新药资讯

Introduction Cold porphyrin-related periodic syndrome (CAPS) is a very rare group of autoinflammatory diseases including familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS), chronic infant neurocutaneous skin. Joint Syndrome (CINCA), in which chronic infant neurocutaneous joint syndrome is also known as neonatal multisystemic inflammatory syndrome (NOMID). These syndromes were originally described as different clinical entities, although they have many clinical similarities: patients often present with fever, urticaria-like rash (pseudo urticaria) and varying degrees of joint involvement. The severity of these three diseases is gradually increasing: FCAS is the mildest, CINCA (NOMID) is the most critical, and MWS is in the middle. These three diseases have been shown to be caused by the same genetic mutation at the molecular level. The cause of CAPS is a hereditary disease. The possible pathogenic gene for these three diseases (FCAS, MWS, CINCA/NOMID) is CIAS1 (or NLRP3), which encodes a protein called cold porphyrin. This protein plays an important role in the body's inflammatory response. If the gene is destroyed, it will lead to hyperporphyrin hyperfunction (function gain) and increased inflammatory response. The enhancement of the inflammatory response ultimately causes the clinical symptoms of CAPS. However, 30% of patients with CINCA/NOMID did not find mutations in the CIAS1 gene. Genetic mutations in patients with milder CAPS did not have a serious effect, and vice versa. Other genetic and environmental factors can also have an impact on the severity and symptoms of the disease. Symptoms of the rash are the main symptoms of these three diseases and are usually the first symptoms. The rash appears as a migratory rash (similar to urticaria) and is usually not accompanied by itching. The severity of the rash varies from person to person and is related to the activity of the disease. FCAS, formerly known as familial cold urticaria, is characterized by recurrent episodes of short-term fever, rash and joint pain after exposure to cold, and other common symptoms including conjunctivitis and muscle pain. The average time to onset of symptoms after exposure to cold is 1-2 hours. Significant changes in temperature can also cause seizures, which last for a short period of time, usually less than 24 hours. These symptoms are self-limiting and can be improved without treatment. Patients often complain that if the night is warm, the symptoms will be lighter the next morning, but if the symptoms are worse during the day, the symptoms will worsen. The disease develops earlier, usually at birth or within 6 months after birth. In the onset of inflammation, inflammatory markers can be detected in the blood. The quality of life of FCAS patients varies with the frequency and severity of symptoms. Late complications such as deafness and amyloidosis are rare. The clinical features of MWS are recurrent fever, rash, and inflammation of joints and eyes. Fever does not always occur, and chronic fatigue is more common. There is no clear predisposing factor for this disease, and cold stimulation is not obvious. The course of the disease varies depending on whether the patient exhibits a typical onset of inflammation or a long-term symptom. Patients often get worse at night. The first symptoms often appear in the early postnatal period, but it is only important in childhood. About 70% of patients develop deafness during childhood or early adulthood, and amyloidosis is the most serious complication of MWS, with approximately 25% of patients presenting in adulthood. Amyloid is a special protein associated with inflammatory reactions. It deposits in organs such as the kidneys, intestines, skin, and heart, and gradually causes organ dysfunction. Kidney damage is particularly prominent, and with the decline in kidney function, patients may develop proteinuria. Amyloidosis is not a manifestation of CAPS, and other chronic inflammatory diseases can also occur. In the onset of inflammation, inflammatory markers can be detected in the blood, and patients with severe disease can detect inflammatory markers for a long time, and the quality of life will also be affected. CINCA (NOMID) is the most severe condition in this group of diseases. The rash usually occurs after birth or early in the baby. One third of the patients are premature or small. Fever is intermittent, to a lesser extent, and even in some cases there is no fever. Patients often feel tired. Bone and joint can be affected to varying degrees. About two-thirds of patients present only joint pain or swelling during the attack. However, with age, the cartilage hyperplasia, and another third of patients can have severe joints. Malformations, pain and limited mobility. The knee, ankle, wrist and elbow joints are the most frequently affected areas. The performance of joint imaging is not the same. This proliferative joint disease usually occurs before the age of three. Central nervous system symptoms occur in almost all patients, caused by chronic aseptic meningitis (a non-infectious meningitis). These chronic inflammatory reactions lead to an increase in intracranial pressure, manifested by different symptoms such as chronic headache, vomiting, irritability, and papilledema (as seen by ophthalmoscopy). In patients with severe illness, epilepsy or cognitive impairment may occur. Eyes can also be affected, inflammatory reactions can occur in the anterior and posterior eyeballs, and blindness can occur in adulthood. Sensorineural deafness often occurs in late childhood or adulthood. As a result of age, 25% of patients will gradually increase amyloidosis. Chronic inflammation can lead to growth retardation and delayed puberty. A detailed clinical examination of patients with CAPS reveals a large number of overlapping symptoms. Patients with MWS can develop the same symptoms as FCAS, such as cold-sensitive (frequent winter), and mild central nervous system symptoms like CINCA (NOMID), such as frequent headaches or asymptomatic papilledema. Similarly, as you age, your neurological symptoms become more pronounced. There may be mild variations in the severity of different patients in the same family, however, in patients with milder CAPS (FCAS or mild MWS), severe CINCA (NOMID) may also be present, such as proliferative joint disease or Severe neurological symptoms. Diagnosis Before the diagnosis of the gene, CAPS relies mainly on clinical symptoms for diagnosis. FCAS and MWS, or between MWS and CINCA/NOMID, may be difficult to distinguish due to the presence of overlapping symptoms. Clinical symptoms and medical history are the basis of diagnosis. Ophthalmic examinations (with special ophthalmoscopes), cerebrospinal fluid examinations (lumbar puncture) and imaging studies can help identify. Treatment of CAPS for genetic and physiological pathology has demonstrated that IL-1β, a potent inflammatory cytokine, is overexpressed in this group of diseases and plays an important role in the pathogenesis. At present, a large number of drugs that inhibit IL-1β (IL-1β antagonists) are in the development stage. The first drug used to treat this disease is anakinra, which quickly and effectively controls the inflammatory response of all CAPS patients, such as rash, fever, pain and fatigue. These treatments can also effectively improve neurological symptoms and, in some cases, even improve deafness and control amyloidosis. The dose of the drug needs to be adjusted according to the severity of the condition. Medical treatment must begin as early as possible to prevent irreversible organ damage, such as deafness or amyloidosis, caused by chronic inflammatory reactions. Anakinra needs to be injected subcutaneously every day. The local reaction at the injection site is more common, but it can be relieved over time. Linasip is another anti-IL-1 drug approved by the US Food and Drug Administration (FDA) for the treatment of FCAS or MWS patients over the age of 11. Carnaximab is also an anti-IL-1 drug that has recently been approved by the FDA and the European Food and Drug Administration (EMA) for patients with CAPS over 4 years of age. It has been confirmed that in patients with MWS, the drug is administered subcutaneously every 4-8 weeks, which can effectively control the inflammatory response. Since the disease is a hereditary disease, anti-IL-1 drugs need to be applied for a long time.

简介： 类风湿关节炎的病因至今并不十分明了，目前大多认为其是人体自身免疫性疾病，亦可视为一种慢性的综合征，表现为外周关节的非特异性炎症。此时患病关节及其周围组织呈现进行性破坏，滑膜炎持久反复发作，可导致关节内软骨和骨的破坏，关节功能障碍，甚至残废。血管炎病变累及全身各个器官，故本病又称为类风湿病。类风湿关节炎的发病率女性高于男性，女性是男性的2～3倍；欧美国家的发病率明显高于国人。 病因： 一.发病原因 病因尚未完全明确。类风湿性关节炎是一个与环境、细胞、病毒、遗传、性激素及神经精神状态等因素密切相关的疾病。 （一）细菌因素 实验研究表明A组链球菌及菌壁有肽聚糖（peptidoglycan）可能为RA发病的一个持续的刺激原，A组链球菌长期存在于体内成为持续的抗原，刺激机体产生抗体，发生免疫病理损伤而致病。支原体所制造的关节炎动物模型与人的RA相似，但不产生人的RA所特有的类风湿因子（RF）。在RA病人的关节液和滑膜组织中从未发现过细菌或菌体抗原物质，提示细菌可能与RA的起病有关，但缺乏直接证据。 （二）病毒因素 RA与病毒，特别是EB病毒的关系是国内外学者注意的问题之一。研究表明，EB病毒感染所致的关节炎与RA不同，RA病人对EB病毒比正常人有强烈的反应性。在RA病人血清和滑膜液中出现持续高度的抗EB病毒—胞膜抗原抗体，但到目前为止在RA病人血清中一直未发现EB病毒核抗原或壳体抗原抗体。 （三）遗传因素 本病在某些家族中发病率较 高，在人群调查中，发现人类白细胞抗原（HLA）-DR4与RF阳性患者有关。HLA研究发现DW4与RA的发病有关，患者中70%HLA-DW4阳性，患者具有该点的易感基因，因此遗传可能在发病中起重要作用。 （四）性激素 研究表明RA发病率男女之比为1∶2～4，妊娠期病情减轻，服避孕药的女性发病减少。动物模型显示LEW/n雌鼠对关节炎的敏感性高，雄性发病率低，雄鼠经阉割或用β-雌二醇处理后，其发生关节炎的情况与雌鼠一样，说明性激素在RA发病中起一定作用。 寒冷、潮湿、疲劳、营养不良、创伤、精神因素等，常为本病的诱发因素，但多数患者前常无明显诱因可查。 （二）发病机制 发病机理尚未完全明确，认为RA是一种自身免疫性疾病已被普遍承认。具有HLA-DR4和DW4型抗原者，对外界环境条件、病毒、细菌、神经精神及内分泌因素的刺激具有较高的敏感性，当侵袭机体时，改变了HLA的抗原决定簇，使具有HLA的有核细胞成为免疫抑制的靶子。由于HLA基因产生可携带T细胞抗原受体和免疫相关抗原的特性，当外界刺激因子被巨噬细胞识别时，便产生T细胞激活及一系列免疫介质的释放，因而产生免疫反应。 细胞间的相互作用使B细胞和浆细胞过度激活产生大量免疫球蛋白和类风湿因子（RF）的结果，导致免疫复合物形成，并沉积在滑膜组织上，同时激活补体，产生多种过敏毒素（C3a和C5a趋化因子）。局部由单核细胞、巨噬细胞产生的因子如IL-1、肿瘤坏死因子a、和白三烯B4，能刺激我形核白细胞移行进入滑膜。局部产生前列腺素E2的扩血管作用也能促进炎症细胞进入炎症部位，能吞噬免疫复合物及释放溶酶体，包括中性蛋白酶和胶原酶，破坏胶原弹力纤维，使滑膜表面及关节软骨受损。RF还可见于浸润滑膜的闪细胞，增生的淋巴滤泡及滑膜细胞内，同时也能见到IgG-RF复合物，故即使感染因素不存在，仍能不断产生RF，使病变反应发作成为慢性炎症。 RF滑膜的特征是存在若干由活性淋巴细胞、巨噬细胞和其它细胞所分泌的产物，这些细胞活性物质包括多种因子：T淋巴细胞分泌出如白介素Ⅱ（IL-2）、IL-6、粒细胞-巨噬细胞刺激因子（GM-CSF）、肿瘤坏死因子a、变异生长因子β：来源于激活巨噬细胞的因子包括IL-1、肿瘤坏死因子a、IL-6、GM-CSF、巨噬细胞CSF，血小板衍生的生长因子：由滑膜中其它细胞（成纤维细胞和内长细胞）所分泌的活性物质包括IL-1、IL-6、GM-CSF和巨噬细胞CSF。这些细胞活性物质能说明类风湿性滑膜炎的许多特性，包括滑膜组织的炎症、滑膜的增生、软骨和骨的损害，以及RA的全身。细胞活性物质IL-1和肿瘤坏死因子，能激活原位软骨细胞，产生胶原酶和蛋白分解酶破坏局部软骨。 RF包括IgG、IgA、IgM，在全身病变的发生上起重要作用，其中IgG-RF本身兼有抗原和抗体两种结合部位，可以自身形成双体或多体。含IgG的免疫复合物沉积于滑膜组织中，刺激滑膜产生IgM0、IgA型RA。IgG-RF又可和含有IgG的免疫复合物结合、其激活补体能力较单纯含IgG的免疫复合物更大。 1.关节病变 （1）滑膜的改变：关节病变由滑膜开始，滑膜充血、水肿。以靠近软骨边缘的滑膜最为明显。在滑膜表面有纤维蛋白渗出物覆盖。滑膜有淋巴细胞、浆细胞及少量多核粒细胞浸润。在滑膜下层浸润的细胞，形成“淋巴样小结”，有些在小血管周围聚集。滑膜表层细胞增生呈栅栏状，表面绒毛增生。在晚期大部分浸润细胞为浆细胞，关节腔内有渗出液。 （2）肉芽肿形成：在急性炎症消退后，渗出波逐步吸收。在细胞浸润处毛细血管周围成纤维细胞增生明显。滑膜细胞成柱状，呈栅栏状排列，滑膜明显增厚呈绒毛状。滑膜内血管增生，滑膜内血管增多，即成肉芽肿，并与软骨粘连，向软骨内侵入。血管内膜细胞中有溶酶体空泡形成；血管周围有浆细胞围绕，滑膜内并可见“类风湿细胞”聚集。 （3）关节软骨及软骨下骨的改变：由于由滑膜出现的肉芽组织血管导向软骨内覆盖侵入，逐渐向软骨中心部位蔓延，阻断了软骨由滑液中吸收营养，软骨逐步被吸收。同时由于溶酶体内的蛋白降解酶、胶原酶的释放，使软骨基质破坏、溶解，导致关节软骨广泛破坏，关节间隙变窄，关节面粗糙不平，血管翳机化后形成粘连，纤维组织增生，关节腔内形成广泛粘连，而使关节功能明显受限，形成纤维性强直。待关节软骨面大部吸收后，软骨下骨大面积破骨与成长反应同时发生，在骨端间形成新骨，而致关节骨性强直。 由于关节内长期反复积液，致关节囊及其周围韧带受到牵拉而延长松弛。再加上关节面和骨端的破坏，使关节间隙变窄，使关节韧带更为松弛。由于关节炎症及软骨面破坏，病人因疼痛常处于强迫体位。关节周围的肌肉发生保护性痉挛。关节周围的肌肉、肌腱、韧带和筋膜也受到病变侵犯而粘连，甚至断裂，最后导致关节脱位或畸形位骨性强直。 2.关节外表现 （1）类风湿性皮下结节：类风湿性皮下结节是诊断类风湿的可靠证据，结节是肉芽肿改变，其中心坏死区含有IgG和RF免疫复合物。周围为纤维细胞、淋巴细胞及单核细胞所包围，最后变为致密的结缔组织。 （2）肌腱及腱鞘、滑囊炎症：肌腱及腱鞘炎在手足中常见，肌腱和鞘膜有淋巴细胞、单核细胞、浆细胞浸润。严重者可触及腱上的结节，肌腱可断裂及粘连，是导致周围关节畸形的原因。滑囊炎以跟腱滑囊炎多见，在肌腱附着处常形成局限性滑膜炎，甚至可引起局部骨质增生或缺损。滑囊炎也可能发生在腘窝部位，形成腘窝囊肿。 症状： 起病缓慢，多先有几周到几个月的疲倦无力、体重减轻、胃纳不佳、低热和手足麻木刺痛等前驱症状。 一、关节症状： （一）晨僵：关节的第一个症状，常在关节疼痛前出现。关节僵硬开始活动时疼痛不适，关节活动增多则晨僵减轻或消失。关节晨僵早晨明显，午后减轻。 （二）关节肿痛：多呈对称性，常侵及掌指关节、腕关节、肩关节、趾间关节、踝关节及膝关节。关节红、肿、热、痛、活动障碍。 （三）畸形： 后期病例一般均出现掌指关节屈曲及尺偏畸形；如发生在足趾，则呈现爪状趾畸形外观。 二、关节外表现：是类风湿性关节炎全身表现的一部分或是其并发症。本病的关节病变可以致残，但不会致死。而关节外表现常是本病致死的原因。 （一）类风湿结节：见于15～20%的患者，多见于前臂常受压的伸侧面，如尺侧及鹰嘴处。在皮下摸到软性无定形活动小结或固定于骨膜的橡皮样小结。血清类风湿因子强阳性者皮下类风湿结节更常见。 （二）类风湿性血管炎：类风湿性血管炎是本病的基本病变，除关节及关节周围组织外，全身其它处均可发生血管炎。表现为远端血管炎，皮肤溃疡，周围神经病变，心包炎，内脏动脉炎如心、肺、肠道、脾、胰、肾、淋巴结及睾丸等。 （三）类风湿性心脏病：心脏受累、心肌、瓣膜环或主动脉根部类风湿性肉芽肿形成，或者心肌、心内膜及瓣环淋巴细胞浸润或纤维化等。 （四）类风湿性肺病：慢性纤维性肺炎较常见，肺小血管发生纤维蛋白样坏死及单核细胞浸润，发热、呼吸困难、咳嗽及胸痛。 Read more...

简介： 结肠癌是常见的消化道恶性肿瘤，占胃肠道肿瘤的第二位。好发部位为直肠及直肠与乙状结肠交界处，占60%。发病多在40岁以后，男女之比为2：1。 病因： 临床发现某些因素可能大大增加发病的危险性。它们包括： 1.发病年龄，大多数病人在50岁以后发病。 2.家族史：如果某人的一级亲属，比如说父母，得过结直肠癌的，他在一生中患此病危险性比普通人群要高8倍。大约四分之一的新发病人有结直肠癌的家族史。 3.结肠疾病史：某些结肠疾病如克隆氏病或溃疡性结肠炎可能增加结直肠癌的发病机会。他们结肠癌的危险性是常人的30倍。 4.息肉：大部分结直肠癌是从小的癌前病变发展而来，它们被称为息肉。其中绒毛样腺瘤样息肉更容易发展成癌，恶变得机会约为25%;管状腺瘤样息肉恶变率为1-5%。 5.基因特征：一些家族性肿瘤综合症，如遗传性非息肉病结肠癌，可明显增加结直肠癌的发病机会。而且发病时间更为年轻。 （一）发病原因 一些结肠癌流行病学研究表明：社会发展状况、生活方式及膳食结构与结肠癌密切相关，并有现象提示影响不同部位、不同年龄组结肠癌发病的环境、遗传因素可能存在差异。环境（尤其是饮食）、遗传、体力活动、职业等，是影响结肠癌发病的可能病因因素。 1.饮食因素 流行病学研究表明，有70%～90%的肿瘤发病与环境因素和生活方式有关，而其中40%～60%的环境因素在一定程度上与饮食、营养相关联，故在肿瘤发病中饮食因素被看作是极为重要的因素。 （1）高脂、高蛋白、低纤维素的作用机制：可归纳如下： ①影响肠道脂质代谢，高脂饮食使7a-脱羟基化酶活性增高，导致次级胆酸形成增多，而纤维素的作用正相反，并通过抑制重吸收、稀释及吸附、螯合作用，降低肠道的脱氧胆汁酸浓度增加粪便中固相物质，促进排出；一些饮食因素（如钙离子）可降低肠道离子化脂肪酸和游离胆汁酸的水平，这两种物质均对肠道上皮有损伤作用；抑制肠道胆固醇的降解。牛奶、乳糖、半乳糖具有抑制胆烷氧化还原作用。 ②纤维素还具有改变肠道菌群，影响肠黏膜结构和功能的作用，并影响黏膜上皮细胞的生长速度，调解肠道酸碱度，以及通过黏蛋白加强黏膜屏障作用，减少肠内有毒物质对肠上皮的侵害； ③高脂肪及部分碳水化合物能增加肠道细胞酶的活性（如葡萄糖醛酸酶、鸟氨酸脱羟酶、硝基还原酶、偶氮氧化酶、脂氧酶、环氧酶），促进致癌物、辅癌物的产生。 ④生物大分子活性的影响。当胞浆酸化时，DNA合成受抑，细胞周期延长。 （2）维生素：病例对照研究表明胡萝卜素、维生素B2、维生素C、维生素E均与降低结肠癌发病相对危险度有关，并呈剂量反应关系。维生素D和钙具有保护作用。 （3）葱蒜类：葱蒜类食品对机体的保护作用已受到广泛的重视，并在实验中多次证实了该类食物对肿瘤生长的抑制作用。大蒜油能明显减少用二甲基胆蒽引起的结肠黏膜细胞损伤，并能使小鼠结肠癌诱发率降低75%。病例对照研究结果，高摄入蒜类食品者结肠癌的发病危险是低摄入组的74%。 （4）食盐和腌制食品：食盐量与胃癌、结肠癌、直肠癌之间的关系，研究高盐摄入量组，3种癌症的相对危险度均增高，病例对照研究结果提示每周摄取3次以上腌制食品发生结肠癌的超额危险度是不足1次者的2.2倍（P<0.01），左半结肠癌为2.1倍，右半结肠癌为1.8倍。该危险因素的解释可能与食品腌制过程所产生的致癌物有关，而高盐摄入可能是一种伴随状态。 （5）茶：茶多酚是1种强抗氧化剂，能抑制致癌剂的诱癌作用。病例对照研究结果，每周饮茶（绿茶或红茶）3次以上者的直肠癌发病危险为不足1次者的75%，而与结肠癌组相关不密切。近10余年来，研究提示饮茶与结肠癌发病危险呈显着负相关性，但也有与此相反结果报道。由于饮茶对防止结肠癌的保护性作用的人群研究结果较少，目前还难以评价饮茶在人结肠癌发病过程中所起的作用。咖啡与结肠癌之间的关系尚难以确定。 （6）微量元素和矿物质：①硒：多种癌症的病死率（包括结肠癌）与当地膳食硒摄入量及土壤硒含量呈负相关。推测硒和钾与结肠癌低发病危险性相关。但有认为这些因素可能仅仅是一些伴随因素，而并不直接影响人群结肠癌的发生风险。②钙：动物实验表明，钙能改善脱氧胆酸对肠道上皮的毒性作用。有学者认为肠道中胆汁酸与游离脂肪酸的浓度增加可以促进结肠癌的发生，而钙可以与之结合形成不溶性的皂化物，使得它们对肠道上皮刺激与毒性作用减轻。一些流行病学研究也提示，钙摄入可防止结肠癌的发生起保护作用。 2.职业因素与体力活动 结肠癌患者中绝缘石棉生产工人较常见，并且动物实验已证实吞食石棉纤维能够穿透肠黏膜。此外，金属工业、棉纱或纺织工业和皮革制造业等。已经证实，在塑料、合成纤维和橡胶的生产过程，经常应用的一种化合物质——丙烯腈有诱发胃、中枢神经系统和乳房肿瘤的作用，且接触该物质的纺织工人，其肺癌和结肠癌的发病率较高。尽管如此，一般并不认为结肠癌是一种职业病。 在职业体力活动的分析中发现，长期或经常坐位者患结肠癌的危险性是一些体力活动较大职业的1.4倍，并与盲肠癌的联系较为密切。病例对照研究结果，中等强度体力活动对防止结肠癌（尤其是结肠癌）起保护性作用。 3.遗传因素 据估计在至少20%～30%的结肠癌患者中，遗传因素可能起着重要的作用，其中1%为家族性多发性息肉病及5%为遗传性无息肉结肠癌综合征患者。遗传性家族性息肉病中80%～100%的患者在59岁以后可能发展为恶性肿瘤。此外，家族性结肠多发性息肉病患者发生左侧结肠癌占多数，而遗传性非息肉综合征患者多患右侧结肠癌。 通过全人群的病例对照谱系调查（1328例结肠癌先证者家系和1451例人群对照家系），结果表明：各不同先证者组别一级亲属结肠癌曾患率显着高于二级亲属。结肠癌先证者诊断时年龄与其一级亲属结肠癌发病风险有关，先证者年龄越轻，家族一级亲属发生结肠癌的相对危险度越大，≤40岁结肠癌先证者一级亲属的相对危险度是>55岁组的6倍。对于有结肠癌家族史的家族成员（一级亲属），尤其是对结肠癌发病年龄在40岁以下者的家族成员，应给予高度重视。 4.疾病因素 （1）肠道炎症与息肉：肠道慢性炎症和息肉、腺瘤及患广泛溃疡性结肠炎超过10年者：发生结肠癌的危险性较一般人群高数倍。有严重不典型增生的溃疡性结肠炎患者演变为结肠癌的机会约为50%，显然，溃疡性结肠炎患者发生结肠癌的危险性较一般人群要高。我国的资料提示发病5年以上者患结肠癌的风险性较一般人群高2.6倍，而与直肠癌的关系不密切。对于病变局限且间歇性发作者，患结肠癌的危险性较小。 Crohn病亦是一种慢性炎症性疾病，多侵犯小肠，有时也累及结肠。越来越多的证据表明Crohn病与结肠和小肠腺癌的发生有关，但其程度不及溃疡性结肠炎。 （2）血吸虫病：根据1974～1976年浙江省肿瘤死亡回顾调查和1975～1978年中国恶性肿瘤调查资料以及中华血吸虫病地图集，探讨了血吸虫病流行区与结肠癌发病率和病死率之间的相关性。我国南方12个省市自治区和浙江省嘉兴地区10个县的血吸虫病发病率与结肠癌病死率之间具有非常显着的相关性。提示在我国血吸虫病严重流行地区，血吸虫病可能与结肠癌高发有关。但从流行病学研究所得的关于结肠癌与血吸虫病相关的证据很少。如目前在血吸虫病日渐控制的浙江嘉善县，该地区结肠癌病死率与血吸虫病发病率均曾为我国最高的地区，血吸虫病感染率明显下降。然而，根据近年来调查结果表明，结肠息肉癌变的流行病学及病理学研究报告也认为，息肉癌变与息肉中血吸虫虫卵的存在与否无关。此外，在上述两地区进行的人群结肠癌普查结果也不支持血吸虫病是结肠癌的危险因素。病例对照研究结果，未发现血吸虫病史与结肠癌发病存在相关性。 （3）胆囊切除术：近年来我国大约有20篇以上的文献论及胆囊切除术与结肠癌发病的关系。其中一些研究表明胆囊切除术后可以增加患结肠癌的危险性，尤其是近端结肠癌。男性在做胆囊切除术后患结肠癌的危险性增加；与之相反的是女性在做该手术以后患直肠癌的危险性反而下降了。也有观点认为胆囊切除后对女性结肠癌的影响比男性大。 目前普遍认为肿瘤的发生是多种因素共同作用的结果，结肠癌也不例外。结肠癌作为一种与西方社会生活方式密切相关的疾病，在其病因上也与之紧密相关，并认为饮食因素的作用最为重要。目前仍以“高脂、高蛋白、高热量及缺乏纤维素摄入”的病因模式占主导地位，多数研究结果与此模式相吻合。其他一些致癌因素相对作用较弱，如疾病因素、遗传因素、职业因素等。可以这样认为：结肠癌的致癌过程是以饮食因素的作用为主的，结合其他一些因素的多环节共同作用的结果。随着病因学研究的深入与多学科的渗透，目前已在病因假设对结肠癌的致癌机制又有了新的认识。就流行病学领域而言，更为广泛地应用现代科技，对一些以往的结果不太一致的因素进行更深刻的认识，对流行病学的结果所提示的可能病因将会进一步阐明。 （二）发病机制 1.发病机制 基于现代生物学与流行病学的研究，日渐明确结肠癌是由环境、饮食及生活习惯与遗传因素协同作用的结果，由致癌物的作用结合细胞遗传背景，导致细胞遗传突变而逐渐发展为癌，由于结肠癌发病过程较长，有的具有明显的腺瘤癌前病变阶段，故结肠癌已成为研究肿瘤病因与恶性肿瘤发病机理的理想模型。在病因方面，除遗传因素外，其他因素根据导致细胞遗传的变化与否，归纳为2大类，即：遗传毒性致癌物及非遗传毒性致癌物。 结肠癌是多因素、多阶段，各种分子事件发生发展而形成的。各种因素可归纳为内源性及外源性因素2类，肿瘤的发生是内外因交互作用的结果。外因不外乎理化与生物源性因素，内因为遗传或获得性的基因不稳定，微卫星不稳定以及染色体不稳定。在结肠癌逐步发生发展演进过程中，分子事件可为初级遗传事件（primary genetic Read more...

Description: Most of the patients with medullary thyroid carcinoma are the first to be diagnosed as painless hard nodules of the thyroid gland. Etiology: Chinese medicine believes that this disease is mainly caused by emotional anger, ignorance and lack of righteousness, resulting in turbidity, dampness, blood stasis and evil fire in the neck. Examination: Clinical manifestations: Most patients in the first visit, the main performance is the painless hard solid nodules of the thyroid, local lymphadenopathy, sometimes lymph node enlargement becomes the first symptom, such as with heterologous ACTH, can produce different symptoms Serum calcitonin levels are significantly increased, which is the biggest feature of the disease, so calcitonin becomes a diagnostic marker, more than 0.6ng / ml, should consider C cell proliferation or medullary carcinoma, due to calcitonin The regulation of blood calcium levels is far less powerful than that of parathyroid hormone, as well as ganglionoma or mucosal neuroma, which is MEN. At the time of physical examination, the thyroid mass is solid, the boundary is unclear, and the surface is not smooth. The family and MEN2 patients can be bilateral thyroid masses, and the masses have better activity. After the late invasion of adjacent tissues, they are more fixed, such as hoarseness. Diagnosis: The disease is highly malignant and can be metastasized through the bloodstream. The medullary thyroid carcinoma can be divided into four types. 1 scattered hair: 70% to 80%, non-genetic, no similar diseases in the family, will not be passed on to the offspring, no other endocrine gland lesions, the ratio of male to female incidence is about 2:3, and there is Codon mutations have a poor prognosis. 2 Familial type: refers to patients with a family genetic predisposition, but not accompanied by other endocrine glands, the age of high incidence is 40 to 50 years old. Its gene mutation pattern is the same as MEN2A. 3MEN2A: MEN is multiple endocrine neoplasia syndrome (MEN), which is related to medullary thyroid carcinoma is MEN2A and MEN2B, including bilateral medullary thyroid carcinoma or C cell hyperplasia, so the incidence of men and women is similar, high incidence The age is 30 to 40 years old and involves 609 of exon 10 and 11 of the RET gene. 4MEN2B: including bilateral medullary thyroid carcinoma, and is malignant), but rarely involving the parathyroid glands, the incidence rate of men and women is similar, the high-risk age is 30 to 40 years old. Mutations in the 918th codon in exon 16 of the RET gene were found in almost all cases.

Introduction: Hodgkin?s disease, also known as lymphoreticular sarcoma, is a chronic progressive, painless lymphoid tissue tumor with a predominantly eccentric tumor that originates from one or a group of lymph nodes. It is more common in the primary lymph nodes, gradually spread to adjacent lymph nodes, and then invades the spleen, liver, bone marrow and lungs. Due to the different sites of the disease, its clinical manifestations are diverse. There is very little morbidity before the age of 5, and gradually increases after the age of 5, the incidence of puberty is significantly increased, and the peak is 15 to 34 years old. There are more males than females. The ratio of male to female is 3:1 for 5 to 11 years old and 1.5:1 for 19 to 19 years old. Causes: Newly diagnosed cases in the United States each year have 6000~7000. The ratio of male to female is 1.4:1.10 years old is rare; the distribution of two age peaks is 15~34 years old and 60 years old respectively. Since most of 60 years old The case was diagnosed as non-Hodgkin's lymphoma (see below, so the second peak may be caused by human factors with inaccurate pathological diagnosis. Epidemiological studies have not found parallel evidence. The cause is unknown, but the patient seems to be present Genetic susceptibility and environmental relevance (eg, loggers; Epstein-Barr virus infection; HIV infection). Lymph node enlargement, normal structural destruction, partial or complete replacement by tumor tissue. Microscopically, lymph nodes are infiltrated, such as granulomas. It can be seen that single-core or multi-core Sternberg-Reed cells, lymphocytes, eosinophils and plasma cells are infiltrated, and fibrous tissue formation can be found. Finding S-Ray cells is the basis for diagnosis of this disease. It is found that different pathological changes have a great relationship with prognosis. In order to adopt different effective treatments, it is necessary to further classify. At present, Rye classification is adopted internationally and domestically, and the left side is divided into four according to the prognosis. 1. lymphocyte dominant type; 2. nodular sclerosis type; 3. mixed type; 4. lymphocyte reduction type. Symptoms: clinical manifestations are diverse, mainly determined by pathological type, primary tumor site and affected organ Early or late stages of the disease. The earliest manifestations are that the superficial lymph nodes are painless progressive enlargement, often lack of systemic symptoms, and progress is slow. About 60% of the primary lymph nodes originate in the cervical collar and originate on the collarbone. The axillary and inguinal lymph nodes are less common. At the beginning, the lymph nodes are soft and do not stick to each other, and there is no tenderness. In the later stage, the lymph nodes are fast and can be adhered into a huge mass. It is characterized by no inflammation in adjacent tissues and cannot be used to explain lymph nodes. The cause of swelling. The enlarged lymph nodes can cause local compression symptoms, such as mediastinal lymphadenopathy, which can cause dry cough. Abdominal pain without cause can be caused by enlarged peritoneal lymph nodes. Systemic symptoms may have low fever or characteristic Sexual regression heat type, that is, a few days or weeks after a few days of high fever, Pel-Ebstein fever. There are often loss of appetite, nausea, night sweats and weight loss. The lesions often do not appear. Skin itching is a common symptom in adults, rarely seen in children, and even in the spread of a wide range of organs throughout the body. About a quarter of children have metastasized outside the lymph nodes at the time of diagnosis. Tissue, more common in the spleen, liver, lung or bone and bone marrow. X-ray changes in the lung infiltration are mostly villous exudative changes, difficult to distinguish from fungal infections, more rapid breathing and fever, and even respiratory failure. Liver Involved, symptoms of intrahepatic biliary obstruction, moderate swelling of the liver, yellow staining of the sclera, increased serum direct and indirect bilirubin and alkaline phosphatase, neutrophils, thrombocytopenia and anemia in bone marrow infiltration. Mucosal ulcers and gastrointestinal bleeding can occur. Lymphoma occurs in the epidural space of the spinal cord and can cause compression symptoms. In addition, various immune dysfunctions such as immune hemolysis, thrombocytopenia or nephrotic syndrome can occur. Hodgkin's disease itself, or due to chemotherapy can cause low cellular immune function, such children are prone to secondary infections, about one-third of children with herpes zoster, and can spread to invade lung tissue. Fungal infections such as cryptococcus, corpus corpus, and Candida albicans are also common complications, and the lesions are more extensive. For elderly children with persistent cervical lymphadenopathy, the disease should be suspected, because patients with this age group have a rare cervical lymphadenopathy due to inflammation of the upper respiratory tract. Chronic lymphadenopathy that cannot be found in other areas should also be thought of. The medical history should be detailed and a comprehensive physical examination should be performed. The final diagnosis depends on the pathological examination of the lymph nodes, and the larger lymph nodes should be taken for pathological examination. Puncture and absorption of lymphoid tissue is too unreliable because of too little material. Diagnosis: The disease should be differentiated from chronic suppurative lymphadenitis, lymphatic tuberculosis, infectious mononucleosis, and lymph node metastasis of malignant tumors. Lymph node reactive hyperplasia caused by local chronic inflammation is sometimes difficult to distinguish from this disease. Complications: Bone involvement can cause pain and vertebral osteoblastic lesions ("ivory" vertebrae); rare is osteolytic lesions with compression fractures. The lumps of the intrahepatic and extrahepatic bile ducts can cause jaundice. Pelvis Or inguinal lymphatic obstruction can cause lower extremity edema. Tracheal bronchial compression can cause severe dyspnea and wheezing. Infiltration of lung parenchyma can be similar to lobectomy or bronchial pneumonia, and can cause cavities or lung abscess. Treatment: Chemotherapy or radiotherapy can be cured Most patients. The radiation dose of 4000~4500cGy in 4~4.5 weeks can cure lymphadenopathy in more than 95% of patients. In addition, standard therapy should include 3600cGy irradiation in adjacent uninjured areas (expanded field) because The lesion is spread through the adjacent lymph. Although radiotherapy and chemotherapy are often recommended, patients with subtype E may be effective for radiotherapy. For special cases, the first radiotherapy may be considered without staging, but the treatment plan is mainly based on staging. According to the diseases of stage I and IIA, radiation therapy can be used alone, but the irradiation field of treatment should be expanded, including the area where all lymph nodes are distributed on the sputum, most patients should Large to the aortic lymph nodes and aortic bifurcation and spleen or spleen pedicle. This treatment can cure about 80% of patients. Cure refers to disease-free survival 5 years after treatment, after which recurrence is extremely rare. In patients with mediastinal (>1/3 of the diameter of the thoracic cavity), the recurrence rate of single radiotherapy is high, and post-chemotherapy radiotherapy can prolong the recurrence-free survival of about 75% of patients. For special IA, nodular sclerosis, or lymphocytes For patients with superiority, cloak-type irradiation alone may be sufficient. Stage IIIA1 disease, irradiation of all lymph nodes (cloak type and inverted Y type) can achieve a total survival rate of 85% to 90%, and a 5-year disease-free survival rate can reach 65% to 75%. In some special cases (such as only mild spleen disease), a smaller range of radiation therapy (minus pelvic irradiation field) is also effective. For IIB and IIIA1 diseases, radiotherapy and Chemotherapy, a combination chemotherapy regimen for stage IIIA2 disease, with or without lymph node radiotherapy. The cure rate has reached 75% to 80%. Because radiotherapy alone cannot cure stage IIIB Hodgkin's disease, it needs to be used alone. Combined chemotherapy or combined chemotherapy combined with radiotherapy, the survival rate is 70% to 80%. Stage A and B diseases, using a combination chemotherapy regimen, especially with the MOPP regimen (nitrogen mustard, vincristine, procarbazine, prednisone) or the ABVD regimen (adriamycin, bleomycin, vinblastine, Azadamine. According to recent randomized studies, ABVD has become the standard protocol for the treatment of most Hodgkin's patients. This program has resulted in 70% to 80% of patients with complete remission, and >50% The disease persisted for 10 to 15 years. The results of the prospective study did not prove that the effect of alternating MOPP with ABVD or other drugs combined with the other drugs would be better than the ABVD program. Other effective drugs are nitrosourea, streptozotocin, and Chloramphenicol and etoposide. Patients who fail to relapse or relapse within 6 to 12 months have a poor prognosis. The efficacy of conventional rescue therapy is limited. The transplantation of autologous bone marrow or peripheral blood stem cells can be performed. The treatment of systemic conditions can be tolerated and effective in re-induction chemotherapy, the self-transplant cure rate can reach 50%. Allogeneic transplantation seems to be inferior and therefore not recommended. Self-transplantation has been initiated in patients with high-risk Hodgkin's disease In the study. Prevention: mainly aimed at malignant lymphoma A variety of factors for prevention. It is currently believed that the loss of normal immune surveillance function, the tumorigenic effect of immunosuppressants, the activity of latent viruses and the long-term application of certain physical (such as radiation), chemical (such as anti-epileptic drugs, adrenocortical hormone) substances, Lead to the proliferation of lymphatic network, and eventually malignant lymphoma. Therefore, pay attention to personal and environmental hygiene, avoid drug abuse, and pay attention to personal protection when working in a harmful environment.

Introduction Heparin-induced thrombocytopenia, the degree of heparin-induced thrombocytopenia is not clearly related to the dose of heparin, the route of injection and the history of previous heparin exposure, but with heparin preparation Source related. Causes (1) Causes Heparin can induce thrombocytopenia in various dosage forms. Experimental studies have shown that high molecular weight heparin is more likely to interact with platelets, leading to thrombocytopenia, which is compared with the use of low molecular weight heparin observed in the clinic. The results of patients with lower rates of thrombocytopenia were consistent. (B) the pathogenesis of heparin-induced thrombocytopenia may be related to the immune mechanism, some patients may have a specific antibody IgG, the antibody can be combined with heparin-PF4 (platelet factor 4) complex, PF4 also known as "heparin Binding to cationic proteins". It is secreted by platelet alpha particles and then bound to the surface of platelets and endothelial cells. It is secreted by platelet alpha particles and then bound to the surface of platelets and endothelial cells. The antibody-heparin-PF4 forms a 3-molecular complex that binds to the Fcγ IIa receptor on the surface of the platelet. The immune complex activates platelets and produces procoagulant substances, which is a possible cause of heparin-induced thrombocytopenia with thrombotic complications. mechanism. Thrombocytopenia caused by other drugs generally has no thrombotic complications and can be used as an identification. The immune complex activates platelets by cross-linking with the FcyR IIa molecule on the surface of the platelets. The His/Arg polymorphism at position 131 of the amino acid chain of FcγR IIa can influence its ability to bind to IgG, and thus can be used as a predictor to predict the individual risk of heparin-induced thrombocytopenia. Symptoms can be classified into transient thrombocytopenia and persistent thrombocytopenia according to the course of clinical course of thrombocytopenia induced by heparin therapy. 1. Most of the temporary thrombocytopenia occurs after the start of heparin treatment, and the platelets are immediately reduced, but generally not less than 50 × 109 / L. It may be related to the induced aggregation of platelets by heparin, which can cause temporary aggregation of platelets and increased platelet adhesion, and platelets are retained in the blood vessels, resulting in transient thrombocytopenia. 2. Persistent thrombocytopenia is less common than the former, usually occurs 5 to 8 days after heparin treatment. If the patient has been treated with heparin, thrombocytopenia may occur immediately, and the number of platelets may be less than 50×109/L. Below 10 × 109 / L. In addition to thrombocytopenia, thrombosis and disseminated intravascular coagulation can be accompanied. Hemorrhagic symptoms are rare, mainly manifested as thrombosis. A history of drugs with heparin can be diagnosed in conjunction with laboratory tests for thrombocytopenia. Treatment (1) Treatment For patients with heparin-induced thrombocytopenia, if the platelet count is not less than 50 × 109 / L, and there is no obvious clinical symptoms, heparin treatment can continue to be used, and the total number of platelets can be recovered by itself. Heparin therapy is discontinued when the number of platelets is less than 50 x 109/L or there is a manifestation of thrombosis. Within a few days of discontinuation of heparin, all changes in platelet and coagulation caused by heparin were corrected, but heparin-dependent antiplatelet antibodies were still detectable. If severe thrombocytopenia is associated with thrombosis, plasma exchange can be performed, platelet transfusion is ineffective, and even thrombosis may be aggravated, causing symptoms similar to thrombotic thrombocytopenic purpura. Prevention is fully aware of the potential for heparin therapy to induce thrombocytopenia, and frequent review of platelet counts is the primary preventive measure. The application of low molecular weight heparin can reduce the incidence of this disease.

简介 结肠直肠癌（carcinoma of colon and rectum）胃肠道中常见的恶性肿瘤，早期症状不明显，随着癌肿的增大而表现排便习惯改变、便血、腹泻、腹泻与便秘交替、局部腹痛等症状，晚期则表现贫血、体重减轻等全身症状。其发病率和病死率在消化系统恶性肿瘤中仅次于胃癌、食管癌和原发性肝癌。 概述 结肠直肠癌carcinoma of colon and rectum是胃肠道中常见的恶性肿瘤，早期症状不明显，随着癌肿的增大而表现排便习惯改变、便血、腹泻、腹泻与便秘交替、局部腹痛等症状，晚期则表现贫血、体重减轻等全身症状。其发病率和病死率在消化系统恶性肿瘤中仅次于胃癌、食管癌和原发性肝癌。中国在世界上属于低发地区，但其发生率在不少地区有程度不等的增加趋势。 本病多发生在中年以上的男性，以40～70岁最为多见，但20世纪末发现30岁以下者亦不少见。男女两性发病比例约为2:1。本病和其他恶性肿瘤一样,发病原因仍不清楚,可以发生在结肠或直肠的任何部位,但以直肠、乙状结肠最为多见，其余依次见于盲肠、升结肠、降结肠及横结肠。癌瘤大多数为腺癌，少数为鳞状上皮癌及粘液癌。本病可以通过淋巴、血液循环及直接蔓延等途径,播散到其他组织和脏器。 根据临床表现、X射线钡剂灌肠或纤维结肠镜检查，可以确诊。治疗的关键在于早期发现、及时诊断和手术根治。本病的预后取决于早期诊断和及时手术治疗。一般癌肿只限于肠壁者预后较好，浸润到肠外者预后较差，年轻患者、癌瘤浸润广泛、有转移者或有并发症者预后不良。 病因 不十分清楚，但是，已经知道可能与以下癌前病变和一些因素有关： ①在许多临床实践中发现结肠息肉可以恶变,其中乳头状腺瘤最易恶变,可达40％；在家族性息肉病的病人中,癌变的发生率则更高,这说明结肠癌与结肠息肉关系密切。 ②部分慢性溃疡性结肠炎可以并发结肠癌,发生率可能比正常人群高出5～10倍。发生结肠癌的原因可能与结肠粘膜慢性炎症刺激有关，一般认为在炎症增生的过程中，经过炎性息肉阶段发生癌变。 ③在中国,血吸虫病并发结肠癌的病例并不少见,但对其因果关系仍有争论。 ④据世界肿瘤流行学调查统计，结肠癌在北美、西欧、澳大利亚、新西兰等地的发病率高,而在日本、芬兰、智利等地较低。研究认为,这种地理分布与居民的饮食习惯有关系，高脂肪饮食者发病率较高。 ⑤结肠癌的发生率可能与遗传因素有关，这已越来越被引起重视。 病理 溃疡型大肠癌好发于左半结肠，癌体较小，早期形成凹陷性溃疡，容易引起出血、穿透肠壁侵入邻近器官和组织。 临床表现　血便为结肠癌的主要症状，也是直肠癌最先出现和最常见的症状。由于癌肿所在部位的不同，出血量和性状各不相同。 息肉型大肠癌病人可出现右下腹部局限性腹痛和腹泻，粪便呈稀水样、脓血样或果酱样，粪隐血试验多为阳性。随着癌肿的增大，在腹部的相应部位可以摸到肿块。 狭窄型大肠癌容易引起肠梗阻，出现腹痛、腹胀、腹泻或腹泻与便秘交替。粪便呈脓血便或血便。 溃疡型大肠癌的病人，可出现腹痛、腹泻、便血或脓血便，并易引起肠腔狭窄和梗阻，一旦发生完全性梗阻，则腹痛加剧，并可出现腹胀、恶心、呕吐，全身情况急剧变化。 在肿瘤的晚期。由于持续性小量便血可引起贫血；长期进行性贫血、营养不良和局部溃烂、感染毒素吸收所引起的中毒症状，导致病人消瘦、精神萎糜、全身无力和恶病质；由于急性穿孔可引起急性腹膜炎；肝脏肿大、腹水、颈部及锁骨上窝淋巴结肿大，常提示为肿瘤的晚期并发生转移。 诊断 本病应该做到早期诊断。对于近期出现排便习惯改变或血便的病人应不失时机地进行直肠指诊、X射线钡剂灌肠、乙状结肠镜或纤维结肠镜检查。X射线钡剂空气双重对比造影可以显示出钡剂充盈缺损、肠腔狭窄、粘膜破坏等征象，从而确定肿瘤的部位和范围。乙状结肠镜及纤维结肠镜检查可以直接观察到全结肠及直肠粘膜形态，对可疑病灶能够在直视下采取活体组织检查，对提高诊断的准确率，尤其对微小病灶的早期诊断很有价值。 直肠指诊检查是诊断直肠癌的最简单而又非常重要的检查方法,它不仅可以发现肿物,而且可以确定肿块的部位、大小、形态、手术方式及其预后，许多直肠癌病人常因为没有及时做此项检查而被误诊为痔、肠炎等，以致长期延误治疗。 粪便隐血试验是一种简单易行的早期诊断的初筛方法,它虽然没有特异性,对待持续、反复潜血阳性而又无原因可寻者，常警惕有结肠癌的可能性,尤其对右半结肠癌更为重要。癌胚抗原(CEA)被认为与恶性肿瘤有关,但对大肠癌无特异性,可以作为诊断的辅助手段之一,由于癌肿切除后血清CEA逐渐下降，当有复发时会再次增高，因此可以用来判断本病的预后或有无复发。 对表现为腹泻、粪便隐血试验阳性、右腹部肿块等症状的右半结肠癌应注意与肠结核、局限性结肠炎、血吸虫病、阿米巴病等疾病相鉴别；对表现为腹痛、腹泻与便秘交替、血便或脓血便等症状的左半结肠癌应注意与痔、痢疾、溃疡性结肠炎、结肠息肉等疾病相鉴别。 治疗 外科治疗 肠癌的根治性治疗方法迄今仍首推外科治疗。 全国第1届肠癌会议提出，浸润性肠癌根治切除的定义是手术时将肉眼所见及扪及的肿瘤，包括原发灶及引流区淋巴结全部清除者为根治性切除，手术时虽能切除病灶，但肉眼或扪及的肿瘤有残留者属于姑息性手术。因此，对病变局限于原发或区域淋巴结者应作根治性手术；局部病变广泛，估计不易彻底切除，但尚无远处转移者可作姑息性切除；局部病变较广泛尚能切除，但已有远处转移，为解除梗阻、改善症状亦可作姑息性切除；局部病灶广泛、粘连、固定，已无法切除，可以作捷径手术或造疹术以解除症状；已有远处转移如肝转移或其他内脏转移，而原发灶尚能切除者可根据病员具体情况考虑是否同时切除，当然此亦属于姑息性手术。手术后综合征：直、结肠癌手术切除后常有肠运动功能的紊乱，大便次数增多；乙状结肠切除后常由于结肠协调性固体运送机能的破坏而造成便秘；肛管、结肠吻合术后常有排便功能的改变，如大便次数增多、失禁等。直肠癌手术后常有排尿功能的障碍，性功能障碍。对肛门非保留的病人，正研究及设计安置在会阴部的“人工肛门”，并能有控制大便便意的装置，以解决病人的排便问题。目前在研究的应用肌肉代替括约肌的肌肉兴奋技术看来是有希望的方法。 放射治疗 近50年来，尽管外科技术有迅猛发展，但大肠癌的手术治愈率、5年生存率始终徘徊在50％左右，治疗失败原因主要为局部复发率较高，故提高大肠癌的治疗效果必须考虑综合治疗。目前研究较多、效果较好的是外科和放射的综合治疗，包括术前放射、术中放射、术后放射、“三明治”放疗等，各种不同的综合治疗有其不同的特点。对晚期直肠癌，尤其是局部肿瘤浸润到附近组织（直肠旁、直肠前组织、腹腔淋巴结、膀胱、尿道、耻骨支）以及有外科禁忌证患者，应用姑息性放射亦常有较满意的疗效。 放疗和外科综合治疗 Read more...

简介 遗传性血管性水肿(hereditary angioedema)系一具有家族史，反复发生软组织急性局限性水肿的疾病。属常染色体显性遗传，其发作与轻微外伤、情绪波动、感染、气温骤变以及月经、雌激素型避孕药等有关。 病因 (一)发病原因 遗传性血管性水肿(hereditary angioedema)为常染色体显性遗传病。其病因是患者血清中C1脂酶抑制因子(一种α2球蛋白)减少或功能缺损，以致C1过度活化，C4及C2的裂解失控，所生成的补体激肽增多，以致使微血管通透性增高，引起水肿。 (二)发病机制 本病是由于C1酯酶抑制物水平降低(85%)或功能异常(15%)所致，为常染色体显性遗传。主要由于C1酯酶抑制物缺乏(85%)或无功能(15%)，使血清中生成活化的C1 -(酯酶)量过高，增强血管通透性，影响Hageman凝血因子的生成，导致皮肤、呼吸道和胃肠黏膜水肿及出血。 症状 【临床表现】 反复发作的急性皮肤粘膜水肿。 ①反复发作的面、颈、躯干及四肢局限性皮下水肿。往往在局部受到轻微外伤时发生。起病突然，局部不痛、不痒，亦无明显潮红，一般持续48～72小时后自然缓解。 ②可发生喉头、呼吸道消化道粘膜水肿。出现呼吸困难、声嘶、窒息，以及腹痛、腹泻、恶心、呕吐等症状。 【诊断要点】 1.婴儿期发病，常有家族史。 2.好发于面、四肢、胃肠及外生殖器部位。 3.突然发生局限性、非炎症性及非凹陷性的皮下水肿，表面呈肤色。无自觉症状，肿胀多持续1～3天，不伴有荨麻疹。 4.常伴反复发作性腹部绞痛、呕吐以及腹胀、水泻。腹部触痛，但无肌强直及反跳痛。 5.偶可因咽喉水肿导致窒息死亡。 6.实验室检查：C1酯酶抑制物(C1 esterase inhibitor，C1inh)缺乏或减低，血清C2、C4含量亦低。 多数患者有家族史。表现为反复发作的皮肤、呼吸道和消化道黏膜局限性非凹陷性水肿，如眼睑皮肤水肿、口唇水肿、喉水肿或腹痛;有明显的自限性，48～72h可自然缓解;水肿的出现可由情绪波动、月经、发热和外伤等因素诱发;伴有恶心、呕吐及腹痛，可因喉头水肿窒息致死，若不治疗，死亡率可高达28%;不伴瘙痒和荨麻疹;抗组胺剂和皮质类固醇激素治疗无效。 诊断 本病应注意与荨麻疹鉴别，据皮肤深在性水肿性斑块，无发热，局部淋巴结不肿大，皮损局部无热感或压痛，发病突然几点即可诊断，并能与丹毒或蜂窝织炎相鉴别。 并发症 本病常见的并发症：常累及眼睑、唇、舌、外生殖器、手、足等部位，伴早发的消化道或呼吸道症状。 治疗 1.凝血酸，1～3g/日，分3次口服。 2.抗组织胺药物，如扑尔敏、苯海拉明、去氯羟嗪等。 3.皮质激素可用强的松口服、氢可的松静滴、地塞米松口服或静滴。 4.输入正常人血浆，可暂时补充C1脂酶抑制因子。 5.局部冷湿敷。 6.发生喉头水肿时，立即给予肾上腺素0.5mg或麻黄素15mg，肌注，并可考虑气管切开。 7.同化激素，如danazol、去氢甲基睾丸素、康力龙等，可诱导C1脂酶抑制物的合成，从而防止发作。 (一)治疗 1.一般疗法 (1)加强护理和营养：以提高患者的抵抗力和免疫力。 Read more...

简介： 非霍奇金淋巴瘤(non-hodgkin’s lymphoma, NHL)是恶性淋巴瘤的一大类型，在我国恶性淋巴瘤中非霍奇金淋巴瘤所占的比例远高于霍奇金病(HD)。近年来很多国家NHL的发病率有一定增高趋向。NHL的病理类型、临床表现和治疗上远比HD复杂。从现有的资料看来，NHL是一组很不均一的疾病，病因、病理、临床表现和治疗都有差异。迄今，总的治愈率也低于HD。病程长短不一，从无明显症状和早期可耐受到迅速死亡。在某些类型NHL，50%的患儿和约20%的成年患者出现白血病样的变化。 病因： (一)发病原因 非霍奇金淋巴瘤的病因涉及病毒、细菌、放射线、某些化学物质以及除莠剂等多种因素。已知EB病毒与高发区Burkitt淋巴瘤和结外T/NK细胞淋巴瘤、鼻型有关。成人T细胞淋巴瘤/白血病与人类亲T细胞病毒Ⅰ型(HTLV1)感染密切关联。胃黏膜相关淋巴组织淋巴瘤是由幽门螺旋杆菌感染的反应性病变起始而引起的恶性变。放射线接触如核爆炸及核反应堆意外的幸存者、接受放疗和化疗的肿瘤患者非霍奇金淋巴瘤发病危险增高。 艾滋病、某些遗传性、获得性免疫缺陷疾病或自家免疫性疾病如共济失调-毛细血管扩张症、联合免疫缺损综合征、类风湿性关节炎、系统性红斑狼疮、干燥综合征(舍格伦综合征，Sj?gren’s syndrome)、低γ球蛋白血症以及长期接受免疫抑制药治疗(如器官移植等疾病)所致免疫功能异常均为非霍奇金淋巴瘤发病的高危因素。 非霍奇金淋巴瘤较霍奇金病常见.美国每年新诊断约50000病例.各年龄组均可发生,发病率随年龄而增高.尽管像白血病一样已有可靠的实验证据提示某些淋巴瘤由病毒引起,但病因仍不明确.例如HTLV-1(逆转录人T细胞白血病-淋巴瘤病毒)已分离出来,而且似乎流行于日本南部,加勒比海,南美和美国东南地区.急性成人T细胞白血病-淋巴瘤,急性发作期临床表现为皮肤浸润,淋巴结肿大,肝脾肿大和白血病.白血病细胞是恶性T淋巴细胞,大多伴迂曲形核.常发生高血钙症,这是由于体液因素而非骨直接受侵犯所致. 在艾滋病中,NHL特别是免疫母细胞和小无裂(Burkitt淋巴瘤)型的发病率增高.已报告原发性侵犯中枢神经系统和弥散性的病变.约30%患者全身淋巴结肿大常先出现于淋巴瘤,提示B细胞多克隆刺激先于淋巴瘤的发生.某些艾滋病伴淋巴瘤可有C-myc基因重排.对化疗可能有效,然而毒性常见和条件性感染连续发生,这将造成生存期短暂. (二)发病机制 由于淋巴细胞的分化阶段不同，因而在受侵的淋巴结或淋巴组织中可出现不同阶段的瘤细胞。在同一病灶中，可有低分化的瘤细胞，也可有分化较为成熟的细胞。随着病变的进展，恶性淋巴瘤的组织学类型可有转变，如结节型可转变为弥漫型。 增生的肿瘤组织可呈单一细胞成分，但由于原始多能干细胞可向不同的方向分化，有时细胞成分可是两种以上或多种多样的。 近年来由于单克隆抗体和免疫组化的广泛应用，已有可能辨别不同分化阶段的T、B淋巴细胞。 发生于包膜下皮质胸腺细胞的肿瘤通常是T细胞急性淋巴细胞白血病和淋巴母细胞淋巴瘤。所有其他T细胞淋巴瘤都是来自比较成熟的T细胞，CD4阳性，其中包括成人T细胞淋巴瘤(ATL)、蕈样霉菌病、Sezary综合征、多数所谓的周围性T细胞淋巴瘤(国际工作分类中的弥漫大细胞、免疫母细胞和混合性淋巴瘤)及半数以上的T细胞慢性淋巴细胞白血病。有一些周围T细胞淋巴瘤、近半数的T细胞慢性淋巴细胞白血病和一些Tγ淋巴增生性疾病，CD8阳性。 B细胞淋巴瘤的特异性抗体较少，但有表面免疫球蛋白表达。最早期的B细胞表面有CD10、CD19的表达，细胞内有终端转移酶并有重键基因的重组。以后细胞表达CD20，细胞浆内产生μ重键，K轻键基因的重组、λ轻键基因的重组及终端转移酶脱失。这些代表发展中的前B细胞阶段。细胞丢失CD10的表达以后即成为不成熟的B细胞，表面有IgM表达。以后细胞表面表达CD21受体(C3d)膜上产生IgD和IgM。所有B细胞的发展阶段都是在抗原刺激下发生的，同时免疫球蛋白基因在接受抗原刺激后被启动而分泌。此后，细胞丢失CD21、CD20和表面免疫球蛋白，获得浆细胞的标记物PC-1和PC-2分泌免疫球蛋白。这是细胞滤泡中心B细胞的发展过程，发生恶性变后即成为淋巴细胞淋巴瘤。 滤泡中心B细胞的成熟和免疫球蛋白基因的启动均受T辅助细胞调控，但也有一些不明的B淋巴细胞。套细胞区的B细胞似乎相对比较少受T细胞的影响，这些细胞CD5阳性，这是一全T细胞标记物，似乎也与免疫球蛋白无关。 多数急性淋巴细胞的白血病来源于前B细胞，Burkitt淋巴瘤及白血病来源于表面IgM阳性的不成熟B细胞，多数滤泡性和弥漫性B细胞淋巴瘤来自成熟的或活化的B细胞。巨球蛋白血症(Waldenstrom综合征)和多发性骨髓瘤则来自分化的终末阶段，慢性淋巴细胞白血病表达CD5，弥漫性中等分化淋巴瘤表达CD5及CD10，可能说明这些是来自套细胞区而不是滤泡中心的B细胞。 有些淋巴瘤的免疫分型及临床表现还很混乱。弥漫大细胞淋巴瘤可能最不均一，可来自B细胞、T细胞及组织细胞。所以，这些病人的预后不完全取决于临床分期。成人T细胞淋巴瘤从免疫表型来说是来自成熟的T细胞，但临床表现很凶险，像来自不成熟T细胞的淋巴母细胞淋巴瘤。这些都有待进一步研究，特别是不同基因在其中的作用。 症状： 本病可见于任何年龄，临床表现可归纳如下： 1.浅表淋巴结肿大或形成结节、肿块 为最常见的首发临床表现，约占全部病例的60%～70%，尤以颈淋巴结肿大最为常见(49.3%)，其次为腋窝、腹股沟淋巴结(各占12.9%，12.7%)。淋巴结肿块大小不等、常不对称、质实有弹性、多无压痛。低度恶性淋巴瘤时，淋巴结肿大多为分散、无粘连，易活动的多个淋巴结，而侵袭性或高度侵袭性淋巴瘤，进展迅速者，淋巴结往往融合成团，有时与基底及皮肤粘连，并可能有局部软组织浸润、压迫、水肿的表现。 2.体内深部淋巴结肿块 可因其发生在不同的部位而引起相应的浸润、压迫、梗阻或组织破坏而致的相应症状。例如，纵隔、肺门淋巴结肿块可致胸闷、胸痛、呼吸困难、上腔静脉压迫综合征等临床表现，腹腔内(肠系膜淋巴结、腹膜后淋巴结)肿块，可致腹痛、腹块、肠梗阻、输尿管梗阻、肾盂积液等表现。 3.结外淋巴组织的增生和肿块 也可因不同部位而引起相应症状。初诊时单纯表现为结外病灶而无表浅淋巴结肿大者约占21.9%。结外病灶以咽环为最常见，表现为腭扁桃体肿大或咽部肿块。胃肠道黏膜下淋巴组织可受侵犯而引起腹痛、腹块，胃肠道梗阻、出血、穿孔等表现。肝脏受淋巴瘤侵犯时可有肿大、黄疸。结外淋巴瘤还可侵犯眼眶致眼球突出，单侧或双侧乳腺肿块，并可侵犯骨髓，致贫血、骨痛、骨质破坏、甚至病理性骨折。颅内受侵犯时，可致头痛、视力障碍等颅内压增高症状。病变亦可压迫末梢神经致神经瘫痪，例如面神经瘫痪。也可以侵入椎管内，引起脊髓压迫症而致截瘫。有些类型的非霍奇金淋巴瘤，特别是T细胞淋巴瘤，易有皮肤的浸润、结节或肿瘤。蕈样霉菌病及Sézary综合征是特殊类型的皮肤T细胞淋巴瘤。还有一种类型的结外淋巴瘤，即鼻和鼻型NK/T细胞淋巴瘤，曾被称为“中线坏死性肉芽肿”、“血管中心性淋巴瘤”，临床上最常见的首发部位为鼻腔，其次腭部、鼻咽和扁桃体。 由于淋巴瘤可从淋巴结(浅表及深部)及各种不同器官的结外淋巴组织发生，在其发展过程中又可侵犯各种不同组织器官，故其临床表现可非常复杂而多样化。不同组织类型的淋巴瘤也常有其临床特点。 4.全身症状 非霍奇金淋巴瘤也可有全身症状，包括一般消耗性症状如贫血、消瘦、衰弱外，也可有特殊的“B”症状(同霍奇金淋巴瘤，包括发热、盗汗及体重减轻)。但一般来说，非霍奇金淋巴瘤的全身症状不及霍奇金淋巴瘤多见，且多见于疾病的较晚期。实际上，在疾病晚期常见的发热、盗汗及体重下降，有时不易区分究竟是本病的临床表现，还是长期治疗(化疗、放疗)的后果，或因晚期免疫功能受损而发生合并感染所致。 1.本病的确诊有赖于组织学活检(包括免疫组化检查及分子细胞遗传学检查)。这些组织学、免疫学和细胞遗传学检查不仅可确诊NHL，还可作出分型诊断，这对了解该病的恶性程度、估计预后及选择正确的治疗方案都至关重要。 凡无明显感染灶的淋巴结肿大，应考虑到本病，如果肿大的淋巴结具有饱满、质韧等特点，就更应该考虑到本病。有时肿大的淋巴结可以因抗炎等措施而暂时缩小，而后又复长大;有的病人浅表淋巴结不大，但较长期有发热、盗汗、体重下降等症状，一段时间后可表现有主动脉旁淋巴结肿大等情况。 2.分期与HD分期相同。 必须与霍奇金病,反应性滤泡增生，急性和慢性白血病,传染性单核细胞增多症,猫爪病，恶性黑色素瘤，结核(特别是有肺门淋巴结肿大的原发性结核),以及引起淋巴结肿大的其他疾病包括苯妥英钠所致的假性淋巴瘤相鉴别.NHL的诊断依赖于对病变淋巴结或相关组织的活检。病理学诊断至少应包括两个部分，即组织学分型和肿瘤细胞的免疫表型，必要时需进行免疫球蛋白和T细胞受体基因重排分析，以及细胞遗传学方面的检测。组织学上通常的诊断标准是正常淋巴结的结构受到破坏,以及包膜和邻近的脂肪被典型的肿瘤细胞侵犯.表型检查可确定细胞来源及其亚型,有助于判断预后,而且对确定治疗方案也可能有价值(见下文).通过免疫过氧化酶检查(常用于未分化恶性肿瘤的鉴别诊断)确定白细胞公共抗原(CD45)存在,而排除转移性癌.本方法可在固定组织上使用来测定白细胞公共抗原.使用免疫过氧化酶方法也可在固定组织上对大多数表面标志进行检查。 诊断： 单靠临床的判断很难作出明确的诊断。不少正常健康人也可在颈部或腹股沟部位触及某些淋巴结，淋巴结的肿大亦可见于细菌、结核或原虫的感染及某些病毒感染。还需要与淋巴结转移癌鉴别。具体鉴别如下： 1.慢性淋巴结炎 一般的慢性淋巴结炎多有感染灶。在急性期感染，如足癣感染，可致同侧腹股沟淋巴结肿大，或伴红、肿、热、痛等急性期表现，或只有淋巴结肿大伴疼痛，急性期过后，淋巴结缩小，疼痛消失。通常慢性淋巴结炎的淋巴结肿大较小，约0.5～1.0cm，质地较软、扁、多活动，而恶性淋巴瘤的淋巴结肿大具有较大、丰满、质韧的特点，必要时切除活检。 2.急性化脓性扁桃体炎 Read more...

Overview Non-functional adrenocortical adenocarcinoma (NACC) is rare in clinical practice, and people are still unable to recognize the cause of the disease. The early diagnosis rate of tumors is not high. Many patients have peripheral infiltration or distant metastasis at the time of treatment, and the progress rate is fast, which causes great difficulty for clinical treatment, and the prognosis is usually poor. With the improvement and popularization of imaging examination methods, adrenal cortical carcinoma is often found by chance during a physical examination or other diseases, accounting for 10% to 20% of adrenal incidents. Therefore, the actual incidence rate has increased in recent years. The age of onset varies from 1 to 80 years old, and is more common in adults or the elderly, with more men than women. It is more common to metastasize to lymph nodes, lungs, and liver, and to bones and brains. Symptoms The clinical symptoms of adrenal cortical carcinoma are atypical, and can be divided into two types: endocrine disorders and endocrine disorders (no function). Clinically, some patients have mixed hormone secretion abnormalities, accounting for about 35% of patients with adrenocortical cancer. Most patients with endocrine disorders showed that Cushing's syndrome combined with female masculinization was the most important manifestation, and abnormal sexual characteristics and primary aldosteronism were relatively rare. Mixed abnormal changes can occur in biochemical tests, both Cushing's syndrome and hypokalemia, and this hypokalemia often appears to be refractory, and conventional potassium supplementation is slow, which may be related to malignant tumors. Unrestricted growth and low degree of differentiation. Non-functioning adrenocortical carcinoma, the onset is slow, the symptoms are different, often fatigue, weight loss, about 1/2 patients with intermittent hypothermia, and the absorption of necrotic tissue in the tumor. About 2/3 of the patients have pain in the side of the abdomen and lumbar pain. The larger the tumor, the pain is aggravated when the position changes, which may be caused by the tumor invading the capsule or twisting and shifting the kidney. At the time of physical examination, 1/3 of the cases can touch the abdominal mass, and in a few cases, the renal artery stenosis caused by the tumor can cause hypertension. Larger tumors can be associated with hypoglycemia. In patients with no functional disorders, there is often an increase in urine 17-KS. Clinically, sometimes the initial manifestations are symptoms of distant metastasis, such as multiple lesions in the lungs, gynecological symptoms of vaginal metastasis, and hematuria in renal metastases. Gastrointestinal hemorrhage due to intestinal metastasis and symptoms such as bone, brain and eye metastasis. Diagnosis 1. Clinical features Adrenal cortical carcinoma is atypical clinical symptoms, which can be divided into two types: endocrine disorders and endocrine disorders (no function). 2. Auxiliary examination (1) Laboratory examination All adrenal cortical tumors should be tested for adrenal function, especially non-functional adrenal cortical tumors. Sometimes, although there are no prominent clinical symptoms, it is not necessarily a non-functional tumor; and those with abnormal laboratory tests may not have corresponding clinical manifestations. Examination of adrenal cortical secretion function, including plasma cortisol, 17-OHCS, 17-KS, CA, VMA and plasma aldosterone, renin activity, electrolytes, sex hormones (androgen, pregnane estrone) and glucose tolerance test, small dose Dexamethasone inhibition test, etc. Non-functional adrenal cortical tumors have more normal blood and urinary cortisol. Because the tumor is too large and consumed too much, hypoproteinemia and hypoglycemia may occur. For example, bilateral large tumors may be associated with blood, urinary cortisol is lower than normal, aldosterone is more normal, and a small number of 17-ketocorticosteroids may have a slight increase. (2) imaging examination B-ultrasound, CT or MRI imaging examination is indispensable in the diagnosis of adrenocortical cancer. In particular, non-functional asymptomatic adrenal tumors need to rely on imaging to confirm the diagnosis to determine whether the adrenal gland is abnormal, whether there is a tumor, to help locate and determine the adrenal properties. Many scholars believe that the vast majority of tumors in adrenocortical carcinoma are larger than 5 cm in diameter. (3) Nuclear medicine examination of adenomas can show uniform radioactive concentration, while adenocarcinoma shows uneven radioactivity concentration. In recent years, positron emission tomography (PET) technology has also been applied to the diagnosis of adrenal malignancies. Becher et al. used 18 fluorinated deoxyglucose (18F-FDG) positron emission tomography to scan 10 patients with adrenocortical carcinoma, and found that the uptake of FDG in all primary and metastatic lesions was significantly enhanced, and the wing sensitivity and specificity were 100. % and 97%. Barzon et al. used 75Se-labeled methylnorcholic acid for adrenal scanning. All non-functioning adenocarcinomas and 70% of functional adenocarcinomas were free of nuclides, and all normal adrenal tissues were absorbed, indicating that radionuclide scanning is in the diagnosis of adrenal gland. There is a certain value in cortical cancer. Treatment 1. The diclofenac treatment regimen, chlorhexidine dichloride (O, P-DDD), alters the metabolism of the adrenal cortex hormones and androgen, inhibits the secretion of corticosteroids, destroys the adrenal cortex, and shrinks the tumor. It is suitable for palliative treatment for patients who cannot be operated, postoperative tumor residual, and metastatic lesions. Long-term treatment is only available for patients who initially have a therapeutic effect. It has been reported in the literature that a good therapeutic effect may be obtained with a concentration of >10 μg/ml or >14 μg/ml of dichlorophenyldichloroethane. However, recent studies have suggested that there is no necessary relationship between concentration and efficacy. The main side effect is neuromuscular toxicity, which is related to the dose used. Modern imaging technology can more accurately determine the therapeutic effect of chlorhexidine. Can be divided into: (1) complete effect, no tumor survival for at least 4 weeks; (2) partial effect, tumor volume reduction > 50% for at least 4 weeks; (3) micro-effect, tumor volume reduced by 25% to 50%. The therapeutic effect of dichlorophenyldichloroethane has been controversial, and most scholars believe that oral treatment with diclofenac in advanced patients is beneficial to the prognosis and prolong survival. For patients who do not respond to treatment, try to combine chlorhexidine with multi-drug chemotherapy. Other steroid synthesis inhibitors such as ketoconazole, aminoglutethimide and other therapeutic effects, there is currently insufficient clinical research evidence. The drug of dichlorobenzene dichloroethane is slow, at least for more than 8 weeks, and the starting dose is small. 500mg daily, if there is no adverse reaction, 4 times a day, then increase 500mg every 3 days, the maximum 12g / d, should pay attention to side effects such as nausea, vomiting, lethargy, blurred vision and salivation, reduce or stop depending on the severity . Prednisone is required to prevent adrenal insufficiency. It has also been reported that after chemotherapy, CTX, vincristine and fluorouracil can be used alone or in combination to achieve short-term results. 2. Chemotherapy of adrenal cortical carcinoma can express multidrug resistance gene (MDR) 21, leading to the secretion of P2 glycoprotein and accelerating the cytotoxic drug failure. Dichlorobenzene dichloroethane can interfere with the function of MDR21 and P2 glycoproteins and antagonize its drug resistance. Therefore, the clinical use of chemotherapeutic drugs and chlorhexidine dichloride is currently used in combination. Commonly used drugs include doxorubicin, cyclophosphamide, fluorouracil, cisplatin, etoposide and the like. The standard for judging the effect of chemotherapy was the same as that of bischlorobenzene dichloride, Berruti et al., and 28 patients with cortical cancer treated with etoposide, doxorubicin, cisplatin and dichlorodichloroethane. 54% had therapeutic effects (completely Effects of the ten-part effect), the most common side effects include gastrointestinal and nervous system reactions. BonacCl and other studies treated 18 patients with cortical carcinoma with etoposide, cisplatin and dichlorodichloroethane, and 33% had therapeutic effects. Multi-drug chemotherapy is also only palliative treatment. Due to the low incidence of cortical cancer, the clinical research, especially the clinical trials of chemotherapy drugs, has a small sample size, and the tumor discovery is more advanced, the progress is faster, and the survival time is shorter. Therefore, the efficacy of combined chemotherapy is still Not sure. For those who are not surgically treated, the use of chlorhexidine alone or in combination with cytotoxic drugs is the most effective treatment. In order to achieve the best results, the amount of the drug is 14 to 20 μg / ml is strictly required. For patients with worsening conditions, the most promising alternative treatments are: etoposide, doxorubicin, cisplatin + mitotan and streptozol ( Streptozotocin) + mitotan (mitotane), these drugs are currently being used in international phase clinical trials. After the tumor is completely removed (for example, by mitoxantrone radiation therapy), adjuvant therapy is necessary because only 35% of the disease-free survivors within 5 years after surgery, but no effective adjuvant treatment has yet been developed. National registries, international cooperation and trials not only provide patients with important new therapeutic instruments, but also facilitate researchers to systematically study the treatment of adrenocortical cancer. However, future treatments for adrenocortical carcinoma will depend to a large extent on a deeper understanding of the pathogenesis of tumor molecules, which also contributes to the development of modern cancer treatments (eg tyrosine kinase inhibitor treatment). ).