Gastrointestinal Ulcers Gastrointestinal Tract

Experimental฀animal฀work฀has฀shown฀that฀simultaneous฀cigarette฀smoking฀markedly฀ impairs฀the฀absorption฀of฀cimetidine,฀thus฀attenuating฀its฀eficacy฀ [323] .฀The฀smoking฀sta- tus฀of฀patients฀was฀found฀to฀be฀unimportant฀for฀treatment฀with฀omeprazole฀ [324] .฀This฀ inding฀has฀been฀conirmed฀in฀clinical฀trials฀in฀patients฀with฀duodenal฀ulcers฀ [325,฀326] .

7.5.3 Cancers of the Gastrointestinal Tract

According฀to฀a฀Polish฀study฀in฀741฀gastric฀cancer฀patients,฀smokers฀of฀non-ilter฀cigarettes฀ had฀an฀increased฀risk฀for฀gastric฀cardia฀cancers฀OR฀=฀3.72;฀CI:฀1.35–10.23,฀compared฀ with฀controls฀ [327] .฀Other฀authors฀have฀also฀reported฀that฀smokers฀are฀at฀increased฀risk,฀ particularly฀for฀tumours฀in฀the฀lower฀oesophagusgastric฀cardia฀ [308,฀328–331] ,฀and฀the฀ number฀of฀cigarettes฀smoked฀daily฀is฀also฀important฀for฀the฀increased฀level฀of฀risk฀ [330] .฀ Compared฀with฀non-smokers,฀current฀smokers฀of฀80฀or฀more฀pack-years฀were฀at฀substan- tially฀higher฀risk฀for฀squamous฀cell฀cancer฀OR฀=฀16.9;฀CI:฀4.1–69.1฀ [332] ,฀and฀the฀risk฀ was฀consistent฀with฀body฀mass฀index฀BMI:฀the฀more฀pack-years฀of฀smoking฀and฀the฀ higher฀the฀BMI,฀the฀greater฀the฀risk.฀However,฀smoking฀is฀also฀regarded฀as฀a฀risk฀factor฀for฀ adenocarcinomas฀in฀the฀distal฀gastric฀region฀and฀for฀diffuse฀gastric฀cancers฀ [331] .฀Among฀ patients฀with฀adenocarcinomas฀and฀malignant฀carcinoids฀of฀the฀small฀intestine฀who฀had฀ already฀experienced฀ulcer฀disease฀n฀=฀36,฀compared฀with฀52-healthy฀controls,฀the฀odds฀ ratio฀for฀cigarette฀smoking฀was฀4.6฀CI:฀1.0–20.7฀ [333] ,฀with฀the฀result฀that฀a฀causal฀rela- tionship฀may฀be฀assumed.฀In฀most฀of฀the฀studies฀the฀risk฀was฀further฀increased฀by฀simulta- neous฀alcohol฀spirits฀intake฀ [328] .฀In฀one฀study฀from฀Russia,฀for฀example,฀heavy฀vodka฀ consumption฀had฀a฀potentiating฀effect฀for฀the฀development฀of฀cancer฀of฀the฀cardia฀in฀men฀ OR฀=฀3.4;฀CI:฀1.2–10.2฀and฀for฀cancer฀of฀sites฀other฀than฀the฀gastric฀cardia฀in฀women฀ OR฀=฀1.5;฀CI:฀1.0–2.3฀ [334] .฀While฀carcinomas฀of฀lower฀sections฀of฀the฀small฀intestine฀ have฀been฀linked฀with฀smoking,฀no฀studies฀have฀been฀conducted฀to฀support฀this฀ [335] .

7.5.4 Pancreatic Cancer

According฀to฀several฀prospective฀studies,฀smoking฀doubles฀the฀risk฀for฀the฀development฀of฀ pancreatic฀cancer฀in฀both฀men฀and฀women฀ [336] .฀K-ras฀mutations,฀associated฀with฀alcohol฀ consumption,฀organochlorines฀and฀smoking,฀have฀been฀implicated฀in฀pancreatic฀carcino- genesis฀ [337] . The฀risk฀is฀increased฀ivefold฀in฀people฀smoking฀40฀cigarettes฀daily.฀In฀terms฀of฀tumour฀ development,฀smokers฀do฀not฀attain฀the฀risk฀level฀of฀non-smokers฀until฀10–15฀years฀after฀ smoking฀cessation฀ [336] .฀As฀also฀with฀urinary฀tract฀cancer,฀cadmium฀has฀recently฀been฀ suggested฀as฀a฀factor฀involved฀in฀the฀development฀of฀pancreatic฀cancer:฀during฀smoking,฀ this฀non-essential฀metal฀is฀absorbed฀in฀trace฀amounts฀and฀is฀known฀to฀accumulate฀particu- larly฀ in฀ the฀ pancreas฀ [338] .฀ An฀ Italian฀ study฀ has฀ now฀ shown฀ that฀ compared฀ with฀ non- smokers,฀cigarette฀smokers฀are฀17.3฀times฀more฀likely฀to฀be฀found฀in฀the฀group฀with฀chronic฀ pancreatitis฀and฀5.3฀times฀more฀likely฀to฀be฀found฀in฀those฀with฀pancreatic฀cancer฀ [339] .฀ Similar฀results฀have฀been฀obtained฀in฀further฀studies฀ [340–344] .฀Smoking฀cessation฀could฀ eliminate฀25฀of฀deaths฀from฀pancreatic฀cancer฀in฀the฀United฀States฀ [343] .฀Current฀cigar฀ smoking,฀especially฀when฀the฀smoke฀is฀inhaled,฀is฀also฀associated฀with฀an฀increased฀risk฀ for฀pancreatic฀cancer฀RR฀=฀2.7;฀CI:฀1.5–4.8฀ [345] .

7.6 Urinary Tract Diseases

Along฀with฀the฀lungs฀and฀heart,฀kidneys฀are฀among฀the฀most฀important฀target฀organs฀for฀the฀ harmful฀effects฀of฀smoking.฀In฀terms฀of฀preserving฀renal฀function฀in฀an฀older฀population,฀ smoking฀is฀counterproductive฀because฀pre-existing฀hypertension฀and฀vascular฀disease,฀in฀ tandem฀with฀smoking,฀will฀damage฀small฀and฀large฀renal฀vessels,฀even฀in฀patients฀without฀ diabetes฀ [346] .฀As฀long฀ago฀as฀1907,฀the฀German฀physician฀Hesse฀advised฀his฀patients฀with฀ nephrosclerosis฀to฀give฀up฀smoking฀ [347] . Sections฀of฀myocardium฀and฀kidney฀from฀autopsied฀subjects฀display฀parallel฀smoking- related฀changes฀in฀terms฀of฀increased฀intima฀thickness฀of฀small฀vessels;฀while฀the฀degree฀of฀ increase฀did฀not฀correlate฀with฀pack-years,฀it฀did฀show฀a฀positive฀correlation฀with฀age฀in฀the฀ kidney฀ [348] .฀ Within-subject฀ variability฀ has฀ so฀ far฀ limited฀ the฀ usefulness฀ of฀ biomarker฀ determinations฀ –฀ e.g.฀ microalbumin,฀ N-acetyl-b- d -glucosaminidase฀ NAG฀ and฀ alanine฀ aminopeptidase฀AAP฀–฀for฀the฀diagnosis฀of฀renal฀function฀ [349] .฀Whereas฀acute฀smoking฀ has฀been฀reported฀to฀have฀no฀inluence฀on฀renal฀albumin฀excretion฀ [350] ,฀microalbuminu- ria฀is฀already฀increased฀in฀the฀presence฀of฀diabetic฀changes฀see฀Sect.฀7.4.2.2. Smoking-induced฀elevations฀in฀blood฀pressure฀and฀heart฀rate฀result฀from฀increased฀secre- tion฀of฀arginine฀vasopressin฀and฀adrenaline,฀whereas฀glomerular฀iltration฀rate฀GFR฀falls฀with฀ a฀simultaneous฀increase฀in฀renal฀vascular฀resistance฀Fig.฀ 7.5 ฀ [351] .฀Overall,฀non-smokers฀ MAP HR GFR ERPF RVR −20 −10 10 20 Nicotine-induced changes [] 30 Nonsmoker smoker 40 Fig. 7.5 ฀฀฀Mean฀percentage฀ changes฀in฀mean฀arterial฀ pressure฀MAP,฀heart฀rate฀ HR,฀glomerular฀iltration฀ rate฀GFR,฀effective฀renal฀ plasma฀low฀ERPF฀and฀ renal฀vascular฀resistance฀ RVR฀in฀9฀smokers฀and฀฀ 10฀non-smokers฀following฀ administration฀of฀4-mg฀ nicotine฀chewing฀gum฀for฀฀ 30฀min฀ [351]