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Harold Gee MD FRCOG

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Circulation 2002;106:2145Effectiveness of creatine monohydrate in mitochondrial 2161 encephalomyopathies virus 2 order 500mg chloramphenicol with amex. Nat Genet 2002;30:394-399 syndrome following articaine administration for local anesthesia chest infection generic 250mg chloramphenicol free shipping. Neurology Maruyama W anabolic steroids purchase genuine chloramphenicol, Naoi M infection xrepresentx lyrics buy chloramphenicol paypal, Ibi T antibiotic names for uti buy cheap chloramphenicol line, Sahashi K antibiotics for uti during first trimester proven chloramphenicol 500 mg, Shamoto M, Fuku N, Kurata M, 1998;50:1055-1060 Yamada Y, Nishizawa K, Akao Y, Ohishi N, Miyabayashi S, Umemoto H, 213. Ketogenic treatment Muramatsu T, Furukawa K, Kikuchi A, Nakano I, Ozawa K, Yagi K. Ann therapy for mitochondrial disease by delivering restriction endonuclease Neurol 2004;56:662-669 SmaI into mitochondria. Correction Genet 1997;6:2239-2242 of translational defects in patient-derived mutant mitochondria 215. Ogasahara S, Yorifuji S, Nishikawa Y, Takahashi M, Wada K, Hazama T, Linked oligodeoxynucleotides show binding cooperativity and can Nakamura Y, Hashimoto S, Kono N, Tarui S. Bupivacaine myotoxicity is controlled carbohydrate intake and Coenzyme Q10 therapy. Ogasahara S, Nishikawa Y, Yorifuji S, Soga F, Nakamura Y, Takahashi M, Fischel-Ghodsian N. Treatment of Kearns-Sayre syndrome with progressive external ophthalmoplegia and son with Pearson with coenzyme Q10. Bresolin N, Bet L, Binda A, Moggio M, Comi G, Nador F, Ferrante C, Carenzi A, 242. Shanske S, Tang Y, Hirano M, Nishigaki Y, Tanji K, Bonilla E, Sue C, Krishna S, Scarlato G. Neurology 1988;38:892-899 in a woman with ocular myopathy and in her son with Pearson syndrome. The treatment of mitochondrial myopathies and J Hum Genet 2002;71:679-683 encephalomyopathies. Am J Hum Genet 1992;50:360-363 multiple vitamins is generally ineffective in treatment of mitochondrial 244. Mitochondrial disorders: genetics, 1999;10:927-933 counseling, prenatal diagnosis and reproductive options. Enquiries regarding this document should be addressed to: the National Cancer Control Program Division of Non-Communicable Diseases Ministry of Health P. Box 30016-00100, Nairobi, Kenya Telephone: +254 202717077/+254 202722599 Email: ps@health. In Kenya there were an estimated 47,887 new cancer cases and 32,987 deaths in 2018. It is the third leading cause of death after infectious and cardiovascular diseases. The increasing cancer burden is due to several factors, including population growth and aging as well as the changing prevalence of certain causes of cancer linked to social and economic development. This is particularly true in rapidly growing economies, where a shift is observed from cancers related to poverty and infections to cancers associated with lifestyles more typical of industrialized countries. Mortality from cancer in Kenya, like in other developing countries, is high mainly because optimal access to timely diagnosis and efective treatment is less common. The Ministry of Health aims to address this challenge through development of these Cancer Treatment Protocols, among other initiatives. The Cancer Treatment Protocols have been developed in line with the National Cancer Control Strategy 2017-2022 Pillar 3 that focuses on Treatment, Palliative Care and Survivorship. The key areas covered are diagnosis, imaging, pathology, surgery, rehabilitation, palliative care and survivorship. It emphasizes a multi-disciplinary team approach which is paramount for quality cancer care. They also complement the National Guidelines for Cancer Management in Kenya released in 2013. These Cancer Treatment Protocols have been developed through an extensive consultative process with various experts in the feld of oncology. They are an important tool meant to be used by health workers in Kenya where cancer services are ofered. They are presented in a simplifed manner using a public health approach to cancer treatment. The aim of this document is to ensure that suspected cancer patients seen in any health facility in Kenya are given due services as per the level of care and are referred in a timely manner to an appropriate management facility, and that their evaluation, treatment, rehabilitation and continuing care through to survivorship or palliation is done in a well co-ordinated manner. It also seeks to ensure best practice in service delivery within the facilities providing any cancer care and treatment services. We thank the top leadership of the Ministry of Health for their support especially the Ofce of the Cabinet Secretary, Principal Secretary, Director General, Department of Preventive and Promotive Health and the Division of Non-Communicable Diseases, whose guidance led to the successful development of these protocols. In a special way, we wish to convey our gratitude to the technical working group and the team leads who worked tirelessly to ensure the successful completion of these protocols. Mary Nyangasi, the Program Officer in charge of Cancer Treatment in the Program who coordinated the entire process. We would like to recognize and appreciate the technical input, commitment and dedication of various experts from public, private and faith-based institutions. Eliud Murugu Njuguna who was supportive, dedicated and passionate about this work. At the time of his demise, he was the team lead for gastrointestinal cancers track. These protocols combine evidencefibased and bestfipractice recommendations, with the aim of ensuring availability of equitable, highfiquality services for cancer patients. They cover aspects of clinical evaluation, diagnosis, imaging, surgery, radiotherapy, chemotherapy, hormone therapy, psychosocial support, palliative care, rehabilitation, and survivorship at the diferent healthcare levels. Chapter 1 addresses the general principles of cancer management including referral timelines and processes. Avoidable deaths from childhood cancers in Kenya result from low awareness, diagnostic challenges, obstacles to accessing care, abandonment of treatment due to cost of care or fatalistic beliefs regarding childhood cancers, inadequate human resource capacity, death from toxicity, and higher rates of relapse, among others. Most childhood cancers lack screening strategies therefore early diagnosis and treatment is critical for good outcomes. It is my expectation that all health facilities providing cancer care will use these protocols as a guide on the continuum of care required for priority cancers in Kenya. In line with the National Cancer Control Strategy 2017-2022, these protocols have been developed with input from specialists within the major hospitals treating cancer patients in Kenya. The protocols will be reviewed regularly, in line with guidance from the Ministry of Health and other national and international guidance, as well as signifcant new research publications. Cancer services should be patient centered and should respond to patient and carer feedback. Excellent communication between professionals and patients is particularly important to improve patient satisfaction. Early Diagnosis and Referral There is evidence that patients with cancer attend health facilities a number of times with symptoms related to their cancer and are treated otherwise before onward referral. These protocols recommend that cancer patients be referred appropriately in a timely manner to the appropriate level of care where the specifc service required in the care pathway is available. These protocols recommend the following minimum timelines in order to minimize delays and improve outcomes: 1. Immediate referral will require admission acutely within a few hours of referral such as in oncological emergencies. Urgent referral will require a 14-day standard from referral to assessment in a cancer centre with rapid assessment by a designated clinician. A 31-day standard from diagnosis to start of treatment (including for recurrent disease). Designated clinicians should cooperate to ensure that an appropriate diagnostic work-up is provided for patients suspected to have cancer. The defnitive diagnosis of cancer is confrmed by histopathological examination of the biopsy specimen. There should be pre-booking systems for appointments at both referring and receiving clinics, where each patient with a new cancer diagnosis should be seen by an oncologist. The referring clinician should also be informed of the diagnosis and decision made. Key points at which to communicate include: Diagnosis, multidisciplinary team discussions, assessment clinic, clinic appointment reviews, treatment reviews, decision points for changes in care planning and decision point for end-offilife care planning Stages of the Referral Pathway Referral sources will include Accident and Emergency department, internal referrals from other departments and referrals from outside facilities among others. List of health care professional membership including core members, disciplines and their roles and responsibilities, chair and co-ordinator; 3. The patient has the right to refuse care provided in this way or limit what information is shared. Where appropriate, participation in clinical trials, including the process for identifying eligible patients, should also be addressed in the terms of reference. Treatment decisions and care is delivered by specialists with knowledge and skills in the relevant aspects of the particular cancer type; 2. Good communications and continuity of care regardless of who or where care is provided; 4. Integrating palliative care from the time of diagnosis improves patient and family experience, which ultimately leads to better patient reported outcomes (Lancet, 2018). Pain is whatever the experiencing person says it is existing whenever the experiencing person says it does (McCafery, 1968). Physical Social Psychological Total Pain Spiritual Pain is one of the most frequent and serious symptoms experienced by patients in need of palliative care. The goal is to prevent or treat as early as possible the symptoms of a disease, side efects caused by treatment of a disease, and psychological, social and spiritual problems related to a disease or its treatment. Integrating Palliative Care in Oncology: the Oncologist as a Primary Palliative Care Provider. In Silbermann, M; Palliative Care: Perspectives, Practices and Impact on Quality of Life. Care of Patients at the End of Life: Surrogate Decision Making for Incapacitated Patients. Planning and implementing palliative care services: A guide for programme managers. It covers the physical, psychosocial and economic issues of cancer, beyond the diagnosis and treatment phases. It includes issues related to the ability to get health care and follow-up treatment, rehabilitation, surveillance for late efects of treatment, screening for recurrence & secondary cancers and quality of life. Family members, friends and caregivers are also considered part of the survivorship experience. Surveillance for recurrence/spread of cancer and screening for subsequent primary cancers at least annually. Interventions for consequences of cancer treatment such as pain and peripheral neuropathy management, lymphedema management, for those who received anthracyclines, assess for anthracycline-induced cardiotoxicity (evaluate for heart failure signs and symptoms, presence of risk factors), need for immunizations. Care co-ordination between specialists and primary care givers with specifc roles delineated to ensure the health needs of the cancer survivor are met. Survivorship care planning: this plan will include a summary of treatment received, follow-up care, surveillance and screening recommended for the survivor, post-treatment needs of the survivor, healthy lifestyle behavior recommendations and information on treatment related side efects and anticipated health risks. Cancer Survivorship Issues: Life after Treatment and Implications for an Aging Population. American Society of Clinical Oncology expert statement on cancer survivorship care planning. Breast cancer tends to occur at a relatively young age (35-50 years) in Kenya, in comparison to Western countries (50-55 years). About 90% of cases occur sporadically, while only 5-10% can be attributed to genetic predisposition. Mammography and ultrasound fndings, category and recommendations are as tabulated below: Table 2. Other disciplines, such as plastic and reconstructive surgeons, speech therapists, occupational/physiotherapists may be included as and when need rises. Various classifcation systems use a combination of these factors to categorize patients into risk factor and prognostic groups. However, due to the heterogeneous nature of breast cancer, individual patients in the same risk category may have diferent clinical outcomes.

Moreover generic antibiotics for acne chloramphenicol 250 mg line, transmission may take place in one anogenital site antibiotic resistance lab high school discount chloramphenicol express, such as the introitus antibiotic resistance and evolution purchase chloramphenicol 250 mg visa, and the infection may be spread by self-inoculation to another site (Winer et al zosyn antimicrobial spectrum cost of chloramphenicol. The possible non-sexual routes include vertical transmission bacteria on skin purchase 500 mg chloramphenicol with amex, fomites and skin contact (Mindel & Tideman antibiotics sun order chloramphenicol online now, 1999; Frega et al. Results from studies of transmission in infants are not consistent, and do not provide a clear indication of the rate of infection among neonates who are exposed perinatally. Differences in samples and techniques may be the reasons for the variability and inconsistency in these results. Age of the mother, birth order of the infant and mode of delivery are considered to be important determinants of transmission. Most infants who develop juvenile-onset recurrent respiratory papillomatosis are the first-born single or twin infant of women who tend to be younger than other mothers who gave birth at the same institutions (Kashima et al. Even if anogenital infections with high viral load are rare in babies, exposure at birth could influence immune response later in life at the time of sexual exposure (Mant et al. Because the basic tenet of analytical epidemiology is the observation of individual subjects, several methodological challenges need to be overcome in studies of couples or of infection that begins with an index subject and is eventually transmitted to partners and spread from that point. However, further studies of multiple infections could be important to guide strategies on vaccines. In some populations, age-specific prevalences decline sharply and reach very low levels at older ages, which is consistent with viral transience as well as lower incidence at older ages (see Figure 9). In general, the prevalence is highest in Africa and South America, lowest in Europe and intermediate in Asia. Studies that focus on older women and their male partners are also needed, particularly cohort studies with repeated measurements that assess male and female sexual practices and immunity. Confirmation of this hypothesis, however, would require that preserved specimens of representative samples from different eras be tested at the same time with the same sensitive testing technology, a proposition that could not be easily implemented. Age Method of detection Prevalence (%) Prevalence of specific high-risk types (%) Prevalence of specific low-risk types (%) study area at range risk (years) Overall High Low 16 18 31 33 35 39 45 51 52 56 58 59 66 6 11 34 40 42 43 53 54 73 risk risk Kjaer et al. However, this question cannot easily be answered by the measurement technologies currently available to epidemiologists. This approach is complemented by a study of longer-term infection with a median follow-up of 5. The sparse data are conflicting as to whether the presence or the absence of any one type alters the duration of any other type-specific infection (analogous to whether types influence the acquisition of each other as mentioned above) (Thomas et al. The fraction depends on the thresholds of the molecular and microscopic tests and clinical specimens examined, and can range widely from 5 to 30% (Schiffman & Kjaer, 2003). Microscopic diagnoses are prone to subjectivity and lack of interobserver reproducibility, particularly when mild or equivocal changes are involved. However, other aspects of infection may contribute to the likelihood that an infection will progress, such as type, load and concurrent abnormalities. The critical step for most women might be whether a precancerous lesion develops as an uncommon outcome of infection (Figure 8). Within this group, viral characteristics, host factors and behavioural co-factors that increase the risk of progression or decrease the probability of viral clearance need to be determined. More rapid progression does occur and should be studied, but it may not be possible to study the full extent of the latency process prospectively. In particular, detection methods that use cytology cannot provide reliable estimates of rates of lesions and those that use histology may have altered the course of the natural history of the disease because frequent cervical biopsies may remove the entire lesion. Overall, these problems tend to affect the comparability of results across studies. A substantial proportion of lesions were biopsied, including cone biopsies, and were classified as persistent without further qualification as to the duration of the sojourn time within each grade, i. Progression rates to invasive cancer for studies that followed up only patients with carcinoma in situ by biopsy ranged from 29 to 36%. In a meta-analysis of studies published since 1970 that included more than 27 000 patients who were followed without treatment, Melnikow et al. Cumulative progression rates to invasive cancer at 24 months by cytological abnormality were 0. In future cohort studies that multiply the number of measurements taken over time, the importance of optimized methods will be even greater if observation and interpretation of the patterns of viral clearance, persistence, possible recurrence and progression are to be anticipated. The first is the cross-reactivity and relatively low sensitivity in terms of types and the second is the fact that infections in other mucosal sites of the body. Prevalence in neonates and primary school children (anal smear or foreskin) showed very low percentages (< 1%). Their significance was not appreciated at the time, but these changes were later called carcinoma in situ and described precursors of cervical cancer. Dysplasias were further divided into mild, moderate and severe, depending on their degree of differentiation. From this terminology, it was implicit that the higher the grade, the closer the lesion was in aggregate to invasion. However, it was emphasized that the diagnostic decision should be taken at an operational level as well as at a morphological level so that the clinician could infer accurately from the diagnosis whether the pathologist believed that the lesion being diagnosed was a true precursor of cancer or not. This simple but important observation led to the concept that cancers were preceded by a precursor state that could be recognized histologically. However, it was not until Papanicolaou and Traut (1943) published their observations on exfoliated cells that it was discovered that these early histological and colposcopical observations could be used as part of mass screening programmes and be translated into schemes for cancer prevention. Similar observations were made by Kottmeier (1961) who followed 31 women with carcinoma in situ prospectively for at least 12 years; 72% of these women developed invasive cancer. There is therefore a discrepancy between the cumulative incidence of carcinoma in situ observed in the natural history studies conducted in British Columbia (Canada), the Netherlands and Denmark, which suggested that a high proportion of carcinomas in situ do regress without treatment, and the cumulative incidence of invasive cancer seen in earlier observational studies (Smith & Pemberton, 1934; Kottmeier, 1961; McIndoe et al. The natural history of cervical precursor lesions of a lower histological grade than carcinoma in situ has been studied by Ho et al. It should be emphasized that perinuclear halos may be produced as a result of other cervical or vaginal infections or may accompany repair or metaplastic processes. The result of this interference with the mitotic process is the formation of biand multinucleated cells and enlarged atypical nuclei, accompanied by heteroploidization. In contrast to low-grade lesions, expression of the viral oncogenes E6 and E7 in high-grade lesions also occurs in the dividing, immature, metaplastic basal stem cells. Other abnormal mitotic figures that are commonly seen include the two-group metaphase, multipolar mitoses in excess of three, lagging metaphase chromosomes, coarsely clumped chromosomes and highly abnormal, bizarre mitotic figures. Areas of microinvasion infiltrate in an irregular fashion and split collagen bundles. Microinvasive foci are commonly accompanied by an inflammatory and desmoplastic response. Moreover, because of the incomplete overview of the endocervical canal and the poorer prognosis of adenocarcinoma of the cervix compared with squamous-cell carcinoma, clinicians always remove intraepithelial lesions of the glandular cells and data on the natural history of these lesions are therefore lacking (Boon et al. The progression to vaginal cancer appears to be slow and the tumours have the morphology of a squamous-cell carcinoma. It has cytological and histological features and organizational alterations similar to those seen in the cervical and vaginal mucous membranes, except for the presence of substantial acanthosis and papillomatosis. The basaloid type is composed generally of small, fairly uniform cells that are hyperchromatic and contain alterations in the distribution pattern of nuclear chromatin. These cell types tend to have low mitotic activity, and abnormal mitotic figures are seldom encountered. It is commonly associated with koilocytosis, and adjacent condylomatous-type changes are frequently seen. The anus has a squamo-columnar junction and a transformation zone similar to that seen in the cervix. Receptive anal intercourse, especially starting at a younger age, is an important risk factor (Frisch et al. Most penile cancers are basaloid, warty, verrucous or keratinizing squamous-cell cancers. Virus-specific cytopathogenic effects are most prominent in the granular layer of the epithelium, where mature virus particles appear and spread throughout the nuclei or in paracrystalline arrays. This specific cytopathic effect is linked to high levels of viral replication in differentiating keratinocytes. Cutaneous warts develop in up to 90% of transplant recipients who survive the onset of immunosuppression by more than 5 years (Leigh et al. The carcinomas are locally destructive but their invasive and metastatic potential is very low (Majewski et al. Such patients have an up to 100-fold increased risk for squamous-cell carcinoma and a 10-fold increased risk for basal-cell carcinoma. Squamous-cell carcinomas appear to arise from these verrucous lesions, which contain multinucleated cells and large numbers of atypical mitoses, koilocytes and parakeratotic peaks (Price et al. In women, the vulva, vestibule, vagina, perineum and perianal region are the most common sites for condylomata acuminata. In a series of 108 male patients, condylomata were located on the penile shaft in 51%, on the shaft and perianal region in 14%, on the shaft and scrotum in 2%, on the shaft and urethral meatus in 15% and on the urethral meatus alone in 18% (Rosemberg, 1991). Progression from anal condyloma to invasive anal cancer, particularly in immunosuppressed patients, has also been reported (Byars et al. This includes the limen vestibuli (junction of the nasal vestibule and the nasal cavity proper), nasopharyngeal surface of the soft palate, mid-zone of the laryngeal surface of the epiglottis, upper and lower margins of the ventricle, undersurface of the vocal folds and the carina and bronchial spurs (Mounts & Kashima, 1984; Kashima et al. The first peak occurs at less than 5 years of age and the second between the ages of 20 and 30 years (Kashima & Shah, 1982; Gissmann et al. Boys and girls appear to be nearly equally affected by juvenile-onset recurrent respiratory papillomatosis in contrast with adult-onset recurrent respiratory papillomatosis, which preferentially affects men over women at a ratio of approximately 3:2 (Kashima et al. This difference reflects the different mode of acquisition: by vertical transmission for the juvenile form and by sexual contact for the adult form. However, only one in 400 infants delivered to these women is estimated to be at risk for subsequent recurrent respiratory papillomatosis (Bauman & Smith, 1996). Recently, it was suggested that these viruses are commensal in healthy individuals (Antonsson et al. This can be accomplished by medical or surgical methods, none of which is capable of removing the virus. Since this is the causative agent of the disease, the possibility of transmission and recurrence is not eliminated. This compound is absorbed in the systemic circulation and should not be used in pregnancy. This is a destructive method that does not permit pathological assessment of involved tissue. The depth of excision may be difficult to control for vulvar and vaginal excision. It uses a radiofrequency alternating current passed along a thin wire loop to excise lesions with minimal thermal artefact. It is designed for self-application as primary or adjuvant therapy of genital warts and is not recommended for mucosal surfaces, such as the vagina. Mild to moderate local inflammation is the most common side-effect, but the drug is well tolerated; no systemic side-effects have been reported. Systemic adverse effects, such as flu-like symptoms and leukopenia, are substantial, even with intralesional use. In spite of this potency, the use of these products is no longer recommended because they engender a large variety of adverse effects and recurrence rates of up to 65% (Wiley et al. In addition, podophyllin and its derivatives are teratogens and should not be used in pregnant patients (von Krogh & Longstaff, 2001). Salicylic acid, in the form of a solution, a gel or a disc soaked with solution, is commonly used for the treatment of non-genital warts in adults and children with clearance rates of up to 75% (Rivera & Tyring, 2004). Other keratolytic compounds, such as glycolic acid, pyruvic acid, formic acid and glutaraldehyde, have also been used, particularly for the treatment of viral warts in children (reviewed by Torrelo, 2002). In a more recent study, the clinical cure rate of an 85% solution of trichloroacetic acid in pregnant patients with cervical condylomata was 83% (Menendez Velazquez et al. However, trichloroacetic acid must be applied with extreme care in order to prevent acid burn to the surrounding skin (Fox & Tung, 2005). Immunomodulating agents In contrast to surgical and cytodestructive therapies of cutaneous and genital warts, the goal of recently developed treatments with antiviral and immunomodulating agents is not simply to remove the lesion, but also to reduce the amount of latent and subclinical viral infection sufficiently in order to diminish the rate of recurrence. In addition, large lesions may be treated and the depth of cryonecrosis is more suitably adapted (Scala et al. Healing occurs by granulation and the post-operative period is relatively painless for the patient. Photodynamic therapy Photodynamic therapy with topical application of amino-laevulinic acid followed by irradiation with light of different wavelengths has been used for some time for the treatment of superficial premalignant and malignant skin tumours (reviewed in Roberts & Cairnduff, 1995). This therapy was later shown to be effective against recalcitrant warts (Stender et al.

Her children played with their Scottish terrier in the next room bacteria resistant to antibiotics buy cheap chloramphenicol 250mg, blissfully oblivious of the landmark date that had just passed for their mother antibiotics for dogs with staph buy cheap chloramphenicol 250 mg online. It provoked an inevitable question: how many such mutations does a real cancer possess in totalfi Once completed bacteria on scalp chloramphenicol 250 mg otc, this effort antimicrobial use discount chloramphenicol 250mg with visa, called the Cancer Genome Atlas antibiotic minocycline discount chloramphenicol 500 mg with mastercard, will dwarf the Human Genome Project in its scope infection xp king best buy chloramphenicol. The initial list of cancers to be sequenced includes brain, lung, pancreatic, and ovarian cancer. Perhaps no one has studied the emerging cancer genome as meticulously or as devotionally as Bert Vogelstein. Every time a gene mutation was encountered in a cancer, the mutated gene was demarcated as a dot on the sheet. In individual specimens of breast and colon cancer, between fifty to eighty genes are mutated; in pancreatic cancers, about fifty to sixty. If one compares two breast cancer specimens, the set of mutated genes is far from identical. But while functionally different, these two forms of mutations cannot easily be distinguished. Driver mutations, on the other hand, strike key oncogenes and tumor suppressors, and only a limited number of such genes exist in the genome. But the same core pathways were characteristically dysregulated in any tumor type, even if the specific genes responsible for each broken pathway differed from one tumor to the next. Cancers that look vastly unlike each other superficially often have the same or similar pathways unhinged. The cancer pessimist looks at the ominous number thirteen and finds himself disheartened. Perhaps not all thirteen need to be targeted to attack complex cancers such as breast or pancreatic cancer. The complete maps of mutations in many tumor types (with their hills, valleys, and mountains) will soon be complete, and the core pathways that are mutated fully defined. Once the mutations have been identified, the mutant genes will need to be assigned functions in cellular physiology. And just as Virchow made the crucial leap from Vesalian anatomy to the physiology of cancer in the nineteenth century, science must make a leap from the molecular anatomy to the molecular physiology of cancer. This seminal transition from descriptive biology to the functional biology of cancer will provoke three new directions for cancer medicine. Once the crucial driver mutations in any given cancer have been identified, we will need to launch a hunt for targeted therapies against these genes. The challenge now is to determine which combinations of such drugs might inhibit cancer growth without killing normal cells. We already know most, if not all, of the major pathways through which cancer-inducing signals move through cells. A few, such as Herceptin and Tarceva, have Food and Drug Administration approval and are in widespread use. Such vast, unwieldy, and methodologically challenging studies are difficult to fund and launch. As Evarts Graham discovered to his dismay, even tobacco smoke, the most common human carcinogen, does not easily induce lung cancer in mice. In 2000, the so-called Million Women Study in the United Kingdom identified estrogen and progesterone, prescribed in hormone-replacement therapy to women to ease menopausal symptoms, as major risk factors for the incidence and fatality from estrogen-positive breast cancer. This theory has spawned intense controversy, activism, and public campaigns over the decades. But although the hypothesis is credible, large-scale human-cohort experiments directly implicating particular pesticides as carcinogens have emerged slowly, and animal studies have been inconclusive. The identification of key activated pathways in cancer cells might provide a more sensitive detection method to discover carcinogens in animal studies. A chemical may not cause overt cancer in animal studies, but may be shown to activate cancer-linked genes and pathways, thus shifting the burden of proof of its potential carcinogenicity. In 2005, the Harvard epidemiologist David Hunter argued that the integration of traditional epidemiology, molecular biology, and cancer genetics will generate a resurgent form of epidemiology that is vastly more empowered in its ability to prevent cancer. Most normal cells, even rapidly growing normal cells, will proliferate over several generations and then exhaust their capacity to keep dividing. The entirety of human blood, for instance, can arise from a single, highly potent blood-forming stem cell (called a hematopoietic stem cell), which typically lives buried inside the bone marrow. In the mid-1990s, John Dick, a Canadian biologist working in Toronto, postulated that a small population of cells in human leukemias also possess this infinite self-renewing behavior. When chemotherapy kills the bulk of cancer cells, a small remnant population of these stem cells, thought to be intrinsically more resistant to death, regenerate and renew the cancer, thus precipitating the common relapses of cancer after chemotherapy. The image belongs very much to Farber and his era, but its essence still haunts us today. Is it possible to eradicate this disease from our bodies and our societies foreverfi The answers to these questions are embedded in the biology of this incredible disease. Oncogenes arise from mutations in essential genes that regulate the growth of cells. Science embodies the human desire to understand nature; technology couples that desire with the ambition to control nature. Medicine, then, is fundamentally a technological art; at its core lies a desire to improve human lives by intervening on life itself. Conceptually, the battle against cancer pushes the idea of technology to its far edge, for the object being intervened upon is our genome. Perhaps cancer, the scrappy, fecund, invasive, adaptable twin to our own scrappy, fecund, invasive, adaptable cells and genes, is impossible to disconnect from our bodies. But if cancer deaths can be prevented before old age, if the terrifying game of treatment, resistance, recurrence, and more treatment can be stretched out longer and longer, then it will transform the way we imagine this ancient illness. Given what we know about cancer, even this would represent a technological victory unlike any other in our history. In the early twentieth century, radiation oncologists try to obliterate the tumor locally using X-rays. By the 1950s, yet another generation of surgeons learns to combine the two strategies, although tempered by moderation. In addition to surgery, radiation, adjuvant chemotherapy, and tamoxifen, she is treated with targeted therapy using Herceptin. But surgery, chemotherapy, radiation, hormonal therapy, and targeted therapy have likely added anywhere between seventeen and thirty years to her survival. Diagnosed at forty, say, Atossa can reasonably be expected to celebrate her sixtieth birthday. She enters an intensive screening program to detect the appearance of a tumor in her unaffected breast. Having excised her breasts preemptively, she will live out her life free of breast cancer. Old observations crystallize into new theories; time past is always contained in time future. The tools that we will use to battle cancer in the future will doubtless alter so dramatically in fifty years that the geography of cancer prevention and therapy might be unrecognizable. Future physicians may laugh at our mixing of primitive cocktails of poisons to kill the most elemental and magisterial disease known to our species. Cancer is indeed the load built into our genome, the leaden counterweight to our aspirations for immortality. But if one looks back even further behind the Greek to the ancestral Indo-European language, the etymology of the word onkos changes. It means to carry, to move the burden from one place to the next, to bear something across a long distance and bring it to a new place. Under the microscope, the biopsy had revealed sheets of spindlelike cells dividing rapidly. Her scans showed spots in her liver, swellings in her lymph nodes, and a spray of masses peppering the left lung. A surgical cure was impossible, and in 2000, no chemotherapy was known to be effective against her kind of sarcoma. The site, like most of its bloggers, was a strange and moribund affair, with desperate folks seeking desperate remedies. But in late April, news of a novel drug began to spread like wildfire through this community. But serendipitously, the chemical inactivates another tyrosine kinase, called c-kit. Eventually her pain made it impossible for her to walk even from her bed to the door and she had to be hospitalized. My meeting with Germaine that evening was not to discuss drugs and therapies, but to try to make an honest reconciliation between her and her medical condition. The six years of survival that she had eked out between 1999 and 2005 had not been static, frozen years; they had sharpened, clarified, and cleansed her. Her daughter, a teenager in 1999 and now a preternaturally mature sophomore at a Boston college, had grown into her ally, her confidante, her sometime nurse, and her closest friend.

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