Objective To assess the value of noninvasive MR imaging biomarkers in evaluating the early efficacy of anti?angiogenesis drugs. Methods Subcutaneous colon cancer xenograft models in thirty nude mice were established. The mice were randomly divided into three groups (n=10 for each): avastin injection group (dose 10 mg/kg), fluorouracil group (dose 150 mg/kg), physiological saline group (dose 20 mg/kg). Dynamic contrast?enhanced (DCE?MRI) and multiple b value diffusion weighted imaging (muti?b?value DWI) were acquired before or 1 h, 24 h and 48 h after the treatment. The parameters of contrast transfer coefficient (Ktrans), reflux constant (Kep), plasma volume fraction (Vp), extravascular extracellular volume fraction (Ve) and various apparent diffusion coefficients (ADCs) (ADC10b, ADChigh and ADCperf) were measured. Forty eight hours after the treatment, the mice were sacrificed following MRI. Aimmunohistochemical examination determined microvessel density (MVD) and proliferating cell nuclear antigen (PCNA) score. A repeated measures analysis of variance was used to compare the difference between the quantitative parameters among the three groups. A multivariate variance analysis was performed to compare the difference between the parameters at the same time point among the three groups. The correlation between MRI quantitative parameters with MVD and PCNA score were analyzed by Pearson and Spearman correlation analysis respectively. Factor analysis method summarized MRI quantitative parameters. Results One hour after the treatment, the parameters of Ktrans, Kep, ADC10b, ADChigh and ADCperf value immediately changed, they were(0.009 ± 0.005)/s,(0.042 ± 0.031)/s,(0.043 ± 0.002)× 10?3 mm2/s,(0.031 ± 0.005)× 10?3 mm2/s,(0.089 ± 0.006)× 10?3 mm2/s, Ktrans, Kep, ADC10b and ADChigh values all had significant differences in the three groups (F=42.058, 25.979, 9.870 and 8.511, respectively, all P<0.05). There were also statistical difference in the change trend of the above parameters among the three groups (F=22.108, 7.280, 65.698 and 19.900, respectively, all P<0.05). The change trend of ADCperf showed significant difference among the three groups (F=38.780, P<0.01). Ktrans, Kep and ADCperf positively correlated with the MVD count and PCNA score (r values were 0.421 to 0.811, both P<0.01), while ADC10b showed a negative correlation (r=-0.656 and-0.560, both P<0.01), ADChigh had negative correlation with the PCNA score (r=-0.568, P<0.05). Ktrans, Vp, Kep and ADCperf were classified as tumor microcirculation factor, whereas ADC10b and ADChigh were normalized for cell metabolism factor through the factor analysis. Conclusions Combination of DCE?MRI and muti?b?value DWI can reflect the early changes of drug therapy from the aspects of tumor microcirculation and cell metabolism. Ktrans, Kep, ADCperf, ADC10b and ADChigh can be taken as noninvasive imaging biomarkers to quantify the early efficacy of anti?angiogenesis drugs.

Calcinosis ; Fibula ; Free Tissue Flaps ; pathology ; Humans ; Reconstructive Surgical Procedures

Objective To evaluate the application of microvascular coupler device (MVCD) in the free-tissue flap transfer for head-and-neck defects reconstruction.Methods Its a retrospective study of the clinical data of 743 patients who received 763 free-tissue flap transfer for head and neck defects reconstruction in Hunan Cancer Hospital from January,2014 to January,2016.For microvascular anastomoses,413 were done manually (the manual group) and 350 done with MVCD (the MVCD group),of which the latter included end-to-end venous anastomosis in 159,endto-side venous anastomosis in 190 and end-to-end arterial anastomosis in 1.The time for anastomosis,rate of blood leakage from the anastomosis and venous thrombosis,and the survival rate of flaps were compared between the manual group and the MVCD group.The impacts of types of anastomosis of end-to-end vs end-to-side (both with MVCD),on the formation of venous thrombosis and survival of flaps were also recorded.The analysis was performed under t-test and chi-square test using SPSS software 19.0 with P ＜ 0.05 for differences with a statistical significance.Results Time for anastomosis was significantly shorter in the MVCD group (4.43±0.51min) than in the manual group (14.75± 2.43min,P＜0.05).The rates of anastomosis leakage were 0 in the MVCD group and 9.7％ in the manual group(P＜0.01),flap necrosis were 0.57％ and 1.69％ (P=0.15),the rate of venous thrombosis were 1.15％ and 3.63％(P=0.02),respectively.There was no significant difference in the time for anastomosis,the rate of venous thrombosis and the survival rate of flaps with end-to-end anastomosis and end-to-side anastomosis with MVCD.Conclusion The application of microvascular coupler device is valuable in the reconstruction of head-and-neck defects with free-tissue flaps because it can significantly shorten the time for anastomosis,decrease the ocurrence of anastomosis leakage and venous thrombosis,reduce the risk of flap failure.

Objective To explore the feasibility and value of dynamic contrast-enhanced (DCE-MRI) parameters in assessing early effects of anti-angiogenesis medicine in targeted therapy for tumors.Methods Twenty BALB/C-nu nude mice were injected subcutaneously with human colon cancer cells HT-29 to the right hind leg.The nude mice were evenly divided into the experimental group and control group with 10 mice in each group.The mice of experimental group were intraperitoneally injected with bevacizumab,and the control group were injected with the same volume of saline.DCE-MRI was performed before medication and one hour,24 h and 48 h after medication.The Ktrans,Kep,Ve and initial area under enhancement curve (iAUC) of DCE-MRI were analyzed.The animals were sacrificed 48 hours after medication.Microvessel density (MVD) of the tumors was detected by immunohistochemistry.One way analysis of variance was performed to analyze parameters of DCE-MRI.The Pearson correlation coefficient was used to analyze the correlation between parameters of DCE-MRI and MVD.Results Under DCE-MRI,the edge of subcutaneous colon cancer xenografts was obviously gradually enhanced,pseudo color indicated high perfusion,the strength degree of the central region was low and which meant low perfusion.The differences in Kep of different time point of experimental group were statistically significant (F=3.752,P=0.016) ; there as no significant difference in other parameters of DCE MRI (all P＞0.05).There was no significant difference in Ktrans and Kep before medication and one hour after medication (all P＞0.05).There were significant difference in Ktrans and Kep 24 hour and 48 hour after medication between experimental group (24 hour∶ (0.095 ± 0.039) min-1 and (0.297 ± 0.141) min-1,48 hour∶ (0.090±0.033) min 1 and (0.314±0.148) min-1) and control group (24 hour∶ (0.150±0.074) nin-1 and (0.494±0.126) min-1,48 hour∶ (0.171±0.045) min-1 and (0.441± 0.092) min-1) (F24h =4.824 and 11.386,F48h =22.605 and 5.455,all P＜0.05).There was no significant difference in Ve and iAUC between two groups at different time points (all P＜0.05).MVD of experimental group was lower than that of control group.Ktrans and Kep were positively correlated with MVD (r=0.745 and 0.400,both P＜0.05).Conclusion Ktrans and Kep parameters of DCE-MRI may be used in monitoring the earlier effects of anti-angiogenesis medicine in targeted therapy for colon cancer.

OBJECTIVE: This study aimd to evaluate the application and clinical effect of improved submental island flap in hypopharyngeal cancer reserved laryngeal function surgery. METHOD: A retrospective review of clinical data was performed on 38 patients of hypopharyngeal cancer reserved laryngeal function using sumental island flaps, by the way of improving in design of vascular pedicle, reconstructive mode of laryngeal and hypopharyngeal function and closing of wound of neck following hypopharyngeal cancer resection. Meanwhile, the effect and prognosis was comprehensively assessed on patients with hypopharyngeal cancer reserved laryngeal function using improved submental island flaps. RESULT: The submental flaps kept alive in all 38 cases. During the follow-up period, 18 cases were dead, and of them, 7 cases died of the second primary carcinoma, included 4 cases of esophagus cancer, 1 case of cancer of soft palate, 2 cases of nasopharyngeal carcinoma; and 5 cases died of cervical or parapharyngeal lymph nodes recurrence; 2 cases died of hepatic metastasis; and 4 cases died of pulmonary metastasis. The overall 5-years survival rate was 52.6%. CONCLUSION Improved submental island flap repairing postoperative defect of hypopharyngeal cancer reserved laryngeal function has many advantages including higher success rate, more security, easy and simple to operate as well as good clinical effects, and is worth to widespread using.
Humans ; Hypopharyngeal Neoplasms ; surgery ; Hypopharynx ; surgery ; Larynx ; Neck ; surgery ; Neoplasm Recurrence, Local ; Prognosis ; Reconstructive Surgical Procedures ; Retrospective Studies ; Surgical Flaps ; Survival Rate

OBJECTIVETo investigate the effect of celecoxib in enhancing the chemosensitivity of oral cancer cells and the correlation of this effect with cell cycle arrest.

METHODSKB/VCR cell line was treated with celecoxib (10, 20, 40, and 80 µmol/L) and/or VCR (0.375, 0.75, 1.5, and 3 µmol/L), and the growth inhibition rates of KB/VCR cells were assessed with MTT assay. Flow cytometry was employed to analyze the distribution of cell cycle. Western blotting was performed to detect the expression of P-glycoprotein (P-gp) and the cell cycle related proteins Cyclin D1 and p21(WAF1/CIP1).

RESULTSLow concentrations of celecoxib (<20 µmol/L) produced no obvious effect on the proliferation of the cells. But at 10 µmol/L, celecoxib significantly enhanced the toxicity of VCR in a time-dependent manner, and the combined treatments for 24, 48, and 72 h caused growth inhibition rates of (37.53∓2.05)%, (46.67∓3.17)% and (54.02∓1.53)%, respectively, significantly higher than those following treatments with celecoxib or VCR alone (P<0.01). Compared with the cells treated with VCR alone , the cells with combined treatments showed a significantly increased cell percentage in G0/G1 phase [(56.08∓0.46)%] with decrease percentages in S phase [(22.83∓0.20)%] and G2/M phase [(21.09%∓0.66)%]. The combined treatment also significantly down-regulated cyclin D1, up-regulated p21(WAF1/CIP1), and reduced P-gp expressions in the cells.

CONCLUSIONSCelecoxib enhances the chemosensitivity of KB/VCR cells by down-regulating P-gp expression, which is partially mediated by modification of cyclin D1 and p21(WAF1/CIP1) to result in cell cycle arrest.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Celecoxib ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Humans ; KB Cells ; Mouth Neoplasms ; drug therapy ; metabolism ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology

Objective To observe the effects of maternal high fat diet (MHFD) during pregnancy and lactation on intestinal barrier function in offspring mice.Methods C57BL/6 pregnant mice were divided into high fat diet (MHFD) group and normal diet group (MND) randomly and were given high fat diet and normal diet during pregnancy (3 weeks) and lactation (3 weeks) respectively.Both groups of offspring mice were naturally given and bodyweight of pups was monitored at birth and weekly.After weaning,the intestinal permeability of offspring mice was detected by fluorescein isothiocyanate conjugated-dextran method (FITC-D).Immunofluorescence was used to detect the expression of ZO-1 in intestinal tissues.HE staining was used to assess the villus length and crypt depth.The intestinal cell proliferation (expression of Ki-67) and Mucin 2 (MUC2) were assessed by immunohistochemistry.PAS staining was used to evaluate the goblet cells.The expression of inflammatory cytokines including IL-1β,IL-6,and TNF-α in intestinal tissue were measured by real-time PCR.Results At the age of 2 and 3 weeks,the offspring in MHFD group were significantly heavier than those in MND group.HE staining showed no obvious microscopic inflammation in both groups of 3 weeks old offspring mice,however,the relative expression levels of IL-1β (1.95±0.53 vs.1.13±0.15;t =3.65,P=0.005),IL-6 (1.40±0.71 vs.0.73±0.17;t=2.72,P=0.04),and TNF-α (1.63±0.53 vs.1.04±0.12;t=2.64,P=0.02) mRNA were significantly higher in the MHFD group.Compared with the 3 weeks old offspring mice in MND group,MHFD significantly increased the permeability of intestine and decreased the expression of ZO-1 in membrane.The number of Ki-67 positive cells (18.00±4.74 vs.24.60±4.17;t =3.31,P=0.004) in each villus,goblet cells (14.70±2.91 vs.28.10±4.95;t =7.38,P＜0.001) and MUC2 positive cells (20.60± 3.13 vs.30.00±3.33;t=6.50,P＜0.001) in each crypt were significantly lower than those in MND group.Conclusion Maternal high fat diet in early life of offspring mice can induce intestinal low grade inflammation and lead to the disruption of intestinal mucosal barrier in offspring mice,which may be involved in the progeny diseases.

Objective:To investigate the feasibility, safety and effectiveness of colonic interposition with vascular anastomosis in reconstructing the entire esophagus and hypopharynx after resection of hypopharyngeal cancer with esophageal cancer.Methods:We conducted a retrospective analysis of 4 male patients with simultaneous multiple primary cancers of the hypopharynx and esophagus, aged 47 to 58, treated in the Department of Head and Neck Surgery at the Hunan Cancer Hospital from February to August 2019. All cases underwent total hypopharyngectomy and total esophagectomy, of whom, three cases presented with total laryngectomy and one case with larynx preservation. Colonic interposition was performed using the left colic artery as a pedicle, with an average colonic length of 48.5 cm. The colon was elevated through the esophageal bed to the neck, and the branch of the colonic mesenteric artery was anastomosed to one of the neck arteries, including the inferior thyroid artery in one case, the transverse cervical artery in two cases, and the superior thyroid artery in one case, and all venous anastomoses were performed with the internal jugular veins.Results:The postoperative neck and abdominal wounds healed well without anastomotic leakage, and all patients were able to resume a regular oral diet within 21-30 days postoperatively. During the follow-up of 48-52 months, two cases died due to tumor recurrence, while the remaining two cases were disease-free survivals.Conclusion:Colonic interposition with vascular anastomosis is a safe and reliable reconstruction method suitable for repairing long-segment upper digestive tract defects after resection of hypopharyngeal cancer with esophageal cancer.

Objective:To evaluate the value of synthetic MRI combined with three dimensional-arterial spin labeling (3D-ASL) imaging in the grading of diffuse glioma and its correlation with tumor cell proliferative activity (Ki-67).Methods:This study was prospective. The clinical and imaging manifestations of 66 patients with diffuse glioma who underwent synthetic MRI combined with 3D-ASL imaging from August 2020 to June 2021 in General Hospital of Ningxia Medical University were analyzed. Among 66 patients, there were 36 males and 30 females, aged 4-76 years, and divided into low grade glioma (LGG) group ( n=25) (WHO Ⅱ) and high grade glioma (HGG) group ( n=41) (WHO Ⅲ and vⅣ). T 1, T 2, proton density (PD) and cerebral blood flow (CBF) of tumor parenchyma were measured by GE ADW4.7 postprocessing software. The Ki-67 label index (Ki-67 LI) in postoperative pathological sections was detected by immunohistochemistry. Independent sample t test or Mann-Whitney U test was used to compare the differences of quantitative parameters between HGG group and LGG group. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of T 1, PD, CBF and the combination. Spearman test was used to analyze the correlation between the parameters and Ki-67 label index (LI). Results:T 1[(1 573±173)ms], PD[(86.2±2.4)pu] and CBF[(129±48)ml·100 g -1·min -1] in HGG group were significantly higher than those in LGG group [(1 376±134)ms, (83.0±2.5)pu and (77±49)ml·100g -1·min -1 respectively], and difference had statistical significance ( t=-4.86, -5.08, -4.24, P<0.01). ROC confirmed that the area under curve (AUC) of T 1, PD and CBF in differentiating HGG from LGG were 0.847, 0.843 and 0.777, respectively. In multi-parameter analysis, the combination of three parameters had the best diagnostic efficiency (AUC=0.973) and the sensitivity and specificity were 87.8% and 100%, respectively. In LGG and HGG groups, there was no correlation between T 1, T 2, PD, CBF and Ki-67 LI. In the overall cohort, T 1, PD and CBF had slight positive correlation with Ki-67 LI ( r=0.394, 0.411 and 0.406, respectively, all P<0.01). There was no correlation between T 2 and Ki-67 LI ( r=-0.100, P=0.423). Conclusion:Synthetic MRI and 3D-ASL can noninvasively evaluate the pathological grade of glioma and predict the expression of Ki-67, among which T 1 and PD are novel imaging marks.

Objective To evaluate surgical treatment outcomes in 6 cases with tremendous neurogenic tumors in the root of neck.Methods Neck-chest-axil-arm "T" incision was used to remove huge tumor in the root of neck.Results The tumors in the root of neck in 6 patients were removed successfully and no serious complication occurred.With postoperative follows-up for 2-6 years (median 4.5 years),only 1 case died due to the recurrence of lesion in vertebral canal in 11 months after surgery and the other cases survived with satisfying therapeutic outcomes.Conclusion Surgery is an effective method to remove advanced tumor in the root of neck and to improve the quality of life for the patients.