Key Points
Question
Is there any difference in the safety of neoadjuvant chemoradiotherapy (nCRT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC) compared with that of neoadjuvant chemotherapy (nCT) followed by MIE?
Findings
In this multicenter randomized clinical trial of 264 patients with ESCC, overall morbidity rates were 47% in the nCRT group and 43% in nCT group, which was not significantly different.
Meaning
This trial shows that the safety of nCRT followed by MIE is similar to that of nCT for the treatment of locally advanced ESCC.
Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison. Fifteen EGFR mutations across twenty NSCLC patients were identified. Firefly NGS, cobas-ARMS and ddPCR all displayed superior sensitivity while ADx-ARMS was better suited for the qualitative detection of EGFR mutations with allele frequency higher than 1% in plasma and tissue samples. We observed high coincidence between the plasma and tissue EGFR mutational profiles for three driver mutations (L858R, exon 19 deletion and G719X) that are known targets of first generation EGFR-TKI therapies among patients who relapsed. Discrepancies between tissue and plasma EGFR mutational profiles were mainly attributable to spatial and temporal tumor heterogeneity, mutation inhibition due to therapy response and drug resistance (T790M). This study illustrates the challenges associated with selection of a technology platform for EGFR ctDNA analysis in the context of treatment evaluation and drug resistance detection.
To identify the risk factors for developing renal involvement and severe kidney disease in Chinese childhood Henoch–Schönlein purpura (HSP) patients.This was a retrospective study of 2731 children with HSP diagnosed between 2012 and 2015. We analyzed their demographic data, clinical manifestations, and laboratory tests retrospectively. Multivariate logistic regression analysis was used to assess the risk factors.Renal involvement occurred in 844 HSP patients (35.60%), and severe kidney disease occurred in 104 HSP patients (4.39%). Age over 6 years old at onset, colder season, more than 8 days interval between symptom onset and diagnosis, residence in rural, recurrence, angioedema, and the central nervous system (CNS) involvement were the significant risk factors for renal involvement. At the same time, age over 6 years at onset, more than 8 days interval between symptom onset and diagnosis, recurrence, angioedema, and CNS involvement were highly associated with severe kidney disease. Angioedema, longer interval between symptom onset and diagnosis, older age at HSP onset, and recurrence are prognostic indicators for renal involvement and severe kidney disease in children with HSP. The onset in colder season and rural residence associated with an increased risk for renal involvement, and the CNS involvement had an increased risk for severe kidney disease.HSP tends not to be self-limiting, and could progress into renal involvement or severe kidney disease for some of the HSP patients. Pediatricians should pay more attention to the children diagnosed with HSP, who also have these risk factors, for potential to develop renal involvement, and severe kidney disease, especially.
Objective. To investigate the expression of kinesin family member 20A (KIF20A) in bladder cancer, the effect of KIF20A on the proliferation and metastasis of bladder cancer cells, and the effect of KIF20A expression on the prognosis of bladder cancer patients. Methods. Bladder cancer tissue and its adjacent tissues were collected from tumour patients. The mRNA and protein expression levels of KIF20A in the tissue samples were detected by qRT-PCR and western blot. Immunohistochemical (IHC) staining was used to identify the expression and distribution of KIF20A proteins in the tissue samples. The relationship between the KIF20A expression and the clinical pathology of bladder cancer was analysed. The effect of the differential expression of KIF20A on the prognosis of patients with bladder cancer was analysed by the TCGA database. The plasmid was transfected into the bladder cell lines T24 and 5637 to construct two stable cell lines with knocked down KIF20A. The effect of KIF20A expression on the proliferation and invasion of T24 and 5637 bladder cells was explored in vitro using the abovementioned stable cell lines. The effect of the KIF20A expression on the proliferation of bladder cancer cells was evaluated by a mouse xenograft model. Results. The expression of KIF20A was significantly higher in the bladder cancer tissues than in the adjacent control tissues. The expression of KIF20A was significantly associated with the degree of pathological differentiation of bladder cancer. Patients with a higher expression of KIF20A had a higher tumour grade and a more advanced stage. The mean survival of patients with a high KIF20A expression was significantly lower than the mean survival of patients with a low KIF20A expression. The in vitro experiments demonstrated that the knockdown of KIF20A significantly inhibited T24 and 5637 cell proliferation and invasion. The in vivo experiments showed that the knockdown of KIF20A significantly inhibited the proliferation of the bladder tumours. Conclusion. KIF20A promotes the proliferation and metastasis of bladder cancer cells. Bladder cancer patients with a high KIF20A expression have a worse tumour differentiation and a poor prognosis. KIF20A may become an independent factor that affects the prognosis of bladder cancer patients and a therapeutic target for bladder cancer.
BackgroundNon-small cell lung cancer (NSCLC) accounts for 80% of lung cancers, and lung squamous cell carcinoma (SQCC) is one of the main types. Advances in the treatment of lung SQCC are lacking when compared to lung adenocarcinoma. The main treatment for early-stage SQCC is surgery. However, factors affecting the efficacy of surgical treatments for early-stage lung SQCC remain unclear. In this study, we examined the significance of commonly used lung SQCC diagnostic markers p63, p40, and cytokeratin (CK)5/6 in prognosis.MethodsSeventy-six cases of early-stage lung SQCC (N0) were obtained from our lung cancer database (January 2000 to December 2009). Tissue microarray and immunohistochemical (IHC) staining were used to detect the expression of p63, p40, and CK5/6. The effect of the expression level of each marker on patients' survival was examined.ResultsSensitivity and specificity of each marker for detecting lung SQCC was 87.0% and 81.0% for p63, 75.9% and 97.9% for p40, and 78.9% and 97.7% for CK5/6. Survival rates of patients with high expression levels of p63 or CK5/6 or both were higher than in patients with low expression levels (P < 0.05). Expression levels of p40 had no effect on survival (P > 0.05). Multivariate analysis showed that high levels of p63 expression p63+CK5/6 co-expression were independent prognostic factors for good survival.ConclusionIHC staining detection of p63 and CK5/6 in specimens should be routinely performed in postoperative early-stage lung SQCC patients. Its significance lies not only in differential diagnosis, but also in determining prognosis.
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