甲氨蝶呤侧链合成新工艺

以对硝基苯甲酸为起始原料,改进了对甲胺基苯甲酰谷氨酸二钠的合成工艺,总收率由原工艺的12%提高到31%,降低了合成甲氨蝶呤的成本。     

Pulmonary alveolar microlithiasis in childhood: clinical and radiological follow-up

This report describes a case of pulmonary alveolar microlithiasis that was diagnosed in an 8.5-year-old girl by high-resolution computed tomography (CT) and open lung biopsy. Presence of symptoms (productive cough, fever), their periodic occurrence (lasting up to 1 week), and comparatively long asymptomatic periods should be emphasized. Despite extensive X-ray abnormalities, tests of pulmonary interstitium involvement and exercise tests revealed normal results. A therapeutic regimen, including disodium etidronate, was administered for 18 months with no significant clinical or radiological improvement.     

The Safety and Efficacy of Single‐Agent Pemetrexed in Platinum‐Resistant Advanced Urothelial Carcinoma: A Large Single‐Institution Experience

Background.

Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance.

Patients and Methods.

Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded.

Results.

One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%–9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival.

Conclusion.

This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.     

Retrospective efficacy and safety analyses of erlotinib,pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non-squamous non-small-cell lung cancer

ObjectiveSeveral guidelines recommend erlotinib, pemetrexed, or docetaxel for second-line chemotherapy in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The aim of this study was to retrospectively evaluate the efficacy of erlotinib, pemetrexed, and docetaxel in epidermal growth factor receptor (EGFR) mutation-negative patients with previously treated advanced non-squamous NSCLC.Materials and methodsWe analyzed the efficacy of these agents in patients with previously treated advanced non-squamous NSCLC who had EGFR wild-type tumors, performance status (PS) of 0, 1, or 2 and received erlotinib, pemetrexed, or docetaxel between December 2007 and September 2011. Variability among patient backgrounds was evaluated using propensity scores to assess comparability. The efficacy of these agents was evaluated in patient subgroups with low variability.ResultsThe propensity scores showed that the backgrounds of the groups that received second-line therapy with each agent had low variability and were adequate for comparison. Patients were divided into the PS0/1 and PS2 groups for analysis. The median progression-free survival (PFS) in patients treated with erlotinib was 2.8 months in the PS0/1 group, as compared with 1.0 month in the PS0/1/2 group and 0.90 months in the PS2 group. PFS in PS0/1 patients who received erlotinib was comparable to that in PS0/1 patients who received pemetrexed (2.5 months) or docetaxel (1.9 months). Overall survival (OS) in erlotinib-, pemetrexed-, and docetaxel-treated PS0/1 patients was 16.1, 7.4 and 10.0 months, respectively. The study had limited power to detect differences in PFS and OS because of the small sample size.ConclusionsErlotinib appears to be a useful second-line option in PS0/1 patients with EGFR mutation-negative advanced non-squamous NSCLC given its mild adverse effects. The results should be carefully interpreted because of the small sample size, limited power, and retrospective nature of the study.     

Hyperintense HCC on hepatobiliary phase images of gadoxetic acid-enhanced MRI: Correlation with clinical and pathological features

Purpose

To retrospectively determine whether the hyperintense hepatocellular carcinomas (HCCs) seen on the hepatobiliary phase of gadoxetic acid-enhanced MR imaging (EOB-MRI) might have different histologic characteristics from usual hypointense HCCs.

Materials and methods

Two hundred three surgically proven HCCs from 192 patients who underwent preoperative EOB-MRI were analyzed. The demographic and histologic characteristics of hyperintense HCCs were compared with usual hypointense HCCs by using the t-test or Fisher's exact test.

Results

By visual assessment, 18 (8.8%) tumors were classified as hyperintense HCCs. Patients with hyperintense HCC were significantly (p < 0.05) older (60.1 vs. 55.2 years) than those with hypointense HCCs. Hyperintense HCCs showed significantly lower rate of microvascular invasion (27.8% vs. 53.5%) and significantly higher rate of peliosis (61.1% vs. 30.8%). Hyperintense HCCs were more frequently expanding type, and none showed infiltrative type or scirrhous histologic pattern.

Conclusions

Hyperintense HCCs seem to have clinical and histologic features that might be related with more favorable outcomes.     

培美曲塞联合顺铂一线治疗晚期非小细胞肺癌临床研究

目的研究培美曲塞联合顺铂治疗晚期非小细胞肺癌的临床疗效及不良反应。方法 52例晚期非小细胞肺癌患者,给予培美曲塞联合顺铂方案全身化疗。培美曲塞:500mg/m2,第1天静脉滴注,顺铂:75mg/m2,第1天静脉滴注,每21天为1个周期,连用2～6个周期。结果 52例患者中非鳞癌41例,鳞癌11例,完全缓解(CR)1例,部分缓解(PR)18例,稳定(SD)13例,进展(PD)20例,总有效率(CR+PR)为36.5%,疾病控制率(CR+PR+SD)为61.5%;不同年龄、性别、临床分期、病理类型之间在有效率和疾病控制率方面差异无统计学意义(P>0.05)。所有患者PFS为4.8个月,非鳞癌患者为5.1个月,鳞癌患者为4.4个月,但两者之间差异无统计学意义(P>0.05);不良反应主要是消化道反应和骨髓抑制,多为Ⅰ～Ⅱ级。结论培美曲塞联合联合顺铂是一线治疗晚期非小细胞肺癌安全、有效的治疗方案。     

培美曲塞联合奈达铂治疗肺腺癌70例的近期疗效及安全性评价

目的观察培美曲塞（pemetrexed,PEM）联合奈达铂治疗晚期肺腺癌的近期疗效和不良反应。方法70例肺腺癌患者,其中35例采用PEM联合奈达铂治疗（治疗组）,另35例采用紫杉醇脂质体联合奈达铂治疗（对照组）,治疗2个周期后评价疗效及毒性反应。结果治疗组总有效率（RR）为60．00％,显著高于对照组的34．29％,差异有统计学意义（χ2=4．644,P=0．031）;Ⅲ-Ⅳ级药物相关性血液学毒性也显著低于对照组（均P〈0．05）。结论PEM联合奈达铂治疗晚期肺腺癌疗效好,不良反应小。     

培美曲塞联合顺铂一线化疗在老年ⅢB／Ⅳ期非小细胞肺癌中的治疗效果

目的观察培美曲塞联合顺铂一线化疗对老年ⅢB／Ⅳ期非小细胞肺癌的治疗效果,并评价此化疗方案所产生的不良反应。方法随机抽取2009年11月～2012年11月我院呼吸内科确诊为ⅢB期和Ⅳ期非小细胞肺癌的老年患者共80例,所有患者接受的化疗方案均为培美曲塞联合顺铂一线化疗。分别统计治疗后鳞癌和非鳞癌的临床疗效和各自的无进展生存时间,对治疗后患者所发生的不良反应进行分级,评价培美曲塞联合顺铂一线化疗对于老年ⅢB／Ⅳ期非小细胞肺癌的治疗效果。结果①所有患者治疗后均未达到完全缓解,非鳞状细胞癌患者的部分缓解率和稳定率高于鳞状细胞癌患者,前者疾病进展率低于后者,但差异不具有统计学意义（P＞0．05）。②非鳞状细胞癌患者治疗的有效率和疾病控制率高于鳞状细胞癌患者,但差异无显著性（P＞0．05）。非鳞癌治疗后无进展生存时间明显长于鳞癌（P＜0．05）。③治疗后患者所发生的不良反应较少,主要表现为骨髓抑制和胃肠道反应,经及时对症治疗后均不影响化疗方案的进一步实施。结论培美曲塞联合顺铂一线化疗治疗老年ⅢB／Ⅳ期非小细胞肺癌临床疗效较好,所发生的不良反应较少,尤其是针对非鳞状细胞癌效果更佳,建议临床推广应用。     

Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoral hypointensity seen on gadoxetate disodium-enhanced hepatobiliary phase images

Purpose:

To determine whether peritumoral hypointensity seen on hepatobiliary phase images of preoperative gadoxetate disodium‐enhanced magnetic resonance imaging (EOB‐MRI) is useful for predicting microvascular invasion of hepatocellular carcinoma (HCC).

Materials and Methods:

This study was approved by the Institutional Review Board. In all, 104 HCC masses in 104 patients who had undergone EOB‐MRI and liver surgery within 1 month after EOB‐MRI were evaluated. Two radiologists independently recorded the presence of a peritumoral hypointensity on hepatobiliary phase. Interobserver agreement was assessed and consensus records were used. Tumor size was measured. A chi‐square test and independent t‐test were used for univariate analysis. Multiple logistic regression was performed to determine factors for predicting microvascular invasion. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of peritumoral hypointensity were calculated.

Results:

Sixty HCCs had microvascular invasion and 44 did not. Interobserver agreement in determining peritumoral hypointensity was excellent (κ = 0.83). By univariate analysis, peritumoral hypointensity and tumor size were significant for predicting microvascular invasion of HCC. On multiple logistic regression analysis, only peritumoral hypointensity was significant in predicting microvascular invasion of HCC (P = 0.013). The sensitivity, specificity, PPV, and NPV of peritumoral hypointensity were 38.3%, 93.2%, 88.5%, and 52.6%, respectively.

Conclusion:

Peritumoral hypointensity on the hepatobiliary phase of EOB‐MRI is not sensitive but has high specificity for predicting microvascular invasion of HCC. J. Magn. Reson. Imaging 2012;35:629‐634. © 2011 Wiley Periodicals, Inc.