I. What is bladder cancer? In layman’s terms, bladder cancer is a malignant overgrowth of cells in the bladder. The most common overgrowth is located in the bladder lumen, which is the mucosal epithelium of the bladder. The mucosal epithelial cells of the bladder are called uroepithelial cells, and the cancer generated from it is called uroepithelial cancer, which accounts for 90-95% of all bladder cancers and is the most common type of bladder cancer. What are the symptoms of bladder cancer? Bladder cancer can cause some mild symptoms, and sometimes people are easy to ignore these symptoms, which include: hematuria is the most common symptom of bladder cancer, especially intermittent painless hematuria, which can be manifested as either carnal hematuria or microscopic hematuria, and the time of hematuria and the amount of bleeding are not consistent with the malignancy, stage, size, number and morphology of the tumor. It is reported that the incidence of bladder cancer manifesting as carnal hematuria is 17%~18.9%, and the incidence of bladder cancer manifesting as microscopic hematuria is 4.8%~6%. Painless hematuria is the most important sign of bladder cancer, and almost all patients with bladder cancer present this sign first. If this signal can be caught and timely examination can be conducted, early detection and early treatment can be achieved and better results can be obtained. Patients with bladder cancer also have urinary frequency, urinary urgency, difficulty in urination and pelvic pain as the first manifestation, which is another common symptom of bladder cancer. Tumors often cause bladder muscle spasm due to the stimulation of combined infection or tumor rupture, which makes bladder irritation symptoms more obvious. It is often associated with diffuse carcinoma in situ or invasive bladder cancer, while Ta and T1 stage tumors do not have such symptoms. Other symptoms include pain in the lumbar region due to ureteral obstruction, lower limb edema, pelvic mass, and urinary retention. Some patients present with weight loss, renal insufficiency, abdominal pain or bone pain at the time of consultation, all of which are advanced symptoms. Note: The above symptoms are not necessarily caused by bladder cancer, but if you have these symptoms, you should consult a doctor for diagnosis and treatment in time. 3.Is there any test to diagnose bladder cancer? Yes. Doctors can use different types of tests to diagnose bladder cancer. 1.Ultrasound examination With the emergence of high-resolution ultrasound probes, the image level of ultrasound examination of bladder and upper urinary tract has been improved continuously, and there is no need to use contrast agent, so ultrasound is more and more widely used as a first-line examination method to diagnose urinary system diseases. Transabdominal ultrasound has a sensitivity of 63-98% and a specificity of 99% for the diagnosis of bladder cancer. The kidneys, ureters and other organs of the abdomen can be examined simultaneously. Transrectal ultrasound shows the bladder triangle, bladder neck and prostate more clearly. Color Doppler ultrasonography can also show the blood flow signal at the base of the tumor, but the blood flow sign of bladder tumor is not very helpful for preoperative tumor staging and grading. 2.CT examination CT has some value in diagnosing bladder tumor and assessing the extent of bladder cancer infiltration (especially showing extra-vesical tumor infiltration). If cystoscopy reveals that the tumor is broad-based and non-tipped, with high malignancy and possible muscle infiltration, CT examination is feasible to understand the extent of tumor infiltration. In recent years, the resolution of multi-row spiral CT has been greatly improved and can detect smaller tumors (1-5mm), but in situ cancer is still not easily detected. It cannot accurately distinguish between non-muscle invasive bladder cancer (Ta l) and T2 stage bladder cancer. It cannot distinguish whether the enlarged lymph nodes are metastases or inflammation, and the history of previous tumor resection may cause overstaging due to the illusion of local inflammatory fatigue response. However, CT is superior in patients with urethral strictures or active bleeding in the bladder that cannot be cystoscopically examined. CTU (CT urinary tract imaging) can be an alternative to conventional IVU, providing more information about the examination, but with the disadvantage of more radiation exposure. Urine exfoliative cytology is one of the main methods for bladder cancer diagnosis and postoperative follow-up. Urine specimens are usually collected by natural urination, or by bladder flushing, which can get more cancer cells and facilitate the improvement of diagnosis rate. Notes for urine specimen collection: ①The specimen must be fresh, the epithelial cells shed from urinary system are easily degenerated or autolysed in urine. However, the first urine in the morning is not suitable for urine cytology due to the high rate of cell lysis. ②Prevent various kinds of contamination: In addition to requiring clean urine containers, prevent vaginal secretions and urine from being contaminated by exogenous substances (such as lubricants). ③The amount of retained specimen should be sufficient, usually not less than 50 ml. Advantages ①Safe, less painful for patients, no adverse reactions and can be repeatedly collected; ②Simple equipment required, easy to operate and can be used for census; ③Higher detection rate of cancer cells, especially for early-stage cancer; ④The collected cells represent a wide range of mucosal exfoliated cells, such as cancer cells of renal pelvis, ureter and evening bladder can be detected in urine cytology smear. Disadvantages ① There is a certain rate of misdiagnosis, still 10-40% false negatives. For example, when cancer cells are emitted in urine, it cannot be determined whether the lesion is in the renal pelvis or the bladder, so it needs to be combined with biopsy or X-ray to confirm the diagnosis. (3) Sometimes it is not easy to make a clear tissue typing of cancer cells. Positive urine cytology means that there is a possibility of uroepithelial cancer in any part of the urinary tract, including: calyces, pelvis, ureters, bladder and urethra. The sensitivity of urine cytology for detecting bladder cancer is 13% to 75% and the specificity is 85% to 100%. The sensitivity is closely related to the malignant grading of cancer cells. The sensitivity of bladder cancer with low grading is lower because, on the one hand, the tumor cells are better differentiated and their characteristics are similar to normal cells, which are not easy to identify; on the other hand, because the cancer cells are relatively tightly adhered to each other, not enough cancer cells are shed into the urine to be detected, so a negative urine cytology does not exclude the existence of low-grade uroepithelial carcinoma; on the contrary, high-graded bladder cancer or carcinoma in situ, both sensitivity and specificity are higher. Factors such as low number of cancer cells in the urine specimen, atypical or degenerative cells, urinary tract infection, stones, bladder perfusion treatment and technical differences of the examiner may affect the results of urine cytology. 4.Urine bladder cancer markers In order to improve the level of non-invasive detection of bladder cancer, research on urine bladder cancer markers has received a lot of attention. The US FDA has approved the use of BTAstat, BTAtrak, NMP22, FDP, ImmunoCyt and FISH for the detection of bladder cancer. Many other markers, such as telomerase, survivin, microsatellite analysis, CYFRA21-1 and LewisX, have shown high sensitivity and specificity in clinical studies for detecting bladder cancer. In China, some scholars have shown that urinary fibronectin ( Fibronectin) helps to identify muscle-infiltrating bladder cancer, and the combined urinary fibronectin to urinary muscle ratios can be used to predict postoperative tumor residual. Although most urine bladder cancer markers show high sensitivity, their specificity is generally lower than that of urine cytology, and so far, there is still no ideal marker that can replace cystoscopy and urine cytology to make adequate judgments on the diagnosis, treatment, postoperative follow-up and prognosis of bladder cancer. It is believed that with the emergence of new technologies, the future of research and application of urine bladder cancer markers is bright. 5.Cystoscopy and biopsy When a patient shows abnormal signs of urination, especially painless carnal hematuria, or repeatedly found microscopic hematuria, he should receive cystoscopy. Cystoscopy is the only means to confirm the diagnosis of bladder cancer before surgery. Cystoscopy can clarify the number, size, morphology (papillary or broad-based), and location of bladder tumors as well as abnormalities in the surrounding bladder mucosa, while biopsy of tumors and suspicious lesions can be performed to clarify the pathological diagnosis. If available, flexible cystoscopy is recommended. Compared with rigid cystoscopy, this method has the advantages of less injury, no blind field of view, and relative comfort. Bladder tumors are usually multifocal and non-muscle invasive bladder cancer can be associated with carcinoma in situ or dysplasia and present as inflammation-like reddish villous mucosal changes or can appear completely normal. Routine random or selective biopsy of the normal bladder mucosa in non-muscle-infiltrating bladder cancer is not recommended because the likelihood of finding carcinoma in situ is low (less than 2%), especially for those with low-risk bladder cancer. However, when urine exfoliation cytology is positive or the bladder mucosa presents abnormally, selective biopsy is recommended to clarify the diagnosis and understand the extent of the tumor. Random biopsy should be considered when urine cytology is positive and the bladder mucosa appears normal and the presence of carcinoma in situ is suspected. If the bladder tumor is carcinoma in situ, multiple carcinomas or the tumor is located in the bladder triangle or neck, there is an increased risk of complicating urethral carcinoma of the prostate, so it is recommended to perform urethral biopsy of the prostate. In addition, if the urine cytology is positive or the urethral mucosa of the prostate shows abnormal, biopsy of this area should also be performed. 6.Urological plain film and intravenous urography (KUB+IVU) Urological plain film and intravenous urography have been considered as routine tests for patients with bladder cancer in order to detect coexisting upper urinary tract tumors. However, the need for this test at the time of initial diagnosis is currently questioned because of the low amount of important information obtained. The incidence of upper urinary tract tumors in a group of 793 patients with bladder tumors was only 1.1% (9 cases), and the IVU made the diagnosis in only 6 cases. CT imaging of the urinary tract (CTU) can be an alternative to conventional IVU examination, providing more examination information and a higher diagnostic accuracy for uroepithelial tumors, with the disadvantage of a greater amount of radiation exposure. 7.MRI examination Conventional MRI is not significantly superior for bladder cancer examination. t1-weighted image of urine is very low signal, low to moderate signal of bladder wall, and high signal of peri-bladder fat. t1-weighted image is useful for examining tumor spread to adjacent fat, lymph node metastasis and bone metastasis, and even evaluating the invasion of adjacent organs except prostate. t2-weighted image T2-weighted images are high signal in the urine, low signal in the normal forceps, and moderate signal in most bladder cancers. Interruption of the tumor beneath the low-signal forced urinary muscle suggests muscle infiltration. Thus, MRI helps in staging the tumor. Because the mean apparent diffusion coefficient (ADC) of bladder tumors is lower than that of surrounding tissue, diffusion-weighted imaging (DWI) provides a better preoperative assessment of tumor T-staging and may be valuable in assessing tumor invasion of surrounding tissue. MRI was superior to CT in terms of staging, with accuracies of 78-90% and 67-85%, respectively. The sensitivity of MRI is much higher than that of CT and even higher than that of nuclear bone scan in detecting the presence or absence of bone metastasis. 8.Bone scan is generally not used routinely. It is only used when patients with infiltrative tumors have bone pain and bone metastases are suspected. Chest examination Preoperative chest X-ray should be done routinely to understand whether there is lung metastasis. The most sensitive test for lung metastasis is chest CT. PET (Positron Emission Tomography) is generally not used for diagnosis because the tracer FDG (Fluorodeoxyglucose) is excreted into the bladder through the kidneys, which affects the diagnosis of smaller tumors, and the high cost limits its application. The use of newer tracers (e.g. choline, methionine, acetic acid) has been reported. 11C-choline and 11C-acetic acid are not excreted through the urinary tract, thus effectively avoiding interference with bladder tumor imaging. Limited data suggest that 11C-choline and 11C-acetate may be a promising tracer for detecting lymph node metastases, but further confirmation is needed. PET/CT is currently considered to be more accurate than CT and MRI in the diagnosis of lymph node metastases, but it is not yet a substitute for MRI and nuclear bone scan in the diagnosis of bone metastases. Who are prone to bladder tumor and need special attention Smokers, workers who have contact with dyes, and those who are frequently exposed to the following substances: spices, rubber, leather, textile printing and dyeing, cables, paints, fuels, tar, pesticides, printing, stoker, electric materials, coal producers, painters, aluminum workers and so on. These are the high-risk groups and need regular medical checkups and timely medical consultation if hematuria occurs. Whether bladder cancer can be diagnosed early or not is crucial to the prognosis of patients. So how to detect and diagnose bladder cancer at an early stage? We should follow the four recipes step by step, namely: abnormal urination should be alerted, initial screening of tumor by urinalysis, confirmation of diagnosis by cystoscopy, and comprehensive evaluation by imaging.