Proctitis

The efficacy of HBO in the management of radiation-induced bowel injury, including proctitis, is less well reported. There is a series of case studies and very small series reporting healing of pain, tenesmus, bleeding, diarrhea, and rectal ulceration.46-51 More significantly, there are a number of retrospective studies describing complete or partial healing of rectal symptoms in patients resistant to conventional therapy for severe injuries. One of the largest retrospective studies describes 36 patients, including 9 with chronic necrotic wounds, 19 with chronic rectal bleeding, and 9 with chronic severe diarrhea.52 After 67 (12-198) HBO sessions, the authors reported 9 complete responses, 12 partial responses, and 11 non-responses (in addition, one patient died from radiation injury, two from cancer, and one from liver cirrhosis). In a study of 38 patients treated with HBO for chronic, uncontrolled rectal bleeding, treatment resulted in an improvement in 61% of cases.53 A third retrospective study of 18 patients reported complete or partial responses after 24 (12-40) sessions of HBO in 7 of 17 cases rectal bleeding, 2 of 4 pain syndromes, 3 of 4 cases of fecal incontinence, and 4 of 8 diarrheal syndromes.54 These experiences are broadly repeated in other studies, including a cohort of 14 patients, 11 of whom presented with rectal bleeding, 5 with diarrhea, and 5 with tenesmus or colic.55 After 40 (20-72) HBO sessions, 9 patients were completely healed, 3 patients improved substantially, and 2 were non-responders.

Although limited in many respects, these reports are encouraging, in that chronic hemorrhage from the bladder or rectum can be reliably scored in a semiquantitative manner, including the number of patients freed from the requirement for repeated blood transfusions over the months and years posttherapy. Taken together, the evidence lends strong support to the hypothesis that HBO is an effective treatment in a proportion of patients suffering complications following radiotherapy for pelvic cancer. However, the data are derived from retrospective studies and are characterized by a lack of consistency with respect to the scoring of symptoms and response criteria. Until well-designed randomized clinical trials are undertaken, patients will continue to be referred to hyperbaric facilities on an ad hoc basis, and effective treatment for a common and major morbidity may continue unrecognized and underutilized.

17.3.1.5 HBO for Radiation-Induced Brachial Plexopathy (Nerve

Damage)

Our first randomized study testing hyperbaric oxygen therapy in patients with radiation-induced complication following treatment for cancer involved 34 volunteers with longstanding radiation-induced brachial plexopathy (RIBP).56 RIBP is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. A group of 34 eligible research volunteers suffering from RIBP were randomized to HBO or control group. The HBO group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibers, was selected as the primary endpoint.

Pretreatment neurophysiological tests were grossly abnormal in the affected hand compared with the unaffected hand in both HBO and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months posttreatment. However, normalization of the warm sensory threshold in two of the HBO group was reliably recorded. Two cases with marked chronic arm lymphedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO. These unexpected observations led to a study of HBO for arm lymphedema.

17.3.1.6 HBO for Radiation-Induced Arm Lymphedema (Arm

Swelling)

Fibrosis is also believed to contribute to the development of lymphedema. The pathophysiology of lymphedema after radiotherapy and/or surgery involves obstruction of lymphatic flow, causing an imbalance between capillary filtration and lymph drainage.5758 Although physical removal of lymphatic vessels at surgery offers a partial explanation, the variable onset, progression rate, and ultimate severity indicate that this is not the only mechanism. Radiotherapy to the axilla is a potent cause of arm lymphedema in its own right, more so after any kind of surgical disturbance of the axilla.59 The continuous accumulation and contraction of scar tissue over many years is considered to be a potent cause of progressive lymphatic obstruction in response to radiotherapy. The most vivid accounts of fibrosis are from the surgical records of affected patients describing scar tissue infiltrating and compressing axillary structures, especially the neurovascular sheath.

A total of 21 eligible research volunteers with a minimum 30% increase in arm volume in the years after axillary/supraclavicular radiotherapy (axillary surgery in 18 of 21 cases) were treated with HBO.78 The volunteers breathed 100% oxygen at 2.4 ATA for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The volume of the ipsilateral limb, measured optoelectronically by a perometer and expressed as a percentage of contralateral limb volume, was selected as the primary endpoint. A secondary end point was local lymph drainage expressed as fractional removal rate of radioisotopic tracer, measured using lymphoscintigraphy. Three out of 19 evaluable patients experienced >20% reduction in arm volume at 12 months. A total of 6 out of 13 evaluable patients experienced a >25% improvement in 99Tc-nanocolloid clearance rate from the ipsilateral forearm measured by quantitative lymphoscintigraphy at 12 months. Overall, there was a statistically significant, but clinically modest, reduction in ipsilateral arm volume at 12 months follow-up compared with baseline (P=0.005). The mean percentage reduction in arm volume from baseline at 12 months was 7.51. Moderate or marked lessening of induration in the irradiated breast, pectoral fold, and/or supraclavicular fossa was recorded clinically in 8 of 15 evaluable patients. Of this group, 12 out of 19 evaluable patients volunteered that their arms felt softer, and 6 reported improvements in shoulder mobility at 12 months. Interpretation of these results is limited by the absence of a control group. However, measurement of limb volume by perometry60,61 is reportedly reliable, and lymphoscintigraphy62 is assumed to be operator independent. Taking all data into account, there is sufficient evidence to justify a doubleblind randomized controlled trial of hyperbaric oxygen in this group of patients.

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