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and intestinal metaplasia (Fig. 5.25), frequently precede and/or accompany intestinal type adenocarcinoma, especially in high incidence areas. Premalignant conditions include gastric polyps, Menetrier disease, gastric ulcer, pernicious anaemia (achlorydia) and previous gastric surgery to reduce acid output [3]. H. pylori strains containing a group of genes named cag induce a great degree of inflammation, and there is an association between infection with a cag positive H. pylori strain and the development of gastric carcinoma [5]. Gastric carcinomas are morphologically heterogeneous, resulting in various classifications based on histological appearance, degree of differentiation, growth pattern, and histogenesis [6]. The major histological types include tubular adenocarcinoma (Fig. 5.27), papillary adenocarcinoma, mucinous adenocarcinoma and signet-ring cell carcinoma. When more than one histological type is observed within the tumour, the diagnosis is based on the predominant histological pattern [7]. Based on their differentiation status, gastric carcinomas are also classified as Histologic type Gene alterations Poorly-differentiated (%) Well-differentiated (%) KRAS mutation 0 10-20 c-met Amplification ≈ 40 ≈20 6.0 kb mRNA ≈ 80 ≈ 50 K-sam amplification 20-30 0 c-erbB2 amplification 0 20-40 Cyclin E amplification 10 10 p53 LOH/mutation ≈ 80 ≈ 60 APC LOH/mutation - 40-60 DCC LOH - 50 Cadherin, catenin deletion 50 - CD44 abnormal transcript 100 100 Genetic instability ≈ 40 ≈10 Table 5.3 Genetic alterations in gastric carcinomas, (≈ = approximately), [15, 16]. 196 Human cancers by organ site well-differentiated adenocarcinoma (composed of well-formed glands, often resembling metaplastic intestinal epithelium) and poorly-differentiated adenocarcinoma (composed of highly irregular glands or single cells that remain isolated). Moderately-differentiated adenocarcinomas show intermediate features between the two. Gastric carcinomas may also be classified as diffuse and intestinal types (Laurén classification) [8]. Intestinal type carcinoma is composed of distinct glandular elements with well-defined lumina, sometimes accompanied by papillary structures or solid components. Diffuse gastric carcinoma is characterized by the lack of cell cohesion, and malignant cells infiltrate the surrounding tissue as single cells or small clusters of cells without glandular lumina [8]. Other classification systems are also in use. Clinical and pathological staging of stomach cancer is based on the TNM system (Box: TNM, p124) in Western countries and the Japanese classification system in Japan [9]. Most gastric carcinomas occur sporadically, but up to 10% have an inherited familial component [10]. Case-control studies also suggest a small but consistent increased risk in first-degree relatives of gastric carcinoma patients [11]. Germline E-cadherin (CDH1) mutations lead to an autosomal dominant predisposition to diffuse gastric carcinoma [12]. Gastric carcinomas may also develop as part of the hereditary nonpolyposis colon cancer (HNPCC) syndrome [13] (Colorectal cancer, p198). They exhibit intestinal type cancers and microsatellite instability. Loss of heterozygosity studies and comparative genomic hybridization (CGH) studies have shown that frequent loss or gain occurs at chromosomal regions 1p, 1q, 3p, 4, 5q (APC locus), 6q, 7q, 9p, 17p (p53 locus), 18q (DCC locus), and 20q [14]. Well- and poorly-differentiated adenocarcinomas frequently show different genetic alterations (Table 5.3), as do diffuse and intestinal types [15,16]. Management Most patients diagnosed with stomach cancer have advanced disease and the prognosis is extremely poor with survival rates rarely exceeding 15%. Differences in classification of cancer lead to apparently much higher survival rates in Japan (Fig. 5.28). Management of stomach cancer Fig. 5.28 Five-year relative survival after diagnosis of gastric carcinoma.
depends on staging. Small intramucosal cancers can be treated endoscopically by endoscopic mucosal resection [17]. For invasive cancer, standard treatment is gastrectomy with regional lymph node dissection [18]. For patients with advanced stage stomach cancer, neo-adjuvant (preoperative) or adjuvant (post-operative) chemotherapy is currently being investigated in research protocols. Drugs most often employed are 5-fluorouracil, doxorubicin and cisplatin, and greatest success has been achieved on the basis of combination regimens rather than single agent treatments. Immunochemosurgery using REFERENCES 1. Ferlay J, Bray F, Parkin DM, Pisani P, eds (2001) Globocan 2000: Cancer Incidence and Mortality Worldwide (IARC Cancer Bases No. 5), Lyon, IARCPress. 2. Muñoz N (1988) Descriptive epidemiology of stomach cancer. In: Reed PI, Hill, MJ eds, Gastric Carcinogenesis, Amsterdam, Excerpta Medica, 51-69. 3. Branicki FJ, Gotley DG (1998) Gastric cancer. In: Morris D, Kearsley J, Williams C, eds, Cancer: a comprehensive clinical guide, Harwood Academic Publishers, 165-169. 4. Miki K, Ichinose M, Ishikawa KB, Yahagi N, Matsushima M, Kakei N, Tsukada S, Kido M, Ishihama S, Shimizu Y (1993) Clinical application of serum pepsinogen I and II levels for mass screening to detect gastric cancer. Jpn J Cancer Res, 84: 1086-1090. 5. Queiroz DM, Mendes EN, Rocha GA, Oliveira AM, Oliveira CA, Cabral MM, Nogueira AM, Souza AF (1999) Serological and direct diagnosis of Helicobacter pylori in gastric carcinoma: a case-control study. J Med Microbiol, 48: 501-506. 6. Hamilton SR and Aaltonen LA, eds (2000) World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System, Lyon, IARCPress. 7. Watanabe H, Jass JR, Sobin LH, eds (1990) Histological Typing of Oesophageal and Gastric Tumours (International Histological Classification of Tumours, 2nd Ed.), Berlin, Springer-Verlag. 8. Laurén PA (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand, 64: 31-49. 9. Ichikura T, Tomimatsu S, Uefuji K, Kimura M, Uchida T, Morita D, Mochizuki H (1999) Evaluation of the New American Joint Committee on Cancer/International Union against cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification. Cancer, 86: 553-558. 10. La Vecchia C, Negri E, Franceschi S, Gentile A (1992) Family history and the risk of stomach and colorectal cancer. Cancer, 70: 50-55. Corynebacterium parvum is practised in Korea, but is still subject to scepticism in Western practice [3]. Annual surveillance endoscopy, post-gastrectomy, has been associated with a small beneficial outcome in terms of gain of life-years, but this may be inflated by the exaggerated assumptions of a high incidence rate of gastric stump cancer and a cure rate of 80% achieved by timely surgery after cancer detection. In advanced stomach cancer, tumour stage, tumour size, histological tumour type, growth pattern, degree of cytological atypia, DNA-nuclear content, stromal 11. Zanghieri G, Di Gregorio C, Sacchetti C, Fante R, Sassatelli R, Cannizzo G, Carriero A, Ponz dL (1990) Familial occurrence of gastric cancer in the 2-year experience of a population-based registry. Cancer, 66: 2047- 2051. 12. Guilford PJ, Hopkins JB, Grady WM, Markowitz SD, Willis J, Lynch H, Rajput A, Wiesner GL, Lindor NM, Burgart LJ, Toro TT, Lee D, Limacher JM, Shaw DW, Findlay MP, Reeve AE (1999) E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum Mutat, 14: 249-255. 13. Watson P, Lynch HT (1993) Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer, 71: 677-685. 14. Becker KF, Keller G, Hoefler H (2000) The use of molecular biology in diagnosis and prognosis of gastric cancer. Surg Oncol, 9: 5-11. 15. Tahara E (1995) Molecular biology of gastric cancer. World J Surg, 19: 484-488. 16. Hirohashi S, Sugimura T (1991) Genetic alterations in human gastric cancer. Cancer Cells, 3: 49-52. 17. Hiki Y, Sakakibara Y, Mieno H, Shimao H, Kobayashi N, Katada N (1991) Endoscopic treatment of gastric cancer. Surg Endosc, 5: 11-13. 18. Maruyama K, Sasako M, Kinoshita T, Okajima K (1993) Effectiveness of systemic lymph node dissection in gastric cancer surgery. In: Nishi M, Ichikawa H, Nakajima T, Maruyama K, Tahara E eds, Gastric Cancer, Tokyo, Springer-Verlag, 293-305. 19. Yoshikawa K, Maruyama K (1985) Characteristics of gastric cancer invading to the proper muscle layer--with special reference to mortality and cause of death. Jpn J Clin Oncol, 15: 499-503. 20. Utsunomiya T, Yonezawa S, Sakamoto H, Kitamura H, Hokita S, Aiko T, Tanaka S, Irimura T, Kim YS, Sato E (1998) Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients. Clin Cancer Res, 4: 2605-2614. reaction, lymphatic and vascular invasion all have prognostic value. Patients with cancers limited to the mucosa and submucosa have a five-year survival of approximately 95%. Tumours that invade the muscularis propria have a 60% to 80% five-year survival, whereas tumours invading the subserosa and serosa have a less than 50% five-year survival on average [19]. There is recent evidence that the type of mucin and polymorphism of the gene encoding mucin may be an important factor determining susceptibility to stomach cancer [20]. WEBSITE NCI Stomach (Gastric) Cancer Homepage: http://www.cancer.gov/cancer_information/cancer_type/ stomach/ Stomach cancer 197
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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
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APOPTOSIS SUMMARY > The term apopto
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Caspase-8 Caspase-3 c-FLIP Procaspa
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ways. Several options are under inv
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INVASION AND METASTASIS SUMMARY > T
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laminin, entactin and also heparan
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Target Example of agent Comments Ad
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organs, and to respond to local gro
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TOBACCO CONTROL SUMMARY > Tobacco-i
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Region Deaths due to % of total dea
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ipated, is primarily attributable t
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smoke. This may be achieved in part
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there is no evidence for the effica
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industries, processes and occupatio
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stoves arises in rural areas of dev
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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 and 160: is around 10% for cancer (out of ev
Page 161 and 162: 45 with one positive rehydrated FOB
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: 100 50 25 10 5 2.5 1 Japan Chile Po
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
Page 211 and 212: Fig. 5.62 Five-year relative surviv
Page 213 and 214: Inheritance of high-penetrance gene
Page 215 and 216: invasive malignant. Malignant germ
Page 217 and 218: OESOPHAGEAL CANCER SUMMARY >Cancer
Page 219 and 220: Fig. 5.76 A radiographic view of an
Page 221 and 222: with a stent; laser recannulation,
Page 223 and 224: Fig. 5.82 Risk of bladder cancer am
Page 225 and 226: Partial cystectomy is appropriate f
Page 227 and 228: poorly known since hypopharyngeal c
Page 229 and 230: Fig. 5.92 Oral leukoplakia with mil
Page 231 and 232: LYMPHOMA SUMMARY > Malignant lympho
Page 233 and 234: T Fig. 5.101 Nuclear magnetic reson
Page 235 and 236: Fig. 5.106 Five-year relative survi
Page 237 and 238: Fig. 5.109 The immediate aftermath
Page 239 and 240: 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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