Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer

AIM To study tumor response, and tolerability of arterially directed embolic therapy(ADET) with polyethylene glycol embolics loaded with irinotecan for the treatment of colorectal cancer liver metastases(CRC-LM). Secondary objectives were to monitor quality of life, time to progression and survival of patients.METHODS Patients were included in the study if they were affected by CRC-LM, refractory to systemic chemotherapy, treated with ADET using polyethylene glycol embolics, and had liver involvement < 50%. Tumor response, performance status(PS), tumor marker antigens, and quality of life(QoL) were monitored at 1, 3 and 6 mo after ADET. QoL was assessed with the Palliative Performance Scale(PPS).RESULTS We treated 50 consecutive CRC-LM patients with ADET using polyethylene glycol embolics. Their tumor response one month after ADET was: 28% of complete response(CR), 48% of partial response(PR), 8% stable disease(SD), and 16% of progression. Tumor response 3 mo after ADET was CR 24%, PR 38%, SD 19% and progression disease(PD) 19%. Tumor response 6 mo after ADET was CR 18%, PR 44%, SD 21% and PD 18%. QoL was 90% PPS at each time point. Median time to progression for patients who progressed was 2.5 mo(range 0.8-6). Median follow-up was 14 mo(0.8-25 range). ADETs were performed with no complications. Observed side effects(mild or moderate intensity) were: Pain in 32% of patients, increase of transaminase levels in 20% and fever in 14%, whereas 30% of patients did not complain any adverse event. CONCLUSION The treatment of unresectable CRC-LM with ADET using polyethylene glycol microspheres loaded with irinotecan was effective in tumor response and resulted in mild toxicity, and good QoL.

PREPARATION AND DRUG RELEASE CHARACTERISTICS OF PINGYANGMYCIN GELATIN MICROSPHERES FOR EMBOLIZATION THERAPY

Objective: To prepare Pingyangmycin gelatin microspheres (PYM-GMS) for carotid artery embolization therapy and to study the release characteristics in vivo and in vitro. Methods: PYM-GMS was prepared by optical double-phase emulsified condensation polymerization. Through UV-spectrophotometer drug content and encapsulation rate were measured. The characteristics of drug release in vitro which could simulate the actual state in vivo were tested by HPLC. Three ways of vein drop, artery perfusion and artery embolization were contrasted. Under the supervision of X-ray, PYM-GMS were perfused into the external carotid artery of rabbits by superselective artery embolization. Blood samples were tested at different time and analyzed statistically. Results: The roundness of PYM-GMS was 1.02?.005. The mean diameter was 85.6 mm, 78% of them ranging from 50-200 mm, which fitted the use of embolization. PYM content and encapsulation rate were 6.8% and 91.3% respectively. 70% of the drug was released in 3 h in the simulated environment in vivo and total drug was released after more than 6 h. After artery embolization with small dosage of PYM-GMS, the local drug concentration was 8 times higher than the blood drug concentration and the high level of local drug concentration was kept for more than 120 min. Conclusion: External carotid artery embolization with PYM-GMS, which significantly reduced the circulating drug level and employment dosage, could prolong the duration higher drug concentration and suit the purpose of targeted tumor therapy.

Efficacy and Safety of Transdermal Fentanyl(TDF)in Treatment of Pain Caused by Interventional Embolization Therapy

Objective： Interventional embolization therapy is well accepted in cancer treatment, but patient may suffer from a moderate-to-severe pain after therapy and its quality of life （QoL） is influenced, this study is to observe the efficacy and safety of transdermal fentanyl （TDF） in the management of pain caused by interventional embolization therapy. Methods： Morphine 10mg and TDF 25μg/h were immediately used in 52 patients who had moderate-to-severe pain complicated by interventional embolization therapy, the pain intensity was evaluated by visual analogue scale （VAS）. If VAS≥4 at t2 h after treatment, the dosage of TDF added into 50 μg/h. At 0h, 12h, 24h, 72h, 1 week, 2 weeks after TD, the vas and adverse events were observed respectively. Result： There was an obvious decrease in VAS at 12h after TDF treatment in the patients of which only 9 patients used 50ug/h dosage after partial splenic embolization （PSE） therapy. Most patients got satisfactory pain relief both the TDF 25 μg/h and TDF 50 μg/h group （VAS 0-1）. The adverse events were nausea, vomiting and dizzy, especially in the TDF 50 μg/h group. No respiratory depression was observed and only one patient got retention of urine. Conclusion： TDF was effective and safe in the treatment of moderate-to-severe pain after interventional embolizafion therapy.

Histopathological study of hepatocellular carcinoma after transcatheter hepatic arterial embolization

AIMS To study the histopathological changes in hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS Histopathological analysis was made in 39 cases of liver neoplasms after TAE and 11 cases of liver neoplasms after digital selective angiography (DSA), including pathological type, histological grade, necrotic degree, capsule, times of treatment, injured vessel and lymphocyte infiltration. RESULTS Six cases with 100% necrosis, 14 cases with 30% 95% necrosis, 19 cases with 0% 5% necrosis after TAE and 11 cases without necrosis after DSA were found histologically. The necrosis was related to the pathological type, capsule, injured vessels, but not to the histological grade, time of treatment and lymphocyte infiltration of the liver neoplasms. CONCLUSIONS TAE is an effective therapy for the late stage HCC. The encapsulated HCC is a preferable indicator for TAE.

A STUDY OF INTRAOPERATIVE TREATMENT MODALITIES FOR NONRESECTABLE PRIMARY LIVER CANCER:A FOLLOW-UP OF 200 CASES

This paper reports the results of intraoperativetreatments with (different modality in 200 patients withnonresectable primary liver carcinoma (PLC) from April1964 to July 1993 in our hospital. PLC was verifiedhistologically in all cases. They were divided into 2 groupsaccording to the methods of treatment. In group 1, 115cases received anticancer agents by hepatic arteryinfusion (HAl). The 1- and 2-year survival rates were10.40/o and 1.7o/o, respectively and only one patientsurvived for 65 months. In group Ⅱ, 85 cases receivedmultimodality treatments (MMT) with variouscombination of hepatic artery chemoembolization(HACE), hepatic artery ligation (HAL), microwavecoagulation of tumor (MWC) and ethanol injection intotumor (EIT). The 1-, 2-, 3- and 5- survival rates were34.1o/o, 21.2o/o, 12-o/o and 6.7o/o, respectively. 5 casessurvived for 41 to 63 months. The tumor was resected atsecond stage in 6 cases after MMT. The results suggestthat MMT is an effective approacb to improve the long-term survival of patients with nonresectable PLC.

Predictors of long-term clinical outcome of patients with acute massive pulmonary embolism after thrombolytic therapy

To assess the in-hospital clinical course and the long-term evolution of acute massive pulmonary embolism after thrombolytic therapy and to identify predictors of adverse clinical outcome Methods A total of 260 patients hospitalized from January 1989 to October 1998 were retrospectively reviewed and followed up for 3 9 to 8 4 years Baseline characteristics and variables pre- and post-thrombolysis were identified Particular attention was paid to the clinical events, including death, recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, and major bleeding attributable to the use of anticoagulants Kaplan-Meier event-free survival curves were generated Univariate analysis by means of the log-rank test was used to test each candidate variable for association with clinical outcome Multivariate analysis with the Cox proportional hazard model was used to determine independent predictors of the long-term outcome Results The in-hospital mortality rate was 8 5%, with 68 2% due to pulmonary embolism itself, and the follow-up mortality rate was 31 7%, with 29 2% due to recurrent embolism Factors associated with an adverse outcome in univariate analysis were: (1) prior thromboembolic diseases; (2) duration of anticoagulant therapy <6 months; (3) inferior vena caval filter placement; (4) acute right ventricular dysfunction/dilation detected echocardiographically after thrombolysis; (5) Doppler recording of pulmonary artery systolic pressure >50 mmHg after thrombolysis; and (6) greater than 30% obstruction of pulmonary vasculature identified by pulmonary ventilation/perfusion scintigraphy before hospital discharge Multivariate analysis identified three independent predictors of poor long-term outcome for patients with acute massive pulmonary embolism after thrombolysis; which were: (1) Doppler recording of pulmonary artery systolic pressure >50 mm Hg, with relative risk of 3 78 and a 95% confidence interval of 2 70 to 4 86; (2) echocardiographic evidence of right ventricular dysfunction/dilatation (relative risk: 2 18; 95% confidence interval: 1 48 to 2 88); and (3) greater than 30% obstruction of pulmonary vasculature documented by lung scan (relative risk: 1 99; 95% confidence interval: 1 25 to 2 70) Conclusion The study showed that Doppler echocardiographic assessments after thrombolytic therapy and ventilation/perfusion scintigraphy prior to hospital discharge are valuable to establishment of new baseline characteristics, which is informative for risk stratification and prognostication of the long-term outcome for patients with acute massive pulmonary embolism

Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma

Background The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma.Methods Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was asessed using Student’s t test, the Chi-squre test and the log-rank test. Results In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43%(30/42) (χ2=10.06, P<0.005), and 9 (21.43%) of the 42 patients showed no gross residual disease after surgery. Blood loss and operative time were significantly decreased in the study group as compared with those in the control group (665.24±37.61 ml: 849.31±41.20 ml, t_1=33.21, P_1<0.001; 4.23±0.21 hours: 6.15±0.38 hours, t_2=28.92, P_2<0.01). In the study group,the mean survival time and the median overall survival were 33.66 months (95% CI, 24.73 to 42.58) and 26.00 months (95% CI, 19.22 to 32.78), respectively. The median disease-free interval was 18.20 months. In the control group, the mean survival time and the median overall survival were 32.38 months (95% CI, 24.92 to 39.84) and 25.00 months (95% CI, 22.80 to 27.20), respectively. The median disease-free interval was 14.20 months.The overall survival rates were not significantly different between the two groups (χ2=6.48,P>0.05).Conclusions Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can’t be improved significantly.

Safety and efficacy of stent placement for treatment of intracranial aneurysms： a systematic review

Objective To evaluate the safety and efficacy of stent placement for the treatment of complex intracranial aneurysms. Data sources We searched six databases, including Pubmed, Embase, SCI-expanded, the Cochrane Library, ISI Proceedings and ProQuest Dissertations ＆ Theses for the relevant studies using multiple key words from December, 1997 to February, 2009. Study selection Thirty-three studies about stent placement for intracranial aneurysms were identified, which reported data from a total of 1069 patients with 1121 intracranial aneurysms. Data extraction We prepared a standardized data extraction form （DEF）, which was used by two independent researchers to extract data from the included 33 studies. Results The overall initial complete occlusion rate was 52.5% （456/869, 95% CI： 49.2%-55.8%）. The overall complication rate was 14.3% （162/1130, 95% CI： 12.3%-16.4%）, of which 3.6% （38/1044, 95% CI： 2.5%-4.8%） were permanent. Clinical follow-up showed a dependence rate of 8.4% （39/465, 95% CI： 5.9%-10.9%）. Angiographic follow-up showed an improvement rate of 24.3% （117/481, 95% CI： 20.5%-28.2%） and a recurrence rate of 12.9% （62/481, 95% CI： 9.9%-15.9%）. Chi-squared tests were performed to compare the following subgroups： self-expandable vs. balloon-expandable stents, unruptured vs. acutely ruptured aneurysms, and with vs. without pre-medication. Statistical significance was reached in eight tests. Conclusions Intracranial stent is a safe and effective tool for embolizing complex intracranial aneurysms. Self-expandable stents are significantly easier and safer than balloon-expandable stents with respect to navigation and deployment through the tortuous cerebral vasculature. Patients with acutely ruptured aneurysms are more likely to be dependent, but not more likelv to suffer more orocedure-related comolications.

Therapeutic efficacy of transcatheter arterial embolization of primary hepatocellular carcinoma: discrepancy in different histopathologic subtypes

Objective To evaluate preliminarily the therapeutic efficacy of transcatheter arterial embolization (TAE) for different histopathologic subtypes of primary hepatocellular carcinoma (HCC). Methods A retrospective study of 226 patients with histopathologically diagnosed primary HCC was performed. The patients were treated with either single TAE, surgical resection of tumor alone, or TAE combined with surgical resection. Follow up information was achieved in 157 of 226 patients. Comparative analyses of survival data and image findings were performed with correlation to histopathologic classification and different therapeutic methods,respectively. Results Eight histopathologic subtypes of primary HCC were found in this group, including HCC of trabecular pattern, pseudoglandular pattern, fibrolamellar HCC and sclerosing HCC, as well as HCC of clear cell, of small cell, poorly differentiated or undifferentiated HCC, and hormonally active HCC. The accumulated survival rate for these 157 patients was 74.52% of 1 year, 53.50% of 2 years, 31.85% and 14.01% of 3 and 5 years, respectively. Fibrolamellar HCC and clear cell HCC had relatively higher survival rate (25.00% and 33.22% of 5 years, respectively) than that of other subtypes, and the median survival time of the latter was 71 months. The mean survival time was 25.06 months (SE=1.87) in single TAE group, 30.38 (SE=2.05) months in surgical resection, and 72 months (SE=6.90) in TAE combined with resection. Conclusions Discrepancies do exist in therapeutic effect of different subtypes of HCC. In this study, clear cell HCC was more sensitive to TAE than other subtypes, and, in contrast, small cell HCC and poorly differentiated or undifferentiated HCC were of lower sensitivity to TAE.

Recurrent myocardial infarctions with normal coronary arteries in a patient with atrial flutter: A case report

Coronary embolism secondary to atrial fibrillation can lead to myocardial infarction independently of atherosclerotic coronary arteries. We encountered a patient repeatedly tortured by atrial fibrillation who presented with recurrent myocardial infarctions with normal coronary anatomy and ischemic stroke. We were frustrated by repeated failures because of some probably inappropriate decisions.