Esophageal cancer is one of the common malignant tumors with high incidence and poor prognosis. Angiogenesis-related pathways play an important role in the occurrence and development of esophageal cancer. Vascular endothelial growth factor (VEGF) is the main mediator of angiogenesis. In addition to promoting angiogenesis and maintaining the survival of neovascularization, VEGF can also directly act on esophageal cancer cells and promote the occurrence and development of tumors. This article reviews the biology of VEGF and its effect on blood vessels, the expression of VEGF in esophageal cancer cells and its influencing factors, the role of VEGF in esophageal cancer cells, the immunomodulatory activity of VEGF and the clinical study of VEGF inhibitors. The purpose of this study is to provide a basis for more rational use of VEGF inhibitors in the treatment of esophageal cancer.
Immunotherapy is an important treatment method in tumor therapy. Among them, programmed death-1/programmed death ligand-1 inhibitors are the immune preparations with mature application and great survival benefit at present. Programmed death-1/programmed death ligand-1 inhibitors brought better clinical benefits to patients with esophageal cancer and provided more favorable choice for the treatment of esophageal cancer. This article introduces the mechanism of action, application in esophageal cancer, and efficacy predictors of programmed death protein-1/programmed death protein ligand-1 inhibitors, aiming to provide a theoretical basis for the more rational use of programmed death protein-1/programmed death protein ligand-1 inhibitors in patients with esophageal cancer.
Objective To present the pooled quantitative evidence of clinical features and current treatments of programmed death 1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitor-associated vasculitis. Methods Medline, Embase, EBM, CNKI, WanFang Data and VIP databases were searched for all available studies reporting PD-1/PD-L1 inhibitor-associated vasculitis till March 23, 2022. We summarized and systematically reviewed the included articles, and analyzed the data results with descriptive statistical methods. Results A total of 38 articles were included, including 43 patients. The median age [median (minimum, maximum)] was 62 (31, 89) years, and most of patients were male (64.3%). Lung cancer was the most common tumor (47.6%). The median onset time of vasculitis [median (minimum, maximum)] was 12 (1, 120) weeks after medication. Small vasculitis (62.8%) and cutaneous vasculitis (26.7%) were the most common types. The Common Terminology Criteria for Adverse Events of vasculitis was predominantly 3-4 (83.7%). After diagnosed with vasculitis, PD-1/PD-L1 inhibitors were discontinued in 81.6% of patients, and glucocorticoid was administrated in 88.4% of patients. After treatment, 90.0% of patients had significant improvement during follow-up. However, when the discontinuation of PD-1/PD-L1 inhibitors, 55.6% of patients tumor progressions, and 35.0% of patients dead. Conclusions Special attention should be paid to the occurrence of vasculitis when using PD-1/PD-L1 inhibitors for malignant tumor therapies. Stopping PD-1/PD-L1 inhibitors and using glucocorticoid are the essential methods to treat vasculitis, but the above treatments may bring a high risk of tumor progression.
Pancreatic cancer (PC) is a highly malignant tumor of the digestive system and has a concealed onset with rapid progression. The majority of PC patients are diagnosed in the middle to late stages, and the effectiveness of traditional treatment methods for advanced pancreatic cancer is limited, which results in a poor prognosis. Immunotherapy, as a novel treatment strategy, aims to suppress tumor growth and metastasis by modulating and enhancing the human immune system. It has become a hot point in current cancer prevention and treatment. This article will elaborate on the newest advancements in immunotherapy for PC. Furthermore, we point out the major challenges of PC immunotherapy.
Objective To observe the effects of intravitreal injection of conbercept for aggressive posterior retinopathy of prematurity (AP-ROP). Methods It is a retrospective case study. Twenty-one patients (40 eyes) with AP-ROP were enrolled in this study. There were 9 males (18 eyes) and 12 females (22 eyes), with the mean gestational age of (28.30±1.79) weeks and the mean birth weight of (1 021.40±316.70) g. All the lesions of 40 eyes were located in posterior zone, with 24 eyes in zone I and 16 eyes in zone II. All the eyes were treated with intravitreal injection of conbercept 0.025 ml (0.25 mg). During follow-up, nonresponders or patients with deterioration were retreated with intravitreal injection of conbercept or photocoagulation; patients with progressive deterioration to stage 4 had received vitrectomy. At the 1, 2, 4, 8, 12, 16, 20, 24 weeks after treatments, the disappearance or decrease of retinal vessel tortuosity and neovascularization, and the growth of the normal retinal vessels toward the peripheral retina were evaluated. Results Thirty-six eyes were cured for only one injection, the cured rate was 90.00%. However, 2 eyes (5.00%) had progressed to stage 4 with contractive retinal detachment, which underwent vitrectomy. Two eyes (5.00%) had received twice injections, whose remaining avascular zone area treated by photocoagulation. No major systemic or ocular complications after injection appeared. All lens remained transparent and no iatrogenic retinal hole was occurred during the follow-up. Conclusion Intravitreal injection of conbercept is effective in the treatment of AP-ROP.
ObjectiveTo compare the short-term efficacy of conbercept and ranibizumab for macular edema in central retinal vein occlusion (CRVO)and explore the relationship between the integrity of ellipsoidal zone and visual acuity. MethodsForty-four eyes of 44 patients with macular edema in CRVO were enrolled into this retrospective and comparative study. There were 15 eyes of 15 males, 29 eyes of 29 females; age ranged from 49-61 years old,with an average age of (54.65±3.10) years. All patients were examined with best-corrected visual acuity (BCVA), intraocular pressure (IOP), slit lamp, fundus photograph, fundus fluorescein angiography (FFA), optical coherence tomography(OCT). BCVA were examined with interactional visual chart and recorded with logarithm of the minimum angle of resolution acuity. Twenty-three eyes were intravitreal injected with conbercept 0.5 mg (group A) and 21 eyes were intravitreal injected with ranibizumab 0.5 mg (group B). There was no statistical difference of age (t=-1.41), gender (χ2= 0.55),the percentage of hypertension patients (χ2=0.27), average BCVA (t=-2.06), IOP (t=-2.52), central macular thickness (CMT) (t=-1.96), number of different integrity of ellipsoidal zone patients (χ2=1.00) and number of different types of macular edema patients (χ2=1.03) among the two groups (P > 0.05). The change in BCVA and CMT at 3, 6 months between the two groups were compared. The relationship between BCVA at 6 months and BCVA, CMT at baseline were explored. The relationship between three groups of ellipsoidal zone and BCVA at baseline were evaluated. The change of BCVA after treatment between the three groups of ellipsoidal zone were Compared. The number of intravitreal injections between two groups was compared. ResultsDuring the 3, 6 months after treatment, the mean BCVA were all improved with statistically difference in group A (t=5.13, 7.39; P < 0.05) and group B (t=6.60, 11.52; P < 0.05). There was no significant difference of BCVA at 3, 6 moths between group A and group B (t=-0.99, -0.40; P > 0.05). During the 3, 6 months after treatment, the mean CMT were all decreased with statistically difference in group A (t=11.58, 15.96; P < 0.05) and group B (t=18.77, 35.16; P < 0.05). There was no significant difference of CMT at 3, 6 months between group A and group B (t=-1.52, -1.63; P > 0.05). In both groups,BCVA at 6 months was related to BCVA at baseline (r= 0.44, 0.62; P < 0.05), but not related to CMT at baseline (r=0.19, 0.01; P > 0.05). In the two groups, BCVA at baseline was related to the integrity of ellipsoidal zone (r=0.97, 0.70; P < 0.05). There was statistical difference of the number of intravitreal injections in the two groups (t=-6.88, P < 0.05). There was no systemic or ocular serious side effects during the follow up. ConclusionsComparing to ranibizumab, conbercept has the same effective to the treatment of macular edema in CRVO, but the number of intravitreal injections is less. The integrity of ellipsoidal zone is related to BCVA.
ObjectiveTo understand the research progress of treatment of hyperkalemia after simultaneous pancreas and kidney transplantation (SPK), and to provide the basis for the prevention and treatment of hyperkalemia after SPK.MethodThe relevant literatures about hyperkalemia after SPK in recent years were reviewed.ResultsThe pancreas and kidney that maintained the stability of serum potassium in different ways had been confirmed in current studies. The newly transplanted organ dysfunction after SPK and the use of drugs after SPK both caused hyperkalemia. The treatment principle of hyperkalemia after SPK was to take corresponding prevention and treatment measures according to different reasons.ConclusionsSPK is the best treatment for diabetic renal failure. Postoperative hyperkalemia is one of the most common complications, and timely and correct management is of great significance to the survival and prognosis of patients.
ObjectiveTo evaluate the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs combined with retinal laser photocoagulation and anti-VEGF drugs alone in the treatment of retinal vein occlusion (RVO) combined with macular edema (ME). MethodsA evidence-based medicine study. Retinal vein occlusion (obstruction), macular edema, anti-vascular endothelial growth factor, bevacizumab, ranibizumab, conbercept, aflibercept, and retinal laser photocoagulation were the Chinese and English search terms. Related literature was searched in China National Knowledge Infrastructure, Wanfang, Weipu, PubMed, Embase, Cochrane Library. RVO combined with ME was selected as the research object, and the treatment plan was a clinical randomized controlled study comparing intravitreal injection of anti-VEGF drugs combined with laser photocoagulation and anti-VEGF drugs alone. The search time range was from January 2011 to February 2021. Repeated, incomplete or irrelevant literature, case reports and review literature were excluded. Review Manager 5.4 statistical software was used to conduct a meta-analysis of the literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were selected as the estimated value of effect size, and the fixed effect model was used for analysis. The evaluation indicators were best corrected visual acuity (BCVA), center macular thickness (CMT), and the number of injections. ResultsAccording to the search strategy, 461 articles were initially retrieved, and 21 articles were finally included for meta-analysis. A total of 1156 patients were enrolled, of which 576 were treated with anti-VEGF drugs combined with laser photocoagulation (combined treatment group), and 580 were treated with anti-VEGF drugs alone (drug treatment group). Meta-analysis results showed that there was no statistically significant difference in BCVA and CMT between the drug treatment group and the combination treatment group at 6, 9, and 12 months after treatment (BCVA: WMD =－0.82, 95%CI －2.38-0.74, P=0.30; CMT: WMD=－3.12, 95%CI －17.25-11.01, P=0.67). For patients with branch retinal vein occlusion and ME, combined therapy can reduce the number of injections more effectively than drug therapy alone (WMD=－0.80, 95% CI －1.18-－0.42, Z=4.10, P＜0.000 1). ConclusionCompared with pure intravitreal injection of anti-VEGF drugs, combined retinal laser photocoagulation can not better improve BCVA and CMT in patients with RVO and ME. For patients with branch retinal vein occlusion and ME, combined retinal laser photocoagulation can effectively reduce the resistance. The number of VEGF injections.
ObjectiveTo analyze the efficacy and safety of immunotherapy and bevacizumab combined with chemotherapy (BIC), bevacizumab combined with chemotherapy (BC), chemotherapy (CT), immunotherapy combined with chemotherapy (IC), bevacizumab combined with immunotherapy (BI), bevacizumab (B) in the first-line treatment of advanced wild-type non-squamous non-small cell lung cancer. MethodsThe PubMed, Embase, Cochrane Library and Web of Science databases were searched to collect phase Ⅱ/Ⅲ randomized controlled trials (RCTs) related to the objectives of the study from January 2010 to December 1, 2022. After two investigators independently screened the literatures, extracted the data and evaluated the risk of bias of the included studies, a reticular meta-analysis was performed using R 3.6.1 software. ResultsA total of 11 RCTs were finally included, including 5 329 patients and six treatment combinations. Meta-analysis results showed that BIC was superior to CT for progression-free survival (PFS) (HR=0.34, 95% CI 0.18 to 0.69), but BIC did not show a significant advantage over the other groups for overall survival (OS). Bayesian ranking results showed that the BIC group had the greatest probability in terms of OS, PFS, and ORR. Among all programmed death ligand 1 (PD-L1) expressing subgroups, there was no significant difference in OS between BIC, BC, IC, CT, BI, and B. Compared with CT, IC was significantly improved in OS (HR=0.68, 95%CI 0.52 to 0.92), PFS (HR=0.58, 95%CI 0.45 to 0.75), and ORR (HR=0.47, 95%CI 0.33 to 0.66). ConclusionIn the first-line treatment of wild-type advanced non-squamous NSCLC, immunotherapy and bevacizumab combined with chemotherapy may improve the efficacy in the short term, but do not change the long-term survival time. Immunotherapy combined with chemotherapy can significantly improve the survival time and prognosis of patients compared with chemotherapy alone. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
ObjectiveTo observe the effect of intravitreal injection of Conbercept with two different doses in the treatment of retinopathy of prematurity (ROP）and explore the clinical feasibility of ROP treatment by lower dose conbercept.MethodsThis was a prospective study. The premature infants were enrolled with pre-threshold type 1, threshold and acute aggressive posterior retinopathy of prematurity (AP-ROP) from March 2018 to June 2019, who received fundus screening in neonatal intensive care unit (NICU) of Henan Provincial People's Hospital, Henan Eye Hospital. They were randomly divided into two groups. The group A (lower dose group) were received intravitreal injection of conbercept with 0.15 mg/0.015 ml, and those in group B (control group) were received intravitreal injection of conbercept with 0.25 mg/0.025 ml. We checked and recorded the lesion area, stage, scope (according to the clock range), additional lesion (plus), etc. Fundus examination should be performed with the pediatric wide-field fundus imaging system within 7 days after treatment. It was used to observe the plus disese, ridge, regression of neovascularization on ridge, and development of retinal vessels to serrated edge or scarring. The follow-up period was at least 24 weeks. The effect evaluation was divided into recovery, improvement, recurrence and aggravation.ResultsThe 43 ROP subjects (84 eyes) were enrolled including 21 cases (40 eyes) in group A and 22 (44 eyes) in group B. There was no significant difference between the two groups in gender (χ2=1.169), birth age (t=0.283), birth weight (t=0.547), hospitalization days in NICU (t=1.187), first examination time (t=1.811), first injection time (t=0.492), follow-up time (t=0.899) and ROP condition (χ2=0.854) (P>0.05). In group A, 21 eyes (52.5%) were cured, 17 eyes (42.5%) were improved, 2 eyes (5.0%) were recurred, and no aggravating cases were found. In group B, 24 eyes (54.5%) were cured, 14 eyes (31.8%) were improved, 6 eyes (13.6%) were recurred, and no aggravating cases were found. There was no significant difference of the cure rate (χ2=2.210, P>0.05) and effective (recovery and improvement) rate (χ2=1.814, P=0.269）between two groups after the first injection.ConclusionIntravitreal injection of conbercept with the two doses should be effective in the treatment of ROP.