Download rectal carcinoma

RECTAL CARCINOMA
ELSHAMI ELAMIN, MD
Central Care Cancer Center
Newton, KS-USA
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RISK 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 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 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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SCREENING
 Patients
with average risk
• Asymptomatic
• >50Y
• No colorectal risk factors

FOBT (33% reduction in mortality)
 Flexible sig (60-80% reduction in mortality)
 Double-contrast BE
 Colonoscopy (Gold standard)
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Patients with increased Risk

First-degree relative with CRC or
adenomatous polyps
 FAP
 F.H. of HNPCC
 Adenomatous polyps
 CRC
 IBD
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Hereditary CRC syndromes
Screening 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)

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 1-2Y
 Genetically +ve: Consider colectomy/TAH/BSO
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Work-up

Laboratory:
– 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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MRI

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 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 scan

Coupled with standard CT
• Can predict preop respectability
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PET Scan

Staging
 Restaging
– 91% sensitivity, ~ 100% specificity for pelvic
disease (CT: 52%, 80%)
– 95% sensitivity for liver disease (CT 74%)
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Staging

Dukes’ classification
– Based on depth of invasion and LN
• A:
• B:
• C:

Limited to bowel wall
Extrarectal tissues
LN +
Modified Dukes’ (Astler-Coller system)
– C1 and C2
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TNM

Stage I:

Stage II:
T1 (invade submucosa)
T2 (invade muscul propria)
T3 (invade through musc propria
A
B1
B2
into subserosa or nonperit. Tissue)
T4 (perforate ves perit or
B3
invade adjacent structure)

Stage III:

StagePrevious
IV:
N1 (1-3 pericolic/rectal) N2 (> 4)
N3 (along vascular trunk)
M1 Next
C
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Prognostic Factors

Adjacent tissue or vascular invasion
 Nodal status
• Micromets (<5mm) same as enlarged LN
• 4 LN vs >4

? Cellular pathologic factors
• S-phase, ploidy

Liver mets
• Normal LFTs:
• Elevated Bil:
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18 month med S
6 wks med S
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Prognostic Factors

CEA
• 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 Ca
Surgical Treatment

Abdominal Perineal Resection (APR)
• Permanent Colostomy

Sphincter Preservation
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APR

Based on:
• Rectal cancer spread via lymphatic pathways in
proximal, lateral and distal direction

Decreases local recurrence
 Improve survival
 Permanent colostomy
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APR

Candidates
• 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
(TME)

Tumor spread into adjacent mesorectum
 >2cm distal extension from the margin carries
poor prognosis
 Decreases local recurrence
 Improve survival
 Standard for mid and lower rectal cancers
 Preserves pelvic autonomic nerve function
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Surgical Options for
Sphincter Preservation
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Local Excision

Lower 1/3 early rectal cancer (T1)
 < 4 cm in diameter
 Mobile lesion
 Involve < 1/4 of circumference of bowel
 Moderate to well differentiated
• From 2 prospective Trials
• T1 : Local excision alone
• T2 : Local excision + CT/RT
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Local Excision with RT

Indications
–
–
–
–
–
T2
Lymphatic/vascular invasion
Poor histology
Positive margin
Fragmented resection
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Endocavitary RT

Selection criteria
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•
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•
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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
(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-Pouch

For low rectal cancer

To prevent incontinence/urgency
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APR vs Sphincter Sparing Resections
(SSR) in Mid-rectal cancers
5YS%
Mayo et al
Patel et al
Jones/Thomson
Williams/Johnston
APR
69
56
52
62
SSR
72
64
67
74
• Local recurrence: APR 8%, SSR 11% (not significant)
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ADJUVANT THERAPY
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Rectal Cancer

Incidence of local failure after resection
–
–
–
–
T1, T2N0:
T3N0:
T3N1:
T3-T4N1:
<10%
15-30%
35-50%
60%
• No successful salvage procedure
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Pre-Operative RT

Improves 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 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 Disease

Treatment 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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CEA

43-89% Sensitivity, 70-90% specificity
 PreOp elevation predicts worse prognosis
– Not useful in determining the need for adjuvant
Elevation correlates with Dukes’ stage
 Persistent 1-month postOp elevation predicts
mets
 Monitor CEA q2-3 moths during chemo
 Modest elevation

• Fatty liver infiltration, hepatitis, pneumonia, GE
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Systemic Chemotherapy
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5-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 = Irinotecan
FOLFOX
 FOLFIRI
 XELOX
 XELIRI

• AVASTIN/ZALTRAP
• ERBITUX/VECTIBIX
• REGORAFENIB
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Regional Therapy
(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
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