Rapamycin and Thalidomide Treatment of a Patient with Refractory Metastatic Gastroesophageal Adenocarcinoma: A Case Report

The use of rapamycin and thalidomide in a patient with metastatic gastroesophageal carcinoma, which led to disease stability associated with a significant tumor marker response and improved clinical quality of life, is reported.     

卵巢环管状性索间质瘤2例

环管状性索间质瘤（ｓｅｘｃｏｒｄｔｕｍｏｒｗｉｔｈａｎｎｕｌａｒｔｕｂｕｌｅｓ）十分罕见 ,在卵巢肿瘤中占０．０６ % ,其生物学行为不太明确，肿瘤较大时偶可显示恶性的行为，有卵巢外浸润或转移，较小的肿瘤行为比较良性。近年来认为此瘤类似粒层细胞 ,属于低度恶性。本文收集两例报道如下 :例１ ,女性 ,３９岁 ,以腹胀２年 ,加重伴气短１周入院治疗。于３年前绝经 ,绝经前２年月经不规则 ,４年前曾做乳腺包块切除术 ,病理诊断为导管内乳头状瘤 ,１２年前曾做过结肠息肉摘除术 ,但未做病理检查。临床检查 :肝脏轻度增大 ,血清碱性磷…     

宫颈微偏腺癌2例并文献复习

目的探讨子宫颈微偏腺癌的临床特征、病理组织学形态、诊断及鉴别诊断。方法复习2例微偏腺癌的相关临床资料，并对其进行组织学观察，结合文献进行探讨。结果微偏腺癌患者白带增多呈水样。子宫颈肥大呈桶状，切面见子宫颈纤维肌层增厚，质地硬，有多个不规则微小囊腔形成。大部分肿瘤细胞异型性小，接近正常宫颈黏液性腺上皮，但腺体大多呈不规则的囊状扩张、扭曲，有鸡爪样触角形成，腺体呈浸润性生长，并有纤维间质反应，肿瘤组织易侵犯脉管和神经组织。结论微偏腺癌是1种较罕见的、细胞学异型性极轻微、宫颈刮片及活检不易明确诊断的、易被诊断为良性而生物学行为为恶性的宫颈腺瘤。     

Association between Smoking and Tumor Progression in Japanese Women with Adenocarcinoma of the Lung

We studied the effect of smoking on tumor progression in 3312 patients with lung cancer registered at the National Matsudo Hospital and National Cancer Center Hospital East between 1977 and 1996. The odds ratios of the following variables for tumor extent (localized versus advanced disease) and hazard ratios for survival were calculated in both sexes separately using the logistic regression and Cox proportional hazard models, respectively: smoking history, number of cigarettes smoked per day, pack-years smoked, age, histological type, and the year of admission. Of the 943 women, 367 (38.9%) were smokers and 694 (73.6%) had adenocarcinoma, whereas of the 2369 men, 2255 (95.2%) were smokers and 1010 (42.6%) had adenocarcinoma. In female adenocarcinoma patients, the odds ratio (95% confidence interval) for advanced disease and the hazard ratio (95% confidence interval) for survival with an increase of 30 cigarettes smoked per day were 2.86 (1.49-5.49) and 1.52 (1.13-2.04), respectively, but in those with non-adenocarcinoma, the odds ratio and hazard ratio were 0.96 (0.41-2.23) and 1.13(0.75-1.70), respectively. In male patients, smoking history influenced tumor progression regardless of histological type, but the odds ratios and hazard ratios were lower than those for women with adenocarcinoma. In conclusion, smoking habit was closelycorrelated with progression of adenocarcinoma in women. This association was not observed in women with non-adenocarcinoma and was weaker in men, suggesting various effects of smoking on lung cancer development depending on gender and the histological typeof the tumor     

Carcinosarcoma of the Uterine Corpus with Alpha-Fetoprotein-Producing Hepatoid Adenocarcinoma: A Report of Two Cases

We report two cases of uterine carcinosarcoma associated with alpha-fetoprotein (AFP)-producing hepatoid adenocarcinoma. Samples were obtained from two women aged 63 and 82 years. Serum AFP levels of the two samples were 10,131 and 401 ng/ml, respectively. Histologically, in both cases the tumor cells were composed of hepatoid adenocarcinoma component and sarcoma component including rhabdomyosarcoma. Immunohistochemical analyses revealed that AFP was expressed in the cytoplasm of the carcinomatous component. After surgery, the patients received six courses of carboplatin/paclitaxel chemotherapy, and the serum levels of AFP decreased to normal range. The first patient is alive and well at the 2-year follow-up, while the second patient died of disease 1 year after initial operative treatment. This is, to our knowledge, the second report of carcinosarcoma of the uterine corpus with AFP-producing hepatoid adenocarcinoma, as proven by immunohistochemical analyses.Key words: Uterine carcinosarcoma, Hepatoid adenocarcinoma, Rhabdomyosarcoma, Alpha-fetoprotein     

脊柱转移瘤82例误诊原因分析

回顾分析1991年至2003年间收治的87例脊柱转移瘤的误诊原因.全组院外误诊率高达94.3%,院内首次门诊误诊率为11.5%.临床表现、实验室和影像学检查等每个环节都很重要,其中X线、疼痛性质、原发病灶隐蔽与否的误诊率分别高达34.7%、31.7%和22.0%,而CT、MRI和ECT判断失误仅占6.9%.详细询问病史、既往史,仔细查体,多元性的选择影像学检查后作出综合性分析是减少误诊的有效方法.     

免疫检测点抑制剂治疗后"超进展"的晚期肺腺癌患者2例及文献复习

目的:免疫检测点抑制剂治疗在多种肿瘤中都表现出了很好的疗效。然而,约10%的患者在治疗中出现肿瘤加速生长的情况,临床上将其称为超进展。对于在接受免疫检测点抑制剂治疗中发生“超进展”的非小细胞肺癌患者来说,仍然需要对其临床病理特征进行更多的研究。方法:我们报导2例分别使用帕博利珠单抗和阿特珠单抗二线治疗的晚期肺腺癌患者。这两例患者均在治疗后出现肿瘤快速进展,根据目前的诊断标准评价为“超进展”。另外,我们通过复习相关文献,探讨“超进展”的定义、风险因素及患者预后。结果:本文中报导的2例“超进展”的患者具有相应的临床特点,但与既往研究中所报导的不完全一致。结论:在接受免疫检测点抑制剂治疗后发生的“超进展”现象具有复杂性,研究“超进展”相关的临床病理特征很有必要。     

Tumor Response and Symptom Palliation from RAINBOW,a Phase III Trial of Ramucirumab Plus Paclitaxel in Previously Treated Advanced Gastric Cancer

BackgroundIn the intent‐to‐treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation.Materials and MethodsTumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire‐Core 30 (EORTC QLQ‐C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR.ResultsIn both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation.ConclusionTreatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. {"type":"clinical-trial","attrs":{"text":"NCT01170663","term_id":"NCT01170663"}}NCT01170663.Implications for PracticeRamucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first‐line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits.     

Evaluation of Tumor DNA Sequencing Results in Patients with Gastric and Gastroesophageal Junction Adenocarcinoma Stratified by TP53 Mutation Status

BackgroundGastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ) are molecularly diverse. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. This qualitative study describes the distinct genomic alterations in GCs and GEJs stratified by TP53 mutation status.Patients and MethodsTumor DNA sequencing results of 324 genes from 3741 patients with GC and GEJ were obtained from Foundation Medicine. Association between gene mutation frequency and TP53 mutation status was examined using Fisher’s exact test. Functional gene groupings representing molecular pathways suggested to be differentially mutated in TP53 wild-type (TP53_WT) and TP53 mutant (TP53_MUT) tumors were identified. The association of the frequency of tumors containing a gene mutation in the molecular pathways of interest and TP53 mutation status was assessed using Fisher’s exact test with a P-value of <.01 deemed statistically significant for all analyses.Results TP53 mutations were noted in 61.6% of 2946 GCs and 81.4% of 795 GEJs (P < .001). Forty-nine genes had statistically different mutation frequencies in TP53_WT vs. TP53_MUT patients. TP53_WT tumors more likely had mutations related to DNA mismatch repair, homologous recombination repair, DNA and histone methylation, Wnt/B-catenin, PI3K/Akt/mTOR, and chromatin remodeling complexes. TP53_MUT tumors more likely had mutations related to fibroblast growth factor, epidermal growth factor receptor, other receptor tyrosine kinases, and cyclin and cyclin-dependent kinases.ConclusionThe mutational profiles of GCs and GEJs varied according to TP53 mutation status. These mutational differences can be used when designing future studies assessing the predictive ability of TP53 mutation status when targeting differentially affected molecular pathways.     

Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From the KEYNOTE-028 and KEYNOTE-158 Studies

IntroductionPembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC.MethodsEligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)–positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review.ResultsEighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5–48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4–29.4); two patients had complete response (one with a PD-L1–positive tumor), and 14 patients had partial response (13 with PD-L1–positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events.ConclusionsPembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.     

GP-T方案治疗非小细胞肺癌合并脑转移的初步报告

目的：观察吉西他滨(健择、GEM) 顺铂(CDDP)联合替尼泊甙(VM-26)治疗非小细胞肺癌(NSCLC)合并脑转移的疗效和毒副反应。方法：2001年2月—2003年3月间收治NSCLC合并脑转移病人18例，采用GP—T进行治疗3个周期。结果：PR8例(44．44％)、SD5例(27．8％)、PD5例(27．8％)。所有合并有头部疼痛的患中，60％疼痛完全缓解，40％部分缓解；11例患肢体活动障碍得到不同程度的缓解(61．11％)。毒副反应方面，主要为骨髓毒性，但大部分为Ⅱ度以下，其中Ⅲ度白细胞下降约占27．78％(无Ⅳ度白细胞下降)；Ⅲ、Ⅳ度血小板下降约各占22．22％和16．67％。结论：GP—T方案对于NSCLC合并脑转移具有一定的疗效，且毒副反应较低，患易于耐受。     

Successful Treatment of Intracranial Germ Cell Tumor: Report of Two Unusual Cases and Literature Review

Primary intracranial germ cell tumor (GCT) is a rare tumor that generally occurs due to developmental anomaly. Although intracranial GCT is sensitive to treatment, a high recurrence rate, treatment-related long-term complications and the heterogeneity of this tumor group make treatment complicated. Moreover, because of its location, hydrocephalus and visual field defect, functional disturbance of the pituitary gland can occur and require attention. Treatment primarily relies on chemotherapy and radiation therapy but the management of intracranial GCT remains unsettled, especially in the case of unusual circumstances such as multifocal tumor or nongerminomatous GCT. Here, we present two unusual cases of intracranial GCT: one case with a bifocal intracranial germinoma, and the other with an intracranial choriocarcinoma. Both cases were treated with neoadjuvant chemotherapy followed by reduced-field radiation therapy without significant treatment-related complication. Further, we performed a PubMed search to investigate the appropriate treatment strategy for this unusual subtype of intracranial GCT.Key Words: Germinoma, Choriocarcinoma, Intracranial germ cell tumor, Chemotherapy, Radiation therapy