hemorrhagic cystitis ( hc ) is a diffuse inflammatory state of the urinary bladder that can occur as a complication of radiotherapy , chemotherapy , or infection . it may result in hemorrhage of the bladder mucosa , which is observed clinically as hematuria . the focus of this article will be on radiation - induced hc , a relatively uncommon but serious complication of radiation therapy . report a 6.5% risk of developing radiation - induced hc in patients treated with radiotherapy due to cervical cancer . radiation - damage of the bladder does not become clinically evident until six months after initiation of the radiotherapy . irradiated tissue sustains damage that results in microscopic obliterative endarteritis and progressive arteriopathy leaving the affected tissue hypocellular , hypovascular , and ischemic . collagen and cells are replaced during the healing process , but complete restoration is unlikely to occur [ 3 , 4 ] . bleeding may also occur as a consequence of the formation of structurally weak and brittle vessels that easily rupture . the use of hyperbaric oxygen treatment ( hbot ) in the treatment of tissue damaged by radiation was pioneered by marx et al . who suggested that hbot enhances healing of tissues subjected to radiation therapy . they were the first to describe the therapeutic effects of hbot in humans  on patients having undergone protracted radiation therapy of the head and neck . in an animal study predating the human study , the authors showed that animals subjected 100% o2 in a hyperbaric environment had an 8 - 9 times higher vascular density in irradiated tissue compared to both a normobaric group and an air - breathing control group . a four - year follow - up study showed that the angiogenic effect was long lasting . oxygen in hyperbaric conditions leads to an increase of oxygen levels in tissues resulting in angiogenesis , increased collagen formation , and an increased number of fibroblasts . the angiogenesis is correlated , at least in part , to the macrophages of the affected tissue , which react to the steep oxygen gradient achieved in a hyperbaric environment . the increase in fibroblasts and collagen creates a connective tissue framework for the new vessels . the elevated level of oxygen also supports the regeneration of damaged tissue , as well as reducing edema , necrosis , and leukocytic infiltration . its overall effectiveness in various pathologies has manifested in many clinical studies and trials [ 4 , 5 , 6 ] . more research is needed to delineate and define the clinical effectiveness and benefits of hbot in each disease entity . the purpose of this study is to evaluate the efficacy of hbot in radiation - induced hc . between the years 2006 and 2010 , ten patients ( seven men and three women ) with radiation - induced hc as a consequence of standard methods of treatment were subjected to hbot . their average age was 68.9 years ; age - range 54 - 81 years . in these patients , four men were initially treated with radio - hormonal therapy or radiation therapy because of prostate cancer . patients in this group received 50 gy of teleradiotherapy , with an additional dosage of 20 - 24 gy . patients in this group received 50 gy of teleradiotherapy with an additional dosage of 16 gy . two women were treated for cervical cancer and one for endometrial cancer . in the case of cervical and endometrial cancers , 30 gy of brachytherapy with 45 - 50 gy of teleradiotherapy were utilized ( details in table 1 ) . patient characteristics abbreviations : m = male , f = female , tuc = transurethral coagulation , c = cyclonamine , e = exacyl , k = vitamin k , b = brachytherapy , t = teleradiotherapy patients in which radiation induced hc was present were initially treated for cancer using radiotherapy and in some cases with additional brachytherapy  table 1 contains the details of this treatment  and hematuria was recognized with an average onset of 4.3 years ( 0.5 - 8 ) after radiotherapy . prior to the advent of hbot , treatment of radiation - induced hc was initially performed utilizing cystoscopic electrocoagulation , oral etamsylate , tranexamic acid , and vitamin k. however , a follow - up performed at 7 - 48 ( average 24.5 ) months revealed that this approach only resulted in temporary improvement , as reappearance of hematuria was observed in all patients . each patient received cystoscopic confirmation of hc , as well as exclusion of urinary tract infection and bladder cancer . one patient received treatment with palliative intent due to persistent hematuria , seeing as the cancer was advanced and no additional treatment with intention of cure was planned . the other patients were without detectible presence of cancer . additionally , five of the patients required blood transfusions due to low hemoglobin values . the transfusions were given both before and during hbot , but were not required after . the hbot was performed in a delta haux - quadro 2700 hyperbaric chamber , engineered to minimize claustrophobia . the treatment schedule consisted of five sessions a week , with a duration of 90 minutes per session . during the sessions , patients were provided with 100% o2 at a pressure of 253312.5 pa ( 2.5 atm ) . sessions were continued until the hematuria disappeared , or until the patient requested to terminate the treatment . the average number of hbo treatments was 43.4 ( 8 - 60 ) [ 43.5 ( 8 - 120 ) ] . one patient received a total of 120 treatments in two sets of 60 , interspaced by four months between each series and two other patients completed a series of 60 treatments . the efficacy of the treatment was assessed every six months by visually evaluating the degree of hematuria . in case of any suspicions of hematuria complete resolution of hematuria was achieved in six of the ten patients ( 60% ) . the maximum follow  up after hyperbarotherapy was 18 months . none of these patients showed signs of hematuria upon completion of hbot , including the patient that received 120 treatments . four patients who suffered from bladder , endometrial , or prostate cancers , were withdrawn from the treatment . in one of the patients with primary bladder cancer , treatment was discontinued because of increasing hematuria and suspicion of bladder cancer recurrence . the other three patients who discontinued their treatments prematurely due to coexisting morbidities had lessened or incomplete cessation of the hematuria . the four patients who had no complete resolution of symptoms were the same patients who did not complete the treatment . according to current standards of treatment , electrocoagulation , with or without pharmacotherapy , is the first step in the treatment of hc . conjugated estrogens have a success rate of 60 - 85% in the treatment of hematuria in hc . the efficacy of conjugated estrogens applies to different etiology of hc and it should be noticed that these results using post high dose chemotherapy are not directly applicable to radiocystitis . pentosan polysulfate , tranexemic acid , aminocaproic acid , alprostadil , dinoprost , silver nitrate , and aluminum can also be used [ 1216 ] . when the hematuria can not be controlled using electrocoagulation or pharmacotherapy , selective embolization of hypogastric arteries can be performed . if this fails , cystectomy and supravesical diversion of urine may have to be performed to control the hematuria . although many studies have shown the benefit of hbot in the treatment of radiation - induced hc , especially in patients who have failed other forms of management , hbot is currently not included in standard treatment [ 2 , 3 , 1720 ] . in the literature on the subject , studies report complete resolution - rates range from 76 - 100% [ 1 , 3 , 2125 ] . although , our study demonstrated slightly lower rates of complete resolution ( 60% ) , it is clear that the treatment contributed significantly to the healing process and health of the patients . in addition to its high efficacy , hbot is safe and well tolerated by patients . side effects are rare and generally well tolerated by the patients [ 9 , 17 ] . they include pharyngotympanic tube problems , pneumothorax , air emboli , as well as cns and pulmonary oxygen - toxicity . furthermore , the benefits of hbot are relatively long lasting when compared to standard methods of treatment . a study by del pizzo involving 11 patients , with a mean follow - up of 5.1 years , showed an asymptomatic period of 2.5 years in eight of the patients , following treatment with hbot . after five years of observation , five out of the eight patients had a recurrence of hematuria and required supravesical urinary diversion . many questions regarding patient selection to hbot remain , as factors such as age , total irradiation dose , and duration of hematuria influence the outcome of hbot . furthermore , there is a lack of data evaluating the effect of hbot in smoking patients or patients with chronic disease . it should be remembered that hc may be caused by pharmacotherapy , such as cyclophosphamide . moreover clotting and coagulation profiles in all cases of hc should be performed to rule out hematuria due to clotting and coagulation disorders . there is no general consensus on the cost - effectiveness of hbot compared to standard methods of treatment , although investigations on the subject seem to suggest that hbot is more cost - effective than standard methods of treatment . in a study similar to this one , they concluded that the average cost per patient was $ 10,000 to $ 15,000 , comparing favorably to the cost of multiple conservative treatments to control symptoms . a review article by wang et al . claims that hbot significantly reduces the length of the patient 's hospital stay , amputation rate , and wound care expenses in musculoskeletal disorders , making it is a cost - effective modality . concerning the treatment of soft tissue radiation necrosis using hbot , boykin et al . showed that hbot achieved a reduction in patient charges by greater than 30% when compared to traditional management . in a study by hampson et al . where a hypobaric treatment was used , a positive outcome occurred in 94% of patients with osteoradionecrosis of the jaw ( n = 43 ) , 76% with cutaneous radionecrosis that caused open wounds ( n = 58 ) , 82% with laryngeal radionecrosis ( n = 27 ) , 89% with radiation cystitis ( n = 44 ) , and 63% with gastrointestinal radionecrosis ( n = 73 ) . a positive outcome of 100% was seen in patients who were treated with oral surgery in a previously irradiated jaw ( n = 166 ) . cianci et al also reported that a reduction in expenses in the treatment of thermal - burn patients with adjunctive hbot . , concerning hbot use in diabetic foot ulcers , concludes that hbot is cost - effective compared with standard care . the authors also mention that additional hbot capacity would be needed if it were to be adopted as the standard care throughout canada . in conclusion , hbot seems to be a promising treatment alternative in refractory hematuria caused by radiation - induced hc . many studies have shown that hbot is a cost - effective alternative in various pathologies , including radiation - induced hc . more cost - benefit analyses should be performed before a definite conclusion can be reached .