23G玻璃体切除术及硅油辅助取出眼内巨大异物的临床观察

目的:研究23G微创玻璃体切除术及硅油辅助下取出眼内巨大异物的手术效果及并发症。方法:回顾性分析2012-02/2015-03在长沙爱尔眼科医院接受治疗、需填充硅油的眼内巨大异物的患者12例12眼,其中男11例11眼,女1例1眼。术前视力光感~0.1,12眼术前均合并视网膜脱离。所有患者均接受23G微创玻璃体切除手术,在切除玻璃体和修复损伤的视网膜后,先行硅油填充,再扩大巩膜切口取出眼内巨大异物。术后6mo取硅油,部分患者联合人工晶状体植入。结果:患者12眼眼内巨大异物均一次性取出,未出现再次跌落损伤视网膜现象,切口无视网膜脱出,不损伤角膜。术后视网膜均复位,未出现术后眼内炎。术后6mo硅油均顺利取出,视力均提高,脱盲率达67%,脱残率达到25%。结论:23G微创玻璃体切除术及硅油辅助下取出眼内巨大异物是一种安全有效的方法。

Vasculogenic mimicry:a novel target for glioma therapy

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

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.

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

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.

Longest survival with primary intracranial malignant melanoma:A case report and literature review

BACKGROUND Primary intracranial malignant melanoma(PIMM)is rare,and its prognosis is very poor.It is not clear what systematic treatment strategy can achieve long-term survival.This case study attempted to identify the optimal strategy for long-term survival outcomes by reviewing the PIMM patient with the longest survival following comprehensive treatment and by reviewing the related literature.CASE SUMMARY The patient is a 47-year-old Chinese man who suffered from dizziness and gait disturbance.He underwent surgery for right cerebellum melanoma and was subsequently diagnosed by pathology in June 2000.After the surgery,the patient received three cycles of chemotherapy but relapsed locally within 4 mo.Following the second surgery for total tumor resection,the patient received an injection of Newcastle disease virus-modified tumor vaccine,interferon,andβ-elemene treatment.The patient was tumor-free with a normal life for 21 years before the onset of the recurrence of melanoma without any symptoms in July 2021.A third gross-total resection with adjuvant radiotherapy and temozolomide therapy was performed.Brain magnetic resonance imaging showed no residual tumor or recurrence 3 mo after the 3rd operation,and the patient recovered well without neurological dysfunction until the last follow-up in June 2022,which was 22 years following the initial treatment.CONCLUSION It is important for patients with PIMM to receive comprehensive treatment to enable the application of the most appropriate treatment strategies.Long-term survival is not impossible in patients with these malignancies.

Thyroid metastasis from breast cancer presenting with enlarged lateral cervical lymph nodes: A case report

BACKGROUND Secondary malignancy of the thyroid occurs infrequently and mainly originates from malignant tumors of the kidney,gastrointestinal tract,lungs,breast,and skin.The correct diagnosis is important but difficult.Importantly,there are major differences in the treatment of primary and metastatic thyroid cancer,which has a significant impact on prognosis and survival.Therefore,how to diagnose thyroid metastasis(TM)correctly before surgery is a major concern for surgeons.CASE SUMMARY We report a 38-year-old woman who presented with palpable cervical lymph nodes after breast cancer(BC)surgery 2 years ago.Ultrasonography and computed tomography revealed thyroid nodules with irregular margins and enlarged cervical lymph nodes.Biopsy was performed for the right largest cervical lymph node,and immunohistochemical analysis revealed negativity for thyroglobulin,estrogen receptor,and progestin receptor and positive for human epidermal growth factor receptor 2.The diagnosis was TM from BC with cervical lymph node metastasis.Total thyroidectomy with bilateral central and lateral neck lymph node dissection was performed.After a 5-mo follow-up,no recurrence or novel distant metastasis was identified.CONCLUSION TM from BC is a rare secondary malignancy.Broad differential diagnosis by biopsy and immunohistochemical analysis needs to be considered.

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

Background： 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. Methods： 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 ofcorticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event （AE）, and neurological condition were measured for 24 months of tbllow-up. The primary efficacy endpoint of this study was overall survival （OS）. The secondary endpoint was progression free survival （PFS）. Results： 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. Conclusions： 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.

Association between glioblastoma cell-derived vessels and poor prognosis of the patients

Background:Vessels with different microcirculation patterns are required for glioblastoma(GBM)growth.However,details of the microcirculation patterns in GBM remain unclear.Here,we examined the microcirculation patterns of GBM and analyzed their roles in patient prognosis together with two well-known GMB prognosis factors(O^(6)-methylguanine DNA methyltransferase[MGMT]promoter methylation status and isocitrate dehydrogenase[IDH]mutations).Methods:Eighty GBM clinical specimens were collected from patients diagnosed between January 2000 and December 2012.The microcirculation patterns,including endothelium-dependent vessels(EDVs),extracellular matrix-dependent vessels(ECMDVs),GBM cell-derived vessels(GDVs),and mosaic vessels(MVs),were evaluated by immunohistochemistry(IHC)and immunofluorescence(IF)staining in both GBM clinical specimens and xenograft tissues.Vascular density assessments and three-dimensional reconstruction were performed.MGMT promoter methylation status was determined by methylation-specific PCR,and IDH1/2 mutations were detected by Sanger sequencing.The relationship between the microcirculation patterns and patient prognosis was analyzed by Kaplan-Meier method.Results:All 4 microcirculation patterns were observed in both GBM clinical specimens and xenograft tissues.EDVs were detected in all tissue samples,while the other three patterns were observed in a small number of tissue samples(ECMDVs in 27.5%,GDVs in 43.8%,and MVs in 52.5%tissue samples).GDV-positive patients had a median survival of 9.56 months versus 13.60 months for GDV-negative patients(P=0.015).In MGMT promoter-methylated cohort,GDV-positive patients had a median survival of 6.76 months versus 14.23 months for GDV-negative patients(P=0.022).Conclusion:GDVs might be a negative predictor for the survival of GBM patients,even in those with MGMT promoter methylation.