 39.72 ml/min at baseline and 117.64 ± 42.23 ml/min at 6 months follow-up. No correlation was found between the changes in urinary β2-M and the changes in other renal function indices at baseline and 6 months follow-up. Short-term TDF therapy is associated with nonsignificant changes either in eGFR or urinary β2-M; these changes are not clinically relevant that indicates disease progression. Therefore, the suitability of urinary β2-M as a screening tool for tenofovir induced tubular dysfunction should be further.

Geriatric Nutritional Risk Index Less Than 92 Is a Predictor for Late Postpancreatectomy Hemorrhage Following Pancreatoduodenectomy: A Retrospective Cohort Study.

Simple SummaryThe definite risk factor of postpancreatectomy hemorrhage (PPH) is still unknown in spite of a lethal complication of pancreatoduodenectomy (PD). In this study, we evaluated whether GNRI is a reliable marker for PPH following PD. The present study retrospectively evaluated 121 patients treated with PD at Ageo Central General Hospital in Japan. Ten patients had developed PPH. Among them, the patients were divided into bleeding group (n = 10) and non-bleeding group (n = 111). The bleeding group had significantly low geriatric nutritional risk index (GNRI) values compared to those in the non-bleeding group (p = 0.001). The cut-off value of GNRI was determined by 92 accounting for a sensitivity 80.0%, specificity 82.9% using receiver operating characteristic curve analysis. A GNRI of <92 was statistically identified as an independently risk factor of PPH risk following PD. Postpancreatectomy hemorrhage (PPH) is the most lethal complication of pancreatoduodenectomy (PD). The main risk factor for PPH is the development of a postoperative pancreatic fistula (POPF). Recent evidence shows that the geriatric nutritional risk index (GNRI) may be predictive indicator for POPF. In this study, we aimed to evaluate whether GNRI is a reliable predictive marker for PPH following PD. The present study retrospectively evaluated 121 patients treated with PD at Ageo Central General Hospital in Japan between January 2015 and March 2020. We investigated the potential of age, gender, body mass index, serum albumin, American Society of Anesthesiologists classification (ASA), diabetes mellitus and smoking status, time taken for the operation, estimated blood loss, and postoperative complications (POPF, bile leak, and surgical site infections) to predict the risk of PPH following PD using univariate and multivariate analyses. Ten patients had developed PPH with an incidence of 8.3%. Among them, the patients were divided into bleeding group (n = 10) and non-bleeding group (n = 111). The bleeding group had significantly lower GNRI values than those in the non-bleeding group (p = 0.001). We determined that the cut-off value of GNRI was 92 accounting for a sensitivity 80.0%, specificity 82.9%, and likelihood ratio of 4.6 using receiver operating characteristic curve analysis. A GNRI of <92 was statistically associated with PPH in both univariate (p < 0.001) and multivariate analysis (p = 0.01). Therefore, we could identify that a GNRI < 92 was an independently potential predictor of PPH risk following PD. We should alert surgeons if patients have low level GNRI before PD.

Genechoc Study Genetic markers of arrhythmic risk in heart failure

Ventricular arrhythmic events are responsible for 50% of death in heart failure but no reliable predictive marker is known to discriminate patients at risk of fatal arrhythmia. Interestingly, familial predisposition has been reported suggesting a role of genetic factors. Identify genetic markers increasing the arrhythmic risk in heart failure population. We prospectively included heart failure patients with left ventricular ejection fraction (LVEF) under 35% and a cardioverter defibrillator in primary prevention in 22 French centres between 2009 and 2017. Patients were followed for 72 months and divided into two groups: cases with an arrhythmic event during follow-up and controls. A Genome Wide Association Study (GWAS) was done. Single Nucleotide Polymorphisms (SNPs) genotyping was performed on Affymetrix Axiom Precision Medicine Research Array plates. 332 cases and 567 controls were included (86% men, mean age at implantation 52 ± 11 years). 78% of patients had ischaemic cardiopathy, 20% had dilated cardiomyopathy. Mean LVEF was 27 ± 5%. No statistical difference was found between cases and controls on clinical parameters or electrocardiographic measures. No locus shows genome-wide significant association ( P < 5.10 − 8) on the GWAS analysis. However, 16 signals with a p-value between 5.10 − 8 and 5.10 − 5 were investigated. eQTL and chromatin conformation point to 35 genes with cardiac expression previously associated with heart failure, cardiomyopathies, arrhythmias and inflammation. Variants identified point to regulatory regions of the genome and may then propose a molecular mechanism predisposing patients to arrhythmias ( Fig. 1 ). No locus raises genome-wide significance, but several signals with a nominal p-value point to relevant genes and pathways. Replication of the GWAS is ongoing on a cohort of 156 new patients with a less severe cardiopathy implanted with a cardioverter defibrillator in secondary prevention.

Development of nomograms to predict therapeutic response and prognosis of non-small cell lung cancer patients treated with anti-PD-1 antibody.

Anti-programmed death-1 (PD-1) antibody changed the treatment of non-small cell lung cancer (NSCLC), however, reliable predictive markers were lacking. We aimed to explore factors associated with response and survival, and develop predictive models. This multicenter retrospective study included a training cohort (n = 92) and validation cohort (n = 111) with NSCLC patients received anti-PD-1 antibody monotherapy in eight Chinese hospitals, and a control cohort (n = 124) with NSCLC patients received chemotherapy. Logistic and Cox models were used to identify factors associated with response and survival respectively. Nomograms were developed based on significant factors, and evaluated by Concordance-index (C-index), area under the curve (AUC) and calibration curve. In training cohort, smoking history (P = 0.027) and higher absolute lymphocyte count (P = 0.038) were associated with response. Female (P < 0.001), age ≥ 65years (P = 0.004) and higher lactate dehydrogenase (LDH, P < 0.001) were associated with shorter progression-free survival (PFS). Higher LDH (P < 0.001) and derived neutrophil-to-lymphocyte ratio (P = 0.035) were associated with poorer overall survival (OS). While these factors were nonsignificant in chemotherapy cohort. Three nomograms to predict response at 6-week after treatment, PFS and OS at 6-, 12- and 18-months were developed, and validated in validation cohort. The C-indices of each nomogram in both cohorts were as follow (training vs validation): 0.706 vs 0.701; 0.728 vs 0.701; 0.741 vs 0.709; respectively. AUC showed a good discriminative ability. Calibration curves demonstrated a consistence between actual results and predictions. We developed predictive nomograms based on easily available factors to help clinicians early assess response and prognosis for NSCLC patients received anti-PD-1 antibody.

Prognostic Value of Changes in Preoperative and Postoperative Serum CA19-9 Levels in Gastric Cancer.

Objective: The prognostic significance of serum CA19-9 levels in gastric cancer patients remains a matter debate. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative serum CA19-9 levels in patients with gastric cancer.Methods: A total of 1,046 gastric cancer patients who underwent curative gastrectomy in West China Hospital of Sichuan University from January 2011 to December 2016 were analyzed retrospectively. Patients were categorized by minimum P-value using X-tile, while the baseline confounders for CA19-9 changes were balanced through propensity score matching (PSM). The relationships between CA19-9 changes and other clinicopathologic features were measured. Univariate and multivariate analysis were performed to explore the risk factors associated with survival outcomes.Results: We included 653 patients. Changes in CA19-9 levels significantly correlated with age, tumor size, macroscopic type, histological grade, T stage and TNM stage. Kaplan–Meier curves revealed that patients with CA19-9 changes <20% had significant better overall survival than those with changes more than 20% (p < 0.001); Cox regression analysis revealed the CA19-9 change (p = 0.010), gender (p = 0.031), histological grade (p = 0.036) and TNM stage (p < 0.001) were independent risk factors for survival after PSM. Stratification analysis indicated that patients with CA19-9 change more than 20% had worse prognosis that those with CA19-9 change no more than 20% in male (p = 0.002), poorly differentiated or undifferentiated type (p = 0.031) and TNM stage III (p = 0.006).Conclusion: Changes in preoperative and postoperative serum CA19-9 levels were closely associated with clinicopathological traits and was an independent prognostic factor in gastric cancer patients. This parameter may be a reliable marker for prediction of survival.

Complications and risk factors regarding the outcomes of canine babesiosis in Central Europe - A retrospective analysis of 240 cases.

The purpose of this study was to investigate retrospectively the prevalence of the complicated and uncomplicated forms of babesiosis and to evaluate various laboratory and clinical parameters of dogs infected with Babesia canis in order to assess their prognostic value regarding the outcomes of the disease. Medical records, complete blood count and serum biochemical analysis from the animal hospital information system of 240 dogs were reviewed and evaluated retrospectively. Binary logistic regression analysis was used to ascertain correlations between alterations in the obtained parameters and survival probability. The results showed that creatinine levels of more than 5 mg/dL and phosphate levels of more than 3 mmol/L have a highly significant link to death (P ≤ 0.001). Albumin levels of <2.2 g/dL (P = 0.003) and a rectal body temperature below 38 °C (P ≤ 0.001) may also serve as prognostic markers for the severity of the disease. If renal involvement was present, 33.9% of the dogs died, while 40.0% of the dogs died in the presence of pancreatitis. The parameters creatinine, phosphate, albumin and rectal temperature serve as reliable predictive markers of an increased risk of death in the case of an infection with B. canis.

Cushing's disease: the desmopressin test as a compelling predictive marker of long-term remission after transsphenoidal surgery.

Transsphenoidal surgery (TSS) is the treatment of choice in Cushing's disease. However, recurrence rates are substantial and currently there are no robust predictors of late prognosis. As accumulating evidence challenge the accuracy of the traditionally used early postoperative cortisol values, alternative tests are required. The study of Cambos et al., published in a recent issue of the European Journal of Endocrinology, adds to the existing data that support a role of the desmopressin test as an early and reliable predictive marker in successfully TSS-treated patients. However, despite these promising data, the use of this test is hampered by the fact that it can be applied only in patients with a documented preoperative positive test. Moreover, the lack of robust criteria to define positive postoperative responses represents another major limitation.

ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment.

A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival (p = 0.009) and overall survival (p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.

Clinical Impact of CD25/CD123 Coexpression in Adult B-Cell Acute Lymphoblastic Leukemia Patients.

This study aimed to determine the clinical impact of CD25+/CD123+ coexpression in adult B-cell acute lymphoblastic leukemia (B-ALL) cases. One hundred and twenty newly diagnosed B-ALL patients (≤60 years old) were included in this study. CD123 and CD25 expression on leukemic blast cells were assessed using flow cytometry. CD25+/CD123+ coexpression was detected in 40/120 B-ALL patients (33.3%). All B-ALL patients showed CD25+/CD123+ coexpression had lower induction of remission response and shorter overall survival as compared to B-ALL cases lacking coexpression. In conclusion, CD25+/CD123+ positive coexpression is a reliable flow cytometry marker for prediction of the outcome of adult B-ALL patients and could be used as a novel parameter for risk stratification of adult B-ALL cases.

Tumor volume reduction evaluated by cone beam computed tomography during stereotactic body radiotherapy for early stage non-small cell lung cancer.

BackgroundWe hypothesized that significant tumor volume reduction (TVR) occurs over the course of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC), and that TVR correlates with clinical outcomes.MethodsWe conducted a retrospective review of patients treated with SBRT for early stage NSCLC across two academic centers. For each patient, we contoured the tumor volume (TV) on cone beam computed tomography (CBCT) images obtained before each treatment fraction. We then calculated TVR based on the TV from the first and last days of treatment. We used log-rank tests to quantify differences in overall survival (OS), progression-free survival (PFS) and recurrence based on TVR.ResultsData from 69 patients and a total of 73 treated tumors were analyzed. The median follow-up for survivors was 51.8 months (range, 6.9 to 80.0 months). The median TVR for the cohort was 10.1% (range, −5.7% to 43.5%). There was no significant difference in either OS (median 33.4 vs. 29.1 months, P=0.79) or PFS (median 26.3 vs. 12.3 months, P=0.43) for those with high TVRs (≥10.1%) vs. low TVRs (<10.1%), respectively. There was a trend toward superior 2-year PFS in the high TVR group (52.2% vs. 36.7%, P=0.062), but this effect diminished on longer follow-up (4-year PFS 31.9% vs. 26.7%, P=0.15). No associations were observed between TVR and local, regional or distant recurrence.ConclusionsWe were not able to demonstrate that TVR is a reliable predictive imaging marker for stage I/II NSCLC treated with SBRT. Future studies with larger sample sizes are needed to clarify a potential relationship between TVR and early outcomes.

Drug Resistance in Non-Hodgkin Lymphomas.

Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

Prognostic value of pre-treatment red blood cell distribution width in lung cancer: a meta-analysis

Objective: In recent years, increasing studies found that pre-treatment red blood cell distribution width (RDW) could predict clinical outcomes in various cancers. However, the prognostic value of pre-treatment RDW in lung cancer was inconsistent. Therefore, we performed a meta-analysis to determine prognostic value of pre-treatment RDW in lung cancer.Methods: We performed a search in PubMed, The Cochrane Library, EMBASE (via OVID), Web of Science, CNKI, Wanfang, VIP, SinoMed databases, then we identified all records up to February 15, 2019. Outcomes of interest were overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the relevance of pre-treatment RDW to OS in lung cancer.Results: We included ten articles in total. Pooled results revealed that elevated pre-treatment RDW was significantly associated with poor OS (HR = 1.55, 95% CI: 1.26–1.92, p < 0.001) and DFS (HR = 1.53, 95% Cl: 1.15–2.05; p = 0.004) in lung cancer. Further subgroup analysis manifested that lung cancer patients with elevated pre-treatment RDW had worse prognosis.Conclusions: A higher value of pre-treatment RDW indicated worse survival of patients with lung cancer. RDW may serve as a reliable and economical marker for prediction of lung cancer prognosis.

MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma

Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to MDM2/4 or EGFR amplifications and melanoma type. Methods: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients’ responses to ICI and survival. Results: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of >50% at the first staging). Hyperprogression occurred more often in case of MDM2/4 or EGFR amplification or <1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival. Conclusions: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.

Reduced serum exosomal miR-874 expression predicts poor prognosis in colorectal cancer.

Emerging evidence has indicated that serum exosomal microRNAs (miRNAs) have promising diagnostic and prognostic value for colorectal cancer (CRC). This study aimed to detect serum exosomal miR-874 expression in CRC patients and assess its potential clinical significance. Blood samples were collected from 125 CRC patients, 45 cases with benign adenomas (AD) and 70 healthy individuals. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to examine serum exosomal miR-874 levels. The results showed that serum exosomal miR-874 levels were significantly downregulated in CRC patients compared to AD cases and healthy controls. Receiver operating characteristic (ROC) curve analysis revealed that serum exosomal miR-874 expression could discriminate CRC patients from healthy controls, as well as patients with AD. In addition, low serum exosomal miR-874 expression was associated with positive distant metastasis, positive lymph node metastasis, poor differentiation, and advanced TNM stage. Moreover, serum exosomal miR-874 expression was identified as a statistically significant independent prognostic factor for overall survival of CRC patients. Collectively, serum exosomal miR-874 expression might serve as a reliable marker for CRC diagnosis and prognosis prediction.

Clinical predictive efficacy of C-reactive protein for diagnosing infectious complications after gastric surgery.

Background:With the popularization of Enhanced Recovery After Surgery (ERAS), identifying patients with complications before discharging becomes important. This study aimed to explore the efficacy of C-reactive protein (CRP) in predicting infectious complications after gastrectomy.Methods:Patients with gastric cancer who underwent gastrectomy at Beijing Cancer Hospital from March 2017 to April 2018 were enrolled in the training set. Complications were prospectively registered. Receiver operating characteristic analysis was performed to assess the diagnostic accuracy of CRP via evaluating the area under the curve (AUC). Patients who had CRP tested on postoperative day (POD) 5 and accepted gastrectomy from April to December 2018 were included in the validation set to validate the cut-off value of CRP obtained from the training set.Results:A total of 350 patients were included (263 patients in the training set and 87 patients in the validation set). Out of these, 24 patients were diagnosed with infectious complications and 17 patients had anastomotic leakage in the training set. The CRP level on POD5 had superior diagnostic accuracy for infectious complications with an AUC of 0.81. The cut-off value of CRP on POD5 at 166.65 mg/L yielded 93% specificity and 97.2% negative predict value (NPV); For anastomotic leakage, the AUC of CRP on POD5 was 0.81. Using the cut-off value of CRP at 166.65 mg/L on POD5 achieved 92% specificity and 98.6% NPV. The optimal cut-off value (CRP 166.65 mg/L on POD5) was validated in the validation set. It achieved 97.5% specificity and 94.0% NPV for infectious complications, and 97.6% specificity and 96.4% NPV for anastomotic leakage.Conclusion:CRP is a reliable predictive marker for the diagnosis of inflammatory complications following gastric surgery. However, this study was based on preliminary data. The validity of this data needs confirmation by a larger number of cases.

Ki67 expression and localization of T cells after neoadjuvant therapies as reliable predictive markers in rectal cancer.

Chemoradiotherapy (CRT) is the standard neoadjuvant therapy for locally advanced rectal cancer (RC). However, neoadjuvant chemotherapy (NAC) also shows favorable outcomes. Although the immunological environment of RC has been thoroughly discussed, the effect of NAC on it is less clear. Here, we investigated the immunological microenvironment, including T cell infiltration, activation, and topological distribution, of resected RC tissue after neoadjuvant therapies and evaluated the correlation between T cell subsets and patient prognosis. Rectal cancer patients (n = 188) were enrolled and categorized into 3 groups, namely CRT (n = 41), NAC (n = 46), and control (surgery alone; n = 101) groups. Characterization of residual carcinoma cells and T cell subsets in resected tissues was performed using multiplex fluorescence immunohistochemistry. The densities of total and activated (Ki67high) T cells in tissues after NAC, but not CRT, were higher than in control. In both CRT and NAC groups, patients presenting with higher treatment effects showed aggressive infiltration of T cell subsets into carcinomas. Multivariate analyses of pathological and immunological features and prognosis revealed that carcinoma Ki67highCD4+ T cells after CRT and stromal Ki67highCD8+ T cells after NAC are important prognostic factors, respectively. Our results suggest that evaluation of T cell activation with Ki67 expression and its tumor localization can be used to determine the prognosis of advanced RC after neoadjuvant therapies.