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Fig. 4.42 The FOBT test for colorectal cancer (shown here is a Hemoccult II ® test). Three consecutive stools samples are applied to the test card. After addition of the reaction solution, a blue coloration indicates the presence of blood. A single positive result among the three samples indicates the need for a clinical examination of the colon. per year per life saved), screening for colorectal cancer in the USA has been evaluated as being below an arbitrary financial threshold adopted in screening (US$ 40,000 per year of life gained) and in this regard compares favourably with protocols for breast or cervical cancer screening. It has been estimated that screening 200,000 people in Australia using the FOBT would detect 250 colorectal cancers and prevent as many as 55 deaths. The FOBT gives the most cost-effective programme, but prevents fewer deaths than other programmes. A single colonoscopy has a greater impact on cancer mortality. Some health authorities in developed countries acknowledge the legitimacy of a screening protocol for colorectal cancer. However, the high cost of a generalized intervention and the limited acceptance of the tests by the population explain its limited application. It has been shown that nurses can perform sigmoidoscopy as competently as doctors, as indicated by the duration of the procedure, the ability to detect neoplasia and the risk of complications. When a lesion is detected in these circumstances, a colonoscopy is performed by a specialist. Evidence of outcome FOBT has been assessed in randomized trials. An American trial [2] was based on an annual rehydrated FOBT in volunteers. The compliance was high (90.2%) and 38% of individuals screened underwent colonoscopy. There was a 33% reduction in specific mortality in the screened group (Table 4.17). Reduction in cancer incidence also occurred. In the two European, population-based, randomized trials [3,4] conducted in the UK and in Denmark with a biennial non-rehydrated FOBT, the compliance was lower (around 60%), only 4% of individuals tested had colonoscopy and the reduction in mortality was less (15%). Screening by sigmoidoscopy has been evaluated in case-control studies. In the Kaiser study [13], rigid sigmoidoscopy was associated with a 59% reduction in mortality from cancer of the rectum and distal colon. Scandinavian trials have shown less compliance and a higher yield of detection with sigmoidoscopy than with the FOBT. A Screening protocols Annual faecal occult blood test Biennial faecal occult blood test Annual faecal occult blood test + fibrosigmoidoscopy every 5 years Fibrosigmoidoscopy every 5 years Colonoscopy every 10 years Colonoscopy once in a lifetime Table 4.16 Options for population-based screening protocols for colorectal cancer (in males and females, from the age of 50 years). cohort study in the USA has shown that screening by endoscopy reduces mortality from colorectal cancer by 50% and incidence by 40% [8]. Primary endoscopic screening is increasingly favoured as compared to the FOBT protocol [9]. There is indirect evidence that primary colonoscopy may reduce cancer mortality. The National Polyp Study in the USA has shown a 75% reduction in the risk of colorectal cancer after polypectomy [10,11]. Among persons of average risk, above age 50, screening by colonoscopy reveals cancer in 0-2.2% and large adenomas in 3-11%. The number of colonoscopies needed to detect one cancer in screening is estimated at 143 for individuals of either sex, aged at least 50, and 64 for males aged at least 60 years. The number of colonoscopies needed to detect one cancer in patients with a positive FOBT is Screened annually Unscreened Number of people 15,550 15,394 Number of colorectal cancers detected 323 356 Number of deaths from colorectal cancer 82 121 Mortality ratio 0.67 1.00 (deaths in screened/deaths in unscreened) Table 4.17 The efficacy of screening by FOBT as reflected by the reduced mortality due to colorectal cancers diagnosed in the group subject to annual screening in comparison with the unscreened group. Screening for colorectal cancer 165
45 with one positive rehydrated FOBT, 9.8 with one positive non-rehydrated FOBT and only 2.7 if two positive non-rehydrated positive FOBT are required. The chance of finding a cancer in the five years after negative colonoscopy is very small. This justifies the tendency towards screening with primary endoscopy to explore at ten-year intervals or once in a lifetime. A recent comparative but non-randomized Finnish study on the endoscopic detection of neoplasia in families fulfilling the Amsterdam REFERENCES 1. Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar MH, Mulrow CD, Woolf SH, Glick SN, Ganiats TG, Bond JH, Rosen L, Zapka JG, Olsen SJ, Giardiello FM, Sisk JE, Van Antwerp R, Brown-Davis C, Marciniak DA, Mayer RJ (1997) Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology, 112: 594-642. 2. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, Ederer F (1993) Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med, 328: 1365-1371. 3. Hardcastle JD, Chamberlain JO, Robinson MH, Moss SM, Amar SS, Balfour TW, James PD, Mangham CM (1996) Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet, 348: 1472-1477. 4. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O (1996) Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet, 348: 1467-1471. 5. Simon JB (1998) Should all people over the age of 50 have regular fecal occult-blood tests? Postpone population screening until problems are solved. N Engl J Med, 338: 1151-1152. 6. Fletcher RH (1998) Should all people over the age of 50 have regular fecal occult-blood tests? If it works, why not do it? N Engl J Med, 338: 1153-1154. 166 Prevention and screening criteria for hereditary nonpolyposis colon cancer has suggested efficacy of colonoscopy in reducing the risk of and mortality from colorectal cancer. International comparisons In countries with a high rate of colorectal cancer, secondary prevention is justified. Mass screening with the FOBT is proposed and reimbursed in Japan, Germany and the Czech Republic for example, but implementation depends upon the accom- 7. Rennert G, Rennert HS, Miron E, Peterburg Y (2001) Population colorectal cancer screening with fecal occult blood test. Cancer Epidemiol Biomarkers Prev, 10: 1165- 1168. 8. Kavanagh AM, Giovannucci EL, Fuchs CS, Colditz GA (1998) Screening endoscopy and risk of colorectal cancer in United States men. Cancer Causes Control, 9: 455-462. 9. Lieberman DA (1997) Endoscopic screening for colorectal cancer. Gastroenterol Clin N Am, 26: 71-83. 10. Winawer SJ, Zauber AG, Ho MN, O'Brien MJ , Gottlieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF (1993) Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med, 329: 1977-1981. 11. Winawer SJ, Zauber AG, O'Brien MJ, Ho MN, Gottlieb L, Sternberg SS, Waye JD, Bond J, Schapiro M, Stewart ET (1993) Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med, 328: 901-906. 12. Kudo S, Kashida H, Tamura S, Nakajima T (1997) The problem of "flat" colonic adenoma. Gastrointest Endosc Clin N Am, 7: 87-98. 13. Friedman GD, Collen MF, Fireman BH (1986) Multiphasic Health Checkup Evaluation: a 16-year followup. J Chronic Dis, 39: 453-463. panying awareness campaign. In the USA, an annual FOBT and/or sigmoidoscopy every five years is recommended. Screening with primary sigmoidoscopy is encouraged in Scandinavian countries and in the United Kingdom. Application of any large-scale endoscopic screening programme is hampered by a shortage of specialists and the high cost of their expertise. WEBSITES Colorectal cancer prevention and control initiatives CDC: http://www.cdc.gov/cancer/colorctl/colorect.htm Colorectal cancer screening, the American Gastroenterological Association: http://www.gastro.org/public/brochures/cc_screening.html
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WORLD HEALTH ORGANIZATION WHO OMS I
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WORLD CANCER REPORT Editors Bernard
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CONTENTS Foreword 9 1 The global bu
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The global burden of cancer Cancer
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Fig. 1.2 Incidence and mortality of
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Central and Southern Europe differ
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Incidence of cancer in South Centra
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from documentation of disease to a
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TOBACCO SUMMARY >In addition to lun
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Fig. 2.3 Smoking by children is inc
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Cancers positively Sex Standardized
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PHARMACOLOGICAL APPROACHES TO SMOKI
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level the dose—response relations
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lipoprotein-associated cholesterol,
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Agent Cancer site/cancer Main indus
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Industry, occupation Cancer site/ca
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to occupational exposures in develo
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Air pollutant WHO Air Quality Guide
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der cancer of the order of 50% is p
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AFLATOXIN B 1 HEPATITIS VIRUS (chro
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Fig. 2.30 Correlation between regio
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MEDICINAL DRUGS SUMMARY > Certain d
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Drug or drug combination Cancer IAR
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Agent or substance Cancer site/canc
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sources of electromagnetic fields [
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CHRONIC INFECTIONS SUMMARY > Infect
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Infection Subclinical Mutagenic fac
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TUMOURS ASSOCIATED WITH HIV/AIDS Ap
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DIET AND NUTRITION SUMMARY > Up to
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Fig. 2.54 The age-adjusted mortalit
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OVERWEIGHT, OBESITY AND PHYSICAL AC
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IMMUNOSUPPRESSION SUMMARY >Persiste
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Fig. 2.64 Cancer following immunosu
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Syndrome Gene Location Cancer site/
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viduals, confirmation of a gene def
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REPRODUCTIVE FACTORS AND HORMONES S
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PHYTO-ESTROGENS AND CANCER PEVENTIO
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Indicator Number of oral contracept
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Mechanisms of tumour development Th
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The stages in tumorigenesis have be
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PRECURSOR LESIONS IN CHEMOPREVENTIO
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CARCINOGEN ACTIVATION AND DNA REPAI
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adducts, a few weeks or months for
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I Reactive oxygen species Methylati
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which remove the mismatched bases,
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Common human oncogenes Many common
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product of the RB1 gene (pRb) and a
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ates a molecular bridge between p53
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potential cancer genes altered thro
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One of the earliest genes to be ide
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Regulation of the cell cycle and co
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CELL-CELL COMMUNICATION SUMMARY > C
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Connexin genes and tumour suppressi
Page 109 and 110: APOPTOSIS SUMMARY > The term apopto
Page 111 and 112: Caspase-8 Caspase-3 c-FLIP Procaspa
Page 113 and 114: ways. Several options are under inv
Page 115 and 116: INVASION AND METASTASIS SUMMARY > T
Page 117 and 118: laminin, entactin and also heparan
Page 119 and 120: Target Example of agent Comments Ad
Page 121 and 122: organs, and to respond to local gro
Page 123 and 124: TOBACCO CONTROL SUMMARY > Tobacco-i
Page 125 and 126: Region Deaths due to % of total dea
Page 127 and 128: ipated, is primarily attributable t
Page 129 and 130: smoke. This may be achieved in part
Page 131 and 132: there is no evidence for the effica
Page 133 and 134: industries, processes and occupatio
Page 135 and 136: stoves arises in rural areas of dev
Page 137 and 138: Climbing plants on trellis at end r
Page 139 and 140: HEPATITIS B VACCINATION SUMMARY > P
Page 141 and 142: Fig. 4.17 Chronic active HBV-associ
Page 143 and 144: HUMAN PAPILLOMAVIRUS VACCINATION SU
Page 145 and 146: Vaccine Site of trial Number of pat
Page 147 and 148: prolonged use. Similar drugs, that
Page 149 and 150: aspirin and other non-steroidal ant
Page 151 and 152: SCREENING FOR BREAST CANCER SUMMARY
Page 153 and 154: Fig. 4.35 Cumulative mortality from
Page 155 and 156: SCREENING FOR PROSTATE CANCER SUMMA
Page 157 and 158: Fig. 4.39 Poster designed for an an
Page 159: is around 10% for cancer (out of ev
Page 163 and 164: eing based on (i) time trends in th
Page 165 and 166: Fig. 4.48 Women at a clinic in Indi
Page 167 and 168: SCREENING FOR ORAL CANCER SUMMARY >
Page 169 and 170: India will provide useful informati
Page 171 and 172: cer incidence following cure of inf
Page 173 and 174: 100 50 25 10 5 2.5 1 Japan Males Fe
Page 175 and 176: Human cancers by organ site Maligna
Page 177 and 178: tobacco smoking: age at start, aver
Page 179 and 180: diagnosis is usually confirmed by h
Page 181 and 182: is frequent and survival rates are
Page 183 and 184: Fig. 5.14 Physician reading digital
Page 185 and 186: Markers of prognosis in breast canc
Page 187 and 188: cer in the contralateral breast (Ch
Page 189 and 190: 100 50 25 10 5 2.5 1 Japan Chile Po
Page 191 and 192: depends on staging. Small intramuco
Page 193 and 194: Fig. 5.30 A diet rich in fresh frui
Page 195 and 196: ane protein involved in cell adhesi
Page 197 and 198: LIVER CANCER SUMMARY > About 560,00
Page 199 and 200: Fig. 5.39 A woman in the Gambia pre
Page 201 and 202: REFERENCES 1. Ferlay J, Bray F, Par
Page 203 and 204: Certain Possible Uncertain Age Andr
Page 205 and 206: Management The dramatic division be
Page 207 and 208: TUMOUR NORMAL Gastrula PGC 2n Impri
Page 209 and 210: CANCERS OF THE FEMALE REPRODUCTIVE
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Fig. 5.62 Five-year relative surviv
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Inheritance of high-penetrance gene
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invasive malignant. Malignant germ
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OESOPHAGEAL CANCER SUMMARY >Cancer
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Fig. 5.76 A radiographic view of an
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with a stent; laser recannulation,
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Fig. 5.82 Risk of bladder cancer am
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Partial cystectomy is appropriate f
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poorly known since hypopharyngeal c
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Fig. 5.92 Oral leukoplakia with mil
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LYMPHOMA SUMMARY > Malignant lympho
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T Fig. 5.101 Nuclear magnetic reson
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Fig. 5.106 Five-year relative survi
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Fig. 5.109 The immediate aftermath
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A B Fig. 5.113 Acute myeloid leukae
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Fig. 5.118 Five-year relative survi
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Fig. 5.120 Age-specific incidence a
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Hereditary condition Mode of inheri
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MELANOMA SUMMARY > Approximately 13
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Fig. 5.131 Primary melanoma with a
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THYROID CANCER SUMMARY > Cancer of
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Papillary carcinoma RET/PTC TRK BRA
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KIDNEY CANCER SUMMARY > Cancer of t
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Stage Clear cell carcinoma Papillar
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TUMOURS OF THE NERVOUS SYSTEM SUMMA
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ing the optic tract, brain stem and
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mut = mutant p53 wt = wildtype p53
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SURGICAL ONCOLOGY SUMMARY > Surgica
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Year Radical mastectomy (%) Modifie
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TELEMEDICINE The prospects for tele
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Equipment Energy 50% depth dose App
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CANCER EDUCATION IN MEDICAL COURSES
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Fig. 6.10 Crystals of cisplatin: mo
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Responsiveness Cancer (in decreasin
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Most of the world’s most common c
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treatment of cancer. The problems l
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duction. It is clear that tumour ce
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REHABILITATION SUMMARY > Rehabilita
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cer and its associated disability.
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REFERENCES 1. Garden FH, Gillis TA
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Cancer pain relief varies and in so
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EMERGING ISSUES IN PALLIATIVE CARE
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Cancer control The negative impact
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priority to cancer control activiti
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Prevention of cancer Every country
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- Assessing the magnitude of the ca
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high-risk women. Further details on
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ecords departments are either rudim
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THE INTERNATIONAL AGENCY FOR RESEAR
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in the capitals/urban areas of four
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in the overall cancer strategy. WHO
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68% 1955 1975 1995 2025 32% 40% by
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Fig. 7.15 A grandfather at work in
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Fig. 7.17 Main causes of death in d
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Contributors and Reviewers Sources
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Dr Vera Luiz da Costa e Silva Tobac
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Georgia Moore Centers for Disease C
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REVIEWERS Dr Sandra E. Brooks 405 W
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2.53 T. Norat and E. Riboli, IARC 2
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Gastroenterology, 118(2 Suppl 1): S
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5.106 & 5.107 IARC/SEER/Osaka Cance
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4.17 R. Lambert, IARC/Adapted from
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Brain cancer, see nervous system tu
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Fibroblast growth factor (FGF), 117
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Microarray, 240 Micronutrients, 65,
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S Saccharin, 64, 85 Salicin, 153 Sa
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