LECTURE: Managing Transitional Cell Carcinoma of the Bladder in Rural Areas – Thursday, August 6, 2020

Cancers are growth of abnormal cells that has lost what is called contact inhibition. Normal cells grow to replace the damaged cells but when the repair is over, they stop growing because of contact inhibition. However, the cancers cells continue to grow. The Urinary bladder cancers are from transitional cells that line the inner surface of the urinary bladder. Rarely other types of cancers can occur in the bladder. Squamous cell carcinoma develops in the thin flat cells of the bladder and forms with chronic infection or irritation.  Adenocarcinoma of the bladder is from the glandular or secretory cells of the bladder. Other cancers like lymphomas and sarcomas can occur in the bladder too.

What causes bladder cancer?
There are many causative agents associated with bladder cancer. This is because most of the unwanted substances are excreted through the bladder and there is significant contact time with the bladder. Using tobacco especially smoking is the most well-known agent. Smoking is the causative agent in half the men and about a third of women. Stopping smoking reduces the risk of cancer. Changes in some genes are associated with bladder cancers and hence having it is much higher when there is a family history of bladder cancer. It is an industrial hazard for those working in factories dealing with paints, dyes, metals, and petroleum products. Rubber, Leather, and textile workers are more prone and so are mechanics and drivers.

Water contaminated with arsenic is another factor associated with bladder cancer and water treated with chlorine also associated with increased incidence. Infection with Shistosomiasis and any chronic irritation like long term catheters; stones, etc. could be a causative factor too.

Top Six Causes of All Cancers in Men and Women
Risk factors of the 158,700 cancers diagnosed in men and 155,600 cancers diagnosed in women each year are given in the Table below. This is for all cancers.

What are the symptoms of bladder cancers?
The following are the common symptoms: Approximately 80 to ­90% of patients with bladder cancer present with painless gross haematuria. All patients with this classic presentation should be considered to have bladder cancer until proof to the contrary is found. Irritative bladder symptoms like burning while passing urine, urgency, increased frequency, etc. can occur in about 20 to 30% of the patients. Patients with advanced disease present with back pain or lower abdominal pain.
Patients with advanced disease could present with swellings and inability to pass urine too.

How can bladder cancer be diagnosed in rural areas?

The best way to diagnose the bladder cancer is to do cystoscopy to have a look inside the bladder and take biopsy and treat at the same time. The following tests are helpful.
1. Urine analysis or simple testing of the urine would show plenty of red blood cells in the urine.
2. Urine cytology: If a pathologist is available, they can have a look at the cells found in urine to see if there is cancer. If it is positive it is helpful but negative cytological examination does not rule out cancer. Recently some studies have shown that some dogs could be trained to identify cancers through smell.
3. Ultrasound examination: This can diagnose the papillary growths and might give some indication of the depth of the cancer.

4. CT scan: This is carried out in advanced centres to identify the extent of the cancer especially in advanced cancers and especially the depth of the cancer. However, it might not be necessary in rural areas in non-invasive cancers. It is important to take a separate deep biopsy during cystoscopy to find out about muscle invasion of the tumour.

Why is staging of the bladder cancer important?
The staging of the cancer is important for two reasons. The treatment of superficial and muscle invasive cancers are different. The staging gives information about the prognosis of the cancer. The spread of the disease could be local, through the lymph to the nearby lymph nodes and through blood to distant places. Chances of spread are much higher once the cancer invades the muscles. Fortunately, many of the cancers present early before it becomes muscle invasive.

Why is muscle invasion very important?
Unlike other cancers the bladder cancers have multicentric in origin. This means that they can appear anywhere in the bladder and can present at varying times. The inner lining of the bladder or transitional epithelium is loosely attached to the muscle and sometimes during surgery [that is not carried out carefully] the entire epithelium could be detached easily, and this poses a serious complication. The good thing about this anatomy is that treatment is easy and could be carried out through normal urinary passages as long as the tumour or cancer remains confined to the inner lining.

What are the available treatment options?
The treatment depends on whether the tumour is superficial or deep involving the muscles. The following are the options:
A. Transurethral resection of Tumour: This means removing the tumour through the normal urinary passages through resectoscope and a cutting loop. This is necessary for confirming the diagnosis and to see if it involved muscles. Hence a separate deep biopsy is essential. The drawback is that it bleeds because the loop only cuts tissues and experience is necessary to resect the tumours in the bladder looking at the two dimensional monitor screen and also because the resectoscope allows movement only in one direction and the entire scope has to be moved for resection.
B. Transurethral vaporization of tumour: This is carried out after resection of biopsy. It makes the tumour vaporize due to much higher heat. This overcomes the problems with resectoscope as it is much easier just to touch the tumour and this  causes vaporization of the tumour.
C. Transurethral vaporization with normal saline: This is the safest method as normal saline is used that gives better vision compared to use of Glycine and has no complications due to dilution hyponatremia.

D. Immunotherapy with intravesical BCG: This has been used for those with what is called CIS or multiple small tumours all over the bladder that would be difficult to resect or vaporize. Usually about 60 vials of BCG are used. They are left in the bladder for about 45 minutes once a week. How it works is not known.
E. Chemotherapy for TCC: Chemotherapy with medicines like Doxorubicin, Mitomycin C, Valrubicin, etc. instilled into the bladder has been tried. Sometimes with extensive tumour when surgery is not possible this may be the only available option. Methotrexate, vincristine, Adriamycin [Doxorubicin] and Cisplatin is a commonly used regime for bladder cancer [MVAC].

F. Radical Cystectomy: Removing the entire bladder along with the lymphatics is necessary for the muscle invasive tumours. This also involves ileal conduit or some other urinary diversion method. It is a major surgery.
G. Radiation therapy: Radiation therapy has been used for advanced bladder tumours.

The common treatment plan for superficial tumours is vaporization of the tumour following confirmation with resection. This is done as follows:
1. Initial resection and biopsy and vaporization of the entire visible tumour.
2. Check cystoscopy every month and vaporization of new tumours. These check
cystoscopies continue every month till there are three negative scopies or three times there
is no tumour.
3. With three negative check cystoscopies these could be done once in three months.

4. With 9 months of no tumour recurrence the check cystoscopies could be carried out once a year. Intravesical BCG could be tried if the tumour seems to cover the entire bladder. Radical Cystectomy could be used for those with muscle invasive tumour who are capable of withstanding such major surgery.

4. With 9 months of no tumour recurrence the check cystoscopies could be carried out once a year. Intravesical BCG could be tried if the tumour seems to cover the entire bladder. Radical Cystectomy could be used for those with muscle invasive tumour who are capable of withstanding such major surgery.

What are the advice given post - ­operatively?
The following are important.
A. The patient should quit smoking if he / she is a smoker.

B. Similarly, if they work in rubber, textile, leather, paint, or chemical industry it would be good to change the environment.
C. Although regular check-ups are advised as above, when there is blood in the urine or burning while passing urine they should report immediately.
D. They should avoid preserved food as many food preservatives contain carcinogens.

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Dr. J. Gnanaraj MS, MCh [Urology], FICS, FARSI, FIAGES is an urologist and laparoscopic surgeon trained at CMC Vellore. He is the Past President and Project Lead for the Project GILLS of the Association of Rural Surgeons of India, the Secretary of the International Federation of Rural Surgeons and board member of the G 4 Alliance. He is also an Adjunct Professor at Karunya University. He has over 400 publications in national and international Journals related to rural surgery and has won many innovations award like the EHA innovation award, Antia Finseth award, the Lockheed Martin award, the Millennium Alliance award, etc., He has few patents and the low cost equipment is listed in the WHO compendium of medical equipment for resource poor setting. He has helped many hospitals start Minimally Invasive Surgeries. The popular innovations that have made MIS possible in rural areas are the Gas Insufflation Less Laparoscopic Surgeries and the Laptop cystoscope. 

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