The oesopagus is a hollow, muscular tube with a stratified squamous epithelium. The muscular coat of the oesophagus is unique, in that the first part is striated muscle, the middle part is mixed striated/smooth muscle, and the distal part is smooth muscle only.
Consequential Late Effects in the Oesophagus
The oesophagus is prone to consequential late effects. This occurs when large doses of radiation obliterate the surface epithelium to such an extent that healing is severely impaired. Studies in animals have shown that the regeneration of the epithelium may form bridges between sides of the tube, leading to stenosis. Alternatively, severe ulceration may lead to fistula formation, particularly to the nearby pleura or lung.
Classical Late Effects in the Oesophagus
Unlike many other tissues, the primary cause of late effects in the oesophagus is related to excessive activity of the immune system and fibroblasts/fibrocytes. Fibrosis of the muscular layer can cause problems with innervation and function of the oesophageal muscles. The formation of a benign stricture is also possible if fibrosis of the submucosa occurs. These factors can all lead to dysphagia.
Summary of Oesophageal Late Effects
The oesophagus may develop consequential late effects if there is extensive loss of epithelial cells. More commonly, late effects are due to impairment of muscle function (due to fibrosis of muscle or involvement of nerves with fibrosis). Oesophageal stenosis is less common, and occurs when fibrosis of the submucosa occurs.
There is less evidence for stomach related late effects than other parts of the digestive tract. Like the rest of the gastrointestinal tract, it consists of an epithelial layer, a submucosa with vessels and nerves, and a surrounding muscular coat. Most evidence comes from small series as well as an army study which treated testicular cancers. There are four late syndromes of the stomach:
- Dyspepsia, with onset 6 months to 4 years after radiation. There is no visible change within the stomach and the cause is unknown.
- Gastritis, with onset 1 - 12 months after radiation. On gastroscopy, there is loss of mucosal folds and atrophy of the mucosa, due to fibrosis of the submucosal layer.
- Late ulceration, with onset 6 months after radiation. This runs a similar course to normal ulcers of the stomach, and may heal sponetaneously or cause perforation.
- Acute ulceration may also occur in the weeks following radiotherapy (more of a subacute reaction than a late reaction). It is unusual for acute ulceration to perforate and is probably due to acute changes in the epithelium rather than the submucosal fibrosis seen in gastritis and late ulceration.
The tolerance dose for the stomach is 45 Gy. Volume effects are hard to quantify.
The small bowel consists of the duodenum, jejunum and ileum. It is about 7 metres long. The duodenum, the short first part, is more susceptible to ulceration than the other parts due to its relation with the stomach.
Typical small bowel late effects
Late effects in the small bowel are due to fibrosis of the submucosa as well as ischaemia due to loss of submucosal blood vessels. Most commonly, this leads to altered transit of faecal material through the bowel, and may cause symptoms of frequency and urgency.
Severe late effects include obstruction, fistula formation or (rarely) perforation.
Like most late effects, the development of these problems is related to fraction size as well as total dose. Telangiectasia is seen but the contribution of this to symptoms (aside from increased rate of bleeding) is unclear.
Tolerance of Small Bowel
The small bowel is a highly mobile organ that lies within the peritoneal cavity. Unless parts of it a fixed due to adhesions, contouring small bowel is unreliable. One method suggested in the recent QUANTEC Red Journal was contouring the entire potential space within the peritoneal cavity. If thisi s done, the volume of tissue receiving 45 Gy or more should be less than 195 cm3.
Large Bowel and Rectum
The large bowel has a similar structure to the small bowel, although the calibre of the lumen is larger and the external longitudinal coat is arranged into three bands (tenea coli). The size of the lumen means that large bowel obstruction is much less common as a late effect than small bowel. Aside from this, the observed symptoms are similar to those seen for small bowel toxicity. The large bowel is usually not contoured separately, with the notable exception of the rectum which has some special features.
Typical large bowel late effects
Late effects mirror those seen in the small bowel, with the notable exception that obstruction is much less common. Transit time of matter through the bowel may be altered, fistula formation is possible, and patients may complain of bleeding, urgency and frequency. Changes are due to fibrosis of the underlying submucosa and vascular insufficiency.
The rectum is the last part of the small bowel, and lies in the posterior pelvis. It has a wide lumen with several folds that assist in continence. The rectum is supported on the levator ani muscles. Due to its position, it often receives significant dose in pelvic treatments.
Common late effects seen in the rectum include loose, frequent stools with urgency. Blood is often present due to telangiectasia of vessels in the submucosa.
The rectum demonstrates a marked dose volume effect, allowing numerous tolerance values to be given for different volumes. These are:
- V50 < 50%
- V60 < 35%
- V65 < 25%
- V70 < 20%
- V75 < 15%
These volume and dose guidelines give a risk of grade II toxicity of less than 15% and grade III toxicity of less than 10%.