417 Polymyalgia rheumatica Polymyalgia rheumatica (PMR) is common in those >70 yrs who have sym metrical aching and morning stiffness in shoulders and proximal limb muscles for >1 month mild polyarthritis, tenosynovitis (e.g., carpal tunnel syndrome [p. 386]; occurs in 10%), depression, fatigue, fever, weight \206\223 , and anorexia. It may come on suddenly or ov er the course of weeks. It overlaps with GCA. : 2:1 Tests ESR usually >40 mm/h; CK usually ; alk phos \206\221 ; mild anemia Differential diagnosis Recent onset RA; hypo thyroid- ism, primary muscle disease, occult malignancy or infection, neck lesions, bilater al subacromial impingement lesions, spinal stenosis. Treatment Prednisone 15 \200\22320 mg/ 24 h PO; decrease dose slowly after symptoms have been controlled at least 1 month (in ligh t of symptoms and ESR). Most need steroids for \200\234 2 yrs. Preventing osteoporosis is essential (p. 305). Giant cell (temporal) arteritis GCA has PMR symptoms in up to 25% of people. Common in the elderly, it is rare under 55 yrs. Symptoms Headache, scalp and temporal artery tenderness ( e.g., on combing hair), jaw claudication, amaurosis fugax, or sudden blindness in one eye. Tests ESR \206\221 , CRP \206\221 , platelets \206\221 , alk phos \206\221 , anemia. If you suspect GCA, do an ESR, start prednisone 1 mg/kg/24 h PO immediately . Some advocate h igher doses IV (up to 1,000 mg) if visual symp- toms (ask an ophthalmologist). Osteoporosis prophylaxis is essential. Get temporal artery biopsy (several cm in length because skip le sions occur) in the next few days. NB : The immediate risk is blindness, but longer term, t he main cause of death and morbidity in GCA is steroid treatment! Reduce prednisone after 5 \200\2237 d in light of symptoms and ESR; increase dose if symp- toms recur. Typical cours e : 1 \200\2232 yrs, although it can reoccur. 418 This page intentionally left blank Oncology Daniel Laheru , M.D. y g o o c n l Contents Introduction 420 Looking after people with cancer 421 Epidemiology 422 Oncology and genetics 423 Screening: Colorectal and breast cancer 425 Scre ening: Lung, pancreatic, and prostate cancer 427 Oncological emergencies 429 Symptom contro l in severe cancer 431 Cancer therapy 433 Radiotherapy 435 O 2 1 Introduction Since Richard Nixon signed the National Cancer Act on December 23, 1971 to foc us and prioritize federal resources to advance cancer clinical and basic science research, there have been a number of notable achieve- ments in cancer treatment, particularly in sol id tumors such as germ cell tumors and hematologic malignancies including Hodgkin \200\231s lymphoma, acute lymphoblastic leukemia, acute myelogenous leukemia, and chronic myelog- en ous leukemia. The sequencing and analysis of the human genome in 2001, followed by the sequ encing of a number of cancers including colorectal cancer, breast cancer, brain tumors, pan creas and neuroendocrine cancers, and head and neck cancers provided researchers with the c ritical tools to begin to identify and differentiate cancer from normal tissue at the genet ic level. Although the implications of these landmark projects are still being realized, it is evident that the identification of critical genes and proteins involved in cell divisio n and growth and metastasis are just the beginning. The full compre- hension of how these g enes control nonlinear cellular signaling matrices has become the new discovery and treatme nt paradigm in oncology. The potential has raised expectations for unprecedented progress i n the near future. However, even as better treatments are being developed, the best treatme nt remains earlier diagnosis and improved screening methods for those at risk. This review will provide only a general overview of the epide- miology, genetics, screening, and treatm ent of some select cancers. 420 Looking after people with cancer y g o o c n O l Table 12.1 Looking after people with cancer No rules guarantee success, but there is no doubt that getting to know your patient, making an agreed management plan, and seeking out the right expert for each stage of treatment (w ith emphasis now in multi- discipline care) all need to be central activities in oncology. These issues focus around communication with patients and families but also with a team of disease-specific experts across disciplines including surgery, medical and radiation oncolo gy, pathology, radiology, interventional dis- ciplines, social work, nutrition, palliative care, and pain services. Psychological support Examples include: \212 Allowing the patient to express anger, fear \200\224or any negative feeling (anger can anes thetize pain). Counseling (e.g., with a breast cancer nurse for mastectomy preparation) Cog nitive and behavioral therapy reduces psychological morbidity associated with cancer treatm ents. Group therapy reduces pain, mood disturbance, and the frequency of maladaptive coping strategies. Meta-analyzes have suggested that psychological support can have some effect o n improving outcome measures such as survival. \212 \212 \212 \212 Advice on breaking bad news 1 Choose a quiet place where you will not be disturbed. 2 Find out what the patient already knows or surmises (often a great deal). 3 Find out how much the person wants to know. You can be surprisingly direct about this. \200\234Are you the sort of person who, if anything were amiss, would want to know all the details? \200\235 4 Give some warning (e.g., \200\234there is some bad news for us to address \200\235). 5 S hare information about diagnosis, treatments, and prognosis. Specifically list supporting p eople (e.g., nurses) and facilities (e.g., hos- pices). Try asking \200\234Is there anythi ng else you want me to explain? \200\235 Don \200\231t hesitate to go over the same ground repeatedly. Allow denial: Don \200\231t force the conversation. 6 Listen to any concerns raised; encourage the airing of feelings. 7 Summarize and make a p lan. Offer availability. 8 Follow through. The most important thing is to leave the patient with 421 the strong impression that you are with him or her. Don \200\231t imagine that a single blueprint will do for everyone. Be prepared to use what ever the patient gives you. This requires close observation of verbal and nonverbal cues. B ecause humans are very complex, we all frequently fail. Don \200\231t be put off: Keep tryi ng. Epidemiology The incidences of selected most-common cancers for men and women worldwide are identified in Table 12.2. These numbers do not include car- cinoma in situ of any site exc ept urinary bladder, nor do they include basal and squamous cell cancers of the skin. The i ncidence reflects an overall increase when compared to recent years. This is thought to be secondary to the continuing growth and aging of the worldwide population, as well as to ext ernal environmental factors such as smoking. The expected worldwide deaths are identified i n Table 12.3. Breast cancer remains the most common cause of cancer (23% of total cancer ca ses) and cancer death (14% of total cancer deaths) in women worldwide. In developing countr ies, breast cancer is now also the leading cause of cancer death, surpassing cervical cance r over the past decade. Lung cancer remains the most common cause of cancer (17% of total c ancer cases) and cancer death (23% of total cancer deaths worldwide) in men worldwide. Mortality rates have slightly increased across all four major cancer sites in men and in wo men, except for female lung cancer, in which rates have been stable. The incidence trends a re mixed, reflective of the recent initiatives in public policy or awareness and screening. Many cancers, including pancreas, breast, and prostate cancers, have continued to demonstr ate slight increases every year. Lung cancer incidence rates are declining in men and level ed off for the first time in women after increasing for many decades. Colorectal cancer inc idence rates are slightly increasing/stable in Western countries. The incremental decrease in incidence rates of prostate cancer and female breast cancer in at least Western countrie s may be attributable to increased screening through prostate-specific antigen (PSA) testin g (for prostate cancer) and mammography (for breast cancer),although currently there is sig nificant controversy regarding the utility of early prostate cancer screening using PSA. Co nversely, the slight increase in colorectal cancer incidence may represent the fact that sc reening tests such as colonoscopy are still completed in the minority of eligible individua ls. The increase in female breast cancer incidence may also reflect increased use of hormon e replacement therapy and/or increased prevalence of obesity. An additional cancer that has noted a slight increase for unclear reasons is hepatocellular cancer. Table 12.2 New worldwide cancer incidence of selected cancers for 2011. 422 Male 1. Lung and bronchus (1,095,200) 2. Prostate (903,500) 3. Colon and rectum (663,600) 4 . Stomach (640,600) 5. Liver (522,400) 6. Esophagus (326,600) 7. Bladder (297,300) 8. Non-H odgkin \200\231s lymphoma (199,600) 8. Ovary (225,500) 9. Leukemia (195,900) 10. Oral cavit y (170,900) Female 1. Breast (1,383,500) 2. Colon and rectum (570,100) 3. Cervix and uteri (529,800) 4. Lung and bronchus (513,600) 5. Stomach (349,000) 6. Corpus uteri (287,100) 7. Liver (225,9 00) 9. Thyroid (163,000) 10. Non-Hodgkin \200\231s lymphoma (156,300) Data modified from Jemal A. Global cancer statistics. CA Cancer J Clin. 2011;Mar-Apr: 61(2) :69 \200\22390. y g o o c n O Table 12.3 Estimated worldwide deaths of selected cancers for 2011. l Male 1. Lung and bronchus (951,000) Female 1. Breast (458,400) 2. Liver (478,300) 3. Stomach (464,400) 4. Colon and rectum (320,600) 5. Esophagus (276,100 ) 6. Prostate (258,400) 7. Leukemia (143,700) 8. Pancreas (138,100) 9. Urinary bladder (112 ,300) 10. Non-Hodgkin \200\231s lymphoma 2. Lung and bronchus (427,400) 3. Colon and rectum (288,100) 4. Cervix uteri (275,100) 5. S tomach (273,600) 6. Liver (217,600) 7. Ovary (140,200) 8. Esophagus (130,700) 9. Pancreas ( 127,900) 10. Leukemia (113,800) (109,500) Data modified from Jemal A. Global cancer statistics. CA Cancer J Clin. 2011;Mar-Apr: 61(2) :69 \200\22390. Oncology and genetics The majority of cancers are believed to be sporadic. However, a numbe r of gene mutations that predispose to cancer have been identified. Much progress has been made at understanding a number of cancers at the genetic level, although it is beyond the s cope of this chapter to provide a comprehensive review of this. However, some of the geneti c underpinnings for some of the most common and notable cancers have recently been describe d (see Table 12.4). Familial colorectal cancer 20% of those with colorectal cancer (CRC) have a family history of the disease. There have been a number of hereditary syndromes identified from this grou p, including familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal ca ncer (HNPCC). The genes responsible for these syndromes have also been identified and chara cterized. FAP accounts for <1% of hereditary CRC but is the best characterized cancer genet ic syndrome. The identified genetic mutation has been mapped to chromosome 5 and is known t o be autosomal dominant. FAP is characterized by innumerable colonic adenomas at an early a ge, with the development of overt cancer in 100% of patients by age 40 \200\22350. Patients who have a mutation in the locus for FAP [adenomatous polyposis coli (APC) gene] or who ha ve one or more first- degree relatives with FAP or an identified APC mutation are at consid erable risk and require yearly colonoscopies at an early age. As the incidence of developin g CRC is essentially 100% in patients with FAP and because of the elevated risk of developi ng metachronous (i.e., with lesions occurring at different times) CRC, these patients are o ften recommended one of three prophylactic surgeries: (1) total proctocolectomy with ileost omy, (2) total proctocolectomy with ileal pouch-anal anastomosis (IPAA), or (3) colectomy w ith ileorectal anastomosis (IRA). Of the hereditary syndromes, HNPCC (Lynch syndrome I and II) is the most common, accounting for 2 \200\2237% of the total. Patients with HNPCC typi cally develop CRC later than patients with FAP, with age of onset during the fourth and fif th decades. The genetic alterations are more heterogeneous 423 than for FAP, with the majority of individuals linked to chromosomes 2, 3, and 7. The molec ular fingerprint of HNPCC is the microsatellite instabil- ity (MSI) phenotype, which is a g ermline mutation caused by a number of genes, particularly MLH1 and MSH2. MSH2/MLH1 gene te sting is the gold standard, but, for a variety of reasons including cost, this testing is p er- formed in only selected cases. The diagnosis of HNPCC is complex as it is based initial ly on both clinical evaluation and a careful assessment of family history, followed by MSI and MSH2/MLH1 testing only if strict clinical crite- ria have been met. Despite a complex d iagnosis algorithm, such screening is thought to underestimate the true incidence of HNPCC. Familial breast cancer In breast cancer, numerous studies have shown that the risk of devel oping breast cancer increases if a first-degree relative is diagnosed with breast cancer. F or example, if a mother or sister has been diagnosed with bilateral breast cancer and the a ge at diagnosis was premenopause, the absolute risk to other first-degree relatives approac hes 50%. If the diagnosis in the affected relative was postmenopause, the risk is reduced t o 10%. 5% of women with breast cancer report a family history. BRCA1 (mapped to chromosom e 17) and BRCA2 (mapped to chromosome 13) mutations account for most cases of breast cancer . Of note, BRCA2 mutations predispose carriers to a number of cancers including pancreas an d colorectal, prostate, gastric, oral cavity, hepatobiliary, and ovarian cancers, as well a s melanoma. The risk of developing male breast cancer is higher in individuals with BRCA2 m utations, whereas the risk of developing ovarian cancer is higher in individuals with BRAC1 mutations. Most of the identified mutations within each of these genes are associated with loss of function, suggesting that BRCA1 and BRCA2 are tumor suppressor genes. Familial prostate cancer 5% of those with prostate cancer have a family history: The genet ic basis is multifactorial. There is a modestly elevated lifetime risk of prostate cancer f or male carriers of BRCA1 and BRCA2 mutations, although the molecular basis of this remains to be elucidated. Mutations in BRCA1/BRCA2 or in the genes on chromosomes 1 and X do not a ccount for all family clusters of prostate cancer, so it is clear that other genes must be involved. In one twin study, 42% of the risk was found to be genetic. Genetic tests can also tell if chemotherapy is likely to work: Chemotherapy fails in 17% of colon cancer patients (i.e., those with certain mutations). 1 424 1 Shown by the microsatellite instability status being \200\234high-frequency. \200\235 Mi crosatellites are stretches of DNA in which a short section is repeated several times. 5-FU chemotherapy only improves survival in microsatellite-stable or low-frequency microsatelli te unstable tumors. Gallinger S. N Engl J Med . 2003; 249: 209. y g o o c n O Table 12.4 Examples of cancers with a familial predisposition l Cancer/syndrome Breast and ovarian cancers Gene BRCA1 Chromosome 17q (p. 423) BRCA2 MSH2 MLH1 PMS2 APC 13q 2p 3p 7p 5q HNPCC (p. 423) Familial polyposis (colorectum) von Hippel \200\223Lindau (kidney, VHL 3p CNS) Carney complex Multiple endocrine neoplasia type I (pituitary, pancreas, thyroid) PRKAR1A 17q 11q MEN1 (p. 304) Multiple endocrine neoplasia RET 10q (p. 304) type 2 Basal cell nevus syndrome PTCH 9q (CNS, skin) Retinoblastoma (eye, bone) Rb Li \200\223Fraumeni syndrome 13q 17p TP53 (multiple) Neurofibromatosis type I NF1 17q (CNS; rare) Neurofibromatosis type 2 NF2 22 (common) (meningiomas, auditory neuromas) Familial melanoma INK4A 9p Screening: Colorectal and breast cancer It is intuitive that the earlier any cancer is iden tified, the higher the likelihood of a curative treatment. The development of a screening t est for cervical cancer (the Pap smear) has been the paradigm for an effective screening te st. This has proven to be true in a number of cancers but has also proven to be surprisingl y elusive or controversial in others. It is again beyond the scope of this general review t o comprehensively identify screening guide- lines for all cancers. Rather, a few of the mos t common or deadliest cancers will be highlighted. The results are summarized in Table 12.5 . 425 Table 12.5 Screening tests and recommendations for screening Recommendations Starting at age 50 if no risk fac- tors, repeat every 10 yrs Cancer CRC Screening test Colonoscopy Breast cancer Lung cancer Pancreas cancer Mammography CT scan EUS Starting at age 40, repeat yearly No recommendations No recommendations, EUS inves- tigatio nal for high risk families Prostate cancer PSA No recommendations Screening for colorectal cancer Data from a number of randomized and non-randomized studies would currently support options including fecal occult blood testing (FOBT) in combination with sigmoidoscopy or colonoscopy alone. The test of choice remains controversial. A recen tly published study from the Veteran \200\231s Administration medical system performed colo noscopy on 2,885 patients at 13 different Veterans Affairs Medical Centers to determine whe ther or not the patients had inva- sive cancer, large colon polyps, or colon polyps that ha d visible or micro- scopic signs suggesting they were precancerous. These findings were cal led \200\234advanced neoplasia \200\235 if they were found on the colonoscopic examina- ti on. The participants also underwent FOBT before the colonoscopy. The researchers then perfo rmed colonoscopy and made careful observations of their findings in the sigmoid colon and r ectum (the regions of the colon that would usually be seen through the sigmoidoscope; exami nation of the rectum and sigmoid colon during the colonoscopy was defined as a sur- rogate for a sigmoidoscopy), and their findings throughout the remainder of the colon (which would usually be seen only with the colonoscope). The researchers then determined what percentag e of cases detected by colonoscopy were also detected by the FOBT tests and were seen in th e area usually examined with the sigmoidoscope, the two less extensive screening techniques . Among patients who had advanced neoplasias detected by their colonos- copy, an FOBT detec ted only 24% of the patients with advanced neoplasias; sigmoidoscopy would have detected 70 %; and combined testing would have detected 76%, meaning that about 25% of all the patients with advanced neoplasias detected by colonoscopy would have been missed if a colonos- copy was not performed. Why, then, do most clinical-practice guidelines provide a number of opt ions and not recommend colonoscopy exclusively? The first reason is that the standard of ca re evidence required to support screening with colonoscopy without reservation is not all d erived from randomized trial data. Evidence- based guidelines frequently restrict their hig hest recommendations to tech- nology that has been proved in large-scale, randomized trials to reduce the burden of illness. Fecal occult-blood testing has been studied in this way; colonoscopy has not. The second reason relates to adherence to recom- mendations and patien ts \200\231 preferences. Colonoscopy may be uncomfort- able and requires a preparative bowe l cleansing schedule. However, if the colonoscopy is negative, it need be performed only on ce every 10 yrs, whereas other tests, such as sigmoidoscopy, must be performed more frequen tly. The third reason is risk. An earlier study in this same patient 426 population reported the risk of serious complications, including bleeding and perforation, was 0.3%. The fourth reason is economic. A mathematical model of the costs and consequence s (measured in terms of life expectancy) of 22 screening strat- egies for colorectal cancer has been published incorporating not only the cost of the screening test (e.g., colonoscop y was assumed to cost $1,012) but that of all subsequent events (e.g., the treatment of met astatic cancer). They suggest that if the cost of colonoscopy could be reduced by 23%, the expenditure required to achieve one more year of life with screening colonoscopy would be s ubstantially reduced, and such screening would be made more economically attractive. The fi fth reason why colonoscopy is not recommended or covered is avail- ability. The current sup ply of clinicians trained in colonoscopy may not be adequate to screen everyone who turns 5 0, let alone the large population between 50 and 75 yrs of age who have not been screened. The American Cancer Society (ACS) recommends that people without risk factors, such as a fa mily history of the disease or inflammatory bowel dis- ease, begin screening at age 50. The ACS has three preferred options for screening of people at average risk: \212 \212 \212 y g o o c n O l A colonoscopy every 10 yrs A yearly FOBT combined with flexible sigmoidoscopy every 5 yrs A double contrast barium enema every 5 yrs Screening for breast cancer The current screening guidelines for breast cancer recommend sc reening mammography for women aged 50 \200\22369. Within the United States, the rec- ommend ations include women \211 40. However, there is some recent debate regarding these guidel ines with respect to the recommendation of screening at age 40. A number of randomized clin ical trials have demonstrated that screening mammography reduces the risk of developing bre ast cancer by about 20 \200\22335% in women aged 50 \200\22369 yrs, with slightly less bene fit in women aged 40 \200\22349. Women in their 40s have a lower incidence of developing br east cancer, as well as having denser breast tissue that could lower the sensitivity of the screening mammography. As such, it has been suggested, based on statistical modeling, that to prevent one breast cancer death after 14 \200\22320 yrs, between 500 and 1,800 women wh o are 40 yrs of age would need to undergo regular screening mammography. 427 Screening: Lung, pancreatic, and prostate cancer Screening for lung cancer The earliest scr eening methods for lung cancer included sputum for cytol- ogy and/or chest radiography and were, on the whole, disappointing since these interventions failed to detect a significant reduction in lung cancer mortality. However, improved imaging modalities, such as high reso lution CT have provided new opportunities. Like all screening tests for cancer, the possibl e benefits must be weighed against the potential risk of the test; the harm of false-positi ve tests, given the subsequent additional tests that may be required to follow-up suspiciou s screening evaluations; and the additional costs. For example, lung cancers classically ap pear on CT scans as noncalcified nodules. However, over 80 \200\22390% of noncalcified nodu les identified by CT are benign. A strategy proposed by the Early Lung Cancer Action Projec t was to determine the rate of growth of nodules. For noncalcified nodules that were <1 cm in diameter, high-resolution CT scanning was repea ted at 3 months. Among individuals who were referred for needle biopsy on the basis of lung growth, the positive predictive value was 90%. In addition, the use of PET scanning integr ated with traditional CT imaging has been proposed as a useful complement. A number of com- prehensive studies have since been completed. The National Lung Screening Trial (NLST) ran domized 53,454 persons at high risk for developing lung cancer (age 55 \200\22374, had a ci garette smoking history of at least 30 pack-years, and, if previous smokers, had quit withi n the past 15 yrs)to either three low-dose CT scans at 1-yr intervals or CXR at same interv als. The rate of positive screening was 24% in the CT group versus 6.9% in the CXR group. 9 6% of the positive CT findings and 94% of the positive findings on CXR were false positive. There were 247 deaths from lung cancer per 100,000 person-years in the CT group versus 309 deaths from lung cancer per 100,000 person-years in the CXR group, representing a 20% rela tive risk reduction in death. 2 In contrast, the Prostate, Lung, Colorectal Cancer and Ovar ian (PLCO) screening trial randomized 154,00 patients considered high risk to either annual CXR \227 4 yrs or observation. No improvement in lung cancer mortality was identified. 3 Currently, neither the ACS nor the U.S. Preventive Services Task Force recommend that CT sc anning be performed in asymptomatic but at-risk individuals. Screening for pancreas cancer As has been the story for other cancers, CT scanning has not proven to be sensitive enough in diagnosing early pancreas cancer. Endoscopic ultra- sonogr aphy is currently used in investigational studies for screening and early detection of fami lial pancreatic cancer and its precursors. Endoscopic ultrasonography (EUS) is a standard, diagnostic, predominantly outpatient technique that involves endoscopy plus high-frequency ultrasound imaging of the pancreas (parenchyma and ducts; unlike ERCP, which images the duc ts) and adjacent areas from the upper gastrointestinal tract. Tissue sam- pling can also be readily performed from multiple sites under EUS guidance without accompanying pain or need for local anesthesia (unlike percutane- ous fine-needle aspiration) with a high diagnostic yield for pancreatic lesions and lymph node metastases. When used for screening high-risk individuals, EUS imaging can be followed by biopsy of pancreatic masses, cystic lesions, or evidence of intraductal papillary mucinous neoplasm (IPMN) and col- lection of pancreatic secretions from the duodenum for molecular marker analysis following secretin stimulation. A recent study for individuals con- sidered at high risk for developing pancreas cancer (de fined as a study patient having \211 3 first-degree family members with pancreas cancer) using EUS as a screening modality identified one early invasive pancreas cancer and one pre invasive cancer. 428 Screening for prostate cancer Screening for prostate cancer remains controversial. Although there has been a decline in prostate cancer mortality, this is thought to be a func- tion of improved treatment as opposed to improved early screening. The PLCO screening trial rand omized 76,693 men to either annual screening with PSA for 6 yrs and digital rectal exam for 4 yrs versus no testing. At the most recent follow-up at 7 \200\22310 yrs there was no rep orted difference in 2 Aberle DR, et al. Reduced lung cancer mortality with low-dose computed tomography screeni ng. N Engl J Med . 2011;365(5):395 \200\223409. 3 Oken M, et al. Screening by chest radiogr aphy and lung cancer mortality: The Prostate, Lung, Colorectal, and Ovarian (PLCO) randomiz ed trial. JAMA. 2011;306(17):1865 \200\2231873. mortality. 4 In addition, the European Randomized Study of Screening for Prostate Cancer (E RSPC) randomized 182,000 patients to either PSA at an average of once every 4 yrs versus a control group. Although there was a reduction in prostate cancer mortality, the study deter mined that for every one death from prostate cancer prevented, 1,410 patients would need to be screened and 48 patients would need to be treated. The U.S. Preventive Services Task Fo rce does not recommend routine screening for prostate cancer with digital rectal examinatio n (DRE), serum PSA, or transrectal ultrasound of the prostate. The ACS, the American Colleg e of Physicians, and the American Urological Association recommend that clinicians advise p atients of the risks and benefits of screening to assist them in deciding whether or not to have these tests performed. In general, men \211 50 yrs with a reasonable certainty of a 10-yr life expectancy should be screened annually or biennially. Patients with an elevated risk of disease (e.g., African Americans and those with a family history) should be screen ed beginning at an earlier age (45 yrs). y g o o c n O l Oncological emergencies A patient who becomes acutely ill can often be made more comfortabl e with simple measures, but some problems require specific treatment. Spinal cord compression Requires urgent and efficient treatment to preserve neurological fu nction. A high index of suspicion is essential. Causes: Typically extradural metastases. Others: Extension of tumor from a vertebral body, direct extension of the tumor, or fracture. Signs and symptoms: Back pain with a root distr ibution, weakness and sensory loss (a level may be found), bowel and bladder dysfunction. T ests: Urgent MRI. Management: Dexamethasone 8 \200\22316 mg IV then 4 mg/6 h PO. Discuss wi th neurosurgeon and clinical oncologist immediately. Superior vena cava (SVC) obstruction with airway compromise SVC obstruction is not an emerg ency unless there is tracheal compression with airway compromise: Usually there is time to plan optimal treatment, and this is to be preferred, rather than rushing into therapy that may not be beneficial. Causes: Typically lung cancer; rarely from causes of mediastinal enl argement (e.g., germ cell tumor), lymphadenopathy (lymphoma), thymus malignancy, thrombotic disorders (e.g., Beh et \200\231s or nephrotic syndromes), thrombus around an IV centra l line, hamartoma, ovarian hyperstimulation, fibrotic bands (lung fibrosis after chemothera py). Signs and symptoms: Dyspnea, orthopnea, swollen face and arm, cough, plethora/cyanosis , headache, engorged veins. Pemberton \200\231s test: On lifting the arms over the head for >1 min, there is increased facial plethora/cyanosis, JVP \206\221 (nonpulsatile), and ins piratory stridor. Tests: Sputum cytology, CXR, CT, venography. Management: Get a tissue dia gnosis if possible, but bronchoscopy may be hazardous. Give dexamethasone 4 mg/6 h PO. Cons ider balloon venoplasty and SVC stenting; e.g., prior to radical or palliative chemo- or ra diotherapy (depending on tumor type). 429 Hypercalcemia Affects 10 \200\22320% of patients with cancer and 40% of those with myeloma. Causes: Lytic bone metastases, production of osteoclast activating fac- tor, 1- -hydrox ylase activity of 25 hydroxy vitamin D in lymphomas, or PTH-like hormones by the tumor. Sym ptoms: Lethargy, anorexia, nausea, 4 Andriole G et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:310 \200\223319. polydipsia, polyuria, constipation, dehydration, confusion, weakness. Most obvious with ser um Ca 2+ >12 mg/dL. Management: Rehydrate with 3 \200\2234 L of 0.9% saline IV over 24 h. A void diuretics. Give bisphosphonate IV (consider maintenance therapy, IV or PO). Best treat ment is control of underlying malignancy. In resistant hypercalcemia, consider calcitonin. See Table 12.6. Raised intracranial pressure Due to either a primary CNS tumor or metastatic disease. Signs and symptoms: Headache (often worse in the morning), nausea, vomiting, papilledema, seizur es, focal neurological signs. Tests: Urgent CT is important to diagnose an expanding mass, cystic degeneration, hemorrhage within a tumor, cerebral edema, or hydrocephalus due to tum or or blocked shunt, since the management of these scenarios can be very different. Managem ent: Dexamethasone 4 mg/6 h PO/IV, radiotherapy, and surgery as appropriate depending on ca use. Tumor lysis syndrome Rapid cell death on starting chemotherapy for rapidly proliferating le ukemia, lymphoma, myeloma, and some germ cell tumors can result in a rise in serum urate, K + , and phosphate, precipitating renal failure. Prevention is with good hydration and rasb uricase or allopurinol 24 h before chemotherapy; dose example if renal function is good: 30 0 mg/12 h PO. If creatinine >1.2 mg/dL: 100 mg on alternate days. Inappropriate ADH secretion (p. 669); febrile neutropenic regimen (p. 625) Table 12.6 Treating hypercalcemia with bisphosphonates Ensure adequate hydration (e.g., with 0.9% saline IVI). Zoledronic acid and pamidronate are two options. Disodium pamidronate Calcium (mg/dL; corrected) <12 12 \200\22314 >14 Single-dose pamidronate (mg) 30 60 90 Infuse slowly, e.g., 30 mg in 300 mL 0.9% saline over 3 h via a large vein. Max dose: 90 mg . Response starts at 3 \200\2235 d, peaking at 1 wk. SE: Flu-like symptoms, bone pain, PO 4 3 \200\223 \206\223, bone pain, myalgia, nausea, vomiting, headache, lymphocytopenia, Mg 2+ \206\223 , seizures (rare). Zoledronic acid is significantly more effective in reducin g serum Ca 2+ than previously used bisphosphonates. Usually, a single dose of 4 mg IVI over 2 h will normalize plasma Ca 2+ within a week. A higher dose should be used if corrected C a 2+ is 12 mmol/L. SE: Flu-like symptoms, bone pain, PO 4 3 \200\223 \206\223, confusion, thirst, taste disturbance, nausea, pulse \206\223 , WBC \206\223 , creatinine \206\221 . 430 Symptom control in severe cancer Pain Do not under treat with analgesia: Aim to prevent or eliminate pain. y g o o c n O l Types of pain Don \200\231t assume that the cancer is the cause (abdominal pain, e.g., may be from constipation). Seek the mechanism. Pain caused by nerve infiltration and damage via local pressure may respond to amitriptyline (e.g., 10 \200\22350 mg at night) rather than opioids. Bone pain (e.g., presenting with back pain) may respond to NSAIDs, radiotherapy, o r a nerve block. Identify each symptom and type of pain. Management (1) Pain is affected by mood, morale, and meaning. Explain its origin to both th e patient and relatives, and plan rehabilitation goals. (2) Use oral analgesics if possible \200\224aim to prevent pain with regular prophylactic doses (e.g., q4h); do not wait for p ain to recur. (3) Modify the pathological process where possible (e.g., radiotherapy, hormo nes, chemotherapy, surgery). With analgesia, work up the pain ladder until pain is relieved (see Table 12.7). Monitor response carefully. Laxatives and antiemetics are often needed w ith analgesics. Adjuvant analgesics: NSAIDs, steroids, muscle relax- ants, anxiolytic, anti depressants. Giving oral morphine: Start with aqueous morphine 5 \200\22310 mg/4 h PO. A do uble dose at night can be used to promote 8 h of sleep. Most patients need no more than 30 mg/4 h PO. A few need much more. Aim to change to extended-release morphine (e.g., MS-Conti n tablets q12h) when daily morphine needs are known. In morphine-resistant pain (persisting when 60 mg/4 h is given), consider adjuvant analgesics, methadone, or ketamine (specialist use only). Vomiting: Prevent from before the first dose of chemotherapy, to avoid anticipa tory vomiting before the next dose. Give orally if possible, but if severe vomiting prevent s this, give rectally or subcutaneously. Agents to try: Metoclopramide 10 mg/8 h PO; ondans etron 4 \200\2238 mg/8 \200\22312 h PO/IV; haloperidol 0.5 \200\2232 mg/24 h (max 5 mg). Sh ortness of breath: Consider supplementary O 2 or morphine. Use of relaxation techniques and benzodiazepines can be effective. Assess for pleural or pericardial effusion. If there is significant pleural effusion, consider thoracocentesis pleurodesis. If there is a malign ant pericardial effusion, consider pericardiocentesis (p. 147), pericardiectomy, pleuroperi cardial windows, external beam radiotherapy, percutaneous balloon pericardiotomy, or perica rdial instillation of immunomodulators or sclerosing bleomycin. Venipuncture problems: Repe ated venipuncture with the attendant risk of painful extravasation and phlebitis may be avo ided by insertion of skin tunneled catheter (e.g., a Hickman line) \200\224a single or mult ilumen line \200\224into a major central vein (e.g., subclavian or internal jugular). It is inserted using a strict antiseptic technique. Patients can look after their own lines at h ome and give their own drugs. Problems include infection, blockage (flush with 0.9% saline or dilute heparin, e.g., every week); axillary, subclavian, or superior vena cava thrombosi s/obstruction; and line slippage. Even more convenient portable delivery devices are availa ble, allowing drugs to be given at a preset time without the patient \200\231s intervention . 431 Table 12.7 The analgesic ladder Rung 1 Aspirin; acetaminophen; NSAID Nonopioid Weak opioid Rung 2 Codeine, dihydrocodeine, dextropropoxy- phene, tramadol, oxycodone (some place this on rung 3) Rung 3 Strong opioid Morphine, diamorphine, hydromorphone, fentanyl adjuvant analgesics. If 1 drug fails to relieve pain, move up ladder; do not try other drugs at the same level. In new, severe pain, rung 2 may be omitted. IV delivery of opioids, haloperidol, cyclizine and metoclopramide, and hyoscine, giving 24 h cover. Or suppositories (below) or fentanyl t rans- dermal patches: If not previously exposed to morphine, start with one low-strength pa tch (25 mcg/h). Remove after 72 h, and place a new patch at a different site. 25, 50, 75, a nd 100 mcg/h patches are made. t \211\210 17 h. Suppositories can also be used if unabl e to tolerate oral route. For pain: Try oxycodone 30 mg suppositories (e.g., 30 mg/8 h 3 0 mg morphine). Agitation : Try diazepam 10 mg/8 h suppositories. Other agents and procedur es to know about (alphabetically listed) \212Bisacodyl tablets (5 mg), 1 \200\2232 at night, help opioid-induced constipation. \212Cholestyramine 4 g/6 h PO (1 h after other drugs) helps itch in jaundice. \212Enemas , e.g., arachis oil, may help resistant constipation. \212H 2 -antagonists (e. g., cimetidine 400 mg/12 h PO) help gastric irritation; e.g., associated with gastric carcinoma. \212Haloperidol 0.5 \200\2235 mg/24 h PO helps agitation, nightmares, hallucina- tions, and vomiting. \212Hydrogen peroxide 6% cleans an unpleasant-feeling coated tongue. \212Hyoscine hydrobr omide 0.4 \200\2230.6 mg/8 h SC or 0.3 mg sublingual helps with vomiting from upper GI obst ruction or bronchial congestion. \212Low-residue diets may be needed for postradiotherapy diarrhea. \212Metronidazole 400 mg/8 h PO mitigates anaerobic odors from tumors; so do charcoal dressings (Actisorb ). \212Nerve blocks may lastingly relieve pleural or other resistant pains. \212Polyethylene glycol sachets 2 \200\2234/12 h for 48 h to shift resistant constipa- tion with overflow. 432 \212Naproxen 250 mg/8 h with food: Fevers caused by malignancy or bone pain from metastases (consider splinting joints if this fails). \212Spironolactone 100 mg bd PO + bumetanide 1 mg/24 h PO for ascites. \212Steroids: Dexa methasone : Give 8 mg IV stat to relieve symptoms of superior vena cava or bronchial obstru ction, or lymphangitis carcino- matosa. Tablets are 2 mg ( 15 mg prednisolone). 4 mg/12 \200\22324 h PO may stimulate appetite, reduce ICP headache, or induce (in some patients) a satisfactory sense of euphoria. \212Supplemental humidified O 2 helps hypoxic dyspnea. \212Thoracocentesis ( bleomycin pleurodesis) helps in pleural effusion.