The clinical factors that accurately predict the response to preoperative treatment in rectal cancer were yet unknown. The carcinoembryonic antigen (CEA) clearance pattern during neoadjuvant ...treatment has been developed and the predictive value explored in rectal cancer patients with elevated CEA levels (> 5 ng/mL).
The training cohort was derived from the FOWARC prospective phase III trial, and 71/483 eligible patients were included. The validation cohort consisted of 75/587 consecutive rectal cancer patients from Xiangya Hospital between 2014 and 2015. The kinetic changes in serum CEA were measured at different time points during the neoadjuvant treatment. An exponential trend line was drawn using the CEA values. The patients were categorized into two groups based on the R
value of the trend line, which indicates the correlation coefficient between the exponential graph and measured CEA values: exponential decrease group (0.9 < R
≤ 1.0) and non-exponential decrease group (R
≤ 0.9).
In multivariate analysis, the patients in the CEA exponential decrease group had significantly high adequate rate of downstaging (ypT0-2N0M0), and pathologic complete response (pCR) rates after neoadjuvant treatment in the training cohort. The predictive values of the CEA clearance pattern for tumor downstaging and pCR were further confirmed in an independent validation cohort.
The CEA clearance pattern was an independent predictor of tumor response to neoadjuvant treatment in patients with rectal cancer. It might serve as an adjunct in the assessment of complete clinical response and guide individualized treatment strategies.
NCT01211210.
Objectives
The present study was committed to investigate the role of miR‐148a‐3p in HCC infected with hepatitis C virus (HCV) and the regulatory mechanism of miR‐148a‐3p/c‐Jun/MAPK signalling ...pathway.
Methods
Differential analysis and GSEA analysis were performed with R packages. QRT‐PCR and Western blot were used to detect RNA or protein level, respectively. The targeted relationship between miR‐148a‐3p and c‐Jun was predicted by TargetScan database and determined by double luciferase reporter assay. MTT assay and flow cytometry were used to evaluate cell proliferation, cell cycle and cell apoptosis, respectively.
Results
C‐Jun was up‐regulated, and MAPK signalling pathway was activated in HCV‐infected HCC cells. C‐Jun expression regulated inflammation‐related gene expression and had an influence on cell proliferation, cell cycle and cell apoptosis. MiR‐148a‐3p, down‐regulated in HCV‐infected HCC cells, could target c‐Jun mRNA to suppress c‐Jun protein expression.
Conclusions
MiR‐148a‐3p suppressed the proliferation of HCC cells infected with HCV through targeting c‐Jun mRNA.
Purpose: To investigate the clinical effectiveness and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for colorectal liver metastasis (CRLM) and evaluate the influencing ...factors of local efficacy.
Methods: From January 2013 to January 2017, 137 CRLM patients accepting US-guided percutaneous MWA were included. The 2450-MHz microwave ablation system and a cooled-shaft antenna were used. All patients were regularly followed up for at least 6 months. Technical success, complete ablation, local tumor progression (LTP), complications and side effects were assessed. Logistic regression analysis was used to identify the independent prognostic factors for LTP.
Results: In total, 411 lesions (mean diameter 15.4 ± 7.2 mm, range 5-67 mm) were treated. Complete ablation was achieved in 99.27% (408/411) of lesions and 97.81% (134/137) of patients. LTP occurred in 5.35% (22/411) of lesions and 16.06% (22/137) of patients. LTP was more likely to occur in lesions larger than 3 cm in diameter (OR: 14.71; p < .001; 95% CI: 3.7 3-57.92), near a large vascular structure (OR: 7.04; p < .001; 95% CI: 2.41-20.60), near the diaphragm (OR: 4.02; p = .049; 95% CI: 1.05-16.11) and in patients with no response to chemotherapy before MWA (OR: 3.25; p = .032; 95% CI: 1.14-15.30). MWA was well tolerated, with a major complication rate of 3.65%, a minor complication rate of 8.03% and a mortality rate of 0%. Fever and pain were the most common side effects after MWA.
Conclusions: US-guided percutaneous MWA of CRLM is a safe and effective method that is expected to become a routine treatment for local tumor control of CRLM.
Serum CEA has been widely used to screen for potential recurrent disease after resection in rectal cancer. However, the influence of baseline CEA on the performance of CEA in recurrence surveillance ...needs to be investigated.
This longitudinal cohort study included 484 patients with nonmetastatic rectal cancer from 18,013 patients in a prospectively enrolled institutional database program of colorectal disease. Baseline CEA levels were determined before treatment, and CEA-based follow-up tests and examinations were applied in the surveillance after treatment.
A total of 62.6% (62/99) overall, 53.5% (23/43) local, and 64.9% (50/77) distant recurrences were seen in patients who had similar CEA levels with their baseline statuses. The sensitivity of elevated CEA levels during surveillance for overall recurrence was significantly lower in patients with negative baseline CEA than in those with elevated baseline CEA levels (41.3% vs 69.4%; P =.007). Moreover, similar results were observed in the surveillance for local (50% vs 61.5%; P =.048) and distant (39.6% vs 72.4%; P =.005) recurrences between these 2 patient groups. However, CEA had comparable and excellent specificity during surveillance for recurrent disease in these groups. The addition of CA19-9 to the CEA assay significantly improved the sensitivity in recurrence surveillance for patients with negative baseline CEA (49.2% vs 41.3%; P =.037). Finally, we identified a subgroup of CEA-turn recurrences characterized by negative CEA at baseline, elevated CEA at recurrence, and worse survival outcomes after recurrence (hazard ratio, 1.88; 95% CI, 1.07-3.30; P =.026).
In patients with rectal cancer with negative baseline CEA, serum CEA had insufficient sensitivity in recurrence surveillance after treatment, and additional surveillance may improve oncologic outcomes. Baseline CEA should be considered before CEA-based surveillance can be applied in the follow-up trials.
Purpose
To analyze whether HBV infection can reduce the risk of colorectal liver metastasis (CRLM) in stage 2 colorectal cancer (CRC).
Methods
The data of postoperative pathological stage 2 CRC ...patients treated at the Sixth Affiliated Hospital of Sun Yat-sen University between 2013 and 2015 were analyzed. The patients were divided into an infection group (group A) and a non-infection group (group B). The correlations between HBV infection and CRLM, 5-year liver disease-free survival, and 5-year overall survival were compared.
Results
A total of 884 patients who met the inclusion criteria were included in the study. Group A included 297 patients (33.60%), and 5 patients (1.68%) had CRLM. Group B included 587 patients (66.40%), and 31 patients (5.28%) had CRLM. The results of correlation analysis and logistic regression analysis showed that HBV infection (P = 0.013, HR = 0.29, 95% CI 0.11–0.77) was a protective factor for CRLM, while CEA > 5 ng/ml (P = 0.002, HR = 3.12, 95% CI 1.51–6.47) and hypertension (P = 0.010, HR = 3.50, 95% CI 1.34–9.09) were risk factors for CRLM. Group A had a significantly better 5-year liver disease-free survival than group B (P = 0.011, HR = 0.31, 95% CI 0.16–0.63), but there was no significant difference in the 5-year overall survival (P = 0.433).
Conclusion
HBV infection may reduce the risk of metachronous liver metastasis in stage 2 colorectal cancer.
Glioma is the most malignant cancer in the brain. As a major vitamin-K-dependent protein in the central nervous system, PROS1 not only plays a vital role in blood coagulation, and some studies have ...found that it was associated with tumor immune infiltration. However, the prognostic significance of PROS1 in glioma and the underlying mechanism of PROS1 in shaping the tumor immune microenvironment (TIME) remains unclear.
The raw data (including RNA-seq, sgRNA-seq, clinicopathological variables and prognosis, and survival data) were acquired from public databases, including TCGA, GEPIA, CGGA, TIMER, GEO, UALCAN, and CancerSEA. GO enrichment and KEGG pathway analyses were performed using "cluster profiler" package and visualized by the "ggplot2" package. GSEA was conducted using R package "cluster profiler". Tumor immune estimation resource (TIMER) and spearman correlation analysis were applied to evaluate the associations between infiltration levels of immune cells and the expression of PROS1. qRT-PCR and WB were used to assay the expression of PROS1. Wound-healing assay, transwell chambers assays, and CCK-8 assays, were performed to assess migration and proliferation. ROC and KM curves were constructed to determine prognostic significance of PROS1 in glioma.
The level of PROS1 expression was significantly increased in glioma in comparison to normal tissue, which was further certificated by qRT-PCR and WB in LN-229 and U-87MG glioma cells. High expression of PROS1 positively correlated with inflammation, EMT, and invasion identified by CancerSEA, which was also proved by downregulation of PROS1 could suppress cells migration, and proliferation in LN-229 and U-87MG glioma cells. GO and KEGG analysis suggested that PROS1 was involved in disease of immune system and T cell antigen receptor pathway. Immune cell infiltration analysis showed that expression of PROS1 was negatively associated with pDC and NK CD56 bright cells while positively correlated with Macrophages, Neutrophils in glioma. Immune and stromal scores analysis indicated that PROS1 was positively associated with immune score. The high level of PROS1 resulted in an immune suppressive TIME
the recruitment of immunosuppressive molecules. In addition, Increased expression of PROS1 was correlated with T-cell exhaustion, M2 polarization, poor Overall-Survival (OS) in glioma. And it was significantly related to tumor histological level, age, primary therapy outcome. The results of our experiment and various bioinformatics approaches validated that PROS1 was a valuable poor prognostic marker.
Increased expression of PROS1 was correlated with malignant phenotype and associated with poor prognosis in glioma. Besides, PROS1 could be a possible biomarker and potential immunotherapeutic target through promoting the glioma immunosuppressive microenvironment and inducing tumor-associated macrophages M2 polarization.
Abstract
Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers’ fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative ...urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.
DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of ...CRC.
A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis.
Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI (1.140-3.48)), and a combination of RIMS2 methylation with KRAS status could predict prognosis better.
RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.
ObjectiveTo better understand the origins, manifestations and current policy responses to patient–physician mistrust in China.DesignQualitative study using in-depth interviews focused on personal ...experiences of patient–physician mistrust and trust.SettingGuangdong Province, China.ParticipantsOne hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient–physician relationships.ResultsOne of the most prominent forces driving patient–physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient–physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient–physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient–physician trust.ConclusionsThe blind pursuit of financial profits at a systems level has eroded patient–physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust.
Neurotrophic tropomyosin receptor kinases (NTRKs) are a gene family function as oncogene or tumor suppressor gene in distinct cancers. We aimed to investigate the methylation and expression profiles ...and prognostic value of NTRKs gene in colorectal cancer (CRC).
An analysis of DNA methylation and expression profiles in CRC patients was performed to explore the critical methylations within NTRKs genes. The methylation marker was validated in a retrospectively collected cohort of 229 CRC patients and tested in other tumor types from TCGA. DNA methylation status was determined by quantitative methylation-specific PCR (QMSP).
The profiles in six CRC cohorts showed that NTRKs gene promoter was more frequently methylated in CRC compared to normal mucosa, which was associated with suppressed gene expression. We identified a specific methylated region within NTRK3 promoter targeted by cg27034819 and cg11525479 that best predicted survival outcome in CRC. NTRK3 promoter methylation showed independently predictive value for survival outcome in the validation cohort (P = 0.004, HR 2.688, 95% CI 1.355, 5.333). Based on this, a nomogram predicting survival outcome was developed with a C-index of 0.705. Furthermore, the addition of NTRK3 promoter methylation improved the performance of currently-used prognostic model (AIC: 516.49 vs 513.91; LR: 39.06 vs 43.64, P = 0.032). Finally, NTRK3 promoter methylation also predicted survival in other tumors, including pancreatic cancer, glioblastoma and stomach adenocarcinoma.
This study highlights the essential value of NTRK3 methylation in prognostic evaluation and the potential to improve current prognostic models in CRC and other tumors.
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