Slide 1

Slide 2

Anatomic Considerations and Patterns of Spread

Slide 3

Slide 4

Rectum 12 to 15 cm in length from the rectosigmoid junction to the puborectalis ring upper third middle third (posterior border of the rectouterine pouch or rectovesical space) lowest third no serosal barrier

Slide 5

Colonic nodal drainage consists of pericolic nodes and nodes in association with the vascular supply to the colon (i.e., mesenteric nodes rectal nodal drainage include the perirectal, presacral, and internal iliac nodes.

Slide 6

Epidemiology, Molecular Cascade, Risk Factors, Hereditary Disease, and Clinical Presentation The median age is in the seventh decade chemical carcinogens Environmental and dietary factors

Slide 7

Factors shown to increase the risk include increasing age, male sex,rectal cancer excessive alcohol use family history of colorectal cancer, increasing height, increasing body mass index, processed meat intake low folate consumption. consumption of fruits and vegetables ? The role of chemopreventive agents (carotenoids, aspirin, and other nonsteroidal anti-inflammatory drugs) ?

Slide 8

Slide 9

Biologic and genetic pathways of development of colorectal cancer proto-oncogenes (mutations in the ras proto- oncogene.) tumor suppressor genes (inactivation adenomatous polyposis coli (APC) and P53)

Slide 10

: microsatellite instability Biology The majority of HNPCCas well as a minority of sporadic colorectal cancers harbor microsatellite instability. mutations in genes encoding enzymes that repair DNA replication errors Studies have suggested that patients with tumors possessing a high frequency of microsatellite instability have a more favorable outcome and develop fewer metastases

Slide 11

Colorectal cancer minimal or no symptoms Nonspecific bowel habits, weakness, intermittent abdominal pain, nausea, and vomiting. The persistence of such symptoms as well as any evidence of iron deficiency anemia should be investigated

Slide 12

Clinical Presentation right colon exophytic,iron deficiency anemia left colon and sigmoid colon deeply invasive, annular, and accompanied by obstruction and rectal bleeding Rectal cancer frequently results in bleeding and alterations in bowel habits.

Slide 13

FIGURE 58.1. Idealized depiction of peritoneal relationships in the colon and rectum. The transverse and sigmoid colon are intraperitoneal, with a complete peritoneal covering (serosa) and mesentery. The ascending and descending colon are retroperitoneal, lack a true mesentery, and usually do not have a peritoneal covering posteriorly or laterally. The upper rectum begins above the peritoneal reflection and has peritoneum anteriorly and laterally. The lower half to two thirds of the rectum is below the peritoneal reflection (infraperitoneal).

Slide 14

Slide 15

Slide 16

Prevention and Early Detection Neoplastic polyps are precursors of colon cancers Most colorectal cancers arise from pre-existing polyps Patients with neoplastic polyps should be considered at high risk for large bowel cancer, and polypectomy may reduce this risk. With the availability of the flexible colonoscope and endoscopic polypectomy, polyps can be removed at a premalignant stage and patients followed closely.

Slide 17

The goal of screening is to detect preinvasive polyps or early invasive cancer. The presence of polyps increases the risk for cancer to approximately 15%. Data from programs in which proctoscopy is performed annually suggest that routinely scheduled polypectomy reduces the development of subsequent bowel cancer by 80% or more.

Slide 18

The American Cancer Society has recommended screening should begin at age 50 in the average risk patient by either: Annual fecal occult blood test and/or flexible sigmoidoscopy every 5 years, Double contrast barium enema every 5 years Colonoscopy every 10 years

Slide 19

patients at high risk adenomatous polyps history of colorectal cancer first-degree relative with colorectal cancer or adenomas inflammatory bowel disease family history or genetic testing

Slide 20

Intensive surveillance is recommended for patients at high risk 1. Computed tomography (CT) colonography 2. genetic fecal testing are being studied Although screening methods can detect colorectal cancer at an early stage,

Pathology (>90%) adenocarcinomas Scc, carcinoid, leiomyosarcoma, and lymphoma. Most grading systems classify adenocarcinoma as well, either moderately or poorly differentiated.

Slide 22

Pathways of Spread invade from mucosa through the bowel wall and beyond, with involvement of lymphatic channels and lymph nodes. Hematogenous spread can occur, primarily to the lung and liver. There is little propensity for colon cancer to spread longitudinally within the bowel wall, in contrast to esophageal or gastric cancers

Slide 23

Patient Evaluation/Staging Pretreatment evaluation 1. pathological confirmation 2. colonoscopy ( synchronous primaries occurring in 3% to 5%) 3. CBC with LFT and CEA 4. abdominal and pelvic CT scan 5. CXR 6. (PET) scan 7. (MRI), 8. Ultrasound

Slide 24

(PET) scan .

Slide 25

Prognostic factors depth of tumor invasion into and beyond the bowel wall the number of involved regional lymph nodes presence or absence of distant metastases The tumor, node, metastasis (TNM) system of the American Joint Committee on Cancer can be used as a clinical (preoperative) or postoperative staging system

Slide 26

Colorectal Tumor, Node, Metastasis Staging, 2002 Tis Carcinoma in situ: Intraepithelial or invasion of lamina propria T1 Tumor invades submucosa T2 Tumor invades muscularis propria T3 Tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues T4 Tumor directly invades other organs or structuresa and/or perforates visceral peritoneum (includes invasion of other segments of colon)

Slide 27

Direct invasion in T4 includes invasion of other segments of the colorectum by way of the serosa; for example, invasion of the sigmoid by a carcinoma of the cecum. Tumor that is adherent to other organs or structures, macroscopically, is classified as T4. However, if no tumor is present in the adhesion, microscopically, the classification should be pT3

Slide 28

N1 Metastasis in one to three regional lymph nodes N2 Metastasis in four or more regional lymph nodes (Tumor nodules in the pericolonic adipose tissue without evidence of residual lymph node are classified as a regional lymph node metastases)

Slide 29

Therapy of Colon Cancer Surgery based on the anatomy and mechanisms by which this disease spreads. avoid cutting across tumor in intramural lymphatics, sufficient lengths of bowel must be resected

Slide 30

Resection results in excellent cure rates average 5-year survival o 97% for T1N0 o 85% to 90% for T2N0 o 65% to 75% for T3T4N0 o 50% (T3N+) and 35% (T4N+)

Slide 31

American Joint Committee on Cancer Stage Grouping MACDukes MNT Stage AAT1I B1AT2 B2BT3IIA B3BT4IIB

Slide 32

C1CM0N1T1-T2IIIA C2/C3CM0N1T3-T4IIIB C1/C2/C3CM0N2Any TIIIC D-M1Any NAny TIV

Slide 33

Adjuvant Chemotherapy addition of 5FU (5-fluorouacil) and leucovorin improves survival for resected stage III patients Capecitabine, an oral 5-FU prodrug, has demonstrated similar overall and disease free survival rates to 5- FU/leucovorin in patients with resected stage III colon cancer 5-FU/leucororin/oxaliplatin in resected stage II or III colon cancer patients showed improved disease-free FU/LV/oxaliplatin as the new standard chemotherapeutic regimen in the adjuvant treatment of completely resected, high-risk colon cancer The efficacy of agents such as bevacizumab and cetuximab as adjuvant therapy is being investigated

Slide 34

Adjuvant Irradiation with or without Concurrent Chemotherapy The potential indications for adjuvant radiation therapy in colon cancer are based on analyses of patterns of failure following resection local failure in colon cancer also depends on anatomic origin 1. ascending and descending colon 2. mid-sigmoid and mid-transverse colon 3. cecal, hepatic/splenic flexure, and proximal/distal sigmoid tumors are variable depending on the amount of mesentery present, tumor extension, and the adequacy of radial margins. When colon cancers adhere to or invade adjacent structures, local failure rates exceed 30% following surgery alone.

Slide 35

In summary, local failure occurs in patients with colonic tumors where there are anatomic constraints on radial resection margins, including tumors adherent to or invading adjacent structures.

Slide 36

To summarize, these studies have suggested that operative bed failures in high-risk patients undergoing resection alone are at least 30%, and that the risk of local failure is reduced by the administration of adjuvant radiation therapy. Irradiated patients included those with T4N0/N+, T3N+ disease (excluding mid-sigmoid and mid- transverse colon) and T3N0 patients with margins of 1 cm IORT Ten to 12.5 Gy for complete resection 12.5 to 15 Gy for microscopic residual ">

IORT No IORT metastases less than T4 disease adequate margins >1 cm IORT Ten to 12.5 Gy for complete resection 12.5 to 15 Gy for microscopic residual 17.5 to 20 Gy for gross residual disease. The risk of peripheral neuropathy was 20% for doses >15 Gy. IORT improves local control, especially with a gross total resection, but not survival for locally advanced rectal cancer.

Slide 106

Reirradiation Recurrent rectal cancer is often approached the same way as T4 disease with an aggressive treatment plan of CHRTby surgery and then adjuvant CHT. IORT is considered The 5-year overall survival is approximately 20%.The local control is about 40% in patients with no prior radiation to 10% to 20% in patients who had prior radiation.

Slide 107

Slide 108

Slide 109