What is the Renal Pelvis and Ureter, What is their Structure?

The renal pelvis and ureters form the upper urinary tract and are part of the urinary excretory system. The renal pelvis is the hollow part in the middle of each kidney, also called the renal pool. The ureters are thin tubes that connect the kidneys to the bladder. Each ureter is approximately 25 to 30 cm long. Urine is your body’s fluid waste and is made by the kidneys. It collects in the renal pelvis and travels through the ureters to the bladder, where it is stored. When the bladder is sufficiently filled with urine, it is excreted out of the body through the urethra.

Both renal pelvis and wall of ureters consist of three separate layers

  • Mucosa:The urothelium (cells lining the pelvis, ureter and bladder) can be considered as the inner lining of both renal pelvises, ureters, bladder and urethra. These urothelial cells, which can stretch and change shape during urine flow, are also called transitional epithelium.

  • Lamina propria:Under the urothelium of both renal pelvis and ureters is a thin layer of connective tissue containing blood vessels, nerves and some glands.

  • muscularis propria : is the thick, outer muscle layer of both renal pelvis and ureters. It consists of involuntary automatically working muscle (smooth muscle). It is responsible for pushing urine from the kidney to the bladder.

Other tissues surrounding the kidneys and ureters include:

  • Adventitia layer:loose connective tissue lining the kidneys and ureters

  • fat layer: A layer of fat surrounding the renal pelvis, kidney, and ureter

What is Pelvic and Ureteral Cancer?

Cancer of the renal pelvis and ureter, or in other words, cancers of the upper urinary tract; These are malignant, malignant cancers that originate in the cells of the renal pelvis (the kidney’s pool) and/or the ureter (a tube that connects the kidney to the bladder). These cancers can spread to all layers in the pelvis and ureter, to neighboring tissues, and to other distant parts and organs of the body. Renal pelvis and ureter cancers are seen 3-4 times more frequently in men than in women, with an average age of 65 years.

Renal pelvis, Urothelial Cancers of Ureters

The renal pelvis, ureter, bladder and urethra (urinary tract) are covered with cells of the same type called transitional epithelium, and cancers of these regions are collectively called urothelial cancers or transitional epithelial cancers. The urothelium cells covering these areas begin to proliferate, grow and become cancerous for a number of reasons, and if not noticed, they continue to spread. According to the place of residence; If it is in the bladder, it is called bladder cancer (most often), if it is located in the ureters, it is called ureter cancer, and if it is in the renal pelvis, it is called renal pelvis cancer. 90% of the cancers of these regions are such cancers, while the remaining 10% are squamous cancers and adeno cancers that originate from the same cells and undergo metamorphosis. Although cancer of the renal pelvis and ureter is most common in the renal pelvis, it can occur simultaneously in the ureters, in several areas, or in the ureters only.

Approximately 20% to 40% of patients with urothelial carcinoma of the pelvis and/or ureters also develop bladder cancer, originating from the same cells, simultaneously or at different times. Therefore, patients diagnosed with cancer of the pelvis and/or ureter should be checked for cancer of the bladder and other parts of the urinary tract. Conversely, in patients with bladder cancer, there is a possibility that this type of cancer in the pelvis and ureter (cancer of the upper urinary tract) may accompany or occur at different times, and this rate is 4%.

Pelvic and/or ureteric cancers (as in bladder cancer) are divided into two groups as superficial (non-invasive) or disseminated (invasive) depending on how much they grow on the walls of these structures.

Superficial (Non-invasive) urothelial carcinoma: Superficial urothelial carcinoma means that the cancer is confined to the inner lining of the pelvis and/or ureter only. They can develop as papillary, that is, in the form of a fluffy cauliflower from the surface or flat (without a stem).

  • Papillary superficial urothelial carcinomas It tends to grow into a small, finger-like projection and into the internal cavity of the pelvis and/or ureter. These superficial papillary urothelial cancers may be low or high grade. However, small papillary cancers generally tend to be low grade. These tumors are called low malignant potential papillary urothelial neoplasms (PUNLMP). Some low-grade tumors also have a small chance of turning into an invasive-spreading cancer.

  • Flat-flat superficial urothelial carcinomas are tumors that grow along the lining of the pelvis and/or ureter. They are usually of high grade and are more likely to descend deeper into the layers of the pelvis and/or ureteral wall. This type of flat urothelial carcinoma more commonly includes carcinoma in situ (CIS) and has a high potential to spread.

Disseminated-Invasive urothelial carcinoma: Invasive urothelial carcinomas have grown into the deeper layers of the renal pelvis and/or ureteral wall. It may have protruded from the wall beyond the pelvis and/or ureter and may have grown into adjacent areas.

Sometimes disseminated-invasive urothelial carcinomas contain different types of cells with the usual urothelial cancer cells and differentiated or differentiated cells from these cells, in which case the prognosis of such cancers is worse. They have different cell types mixed in. These different cell groups include squamous cells, secretory gland cells, and small cells.

There are rare subtypes of urothelial carcinoma called variant type. These subtypes usually grow and spread rapidly and tend to have a worse course than normal urothelial carcinoma.

Variant types of renal pelvis and ureteral cancer include:

  • Nested(introverted layer by layer)

  • microcystic

  • micropapillary

  • Lymphoepithelioma-like

  • plasmacytoid

  • sarcomatoid

  • giant cell

  • Poorly differentiated (poorly differentiated)

  • rich in oil

  • transparent cell

Rare renal pelvis and ureteral cancers

Squamous cell carcinoma: Squamous cell carcinoma of the pelvis and/or ureter arises from smooth-squamous cells in the inner lining of the renal pelvis and ureter. It is usually associated with long-term (chronic) irritation or inflammation of the pelvis and ureter. This irritation is due to urinary stones or chronic urinary tract infections. Squamous cell carcinoma usually has a high potential to spread and is usually already spread when diagnosed and is treated with surgery and/or chemotherapy.

Adenocarcinoma: Adenocarcinoma originates from the glandular cells in the pelvis and ureter, or more often, it occurs when adenocarcinomas in other organs of the body metastasize to the pelvis and ureter, as a secondary cancer. Therefore, for a correct diagnosis, it is necessary to know where adenocarcinoma starts. There are many subtypes including mucinous, signet ring and clear cell. Their course is quite poor and is treated with surgery and chemotherapy. The probability of recurrence is high.

What Causes Kidney Pelvis and Ureteral Cancers and What Are the Risk Factors?

A risk factor is a substance or condition that increases the likelihood of developing cancer. We cannot say that people with these factors develop cancer, although these risk factors play a leading role in the onset of cancer, the exact cause of this and other body cancers is unknown. Cancer of the pelvis and ureter can develop even in those who do not have any risk factors. But most cancers occur as a result of many risk factors. Even if coffee and alcohol do not appear to be risk factors for cancers of the pelvis and ureter, alcohol consumption in particular is considered to be a general risk factor for this and other cancers in the body.

Certain known risk factors for cancers of the pelvis and ureter are: There is evidence that the following factors increase the risk of cancer of the pelvis and ureter.

  • Smoking

  • Aristolochic acids

  • Balkan endemic nephropathy

  • Chronic kidney stones and/or infections

  • Use of a pain reliever called phenacetin

Possible risk factors for pelvic and ureteral cancers are: The following risk factors are normally known risk factors for bladder cancer. Since these are similar cancers, it is thought that these risk factors may also increase the risk of cancer of the renal pelvis and ureter. Therefore, it is considered as a possible risk factor.

  • Arsenic

  • Occupational exposures

Smoking:It is a definite risk factor for renal pelvis and ureter cancer, the risk increases as the duration of smoking and the number of cigarettes increase.

Aristolochic acids: Aristolochic acids occur naturally in a variety of plant species. This substance is used in traditional Chinese medicine as a pain reliever and anti-inflammatory for joint pain, and kidney damage and cancer of the pelvis and ureter are more common in those who use this herbal product.

Balkan endemic nephropathy: Balkan endemic nephropathy is a kidney disease that is prevalent especially in the Balkan countries (Serbia, Bulgaria, Romania, Macedonia and Bosnia-Herzegovina) and mostly in rural areas of these countries. Kidney damage and cancer of the pelvis and ureter are observed more frequently in patients with this disease. In the studies conducted in this region, it has been determined that the seeds of plants containing Aristolochic acid are dense and those living in these regions, especially in rural areas, consume the plants containing this substance. However, there is still evidence that Balkan nephropathy is a genetic, familial disease. because

Chronic kidney stones or urinary tract infections:People with persistent kidney stones or kidney infections have a higher risk of rare squamous cell carcinoma, usually of the renal pelvis and/or ureters.

Usage of Phenacetin: Phenacetin is a type of pain reliever. People who have taken 3 or more phenacetin pills a day for several years have a higher risk of cancer of the renal pelvis and ureter.

Arsenic: Arsenic in drinking water is a ‘risk for patients. Also renal pelvis and ureter recipients.

Occupational exposures: There are several occupational exposures that increase the risk of bladder cancer and can also increase the risk of pelvis and bladder cancer. These are workplace exposures to certain chemicals called aromatic amines.

The lines of business most exposed to aromatic amines are:

  • paint industry

  • Rubber production

  • Textile and paint

  • Production of aluminum and other metals

What Are the Symptoms of Pelvic and Ureteral Cancer?

Cancer of the renal pelvis and/or ureter may not show any symptoms or complaints in the early stages. Signs and complaints usually occur as the tumor grows or spreads into the pelvis and ureter wall.

Symptoms of cancer of the renal pelvis and/or ureter include:

  • bleeding in the urine, bloody urine

  • Backache,

  • flank pain just below the ribs, kidney pain

  • burning or pain when urinating

  • The need to urinate more often than usual (frequent urination)

  • Tiredness

  • Loss of appetite

  • unexplained weight loss

How is Pelvis and Ureteral Cancer Diagnosed?

While the diagnostic process can seem long and frustrating, it’s normal to be worried. It is important to remember that symptoms of other non-cancerous causes may be similar to those of cancer of the pelvis and ureter. A series of examinations and analyzes may be required to separate all these from each other. In addition, after the diagnosis of pelvic and ureter cancer, many imaging tests are required for staging and grading.

Health history and physical examination:It includes an inquiry with a record of your health history, your symptoms and risks, and any past medical events and problems.

Your doctor will ask the following questions about your background and family history:

  • Blood in the urine, bloody urination

  • Smoking, tobacco consumption

  • Chronic kidney stones or infections of the kidney and urinary tract infections

  • Occupational exposures: risky business interests such as paint, rubber, metals, textiles and paints

  • Does anyone in the family have urinary tract cancers?

  • The risks of pelvis and ureter cancer are questioned in the patient or family

Physical examination: Physical examination may reveal:

  • Palpable swelling, mass, or enlarged lymph node may be felt on abdominal examination

  • Kidney examination may be painful, which may be similar to the findings detected on examination for kidney stones.

  • Lower abdominal examination (Pelvic examination) or digital rectal examination may be required

Urine test: Blood cells, bacteria (germs) and debris cells in the urine sample are examined. It is often one of the first tests to check for abnormalities in the urine and problems in the urinary tract. The presence of blood in the urine (hematuria) is the first symptom of cancers related to kidney, urinary tract and bladder. However, the presence of blood in the urine does not always indicate a bad disease, on the contrary, bleeding in the urine is mostly caused by non-cancer reasons such as stones and infection. When urine is detected, it should be supported by other tests.

Urine culture: Urine culture helps detect bacteria and other microbes that can cause infection. In the laboratory, urine is kept in environments where microbes can reproduce for one day, and if bacteria has grown after one day, this is isolated and the type of bacteria is determined.

Urine cytology: Urine cytology refers to the examination of debris cells in a urine sample or urinary tract irrigation in the pathology laboratory. Urine cytology can be used to look for abnormal cells, including cancer cells. It is highly diagnostic especially in high grade cancers.

Complete blood count: A complete blood count measures the number and quality of white blood cells, red blood cells, and platelets. It can be done to detect anemia caused by prolonged bleeding from the urinary tract. It can also be used to check whether the infection is reflected in the blood picture, if any.

Blood Biochemistry: Blood chemistry tests, Kidney function tests, Liver function tests are usually requested. Renal dysfunction may be an expression of a blocked kidney or failure, and abnormal liver function tests may indicate liver metastasis or liver failure. Alkaline phosphatase is most abundant in bone and liver cells. An increased level of alkaline phosphatase may mean that the cancer has spread to the bone and/or liver.

Ureteroscopy and cystoscopy: Ureteroscopy uses a thin tube (endoscope) with a light and camera at the end (called a ureteroscope) to look inside the ureters and renal pelvis. If there is a tumor or abnormal area, it is a very important diagnosis, treatment and follow-up method used to perform a biopsy from there or to perform first-line treatment.

Again, cystoscopy is used to look inside the bladder and urethra (urinary tract) and is the first step of the endoscopic examination. Ureteroscopy and cystoscopy are performed consecutively in the same session, usually cystoscopy is performed first and then continued with ureteroscopy if necessary.

Biopsy: Biopsy or treatment material and washing water samples taken during endoscopy are sent to the pathology laboratory in accordance with the technique. The pathologist examines them and reports with a report whether there is evidence of cancer or any other pathological problem.

Retrograde pyelography: Retrograde pyelography is an x-ray that allows visualization of the entire urinary tract, including the kidneys and ureters. A dyed contrast agent is injected directly into the urinary system through a tube inserted into the ureter using the cystoscope. This procedure is also used to find out what is blocking the flow of urine.

Computed tomography: A computed tomography (CT) scan uses special x-ray equipment to create 3-dimensional and cross-sectional images of organs, tissues, bones, and blood vessels in the body. A computer converts images into detailed pictures. A CT scan of the abdomen and pelvis is used for tumor or urinary tract obstruction. It is also used to check if cancer has spread to the lymph nodes, liver, or other organs and tissues around the renal pelvis and ureter. A chest CT scan may be needed to check if the cancer has spread to the lungs.

CT urography, It is used for imaging all urinary tracts. After the injection of the dye (contrast substance) concentrated in the urine, tomographic images are taken at certain times, this helps us to visualize all the upper and lower urinary tracts, which gives important clues in the diagnosis and follow-up of pelvis and ureter cancer.

Magnetic resonance imaging (MRI): It uses strong magnetic media and radiofrequency waves to create cross-sectional images of organs, tissues, bones, and blood vessels. The computer converts images into 3D pictures. It is used to check whether cancer has spread to organs or areas outside the urinary tract.

Ultrasonography: Ultrasound uses high-frequency sound waves to create images of tissues. It can be used to check if cancer has spread to other organs or areas in the pelvis and abdomen. Ultrasound can also be used to check the drum of the kidneys.

chest x-ray: A chest X-ray may be taken to check if the cancer has spread to the lungs.

Bone scan: Bone scanning is an important examination used to show whether the bones keep this substance homogeneously by giving the radioactive substance called radiopharmaceuticals and held by the bones. With this, images of the entire skeletal system can be revealed. This test is used to check whether the cancer has spread to the bone. It is usually only done if you have complaints such as bone pain or if the blood alkaline phosphatase level is high.

Grading of pelvic and ureteral cancer

Rating refers to how cancer cells look compared to normal, healthy cells. Knowing the extent of the cancer gives you an idea of ​​the health cancer’s rampage, how fast it can grow, and how likely it is to spread. This information is of importance that can completely change the treatment plan. Grading can also help predict the course of the disease and the extent to which the cancer may respond to treatment.

For the grade, the pathologist looks at a sample of tissue from the renal pelvis or ureter under the microscope. They look at how different the cells look from normal cells (called differentiation) and other characteristics of the tumor, such as the size and shape of the cells and how the cells are arranged. They can usually tell how fast the tumor is growing by looking at how many cells are dividing.

The pathologist assigns a grade of 1 to 3 for cancer of the pelvis and/or ureter. A lower number means the cancer is a lower grade.

  • Low-grade cancers (Grade I), have well-differentiated cancer cells. The cells are abnormal but very similar to normal cells and arranged very similarly to normal cells. Low-grade cancers tend to grow slowly and are less likely to spread.

  • High-grade cancers (Grade III) have poorly differentiated or undifferentiated cancer cells. Cells are not like normal cells and are arranged very differently. High-grade cancers tend to grow faster than low-grade cancers and are more likely to spread.

  • Intermediate cancers (Grade II)form a group of tumors between low and high grade tumors these are horny tumors neither low nor high grade, but a grade between the two groups

Staging of Pelvic and Ureteral Cancers

Staging describes or classifies cancer based on how far the cancer has spread and where it was when it was first diagnosed. The information obtained from the tests determines the size of the tumor, in which parts of the organ there is cancer, whether the cancer has spread from where it started, and if it has spread, where it has spread, and the stage of the cancer is determined with this information. Determined phase; It is used for treatment planning, follow-up and predicting the course of cancer.

The most common staging system for renal pelvis and ureter cancer is the TNM (T: Tumor, N: Lymph metastasis, M: Distant organ metastasis) system, as in other cancer types. For cancer of the renal pelvis and ureter, there are 5 stages – stage 0, followed by stages 1 to 4. Stages 1 to 4 are usually written as Roman numerals I, II, III, and IV. In general, the higher the stage number, the more the cancer has spread.

The words local, regional or distant are used when defining the stage of cancer. Local means that the cancer is only in the Renal pelvis or ureter and has not spread to other parts of the body. Regional means that the cancer is confined to the renal pelvis or the area adjacent to the ureter. Distant means that the cancer has spread to tissues and organs in distant parts of the body.

The staging for renal pelvis and ureter cancer is as follows:

  • Stage 0 (or carcinoma in situ):The tumor is only in the renal pelvis and/or the inner lining of the ureter.

  • Stage I:The tumor has grown beyond the inner lining of the renal pelvis and/or into the connective tissue layer just below the inner lining of the ureter.

  • Stage II:The tumor has grown through the connective tissue into the renal pelvis and/or the muscle layer of the ureter.

  • Stage III:The tumor has grown through the muscle layer and has grown into the kidney or adipose tissue surrounding the renal pelvis or ureter.

  • Stage IV:In case of any of the following:

-The tumor has spread to nearby organs or the surrounding adipose tissue via the kidney.

The cancer has spread to nearby lymph nodes.

The cancer has spread to other parts of the body (distant metastases), such as the lungs, liver, or bone. This is also called metastatic renal pelvis and ureteral cancer.

Cancer of the renal pelvis and ureter that recurred after primary therapy

Recurrent renal pelvis and ureter cancer can recur after the cancer has been treated, and if the recurrence occurs in the pelvis and ureter, it is called local recurrence. If it recurs in tissues or lymph nodes close to where it started, it is called regional recurrence. If it recurs in another part of the body. this is called distant metastasis or distant recurrence.

Cancer of the renal pelvis and/or ureter most commonly spreads to the following organs and tissues:

  • Bladder

  • to adjacent tissues around the renal pelvis

  • Adipose tissue around the kidney and ureter

  • to lymph nodes

  • To the prostate

  • To the womb(uterus)

  • vagina

  • to the abdominal or pelvic wall

  • to the lungs

  • to the bones

  • to the liver

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