Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Lymphoma, Non-Hodgkin/drug therapy* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective:To investigate the prognostic value of bone marrow (BM) 18F-fluorodeoxyglucose ( 18F-FDG) uptake pattern of pretreatment positron emission tomography/computed tomography (PET-CT) in extranodal NK/T cell lymphoma (ENKTL) patients. Methods:We retrospectively collected clinical data from a series of 63 ENKTL patients with stageⅡ~Ⅳ, who have received both 18F-FDG PET-CT and bone marrow biopsy (BMB) prior to treatment. According the BM 18F-FDG uptake pattern of PET-CT, the patients were divided into three groups: focal BM FDG uptake higher than liver (fPET+ ), diffuse BM uptake higher than liver (dPET+ ) and normal BM uptake (lower than liver) (nPET). The Kaplan-Meier method and Log-rank test were respectively used for survival analysis and univariate analysis, and COX proportional hazards model for multivariate analysis. Results:Among the 63 patients, 22 patients had nPET, 24 patients showed dPET+ , and 17 patients had fPET+ . BMB positive was found in 8 patients, and negative in 55 patients. Thirty-seven patients had disease progression or relapse, and 31 patients died. The 3-years progression free survival (3y-PFS) rates of fPET+ patients and nPET patients were 14.7% and 63.6% ( P=0.006). The 3-years overall survival (3y-OS) rates were 18.8% and 64.8% ( P=0.005). The 3y-PFS of dPET+ patients and nPET patients were 35.6% and 63.6% ( P=0.161), 3y-OS were 47.9% and 64.8% ( P=0.280). Univariate analysis showed that lactate dehydrogenase (LDH) level, Epstein-Barr virus DNA (EBV-DNA), Korean prognostic index (KPI) and BM 18F-FDG were related with PFS and OS (all P<0.05). Multivariate analysis showed EBV-DNA and BM 18F-FDG were independent predictors for PFS ( P<0.05). EBV-DNA was also an independently predictor for OS ( P<0.05). Conclusions:PET/CT-directed BM patterns are meaningful in predicting prognosis of newly diagnosed ENKTL patients. Focal BM 18F-FDG uptake pattern is an independent predictor for PFS.

Objective:To investigate the prognostic value of bone marrow (BM) 18F-fluorodeoxyglucose ( 18F-FDG) uptake pattern of pretreatment positron emission tomography/computed tomography (PET-CT) in extranodal NK/T cell lymphoma (ENKTL) patients. Methods:We retrospectively collected clinical data from a series of 63 ENKTL patients with stageⅡ~Ⅳ, who have received both 18F-FDG PET-CT and bone marrow biopsy (BMB) prior to treatment. According the BM 18F-FDG uptake pattern of PET-CT, the patients were divided into three groups: focal BM FDG uptake higher than liver (fPET+ ), diffuse BM uptake higher than liver (dPET+ ) and normal BM uptake (lower than liver) (nPET). The Kaplan-Meier method and Log-rank test were respectively used for survival analysis and univariate analysis, and COX proportional hazards model for multivariate analysis. Results:Among the 63 patients, 22 patients had nPET, 24 patients showed dPET+ , and 17 patients had fPET+ . BMB positive was found in 8 patients, and negative in 55 patients. Thirty-seven patients had disease progression or relapse, and 31 patients died. The 3-years progression free survival (3y-PFS) rates of fPET+ patients and nPET patients were 14.7% and 63.6% ( P=0.006). The 3-years overall survival (3y-OS) rates were 18.8% and 64.8% ( P=0.005). The 3y-PFS of dPET+ patients and nPET patients were 35.6% and 63.6% ( P=0.161), 3y-OS were 47.9% and 64.8% ( P=0.280). Univariate analysis showed that lactate dehydrogenase (LDH) level, Epstein-Barr virus DNA (EBV-DNA), Korean prognostic index (KPI) and BM 18F-FDG were related with PFS and OS (all P<0.05). Multivariate analysis showed EBV-DNA and BM 18F-FDG were independent predictors for PFS ( P<0.05). EBV-DNA was also an independently predictor for OS ( P<0.05). Conclusions:PET/CT-directed BM patterns are meaningful in predicting prognosis of newly diagnosed ENKTL patients. Focal BM 18F-FDG uptake pattern is an independent predictor for PFS.

Objective To summarize the clinical characteristics and prognosis of subcutaneous panniculitis-like T-cell lymphoma(SPTCL). Methods This study retrospectively analyzed the clinical data of 5 SPTCL patients diagnosed in the First Affiliated Hospital with Nanjing Medical University, and presented with a corresponding literature review. Results Four patients initiated symptoms with rash. Three patients had hepatomegaly and/or splenomegaly, and one was accompanied with hemophagocytic lymphohistiocytosis (HLH). Tumor cells diffusely infiltrated into subcutaneous tissues with hemotoxylin and eosin staining, and rimmed around single adipocyte. The neoplastic cells consistently expressed proteins of CD3, CD43 and CD45RO, and characteristically had the phenotype of CD4- CD8+CD56- T cells which expressed cytotoxic proteins. Two of five patients received DHAP courses as initial treatment, and three patients took the DA-EPOCH recipe. Two patients received autologous stem cell transplantation as second-line treatment. Median overall survival(OS)time was not reached(range 4-107 months), and five-year survival rate was 75 %. While the OS time of patient with HLH was only 10 months. Conclusion Patients with SPTCL own a relatively good prognosis,but those accompanied with HLH have poor outcome.

Background and objectiveVideo-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, longterm outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART).MethodsBetween 1994 and 2012, data of 1,117 patients hav-ing surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival.Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5%vs 73.9%,P=0.028), resection rate (98.8%vs 88.7%,P<0.001) and less recurrence (2.9%vs 16.0%,P<0.001). Five-year overall survival was 92% atfer VATS and 92% atfer open thymectomy, with no signiifcant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011).Cox proportional hazards model revealed that WHO classiifcation, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no signiifcant impact on long-term outcome.ConclusionhTis study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malig-nancies. And it may offer better perioperative outcomes, as well as equal oncological survival.

Objective:To explore the feasibility of the newly developed micro‐irrigation tube in the application to fistula complicated with empyema after esophagectomy .Methods:From Jan 2012 to Dec 2014 ,5 patients with fistula complicated with empyema after esophagectomy ,admitted in Zhongshan Hospital ,Fudan University ,accepted the therapy with a new type of micro‐irrigation tube .Among them ,4 patients were male and the other 1 was female .Three patients accepted left transthoracic esophagectomy and the other 2 underwent right thoracoabdominal esophagectom .Four patients got anastomotic stoma fistula , and the other 1 patient got stump fistula .The micro‐irrigation tube was composed of anesthesia epidural catheter ,double pipe joint and bottle water seal joint .Along the chest dralnage tube ,the micro‐irrigation tube was placed into the empyema cavity . Results:There was no serious adverse reaction except for the symptoms of cough and acid reflux in 2 patients .All the 5 patients were discharged smoothly with fistula healed and chest tube drawn .Conclusions:The application of micro‐irrigation tube in fistula complicated with empyema after esophagectomy is safe and feasible .

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Fluorodeoxyglucose F18 ; Humans ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; drug therapy ; pathology ; Male ; Middle Aged ; Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; Tomography, X-Ray Computed

BACKGROUNDThe anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) and congenital left main coronary artery atresia (CLMCA-A) are two kinds of very rare coronary heart diseases which affect heart function profoundly. This study aimed to retrospectively illustrate the clinical features and therapy experience of ALCAPA and CLMCA-A patients.

METHODSFrom April 1984 to July 2012, in Beijing Anzhen Hospital, 23 patients were diagnosed with ALCAPA and 4 patients with CLMCA-A. We summarized the clinical data of the 27 cases and retrospectively analyzed the clinical manifestation, diagnosis, and treatments of these two kinds of congenital coronary abnormalities.

RESULTSThe 23 patients (13 males and 10 females, aged ranging from 2.5 months to 65 years) identified with ALCAPA were classified into infantile type (age of onset younger than 12 months, 16 cases) and adult type (age of onset older than 12 months, 7 cases). Four patients were diagnosed with CLMCA-A (three males and one female, aged ranging from 3 months to 2 years). The main clinical manifestations of infantile-type ALCAPA and CLMCA-A include repeated respiratory tract infection, heart failure, dyspnea, feeding intolerance, diaphoresis, and failure to thrive. And these two congenital coronary abnormalities might be misdiagnosed as endocardial fibroelastosis, dilated cardiomyopathy, and acute myocardial infarction. As for the adult-type ALCAPA, cardiac murmurs and discomfort of the precordial area are the most common presentations and might be misdiagnosed as coronary heart disease, myocarditis, or patent ductus arteriosus. In ECG examination: Infantile-type ALCAPA and CLMCA-A showed abnormal Q waves with T wave inversion in leads I, avL, and V4-V6, especially in lead avL. However, ECG of adult-type ALCAPA lacked distinct features. In chest radiography: pulmonary congestion and cardiomegaly were the most common findings in infantile-type ALCAPA and CLMCA-A, while pulmonary artery segment dilation was more common in adult type. In echocardiography, the common features of infantile-type ALCAPA and CLMCA-A included left ventricular enlargement, left ventricular systolic function normal or mildly reduced in CLMCA-A or significantly reduced in ALCAPA, and moderate to large mitral valve. It was performed in 9 of 23 cases of ALCAPA and showed the origin of the dilated right coronary artery (RCA) from the right sinus of the aortic root and absence of LCA origin in angiography. After opacification of RCA, reverse flow in the LCA and pulmonary artery was visualized through coronary artery collateral circulation. Angio was performed in three of the four cases of CLMCA-A and showed left main coronary artery was a blind end, with diameter of only 1.1-2.0 mm. Treatment and prognosis: 21 patients with ALCAPA had cardiac surgery and 6 of them died postoperatively. Fifteen postoperative patients survived without overt symptoms within the follow-up period of 6-166 months (median 17 months). As for treatment of CLMCA-A, four patients took digoxin and diuretics without undergoing cardiac surgery. Their clinical symptoms improved during the close follow-ups.

CONCLUSIONSALCAPA and CLMCA-A are two rare coronary artery abnormalities that affect cardiac function in infants and children. In younger patients with cardiomegaly and heart dysfunction these two congenital coronary diseases should be noticed.

Adult ; Aged ; Bland White Garland Syndrome ; diagnosis ; pathology ; surgery ; Cardiac Surgical Procedures ; Child ; Child, Preschool ; Coronary Vessel Anomalies ; pathology ; surgery ; Coronary Vessels ; pathology ; surgery ; Echocardiography ; Electrocardiography ; Female ; Humans ; Infant ; Male ; Middle Aged ; Pulmonary Artery ; pathology ; surgery ; Young Adult