DAG方案治疗老年人低增生性急性髓系白血病18例

 目的　观察低标准剂量DAG方案治疗老年人低增生性急性髓系白血病（AML）的疗效。方法　柔红霉素（DNR）40 mg／d，静脉注射，第1天至第3天；阿糖胞苷（Ara-C）100 mg／次，1次／12 h，静脉滴注，第1天至第7天；粒细胞集落刺激因子（G-CSF）150 μg／d，皮下注射，第1天至第7天，休息14 d，重复化疗，2个疗程后评价疗效。结果　完全缓解（CR）9例（50.0 %），部分缓解（PR）5例（27.7 %），总有效率77.7 %。结论　DAG方案治疗老年人低增生AML疗效显著，值得临床推广应用。     

妊娠合并急性早幼粒细胞白血病成功足月分娩一例

患者女，27岁，平时月经规律，末次月经2009年12月30日，预产期2010年9月27日。患者孕早期证实妊娠后于外院定期产前检查，孕16周始出现刷牙时牙龈出血，未予重视，以后反复牙龈出血，     

Lack of toxicity in a patient with germline TP53 mutation treated with radiotherapy

Li–Fraumeni syndrome is an autosomal dominant disorder characterized by germline TP53 mutation and increased susceptibility to cancer. Despite certain in vitro findings and a theoretical rationale for patients with TP53 mutation to be more radiosensitive and more prone to developing radiotherapy (rt)–induced secondary malignancies, corresponding clinical data remain elusive. Here, we report the case of a woman with TP53 mutation who was treated with adjuvant pelvic rt for stage ib uterine leiomyosarcoma in 2000, with radioactive iodine for papillary thyroid cancer in 2001, and with palliative rt to the humerus in 2010 for metastatic uterine leiomyosarcoma. She has not developed any acute or late rt-related toxicity, nor any secondary malignancies, since her first rt treatment. The literature review describes the potential risks and benefits of using irradiation in patients with TP53 mutation.     

A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours

This dose escalation study was designed to determine the recommended dose of the multi-targeted cell cycle inhibitor indisulam in combination with capecitabine in patients with solid tumours and to evaluate the pharmacokinetics of the combination. Thirty-five patients were treated with indisulam on day 1 of each 21-day cycle. Capecitabine was administered two times daily (BID) on days 1-14. Plasma concentrations of indisulam, capecitabine and its three metabolites were determined for pharmacokinetic analysis. The main dose-limiting toxicity was myelosuppression. Hand/foot syndrome and stomatitis were the major non-haematological toxicities. The recommended dose was initially established at indisulam 700 mg m(-2) and capecitabine 1250 mg m(-2) BID. However, during cycle 2 the recommended dose was poorly tolerated in three patients. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID proved to be safe at cycle 1 and 2 in nine additional patients. Indisulam pharmacokinetics during cycle 1 were consistent with pharmacokinetic data from phase I mono-therapy studies. However, exposure to indisulam was remarkably increased at cycle 2 due to a drug-drug interaction between capecitabine and indisulam. Partial response was confirmed in two patients, one with colon carcinoma and the other with pancreatic carcinoma. Seventeen patients had stable disease. Indisulam (700 mg m(-2)) in combination with capecitabine (1250 mg m(-2) BID) was well tolerated during the first cycle. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID was considered safe in multiple treatment cycles. The higher incidence of toxicities observed during cycle 2 can be explained by a time-dependent pharmacokinetic drug-drug interaction.     

放化疗联合脑转移瘤放疗治疗非小细胞肺癌脑转移的临床疗效分析

目的 分析化疗同期胸部三维放疗联合脑转移瘤放疗治疗非小细胞肺癌（non-small cell lung cancer,NSCLC）单纯脑转移的疗效及影响预后的因素。方法 回顾性分析52例单纯脑转移且脑转移瘤及原发肿瘤均接受放疗的NSCLC患者的临床资料,Kaplan-Meier法计算生存率并行log-rank 检验,Cox回归模型行多因素预后分析。结果 全组患者中位随访时间为13.5个月（4～49个月）,中位生存期为13.0个月（95% CI：11.2～14.8）,1年、2年、3年生存率分别为53.8%、13.5%和3.8%。胸部原发肿瘤体积＜118 cm³组和≥118 cm³组的中位生存期分别为14.0个月（95% CI：11.6～16.4）和12.0个月（95%  CI：10.7～13.3）,1年生存率分别为66.7%和42.9%,2年生存率分别为20.8%和0,3年生存率分别为8.3%和0,两组总生存率比较差异有统计学意义（χ²=5.648,P=0.017）。胸部原发肿瘤放疗剂量（dose to PTV,DTPTV）≥66 Gy组和DTPTV＜66 Gy组的中位生存期分别为13.0个月（95%  CI：10.8～15.2）和14.0个月（95%  CI：10.8～17.2）,两组比较差异无统计学意义（χ²=0.064,P=0.80）。多因素预后分析显示,原发肿瘤体积是影响总生存率的独立预后因素。结论 化疗同期胸部三维放疗联合脑转移瘤放疗治疗NSCLC单纯脑转移取得较好疗效,原发肿瘤体积较小的患者生存获益更大。     

青黄散治疗86例慢性粒细胞白血病临床观察

 目的　进一步验证青黄散治疗慢性粒细胞白血病（CML）的临床疗效。方法　用单纯中药青黄散治疗CML 86例,部分患者（28例）配合汤药（活血化瘀）。结果　86例患者中,完全缓解62例（72.1 %）,部分缓解14例（16.3 %）,进步8例（9.3 %）,无效2例（2.3 %）,总有效率97.7 %。该组病例服药1周自觉症状改善。肝大者44例,用药后39例较治疗前缩小或缩至正常;脾大者70例,治疗后69例较治疗前缩小,其中60例脾大完全消失,仅1例治疗前后无改变。脾开始缩小时间平均15.5 d,缩至最小平均62.9 d。白细胞数治疗后平均10.4 d开始下降,降至正常范围平均54.8 d。主要不良反应为消化道症状,其次是皮肤色素沉着、皮肤过度角化,从小剂量开始一般可以避免。结论　青黄散可诱导CML缓解,并可改善临床症状,消除白血病细胞的浸润,对血红蛋白及血小板无显著影响。     

Cyclooxygenase inhibitors use is associated with reduced risk of esophageal adenocarcinoma in patients with Barrett's esophagus: a meta-analysis

Background:

Esophageal adenocarcinoma (EAC) has high mortality and is increasing in incidence. Barrett''s esophagus (BE) increases the risk for EAC. Studies have reported inconsistent findings on the association between use of cyclooxygenase (COX) inhibitors and the risk of neoplastic progression in BE patients. Therefore, we performed a meta-analysis to investigate this association.

Methods:

A meta-analysis was undertaken among a total of 9 observational studies using fixed- and random-effects models, comprising 5446 participants; 605 had EAC or high-grade dysplasia (HGD).

Results:

Overall, COX inhibitors use was associated with a reduced risk of EAC/HGD among BE patients (relative risk (RR)=0.64, 95% confidence interval (CI)=0.53–0.77). Aspirin use also reduced the risk of EAC/HGD (RR=0.63, 95% CI=0.43–0.94), as well as non-aspirin COX inhibitors (RR=0.50, 95% CI=0.32–0.78). The chemopreventive effect seemed to be independent of duration response.

Conclusions:

Cyclooxygenase inhibitors use is associated with a reduced risk of developing EAC in patients with BE. Both low-dose aspirin and non-aspirin COX inhibitors are associated with a reduced risk of neoplasia. More well-designed randomised controlled trials are needed to increase our understanding of the chemopreventive effect of COX inhibitors.     

Paraneoplastic syndromes associated with lung cancer

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.     

Efficacy of therapy for hepatocellular carcinoma with portal vein tumor thrombus: chemoembolization and stent combined with iodine-125 seed

The purpose of this study is to analyze the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein stent and 125I implantation for the treatment of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma. Fifty-six patients from our department diagnosed with advanced hepatocellular carcinoma with PVTT between January 2008 and December 30, 2010 were divided into two groups. Patients in Group A were treated with TACE and portal vein stent; patients in Group B were treated with TACE, portal vein stent and 125I implantation. The success rate of TACE with portal vein stent and 125I implantation was 100%, with no severe surgery-related complications. After an 8 mo follow-up, the total clinical benefit rates were 56.7 and 88.5% for Groups A and B, respectively (p < 0.05). The median survival times (mOS) for the two groups were 5.7 and 8.9 mo, respectively (p < 0.05). The median time of progression (mTTP) of the two groups were 5.3 and 7.9 mo, respectively (p < 0.05). The 2, 6, 8, 12 and 18 mo patency rates in Group A were 100, 93.3, 83.3, 53.3 and 36.6%. Those in Group B were 100, 100, 92.3, 84.6 and 80.7%. The 2, 6 and 8 mo patency rates showed no statistical differences (p > 0.05), but the 12 and 18 mo rates did (p < 0.05). Our results suggest that TACE combined with portal vein stent and 125I implantation are both safe and effective, and 125I implantation can further postpone the restenosis of the portal vein effectively.     

Long-term results of screening with magnetic resonance imaging in women with BRCA mutations

Background:

The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study.

Methods:

From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography.

Results:

In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28 previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three patients died of other causes. None of the 24 survivors has had a distant recurrence at a median follow-up of 8.4 years since diagnosis.

Conclusion:

Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will detect the majority of breast cancers at a very early stage. The absence of distant recurrences of incident cancers to date is encouraging. However, longer follow-up is needed to confirm the safety of breast surveillance.     

Gallbladder carcinoma in a pregnant patient with Crohn's disease complicated with gallbladder involvement

Primary gallbladder (GB) carcinoma and Crohn’s disease (CD) of the GB are individually rare. We present a case of a pregnant woman with CD found to have GB involvement and primary GB carcinoma. A 34-year-old female at 6 wk gestation with a 21 year history of CD of uncertain extent presented with 3 mo of diarrhea, urgency and abdominal pain. During work-up, she was found to have elevated transaminases and an abnormal alkaline phosphatase. Imaging revealed two gallbladder polyps both greater than 1 cm in size. Resection and histological evaluation was consistent with Crohn’s involvement of the GB, poorly differentiated adenocarcinoma of the GB with invasion through the muscularis propria and matted lymph nodes in the porta hepatis positive for metastatic carcinoma (stage pT2N1). Six cases of CD involving the GB, two cases of primary GB carcinoma in CD, and ten cases of cholangiocarcinoma in pregnancy have been published. This is the only case that describes all three factors. Common features in CD of the GB include acute cholecystitis, ileal involvement, and presence independent of active intestinal disease. Common features in CD patients with GB malignancy include younger age of detection, a long history of CD, extensive colonic and ileal involvement of disease, the absence of cholelithiasis, and pre-existing gallbladder disease (primary sclerosing cholangitis and gallbladder polyps). Pregnancy is specific to this case. The role of CD in the development of GB malignancy is not well understood nor is the contribution of pregnancy to the spread of disease. Chronic inflammation and immunosuppression compounded by hormonal influence is implicated.