Content uploaded by NIALL Davis
Author content
All content in this area was uploaded by NIALL Davis on Aug 28, 2018
Content may be subject to copyright.
Accepted Article
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/bju.14516
This article is protected by copyright. All rights reserved.
MR. NIALL F DAVIS (Orcid ID : 0000-0002-5298-1475)
DR. DECLAN MURPHY (Orcid ID : 0000-0002-7500-5899)
DR. NATHAN LAWRENTSCHUK (Orcid ID : 0000-0001-8553-5618)
Article type : Review
Current management of radiation cystitis: A review and practical guide to
clinical management
Claire Pascoe1,2, Catriona Duncan2,3, Benjamin W Lamb4, Niall F Davis2, Thomas H Lynch5, Declan G
Murphy1, Nathan Lawrentschuk1,2
1. Department of Cancer Surgery, Peter MaCallum Cancer Centre, Melbourne, Australia
2. Department of Urology, Austin Health Heidelberg, Australia
3. North Eastern Urology, Heidelberg, Australia
4. Department of Urology, Cambridge University Hospitals NHS Foundation Trust, Cambridge,
United Kingdom.
5. Department of Urology, St James Hospital, Dublin 8, Ireland.
Corresponding Author
A/Prof Nathan Lawrentschuk
E: lawrentschuk@gmail.com
M: +61 488 088 240
Accepted Article
This article is protected by copyright. All rights reserved.
Keywords: radiation, radiotherapy, cystitis, management, haemorrhage, bleeding, bladder
Abbreviation
Term
ATMs
atmospheres
BPH
Benign prostatic hypertrophy
CBI
Continuous bladder irrigation
CR
Complete response
GAG
glycosaminoglycan
HBO(T)
Hyperbaric oxygen (therapy)
IMRT
Image modulated radiation therapy
NKTCs
Natural killer cells
NR
Not recorded
PR
Partial response
QoL
Quality of Life
SPP
Sodium pentosan polysulphate
TCDO
tetrachlorodecaoxygen
TF
Treatment failure
YAG
Yttrium-aluminium-garnet
Abstract
Haemorrhage is a frequent complication of radiation cystitis leading to emergency presentations in
patients with prior pelvic radiation therapy. Standard initial patient management strategies involve
resuscitation, bladder washout with clot evacuation and continuous bladder irrigation. Beyond this,
definitive surgical treatment is associated with significant morbidity and mortality. Alternative less
invasive management options for non-emergent haemorrhagic cystitis include systemic medical
therapies, hyperbaric oxygen, intra-vesical therapies and laser ablation. However, evidence to
support and compare treatment for haemorrhagic radiation cystitis is limited. Herein, a literature
Accepted Article
This article is protected by copyright. All rights reserved.
search pertaining to the current management of haemorrhagic cystitis was conducted. With
evaluation of existing literature, this narrative review also provides a stepwise clinical algorithm to
aid the urologist in treating patients presenting with complications associated with radiation cystitis.
1.0 Introduction
Chronic haemorrhagic cystitis occurs up to 5% of patients following pelvic radiotherapy [1]. Although
the advent of intensity modulated radiation therapy (IMRT) may decrease radiation induced bladder
toxicity; robust data on long-term outcomes are limited [2]. The response of the urinary bladder to
radiation treatment can be classified into acute or subacute reactions that typically occur within 3-6
months of radiation treatment and late reactions that occur after six months. Delayed radiation
induced endothelial cell damage and perivascular fibrosis result in ischaemia and obliterative end
arteritis leading to a range of symptoms including urinary frequency, urgency, pelvic pain and
haematuria[3].
Complications associated with radiotherapy account for up to 7% of emergency urology admissions
[4]. Initial management of radiation cystitis with haemorrhage frequently involves a sequential
algorithm consisting of initial resuscitation and reversal of anticoagulation as clinically appropriate,
copious bladder washouts with clot evacuation, followed by continuous bladder irrigation (CBI) and
blood transfusions as required. Characteristic cystoscopy findings are telangiectasia with friable
erythematous mucosa [5]
of life (QoL) with persistent bleeding resulting in life threatening hypovolaemic shock [6]. The
management of complex patients on anticoagulation requires balanced clinical decisions regarding
the risks and benefits of blood transfusions and cessation of anticoagulation by the treating
physician, however often short periods without anticoagulation may be required to interrupt the
pathological cycle. Urinary diversion and cystectomy for end-stage haemorrhagic cystitis is
associated with a 44% mortality rate [7, 8]. Alternative less invasive management options for non-
Accepted Article
This article is protected by copyright. All rights reserved.
emergent haemorrhagic cystitis include systemic medical therapies, hyperbaric oxygen, intravesical
therapies and laser ablation. These treatment strategies have several limitations including difficulty
obtaining and administering some of the more historical treatments, such as formalin and alum, in
the contemporary clinical setting. There is also a dearth of level one evidence for the efficacy of such
treatments. A further limitation is the absence of a pre-determined management algorithm
regarding best clinical practice for patients presenting with symptomatic radiation induced
haemorrhagic cystitis. In this narrative review, we summarise available therapies for treating chronic
radiation induced hemorrhagic cystitis and propose a practical management algorithm.
2.0 Methods
A literature search was undertaken using Medline, Embase, Pub Med and Google Scholar. The
following terms were entered into the search algorithm to identify peer-reviewed articles that
investigated management strategies for radiation induced hemorrhagic cystitis:
, , haemorrhage or hemorrhage A further search of commonly used
Results were limited to publications in the English language,
involving adult human patients and published after 1990. Reference lists were checked to identify
relevant studies not captured in the initial search. Reviews and case reports were excluded and,
where possible, studies including patients who had received either radiation or cyclophosphamide,
as a precursor, were filtered to assess intervention effect on those who received radiation therapy
only. Abstracts and complete manuscripts were reviewed individually by two authors and
discrepancies reviewed by a third party.
Accepted Article
This article is protected by copyright. All rights reserved.
radiation therapy and pelvic radiation for any cause. For comparative purposes, outcomes were
classified as either complete response (CR) corresponding to resolution of haematuria, partial
response (PR) corresponding to improvement but not resolution of haematuria or treatment failure
(TF) corresponding to requirement of alternative intervention for persistent severe haematuria.
a trial.
224 manuscripts were identified through database search and a further five were included after
identification through other sources. After removal of duplicates and further screening by title and
abstract to ensure adherence with inclusion and exclusion criteria 51 articles were further assessed
for eligibility. Due to the heterogeneity of the clinical causes for haemorrhagic cystitis, articles were
excluded due to absence of previous pelvic radiation as a underlying cause of the haemorrhagic
cystitis. A total of 28 studies were included for qualitative synthesis. Within these studies, patient
groups were small and not divided by underlying malignancy and as such all eligible studies including
patients with haemorrhagic radiation cystitis were reviewed.
3.0 Treatment options
A variety of treatment options are described for radiation induced hemorrhagic cystitis. These
management strategies can be subclassified into systemic medical therapies, hyperbaric oxygen,
intravesical, ablative, interventional radiological and definitive surgical techniques. Their advantages,
disadvantages and most recent comparative data on clinical efficacy are discussed in detail below.
Accepted Article
This article is protected by copyright. All rights reserved.
3.1 Systemic therapies
Medical systemic therapies for haemorrhagic cystitis are appealing as they are non-invasive
and circumvent inpatient hospital admission (Table 1). WF10 is an intravenous formulation,
manufactured from the drug substance OXO K993, also referred to as
Tetrachlorodecaoxygen (TCDO). Its proposed mechanism of action for treating haemorrhagic
radiation cystitis relies on the model of a post irradiated bladder being in a state of chronic
inflammation. WF10 induces natural immunity and stimulates cellular defence mechanisms
through its actions on natural killer cells (NKTCs), cytotoxic T-lymphocytes, and modification
of the monocyte-macrophage system. It reduces inflammation promptly so that a host-
derived healing can commence [9]. In one randomised controlled trial, Veerasan et al.
demonstrated that patients treated with WF10 (n=37) had a significantly decreased rate of
recurrent haematuria recurrence after 12 months (47% vs 77%, p=0.01) [9]. A potential
limitation to this study is that the treatment failure group in both arms may be over-
response rate with WF10 in detail.
Sodium pentosan polysulphate (SPP) is a synthetic sulphated polysaccharide that is used to
decrease urothelial permeability by replacing defective GAGs. Sandhu et al. assessed SPP,
oral administration of 100mg three times daily, for managing radiation induced
haemorrhagic cystitis in 60 patients. In total, 51 patients were available for follow-up and
the dose was gradually reduced to a maintenance dose of 100 mg in 21 patients due to PR.
In 10 patients SPP was stopped due to CR. A limitation with medical therapies, as noted by
[10]. The onset of action was 1-8 weeks. In this timeframe, 15
patients required inpatient admission for bladder irrigation; of which 5 required irrigation
under general anaesthetic and 14 required blood transfusions [10].
Accepted Article
This article is protected by copyright. All rights reserved.
Tranexamic acid has been used to treat urological haemorrhagic emergencies however
evidence of efficacy in the haemorrhagic radiation cystitis patient is lacking. It can be
administered in the initial resuscitation and conservative management phases of active
haemorrhage in patients with prior radiotherapy. As tranexamic acid acts by inhibiting
fibrinolysis, attention must be directed at preventing formation of large thrombi with
resultant clot urinary retention. Tranexamic acid has been associated with increased risk of
thromboembolic events however the evidence not clear. It may be considered in
problematic acute surgical bleeding such as in haemorrhagic radiation cystitis however
complications of clot retention limit its use. [11]
3.2 Hyperbaric oxygenation
The underlying pathophysiology of radiation cystitis involves a progressive end arteritis that
leads to poor tissue oxygenation and eventual tissue ischemia. Necrosis and tissue sloughing
ensues with fibroblast deposition on ischaemic tissue layers. Compensatory
neovascularisation and telangiectasia leads a friable vascular network with resultant
haematuria. Hyperbaric oxygen (HBO) therapy increases oxygen delivery to tissues by
increasing the amount of dissolved oxygen in the plasma to induce and restore normal
reparation of granulocytes and fibroblasts. Administration of HBO has been shown to induce
neo-[12-14]. Studies reporting on
outcomes of HBO are mainly retrospective in patients who have failed conservative
management for radiation-induced haemorrhagic cystitis. Their main findings are
summarised in table 2 with complete resolution of haematuria occurring in 34-87.5% of
patients. Commencement of HBO within 6 months of haematuria increases the potential of
complete resolution to 96% [15]. With HBO, patients spend 90 minutes 5-7 days per week in
a hyperbaric chamber inspiring 100% oxygen between 2-2.4 atmospheres (ATMs). A total of
Accepted Article
This article is protected by copyright. All rights reserved.
40 HBO treatments extending over an 8-week period are typically administered [16]. The
follow up of patients following HBO varied between 12-120 months, with the majority of
patients being followed up for a mean of 24 months of less, as outlined in table 2. As such,
the evidence for long-term efficacy of HBO in the treatment of haemorrhagic radiation
cystitis is lacking.
3.3 Intravesical therapies
Contemporary evidence and outcomes for intravesical therapies are summarised in Table 3.
Response rates with these agents typically range from 60-90%. Historical evidence-based
intravesical therapies for the treatment of haemorrhagic radiation cystitis are instillations of
formalin and alum [17]. Formalin functions by precipitating cellular proteins within the
epithelial layer causing occlusion fixation of the telangiectatic and friable microvasculature.
There is limited contemporary evidence on the use of formalin and devastating
complications, such as patient mortality, have been described with concentrations of 2-4%.
Notably, lower concentrations demonstrate equivalent clinical efficacy with a lower
complication rate [18, 19]. A contemporary study of 8 patients with haemorrhagic radiation
cystitis, treated with formalin instillation, 7 of whom had failed other therapies, describes a
response in 6, patients. However, 5 of the 8 patients required blood transfusions within 30
days of instillation, one patient developed acute kidney injury and respiratory failure
requiring intensive care management. Urinary diversion was required in 2 patients that did
not respond and in 1 patient that developed recurrent symptoms [20]. Therefore, formalin is
only recommended in cases of intractable haemorrhagic cystitis that may require urinary
diversion [21]. Aluminium salts (usually potassium or ammonium aluminium sulphate) act by
precipitating proteins on the surface of cells. Intravesical instillation of alum is not as
effective as formalin but is associated with an improved side-effect profile and may
Accepted Article
This article is protected by copyright. All rights reserved.
represent an early treatment option if initial more conservative measures are unsuccessful.
[17]
More recently, novel intravesical therapies have aimed to replenish the glycosaminoglycan
(GAG) protective layer to reduce exposure of underlying epithelial cells to host urine.
Hyaluronic acid is a major mucopolysaccharide than can be instilled into the urinary bladder.
It has immunomodulatory properties that enhance connective tissue healing [22]. Epsilon
aminocaproic acid inhibits fibrinolysis to counteract urokinase on exposed telangiectatic
vessels in the post-radiation bladder and can be instilled into the bladder. Singh et al.
described intravesical instillation in 37 patients with intractable haemorrhage associated
with radiation or chemotherapy induced cystitis and reported a partial or complete response
rate in 34 patients (92%) [23]. Other intravesical therapies have been described in smaller
er nitrate (0.01-0.4%) was ineffective for managing haemorrhage in 9
patients with radiation cystitis [24]. Several other agents, including prostaglandins,
botulinum toxin, polydeoxyribonucleotides and early placental extract, have also been
reported with limited response rates [22].
3.4 Ablative therapies
Ablation and coagulation of ruptured submucosal vasculature with laser (yttrium-
aluminium-garnet [YAG] and Greenlight©) therapy or argon beam therapies is advantageous
as both modalities can immediately control haemorrhage and are associated with complete
response in 75-97.5% of cases (Table 4). Disadvantages with these modalities are
requirement of general or spinal anaesthesia. Greenlight© laser can ablate blood vessels
with selective absorption of green light by intravascular oxy-haemoglobin thereby sparing
Accepted Article
This article is protected by copyright. All rights reserved.
the surrounding tissue [25]. Conversely, the YAG laser is non-selective and has an increased
risk of bladder or bowel perforation in conjunction with irritative post procedural urological
symptoms due to sloughing of necrotic tissue [26]. Argon beam coagulation does not use
laser technology. Instead, the bladder is filled with argon gas and an argon probe is directed
approximately 3mm from the vessel and a monopolar current is aimed towards it. Uniquely,
argon ablative therapy has a safety mechanism for preventing perforation as the current
follows the path of least resistance and moves onto adjacent tissue after coagulation has
been achieved. Also, the depth of ablation can be altered by adjusting power and gas flow
settings [5].
3.5 Interventional radiological
There is limited evidence on arterial embolisation for managing haemorrhagic radiation
cystitis. Small case series describe clinical scenarios of haemorrhagic radiation cystitis
combined with additional causes of intractable haematuria originating from the urinary
bladder or prostate gland. In these series, resolution of haematuria varies from 90-100% and
is dependent on the underlying patient group requiring embolisation [27, 28]. Long-term
resolution of haematuria ranges from 70-81% after a median follow-up of 16-18 months.
Loffroy et al [29] found that embolisation can be selected to treat any cause of intractable
haematuria (including radiation cystitis) as complete resolution occurs in 92.6-100% of
patients. Notably, depending on the selectivity of embolization, ischaemic complications
occur in 10-62.5% and may include skin or bladder necrosis, gluteal paresis, Brown-Sequard
syndrome, and perineal or buttock pain.
Accepted Article
This article is protected by copyright. All rights reserved.
3.6 Definitive surgical treatment
Urinary diversion with or without cystectomy can be performed if all other less invasive
treatment modalities have failed. One series on 21 patients undergoing cystectomy and
urinary diversion for intractable haemorrhagic cystitis demonstrated that 42% of patients
developed a complication that was either Clavien-Dindo Grade III or Grade IV during the
perioperative period. Furthermore, the 90 day mortality was 16% and overall survival at one
year was 84% [8].
4.0 Management algorithm
There are no widely adopted definitive treatment algorithms for managing patients with radiation-
induced haematuria. Therefore, definitive and effective treatment of this patient population is often
challenging for the urologist. To optimise clinical outcomes in this difficult patient cohort; we
propose the following stepwise, evidence-based approach to treatment of the acutely haemorrhagic
patient (Fig. 1). A clinical guide to each step in the algorithm can be found in Table 5.
4.1 Haemorrhagic radiation cystitis with active bleeding
Acute active bleeding in the setting of previous pelvic radiotherapy can result in
hypovolaemic shock. Therefore, we advocate inpatient admission for patients with acute
haemorrhagic radiation cystitis. Initial management involves stabilisation with fluid
resuscitation, insertion of a large 24-26Fr 3-way indwelling catheter (IDC), manual washout
with extensive clot evacuation and commencement of continuous bladder irrigation (CBI).
Tranexamic acid, administered orally, intravenously or intravesically, may be considered in
the initial conservative management of urological haemorrhage.[30]
Accepted Article
This article is protected by copyright. All rights reserved.
A thorough patient history and physical examination should be performed to exclude other
causes of haematuria such as urinary tract infection, anti-thrombotic agents, pre-existing
urological malignancy, benign prostatic hyperplasia (BPH), urinary stone disease and known
underlying coagulopathies. Laboratory investigations including full blood count, blood urea,
serum creatinine and coagulation profile should be performed. Urinalysis and urine culture
should be performed to rule out infection. Urine cytology can be performed if the patient is
at risk of bladder cancer however this may be difficult to interpret. Computed Tomography
(CT) with intravenous pyelography may be performed to rule out upper tract bleeding.
Rigid cystoscopy should initially be performed in all patients to further rule out bladder
malignancy and confirm the diagnosis of radiation cystitis. At this stage further clot
evacuation and fulguration with diathermy can be performed at this time if required. If
conservative measures fail, ablative therapies should be performed which may lead to
immediate control of the bladder haemorrhage. This process can be repeated if required. If
ablative resources are not available, then intravesical aluminium may be administered.
When minimally invasive measures are unsuccessful we recommend consideration of
bladder preserving urinary diversion with bilateral nephrostomies or an ileal conduit.
Embolisation can also be considered at this time. If bleeding persists despite urinary
diversion, intravesical formalin at a non-toxic concentration may be considered however
definitive cystectomy may at this stage be required. Finally, we suggest consolidation with
hyperbaric oxygen in patients undergoing bladder preservation treatment strategies once
bleeding has been controlled and the patient is stable.
Accepted Article
This article is protected by copyright. All rights reserved.
4.2 Haemorrhagic radiation cystitis with bothersome intermittent bleeding.
Bothersome intermittent bleeding can be defined as multiple episodes of frank haematuria
for which patients seek medical attention or microscopic haematuria resulting in a
haemoglobin drop that requires medical attention. As detailed above, these patients should
undergo thorough clinical investigation to rule out other cause for bladder haemorrhage.
Part of this diagnostic work up should initially include a rigid cystoscopy to further rule out
other cause for bleeding including bladder malignancy and enable diagnosis of radiation
cystitis. Bladder wash out and fulguration or ablation of bleeding or immanently bleeding
vessels can be performed at this time.
Hyperbaric oxygen for management of haemorrhagic radiation cystitis has the most robust
evidence for efficacy, however it is cumbersome for patients requiring long duration of
treatment and a certain level of fitness that many patients with radiation cystitis will not
achieve. Patients with intermittent self-limiting episodes of bleeding should be prescribed
hyperbaric oxygenation, where possible, and considered for medical systemic or intravesical
therapies. There are no direct comparative trials between oral and intravesical therapy for
the management of haemorrhagic radiation cystitis. As such, we advocate a step-by-step
management algorithm that can be tailored to the specific clinical situation of each patient
with consideration of the side effect profile and acceptability of the intervention. These
patients should also be offered regular follow-up appointments in the urology outpatients
department.
Accepted Article
This article is protected by copyright. All rights reserved.
Future perspectives and conclusions
The relationship between novel pelvic radiation techniques and haemorrhagic radiation cystitis will
completed. In the interim, many treatment options are available for the management of chronic
radiation cystitis, however level one evidence is lacking. Medical systemic therapies are appealing as
they are non-invasive but are most efficient for chronic haemorrhagic radiation cystitis. Hyperbaric
oxygen therapy is also non-invasive but requires commitment from patients and is not freely
available as a healthcare resource. Intravesical therapy is associated with an acceptable short-term
response rate, however limited evidence is available on durability. If laser ablative therapies are
required, selection of the green light spectrum is preferable due to its more favourable safety-profile
compared to YAG-laser. Most importantly, we advocate a stepwise management algorithm with
multimodal treatment in patients presenting with severe acute haemorrhagic radiation cystitis.
6.0 References
[1] Smit SG, Heyns CF. Management of radiation cystitis. Nature Reviews Urology. 2010 Apr:
7:206-14
[2] Zelefsky M. J CH, Hunt M, Yamanda Y, Shippy A and Amold H. Long-term outcome of high
dose intensity modulated radiation therapy for patients with clinically localised prostate cancer. . J
Urol. 2006: 176:1415-9
[3] Marks LBC, P R; Dugan, T C; Anscher, M S. The response of the urinary bladder, urethra, and
ureter to radiation and chemotherapy. [Review] International journal of radiation oncology, biology,
physics. 1995: 31:1257-80
[4]
complications presenting to a urology department: a more common problem than previously
thought? BJU International. 2018:
[5] Wines MP, Lynch WD. A new minimally invasive technique for treating radiation cystitis: the
argon-beam coagulator. BJU International. 2006 Sep: 98:610-2
Accepted Article
This article is protected by copyright. All rights reserved.
[6] Al Hussein Al Awamlh B, Lee DJ, Nguyen DP, Green DA, Shariat SF, Scherr DS. Assessment of
the quality-of-life and functional outcomes in patients undergoing cystectomy and urinary diversion
for the management of radiation-induced refractory benign disease. Urology. 2015 Feb: 85:394-400
[7] Cheng C aFK. Management of severe chronic radiation cystitis Ann Acad Med Singapore.
1992: 21:368-71
[8] Linder BJ, Tarrell RF, Boorjian SA. Cystectomy for refractory hemorrhagic cystitis:
contemporary etiology, presentation and outcomes. J Urol. 2014 Dec: 192:1687-92
[9] Veerasarn V, Khorprasert C, Lorvidhaya V, et al. Reduced recurrence of late hemorrhagic
radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm,
open-label trial. Radiotherapy & Oncology. 2004 Nov: 73:179-85
[10] Sandhu SS, Goldstraw M, Woodhouse CR. The management of haemorrhagic cystitis with
sodium pentosan polysulphate. BJU Int. 2004 Oct: 94:845-7
[11] Reed R, Woolley, T. Uses of tranexamic acid. Continuing Education in Anaesthesia Critical
Care & Pain. 2015: 15:32-7
[12] Anderson LH WB, Herring RF, Mehm WJ. Influence of intermittent hyperoxia on hypoxic
fibroblasts. J Hyperbaric Med. 1992: 7:103-14
[13] Weiss JP MD, Neville EC, Hanno PM. . Primary treatment of radiation- induced hemorrhagic
cystitis with hyperbaric oxygen: 10-year experience. . J Urol 1994: 151:1514-7
[14] Muhonen A HM, Gronroos T, Bergman J, Knuuti J, Hinkka S, et al. Osteoblastic activity and
neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen
treatment. Int J Oral Maxillofac Surg 2004: 33:173-8
[15] Chong KT, Hampson NB, Corman JM. Early hyperbaric oxygen therapy improves outcome for
radiation-induced hemorrhagic cystitis. Urology. 2005 Apr: 65:649-53
[16] Ribeiro de Oliveira TM, Carmelo Romao AJ, Gamito Guerreiro FM, Matos Lopes TM.
Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. Int J Urol. 2015
Oct: 22:962-6
[17] Smit SG, Heyns CF. Management of radiation cystitis. Nature reviews Urology. 2010 Apr:
7:206-14
[18] Dewan AK, Mohan GM, Ravi R. Intravesical formalin for hemorrhagic cystitis following
irradiation of cancer of the cervix. International Journal of Gynaecology & Obstetrics. 1993 Aug:
42:131-5
[19] Lojanapiwat B, Sripralakrit S, Soonthornphan S, Wudhikarn S. Intravesicle formalin
instillation with a modified technique for controlling haemorrhage secondary to radiation cystitis.
Asian J. 2002 Jul: 25:232-5
[20] Ziegelmann MJ, Boorjian, S., Joyce, D., Montgomery, B., Linder, B. Intravesical formalin for
haemorrhagic cystitis: a contemporary cohort. The Canadian journal of urology. 2017: 11:E79-82
Accepted Article
This article is protected by copyright. All rights reserved.
[21] Denton AS, Clarke NW, Maher EJ. Non-surgical interventions for late radiation cystitis in
patients who have received radical radiotherapy to the pelvis. The Cochrane database of systematic
reviews. 2002:Cd001773
[22] Browne CD, N.F.; Mac Craith, E., Lennon, G.M., Mulvin, D.W., Quinlan, D.M., McVey, G.P.,
Galvin, D.J. A Narrative Review on the Pathophysiology and Management for Radiation Cystitis.
Advances in Urology. 2015: 2015
[23] Singh I, Laungani GB. Intravesical epsilon aminocaproic acid in management of intractable
bladder hemorrhage. Urology. 1992 Sep: 40:227-9
[24] Montgomery BD, Boorjian SA, Ziegelmann MJ, Joyce DD, Linder BJ. Intravesical silver nitrate
for refractory hemorrhagic cystitis. Turkish journal of urology. 2016 Sep: 42:197-201
[25] Talab SS, McDougal WS, Wu CL, Tabatabaei S. Mucosa-sparing, KTP laser coagulation of
submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach.
Urology. 2014 Aug: 84:478-83
[26] Hoffman RM1 MR, Slaton JW, Wilt TJ. Laser prostatectomy versus transurethral resection for
treating benign prostatic obstruction: a systematic review. The Journal of Urology. 2003 Jan 2003:
169:210-15
[27] ,D.; Loffroy, R.
Outcome of Transcatheter Arterial Embolization for Bladder and Prostate Hemorrhage. THE
JOURNAL OF UROLOGY. 2010: 183:1947-53
[28] Korkmaz MS, B.; Aras, B.; Bozkaya, H., Cinar, C., Guneyli, S., Gok, M., Adam, G., Duzgun, F.,
Oran, I. The short- and long-term effectiveness of transcatheter arterial embolization in patients
with intractable hematuria. Diagnostic and Interventional Imaging. 2016: 97:197-201
[29] Loffroy R, Pottecher P, Cherblanc V, et al. Current role of transcatheter arterial embolization
for bladder and prostate hemorrhage. Diagn Interv Imaging. 2014 Nov: 95:1027-34
[30] Thompson A, Adamson, A., Bahl, A., Borwell, J., Dodds, D., Heath, C., Huddart, R.,
McMenemin, R., Patel, P., Peters, J., Payne, H. Guidelines for the diagnosis, prevention and
management of chemical- and radiation-induced cystitis. Journal of Clinical Urology. 2013: 7:25-35
[31] Yoshida T, Kawashima A, Ujike T, Uemura M, Nishimura K, Miyoshi S. Hyperbaric oxygen
therapy for radiation-induced hemorrhagic cystitis. Int J Urol. 2008 Jul: 15:639-41
[32] Degener S, Pohle A, Strelow H, et al. Long-term experience of hyperbaric oxygen therapy for
refractory radio- or chemotherapy-induced haemorrhagic cystitis. BMC urology. 2015: 15:38
[33] Corman JM, McClure D, Pritchett R, Kozlowski P, Hampson NB. Treatment of radiation
induced hemorrhagic cystitis with hyperbaric oxygen. J Urol. 2003 Jun: 169:2200-2
[34] Neheman A, Nativ O, Moskovitz B, Melamed Y, Stein A. Hyperbaric oxygen therapy for
radiation-induced haemorrhagic cystitis. BJU International. 2005 Jul: 96:107-9
Accepted Article
This article is protected by copyright. All rights reserved.
[35] Polom W, Klejnotowska A, Matuszewski M, Sicko Z, Markuszewski M, Krajka K. Hyperbaric
oxygen therapy (HBOT) in case of hemorrhagic cystitis after radiotherapy. Cent. 2012: 65:200-3
[36] Schwalenberg T, Berger FP, Horn LC, Thi PH, Stolzenburg JU, Neuhaus J. Intravesical
Glycosaminoglycan Replacement with Chondroitin Sulphate (Gepan() instill) in Patients with Chronic
Radiotherapy- or Chemotherapy-Associated Cystitis. Clin Drug Invest. 2015 Aug: 35:505-12
[37] Shao Y, Lu GL, Shen ZJ. Comparison of intravesical hyaluronic acid instillation and hyperbaric
oxygen in the treatment of radiation-induced hemorrhagic cystitis. BJU International. 2012 Mar:
109:691-4
[38] Vasssilis K EM, Andreas F, Ivelina B, Charalampos A, et al. Use of Hyaluronic Acid (Cystistat)
for the Treatment of Late Radiation Induced Cystitis in Patients after Prostate Irradiation. Journal of
Bioequivalence & Bioavailability. 2014: 6:018-22
[39] Westerman MEB, S.A.; Linder, B.J. Safety and Efficacy of Intravesical alum for intractable
haemorrhagic cystitis: A contemporary evaluation. Int Braz J Urol. 2016: 42:1144-9
[40] Goswami AKM, R.K.; Nath, R.; Sharma, S.K. How safe is 1% Alum irrigation in controlling
intractable vesical hemorrhage? J Urol. 1993: 149:264-7
[41] Vicente JR, G.; Caffaratti, J.;. Intravesical formalin for the treatment of massive haemorrhagic
cystitis: retrospective review of 25 cases. European urology. 1990: 18:204-6
[42] Ravi R. Endoscopic neodymium:YAG laser treatment of radiation-induced hemorrhagic
cystitis. Lasers in Surgery & Medicine. 1994: 14:83-7
[43] Martinez DR, Ercole CE, Lopez JG, Parker J, Hall MK. A Novel Approach for the Treatment of
Radiation-Induced Hemorrhagic Cystitis with the GreenLightTM XPS Laser. Int Braz J Urol. 2015 May-
Jun: 41:584-7
[44] B. Lamb CP, D. Christidis, DG. Murphy, N. Lawrentschuk and TE. Manning. Green Light Laser
for management of hemorrhagic cystitis a novel technique and initial results. BJU Int. 2018:
121:58-91
[45] Veerasarn V, Boonnuch W, Kakanaporn C. A phase II study to evaluate WF10 in patients with
late hemorrhagic radiation cystitis and proctitis. Gynecol Oncol. 2006 Jan: 100:179-84
[46] Sandhu SS, Goldstraw M, Woodhouse CR. The management of haemorrhagic cystitis with
sodium pentosan polysulphate. BJU Int. 2004 Oct: 94:845-7
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
