Despite great efforts and advancement in the treatment of cancer,tumor recurrence and metastasis remain significant challenges and demand novel therapy strategies.Recently,advances in biomaterials and drug delivery sy...Despite great efforts and advancement in the treatment of cancer,tumor recurrence and metastasis remain significant challenges and demand novel therapy strategies.Recently,advances in biomaterials and drug delivery systems have facilitated the development of the local therapy of cancer,among which electrospun nanofibrous scaffolds show great promise owing to their porous structure,relatively large surface area,high drug loading capacity,similarity with the native extracellular matrix,and possibility of the combination of various therapies.Here,we review this rapidly developing field of electrospun nanofibrous scaffolds as a drug delivery system for cancer local therapy,in particular addressing stimuli-responsive drug release,as well as its combination with stem cell and immune therapy.Challenges and future perspectives are also discussed.展开更多
Background:Surgery and radiotherapy are considered local therapies for small cell lung cancer(SCLC).The present study aimed to select candidates for surgery as local therapy among patients with stage I or II SCLC,base...Background:Surgery and radiotherapy are considered local therapies for small cell lung cancer(SCLC).The present study aimed to select candidates for surgery as local therapy among patients with stage I or II SCLC,based on the eighth edition of the TNM classification for lung cancer.Methods:Patients diagnosed with SCLC between 2004 and 2013 were selected from the Surveillance,Epidemiology,And End Results database.The TNM stage of SCLC in these patients was re-classified according to the eighth edition of the TNM classification for lung cancer.Patients with stage I or II SCLC were included in the present study.Overall survival(OS)and lung cancer-specific survival(LCSS)were separately compared in the different TNM stages between patients who received surgery and radiotherapy as local therapy.Multivariate analysis was applied to evaluate multi-ple factors associated with survival.Results:Among the 2129 patients included in the present study,387(18.2%)received surgery,1032(48.5%)under-went radiotherapy as local therapy,154(7.2%)underwent surgery and radiotherapy,and 556(26.1%)did not undergo either surgery or radiotherapy.Among patients with T1-2N0(tumor size≤50 mm without positive lymph nodes)dis-ease,patients who underwent surgery had higher 5-year OS and LCSS rates than patients who received radiotherapy(T1N0:46.0%vs.23.8%,P<0.001,and 58.4%vs.36.4%,P<0.001,respectively;T2N0:42.6%vs.24.7%,P=0.004,and 48.8%vs.31.3%,P=0.011,respectively).Multivariate analysis results revealed that surgery was associated with low risk of death.However,among T3N0 or T1-2N1(stage IIB)SCLC patients,patients who underwent surgery did not have higher 5-year OS and LCSS rates than patients who received radiotherapy(T3N0:16.2%vs.26.5%,P=0.085,and 28.7%vs.30.9%,P=0.372,respectively;T1-2N1:20.3%vs.29.0%,P=0.146,and 25.6%vs.35.5%,P=0.064,respectively).Conclusions:Based on the assumption that the overwhelming majority of stage I or II SCLC patients who underwent surgery or radiotherapy also received certain types of systemic therapy,only patients with T1-2N0 SCLC may benefit from surgery as local therapy.Patients with T3N0 or T1-2N1 SCLC may consider radiotherapy as local therapy.展开更多
Improvements in early screening,new diagnostic techniques,and surgical treatment have led to continuous downward trends in hepatocellular carcinoma(HCC)morbidity and mortality rates.However,high recurrence and refract...Improvements in early screening,new diagnostic techniques,and surgical treatment have led to continuous downward trends in hepatocellular carcinoma(HCC)morbidity and mortality rates.However,high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC.The clinical characteristics and prognosis of recurrent HCC are heterogeneous,and guidelines on treatment strategies for recurrent HCC are lacking.Therapies such as surgical resection,radiofrequency ablation,and transhepatic arterial chemoembolization are effective for tumors confined to the liver,and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis.With the deepening of the understanding of the immune microenvironment of HCC,blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC.In addition,improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment.Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC.This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment,demonstrates the basis for combining local treatment and systemic treatment,and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.展开更多
Objective:It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury,but the optimized parameters and effective mechanism were unclear.In the present study,we investigated the...Objective:It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury,but the optimized parameters and effective mechanism were unclear.In the present study,we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury(SNI).Methods:Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups:sham group,SNI group,SNI+A-1 mm group,SNI+A-2 mm group,and SNI+A-4 mm group(A refers to the amplitude;n=10 per group).Starting on the 7th day after model initiation,local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1,2 or 4 mm for 5 min.The sciatic function index(SFI)was assessed before surgery and on the 7th,14th,21st and 28th days after surgery.Tissues were harvested on the 28th day after surgery for morphological,immunofluorescence and Western blot analysis.Results:Compared with the SNI group,on the 28th day after surgery,the SFIs of the treatment groups were increased;the difference in the SNI+A-2 mm group was the most obvious(95%confidence interval[CI]:[5.86,27.09],P<0.001),and the cross-sectional areas of myocytes in all of the treatment groups were improved.The G-ratios in the SNI+A-1 mm group and SNI+A-2 mm group were reduced significantly(95%CI:[-0.12,-0.02],P=0.007;95%CI:[-0.15,-0.06],P<0.001).In addition,the expressions of S100 and nerve growth factor proteins in the treatment groups were increased;the phosphorylation expressions of ERK1/2 protein in the SNI+A-2 mm group and SNI+A-4 mm group were upregulated(95%CI:[0.03,0.96],P=0.038;95%CI:[0.01,0.94],P=0.047,respectively),and the phosphorylation expression of Akt in the SNI+A-1 mm group was upregulated(95%CI:[0.11,2.07],P=0.031).Conclusion:Local vibration therapy,especially with medium amplitude,was able to promote the recovery of nerve function in rats with SNI;this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.展开更多
To combine localized drug release with multimodal therapy for malignant tumor, a composite hydrogel as an integrative drug delivery system was facilely prepared. The system contains spinach extract （SE）, reduced gra...To combine localized drug release with multimodal therapy for malignant tumor, a composite hydrogel as an integrative drug delivery system was facilely prepared. The system contains spinach extract （SE）, reduced graphene oxide （rGO） and gold nanocages （AuNCs）. SE conduces to the formation of hydrogel, and also serves as a green material for improving the biocompatibility of hydrogel, and a natural pho- tosensitizer for killing tumor cells under laser radiation （fi60 nm）. AuNts show obvious photothermy and can enhance the generation of cytotoxic singlet oxygen （102）. The composite hydrogel shell on tumor cells exhibits several competitive advantages including enhanced antitumor effect by retaining the high con- centration of drugs around cancer cell, excellent PDT/FFr compatibility as well as high loading and controllable release of fluorouracil （5-FU） for synergetic multimodal treatment. The survival rate of HeLa cells incubated with 5-FU loaded hydrogel under NIR radiation for 10 min sharply decreases to 1.2%, in- dicating remarkably improved antitumor effects. These results demonstrate that the hydrogel is an excellent delivery carrier for localizable, NIR-responsive and combined PTT/PDT/Chemo synergetic antitumor.展开更多
Objective To observe IL-1B,IL-6 and TNF-a level change of the joint fluid in the experimental knee joint degeneration and the effect of the local loosening therapy.Methods Thirty rabbits were divided into 3 groups at ...Objective To observe IL-1B,IL-6 and TNF-a level change of the joint fluid in the experimental knee joint degeneration and the effect of the local loosening therapy.Methods Thirty rabbits were divided into 3 groups at random:ten in the normal contrast group,ten in the blank model group and ten in the loosening therapy group to observe the IL-1B,IL-6 and TNF-a change of the joint fluid before and after the treatment in each group.Result IL-1B,IL-6 and TNF-a level in the blank model group was obviously higher than that in the normal group.(P<0.05).IL-1B,IL-6 and TNF-a level in the treatment group was obviously lower than that in the normal group.(P<0.05).Conclusions 1)IL-1B,IL-6 and TNF-a level of the joint fluid in the blank model group was obviously higher than that in the normal group.2)Loosening soft tissues of the knees can improve IL-1B,IL-6 and TNF-a level of the joint fluid.展开更多
We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detors...We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detorsion, torsion/detorsion plus intraperitoneal ozone （O-IP）, and torsion/detorsion plus intratesticular ozone （O-IT）. The O-IP ozone group received a 4 mg kg-1 intraperitoneal injection of ozone, and the O-IT group received the same injection epididymally. At 4 h after detorsion, the rats were sacrificed and orchiectomy materials were assessed histopathologically. Spermatogenesis in the seminiferous tubules and damage to the Sertoli cells were histopathologically evaluated in the testes using the Johnsen scoring system, i-NOS and e-NOS activities in the testis tissue were also evaluated. Torsion-detorsion caused a decreased Johnsen score and increased apoptosis of spermatogonial and Sertoli cells. Ozone injection prevented increases in Johnsen score and i-NOS level, e-NOS level of the O-IP group was significantly lower than that of the O-IP group, and i-NOS level of the O-IT group was significantly lower than that of the O-IP group. Local ozone therapy is more effective than systemic ozone therapy at improving IRI-related testicular torsion. Our study is the first to show that the efficacy of intratesticular implementation of ozone therapy is higher than that of intraperitoneal ozone therapy.展开更多
Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases beca...Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases because they can be cured by removal of oligometastatic lesions. One of the most frequently reported tumor histologies for oligometastases is colorectal cancer. Resection is the standard therapy in most settings of oligometastases. Recently, studies have shown that stereotactic body radiotherapy (SBRT) may become a treatment option that provides high local control with minimal morbidity. Two-year local control rates following SBRT for hepatic and pulmonary oligometastases are almost over 80% and are even higher for patients treated with high-dose regimens. The indications of SBRT for other metastatic sites or conditions include isolated lymph nodes, spinal and adrenal metastasis, and post-surgical pelvic recurrence. Many retrospective studies have indicated that SBRT for various lesions results in good outcomes with low morbidity, both in the curative and palliative setting. However, few reports with a high level of evidence have indicated the efficacy of SBRT compared to standard therapy. Hereafter, the optimal indication of SBRT needs to be prospectively investigated to obtain convincing evidence.展开更多
The treatment of liver metastases is undergoing a transformation from single-modality therapy to multimodal combination therapy,with local interventional treatments playing an increasingly important role.This review e...The treatment of liver metastases is undergoing a transformation from single-modality therapy to multimodal combination therapy,with local interventional treatments playing an increasingly important role.This review explores the synergistic effects between local interventional therapy and systemic treatment,the reconstruction of interventional therapy indications driven by advances in systemic treatment,and the impact of local interventional therapy on systemic treatment“switching”strategies.Through multidisciplinary collaboration and innovative interventional materials and techniques,local interventional therapy has evolved from a traditional palliative approach to become an essential component in the comprehensive treatment system for liver metastases.展开更多
BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores ...BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores the potential of retroauricular subperiosteal injection as a localized drug delivery method for a more effective and safe treatment.AIM To compare the efficacy of retroauricular subperiosteal injection vs systemic intravenous glucocorticoid(GC)administration for SD in patients with DM and assess the effects on blood glucose levels.METHODS A total of 128 cases of type 2 DM(T2DM)with SD diagnosed and treated in Zibo Central Hospital from February 2021 to July 2023 were divided into two groups:An observation group(66 cases receiving retroauricular subperiosteal injection of methylprednisolone)and a control group(62 cases receiving systemic intravenous administration of methylprednisolone).The two groups were compared in terms of therapeutic efficacy,hearing recovery,blood glucose level changes,and incidence of adverse reactions.Binary logistic regression was used to analyze the factors affecting therapeutic efficacy.RESULTS The observation group showed a significantly higher total effective rate(90.91%)compared with the control group(75.81%,P<0.05).Additionally,pure-tone hearing threshold,fasting plasma glucose,and 2-hour postprandial blood glucose were significantly lower in the observation group compared with the control group(P<0.05).The incidence of adverse reactions was also lower in the observation group than in the control group(7.58%vs 22.58%,P<0.05).A T2DM course longer than 5 years and systemic intravenous GC administration were identified as independent risk factors for treatment inefficacy(P<0.05).INTRODUCTION Sudden deafness(SD)is a clinical emergency characterized by rapid-onset hearing loss that is often accompanied by clinical symptoms such as tinnitus and vertigo[1].Although its pathogenesis remains unclear,it is supposedly associated with factors,including inner ear microcirculation disorders,autoimmune diseases,and viral infections[2,3].Patients with diabetes are particularly susceptible to microvascular complications due to poor long-term glycemic control,affecting the ear’s microcirculation,subsequently increasing the risk of SD[4].Type 2 diabetes mellitus(T2DM),a chronic metabolic disease,causes multiple microvascular damages throughout the body,complicating SD treatment in patients with diabetes[5,6].Inner ear microcirculation disturbances in patients with diabetes may exacerbate the risk of SD,and its pathological process may be related to vascular endothelial dysfunction,inflammatory reactions,and hemorrhological changes caused by diabetes mellitus(DM)[7].Current SD treatments include glucocorticoids(GCs),vasodilators,and hyperbaric oxygen therapy[8].GCs are widely used due to their anti-inflammatory and immunosuppressive effects[9].However,systemic GCs may cause blood glucose(BG)fluctuations and even increase the risk of complications in patients with DM,limiting their clinical use in this population[10].Therefore,there is a compelling and immediate need for a local alternative solution that minimally affects the metabolic mechanisms.In recent years,retroauricular subperiosteal injection has emerged as a localized administration modality for treating SD[11].This method allows drugs to directly act on the inner ear,avoiding the side effects of systemic administration and having a minor impact on BG levels,providing a potentially effective treatment for patients with diabetes[12].However,there is limited clinical evidence to compare the efficacy and glycaemic effects of retroauricular subperiosteal injection vs systemic intravenous GC administration in patients with SD and diabetes.This study aimed to explore the efficacy of retroauricular subperiosteal injection and systemic intravenous GC administration for treating patients with SD and DM and their effects on BG,providing a safer and more effective clinical treatment approach.展开更多
BACKGROUND Given the low survival rate in pancreatic cancer,new therapeutic techniques have been explored,especially for unresectable or borderline resectable disease.Endoscopic ultrasound(EUS)provides real-time imagi...BACKGROUND Given the low survival rate in pancreatic cancer,new therapeutic techniques have been explored,especially for unresectable or borderline resectable disease.Endoscopic ultrasound(EUS)provides real-time imaging and minimally invasive access for local and targeted injection of anti-tumor agents directly into the pancreatic tumor.Limited studies have been reported using this technique for the treatment of pancreatic ductal adenocarcinoma(PDAC).AIM To evaluate the progress made with EUS-guided injectable therapies in the treatment of PDAC.METHODS All original articles published in English until July 15,2021,were retrieved via a library-assisted literature search from Ovid Evidence-Based Medicine Reviews and Scopus databases.Reference lists were reviewed to identify additional relevant articles.Prospective clinical studies evaluating the use of EUS-guided injectable therapies in PDAC were included.Studies primarily directed at non-EUS injectable therapies and other malignancies were excluded.Retrieved manuscripts were reviewed descriptively with on critical appraisal of published studies based on their methods and outcome measures such as safety,feasibility,and effectiveness in terms of tumor response and survival.Heterogeneity in data outcomes and therapeutic techniques limited the ability to perform comparative statistical analysis.RESULTS A total of thirteen articles(503 patients)were found eligible for inclusion.The EUS-injectable therapies used were heterogeneous among the studies consisting of immunotherapy(n=5)in 59 patients,chemotherapy(n=1)in 36 patients,and viral and other biological therapies(n=7)in 408 patients.Eleven of the studies reviewed were single armed while two were double armed with one randomized trial and one non-randomized comparative study.Overall,the included studies demonstrated EUS-guided injectable therapies to be safe and feasible with different agents as monotherapy or in conjunction with other modalities.Promising results were also observed regarding their efficacy and survival parameters in patients with PDAC.CONCLUSION EUS-guided injectable therapies,including immunotherapy,chemotherapy,and viral or other biological therapies have shown minimal adverse events and potential efficacy in the treatment of PDAC.Comparative studies,including controlled trials,are required to confirm these results in order to offer novel EUS-based treatment options for patients with PDAC.展开更多
The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease(OMD).According to those criteria,all lesions(both ...The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease(OMD).According to those criteria,all lesions(both primary and metastatic)should be amenable to radical intent treatment with acceptable toxicity.Several retrospective studies have shown that adding local ablative therapy to the treatment of OMD improves outcomes;however,due to the diverse selection criteria and treatment strategies used in those studies,it is difficult to compare directly results to draw definitive conclusions.In recent years,prospective phase II trials,such as the SABR-COMET and"Oligomez"trials,have shown that stereotactic body radiation therapy(SBRT)improves outcomes in patients with OMD.More recently,interim results of the randomised phase 3 SINDAS trial were reported at the annual meeting of the American Society of Clinical Oncology 2020 demonstrating that upfront SBRT added to systemic treatment with tyrosine kinase inhibitors yielded a significant benefit in both progression-free survival and overall survival in patients with epidermal growth factor receptor-mutant oligometastatic non-small cell lung cancer.In the present editorial,we review the definition and historical context of advanced non-small cell lung cancer with OMD.In addition,we review the scientific evidence for local ablative therapy and SBRT and discuss the results of recently published prospective studies.We also discuss in depth the results of the SINDAS study,including the strengths and weaknesses of the study and the barriers to extrapolating these results to routine clinical practice.展开更多
Objectives To investigate the feasibility and effect of local deliveryof c-myc antisense oligodeoxynucleotide (ASODN) by gelatin coated Platinium-Iridium stent to prevent restenosis in a normal rabbit carotid artery. ...Objectives To investigate the feasibility and effect of local deliveryof c-myc antisense oligodeoxynucleotide (ASODN) by gelatin coated Platinium-Iridium stent to prevent restenosis in a normal rabbit carotid artery. Methods Gelatin coated Platinium-Iridium stent were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomized to the control group and the treated group receiving c-myc ASODN (n=16 respectively).7, 14, 30,90 days following the stenting procedure, morphometry for caculation of neointimal area and mean neointimal thickness were performed.The expression of c-myc protein was detected by immunohistochemical methods. Results 32 stents were successfully implanted into the right carotid arteries in 32 animals.Morphometric analysis showed that neointimal area and mean neointimal thickness siginificantly increased continuously up to 12 weeks after stent implantation,and at each time point , neointimal area and mean neointimal thickness were siginificantly smaller in the treated group than control group. (P<0.001,respectively).c-myc protein expression was weak positive or negative in treated group and positive in control group. Conclusions Gelatin coated Platinium-Iridium stent mediated local delivery of c- myc ASODN is feasibility , and it can inhibit neointimal hyperplasia to prevent restenosis in a normal rabbit carotid artery.展开更多
Objectives To assess thefeasibility, efficiency and tissue distribution of local delivered c - myc antisense oligonucleotides (ASODN) by implanted gelatin coated Platinium - Iridium (Pt -Ir) stent. Methods Gelatin coa...Objectives To assess thefeasibility, efficiency and tissue distribution of local delivered c - myc antisense oligonucleotides (ASODN) by implanted gelatin coated Platinium - Iridium (Pt -Ir) stent. Methods Gelatin coated Pt - Ir stent which absorbed carboxyfluorescein - 5 - succimidyl ester (FAM) labeled c - myc ASODN were implanted in the right carotid arteries of 6 rabbits under vision. Blood samples were collected at the indicated times. The target artery, left carotid artery, heart , liver and kidney obtained at 45 minutes , 2 hours and 6 hours. The concentration of c - myc ASODN in plasma and tissues were determined by Thin Layer Fluorome-try. Tissue distribution of c - myc ASODN were assessed by fluorescence microscopy. Results At 45 min, 2 h, 6 h, the concentration of FAM labeled c -myc ASODN in target artery was 244. 39, 194. 44, 126. 94(μg/g tissues) respectively, and the delivery efficiency were 44. 4% , 35. 4% and 23. 1% respectively. At the same indicated time point, the plasma concentration was 8. 41, 5. 83, 14. 75 (μg/ml) respectively. Therefore c - myc ASODN concentrations in the target vessel were 29, 33 and 9 -fold higher than that in the plasma. There was circumferential distribution of labeled c - myc in the area of highest fluorescein coinciding with the site of medial dissecting from stent-ing, and the label was most intense in target vessel media harvested at 45 min time point and then dispersed to adventitia. Conclusions Gelatin coated Pt - Ir stent mediated local delivery of c - myc ASODN is feasible and efficient. The localization of ASODN is mainly in target vessel wall.展开更多
Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects,substantial tumor recurrence,and long-lasting bone reconstruction post tumor resection.Magnesium and...Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects,substantial tumor recurrence,and long-lasting bone reconstruction post tumor resection.Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices.Here,by deposition of calcium-based bilayer coating on the surface,a Mg-based composite implant platform is developed with tailored degradation characteristics,simultaneously integrated with chemotherapeutic(Taxol)loading capacity.The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles,not only in eliciting desirable osteoinductivity,but allows for modification of tumor microenvironment(TME)owing to the continuous release of degradation products.Specifically,the sustainable H_(2) evolution and Ca^(2+) from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction,which in turn leads to significant tumor-growth inhibition in vivo.In addition,the local chemotherapeutic delivery of the implant minimizes toxicity and side effects,but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model.Taken together,a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.展开更多
AIM:To compare the long-term outcome of percutaneous vs surgical radiofrequency ablation(RFA) for hepatocellular carcinoma(HCC) in dangerous locations.METHODS:One hundred and sixty-two patients with HCC in dangerous l...AIM:To compare the long-term outcome of percutaneous vs surgical radiofrequency ablation(RFA) for hepatocellular carcinoma(HCC) in dangerous locations.METHODS:One hundred and sixty-two patients with HCC in dangerous locations treated with percutaneous or surgical RFA were enrolled in this study.The patients were divided into percutaneous RFA group and surgical RFA group.After the patients were regularly followed up for a long time,their curative rate,hospital stay time,postoperative complications and 5-year local tumor progression were compared and analyzed.RESULTS:No significant difference was observed in curative rate between the two groups(91.3% vs 96.8%,P = 0.841).The hospital stay time was longer and more analgesics were required while the incidence of bile duct injury and RFA-related hemorrhage was lower in surgical RFA group than in percutaneous RFA group(P < 0.05).The local progression rate of HCC in dangerous locations was significantly lower in surgical RFA group than in percutaneous RFA group(P = 0.05).The relative risk of local tumor progression was 14.315 in percutaneous RFA group.CONCLUSION:The incidence of severe postoperative complications and local tumor progression is lower after surgical RFA than after percutaneous RFA.展开更多
BACKGROUND Melanoma brain metastasis is a common cause of death in melanoma patients andis associated with a poor prognosis. There are relatively few reports onintracranial infections after brain metastasis resection....BACKGROUND Melanoma brain metastasis is a common cause of death in melanoma patients andis associated with a poor prognosis. There are relatively few reports onintracranial infections after brain metastasis resection.CASE SUMMARY Here we report a case of melanoma brain metastases in a patient harboring aBRAF V600E mutation, who experienced intracranial tumor progression despiteprevious combined treatment with a programmed death (PD)-1 inhibitor, axitinib,and vemurafenib. She repeatedly underwent local therapy, including stereotacticradiosurgery and intracranial surgery, and developed central nervous systeminfection. Treatment with vemurafenib combined with cobimetinib resulted in anintracranial progression-free survival of 10 mo. During the coronavirus disease2019 (COVID-19) pandemic, the patient did not visit the hospital for regularvemurafenib treatment, and experienced intracranial progression afterinvoluntary drug reduction for 1 mo. The patient subsequently received varioussystemic treatments including vemurafenib, PD-1 inhibitor, and chemotherapy,with an overall survival of 29 mo as of September 2020.CONCLUSION We report the first case of melanoma brain metastases with co-occurringintracranial infection and unintended drug reduction during the COVID-19outbreak. Long-term control of the intracranial lesions was achieved withsystemic and local therapies.展开更多
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide. It is the fifth most common cancer in the world, and the third most common cause of cancer-related death. Without specific treatment, the...BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide. It is the fifth most common cancer in the world, and the third most common cause of cancer-related death. Without specific treatment, the prognosis is very poor. The goal of management is 'cancer control'-a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their families. This article aims to review the current management of HCC and its recent advances. DATA SOURCES: A MEDLINE database search was performed to identify relevant article using the keywords 'hepatocellular carcinoma', 'hepatectomy', 'liver transplantation', and 'local ablative therapy'. Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS: Liver resection and liver transplantation remain the options that give the best chance of a cure. Recent evidence suggests that local ablative therapy may offer comparable survival results in patients with small HCC, and preserved liver function. Transarterial chemoembolization (TACE) is the most promising palliative modality for unresectable HCC, but other techniques, such as transarterial radioembolization (TARE), and local ablative therapy, have also shown comparable results. CONCLUSIONS: Early diagnosis of HCC remains a key goal in improving the prognosis of patients. During the last two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC.展开更多
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However,...BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However, only 20% of HCCs can be surgically treated. And most of surgically-noneligible patients have to receive interventional managements including local ablation and transarterial chemoembolization (TACE). In this paper, we review the interventional treatments of HCC. DATA SOURCES: A literature search of PubMed database was conducted and research articles were reviewed. RESULTS: Percutaneous ethanol injection (PEI) is usually applied to small HCC for a complete necrosis. Radiofrequency ablation, an alternative to PEI, also causes tumor necrosis and needs fewer times of ablation. Other methods such as acetic acid injection, laser, microwave, etc have enriched local ablation for HCC. High intensity focus ultrasound (HIFU) is thought to be promising. TACE, another common modality, can improve the survival rate of patients with HCC. The newly developed embolic agents and adjuvant rAd-p53 gene therapy are well reported. CONCLUSIONS: Surgically-noneligible HCC can be treated with interventional procedures. Each method has its advantages and disadvantages. However, it is still pressing to develop ablative methods as well as new embolic agents for a better prognosis of HCC.展开更多
基金supported by the Natural Science Foundation of China(81930051 and 51873107)Shanghai Talent Development Fund(2018099).
文摘Despite great efforts and advancement in the treatment of cancer,tumor recurrence and metastasis remain significant challenges and demand novel therapy strategies.Recently,advances in biomaterials and drug delivery systems have facilitated the development of the local therapy of cancer,among which electrospun nanofibrous scaffolds show great promise owing to their porous structure,relatively large surface area,high drug loading capacity,similarity with the native extracellular matrix,and possibility of the combination of various therapies.Here,we review this rapidly developing field of electrospun nanofibrous scaffolds as a drug delivery system for cancer local therapy,in particular addressing stimuli-responsive drug release,as well as its combination with stem cell and immune therapy.Challenges and future perspectives are also discussed.
基金Supported by Grants Nos.81200034,81470244 and 81622001 from the National Natural and Science Foundation of China.
文摘Background:Surgery and radiotherapy are considered local therapies for small cell lung cancer(SCLC).The present study aimed to select candidates for surgery as local therapy among patients with stage I or II SCLC,based on the eighth edition of the TNM classification for lung cancer.Methods:Patients diagnosed with SCLC between 2004 and 2013 were selected from the Surveillance,Epidemiology,And End Results database.The TNM stage of SCLC in these patients was re-classified according to the eighth edition of the TNM classification for lung cancer.Patients with stage I or II SCLC were included in the present study.Overall survival(OS)and lung cancer-specific survival(LCSS)were separately compared in the different TNM stages between patients who received surgery and radiotherapy as local therapy.Multivariate analysis was applied to evaluate multi-ple factors associated with survival.Results:Among the 2129 patients included in the present study,387(18.2%)received surgery,1032(48.5%)under-went radiotherapy as local therapy,154(7.2%)underwent surgery and radiotherapy,and 556(26.1%)did not undergo either surgery or radiotherapy.Among patients with T1-2N0(tumor size≤50 mm without positive lymph nodes)dis-ease,patients who underwent surgery had higher 5-year OS and LCSS rates than patients who received radiotherapy(T1N0:46.0%vs.23.8%,P<0.001,and 58.4%vs.36.4%,P<0.001,respectively;T2N0:42.6%vs.24.7%,P=0.004,and 48.8%vs.31.3%,P=0.011,respectively).Multivariate analysis results revealed that surgery was associated with low risk of death.However,among T3N0 or T1-2N1(stage IIB)SCLC patients,patients who underwent surgery did not have higher 5-year OS and LCSS rates than patients who received radiotherapy(T3N0:16.2%vs.26.5%,P=0.085,and 28.7%vs.30.9%,P=0.372,respectively;T1-2N1:20.3%vs.29.0%,P=0.146,and 25.6%vs.35.5%,P=0.064,respectively).Conclusions:Based on the assumption that the overwhelming majority of stage I or II SCLC patients who underwent surgery or radiotherapy also received certain types of systemic therapy,only patients with T1-2N0 SCLC may benefit from surgery as local therapy.Patients with T3N0 or T1-2N1 SCLC may consider radiotherapy as local therapy.
基金Supported by the Natural Science Foundation of Tianjin Science and Technology Bureau,China,No.21JCZDJC01050Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034ATianjin Municipal Health Science and Technology Project,No.TJWJ2021ZD003,No.KJ20068,No.KJ20129,and No.TJWJ2022XK029。
文摘Improvements in early screening,new diagnostic techniques,and surgical treatment have led to continuous downward trends in hepatocellular carcinoma(HCC)morbidity and mortality rates.However,high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC.The clinical characteristics and prognosis of recurrent HCC are heterogeneous,and guidelines on treatment strategies for recurrent HCC are lacking.Therapies such as surgical resection,radiofrequency ablation,and transhepatic arterial chemoembolization are effective for tumors confined to the liver,and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis.With the deepening of the understanding of the immune microenvironment of HCC,blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC.In addition,improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment.Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC.This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment,demonstrates the basis for combining local treatment and systemic treatment,and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.
基金partially supported by research grants from the National Natural Science Funding of China(No.81603713)。
文摘Objective:It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury,but the optimized parameters and effective mechanism were unclear.In the present study,we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury(SNI).Methods:Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups:sham group,SNI group,SNI+A-1 mm group,SNI+A-2 mm group,and SNI+A-4 mm group(A refers to the amplitude;n=10 per group).Starting on the 7th day after model initiation,local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1,2 or 4 mm for 5 min.The sciatic function index(SFI)was assessed before surgery and on the 7th,14th,21st and 28th days after surgery.Tissues were harvested on the 28th day after surgery for morphological,immunofluorescence and Western blot analysis.Results:Compared with the SNI group,on the 28th day after surgery,the SFIs of the treatment groups were increased;the difference in the SNI+A-2 mm group was the most obvious(95%confidence interval[CI]:[5.86,27.09],P<0.001),and the cross-sectional areas of myocytes in all of the treatment groups were improved.The G-ratios in the SNI+A-1 mm group and SNI+A-2 mm group were reduced significantly(95%CI:[-0.12,-0.02],P=0.007;95%CI:[-0.15,-0.06],P<0.001).In addition,the expressions of S100 and nerve growth factor proteins in the treatment groups were increased;the phosphorylation expressions of ERK1/2 protein in the SNI+A-2 mm group and SNI+A-4 mm group were upregulated(95%CI:[0.03,0.96],P=0.038;95%CI:[0.01,0.94],P=0.047,respectively),and the phosphorylation expression of Akt in the SNI+A-1 mm group was upregulated(95%CI:[0.11,2.07],P=0.031).Conclusion:Local vibration therapy,especially with medium amplitude,was able to promote the recovery of nerve function in rats with SNI;this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.
基金supported by the National Natural Science Foundation of China (Nos. 21171001, 51372004, 21571002 and 21371003)the Anhui Province Key Laboratory of Environmentfriendly Polymer Materials+1 种基金the Anhui Provincial College Student Innovation Fund Project (No. 201510375048)Key Project of the Natural Science Foundation of the Provincial Education Department (No. KJ2016A679)
文摘To combine localized drug release with multimodal therapy for malignant tumor, a composite hydrogel as an integrative drug delivery system was facilely prepared. The system contains spinach extract （SE）, reduced graphene oxide （rGO） and gold nanocages （AuNCs）. SE conduces to the formation of hydrogel, and also serves as a green material for improving the biocompatibility of hydrogel, and a natural pho- tosensitizer for killing tumor cells under laser radiation （fi60 nm）. AuNts show obvious photothermy and can enhance the generation of cytotoxic singlet oxygen （102）. The composite hydrogel shell on tumor cells exhibits several competitive advantages including enhanced antitumor effect by retaining the high con- centration of drugs around cancer cell, excellent PDT/FFr compatibility as well as high loading and controllable release of fluorouracil （5-FU） for synergetic multimodal treatment. The survival rate of HeLa cells incubated with 5-FU loaded hydrogel under NIR radiation for 10 min sharply decreases to 1.2%, in- dicating remarkably improved antitumor effects. These results demonstrate that the hydrogel is an excellent delivery carrier for localizable, NIR-responsive and combined PTT/PDT/Chemo synergetic antitumor.
基金Project(99JJy2081)supported by the Natural Science Foundation of Hunan Province
文摘Objective To observe IL-1B,IL-6 and TNF-a level change of the joint fluid in the experimental knee joint degeneration and the effect of the local loosening therapy.Methods Thirty rabbits were divided into 3 groups at random:ten in the normal contrast group,ten in the blank model group and ten in the loosening therapy group to observe the IL-1B,IL-6 and TNF-a change of the joint fluid before and after the treatment in each group.Result IL-1B,IL-6 and TNF-a level in the blank model group was obviously higher than that in the normal group.(P<0.05).IL-1B,IL-6 and TNF-a level in the treatment group was obviously lower than that in the normal group.(P<0.05).Conclusions 1)IL-1B,IL-6 and TNF-a level of the joint fluid in the blank model group was obviously higher than that in the normal group.2)Loosening soft tissues of the knees can improve IL-1B,IL-6 and TNF-a level of the joint fluid.
文摘We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detorsion, torsion/detorsion plus intraperitoneal ozone （O-IP）, and torsion/detorsion plus intratesticular ozone （O-IT）. The O-IP ozone group received a 4 mg kg-1 intraperitoneal injection of ozone, and the O-IT group received the same injection epididymally. At 4 h after detorsion, the rats were sacrificed and orchiectomy materials were assessed histopathologically. Spermatogenesis in the seminiferous tubules and damage to the Sertoli cells were histopathologically evaluated in the testes using the Johnsen scoring system, i-NOS and e-NOS activities in the testis tissue were also evaluated. Torsion-detorsion caused a decreased Johnsen score and increased apoptosis of spermatogonial and Sertoli cells. Ozone injection prevented increases in Johnsen score and i-NOS level, e-NOS level of the O-IP group was significantly lower than that of the O-IP group, and i-NOS level of the O-IT group was significantly lower than that of the O-IP group. Local ozone therapy is more effective than systemic ozone therapy at improving IRI-related testicular torsion. Our study is the first to show that the efficacy of intratesticular implementation of ozone therapy is higher than that of intraperitoneal ozone therapy.
文摘Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases because they can be cured by removal of oligometastatic lesions. One of the most frequently reported tumor histologies for oligometastases is colorectal cancer. Resection is the standard therapy in most settings of oligometastases. Recently, studies have shown that stereotactic body radiotherapy (SBRT) may become a treatment option that provides high local control with minimal morbidity. Two-year local control rates following SBRT for hepatic and pulmonary oligometastases are almost over 80% and are even higher for patients treated with high-dose regimens. The indications of SBRT for other metastatic sites or conditions include isolated lymph nodes, spinal and adrenal metastasis, and post-surgical pelvic recurrence. Many retrospective studies have indicated that SBRT for various lesions results in good outcomes with low morbidity, both in the curative and palliative setting. However, few reports with a high level of evidence have indicated the efficacy of SBRT compared to standard therapy. Hereafter, the optimal indication of SBRT needs to be prospectively investigated to obtain convincing evidence.
基金funded by the National Natural Science Foundation of China,grant number 82172038.
文摘The treatment of liver metastases is undergoing a transformation from single-modality therapy to multimodal combination therapy,with local interventional treatments playing an increasingly important role.This review explores the synergistic effects between local interventional therapy and systemic treatment,the reconstruction of interventional therapy indications driven by advances in systemic treatment,and the impact of local interventional therapy on systemic treatment“switching”strategies.Through multidisciplinary collaboration and innovative interventional materials and techniques,local interventional therapy has evolved from a traditional palliative approach to become an essential component in the comprehensive treatment system for liver metastases.
文摘BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores the potential of retroauricular subperiosteal injection as a localized drug delivery method for a more effective and safe treatment.AIM To compare the efficacy of retroauricular subperiosteal injection vs systemic intravenous glucocorticoid(GC)administration for SD in patients with DM and assess the effects on blood glucose levels.METHODS A total of 128 cases of type 2 DM(T2DM)with SD diagnosed and treated in Zibo Central Hospital from February 2021 to July 2023 were divided into two groups:An observation group(66 cases receiving retroauricular subperiosteal injection of methylprednisolone)and a control group(62 cases receiving systemic intravenous administration of methylprednisolone).The two groups were compared in terms of therapeutic efficacy,hearing recovery,blood glucose level changes,and incidence of adverse reactions.Binary logistic regression was used to analyze the factors affecting therapeutic efficacy.RESULTS The observation group showed a significantly higher total effective rate(90.91%)compared with the control group(75.81%,P<0.05).Additionally,pure-tone hearing threshold,fasting plasma glucose,and 2-hour postprandial blood glucose were significantly lower in the observation group compared with the control group(P<0.05).The incidence of adverse reactions was also lower in the observation group than in the control group(7.58%vs 22.58%,P<0.05).A T2DM course longer than 5 years and systemic intravenous GC administration were identified as independent risk factors for treatment inefficacy(P<0.05).INTRODUCTION Sudden deafness(SD)is a clinical emergency characterized by rapid-onset hearing loss that is often accompanied by clinical symptoms such as tinnitus and vertigo[1].Although its pathogenesis remains unclear,it is supposedly associated with factors,including inner ear microcirculation disorders,autoimmune diseases,and viral infections[2,3].Patients with diabetes are particularly susceptible to microvascular complications due to poor long-term glycemic control,affecting the ear’s microcirculation,subsequently increasing the risk of SD[4].Type 2 diabetes mellitus(T2DM),a chronic metabolic disease,causes multiple microvascular damages throughout the body,complicating SD treatment in patients with diabetes[5,6].Inner ear microcirculation disturbances in patients with diabetes may exacerbate the risk of SD,and its pathological process may be related to vascular endothelial dysfunction,inflammatory reactions,and hemorrhological changes caused by diabetes mellitus(DM)[7].Current SD treatments include glucocorticoids(GCs),vasodilators,and hyperbaric oxygen therapy[8].GCs are widely used due to their anti-inflammatory and immunosuppressive effects[9].However,systemic GCs may cause blood glucose(BG)fluctuations and even increase the risk of complications in patients with DM,limiting their clinical use in this population[10].Therefore,there is a compelling and immediate need for a local alternative solution that minimally affects the metabolic mechanisms.In recent years,retroauricular subperiosteal injection has emerged as a localized administration modality for treating SD[11].This method allows drugs to directly act on the inner ear,avoiding the side effects of systemic administration and having a minor impact on BG levels,providing a potentially effective treatment for patients with diabetes[12].However,there is limited clinical evidence to compare the efficacy and glycaemic effects of retroauricular subperiosteal injection vs systemic intravenous GC administration in patients with SD and diabetes.This study aimed to explore the efficacy of retroauricular subperiosteal injection and systemic intravenous GC administration for treating patients with SD and DM and their effects on BG,providing a safer and more effective clinical treatment approach.
文摘BACKGROUND Given the low survival rate in pancreatic cancer,new therapeutic techniques have been explored,especially for unresectable or borderline resectable disease.Endoscopic ultrasound(EUS)provides real-time imaging and minimally invasive access for local and targeted injection of anti-tumor agents directly into the pancreatic tumor.Limited studies have been reported using this technique for the treatment of pancreatic ductal adenocarcinoma(PDAC).AIM To evaluate the progress made with EUS-guided injectable therapies in the treatment of PDAC.METHODS All original articles published in English until July 15,2021,were retrieved via a library-assisted literature search from Ovid Evidence-Based Medicine Reviews and Scopus databases.Reference lists were reviewed to identify additional relevant articles.Prospective clinical studies evaluating the use of EUS-guided injectable therapies in PDAC were included.Studies primarily directed at non-EUS injectable therapies and other malignancies were excluded.Retrieved manuscripts were reviewed descriptively with on critical appraisal of published studies based on their methods and outcome measures such as safety,feasibility,and effectiveness in terms of tumor response and survival.Heterogeneity in data outcomes and therapeutic techniques limited the ability to perform comparative statistical analysis.RESULTS A total of thirteen articles(503 patients)were found eligible for inclusion.The EUS-injectable therapies used were heterogeneous among the studies consisting of immunotherapy(n=5)in 59 patients,chemotherapy(n=1)in 36 patients,and viral and other biological therapies(n=7)in 408 patients.Eleven of the studies reviewed were single armed while two were double armed with one randomized trial and one non-randomized comparative study.Overall,the included studies demonstrated EUS-guided injectable therapies to be safe and feasible with different agents as monotherapy or in conjunction with other modalities.Promising results were also observed regarding their efficacy and survival parameters in patients with PDAC.CONCLUSION EUS-guided injectable therapies,including immunotherapy,chemotherapy,and viral or other biological therapies have shown minimal adverse events and potential efficacy in the treatment of PDAC.Comparative studies,including controlled trials,are required to confirm these results in order to offer novel EUS-based treatment options for patients with PDAC.
文摘The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease(OMD).According to those criteria,all lesions(both primary and metastatic)should be amenable to radical intent treatment with acceptable toxicity.Several retrospective studies have shown that adding local ablative therapy to the treatment of OMD improves outcomes;however,due to the diverse selection criteria and treatment strategies used in those studies,it is difficult to compare directly results to draw definitive conclusions.In recent years,prospective phase II trials,such as the SABR-COMET and"Oligomez"trials,have shown that stereotactic body radiation therapy(SBRT)improves outcomes in patients with OMD.More recently,interim results of the randomised phase 3 SINDAS trial were reported at the annual meeting of the American Society of Clinical Oncology 2020 demonstrating that upfront SBRT added to systemic treatment with tyrosine kinase inhibitors yielded a significant benefit in both progression-free survival and overall survival in patients with epidermal growth factor receptor-mutant oligometastatic non-small cell lung cancer.In the present editorial,we review the definition and historical context of advanced non-small cell lung cancer with OMD.In addition,we review the scientific evidence for local ablative therapy and SBRT and discuss the results of recently published prospective studies.We also discuss in depth the results of the SINDAS study,including the strengths and weaknesses of the study and the barriers to extrapolating these results to routine clinical practice.
文摘Objectives To investigate the feasibility and effect of local deliveryof c-myc antisense oligodeoxynucleotide (ASODN) by gelatin coated Platinium-Iridium stent to prevent restenosis in a normal rabbit carotid artery. Methods Gelatin coated Platinium-Iridium stent were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomized to the control group and the treated group receiving c-myc ASODN (n=16 respectively).7, 14, 30,90 days following the stenting procedure, morphometry for caculation of neointimal area and mean neointimal thickness were performed.The expression of c-myc protein was detected by immunohistochemical methods. Results 32 stents were successfully implanted into the right carotid arteries in 32 animals.Morphometric analysis showed that neointimal area and mean neointimal thickness siginificantly increased continuously up to 12 weeks after stent implantation,and at each time point , neointimal area and mean neointimal thickness were siginificantly smaller in the treated group than control group. (P<0.001,respectively).c-myc protein expression was weak positive or negative in treated group and positive in control group. Conclusions Gelatin coated Platinium-Iridium stent mediated local delivery of c- myc ASODN is feasibility , and it can inhibit neointimal hyperplasia to prevent restenosis in a normal rabbit carotid artery.
文摘Objectives To assess thefeasibility, efficiency and tissue distribution of local delivered c - myc antisense oligonucleotides (ASODN) by implanted gelatin coated Platinium - Iridium (Pt -Ir) stent. Methods Gelatin coated Pt - Ir stent which absorbed carboxyfluorescein - 5 - succimidyl ester (FAM) labeled c - myc ASODN were implanted in the right carotid arteries of 6 rabbits under vision. Blood samples were collected at the indicated times. The target artery, left carotid artery, heart , liver and kidney obtained at 45 minutes , 2 hours and 6 hours. The concentration of c - myc ASODN in plasma and tissues were determined by Thin Layer Fluorome-try. Tissue distribution of c - myc ASODN were assessed by fluorescence microscopy. Results At 45 min, 2 h, 6 h, the concentration of FAM labeled c -myc ASODN in target artery was 244. 39, 194. 44, 126. 94(μg/g tissues) respectively, and the delivery efficiency were 44. 4% , 35. 4% and 23. 1% respectively. At the same indicated time point, the plasma concentration was 8. 41, 5. 83, 14. 75 (μg/ml) respectively. Therefore c - myc ASODN concentrations in the target vessel were 29, 33 and 9 -fold higher than that in the plasma. There was circumferential distribution of labeled c - myc in the area of highest fluorescein coinciding with the site of medial dissecting from stent-ing, and the label was most intense in target vessel media harvested at 45 min time point and then dispersed to adventitia. Conclusions Gelatin coated Pt - Ir stent mediated local delivery of c - myc ASODN is feasible and efficient. The localization of ASODN is mainly in target vessel wall.
基金supported by the National Key Research&Development Program of China(2021YFE0204900)the National Natural Science Foundation of China(52222108)Science and Technology Commission of Shanghai Municipality(22ZR1432000,23JC1402400).
文摘Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects,substantial tumor recurrence,and long-lasting bone reconstruction post tumor resection.Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices.Here,by deposition of calcium-based bilayer coating on the surface,a Mg-based composite implant platform is developed with tailored degradation characteristics,simultaneously integrated with chemotherapeutic(Taxol)loading capacity.The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles,not only in eliciting desirable osteoinductivity,but allows for modification of tumor microenvironment(TME)owing to the continuous release of degradation products.Specifically,the sustainable H_(2) evolution and Ca^(2+) from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction,which in turn leads to significant tumor-growth inhibition in vivo.In addition,the local chemotherapeutic delivery of the implant minimizes toxicity and side effects,but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model.Taken together,a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.
文摘AIM:To compare the long-term outcome of percutaneous vs surgical radiofrequency ablation(RFA) for hepatocellular carcinoma(HCC) in dangerous locations.METHODS:One hundred and sixty-two patients with HCC in dangerous locations treated with percutaneous or surgical RFA were enrolled in this study.The patients were divided into percutaneous RFA group and surgical RFA group.After the patients were regularly followed up for a long time,their curative rate,hospital stay time,postoperative complications and 5-year local tumor progression were compared and analyzed.RESULTS:No significant difference was observed in curative rate between the two groups(91.3% vs 96.8%,P = 0.841).The hospital stay time was longer and more analgesics were required while the incidence of bile duct injury and RFA-related hemorrhage was lower in surgical RFA group than in percutaneous RFA group(P < 0.05).The local progression rate of HCC in dangerous locations was significantly lower in surgical RFA group than in percutaneous RFA group(P = 0.05).The relative risk of local tumor progression was 14.315 in percutaneous RFA group.CONCLUSION:The incidence of severe postoperative complications and local tumor progression is lower after surgical RFA than after percutaneous RFA.
基金Beijing Municipal Administration of Hospitals’Youth Programme,No.QML20181101Beijing Municipal Administration of Hospitals Incubating Program,No.PX2017042.
文摘BACKGROUND Melanoma brain metastasis is a common cause of death in melanoma patients andis associated with a poor prognosis. There are relatively few reports onintracranial infections after brain metastasis resection.CASE SUMMARY Here we report a case of melanoma brain metastases in a patient harboring aBRAF V600E mutation, who experienced intracranial tumor progression despiteprevious combined treatment with a programmed death (PD)-1 inhibitor, axitinib,and vemurafenib. She repeatedly underwent local therapy, including stereotacticradiosurgery and intracranial surgery, and developed central nervous systeminfection. Treatment with vemurafenib combined with cobimetinib resulted in anintracranial progression-free survival of 10 mo. During the coronavirus disease2019 (COVID-19) pandemic, the patient did not visit the hospital for regularvemurafenib treatment, and experienced intracranial progression afterinvoluntary drug reduction for 1 mo. The patient subsequently received varioussystemic treatments including vemurafenib, PD-1 inhibitor, and chemotherapy,with an overall survival of 29 mo as of September 2020.CONCLUSION We report the first case of melanoma brain metastases with co-occurringintracranial infection and unintended drug reduction during the COVID-19outbreak. Long-term control of the intracranial lesions was achieved withsystemic and local therapies.
文摘BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide. It is the fifth most common cancer in the world, and the third most common cause of cancer-related death. Without specific treatment, the prognosis is very poor. The goal of management is 'cancer control'-a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their families. This article aims to review the current management of HCC and its recent advances. DATA SOURCES: A MEDLINE database search was performed to identify relevant article using the keywords 'hepatocellular carcinoma', 'hepatectomy', 'liver transplantation', and 'local ablative therapy'. Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS: Liver resection and liver transplantation remain the options that give the best chance of a cure. Recent evidence suggests that local ablative therapy may offer comparable survival results in patients with small HCC, and preserved liver function. Transarterial chemoembolization (TACE) is the most promising palliative modality for unresectable HCC, but other techniques, such as transarterial radioembolization (TARE), and local ablative therapy, have also shown comparable results. CONCLUSIONS: Early diagnosis of HCC remains a key goal in improving the prognosis of patients. During the last two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC.
文摘BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However, only 20% of HCCs can be surgically treated. And most of surgically-noneligible patients have to receive interventional managements including local ablation and transarterial chemoembolization (TACE). In this paper, we review the interventional treatments of HCC. DATA SOURCES: A literature search of PubMed database was conducted and research articles were reviewed. RESULTS: Percutaneous ethanol injection (PEI) is usually applied to small HCC for a complete necrosis. Radiofrequency ablation, an alternative to PEI, also causes tumor necrosis and needs fewer times of ablation. Other methods such as acetic acid injection, laser, microwave, etc have enriched local ablation for HCC. High intensity focus ultrasound (HIFU) is thought to be promising. TACE, another common modality, can improve the survival rate of patients with HCC. The newly developed embolic agents and adjuvant rAd-p53 gene therapy are well reported. CONCLUSIONS: Surgically-noneligible HCC can be treated with interventional procedures. Each method has its advantages and disadvantages. However, it is still pressing to develop ablative methods as well as new embolic agents for a better prognosis of HCC.
