transitional cell carcinoma of the bladder
Introduction
Introduction to bladder transitional cell carcinoma Bladder tumor (tumorofbladder) is the most common tumor in the urinary system, accounting for 6% of male tumors and 2.5% of mortality. The cause is not fully understood, but it is related to the environment, smoking and genetic factors. Many scholars have P53 gene on bladder cancer. The impact of biological behavior is of great concern and has become a routine inspection project abroad. The age of bladder tumors is more than 40 years old, and superficial papillary tumors account for about 80%, and 30% are multiple tumors. Indifferent bladder cancer with poor differentiation often occurs in elderly patients. Transitional cell carcinoma (94%) was followed by adenocarcinoma and squamous cell carcinoma. basic knowledge The proportion of illness: 0.001% Susceptible population: high-risk age is 40 years old or older Mode of infection: non-infectious Complications: renal failure
Cause
Bladder transitional cell carcinoma
Genetic susceptibility (25%):
The incidence of bladder cancer varies by as much as 10 times in the world, highest in Western Europe and North America, and low in Eastern Europe and some Asian countries. Interestingly, the genetics of the United Kingdom, Australia, and New Zealand are similar, and the incidence of bladder cancer is similar. Egypt Schistosomiasis causes bladder cancer to account for 18% of all cancers in Egypt. Transitional cell carcinoma in Taiwan may be related to peripheral blood vessel "black foot disease". Bladder tumors are closely related to gender age, and the incidence rate is 2 to 10 times higher than that of females; 60 years old The incidence rate is high in the future, and it may be because the environmental carcinogenic factors have to wait for a long time. Bladder cancer rarely occurs before the age of 40, and young bladder cancer is often a well-differentiated papillary transitional cell carcinoma, and rarely recurs after treatment. .
Risk factors (20%):
Bladder cancer is related to the environment, occupation, smoking, infection, chronic inflammation, stones, foreign body, pelvic irradiation, cytotoxic chemotherapy drugs, etc. It is believed that 25% to 27% of bladder cancer is related to occupation, 1/2 male, 1/3 Women are related to smoking.
Industrial workers in the dye textile industry have a high incidence of bladder cancer. It has been recognized that 2-naphthylamine, 1-naphthylamine, benzidine and 4-nitrobisbiphenyl are chemical industrial carcinogens. These substances are metabolized by the liver and reduced to Alpha-aminonaphthoic acid, which acts on the urothelium and causes occupational bladder cancer, has the highest incidence of bladder cancer in urinary tumors due to the longest retention of urine in the bladder.
The relative risk of bladder cancer in smoking is 2-10, and it is related to the amount of smoking. About 1/3 of bladder cancer has a long history of smoking. The cancer caused by smoking may be related to many chemical carcinogens in cigarettes. The metabolism of tryptophan in the urine of smokers The product increased by 50%. After smoking stopped, the level of tryptophan metabolism returned to normal, and the tryptophan metabolite was confirmed to be potentially carcinogenic.
Bladder cancer caused by bladder infection is squamous cell carcinoma, more than transitional cell carcinoma, schistosomiasis, calculus, chronic cystitis caused by bladder diverticulum often lead to squamous cell carcinoma, 80% of paraplegic patients have squamous metaplasia, 5% scale Cancer, urinary retention may also be the cause of bladder cancer.
Some drugs can cause urothelial tumors. At present, the painkiller phenacetin has been confirmed. Because it has the same chemical structure as aniline, the dosage is too large, which can cause renal pelvis and bladder transitional cell carcinoma. In addition, cyclophosphamide can also be increased. The risk of bladder cancer is 9 times more likely for cancer patients and non-tumor patients such as systemic lupus erythematosus and rheumatoid arthritis.
Large doses of cervical cancer radiotherapy for cervical cancer increase the chance of bladder cancer by a factor of four, which is related to the amount of radiation and the duration of exposure.
Biological characteristics (20%):
Studies on the biological behavior of bladder cancer have shown that the occurrence of bladder cancer is a multi-stage process involving multiple gene mutations, which can be divided into early and late stages. Early mutations lead to the initial transformation of urothelial cells. Late mutations make inferior cells invasive and metastatic, and the identification of bladder cancer gene mutations has made great progress, but no one (several) of chromosome or gene changes are found in all bladder tumors, and A variety of different genetic factors, mutations seem to lead to the same tumor morphology, which illustrates the diversity of DNA targets for carcinogenic factors and their effects, so far no mutations have been found that have a decisive influence on bladder cancer, but can not Therefore, it denies the important role of various mutations in the development of tumors. It has been hypothesized that there are two ways to develop bladder cancer, one is the transformation of undead stem cells, and the other is the transformation of basal cells into cells after viral infection. Undead, both pathways include the development of superficial to invasive final metastasis, in different hairs Different gene mutations play a role in the stage. In the first pathway, the deletion of the 9q chromosome transforms stem cells into superficial cancer, and the inactivation of P53 and Rb tumor suppressor genes and the activation of H-ras further develop the lesions. The initial change in the pathway is that viral carcinogenic factors inactivate P53 and Rb tumor suppressor genes, and subsequent mutations in other genes lead to tumorigenesis and development. At the same time as oncogenes and tumor suppressor genes, oncologists are beginning to pay attention to cancer cells. The process of information transfer from the surface to the nucleus attempts to reveal the occurrence and development of the tumor.
Pathogenesis
Normal bladder urothelium is a transitional epithelium, about 3 to 7 layers thick. There are large umbrella cells on the surface of normal epithelial cells covering some small cells in the lower layer. The surface of the umbrella cells is often binuclear or multinucleated, and the size and shape of the cells. It changes with the degree of expansion of the bladder. In the deep mucosa, the cells are round, elliptical, elongated or columnar, embedded in the fibrous basement membrane. This structure allows the cells to slide between the cells when the urinary tract migrates to the epithelium. Proliferative changes (proliferation and metaplasia) can occur when inflammation, chronic irritation, or carcinogens respond.
More than 90% of bladder cancers are transitional cell carcinomas, and their growth is diverse, including papillary, pedunculated infiltration, nodular and intraepithelial growth, which has greater variability potential; therefore, transitional cell carcinoma may contain Spindle cells, squamous epithelial cells and glandular epithelial cells, 1/3 of bladder cancer can appear in the above components, transitional cell carcinoma occurs in the basal and lateral walls of the bladder triangle, but transitional cell carcinoma can occur in any part of the bladder. About 70% of bladder cancers are papillary, 10% are nodular, and 20% are mixed. According to the degree of tumor cell differentiation, the tumors are classified into grade I, grade II and grade III. Grade I cancer cells are well differentiated, transitional epithelium. More than 7 layers, the cells are mildly metamorphosed and pleomorphic, the proportion of nuclear cytoplasm is increased, the mild dysfunction from basal to superficial cells, mitosis is like occasional, and the tumor cells of grade II cancer are from the basal layer to The surface layer is highly disordered, extremely lossy, the proportion of nuclear cytoplasm is significantly increased with nuclear polymorphism, nucleoli is coarse, mitosis is more common, grade III cancer is poorly differentiated, nuclear polymorphism is significant, and mitosis is more common. Tumor cells and Often little resemblance transitional epithelium.
1. Tumor spread The spread of bladder cancer includes direct infiltration of the tumor at the primary site, or lymphatic, blood line and planting to other sites.
(1) Direct diffusion: Invasive growth of bladder cancer can penetrate the entire bladder wall, extend to the fat around the bladder, adhere to the pelvic wall to form a fixed mass, or spread to the top peritoneum, or directly spread to adjacent organs.
(2) Lymph node metastasis and hematogenous metastasis: Lymph node metastasis of bladder cancer is more common, mostly pelvic lymph node metastasis (78%), of which closed-cell lymph nodes account for 74%, followed by extra-orbital lymph nodes, 65%, and common peroneal lymph nodes 20%. The para-bladder lymph nodes are rare in 16%. The distant metastasis is more common in advanced bladder cancer. The common metastatic sites are liver (38%), lung (36%), bone (27%), adrenal gland (21%), and colorectal (13 %)Wait.
2. Implantation metastasis can occur in the abdominal wall incision after open surgery, bladder neck, prostate and urethra after transurethral resection, but it is extremely rare.
3.TNM staging
Bladder tumor TNM staging:
Tx: Primary tumor cannot be assessed.
To: No primary tumor was found.
Tls: primary cancer.
Ta: papilloma, non-invasive papillary carcinoma.
T1: The tumor invades the submucosa (the lamina propria).
T2: The tumor invades the superficial muscle layer.
T3a: The tumor invades the deep muscle layer.
T3b: Tumors invade the fat around the bladder.
T4: The tumor invades adjacent organs such as the prostate/uterus/vagina/pelvic or abdominal wall.
Nx: No estimate of lymph node metastasis.
N0: No lymph node metastasis was found.
N1: Single lymph node metastasis, <2 cm in diameter.
N2: single or multiple lymph node metastasis, 2 to 5 cm in diameter.
N3: Single or multiple lymph node metastases, > 5 cm in diameter.
Mx: The distant transfer cannot be estimated.
M0: No distant metastasis was found.
M1: Transfer in the distance.
Prevention
Bladder transitional cell carcinoma prevention
1. First-level prevention to establish good living habits, quit smoking, maintain a healthy psychological state, vigorously strengthen the environment, labor health legislation, supervision and management, and strengthen people who may be exposed to dyes, rubber and plastics industries, etc. should regularly check and take certain monitoring measures. Taking vitamin B6 is expected to block the abnormal metabolism of tryptophan, and it should be actively treated for chronic cystitis, leukoplakia, stones, and schistosomiasis.
2. Secondary prevention screening can detect bladder cancer at an early stage. Generally, simple urine routine and urine exfoliative cytology are performed. Hematuria is the first and most common clinical manifestation of bladder cancer, and it is often painless intermittent. It should be further Urine cytology, cystoscopy and X-ray filming, once diagnosed, should be treated as soon as possible, according to the location, size, number of infiltration, depth of invasion can be used for transurethral resection of the tumor, partial resection of the bladder, total cystectomy, etc. The treatment of superficial bladder tumor with internal heat saline has a certain effect. The tumor is affected by ischemia and heat and necrosis. Radiotherapy can be used simultaneously with surgical treatment or alone for surgical contraindications. Chemotherapy usually uses intravesical instillation of chemotherapy drugs. The main purpose is to prevent postoperative recurrence of tumors. Intravesical instillation of lyophilized BCG (BCG) is effective in the treatment of bladder carcinoma in situ, and can be used for postoperative prevention of recurrence. Superficial bladder tumors are treated with laser or laser hematoporphyrin derivative. Have a certain effect, after the surgical treatment to prevent recurrence, the cystoscopy should be reviewed regularly, maintained every 2 months for 2 years, half a year 1 It was maintained for another 2 years, and then maintained for life for 1 year. In order to exclude urothelial tumors of the upper urinary tract, intravenous pyelography was performed if necessary.
3. Three-stage prevention of advanced bladder cancer can not tolerate total cystectomy. Simple ureteral sigmoid transplantation is used. Patients are in poor condition. Renal insufficiency is difficult to tolerate intestinal urinary diversion or reconstruction surgery can be performed on ureteral skin. Curcuma, patients with advanced pain, symptomatic, can be symptomatic, supportive treatment.
Complication
Bladder transitional cell carcinoma complications Complications, renal failure
If the cancer involves the ureteral orifice, there may be pain in the kidney area, hydronephrosis of the kidney, infection, and renal failure.
Symptom
Bladder transitional cell cancer symptoms Common symptoms Hematuria, dysuria, urinary frequency, urgency, weight loss, repeated bleeding, cachexia, urinary incontinence, pelvic mass, chest pain
The main symptom of bladder cancer is hematuria. Almost all patients have hematuria. About 85% of them are first symptoms, most of them are gross hematuria, but microscopic hematuria often occurs before gross hematuria. Early in the lesion, Carson et al. (1979 Further examination of 200 cases of patients with microscopic hematuria revealed that 22 cases were bladder cancer, accounting for 11%; 38 cases with no etiology were followed up for 2 years, and 6 cases were found.
The characteristics of gross hematuria are painless, mostly hematuria, or early or late hematuria, which occurs intermittently and persists. The interval varies from several days to several months. Generally, the early interval Longer, gradually shorten the interval with the development of the disease, the degree of hematuria depends on the amount of bleeding, manifested as washing water, accompanied by irregular or flaky blood clots, and even a large number of blood clots filled with bladder, the size of the general tumor is proportional to the degree of hematuria In severe cases, hemorrhagic anemia can occur, and there are also small tumors, repeated bleeding and anemia.
Bladder irritation symptoms, ie frequent urination, urgency, and dysuria, are another major symptom of bladder cancer, accounting for about 10% of the initial symptoms of bladder cancer. The cancer damages the function of bladder defense infection, and the cancer resembles foreign body in the bladder. It hinders the elimination of infection, so 40% of bladder cancer is accompanied by urinary tract infection. Extensive carcinoma of the in situ or invasive carcinoma can first cause obvious symptoms of bladder irritation, and even urinary incontinence, suprapubic area, penis and perineal pain. The cancer is located in the neck of the bladder or infiltrates the neck. The large amount of necrosis or large cancer in the cancer tissue can reduce the bladder capacity or accompany stones, which can cause bladder irritation. Any bladder with irritation or "carrion" Cancer, mostly advanced or invasive, has a poor prognosis.
Bladder neck or cancer involving the neck and prostate, cancerous tissue with pedicle cancer and large necrosis in the neck, can block the neck and appear dysuria, late limb edema, pelvic mass, cough, chest pain Such as metastatic symptoms and weight loss, anemia and other cachexia.
Examine
Examination of bladder transitional cell carcinoma
1. Exfoliative cytology is convenient and easy to repeat, but the early tumor positive rate is low, 1 flow cytometry: this method can measure tumor DNA content, aneuploid cell number, on-site carcinoma and high Period, the diagnostic accuracy of advanced tumors is high, up to 90%, 2 acridine orange test: tumor cells are impregnated with acridine orange fluorescein, and fluorescence microscopy can show the cellular ribonucleic acid (RNA) and deoxyribonucleic acid The (DNA) quantitative image also shows the morphological structure of the cells, which helps to determine the tumor cells and their vital state.
2. Tumor markers not only contribute to tumor diagnosis, but also have predictive significance for the biological behavior of tumors. 1 Bladder tumor antigen (BTA): Bladder tumor secretes proteolytic enzymes, which degrades bladder basement membrane into type IV collagen, fiber. The basic components such as protein lignin and laminin, these degradation products are discharged into the adjacent urine to form a basement membrane complex, the so-called bladder tumor antigen (BTA), which is a specific polypeptide with a relative molecular mass of 16,000 to 165,000. BTA reagent is a method for detecting bladder tumor membrane antigen. It has high sensitivity and specificity for transitional cell epithelial cancer. There are currently two kinds of BTA reagents: BTA stat and BTA test. The status of two BTA reagents in diagnosis is In parallel, in the sensitivity and specificity studies, the sensitivity and specificity of BTA stat and BTA test were 65.90%, 63.63% and 82.89%, and 81.57%, respectively. There was no significant difference if two reagents were combined. , the diagnostic specificity is significantly improved without reducing the sensitivity, which means that the combined application can reduce the false positive rate and avoid the false positive result. For further examination or treatment, BTA is a kit. Medical staff are not limited by time, location, equipment, and without special training. The results can be obtained in 5 minutes. No trauma is required. Only 20 ml of urine is needed. The test within 48 h does not affect the results. There are certain false positives and false negatives in BTA test. It can not be used to diagnose bladder cancer independently. In addition, BTA reagent is expensive and it is difficult to fully promote it. 2Lewis X antigen detection: Lewis X is an ABO blood group-associated antigen, which is absent in normal urothelium, and 5% to 89% of transitional cell carcinoma can detect Lewis X, and is independent of tumor grade, 3-nuclear matrix protein 22 (nuclear) Matrix protein22, NMP22): NMP22 is a nuclear mitotic protein. NMP22 in bladder tumor cells is more than 25 times that of normal cells. The sensitivity for diagnosis of bladder cancer is 48% to 90%, specificity is 70% to 92%, and NMP22 is Advanced, high-grade bladder cancer is highly sensitive, can be used for follow-up monitoring without stones, inflammation, etc., 4 fibrin degradation products (FDP): fast The sensitivity of ELISA in the determination of urinary FDP for the diagnosis of bladder cancer is 68%, and the sensitivity to T2 to T4 bladder cancer is as high as 100%. 5Galcerase detection hyaluronidase, HAase: Glycerase is an extracellular Endogenous glycosidase, which degrades the matrix hyaluronic acid, plays an important role in tumor progression. Gelase technology is used to detect the activity of hyaluronidase in the urine of G2 and G3 bladder cancer, with sensitivity ranging from 92% to 100%. Telomerase: Telomerase is a protective structure at the end of the chromosome, which gradually shortens with cell division until cell death. The role of telomerase is to extend telomeres. telomerase activity in various tumor cells has been found. Enhanced, the method for the diagnosis of bladder cancer including low-grade, low-stage tumors, sensitivity up to 91%.
3. Imaging examination
(1) B-ultrasound: 1 The most commonly used transabdominal route can obtain the basic image of the size, number, location and width of the base, providing a basis for the identification of phase A and phase C. It is easy to operate, painless and repeatable. The advantages of the operation, because the pelvis limits the conduction of sound waves, and the thickness of the abdominal wall, scars, intestinal gas and cancer bleeding and other factors, the diagnosis rate is relatively low, 2 cross-sectional examination through the rectal route can accurately show the front of the bladder The wall, the two side walls and the base of the tumor, but the top, the neck is not satisfied, the longitudinal examination shows clear to the bottom of the bladder, the triangle and the neck tumor, can accurately measure the size, and to some extent understand the tumor infiltration Depth, 3 transurethral route can clearly show the location and size of the bladder tumor, accurately determine the depth of tumor infiltration, can also show the bilateral ureteral lower segment, the inner wall of the bladder wall, bilateral seminal vesicles and prostate image, the examination for bladder cancer The coincidence rate between preoperative clinical staging and postoperative pathological findings is as high as 90% to 94%. The disadvantage is the deep infiltration of the tumor and the pelvic organs around the bladder. Inadequate display.
(2) IVU: At the same time, the upper urinary tract condition can be clarified, and the larger tumor can be found in the bladder area.
(3) CT, MRI: CT is the most accurate non-invasive examination for the diagnosis and clinical staging of bladder cancer. In addition to determining the size of the tumor and the depth of invasion of the bladder wall, it can also provide information about the pelvic and retroperitoneal lymph nodes. No metastasis, information on the presence or absence of metastasis of the liver or adrenal gland, has special significance for the diagnosis of bladder cancer and intracanal cancer. Enhanced CT and spiral CT scan can increase the accuracy of staging. MRI can provide images of multiple sections. Therefore, it can provide a better local anatomical relationship, but it is not superior to CT in clinical stage.
4. Cystoscopy is the most important method for the diagnosis of bladder tumors. It can be used to determine whether there are tumors, numbers, sizes, shapes, pedicles, etc., and biopsy can be performed.
Diagnosis
Diagnosis and differentiation of bladder transitional cell carcinoma
Clinically, it is intermittent, painless, and the whole eye is treated with hematuria. Laboratory examination, imaging and cystoscopy plus biopsy are the most important methods for diagnosis.
1. Bladder stones pass through the X-ray film of the bladder area, with or without opacity shadow, can make a preliminary identification, negative calculus can also show a filling defect, and bladder cancer combined with stones is not uncommon, cystoscopy is the main means In addition to seeing stones under the cystoscope, papillary or villous new organisms can be seen, and the diagnosis is further confirmed by biopsy.
2. Ureteral cysts are less common in hematuria. Hematuria can also be present in the case of infection. It is not as serious as bladder tumors. The cystography has a negative shadow in the bladder triangle. The negative image is a snake head. It is located in the triangle area and has a smooth surface. The examination is a cystic mass, with the discharge of urine, with a change in contraction, cystoscopy, see a blister-like bulge in the ureteral orifice, covered by the bladder mucosa, clear blood vessels, and peristalsis consistent with urination.
3. Bladder tuberculosis Bladder tuberculosis generally has a history of kidney or tuberculosis, low fever, night sweats, loss of appetite and other systemic symptoms, rice soup pyuria, urine test a large number of pus cells, urinary tuberculosis culture 60% positive, urine exfoliated cell examination No tumor cells, cystography and B-ultrasound, no space-occupying lesions in the bladder, cystoscopy, inflammatory changes in the bladder and tuberculous nodules, ulcers, no neoplasms, inflammation, ulcer wounds need attention and villous bladder The identification of cancer, the biopsy of cystoscopy is of great value for differential diagnosis.
4. Prostatic hyperplasia of prostatic hyperplasia can have gross hematuria. The mid-lobular hyperplasia of the bladder and the bladder tumor need to be differentiated. The tumor grows at the junction of the bladder neck or the bladder urethra. It can have dysuria, benign prostatic hyperplasia, and is characterized by dysuria. The medical history is relatively long. From a few years to a decade, the difficulty of urinating has gradually increased. The rectal examination touches the enlarged prostate, the middle groove disappears, and the cystography shows the impression on the bladder neck. Shadow, smooth surface, curved, cystoscopy, in addition to seeing prostate enlargement, no new organisms in the bladder, biopsy for suspicious cases, to help diagnose.
5. Bladder polyps This disease is rare, mostly occurs in chronic inflammation, parasitic and foreign body stimulation, secondary irritation has bladder irritation, generally no dysuria, cystography shows intravesical filling defects, the disease is mainly differentiated from bladder malignant tumors The hematuria of the bladder polyps is not as serious as that of malignant tumors. No tumor cells can be found in the urine. Cystoscopy, the surface of the polyps is smooth and there is no pedicle. The bladder malignant tumors are cauliflower-like or villous, and are easy to bleed. Biopsy has Help to confirm the diagnosis.
6. Kidney, ureteral tumors, hematuria characterized by intermittent painless full-length gross hematuria, similar to bladder cancer, can occur alone or with bladder cancer, must be distinguished, bladder cancer hematuria may be associated with bladder irritation or Beginning or terminal aggravation, hematuria color is mostly bright red, blood clots are mostly agglomerate, kidney, ureteral tumor without bladder irritation, hematuria is mostly dark red, sometimes accompanied by cord-like blood clots, renal parenchymal tumors often accompanied Low back pain and lumps are generally difficult to identify by B-ultrasound, IVU, CT and MRI.
7. Glandular cystitis is a precancerous lesion of the bladder. The clinical manifestations are sometimes similar to those of bladder cancer. Cystoscopy and biopsy are needed to identify.
