乳腺癌根治术后锁骨上淋巴结转移及远处转移病例临床分析

目的　探讨乳腺瘤根治术后锁骨上淋巴结转移及远处转移病例的临床病程及预后。方法　共收治109例,其中锁骨上淋巴结转移26例(A组);远处转移83例(B组)。总结两组病例初次治疗后出现转移的时间(简称为转移时间)及生存率等情况。结果　A、B两组病例的转移时间(中位数)为16及21个月,P>0.05。A组54%在135个月(2～34个月)内出现远处转移;B组37%在6个月(0～80个月)内出现其他部位的远处转移,P>0.05。两组病例的2年和5年生存率分别为442%、109%(A组)及431%、136%(B组),P>0.05。结论　本文提示乳腺癌术后锁骨上淋巴结转移病例的临床病程及生存率与远处转移病例的相近。     

乳腺癌雌二醇、泌乳素和CEA检测的临床意义

目的　探讨雌二醇 (E2 )、泌乳素 (PRL)和癌胚抗原 (CEA )的检测在乳腺癌诊断、随访及预后中的临床意义。方法　 2 93例乳腺癌均经病理证实。术前检测E2 、PRL 2 0 8例 ,CEA 15 8例 ,术后 3个月复查 ,并对复发或有远处转移病例再复查。结果　 2 0 8例乳腺癌术前E2 血清值均正常。PRL增高 10 2例 (49.0 4%) ,CEA增高 12例 (7.5 8)。PRL、CEA血清值的增高与肿瘤大小呈正相关 (P <0 .0 5 )。术前PRL、CEA血清值增高组病例 ,术后 3个月复查均降至正常。但有复发或远处转移后 87.0 9%再次升高。其 5年生存率为 5 3 .4%。术前血清值正常组复发病例 2 4.0 0 ?A、PRL血清值增高 ,其 5年生存率为 6 1.2 %,P <0 .0 5。结论　乳腺癌病例E2 检测意义不大。PRL、CEA血清值异常率与肿瘤大小呈正相关。其血清值表达增高组预后较差。PRL、CEA对该组病例术后复发或远处转移的监测具有重要意义。     

早期乳腺癌改良根治术与保乳手术的疗效比较

目的比较改良根治术与保乳手术治疗对早期乳腺癌的临床疗效。方法按照手术方式将155例乳腺癌患者分为保乳组(40例)和改良组(115例),保乳组行保乳手术+术后放、化疗,改良组行改良根治术+术后化疗,比较两组患者1、3、5年生存率、局部复发率以及远处转移率。结果保乳组死亡1例,改良组死亡4例,死亡原因均为非乳腺癌原因;保乳组2例发生远处转移,其中1例为肺转移,1例为骨(脊柱)转移,术后生活质量未受明显影响;改良组6例发生远处转移,其中4例为肺转移,2例为骨转移,术后生活质量未受明显影响;两组患者1、3、5年生存率、局部复发率、远处转移率比较,差异无统计学意义(P>0.05)。结论保乳手术+术后放、化疗对早期乳腺癌的远期疗效与改良根治术+术后化疗相近,但保乳手术创伤小、术后恢复时间短、能够保留乳房的美观外形,临床应用价值更高。     

乳腺癌术后综合治疗

目的　探讨乳腺癌术后行放化疗对预后的影响。方法　选取我院 1994年 1月～ 1996年 12月收治乳腺癌 3 8例 ,其中Ⅰ期 3例、ⅡA 期 10例、ⅡB 期 13例、ⅢA 期 12例。行根治术或单纯乳腺癌切除术 ,术后行常规放疗预防照射 5 0Gy ,并同时行至少 2个疗程以上CMF方案或CAF方案化疗。结果　全组 3、5年生存率分别是 84 2 %、68 4%。Ⅰ、ⅡA、ⅡB、ⅢA5年生存率分别是 10 0 %、10 0 %、76 9%、2 5 % (P值 <0 .0 5 ) ;腋淋巴结阴性、腋淋巴结转移数 1～ 3个及≥ 4个的 5年生存率分别是 10 0 %、85 7%、2 3 1% (P <0 .0 1)。 5年内有 13例 (占 3 4 2 % )发生远处转移。结论　乳腺癌术后行放化疗可提高远期生存率 ,减少远处转移     

保留皮肤的青年乳腺癌改良根治术后即刻乳房再造与改良根治术的比较分析

目的:比较保留皮肤的乳腺癌改良根治术后即刻乳房再造与改良根治术对青年患者的疗效,并对乳房再造患者的预后因素进行分析。方法:回顾性分析柳州市人民医院2008年7 月至2014年6 月收治并行保留皮肤的乳腺癌改良根治术后即刻乳房再造组（60例）与改良根治术组（68例）的青年乳腺癌患者临床病理资料,比较两组间局部复发、无瘤生存及总生存,并分析年龄、肿瘤大小、是否保留乳头乳晕等因素对乳房再造患者生存的影响。结果:所有病例随访15～88个月,中位时间51个月。即刻乳房再造组局部复发3 例,远处转移8 例,死亡5 例,3 年无瘤生存率91.7% ,5 年无瘤生存率81.7% ,总生存率91.7%;改良根治术组局部复发2 例,远处转移9 例,死亡5 例,3 年无瘤生存率94.1 % ,5 年无瘤生存率83.8% ,总生存率92.6% ,两组比较均差异无统计学意义（均P > 0.05）。 即刻乳房再造组患者预后分析显示,淋巴结转移及雌孕激素受体阴性与无瘤生存率、总生存率相关（均P <0.05）。 结论:青年乳腺癌患者保留皮肤的改良根治术后即刻乳房再造组与改良根治术组在局部复发及远期生存方面无显著性差异,对于早期青年乳腺癌患者是安全的,保留乳头乳晕并未增加肿瘤复发风险,淋巴结转移及雌孕激素受体阴性是影响预后的主要因素。      

早期乳腺癌保乳治疗的临床研究分析

目的通过早期乳腺癌保乳治疗和改良根治术的比较,探讨早期乳腺癌保乳治疗后的疗效、美容效果和心理变化等问题。方法对68例早期乳腺癌行保乳治疗(本院手术和放化疗59例,外院手术本院放化疗的9例),并与同期行改良根治术治疗的76例早期乳腺癌行对比研究。保乳治疗的全部病例均为女性,年龄范围为28—62岁,平均年龄44．5岁。按全国乳腺癌协作组标准选择病例。保乳术后常规行全乳腺放疗和瘤床加量。改良根治术患者年龄25—68岁,平均47．6岁。改良根治术后放疗的范围根据肿块大小和淋巴结转移情况决定。采用CAF方案化疗。ER／PR阳性的患者均给予口服三苯氧胺内分泌治疗。对68例保乳治疗和76例改良根治术患者的心理变化、性生活和婚姻稳定情况也进行了通信或问讯调查。结果68例保乳治疗患者无局部复发病例,3例出现远处转移(1例为骨转移,1例为骨、肝、肺多发转移,1例为肺、肝转移)。美容效果良好者91．2％,一般者5．6％,差者2．9％。76例改良根治术病例无局部复发,4例出现远处转移(2例为骨转移,1例为脑转移,1例为多发脏器转移)。两个组的近期疗效差异无统计学意义(XP=0．813)。结论早期乳腺癌保乳治疗的疗效与改良根治术基本相同,美容效果和心理的恢复优于改良根治术,是一种值得推广的治疗方法。     

乳腺癌首次治疗后复发的再治疗分析（附71例报告）

目的 :探讨乳腺癌首次治疗后复发转移患者再治疗后的生存及预后情况。方法 :回顾性分析局部复发的乳腺癌患者采用放疗或化疗结合放疗 ,远处转移乳腺癌患者采用转移灶局部放疗和全身化疗的效果。结果 :(1)首次治疗后复发及转移未再治疗 2 0例 1年内死亡 ,胸壁或 和淋巴结复发治疗后 1年、3年、5年生存率分别为72 73% (2 4 33)、4 8 38% (15 31)、18 5 2 % (5 2 7) ,远处转移患者经治疗后 1年、3年、5年生存率分别为 6 1 11%(11 18)、16 6 7% (3 18)、6 6 7% (1 15 ) ;(2 )再治疗后局部复发组死于复发 8例 ;远处转移组 4例死于转移灶未控 ,13例死于多部位癌转移。结论 :采用综合治疗为主方案 ,可提高复发和转移的乳腺癌患者的生存质量     

MMP-9的表达及微血管密度与乳腺癌生物学特性的相关性

目的　探讨基质金属蛋白酶 -9(MMP -9)的表达和微血管密度与乳腺癌生物学特性的相关性。方法　对原发性乳腺癌组织标本 ,采用标准链霉菌抗生物素蛋白 -过氧化物酶亲合免疫组织法 ,检测肿瘤组织中MMP -9的表达和微血管密度(MVD)。结果　MMP -9的阳性表达率为 42 %;MVD均值为 2 5 .3± 9.1;无腋淋巴结转移组、高分化组、无远处转移组及 5年生存组的MMP -9表达水平分别低于有腋淋巴结转移组、低分化组、远处转移及死亡组 ,有显著性差异 (P <0 .0 5 ) ;MVD值增大提示乳腺癌低分化、发生淋巴结转移和远处转移及预后差 ;MMP -9表达与乳腺癌血管生成有关 ,MMP -9高表达组MVD值大于MMP -9低表达组 (P <0 .0 5 )。结论　MMP -9表达水平及MVD与乳腺癌生长、转移及患者预后相关 ,此结果为临床建立新的乳腺癌预后预测因子和指导临床治疗提供依据。     

头颈部腺样囊性癌血行转移的临床研究

目的 :观察头颈部腺样囊性癌远处转移情况、影响因素以及其对生存的影响。方法 :回顾性分析 5 1例头颈部腺样囊性癌的临床资料。结果 :远处转移率为 4 1 2 % (2 1 5 1) ;单部位和多部位远处转移分别占 71 4 % (15 2 1)和 2 8 6% (6 2 1) ;肺、骨、肝和脑的转移依次占 81 0 % (17 2 1)、2 3 8% (5 2 1)、14 3% (3 2 1)和 9 5 % (2 2 1)。远处转移的平均发生时间在首次治疗后 5 36年。远处转移组和未远处转移组的生存期、10年生存率分别为 9 81年和 14 31年 ,5 3 8%和 4 1 0 %。远处转移后平均生存期为 2 5 5年 ,2年生存率为 4 7 8%。单纯肺转移组与肺外转移组Log rank检验生存差异有显著性 (P =0 0 32 ) ,其平均生存期、2年生存率分别为 3 4 8年和 1 4 9年 ,72 7%和 2 0 0 %。分析结果还表明 ,远处转移率与患者的性别、年龄、病程长短以及侵犯解剖部位多少无关 ,但与首次手术是否规范 (P =0 0 2 5 )、术后综合治疗是否规范 (是否术后辅以放疗 ) (P =0 0 4 5 )以及是否局部复发 (P =0 0 4 3)相关。结论 :头颈部腺样囊性癌生存期长 ,远处转移率高 ,远处转移出现的时间较晚 ,出现远处转移后患者仍可长期生存。通过根治性手术加术后放疗可能能够降低远处转移率     

保乳术治疗早期乳腺癌患者的临床疗效及对生活质量的改善作用

目的探讨保乳术治疗早期乳腺癌临床疗效,并观察其对患者生活质量的影响。方法 70例乳腺癌患者,其中35例采用改良根治术治疗者为对照组;另35例采用保乳术治疗,为观察组。两组术后均采用CMF化疗方案治疗,雌激素受体或孕激素受体(ER/EP)阳性者行内分泌治疗,观察组术后行全乳放疗及瘤床加量放疗。于术后2个月统计两组术后并发症及乳房美容情况,随访3年,统计两组局部复发、生存率、远处转移情况,并采用乳腺癌生命质量测定量表调查两组生活质量。结果观察组术后2个月并发症发生率2.86%,明显低于对照组(17.14%),χ~2=3.96,P=0.04;观察组术后2个月乳房美容优良率91.43%,明显高于对照组(0),χ~2=58.94,P=0.00。观察组与对照组患者3年生存率[94.29%vs97.14%]、局部复发率[2.86%vs5.71%]及远处转移率[8.57%vs11.43%]比较,差异均无统计学意义,P>0.05。观察组生理功能、躯体疼痛、生理职能、活力、总体健康、社会功能、情感职能及精神健康得分明显高于对照组相比,P<0.05。结论采用保乳术与改良根治术治疗早期乳腺癌均可取得较好疗效,但前者术后并发症少且具有较好的乳房外形,从而有利于改善患者生活质量。     

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).     

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.     

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.     

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.     

Endometrial cancers and predisposition

As nearly 5% of all endometrial cancers occur because of a predisposition, this possibility has systematically to be explored. The hallmarks of predisposition, a young age at diagnosis, a personal or a familial history of cancer, have to be searched systematically. The identification of a predisposition in a family has a major impact on the management of the proband or his relatives. The endometrial cancer main predisposition is Lynch's syndrome. In this review, we will focus on this condition and describe its clinical manifestations, the underlying molecular mechanisms, the cancer risks and the management guidelines. We will also get onto some far less frequent other predispositions.