Removal of giant intraocular foreign body with the assistance of silicone oil tamponade in 23G vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the outcomes and safety of minimally invasive 23G pars plana vitrectomy(PPV) combined with silicone oil tamponade for the removal of giant intraocular foreign body (IOFB).METHODS:A total of 12 cases diagnosed with giant IOFB were included in this retrospective study in which 11 eyes of 11 males and 1 eye of 1 female were treated in Changsha Aier Eye Hospital between February 2012 and March 2015.Among these patients,the preoperative best corrected visual acuity varied from light perception to 0.1 with retinal detachment identified in all 12 eyes.All patients underwent 23G minimally invasive PPV.After the vitreous was removed and the damaged retina was repaired,silicone oil was filled,and then the scleral incision was extended to remove the giant IOFB.Lens extraction and intraocular lens implantation were performed in some patients when necessary.Silicone oil was removed 6mo later.RESULTS:The giant IOFB was removed successfully just with 1 attempt in each of 12 eyes,and no IOFB fell and reinjured the retina or damaged the cornea during the procedure.All retinas were reattached and no endophthalmitis was observed in any patients postoperatively.The silicone oil was removed successfully after 6mo,and by then the visual acuity was improved in all cases.Sixty-seven percent of patients became free of blindness and 25％ free of visual disability.CONCLUSION:Removing giant IOFB through 23G PPV assisted with silicone oil tamponade is safe and effective.

Analysis of the results detected by ultrasound biomicroscopy before patients with rhegmatogenous retinal detachment perform pars plana vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

?AlM: To analyze the result of ultrasound biomicroscopy ( UBM ) of patients with rhegmatogenous retinal detachment ( RRD ) who need to perform pars plana vitrectomy ( PPV ) to explore the value of clinical application of UBM at preoperation. ?METHODS:Patients who underwent PPV for RRD in our hospital from January to December 2014 were selected. The preoperative results of UBM were recorded and the positive findings of UBM were analyzed, the value of preoperative application of UBM was investigated. ?RESULTS:Totally 356 cases (357 eyes) of patients with RRD were received PPV. All patients were examined by UBM, 122 eyes ( 34. 17%) were positive, 56 eyes were ciliochoroidal detachment, 28 eyes were narrow anterior chamber angle, 6 eyes were chamber angle-closure, 28 eyes were ciliary body cyst, 4 eyes were iris cyst, 11 eyes were anterior proliferative vitreoretinopathy, 1 eye was retinal cyst. There were 12 eyes existing two lesions at the same times. ln this study, patients with choroidal detachment was detected by UBM in 56 eyes, the positive rate was 15. 7%, while 25 eyes was detected by B -ultrasonography, the positive was 7. 0%. The difference was statistical significant(χ2=13. 382, P ?CONCLUSlON: The patients with RRD have underwent PPV for the condition of illness, preoperative UBM can be examined to detect the condition of anterior chamber angle, iris, ciliary and anterior choroid, which is significant for comprehensively understanding the preoperative condition of patients, estimating the difficulty of the operation, and guiding operation and the postoperative follow-up.

Clinical study on the incidence of vancomycin intraocular injection in treatment with suppurative endophthalmitis / 国际眼科杂志(Guoji Yanke Zazhi)

? AlM: To estimate the clinical significance of the microculture of humor and vitreous and vancomycin intraocular injection in treatment of suppurative endophthalmitis associated with intraocular foreign bodies. ?METHODS: Totally 65 patients with penetrating eye trauma and retained intraocular foreign bodies in emergency operation and intraocular injection from January 2012 to September 2014 were regarded as the study group, another 62 patients with penetrating eye trauma and retained intraocular foreign bodies in emergency operation without intraocular injection before August 2011 were regarded as the control group. Aqueous humor and vitreous humor were taken from each patient of the study group and the control group for bacteria and fungus cultivation. The study group was treated with 1mg vancomycin intraocular injection after operation, while the control group was not. ?RESULTS: The incidence of endophthalmitis in the control group was 16% ( 10 cases ) , while in the study group was 3% ( 2 cases ) , with significant difference between two groups (x2 =6. 32, P0. 05). The positive rate of vitreous humor germiculture in study group was 14% (9 cases), and the incidence of endophthalmitis was 3%. The positive rate of vitreous humor germiculture in control group was 11% (7 cases) and the incidence of endophthalmitis was 16%, with significant differences between two groups (P<0. 05).?CONCLUSlON: lntraocular foreign bodies treated with emergency operation and vancomycin intraocular injections can decrease the incidence of suppurative endophthalmitis and have a good vision prognosis for the second stage of operation.

Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center, Randomized, Parallel, Open-label, Phase II Clinical Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.</p><p><b>METHODS</b>A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS).</p><p><b>RESULTS</b>The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively.</p><p><b>CONCLUSIONS</b>Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.</p>

Analysis of phakic before intraocular lens implantation for fundus examination / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the findings of the eyes which were examined preoperatively by three mirror contact lens before the implantation of implantable collamer lens ( ICL) . To analysis the retinal pathological changes and to explore the clinical analysis of early diagnosis and treatment in retinopathy on fundus examination before operation. METHODS:The retrospective case series study included 127 eyes of 64 patients who underwent phakic intraocular lens implantation were received the fundus examination by three mirror from April 2011 to April 2012 in our hospital. The age, refractive diopter, the findings of Goldmann three mirror examination and the condition of retinal photocoagulation were analysed and concluded.RESULTS:A total of 34 eyes (26. 8%) out of all 127 eyes ( 64 cases ) were found to have peripheral retinal pathological changes. Eight eyes ( 6. 3%) with retinal holes, 15 eyes(11. 8%) with retinal lattice degeneration, 5 eyes ( 3.9%) with retina cream degeneration, 3 eyes (2.4%)with retinal paving stone degeneration,2 eyes with vitreoretinal adhesion and traction, 1 eye ( 0. 8%) with retinal hemorrhage. Twenty-five cases were given retinal photocoagulation and then received the ICL implantation after 3mo. The follow - up time was 1a. No retinal detachment happened. CONCLUSION: Phakic before intraocular lens implantation for fundus examination by three mirror is contributed to find the peripheral retinal pathological changes and abnormity. And make the appropriate treatment before operation for improving the security of operation, it can also give help to the postoperative follow-up of the fundus of these patients.

Vasculogenic mimicry: a novel target for glioma therapy / 癌症

Anti-angiogenic therapy has shown promising but insufficient efficacy on gliomas. Recent studies suggest that vasculogenic mimicry (VM), or the formation of non-endothelial, tumor-cell-lined microvascular channels, occurs in aggressive tumors, including gliomas. There is also evidence of a physiological connection between the endothelial-lined vasculature and VM channels. Tumor cells, by virtue of their high plasticity, can form vessel-like structures themselves, which may function as blood supply networks. Our previous study on gliomas showed that microvessel density was comparably less in VM-positive tumors than in VM-negative tumors. Thus, VM may act as a complement to ensure tumor blood supply, especially in regions with less microvessel density. Patients with VM-positive gliomas survived a shorter period of time than did patients with VM-negative gliomas. Although the detailed molecular mechanisms for VM are not fully understood, glioma stem cells might play a key role, since they are involved in tumor tissue remodeling and contribute to neovascularization via transdifferentiation. In the future, successful treatment of gliomas should involve targeting both VM and angiogenesis. In this review, we summarize the progress and challenges of VM in gliomas.

Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells / 癌症

O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells (GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide (TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line (SF-767) and 7 MGMT-negative cell lines (U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB (NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines (P < 0.05). However, there was no significant difference in the 50% inhibition concentration (IC50) of TMZ between MGMT-positive and MGMT-negative GSCs (P > 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132 (an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone (P <0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.

Histone deacetylase inhibitor, 2-propylpentanoic acid, increases the chemosensitivity and radiosensitivity of human glioma cell lines in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to investigate the effects of 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity and radiosensitivity in human glioma cell lines.</p><p><b>METHODS</b>Human glioma cell lines, T98-G, and SF295, were treated with temozolomide (TMZ) or irradiation (IR), with or without VPA (1.0 mmol/L). Then, cytotoxicity and clonogenic survival assay was performed. Cell cycle stage, apoptosis, and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay. One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.</p><p><b>RESULTS</b>Mild cytotoxicity of VPA was revealed in both cell lines, T98-G and SF295, with the 50% inhibiting concentration (IC50) value of (3.85 ± 0.58) mmol/L and (2.15 ± 0.38) mmol/L, respectively; while the IC50 value of TMZ was (0.20 ± 0.09) mmol/L for T98-G and (0.08 ± 0.02) mmol/L for SF295. Moreover, if combined with VPA (1.0 mmol/L) for 96 hours, the sensitivity of glioma cells to TMZ was significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58. However, when VPA was combined with IR, the SF2 of T98-G and SF295 dropped to 0.39 (P = 0.047) and 0.49 (P = 0.049), respectively. Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P < 0.01).</p><p><b>CONCLUSION</b>VPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy, and thus could be a potential sensitizer of glioma treatment.</p>

Long-term molecular changes in WHO grade II astrocytomas following radiotherapy / 癌症

Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas (LGGs) facilitates the understanding of LGG response to radiotherapy. In this study, we used immunohistochemistry to analyze the expression of Ki-67, tumor protein P53 (TP53), P21, and P27 in 8 paired WHO grade II astrocytoma samples. The interval between radiotherapy (RT) and the second surgery was more than 3 months in all cases. The average Ki-67 labeling index (LI) was 5.3% in pre-RT samples and 11.54% in post-RT samples. Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation. Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery. TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation. Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed. Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI, but the effect attenuates with time. In addition, there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki-67 level or TP53 expression in initial samples.

Significance of nerve growth factor expression in the prostate tissue of spontaneously hypertensive rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the changes of the expressions of the nerve growth factor (NGF) and its mRNA in the prostate tissues of spontaneously hypertensive rats (SHR) of different ages and their significance.</p><p><b>METHODS</b>SHRs and normotensive Wistar Kyoto (WKY) rats were killed at 1 month (young), 6 months (adult) and 12 months (aging), respectively, 5 in each group. Their prostate indexes were calculated, and the expressions of NGF and its mRNA in the ventral prostate tissue were detected by immunohistochemistry and RT-PCR.</p><p><b>RESULTS</b>The prostate indexes of the SHR and WKY groups were 1.16 +/- 0.06 and 1.03 +/- 0.09 at 1 month, 1.12 +/- 0.14 and 0.93 +/- 0.07 at 6 months, and 1.11 +/- 0.05 and 0.96 +/- 0.09 at 12 months, significantly higher in the former group than in the latter either at 6 or at 12 months (P < 0.05), but with no obvious difference at 1 month (P > 0.05). The expressions of NGF and its mRNA in the ventral prostate tissue were detected in all groups, and elevated gradually with the increase of age (P < 0.05). Among those of the same age, the expression levels were markedly higher in the SHR than in the WKY group (P < 0.05).</p><p><b>CONCLUSION</b>In SHRs with benign prostate hyperplasia (BPH), the enhanced excitation of the sympathetic nervous system may be a common mechanism underlying BPH and hypertension, and NGF plays an important role in it.</p>

Nimotuzumab in combination with chemotherapy for patients with malignant gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.</p><p><b>METHODS</b>The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.</p><p><b>RESULTS</b>Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.</p><p><b>CONCLUSIONS</b>Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.</p>

Glioblastoma stem cells resistant to temozolomide-induced autophagy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have demonstrated the existence of a small fraction of cells with features of primitive neural progenitor cells and tumor-initiating function in brain tumors. These cells might represent primary therapeutic target for complete eradication of the tumors. This study aimed to determine the resistant phenotype of glioblastoma stem cells (GSCs) to temozolomide (TMZ) and to explore the possible molecular mechanisms underlying TMZ resistance.</p><p><b>METHODS</b>Freshly resected glioblastoma specimen was collected and magnetic isolation of GSCs was carried out using the Miltenyi Biotec CD133 Cell Isolation kit. The cytotoxic effect of TMZ on CD133(+) and CD133(-) glioblastoma cells was determined by using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Autophagy-related proteins (Beclin-1, LC3 and Atg5) and cleaved caspase-3 (p17) were analyzed by Western blotting. Immunofluorescent staining was used to detect Atg5, glial fibrillary acidic protein (GFAP) and CD133 expression in glioblastoma cells. Statistical analysis was carried out using SPSS 10.0 software. For all tests, the level of statistical significance was set at P < 0.05.</p><p><b>RESULTS</b>CD133(+) glioblastoma cells exhibited neurosphere-like growth in vitro and high expression of CD133 stem cell marker. The growth-inhibiting rate in CD133(-) glioblastoma cells treated with 5 or 50 micromol/L TMZ was significantly higher than that in CD133(+) glioblastoma cells ((14.36 +/- 3.75)% vs (2.54 +/- 1.36)% or (25.95 +/- 5.25)% vs (2.72 +/- 1.84)%, respectively, P < 0.05). Atg5, LC3-II and Beclin-1 levels were significantly lower in CD133(+) glioblastoma cells than those in autologous CD133(-) cells after TMZ treatment (P < 0.05). Caspase-3 was mildly activated only in CD133(-) glioblastoma cells after exposure to TMZ (P < 0.05). Immunofluorescent staining revealed elevated expression of Atg5 in GFAP(+) cells following TMZ treatment.</p><p><b>CONCLUSIONS</b>The GSCs display strong capability of tumor's resistance to TMZ. This resistance is probably contributed by the CD133(+) cells with down-regulation of autophagy-related proteins. Future treatment should target this small population of cancer stem cells in tumors to improve survival of patients.</p>

Postoperative diabetes insipidus after transsphenoidal resection of pituitary tumor / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the prevention and treatment of postoperative diabetes insipidus after removal of pituitary tumor through transsphenoidal operation, to decrease the incidence of postoperative complications and improve the treatment of pituitary tumor.</p><p><b>METHODS</b>The clinical data of 86 cases of transsphenoidal resection of pituitary tumor in recent 8 years were retrospectively reviewed, including 35 endoscopic operation and 51 microscopic operation. The incidence, prevention and treatment of diabetes insipidus were statistically analysed.</p><p><b>RESULTS</b>There were 18 cases of postoperative diabetes insipidus in total of 86 operations, including 15 acute cases, 3 delayed cases. Twelve were temporary , which recovered within 1 week. After prompt treatment, 14 recovered within 1 week, 4 recovered within 2 weeks. No persistent diabetes insipidus was found.</p><p><b>CONCLUSIONS</b>The key points to prevent postoperative diabetes insipidus lay in the improvement of operative skills, careful protection during operation and avoidance of unnecessary injury. In case of diabetes insipidus occurred, rational use of antidiuretics and correction of electrolyte balance were effective in the treatment of postoperative diabetes insipidus.</p>

Correlation of DNA-PK activity with anti-cancer drug-sensitivity in human gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between DNA-dependent protein kinase (DNA-PK) activity and anti-cancer drug sensitivity in human glioma tissues.</p><p><b>METHODS</b>Human glioma specimens were primarily cultured and its sensitivity to several anti-cancer drugs were evaluated by MTT assay. Nuclear protein was extracted from the glioma sample of the same patient and its DNA-PK activity was determined by a biotinylated DNA-PK assay with p53-derived peptide as a specific substrate.</p><p><b>RESULTS</b>DNA-PK activity varied widely among these glioma samples. Of all 36 samples, 16 showed higher DNA-PK activity (relative activity > or = 0.40) and 20 samples with lower DNA-PK activity (relative activity < 0.40). The gliomas sensitive to DDP and VCR as evaluated by inhibition rate (IR > or = 50%) under plasma peak concentration (PPC) showed lower DNA-PK activity than the resistant ones (IR < 50%) (t = -3.445, P < 0.01). Furthermore, the gliomas with higher DNA-PK activity showed lower inhibition rate (IR < 50%) than those with lower DNA-PK activity ones (t = -2.145, P < 0.05).</p><p><b>CONCLUSION</b>DNA-PK activity is significantly associated with anti-cancer drug sensitivity to DDP and VCR in human gliomas. DNA-PK activity could be used as a new biomarker for the chemotherapy sensitivity of human gliomas.</p>