甲磺酸伊马替尼治疗手术后复发和/或转移的胃肠道间质瘤的疗效分析

目的:评价甲磺酸伊马替尼治疗无法手术完全切除、术后复发和(或)转移性胃肠间质瘤(GIST)的临床疗效及不良反应。方法:2004年8月～2007年2月间经术后病理证实为GIST,术中无法完全切除病灶或术后复发、转移,失去手术机会,给予甲磺酸伊马替尼治疗400～600mg/d口服的患者21例。结果:21例全部随访,完全缓解(CR)者2例(9.5%),部分缓解(PR)者11例(52.4%),病情稳定(SD)者5例(23.8%),病情进展(PD)3例(14.3%),其中死亡2例(9.5%)。患者获益(CR+PR+SD)率(85.7%),1年、2年生存率分别为100%、83.3%。结论:甲磺酸伊马替尼治疗GIST疗效肯定,不良反应轻,毒性可耐受。     

甲磺酸罗哌卡因复合盐酸奈福泮用于剖宫产术后硬膜外自控镇痛的临床研究

目的 比较剖宫产术后两种硬膜外自控镇痛效果及恶心呕吐、嗜睡、尿潴留发生率.方法 60例剖宫产患者随机分成两组,每组各30例,术毕分别接硬膜外自控镇痛泵.I组:0.15%盐酸布比卡因加曲马多;Ⅱ组:0.179%甲磺酸罗哌卡因加盐酸奈福泮,观察并记录术后48 h内各时点的视觉模拟评分(VAS)和对应时点下肢运动阻滞程度(Bromage评分)及术后恶心呕吐、嗜睡、尿潴留等不良反应发生率.结果 两组术后6、12、24、36 h VAS比较差异无统计学意义(P>0.05);Bro-Inage评分Ⅰ组各时点分别为(2.75±0.49)分、(1.51±0.42)分、(0.92±1.08)分、(0.89±0.12)分,Ⅱ组分别为(1.31±0.57)分、(0.35±0.31)分、(0.08±0.30)分、(0.06±0.28)分,两组比较差异有统计学意作者单位:252601 山东临清,聊城市第二人民医院麻醉科义(P<0.05);恶心呕吐、嗜睡、尿潴留发生率Ⅰ组分别为16.7%、13.3%、50.0%,Ⅱ组分别为6.7%、3.3%、10.0%,两组比较差异有统计学意义(P<0.01).结论 甲磺酸罗哌卡因复合盐酸奈福泮行硬膜外自控镇痛效果确切,在运动功能恢复,降低恶心呕吐、嗜睡、尿潴留发生率方面显示明显优越性.     

Priapism induced by intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate

This is a case of priapism (21 h) following an intracavernosal injection of vasoactive intestinal polypeptide (VIP) 25 mcg with phentolamine mesylate (PM) 1 mg responding to venesection and intracavernosal injection of 1 mg metaraminol.     

Cytogenetic remission with imatinib therapy in hypereosinophilic syndrome with trisomy 8 and resolution of severe cardiac dysfunction

We report a 50-year-old patient with idiopathic hypereosinophilic syndrome with trisomy 8 who experienced a complete and durable hematological and cytogenetic remission with low-dose imatinib therapy. He also had a significant reversal of cardiac dysfunction with a reduction in cardiac hypertrophy, resolution of pericardial effusion and mitral and tricuspid regurgitation. He remained in remission 3 years after therapy.     

Lack of clinical efficacy of imatinib in metastatic melanoma

This two-centre phase-II trial aimed at investigating the efficacy of imatinib in metastasised melanoma patients in correlation to the tumour expression profile of the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R). The primary study end point was objective response according to RECIST, secondary end points were safety, overall and progression-free survival. In all, 18 patients with treatment-refractory advanced melanoma received imatinib 800 mg day(-1). In 16 evaluable patients no objective responses could be observed. The median overall survival was 3.9 months, the median time to progression was 1.9 months. Tumour biopsy specimens were obtained from 12 patients prior to imatinib therapy and analysed for c-kit, PDGF-Ralpha and -Rbeta expression by immunohistochemistry. In four cases, cell lines established from these tumour specimens were tested for the antiproliferative effects of imatinib and for functional mutations of genes encoding the imatinib target molecules. The tumour specimens stained positive for CD117/c-kit in nine out of 12 cases (75%), for PDGF-Ralpha in seven out of 12 cases (58%) and for PDGF-Rbeta in eight out of 12 cases (67%). The melanoma cell lines showed a heterogenous expression of the imatinib target molecules without functional mutations in the corresponding amino-acid sequences. In vitro imatinib treatment of the cell lines showed no antiproliferative effect. In conclusion, this study did not reveal an efficacy of imatinib in advanced metastatic melanoma, regardless of the expression pattern of the imatinib target molecules c-kit and PDGF-R.     

Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate

BACKGROUND: There is a lack of effective treatment for metastatic adenoid cystic carcinoma (ACC), a usually indolent tumor. We studied the efficacy of imatinib mesylate, a potent inhibitor of KIT tyrosine kinase, in patients with KIT-positive metastatic ACC. METHOD: Five patients with lung metastasis were treated in a pilot study with imatinib 400 mg by mouth twice a day. Mutations of c-kit and platelet-derived growth factor receptor (PDGFR)-alpha in tumors from these patients were analyzed. RESULTS: Disease progression was noted in three of five patients during the short treatment periods, ranging from 2 to 3 weeks. Three patients died of disease within 6 months. No detectable mutations were found in c-kit and PDGFR-alpha. CONCLUSION: We observed an unexpected high progression rate of metastatic ACC within short periods during imatinib treatment. Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution.     

Concurrent male gynecomastia and testicular hydrocele after imatinib mesylate treatment of a gastrointestinal stromal tumor

We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and noncommunicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST.     

Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans

To document the clinical activity of imatinib mesyalte in a child with a dermatofibrosarcoma protuberans (DFSP). An 18-month-old girl presented with a large extremity DFSP. As surgical resection would have caused unacceptable functional defects, imatinib mesylate was administered to induce tumor reduction and or stabilization. After 23 weeks of therapy, magnetic resonance imaging (MRI) of the tumor showed a reduction in the subcutaneous thickness in the transverse plane. The drug was tolerated well without any adverse reactions. Imatinib mesylate offers a non-surgical alternative for the treatment of large DFSP in children.     

Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. The presence of mutations in the superoxide dismutase gene (SOD1) has led to theories regarding a role for oxidative stress in the pathogenesis of this disease. A primary cause of oxidative stress is perturbations in cellular iron homeostasis. Cellular iron mismanagement and oxidative stress are associated with a number of neurodegenerative diseases. One mechanism by which cells fail to properly regulate their iron status is through a mutation in the Hfe gene. Mutations in the Hfe gene are associated with the iron overload disease, hemochromatosis. In the current study, 31% of patients with sporadic ALS carried a mutation in the Hfe gene, compared to only 14% of patients without identifiable neuromuscular disease, or with neuromuscular diseases other than ALS (p<0.005). To determine the cellular consequences of carrying an Hfe mutation, a human neuronal cell line was transfected with genes carrying the Hfe mutation. The presence of the Hfe mutation disrupted expression of tubulin and actin at the protein levels potentially consistent with the disruption of axonal transport seen in ALS and was also associated with a decrease in CuZnSOD1 expression. These data provide compelling evidence for a role for the Hfe mutation in etiopathogenesis of ALS and warrant further investigation.