COLORECTAL CANCER power point prese.pptx

Colorectal cancer

1. COLORECTAL CANCER PRESENTER: DR SSEBANENYA WILLIAM MODULATOR: DR. SR. NASSALI GORRETTI DATE: 06 th OCT 2023

2. CONT OUTLINE EPIDEMIOLOGY ANATOMY ANATOMICAL DISTRIBUTION OF CRC RISK FACTORS SPREAD PATHOGENESIS INVESTIGATIONS TREATMENT

3. Epidemiology Colorectal cancer is the third most common cancer worldwide Accounts for approximately 10% of all cancer cases and is the second leading cause of cancer-related deaths worldwide In 2020, more than 1.9 million new cases of colorectal cancer and more than 930 000 deaths due to colorectal cancer were estimated to have occurred worldwide By 2040 the burden of colorectal cancer will increase to 3.2 million new cases per year (an increase of 63%) and 1.6 million deaths per year (an increase of 73%). WHO 11 th Jul 2023

4. The incidence rates were highest in Europe and Australia and New Zealand, and the mortality rates were highest in Eastern Europe Colorectal Cancer in Uganda: A 10-Year, Facility-Based, Retrospective Study Godfrey Wekha , 1 Nelson Ssewante , 1 Angelique Iradukunda , 1 Micheal Jurua , 1 Shadia Nalwoga , 1 Sharon Lanyero , 1 Ronald Olum , 1 and Felix Bongomin 2 , 3 Revealed prevalence of 9.3% among admitted patients with lower GIT symptoms ( jan 2010 – Dec 2020). Published online 2021 Oct 7

5. ANATOMY The colon is 150cm long Divided into cecum, ascending, transverse, descending and sigmoid colon Transverse and sigmoid colon have a mesentery and are entirely intraperitoneal Ascending and descending colons – partially extraperitoneal Blood supply is by superior and inferior mesenteric arteries

6. Colonic wall has – Mucosa Submucosa Muscularis propria (inner circular layer and outer longitudinal layer comprising of 3 narrow bands tenia coli) serosa

7. Distribution of colorectal cancer Distribution of colorectal cancer Caecum –22% Ascending colon-12% Hepatic flexure- 10% Transverse colon- 10% Splenic flexure- 3% Descending colon-7% Sigmoid – 35% Rectum -14% 3% of tumors are synchronous 3% are metachronus

8. Distribution of colorectal cancer Distribution of colorectal cancer Caecum –22% Ascending colon-12% Hepatic flexure- 10% Transverse colon- 10% Splenic flexure- 3% Descending colon-7% Sigmoid – 35% Rectum -14% 3% of tumors are synchronous 3% are metachronus

9. Risk factors – exact cause is not known Age- more common in patients above 50yrs though it can affect any age Diet – low in indigestible fibres and high in animal fat, selenium deficiency, high anaerobic bacterial count in feces Personal medical history- previous H/O CRC, prior H/O Ca ovary, uterus, and breast have increased risk of colorectal cancers Family medical history- first degree relatives of persons who had CRC esp. if the relative had cancer at a younger age. 80% are sporadic and 20% hereditary Genetic factors: familial adenomatous polyposis(FAP) IBD – chron’s d’se and ulcerative colitis Irradiations and immunosuppressive drugs

10. cont Polyps – common > 50yrs The risk of malignant change in benign polyp depends on different factors including size, number, histological types of adenomas Smoking esp. for >35yrs

11. Spread Locally- spread through the intestinal wall to nearby structures- bladder, uterus, ovaries Lymphatic spread – to epicolic group of LN, then paracolic and then main groups of LN arranged around the main arteries Hematogenous spread – through IMV &SMV to liver, bones and lung Spread by implantation

12. Pathogenesis of colorectal cancer

13. Mutations may cause activation of oncogenes (K- ras ) and/or inactivation of tumor suppressor genes (APC, deleted in colorectal carcinoma [DCC], p53). Mutations in both alleles of APC( tumor suppressor gene) are necessary to initiate polyp formation In FAP, the site of mutation correlates with the clinical severity of the disease specific mutation in a family may help guide clinical decision making

14. APC inactivation alone does not result in a carcinoma. Instead, this mutation sets the stage for the accumulation of genetic damage that results in malignancy K- ras is the most affected gene and a signaling molecule in the epidermal growth factor receptor (EGFR) pathway When active, K- ras binds GTP; hydrolysis of GTP to GDP then inactivates the G-protein K- ras mutations results in inability to hydrolyze GTP, thus leaving the G-protein permanently in the active form leading to uncontrolled cell division

15. p53 crucial for initiating apoptosis in cells with irreparable genetic damage. Mutations in p53 are present in 75% of colorectal cancers. DCC and SMAD4 are tumor suppressor genes located at chromosome 18 q. Deletion of this chromosome is found in 70% of colorectal cancers

16. Staging of colon and rectal cancer according to UICC

17. Cont ,

18. RECTAL CANCER DIAGNOSIS

19. Investigations DRE –craggy ulcerated mass( rectal tumors) FOB CBC –iron deficiency anemia especially in right side Ca Electrolytes ESR – increase but not specific Carcino -embryonic antigen Imaging Plain X-ray- signs of obstruction and dilated bowel CXR –lung metastasis Barium enema irregular filling defects(apple core deformity) – negative by no means exclude the carcinoma USS- can detect mass, presence of metastssisin the liver or pelvic organs Intrarectal USS – good for diagnosis and staging of Ca esp. rectal cancer CT scan – good for evaluation of resectability MRI- has lower sensitivity and higher specificity than tumor staging

20. ENDOSCOPIES sigmoidoscopy – rigid or flexible sigmoidoscopy Colonoscopy – should be carried in all cases as in 3% of cases there will be synchronous tumor colonoscopy Biopsy

21. Treatment Multidisciplinary GOALS OF TREATMENT Early disease Remove cancer cells Kill cancer cells Keep cancer cells from returning Advanced disease Slow or stop growth of cancer cells Manage quality of life concerns Surgical management Can be used as cure or for palliation for the incurable cancer

22. Tumuor Resection . The objective in treatment of carcinoma of the colon is to remove the primary tumor along with its lymphovascular supply Lymphatics accompany main blood supply If all the tumor cannot be resected, palliation is considered ‘ debulking ’ no so effective in colorectal tumors Caecum and ascending colon right hemicolectomy Vessels divided- ileocaecal and right colic Anastomosis between terminal ileum and transverse colon Transverse colon -close to hepatic flexure – rt hemicolectomy -mid transverse – extended right hemicolectomy ( up to descending plus omentum removed en-bloc with tumor - Splenic flexure- subtotal colectomyu (up to sigmoid )

23. Descending colon -Lt hemicolectomy Vessels divided- Inf. Mesenteric, LT colic,sigmoid Sigmoid colon High ant.resection Vessels ligated- IM,LT colic and sigmoid Anastomoses of mid- descending colon to upper rectum

24. Stage specific treatment Stage 0 (Tis, N0, M0) Polyps containing carcinoma in situ (high-grade dysplasia) Polypectomy and pathologic margins should be free of dysplasia Where a polyp cannot be removed entirely a segmental resection is recommended . Stage I: The Malignant Polyp (T1, N0, M0) polyp that was thought to be benign will be found to harbor invasive carcinoma after polypectomy Invasive carcinoma in the head of a pedunculated polyp with no stalk involvement carries a low risk of metastasis (<1%)

25. Stages I and II: Localized Colon Carcinoma (T1-3, N0,M0). Most of these patients can get cured by surgical resection of the tumor Stage I with completely resected tumor can develop local or distant recurrences – adjuvant Rx not necessary 46% of Stage II with completely resected tumor die of colon cancer – adjuvant chemotherapy is suggested in some young patients, tumors with “high-risk” histologic findings )

26. Stage III: Lymph Node Metastasis ( Tany , N1, M0 ) Patients are at high risk of both local and distant recurrences Adjuvant chemotherapy is recommended MSI-high stage III disease do not benefit from 5-fluorouracil based chemotherapy. Molecullar filling is important Stage IV: Distant Metastasis ( Tany , Nany , M1). Survival is extremely limited in stage IV colon carcinoma. Patients with resectable metastases may benefit from metastasectomy The rest of the patients focus of treatment is palliation eg colonic stenting for obstructing lesions