Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma.

BACKGROUND: Bile duct obstruction is a common issue for patients with advanced cholangiocarcinoma (CCA). Percutaneous transhepatic cholangial drainage (PTCD) is often required to relieve the obstruction. However, PTCD may alter the intestinal microbiota, which can affect the efficacy of immunotherapy. Antibiotics (ATB) can also have significant immunomodulatory effects by perturbing the gut microbiota. Therefore, this study aimed to investigate whether PTCD or ATB therapy is associated with overall survival (OS) or progression-free survival (PFS) in patients with advanced CCA receiving first-line chemotherapy plus immune checkpoint blockade (ICB) in clinical practice. We also explored whether the gut microbiota changes after receiving PTCD. METHODS: We conducted a single-center retrospective analysis of PTCD and ATB therapy in patients with advanced CCA. PTCD was performed before ICB initiation, and ATB was administered within 1 month before and 6 weeks after ICB initiation. Our primary outcomes were PFS and OS. Moreover, we used 16s rRNA sequencing to analyze fecal and bile samples obtained from patients who underwent PTCD. RESULTS: In total, 107 patients with CCA were included. Among patients who did not undergo PTCD, ICB plus chemotherapy significantly improved OS vs. chemotherapy alone (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.09-0.45, p < 0.0001). PFS was also significantly improved in patients who received ICB plus chemotherapy compared with chemotherapy alone (HR 0.36, 95% CI 0.16-0.80, p = 0.0024). However, ICB plus chemotherapy did not improve survival compared with chemotherapy alone among patients who received PTCD. Overall changes in the fecal microbiota of patients after PTCD involved significant reductions in which Escherichia - Shigella. CONCLUSIONS: The use of ATB or PTCD in patients with CCA receiving ICB was associated with worse OS compared with chemotherapy alone, and PTCD affects the gut microbiota. Escherichia - Shigella was significantly reduced in feces of patients after PTCD.

Effect of Enhanced Recovery after Surgery (ERAS) Concept and Cluster Nursing on Psychological State and Pain of Oral Outpatients Undergoing Root Canal Therapy.

Objective: The effect of the concept of enhanced recovery after surgery (ERAS) and pain of patients undergoing root canal therapy in oral clinic. Methods: 200 participants in an oral clinic from March 2020 to March 2022 were enrolled in our study. The control group (n = 100) accepted ERAS-based care and the research group (n = 100) accepted ERAS concept and cluster nursing. Nursing satisfaction, comfort, self-efficacy, subjective well-being, self-rating anxiety scale (SAS), and self-rating depression scale (SDS) scores were compared. Results: The research group had 100% satisfaction rate; the control group had 87% satisfaction rate. After nursing, the scores of comforts and self-efficacy of the two groups increased and the scores of comforts and self-efficacy of the research group were higher than those of the control group. After nursing, the scores of subjective well-being of the two groups increased. Furthermore, the higher scores of life satisfaction, interpersonal harmony, and self-efficacy in the research group were found. There was no significant difference in the scores of SAS and SDS between the two groups before nursing (P > 0.05), but after nursing, the scores of SAS and SDS in the two groups decreased, and the scores of SAS and SDS in the research group were lower than those in the control group, and there are statistically significant differences between the groups (P < 0.05). The scores of visual analogue score (VAS) and numerical rating scale (NRS) following intervention decreased, and there are statistically significant differences between the groups (P < 0.05). The less physiological, psychological, social functions, and health self-cognition in the research group were displayed, and there are statistically significant differences between groups (P < 0.05). Conclusion: The adoption of the concept of ERAS and cluster nursing can effectively improve the psychological state and pain score of oral outpatients undergoing root canal therapy, improve comfort and self-efficacy, and enhance subjective well-being and quality of life. ERAS and cluster nursing is of great significance in relieving pain after root canal therapy in the outpatient department, reducing patients' pain and improving patients' quality of life.

A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery.

The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.

Clinical significance of serum dynamics of HSP90a level in esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

PURPOSE: We evaluate whether the change of heat shock protein 90a (HSP90a) level before and after definitive chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC) affects tumor response and overall survival (OS). This study aimed to investigate the role of HSP90a reduction ratio after CRT. METHODS: Correlations between pre-CRT HSP90a levels and the tumor response to CRT were analysed. Patients were divided into three groups (Group 1: Serum HSP90a levels pretreatment CRT less than 124 ng/mL; Group 2: pre-CRT HSP90a of 124 ng/mL or more with HSP90a reduction ratio of 65% or more; Group 3: pre-CRT HSP90a of 124 ng/mL or more with HSP90a reduction ratio less than 65%), and their oncologic outcomes were compared. RESULTS: The rates of good response in HSP90a low (pre-CRT HSP90a ≤ 124 ng/mL) and high groups (pre-CRT HSP90a ≤ 124 ng/mL) were 67.3% (68/101) and 37.78% (20/79), respectively (P= 0.004). The rates of good response were significantly higher in Group 1 than in Groups 2 and 3 (58.5% vs. 46.0% and 27.8%, respectively; P= 0.013). The results from statistical analysis indicated that the tumor response was significantly associated with the serum levels of pre-CRT HSP90a and HSP90a Group (P< 0.05). The OS rate was not different between Groups 1 and 2 but was significantly lower in Group 3. HSP90a Group were independent prognostic factors for OS. CONCLUSIONS: HSP90a levels could be of clinical value as a predictor of response to CRT HSP90a reduction ratio might be an independent prognostic factor for in ESCC patients treated with definitive CRT.

Minimum absolute lymphocyte counts during radiation are associated with a worse prognosis in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Peripheral blood lymphocytes play an important role in antitumour immunity. We examined the relationship between the minimum absolute lymphocyte counts (Min ALCs) during radiotherapy (RT) and clinical outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Data from a total of 69 HCC patients who had received RT were retrospectively analysed. Peripheral blood lymphocytes were measured before RT, weekly during RT and after RT. Regression and mixed-effect models were used to assess the relationships with and potential predictors of overall survival (OS). Receiver-operating characteristic (ROC) curve analysis was used to define optimal cut-off points of continuous variables for outcomes. RESULTS: The median follow up was 30 months (range, 4-68 months). The median survival time (MST), 1-year OS rate and 2-year OS rate of the whole group were 25 months, 51% and 39%, respectively. The average circulating lymphocyte counts declined during RT (1493.19 versus 503.48 cells/µl, p < 0.001). A lower Min ALC was associated with worse OS (p = 0.001), with a cut-off value of 450 cells/µl (sensitivity and specificity, 50% and 70.6%, respectively). The MSTs, 1-year OS rates and 2-year OS rates were 15 months versus 47 months, 27% versus 78% and 4% versus 71% for patients with relatively lower (⩽450 cells/µl) and higher Min ALCs (>450 cells/µl), respectively (p < 0.001). After adjusting for potential confounders, multivariate Cox regression analysis demonstrated that Min ALC independently predicted patients' OS (HR, 0.32; 95% CI, 0.15-0.69). CONCLUSIONS: Lower Min ALCs during RT may act as a worse prognostic factor for HCC after RT.

Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis.

PURPOSE: Numerous studies have tried to combine transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR), overall survival (OS), and adverse events. RESULTS: Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07-5.80; P<0.001) and OS (HR, 0.69; 95% CI, 0.57-0.83; P=0.001), but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67-2.79; P=0.390). The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478-13.56; P<0.001) and thrombocytopenia (OR, 3.77; 95% CI, 1.06-13.43; P=0.041) was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group. CONCLUSION: Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could bring higher ORR of PVTT and better survival benefits. This combination therapy was also associated with a significantly increased risk of adverse events. However, they were mostly mild to moderate and successfully treated with conservative treatment.

Superiority of helical tomotherapy on liver sparing and dose escalation in hepatocellular carcinoma: a comparison study of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: To compare the difference of liver sparing and dose escalation between three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) for hepatocellular carcinoma. PATIENTS AND METHODS: Sixteen unresectable HCC patients were enrolled in this study. First, some evaluation factors of 3DCRT, IMRT, and HT plans were calculated with prescription dose at 50 Gy/25 fractions. Then, the doses were increased using HT or IMRT independently until either the plans reached 70 Gy or any normal tissue reached the dose limit according to quantitative analysis of normal tissue effects in the clinic criteria. RESULTS: The conformal index of 3DCRT was lower than that of IMRT (P<0.001) or HT (P<0.001), and the homogeneity index of 3DCRT was higher than that of IMRT (P<0.001) or HT (P<0.001). HT took the longest treatment time (P<0.001). For V 50% (fraction of normal liver treated to at least 50% of the isocenter dose) of the normal liver, there was a significant difference: 3DCRT > IMRT > HT (P<0.001). HT had a lower D mean (mean dose) and V 20 (V n, the percentage of organ volume receiving ≥n Gy) of liver compared with 3DCRT (P=0.005 and P=0.005, respectively) or IMRT (P=0.508 and P=0.007, respectively). D mean of nontarget normal liver and V 30 of liver were higher for 3DCRT than IMRT (P=0.005 and P=0.005, respectively) or HT (P=0.005 and P=0.005, respectively). Seven patients in IMRT (43.75%) and nine patients in HT (56.25%) reached the isodose 70 Gy, meeting the dose limit of the organs at risk. CONCLUSION: HT may provide significantly better liver sparing and allow more patients to achieve higher prescription dose in HCC radiotherapy.

MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells.

Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer­associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)­21 in the development of radiation resistance in non­small cell lung cancer cells. A radiation­resistant cell line was generated from A549 cells. Significant upregulation of miR­21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR­21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia­inducible factor­1α (HIF1α) was upregulated by miR­21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR­21­inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR­21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.

Nutrient flow and distribution in conventional cage, enriched colony, and aviary layer houses.

This study was carried out to measure the mass flow and distribution of nutrients (N, C, S, P, and K) as well as solids and moisture in conventional cage (CC), enriched colony (EC), and aviary (AV) laying-hen houses with Lohmann LSL lite hens located on a commercial laying-hen farm in Iowa. The weight of consumed feed and water, and amounts of eggs and manure production were collected weekly from each house for 2 entire flocks for a total of 28 mo. Samples of feed, egg, manure, litter, and hens were regularly taken and analyzed for total solids and nutrients (N, C, S, P, and K). The nutrient losses to the atmosphere were calculated using a mass balance approach. The losses of nutrients were calculated by subtracting the nutrient contents in eggs, manure, and layer body weight gain from the nutrients intake. The research results showed that the feed intake and manure production rates were similar in the 3 houses. The average nutrient intake in feed, in g d(-1) hen(-1), for the 3 houses was 42.0 C, 2.96 N, 0.36 S, 0.55 P, and 0.79 K. The nutrient intake was partitioned as follow: C - 18% in eggs, 28% in manure, and 54% in air losses; N - 34% in eggs, 58% in manure, and 8% in air losses; S - 26% in eggs, 68% in manure, and 6% in air losses; P - 17% in eggs, 79% in manure, and 3.1% in air losses; and K - 9% in eggs, 89% in manure, and 1.6% in air losses. Manure removed from the EC house was drier than manure from the CC or AV house. Among the 3 hen houses studied, the EC house had the lowest nutrient losses and the AV house had the highest losses. Nutrient loss in CC was statistically similar to EC. But loss of N, C, and S in AV differed from CC and EC. Furthermore, the loss of P and K in the 3 housing systems was statistically similar. The AV had a doubled mortality rate compared to CC and EC.

The prognostic role of TCF4 expression in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy.

BACKGROUND: At present no useful factors to predict the sensitivity to neoadjuvant chemoradiotherapy (nCRT) have been established in patients with locally advanced rectal cancer (LARC). OBJECTIVE: The objective of this study was to explore the prognostic role of T cell factor 4 (TCF4) expression in predicting tumor response to nCRT and tumor outcomes for patients with LARC. METHODS: The study enrolled 96 patients who underwent nCRT followed by total mesorectal excision (TME). The TCF4 expression of all patients' biopsies before nCRT was evaluated by Immunohistochemical staining method. RESULTS: After completion of nCRT, 5 cases (5.2%) achieved clinical complete response (cCR) thus the remaining 91 patients underwent a standardized total mesorectal excision (TME) procedure. There were 44 patients (45.8%) achieved good tumor response (including TRG 3-4 and 5 cCR patients) while poor response (TRG 0-2) was achieved in 52 patients (54.2%). Our results demonstrated that patients with low expression of TCF4 were more sensitive to nCRT than those with high TCF4 expression (P=0.031). Low TCF4 expression before nCRT and good response were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment TCF4 expression was an independent prognostic factor. CONCLUSIONS: Our data revealed that low TCF4 protein expression was a useful predictive factor of good tumor response to nCRT and good outcomes in patients with LARC.

Prognostic value of serum γ-glutamyl transferase in unresectable hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization combined with conformal radiotherapy.

The detection of γ-glutamyl transferase (GGT) has previously been reported to be useful in the diagnosis in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the baseline serum GGT levels in patients with intermediate HCC (Barcelona Clinic Liver Cancer stage B) following treatment with transcatheter arterial chemoembolization (TACE) combined with three-dimensional conformal radiotherapy (3DCRT). A total of 154 intermediate HCC patients with Child-Pugh grade A were retrospectively investigated. Receiver operating characteristic (ROC) analysis was used to determine the optimal threshold for the GGT serum levels, and univariate and multivariate analyses were used to establish the prognostic factors. The median overall survival (OS) time was 24.3 months. The optimal threshold for GGT was 85 U/L (sensitivity, 75.13%; specificity, 69.81%; and area under the ROC curve, 0.763). The one-, three- and five-year OS rates were 79.9, 49.7 and 17.2%, respectively, for patients with low GGT levels (≤85 U/l) and 52.3, 22.1 and 8.5%, respectively, for patients with high GGT levels (>85 U/l) (P=0.007). The results indicated that the serum GGT level was an independent prognostic factor (hazard ratio=2.32; P=0.007) for OS. Furthermore, in subgroups stratified according to serum α-fetoprotein, gross tumor volume and radiation dose, serum GGT was also found to correlate with OS (P<0.05). Therefore, the baseline GGT level may be a significant prognostic factor for intermediate HCC patients with Child-Pugh grade A following TACE combined with 3DCRT.

The prognostic role of EZH2 expression in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been implemented as a standard treatment strategy in locally advanced rectal cancer (LARC). However, there is a wide spectrum of response to nCRT. The aim of this study was to determine whether enhancer of zeste homologue 2 (EZH2 ) expression could predict response to nCRT and outcomes for patients in LARC. METHOD: The study examined the EZH2 expression in 112 biopsies by immohistochemistry. The associations between EZH2 and clinical characters were analyzed. RESULTS: EZH2 expression in biopsy tissue was significantly related to increased tumor cell proliferation, as assessed by Ki-67 expression with a cutoff value of 37% (p <0.001). High EZH2 expression was correlated closely with low differentiation (p = 0.029), high CEA level (p = 0.041), T4 status (p = 0.011) and node metastasis (p =0.045). By univariate and multivariate analysis, we observed low EZH2 expression could reliably and independently predict the good response to nCRT ( p = 0.026 and p = 0.023) and down-staging ( p = 0.021 and p = 0.027). In univariate analysis, high EZH2 expression was significantly associated with poor 5-year disease-free survival (p = 0.025) and 5-year overall survival (p = 0.032). In multivariate analysis, EZH2 was a prognostic factor for 5-year DFS (HR = 2.287; 95% CI 1.137-4.602, p = 0.020) but not for 5-year OS (HR = 2.182; 95% CI 0.940-5.364, p = 0.069). CONCLUSION: Our study revealed that low EZH2 expression in biopsy tissue might be a useful predictive factor of good tumor response to nCRT and longer 5-year DFS in patients with LARC. However this is a relatively small retrospective study, to further validate the role of EZH2 in rectal cancer, large consistent cohort studies are needed.

PDCD4 as a predictor of sensitivity to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.

OBJECTIVE: The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. METHODS: Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). RESULTS: Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. CONCLUSION: Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

A comparison of liver protection among 3-D conformal radiotherapy, intensity-modulated radiotherapy and RapidArc for hepatocellular carcinoma.

PURPOSE: The analysis was designed to compare dosimetric parameters among 3-D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and RapidArc (RA) to identify which can achieve the lowest risk of radiation-induced liver disease (RILD) for hepatocellular carcinoma (HCC). METHODS: Twenty patients with HCC were enrolled in this study. Dosimetric values for 3DCRT, IMRT, and RA were calculated for total dose of 50 Gy/25 f. The percentage of the normal liver volume receiving >40, >30, >20, >10, and >5 Gy (V(40), V(30), V(20), V(10) and V(5)) were evaluated to determine liver toxicity. V5, V(10), V(20), V(30) and D(mean) of liver were compared as predicting parameters for RILD. Other parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V(110%)) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (D(mean)) for the organs at risk (OARs) and the maximal dose at 1% volume (D1%) for the spinal cord. RESULTS: The D(mean) of IMRT was higher than 3DCRT (p = 0.045). For V5, there was a significant difference: RA > IMRT >3DCRT (p <0.05). 3DCRT had a lower V(10) and higher V(20), V(30) values for liver than RA (p <0.05). RA and IMRT achieved significantly better CI and lower V(110%) values than 3DCRT (p <0.05). RA had better HI, lower MUs and shorter delivery time than 3DCRT or IMRT (p <0.05). CONCLUSION: For right lobe tumors, RapidArc may have the lowest risk of RILD with the lowest V(20) and V(30) compared with 3DCRT or IMRT. For diameters of tumors >8 cm in our study, the value of Dmean for 3DCRT was lower than IMRT or RapidArc. This may indicate that 3DCRT is more suitable for larger tumors.

NSE can predict the sensitivity to definitive chemoradiotherapy of small cell carcinoma of esophagus.

Patients with esophageal small cell carcinoma undergoing definitive chemoradiotherapy (CRT) seem to have disparity in tumor response. The identification of CRT sensitivity-related tumor markers would be helpful for selecting patients most likely to benefit from CRT. The aim of this study was to examine the predictive value of biological markers in small cell carcinoma of the esophagus (SCEC) patients treated with definitive CRT. Pretreatment serum levels of neurone-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and carcinoembryonic antigen (CEA) were measured by immunoradiometric assays, while the tumor responses were evaluated according to the World Health Organization response criteria. The relationships between pretreatment expression of NSE, CYFRA21-1, CEA, and the tumor response to CRT were analyzed. The effective rates (complete response + partial response) in NSE high and low groups were 10.80 % (9/82) and 37.98 % (31/82), respectively (P = 0.003).The results from statistical analysis indicated that the effectiveness of CRT was significantly associated with the serum levels of NSE before treatment (P = 0.002). The overall survival (OS) of the patients with high NSE levels was worse than that of those with low NSE levels (P = 0.004). In multivariate analysis, low level of NSE was the most significant independent predictor of good OS (P = 0.003). The result showed a promising predictive value of NSE regarding to the sensitivity of tumors to CRT. NSE may be a reliable surrogate marker of CRT efficacy in patients with SCEC.

Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases.

OBJECTIVE: The objective of this study was to identify clinical predictive factors for tumor response after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). METHODS: All factors were evaluated in 88 patients with LARC treated with nCRT. After a long period of 4-8 weeks of chemoradiotherapy, 3 patients achieved clinical complete response (cCR) and thus aggressive surgery was avoided, and the remaining 85 patients underwent a curative-intent operation. The response to nCRT was evaluated by tumor regression grade (TRG) system. RESULTS: There were 32 patients (36.4%) with good tumor regression (TRG 3-4) and 56 (63.6%) with poor tumor regression (TRG 0-2). Lymphocyte counts and ratios were higher in good response cases (P=0.01, 0.03, respectively) while neutrophil ratios and N/L ratios were higher in poor response cases (P=0.04, 0.02, respectively). High lymphocyte ratios before nCRT and good tumor regression (TRG3-4) were significantly associated with improved 5-year disease-free survival (P<0.05). Pretreatment nodal status was also significantly associated with 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment lymphocyte ratio and lymph nodal status were independent prognostic factors. CONCLUSION: Our study suggested that LARC patients with high lymphocyte ratios before nCRT would have good tumor response and high 5-year DFS and OS.

Photocatalytic oxidation of NOx over TiO2/HZSM-5 catalysts in the presence of water vapor: Effect of hydrophobicity of zeolites.

TiO(2) hybridized with HZSM-5 zeolites photocatalysts were prepared by a simple solid state dispersion method. The physicochemical properties of the catalysts were characterized by X-ray diffraction, UV-vis diffuse reflectance and FT-IR spectroscopy. The photocatalytic oxidation of NO(x) over TiO(2)/HZSM-5 having different Si/Al ratios was carried out under various levels of humidity and different pre-adsorption times in dark. The TiO(2)/HZSM-5 composite catalysts exhibited higher NO conversion and lower NO(2) formation than pure TiO(2). Pre-adsorption with water vapor and the high humidity during the photoreaction were harmful to the reactivity of TiO(2) hybridized with hydrophilic HZSM-5 zeolite. However, the photocatalytic reactivity of TiO(2) hybridized with hydrophobic zeolite varied little with increase in humidity. The results indicated that the high photocatalytic reactivity of TiO(2)/HZSM-5 catalysts is largely depended on the hydrophobicity of the zeolites.

Cytokeratin 19 fragment antigen 21-1 as an independent predictor for definitive chemoradiotherapy sensitivity in esophageal squamous cell carcinoma.

BACKGROUND: Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT. METHODS: Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival (OS) was estimated by univariate and multivariate analysis. RESULTS: The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P = 0.001 and P = 0.023, respectively). It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P = 0.041). By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P = 0.002). The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P = 0.001). In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS (P = 0.007). CONCLUSIONS: CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.

Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy.

PURPOSE: To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). METHODS: Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. RESULTS: The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). CONCLUSIONS: Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

Prognostic value of Smac expression in rectal cancer patients treated with neoadjuvant therapy.

The objective was to evaluate expression of second mitochondria-derived activator of caspase (Smac) expression before and after treatment in patients treated with preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer and to correlate the clinicopathological characteristics and level of Smac expression with pathologic response and outcome. Expression of biomarker was evaluated by immunohistochemistry in tumor samples from 98 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy plus concurrent chemotherapy. All patients received a standardized total mesorectal excision procedure after a long interval of 4-6 weeks. For Smac, patients with a good response to neoadjuvant CRT tended to have higher pre-therapy levels (P = 0.007). The level of Smac expression decreased after neoadjuvant therapy (P = 0.016). High expression of Smac before CRT, and high Dworak's tumor regression grade (TRG) were significantly associated with improved 5-year disease-free survival (P < 0.05). Pretreatment nodal status also was significantly associated with 5-year disease-free survival and 5-year local relapse-free survival (P < 0.05). Multivariate analysis confirmed that the pretreatment expression of Smac and Lymph nodal status were independent prognostic factors. Our study suggests that high expression of Smac before neoadjuvant CRT could predict good outcome in locally advanced rectal cancer patients.