Clinical observation of apatinib mesylate in the treatment of metastatic renal carcinoma / 国际肿瘤学杂志

Objective:To assess the efficacy and safety of apatinib mesylate in the treatment of metastatic renal carcinoma.Methods:Between October 2018 and April 2020, 32 patients with metastatic renal carcinoma were enrolled in the Department of Oncology of Shiyan People′s Hospital of Hubei Province, Taihe Hospital and Sinopharm Dongfeng General Hospital. Apatinib mesylate was administered at an initial dose of 500 mg once daily. The main research end point was progression-free survival (PFS), secondary study destination included objective response rate (ORR), disease control rate (DCR) and safety. Multivariate analysis of PFS was carried out by Cox regression.Results:The median follow-up time was 6.5 months (from 2 to 10). All 32 patients could be evaluated for efficacy. Efficacy evaluation showed 0 cases of complete remission, 14 cases (43.75%) of partial remission, 10 cases (31.25%) of stable disease, 8 cases (25.00%) of progressive disease, the ORR was 43.75% (14/32), and DCR was 75.00% (24/32). The PFS of patients had no significant correlation with gender, age, pathological type and previous surgery (all P>0.05), but was significantly correlated with the site of metastasis ( HR=0.032, 95% CI: 0.003-0.411, P=0.008). The median PFS for all patients was 9.5 months (8.3-10.7 months), and there was a significant difference in the median PFS between patients with lung metastasis ( n=21) and those with other sites ( n=11) (9.5 months vs. 6.2 months, χ2=14.812, P<0.001). The main adverse reactions were hypertension (37.50%, 12/32), hand-foot syndrome (31.25%, 10/32), proteinuria (18.75%, 6/32), neutropenia (25.00%, 8/32), anemia (28.13%, 9/32), thrombocytopenia (18.75%, 6/32), nausea/vomiting (15.63%, 5/32) and elevated transaminase (15.63%, 5/32), most of which were grade 1 or 2. The incidence of grade 3 adverse reactions was 28.13% (9/32), without grade 4 adverse reactions. After dosage reduction and symptomatic treatment, the symptoms could be controlled. Conclusion:Apatinib mesylate can effectively prolong PFS in metastatic renal carcinoma patients with good safety, and can be used as a treatment option for metastatic renal carcinoma.

Effect and mechanism of Imatinib mesilate on intimal hyperplasia of rabbit carotid artery after ballon injury / 天津医药

Objective To investigate the effect and mechanism of Imatinib mesilate (Imatinib) on intimal hyperplasia of rabbit carotid arteries after balloon injury. Methods Thirty adult Newzealand rabbits were randomly divided into three groups:group A, B and C. Their right carotid arteries were injuried then administered with 0, 25 or 50 mg/kg of Imatinib dai?ly for 14 consecutive days when the rabbits were sacrificed. The carotid arteries were harvested and sectioned for HE-stain?ing and immunohistochemisty staining. Real-Time PCR was used to examine transcription levels of PDGF-B and PDGFR-βmRNA. The plasma level of PDGF-BB was assayed by ELISA. Results Arterial intimal hyperplasia and stenosis following balloon injury were seen in three groups. Thickness and area of neointima, ratio of thickness of intima to media, ratio of area of intima to media and mRNA level of PDGF-β are all higher in group A than those in group B than those in group C (P<0.01). By contrast, the mRNA transcription level of PDGFR-β increased significantly in group C than that in group A (1.236±0.356 vs 0.708±0.372;t=2.91;P<0.01). Plasma level of PDGF-BB increased in all three groups after balloon injury than that in the baseline (P<0.01). The transcription level of PDGF-BB is higher in group A than that in group B and in group C (ng/L:23.464±3.542, 19.504±2.454, 16.588±1.207, F=17.322, P<0.05). There was no difference between group B and C. There was positive correlation between mRNA transcription level of PDGF-B and plasma level of PDGF-BB ( r=0.806, P<0.01). Conclusion Vascular injury can cause intimal hyperplasia and increased PDGF-B mRNA transcription. Imatinib mesilate could inhibit the intimal hyperplasia through down regulating PDGF-B mRNA transcription.

Tumor estromal gastrointestinal: análise de 146 casos do centro de referência do Instituto Nacional do Câncer - INCA / Gastrointestinal stromal tumor: analysis of 146 cases of the center of reference of the National Cancer Institute - INCA

OBJETIVO: Avaliar os resultados do tratamento de GIST no INCA. MÉTODOS: Análise retrospectiva de todos os casos de GIST tratados no INCA no período de 1997 a 2009. RESULTADOS: Analisamos 146 pacientes, com média de idade de 44,5 anos e predomínio do sexo feminino. O principal sintoma foi dor abdominal. Tivemos ocorrência de segundo primário em 22 por cento dos casos e na imuno-histoquímica, 92 por cento foram positivos para CD117. A localização mais frequente foi estômago e predominou o grupo de alto risco. A cirurgia foi R0 (extenso) em 70 por cento e os principais sítios de metástases foram fígado e peritônio. A sobrevida global foi, respectivamente, em dois e cinco anos de 86 por cento e 59 por cento. Houve significante diferença entre a sobrevida global (p=0,29) do grupo de alto risco versus os demais. CONCLUSÃO: Os nossos pacientes apresentam-se principalmente sob forma de doença de alto risco com repercussão óbvia na sobrevida. O uso de Imatinib melhorou a sobrevida dos pacientes com doença metastática e recidivada. Devemos estudar seu uso no cenário de adjuvância e neoadjuvancia visando melhorar os índices do grupo de alto risco. A criação de centros referenciais é uma necessidade para o estudo de doenças pouco frequentes.

OBJECTIVE: To evaluate the treatment of GIST in INCA. METHODS: We conducted a retrospective analysis of all cases of GIST treated at INCA in the period from 1997 to 2009. RESULTS: We analyzed 146 patients with a mean age of 44.5 years and female predominance. The main symptom was abdominal pain. We observed the occurrence of a second primary tumor in 22 percent of cases and 92 percent of the immunohistochemistry exams were positive for CD117. The most frequent location was in the stomach and the high-risk group was predominant. Surgery was considered R0 (extensive) in 70 percent of the cases and the main sites of metastases were liver and peritoneum. Overall survival in two and five years was, respectively, 86 percent and 59 percent. There was a significant difference between overall survival (p = 0.29) of the high-risk group versus the other. CONCLUSION: Our patients presented mainly in the form of high-risk disease, with obvious impact on survival. The use of imatinib improved survival of patients with recurrent and metastatic disease. We should study its use in the setting of adjuvant and neoadjuvant therapy to improve results of the high risk group. The creation of reference centers is a need for the study of rare diseases.

Neurotoxic effects of intrathecal different concentrations of ethanesulfonic acid ropivacaine on spinal cord in rats / 中华麻醉学杂志

Objective To evaluate the neurotoxic effects of intrathecal (IT) different concentrations of ethanesulfonic acid ropivacaine on spinal cord in rats. Methods Sixty healthy Wistar rats of both sexes weighing 210-220 g in which IT catheters were successfully placed according to Yaksh et al. were randomly divided into 5 groups (n= 12 each). The animals received 0.9% NaCl solution 0.4 ml (group C); 0.224%, 0.447%,0.671%, 0.894% ethanesulfonic acid ropivacaine 0.4 ml (group R1-4 ). The onset time and duration of the block were recorded. The animals were killed on 7th day after IT administration. The L4,5 segment of the spinal cord were removed for neuropathologic examination with electron microscope. The spinal cord injury was scored.Neurotoxicity was defined as the spinal cord injury score ≥ 2 and the spinal neurotoxicity was recorded. Results Onset time was shorter and duration of the block was prolonged with increasing concentrations of ethanesulfonic acid ropivacaine. The incidence of the spinal neurotoxicity was 0, 0, 17%, 42% and 100% in group C, R1, R2, R3 and R4 respectively. The incidence of the spinal neurotoxicity was gradually increased with increasing concentrations of ethanesulfonic acid ropivacaine. Conclusion IT ethanesulfonic acid ropivacaine can produce neurotoxicity to the spinal cord and it depends on the concentration.

A comparison of ropivacaine mesylate and ropivacaine hydrochloride for patient-controlled epidural analgesia after transabdominal hysterectomy / 中华麻醉学杂志

Objective To compare the effect of ropivacaine mesylate with ropivacaine HC1 for patient-controlled epidural analgesia ( PCEA) after transabdominal hysterectomy. Methods Forty-four ASA 1 or D patients aged 18-65 yrs weighing 45-80 kg undergoing elective abdominal hysterectomy performed under epidural anesthesia with either 0.75% ropivacaine HO (control group, n = 22) or 0.894% ropivacaine mesylate (study group, n= 22) . An epidural catheter was placed at L2,3 and advanced 3 cm into the epidural space. After operation PCEA was performed with 0.2% ropivacaine HCl ( control group) or 0.237 % ropivacaine mesylate (study group) respectively. Postoperative pain was assessed using VAS (0-10, 0 = no pain, 10 = worst pain) . Motor blockade was assessed using the Bromage scoring system. The patients' satisfaction level and adverse events were also recorded. Results There were no significant differences in VAS scores, motor blockade and incidence of adverse events between the two groups. The number of effective pressing in study group was significantly less than that in control group. Starting from 4h after operation the drug consumption in study group was significantly less than that in control group. Conclusion 0.237 % ropivacaine mesylate can be used for PCEA after transabdominal hysterectomy as safely as 0.2% ropivacaine HCl.