Synergy : BJU International 85 (3), 372-374

Therapeutic irradiation is commonly used to treat clinically localized prostate cancer. Although radiation therapy is effective for localized prostate cancer, the rectum is often affected because of its proximity to the treated tumour [1,2]. The incidence of severe chronic radiation proctitis induced by pelvic irradiation is reported to be 2–5%[3,4]. The symptoms of chronic radiation proctitis include diarrhoea, tenesmus, abdominal pain and rectal bleeding [5], and perforation, necrosis, stenosis and ulceration of the intestine may occur. The natural history of chronic radiation proctitis is unpredictable. While some patients with mild symptoms may experience remission, others suffer a progressively worsening course that can result in a life–threatening condition.

Chronic radiation proctitis is generally considered to be difficult to manage. Medical treatment with a low–residue diet and steroidal or nonsteroidal enemas has been disappointing [6]. Laser therapy or electrocoagulation is often used to halt rectal bleeding. Although these attempts are initially successful in many patients, recurrence of bleeding is a common problem [3]. Although faecal diversion is the most common operative procedure, this may not always control rectal bleeding and surgical resection of the involved segment may be necessary [7]. Surgical complications are common, with a morbidity and mortality of 10–80%[8,9]; thus an effective alternative treatment is required, particularly as medical treatment often fails. Hyperbaric oxygen therapy (HBOT) was recently reported to be safe and effective for the treatment of chronic radiation proctitis [10,11]. We report the outcome of HBOT in four patients with chronic radiation proctitis.

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Between 1990 and 1998, 27 patients with localized prostate cancer underwent pelvic irradiation. Of these patients, four had chronic radiation proctitis and were treated with HBOT at our institution. Although all patients had previously received several medical treatments for the relief of the symptoms associated with radiation proctitis, the treatments had failed. Before HBOT the patients underwent flexible sigmoidocolonoscopy and were questioned about Eustachian tube dysfunction, pneumothorax and general physical conditions. After having given signed, informed consent, patients received 100% oxygen in a multiplace chamber (KHO–301B, Kawasaki Engineering Co., Japan) at 0.2 MPa (absolute) for 60 min sessions and 5 days/week; the number of sessions varied according to the clinical response.

Patients were questioned about their symptoms and the degree to which each had improved. Complete improvement was defined if the symptoms had resolved completely, or almost completely, by the end of HBOT and remained so during follow–up. Partial improvement meant a sustained improvement of at least 3 months, with subsequent relapse or less than complete resolution of symptoms. To evaluate the subjective improvement, patients underwent flexible sigmoidocolonoscopy after HBOT. Disease progression during HBOT was evaluated by serum PSA levels measured before and after treatment.

The four patients were aged 70, 67, 75 and 73 years; three patients received > 65 Gy of megavoltage X–rays to the prostate. The interval between completing radiation therapy and initiating HBOT was 18, 9, 12 and 5 months, with the follow–up at 13, 12, 12 and 11 months, respectively. Three patients received 30 HBOT treatments and one had 60. Three patients had moderate to severe rectal bleeding, one of whom (patient no. 1) required transfusion before HBOT. Flexible sigmoidocolonoscopy of these patients revealed abnormalities typical of chronic radiation proctitis, e.g. erythema, bleeding, telangiectases and ulceration (Fig.1a).

The patients had a significant improvement in rectal bleeding by the completion of HBOT. Sigmoido–colonoscopy of these patients after HBOT showed an improvement in the mucosal appearance (Fig. 1b). In the second patient the rectal bleeding relapsed 3 months after HBOT, and the third patient continues to have minor rectal bleeding and occasional minimal rectal discomfort; the remaining patient had severe persistent proctalgia with no rectal bleeding. Although endoscopic evaluation showed no significant change in his rectal mucosa, chronic radiation proctitis was diagnosed from the clinical symptoms and the elimination of other possible causes. He had no appreciable change in symptoms during HBOT and was unchanged at follow–up. No patient rejected or terminated the treatment because of the adverse effects. One patient (no. 4) had mild claustrophobia but wished to continue HBOT. During HBOT no patient had clinical disease progression; patient no. 1 had a modest rise in serum PSA values after HBOT.

Advantages and disadvantages

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The incidence of severe radiation proctitis is known to relate to the total radiation dose [12]. With doses of up to 50 Gy, the incidence increases rapidly and becomes > 30% when external therapy is > 70 Gy. Radiation enteritis occurs in two forms; acute injury is seen shortly after the radiotherapy and is caused primarily by direct injury to the mucosal cells [13], whereas chronic radiation injury becomes manifest after a latent period of several months to years. This form of injury occurs as a result of progressive obliterative endoarteritis which ultimately leads to ischaemic tissue, resulting in ulceration and bleeding [14]. With limited microvasculature available in areas of irradiation, wound healing is commonly impaired, as the delivery of nutrients, oxygen and antibiotics is compromised, and the wound is unlikely to heal once extensive breakdown of irradiated tissue occurs.

Zel [15] reported the five major mechanisms of action of HBOT as tissue hyperoxygenation, capillary angiogenesis, oedema reduction, leukocyte activation and increased intracellular transport of antibiotics across cell membranes. Hyperbaric oxygen can successfully ameliorate the ischaemia caused by radiation–induced obstruction of microvessels, by affecting red blood cells, oxygen transport and tissue exchange, and therefore the partial pressure of oxygen in tissues with microvascular insufficiency. Hyperbaric oxygen also has an angiogenic effect and has been shown to cause an 8–9–fold increase in the vascular density of soft tissues over that in air–breathing controls in an animal model [16]. Furthermore, tissue hyperoxia decreases tissue oedema, increases fibroblast proliferation and enhanced leukocyte activation for bacterial killing [17]. These conditions produce an environment in which healthy granulation tissue can grow. There are several reported series showing the benefits of HBOT in the treatment of radiation injury, e.g. severe radiation cystitis and radiation necrosis [17]; the present results, although anecdotal, suggest that HBOT is beneficial. Evidence from three of the present patients suggests that HBOT reversed the underlying submucosal fibrovascular damage; spontaneous remissions in such cases have been reported to be very rare [4]. Warren et al.[11] also reported outcomes of 14 patients with radiation proctitis, of whom eight had complete resolution of symptoms and one had a substantial improvement. Furthermore, Woo et al.[10] reported that symptoms partially or completely resolved after HBOT in 10 of 18 patients.

Although the treatment of radiation proctitis with hyperbaric oxygen is effective, there are some adverse effects related to the high atmospheric pressure and hyperoxia, i.e. middle ear and sinus barotrauma, pulmonary and CNS oxygen toxicity and chest tightness [18]. Other complications include claustrophobia, visual change and euphoria [10]. In the present study, only one patient had transient mild claustrophobia, and therefore HBOT is considered to be relatively free of adverse effects.

Because HBOT improves the microvascular environment it could cause disease progression (local invasion and distant metastasis). However, Woo et al.[10] reported that only one of 14 patients with prostate cancer had a transient rise in PSA level after HBOT. In the present study, there was a modest rise in PSA level in one of four patients and no patient had clinical disease progression during treatment.

Although the short–term benefits of HBOT for chronic radiation proctitis have been reported, the long–term efficacy is unclear. In the previous reports [10,11] the mean follow–up was 17 and 14 months, respectively. The four present patients were followed for 11–13 months after completing HBOT. A larger, long–term study should be conducted to clarify this issue. With the increasing incidence of localized prostate cancer, radiation proctitis will probably become more significant. HBOT offers a noninvasive, effective therapeutic alternative to treat chronic radiation proctitis and thus should be proposed as an alternative before surgical intervention.

References

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