Download - RECTAL CARCINOMA
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RECTAL CARCINOMARECTAL CARCINOMA
ELSHAMI ELAMIN, MD
Central Care Cancer Center
Newton, KS-USA
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RISK FACTORSRISK FACTORS
Dietary factors• Fat• ? Fiber• ? Calcium• ? Vitamins (E, -carotene)
Aspirin/NSAIDs (Cox inhibitors)• Sulindac reduces polyps in FAP pts• Aspirin lower risk of CRC
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RISK FACTORSRISK FACTORS
Genetic Factors– FAP(APC gene = Tumor suppressor gene)
• 1-2% of CRC• Invasive cancer occurs at ~ 42Y
– HNPCC (MMR mutations)• Hx of > 3 family members involving 2
generations with one diagnosed before age 50• 4-6% incidence• Rt-sided cancer• Caused by defective DNA mismatch repair genes
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Steps for Colorectal CarcinogenesisSteps for Colorectal Carcinogenesis
1- Mutation at MCC and APC genes
2- K-ras oncogene activates adenoma to carcinoma
3- Mutation of p53 tumor suppressor gene
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SCREENINGSCREENINGPatients with average risk
• Asymptomatic• >50Y• No colorectal risk factors
FOBT (33% reduction in mortality)Flexible sig (60-80% reduction in mortality)Double-contrast BEColonoscopy (Gold standard)
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Patients with increased RiskPatients with increased Risk
First-degree relative with CRC or adenomatous polyps
FAPF.H. of HNPCCAdenomatous polypsCRCIBD
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Hereditary CRC syndromesHereditary CRC syndromesScreening and ManagementScreening and Management
FAP– Genetic counseling/gene testing
• Is cost-effective
– Genetic mutation not identified:• Flex sig at puberty and annualy
• Colonoscopy if +ve sig
– +ve FAP• Total colectomy
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HNPCC (Lynch syndrome)HNPCC (Lynch syndrome)
Lynch I:– No associated cancers
Lynch II:– Associated with ovarian, uterine cancers
Genetic testing– Difficult due to multiple mutations
• MLH1, MSH2 mutations
Screening begin at 20Y and every 1-2YGenetically +ve: Consider colectomy/TAH/BSO
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Work-upWork-upLaboratory:
– LFTs– CBC, Iron profile– CEA
Preoperative CT scan– Colon cancer: Adjacent organ invasion/Liver met– Rectal: Adjacent organ invasion/LN spread
• For preop RT
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MRIMRI
Bowel wall penetration– MRI: 64%, CT: 62%
Sensitivity for LN met: 15-40%Endorectal surface coil MRI for N1
– 72% specificity
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Transrectal USTransrectal US
Evaluation for preop cheop/RT• Only 83-88% specific in separating T-T2 from T3-T4
LN specificity• 28% for 5mm LN
• 62% for 7mm
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CEA scanCEA scan
Coupled with standard CT
• Can predict preop respectability
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PET ScanPET ScanStagingRestaging
– 91% sensitivity, ~ 100% specificity for pelvic disease (CT: 52%, 80%)
– 95% sensitivity for liver disease (CT 74%)
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StagingStagingDukes’ classification
– Based on depth of invasion and LN• A: Limited to bowel wall
• B: Extrarectal tissues
• C: LN +
Modified Dukes’ (Astler-Coller system)– C1 and C2
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TNMTNMStage I: T1 (invade submucosa) A
T2 (invade muscul propria) B1Stage II: T3 (invade through musc propria B2
into subserosa or nonperit. Tissue)
T4 (perforate ves perit or B3 invade adjacent structure)
Stage III: N1 (1-3 pericolic/rectal) N2 (> 4) C
N3 (along vascular trunk)
Stage IV: M1
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Prognostic FactorsPrognostic FactorsAdjacent tissue or vascular invasionNodal status
• Micromets (<5mm) same as enlarged LN
• 4 LN vs >4
? Cellular pathologic factors• S-phase, ploidy
Liver mets• Normal LFTs: 18 month med S
• Elevated Bil: 6 wks med S
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Prognostic FactorsPrognostic FactorsCEA
• Weak prognostic factor
• Persistant CEA elevation = Residual dz
• May increase initially during adjuvant
Not prognostic factors• Age, Sex, Tumor size
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Rectal CaRectal CaSurgical TreatmentSurgical Treatment
Abdominal Perineal Resection (APR)• Permanent Colostomy
Sphincter Preservation
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APRAPRBased on:
• Rectal cancer spread via lymphatic pathways in proximal, lateral and distal direction
Decreases local recurrenceImprove survivalPermanent colostomy
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APRAPRCandidates
• Primary sphincter dysfunction
• Tumor invading anal canal
• High risk for local recurrence• Bulky disease
• Poorly differentiated involving lower 1/3
• Direct extension into adjacent organs
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Total Mesorectal Excision Total Mesorectal Excision (TME)(TME)
Tumor spread into adjacent mesorectum>2cm distal extension from the margin carries
poor prognosisDecreases local recurrenceImprove survivalStandard for mid and lower rectal cancersPreserves pelvic autonomic nerve function
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Surgical Options for Surgical Options for Sphincter PreservationSphincter Preservation
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Local ExcisionLocal ExcisionLower 1/3 early rectal cancer (T1)< 4 cm in diameterMobile lesionInvolve < 1/4 of circumference of bowelModerate to well differentiated
• From 2 prospective Trials• T1 : Local excision alone
• T2 : Local excision + CT/RT
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Local Excision with RTLocal Excision with RTIndications
– T2– Lymphatic/vascular invasion– Poor histology– Positive margin– Fragmented resection
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Endocavitary RTEndocavitary RTSelection criteria
• Distal lesion
• No disease beyond bowel wall
• No major extension to anal canal
• T < 3x5 cm
Local failure• 5-20%
• Salvage radical surgery
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Low Anterior Resection Low Anterior Resection (LAR)(LAR)
1- Bowel divided at 5cm above rectal tumor
2- Ligation of superior hemorrhoidal artery
3- Total Mesorectal Excision (TME) for mid/lower rectal tumors
4- 11/2 - 2cm distal margin
5- Colo-Rectal anastomosis
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Colonic J-PouchColonic J-Pouch
For low rectal cancer
To prevent incontinence/urgency
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APR vs Sphincter Sparing Resections APR vs Sphincter Sparing Resections (SSR) in Mid-rectal cancers(SSR) in Mid-rectal cancers
5 Y S %
APR SSR
Mayo et al 69 72
Patel et al 56 64
Jones/Thomson 52 67
Williams/Johnston 62 74
• Local recurrence: APR 8%, SSR 11% (not significant)
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ADJUVANT THERAPYADJUVANT THERAPY
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Rectal CancerRectal CancerIncidence of local failure after resection
– T1, T2N0: <10%– T3N0: 15-30%– T3N1: 35-50%– T3-T4N1: 60%
• No successful salvage procedure
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Pre-Operative RTPre-Operative RTImproves local control (Several studies)
– Improves OS (Only one study)
Downside– Overtreatment of T1, T2
• Use Transrectal US
– Treatment of patient with hepatic mets• Use spiral CT
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Locally Advanced Rectal CancerLocally Advanced Rectal Cancer
PreOp external RT + IntraOp RT• 67%5Y local control, 57% DFS
PreOp RT or Chemo/RT• 70-85% resectability and sphincter sparing surgery
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Locally Recurrent DiseaseLocally Recurrent DiseaseTreatment options depend on
– Local extent• Isolated suture line recurrence after LAR
– APR + Chemo/RT if no prior RT
• Local recurrence without prior RT
– PreOp chemo/RT, Surgery + IORT
• Poor long-term DFS even with complete resection
– Symptoms– Distant mets– Prior adjuvant therapy
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CEACEA43-89% Sensitivity, 70-90% specificityPreOp elevation predicts worse prognosis
– Not useful in determining the need for adjuvant
Elevation correlates with Dukes’ stagePersistent 1-month postOp elevation predicts
metsMonitor CEA q2-3 moths during chemoModest elevation
• Fatty liver infiltration, hepatitis, pneumonia, GE
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Systemic ChemotherapySystemic Chemotherapy
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5-FU5-FU 5 days IVP regimen:
• Mucositis, diarrhea, neutropenia
Wkly IVP regimen:• Diarrhea
CI regimen/Capecitabine:• Hand-foot syndrome, mucositis
• Diarrhea or neutropenia
High dose regimen 24-48hrs• Altered MS, angina-like chest pain
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Oxaliplatin = IrinotecanOxaliplatin = Irinotecan
FOLFOXFOLFIRIXELOXXELIRI
• AVASTIN/ZALTRAP• ERBITUX/VECTIBIX• REGORAFENIB
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Regional TherapyRegional Therapy(Liver Mets)(Liver Mets)
HAI of FUDR via an implanted pump• Addition of dexamthazone reduces sclerosing
cholangitis and enhances RR
Chemoembolization• 3mg/ml Adria + 3mg/ml MC + 10mg/ml CDDP with
bovine collagen
• Postembolization syndrome (fever, RtUQ pain, N/V, lethargy, hematologic toxicity)
Resection