Congenital anomalies of ureters

Duplicated ureter is a condition in which there are two ureters that drain the same kidney. It occurs when the ureteric bud, which the ureter develops from, splits into two ureters. If this splitting is incomplete can we be left with a bifid ureter, where two ureters drain the same kidney, but the two ureters unite before draining into the bladder at a single ureteric orifice. These conditions have no clinical significance.

Ureteropelvic junction obstruction is defined as an obstruction of the flow of the urine from the renal pelvis to the proximal ureter. It’s a congenital malformation that is more frequent in male children but female adults. It may lead to hydronephrosis.

Congenital megaureter is an uncommon condition where the ureter is abnormally dilated. It increases the risk for infections.

Ureteral diverticulum is a very rare condition (with only 45 cases described in literature as of 2013). It increases the risk for infections.

Ureteral elongation and ureteral tortuosity are very rare but may increase the risk of infection.

Inflammation and tumours of the ureters

Ureteritis: Most cases of ureteritis are due to bacterial infections. It is rarely primary, but rather due to an ascending cystitis, descending pyelonephritis or due to spread from adjacent inflammatory lesions like an appendicitis. The infection may also reach the ureter by lymphatic spread.

Any of the previously mentioned abnormalities of the ureter predisposes to infective ureteritis.

Follicular ureteritis is a rare condition where there are lymphoid nodules in the ureter. Cystic ureteritis is another rare condition where the cysts grow in the ureter.

Fibroepithelial polyp is the most frequent benign tumor of the ureter. It’s very rare.

Urothelial carcinoma may occur in the ureter, commonly together with pelvic and bladder tumors. This type of cancer is described in more detail later in this topic.

Ureteric obstruction

Obstruction of the ureter is usually due to smaller kidney stones. This causes an excruciating colicky pain called renal colic.

Obstruction may also be caused by strictures, either congenital or acquired due to inflammation. Massive haematuria may cause clots to form inside the ureter.

Retroperitoneal fibrosis is an uncommon disease with autoimmune background where fibrosis encases and compresses the obstruction.

The ureter may also be obstructed from the outside, due to:

Pregnancy
Inflammation of structures around the ureter
- Salpingitis
- Diverticulitis
- Peritonitis
Endometriosis
Tumors
- Rectum
- Bladder
- Prostate
- Ovaries
- Uterus
- Cervix

Obstruction of the ureter leads to hydroureter, pyelectasis and hydronephrosis. This predisposes to infection and therefore pyelonephritis.

Congenital anomalies of the urinary bladder

Bladder diverticulum may be congenital or acquired. In both cases it rises due to weakness of the muscles of the bladder wall. The acquired form is more common and occurs when there is downstream obstruction, such as due to benign prostatic hyperplasia. Diverticulum predisposes to infections, formation of stones, vesicoureteric reflux and tumors.

Bladder exstrophy or ectopic bladder refers to the presence of the bladder on the outside of the body. It occurs due to defects of the abdominal wall and the anterior bladder wall. The bladder is actually everted or inside-out and must be treated with surgery. It increases the risk for adenocarcinoma.

Inflammation of the bladder

Cystitis is an inflammation of the bladder wall. It’s typically caused by a lower urinary tract infection, but it can also be caused by radiation, cytotoxic drugs or renal tuberculosis. Common pathogens are:

Gram negative bacteria (like E. Coli)
Chlamydia
Mycoplasma
Viruses, especially adenovirus

Haemorrhagic cystitis can be caused by cytotoxic drugs, adenovirus, BK virus and by catheterization.

Chronic cystitis can be caused by:

Follicular cystitis, which is similar to follicular ureteritis
Eosinophil cystitis
Interstitial cystitis – also called bladder pain syndrome
Malakoplakia – a condition where yellow, large plaques are present on the mucous membrane

Common symptoms of cystitis are urgency, lower abdominal pain and dysuria.

Bladder cancer

Bladder cancer is the most common cancer of the urinary system. The most common histological type is urothelial carcinoma, previously called transitional cell carcinoma (90% of cases), and 90% of urothelial carcinoma cases are in the bladder. The other histological types of bladder cancer are squamous cell carcinoma and adenocarcinoma.

Urothelial carcinoma can occur anywhere there is urothelium, although it occurs most commonly in the bladder and renal pelvis and more rarely in the ureters and urethra. It's usually asymptomatic in early stages, and the most common presenting symptom is painless gross haematuria, which is present in 80% of bladder cancer patients.

Bladder cancer is mostly a disease of older men. In the majority of cases, the disease is not muscle-invading and therefore has high chances of cure and good prognosis.

Risk factors

Urothelial carcinoma is the second most frequent cancer in smokers, after lung cancer of course. This is because the urothelium is exposed to the toxins in the cigarette smoke after it has been excreted by the kidney. It’s also associated with occupational toxins like aromatic hydrocarbons and arsenic. Other risk factors include:

Lynch syndrome
Family history of urothelial cancer
Previous radiation to the pelvis

Squamous cell bladder cancer is related to urinary schistosomiasis (a parasite specially in endemic countries like Egypt), chronic bladder irritation and infection.

Pathology

90% of bladder cancer cases are urothelial carcinoma, previously called transitional cell carcinoma.

Classification

The new WHO classification of urothelial carcinoma distinguishes between flat and papillary urothelial lesions:

Flat lesions
- Urothelial dysplasia
- Urothelial carcinoma in situ – flat carcinoma
Papillary lesions
- Urothelial papilloma – exophytic growth with normal-looking urothelium
- Urothelial neoplasm of low malignant potential – similar to papilloma but thicker urothelium
- Low grade papillary urothelial carcinoma – minimal atypia. retained polarity of cells.
- High grade papillary urothelial carcinoma – high atypia. loss of polarity.

Less than 10% of low-grade cancers invade, but as many as 80% of high-grade cancers do. Invasion majorly affects the prognosis; 5-year survival is 90% in non-invasive cancer but only 10% in invasive cancer. The degree of which the urothelial tumor has invaded the bladder wall is important in the prognosis. Invasive tumors may extend not only into the bladder wall but to adjacent structures like the prostate, seminal vesicles, ureters and retroperitoneum. Haematogenous dissemination usually involves the liver, lungs and bone marrow.

Polychronotropy

Urothelial carcinoma shows polychronotropy, which means that when one urothelial carcinoma is found it is very likely that other urothelial tumors are present or currently developing at other places of the mucous membrane. Because of this, urothelial carcinoma has a high risk of recurrence.

Pathogenesis

Carcinogenesis involves deletions of tumor-suppressor genes on chromosome 9p or 9q. The p16 or p53 genes are commonly involved.

Other histological types

Adenocarcinoma is rare and histologically identical to gastrointestinal adenocarcinomas.

Squamous cell carcinoma is rare and related to chronic inflammation of the bladder, especially schistosomiasis.

Clinical features

The most common symptom is painless gross haematuria. There may also be symptoms of bladder irritation, like dysuria, pollakisuria, and urgency.

Diagnosis and evaluation

Haematuria on urine analysis is seen in most cases of bladder cancer. Urine cytology may show cancer cells.

Patients suspected of having bladder cancer should be referred to cystoscopy. Cystoscopy allows for taking biopsy sample, cytology sample, or even resecting the tumour in its entirety in some cases.

Stages

Non-muscle invasive bladder cancer (NMIBC), also called stage I, refers to when the disease has not invaded the muscle of the urinary bladder. Muscle-invasive disease (MIBC) may be stage II or III, depending on how far it has spread locally. Metastatic disease is stage IV, where metastasis is present.

Non-muscle invasive and muscle-invasive disease can only be distinguished by transurethral resection of the bladder or by MRi. CT cannot distinguish them.

Management

Management for non-metastatic disease (stages I - III) involves either cystoscopic surgical removal of the tumour (TUR-B), complete surgical removal of the bladder (radical cystectomy), or radiotherapy + chemotherapy. For metastatic disease, only chemotherapy and/or immunotherapy is indicated.