Annual report on status of cancer in China, 2011

FOLFOXIRI方案一线治疗转移性结直肠癌的研究进展董秋霞;黄镜【摘要】转移性结直肠癌的主要治疗手段是全身化疗。

目前5-氟尿嘧啶、奥沙利铂及伊立替康仍然是治疗结直肠癌最基本也是最有效的化疗药物，这三种药物联合的化疗方案（FOLFOXIRI）较两药联合的方案可以显著延长患者的生存时间，但同时也增加了患者的毒副反应。

如何在确保疗效的前提下减少化疗药物的相关毒副反应成为治疗的关键。

【期刊名称】《癌症进展》【年(卷),期】2014(000)005【总页数】6页(P464-468,473)【关键词】结直肠癌;奥沙利铂;伊立替康;氟尿嘧啶【作者】董秋霞;黄镜【作者单位】青海省第五人民医院肿瘤一科，西宁 810007;中国医学科学院肿瘤医院内科，北京 100021【正文语种】中文【中图分类】R735.1结直肠癌在我国发病率与死亡率已分别占恶性肿瘤的第六位和第五位[1]。

对于转移性结直肠癌，主要的治疗手段是全身化疗。

尽管针对结直肠癌的有效药物如奥沙利铂（Oxaliplatin，OXA）、伊立替康（Irinotecan，IRI）、卡培他滨（Capecitabine，CAP）及靶向药物等的不断出现，5-氟尿嘧啶（5-Fluorouracil，5-FU）仍被认为是治疗转移性结直肠癌治疗的基础药物。

研究证实以氟尿嘧啶类药物（5-FU或CAP）为基础联合IRI或OXA的双药联合方案的总有效率（overall response rate，ORR）为20%～47%、无进展生存时间（progression free survival，PFS）为5.9～9个月、总生存时间（overall survival，OS）为15.1～21.5个月，且相互之间疗效均无显著差异[2-7]。

但在Ⅲ期临床研究中，三药或两药联合抗靶向药物血管内皮生长因子﹙vascular endothelial grow th factor，VEGF﹚或表皮生长因子受体﹙epidermal grow th factor receptor，EGFR﹚单抗方案相比传统两药方案，有效率及生存时间（ORR：39%～68%；PFS：7.2～10.6个月；OS： 19.9～27.7个月）[4-8]明显提高。

绝密★启用前2020年全国硕士研究生招生考试英语（一）（科目代码：201）☆考生注意事项☆1.答题前，考生须在试题册指定位置上填写考生编号和考生姓名；在答题卡指定位置上填写报考单位、考生姓名和考生编号，并涂写考生编号信息点。

2.考生须把试题册上的“试卷条形码”粘贴条取下，粘贴在答题卡的“试卷条形码粘贴位置”框中。

不按规定粘贴条形码而影响评卷结果的，责任由考生自负。

3.选择题的答案必须涂写在答题卡相应题号的选项上，非选择题的答案必须书写在答题卡指定位置的边框区域内。

超出答题区域书写的答案无效；在草稿纸、试题册上答题无效。

4.填（书）写部分必须使用黑色字迹签字笔书写，字迹工整、笔迹清楚；涂写部分必须使用2B铅笔填涂。

5.考试结束，将答题卡和试题册按规定交回。

（以下信息考生必须认真填写）考生编号考生姓名SectionⅠUse of EnglishDirections:Read the following text.Choose the best word(s)for each numbered blank and mark A,B,C or D on the ANSWER SHEET.(10points)Even if families don’t sit down to eat together as frequently as before,millions of Britons will nonetheless have got a share this weekend of one of that nation’s great traditions:the Sunday roast.1a cold winter’s day,few culinary pleasures can 2it.Yet as we report now,the food police are determined that this3should be rendered yet another guilty pleasure4to damage our health.The Food Standards Authority(FSA)has5a public warning about the risks of a compound called acrylamide that forms in some foods cooked6high temperatures.This means that people should7crisping their roast potatoes,reject thin-crust pizzas and only8toast their bread.But where is the evidence to support such alarmist advice?9studies have shown that acrylamide can cause neurological damage in mice,there is no10evidence that it causes cancer in humans.Scientists say the compound is11to cause cancer but have no hard scientific proof12the precautionary principle,it could be argued that it is13to follow the FSA advice.14,it was rumoured that smoking caused cancer for years before the evidence was found to prove a15.Doubtless a piece of boiled beef can always be16up on Sunday alongside some steamed vegetables,without the Yorkshire pudding and no wine.But would life be worth living?17,the FSA says it is not telling people to cut out roast foods18,but to reduce their lifetime intake.However,their19risks coming a cross as being pushy and overprotective.Constant health scares just20with one listening.1.[A]In[B]Towards[C]On[D]Till2.[A]match[B]express[C]satisfy[D]influence3.[A]patience[B]enjoyment[C]surprise[D]concern4.[A]intensified[B]privileged[C]compelled[D]guaranteed5.[A]issued[B]received[C]ignored[D]cancelled6.[A]under[B]at[C]for[D]by7.[A]forget[B]regret[C]finish[D]avoid8.[A]partially[B]regularly[C]easily[D]initially9.[A]Unless[B]Since[C]If[D]While10.[A]secondary[B]external[C]conclusive[D]negative11.[A]insufficient[B]bound[C]likely[D]slow12.[A]On the basis of[B]At the cost of[C]In addition to[D]In contrast to13.[A]interesting[B]advisable[C]urgent[D]fortunate14.[A]As usual[B]In particular[C]By definition[D]After all15.[A]resemblance[B]combination[C]connection[D]pattern16.[A]made[B]served[C]saved[D]used17.[A]To be fair[B]For instance[C]To be brief[D]In general18.[A]reluctantly[B]entirely[C]gradually[D]carefully19.[A]promise[B]experience[C]campaign[D]competition20.[A]follow up[B]pick up[C]open up[D]end upSectionⅡReading ComprehensionPart A Directions:Read the following four texts.Answer the questions after each text by choosing A,B, C or D.Mark your answers on the ANSWER SHEET.(40points)Text 1A group of Labour MPs, among them Yvette Cooper, are bringing in the new y ear with a call to institute a UK "town of culture" award. The proposal is that itshould sit alongside the existing city of culture title, which was held b y Hull in 2017, and has been awarded to Coventry for 2021. Cooper and her colleagues argue that the success of the crown for Hull, where it brought in位20m of investment and an avalanche of arts, ought not to be confined to cities. Britain's towns, it is true, are not prevented from appl y ing, but the y generall y lack the resources to put together a bid to beat their bigger competitors. A town of culture award could, it is argued, become an annual event, attracting funding and creating jobs.Some might see the proposal as a boob y prize for the fact that Britain 1s no longer able to appl y for the much more prestigious title of European capital of culture, a sought-after award bagged b y Glasgow in 1990 and Liverpool in 2008. A c y nic might speculate that the UK is on the verge of disappearing into an endless fever of self-celebration in its desperation to reinvent itself for the post-Brexit world: after town of culture, who knows what will follow-village of culture? Suburb of culture? Hamlet of culture?It is also wise to recall that such titles are not a cure-all. A badl y run "y ear of culture" washes in and washes out of a place like the tide, bringing prominence for a spell but leaving no lasting benefits to the community. The reall y successful holders of such titles are those that do a great deal more than fill hotel bedrooms and bring in high-profile arts events and good press for a y ear. The y transform the aspirations of the people who live there; the y nudge the self-image of the cit y into a bolder and more optimistic light. It is hard to get right, and requires a remarkable degree of vision, as well as cooperation between city authorities, the private sector, communit y groups and cultural organisations. But it can be done: Glasgow's y ear as European capital of culture can certainl y be seen as one of a complex series of factors that have turned the cit y into the powerhouse of art, music and theatre that it remains toda y.A "town of culture" could be not just about the arts but about honouring a town's peculiarities—helping sustain its high street, supporting local facilities and above all celebrating its people. Jerem y Wright, the culture secretary, should welcome this positive, hope-filled proposal, and turn it into action.21. Cooper and her colleagues argue that a "town of culture" award could[A] consolidate the town-cit y ties in Britain.[BJ promote cooperation-among Britain's towns.[CJ increase the economic strength of Britain's towns.[DJ focus Britain's limited resources on cultural events.22. According to Paragraph 2, the proposal might be regarded b y some as[A] a sensible compromise.[BJ a self-deceiving attempt.[CJ an e y e-catching bonus.[DJ an inaccessible target.23. The author suggests that a title holder is successful onl y if it[A] endeavours to maintain its image.[B] meets the aspiration of its people.[C] brings its local arts to prominence.[DJ commits to its long-term growth.24. Glasgow is mentioned in Paragraph 3 to present[A] a contrasting case.[B] a supporting example.[C] a background story.[D] a related topic.25. What is the author's attitude towards the proposal?[A] Skeptical.[B] Objective.[C] Favourable.[D] Critical.Text2Scientific publishing has long been a licence to print mone y. Scientists need journals in which to publish their research, so the y will suppl y the articles without monetary reward. Other scientists perform the specialised work of peer review also for free, because it is a central element in the acquisition of status and the production of scientific knowledge.With the content of papers secured for free, the publisher needs onl y find a market for its journal. Until this century, university libraries were not very price sensitive. Scientific publishers routinel y report profit margins approaching 40% on their operations at a time when the rest of the publishing industry is in an existential crisis.The Dutch giant Elsevier, which claims to publish 25% of the scientific papers produced in the world, made profits of more than砂OOm last y ear, while UK universities alone spent more than£210m in 2016 to enable researchers to access their own publicl y funded research; both figures seem to rise unstoppabl y despite increasingl y desperate efforts to change them.The most drastic, an thoroughl y illegal, reaction has been the emergence of Sci-Hub, a kind of global photocopier for scientific papers, set up in 2012, which now claims to offer access to every paywalled article published since 2015. The success of Sci-Hub, which relies on researchers passing on copies the y have themselves legall y accessed, shows the legal ecos y stem has lost legitimac y among its users and must be transformed so that it works for all participants.In Britain the move towards open access publishing has been driven b y funding bodies. In some wa y s it has been very successful. More than half of all British scientific research is now published under open access terms: either freel y available from the moment of publication, or paywalled for a y ear or more so that the publishers can make a profit before being placed on general release.Yet the new s y stem has not y et worked out an y cheaper for the universities. Publishers have responded to the demand that the y make their product free to readers b y charging their w门ters fees to cover the costs of prep ring an article. These range from around眨00to $5,000, and apparentl y the work gets more expensive the more that publishers do it. A report last y ear pointed out that the costs both of subscriptions and of these "article preparation costs" had been steadil y rising at a rate above inflation.In some wa y s the scientific publishing model resembles the econom y of the social internet: labour is provided free in exchange for the hope of status, while huge profits are made b y a few big伍ms who run the market places. In both cases, we need a rebalancing of power.26. Scientific publishing is seen as "a licence to print money" partly because[A] its funding has enjoyed a steady increase.[B] its marketing strategy has been successful.[C] its payment for peer review is reduced.[D] its content acquisition costs nothing.27. According to Paragraphs 2 and 3, scientific publishers Elsevier have[A] thrived mainly on university libraries.[B] gone through an existential crisis.[C] revived the publishing industry.[D] financed researchers generously.28. How does the author feel about the success of Sci-Hub?[A] Relieved.[B] Puzzled.[C] Concerned.[D] Encouraged.29. It can be learned from Paragraphs 5 and 6 that open access terms[A] allow publishers some room to make money.[B] render publishing much easier for scientists.[C] reduce the cost of publication substantially.[D] free universities from financial burdens.30. Which of the following characterizes the scientific publishing model?[A] Trial subscription is offered.[B] Labour triumphs over status.[C] Costs are well controlled.[D] The few feed on the many.Text3Progressives often support diversity mandates as a path to equality and a wa y to level the pla y ing field. But all too often such policies are an insincere form of virtue-signaling that benefits onl y the most privileged and does little to help average people.A pair of bills sponsored b y Massachusetts state Senator Jason Lewis and House Speaker Pro Tempore Patricia Haddad, to ensure "gender parity" on boards and commissions, provide a case in point.Haddad and Lewis are concerned that more than half the state-government boards are less than 40 percent female. In order to ensure that elite women have more such opportunities, the y have proposed imposing government quotas. If the bills become law, state boards and commissions will be required to set aside 50 percent of board seats for women b y 2022.The bills are similar to a measure recentl y adopted in Califomia, which last y ear became the first state to require gender quotas for private companies. In signing the measure, California Governor Jerry Brown admitted that the law, which expressl y classifies people on the basis of sex, is probabl y unconstitutional.The US Supreme Court frowns on sex-based classifications unless the y are designed to address an "important" polic y interest, Because the California law applies to all boards, even where there is no history of prior discrimination, courts are likel y to rule that the law violates the constitutional guarantee of "equal protection".But are such government mandates even necessary? Female participation on corporate boards ma y not currentl y mirror the percentage of women in the general population, but so what?The number of women on corporate boards has been steadil y increasing without government interference. According to a study b y Catal y st, between 2010 and 2015 the share of women on the boards of global corporations increased b y 54 percent.Requiring companies to make gender the primary qualification for board membership will inevitabl y lead to less experienced private sector boards. That is exactl y what happened when Norwa y adopted a nationwide corporate gender quota.Writing in The New Republic, Alice Lee notes that increasing the number of opportunities for board membership without increasing the pool of qualified women to serve on such boards has led to a "golden skirt" phenomenon, where the same elite women scoop up multiple seats on a variety of boards.Next time somebod y pushes corporate quotas as a wa y to promote gender equity, remember that such policies are largel y self-serving measures that make their sponsors feelgood but do little to help average women.31. T he author believes that the bills sponsored by Lewis and Haddad will[A] help little to reduce gender bias.[B] pose a threat to the state government.[C] raise women's position in politics.[D] greatly broaden career options.32. Which of the following is true of the Califormia measure?[A] It has irritated private business owners.[B] It is welcomed by the Supreme Court.[C] It may go against the Constitution.[D] It will settle the prior controversies.33. The author mentions the study by Catalyst to illustrate[A] the harm from arbitrary board decision.[B] the i mp ortance of constitutional guarantees.[C] the pressure on women in global corporations.[D] the needlessness of government interventions.34. Norway's adoption of a nationwide corporate gender quota has led to[A] the underestimation of elite women's role.[B] the objection to female participation on boards.[C] the entry of unqualified candidates into the board.[D] the growing tension between labor and management.35. Which of the following can be inferred from the text?[A] Women's need in employment should be considered.[B] Feasibility should be a prime concern in policymaking.[C] Everyone should try hard to promote social justice.[D] Major social issues should be the focus of legislation.Text4Last Thursda y, the French Senate passed a di g ital services tax, which would impose an entirel y new tax on lar g e multinationals that provide di g ital services to consumers or users in France. Di g ital services include everythin g from providin g a platform for sellin g g oods and services online to tar g etin g advertisin g based on user data, and the tax applies to gross revenue from such services. Man y French politicians and media outlets have referred to this as a " GAF A tax," meanin g that it is desi g n ed to appl y primaril y to companies such as Goo g le, Apple, Facebook and Amazon—in other words, multinational tech companies based in the United States.The di g ital services tax now awaits the si g n ature of President Emmanuel Macron, who has expressed support for the measure, and it could g o into effect within the next few weeks. But it has already sparked si g n ificant controvers y, with the United States trade representative openin g an investi g ation into whether the tax discriminates a g ainst American companies, which in tum could lead to trade sanctions a g ainst France.The French tax is not just a unilateral move b y one countr y in need of revenue. Instead, the di g ital services tax is part of a much lar g er trend, with countries over the past few y ears proposin g or puttin g in place an alphabet soup of new international tax provisions. The y have included Britain's DPT. (diverted profits tax), Australia's MAAL (multmat1onal anti-avoidance law), and India's SEP (si g n ificant economic presence) test, to name but a few. At the same time, the European Union, Spain, Britain and several other countries have all seriousl y contemplated di g ital services taxes.These unilateral developments differ in their specifics, but the y are all desi g n ed to tax multinationals on income and revenue that countries believe the y should have a ri g ht to tax, even if international tax rules do not grant them that ri g ht. In other words, the y all share a view that the international tax s y stem has failed to keep up with the current econom y.In response to these man y unilateral measures, the Or g anization for Economic Cooperation and Development (OECD) is currentl y workin g with 131 countries to reach a consensus b y the end of 2020 on an international solution. Both France and the United States are involved in the or g anization's work, but France's di g ital services tax and the American response raise questions about what the future holds for the international tax s y stem.France's planned tax is a clear warnin g: Unless a broad consensus can be reached on reformin g the international tax s y stem, other nations are likel y to follow suit, and American companies will face a cascade of different taxes from dozens of nations that will prove burdensome and costl y.36.The French Senate has passed a bill to[A] regulate digital services platforms.[B] protect French companies" interests.[C] impose a levy on tech multinationals.[D] curb the influence of advertising.37. It can be learned from Paragraph 2 that the digital services tax[A] may trigger countermeasures against France.[B] is apt to arouse criticism at home and abroad.aims to ease mtemat10nal trade tensions.[C][D] will prompt the tech giants to quit France.38. The countries adopting the unilateral measures share the opinion that[A] redistribution of tech giants'revenue must be ensured.[B] the current international tax system needs upgrading.[C] tech multinationals'monopoly should be prevented.[D] all countries ought to enjoy equal taxing rights.39. It can be learned from Paragraph 5 that the O ECD's current work[A] is being resisted by US companies.[B] needs to be readjusted immediately.[C] is faced with uncertain prospects.[D] needs to in involve more countries.40. Which of the following might be the best title for this text?[A] France Is Confronted with Trade Sanctions[B] France leads the charge on Digital Tax[C] France Says" NO" to Tech Multinationals[D] France Demands a Role in the Digital EconomyPartBDirections:Read the following text and answer the questions b y choosing the most suitable subheading from the list A-G for each of the numbered paragraphs (41-45). There are two extra subheadings. Mark y our answers on the ANSWER SHEET. (10 points)[A] E y e fixations are brief[B] Too much e y e contact is instinctivel y felt to be rude[C] E y e contact can be a friendl y social signal[D] Personalit y can affect how a person reacts to e y e contact[E] Biological factors behind e y e contact are being investigated[F] Most people are not comfortable holding e y e contact with strangers[G] E y e contact can also be aggressive.In a social situation, e y e contact with another person can show that y ou are pa y ing attention in a friendl y wa y. But it can also be antagonistic such as when a political candidate turns toward their competitor during a debate and makes e y e contact that signals hostilit y.Here's what hard science reveals about e y e contact: 巳We know that a typical infant will instinctivel y gaze into its mother's e y es, and she will look back. This mutual gaze is a major part of the attachment between mother and child. In adulthood, looking someone else in a pleasant wa y can be a complimentary sign of pa y ing attention. It can catch someone's attention in a crowded room, "E y e contact and smile" can signal availability and confidence, a common-sense notion supported in studies b y ps y chologist Monica Moore.尸Neuroscientist Bonnie Au y eung found that the hormone oxytocin increased the amount of e y e contact from men toward the interviewer during a brief interview when the direction of their gaze was recorded. This was also found in high-functioning men with some autistic spectrum symptoms, who ma y tend to avoid e y e contact. Specificbrain re g ions that respond durin g direct g aze are bein g explored b y other researches, usin g advanced methods of brain scannin g.巳With the use of e y e-trackin g technology, Julia Minson of the Harvard Kenned y School of Government concluded that e y e contact can signal very different kinds of messa g es, dependin g on the situation. While e y e contact may be a sign of connection or trust in friendl y situations, it's more likel y to be associated with dominance or intimidation in adversarial situations. "Whether y ou're a politician or a parent, it mi g ht be helpful to keep in mind that tryin g to maintain e y e contact ma y backfire if ou're tryin g to convince someone who has a different set of beliefs than y ou,"said yMinson.巳When we look at a face or a picture, our e y es pause on one spot at a time, often on the e y es or mouth. These pauses typicall y occur at about three per second, and the e y es then jump to another spot, until several important points in the ima g e are re g istered like a series of snapshots. How the whole ima g e is then assembled and perceived is still a m y stery althou g h it is the subject of current research.巳In people who score hi g h in a test of neuroticism, a personality dimension associated with self-consciousness and anxiety, e y e contact tri gg ered more activity associated with avoidance,accordin g to the Finnish researcher Jari Hietanen and colleagues "Our findin g s indicate that people do not onl y feel different when the y are the centre of attention but that their brain reactions also differ." A more direct findin g is that people who scored hi g hl y for ne g ative emotions like anxiet y looked at others for shorter periods of time and reported more comfortable feelin g s when others did not look directl y at them.Part C Directions:Read the following text carefull y and then translate the underlined segments into Chinese. Your translation should be written neatl y on the ANSWER SHEET. (10 points)Following the explosion of creativit y in Florence during the 14th century known as the Renaissance, the modern world saw a departure from what it had once known. It turned from God and the authority of the Roman Catholic Church and instead favoured a more humanistic approach to being. Renaissance ideas had spread throughout Europe well into the 17th century,with the arts and sciences flourishing extraordinaril y among those with a more logical disposition. (46) with the Church's teachin s and wa s of thinkin ecli sed b the Renaissance the a between the Medieval and modern eriods had been brid ed leadin to new and unex lored intellectual territories.During the Renaissance, the great minds of Nicolaus Copernicus, Johannes Kepler and Galileo Galilei demonstrated the power of scientific study and discovery.(4 7) Before each of their revelations man thinkers at the time had sustained more ancient wa s of thinkin includin the eocentric view that the Earth was at the centre of o ur universe. Copernicus theorized in 1543 that all of t he planets that we knew of revolved not around the Earth, but the Sun, a s y stem that was later upheld b y Galileo at his own expense. Offering up such a theory during a time of high tension between scientific and religious minds was branded as heres y and an y such heretics that continued to spread these lies were to be punished b y imprisonment or even death. (48) Des ite attem ts b the Church to su ress. this new eneration of lo icians and rationalists more ex lanations for how the universe functioned were bein made at a rate that the people could no longer ignore.It was with these great revelations that a new kind of philosoph y founded in reason was born.The Church's long-standing dogma was losing the great battle for truth to rationalists and scientists. This ver y fact embodied the new wa y s of thinking that swept through Europe during most of 17th centur y. (49) As many took on the duty of t·n to inte ate reasonin and scientific hiloso hies into the world the Renaissance was over and it was time for a new era -the A e of Reason.The 17th and 18th centuries were times of radical change and curiosit y, Scientific method, reductionism and the questioning of Church ideals was to be encouraged, as were ideas of liberty, tolerance and progress. (50) Such actions to seek knowledge and to understand what information we alread knew were ca tured b the Latin hrase'sa ere aude'or'dare to know'after Immanuel Kant used it in his essa y An Answer to the Question: What is Enlightenment?. It was the purpose and responsibility of great minds to go forth and seek out the truth, which the y believed to be founded in knowledge.Section III WritingPart A51. Directions:The Students Union of y our university has assi gn ed y ou to inform the international students about an upcoming singing contest. White a notice in about 100 words. Write your answer on the ANSWER SHEET.Do not use your own name in the notice. (10 points)PartB52. Directions:Write an essa y of 160-200 words based on the picture below. In y our essa y , y ou should1) describe the picture briefl y ,2) interpret the implied meaning, and3) give y our comments.You should write neatl y on the ANSWER SHEET. (20 points)I .I 习惯。

结直肠癌的现状结直肠癌（CRC）是最常见的消化道恶性肿瘤之一。

过去几十年里，由于饮食结构和生活习惯的变化，我国城乡居民的结直肠癌发病率呈持续性升高。

CRC目前已成为我国发病率前5的恶性肿瘤[1]。

CRC的症状常表现为腹痛、便血、黑便，大便习惯改变及贫血等。

由于临床症状的出现常处于晚期，且不能与炎症性肠病、痔疮等良性病变特异区分，因此无症状期的早期筛查是提高CRC存活率、改善预后的根本措施。

结直肠癌常用的筛查手段根据《中国早期结直肠癌筛查及内镜诊治指南》的推荐，CRC的早期筛查手段主要包括：粪便潜血试验（FOBT）FOBT是目前国际通用的、也是我国临床上最被广泛使用的CRC无创筛查手段。

Zhang等[2]的大数据分析显示，免疫化学法大便隐血试验（iFOBT）筛查减少了59%的CRC死亡率，与结肠镜效果接近（61%），显著优于乙状结肠镜（33%）。

结肠镜/乙状结肠镜结肠镜下病理活检是目前诊断CRC的金标准，但由于其有创性且费用高昂，在我国一般不直接作为初筛方案。

乙状结肠镜由于自身的局限性，会遗漏大量结肠病变，对近端CRC发病率无明显降低作用。

其他筛查方法其他方法如基因甲基化、虚拟结肠镜检查及结肠胶囊内镜等，由于费用等问题，目前在我国推广有相当的难度。

综上而言，iFOBT由于具有灵敏度高、费用少、无创性及操作方便等诸多优点，因而是目前我国CRC早期筛查最适合、也是最被广泛应用的检测方法。

发展中的iFOBT检测技术iFOBT用的是什么检测原理和筛查指标？其在使用中可能存在哪些问题？在未来具有怎样的改进和发展方向？下面我们通过回顾iFOBT的发展历程来进一步了解该检测方法：指标迭代：从单项到联检经典指标：血红蛋白（Hb）Hb是最先也是最常被使用的便隐血和检测指标，在高等动物体内具有运载氧的功能。

每分子Hb由4个亚基组成，分别为2个α亚基和2个β亚基。

消化道病变时会有少量出血并释放血红蛋白，通过免疫反应对粪便Hb指标进行检测即可提示消化道的病变情况。

252例结直肠癌组织中KRAS、NRAS、 BRAF、PIK3CA的基因突变分析刘影;郑细闰;朱亚珍;何青莲;郑广娟【摘要】目的分析结直肠癌(colorectal cancer,CRC)组织中KRAS、NRAS、BRAF和PIK3CA基因的常见突变类型及其与临床病理指标的关系.方法对252例CRC石蜡包埋组织进行DNA提取,采用Sanger测序法对KRAS、NRAS、BRAF和PIK3CA基因进行检测,分析各个基因的突变率与临床病理特征的关系,并统计各个基因的突变类型.结果 252例CRC中,KRAS、BRAF、NRAS和PIK3CA突变发生率在性别、年龄、肿瘤部位、病理分期和有无淋巴结转移上差异均无统计学意义(P＞0.05);检测阳性突变共140例(55.5％),其中KRAS 113例(44.8％),NRAS 1例(0.4％),BRAF 19例(7.5％),PIK3CA 28例(11.1％),包括PIK3 CA与KRAS、NRAS、BRAF基因发生双突变21例(8.3％);KRAS的主要突变类型包括G12A、G12C、G12D、G12R、G12S、G12V、G13D、T20M、A59T、Q61H、Q61L、Q61P;NRAS仅有1例突变为G12D;BRAF的主要突变类型为V600E、D594G、K601E;PIK3CA的主要突变类型包括E542K、E545K、Q546K、Q546P、Q546R、M1043I、H1047R.PIK3CA与KRAS、NRAS、BRAF之间会发生交叉突变,但KRAS、NRAS、BRAF三者之间基本不存在交叉突变.结论 CRC中KRAS阳性突变率居高,PIK3CA次之,BRAF、NRAS突变率最低,且PIK3CA常与KRAS、NRAS、BRAF发生交叉突变.对CRC患者行KRAS、NRAS、BRAF、PIK3CA等多基因检测,可正确指导并选择抗EGFR单抗药,从而实现真正意义上的个体化靶向治疗.【期刊名称】《临床与实验病理学杂志》【年(卷),期】2016(032)008【总页数】6页(P851-855,859)【关键词】结直肠肿瘤;Sanger测序;KRAS;PIK3CA;靶向治疗【作者】刘影;郑细闰;朱亚珍;何青莲;郑广娟【作者单位】广东省中医院病理科,广州510120;广东省中医院病理科,广州510120;广东省中医院病理科,广州510120;广东省中医院病理科,广州510120;广东省中医院病理科,广州510120【正文语种】中文【中图分类】R735.3美国最新癌症统计结果显示，结直肠癌(colorectal cancer, CRC)发病率居全球常见恶性肿瘤的第3位，病死率居第4位[1]。

REPORTSerum Levels of ProstateSpecific Antigen Among Japanese-American and Native Japanese Men Atsuko Shibata, Alice S. Whittemore, Kyoichi Imai, Laurence N. Kolonel, Anna H. Wu, Esther M. John, Thomas A. Stamey, Ralph S. Paffenbarger*Background: Fourfold to sixfold higher prostate cancer rates in JapaneseAmerican men in the United States compared with Japanese men in Japan have been cited to support a role for environmental risk factors in the etiology of the disease. To examine the hypothesis that part or all of the elevated prostate cancer rates in JapaneseAmerican men may reflect more intensive prostate cancer screening in the United States than in Japan, we compared prostate-specific antigen (PSA) levels in community-based samples of serum from men without prostate cancer. Methods: Japanese-American men aged 40–85 years and native Japanese men aged 40–89 years with no history of prostate cancer provided sera, respectively, in the United States from March 1990 through March 1992 (n = 237) or in Japan from January 1992 through December 1993 (n = 3522). Age-specific PSA levels were used to estimate the prevalences of undetected prostate cancer in the two populations. Results: Age-specific mean PSA levels were significantly lower in JapaneseAmericans than in native Japanese (two-sided P<.001). The prevalence of an elevated PSA level increased with age in both populations and exceeded 5% among men aged 60 years or more. Combined with data on prevalence of detected prostate cancer in the two populations, our data suggest that some1716 REPORT10.0% of Japanese-Americans aged 75 years have prostate cancer, with 31% of that fraction remaining undiagnosed. The corresponding estimates in Japan are a total cancer prevalence of 5.4%, of which 81% has not been detected clinically. Conclusions: The total cancer prevalence ratio 10.0/5.4 = 1.9 (95% confidence interval = 1.5–2.3) in Japanese-American men compared with Japanese men in Japan suggests an increased risk for JapaneseAmerican men, but of less magnitude than the fourfold to sixfold increase indicated by the incidence data. [J Natl Cancer Inst 1997;89:1716–20]. Prostate cancer incidence and mortality rates in Japan are lower than the corresponding rates in all other developed countries, including those for JapaneseAmericans (1–3). During the period of 1983–1987, the average annual ageadjusted prostate cancer incidence rates were 47.2 and 51.0 per 100 000 for Japanese men in Los Angeles and Hawaii, respectively. These rates are roughly four times higher than the average 12.1 per 100 000 of age-adjusted incidence rates from six regions in Japan during the same time period (1). Prostate cancer incidence has increased from the period of 1983– 1987 to that of 1988–1992 in both populations, but the increase in JapaneseAmericans is larger; incidence rates in 1988–1992 were 82.4 and 92.8 per 100 000 in Los Angeles and Hawaii, respectively, which are approximately six times higher than the average 13.9 per 100 000 of rates in Japan. In 1983–1987, the age-adjusted mortality rates for prostate cancer (per 100 000) were 9.6 for Japanese in Los Angeles and 3.5 for Japanese in Japan, resulting in a less marked 2.7-fold rate ratio (2,4). All of these rates are adjusted to the age distribution of the 1970 U.S. census population. The higher rates of prostate cancer in Japanese-American men than in native Japanese men have prompted the hypothesis that lifestyle characteristics play amajor role in prostate carcinogenesis (5). However, part or all of the increased incidence in Japanese-Americans may reflect more intensive screening in the United States by measurement of prostate-specific antigen (PSA) levels, digital rectal examination, and transurethral ultrasound or more prevalent transurethral resection of the prostate for benign prostatic hyperplasia. Such intensive screening would increase the number of reported cases, some of which might never have been diagnosed otherwise (6). This is plausible because the high prevalence of prostate cancer found incidentally at autopsy or at transurethral resection of the prostate makes the reported incidence rates dependent on the frequency of medical procedures that increase the chance of finding such latent disease (5). To examine this issue, we compared serum PSA levels in Japanese-American men with those in native Japanese men; the men in both groups had no history of clinical prostate cancer. We used the proportions of these men with elevated PSA levels to obtain estimates of the prevalence of undetected prostate cancer in the two populations. When added to the prevalences of detected cancer obtained from the incidence data cited above, these estimates provide estimates of the total cancer burden among Japanese men in the United States and in Japan.*Affiliations of authors: A. Shibata, A. S. Whittemore, R. S. Paffenbarger, Department of Health Research and Policy, Stanford University School of Medicine, CA; K. Imai, Department of Urology, Gunma University School of Medicine, Maebashi, Japan; L. N. Kolonel, Cancer Research Center of Hawaii, University of Hawaii, Manoa; A. H. Wu, Department of Preventive Medicine, University of Southern California, Los Angeles; E. M. John, Northern California Cancer Center, Union City; T. A. Stamey, Department of Urology, Stanford University School of Medicine, CA. Correspondence to: Atsuko Shibata, M.D., Ph.D., Department of Health Research and Policy, Stanford University School of Medicine, HRPRedwood Bldg., Rm. T211, Stanford, CA 943055405. E-mail: shibata@ See ‘‘Notes’’ following ‘‘References.’’ © Oxford University PressDownloaded from / at Academy of Military Medical Sciences OF Chinese PLA on May 31, 2012Journal of the National Cancer Institute, Vol. 89, No. 22, November 19, 1997Subjects and MethodsSubjectsMeasurements of serum PSA levels in JapaneseAmericans were obtained from 237 men aged 40–85 years who participated as control subjects in a population-based, case–control study of prostate cancer conducted in Hawaii (statewide), Los Angeles County, and the San Francisco Bay Area during the period from March 1990 through March 1992. These men had no clinical history of prostate cancer and were frequency matched by age (5-year intervals) and by region of residence to prostate cancer case patients identified through the local populationbased cancer registries. Details of the control subject selection and blood sample collection were described elsewhere (7). No screening tests were performed on the men to exclude the possibility of undiagnosed prostate cancer. Serum PSA levels in Japan were based on a sample of 3522 men aged 40–89 years who had no history of prostate cancer and who participated in a community-based mass screening program for prostate cancer conducted in 22 regions of Gunma Prefecture, Japan, from January 1992 through December 1993. Characteristics of the men and their screening outcomes were reported elsewhere (8). No subjects were excluded because they had benign prostatic hyperplasia, previously undetected prostate cancer, or other pathologic conditions of the prostate identified in the screening program. Protocols in both countries were approved by the institutional review boards of all participating centers.other screening procedures among the Japanese subjects; therefore, we were unable to address the impact of choosing other cutoff points on our results. The 95th percentile has been used by other authors in their reports of age-specific reference values for serum PSA testing. The age-specific 95th percentile levels used in this study, as well as those in similar groups of U.S. white men, are shown in Table 1 (8,10–12).undetected cancer to estimate total cancer prevalence. The variance of the latter was taken to be that of the estimated prevalence of undetected cancer. We obtained confidence intervals for the ratio R of total cancer prevalence in the United States to that in Japan by using the delta method (16) to estimate the variance of logR, using a Gaussian approximation to obtain confidence limits for logR, and then exponentiating these limits.Statistical MethodsPrevious analyses in U.S. whites and AfricanAmericans suggest that PSA levels in men without clinical evidence of prostate cancer increase exponentially with age (12–14). Accordingly, we used ordinary least-squares regression to estimate the parameters a and b in the relation log(PSA) a + b*age in each population. We used analysis of covariance to test for differences in age-specific PSA levels between the United States and Japan. We also used logistic regression to evaluate how the prevalence P of an elevated PSA varied with age and country of residence. These statistical analyses were performed with the use of the SAS statistical package (15). All P values resulted from use of twotailed statistical tests. The prevalence of an undetected cancer was estimated as P − 0.05, as described in the ‘‘Appendix’’ section. The variance of this prevalence (i.e., the variance of P) at a given age was estimated from the covariance matrix of the logistic regression parameters by use of the delta method (16). We used incidence data to estimate the cumulative risk R of having a clinically diagnosed prostate cancer by specified ages in each of the two populations. Specifically, we took the cumulative risk at the end of the ith age interval to be Ri = 1 − expResultsThe 237 Japanese-American men were older at serum collection (mean age 70.2 years; standard deviation [SD] 6.7 years) than the 3522 men in Japan (mean age 65.8 years; SD 7.8 years) (P<.001). Since PSA levels in healthy men increase with age, we compared PSA levels of the two populations within specific age groups. Fig. 1 shows geometric mean PSA levels for Japanese men in the United States and in Japan, by 10-year age group, with age groups 40–49 years and 50–59 years combined in the United States because of small numbers in the former group. The curves represent the fitted relation PSA exp(a + b*age), with age measured in years. The parameter estimates (and standard errors [SEs] in parentheses) are a −1.842 (0.695) and b 0.028 (0.010) in the United States and a −0.988 (0.114) and b 0.019 (0.002) in Japan. PSA levels increased with age in both countries (P<.01). Apart from the anomalous drop in Japan in the age group 80–89 years, the log-linear relation provides a reasonably good fit to the data. (In neither country did adding a quadratic term to the loglinear regression substantially improve the fit.) Age-specific mean PSA levels were significantly lower in the United States than in Japan (P<.001). Fig. 2 shows the prevalence P of an elevated PSA level in each of the two countries. The curve represents the fittedDownloaded from / at Academy of Military Medical Sciences OF Chinese PLA on May 31, 2012Measurements of Serum PSA LevelsSerum PSA concentrations among the JapaneseAmericans were measured in the laboratory of the Department of Urology, Stanford University, with the use of an automated, polyclonal–monoclonal immunochemiluminometric assay formatted for use on the Ciba Corning ACS: 180 system (Ciba Corning Diagnostics Corp., East Walpole, MA) (9). These measurements were converted to Tandem-R monoclonal–monoclonal assay values (Hybritech Inc., San Diego, CA) by use of the equation Tandem-R 0.556*ACS + 0.038 (R2 .977) obtained by linear regression from a calibration study in the same laboratory. Serum PSA concentrations for the men in Japan were measured with the use of Tosoh PSA kits in the laboratory of the Department of Urology, Gunma University. These measurements were converted to the Tandem-R equivalent by use of the equation Tandem-R 1.0122*Tosoh + 0.1377 (R2 .980) obtained by linear regression in the same laboratory. Analysis based on the Tandem-R values of a subset of 1647 men whose PSA levels had been measured by both Tandem-R and Tosoh methods gave very similar results (data not shown). These findings indicated that international differences are not confounded by assay differences. A serum PSA value was categorized as elevated if it exceeded the 95th percentile of PSA levels among those men in the same 10-year age group who showed no evidence of prostate cancer as judged by digital rectal examination and transurethral ultrasound in the same screening program in Gunma Prefecture, Japan (8). We did not have access to the original dataset containing PSA values and results of( )i j=1rj ,where rj is the age-specific incidence rate in the jth 5-year age group. For Japanese-Americans, we used the average of age-specific incidence rates in 1988– 1992 from two populations (Los Angeles and Hawaii, provided by A. H. Wu and L. N. Kolonel). For rates in Japan, we used the average of rates from four populations (Hiroshima, Miyagi, Nagasaki, and Yamagata) during the same or overlapping time periods [(17); Tsubono Y, Soda M, Sato Y: personal communication]. These cumulative risks give the prevalence of having a prior clinically detected prostate cancer among men of various ages. This prevalence was then added to the estimated prevalence ofTable 1. 95th percentiles of serum prostate-specific antigen (PSA) (ng/mL) values among community-based samples of men with no clinical evidence of prostate cancer* Japanese men in Japan† Population reference: age, y 40–49 50–59 60–69 70–79 80–89 Imai et al. (8) 2.1 2.9 4.0 5.2 5.9 Oesterling et al. (10) 2.0 3.0 4.0 5.0 NA U.S. white men† Morgan et al. (11) 2.1 3.6 4.3 5.8 NA Oesterling et al. (12) 2.5 3.5 4.5 6.5 NA*NA not available. †Values in columns serum PSA levels in ng/mL.Journal of the National Cancer Institute, Vol. 89, No. 22, November 19, 1997REPORT 1717Fig. 1. Geometric mean prostate-specific antigen (PSA) levels (±standard errors) in 10-year age groups among JapaneseAmerican men in the United States ( ) and Japanese men in Japan ( ). The age groups 40–49 years and 50–59 years have been combined for Japanese-Americans because of the small number in the former group (n 2). Curves represent the fitted relations; PSA exp(−1.842 + 0.028*age) in the United States (solid line) and PSA exp(−0.988 + 0.019*age) in Japan (dotted line), with age given in years.incidence ratios of 4.1 (i.e., for the period 1983–1987) and 6.3 (i.e., for the period 1988–1992) cited earlier.DiscussionWe have used age-specific estimates of the prevalence of elevated PSA levels to estimate the prevalence of undetected prostate cancer in Japanese-American and native Japanese men. The data suggested that prostate cancer detection rates in Japanese-Americans are considerably higher than those in native Japanese men. We found that, among men aged 75 years, some 69% of prostate cancers are detected in the United States, in contrast to only 19% of cancers in Japan. By adding the estimated prevalence of undetected prostate cancer to the prevalence of detected cancer obtained from published incidence data, we calculated that the total cancer prevalence in Japanese-Americans in this age group was approximately 1.9 times that of native Japanese men, in contrast to the fourfold and sixfold incidence ratios. These findings are consistent with those of Shimizu et al. (6), who estimated the rates that would prevail in Japan if cancers were detected and registered as systematically in Japan as they are in the United States. Using the relative prevalences of cancer at autopsy in the two populations to estimate their relative prevalences of localized cancers, these authors estimated the number of localized cancers that would be registered in Japan if detection rates were similar to those of the United States. When this number was added to the existing counts of aggressive cancers, the resulting total incidence in Japan was three to four times the published incidence, suggesting that most of the incidence differences between Japanese-Americans and Japanese in Japan are due to differences in detection rates. Age-adjusted death rates from prostate cancer among Japanese-Americans are roughly 2.7 times those among Japanese in Japan. This ratio is larger than our estimated prevalence ratio of 1.9, although it is smaller than the incidence ratios of 4.1 and 6.3. Interpretation of the mortality rate ratio is complicated by possible international differences in cause-of-death certification and coding. In the absence of such differences, the higher mortality rate ratio compared with the prevalence ratioDownloaded from / at Academy of Military Medical Sciences OF Chinese PLA on May 31, 2012logistic relation log[P/(1 − P)] a + b*age, with age measured in years. The parameter estimates (and SEs in parentheses) are a −4.6477 (2.767) and b 0.0295 (0.039) in the United States and a −5.1362 (0.584) and b 0.0383 (0.009) in Japan. The prevalence of an elevated PSA level increased with age in Japan (P<.0001). We found no statistically significant relationship between the prevalence of elevated PSA levels and age in the U.S. subjects (P .44) because of the small sample size. There was no statistically significant difference in prevalence of elevated PSA levels between the Japanese-American and native Japanese subjects (P .59). In both countries, the prevalence exceeded 5% in all men aged 60 years or more. In the ‘‘Appendix’’ section, we show that the prevalence P of an elevated PSA level in a given population of men without clinical cancer is approximately P 0.05 + PCA(1 − d). Here PCA is the true (unknown) prevalence of a prostate cancer sufficiently advanced to produce an elevated PSA, and d is the proportion of1718 REPORTsuch cancers that are detected clinically. Thus, P − 0.05 represents approximately the prevalence PCA(1 − d) of undetected prostate cancer. Estimated prevalences of undetected and detected cancer are shown in Fig. 3 for each of the two populations. It is evident that undetected cancers comprise most of the cancer burden in Japan, but not in the United States. For example, among men aged 75 years in Japan, the prevalences of detected and undetected cancers are 1.0% and 4.4%, respectively, for a total cancer prevalence of 1.0% + 4.4% 5.4% and a detection rate of 1.0/ 5.4 0.19. In contrast, the corresponding estimates in the United States are 6.9% and 3.1%, giving a total cancer prevalence of 10.0% and a detection rate of 6.9/10.0 0.69. Thus, the ratio of total cancer prevalence in Japanese-Americans aged 75 years compared with Japanese men of this age in Japan is 10.0/5.4 1.9 (95% confidence interval 1.5–2.3). While supportive of an increased cancer prevalence among Japanese-Americans, this ratio is nevertheless smaller than theJournal of the National Cancer Institute, Vol. 89, No. 22, November 19, 1997Fig. 2. Proportions P (±standard errors) of men with elevated prostate-specific antigen (PSA) levels, defined as exceeding the age-specific reference ranges for Japanese men (8), in 10-year age groups for Japanese-American men in the United States ( ) and Japanese men in Japan ( ). The age groups 40–49 years and 50–59 years have been combined for JapaneseAmericans. Curves represent the fitted relation; log[P/(1 − P)] −4.6477 + 0.0295*age in the United States (solid line) and log[P/(1 − P)] −5.1362 + 0.0383*age in Japan (dotted line), with age given in years.of 1.9 would suggest that a higher proportion of prostate cancers are fatal among Japanese-Americans than among native Japanese men.Our study has some limitations that warrant consideration in interpreting the results. While Japanese-American men comprise an age-stratified random sampleof men without clinical cancer, men in Japan were participants in a screening program who could have been selfselected because of prostate conditions. In addition, the sparse numbers of JapaneseAmerican men limit the precision with which mean PSA levels can be estimated. The small sample size of JapaneseAmerican subjects may also explain why we found neither a statistically significant relationship of age and elevated PSA levels in these men nor a statistically significant difference in the proportion of men with elevated PSA levels between the two populations. Furthermore, our estimates of undetected cancer prevalence include only those cancers causing an elevated PSA level, whereas the detected cancer prevalence rates include some cancers still too small to do so. Finally, we have assumed that the age-specific 95th percentiles of PSA levels observed in men without clinical evidence of cancer in Japan are the same as those that would be observed among a similar sample of Japanese-Americans. These limitations seem unlikely to alter the basic conclusion that PSA levels in a random sample of Japanese-Americans without a clinical history of prostate cancer are lower than those in a comparable sample of Japanese men in Japan. This apparently paradoxical finding is actually what one would expect from more intensive screening for the disease among Japanese-American men than among Japanese men in Japan. Additional com-Downloaded from / at Academy of Military Medical Sciences OF Chinese PLA on May 31, 2012Fig. 3. Prevalence of detected prostate cancer (solid lines) and of all (detected and undetected) prostate cancer (dotted lines) for Japanese-American men in the United States and Japanese men in Japan. Detected cancer prevalence was estimated from published incidence data as described in the text. Total cancer prevalence is the sum of detected cancer and undetected cancer prevalence, with the latter estimated as P − 0.05, where P is the prevalence of an elevated PSA, as shown in Fig. 2.Journal of the National Cancer Institute, Vol. 89, No. 22, November 19, 1997REPORT 1719parative studies of PSA levels, prostate cancer incidence, and prostate cancer prevalence at autopsy in the two populations are needed to confirm the present findings. If confirmed, these results indicate that the differences in incidence between Japanese-American men and Japanese men in Japan are smaller than implied by incidence data and suggest that the proportion of prostate cancers attributable to environmental factors may be smaller than that previously supposed.P = 0.05 + PCA(1 − d).[2]The error due to this approximation is practically negligible; e.g., given PCA 0.16 and d 0.69, the prevalence P is calculated as 0.103 by the exact method (expression 1) and 0.996 by approximation (expression 2), respectively. Expression 2 indicates that the excess prevalence P − 0.05 is approximately the proportion PCA(1 − d) of men with undetected prostate cancer.AppendixThe prevalence P of having an elevated PSA level in a population of men of a given age without a clinical history of prostate cancer can be approximated as follows: In a population of N men of the given age, let PCA represent the proportion of men who have developed prostate cancer sufficiently advanced to produce an elevated PSA level. A fraction d of these NPCA cancer cases will have come to clinical attention. These NdPCA men have been excluded from the present study, leaving N − NdPCA men for analysis. By definition of ‘‘elevated’’ PSA level, 5% of the N − NPCA men without prostate cancer have elevated PSA levels. In addition, all of the NPCA(1 − d) men with undetected cancer have elevated PSA levels. Thus, the total number of men with elevated PSA levels is 0.05N(1 − PCA) + NPCA(1 − d). The prevalence P of elevated PSA levels is thus P= number with elevated PSA number analyzed) = 0.05 1 − PCA + PCA(1 − d)] (1 − dPCA). [1]References(1) Parkin DM, Muir CS, Whelan SL, Gao YT, Ferlay J, Powell J. Cancer incidence in five continents. Volume VI. Lyon (France): International Agency for Research on Cancer, 1992. (2) Bernstein L, Ross RK. Cancer in Los Angeles County. A portrait of incidence and mortality 1972–1987. Los Angeles: University of Southern California, 1991. (3) Kolonel LN, Hankin JH, Nomura AM. Multiethnic studies of diet, nutrition, and cancer in Hawaii. In: Hayashi Y, Nagao M, Sugimura T, Takayama S, Tomatis L, Wattenberg LW, et al, editors. Diet, nutrition and cancer: Proceedings of the 16th International Symposium of the Princess Takamatsu Cancer Research Fund, Tokyo, 1985. Tokyo: Japan Scientific Societies Press, 1986:29–40. (4) Aoki K, Kurihara M, Hayakawa N, Suzuki S. Death rates for malignant neoplasms for selected sites by sex and five-year age group in 33 countries 1953–57 to 1983–87. Nagoya: The University of Nagoya Coop Press, 1992. (5) Nomura AM, Kolonel LN. Prostate cancer: a current perspective. Epidemiol Rev 1991;13: 200–27. (6) Shimizu H, Ross RK, Bernstein L. Possible underestimation of the incidence rate of prostate cancer in Japan. Jpn J Cancer Res 1991; 82:483–5. (7) Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR, et al. Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J Natl Cancer Inst 1995;87:652–61. (8) Imai K, Ichinose Y, Kubota Y, Yamanaka H, Sato J. Diagnostic significance of prostate specific antigen and the development of a mass screening system for prostate cancer. J Urol 1995;154:1085–9.(9) Boland J, Carey G, Krodel E, Kwiatkowski M. The Ciba Corning ACS: 180 benchtop immunoassay analyzer. Clin Chem 1990;36: 1598–601. (10) Oesterling JE, Kumamoto Y, Tsukamoto T, Girman CJ, Guess HA, Masumori N, et al. Serum prostate-specific antigen in a communitybased population of healthy Japanese men: lower values than for similarly aged white men. Br J Urol 1995;75:347–53. (11) Morgan TO, Jacobsen SJ, McCarthy WF, Jacobson DJ, McLeod DG, Moul JW. Age-specific reference ranges for prostate-specific antigen in black men. N Engl J Med 1996;335:304–10. (12) Oesterling JE, Jacobsen SJ, Chute CG, Guess HA, Girman CJ, Panser LA, et al. Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. JAMA 1993; 270:860–4. (13) Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R, et al. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA 1992;267:2215–20. (14) Whittemore AS, Lele C, Friedman GD, Stamey T, Vogelman JH, Orentreich N. Prostatespecific antigen as predictor of prostate cancer in black men and white men. J Natl Cancer Inst 1995;87:354–60. (15) SAS Institute, Inc. SAS/Stat user’s guide, release 6.03 edition. Cary (NC): SAS Institute, Inc., 1988. (16) Bishop YM, Fienberg SE, Holland PW. Discrete multivariate analysis: theory and practice. Cambridge (MA): MIT Press, 1975. (17) Sanada K, Kimura S, Fukuhara T, Fujita Y, Mabuchi K. Cancer incidence in Japan, Hiroshima City, 1986–1990. In: Parkin DM et al, editors. Cancer incidence in five continents. Volume VII. Lyon (France): International Agency for Research on Cancer. In press.Downloaded from / at Academy of Military Medical Sciences OF Chinese PLA on May 31, 2012NotesSupported in part by Public Health Service grants CA49446 and CA47448 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. We thank Anna Felberg for computing assistance, Drs. Richard Gallagher and Dee West for support in conducting the study, and Drs. Y. Fujita, Y. Tsubono, M. Soda, and Y. Sato for providing the latest incidence rates of prostate cancer in Japan. Manuscript received May 30, 1997; revised August 22, 1997; accepted September 8, 1997.When prostate cancer prevalence is small (i.e., PCA<0.20, as is true in these two low-risk populations), then 0.05(1 − PCA) ∼ 0.05 and 1 − dPCA ∼ 1. Thus, expression 1 can be approximated by1720 REPORTJournal of the National Cancer Institute, Vol. 89, No. 22, November 19, 1997。

一、范围二、术语与定义三、缩略语CIN：（Cervical intraepithelial neoplasia）宫颈上皮内瘤变CTV：（clinical target volume）临床靶区LEEP：（Loop Electro-surgical Excisional Procedure）宫颈环形电切术PTV：（planning target volume）计划靶区图1 子宫颈癌诊断与治疗流程（一）高危因素。

（二）症状。

（三）体征。

妇科检查是临床分期的最重要手段。

（四）辅助检查。

报告格式：b.诊断总的范围c.描述性诊断标本量对诊断评价的意义：评价满意评价满意但是受限于---（具体原因）评价不满意（具体原因）诊断总的范围（最适的）：正常范围内良性细胞学改变：见描述性诊断上皮细胞特殊：见描述性诊断描述性诊断：良性细胞学改变感染-滴虫阴道炎-其它与下列因素有关的反应性细胞学改变：-放疗-其它上皮细胞特殊：鳞状上皮细胞：·未明确诊断意义的不典型鳞状细胞* ·鳞状上皮内低度病变包含：- HPV+ *-轻度非典型增生/CIN1·鳞状上皮内高度病变包含：-中、重度非典型增生·鳞状细胞癌腺上皮细胞：·子宫内膜腺癌·子宫外腺癌·腺癌，非特异性·与年龄与病史相符的激素水平模式·与年龄与病史不相符的激素水平模式;特异性（NOS）·不能评价的激素水平;特异性CIN：宫颈上皮内病变；CIS：原位癌*不明意义的非典型鳞状/腺细胞应进行进一步追查，以证实是反应性还是癌前病变或者癌。

+ HPV感染的细胞学改变包含在低度鳞状上皮病变内。

3．腔镜检查4．影像学检查（5）骨扫描：仅用于怀疑有骨转移的患者。

5．肿瘤标志物检查（一）子宫颈癌的组织学分类。

WHO子宫颈癌组织学分类（2003）上皮性肿瘤鳞状上皮肿瘤及其癌前病变鳞状细胞癌，非特殊类型8070/3 角化型8071/3非角化型8072/3基底细胞样8083/3疣状8051/3湿疣状8051/3乳头状8052/3淋巴上皮瘤样8082/3鳞状上皮移行细胞癌8120/3早期浸润性（微小浸润性）鳞状细胞癌8076/3 鳞状上皮内肿瘤宫颈鳞状上皮内肿瘤(CIN)3级8077/2原位鳞状细胞癌8070/2良性鳞状上皮病变尖锐湿疣鳞状上皮乳头状瘤8052/0纤维上皮性息肉腺上皮肿瘤及其癌前病变腺癌8140/3 粘液腺癌8480/3宫颈型8482/3肠型8144/3印戒细胞型8490/3微小偏离型8480/3绒毛腺型8262/3 子宫内膜样腺癌8380/3透明细胞腺癌8310/3浆液性腺癌8441/3 中肾管型腺癌9110/3早期浸润性腺癌8140/3原位腺癌8140/2腺体不典型增生良性腺上皮病变苗勒氏管源性乳头状瘤宫颈管内膜息肉其他上皮性肿瘤腺鳞癌8560/3 毛玻璃细胞亚型8015/3腺样囊性癌8200/3腺样基底细胞癌8098/3神经内分泌肿瘤类癌8240/3非典型类癌8249/3小细胞癌8041/3 大细胞神经内分泌癌8013/3 未分化癌8020/3间叶性肿瘤与肿瘤样病变平滑肌肉瘤8890/3子宫内膜样间质肉瘤，低度恶性8931/3未分化宫颈管肉瘤8805/3葡萄状肉瘤8910/3 腺泡状软组织肉瘤9581/3血管肉瘤9120/3恶性外周神经鞘肿瘤9540/3 平滑肌瘤8890/0生殖道型横纹肌瘤8905/0手术后梭形细胞结节上皮与间叶混合性肿瘤癌肉瘤（恶性苗勒氏管源性混合瘤；化生性癌）8980/3 腺肉瘤8933/3 Wilms肿瘤8960/3腺纤维瘤9013/0腺肌瘤8932/0黑色素细胞肿瘤恶性黑色素瘤8720/3蓝痣8780/0杂类肿瘤生殖细胞型肿瘤卵黄囊瘤9071/3表皮样囊肿9084/0成熟性囊性畸胎瘤9080/0淋巴造血组织肿瘤恶性淋巴瘤(特殊类型)白血病（特殊类型）继发性肿瘤局部淋巴结（N ）Nx ：局部淋巴结无法评估N0：没有局部淋巴结转移N1：有局部淋巴结转移远处转移（M ）Mx ：远处转移无法评估M0：无远处转移M1：有远处转移CIN 分级CIN2（中度非典型增生） 细胞异型性明显，排列较紊乱，特殊增殖细胞占据上皮层下2/3。

2011年6月大学英语四(CET-4)级真题试卷Part I Writing (30 minutes)Directions:For this part, you are allowed 30 minutes to write a short essay on the topic of Online Shopping. You should write at least 120 words following the outline given bellow:Online Shopping1.现在网上购物已成为一种时尚2.网上购物有很多好处，但也有不少问题3.我的建议Part II Reading Comprehension(Skimming and Scanning) (15 minutes) Directions: In this part, you will have 15 minutes to go over the passage quickly and answer the questions on Answer Sheet 1. For questions 1 - 7, choose the best answer from the four choices marked A), B), C) and D). For questions 8-10, complete the sentences with the information given in the passage.British Cuisine: the Best of Old and NewBritish cuisine(烹饪) has come of age in recent years as chefs(厨师) combine the best of old and new.Why does British food have a reputation for being so bad? Because it is bad! Those are not the most encouraging words to hear just before eating lunch at one of Hong Kong's smartest British restaurants, Alfie's by KEE, but head chef Neil Tomes has more to say."The past 15 years or so have been a noticeable period of improvement for food in England," the English chef says, citing the trend in British cuisine for better ingredients, preparation and cooking methods, and more appealing presentation. Chef such as Delia Smith, Nigel Slater, Jamie Oliver and Gordon Ramsay made the public realise that cooking - and eating - didn't have to be a boring thing. And now, most of the British public is familiar even with the extremes of Heston Blumenthal's molecular gastronomy, a form of cooking that employs scientific methods to create the perfect dish."It's no longer the case that the common man in England is embarrassed to show he knows about food," Tomes says.There was plenty of room for improvement. The problems with the nation's cuisine can be traced back to the Second World War. Before the war, much of Britain's food was imported and when German U-boats began attacking ships bringing food to the country, Britain went on rations(配给)."As rationing came to an end in the 1950s, technology picked up and was used to mass-produce food," Tomes says. "And by then people were just happy to have a decent quantity of food in their kitchens."They weren't looking for cured meats, organic produce or beautiful presentation; they were looking for whatever they could get their hands on, and this prioritisation of quantity over quality prevailed for decades, meaning a generation was brought up with food that couldn't compete with neighbouring France, Italy, Belgium or Spain.Before star chefs such as Oliver began making cooking fashionable, it was hard to find a restaurant in London that was open after 9pm. But in recent years the capital's culinary(烹饪的) scene has developed to the point that it is now confident of its ability to please the tastes of any international visitor.With the opening of Alfie's in April, and others such as The Pawn, two years ago, modern British food has made its way to Hong Kong. "With British food, I think that Hong Kong restaurant are keeping up," says David Tamlyn, the Welsh executive chef at The Pawn in Wan Chai. "Hong Kong diners are extremely responsive to new ideas or presentations, which is good news for new dishes."Chefs agree that diners in Hong Kong are embracing the modern British trend. Some restaurants are modifying the recipes(菜谱)of British dishes to breathe new life into the classics, while other are using better quality ingredients but remaining true to British traditional and tastes.Tamlyn is in the second camp. "We select our food very particulary. We use US beef, New Zealand lamb and for our custards(牛奶蛋糊) we use Bird's Custard Powder," Tamlyn says. "Some restaurants go for custard made fresh with eggs, sugar and cream, but British custard is different, and we stay true to that."Matthew Hill, senior manager at the two-year-old SoHo restaurant Yorkshire Pudding, also uses better ingredients as a means of improving dishes. "There are a lot of existing perceptions about British food and so we can't alter these too much. We're a traditional British restaurant so there are some staples(主菜) that will remain essentially unchanged."These traditional dishes include fish and chips, steak and kidney pie and large pieces of roasted meats. At Alfie's, the newest of the British restaurants in town and perhaps the most gentlemen's club-like in design, Neil Tomes explains his passion for provenance(原产地). "Britain has started to become really proud of the food it's producing. It has excellent organic farms, beautifully crafted cheeses, high-quality meats."However, the British don't have a history of exporting their foodstuffs, which makes it difficult for restaurants in Hong Kong to source authentic ingredients."We can get a lot of our ingredients once a week from the UK," Tamlyn explains. "But there is also pressure to buy local and save on food miles, which means we take our vegetables from the local markets, and there are a lot that work well with British staples."The Phoenix, in Mid-Levels, offers the widest interpretation of "British cuisine", while still trying to maintain its soul. The gastro-pub has existed in various locations in Hong Kong since 2002. Singaporean head chef Tommy Teh Kum Chai offers daily specials on a blackboard, rather than sticking to a menu. This enables him to reinterpret British cuisine depending on what is available in the local markets."We use a lot of ingredients that people wouldn't perhaps associate as British, but are presented in a British way. Bell peppers stuffed with couscous, alongside ratatouille, is a very popular dish."Although the ingredients may not strike diners as being traditional, they can be found in dishes across Britain.Even the traditional chefs are aware of the need to adapt to local tastes and customs, while maintaining the Brutishness of their cuisine.At Yorkshire Pudding, Hill says that his staff asks diners whether they would like to share their meals. Small dishes, shared meals and "mixing it up" is not something commonly done in Britain, but Yorkshire Pudding will bring full dished to the table and offer individual plates for each dinner. "That way, people still get the presentation of the dishes as they were designed, but can carve them up however they like," Hill says.This practice is also popular at The Pawn, although largely for rotisseries(烤肉馆), Tamlyn says. "Some tables will arrive on Sunday, order a whole chicken and a shoulder of lamb or a baby pig, and just stay for hours enjoying everything we bring out for them."Some British traditions are too sacred(神圣的) to mess with, however, Tomes says. "I'd never change a full English breakfast."1. What is British food generally known for?A) Its unique flavor. B) Its bad taste.C) Its special cooking methods D) Its organic ingredients.2. The Second World War led to ____ in Britain.A) an inadequate supply of food B) a decrease of grain productionC) an increase in food import D) a change in people's eating habits3. Why couldn't Britain compete with some of its neighboring countries in terms of food in the post-war decades?A) Its food lacked variety. B) Its people cared more for quantity.C) It was short of well-trained chefs. D) It didn't have flavorful food ingredients.4. With culinary improvement in recent years, London's restaurants are now able to appeal to the tastes of ____.A) most young people B) elderly British dinersC) all kinds of overseas visitors D) upper-class customers5. What do Hong Kong diners welcome, according to Welsh executive chef David Tamlyn?A) Authentic classic cuisine. B) Locally produced ingredients.C) New ideas and presentations. D) The return of home-style dishes.6. While using quality ingredients, David Tamlyn insists that the dishes should ____.A) benefit people's health B) look beautiful and invitingC) be offered at reasonable prices D) maintain British traditional tastes7. Why does Neil Tomes say he loves food ingredients from Britain?A) They appeal to people from all over the world. B) They are produced on excellent organic forms.C) They are processed in a scientific way. D) They come in a great variety.8. Tamlyn says that besides importing ingredients from Britain once a week, his restaurant also buys vegetables from ____________________.9. The Phoenix in Mid-Levels may not use British ingredients, but presents its dishes ________________.10. Yorkshire Pudding is a restaurant which will bring full dishes to the table but offer plates to those diners who would like to ___________________________.Part III Listening Comprehension (35 minutes)Section ADirections:In this section, you will hear 8 short conversations and 2 long conversations. At the end of each conversation, one or more questions will be asked about what was said. Both the conversation and the questions will be spoken only once. After each question there will be a pause. During the pause, you must read the four choices marked A), B), C) and D), and decide which is the best answer. Then mark the corresponding letter on Answer Sheet 2 witha single line through the centre.11. A) He is careless about his appearance.B) He is ashamed of his present condition.C) He changes jobs frequently.D) He shaves every other day.12. A) Jane may be caught in a traffic jam.B) Jane should have started a little earlier.C) He knows what sort of person Jane is.D) He is irritated at having to wait for Jane.13. A) Training for the Mid-Atlantic Championships.B) Making preparations for a trans-Atlantic trip.C) Collecting information about baseball games.D) Analyzing their rivals' on-field performance.14. A) He had a narrow escape in a car accident.B) He is hospitalized for a serious injury.C) He lost his mother two weeks ago.D) He has been having a hard time.15. A) The woman has known the speaker for a long time.B) The man had difficulty understanding the lecture.C) The man is making a fuss about nothing.D) The woman thinks highly of the speaker.16. A) He has difficulty making sense of logic.B) Statistics and logic are both challenging subjects.C) The woman should seek help from the tutoring service.D) Tutoring services are very popular with students.17. A) Her overcoat is as stylish as Jill's.B) Jill missed her class last week.C) Jill wore the overcoat last week.D) She is in the same class as the man.18. A) A computer game.B) An imaginary situation.C) An exciting experience.D) A vacation by the sea.Questions 19 to 21 are based on the conversation you have just heard.19. A) Beautiful scenery in the countryside.B) Dangers of cross-country skiing.C) Pain and pleasure in sports.D) A sport he participates in.20. A) He can't find good examples to illustrate his point.B) He can't find a peaceful place to do the assignment.C) He doesn't know how to describe the beautiful country scenery.D) He can't decide whether to include the effort part of skiing.21. A) New ideas come up as you write.B) Much time is spent on collecting data.C) A lot of effort is made in vain.D) The writer's point of view often changes.Questions 22 to 25 are based on the conversation you have just heard.22. A) Journalist of a local newspaper.B) Director of evening radio programs.C) Producer of television commercials.D) Hostess of the weekly "Business World".23. A) He ran three restaurants with his wife's help.B) He and his wife did everything by themselves.C) He worked both as a cook and a waiter.D) He hired a cook and two local waitresses.24. A) He hardly needs to do any advertising nowadays.B) He advertises a lot on radio and in newspapers.C) He spends huge sums on TV commercials every year.D) He hires children to distribute ads in shopping centers.25. A) The restaurant location.B) The restaurant atmosphere.C) The food variety.D) The food price.Section BDirections: In this section, you will hear 3 short passages. At the end of each passage, you will hear some questions. Both the passage and the questions will be spoken only once. After you hear a question, you must choose the best answer from the four choices marked A), B), C) and D). Then mark the corresponding letter on Answer Sheet 2 with a single line through the centre.Passage One26. A) Its protection is often neglected by children.B) It cannot be fully restored once damaged.C) There are many false notions about it.D) There are various ways to protect it.27. A) It may make the wearer feel tired.B) It will gradually weaken the eyes of adults.C) It can lead to the loss of vision in children.D) It can permanently change the eye structure.28. A) It can never be done with high technology.B) It is the best way to restore damaged eyesight.C) It is a major achievement in eye surgery.D) It can only be partly accomplished now.Passage Two29. A) They think they should follow the current trend.B) Nursing homes are well-equipped and convenient.C) Adult day-care centers are easily accessible.D) They have jobs and other commitments.30. A) They don't want to use up all their life savings.B) They fear they will regret it afterwards.C) They would like to spend more time with them.D) They don't want to see their husbands poorly treated.31. A) Provide professional standard care.B) Be frank and seek help from others.C) Be affectionate and cooperative.D) Make use of community facilities.Passage Three32. A) Health and safety conditions in the workplace.B) Rights and responsibilities of company employees.C) Common complaints made by office workers.D) Conflicts between labor and management.33. A) Replace its out-dated equipment.B) Improve the welfare of affected workers.C) Follow the government regulations strictly.D) Provide extra health compensation.34. A) They requested to transfer to a safer department.B) They quit work to protect their unborn babies.C) They sought help from union representatives.D) They wanted to work shorter hours.35. A) To show how they love winter sports.B) To attract the attention from the media.C) To protect against the poor working conditions.D) To protect themselves against the cold weather.Section CDirections: In this section, you will hear a passage three times. When the passage is read for the first time, you should listen carefully for its general idea. When the passage is read for the second time, you are required to fill in the blanks numbered from 36 to 43 with the exact words you have just heard. For blanks numbered from 44 to 46 you are required to fill in the missing information. For these blanks, you can either use the exact words you have just heard or write down the main points in your own words. Finally, when the passage is read for the third time, you should check what you have written.Contrary to the old warning that time waits for no one, time slows down when you are on the move. It also slows down more as you move faster, which means astronauts(宇航员) someday may (36)__________ so long in space that they would return to an Earth of the (37)__________ future. If you could move at the speed of light, your time would stand still. If you could move faster than light, your time would move (38)__________ .Although no form of matter yet (39)__________ moves as fast as or faster than light, (40)__________ experiments have already confirmed that accelerated (41)__________ causes a traveler's time to be stretched. Albert Einstein (42)__________ this in 1905, when he (43)__________ the concept of relative time as part of his Special Theory of Relativity. A search is now under way to confirm the suspected existence of particles of matter (44)_________________________________________________________________________________________ .An obsession(沉迷)with time-saving, gaining, wasting, losing, and mastering it-(45)___________________________________________________________________________________________________________________ . Humanity also has been obsessed with trying to capture the meaning of time. Einstein (46)_______________________________________________________________________________________________. Thus, time and time's relativity are measurable by any hourglass, alarm clock, or an atomic clock that can measure a billionth of a second. Part ⅣReading Comprehension (Reading in Depth) (25 minutes)Section ADirections:In this section, there is a passage with ten blanks. You are required to select one word for each blank from a list of choices given in a word bank following the passage. Read the passage through carefully before making your choices. Each choice in the bank is identified by a letter. Please mark the corresponding letter for each item on Answer Sheet 2 with a single line through the centre. You may not use any of the words in the bank more than once.The popular notion that older people need less sleep than younger adults is a myth, scientists said yesterday.While elderly people 47 to sleep for fewer hours than they did when they were younger, this has a(n) 48 effect on their brain's performance and they would benefit from getting more, according to research.Sean Drummond, a psychiatrist (心理医生) at the University of California, San Diego, said that older people are more likely to suffer from broken sleep, while younger people are better at sleeping 49 straight through the night.More sleep in old age, however, is 50 with better health, and most older people would feel better and more 51 if they slept for longer periods, he said."The ability to sleep in one chunk (整块时间) overnight goes down as we age but the amount of sleep we need to 52 well does not change," Dr Drummond told the American Association for the Advancement of Science conference in San Diego."It's 53 a myth that older people need less sleep. The more healthy an older adult is, the more they sleep like they did when they were 54 . Our data suggests that older adults would benefit from 55 to get as much sleep as they did in their 30s. That's 56 from person to person, but the amount of sleep we had at 35 is probably the sameDirections:There are 2 passages in this section. Each passage is followed by some questions or unfinished statements. For each of them there are four choices marked A), B), C) and D). You should decide on the best choice and mark the corresponding letter on Answer Sheet 2 with a single line through the centre.Passage OneSeveral recent studies have found that being randomly (随机地) assigned to aroommate of another race can lead to increased tolerance but also to a greater likelihood (可能性) of conflict.Recent reports found that lodging with a student of a different race may decrease prejudice and compel students to engage in more ethnically diverse friendships.An Ohio State University study also found that black students living with a white roommate saw higher academic success throughout their college careers. Researchers believe this may be caused by social pressure.In a New York Times article, Sam Roakye-the only black student on his freshman year floor-said that "if you're surrounded by whites, you have something to prove."Researchers also observed problems resulting from pairing interracial students in residences.According to two recent studies, randomly assigned roommates of different race are more likely to experience conflicts so strained that one roommate will move out.An Indiana University study found that interracial roommates were three times as likely as two white roommates to no longer live together by the end of the semester.Grace Kao, a professor at Penn said she was not surprised by the findings. "This may be the first time that some of these students have interacted, and lived, with someone of a different race," she said.At Penn, students are not asked to indicate race when applying for housing."One of the great things about freshman housing is that, with some exceptions, the process throws you together randomly," said Undergraduate Assembly chairman Alec Webley. "This is the definition of integration.""I've experienced roommate conflicts between interracial students that have both broken down stereotypes and reinforced stereotypes," said one Penn resident advisor (RA). The RA of two years added that while some conflicts "provided more multicultural acceptance and melding (融合)," there were also "jarring cultural confrontations."The RA said that these conflicts have also occurred among roommates of the same race.Kao said she cautions against forming any generalizations based on any one of the studies, noting that more background characteristics of the students need to be studies and explained.57. What can we learn from some recent studies?A) Conflicts between studies of different races are unavoidable.B) Students of different races are prejudiced against each other.C) Interracial lodging does more harm than good.D) Interracial lodging may have diverse outcomes.58. What does Sam Boakye's remark mean?A) White students tend to look down upon their black peers.B) Black students can compete with their white peers academically.C) Black students feel somewhat embarrassed among white peers during the freshman year.D) Being surrounded by white peers motivates a black student to work harder to succeed.59. What does the Indians Univerisity study show?A) Interracial roommates are more likely to fall out.B) Few white students like sharing a room with a black peer.C) Roommates of different races just don't get along.D) Assigning students' lodging randomly is not a good policy.60. What does Alec Webley consider to be the "definition of integration"?A) Students of different races are required to share room.B) Interracial lodging is arranged by the school for freshmen.C) Lodging is assigned to students of different races without exception.D) The school randomly assigns roommates without regard to race.61. What does Grace Kao say about interracial lodging?A) It is unscientific to make generalizations about it without further study.B) Schools should be cautious when making decisions about student lodging.C) Students' racial background should be considered before lodging is assigned.D) Experienced resident advisors should be assigned to handle the problems.Passage TwoGlobal warming is causing more than 300,000 deaths and about $125 billion in economic losses each year, according to a report by the Global Humanitarian Forum, an organization led by Kofi Annan, the former United Nations secretary general.The report, to be released Friday, analyzed data and existing studies of health, disaster, population and economic trends. It found that human-influenced climate change was raising the global death rates from illnesses including malnutrition (营养不良) and heat-related health problems.But even before its release, the report drew criticism from some experts on climate and risk, who questioned its methods and conclusions.Along with the deaths, the report said that the lives of 325 million people, primarily in poor countries, were being seriously affected by climate change. It projected that the number would double by 2030.Roger Pielke Jr., a political scientist at the University of Colorado, Boulder, who studies disaster trends, said the Forum's report was " a methodological embarrassment" because there was no way to distinguish deaths or economic losses related to human driven global warming amid the much larger losses resulting from the growth in populations and economic development in vulnerable (易受伤害的) regions. Dr. Pielke said that "climate change is an important problem requiring our utmost attention." But the report, he said, "will harm the cause for action on both climate change and disasters because it is so deeply flawed (有瑕疵的)"However, Soren Anderasen, a social scientist at Dalberg Global Development Partners who supervised the writing of the report, defended it, saying that it was clear that the numbers were rough estimates. He said the report was aimed at world leaders, who will meet in Copenhagen in December to negotiate a new international climate treaty.In a press release describing the report, Mr. Annan stressed the need for the negotiations to focus on increasing the flow of money from rich to poor regions to help reduce their vulnerability to climate hazards, while still curbing the emissions of the heat-trapping gases. More than 90% of the human and economic losses from climate change are occurring in poor countries, according to the report.62. What is the finding of the Global Humanitarian Forum?A) Global temperatures affect the rate of economic development.B) Rates of death from illness have risen due to global warming.C) Malnutrition has caused serious health problems in poor countries.D) Economic trends have to do with population and natural disasters.63. What do we learn about the Forum's report from the passage?A) It was challenged by some climate and risk experts.B) It aroused a lot of interest in the scientific circles.C) It was warmly received by environmentalists.D) It caused a big stir in developing countries.64. What does Dr. Pielke say about the Forum's report?A) Its statistics look embarrassing.B) It is invalid in terms of methodology.C) It deserves our closest attention.D) Its conclusion is purposely exaggerated.65. What is Soren Andreasen's view of the report?A) Its conclusions are based on carefully collected data.B) It is vulnerable to criticism if the statistics are closely examined.C) It will give rise to heated discussions at the Copenhagen conference.D) Its rough estimates are meant to draw the attention of world leaders.66. What does Kofi Annan say should be the focus of the Copenhagen conference?A) How rich and poor regions can share responsibility in curbing global warming.B) How human and economic losses from climate change can be reduced.C) How emissions of heat-trapping gases can be reduced on a global scale.D) How rich countries can better help poor regions reduce climate hazards.Part ⅤCloze (15 minutes)Directions:There are 20 blanks in the following passage. For each blank there are four choices marked A), B), C) and D) on the right side of the paper. You should choose the ONE that best fits into the passage. Then mark the corresponding letter on Answer Sheet 2 with a single line through the centreWhen it comes to eating amart for your heart, stop thinking about short-term fixes and simplify your life with a straightforward approach that will serve you well for years to come.Smart eating goes beyond analyzing every bite of food you lift 67 your mouth. "In the past we used to believe that 68 amounts of individual nutrients (营养物) were the 69 to good health," says Linda Van Horn, chair of the American Heart Association's Nutrition Committee. "But now we have a 70 understanding of healthy eating and the kinds of food necessary to 71 not only heart disease but disease 72 general," she adds.Scientists now 73 on the broader picture of the balance of food eaten 74 several days or a week 75 than on the number of milligrams (毫克) of this or that 76 at each meal. Fruits, vegetables and whole grains, for example, provide nutrients and plant-based compounds 77 for good health. "The more we learn, the more 78 we are by the wealth of essential substances they 79 ," Van Horn continues, "and how they 80 with each other to keep us healthy."You'll automatically be 81 the right heart-healthy track if vegetables, fruits and whole grains make 82 three quarters of the food on your dinner plate. 83 in the restaurant one quarter with lean meat or chicken, fish or eggs.。

临床药师对肿瘤患者的药物重整实践陈敏;张国伟;杜鸣;夏飞;许鑫;胡光煦;廖亚玲;高礼杰【摘要】OBJECTIVE:To probe into the effect of clinical pharmacists in medication reconciliation practice on cancer patients, and provide safe, effective and precise medication regimens for cancer patients. METHODS:Medication on 5 cancer patients was analyzed by clinical pharmacists, so as to formulate medication reconciliation regimen. RESULTS & CONCLUSIONS:For different situations of 5 cancer patients, clinical pharmacists had found latent adverse drug reactions after inquiring about medication history, monitoring on medical orders during hospital stays and post-discharge follow-up clinics, and carried out intervention on inappropriate drug selection and irrational drug combination, so as to assist clinicians with optimizing medication regimen and ensure rational drug application for patients.%目的:探讨临床药师在肿瘤患者药物重整实践中的作用,为肿瘤患者提供安全、有效、精准的用药方案.方法:临床药师对5例肿瘤患者用药情况进行分析,制订药物重整方案.结果与结论:针对5例患者的不同情况,临床药师通过询问既往用药史、进行住院期间用药医嘱监护及出院后用药随诊,发现了潜在的药害事件,并对药物选择不当、联合用药不合理等情况进行了干预.协助临床医师优化了用药方案,保障了患者用药合理性.【期刊名称】《中国医院用药评价与分析》【年(卷),期】2017(017)007【总页数】3页(P989-990,993)【关键词】临床药师;药物重整;肿瘤患者;用药偏差【作者】陈敏;张国伟;杜鸣;夏飞;许鑫;胡光煦;廖亚玲;高礼杰【作者单位】湖北省第三人民医院药学部,湖北武汉 430033;广州军区武汉总医院药学部,湖北武汉 430070;湖北省第三人民医院药学部,湖北武汉 430033;湖北省第三人民医院药学部,湖北武汉 430033;湖北省第三人民医院药学部,湖北武汉430033;湖北省第三人民医院药学部,湖北武汉 430033;湖北省第三人民医院药学部,湖北武汉 430033;湖北省第三人民医院药学部,湖北武汉 430033【正文语种】中文【中图分类】R969.3药物重整(medication reconciliation, Med-Rec)最早由Pronovost等[1]于2003年提出，之后经多次修订，并无统一定义。

CK2在非小细胞肺癌中的研究进展金承基;宋萍;袁荣霞【摘要】蛋白激酶CK2是一种在真核细胞中普遍存在的高度保守的丝氨酸/苏氨酸蛋白激酶.CK2在人类的许多肿瘤中均呈过表达,目前已有研究表明CK2在非小细胞肺癌(NSCLC)中的表达水平与肿瘤细胞的增殖、迁移、侵袭及患者的临床预后密切相关.CK2通过不同的方式在肿瘤中发挥作用,包括肿瘤细胞凋亡的抑制、相关信号通路的调节、对DNA损伤的修复及细胞周期的调节.CK2极有可能成为继表皮生长因子受体(EGFR)之后的用于NSCLC治疗的又一新的靶点.CK2抑制药如GIGB-300、CX-4945,在相关的NSCLC治疗的研究中显示出巨大的潜能.本文就CK2的结构、生物学功能及其在NSCLC中的作用和相关机制的研究进展作一综述.【期刊名称】《癌症进展》【年(卷),期】2018(016)014【总页数】4页(P1699-1701,1757)【关键词】蛋白激酶2;非小细胞肺癌;过表达;信号通路;表皮生长因子受体【作者】金承基;宋萍;袁荣霞【作者单位】江苏大学附属医院呼吸内科,江苏镇江 2120010;江苏大学附属医院呼吸内科,江苏镇江 2120010;江苏大学附属医院呼吸内科,江苏镇江 2120010【正文语种】中文【中图分类】R734.2根据全球肿瘤报告的统计显示，2012年全球范围内大约有1410万的肿瘤新发病例和820万的肿瘤死亡病例，其中，肺癌新发病例为180万，约占全部恶性肿瘤的13%；肺癌死亡病例约为160万，占肿瘤死亡病例的19.5%；肺癌的发病率和病死率已位居全球男性肿瘤发病率及病死率的首位，也是全球女性肿瘤死亡的第二大病因[1]。

同样，2014年发布的有关中国2010年肿瘤发病率和病死率的统计数据显示，肺癌的发病率和病死率位居全部恶性肿瘤的首位，可见肺癌已严重威胁人类的生命健康[2]。

其中，非小细胞肺癌（non-small cell lung cancer，NSCLC）约占原发性肺癌的80%，其大多起病隐匿，常难以被早发现、早诊断、早治疗；肺癌患者被发现时大多已属于中晚期，失去了手术切除治疗的最佳机会，而通过药物控制肺癌的进展，从而使肺癌成为一种慢性疾病逐渐成为肺癌治疗的一种趋势。

Global Cancer StatisticsAhmedin Jemal,DVM,PhD1;Freddie Bray,PhD2;Melissa M.Center,MPH3;Jacques Ferlay,ME4;Elizabeth Ward,PhD5;David Forman,PhD6AbstractThe global burden of cancer continues to increase largely because of the aging and growth of the world population alongsidean increasing adoption of cancer-causing behaviors,particularly smoking,in economically developing countries.Based on the GLOBOCAN2008estimates,about12.7million cancer cases and7.6million cancer deaths are estimated to have occurred in 2008;of these,56%of the cases and64%of the deaths occurred in the economically developing world.Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females,accounting for23%of the total cancer cases and14%of the cancer deaths.Lung cancer is the leading cancer site in males,comprising17%of the total new cancer cases and23%of the total cancer deaths.Breast cancer is now also the leading cause of cancer death among females in eco-nomically developing countries,a shift from the previous decade during which the most common cause of cancer death was cer-vical cancer.Further,the mortality burden for lung cancer among females in developing countries is as high as the burden for cer-vical cancer,with each accounting for11%of the total female cancer deaths.Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes,the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries,most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment.A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control,vaccination(forliver and cervical cancers),and early detection and treatment,as well as public health campaigns promoting physical activity anda healthier dietary intake.Clinicians,public health professionals,and policy makers can play an active role in accelerating the application of such interventions globally.CA Cancer J Clin2011;61:69–90.V C2011American Cancer Society,Inc. IntroductionCancer is the leading cause of death in economically developed countries and the second leading cause of deathin developing countries.1The burden of cancer is increasing in economically developing countries as a result of population aging and growth as well as,increasingly,an adoption of cancer-associated lifestyle choices including smoking,physical inactivity,and‘‘westernized’’diets.In this article,we provide an overview of the global cancer burden,including the estimated number of new cancer cases and deaths in2008and the incidence and mortality rates by region for selected cancer sites.These statistics are based on GLOBOCAN2008,2the standard set of worldwide estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer(IARC)for2008.We comment on the recent incidence and mortality patterns observed for a number of common cancer forms,alongside established preventive measures that can reduce the worldwide cancer burden. Data Sources and MethodsIncidence data(the number of newly diagnosed cases each year)are derived from population-based cancer registries,which may cover entire national populations but more often cover smaller,subnational areas,and, particularly in developing countries,only urban environments,such as major cities.Although the quality of1Vice President,Surveillance Research,American Cancer Society,Atlanta,GA;2Deputy Head,Section of Cancer Information,International Agency for Research on Cancer,Lyon,France;3Epidemiologist,Surveillance Research,American Cancer Society,Atlanta,GA;4Informatics Officer,Section of Cancer Information,International Agency for Research on Cancer,Lyon,France;5National Vice President,Intramural Research,American Cancer Society,Atlanta, GA;6Head,Section of Cancer Information,International Agency for Research on Cancer,Lyon,France.Corresponding author:Ahmedin Jemal,DVM,PhD,Surveillance Research,American Cancer Society,250Williams Street,NW,Atlanta,GA30303-1002; ahmedin.jemal@DISCLOSURES:The authors report no conflicts of interest.V C2011American Cancer Society,Inc.doi:10.3322/caac.20107.Available online at and VOLUME61_NUMBER2_MARCH/APRIL201169information from most of the developing countries might be considered,in relative terms,of limited qual-ity,it often remains the only source of information available on the profile of cancer and as such provides valuable information.The total number of cancer deaths by country are collected annually and are made available by the World Health Organization (WHO).3The advantages of this source of data are its national coverage and long-term availability,although not all datasets are of the same quality or complete-ness.Provisional estimates of the age-and sex-specific deaths from cancer(of all types)for2008have been used1in regions of the world with either no death in-formation or where official statistics are deemed unre-liable,and corrected for possible incompleteness. Incidence and mortality rates(number of cases or deaths per100,000persons per year)were estimated in GLOBOCAN2by country,using the most recently available data collected at the IARC or avail-able in routine reports from the registries themselves. National incidence rates were estimated using one of several methods,dependant on the availability and quality of data,in the following order of priority:1.National incidence data.When historical dataand a sufficient number of recorded cases were available,incidence rates were projected to2008.2.National mortality data and local registry data.Estimation of incidence based on regression models,specific for sex,site,and age,derived from subnational or regional cancer registry data.3.Regional incidence data from one or more can-cer registries but no mortality data.National incidence derived from a single set or a weighted average of local rates.4.Frequency data.Only data on the relative fre-quency of different cancers(by sex,site,and age groups)available.These proportions are applied to estimates of the all-cancer incidence rate for the country,derived from cancer registry data within the same region.5.No data available.Country-specific rates equated tothose of neighboring countries in the same region. Similar procedures were used to estimate country-specific mortality rates,in the following order of priority:1.National mortality data.Projections to2008where possible.2.Sample mortality data.The age-and sex-specificall-cancer mortality envelopes provided nationallyfor2008by the WHO were partitioned by site using the sample mortality data.3.No mortality data.National mortality was derivedfrom incidence and cancer-and country-specific survival probabilities(based on level of gross domestic product),and then scaled to the WHO all-cancer mortality envelope for2008. Country-specific incidence and mortality rates were prepared for27types of cancer(including Kaposi sarcoma[KS]for sub-Saharan African coun-tries),by sex and for10age groups(0-14,15-39, 40-44,45-49,…70-74,and75þyears).A full description of the data and methods used for each country and the corresponding results are available in GLOBOCAN2008(available at http://www. globocan.iarc.fr).4Estimates for the20world regions (Fig.1)and for more and less developed regions,as defined by the United Nations(UN),5were obtained as the population-weighted average of the incidence and mortality rates of the component countries. These rates were age-standardized(ASRs)(per 100,000person-years)using the World Standard Population as proposed by Segi and modified by Doll et al.6,7The cumulative risk of developing or dying from cancer before the age of75years(in the absence of competing causes of death)was also calculated and is expressed as a percentage. Results and DiscussionEstimated Number of New CancerCases and DeathsAbout12.7million cancer cases and7.6million cancer deaths are estimated to have occurred in2008world-wide(Fig.2),with56%of the cases and64%of the deaths in the economically developing world.Breast cancer in females and lung cancer in males are the most frequently diagnosed cancers and the leading cause of cancer death for each sex in both economically developed and developing countries,except lung can-cer is preceded by prostate cancer as the most frequent cancer among males in economically developed coun-tries.These cancers were followed,without specific rank order,by stomach and liver cancers in males and cervix and lung cancers in females in economically developing countries and by colorectal and lung can-cers in females and colorectal and lung or prostate cancers in males in the economically developed world.70CA:A Cancer Journal for CliniciansIncidenceand Mortality Rates for All Cancers Combined and Top 22Cancer SitesWhile incidence rates for all cancers combined in economically developed countries are nearly twice as high as in economically developing countries in both males and females (Table 1),mortality rates for all cancers combined in developed countries are only 21%higher in males and only 2%higher in females.Such disparities in incidence and mortality patterns between developed and developing countries will reflect,for a given cancer,regional differences in the prevalence and distribution of the major risk factors,detection practices,and/or the availability and use of treatment services.Prostate,colorectal,female breast,and lung cancer rates are 2to 5times higher in developed countries compared with developing countries,a result of variations in a disparate set of risk factors and diagnostic practices.The converse is true for cancers related to infections such as stomach,liver,and cervical cancers (Table 1).Table 2shows the overall cancer incidence and mortality rates by sex according to world areas.The incidence rate for both sexes combined is more than 3times as high in Australia/New Zealand as that in Middle Africa.It should also be noted that cancer tends to be diagnosed at later stages in many developing coun-tries compared with developed countries and this,combined with reduced access to appropriate thera-peutic facilities and drugs (Fig.3),has an adverse effect on survival.A recent comparative survey of cancer survival rates in Africa,Asia,and Central America 8based on patients diagnosed in the 1990s indicates substantially lower survival rates in parts of Africa,India,and the Philippines than for those diagnosed in Singapore,South Korea,and parts of China.For example,breast cancer 5-year survival rates were 50%or less in the former populations and over 75%in the latter.Such comparisons were simi-lar to those observed in the CONCORD study 9for an earlier time period.Selected CancersFemale Breast CancerBreast cancer is the most frequently diagnosed can-cer and the leading cause of cancer death in females worldwide,accounting for 23%(1.38million)of the total new cancer cases and 14%(458,400)of the total cancer deaths in 2008(Fig.2).About half the breast cancer cases and 60%of the deaths are estimated to occur in economically developing countries.In general,incidence rates are high in Western andFIGURE 1.Twenty World Areas.VOLUME 61_NUMBER 2_MARCH/APRIL 201171FIGURE2.Estimated New Cancer Cases and Deaths Worldwide for Leading Cancer Sites by Level of Economic Development,2008.Source:GLOBOCAN 2008.72CA:A Cancer Journal for CliniciansTABLE1.Incidence and Mortality Rates and Cumulative Probability of Developing Cancer by Age75by Sex and Cancer Site for More Developed and Less Developed Areas,2008MORE DEVELOPED AREAS LESS DEVELOPED AREASINCIDENCE MORTALITY INCIDENCE MORTALITYASR CUMULATIVE RISK(%)[AGE0-74]ASRCUMULATIVE RISK(%)[AGE0-74]ASRCUMULATIVE RISK(%)[AGE0-74]ASRCUMULATIVE RISK(%)[AGE0-74]MalesAll cancers*(C00-97,but C44)300.130.1143.915.0160.317.0119.312.7Bladder(C67)16.6 1.9 4.60.5 5.40.6 2.60.3Brain,nervous system(C70-72) 6.00.6 3.90.4 3.20.3 2.60.3Colorectum(C18-21)37.6 4.415.1 1.712.1 1.4 6.90.8Esophagus(C15) 6.50.8 5.30.611.8 1.410.1 1.2Gallbladder(C23-24) 2.40.3 1.60.2 1.40.2 1.10.1Hodgkin lymphoma(C81) 2.20.20.40.00.90.10.60.1Kidney(C64-66)11.8 1.4 4.10.5 2.50.3 1.30.1Larynx(C32) 5.50.7 2.40.3 3.50.4 2.10.3Leukemia(C91-95)9.10.9 4.80.5 4.50.4 3.70.3Liver(C22)8.1 1.07.20.918.9 2.217.4 2.0Lung(C33-34)47.4 5.739.4 4.727.8 3.324.6 2.9Melanoma of skin(C43)9.5 1.0 1.80.20.70.10.30.0Multiple myeloma(C88þC90) 3.30.4 1.90.20.90.10.80.1Nasopharynx(C11)0.60.10.30.0 2.10.2 1.40.2Non-Hodgkin lymphoma(C82-85,C96)10.3 1.1 3.60.4 4.20.5 3.00.3Oral cavity(C00-08) 6.90.8 2.30.3 4.60.5 2.70.3Other pharynx(C09-10,C12-14) 4.40.5 2.20.3 3.00.4 2.50.3Pancreas(C25)8.2 1.07.90.9 2.70.3 2.50.3Prostate(C61)62.07.810.60.912.0 1.4 5.60.5Stomach(C16)16.7 2.010.4 1.221.1 2.516.0 1.9Testis(C62) 4.60.40.30.00.80.10.30.0Thyroid(C73) 2.90.30.30.0 1.00.10.30.0FemalesAll cancers*(C00-97,but C44)225.522.087.39.1138.014.085.49.0Bladder(C67) 3.60.4 1.00.1 1.40.20.70.1Brain,nervous system(C70-72) 4.40.4 2.60.3 2.80.3 2.00.2Breast(C50)66.47.115.3 1.727.3 2.810.8 1.2Cervix uteri(C53)9.00.9 3.20.317.8 1.99.8 1.1Colorectum(C18-21)24.2 2.79.7 1.09.4 1.1 5.40.6Corpus uteri(C54)12.9 1.6 2.40.3 5.90.7 1.70.2Esophagus(C15) 1.20.1 1.00.1 5.70.7 4.70.5Gallbladder(C23-24) 2.10.2 1.50.2 2.20.3 1.70.2Hodgkin lymphoma(C81) 1.90.20.30.00.50.10.30.0Kidney(C64-66) 5.80.7 1.70.2 1.40.20.80.1Larynx(C32)0.60.10.20.00.60.10.40.0Leukemia(C91-95) 6.00.6 2.90.3 3.60.3 2.90.3Liver(C22) 2.70.3 2.50.37.60.97.20.8VOLUME61_NUMBER2_MARCH/APRIL201173Northern Europe,Australia/New Zealand,and North America;intermediate in South America,the Carib-bean,and Northern Africa;and low in sub-Saharan Africa and Asia(Fig.4).The factors that contribute to the international variation in incidence rates largely stem from differences in reproductive and hormonal factors and the availability of early detection ser-vices.10,11Reproductive factors that increase risk include a long menstrual history,nulliparity,recent use of postmenopausal hormone therapy or oral con-traceptives,and late age atfirst birth.12Alcohol con-sumption also increases the risk of breast cancer.13,14 The breast cancer incidence increases observed in many Western countries in the late1980s and1990s likely result from changes in reproductive factors (including the increased use of postmenopausal hor-mone therapy)as well as an increased screening inten-sity.15Incidence rates in some of these counties, including the United States,United Kingdom,France, and Australia,sharply decreased from the beginning of the millennium,partly due to lower use of com-bined postmenopausal hormone therapy.16-21In con-trast,breast cancer death rates have been decreasing in North America and several European countries over the past25years,largely as a result of early detection through mammography and improved treat-ment.10,15,22In many African and Asian countries however,including Uganda,South Korea,and India, incidence and mortality rates have been rising,23,24 with changes in reproductive patterns,physical inac-tivity,and obesity being the main contributory fac-tors10,25,26;increases in breast cancer awareness and screening activity may be partially responsible for the rising incidence in these populations.Maintaining a healthy body weight,increasing physical activity,and minimizing alcohol intake are the best available strategies to reduce the risk of developing breast cancer.27Early detection through mammography has been shown to increase treat-ment options and save lives,although this approach is cost prohibitive and not feasible in most economi-cally developing countries.28Recommended early detection strategies in these countries include the promotion of awareness of early signs and symptoms and screening by clinical breast examination.29 Colorectal CancerColorectal cancer is the third most commonly diag-nosed cancer in males and the second in females, with over1.2million new cancer cases and608,700 deaths estimated to have occurred in2008(Fig.2). The highest incidence rates are found in Australia and New Zealand,Europe,and North America, whereas the lowest rates are found in Africa andTABLE1.(Continued)MORE DEVELOPED AREAS LESS DEVELOPED AREASINCIDENCE MORTALITY INCIDENCE MORTALITYASR CUMULATIVE RISK(%)[AGE0-74]ASRCUMULATIVE RISK(%)[AGE0-74]ASRCUMULATIVE RISK(%)[AGE0-74]ASRCUMULATIVE RISK(%)[AGE0-74]Lung(C33-34)18.6 2.313.6 1.611.1 1.39.7 1.1 Melanoma of skin(C43)8.60.9 1.10.10.60.10.30.0 Multiple myeloma(C88þC90) 2.20.3 1.30.10.70.10.60.1 Nasopharynx(C11)0.20.00.10.0 1.00.10.60.1 Non-Hodgkin lymphoma(C82-85,C96)7.00.8 2.20.2 2.80.3 1.90.2 Oral cavity(C00-08) 2.40.30.60.1 2.60.3 1.50.2 Other pharynx(C09-10,C12-14)0.80.10.30.00.80.10.60.1 Ovary(C56)9.4 1.0 5.10.6 5.00.5 3.10.4 Pancreas(C25) 5.40.6 5.10.6 2.10.3 2.00.2 Stomach(C16)7.30.8 4.70.510.0 1.18.10.9 Thyroid(C73)9.10.90.40.0 3.40.40.70.1 ASR indicates age-standardized rate per100,000.Rates are standardized to the World Standard Population.*Excludes nonmelanoma skin cancer.Source:GLOBOCAN2008.74CA:A Cancer Journal for CliniciansSouth-Central Asia(Fig.5).Rates are substantially higher in males than in females.Colorectal cancer incidence rates are rapidly increas-ing in several areas historically at low risk,including Spain,and a number of countries within Eastern Asia and Eastern Europe.30,31Notably,rates among males in the Czech Republic and Japan have already exceeded the peak of incidence observed in the United States,Canada,and Australia,where rates are declin-ing or stabilizing.30,31Such unfavorable trends are thought to reflect a combination of factors including changes in dietary patterns,obesity,and an increased prevalence of smoking.30-34The United States is the only country with significantly decreasing incidence rates in both males and females in the most recent time period,which largely reflects detection and re-moval of precancerous lesions through colorectal can-cer screening.18,31While colorectal cancer death rateshave been decreasing inseveral Western coun-tries,31largely resultingfrom improved treatmentand increased awarenessand early detection,18,35-37rates continue to increasein many countries withmore limited resourcesand health infrastructure,particularly in Central andSouth America and East-ern Europe.31Modifiable risk factorsfor colorectal cancer in-clude smoking,physicalinactivity,overweight andobesity,red and processedmeat consumption,andexcessive alcohol consump-tion.38-40Population-basedcolorectal screening pro-grams are feasible only ineconomically developedcountries,although futureattention should also befocused in those areas ofthe world with an agingpopulation and increas-ingly westernized lifestyle(eg,Brazil).41-44Accordingto a recent randomized trial in the United Kingdom,a one-timeflexible sig-moid-oscopy screening between55and64years of age reduced colorectal cancer incidence by33%and mor-tality by43%.45Lung CancerLung cancer was the most commonly diagnosed can-cer as well as the leading cause of cancer death in males in2008globally(Fig.2).Among females,it was the fourth most commonly diagnosed cancer and the second leading cause of cancer death.Lung cancer accounts for13%(1.6million)of the total cases and18%(1.4million)of the deaths in2008.In males,the highest lung cancer incidence rates are in Eastern and Southern Europe,North America, Micronesia and Polynesia,and Eastern Asia,while rates are low in sub-Saharan Africa(Fig.6).InTABLE2.Estimated Age-Standardized Incidence and Mortality Rates Per100,000byWorld Area,2008*INCIDENCE MORTALITYMALE FEMALE OVERALL MALE FEMALE OVERALLEastern Africa121.2125.3122.8105.495.999.9Middle Africa88.196.791.878.575.676.4Northern Africa109.298.9103.289.568.278.0Southern Africa235.9161.0189.6172.1108.1133.2Western Africa92.0123.5107.680.191.285.4Eastern Asia222.1158.1188.4155.587.3120.1South-Central Asia99.7110.8104.678.071.774.5South-Eastern Asia143.9141.7141.5112.389.499.5Western Asia152.8119.5133.8113.974.392.2Caribbean196.3153.5172.6116.686.299.9Central America136.2134.4134.484.780.682.0Northern America334.0274.4299.9122.491.5105.1South America186.7162.9171.9116.688.2100.3Central and Eastern Europe259.2184.2210.6181.594.0128.1Northern Europe292.3249.5266.1134.699.7114.5Southern Europe289.9212.2245.0149.981.2111.7Western Europe337.4250.9287.7138.484.3108.0Australia/New Zealand356.8276.4313.3125.686.0104.1Melanesia146.0133.4138.5119.895.9106.8Micronesia153.8164.4157.5104.770.386.1Polynesia225.0201.5209.8133.687.9109.1*Excludes nonmelanoma skin cancer.Source:GLOBOCAN2008.VOLUME61_NUMBER2_MARCH/APRIL201175females,the highest lung cancer incidence rates are found in North America,Northern Europe,and Aus-tralia/New Zealand.Despite their lower prevalence of smoking (less than 4%adult smokers),46Chinese females have higher lung cancer rates (21.3cases per 100,000females)than those in certain European countries such as Germany (16.4)and Italy (11.4),with an adult smoking prevalence of about 20%.46The relatively high burden of lung cancer in women is thought to reflect indoor air pollution from unventi-lated coal-fueled stoves and from cooking fumes in China.47-49Other known risk factors for lung cancer include exposure to several occupational and environ-mental carcinogens such as asbestos,arsenic,radon,and polycyclic aromatic hydrocarbons.50The observed variations in lung cancer rates and trends across countries or between males and females within each country largely reflect differences in the stage and degree of the tobacco epidemic.51,52Smok-ing accounts for 80%of the worldwide lung cancer burden in males and at least 50%of the burden in females.53,54Male lung cancer death rates are decreas-ing in most Western countries,including many Euro-pean countries,North America,and Australia,where the tobacco epidemic peaked by the middle of the last century.52,55,56In contrast,lung cancer rates are increas-ing in countries such as China and several other coun-tries in Asia and Africa,where the epidemic has been established more recently and smoking prevalence continues to either increase or show signs of stability.10,47,51Generally,lung cancer trends among females lag behind males because females started smoking in large numbers several decades later than males.57Therefore,lung cancer rates in females are increasing in many countries 52except the United States,Can-ada,the United Kingdom,and Australia,where they are plateauing.Notably,in Spain,France,Belgium,and the Netherlands rates are increasing in more recent female birth cohorts,suggesting that the lung cancer burden in females in these countries will likely continue to increase for several decades barring any major interventions.52Most of the worldwide burden of lung cancer could be avoided by applying proven tobacco control inter-ventions that include raising the price of cigarettes and other tobacco products,banning smoking in public places,the restriction of advertising of tobacco prod-ucts,counter advertising,and treating tobacco depend-ence.58To illustrate,a 10%increase in cigarette prices has been shown to reduce cigarette consumption by 3%to 5%.59In 2003,the WHO established the Framework Convention on Tobacco Control to enable international coordinated efforts to curb thetobaccoFIGURE 3.Number of People Served by Each Radiotherapy Center by Country.Sources:International Atomic Energy Agency,Directory of RadiotherapyCenters,/nuhu/dirac/,Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat,World Population Prospects:The 2008Revision,and /unpp.76CA:A Cancer Journal for Cliniciansepidemic.60The United States is among the few coun-tries that have yet to ratify the treaty.Prostate CancerProstate cancer is the second most frequently diag-nosed cancer and the sixth leading cause of cancerdeath in males,accounting for 14%(903,500)of the total new cancer cases and 6%(258,400)of the total cancer deaths in males in 2008(Fig.2).Incidence rates vary by more than 25-fold worldwide,with the highest rates recorded primarily in the developed countries of Oceania,Europe,and North America (Fig.7),largely because of the wide utilization of pros-tate-specific antigen (PSA)testing that detects clini-cally important tumors as well as other slow-growing cancers that might otherwise escape diagnosis.In con-trast,males of African descent in the Caribbean region have the highest prostate cancer mortality rates in the world,which is thought to reflect partly difference in genetic susceptibility.61,62Temporal trends in incidence rates in countries with higher uptake of PSA testing such as the United States,Australia,Canada,and the Nordic countries followed similar patterns.63,64Rates rose rapidly in the early 1990s,soon after the introduction of PSA test-ing,followed by a sharp decline due to a smaller pool of prevalent cases.In other high-income countries with a low and gradual increase in the prevalence of PSA testing,such as Japan and the United Kingdom,rates continue to increase slightly.63Death rates for prostate cancer have been decreas-ing in many developed countries,includingFIGURE 5.Age-Standardized Colorectal Cancer Incidence Rates by Sex and World Area.Source:GLOBOCAN2008.FIGURE 6.Age-Standardized Lung Cancer Incidence Rates by Sex andWorld Area.Source:GLOBOCAN2008.FIGURE 4.Age-Standardized Breast Cancer Incidence and MortalityRates by World Area.Source:GLOBOCAN 2008.VOLUME 61_NUMBER 2_MARCH/APRIL 201177Australia,Canada,the United Kingdom,the United States,Italy,and Norway in part because of the improved treatment with curative intent.63,65,66The role of PSA testing in the reduction of the pros-tate cancer mortality rates at the population level has been difficult to quantify.A large US-based randomized trial on the efficacy of PSA testing in reducing mortality from prostate cancer found no ben-efit,67while another similar European-based trial found a modest benefit.68Differences in study design,sample size (statistical power),follow up,and possible contamination of controls may have contributed to the different findings between these 2studies.In contrast to the trends in Western countries,incidence and mor-tality rates are rising in several Asian and Central and Eastern European countries,such as Japan.63,65Older age,race (black),and family history remain the only well-established risk factors and there are no estab-lished preventable risk factors for prostate cancer.69Stomach CancerA total of 989,600new stomach cancer cases and 738,000deaths are estimated to have occurred in 2008,accounting for 8%of the total cases and 10%of total deaths (Fig.2).Over 70%of new cases and deaths occur in developing countries.Generally,stomach can-cer rates are about twice as high in males as in females(Table 1).The highest incidence rates are in Eastern Asia,Eastern Europe,and South America and the low-est rates are in North America and most parts of Africa (Fig.8).Regional variations in part reflect differences in dietary patterns,particularly in European countries,and the prevalence of Helicobacter pylori infection.70Stomach cancer rates have decreased substantially in most parts of the world,71in part due to factors related to the increased use and availability of refriger-ation including the increased availability of fresh fruits and vegetables,and a decreased reliance on salted and preserved foods.Other major determinants for the favorable trends are reductions in chronic H.pylori infection in most parts of the world 72-74and smoking in some parts of the developed world.71In Japan,mor-tality rates may have declined via the introduction of screening using photofluorography,75which may have also contributed to the persistently high incidence rates in the country.Liver CancerLiver cancer in men is the fifth most frequently diag-nosed cancer worldwide but the second most fre-quent cause of cancer death.In women,it is the seventh most commonly diagnosed cancer and the sixth leading cause of cancer death.An estimated 748,300new liver cancer cases and 695,900cancerFIGURE 7.Age-Standardized Prostate Cancer Incidence and Mortality Rates by World Area.Source:GLOBOCAN2008.FIGURE 8.Age-Standardized Stomach Cancer Incidence Rates by Sexand World Area.Source:GLOBOCAN 2008.78CA:A Cancer Journal for Clinicians。