以替尼泊苷为主的化疗方案治疗中枢神经系统淋巴瘤

目的：观察以替尼泊苷为主的化疗方案治疗中枢神经系统淋巴瘤的疗效。方法：8例原发性／继发性中枢神经系统(CNS)非霍奇金淋巴瘤(NHL)患者，给予COP+VM-26方案化疗，7例给予全颅放疗，4例在放、化疗前手术切除颅内病灶。结果：4例原发性CNS-NHL患者中3例手术切除后化疗，1例患者未手术，仅采用放疗和化疗，4例均获得了完全缓解，中位无病生存时间23.5月，中位总体生存时间29月；对系统性NHLⅣ期伴有颅内浸润的患者，该方案可以迅速缓解CNS症状，3／4例CR。结论：以替尼泊苷为主的化疗方案对CNS-NHL疗效较好。CNS-NHL的治疗应采用综合疗法，即手术+化疗+放疗。     

原发性中枢神经系统淋巴瘤的临床特征分析

 目的　分析原发性中枢神经系统淋巴瘤（PCNSL）的临床特征,探讨影响疾病的预后因素,并对不同的治疗方案进行评价。方法　回顾性分析初发PCNSL患者的临床资料、治疗经过及随访结果,应用Log-rank进行单因素分析,应用COX回归模型进行生存资料的多因素分析。结果　共收集PCNSL初发病例64例,中位年龄54.9岁,男性多于女性,肿瘤单发62 %（40／64）,深部病变占54 %（33／61）。在我科诊治的具有完整治疗资料的患者26例,其中19例患者初始治疗为单纯化疗,6例为全颅放疗（WBRT）后1个月进行化疗,1例患者初治时仅行WBRT。中位生存时间为17个月,血红蛋白≥9 g／L患者的生存时间长于血红蛋白＜9 g／L患者。年龄>60岁、性别、体能状态、病变部位等因素对预后无明显影响。应用含大剂量甲氨蝶呤（HD-MTX）或替尼泊苷的方案化疗者的预后优于未使用者,化疗联合放疗可能有助于改善患者的预后（χ2＝3.24,P＝0.07）,应用CHOP方案（环磷酰胺、多柔比星、长春新碱、泼尼松）、利妥昔单抗、鞘内注射化疗药物等与预后关系不大;多因素分析提示HD-MTX是影响PCNSL患者生存时间的独立有利因素,颅内病灶部位、病灶的多少、是否联合放化疗等均不是影响预后的独立因素。结论　PCNSL预后较差,应用HD-MTX、替尼泊苷等药物可改善患者的预后,贫血尤其中重度贫血患者预后不良。     

原发性中枢神经系统淋巴瘤18例

 目的　研究原发性中枢神经系统淋巴瘤（PCNSL）的临床、病理特点及治疗方法。方法　回顾性分析18例PCNSL患者的临床表现、病理特征及治疗效果。结果　18例PCNSL,单病灶14例（77.8 %）,多病灶4例（22.2 %）,最常见部位为额叶6例（27.8 %）、颞叶5例（22.2 %）,主要临床表现为头痛、恶心、呕吐13例（72.2 %）。病理检查皆为B细胞来源,其中弥漫性大B细胞淋巴瘤12例（66.7 %）。全组中位生存期（MST）15.5个月,2年生存率33.3 %。结论　PCNSL临床表现无特异性,病理以弥漫性大B细胞为主, 全脑放疗结合大剂量化疗是最佳治疗手段     

原发性中枢神经系统淋巴瘤治疗进展

原发性中枢神经系统淋巴瘤（PCNSL）恶性度高,预后较差。PCNSL目前无标准治疗方案,单纯手术或单纯放疗效果较差,以氨甲喋呤（HD-MTX）为基础的综合治疗可改善患者生存率。综合化疗后的放疗以全脑放疗为首选,但放疗可导致老年患者神经毒性。化疗后自体干细胞移植及靶向药物可改善患者预后,并可降低神经毒性发生率。     

维布妥昔单抗联合化疗治疗32例恶性淋巴瘤的临床观察

目的 回顾性分析维布妥昔单抗联合化疗治疗恶性淋巴瘤的临床疗效和安全性。方法 收集32例CD30阳性淋巴瘤患者资料,其中霍奇金淋巴瘤14例,弥漫大B细胞淋巴瘤2例,成熟T/NK细胞淋巴瘤16例。所有患者均接受化疗联合维布妥昔单抗的治疗至少2周期,每2个周期结束后依据Lugano标准进行疗效评价。结果 4周期治疗后完全缓解率为22%,总缓解率为50%。1～2级毒性16例（50.0%）,3级及以上毒性16例（50.0%）。最常见的不良反应是中性粒细胞减少（50.0%）、肺炎（46.9%）、贫血（43.8%）。最常见的3级及以上不良反应是肺炎（18.8%）和发热（12.5%）。4例因严重不良反应停止使用维布妥昔单抗。结论 维布妥昔单抗治疗复发难治性CD30阳性霍奇金淋巴瘤及外周T细胞淋巴瘤的疗效确切,总体安全性尚可。     

培美曲塞为主的化疗方案治疗中老年非霍奇金淋巴瘤回顾性分析CSCD

目的回顾性分析培美曲塞为主的化疗方案治疗中老年非霍奇金瘤患者的安全性及有效性。方法回顾性收集2016年11月至2018年10月中国医学科学院肿瘤医院收治的以培美曲塞为主的化疗方案治疗的非霍奇金淋巴瘤患者临床资料,并对相关文献进行系统性综述。结果共纳入10例非霍奇金淋巴瘤患者,7例为弥漫大B细胞淋巴瘤,2例为血管免疫母T细胞淋巴瘤,1例为结外NK/T细胞淋巴瘤。肿瘤复发或一线治疗进展后接受培美曲塞为主的化疗方案,弥漫大B细胞淋巴瘤有4例达到部分缓解,3例疾病进展,出现的不良反应主要为Ⅰ~Ⅱ度骨髓抑制及胃肠道反应。结论培美曲塞为主的化疗方案治疗弥漫大B细胞淋巴瘤患者,尤其是原发性中枢神经系统淋巴瘤,可能有一定的有效性,且安全性可控。     

34例原发性中枢神经系统恶性淋巴瘤临床分析

目的：分析免疫功能正常的中国人原发性中枢神经系统淋巴瘤（PCNSL）的临床资料,探讨PCNSL的临床特征,评价大剂量甲氨蝶呤（HD-MTX）加全脑放疗（WBRT）治疗PCNSL的疗效.方法：回顾性分析34例经病理证实的PCNSL患者的临床资料以及治疗效果,Kaplan-Meier法分析患者生存期.结果：34例PCNSL患者中B细胞淋巴瘤31例（91.2%）,T细胞淋巴瘤3例（8.8%）;所有患者治疗后评价完全缓解率（CR）41.2%,2年生存率60.2%;病理类型和是否接受HD-MTX加放疗是影响PCNSL生存期的主要原因（P＜0.05）.结论：PCNSL以颅内高压为主要表现,B细胞亚型占绝对优势,具有独特的预后因素,HD-MTX联合放疗是PCNSL有效的治疗方法.     

31例原发性中枢神经系统恶性淋巴瘤临床分析

目的：分析免疫正常的原发性中枢神经系统恶性淋巴瘤患者的临床表现、影像学特点和病理表现并探讨其诊断、治疗方法方法：回顾分析1995年7月至2006年6月经病理证实的31例原发中枢神经系统恶性淋巴瘤病例的临床、实验室检查、影像学、病理结果及治疗效果．18例采用手术＋放疗＋化疗方法．5例单纯手术；台疗、其中化疗CH（）P方案11例，替尼泊苷（VM26）＋司莫司汀（me-CCNU）7例结果：原发性中枢神经系统恶性淋巴瘤临床表现复杂，无特异性，主要为颅内压增高和神经功能缺损为主，误诊率高脑脊液检查无阳性结果．31倒均为B细胞淋巴瘤31倒中获随访24例．随访时间6～98个月，其中手术＋放疗＋化疗组中位生存期20个月，单纯手术组中位生存期10个月结论：原发性中枢神经系统恶性淋巴瘤缺乏特异性临床表现，术前难以确诊，预后不良病理检查是确诊的唯一方法。应采取综合治疗手术的主要目的是解除肿瘤引起的颅内高压，单纯手术后，短时间内复发．应该采取手术、放疗、化疗综合治疗．这是延长生存期和改善生存质量的关键     

HA联合替尼泊苷或表柔比星治疗急性髓系白血病疗效观察

目的:探讨高三尖杉脂碱+阿糖胞苷联合替尼泊苷（HAT）或表柔比星（HAE)治疗急性髓系白血病（AML)的疗效及毒副反应。方法:回顾性分析了初治急性髓系白血病患者以HAT或HAE方案进行诱导化疗的疗效和毒性反应。统计完全缓解率（CR）及总生存（OS）率分析。结果:初治AML患者在HAT和HAE组一疗程诱导化疗CR率分别为90%和81%。两组中CR患者3年实际OS率分别为33.3%和53.8%。至随访结束HAT组无复发生存22.2%,HAE组30.7%。预期5年总生存率HAT组为20%,HAE组为44%。化疗相关的毒副反应主要为造血抑制和感染,患者可以耐受。结论:HA联合替尼泊苷或表柔比星诱导化疗疗效满意,不良反应可以耐受,可以作为一线诱导化疗方案。     

原发性中枢神经系统淋巴瘤35例临床及预后分析

目的：探讨原发中枢神经系统淋巴瘤（PCNSL）临床特点、诊治方案及临床疗效。方法：总结2001年1月-2008年1月收治的35例PCNSL患者,均经病理证实为B细胞来源非霍奇金淋巴瘤并接受放疗,其中25例放疗后接受化疗。结合文献对原发性中枢神经系统淋巴瘤患者的临床特点、病理学检查、影像学表现、治疗及预后进行回顾性分析。结果：本病以中老年人多见,发病急,病程短,病情进展快。临床表现复杂,颅内高压为主要表现之一。CT、MRI增强扫描病灶多呈均匀明显强化,可单发或多发。35例患者中位生存时间23月,1年生存率74．3％,3年生存率25．7％,5年生存率5．71％。肿瘤全切及局部切除者,生存率未见明显统计学差异（P=0．053）,加化疗疗效优于不加化疗（P=0．012）。结论：PCNSL临床表现多样,影像学缺乏特异性,极易误诊,确诊需要依靠病理学检查,最佳治疗方案是手术加放疗、化疗的联合治疗。PCNSL侵袭性强,生存期短,其预后主要与发病年龄、多灶性、一般状态有关。     

The medically important dematiaceous fungi and their identification

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).     

Orale Langzeitbehandlung von Onychomykosen mit Ketoconazol

Zusammenfassung: An der Studie zur Wirksamkeit und Anwendungssicherheit von Ketoconazol nahmen 27 Männer im Alter von 20 bis 80 (Median: 57) Jahre, davon 18 mit Onychomykosen und 9 als KontroUen bei den Laborwertbestimmungen, teil. Während des ersten Behandlungsmonats erhielten je 9 Patienten 200 mg und 400 mg Ketoconazol täglich. Danach wurden beide Gruppen 6 Monate mit 200 mg/d weiterbehandelt. Die klinische Beurteilung sowie hämatologische, biochemische und Plasmaspiegeluntersu-chungen erfolgten mindestens monafich, mykologische Untersuchungen wurden vor Aufnahme und bei Beendigung der Therapie vorgenommen. Erne letzte klinische Unter-suchung erfolgte 1 Jahr nach Beginn der Studie. Nach 7 Monaten Behandlung wurden 23 von 30 Nägeln mit “gebessert” bis “stark gebessert” beurteilt, nach dem behandlungsfreien Intervall galt dies für 28 von 30 Nägeln. Die Plasmaspiegel waren mit 200 mg/d ausreichend und uber den Behandlungszeit-raum konstant. Dies spricht für gute orale Resorption und Abwesenheit von Enzyminduktion. Die Laborwerte zeigten im Vergleich zu den Kontrollen und den Werten vor Behandlung keine signifikanten Abweichungen, so daß myelo-, nephro- und hepatotoxische Wirkungen von 400 bzw. 200 mg/d ausgeschlossen werden können. Der Lipidhaushalt wurde nicht beeinfluat und es trat unter Therapie als Folge der Ketoconazolwirkung lediglich Lanosterin im Serum auf. Nach Beendigung der Therapie ging der Lanosteringehalt schnell zurück. Damit erweist sich Ketoconazol in den angewandten Dosen als ein gut verträgliches und zur Langzeitbehandlung von Onychomykosen geeignetes Antimykotikum. Summary: Twenty-seven males with a median age of 57 (range: 20 to 80) years took part in this study on the efficacy and safety of ketoconazole. Eighteen men suffered from onychomycosis; nine served as controls in the safety evaluation. During the first month of treatment, nine patients received 200 mg and the nine other 400 mg ketoconazole daily. Then the treatment was uniformly continued with 200 mg/d for 6 months. Clinical evaluation and haematological, biochemical and plasma level investigations were carried out at least at monthly intervals; mycological controls were performed at the start and end of therapy. A final clinical evaluation was carried out one year after the start of the study. After 7 months of treatment, moderate or definite clinical improvement was obtained in 23 out of 30 nails. After 5 more months without antimycotic treatment this was the case in 28 of 30 nails. Plasma levels obtained with 200 mg ketoconazole daily were adequate and constant during the entire treatment period. This indicates a good oral resorption as well as the absence of induction of hepatic enzymes. The laboratory values did not show significant deviations as compared with the controls or with the pretreatment values. This excludes myelo-, nephro- and hepatotoxic effects of 400 and 200 mg ketoconazole daily. The lipid metabolism was not influenced, the only difference was the occurrence of lanosterol in the serum, which is a result of the mechanism of action of ketoconazole. After the medication period the lanosterol levels subsided rapidly. In the applied doses ketoconazole is a well-tolerated and effective drug for the systemic long-term treatment of onychomycosis.     

Laboratory Techniques Alternative to In Vivo Experiments for Studying the Liberation, Penetration and Fungicidal Action of Topical Antimycotic Agents in the Skin, Including Ciclopiroxolamine

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitätstest mit direkter Inokulation (D-GAT) wurde mit Handelspräparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations-Gewebeaktivitätstest (UFT-GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächst die Hautoberfläche inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberfläche bis zu 18 Stunden lang überwiegend Cremes von als fungizid publizierten Antimykotika ein. Während sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflächen mit Ciclopiroxolamin-Creme und -Lotion die weitaus höchste Verminderung lebensfähiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen mußten Homogenisierung und Verdünnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtötung vorgetäuscht worden wäre. Wegen der vorerst noch hohen Streuung der Ergebnisse können kleinere Wirksamkeitsunterschiede noch nicht sicher erfaßt werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz für Haut vom Menschen dienen und dürfte damit wesentlich zur Einschränkung von Versuchen am lebenden Tier und von Prüfungen am Menschen beitragen.     

Efficiency of crude and purified fungal antigens in serodiagnosis to discriminate mycotic from other respiratory diseases

Mycotic immunodiagnosis was performed in 186 hospitalized patients with different respiratory diseases, mostly considered as tuberculosis and others with a doubtful diagnosis. Crude histoplasmin, coccidioidin, paracoccidioidin, blastomycin, candidin, aspergillin, and sporotrichin, as well as purified polysaccharide-protein complexes (PPC) of Histoplasma capsulatum, Coccidioides immitis, and Paracoccidioides brasiliensis were used as antigens. Immune tests used included skin test (ST), gel immunodiffusion (ID), counterimmunoelectrophoresis (CIE), complement fixation (CF), and ELISA. A possible association with candidosis was observed in 17% of patients with tuberculosis and diabetes; one presumptive paracoccidioidomycosis, one confirmed aspergillosis, and six cases of active histoplasmosis were determined. Candidin ST showed 29% of positive reactions with an increased frequency in patients between 31 and 55 years of age. CF test showed the highest positivity percentages with crude antigens, specially for Candida antigen (26.3%) and histoplasmin (18.2%). Cross reactions were evident with crude antigens but decreased when PPC's were used in ELISA.     

Isoconazole nitrate in the treatment of tropical dermatomycoses

Summary. A total of 54 patients with culturally proven tropical dermatomycoses, comprising 23 with various types of dermatophytoses, one with foot infection due to Trichosporon beigelii and one with foot infection due to Geotrichum candidum , two with candidoses of the groin and 27 with pityriasis versicolor, were included in a clinical trial of efficacy of 1% isoconazole cream (Travogen^R, Schering, Berlin, Germany). Five patients were not evaluable. A clinical and mycological cure was achieved in 29 cases in 3–4 weeks. In 15 (31%) of the remaining patients treatment was required for 5–6 weeks, while another three patients required treatment for 8 weeks. In two patients the disease proved to be resistant to treatment with the drug.
Zusammenfassung. Insgesamt 54 Patienten mit kulturell gesicherter Dermatomykose, (23 unterschiedliche Dermatophytosen, eine Trichosporon beigelii - und eine Geotrichum candidum -Fußinfektion, 2 Candidosen der Leistengegend und 27 Pityriasis versicolor) wurden in einer klinischen Wirksamkeits-studie mit 1% iger Isoconazol-Creme (Travogen^R, Schering, Berlin, Deutschland) behandelt. Fünf Patienten waren nicht auswertbar. Eine klinische und mykologische Heilung wurde bei 47 von 49 Patienten (96%) erreicht. Bei 29 patienten (59%) wurde die Heilung bereits nach 3–4 Wochen Behandlung erreicht. Weitere 15 Patienten (31%) benötigten 5–6 Wochen und drei Patienten 8 Wochen Behandlungsdauer. Zwei Mykosesituationen erwiesen sich als therapieresistent.     

Large-scale molecular characterization and analysis of gastric cancer

The recent effort by The Cancer Genome Atlas （TCGA） Network has revealed that gastric cancer, which is a leading cause of cancerrelated deaths worldwide with a 5-year survival rate less than 25%, is a much more heterogeneous disease than previously thought. And yet, conventional treatment approaches and clinical trials have assumed it is a single disease. Although it is well known that under the microscope, gastric cancer cells appear quite different, the current classification scheme recognizes two main categories of gastric cancer： diffuse and intestinal.     

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma''s compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.