An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM： To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema（DME） resistant to anti-vascular endothelial growth factor（VEGF） therapy.METHODS： Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant（Ozurdex~） was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity（BCVA） measured with Early Treatment Diabetic Retinopathy Study（ETDRS） and central macular thickness（CMT） exams were carried out at baseline（T0）and after 1（T1）,3（T3）,4（T4）,6（T6）,9（T9）,12（T12）,15（T15）,and 18mo（T18） post injection. RESULTS： Repeated measures ANOVA showed an effect of treatment on ETDRS（P〈0.0001）.Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15（P 〈0.001） as compared to baseline value（T0）.At T6,T12,and T18,ETDRS values were still statistically higher than baseline（P〈0.001 vs T0）.However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment（P 〈0.0001）.CMT decreased significantly at T1,T3,T4,T9,and T15（P〈0.001）.At T6（P〈0.01）,T12 and T18（P〈0.001） CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION： Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Prophylaxis with intraocular pressure lowering medication and glaucomatous progression in patients receiving intravitreal anti-VEGF therapy

AIM: To investigate whether pretreatment with pressurelowering medication prior to anti-vascular endothelial factor(VEGF) injections had an effect on glaucomatous progression in patients with preexisting glaucoma or ocular hypertension(OHT).METHODS: A total of 66 eyes from 54 patients with a preexisting diagnosis of glaucoma or OHT, treated with six or more anti-VEGF injections were selected for chart review. Primary outcome measures were rate of visual field loss in d B/year, rate of change in retinal nerve fiber layer(RNFL) thickness in microns/year, and need for additional glaucoma intervention.RESULTS: The number of eyes requiring additional glaucoma medication was 5 of 20(25.0%) and 14 of 46(30.4%) for the pretreated and non-pretreated groups, respectively. The number of eyes requiring glaucoma laser or surgery was 4 of 20(20.0%) and 13 of 46(28.3%) for the pretreated and non-pretreated groups, respectively. Estimated mean rate of pattern standard deviation decline was not significant in either group(P>0.073), with no difference between groups(P=0.332). Although both groups showed significant RNFL change from baseline(P<0.011), no difference was detected between groups(P=0.467).CONCLUSION: Pretreatment has no detectable effect on structural or functional glaucomatous progression. Patients receiving repeated injections may be at risk for glaucomatous complications requiring invasive intervention.

Prediction of the short-term efficacy of anti-VEGF therapy for neovascular age-related macular degeneration using optical coherence tomography angiography

Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related macular degeneration(nAMD)after anti-vascular endothelial growth factor(anti-VEGF)therapy.Methods Patients with type 1,type 2,or mixed-type neovascularization(NV)were prospectively included.Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept(0.5 mg)and were switched to a pro re nata(PRN)treatment strategy.OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months.CNV lesions were manually segmented,and the CNV area,vessel area,greatest vascular caliber(GVC),and greatest linear dimension(GLD)were compared between responders and non-responders.Two masked graders independently measured the above-mentioned parameters using OCTA,and consistency was assessed using the intraclass correlation coefficient(ICC)values.Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area,GLD,and GVC on the 6-month response to anti-VEGF agents.Results Among the 60 eyes of 60 patients with nAMD,39 were responders and 21 were non-responders.The proportion of CNV types was significantly different between responders and non-responders(P=0.009).Patients with type 2 or mixed NV seemed more likely to respond to the treatment(28.2%vs.0.0%,and 30.8%vs.23.8%,respectively).The change in GVC showed a significant difference between responders(−4.98±17.17μm)and non-responders(11.01±14.10μm)after three monthly intravitreal anti-VEGF injections.Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC,injection number,and CNV type(adjusted OR=1.083;P=0.008).Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy.Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography

Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented by optical coherence tomography angiography(OCTA)in diabetic eyes.Methods:In this retrospective study,IRMAs were evaluated with multimodal imaging(fundus photography,fluorescein angiography,OCTA)in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema(DME)and/or proliferative diabetic retinopathy(PDR)and compared to diabetic control eyes with similar diabetic retinopathy(DR)severity that did not receive anti-VEGF therapy.The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline,then after anti-VEGF therapy in treated eyes or after observation in control eyes.Characterization of interval changes in an IRMA were based on the following parameters:branching,vessel caliber and area of adjacent capillary non-perfusion.Results:The treated group included 45 IRMA foci from 15 eyes of 11 patients,while the control group included 27 IRMA foci from 15 eyes of 14 patients.Following anti-VEGF treatment,enface OCTA demonstrated that 14 foci of IRMA(31%)demonstrated regression with normalization of appearance of the capillary bed,20 IRMAs(44%)remained unchanged,six IRMAs(13%)progressed with enlargement or development of new IRMAs and five IRMAs(11%)demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out.In the control group,17 IRMA(63%)remained stable,8 IRMAs(29.6%)progressed and 2 experienced total obliteration(7.4%).The difference in rank order between the two groups was statistically significant(p=0.022).Conclusions:In eyes with DR status post anti-VEGF therapy,foci of IRMAs have a variable course demonstrating one of four possible outcomes:regression,stabilit,progression or complete obliteration.In contrast,none of the untreated control diabetic eyes demonstrated regression of IRMAs,consistent with known progression of DR severity in high risk eyes.Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.

When combination therapy isn't working: Emerging therapies for the management of inflammatory bowel disease

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.

Anti-VEGF therapy prevents Müller intracellular edema by decreasing VEGF-A in diabetic retinopathy

Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

Anti-EGFR and anti-VEGF agents:Important targeted therapies of colorectal liver metastases

Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, &#x0201c;new&#x0201d; RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into question because of the inferior prognosis in the COIN trial and the NORDIC-VII trial. Also, bevacizumab plus oxaliplatin-based chemotherapy was questioned because of the NO16966 trial. By the update and further analysis of the COIN trial and the NORDIC-VII trial, cetuximab plus FOLFOX was reported to be reliable again. But bevacizumab plus oxaliplatin-based chemotherapy was still controversial. In addition, some trials have reported that bevacizumab is not suitable for conversion therapy. The results of the FIRE-III trial showed that cetuximab led to a significant advantage over bevacizumab in response rate (72% vs 63%, P = 0.017) for evaluable population. With the balanced allocation of second-line treatment, the FIRE-III trial was expected to provide evidence for selecting following regimens after first-line progression. There is still no strong evidence for the efficacy of targeted therapy as a preoperative treatment for resectable CLM or postoperative treatment for resected CLM, although the combined regimen is often administered based on experience. Combination therapy with more than one targeted agent has been proven to provide no benefit, and even was reported to be harmful as first-line treatment by four large clinical trials. However, recent studies reported positive results of erlotinib plus bevacizumab for maintenance treatment. The mechanism of antagonism between different targeted agents deserves further study, and may also provide greater understanding of the development of resistance to targeted agents.

Comparison of the efficacy of anti-VEGF monotherapy versus PDT and intravitreal anti-VEGF combination treatment in AMD： a Meta-analysis and systematic review

AIM：To compare the effect of anti-vascular endothelial growth factor（VEGF） monotherapy versus photodynamic therapy（PDT） and anti-VEGF combination treatment in age-related macular degeneration（AMD）.METHODS：A computerized online search was performed using PubMed,Web of Science and the Cochrane Library.Studies that compared anti-VEGF monotherapy with PDT and anti-VEGF combination treatment of AMD and were designed as randomized controlled trials were included.The means and standard deviations of the best-corrected visual acuity（BCVA）,central retinal thickness（CRT）,number of treatments and proportions of patients who gained BCVA ≥15,10,5,or 0 letters at 12^（th） month were extracted.A systematic review and Meta-analysis of the comparison of the two approaches was conducted using Review Manager 5.2.Subgroup.A sensitivity analysis was also performed.RESULTS：Eight studies were included.When the subgroup and sensitivity analysis was conducted,the results indicated that in the findings that included the monotherapy group and PDT（standard fluence,SF）group of Kaiser＇s study,the patients in the monotherapy group had a better BCVA compared with the combination group at 12^（th） month in the PDT（SF） subgroup[weighted mean difference（WMD）：3.54;95% Cl：0.36 to 6.73;P=0.03],and there were more patients who gained ≥15 letters of BCVA in the monotherapy group compared with the combination group in the total result[odds ratio（OR）：1.41;95% Cl：1.02 to 1.95;P=0.04].The same conclusion was obtained in the total result that included the monotherapy group and PDT（reduced fluence,RF）group of Kaiser＇s study（OR：1.56;95% CI：1.13 to 2.15;P=0.007）.However,there were no significant differences in the other indexes between the two therapies.CONCLUSION：We found that anti-VEGF monotherapy is more effective on the recovery of visual acuity than combination therapy and more researches with lager sample size should be performed to study on the effect of the two therapy approaches on CRT and number of injections.

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

Combining chemotherapy and targeted therapies in metastatic colorectal cancer

Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

Laser therapy versus intravitreal injection of anti-VEGF agents in monotherapy of ROP:a Meta-analysis

AIM:To compare the efficacy and safety between laser therapy and anti-vascular endothelial growth factor(VEGF)agents intravitreal injection monotherapy in type-1 retinopathy of prematurity(ROP)and aggressive posterior retinopathy of prematurity(APROP).METHODS:A systematic literature search was performed in PubMed,Cochrane Library,and Embase for original comparable studies.We included studies that compare laser therapy and intravitreal injections of anti-VEGF agents monotherapy in ROP regardless of languages and publication types.RESULTS:Complication incidence was significantly higher in laser therapy group(OR:0.38;95%CI:0.19-0.75;P=0.005).Spherical equivalent(SE)was higher in laser therapy[weighted mean difference(WMD):2.40,95%CI:0.88-3.93;P=0.002].The time between treatment and retreatment was longer in laser therapy group(WMD:8.45,95%CI:5.35-11.55;P<0.00001).Recurrence incidence(OR:0.97;95%CI:0.45-2.09;P=0.93)and retreatment incidence(OR:1.24;95%CI:0.56-2.73;P=0.59)were similar in two approaches.Subgroup analysis between type-1 ROP and APROP was not significant except SE reported in the included studies(P<0.0001).CONCLUSION:This Meta-analysis outcome indicates anti-VEGF agents are as effective as laser treatment,and safer than laser in type-1 ROP and APROP.The degree of myopia in APROP is higher than type-1 ROP.More randomized controlled trials in large sample size should be conducted in the future.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography

Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented by optical coherence tomography angiography(OCTA)in diabetic eyes.Methods:In this retrospective study,IRMAs were evaluated with multimodal imaging(fundus photography,fluorescein angiography,OCTA)in treatment-naive diabetic eyes before and after anti-VEGF treatment for diabetic macular edema(DME)and/or proliferative diabetic retinopathy(PDR)and compared to diabetic control eyes with similar diabetic retinopathy(DR)severity that did not receive anti-VEGF therapy.The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline,then after anti-VEGF therapy in treated eyes or after observation in control eyes.Characterization of interval changes in an IRMA was based on the following parameters:branching,vessel aliber and area of adjacent capllary non-perfusion.Results:The treated group included 45 IRMA foci from 15 eyes of 11 patients,while the control group included 27 IRMA foci from 15 eyes of 14 patients.Following anti-VEGF treatment,enface OCTA demonstrated that 14 foci of IRMA(31.1%)demonstrated regression with normalization of appearance of the capillary bed,20 IRMAs(44.4%)remained unchanged,6 IRMAs(13.3%)progressed with enlargement or development of new IRMAs and 5 IRMAs(11.1%)demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out.In the control group,17 IRMAs(63.0%)remained stable,8 IRMAs(29.6%)progressed and 2 experienced total obliteration(7.4%).The dfference in rank order between the two groups was statistically significant(P=0.022).Conclusions:In eyes with DR status post anti-VEGF therapy,foci of IRMAs have a variable course demonstrating one of four possible outcomes:regression,stability,progression or complete obliteration.In contrast,none of the untreated control diabetic eyes demonstrated regression of IRMAs,consistent with known progression of DR severity in high risk eyes.Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as wellas the response to anti-VEGF treatment.