Diagnosis & management of colorectal cancer

1. Diagnosis & management of colorectal cancer Dr.Adisai Pattatang

2. Pathogenesis

3. Gene mutation ที่เกี่ยวข้องกับการเกิด CRC มี 2 กลุ่ม คือ5 1. Tumor suppressor gene เช่น adenomatous polyposis coli gene (APC), deleted cancer gene (DCC) และ P53 เป็นต้น โดยลักษณะ mutation ที่เกิดขึ้นมักเป็น loss of heterozygosity (LOH)

4. 2. Mismatch repair gene (MMR) ลักษณะของ Mutation ที่เกิดขึ้นคือ Microsatellite instability (MSI) ถ้า CRC เกิดจาก gene mutation แบบ LOH ซึ่งมักเป็นกลไกของการเกิด sporadic colon cancer เป็นส่วนใหญ่

5. พบว่ามักเป็นมะเร็งที่ left colon มี DNA เป็น aneuploid ผู้ป่วยมักอายุมากกว่า 60 ปี มีความรุนแรงของพยาธิสภาพมากกว่า เกิด metastasis ได้มากกว่า และตอบสนองต่อ chemotherapy ได้น้อยลง

6. แต่ถ้า CRC เกิดจาก gene mutation แบบ MSI จะพบว่าเป็นมะเร็งที่ right colon มากกว่า มี prognosis ดีกว่า และจะสอบสนองต่อการรักษาด้วย chemotherapy ดีกว่า6

7. Adenocarcinomas (98%)comprise most rectal cancers and are the focus of this discussion. Other rare rectal cancers, including carcinod (0.1%), lymphoma (1.3%), and sarcoma (0.3%), are not discussed.

8. Squamous cell carcinomas may develop in the transition area from rectum to analverge and are considered analcarcinomas.

10. Most (15-20%) colorectal cancers develop in people with either a positive family history or a personal history of colorectal cancer or polyps.

11. The remaining cases occur in people with certain genetic predispositions, such as hereditary nonpolyposis colorectal cancer (HNPCC, 4-7%) or familial adinomatous polyposis (FAP, 1%) or in people with inflammatory bowel disease (IBD, 1%).

12. Epidemiology

13. In USA each year • Approximately 135,000 new cases and 55,000 death • Two thirds of these cases occur in colon and one thirds occur in rectum.

16. - Approximately 75% of colorectal cancers are sporadic and develop in people with no specific risk factors. The remaining 25% of cases occur in people with significant risk factors.

17. Race:- Western nations tend to have a higher incidence than Asian and African countries; however, within the United States, little difference in incidence exists among whites, African Ameicans, and Asian Americans.

18. - Among religious denominations, colorectal cancer occurs more frequently in the Jewish population.

19. Sex: The incidence of colorectal malignancy is slightly higher in males than in females.Age: Incidence peaks in the seventh decade; however, cases have been reported in young children

20. Incidence in Thailand

23. Clinical manifestation

24. History:- Bleeding - This is the most common symptom of rectal cancer and occurs in 60% of patients. - Bleeding often is attributed to other causes (eg, hemorrhoids), especially if the patient has a history of other problems.

25. - Profuse bleeding and anemia are rare. - Bleeding may be accompanie by the passage of mucus, which warrants further investigation.

26. - Occult bleeding: This is detected on screening fecal occult blood test (FOBT) in 26% of cases

27. - Change in bowel habits - Present in 43% of patients, this symptom has several different presentations. Often, it occurs in the form of diarrhea, particularly if the tumor has a large villous component.

28. - These patients may have hypokalemia on laboratory studies. - The capacity of the rectal reservoir may mask the presence of a small lesion. - Some patients experience a change in caliber of the stool.

29. - Large tumors can cause obstructive symptoms. - Tumors located low in the rectum can cause a feeling of incomplete evacuation and tenesmus.

30. Abdominal pain - Partial large bowel obstruc- tion may cause colicky abdominal pain and bloating , present in 20% of cases.

31. - Back pain is usually a late sign caused by a tumor invading or compressing nerve trunks. - Urinary symptoms may occur if the tumor is invading or compressing the bladder or prostate.

32. - Malaise: This nonspecific entity is the presenting symptom in 9% of cases. - Bowel obstruction: Complete obstruction of the large bowel is rare and is the presenting symptom in 9% of cases.

33. - Pelvic pain: This late symptom usually indicates nerve trunk involvement and is present in 5% of cases. - Other presentations include emergencies such as peritonitis from perforation(3%) or jaundice, which may occur with liver metastases (<1%).

34. Physical:- Physical examination is performedwith specific attention to possible metastatic lesions, including enlarged lymph nodes or hepatomegaly. The remainder of the colon is also examined.

35. Digital rectal examination - The easy accessibility of the rectum provides an opportunity to readily detect abnormal lesions via digital rectal examination (DRE). The average finger can reach approximately 8 cm above the dentate line.

36. - Tumors can be assessed for size, ulceration, and presence of any pararectal lymph nodes. Fixation of the tumor to surrounding strctures (eg. Sphincters, prostate, vagina) also can be assessed.

37. - DRE also permits a cursory evaluation of the patient’s sphincter function. This information is necessary when determining whether a patient is a candidate for a sphincter-sparing procedure.

38. IMAGING

39. BE :Apple core appearrance

40. - Chest radiograph: Obtain a chest radiograph to rule out pulmonary metastases and to determine whether the patient has any gross underlying pulmonary disease, including emphysema.

41. CT scan : This study is generally used to determine the presence or absence of metastases.- CT scans can identify lesions in the liver, adrenals, ovaries, lymph nodes, and other organs.

42. - In 10% of patients, the CT scan misses small liver lesions. - When combined with an angiogram, a CT scan is 95% accurate in identifying liver metastases.

43. - Some information can be gleaned from a CT scan regarding depth of penetration of the primary rectal tumor. When performed with rectal contrast given as an enema, accurately in 84% of cases.

44. - CT scan detects lymph nodes larger than 1 cm in 75% of cases - CT scans are helpful in determining whether patients require preoperative chemoradiation therapy.

45. MRI actually is the most sensitive test for determining the presence of liver metastases and often is used if liver resection is considered. MRI

46. Endorectal ultrasound

47. - Endorectal ultrasound (ERUS) is an invaluable tool in assessing depth of invasion of rectal cancers; it is 72-94% accurate.

50. - The accuracy of detection of lymph node involvement ranges from 73-86%. • Most of these nodes are larger than 1 cm. Smaller nodes can be detected, but the accuracy of determining tumor involvement is substantially lower.