Carcinomar
Cancer hospital还是tumor hospital
探讨与争鸣Cancer hospital 还是tumor hospital欧周罗(复旦大学肿瘤医院，上海200032)中图分类号:N04;R73文献标识码:A文章编号:1673－8578(2012)02－0033－02收稿日期:2012－02－07作者简介:欧周罗(1958—)，男，陕西凤翔人，博士，复旦大学教授，研究方向为肿瘤分子生物学。
通信方式:ouzhouluo@yahoo．com．cn．复旦大学肿瘤医院的英译名一为Fudan Uni-versity Cancer Hospital (FUCH )，二为Fudan Univer-sity Shanghai Cancer Center (FUSCC )，后者大概是为了同国外为数众多的癌症中心(cancer center )如得克萨斯大学MD 安德生(MD Anderson )癌症中心(MDACC )、纽约斯挪恩－柯特林(Sloan-Kettering )纪念癌症中心(MSKCC )、新加坡的国立癌症中心(NCC )等取得一致的英文名称，但多数学者提到肿瘤医院时首先想到的还是cancer hospital ，不久前当我初次听到法国专家将本院简称为“复驰”(FUCH )的时候甚至还有点诧异。
然而，路过肿瘤医院门前的49路公交车英文报站时用的却不是cancer hospital 而是tumor hospital ，其他公交线路亦然。
不言而喻，由于无数次反复强化的关系，tumor hospital 已经印在了许多乘客的脑海中。
究竟是学术界的cancer hospital 更准确，还是民间人士的tumor hospital 较贴切呢?如果将英文的“cancer ”“tumor ”分别直译为中文的“癌”“肿瘤”的话，看似简单明了，但cancer hospital 倒译回来可就成了“癌医院”，而国人显然已经接受并习惯于肿瘤医院这一称谓，很多人也许未曾听说过“癌医院”。
含有car的英语单词
以下是一些含有"car"的英语单词：
1.Carriage - 这个词通常用来描述一种四轮马车，或者火车的车厢。
2.Caramel - 是一种焦糖或糖蜜制品，也可以作为动词使用，意为“把……做成
焦糖色”。
3.Carcass - 指动物（尤其是家畜）的躯体，尤指去掉头、腿和内脏之后的躯
体。
4.Carcinoma - 这是一种恶性肿瘤，尤其是上皮组织的癌症。
5.Cardiac - 这个词与心脏有关，如“cardiac arrest”（心脏骤停）。
6.Cargo - 通常指船、飞机或车辆等运输工具装载的货物。
7.Carillon - 是一种大型钟琴，也指一组教堂钟。
8.Caribou - 这是一种生活在北美洲的驯鹿。
9.Carjacking - 指强行抢劫汽车的犯罪行为。
10.Carnal - 这个词通常用来描述与性有关的，或者肉体的。
请注意，这些词的含义可能会根据上下文的不同而有所变化。
所以，在使用这些词时，一定要清楚其含义，并根据上下文来正确理解。
特殊毒性试验
三、人群流行病学调查
➢ 动物致癌试验，根据阳性结果 检出潜在的人类致癌物
➢ 描述流行病学调查或临床观察 发现怀疑人类致癌物
➢ 病例-对照研究 ➢ 队列研究
四、致癌作用模型
转基因动物 (transgenic animal)
借助基因工程技术将确定的外源基因通 过生殖细胞或早期胚胎导入动物个体的染色 体上，在其基因组内稳定地整合经导入的外 源基因，并能遗传给后代的一类动物
化学、物理或生物等致癌因素作用于细胞 后，引起原癌基因突变使之激活，转变成癌 基因后才会导致细胞癌变
2．抑癌基因 (anti-oncogene)
正常细胞分裂生长的负性调节因子， 其编码的蛋白质能够降低或抑制细胞分裂 活性，或称为肿瘤抑制基因(tumor suppressor gene)、肿瘤易感基因(tumor susceptibility gene)
致癌毒性试验
肿瘤(tumor，neoplasm) ：有分裂潜能的细胞 受致癌因素作用后发ቤተ መጻሕፍቲ ባይዱ恶性转化和克隆性增生 所形成的新生物
良性肿瘤：呈膨胀生长，与周围组织有明显的 界限，多有包膜，它们生长常有“自限性”， 对机体破坏较小
恶性肿瘤：癌和肉瘤
癌(carcinoma)：由上皮细胞来源的恶性肿瘤
肉瘤(sarcoma)：由间质细胞来源的恶性肿瘤
第三节
观察化学毒物致癌作用的 基本方法
化学致癌物的判别
➢ 人群流行病学调查：两项以上由不同 研究者在不同地点、不同对象中以不同 调查方法获得的结论相符的证据；
➢ 动物实验证据：两项按现行常规设计 进行，符合GLP（good laboratory practice），在不同物种动物中所得结果 一致的动物致癌物鉴定资料。
结肠癌-carcinoma colon
USG of Whole Abdomen Chest X-Ray X-Ray of specific site involving bone pain CT- Scan MRI
-For local invasion - To see the extent
Other Investigations : - Carcino-Embryonic Ag (CEA) - Stool Cytology - IHC markers (KERATIN) - - DNA flow Cytometry - Immunoscintigraphy
CT scan is also used for the TNM staging of Ca Colon .
It is helpful for detecting distant metastases.
DUKE’S STAGING
A- lesion confined to bowel wall, mucosa & submucosa.
Morphological Types 1. Annular Stricture 2. Tubular 3. Cauliflower 4. Excavated or Ulcerated
Clinical Features Depend upon1. Tumor Location 2. Tumor Size 3. Presence of Metastases
Proctoscopy Sigmoidoscopy / Procto-Sigmoidoscpy with
Biopsy Flexible Sigmoidoscopy Colonoscopy with Biopsy ( GOLD STANDARD) Barium Enema CT Colonography
Nasopharyngeal-carcinoma_2015_The-Lancet
SeminarNasopharyngeal carcinomaMelvin L K Chua, Joseph T S Wee, Edwin P Hui, Anthony T C ChanEpidemiological trends during the past decade suggest that although incidence of nasopharyngeal carcinoma isgradually declining, even in endemic regions, mortality from the disease has fallen substantially. This fi nding isprobably a re sult of a combination of life style modifi cation, population scre e ning couple d with be tte r imaging,advances in radiotherapy, and eff ective systemic agents. In particular, intensity-modulated radiotherapy has driventhe improvement in tumour control and reduction in toxic eff ects in survivors. Clinical use of Epstein-Barr virus(EBV) as a surrogate biomarker in nasopharyngeal carcinoma continues to increase, with quantitative assessmentof circulating EBV DNA use d for population scre e ning, prognostication, and dise ase surve illance. Randomise dtrials are inve stigating the role of EBV DNA in stratification of patie nts for tre atme nt inte nsifi cation anddeintensifi cation. Among the e xciting de ve lopme nts in nasopharynge al carcinoma, vascular e ndothe lial growthfactor inhibition and novel immunotherapies targeted at immune checkpoint and EBV-specifi c tumour antigensoff er promising alternatives to patients with metastatic disease.IntroductionNasopharyngeal carcinoma is a cancer arising from the nasopharynx epithelium. Within the boundaries of the nasopharynx, the tumour epicentre is frequently seen at the fossa of Rosenmüller, from where the tumour invades adjacent anatomical spaces or organs. Despite being of a similar cell or tissue lineage, distinct diff erences exist between nasopharyngeal carcinoma and other epithelial tumours in the head and neck region. Compared with other cancer types, nasopharyngeal carcinoma is uncommon, albeit with a very unique pattern of geographical distribution. Worldwide, 86 500 cases of nasopharyngeal carcinoma were reported in 2012, accounting for only 0·6% of all cancers diagnosed in that year. 71% of new cases were in east and southeast parts of Asia, with south-central Asia, and north and east Africa accounting for the remainder (appendix).1Besides geographical variation, some ethnic groups also seem to have a predisposition for nasopharyngeal carcinoma—eg, the Bidayuh in Borneo, Nagas in northern India, and Inuits in the Artic, in whom age-standardised incidence is reportedly higher than 16 per 100 000 person-years in men.2 In terms of demographic trends, men are two to three times more likely to develop the disease than are women, and peak age of disease occurrence is between 50 and 60 years. In view of the heterogeneous epidemiological patterns, it is possible that other factors, not limited to genetic susceptibility, are implicated in the pathogenesis of nasopharyngeal carcinoma.Pathology and risk factorsMorphologically, an abundance of lymphoid cells is often seen intermixed with transformed epithelial cells, but nasopharyngeal carcinoma is widely regarded to be squamous in origin. Depending on the degree of diff erentiation, nasopharyngeal carcinoma is categorised into three pathological subtypes on the basis of WH O criteria. Diff erentiated tumours with surface keratin are defined as type I, whereas types II and III refer to non-keratinising differentiated and undiff erentiated tumours, respectively. In 1991, types II and III werecombined into a single category of non-keratinisingcarcinoma. The use of the numerical categorisation wassubsequently dropped, and a third category, the basaloidsquamous carcinoma, was added (fi gure).3 Each of thesedefinitions is also closely related to geographicaldistribution and epidemiological factors. In regionswhere nasopharyngeal carcinoma is endemic, non-keratinising subtypes constitute most cases (>95%)4,5 andare invariably associated with Epstein-Barr virus (EBV)infection, whereas type I disease is more common inother parts of the world.EBV infection is perhaps the most extensively studiedaetiological factor for nasopharyngeal carcinoma. On thebasis of in-situ hybridisation techniques to EBV-encodedRNAs, the virus is detected exclusively in all tumour cellsbut not in normal nasopharyngeal epithelium, suggestingthat EBV activation is necessary in the pathogenesis ofnasopharyngeal carcinoma. This notion is furthersupported by reports that similar techniques undertakenon preinvasive lesions identifi ed the presence of EBV evenduring the initial phases of malignant transformation.6,7Yet, the inability to detect EBV in nasopharyngeal biopsySearch strategy and selection criteriaWe searched the PubMed and MEDLINE databases for articlespublished in English from Jan 1, 2000, to Dec 31, 2014, withthe keywords “nasopharyngeal carcinoma”, “epidemiology”,“pathology”, “genetics”, “Epstein-Barr virus”, “humanpapilloma virus”, “staging”, “imaging”, “functional magneticresonance imaging”, “positron emission tomography”,“radiotherapy”, “intensity-modulated radiotherapy”,“adaptive radiotherapy”, “chemotherapy”, “salvage therapy”,“immunotherapy”, “clinical trials”, and “meta-analysis”.Priority was given to large contemporary clinical trials orstudies in human beings. Selected references were judged onrelevance and mainly consisted of publications from the past5 years, but did not exclude widely referenced and highlyregarded older seminal work. Abstracts of recent pertinentmedical conferences were also included for latest updates.Published OnlineAugust 28, 2015/10.1016/S0140-6736(15)00055-0Division of Radiation Oncology,National Cancer CentreSingapore, Singapore(M L K Chua FRCR,J T S Wee FRCR); Duke-NUS,Graduate Medical School,Singapore (M L K Chua,J T S Wee); and State KeyLaboratory of Oncology inSouth China, Sir Y K Pao Centrefor Cancer, Department ofClinical Oncology, Hong KongCancer Institute, The ChineseUniversity of Hong Kong,Hong Kong, China (E P Hui FRCP,Prof A T C Chan FRCP)Correspondence to:Dr Melvin L K Chua, Division ofRadiation Oncology, NationalCancer Centre Singapore,11 Hospital Drive,Singapore 169610, Singaporemelvin.chua.l.k@.sgSeminarsamples from high-risk individuals suggests that other factors are needed for the EBV-infected epithelial cell to undergo malignant transformation. Recent work has proposed that deregulation of cell-cycle checkpoint through p16 inactivation and cyclin D1 overexpression promotes maintenance of the viral genome, favouring transition of low-grade dysplasia to higher grade lesions.8,9 Intrinsic genetic determinants such as 3p and 9p deletions have also been suggested as mechanisms of susceptibility to EBV infection and its downstream eff ects.10 Epigenetic modifi cations that are associated with a tumorigenic phenotype have been identifi ed in EBV-infected epithelial cells and were shown to persist even in the absence of the virus (appendix).11Another viral cause for nasopharyngeal carcinomaperhaps more associated with the non-endemic form ishuman papillomavirus (HPV). Limited evidence on viralepidemiology is available for H PV and nasopharyngealcarcinoma because the non-endemic form has a lowprevalence worldwide. Nonetheless, small-scale studies have suggested that HPV might be a contributing factor in keratinising and even non-keratinising nasopharyngeal carcinoma in white people.12–16 These studies also suggest that EBV and HPV infection are nearly always mutually exclusive. Prognosis diff ered between EBV-associated and HPV-associated nasopharyngeal carcinoma; patients with H PV-associated tumours had poorer survival and local control, whereas distant failures were more common with EBV-associated tumours.16 Nevertheless, patients with non-viral-associated nasopharyngeal carcinoma (ie, H PV-negative, EBV-negative tumours) had worse outcomes than patients with viral-associated tumours (table 1). Such fi ndings lend further support to the notion that non-viral-related oncogenic signalling contributes to a more aggressive tumour phenotype, but the exact underlying mechanisms remain elusive.Apart from viruses, there is also substantial interest in genetic susceptibility as a determinant of risk for nasopharyngeal carcinoma in endemic regions. Studies have mainly been small-scale case-control comparisons reporting associations of genes involved in immune responses, DNA repair, and metabolic pathways.17,18 Nonetheless, with the advent of high-throughput whole-genome sequencing, genome-wide association studies of large cohorts of patients with nasopharyngeal carcinoma and high-risk individuals have now identifi ed a susceptibility locus within the MH C region of chromosome 6p21 that codes for the HLA genes (HLA-A , HLA-B , HLA-C , HLA-DQ , HLA-DR , HLA-F ).19–24 Other non-HLA susceptibility loci that were also identifi ed from genome-wide association studies were GABBR1 (on chromosome 6p21), HCG9 (6p21), TNFRSF19 (13q12), MECOM (3q26), and CDKN2A and CDKN2B (9p21).19,20 Additionally, a systematic review of 83 related studies further highlighted the relevance of a few other genes involved in DNA repair (RAD51L1), cell-cycle checkpoint regulation (MDM2, TP53), and cell adhesion and migration (MMP2).18 Among them, the DNA double-strand break repair pathway has been validated in a cohort of 2349 individuals from H ong Kong as a potential determinant of nasopharyngeal carcinoma risk.25Large-scale epidemiological studies have proposed associations between several dietary and social practices and an increased risk of nasopharyngeal carcinoma. Most notably, a history of salted fi sh consumption has been reported to be common in patients with nasopharyngeal carcinoma.26 Specifi cally, N-nitrosamine is believed to be the associated carcinogen, and long-term exposure is associated with a two-fold increase in risk of developing the disease. Other risk factors are consumption of preserved foods, herbal teas, slow-cooked soups, and alcohol, and smoking habits; however, such links were often inconsistent between studies, and even when present, were weaker than that seen for salted fi sh. In a proof-of-concept study, exposure of cells to nicotine in vitro promoted EBV replication and expression of its lytic gene products.27Figure: Light microscopic appearance of nasopharyngeal carcinoma(A) Keratinising squamous cell carcinoma; haematoxylin and eosin (H&E) stain, magnifi cation 200×. (B) Non-keratinising carcinoma, diff erentiated subtype; H&E stain, magnifi cation 400×. (C) Non-keratinising carcinoma,undiff erentiated subtype; H&E stain, magnifi cation 400×. (D) Detection of Epstein-Barr virus-encoded small RNA by in-situ hybridisation.A BC D Epidemiology Overall survival Local control Distantmetastasis-free survivalHPV-negative/EBV-positive Endemic regions Most superior Most superior LowestHPV-positive/EBV-negative Non-endemic regions Moderate Moderate ModerateHPV-negative/EBV-negative Non-endemic regions Lowest LowestModerate HPV=human papillomavirus. EBV=Epstein-Barr virus.Table 1: Characteristics of the diff erent types of viral-associated nasopharyngeal carcinomaSee Online for appendixSeminarPopulation screening in endemic areasIn view of the prevalence of nasopharyngeal carcinoma in southern China, population screening presents an attractive strategy for early diagnosis and, consequently, better outcomes. Immunoserology (IgA antibodies against EBV capsid antigen [VCA-IgA], early antigen [EA-IgA], EBV nuclear antigen 1 [EBNA1-IgA], and EBV-specific DNase antibodies) and EBV DNA-based screening methods have been studied. From the early studies consisting of case-control and prospective testing, immunoseropositivity is estimated to be predictive of nasopharyngeal carcinoma susceptibility after a year, and detection sensitivity is enhanced when combining a panel of markers (appendix).28 Nonetheless, false-positive rates of 2–18% have been reported with serological testing alone.29 A promising method to reduce false-positive rates could entail use of a confi rmatory non-invasive test after positive serology. In a study that incorporated this strategy, the combination of serum VCA-IgA antibody and circulating EBV DNA had an overall sensitivity (defi ned as positive result of either marker) of 99%, but EBV DNA accurately identifi ed 75% of false-positive VCA-IgA-detected cases.30 A large-scale prospective screening study (NCT02063399) for nasopharyngeal carcinoma with use of plasma EBV DNA is in progress and plans to recruit almost 20 000 healthy men aged between 40 and 60 years (appendix). Symptoms and diagnosisClinical presentation of nasopharyngeal carcinoma is correlated with the extent of primary and nodal disease. Possible routes of primary tumour invasion are anterior spread into the nasal cavity, pterygoid fossa, and maxillary sinuses; lateral involvement beyond the pharyngobasilar fascia into the parapharyngeal and infratemporal spaces; and base of skull, clivus, and intracranial structures when the disease extends posteriorly and superiorly. H ence, depending on the anatomical structures aff ected, clinical presentation varies accordingly, ranging from non-specifi c symptoms of epistaxis, unilateral nasal obstruction, and auditory complaints to cranial nerve palsies (cranial nerves third, fifth, sixth, and 12th being most aff ected). Nodal metastasis in the neck is a frequent clinical fi nding in nasopharyngeal carcinoma, occurring in roughly three-quarters of all patients. Retropharyngeal and level 2 neck nodes are typically the fi rst and second echelons of spread, respectively, and skipped metastasis does not usually occur in the lower neck in the absence of disease at the upper nodal stations.31Nasendoscopy is routine in eliciting a tumour in the nasopharynx. Biopsy samples are obtained for pathological diagnosis, and in the rare instance when no tumour is visible, blind or radiology-guided targeted biopsies, or both, are done if the index of suspicion is high. Diff erential diagnoses of a malignant tumour in the nasopharynx are lymphoma, extramedullary plasma c ytoma, melanoma, rhabdomyosarcoma, and adenoid cystic carcinoma. Benign condition-like tuberculosis of the nasopharynx could also present with a similar range of symptoms, and ought to be considered in immuno c ompromised individuals. Characteristic histological features constitute the microscopic morphology of nasopharyngeal carcinoma, but at times, distinguishing between the undiff erentiated subtype and lymphoma might be diffi cult. In such instances, immuno h istochemical markers specifi c to individual tumour types (leucocyte common antigen, lymphoma; S100, melanoma; MNF116, a pancytokeratin marker) and in-situ hybridisation to EBV-encoded RNAs can supplement haematoxylin and eosin staining. Other useful investigations for confi rming a diagnosis of naso-pharyngeal carcinoma are quantitative assessments of plasma immunoserology and EBV DNA.32,33Staging and prognosisNasopharyngeal carcinoma is classifi ed by the joint Union for International Cancer Control TNM Classifi cation of Malignant Tumours and the American Joint Committee on Cancer staging system. This classifi cation system was updated in 2009 and introduced several modifi cations to the staging of primary and nodal disease for the seventh edition (appendix).34Besides tumour burden as refl ected by the TNM stage classification, other clinical and molecular prognostic variables have also been proposed. A history of smoking, low-penetrance allelic variation of DNA repair genes, overexpression of serglycin and p53, chromatin modification, ERBB-PI3K signalling, and raised plasma EBV DNA are among some highlighted determinants of prognosis.35–39 Notably, quantifi cation of plasma EBV DNA before treatment has been shown to independently predict for odds of recurrence and survival, complementing the TNM stage classifi cation.40,41 Large cohort studies have further qualified that strength of prognostication with EBV DNA is enhanced when combined with other unrelated biomarkers such as fi brinogen, plasma D-dimer, and C-reactive protein.42–44Imaging studiesOptimum imaging is crucial for staging and radiotherapy planning of nasopharyngeal carcinoma. MRI provides better resolution than CT in terms of assessing parapharyngeal spaces, marrow infi ltration of the skull base, intracranial disease, and deep cervical nodes. The advent of functional MRI adds a biological dimension. Parameters of cellularity (diff usion) and perfusion have been correlated to clinical stage of nasopharyngeal carcinoma.45 Likewise, ¹⁸F-fl uorodeoxyglucose (¹⁸F-FDG)-PET provides metabolic parameters (maximum standardised uptake value and total lesion glycolysis) that could be interpreted to represent tumour biology and predict clinical outcomes.46,47 It is also sensitive and accurate for the detection of nodal metastasis, but lacks the soft-tissue resolution of MRI for assessment of primary tumour.48,49SeminarIn terms of distant metastasis staging, several studies have concluded that ¹⁸F-FDG-PET is substantially more sensitive (70–80% vs about 30%) and accurate (>90% vs 83–88%) than conventional work-up consisting of chest radiography, abdominal ultrasound, and skeletal scinti g raphy.50,51 In the assessment of bone metastasis, also the most common site of distant spread, a direct comparison between ¹⁸F-FDG-PET and skeletal scintigraphy showed that ¹⁸F-FDG-PET is substantially more sensitive with similar specifi city. Thus, MRI and ¹⁸F-FDG-PET are recommended as the preferred modalities for staging in patients with TNM stage III, IVA, or IVB nasopharyngeal carcinoma, or raised plasma EBV DNA load of 4000 copies per mL or more.52Radiotherapy in the management of nasopharyngeal carcinoma Radiotherapy is the primary and only curative treatment for nasopharyngeal carcinoma. In centres where modern radiation technology is available, intensity-modulated radiotherapy (IMRT) is the preferred method. Briefl y, this technique caters for delivery of tumoricidal doses to gross tumour and subclinical disease, while minimising doses to adjacent normal tissues. Such a technology is particularly advantageous in nasopharyngeal carcinoma, in view of the late toxic eff ects reported in patients treated with crude two-dimensional (2D) radiotherapy techniques (appendix).53The recent improvement in disease control and survival in patients with nasopharyngeal carcinoma is partly attributable to IMRT. Early studies by independent groups reported 3-year local control and survival rates of 80–90%, even for advanced stages.54,55 In a randomised study by Peng and colleagues,56 IMRT contributed to an absolute improvement in 5-year locoregional control of 7·7% compared with conventional 2D radiotherapy. Additionally, a review of 1593 patients who were treated at a single institution with progressive radiotherapy techniques (2D radio t herapy, 3D radiotherapy, and IMRT) over two decades (1994 to 2010) also showed increased disease-specifi c and overall survival in individuals who received IMRT (disease-specifi c survival: 85% with IMRT vs 81% with 3D radiotherapy vs 78% with 2D radiotherapy; overall survival: 80% with IMRT vs 73% with 3D radiotherapy vs 71% with 2D radiotherapy; appendix).57The clinical yield of modifying fraction size (hyper-fractionation) and overall treatment time (acceleration) in patients with nasopharyngeal carcinoma is uncertain. Early studies testing a hyperfractionated, twice-daily regimen did not show a benefi t in tumour control, and even more concerning, reported increased incidences of late eff ects compared with conventionally fractionationated radiotherapy.58,59 Nonetheless, two other prospective trials did suggest effi cacy with altered fractionation schedules. Pan and colleagues 60 showed that a hyperfractionated radiotherapy regimen resulted in absolute improvements of 11·7% in locoregional control and 16·1% in overall survival at 5 years, without incurring incremental late neurological toxic eff ects, compared with conventionally fractionated radiotherapy. The NPC-9902 trial compared an accelerated regimen of six times a week with conventional fractionation, with or without concurrent chemotherapy, in patients with T3–4N0–1 nasopharyngeal carcinoma.61 Although concurrent chemotherapy and accelerated fractionation reduced the risk of treatment failure compared with conventionally fractionated radiotherapy alone (hazard ratio [H R] for failure-free survival 0·35, 95% CI 0·14–0·84), neither accelerated radiotherapy alone nor the combination of chemotherapy plus conventional radiotherapy improved outcomes compared with the control group. Since concurrent chemoradiotherapy is the established standard treatment of locally advanced nasopharyngeal carcinoma, the fi ndings of the NPC-9902 trial are certainly peculiar and the question remains whether altered fractionation improves the therapeutic ratio over and above combination chemotherapy. The NPC-0501 trial was a study designed in part to address this clinical conundrum.62 Preliminary results suggest that accelerated radiotherapy fractionation provides no therapeutic benefi t in patients with advanced disease receiving concurrent systemic treatment compared with conventional fractionation (H R for progression-free survival 1·13, 95% CI 0·82–1·54; appendix).Chemotherapy in non-metastatic disease The strategy of combining chemotherapy with radio-therapy is another pivotal advancement in the treatment of locally advanced nasopharyngeal carcinoma. Since the publication of the seminal INT-0099 trial, several trials have substantiated the benefi ts in disease control and survival reported with chemoradiotherapy, henceforth establishing this treatment as the standard of care in this subgroup (table 2).63–71 Combination regimens varied between studies, but for the most part, cisplatin was the chemotherapy of choice. In terms of dosing schedules, either 30–40 mg/m² once a week or 100 mg/m² every 3 weeks is accepted practice; however, these schedules were never prospectively compared. Nonetheless, any diff erences in radiosensitisation eff ects and toxic eff ects profi les between dosing schedules are likely to be negligible relative to the importance of cisplatin dose intensity, for which 200 mg/m² is the threshold for optimum effi cacy.72–74 Other concurrent agents with similar effi cacy to cisplatin are uracil plus tegafur (a prodrug of fl uorouracil) and oxaliplatin.69,70 Overall, meta-analyses examining the eff ects of chemoradiotherapy in nasopharyngeal carcinoma have consistently generated HR estimates of 0·64–0·79 for overall survival, 0·67–0·71 for distant metastasis-free survival, and 0·59–0·73 for locoregional control in favour of chemoradiotherapy over radiotherapy alone.75–77 For TNM stage II nasopharyngeal carcinoma, Chen and colleagues 71 reported a benefi t inSeminaroverall survival with chemoradiotherapy compared with radiotherapy alone mainly through improvement in distant failures. Nonetheless, because local control remains excellent with radiotherapy alone in this subgroup, some centres prefer to restrict chemoradiotherapy to individuals with a presumed high risk of distant metastasis (single or unilateral bulky node[s] 4–6 cm or EBV DNA >4000 copies per mL).Part of the current controversy around supportive evidence for combination treatment relates to the roles of induction and adjuvant chemotherapy. Regarding adjuvant chemotherapy, it typically consisted of cisplatin (20 mg/m² daily for 4 days) and fl uorouracil (1 g/m² daily for 4 days) given every 4 weeks for three cycles. Trends seen in specifi c trials of adjuvant chemotherapy showed that additional treatment after radiotherapy was poorly tolerated, with 55–75% compliance at best.63–65,71 Compounding the clinical dilemma, several trials designed specifi cally to investigate the benefi ts of adjuvant treatment largely did not show a survival advantage.69,78 These results contradict the fi ndings of other retrospective analyses that suggested an improvement in survival and reduction of distant metastasis when two or more cycles of adjuvant chemotherapy were delivered.73,79 Notably, in the trial byChen and colleagues,78 despite selecting for patientswho were at risk of developing distant metastasis (defi ned as clinical presentation of T3–4N1 or N2–3disease), the results of preliminary analyses after amedian follow-up of 37·8 months suggested similarclinical endpoints irrespective of treatment assignment(2-year outcomes for chemoradiotherapy vschemoradiotherapy plus adjuvant chemotherapy,failure-free survival 84% vs 86%; distant metastasis-freesurvival 86% vs 88%; overall survival 92% vs 94%).While we await long-term results, further evidenceregarding the eff ectiveness of adjuvant chemotherapycan be inferred from published meta-analyses. Independent pooled analyses of chemoradiotherapy trials based on whether adjuvant chemotherapy wasincorporated in the test group suggested similar benefi tsin overall survival with either approach compared withradiotherapy (H R 0·66–0·80 for chemoradiotherapy; 0·64–0·83 for chemoradiotherapy with adjuvant).75–77However, an updated network meta-analysis reported afavourable trend for overall survival (H R 0·84, 95% CI0·67–1·03) and distant failure-free survival (H R 0·90,0·69–1·17), and a significant advantage in terms ofSeminarSeminarlocoregional failure-free survival (H R 0·67, 0·46–0·95) with chemoradiotherapy followed by adjuvant chemotherapy compared with chemoradiotherapy alone.80 The probabilities for being ranked as the most eff ective treatment for overall survival were 84% for chemoradiotherapy followed by adjuvant chemotherapy and 3% for chemoradiotherapy alone. None of the meta-analyses included the latest trials from Singapore (NCT00997906) and Guangzhou (NCT01245959), which adopted chemoradiotherapy alone as the standard treatment (table 3).Induction chemotherapy was once thought to be a potentially more feasible and eff ective strategy of treatment intensifi cation than adjuvant sequencing. H owever, early phase 3 studies assessing various combinations of induction chemotherapy before radiotherapy alone have mostly been inconclusive. Generally, despite suggestions of better disease control, none of the studies actually reported an improvement in overall survival, although a combined exploratory analysis of the Asian Oceania Clinical Oncology Association (AOCOA) and Guangzhou trials did later report a benefi t in survival and distant failures in patients with T1–2N0–1 disease.84 Interest, however, was subsequently renewed after promising reports of 2-year and 3-year overall survival of 71–95% from smaller phase 2 studies that used induction chemotherapy and chemoradiotherapy.81,85–88 In a randomised phase 2 comparison of chemoradiotherapy (cisplatin) with or without induction cisplatin and docetaxel, H ui andcolleagues 81 reported that 3-year progression-free survival and overall survival was 88% and 94% in the experimental group compared with 60% and 68% in the control group, respectively. By contrast with these fi ndings, a series of randomised trials have yet to reproduce these favourable results (table 3). Fountzilas and colleagues 82 tested an induction regimen consisting of epirubicin, cisplatin, and paclitaxel, and reported no diff erence in response rates, progression-free survival, and overall survival when the triplet combination was added to chemoradiotherapy. Tan and colleagues 83 recently reported a phase 3 study of 172 patients with advanced nasopharyngeal carcinoma and reported that locoregional control, distant metastasis-free survival, and overall survival did not diff er between groups with the addition of induction gemcitabine, carboplatin, and paclitaxel to chemoradiotherapy. Finally, the six-arm NPC-0501 study (a 2 × 3 factorial study of concurrent cisplatin and conventional or accelerated radiotherapy, in combination with induction cisplatin plus capecitabine, or induction cisplatin plus fl uorouracil, or adjuvant cisplatin plus fl uorouracil) showed that overall chemotherapy tolerance was similar between patients who received induction or adjuvant chemotherapy, and variation in sequencing of cisplatin and fl uorouracil did not achieve a statistically signifi cant improvement in progression-free survival and overall survival.62 In summary, the role of induction chemotherapy in the management of locally advanced nasopharyngeal carcinoma remains investigational, and current evidence precludes its routine use in patients planned for chemoradiotherapy.A better patient stratifi cation for treatment intensifi cation and deintensifi cation is clearly needed. A subgroup analysis of the Taiwanese chemoradiotherapy trial showed that chemoradiotherapy was benefi cial in patients without high-risk features such as N3 or T4N2 disease or bulky nodal metastases (at least one node >4 cm), whereas patients harbouring any of these disease characteristics had poorer outcomes with chemo-radiotherapy.89 These fi ndings might be preliminary, but they highlight the importance of improvising patient stratifi cation beyond the TNM staging system. The incorporation of prognostic biomarkers is a potential strategy. Two phase 3 trials are underway, in which patients are randomly assigned to adjuvant regimens of diff ering intensities depending on whether EBV DNA is detectable after chemoradio t herapy (NRG-N001, NCT02135042; NPC-0502, NCT00370890). Findings that persistent EBV DNA detection is strongly associated with a high likelihood of tumour recurrence and poor prognosis lend support to both trials.40,41,90–92 Coincidentally, a retrospective analysis from Taiwan showed that in a cohort of 85 patients who had persistent EBV DNA titres after radiation, adjuvant tegafur and uracil substantially reduced distant failure and improved survival (appendix).93Disease surveillance and toxic eff ectsInitial post-treatment assessment entails monitoring of acute eff ects and tumour response. Common acute radiotherapy-related eff ects include mucositis, dysphagia, dermatitis, and xerostomia. Clinical symptoms typically improve within weeks after treatment cessation, but in instances of grade 3 or 4 reactions, these can persist, leading to consequential late eff ects. Chemoradiotherapy is invariably associated with higher incidences of haematological and non-haematological acute toxic eff ects compared with radiotherapy alone.94,95 Unlike its benefi ts in reducing late eff ects, IMRT seems to have a limited role in mitigating acute toxic eff ects. Pharmacological interventions for acute xerostomia and mucositis are mostly ineff ective, although studies have suggested eff ective relief of mucositis with palifermin (recombinant human keratinocyte growth factor) and doxepin rinse (tricyclic antidepressant).96–98Comprehensive assessment of tumour response includes clinical examination, nasendoscopy with or without biopsy, EBV DNA titre measurement, and radiological imaging.99 Nasendoscopy is restricted to assessing superfi cial lesions and a positive biopsy sample 10 weeks after treatment has been shown to probably represent persistent residual disease.100 For deeper lesions within the skull base, radiological assessment is necessary, but it might pose a challenge。
简述良性肿瘤与恶性肿瘤的区别9、简述cancer、carcinoma、sarcoma的
1、简述良性肿瘤与恶性肿瘤的区别9、简述cancer、carcinoma、sarcoma的定义和关系（请各举例３个carcinoma、sarcoma）。
简述细胞原癌基因的分类以及激活机制23、简述cancer、carcinoma、sarcoma的定义和关系（请各举例３个carcinoma、sarcoma）。
24、简述肿瘤浸润的途径有哪些25、简述肿瘤对机体有哪些影响？26、细胞凋亡（apotosis）在细胞生长发育过程中具有十分重要意义，请简述其生物学意义以及包括的阶段27、癌基因有多种分类方法，根据癌基因产物的功能分类有哪几种？28、叙述细胞凋亡的形态学和生化特征。
1．试述化学致癌物影响人类健康、导致人类肿瘤的主要途径，并各举2例2．简述基因与肿瘤形成的关系3．简述遗传性肿瘤综合症的特点4．试述癌基因的定义，并举例。
（至少3个）5，试简述抑癌基因的可能功能。
1、肿瘤流行病学研究可归纳为哪几个主要方面？2、分子流行病学研究中生物标志物的分类？3、研究肿瘤流行病学的意义？4、当前我国癌症发病增高的主要原因有哪些？呼吸系统的内镜包括哪些？22.消化系统的内镜包括哪些？23.内镜诊断的常用方法？24.内镜的发展史上，依次出现过那些种类的内镜？25.胶囊内镜的优点？26. 气管镜检查的并发症包括哪些？27. 气管镜检查的范围。
28.胃镜检查的范围。
29.胃镜检查的适应证。
30.胃镜检查的禁忌证。
31.结肠镜检查的适应证。
32.结肠镜检查的禁忌证。
33.十二直肠镜的应用有哪些？34. ERCP 的适应证。
35.ERCP的禁忌证。
36.小肠镜的检查方法。
37. 小肠镜检查适应证。
38. 结肠镜肠穿孔类型。
39. 介入超声诊断的意义。
40. 腹腔镜的适应证。
5、在肿瘤病理学中，目前有较多的新技术、新方法，它们多有哪些方面？20、对于实体肿瘤一般形态学表现在哪几方面？21、病理学检查诊断诊断时，存在的不足，其主要可能有哪方面？22、简述良性肿瘤与恶性肿瘤的区别23、外科病理学医师提高冰冻切片诊断准确性的措施有哪些？24、病理申请单的填写规范与病理诊断的准确性是相关的，申请单应该填写哪些内容？25、简述冰冻切片的指征？1．肿瘤的临床诊断应该包括哪3个方面?2．常用肿瘤标志物有哪些？3．AFP，中文名称甲胎蛋白，英文名称是什么？可用于诊断什么恶性肿瘤?4．PSA，中文名称前列腺特异性抗原，英文名称是什么？可用于诊断什么恶性肿瘤？5．肿瘤的高危因素的定义是什么？6．肿瘤的发生与生活习惯密切相关。
癌细胞CancercellPPT课件
这是癌细胞的基本特征。
●在分化程度上癌细胞低于良性肿瘤细胞，且失去了
许多原组织细胞的结构和功能
3.细胞间相互作用改变（识别改变；表达水解酶类；产生新的表
面抗原）
4.蛋白表达谱系或蛋白活性改变（胚胎细胞蛋白、端粒酶活性升
高）
5.mRNA转录谱系的改变（少数基因表达不同；突变位点
不同，表型多变）
6.染色体非整倍性
去分化现象；对生长因子需要量降低；代谢旺盛 线粒体功能障碍：即使在氧供应充分的条件下也主要是糖酵解途径获取能量。
与三个糖酵解关键酶（己糖激酶、磷酸果糖激酶和丙酮酸激酶）活性增加和同 工酶谱的改变，以及糖原异生关键酶活性降低有关。 可移植性：正常细胞移植到宿主体内后，由于免疫反应而被排斥，多不易存活。 但是肿瘤细胞具有可移植性，如人的肿瘤细胞可移植到鼠类体内，形成移植瘤。
致癌因素
内因：恶性肿瘤的形成往往涉及多个基因的改变 外因：多种理化因子致癌
根据其性质分为：化学、生物和物理致癌物三大类 根据它们在致癌过程中的作用，可分为；
1.启动剂：可直接改变DNA的成分或结构。 2.促进剂：本身不能诱发肿瘤，但有促进作用。
如糖精可促进膀胱癌的发生，苯巴比妥促进肝癌的发 生。 3.完全致癌物：兼具启动和促进两种作用。
(2)如果我们把原癌基因切除，就会避免 癌症的发生，对吗？为什么？
鼠白血病毒 Mouse Leukemia Virus
三、物理因素
（一）、电离辐射 辐射致癌的机制： ①染色体或基因的突变； ②基因表达改变； ③激活潜伏的致癌病毒。
（二）、紫外线 可引起细胞DNA断裂、交联和染色体畸变，抑制
皮肤的免疫功能，诱发皮肤癌、基底细胞癌和黑色 素瘤。
癌发生涉及的基因及其作用
医学词根
carcino- 癌：carcinoma atypical 不典型癌alb- 白：alba lochia 白色恶露leuco- 白，白细胞，褪色，无色：leucoagglutinin白细胞凝集素；leuco base无色基leuko- 白，白细胞，褪色，无色: leukocytes白细胞; leukoblast白细胞母细胞,成白细胞细胞centi- 百分之一,厘: centimeter厘米,公分hect- 百：hectare 公顷hemi- 半,偏侧,单侧: hemiablepsia偏盲; hemialgia偏侧痛semi- 半，一半：semiantigen半抗原dorsi- ,dorso- 背，背侧: dorsibronchus背支气管; dorsispinal脊柱背侧的opistho- 背，后面：opisthocheilia唇后缩naso- 鼻：nasoantrostomy 鼻上颌窦造口术rhino- 鼻，鼻样结构：rhinoantritis 鼻上颌窦炎prop- 丙：Prop acil丙基硫氧嘧啶patho- 病理：pathoanatomy病理解剖学；pathobolism新陈代谢异常,病理性代谢morbido- 病：morbid oberity病理性肥胖-igo 病：aurigo黄疸；bullous impetigo大疱性脓疱病-metry 量度法,测量法: acidimetry 酸量滴定法,酸量法lamino- 层：laminograph体层照像机,断层照像机longi- 长度：Longicil苄星青霉素(长效青霉素)entero- 肠,肠道: entero-adenitis肠腺炎; enteroantigen肠抗原intesino- 肠：intestinalization肠化生-plasty 成形术,整复术,整形术,形成: Angioplasty 血管成形术gingivo- 齿龈：gingivoectomy龈切除术; gingivolabial龈唇的ulo- 瘢,瘢痕,龈,牙龈,齿龈: ulocace 龈溃疡; ulodermatitis成瘢痕皮炎hapto- 接触，结合，触觉：haptospore附着孢子thigmo- 触或机体接触的: thigmocyte血小板; thigmomorphosis接触膨大-centesis 穿刺: abdominocentesis 腹腔穿刺术hypophyso- 垂体：hypophysoma垂体瘤；hypophysoprivic垂体分泌缺乏的cheilo- 唇：cheiloplasty 唇成形术；cheilotomy 唇切除术labio- 唇：labiomental 唇颏的-ol 醇，酚：allyl guaiacol丁香油酚,丁香酸anti- (against):antibiotics 抗生素，antioxidants 抗氧化物antiseptic n. 杀菌剂,adj. 防腐的hyper-(above): hypertension 高血压，hyperoxia 高氧症hyperthermia过热sym- ,syn- (together): symphony交响乐，symptom n. 症状,症候,征兆syndrome 综合征pre-(before,in front of): predispose使易害,造成…的因素, premature早熟的,过早的infra-(beneath): infrastructure 基础，基础结构，infrared adj. & n.红外线(的)，infrasonic 听域下的physi-(nature): physiopathologic 病理生理的，physiotherap物理治疗psych-(mind): psychosocial精神社会的,社会心理的,心理社会的, psychiatric 精神病的,精神病学的,psychoactive对精神起作用的,影响精神行为的,精神活性药,精神活性的pedia-（child）：pediatrics 儿科学，pediatrist 儿科学家dent- （tooth）：dentistry 口腔医学,牙科学，denture假牙-iatrics（treatment，healing）：amblyopiatrics 弱视矫正法morpho-（form）：morphocytology细胞形态学，morphologic形态学的，morphography形态论chromo-（color）：chromosome染色体，chromogenesis 色素生成chrono-（time）：chronic慢性的；chronological 年代学的bio-（life）：biochemical生物化学的；biopsy活组织检查biomedical生物医学的necro-（dead）：Necrosis坏死；necropsy尸检necrology死亡统计,死亡统计学-genesis（origination，production）：pathogenesis发病机制；Biogenesis 生源论Cytogenesis细胞发生-plasm，-plasia（a thing formed，forming）：hyperplasia增生aplasia不发育neoplasm肿瘤lipo-（fat）：hyperlipoprotein emia高脂蛋白血症lipoarthritis关节脂肪组织炎lipoprotein脂蛋白proteo-（protein）：proteolipid蛋白脂,含蛋白脂质；proteopeptic蛋白质消化的；proteometabolism蛋白代谢；glyco—（sweet，sugar）：hypoglycaemia低血糖glycogenesis糖原生成；glycolysis糖酵解chole-（bile胆汁）：cholesterol胆固醇；cholelith 胆石；cholemia 胆血症医学英语词汇通常拼写较长而复杂，且与普通的英文词汇有较大的差异，不容易记忆。
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OCULAR SURGERY NEWS 4/15/00Radiosurgery can be useful in the treatment of basal cell carcinoma of the eyelidsIn selected cases of basal cell carcinomas, when the tumor is small and its borders are well defined, radiosurgery may be an alternative to traditional surgery.Maurizio Santella, MD; U. Benelli, MD; G. Aimino, MD; G. Davi, MD; A. Morocutti, MD; Herve M. Byron, MDBasal cell carcinoma is a malignant tumor derived from cells of the basal cell layer of the epidermis. The etiology of basal cell carcinoma is linked to excessive ultraviolet light exposure in fair-skinned individuals. Other predisposing factors include ionizing radiation and scars. While metastases are rare, local invasion is common and can be very destructive.Basal cell carcinoma is the most common malignant tumor of the eyelids; it comprises 85% to 90% of all malignant epithelial eyelid tumors at this site. Over 99% of basal cell carcinomas occur in Caucasians; about 95% of these lesions occur between the ages of 40 and 80 years, with an average age at diagnosis of 60 years.Ocular manifestations---Local malignancy ofbasal cell carcinoma.Two-thirds of basal cellcarcinomas affect thelower eyelid. Themedial canthus and upper eyelid are involved with a nearly equal incidence of about 15%. The lateral canthus is only rarely involved (5%). Based upon their histopathologic presentation, basal cell carcinomas may be classified into five basic types: nodular-ulcerative, pigmented, morphea or sclerosing, superficial and fibroepithelioma.The diagnosis of basal cell carcinoma is initially made from its clinical appearance, especially with the nodulo-ulcerative type with its raised pearly borders and central ulcerated crater. Definitive diagnosis, however, can only be made on histopathologic examination of biopsy specimens.Treatment---Ellman IEC device.The goal of therapy is the complete removal of tumorcells with preservation of unaffected eyelid and periorbitaltissues. While nonsurgical treatments such ascryotherapy, electrodesiccation and laser ablation areadvocated by some, surgical therapy is generally accepted as the treatment of choice for removal of basal cell carcinomas.In selected cases of basal cell carcinomas (especially in the superficial or pigmented types), when the tumor is small and its borders are well defined, radiosurgery at 4 MHz could be a valid alternative to traditional surgery. RadiosurgeryRadiosurgery is an atraumatic method of cutting and coagulating soft tissue by means of ultra high frequency radiowaves passing through the tissue cells.The radiosurgical unit produces radiowaves at 4 MHz, which are transmitted to a metallic wire electrode and a passive metallic ground plate. The unit that we used in this study, and that delivers the patented frequency and selection of waveforms, is the Ellman (Hewlett, N.Y.) IEC device.The soft tissue is placed between the two electrodes and the radio signal is directed from the active to the passive electrode. The passage of ultra high frequency radiowaves causes the cells to heat up as a result of the tissue’s natural resistance to the radiosignal. The cutting effect is achieved as a result of cell modulation or volatilization, which results from the heat generated by the tissue’s natural resistance to the passage of the active electrode. The radio signal is directed through the tissues by the active microwire electrode. The radiowaves generated by the radiosurgical unit may be modified in their waveform and power, and the frequency remains constant.Using a fully rectified and filtered waveform, a biopsy may be easily accomplished without any necrosis of the cells along the incision. For large lesions, it is extremely important that the biopsy includes adjacent normal tissue.StudyIn our study, 10 selected cases of basal cell carcinoma of eyelids (nodular and/or superficial basal cell carcinomas) have been treated with radiofrequency with local anesthesia. Six cases were located on the lower eyelid, two cases on the upper eyelid and two cases on the medial canthus. When a lesion develops clinical features that suggest malignant degeneration, such as a rapid and irregular growth, bleeding and ulceration, radiosurgery was not employed. It is, therefore, mandatory to always perform a histologic examination of the biopsied tissue.All patients have been treated by the same surgeon. The biopsy confirmed the diagnosis of basal cell carcinoma. After treatment (3 years follow-up), the cosmetic result was very good and no complications were noted.ConclusionsRadiosurgery at 4 MHz may be very useful in the treatment of well-delimited basal cell carcinoma of the eyelids. This kind of seemingly easy excisional procedure may be complicated by anatomical and histological differences of each tumor.However, if it is correctly performed, it gives satisfactory results. It is mandatory to perform a histologic examination of all biopsied tissue.Complete surgical excision of basal cell carcinoma almost always is curative, since these lesions rarely metastasize. The incidence of metastasis ranges from 0.028% to 0.55%. Tumor-related death is exceedingly rare; but when it does occur, it usually is caused by direct orbital and intracranial extension.Patient with pigmented lesion of the inferior eyelid before, during and after radiosurgery.For Your Information:∙Herve M. Byron, MD, can be reached at 114 Roberts Road, Englewood Cliffs, NJ 07632; (201) 567-9479; fax: (201)568-7765; e-mail: byronmd@. Dr. Byron has nodirect financial interest in any of the products mentioned inthis article. He is a paid consultant for Ellman International.∙Ellman International can be reached at 1135 Railroad Ave., Hewlett, NY 11557-2316; (516) 569-1482; fax: (516)569-0054; e-mail: ellman@.Reference:∙Lee SB, Saw SM, Eong KG, Chan TK, Lee HP. Incidence of eyelid cancers in Singapore from 1968 to 1995. Br JOphthalmol. 1999;8:595-597.∙Lindgren G, Diffey BL, Larko O. Basal cell carcinoma of the eyelids and solar ultraviolet radiation exposure. Br JOphthalmol. 1998;82:1412-1415.∙Pieh S, Kuchar A, Novak P, Kunstfeld R, Nagel G, Steinkogler FJ. Long-term results after surgical basal cell carcinomaexcision in the eyelid region. Br J Ophthalmol. 1999;83:85-88.。