Radiation cystitis is a complication after radiotherapy of tumors of the pelvis, characterized by changes in the bladder wall. Some malignant neoplasms of the bladder imply a directional radiation.
Manifestations of radiation cystitis is variable: from mild periodic symptoms of dysuria with painless microhematuria to severe complications – total hematuria, severe pain, persistent urinary incontinence, fistulas, etc.
Organs, the irradiation of which there is a risk of post-radiation cystitis:
Radiation therapy is used as a primary, accessory or palliative treatment and often complements conservative or surgical therapy of malignant neoplasms.
At the present time, there is the latest techniques of radiation that only affect the tumor, but even when carrying out targeted therapy in process involved the surrounding tissue due to the proximity of the cancer to adjacent pelvic organs.
Acute radiation cystitis relieved with symptomatic treatment, and later inflammation of the urinary bladder after irradiation is a few months and is difficult to treat. In the late period is the accession of hematuria, which can lead to anemia and weight prediction.
Etiology and pathophysiology
The irradiation is performed using a variety of sources and may affect directly the tumor (brachytherapy) or radiation exposure is external beams. During treatment there is a transfer of ionizing radiation to the tumor cell and block mitosis, making it impossible division. Radiation when interacting with the intracellular fluid leads to the formation of free radicals that contribute to cell death.
Particularly sensitive to radiation damage to abnormal cells, but suffer from usual. Peak sensitivity to the radiation falls on the M and G2 phases of the cell reproductive cycle.
Co-administration of chemotherapeutic drugs enhances the destruction of abnormal cells, the risk of trauma to the tissues of the bladder increases.
Changes that causes radiation:
- subendothelial proliferation;
- thickening of the mucosa;
- vascular changes, circulatory disorders;
- fibrous replacement;
In these processes develops ischemia of mucosa and epithelial damage. On the background of the aggressive impact of urine progresses submucosal fibrosis, which is accompanied by increased pain.
Postradiation cystitis klassificeret at the time of occurrence as early (before 12 months) and late (over 12 months).
For the first variant is characterized by:
- surface erosion;
- submucosal inflammation and fibrosis;
- epithelial atypia;
- the violation of innervation.
For late radiation cystitis fibrotic process affects the blood vessels, causing occlusion and necrotization. Due to the massive damage of the epithelium on the background of ischemia and fibrosis occurs atrophy of the muscles of the bladder, and there are disorders of urination (atonic or neurogenic bladder).
The risk of secondary complications depends on 3 main factors:
- volume, area and localization of the lesions;
- the daily dose of radiation and the duration of the course;
- the total radiation dose.
The incidence of radiation cystitis is variable because of difficulties in data collection, differences in radiation load, and the used size field, and because of the fact that various tumors are localized in different areas, which implies a different amount of impact on the bladder.
The likelihood of development of radiation cystitis, depending on the location of the tumor:
Injuries of the genitourinary system in intensive-modulated radiation therapy
It is proved that intensively-modulated radiation therapy (IMRT) delivers higher doses to the target area while minimizing complications. IMRT is increasingly used for the treatment of prostate cancer.
The complication rate with IMRT is slightly lower than at 3-dimensional (3D) conformal radiation therapy.
After treatment for prostate cancer the complications of the rectum are much less likely with conformal radiotherapy compared to conventional radiotherapy (19% vs 32%); but the frequency of negative side effects from the bladder are the same, due to the proximity of the bladder neck and the urethra.
IMRT showed a significant reduction of kidney effects in comparison with conformal radiotherapy 3D.
After cancer treatment bladder acute symptoms that occur during treatment and last longer than 12 months, are usually alone and are recorded at 50-80% of patients, regardless of tumor type.
Than may be complicated by radiation cystitis
- Postradiation complications are recurrent in nature and will include the following: hemorrhagic cystitis;
- the formation of a fistula;
- the development of contracture of the bladder neck;
- the formation of a purulent focus;
- a decrease in bladder volume (microcyst);
- dysfunctional disorders: urinary incontinence, urgent urination, urinary retention, frequent urination, etc.
Neoplasia of the urinary bladder is rare.
Symptoms and signs of cystitis after irradiation
Clinical manifestations are similar to those of acute inflammatory process in the bladder include the symptoms of dysuria: cramps during urination, abdominal pain, irresistible urge, incontinence of urine, appearance of blood in the urine, etc.
For late radiation cystitis due to ischemia and fibrosis, the clinical symptoms, in addition to the typical, presented a number of complications:
The severity of radiation complications associated with the bladder, evaluate on a scale (RTOG):
- 1 degree – slight epithelial atrophy, microhematuria, minor vasodilation;
- Stage 2 – frequent urination, multiple expansion of blood vessels, intermittent macroscopic hematuria, intermittent urinary incontinence;
- Stage 3 – frequent urination with urgent urging, modified the blood vessels across the surface of the bladder, persistent incontinence, reduced bladder capacity (< 150 ml), recurrent gross hematuria, frequent urination (up to 40 times a day);
- 4 degree – area of necrosis, fistula, pronounced hemorrhagic cystitis, bladder capacity (<100 ml), refractory incontinence requiring permanent catheterization or surgery.
- Stage 5 – death.
Radiation cystitis can mimic many different diseases. Neoplasia, urinary tract infection, urolithiasis have similar symptoms. Initial diagnosis includes the following:
In case of complaints about the appearance of blood in urine prescribed the blood test with investigation of the coagulation system.
The functional ability of the kidneys demonstrates the urea and creatinine blood.
Some patients, according to testimony carried urodynamic studies.
Instrumental diagnostics – cystoscopy, excretory urography and MRI rule out causes of gross hematuria not associated with the passage of the radiation therapy.
Biopsy of the bladder wall with post-radiation cystitis is associated with the risk of constant bleeding and the formation of sinus tracts. Absolute indication for biopsy – suspected bladder cancer.
Urodynamic studies are needed if the diagnosis remains unclear after history and examination and help to diagnose microcyst, instability of the detrusor, the amount of residual urine, reduction of streaming speed with urination. These signs may be accompanied by radiation cystitis, but is not specific for this disease.
Cystoscopy cystitis after irradiation
Zitostaticescoe study is used to confirm the diagnosis and rule out other conditions: bladder cancer or other recurrent metastatic tumors. If necessary, cystoscopy can be combined with retrograde pielografia.
When zitostaticescoy picture of the changes in the mucosa of the bladder after irradiation are characterized by the following changes:
- vascular changes (expansion, rupture);
- threads of fibrin;
- erosive defects;
- swelling of the mucous membranes;
- pronounced folding.
For diagnosis can be used IVP, MRI, ultrasound.
Treatment of radiation cystitis
Schema therapy for radiation cystitis depends on the severity of symptoms and urological study data.
If the patient has no complaints, and quality of life is satisfactory, the chosen tactics of active surveillance and prophylactic administration of herbal remedies and soft uroseptics, especially in autumn and spring.
A complication of the formation of a fistula involves surgical intervention.
Endoscopic sclerotherapy was effective from a limited number of patients with hematuria on a background of post-radiation cystitis. Method includes injection of sclerosing drug into the bleeding areas (for example, 1% of ethoxysclerol), provided that conservative therapy has not contributed to the disappearance of hematuria.
In recent years, for control used hyperbaric oxygenation, after which the effect of conservative treatment above. Oxygen stimulates angiogenesis in the background, the normalization condition of the vessels, reducing their diameter, the disappearance of edema.
But if fibrotic changes and significant ischemia, hyperbaric oxygenation in radiation cystitis prevents further spread of the process.
The research was conducted, which showed that when 7-year observation objective and subjective improvement of symptoms was observed in 72-83% of patients. Relapses were absent in 74% of these patients the radiation dose was lower by 18% than in patients with recurrences.
Drugs with radiation cystitis
Pharmacological therapy for radiation cystitis is aimed at relieving symptoms.
Urgent urge to urinate decrease in the appointment antiholinergicakih drugs. Other causes of dysuria with pain can be used analgesic Phenazopyridine (European).
Indications: symptomatic relief of pain, burning in the background of inflammatory process in urinary bladder trauma, including after medical interventions: surgeries, endoscopic procedures, long-term functioning of the catheter.
No-Spa, Papaverine, Spazgan may relieve symptoms of dysuria.
If there is no pain, but there are complaints, characteristic for overactive bladder, to improve the condition will help the administration to do this, use:
- Oblepihovoe oil;
- The hydrocortisone.
Simultaneous infusion of several drugs, for example, 10% Sintomitsinovoy emulsion and 2% solution of Lidocaine or 0.5% Novocaine.
In severe bleeding, establishing irrigation system, additionally introduced into the bladder aminocaproic acid.
Water 5% solution of Formalin is used for endoscopic treatment of bleeding points, the exposure time of 15 minutes.
For bladder instillation is used 1-10% aqueous solution of formalin, which is introduced through treacherous epicystostomy. The exposure duration 14 min for 10% solution and 23 minutes to 5 %. Manipulation requires anesthesia.
The effect of the infusion is 52-89%, and the recurrence rate is 20-25%.
Alum (1%) is caused by loss of protein in the extracellular space and cellular membranes, due to the narrowing of the extracellular matrix and tamponade of bleeding vessels, stops. Capillary epithelium also sklerosiruta.
In severe hematuria intravenously administered Aminocaproic acid – fibrinolysis inhibitor. Dosage: 200 mg aminocaproic acid per 1000 ml of isotonic solution of sodium chloride.
Intravenous infusion is carried out depending on the severity of bleeding and continue for 24 hours after stopping it.
In 91% of patients treated with aminocaproic acid, bleeding during radiation cystitis is terminated or significantly reduced.
The mechanism of action of estrogens in radiation cystitis is unknown, but there is evidence that they reduce the duration of bleeding. Dosage: 5 mg/day orally for 4-7 days.
Means to improve the rheological properties of blood
The mechanism of action of pentoxifylline is based on the improvement of blood rheological properties, restoration of microcirculation, which allows ischemia.
Dosage: 400 mg 3 times daily, duration 6 weeks.
Pentosan polysulfate sodium protects the transitional epithelium, restore the glycosaminoglycan layer of the bladder. Dosage: 100 mg orally 3 times a day until resolution of symptoms, a minimum of 4 weeks. The frequency of responses in radiation cystitis is 71-100%, and the recurrence rate of 23%.
As a supporting therapy for radiation cystitis admission of herbal medicinal products: a Kanefron, Vitalizing, Monorail (dietary SUPPLEMENTS based on cranberries).
To use antibiotics in radiation cystitis if there are no inflammatory signs in the General analysis of urine and the growth of pathogenic microorganisms in the cultures are not substantiated.
Means to improve reparative processes
Candles with Methyluracil appoint 2-3 week courses, if necessary, repeat the treatment.
Vitamins b, P, C promotes healing of wounds and strengthens the vascular wall.
Indications for surgery
Surgery is used to treat severe complications that are not amenable to conservative therapy:
- ongoing gross hematuria that is resistant to the instillation, or cause anemia;
- microcyst with symptoms of urinary incontinence and frequent urination;
- specific complications of radiotherapy: fistula, gidroenergeticheskiy transformation of the kidneys, stricture).
Surgical intervention for hemorrhagic cystitis include the following:
- cystoscopy and fulguration;
- percutaneous nephrostomy;
- revision of suturing the bleeding vessels;
- embolization of internal iliac arteries;
Cystectomy with post-radiation haemorrhagic cystitis associated with high rates of postoperative complications and mortality. It should be used only after unsuccessful conservative therapy.