2.9 Lower Digestive System - RECTAL CANCER Cheat Sheet (DRAFT) by Molly

Struct­urally, the four major regions of the large intestine are the cecum, colon, rectum and anal canal.

The colorectum is lined with columnar epithelium as far as the dentate line in the middle of the anal canal, where sensitive squamous epithelium in continuity with that of the perineum takes over.

The defecation reflex occurs in response to distention of the rectal wall, receptors send sensory nerve impulses to the descending colon, sigmoid colon, rectum and anus. The resulting contra­ction of the longit­udinal rectal muscles shortens the rectum, thereby increasing the pressure within it.

The amount of bowel movements that a person has over a given period of time depends on various factors such as diet, health and stress. The normal range of bowel activity varies from two or three bowel movements per day to three or four bowel movements per week.

In Australia, there are more than 12,500 new cases diagnosed each year. The risk of being diagnosed by age 85 is 1 in 10 for men and 1 in 15 for women. More than 4372 people die of colorectal cancer each year.

Hereditary non-po­lyposis colorectal cancer (HNPCC) results from defects in MMR genes and represents the most common form of hereditary colorectal cancer. Less than 5% of all colorectal cancer cases are HNPCC.

Other risk factors include: personal history of colorectal adenomas, first degree family history of colorectal cancer or colorectal adenomas, inflam­matory bowel disease, obesity and smoking.

The epithelium of the mucosa is simple columnnar epithelium that contains mostly absorptive and goblet cells.

Solitary lymphatic nodules are also found in the lamina propria of the mucosa and may extend through the muscularis mucosae.

Decision making is strongly influenced by patient preference and co-mor­bid­ities, as well as tumour staging and other prognostic factors. Many of the latter are determined primarily by the pathol­ogist. The amount and complexity of inform­ation required from the pathol­ogist has increased apace with the develo­pment of increa­singly sophis­ticated surgical and adjuvant or neo-ad­juvant treatm­ents.

Pathol­ogical reporting of rectal cancer provides important prognostic inform­ation about the risk of both systemic relapse and local pelvic recurr­ence. Ideally, the report should provide the clinician with all the known pathol­ogical variables that have been shown to influence prognosis. These include:

For the surgeon, the pathology report of a rectal cancer specimen has added signif­icance. If circum­fer­ential margins are carefully examined and reported they provide useful feedback on the quality of surgery and an indication of the risk of local recurrence in a given patient.

Uniformity of staging allows direct comparison of patient outcomes between centres.

The colonic and rectal mucosa are only one cell thick and have a glandular archit­ecture of epithelial cell inter-­spread with goblet cells that synthesize mucus.

Over the past decades several classi­fic­ation systems have been in use intern­ati­onally to stage rectal tumours.

The TNM system has three main advantages over the other systems.

Secondly, it has a compre­hensive set of defini­tions and rules of applic­ation that ensure uniform use.

As newer anatomic and molecular markers are uncovered and their value in rectal cancer staging, predic­tab­ility to treatment response and treatment selection is defined, the role of such markers in the TNM system may need consid­era­tion.

Accurate initial staging can influence therapy by determ­ining the type of surgical interv­ention and the choice of neo-ad­juvant therapy to maximise the likelihood of clear margins.

Additi­onally clinical evaluation and staging procedure may include:

2. Complete colono­scopy to eliminate cancers elsewhere in the bowel.

The natural history of rectal cancer demons­trates major lymphatic spread in a cephalad direction contained within the peri-r­ectal fascia and along the mesore­ctum, that is commonly dissected by standard TME (total mesorectal excision) surgery.

Rectal cancer is an ideal model for cancer screening due to its relatively well defined natural history and when diagnosed in the early stages effective treatment can be offered.

Early stage tumours are also candidates for removal of the tumour through a flexible endoscope or other minimally invasive surgery approa­ches.

Pre-op­erative staging is used to determine the indication for neoadj­uvant therapy as well as the indication for local excision versus radical cancer resection. Local excision is likely to be curative for patients with a primary tumour that is limited to the sub-mucosa (T1N0M0), without high-risk features and in the absence of metastatic disease.

Once the tumour invades the muscularis propria (T2), radical rectal resection in acceptable operative patients is recomm­ended. In patients with transmural or node positive disease (T3, T4 and/ or N1) with no distant metast­ases, preope­rative chemor­adi­ation followed by radical resection according to the principles of total mesorectal excision has become widely accept­able.

-total mesorectal excision (TME)
-autonomic nerve preser­vation (ANP)
-circumferential resection margin (CRM)
-distal resection margin
-sphincter preser­vation
-options for restor­ation of bowel continuity
-laparoscopic approaches
-postoperative quality of life

1. post-o­per­ative chemo-­rad­iation with different 5-fluo­rou­racil (5-FU) based schedules

3. long course radiation therapy with or without chemot­herapy

Local control and acute and late effects on normal tissue are dependent on the volume, total dose, dose per fraction and overall treatment time. To achieve a high probab­ility of steril­isation of micros­copic disease, a dose of the order of 50Gy in 25 fractions given over 5 weeks is required.

n increasing body of data suggests the superi­ority of pre-op­erative radiot­herapy combined with chemot­herapy in terms of local control, diseas­e-free survival and reduction of bowel toxici­ties. As mentioned above there are two types of pre-op­erative radiot­herapy:

Short-­course pre-op­erative radiot­herapy is delivered one week before surgery in 5 daily fractions of 5 Gy without any chemot­herapy.

Probably the most important argument in favour of pre-op­erative radiation therapy is tumour regres­sion, which may improve the likelihood of a successful resection with free margins. The possib­ilities of preserving the sphincter are increased for regressing tumours arising in the distal rectum.

After pre-op­erative chemo- and radiot­herapy, a pathologic complete response rate of 10–25% has been reported as well as a tumour down staging rate of 40–80% with both improved local control and survival.

The advantage of preope­rative radiation therapy planning relies on the presence of tumour tissue, which can be easily located and radiol­ogi­cally defined for target­-volume defini­tion. The GTV and CTV can be delineated as soft tissue anatomy on CT images, often accomp­anied by other imaging modalities (Positron Emission Tomography (PET), and MRI). Unfort­una­tely, the standard CT-based GTV deline­ation remains associated with consid­erable inaccuracy and extension of rectal carcinoma into the rectal wall or peri-r­ectal tissue structures usually is not visible.

The planning target volume (PTV) used in many clinical centres for rectal radiation therapy is therefore large and concave, due to the inclusion of the primary tumour or its surgical bed, the local lympha­tics, and the pre-sacral area.

Small bowel toxicity due to the close proximity and large PTV is common.

The planning of rectal cancer involves taking the inform­ation acquired at simula­tion/CT and optimising the dose distri­bution for the CT for that patient.

For long course pre-op­erative radiation therapy the prescribed doses is usually 45 Gy in 25 fractions to the tumour bed and regional lymph nodes, treating all fields once a day, five times a week. A reduced field size may then be delivered up to 50.4 Gy, and sometimes 54 Gy, for those patients with gross or micros­copic residual disease and is treated on consec­utive treatment days.

The prescribed doses equate to 1.8 Gy per fraction. (This is lower than the 2 Gy per day used for many other treatment sites.) The smaller fraction size is essential due to the large size of the fields, and the inclusion of some bowel in the fields should reduce some of the toxicity.

For this reason adjuvant chemot­herapy has a good rationale.

Regardless of whether chemot­herapy is delivered pre-op­era­tively or post-o­per­atively it has been shown to have no effect on overall survival, however is seen to increased local control.

Chemot­herapy schedules for rectal cancer usually have a 5- florou­racil (5-FU) base, combined with leucov­orin, capeci­tabine, oxalip­latin or irinot­ecan. The pre-op­erative toxicity of these drug combin­ations has been found to relatively low. In the post-o­per­ative setting, the toxicity of chemot­herapy depends on the individual patient and the local situation after surgery.

There is strong evidence though that both pre-op­erative and post operative radiation therapy for rectal patients results in adverse effects to bowel function.

These conditions are usually transient and resolve within a few weeks following the completion of radiation. Management involves the use of antisp­asmodic and/or anti-c­hol­inergic medica­tions.

Late onset compli­cations from chemo-­rad­iation for rectal patients include:

Late onset compli­cations occur less frequently than acute side effects but are more serious. The initial symptoms commonly occur 6–18 months following completion of radiation therapy.

The primary goals of post therapy follow up for rectal cancer patients are: improve survival, manage treatment toxicities and adverse effects, assess the efficacy of the initial therapy, detect new malign­ancies, detect potential curable recurr­ence, provide supportive care to the patient and carers, and assist in the mainte­nance or improv­ement of quality of life.