Clinical Oncology

1. Carcinoma Colon
Dr. Md. Ruhul Amin
MD Resident, Phase B
Department of Oncology, KYAMCH

2. Introduction:

4. Etiology:
Environmental factors:

5. Genetic factors:

7. HNPCC:
• Autosomal dominant
• 3% of all CRC
• 70% lifetime risk of developing CRC before 50 years of age
• Results from germ line mutation of MMR genes: MLH1, MSH2, MSH6, PMS2
• A variant involves skin tumors and designated as Muir-Torre syndrome
• Other related cancers:
 Ovary
 Endometrium
 Stomach
 Small bowel
 Urothelium
 Biliary tract

8. FAP:
• Autosomal dominant
• Germ line mutation in APC gene
• 0.5% of all CRC
• 100 to 1000 colonic polyps by 20 years
• Lifetime risk of CRC 100% at a median age of 39
• Prophylactic colectomy can prevent CRC
• Individuals with greater than 10 cumulative colorectal adenomas referred for
genetic testing
• Annual colonoscopy are recommended around age of 10 years
• Proctocolectomy with ileal pouch anal anastomosis is the standard surgery

9. Molecular Pathogenesis:
• Chromosomal instability pathway:

11. • Microsatellite instability pathway:

13. Histopathological types:
• Adenocarcinoma
• Mucinous carcinoma
• Signet ring cell carcinoma
• Medullary carcinoma
• Squamous cell carcinoma
• Adenosquamous carcinoma
• Small cell carcinoma
• Undifferentiated carcinoma

14. Clinical presentation:
• Change in bowel habit
• Abdominal pain
• Palpable abdominal mass
• Weight loss
• Weakness
• Haematochezia
• Melena
• Obstruction
• Features of metastasis- Lymphadenopathy, hepatomegaly, jaundice, pulmonary
symptoms
• Features of complication- Acute GI bleeding, obstruction, perforation

15. Investigations:
• Biochemical- CBC, LFT, Serum electrolytes, Serum CEA, Fecal OBT
• Imaging-
 USG whole abdomen
 X-ray chest P/A view
 CECT chest & abdomen
 MRI abdomen and pelvis
 PET-CT scan not routinely done
 Barium enema
• Invasive-
 Full video colonoscopy & biopsy
• Genetic tests-
 KRAS, NRAS & BRAF mutation status
 MSI testing or IHC for MMR proteins in patient <50 years

16. Screening:

18. Staging:

21. Treatment:
• Stage I - Colectomy + LND
• Stage IIA - Colectomy + LND. For high risk features consider
adjuvant chemo
• Stage IIB - Colectomy + LND. Consider adjuvant chemo
• Stage III - Colectomy + LND + adjuvant chemo

22. Adjuvant treatment is needed for high risk patients
• Inadequate LN sampling
• Positive LN
• Close or positive margin
• LVSI, PNI
• Patient present with obstruction or perforation
• High level of pre or postoperative CEA
• Patients with MSI-H
• Poorly differentiated histology
• High level of CA 19.9
• Macroscopically infiltrating type tumor

23. Stage IV – Patients are divided into three categories:
1. Metastasis with resectable disease
2. Metastasis with potentially resectable disease
3. Metastasis with unresectable disease

24. Hepatic metastasis:
Criteria of resectability-
• Lesion number 3-4
• Lesion size </= 3 cm
• Surgical margin > 1 cm feasible
• No extrahepatic disease
• Single anatomical lobe

25. Recent guideline:
1. The disease needs to be completely resected. An R0 resection of both the intra- and
extrahepatic disease sites must be feasible.
2. At least two adjacent liver segments need to be spared.
3. Vascular inflow and outflow, as well as biliary drainage to the remaining segments, must
be preserved.
4. The volume of the liver remaining after resection must be adequate
• 20% of the total estimated liver volume for normal parenchyma
• 30%–60% if the liver is injured by chemotherapy, steatosis or hepatitis
• 40%–70% in the presence of cirrhosis

26. Surgery:
Colonoscopic resection of polyps and surgery for stage I tumor–
Carcinoma in situ as well as stage I invasive carcinomas found in a well
pedunculated polyp can be treated with colonoscopic resection, and no further
surgical management is needed as long as there is a negative margin >2 mm and the
tumor is well-differentiated without lymphovascular invasion or extension of
malignant cells beyond the stalk.

27. Anatomical resection of bowel:
Lesion in the cecum and ascending
colon –
Right hemicolectomy:
• Terminal 10 cm of ileum, cecum, ascending colon,
right colic flexure and right half of transverse
colon.
• The ileocolic, right colic, and right branch of
middle colic vessels are then ligated and divided.
• Ileotransverse anastomosis is done

28. Lesions in transverse colon –
• Lesion located proximal and near the
hepatic flexure –
Extended right hemicolectomy. Include the
middle colic vessel. Anastomosis is between
the ileum and the remaining colon.
• Lesion at the mid portion of transverse
colon: Transverse colectomy

29. Lesions in descending and sigmoid colon –
• Lesion in the descending colon: Left
hemicolectomy
• Lesion in the sigmoid colon: Sigmoid
colectomy or extended left
hemicolectomy

30. Palliative resection of colon –
Needed for complication by cancer such as bleeding, obstruction and perforation
• Resection of the tumor and primary anastomosis with or without a diversion is
ideal
• Sometimes transverse loop colostomy or a colostomy and mucous fistula can be
performed to temporize the situation and allow the patient to be prepared and
resuscitated adequately for a definitive resection at a second exploration.
• Bypass operations
• Place an endoscopic stent either for temporary decompression or for definitive
palliation of unresectable lesions
• Surgical debulking
• Surgical metastasectomy

31. Adjuvant Chemotherapy:
• FOLFOX and CAPOX are the regimens of choice
• Should be started within 8 weeks of surgery
• Duration of treatment is 6 months
• Irinotecan based regimens should not be used
• Targeted Therapy should not be used
• 5FU without oxaliplatin remains an option for elderly patients
• MSI predicts lack of response to 5FU

32. Targeted therapy:
Anti VEGF antibody
1. Bevacizumab:
• First line or second line treatment
• Needs to be given with other cytotoxic drug regimens (FOLFOX or FOLFIRI)
• Survival benefit over cytotoxic drug alone
2. Ramucirumab and Aflibercept can be used as second line therapy

33. Anti EGFR antibody:
• Cetuximab and Panitumumab can be combined with oxaliplatin or irinotecan
based chemotherapy
• Improved progression free survival in KRAS and NRAS wild-type tumors.
• KRAS and NRAS mutation is present in 40-50% of patients and predict resistance
to these two drugs
• Unlike Bevacizumab these two drugs can be used as single agent without
cytotoxic drugs

34. Tyrosine Kinase Inhibitors:
• Regorafenib can be used as third line treatment
• After progression on oxaliplatin, 5FU, irinotecan, bevacizumab and
cituximab

35. MTT used in metastatic CRC:

36. Radiotherapy:
No survival benefit with add RT in adjuvant setting
Adjuvant tumor bed irradiation with concurrent 5-FU–based CT should be
considered for patients –
• With tumors invading adjoining structures
• With tumors complicated by perforation or fistula
• Where incomplete resection is performed

37. Follow up:
• Physical examination and blood CEA monitoring every 3 months for the first 3
years and every 6 months up to 5 years
• CT scans of the chest, pelvis and abdomen are recommended once a year for the
first 3 years
• Colonoscopy is recommended at 1 year after resection and then 3 years later, and
then every 5 years
• Positron emission tomography (PET) scans are specifically not recommended for
routine screening and surveillance

38. Thank You