Percutaneous cryotherapy for metastatic bladder cancer: experience with 23 patients.

Bladder cancer is the most common malignancy of the urinary tract and in many patients is metastatic at diagnosis. Chemotherapy is the standard treatment for these patients but has serious side effects and in many patients is not tolerated. To avoid the side effects of systemic chemotherapy, patients with late stage bladder cancer have sought cryotherapy in our hospital. We reviewed data for the past 4 years to evaluate the safety and efficiency of percutaneous cryotherapy in 23 patients. Within 3 days after cryosurgery, all complications of bladder cancer (e.g. hematuria, urinary irritation, hypogastralgia, lumbago) had decreased to some degree. No new complications (e.g. bladder perforation) occurred and all complications had disappeared completely after 2 weeks. The progression-free survival (PFS) of these patients was 14 ± 8 months. There was no effect on PFS of tumor location or histopathology; however, differentiation status and tumor size influenced the therapeutic effect of percutaneous cryoablation. In conclusion, percutaneous cryotherapy may be a safe and efficacious therapeutic option in the treatment of metastatic bladder cancer.

Cryoprotective therapy for hepatocellular carcinoma: study of 51 patients with a single lesion.

Percutaneous cryoablation is a potentially curative treatment for hepatocellular carcinoma (HCC). After liver cryosurgery, rapid elevations of transaminases and bilirubin are common, but are usually transient and normalize within a few days. This study retrospectively reviewed clinical data from 51 patients who underwent liver cryoablation in our hospital during the past 4.5 years. Sixty-six percutaneous cryoablations were performed in these patients and transaminase and bilirubin levels before and after the procedure were observed. Although most patients received liver-protective treatment before cryosurgery, transaminase levels were double (mean alanine transaminase (ALT) and aspartate transaminase (AST) were 71 U/L and 85 U/L, respectively) the normal ranges in our hospital. One day after cryosurgery, ALT and AST had increased 3.3-fold (peak mean was 241 U/L) and 5-fold (peak mean was 427 U/L), respectively, but were close to the preoperative level 5 days post-cryosurgery. No significant increase of serum bilirubin was observed. Serum transaminase and bilirubin levels were compared between hepatitis B positive and hepatitis B negative patients. Only in the hepatitis B positive group were total bilirubin (74 µmol/L/23 µmol/L=3.2) and direct bilirubin (45 µmol/L/12 µmol/L=3.8) more than 3 times the preoperative level 7-9 days after treatment. Overall, ALT and AST are valuable as indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, serum bilirubin was 3 times the preoperative level 7-9 days after cryosurgery. Liver-protective treatment may alleviate liver function impairment due to cryosurgery.

Treatment of central type lung cancer by combined cryotherapy: experiences of 47 patients.

Most patients with central type lung cancer (CTLC) are not candidates for surgery; systemic chemotherapy and external beam radiotherapy are the main treatments but have not greatly affected patient outcome. Combined percutaneous and endobronchial cryotherapy has been used successfully to treat CTLC; this study aimed to determine its feasibility and safety. Forty-seven patients with unresectable CTLC (22 endotracheal, 26 tracheal wall and 21 extratracheal tumors) underwent 69 sessions of combined percutaneous cryosurgery, endobronchial cryosurgery and airway stenting. The long diameter of all tumors was <5 cm. Biopsy showed non-small cell lung cancer (NSCLC) in 40 patients (medium or well differentiated in 20 cases, poorly differentiated in 20) and small cell lung cancer (SCLC) in seven. Within 3 days after treatment, ventilatory capacity and performance status had obviously increased and cough, signs of dyspnea, hemoptysis and atelectasis improved significantly, but symptoms of pneumothorax and pleural effusion emerged. After 2 weeks, all complications had disappeared completely, as had cough. Progression-free survival (PFS) for endotracheal tumors (8 ± 4 months) was shorter than that for tracheal wall (13 ± 6 months, P < 0.05) and extratracheal (14 ± 8 months, P < 0.01) tumors. The PFS of NSCLC (11 ± 5 months) was significantly longer than that of SCLC (4 ± 2 months, P < 0.0001). The PFS of medium or well differentiated CTLC (15 ± 8 months) was significantly longer than that of poorly differentiated CTLC (7 ± 3 months, P < 0.0001). In conclusion, combined cryotherapy is a safe and effective treatment for CTLC, with PFS largely influenced by tumor location and pathologic type.

Therapeutic outcomes of combining cryotherapy, chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer.

Currently there are no effective therapies for the treatment of metastatic non-small cell lung cancer (NSCLC). Here, we conducted a retrospective study of 161 patients to evaluate the therapeutic effects of combining cryosurgery, chemotherapy and dendritic cell-activated cytokine-induced killer cells (DC-CIK) immunotherapy. The overall survival (OS) after diagnosis of metastatic NSCLC to patient death was assessed during a 5-years follow-up period. OS of patients who received comprehensive cryotherapy was (median OS, 20 months; n = 86) significantly longer than that of patients who did not received cryotherapy (median OS, 10 months; n = 75; P < 0.0001). Five treatment combinations were selected: chemotherapy (n = 44); chemo-immunotherapy (n = 31); cryo-chemotherapy (n = 32); cryo-immunotherapy (n = 21); and cryo-chemo-immunotherapy (n = 33). A combination of cryotherapy with either chemotherapy or immunotherapy lead to significantly longer OS (18 months and 17 months, respectively) compared to chemotherapy and chemo-immunotherapy (8.5 months and 12 months, respectively; P < 0.001); however, the median OS of patients who underwent cryo-chemo-immunotherapy was significantly longer (27 months) compared to the other treatment programs (P < 0.001). In conclusion, a combination of cryotherapy, chemotherapy and DC-CIK immunotherapy proved the best treatment option for metastatic NSCLC in this group of patients.

Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery.

Esophageal cancer is common in China. There is a lack of treatment strategies for metastatic esophageal cancer (MEC) after radical surgery on the primary tumor. Cryoablation is an attractive option because tumor necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. One hundred and forty patients met the inclusion criteria from May, 2003 to March, 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. No severe complications occurred during or after cryoablation. Overall survival (OS) was assessed according to therapeutic protocol, pathologic type, treatment timing and number of procedures. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; P = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; P = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; P = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; P = 0.0172); and the OS for cryo-immunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; P = 0.0011). Thus, comprehensive cryotherapy may have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation may be associated with a better prognosis.

Alleviating the pain of unresectable hepatic tumors by percutaneous cryoablation: experience in 73 patients.

Pain caused by liver tumors can be alleviated by cryoablation, but little is known about the analgesic effects and duration of pain alleviation. We retrospectively reviewed the changes in the severity of pain before and after percutaneous cryoablation of hepatic tumors. Each patient enrolled in this study had a single hepatic tumor; patients with large tumors (major diameter, P5 cm) underwent transarterial chemoembolization (TACE) first and then cryoablation. Severe abdominal pain that was not controlled with long-lasting oral analgesics was treated with opioid injections. In all 73 study patients, severe abdominal pain was gradually eased 5 days after cryosurgery, completely disappeared after 15 days and did not recur for more than 8 weeks. There were no differences in analgesic effects between patients with hepatocellular carcinomas and those with liver metastasis (P > 0.05). The patients were divided into four groups depending on their pain outcomes: (i) immediate relief (n = 6), severe abdominalgia was no longer present after cryosurgery; (ii) delayed relief (n = 11), severe abdominalgia disappeared gradually within 15 days after the cryosurgery; (iii) always pain-free (n = 39), severe abdominalgia was not present before or after treatment; and (iv) new pain (n = 17), abdominalgia developed after treatment and disappeared within 15 days. In summary, percutaneous cryoablation of hepatic tumors caused short-term pain in some patients, but this pain disappeared within 15 days. Moreover, the pain-relieving effect of this treatment was sustained for at least 8 weeks, without severe side effects.

Irreversible electroporation ablation of tumor: an analysis of perioperative complications / 介入放射学杂志

Objective To summarize and analyze the perioperative complications of irreversible electroporation (IRE) ablation in treating tumors at different locations and to discuss their managements. Methods A total of 200 patients with tumors, including pancreatic tumor (n=71), liver tumor (n=64) and other tumors (n =65), were enrolled in this study. All patients received IRE ablation treatment. The perioperative complications were recorded and the data were statistically analyzed. The causes of severe complications and the treatment of complications were discussed. Results None of the patients died during the course of IRE ablation procedure. Severe postoperative complications occurred in the patients with pancreatic tumor or liver tumor, including duodenal artery bleeding in 3 patients with pancreatic tumor, which occurred at 10 days, 11 days and 15 days after IRE ablation respectively, and gastrointestinal bleeding (n =1) and biliary septic shock (n=1) in 2 patients with liver tumor, which occurred at 9 days after IRE ablation, the clinical symptoms were controlled after interventional embolization and/or vascular ligation together with anti-infective therapy. All minor complications were relieved after symptomatic treatment within 14 days. Conclusion IRE ablation has less systemic inflammatory response, and both the intraoperative and postoperative adverse reactions can be easily controlled, besides, IRE ablation has higher clinical safety. Although IRE ablation procedure may damage the internal or peripheral vessels of the pancreatic tumor, this severe complications can be effectively avoided if proper measures are adopted based on the causes of complications. (J Intervent Radiol, 2018, 27: 223-227)

Irreversible electroporation ablation for the treatment of malignant tumors of liver: present clinical situation / 介入放射学杂志

The incidence of liver cancer has been increasing year by year.In China,the incidence of liver cancer is 25.7/10 million.However,when the important organs have been involved or when the malignant liver tumors are located adjacent to the hepatic portal vital organs,the lesions are usually difficult to be surgically removed,and the curative results of chemotherapy and radiotherapy for such lesions are often poor.In recent years,along with the gradual rise of ablation techniques,the irreversible electroporation (IRE),regarded as a new ablation method that uses non-thermal energy,has been widely employed in clinical practice.Through generating instantaneous high voltage electrical pulses,IRE produces irreversible nanoscale damage to the cell membrane.Both domestic and foreign researches have indicated that for the treatment of inoperable primary or metastatic liver tumors IRE can effectively inactivate the tumor tissue while the lumen architecture of the vessels can be preserved and large vessel or bile duct will not be damaged.This paper aims to make a comprehensive review about IRE device structure,mechanism of therapeutic action,preclinical studies,clinical application methods and clinical efficacy in order to provide reference for the application of this technology in clinical practice.(J Intervent Radiol,2017,26:285-289)

Clinical application of MR diffusion-weighted imaging in evaluating the short-term curative effect of cryoablation for pancreatic carcinoma / 介入放射学杂志

Objective To discuss the clinical value of magnetic resonance diffusion-weighted imaging (MR-DWI) in distinguishing tumor remnants from tumor necrosis of pancreatic carcinoma after cryoablation treatment.Methods Conventional MRI T1WI,T2WI scan,DWI sequence and dynamic enhanced MRI scan were performed in 26 patients with pancreatic carcinoma who were received cryoablation treatment.The changes in MRI signals after cryoablation treatment were recorded.The apparent diffusion coefficient (ADC) values of the normal pancreas,preoperative tumor tissue,postoperative remnants and necrosis tissue were calculated,and the results were compared.The correlation between the ADC values and the size of the tumor was evaluated,and the differences in ADC values among the tumors that had different diameter,location and staging were statistically analyzed.Results Of the 26 patients,complete necrosis of tumor was obtained in 16.The necrotic tumor tissue displayed low-signal on T1WI,high-signal on T2WI and low-signal on DWI,with no enhancement on dynamic enhanced imaging.Active residual tumor tissue was detected in 9 patients,among them the residual tumor diameter ＞5 cm was seen in 7 patients;the residual rate was 34.6％.ADC values of the following tissue,from low to high in order,were preoperative pancreatic tumor tissue (1.022± 0.126)x10-3 mm2/s,postoperative residual tumor tissue (1.130±0.155)x10-3 mm2/s,normal pancreatic tissue (1.924±-0.124)×10-3 mm2/s and postoperative necrosis tissue (2.312-±0.214)×10-3 mm2/s.No statistically significant difference in ADC values existed between preoperative pancreatic tumor tissue and postoperative residual tumor tissue (P=0.452),while statistically significant difference in ADC values existed between normal pancreatic tissue and postoperative necrosis tissue (P＜0.001).The ADC values of pancreatic tumor tissue bore a negative correlation with the tumor size (R=-0.43,P=0.027 2),while the ADC values lacked the relationship to the tumor location as well as to the tumor staging (P=0.738 8 and P=0.089 5 respectively).Conclusion MR-DWI can effectively distinguish the residual tumor tissue from the necrotic tumor tissue of pancreatic carcinoma after cryoablation treatment,which provides reliable basis for further clinical diagnosis and treatment.

Mechanism of FTY720 on cardiovascular complications of diabetes mellitus / 实用医学杂志

Objective To study the mechanism of FTY720 on type Ι diabetic rats. Methods The typeⅠdiabetes rat model was established by feeding male SD rats with high energy urea and injecting into the abdominal cavity with low dose cephalosporins (STZ, 30 mg/kg). In the following, the treated rats were divided into two groups: model group and FTY720 group. Another group of untreated rats was assigned as normal control group. FTY720 group was given 1 mg/kg FTY720, the normal control group and model group was given the equal amount of water. Results The cardiac function of FTY720 group was recovered markeyly. FTY720 activated the expression of vascular endothelial cells S1P1 , diabetes and reduced the expessions of S1P3 and PKCβ Ⅱand it restored the migration ability of diabetes cardiovascular endothelial cell , as well as the abnormally elevated cardiovascular endothelial cells induced by high sugar permeability. Conclusion The S1P1 and S1P3 cut is an important reaction pathway to the complications of diabetes and cardiovascular dysfunction. FTY720 may reduce the damage to core blood vessels caused by diabetes , and pathological angiogenesis which functionally depends on the PKCβⅡ signaling pathways. Therefore, FTY720 may provide a potential therapy for cardiovascular function impaired by diabetes.

Proteomic identification of CIB1 as a potential diagnostic factor in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), among the most common malignancies worldwide, remains a major threat to public health, and there is an urgent need to identify novel biomarkers for diagnosis, prognosis and targets for anti-cancer treatment. In this study, two-dimensional polyacrylamide gel electrophoresis coupled with ESI-Q-TOF MS/MS analysis was used to identify differentially expressed proteins among the HCC tumour centre, tumour margin and nontumourous liver tissues. In total, 52 spots with significant alteration were positively identified byMS/MSanalysis. Altered expression of representative proteins, including CIB1, was validated by Western blotting. Immunostaining suggested an increase tendency of CIB1 expression from nontumourous liver tissue to tumour centre. Knockdown of CIB1 expression by RNA interference led to the significant suppression of the cell growth in hepatoma HepG2 cells. These data suggest that CIB1 may be used as a novel prognostic factor and possibly an attractive therapeutic target for HCC.

Safety and short-term effect of irreversible electroporation ablation of hepatic neoplasms / 中华放射学杂志

Objective To explore the safety and short?term efficacy of irreversible electroporation (IRE)ablation which is a novel ablation technology in unresectable hepatic neoplasms. Methods Patients with pathologically diagnosed as liver cancer or liver metastases were prospectively enrolled. The patients were not suitable for surgery with PS score ≤ 2. Exclusion criteria included who was not tolerate general anesthesia, severe liver and kidney dysfunction, and with cardiac pacemaker. A total of 16 patients were included in this study. There was 12 males and 4 females, aged 40 to 86 years with mean age (60 ± 10)y. Ultrasound and CT guided percutaneous IRE ablation was performed. Perioperative hemodynamic changes were reviewed. Liver and kindey function before and 7 d after ablation was compare by t test. The adverse reactions within 30 d after ablation treatment were recorded. CT and MR scans within 1 month were performed and the 30 d curative effect was evaluated by the modified RECIST criteria. Results All patients received IRE treatment successfully, and some patients experienced adverse reactions within 30 days after ablation, including abdominal pain in 7 cases, peritoneal effusion in 5 cases, hydrothorax in 4 cases, fever in 3 cases, cough, nausea and vomiting in 2 cases, biliary tract infection and thrombocytopenia in 1 case. After symptomatic treatment, these symptoms were improved. Severe complications, such as massive haemorrhage and bile leakage didn't occur. At 30 days after ablation, the curative effects were evaluated. Complete response (CR) was achieved in 1 patient , partial response (PR) was achieved in 12 patients, stable disease (SD) was in 2 patients , and progressive disease(PD) was 1 patients . The tumor relief rate (complete response+partial response) was 81.3%. Conclusions IRE ablation in the treatment of unresectable hepatic malignant tumor could have many advantages, including high safety, mild adverse reactions, and short?term efficacy. However, its long?term effect still need further observation.

Effect of Out-hospital Health Education on Quality of Life of Heart Failure Patients with Dilated Cardiomyopathy / 中国康复理论与实践

Objective To explore the effect of out-hospital health education on quality of life of heart failure patients with dilated cardio-myopathy. Methods 60 cases of heart failure patients with dilated cardiomyopathy were selected and divided into follow-up group and con-trol group with 30 cases in each group. The follow-up group accepted out-hospital health education, while the control group only accepted conventional in-hospital health education. Then World Health Organization Quality Of Life-Brief (WHOQOF-BRIEF) was used to evaluate their quality of life 6 months after discharge. Results The score of WHOQOF-BRIEF was higher in the follow-up group than in the control group (P<0.05). The satisfactory degree of nurse-patient relationship was better in the follow-up group than in the control group (P<0.05). Conclusion Out-hospital health education can improve the quality of life of heart failure patients with dilated cardiomyopathy.

A comparison of dual- and triple-freeze protocols for liver cryoablation in a Tibet pig / 中华肝胆外科杂志

Objective This study compares a dual-freeze protocol with a triple freeze protocol for hepatic cryoablation in the Tibetan pig model.Method Cryoablation with a dual-(10-5-10-5 min)and triple-freeze (5-5-5-5-10-5 min) protocol for the normal livers of 9 Tibet pigs was performed under exposed operation.Temperature changes of cryoprobes and diameter changes of iceballs were measured during the ablation,and seven days later the pathological changes of cryozones were reviewed and the surface and depth cryolesions were measured.Results Compared with cryoablation with two freeze-thaw cycles,there was a greater iceball diameter for cryoablation by three freeze-thaw cycles.Also,seven days after cryosurgery,there were similar surface and deep cryolesions in dual-and triple-freeze protocols.Pathologically,the triple freezing protocol was associated with a longer zone of complete necrosis.Conclusions With the same freezing time (20 min),the triple-freeze protocol may become a more powerful liver-ablation method in cryosurgical application.

Effects of UVB Irradiation and Calcium on the Expression of Pemphigus Antigens by Human Keratinocytes / 中华皮肤科杂志

Objective To investigate the effects of UVB irradiation and calciu m at different concentrations on the expression of pemphigus antigens by culture d human keratinocytes. Methods Human keratinocyte cultures were treated with eit her 2 mmol/L calcium added to the serum free media, or exposure to UVB irradiat ion. Immunofluorescence staining was performed with sera from patients with pemp higus vulgaris (PV) or pemphigus foliaceus (PF) as the first antigen. Extracts f rom both epidermis and keratinocytes were run on SDS-PAGE according to Laemmli ′s method and transferred to nitrocellulose membrane for immunoblot with PV and PF sera. Results Specific staining with PV sera was always detectable on kerati nocyte culture by immunofluorescence assay with or without high concentrations o f calcium while PF antigen was detected on stratified cells only. However, expos ure to UVB irradiation could not evoke keratinocyte culture express PF antigen. The reactivities were found at 160 kd band with PF sera while at both 160 kd and 130 kd bands with PV sera. Conclusions Monolayer or stratified keratinocytes ca n produce PV antigen, by increasing the concentration of calcium in the culture media, the human cultured kera tinocytes can be induced to stratify and express PFA. Human keratinocytes can not express PF antigen after exposure to UVB in intro.

Effects of angiotensin II and losartan on collagen synthesis in rat hepatic stellate cells / 中国病理生理杂志

AIM: To investigate the effects of angiotensin II (Ang II) and AT_(1a) receptor antagonist (losartan) collagen synthesis in rat hepatic stellate cells (HSCs). METHODS: ① Rat HSCs were isolated, cultured and identified. ② Rat HSCs were incubated in the medium with different concentrations of AngII or losartan, then the quantity of collagen was examined by [~3H]-proline release assay. RESULTS: ① The yield of HSCs was 2?10~7-(3?10~7/per) rat, their viability and purity was more than 95% and 90%, respectively. ② The yield of collagen in HSCs significantly got a rise in a concentration-dependent manner when HSCs were incubated with AngII (10~(-6)mol/L-10~(-10) mol/L) (P

Action of Staphylococcal Exfoliative Toxin A on Pemphigus Antigens Expressed on Human Keratinocytes / 中华皮肤科杂志

Objective To study the action and mechanism of staphylococcal exfoliative toxin A(E-TA)on pemphigus foliaceus antigen(PFA)and pemphigus vulgaris antigen(PVA)expressed on cultured human keratinocytes.Methods Stratified human keratinocytes were incubated with ETA and then stained with sera from patients with pemphigus foliaceus or pemphigus vulgaris as the first antibodies and FITC-la-beled sheep anti-human IgG as the second antibody.Total protein was harvested from the cells pretreated with ETA and run on SDS-PAGE for Western blot with the same antibodies.Simultaneously,supernatants of the keratinocytes before and after ETA treatment were collected for detection of the levels of IL-1?,IL-6with ELISA kits.The caseinolytic activities of the supernatants were tested by spectrometry in which casein was used as a non-specific substrate.Results Down-expression of PFA was shown after ETA treatment while no change of PVA expression was found.The high intensity and continuous linear appearance of fluo-rescent staining before ETA treatment became weak and discontinuous after ETA treatment,which were re-covered gradually in24hours.The degradation of proteins recognized by PF sera after ETV treatment was revealed by Western blot.The decreasing tendency of IL-1?concentration was found in the supernatants of cell culture after ETA treatment,but IL-6level was too low to be detected.Increased caseinolytic activities were found in the supernatants,and declined36hours after ETA treatment.Conclusions ETA acts on PFA expressed on keratinocytes in vitro,which is reversible along with withdrawal of ETA.The mechanism of E-TA act on PFA may be related to proteolytic action instead of promoting cytokine secretion.