Tumor angiogenesis is a complicated pathologic process, which plays an important role in the growth and metastasis of most solid tumors. Targeting at the angiogenesis and inhibiting tumor growth or metastasis, specific antibodies or inhibitors of tumor angiogenesis have been developed for this purpose. We summarized recent researches about the mechanism of tumor angiogenesis and the development of tumor angiogenesis inhibitors in this review.

Background and purpose:The genetic and epidemic events that mediate the progression from in-situ to invasive prostate carcinoma are poorly understood.Stoma factors may facilitate the growth and invasion of tumor cells that have lost regulatory mechanisms.However,in situ carcinoma cells are separated from the stoma by a continuous layer of basal epithelial cells.During progression to invasive carcinoma,the basal cell layer becomes disrupted and tumor cells adhere to the basement membrane.This paper discussed the role of Laminin-5 secreted by basal epithelial cells that participated in the invasion of in situ prostate cancer cells.Methods:BPH-1 cells were used as an in vitro model of pre-invasive prostate cancer cells in order to investigate the migration-promoting activity of secreted factors from basal epithelial cells.Adhesion proteins and chemotactic factors that stimulate adhesion,planar polarization,migration were studied by techniques such as immunofluorescent analysis,immunoprecipitation and Western blot.Results:The results showed that the conditioned medium of basal epithelial cells(PEC-CM) contained adhesion proteins and chemotactic factors that stimulated adhesion,planar polarization,migration,and could phosphorylate Akt.LY294002 and Wortmannin partially inhibited PEC-CM-triggered migration(P

Objective: To explore the causes and management of the complications in diabetic foot treated with tibial transverse transport (TTT). Methods: Between September 2015 and September 2019, 196 patients with diabetic foot were treated with TTT. There were 109 males and 87 females, with an average age of 67.6 years (range, 45-86 years). According to Wagner's classification, there were 124 cases of grade 3, 62 cases of grade 4, and 10 cases of grade 5; the course of disease was 1-12 months, with an average of 2.6 months. All patients underwent the minimally invasive tibial osteotomy. The osteotomy site was the middle and lower tibia in 62 cases and the middle and upper tibia in 134 cases. The area of osteotomy was 20 cm 2 in 83 cases and 7.5 cm 2 in 113 cases. The osteotomy block was moved back and forth once in 92 cases and twice in 104 cases. The complications were recorded, including secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection. Results: Among 196 patients, 41 cases (20.9%) had complications. Nine cases (4.6%) had secondary fracture at tibial osteotomy, among which 6 cases (9.6%) of middle and lower segment osteotomies and 3 cases (2.2%) of middle and upper segment osteotomies. The incidence between the patients with different osteotomy sites was significant ( χ2=5.354, P=0.021). The area of osteotomy was 20 cm 2 in 5 cases (6.0%) and 7.5 cm 2 in 4 cases (3.5%). There was no significant difference in the incidence between patients with different areas ( χ2=0.457, P=0.499). Skin necrosis occurred in the osteotomy area in 12 cases (6.1%), all of which were moved back and forth once. There was a significant difference in the incidence between patients who were treated with transport once and twice ( P=0.001). There were 18 cases (9.1%) with pin tract infection, including 12 cases (6.1%) with mild infection and 6 cases (3.0%) with severe infection. There was no significant difference in the incidence between the patients with mild and severe infections ( P=0.107). Conclusion: TTT is an effective method to treat diabetic foot, but there are complications such as secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection during transport. Preoperative evaluation of indication, standardization of osteotomy mode, size and position of osteotomy block, establishment of individualized removal plan, and strengthening of pin track nursing after operation can effectively reduce complications.

ObjectiveTo evaluate the therapeutic effect and toxicities of gemcitabine combined with cisplatin in the treatment of advanced or metastatic transitional cell carcinoma (TCC) of urinary tract. Methods Eighteen patients with advanced or metastatic TCC of urinary tract (15 cases of bladder TCC,2 of renal pelvic TCC,and 1 of ureteral TCC),who were pathologically confirmed,were treated with GC regimen (gemcitabine 1000 mg/m 2,iv infusion on day 1 and day 8;cisplatin 30 mg/m 2,iv infusion on day 2,day 8 and day 9).Before treatment, Karnofsy score for each patient was evaluated with a result of ≥60;liver and renal functions and blood routine test were normal.GC regimen was repeated for 2-3 cycles every 3-4 weeks and the response rate was evaluated.ResultsThree patients (16.7%) had complete response; 7(38.9%), partial response;5(27.8%),no response;and 3(16.7%) had progression.The overall response rate was 55.6%. The main toxic effects included decrease in white cell count (10 cases),anemia (7),nausea and vomiting (10) and constipation (8),which were mild or moderate and disappeared after stopping treatment.No chemotherapy-associated death occurred.ConclusionsGemcitabine combined with cisplatin in the treatment of advanced or metastatic transitional cell carcinoma of urinary tract is effective,and the toxicity is mild and tolerated. It is suggested that GC regimen can be used as the first line chemotherapy.

Objective To construct a nomogram for estimating disease free survival of node-positive penile cancer treated with surgery.MethodsThe clinicopathological data of 32 node-positive penile squamous cell carcinoma patients were retrospectively reviewed.All patients had undergone primary tumor excision and regional lymphadenectomy.The pathological records showed that 10 were N1,13 were N2 and 9 were N3.Median level of preoperative squamous cell carcinoma antigen (SCCAg) was O.9 μg/L.With a median follow-up of 16.5 months,13 patients developed recurrence.Based on the stage,histological grade and preoperative serum squamous cell carcinoma antigen level,a nomogram was drawn on the basis of the Cox regression model.Results Stage and preoperative serum SCCAg levels were independent prognostic factors for disease free survival in node-positive penile cancer treated with surgery.The hazard ratio of SCCAg level and N stage was 2.76 (95％ CI:1.40-5.44,P=0.0034) and 28.51 (95％ CI:2.55 -319.11,P =0.0066).The nomogram demonstarted good discrimination and calibration with a concordance index of 0.855.Conclusions Based on the N stage and preoperative serum SCCAg level,a nomogram to predict disease free survival in node-positive penile cancer treated with surgery was set up.The prediction model could be helpful in predicting the risk of recurrence.

Objective To construct and evaluate a nomogram for predicting the risk of regional lymph node metastases according to pathological features of the primary penile squamous cell carcinoma. Methods The clinical and pathological data of 73 patients who had undergone partial/radical penectomy and ilio/inguinal lymphadenectomy for squamous cell carcinoma of the penis from 1990 to 2005 were retrospectively collected. The expressions of molecular markers (p53, Ki-67, E-cadherin and MMP-9) were determined by immunohistochemistry. A logistic regression model was used to construct the nomogram. Results Tumor grade, the expression level of p53 and lymphovascular invasion were independent prognostic factors of regional lymph node involvement (P<0. 05). The nomogram predicting the risk of metastatic lymph node involvement showed a good concordance index (0. 92) and good calibration. Conclusions Based on the pathological findings of primary tumor, a nomogram to predict the probability of regional lymph node involvement in penile squamous cell carcinoma patients is constructed. This statistical tool is not only helpful in judging individualizing tumor risk, but also in facilitating patients communication in treatment options.

Objective To construct and evaluate a nomogram for predicting the risk of peri-operative complications after radical retro-pubic prostatectomy (RRP) with standard classification criteria.Methods The peri-operative complications and clinicopathological data of 240 patients (50-82 years old) who had undergone RRP for prostate cancer from June 2006 to June 2011 were retrospectively collected.Gleason score:95 cases ＜ 7; 145 patients ≥ 7;Clinical staging:cT1 is 1 case (0.4％),T2a 5 cases (2.1％),T2b 7 cases (2.9％),T2c 162 cases (67.5％),T3a 26 cases (10.8％),T3b 39 cases (16.3％).The peri-operative complications (in 30 days after surgery) were classified by Clavien-Dindo Classification system (the occurrence rates are as follows:rectum injury 1.6％,wound infection 2.0％,deep venous thrombosis 1.2％,urinary leak 5.0％,lymphocele 4.5％,myocardial infarction 5.8％,second look operation 1.6％),and a logistic regression model was used to construct the nomogram.Results BMI,N staging and Blood loss more than 200ml during surgery were independent prognostic factors of RRP morbidity in multivariate logistic regression.The nomogram predicting the risk of peri-operative complications showed relative good concordance index (0.633) and good calibration. Conclusions Based on the clinicopathological factors,a nomogram to predict the probability of peri-operative complications in patients undergone RRP was constructed.This statistical tool may be beneficial in judging operation risk and help consulting with patient before or after surgery.

Objective To evaluate the prognostic value of bilateral inguinal lymph node metastases in node-positive penile cancer. Methods Sixty patients with surgically resected node-positive penile cancer were analyzed. All the patients underwent regional lymph node dissection. Recurrence free survival curves were plotted by Kaplan-Meier method and compared by the Log-rank test. Multivariate survival analysis was performed using Cox regression model. Results Of all the patients, 18 cases had bilateral inguinal lymph node metastases. The 3-year recurrence free survival rate in patients with bilateral invovlement was significantly lower than those with unilateral disease (26.7 % vs 65.3 %, χ2 =10.6, P=0.001). In order to evaluate wether the prognostic significance of bilateral lymph node metastases was dependent of increased number of positive nodes, the two predictors were included in multivariate survival analysis.Both the number of metastatic nodes and bilateral nodal disease were independent prognostic factors (P ＜0.05).Comparisons of survival curves showed those patients with bilateral nodal disease and more than 2 metastatic nodes had worst outcome. Conclusion Bilateral inguinal lymph node metastases is an important prognostic factor in penile cancer irrespective of the number of positive lymph node.

Background and purpose:Bladder cancer radical surgery is dififcult with many perioperative complications, and the learning curve is long. To introduce the clinical application of complete retrograde radical cystectomy and consequent abdominal cavity reconstruction in male bladder cancer, and to provide a standardized surgical procedure with minimum perioperative complications and short learning curve. Methods:From Apr. 2012 to Apr. 2013, 110 cases of male patients with bladder cancer received this procedure in our department, with a median age of 64 (35-83) years;Preoperative characters, surgical parameters, perioperative complications, pathology, long-term complications and short-term prognosis were collected and analyzed. Results:The median number of lymph nodes resected in operation was 12 (8-16);Neurovascular bundles were reserved bilaterally in 65 cases, and unilaterally in 31 cases;The complete procedure including urinary diversion took 4.4 (2.2-6.0) hours, with a median time of opened abdominal cavity of 43.0 (5.0-75.0) minutes;The median blood loss was 140.0 (50.0-600.0) mL, and 4 patients needed transfusion; Median time of abdominal and pelvic drainage was 10.0 (6.0-15.0) days, the median gastrointestinal recovery time was 2.5 (1.0-12.0) days, and the median postoperative hospital stay was 17.0 (10.0-39.0) days;Grade 2 Clavien-Dindo classiifcation (CDC) of surgical complications that required medical intervention were found in 19 cases, CDC grade 3 or above were found in 8 cases;Mild to moderate postoperative ileus happened in 5 cases, all recovered in median 2 (1-4) weeks with supportive treatments;There were no perioperative deaths. All samples were sent to pathological analyses. After a median follow-up of 9 (3-15) months, no complications of or above CDC grade 3 happened, and there were no recurrence. Conclusion:Complete retrograde radical cystectomy in male bladder cancer provided clear anatomical approach, reliable neurovascular bundle preservation, less blood loss, limited abdominal organs disturbance and better surgical exposure; With respect to tumor control, more peritoneal was retained for subsequent abdominal cavity reconstruction. The introduced procedure effectively speeded up gastrointestinal recovery, reduced postoperative complications, especially the incidence of ileus and its severity, and shortened hospital stay. The learning curve of this procedure for urologists was short, and further investigation was warranted.

Objective To determine the effect of moderate hypothermia on coagulation in patients with severe traumatic brain injury (sTBI) and investigate the clinical significance of thrombelastogram (TEG) monitoring.Methods Seventy-five patients with sTBI were randomly assigned to hypothermia group (conventional treatment + moderate hypothermia within 24 hours posttrauma,n =38) and control group (conventional treatment alone,n =38).TEG aided in monitoring coagulation function by measuring clot reaction time (R),clot formation time (K),clotting rate (α),maximal amplitude (MA),and percent fibrinolysis at 30 minutes after MA (LY30).Meantime,the intracranial pressure,vital signs,blood gas values,and blood electrolytes were also measured.Outcome was evaluated by using Glasgow outcome scale (GOS).Results The two groups were similar on admission with respect to R,K,α,MA,and LY30 (P ＞ 0.05),but the coagulation index in hypothermia group was significantly different from that in control group at days 1,2,3 and 7 posttreatment (P ＜ 0.05).Moreover,moderate hypothermia therapy demonstrated decrease of intraeranial pressure (P ＜ 0.01),with no severe complications,low mortality and improved outcome in comparison with control group.Conclusion Moderate hypothermia improves the hypercoagulability in patients with sTBI without increasing the risk of hyperfibrinolysis and protects brain tissue by decreasing intracranial pressure.