IC 17 Pharmacist-Led Management of Lower GIT Conditions PDF

✅ IC 17 Pharmacist - led management of lower GIT conditions Learning outcomes Recognise colon & rectal cancer global & local incidence Global incidence? 9.6% of 20 mil new cases...

✅ IC 17 Pharmacist - led management of lower GIT conditions Learning outcomes Recognise colon & rectal cancer global & local incidence Global incidence? 9.6% of 20 mil new cases mortality? 9.3% of 9.7 mil deaths SG incidence? M: 16.3% - 2nd most common after prostate cancer F: 12.9% - 2nd most common aft breast cancer Recall risk factors for colon & rectal cancer development Personal med history Age: > 50 - US: 45 Adenomatous polyps - generally asymptomatic → colonoscopy to detect Symptoms: bleeding - How? faeces moving thru colon: more dry → abrasion w polyps Colorectal cancer IC 17 Pharmacist - led management of lower GIT conditions 1  IBD CD, UC Chronic underlying inflammation, oxidative stress, release various cytokines → promote tumorigenesis Type II DM: hyperinsulinemia & elevated free insulin - like growth factor - 1 (IGF - 1) levels → promote tumour cell proliferation Fam history → inherited genetic risk Colorectal cancer, adenomatous polyps - Why? inherited genes, shared environmental factors, combi → increase risk hereditary syndromes - somatic: 2/3, genetic; germline: 1/3 familial adenomatous polyposis (FAP): What? mutation in tumour suppresor gene APC Lynch syndrome: What? genes involved in DNA repair pathway - MLH1, MSH2 genes Ethnicity: chinese higher risk in SG Lifestyle factors Sedentary - r/s? inverse between physical activity & colon cancer risk x rectal cancer Overwt & obesity: What? dose response r/s w elevated BMI, waist circumference, waist to hip ratio Alcohol intake ≥ 30g / day; ~ 2 drinks → significant +ve associations Smoking: 40 cigarettes; 2 packs a day → increase CRC risk by 40%, doubles CRC death risk Processed meat: 50g / day → significant increase CRC risk Red meat: +ve association but x significant for CRC significant for colon cancer HDI; human development index: What? statistic composite index of life expectancy, edu 7 per capita income indicators r/s? HDI increase → incidence rates tend to rise uniformly IC 17 Pharmacist - led management of lower GIT conditions 2  Why? change in lifestyle factors - more sedentary & diet - increase animal - source food intake Describe how inherited & acquired genetic susceptibility contributes to colon & rectal cancer pathophysiology Colorectal tumorigenesis: What? multistep process - several genetic & phenotypic alterations → dysregulated cell growth → proliferation → tumour development Contributors? genomic instability oncogene pathway activation silence tumour suppressor genes DNA mismatch repairs activate growth factor pathways Diagram? Mutation accumulation within colonic epithelium confers selective growth advantage to affected cells Mutation 1: inherited - based on genetic risk factors Low - grade dysplasia determine by histology IC 17 Pharmacist - led management of lower GIT conditions 3  Recognise NSAIDs role for colorectal cancer chemoprevention Strategies to prevent colon & rectal cancer - emphasis on chemoprophylaxis Prevention Primary: What? prevent CRC in population at risk How? modify lifestyle factors confer risk of developing & protective therapeutics - eg. vaccination Eg. eat more fruits & veg daily reduce red meat intake reduce processed meat - ham, sausages, bacon, ba kwa avoid cooking meat at high temp - char - grilling, deep drying, barbequing limit alcohol intake - daily limit: M: 2 drinks, F: 1 drink exercise regularly maintain healthy wt quit smoking IC 17 Pharmacist - led management of lower GIT conditions 4  Chemoprevention aspirin efficacy: 20 - 40% reduction in risk of colonic adenomas & CRC in average risk individuals but evidence to date x sufficient → x warranted in gen population dose? 75 - 100mg - low high dose - 600mg/day → benefit for pt w hereditary nonpolyposis CRC cons? chronic use → irritation to GIT → PUD, GERD selective COX - 2 inhibitors; NSAIDs Efficacy? colorectal neoplasia prevention → unlikely widespread use in cancer prevention Cons? traditional NSAIDs: x COX - 2 selectivity → chronic use: increased CV risk Secondary: What? stagnate / inhibit / reverse carcinogenesis How? early detection, treatment, remove precancerous / early cancerous lesions Diagram? IC 17 Pharmacist - led management of lower GIT conditions 5  Most appropriate screening strategies for colon & rectal cancer Why? majority from adenomatous polyps → multiple gene mutation → detectable premalignant phase: malignant transformation relatively asymptomatic Prevalence? up to 25% of age 50 r/s? increase w age most - 90% remove at colonoscopy → preclude need for surgery Screening remove polyps during colonoscopy - gold standard → prevent cancer detect early cancers w gd chance of cure Cons? expensive prep bowel → inconvenient What screening strategies? Annually High - sensitively guaiac fecal occult blood test (HSgFOBT) - x in SG / UK Fecal immunochem test (FIT): What? detect hidden blood in stool - Causes? polyps, haemorrhoids Every 1 - 3 yrs Stool DNA - FIT Every 5 yrs computed tomography colonoscopy flexible sigmoidoscopy Every 10 yrs IC 17 Pharmacist - led management of lower GIT conditions 6  flexible sigmoidoscopy + annual FIT colonoscopy Who? 45 / 50 - 75 > 75 yrs old: discuss decision to screen, consider overall health status - life expectancy, comorbid conditions, prior screening history, preferences Pt risk factors grp Average: What? asymptomatic, fam history limited to non - 1st degree relatives Tool? colonoscopy Age to start? 50 Frequency? every 5 - 10 yrs High - tool? colonoscopy colorectal cancer in 1st degree relatives age 60 / younger, ≥ 2 1st degree relatives Age to start? 10 yrs before youngest case in fam / 40 yrs old - whichever earlier Frequency? every 5 yrs CRC in 1st degree relatives > 60 Age to start? 50 Frequency? every 10 yrs Personal history: colorectal polyps high risk features: > 1cm, multiple. villous architecture; more cauliflower: 1 - 3 yrs aft polypectomy low risk polyps: 3 - 5 yrs aft polypectomy Personal history of colorectal malignancy Age to start? 1 yr aft resection Frequency? every 1 - 3 yrs Personal history of ovarian / endometrial cancer IC 17 Pharmacist - led management of lower GIT conditions 7  Age to start? aft resection V high risk fam history of familial adenomatous polyposis Tool? flexible sigmoidoscopy, consider genetic counseling & testing Age to start? 10 - 12 yrs aft puberty Frequency? yrly fam history of hereditary non - polyposis CRC Tool? colonoscopy, consider genetic counselling & testing Age to start? 20 - 25 Frequency? every 1 - 2 yrs IBD tool? colonoscopyd frequency? every 1 - 2 yrs Types? L side colon; ascending colon: age to start? from 15th yr of diagnosis Pan - colitis: age to start? from 8th yr of diagnosis How to choose? Screening test: inexpensive, reliable, acceptable Sensitivity & selectivity → accuracy of test reports condition’s presence / absence Sensitivity; true +ve rate: What? probability of +ve test conditioned on truly being +ve Specificity; true -ve rate: What? probability of -ve test conditioned on truly being -ve Cost effectiveness Pros? screening increase life expectancy of SG between 50 - 70 yrs old IC 17 Pharmacist - led management of lower GIT conditions 8  FOBT: most cost effective population screening methods Colonoscopy: more cost effective if compliance to screening recco - How? 1 / 2x in life time → higher compliance vs annual FOBT But x clear choice → based on info on effectiveness, risks, costs → individual screening Options? Faecel occult blood testing (FOBT) / Faecal Immunochem test (FIT) Efficacy? 33% reduction in CRC mortality MOA? detect human haemoglobin from partially digested blood in stool but other causes? haemorrhoids, NSAID induced bleeding in GIT, infective colitis, IBD, Coelic disease Pros? non - invasive dietary restriction Cons? Adenomas detection ≥ 1cm Sensitivity: 48% Specificity: 96% Colonoscopy What? Gold standard for complete large bowel evaluation, screening investigation of choice in high risk pt Remove asymptomatic polyps before malignant transformation at same setting Pros? high sensitivity & specificity long screening interval - Eg. 5 yrs Cons? IC 17 Pharmacist - led management of lower GIT conditions 9  higher cost full bowel prep sedation dietary restrictions: Water, laxatives Barium emema Sigmoidoscopy - flexible What? endoscopic procedure examine colon’s lower half Pros? simpler prep: emema beforehand lower complications risk - perforations, bleeding Cons? miss polyps in proximal 1/2 of colon → further colonoscopy if polyps detected combine w FOBT → superior sensitivity CT colonoscopy - virtual colonoscopy Highlighted in yellow: might not be as effective & reliable as FOBT / colonoscopy in large - scale population screening Barriers to screening Perceived costs - but got subsidies schemes Concerns over bowel prep Signs & symptoms of colon & rectal cancer Distribution Ascending: 20 - 30% Transverse: 10% Descending: 60% Treatment modalities for colon & rectal cancer IC 17 Pharmacist - led management of lower GIT conditions 10  Summary Factors of CRC risk advancing age inherited & acquired genetic susceptibilities lifestyle choices IBD environment Meds to reduce CRC risk regular use of aspirin, NSAIDs, Ca2+ intake → but x currently recommended for routine cancer prevention Effective CRC screening prog: regular entire colon examination - When start? 50 for average risk pt colorectal adenomas can progress to cancer → shld remove IC 17 Pharmacist - led management of lower GIT conditions 11