Porous Se@SiO2 nanocomposites play a potential inhibition role in hyperoxaluria associated kidney stone by exerting antioxidant effects.

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

Triangular prismatic JJ stent does not cause more discomfort than tubular ones: a randomised controlled trial comparison.

OBJECTIVE: To compare the stent-related symptoms (SRS) of three commonly used, readily accessible ureteric JJ stents after uncomplicated flexible ureteroscopic lithotripsy (FURL), in a prospective randomised controlled single-blind parallel-group study, in order to see whether structural difference might influence SRS. PATIENTS AND METHODS: Patients undergoing FURL were randomised into three groups: the Cook Group received conventional 6 F Cook Universa Soft JJ stents as control, the Kang Yi Bo (KYB) Group received 6 F KYB anti-reflux JJ stents, and the Urovision Group received 7 F Urovision Visiostar ESWL JJ stents. The ureteric stent symptom questionnaire (USSQ) was administered at 1 week, 4 weeks (before stent removal), and 5 weeks (one week after stent removal as baseline evaluation) after stent insertion. Both raw and baseline-adjusted USSQ domain subscores at 1 week and 4 weeks were compared. RESULTS: A total of 146 patients were included in the analysis. The KYB Group showed significantly lower P6&7 subscore yet higher urinary symptoms score 1 week and 4 weeks after stents insertion than both Cook and Urovision, whilst the Urovision Group achieved similar scores in most domains with Cook. CONCLUSIONS: Although the KYB anti-reflux JJ stent might prevent vesicoureteral reflux, it induces significantly stronger urinary symptoms, both at 1 week or 4 weeks after stent insertion, with or without baseline correction. Despite the unique triangular prismatic shape, the Urovision Visiostar stent does not cause heavier urinary symptoms or pain compared to the conventional cylinder shape counterparts.

Prognostic value of Hematoxylin and eosin staining tumor-infiltrating lymphocytes (H&E-TILs) in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) by routine hematoxylin and eosin staining (H&E-TILs) are a robust prognostic biomarker in various cancers. However, the role of H&E-TILs in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT) has not been reported. The purpose of this study was to assess the prognostic value of H&E-TILs in ESCC treated with CCRT. METHODS: The clinical data of 160 patients with ESCC treated with CCRT in our center between Jan. 2014 and Dec. 2021 were collected and retrospectively reviewed, and propensity score matching (PSM) analyses were performed. The H&E-TILs sections before CCRT were reassessed by two experienced pathologists independently. The H&E-TILs sections were classified into a positive group (+, > 10%) and a negative group (-, ≤ 10%) using 10% as the cutoff. The effects of H&E-TILs on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were explored using the Kaplan‒Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model. RESULTS: The short-term response to CCRT and the OS (P < 0.001), DMFS (P = 0.001), and LRFS (P < 0.001) rates were significantly different between the H&E-TILs (+) and H&E-TILs (-) groups. Subgroup analysis showed that H&E-TILs(+) with CR + PR group had a longer survival than H&E-TILs(-) with CR + PR, H&E-TILs(+) with SD + PD and H&E-TILs(-) with SD + PD group, respectively(P < 0.001). Furthermore, based on TCGA data, patients in the high TILs group had a better prognosis than those in the low TILs group. Multivariate analyses indicated that H&E-TILs and the short-term response to CCRT were the only two independent factors affecting OS, PFS, DMFS, and LRFS simultaneously, and H&E-TILs expression was associated with an even better prognosis for those patients with CR + PR. CONCLUSIONS: H&E-TILs may be an effective and beneficial prognostic biomarker for ESCC patients treated with CCRT. Patients with H&E-TILs (+) with PR + CR would achieve excellent survival. Further prospective studies are required to validate the conclusions.

Evaluation of the safety and efficiency of color Doppler ultrasound-guided percutaneous nephrolithotomy in clinical practice: results from a retrospective study.

This study evaluated the clinical value of color Doppler ultrasound-guided percutaneous nephrolithotomy (PCNL) in avoiding bleeding caused by punctured blood vessels. Herein, we retrospectively included patients who underwent color Doppler ultrasound-guided PCNL or PCNL using the conventional channel technique from August 2018 to August 2022. The clinical characteristics of patients during surgery, complications, and hospital stay were recorded and compared. Overall, 228 patients were enrolled, with 126 patients (age, 47.6 ± 13.2 years; men: 57.14%) in the color Doppler ultrasound-guided PCNL group and 102 patients (age, 46.6 ± 12.3 years) in the B-mode ultrasound-guided puncture group. The total operation time (63.5 ± 15.5 vs. 61.3 ± 16.3 min, p = .5236) and stone clearance rate (86.50% vs. 83.33%, p = .7139) were similar between the two groups. However, the puncture time for the color Doppler ultrasound-guided PCNL group was longer than that for the B-mode ultrasound-guided puncture group (5.1 ± 2.3 vs. 2.6 ± 1.6 min, p = .0019). Moreover, the length of postoperative hospital stay in the color Doppler ultrasound-guided PCNL group reduced significantly by ∼1 day compared with that in the B-mode ultrasound-guided puncture group (4.5 ± 1.6 vs. 5.6 ± 2.1 days, p = .0087). The blood transfusion rate (1.58% vs. 4.9%, p = .0399), sedation-related adverse event rate (0.79% vs. 2.9%, p = .0332), perineal hematoma incidence (0% vs. 2.94%, p < .0001), and serum decreased hemoglobin levels (12.2 ± 9.7 vs. 23.5 ± 10.1 g/L, p < .001) after color Doppler ultrasound-guided PCNL were significantly lower than those after B-mode ultrasound-guided puncture. The stone clearance rate was similar between the two groups, with a similar operation time. Moreover, color Doppler ultrasound-guided PCNL shortened the postoperative hospital stay and decreased Hb levels, blood transfusion rate, and perineal hematoma incidence.

Frenulum Protection Technique in Disposable Circumcision Suture Device for Adult Males.

PURPOSE: To evaluate the efficacy of frenulum protection technique of the disposable circumcision suture device (DCSD) in adult males. MATERIALS AND METHODS: Atotal of 53 adult males were diagnosed with redundant prepuce and underwent circumcision with DCSD using frenulum protection technique. The main preoperative and postoperative measure of the length of penile frenulum was evaluated. Other data such as edema rate, intraoperative blood loss, operation time, postoperative pain, staple falling off time, incision infection rate, and evaluation of satisfaction rate with penis appearance were documented in the study. RESULTS: There was no significant difference in preoperative and postoperative frenulum length for each patient. The mean length of the penile frenulum before and after surgery was 2.25 ± 0.36 cm and 2.23 ± 0.39 cm, respectively (p = .31). The rate of frenulum length preservation was 100%. All the patients had no excessive resection of the frenulum and no serious complication happened after surgery. The satisfaction rate of postoperative penis appearance from patients' evaluation was 98.1% (52/53). CONCLUSION: The frenulum protection technique was simple and operable, which could help the operator to accurately identify the most distal position of the frenulum and retain a sufficient length of frenulum during DCSD circumcision.

Stereotactic Body Radiotherapy Boost with the CyberKnife for Locally Advanced Cervical Cancer: Dosimetric Analysis and Potential Clinical Benefits.

(1) Aim: To compare the treatment plans of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) and high-dose-rate (HDR) intracavitary/interstitial brachytherapy (IC/ISBT) and examine the feasibility of CK-SBRT as a viable alternative to BT in patients with locally advanced cervical cancer (LACC). (2) Methods: A BT plan of 28 Gy in four fractions delivered previously to 20 patients with LACC was compared with a CK plan based on the same CT images with structures delineation for BT. The SBRT treatment plan was further divided according to two different approaches, with the high-risk planning target volume (HR-PTV) defined by the high-risk clinical target volume (HR-CTV) without and with a 5 mm margin, which were named CK-CTV plan and CK-PTV plan, respectively. The dose distributions and dosimetric parameters of the target volumes and organs at risk (OARs) were recorded and compared for the three boost plans. Radiobiological metrics were calculated based on the EUD for the hybrid plans. Additionally, the relationship between tumor volume and tolerance doses for the OARs in the BT plan and CK-PTV plan was investigated. (3) Results: Target coverage was better with the CK plan than with the BT plan, as the D95%, D98%, HI and CI of the CK-CTV plan and CK-PTV plan were higher than those of the BT plan; an exception was the D50%. Similarly, the TCP of the target was also significantly in favor of the CK hybrid plans (p < 0.01). For the OARs, the CK-CTV plan was superior to the BT plan as regards the rectum D2cc, bladder D2cc and bladder Dmax. The CK-PTV plan could achieve dosimetric parameters comparable to those of the BT plan for OARs concerning the small residual tumor volume. The NTCP of the rectum for the WPI+CK-CTV plans was significantly lower than that of the WPI+BT plans (p < 0.01). (4) Conclusions: CK-based SBRT can achieve better target coverage, dose sparing for the OARs and radiobiological effects compared with the BT plan for tumors that are not excessively large. CK-based SBRT could be an alternative option to administer a radiation boost for patients with LACC.

Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer.

Background: As a new-generation androgen-receptor antagonist, enzalutamide is a first-choice drug for advanced prostate cancer (PCa) patients. However, secondary resistance to enzalutamide poses a new challenge in the treatment of cancer. Long non-coding RNA (lncRNA) regulates cell function through many levels and mechanisms, and also plays an important role in the biological behaviors of tumors. Methods: LncRNA microarrays were used to detect enzalutamide-resistant related lncRNA in Enzalutamide-resistant C4-2 (C4-2 ENZ-R) cells and corresponding parent cells. Cell Counting Kit 8, flow cytometry, and transwell assays were used to test the effect of lncRNA NONHSAT210528 on the function of PCa cells. RNA pulls down and the luciferase report gene was used to detect the competitive endogenous RNA (ceRNA) mechanism. The culture supernatant of C4-2 and C4-2b cells was transferred to the lower chamber for transwell assay of human umbilical endothelial cells (HUVECs). Results: The lncRNA microarray analysis showed that there were significant differences in the expression of many lncRNAs between the C4-2 ENZ-R and C4-2 cells. The real-time polymerase chain reaction (PCR) detection showed that the expression of lncRNA NONHSAT210528 was significantly higher in the C4-2 ENZ-R cells than the C4-2 cells. The Transwell assays showed that lncRNA NONHSAT210528 overexpression increased the invasion of the C4-2 and C4-2b cells. The cell-wound scratch and the transwell assays showed that the culture supernatant of C4-2 and C4-2b cells with overexpressed lncRNA NONHSAT210528 promoted the migration and invasion of HUVECs. Furthermore, lncRNA NONHSAT210528 regulated the expression of YOD1 dependent on miR-21. Conclusions: Enzalutamide-resistant related lncRNA NONHSAT210528 appears to promote the proliferation and invasion of PCa cells by functioning as a ceRNA and regulating the miR-21-5p/YOD1 signal pathway.

Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy.

Programmed death-1 homolog (PD-1H) is a coinhibitory molecule that negatively regulates T cell-mediated immune responses. In this study, we determined whether ablation of T cell-associated PD-1H could enhance adoptive T cell therapy in experimental tumor models. The expression of PD-1H is upregulated in activated and tumor-infiltrating CD8+ T cells. Activated CD8+ T cells from PD-1H-deficient (PD-1H-KO) mice exhibited increased cell proliferation, cytokine production, and antitumor activity in vitro. Adoptive transfer of PD-1H-KO CD8+ T cells resulted in the regression of established syngeneic mouse tumors. Similar results were obtained when PD-1H was ablated in T cells by CRISPR/Cas9-mediated gene silencing. Furthermore, ablation of PD-1H in CAR-T cells significantly improved their antitumor activity against human xenografts in vivo. Our results indicate that T cell-associated PD-1H could suppress immunity in the tumor microenvironment and that targeting PD-1H may improve T cell adoptive immunotherapy.

A lncRNA-immune checkpoint-related gene signature predicts metastasis-free survival in prostate adenocarcinoma.

Background: The 5-year overall survival rate in metastatic prostate adenocarcinoma (PRAD) is extremely low. Genomic studies of PRAD have improved our understanding of disease biology. However, the role of immune checkpoint genes (ICGs) in PRAD remains unclear. Methods: Univariate and multivariate analyses were used to analyze genes associated with metastasis-free survival (MFS) in The Cancer Genome Atlas (TCGA)-PRAD dataset. The expressions of ADORA2A and TNFRSF18 were detected via immunohistochemical assay and real-time fluorescence quantitative PCR (RT-PCR) assay in our in-house cohort. The expression of long non-coding RNAs (lncRNAs) AL139287.1, SLC9A3-AS1, and SNHG12 were detected via RT-PCR assay in our in-house cohort. Stepwise regression, Cox regression, and nomogram analyses were used to evaluate the prognostic role of these genes in both the TCGA dataset and in-house cohort. The "pRRophetic" R package was used to evaluate drug sensitivity in the TCGA cohort according to the gene mRNA expression level. Results: In our study, univariate and multivariate analyses revealed that the mRNA expressions of two ICGs, ADORA2A and TNFRSF18, were independent factors affecting MFS in PRAD patients. A prognostic 2-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. The expressions of AL139287.1, SLC9A3-AS1, and SNHG12 were correlated with ADORA2A and TNFRSF18. A prognostic lncRNA-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. In addition, correlation analyses between the sensitivity of doxorubicin, erlotinib, gemcitabine, or vinorelbine and AL139287.1, SLC9A3-AS1, SNHG12, ADORA2A, and TNFRSF18 were conducted. Conclusions: Our results provide new targets for predicting tumor metastasis in PRAD and treating patients with metastatic PRAD.

PD-1H Expression Associated With CD68 Macrophage Marker Confers an Immune-Activated Microenvironment and Favorable Overall Survival in Human Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed. Programmed Death-1 Homolog (PD-1H) is a negative checkpoint regulator that inhibits antitumor immune responses. Here, PD-1H expression in 114 patients with ESCC was evaluated by immunohistochemistry. Next, 12 randomly selected tumor tissue sections were used to assess the colocalization of PD-1H protein and multiple immune markers by multiplex immunohistochemistry. Our results demonstrated that PD-1H was expressed at high frequency in ESCC tumor tissues (85.1%). PD-1H protein was predominantly expressed in CD68+ tumor-associated macrophages and expressed at low levels in CD4+ T cells and CD8+ T cells in ESCC tumor tissues. Furthermore, based on ESCC data in The Cancer Genome Atlas (TCGA), the gene expression levels of PD-1H were positively associated with the infiltration levels of immune-activated cells especially CD8+ cytotoxic T cells. In contrast, the gene expression levels of PD-1H were negatively correlated with myeloid-derived suppressor cells (MDSCs). Importantly, PD-1H expression in tumor sites was significantly correlated with favorable overall survival in patients with ESCC. Collectively, our findings first provided direct information on the PD-1H expression pattern and distribution in ESCC, and positive correlation of PD-1H expression with overall survival suggested PD-1H expression levels could be a significant prognostic indicator for patients with ESCC. Future studies need to explore the immunoregulatory of PD-1H in the tumor microenvironment of ESCC.

Influence of Using a Contrast-Enhanced CT Image as the Primary Image on CyberKnife Brain Radiosurgery Treatment Plans.

BACKGROUND AND PURPOSE: This study aimed to quantify the differences between pre- and post-contrast agent (CA) CT for CyberKnife brain SRS plans. MATERIALS AND METHODS: Twenty-five patients were retrospectively analyzed. They were divided into two categories, inhomogeneous cases (13 patients) and homogeneous cases (12 patients), according to whether the tumor was close to the cavity and inhomogeneous tissues or not. The pre-CA and post-CA plans were designed and calculated using the same monitor unit and paths as those in the ray-tracing algorithm, respectively. RESULTS: The CT number difference of tumor between pre- and post-CA was significant (on average, 24.78 ± 18.56 HU, P-value < 0.01). The deviation value of the target was the largest at approximately 37 HU (inhomo-) and 13 HU (homo-) (P < 0.01), and the values of the organs at risk (OARs) were not statistically significant (P-value > 0.05). However, it was not statistically significant for the dose difference between the two groups with the injection of CA (P-value > 0.05). The absolute effective depth difference generally remained at a level of 1 mm, but the dose difference was quitely fluctuated sometimes more than 20%. The absolute effective depth difference of the inhomo-case (0.62 mm) was larger than that of the homo-case (0.37 mm) on median, as well as the variation amplitude (P-value < 0.05). Moreover, the relative dose differences between the two cases were 0.38% (inhomo-) and 0.2% (homo-), respectively (P-value < 0.05). At the criterion of 1 mm/1%, the gamma pass rate of the homo-case (95.89%) was larger than that of the inhomo-case (93.79%). For the OARs, except for the cochlea, the two cases were almost the same (>98.85%). The tumor control probability of the target was over 99.99% before and after injection of a CA, as well as the results for the homo-case and inhomo-case. CONCLUSIONS: Considering the difference of evaluation indexes between pre- and post-CA images, we recommended plain CT to be employed as the primary image for improving the CK treatment accuracy of brain SRS, especially when the target was close to CA-sensitive OARs and cavity.

Optimal acupoint and session of acupuncture for patients with chronic prostatitis/chronic pelvic pain syndrome: a meta-analysis.

BACKGROUND: The study aims to perform a meta-analysis of published trials and evaluate the efficacy of acupuncture on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) by symptom score reduction, optimal acupuncture session, and most frequently used acupoints. METHODS: A literature search was performed for randomized controlled trials (RCTs) comparing efficacy of acupuncture with sham acupuncture or standard medication on CP/CPPS. The primary outcome was the reduction of National Institute of Health-Chronic Prostatitis Index (NIH-CPSI) total score and its subscales. The optimal acupuncture session to reach its clinical efficacy and most common compatibility rule of acupoints were also evaluated. RESULTS: Ten trials involving 770 participants were included. Meta-analysis showed compared with sham acupuncture, acupuncture yielded significant reduction in NIH-CPSI total score [weighted mean difference (WMD): 7.28, 95% confidence interval (95% CI): 5.69-8.86), and provided better pain relief (WMD: 3.57, 95% CI: 2.07-5.08), urinary symptoms improvement (WMD: 1.68, 95% CI: 1.13-2.22), and quality of life (QOL) (WMD: 2.38, 95% CI: 1.41-3.36). Compared with standard medication, acupuncture were more efficacious in reducing NIH-CPSI total score (WMD: 3.36, 95% CI: 1.27-5.45), also showed significant greater pain relief (WMD: 2.36, 95% CI: 1.67-3.06), marginal advantage in improving QOL (WMD: 0.98, 95% CI: 0.12-1.83) but no difference in reducing urinary symptom (WMD: -0.03, 95% CI: -1.30 to 1.24). Four acupuncture sessions were the minimum "dose" to reach clinical efficacy, and prolonged acupuncture sessions continuously improved urinary symptoms and QOL. The majority of acupoint selection strategies were based on the combination of any three acupoints from CV3, CV4, BL32, SP6, and SP9. CONCLUSIONS: Acupuncture has promising efficacy for patients with CP/CPPS, especially category IIIB, in aspects of relieving pain and urinary symptoms and improving the QOL. Acupuncture may serve as a standard treatment option when available, and a tailored comprehensive treatment strategy for CP/CPPS is the future trend.

Primary tumor regression patterns in esophageal squamous cell cancer treated with definitive chemoradiotherapy and implications for surveillance schemes.

Purpose: The primary tumor regression patterns of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT) were investigated to determine an optimal surveillance scheme. Method: The clinical data and radiology images of patients before CRT, at completion of CRT and every 1-3 months for the subsequent 12 months or until disease progression were retrospectively reviewed to define the patterns of primary tumor regression after CRT. Survival rates were analyzed statistically in order to determine an optimal surveillance scheme. Results: A total of 82 patients were enrolled in the present study for analysis. At the first surveillance visit date at the end of CRT, a total of 21 patients achieved complete response (early-CR), 29 patients reached incomplete response (IR), 25 patients maintained stable disease (SD) and 7 patients encountered progression of disease (PD). During subsequent surveillance, a total of 14 IR patients regressed continuously to CR (later-CR), 15 patients maintained IR (early-IR) and 9 SD patients gradually regressed to IR (later-IR). At full tumor regression (FTR), a total of 21, 14, 15, 9, 16 and 7 patients were defined as early-CR, later-CR, early-IR, later-IR, SD and PD, respectively. The median FTR time for later-CR and later-IR was 7.5 and 7 weeks, respectively. The 3-year overall survival rate of the early-CR group was 85.7% (P<0.001), which was higher compared with the later-CR (16.7%), early-IR (20%), later-IR (11.1%), SD (6.3%) and PD (0%) groups. Conclusion: The early-CR following CRT is a robust prognostic predictor in patients with ESCC. To optimize the determination of tumor regression, ≥7 weeks after CRT is an optimal initial surveillance visit date. The surveillance of non-CR patients should concentrate on symptoms, nutrition and psychosocial support, rather than screening for recurrence of the disease.

Proposed revision of the 8th edition AJCC clinical staging system for esophageal squamous cell cancer treated with definitive chemo-IMRT based on CT imaging.

PURPOSE: To validate and propose revision of the 8th edition American Joint Committee on Cancer (AJCC) clinical staging system for esophageal squamous cell cancer (ESCC) patients treated with definitive intensity-modulated radiation therapy combined with concurrent chemotherapy (Chemo-IMRT) based on computed tomography (CT) imaging. METHODS: The clinical data of patients with ESCC treated with Chemo-IMRT were collected and retrospectively reviewed. All CT images were independently reevaluated and restaged according to the 8th edition AJCC staging system. The overall survival (OS) rates were analyzed statistically. ROC curves of the various parameters of the primary tumor and metastatic lymph nodes were generated in order to identify the cutoff values correlated to patient survival using the area under curve. RESULTS: The gross tumor volume of the primary tumor (GTV-prT) and the clinical N stage (cN) were independent factors that influenced OS. The 5-year OS rate of patients with GTV-prT ≤28 cm3, GTV-prT > 28 and ≤ 56 cm3, and GTV-prT > 56 cm3 were 54.6, 31.1 and 18.6%, respectively. The 5-year OS rate of patients with cN0, cN1 SLNM (-), cN2 SLNM (-), cN3 SLNM (-) and SLNM (+) were 62.8 (P < 0.001), 34.0 (P = 0.16), 20.0 (P = 0.785), 0 (P < 0.001) and 26.9%, respectively. After restaging the SLNM as regional MLNs, the 5-year OS rates of the patients with cN0, 1, 2 and 3 were 62.8, 36.3, 23.7 and 7.8%, respectively. Various GTV-prT were combined with the cN to establish a new clinical TNM staging system: I, GTV-prT1 and cN0; II, GTV-prT2 or 3 and cN0, GTV-prT1 and cN1; III, GTV-prT1 and cN2, GTV-prT2 and cN1,2; Iva, GTV-prT3 and cN1,2; IVb, GTV-prTany and cN3; IVc, TanyNanyM1. Subsequently, the OS differed significantly between the adjacent GTV-prT cN categories, except those of stage I vs. II. CONCLUSION: The SLNM should be dealt with as a regional rather than a distant disease in patients with ESCC when treated with CRT. The proposed nonsurgical staging system based on the GTV-prT and N appears to be a simple and accurate prognosis predictor for patients with ESCC who have undergone definitive Chemo-IMRT.

Long Noncoding RNA FAM201A Mediates the Radiosensitivity of Esophageal Squamous Cell Cancer by Regulating ATM and mTOR Expression via miR-101.

Background: The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC. Methods: Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive (n = 3) and radioresistant (n = 3) ESCC tumor tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in 35 ESCC tumor tissues (20 radiosensitive and 15 radioresistant tissues, respectively) to validate the lncRNA that contributed the most to the radiosensitivity of ESCC (named the candidate lncRNA). MTT, flow cytometry, and western blot assays were conducted to assess the effect of the candidate lncRNA on radiosensitivity in vitro in ECA109/ECA109R ESCC cells. A mouse xenograft model was established to confirm the function of the candidate lncRNA in the radiosensitivity of ESCC in vivo. The putative downstream target genes regulated by the candidate lncRNA were predicted using Starbase 2.0 software and the TargetScan database. The interactions between the candidate lncRNA and the putative downstream target genes were examined by Luciferase reporter assay, and were confirmed by PCR. Results: A total of 113 aberrantly expressed lncRNAs were identified by microarray analysis, of which family with sequence similarity 201-member A (FAM201A) was identified as the lncRNA that contributed the most to the radiosensitivity of ESCC. FAM201A was upregulated in radioresistant ESCC tumor tissues and had a poorer short-term response to radiotherapy resulting in inferior overall survival. FAM201A knockdown enhanced the radiosensitivity of ECA109/ECA109R cells by upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) expression via the negative regulation of miR-101 expression. The mouse xenograft model demonstrated that FAM201A knockdown improved the radiosensitivity of ESCC. Conclusion: The lncRNA FAM201A, which mediated the radiosensitivity of ESCC by regulating ATM and mTOR expression via miR-101 in the present study, may be a potential biomarker for predicting radiosensitivity and patient prognosis, and may be a therapeutic target for enhancing cancer radiosensitivity in ESCC.

Predictive value of carcinoembryonic antigen and carbohydrate antigen 19-9 related to downstaging to stage 0-I after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVE: To explore the value of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in predicting downstaging to stage 0-I cancer after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer. MATERIALS AND METHODS: We respectively investigated pretreatment CEA, pretreatment CA19-9, posttreatment CEA, posttreatment CA19-9, pre-post-CA19-9 ratio, and pre-post-CEA ratio in 674 patients with locally advanced rectal cancer receiving nCRT and determined the patients' thresholds by using the receiver operating characteristic curve analysis. The association between downstaging (stage 0-I after nCRT), pathological complete response, and clinicopathological parameters was evaluated using the Pearson χ2 test. The clinicopathological parameters which were found to be significantly associated with downstaging were analyzed by logistic regression models and were incorporated into a scoring system. RESULTS: Multivariate analysis showed that pretreatment CA19-9 level, posttreatment CEA level, pre-post-CEA ratio, and pre-post-CA19-9 ratio were significantly correlated with downstaging. Area under the curve of the scoring system was higher than that of parameters alone. CONCLUSION: The 4-factor scoring system with CA19-9 level, posttreatment CEA level, pre- post-CEA ratio, and pre-post-CA19-9 ratio is of more value in predicting downstaging to stage 0-I patients with locally advanced rectal cancer after nCRT than using the parameters alone.

Pretreatment Tumor Thickness as a Predictor of Pathologic Complete Response to Neoadjuvant Chemoradiation Therapy for Stage II/III Rectal Adenocarcinoma.

OBJECTIVES: To evaluate pretreatment tumor thickness in predicting pathologic complete response (pCR) of stage II/III rectal adenocarcinoma to neoadjuvant chemoradiation (chemoradiotherapy [CRT]). METHODS: We retrospectively analyzed 185 patients who were diagnosed with stage II or III rectal adenocarcinoma from January 2011 to July 2013 and treated with neoadjuvant intensity-modulated radiation therapy (45 Gy in 1.8-Gy fractions to pelvis and 50 Gy in 2-Gy fractions to rectal tumor as an integrated boost) or 3 dimensionally conformal radiation therapy (45 Gy in 1.8-Gy fractions to pelvis followed by an additional 5.4-Gy to rectal tumor) concurrently with two 3-week cycles of chemotherapy (oxaliplatin 130 mg/m on day 1 and capecitabine 825 mg/m, twice per day from day 1 to 14, cycle 2 starts on week 4). One week after CRT, 36% patients received 1 more cycle of the above chemotherapy and 55% received 1 to 2 cycles of FOLFOX6. Tumor response was categorized as pCR and non-pCR. Tumor thickness measured on magnetic resonance imaging was collected. A multivariate logistic regression model was used to evaluate the association of potential predictors and pCR. RESULTS: Thirty-eight patients (20.5%) reached pCR. Multivariate analysis found the pretreatment tumor thickness to be associated with higher probability of pCR after adjusting for radiation therapy-surgery interval time and pretreatment carcino-embryonic antigen level. The pretreatment carcino-embryonic antigen level was associated with pCR in the univariate analysis but lost the association in the multivatiate model. The pretreatment T or N stage, tumor volume, distance from tumor to anal verge, craniocaudal length of tumor, radiation therapy technique, and patient age and sex were not associated with pCR. CONCLUSIONS: We concluded that pretreatment tumor thickness is an independent predictor for pCR of stage II/III rectal adenocarcinoma to the neoadjuvant CRT.

Neoadjuvant chemotherapy may not benefit esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

BACKGROUND: To assess the efficacy of neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (CRT). METHODS: The clinical data of patients with ESCC treated with chemoradiotherapy with or without NAC were collected and retrospectively reviewed. The overall survival, locoregional failure-free survival, and distant failure-free survival were analyzed statistically. RESULTS: A total of 60 patients fulfilled the inclusion criteria, of which 41 were treated with NAC-CRT and 19 were treated with CRT-alone. Patient characteristics were well balanced between the NAC-CRT and CRT-alone groups, except for the ECOG scores. The tumor response to NAC included 11 patients (26.8%) with partial response (PR), 25 patients (61.0%) with stable disease (SD), 5 patients (12.2%) with progression disease (PD), and no patients with complete response (CR). After CRT, 21 patients achieved CR (14 after NAC-CRT and 7 after CRT-alone), 30 had PR (19 and 11, respectively), 6 maintained SD (5 and 1, respectively), and 3 patients (all in the NAC-CRT group) developed PD. Twenty-nine patients (18 in NAC-CRT and 11 in CRT-alone) succumbed to the disease from locoregional or distant failure, one patient in the NAC-CRT group died of radiation pneumonitis, one patient in the CRT-alone group died from unknown reasons, and 29 patients remained alive. The overall survival, locoregional failure-free survival, and distant failure-free survival at 1 and 2 years in all the patients were 64.9% and 40.5%, 58.6% and 52.0%, and 85.7% and 79.3%, respectively. The overall survival, locoregional failure-free survival, and distant failure-free survival between the NAC-CRT group and the CRT-alone group were not significantly different. CONCLUSION: In patients with ESCC treated with definitive CRT, NAC treatment using the current regimen does not prolong overall survival, locoregional failure-free survival or distant failure-free survival. Further development of NAC treatment is urgently needed.

Preliminary study of clinical application on IMRT three-dimensional dose verification-based EPID system.

The three-dimensional dose (3D) distribution of intensity-modulated radiation therapy (IMRT) was verified based on electronic portal imaging devices (EPIDs), and the results were analyzed. Thirty IMRT plans of different lesions were selected for 3D EPID-based dose verification. The gamma passing rates of the 3D dose verification-based EPID system (Edose, Version 3.01, Raydose, Guangdong, China) and Delta4 measurements were then compared with treatment planning system (TPS) calculations using global gamma criteria of 5%/3 mm, 3%/3 mm, and 2%/2 mm. Furthermore, the dose-volume histograms (DVHs) for planning target volumes (PTVs) as well as organs at risk (OARs) were analyzed using Edose. For dose verification of the 30 treatment plans, the average gamma passing rates of Edose reconstructions under the gamma criteria of 5%/3 mm, 3%/3 mm, and 2%/2 mm were (98.58 ± 0.93)%, (95.67 ± 1.97)%, and (83.13 ± 4.53)%, respectively, whereas the Delta4 measurement results were (99.14% ± 1.16)%, (95.81% ± 2.88)%, and (84.74% ± 7.00)%, respectively. The dose differences between Edose reconstructions and TPS calculations were within 3% for D95% , D98% , and Dmean in each PTV, with the exception that the D98% of the PTV-clinical target volume (CTV) in esophageal carcinoma cases was (3.21 ± 2.33)%. However, the larger dose deviations in OARs (such as lens, parotid gland, optic nerve, and spinal cord) can be determined based on DVHs. The difference was particularly obvious for OARs with small volumes; for example, the maximum dose deviation for the lens reached (-6.12 ± 5.28)%. A comparison of the results obtained with Edose and Delta4 indicated that the Edose system could be applied for 3D pretreatment dose verification of IMRT. This system could also be utilized to evaluate the gamma passing rate of each treatment plan. Furthermore, the detailed dose distributions of PTVs and OARs could be indicated based on DVHs, providing additional reliable data for quality assurance in a clinic setting.