前列腺癌pT3亚型细分建议:精囊侵犯加前列腺腺外扩散比单独精囊侵犯的生化复发和淋巴结转移率更高

2020年美国前列腺癌发病率为21％,病死率为10％.术前血清PSA、预后分期肿瘤淋巴结转移、手术切缘状态和组织学分级[格里森评分和国际泌尿外科病理学会( ISUP)分组]被列为最高级别(Ⅰ类)证据.AJCC第8版TNM分期将前列腺癌pT3分为pT3a和pT3b,前者仅前列腺腺外扩散(EPE),后者为精囊侵犯(SVI)...     

根治性前列腺癌切除术切缘阳性114例临床病理分析

目的分析根治性前列腺癌切除术切缘阳性的临床病理特征, 探讨其影响因素。方法回顾性分析2018年6月至2021年6月北京医院病理科根治性前列腺癌切除术274例患者的临床病理资料。用墨汁涂抹根治性前列腺癌标本切缘, 依据癌组织是否侵犯墨汁涂抹标记的切缘分为切缘阳性组、切缘阴性组, 比较两组患者的临床病理特征[年龄、术前前列腺特异性抗原(PSA)、病灶数量、病变部位、术后病理Gleason评分、肿瘤负荷、术后病理分期], 评价影响切缘阳性的相关危险因素。结果 274例标本中, 114例切缘阳性, 160例切缘阴性, 切缘阳性占41.6%。平均年龄68.3岁, 切缘阳性组平均年龄68.0岁, 切缘阴性组平均年龄68.6岁, 差异无统计学意义(P>0.05)。所有病例术前PSA水平均值为15.8 μg/L, 切缘阳性组为21.5 μg/L, 切缘阴性组为11.3 μg/L, 差异具有统计学意义(P<0.001), 且随着PSA水平(<10 μg/L、10～20 μg/L、>20 μg/L)的升高, 切缘阳性率越高(分别为31.1%、48.7%、69.4%)。病灶数量118...     

偶发性前列腺癌5例临床病理分析

目的探讨偶发性前列腺腺癌的发生率、临床及病理特点。方法收集40例复旦大学附属肿瘤医院因膀胱癌而行膀胱前列腺根治切除标本中偶然发现的前列腺腺癌5例,观察并分析其临床表现、病理学特点。结果临床表现:40例膀胱前列腺根治切除标本中有5例合并前列腺腺癌,发生率为12.5%(5/40)。患者平均年龄66岁(63～70岁)。4例表现为肉眼血尿,1例为镜下血尿。术前血PSA水平仅1例为6.55 ng/ml(参考值4.0 ng/ml),另外4例PSA水平均<4.0 ng/ml。病理检查:5例均为腺泡源性腺癌,4例Gleason分级评分均为6(3+3),1例Gleason分级评分为7(4+3)。临床病理TNM分期:3例为T1a,2例为T1b。结论前列腺癌可与尿路上皮癌合并发生,往往血PSA水平正常或稍高于正常。Gleason评分较低,癌灶常较局限,如取材不充分可能会漏诊。     

规范化扩大盆腔淋巴结清扫术在前列腺癌根治术中的应用

目的 探讨前列腺癌根治术中扩大盆腔淋巴结清扫术(e-PLND)规范化技术及其临床疗效。方法 回顾性分析2004年1月—2014年12月127例前列腺癌行前列腺根治+e-PLND患者的临床资料。患者年龄47～78岁,平均66.2岁。术前前列腺特异性抗原(PSA)平均13.1 μg/L, Gleason评分平均6.8分。按前列腺癌危险因素分级:低危组49例、中危组46例、高危组32例;盆腔淋巴结按解剖部位分为5组9区:髂外、髂总、闭孔、髂内淋巴结组左右两侧分别为1个区,骶前淋巴结组为1个区。患者均在全身麻醉下经下腹正中切口行前列腺根治+e-PLND。比较低危组、中危组、高危组淋巴结转移率;比较淋巴结转移阳性患者中,不同解剖部位淋巴结组的转移率。观察术中、术后并发症发生情况。术后每3个月复查PSA,观察生化复发情况。采用Kaplan-Meier非参数法,统计患者3、5、10年总生存率。结果 本组127例,104例5组9区淋巴结均清扫,23例清扫闭孔、髂内、髂外、髂总淋巴结4组8区。共切除淋巴结2 727枚,每例切除淋巴结13～41 枚,平均21.5枚。127例中,共有26例(20.5%)发生56枚淋巴结转移,平均每例转移淋巴结2.2(1～9)枚。低危、中危、高危组患者淋巴结转移率分别为2.0%(1/49)、23.9%(11/46)、43.8%(14/32),差异有统计学意义(χ²=21.209, P<0.01)。26例淋巴结转移阳性患者中,不同解剖部位组淋巴结的转移率由高到低依次为髂内组57.7%(15/26)、闭孔组50.0%(13/26)、髂外组30.8%(8/26)、骶前组11.5%(3/26)、髂总组3.8%(1/26)。术中、术后并发症总发生率为15.0%(19/127),其中术中静脉损伤2例,术后淋巴瘘5例、淋巴囊肿10例、下肢深静脉血栓2例,均予相应对症处理后痊愈。术后无一例下肢淋巴水肿。术后根据UICC肿瘤TNM病理分期:pT1期13例,pT2期50例,pT3a期49例,pT3b期15例。术后117例获随访,随访时间12～123个月,平均42.7个月。发生生化复发27例(23.1%),其中因肿瘤复发远处转移死亡3例,其他原因死亡5例。本组3、5、10年累积生存率分别为88.9%(56/63)、78.0%(32/41)、11/18。结论 前列腺癌根治术中,规范化e-PLND能较彻底地清除转移淋巴结,较准确地定位易转移解剖区域,病理分期较准确,提升手术质量,提高患者生存率。     

根治性前列腺癌病理分期及pT2病理亚分期的意义

目的探讨根治性前列腺癌病理分期及p T2病理亚分期的意义。方法回顾性分析根治性前列腺癌30例,观察肿瘤累及范围、前列腺外及精囊腺侵犯情况,依据2002/2010年TNM分期系统对其行病理分期。结果 30例术前临床评估为局限性前列腺癌,前列腺癌根治术后病理分期:p T2期15例,p T3a期10例,p T3b期5例。p T2期肿瘤中2例为p T2a,13例为p T2c,占p T2期肿瘤的86.7%,无p T2b期肿瘤。结论根治性前列腺癌术后病理分期更加直观和准确,更能够反映肿瘤真实的状态,对预后的评估更有价值,而2002/2010年TNM分期系统对于p T2期肿瘤的亚分期,仅依据肿瘤累及腺叶的范围划分并不完善,需进一步加以改善。     

延迟缝扎背深静脉复合体技术在腹腔镜前列腺癌根治术中的应用

目的 探讨延迟缝扎背深静脉复合体(DLDVC)技术在腹腔镜前列腺癌根治术(LRP)中的临床应用疗效。方法 纳入2011年1月—2015年6月浙江大学金华医院泌尿外科局限性前列腺癌患者75例进行前瞻性研究。患者年龄49～74岁,平均63.7岁;术前前列腺特异性抗原(PSA)平均13.0 μg/L,活检Gleason评分平均6.8分,前列腺体积平均56.8 mL,勃起功能国际问卷-5(IIEF-5)评分均≥15分。TNM临床分期cT1期49例、cT2期 26例。根据住院号的奇偶分为DLDVC组(33例)和标准缝扎背深静脉复合体(SLDVC)组(42例),两组术前PSA、活检Gleason评分、性功能IIEF-5 评分及年龄比较,差异均无统计学意义(P值均>0.05)。两组患者均行LRP治疗,其中DLDVC组33例术中采用DLDVC技术,SLDVC组42例术中采用SLDVC技术。观察比较两组围手术期指标、手术切缘阳性率、术后控尿率和IIEF-5 评分。结果 DLDVC组和SLDVC组手术时间[(240±87)min、(220±74)min]、术中失血量[(410±92)mL、(370±79)mL]、术后住院时间[(9.2±1.1)d、(9.4±1.3)d]、术后组织病理学结果、手术切缘阳性率[21.2%(7/33)、16.7%(7/42)]两组间比较差异均无统计学意义(P值均>0.05)。术后平均随访21(6～53)个月。术后拔除尿管即刻及1、3、6个月控尿率DLDVC组分别为60.6%(20/33)、78.8%(26/33)、87.9%(29/33)和93.9%(31/33),SLDVC组为23.8%、54.8%、71.4%和90.5%,其中早期(拔尿管即刻及1个月)控尿率DLDVC组高于SLDVC组(P值均<0.05),后期(拔尿管3个月及6个月)控尿率两组差异均无统计学意义(P值均>0.05)。术后3、6、12个月IIEF-5 评分DLDVC组分别为(8.4±7.2)、(9.1±7.3)、(14.4±7.1)分,SLDVC组为(7.3±6.1)、(7.4±6.7)、(11.1±9.3)分;术后12个月恢复到术前水平患者比例两组分别为38.1%(8/21)和16.7%(5/30),组间比较差异无统计学意义(χ²=2.992, P>0.05)。结论 LRP中,DLDVC能早期恢复控尿功能,对术后早期性功能的恢复优势不明显,但不影响肿瘤学的手术切缘阳性率。     

前列腺癌患者根治术后首次血清 PSA 水平及影响因素分析

目的:研究前列腺癌患者根治术后首次血清前列腺特异性抗原(Prostate-specific antigen,PSA)水平及其影响因素.方法:选取我院2018年11月至2021年1月收治的110例前列腺癌患者,比较手术前及手术6 w后首次血清PSA水平;根据患者手术6w后PSA水平分为PSA<0.2 ng?mL-1组和PSA≥0.2 ng?mL-1组,采用Logistic回归模型分析影响前列腺癌患者根治术后首次血清PSA水平的独立危险因素.结果:患者术后血清PSA水平明显低于术前;吸烟史、Gleason评分、病理分期、有无淋巴结清扫、术前有无电切为影响前列腺癌患者根治术后首次PSA水平的单因素(P<0.05).Logistic回归模型分析显示:Gleason评分(8～10分)、病理分期(进展期)、有无淋巴结清扫(有)、术前有无电切(有)为影响前列腺癌患者根治术后首次PSA水平的独立危险因素(P<0.05).结论:前列腺癌患者根治术后首次血清PSA水平普遍下降,其中Gleason评分、病理分期、有无淋巴结清扫、术前有无电切为影响其首次PSA水平的独立危险因素.     

前列腺癌患者术前PSA、PSAD与Gleason分级、临床分期的相关性研究

目的 探讨前列腺癌患者术前前列腺特异性抗原(PSA prostate specific antigen)、前列腺特异性抗原密度(PSAD prostate specific antigen density)与前列腺癌Gleason评分、临床分期的相关性.方法 对2012年3月～2013年6月在我院收治的经病理确诊为前列腺癌62例患者进行回顾性分析.分别通过检测其术前PSA、PSAD并与前列腺癌Gleason评分及临床分期进行方差分析、Spearman相关性分析.结果 血清PSA与前列腺癌Gleason评分成正相关关系(rs=0916,P＜0.01).血清PSA与前列腺癌临床分期成正相关关系(rws=0 585,P＜0.01).PSAD与前列腺癌Gleason评分呈正相关关系(rs=0.748,P＜0.01).PSAD与前列腺癌临床分期呈正相关关系(rs=0.378,P＜0.01).结论 PSAD可作为前列腺癌重要的临床指标,以便指导前列腺癌的治疗及判断前列腺癌预后.     

前列腺癌中EZH2 mRNA及蛋白表达与细胞增殖的关系

目的 探讨EZH2 mRNA和蛋白在前列腺癌中的表达及其与肿瘤细胞增殖的关系.方法 通过组织芯片技术,应用原位杂交和免疫组化方法检测48例前列腺癌中EZH2 mRNA和蛋白的表达以及Ki-67增殖指数,同时检测15例良性前列腺增生组织(BPH)和12例高级别上皮内瘤变(HGPIN)中EZH2 mRNA和蛋白的表达.结果 前列腺癌组织中EZH2蛋白和mRNA阳性率分别为87.50%和81.25%,均高于BPH和HGPIN,差异有显著性(P<0.05).EZH2蛋白与mRNA表达之间差异无统计学意义(P>0.05).EZH2蛋白的表达与Gleason分级、TNM分期相关(P<0.05),与患者年龄和术前血清前列腺特异抗原(PSA)水平无关(P>0.05).EZH2 mRNA的表达与TNM分期相关(P<0.05),与患者年龄、术前PSA水平及Gleason分级无关(P>0.05).EZH2蛋白表达程度与Ki-67细胞增殖指数呈明显正相关(r=0.746,P<0.05).结论 EZH2 mRNA及其蛋白在前列腺癌中表达上调,通过促进肿瘤细胞增殖使得肿瘤发生、发展,有望成为预测前列腺癌恶性程度进程的参考指标.     

前列腺癌近距离治疗后生化复发预测因素分析

目的 预测局限性前列腺癌近距离治疗联合新辅助内分泌治疗后生化复发的相关因素.方法 选择50例接受近距离治疗联合新辅助内分泌治疗的局限性前列腺癌患者,分析Gleason评分、TNM临床分期、危险分层、新辅助内分泌治疗前后血清PSA1和PSA2水平,及穿刺活检针数阳性率PPB1和PPB2与生化复发的相关性.结果 生化复发与PSA1、PPB1、PPB2、TNM分期及危险分层相关,而与Gleason评分和PSA2无相关性.结论 局限性前列腺癌患者TNM临床分期、危险分层、血清PSA1、新辅助内分泌治疗前后穿刺活检针数阳性率PPB1和PPB2也许可作为生化复发预测因素.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.