Radiation cystitis is a reaction of bladder tissues to ionizing radiation carried out as part of the treatment of malignant pelvic tumors. The symptoms depend on the radiation load received, range from minor discomfort during urination, frequent urge and microhematuria to severe pain, the appearance of recurrent bleeding, life-threatening. The diagnosis is confirmed by urinalysis, cystoscopy. Treatment of radiation cystitis is determined by the degree of severity of the lesion, can be conservative or operative with the implementation of cystectomy, solving the issue of urine diversion.
ICD 10
N30.4 Radiation cystitis
Meaning
Radiation cystitis is registered in 5-21% of patients as a complication of radiation therapy. The most common symptoms appear after treatment of bladder cancer (18%), prostate (14%), cervix (5%). Pathology develops on average 32 weeks after treatment, more often in men than in women (2.8:1). Conformal radiation therapy, brachytherapy are associated with a lower probability of occurrence of radiation cystitis compared to conventional. But even with such treatment, accidental irradiation of nearby tissues is inevitable due to the penetration of neoplasms into surrounding organs or due to the proximity of cancer to neighboring pelvic structures.
Causes
During radiation therapy, the energy of ionizing radiation is transferred to the molecules of tumor cells and tissues of neighboring organs, in particular, to the bladder, rectum. As a result of alteration, trophic, blood supply is disrupted, and fibrotic-sclerosing changes develop later. Radiation cystitis causes radiation therapy for tumors of:
- the prostate gland;
- vaginas, uterus, her cervix, ovaries;
- bladder;
- colon, rectum.
The localization of the neoplasm, the stage of the disease, the daily and total radiation dose (number of sessions), the type of radiation therapy have a certain significance. Contributing factors to cystitis include:
- a general decrease in the immune reactivity of the body against the background of a malignant neoplasm;
- performed surgical intervention, for example, transurethral resection (TUR) of the prostate or the bladder wall with a tumor;
- simultaneous chemotherapy;
- urological diseases: concomitant inflammatory process, cystolithiasis, diverticula;
- pathologies predisposing to poor healing, local ischemia: AIDS, diabetes mellitus, vascular diseases;
- fatness (BMI >30 kg/m2);
- carrying out hormonal treatment for prostate cancer;
- chronic nicotine intoxication (≥ 1 pack per day).
Pathogenesis
Radiation interacts with intracellular fluid, resulting in the release of free radicals that disrupt DNA synthesis, which leads to cell death. Against the background of therapy, the membranes of both cancer and healthy cells are damaged, changes affect the vessels. Subendothelial proliferation, edema gradually deplete the blood supply to the irradiated area. Neovascularization, inadequate regeneration provoke the formation of fragile surface vessels responsible for macrohematuria in hemorrhagic cystitis.
The deposition of collagen triggers scarring processes, promotes further obliteration of blood vessels, resulting in hypoxia, necrosis. In the bladder, against the background of mucosal ischemia, the urothelium is damaged, which causes submucosal fibrosis, since subepithelial tissues are exposed to the caustic effects of urine. The formation of ulcers, nerve damage, and radiation fibrosis ensure the appearance of detailed clinical symptoms.
Classification
Radiation cystitis can be early, occurring within 4 weeks or 6-12 months after therapy, and late, with the appearance of symptoms a year or later. There are acute and chronic course of radiation inflammation. Specialists in the field of oncourology use a special scale to assess the severity of changes in the bladder exposed to radiation:
- Grade 1 implies minor epithelial atrophy and vasodilation, the detection of single erythrocytes in the urine. Clinical manifestations are more often absent.
- Grade 2 is characterized by the detection of multiple telangiectasias, episodes of macrohematuria. Urination is more frequent, there are complaints of urinary incontinence.
- Grade 3 is represented by a modification of vessels over the entire surface, the formation of a microcyst (a decrease in the capacity of the organ), persistent urinary incontinence, debilitating urge to urinate up to 40 episodes per day, including nocturia, recurrent macrohematuria.
- Grade 4 cystoscopy reveals areas of necrotization, signs of total hemorrhagic cystitis with petechiae, bladder capacity with tight filling of less than 100 ml, there is a complete loss of control over urination, requiring auxiliary measures (catheterization or cystectomy). Blood, protein, and the exfoliated epithelium are constantly present in the urine.
- Grade 5 is the most unfavorable in prognostic terms, hematuria leads to the development of life-threatening anemia, the formation of fistulas. The most pronounced pain syndrome and a high risk of death are determined.
Symptoms of radiation cystitis
Immediately or a few weeks after receiving a significant dose of radiation at the same time, an acute inflammatory process develops. As a rule, early cystitis is self-limited, the symptoms are similar to acute infectious inflammation, include pains with frequent urination and after, abdominal pain, urgent urge to urinate. There may be blood in the urine, but microhematuria is more typical. There is a good response to therapy.
Radiation cystitis, which occurred several months or years after treatment, can manifest itself with constant dysuria, severe pain, urge to urinate every 10-15 minutes due to the formation of microcysts, urine excretion with blood, persistent incontinence. Macrohematuria becomes recurrent, significant blood loss is detected. An increase in temperature indicates secondary bacterial infection.
Complications
Radiation cystitis is complicated by the addition of infection with the development of bacterial inflammatory process in the kidneys (pyelonephritis in 20%), progressive decrease in capacity or scarring of the organ and neoplasia (less than 2%), fistula formation (2%), cervical contracture (3-5%). With severe radiation inflammation, an uncupable chronic pain syndrome occurs, which significantly worsens the quality of life.
Bleeding from modified vessels (hemorrhagic cystitis in 3-5%) is often accompanied by anemia, sometimes the frequency and severity of bleeding is so significant that cystectomy is required, since repeated coagulations only aggravate the fibrotic-sclerotic process. Hematuria may be accompanied by the formation of clots, which lead to acute urinary retention due to the hemotamponade of the urethra.
Diagnostics
The passage of treatment using ionizing radiation with the delayed appearance of typical complaints is the main criterion on the basis of which the urologist makes a preliminary diagnosis of radiation cystitis. Considering that these symptoms may indicate a number of other pathological processes, the passage of an in-depth clinical and urological examination, which includes:
- Laboratory tests. Micro- or macrohematuria, protein, epithelium, sometimes bacteria, leukocytes are detected in urine test. Bakposev is produced to exclude urinary tract infection. Urine cytology is justified in case of suspected bladder cancer. In the results of the blood test, attention is paid to hemoglobin, hematocrit, platelet level. The coagulogram allows to exclude violations in the work of the coagulation system.
- Instrumental diagnostics. The main study is a cystoscopy, which allows you to exclude other causes of complaints, for example, a stone or a bladder tumor. A typical picture is multiple telangiectasia on the background of edematous mucosa, at an advanced stage – multiple erosions. Other imaging methods (MRI, CT, excretory urography) are prescribed to exclude fistulas and other causes of hematuria.
- Biopsy of the bladder wall. Morphological examination is carried out after receiving ambiguous results of ultrasound, cystoscopy and CT or MRI with a high probability of a tumor process. Before performing a biopsy, the potential risk of bleeding from superficial vessels as a result of trauma is taken into account.
Differentiation is carried out between urocystolithiasis, the spread of the tumor from the pelvis to the bladder, the progression of cancer accompanied by bleeding, pain syndrome. CT and MRI are becoming the main diagnostic procedures in this clinical situation.
Treatment
Therapeutic measures depend on the severity of the process, in each case are determined individually. The first and second degrees of cystitis after irradiation require active tactics only in the presence of complaints. Cystectomy is considered as an extreme option for the treatment of post-radiation cystitis, performed if conservative therapy is unsuccessful.
Medical treatment
Radiation-induced hematuria can be mild or life-threatening, in the second case resorting to resuscitation measures, transfusion of blood components. The list of drugs for treatment includes:
- anticholinergic agents;
- analgesic agents;
- fibrinolytics;
- medications that improve blood circulation;
- alpha-1-adrenoblockers.
Instillation into the bladder
Infusion of solutions is the next stage of treatment if oral therapy for radiation cystitis and an established irrigation system are ineffective. The following drugs are used:
- Hyaluronic acid. Mucopolysaccharide, present in connective and epithelial tissues, inhibits the formation of immune complexes, neutralizes the functions of neutrophils in regulating the proliferation of fibroblasts, endothelial cells. Chondroitin sulfate has a similar effect.
- Aminocaproic acid. Stabilizes the blood clotting process by fibrinolysis.
- Formalin. 1% solution is a tissue fixative that denatures the surface layer of the urothelium, providing hemostasis. Treatment is accompanied by severe pain, which requires the appointment of analgesics. The risk of side effects is high.
- Aluminum salts. 1% aluminum-ammonium sulfate or aluminum-potassium sulfate causes protein deposition on the cell surface and in interstitial spaces, which allows bleeding to stop.
- Placental extract. It is effective in epithelialization of erosions, ulcers.
Surgical treatment
If conservative therapy and intravesical instillations cannot stop the bleeding, various endoscopic or percutaneous interventions are resorted to. Cystoscopy with fulguration of problem areas, evacuation of a blood clot, electrocoagulation are reasonable steps in further tactics. Types of interventions for radiation cystitis:
- Introduction of botulinum toxin A. The drug is injected into the bladder wall in the absence of the effect of anticholinergic drugs. Treatment is aimed at increasing the capacity of the bladder, reducing the frequency of urination, relieving urgent urges.
- Application of percutaneous nephrostomy drainage. The removal of urine from the kidneys contributes to the regeneration of the urothelium of the lower urinary tract. After 3-6 months, the anatomically correct outflow of urine is restored.
- Endoscopic sclerotherapy. The introduction of sclerosant into bleeding areas is not effective in 100% of cases, but in most patients with intractable hemorrhagic cystitis, it reduces the severity of symptoms, hemostasis.
- Embolization of vessels. Helps to stop bleeding in refractory radiation hemorrhagic cystitis.
- Palliative cystectomy. Organ-bearing surgery is indicated for recurrent hematuria with the failure of all types of treatment, the formation of a fistula, microcysts (volume less than 200 ml) with debilitating urge to urinate, persistent pain syndrome. Urine is removed by creating a large intestine conduit or performing a bilateral transcutaneostomy.
Physical therapy
Hyperbaric oxygen therapy (oxygenation) promotes normalization of angiogenesis, mobilization of stem cells, stopping bleeding due to activation of fibrinolysis processes, resolution of ischemia. It is used as an additional method of treatment of radiation cystitis. Conducting oxygenobarotherapy does not have any adverse effects.
Prognosis and prevention
Radiation cystitis, which developed 4-6 weeks after the start of the LT sessions, has a more favorable prognosis. Improvement occurs after about 1.5 months, but in 5-20% the process turns into a persistent form with recurrent clinical manifestations after a few months or even 10-20 years. Chronic forms are less favorable.
Prevention involves choosing the type of radiation therapy with maximum effect on the tumor, but not on neighboring tissues, performing instillations based on hyaluronic acid for preventive purposes, taking herbal diuretics. Studies have shown a reduction in cystitis symptoms when using supplements containing cranberry extract.
