Pathological response and serum VEGF changes during chemoradiotherapy for esophageal carcinoma.

The aim of this study was to observe pathological response and change in serum vascular endothelial growth factor (VEGF) in esophageal carcinoma (EC) during chemoradiotherapy (CRT).Eighty-nine patients diagnosed with EC were treated with radiotherapy at the Department of Radiotherapy of the Second People's Hospital of Changzhou between May 2008 and December 2014, including 65 patients with CRT. Gastroscopy and pathological examination were conducted 4 weeks afterwards. The pathological responses were classified as complete response (CR) and non-CR. Serum samples were collected from the patients before radiotherapy, during week 4 of radiotherapy, and 1 week after radiotherapy. The VEGF changes were classified as increase, stable, and decrease.The median overall survival (OS) and median progression-free survival (PFS) in the pathological CR group was significantly longer than that of the non-CR group (P < .001). The 1-, 3-, and 5-year OS rates in the non-CR group were lower than that in the CR group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the non-CR group were lower than that in the CR group (P < .05). VEGF serum level was decreased during and after radiotherapy compared with pre-radiotherapy, and the differences were statistically significant (P < .05). The 1-, 3-, and 5-year OS rates in the increased group were lower than that in the decreasing group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the increasing group were lower than that in the decreasing group (P < .05). Pathological response (P < .05), serum VEGF trend (P < .05), and tumor-node-metastasis stage (P < .05) in response to CRT were factors that influenced patient prognosis.Pathological response and serum VEGF change during CRT can predict prognosis of nonsurgical patients with EC. Monitoring these changes is of significance in individualized treatment.

Pathologic response during chemo-radiotherapy and variation of serum VEGF levels could predict effects of chemo-radiotherapy in patients with esophageal cancer.

BACKGROUND: To investigate the relationship between pathologic tumor response to concurrent chemo- radiotherapy and variation of serum VEGF in patients with esophageal cancer. MATERIALS AND METHODS: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. RESULTS: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. CONCLUSIONS: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer.

AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC). METHODS: Serum samples from 86 EC patients were collected before, during, and after radiotherapy, and the vascular endothelial growth factor (VEGF) level was examined by ELISA. According to the change in serum VEGF level during radiotherapy, the patients were divided into two groups: in the drug group, VEGF level was increased or remained unchanged, and thalidomide was administered up to the end of radiotherapy; in the non-drug group, VEGF level was decreased and radiotherapy was given alone. Thirty healthy volunteers served as controls. The efficacy and safety of radiotherapy plus thalidomide therapy were investigated. RESULTS: The 86 EC patients had a significantly higher level of VEGF compared with the 30 healthy controls before radiotherapy (P < 0.01), and the VEGF level was significantly correlated with primary tumor size, lymph node metastasis, histopathologic type, and clinical stage (P < 0.01). Of 83 evaluable cases, VEGF level was significantly decreased after radiotherapy in 32 patients in the drug group (P < 0.05), with an effective rate of 71.88%. The incidence of dizziness and/or burnout in the drug group and non-drug group was 62.50% and 15.69%, respectively (P = 0.000), and the incidence of somnolence was 12.50% and 0%, respectively (P = 0.019). No significant differences were observed. CONCLUSION: Thalidomide can down-regulate serum VEGF level in EC patients, and combined with radiotherapy may improve treatment outcome. Thalidomide was well tolerated by EC patients.

Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines.

AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics. METHODS: A serum-free medium (SFM) suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres. A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells. Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays. Furthermore, different cells after different doses of irradiation were tested to evaluate the change in sphere formation, cell cycle and CD44(+)CD271(+) expression of tumor stem-like spheroid cells using flow cytometry before and after irradiation. RESULTS: The cells were observed to generate an increased number of spheres in SFM with increasing cell passage. Radiation increased the rate of generation of stem-like spheres in both types of cells. The average survival fraction (SF2) of the cultured KYSE-150 compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81 ± 0.03 vs 0.87 ± 0.01 (P < 0.05), while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69 ± 0.04 vs 0.80 ± 0.03, P < 0.05. In the esophageal parental cells, irradiation dose-dependently induced G2 arrest. Stem-like esophageal spheres were resistant to irradiation-induced G2 arrest without significant changes in the percentage population of irradiated stem-like cells. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE150 parental cells was 1.08% ± 0.03% vs 1.29% ± 0.07% vs 1.11% ± 0.09%, respectively; the CD44(+)CD271(+) cell percentage for TE1 parental cells was 1.16% ± 0.11% vs 0.97% ± 0.08% vs 1.45% ± 0.35%, respectively. The differences were not statistically significant. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE-150 stem-like spheres was 35.83% ± 1.23% vs 44.9% ± 1.67% vs 57.77% ± 1.88%, respectively; the CD44(+)CD271(+) cell percentage for TE1 stem-like spheres was 16.07% ± 0.91% vs 22.67% ± 1.12%, 16.07% ± 0.91% vs 33.27% ± 1.07%, respectively. The 4 and 8 Gy irradiated KYSE-150 and TE-1 stem-like spheres were compared with the 0 Gy irradiated group, and the differences were statistically significant (P < 0.05). CONCLUSION: The KYSE-150 and TE-1 stem-like spheres are more radioresistant than their parental cells which may suggest that cancer stem cells are related to radioresistance.

Theory of mind deficits in patients with esophageal cancer combined with depression.

AIM: To characterize the two components of theory of mind (ToM) in patients with esophageal cancer combined with depression. METHODS: Sixty-five patients with esophageal cancer combined with depression (depressed group) and 62 normal controls (control group) were assessed using reading the mind in the eyes test, faux pas task, verbal fluency test, digit span test and WAIS IQ test. The depressed group was divided into two subgroups including psychotic depressed (PD) group (32 cases) and nonpsychotic depressed (NPD) group (33 cases). The clinical symptoms of patients were assessed using Beck depression inventory version II and brief psychiatric reacting scale (BPRS). RESULTS: There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components (mind reading: t = 7.39, P < 0.01) and tests involving ToM social cognitive components (faux pas questions: t = 13.75, P < 0.01), respectively. A significant difference was also found among the PD group, the NPD group and the control group on mind reading (F = 32.98, P < 0.01) and faux pas questions (χ² = 78.15, P < 0.01), respectively. The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions (P < 0.05). The PD group performed significantly worse than the NPD group on tasks involving ToM (mind reading: F = 18.99, P < 0.01; faux pas questions: F = 36.01, P < 0.01). In the depressed group, there was a negative correlation between ToM performances and BPRS total score (mind reading: r = -0.35, P < 0.01; faux pas questions: r = -0.51, P < 0.01), and between ToM performances and hostile suspiciousness factor score (mind reading: r = -0.75, P < 0.01; faux pas questions: r = -0.73, P < 0.01), respectively. CONCLUSION: The two components of ToM are both impaired in patients with esophageal cancer combined with depression. This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression.

[A prospective multicenter randomized double-blinded controlled clinical trial on effects of tiantai no.1 in treating mild cognitive impairment].

OBJECTIVE: To observe the clinical effectiveness and safety of Tiantai No. 1 (TT1) in treating mild cognitive impairment (MCI). METHODS: With randomized double-blinded method adopted, the 128 MCI patients, selected according to the commonly accepted standard for MCI diagnosis, were assigned to 2 groups, the treatment group (65 cases) treated with TT1 and the control group (63 cases) treated with placebo for six months. Besides, a normal control group with 30 healthy elders was set up. Changes of comprehensive cognitive function, instant memory, short-term memory, calculation ability, orientating ability of time and space, language understanding ability as well as Chinese medicine syndromes before and after treatment were observed and compared. RESULTS: The cognitive function of MCI patients was significantly lower than that of healthy elders (P<0.01). The comprehensive cognitive function, and all the above-mentioned abilities were significantly improved (P<0.05, P<0.01) in the TT1 treated group after treatment, with an effect significantly better than that in the placebo treated group (P<0.01). Overall evaluation of effect and safety suggested that the clinical effectiveness index (CEI) of TT1 was notably higher than that of the placebo. And it was found in one-year follow-up that the incidence of developing to Alzheimer's disease (AD) in the treatment group was strikingly lower than that in the control group (P<0.01). CONCLUSION: TT1 can significantly improve the cognitive function of MCI patients, and reduce their incidence of developing to AD.

Serum transforming growth factor-beta1 level reflects disease status in patients with esophageal carcinoma after radiotherapy.

AIM: To evaluate the relationship between changes in serum transforming growth factor beta1 (TGFbeta1) level and curative effect of radiotherapy (RT) in patients with esophageal carcinoma. METHODS: Ninety patients with histologically confirmed esophageal carcinoma were enrolled. Serum samples for TGFbeta1 analysis were obtained before and at the end of RT. An enzyme-linked immunosorbent assay was used to measure serum TGFbeta1 level. Multivariate analysis was performed to investigate the relationship between disease status and changes in serum TGFbeta1 level. RESULTS: Serum TGFbeta1 level in patients with esophageal carcinoma before RT was significantly higher than that in healthy controls (P < 0.001). At the end of RT, serum TGFbeta1 level was decreased in 67.82% (59/87) of the patients. The overall survival rate at 1, 3 and 5 years was 48.28% (42/87), 19.54% (17/87) and 12.64% (11/87), respectively. Main causes of death were local failure and regional lymph node metastasis. In patients whose serum TGFbeta1 level decreased after RT, the survival rate at 1, 3 and 5 years was 61.02% (36/59), 28.81% (17/59) and 18.64% (11/59), respectively. The survival rate at 1 year was 17.86% (5/28) in patients whose serum TGFbeta1 level increased after RT, and all died within 18 mo (P < 0.01). CONCLUSION: Serum TGFbeta1 level may be a useful marker for monitoring disease status after RT in patients with esophageal carcinoma.

Randomized clinical trial on seven-day-per-week continuous accelerated irradiation for patients with esophageal carcinoma: preliminary report on tumor response and acute toxicity.

AIM: Tumor response and normal tissue toxicity of seven-day-per-week continuous accelerated irradiation (CAIR) for patients with esophageal carcinoma were evaluated and compared to conventional irradiation (CR). METHODS: Sixty patients with squamous cell carcinoma of the esophagus were randomized into two groups: the CAIR group (30 patients) and the CR group (30 patients). Patients in the CAIR group received radiotherapy (RT) with 2 Gy/fraction per day at 7 d/wk with a total dose of 50-70 Gy (average dose 64.2 Gy). The overall time of irradiation was 3.6-5.0 wk (average 4.6 wk). RT in the CR group was 2 Gy/fraction per day at 5 d/wk with a total dose of 40-70 Gy (average dose 61.7 Gy). The overall time of irradiation was 4.0-7.0 wk (average 6.4 wk). RESULTS: The data showed that the immediate tumor response to RT was better in the CAIR group than in the CR group. Efficiency rates (CR plus PR) were 82.8% (24/29) and 58.6% (17/29), respectively (P = 0.047). In both groups the incidences of esophagitis and tracheitis were insignificant (P = 0.376, 0.959), and no patient received toxicity that could not be tolerated. CONCLUSION: CAIR shortens overall treatment time and is well tolerated by patients. It may be superior to CR in enhancing the local response of tumor, but its remote effect for esophageal carcinoma awaits further follow-up.

A biomechanical study of the cortex-anchorage vertebral screw.

OBJECTIVE: To obtain a comprehensive understanding on the effect of the improvement of fixation strength and on the optimal design in various geometrical parameters of a new screw system through biomechanical analyses. DESIGN: A new screw with the cortex-anchorage was designed and manufactured to improve the fixation of the instrumentation for osteoporotic spine. There were four expandable wings distributed around the screw after insertion. BACKGROUND: Screw loosening or loss of correction caused by insufficient mechanical stability on the bone-screw interface is frequently found in osteoporotic subjects. Similarly, the removal and replacement of a screw in a revision procedure substantially decreases its mechanical fixation. Since cortex is the most rigid part in the vertebral body, emphasis on the cortex-anchorage may offer an optimal fixation of screws. METHODS: The biomechanical evaluation that consists of the pullout test and the finite element analysis was applied to identify the stabilizing effect and the optimal design for the new screw system. In the pullout experiment, the porcine vertebral body with a hollow block of cancellous bone was proposed to simulate an osteoporotic spine. This osteoporotic model was specially simulated the degeneration and destruction of the cancellous bone in vertebrae. In the finite element analysis, the reduction of elastic modulus was used in various levels of vertebral degeneration. RESULTS: Pulling screws out of vertebral bodies with a hollow block of cancellous bone, the mean pullout force was 729 (SD 159) N for the conventional screws, and 1072 (SD 179) N for the new screw system. The finite element analysis showed that the longer screw with bi-cortex fixation was the better option in reducing the bony stress and increased the stability. As the height of wings changed, the stress distributed on vertebral body indicated the lowest in fixation by a screw with the largest wings. Nevertheless, there existed a least displacement of vertebral body and moderately low stress on wings' lateral end when assembled with the middle size wings. CONCLUSION: The stabilization function of expansive wings of the new screw system was enhanced in the osteoporotic vertebra and better than that of a conventional screw. The finite element analysis showed a middle size wing could help the screw to reduce the risk of failure and to improve the vertebral stability. RELEVANCE: Screw loosening or loss of correction caused by insufficient mechanical stability on the bone-screw interface is frequently found in osteoporotic subjects. From the biomechanical point of view, this study had shown that a new design of screw could improve the fixation of the instrumentation for osteoporotic spine. With further investigations that includes the clinical proof and the development of a cortex-anchorage vertebral screw may provide a valuable alternative to the spinal instrumentation for the patients with osteoporosis.