SURGERY
Surgery was performed under sedation (detomidine
hydrochloride1 (0.01 mg /kg bwt, iv), butorphanol
tartrate2 (0.025 mg/kg bwt, iv) and
azepromazin3 (10 mg /kg, iv)).
First the bladder was emptied and flushed with sterile 0.9% saline
solution via catheterisation. Under cystoscopic guidance, the ureteral
tumor was identified. A lasercautery snare (200 cm long, 25 mm diameter,
Fa. Storz) was advanced through the scope’s working port and into the
bladder. Under cystoscopic vision, the cautery snareloop was opened and
lassoed around the mass and manipulate down to the orifice of the
ureter. A 15-watt medical diode laser (Model Elli, Fa. Wuhan Gigaa
Optronics Technology Co., Ltd.) was applied briefly, while the snare was
gently closed under slight tension. The mass fell on the bladder floor.
The thin remnant stalk was then observed to assess for bleeding and
retracted within the ureter. Due to the reactive intraoperative swelling
of the mucosa, it was not possible to enter the ureter endoscopically at
the end of the surgery.
The resected mass was retrieved by flashing the bladder with sterile
0.9% saline solution via catheterisation and was fixed in a 10%
neutral buffered formalin.
Histopathology results
Histological examination of the mass identified a mucosal polyp with
high-grade superficial ulcerative ureteritis with reactive mucosal
hyperplasia and partial formation of granulation tissue.
In context of the history of the horse, these findings tended to suggest
the presence of a mechanically traumatized mucosal polyp with reactive
mucosal hyperplasia. Clear indications of a malignant progression in the
sense of a transitional cell carcinoma were not found on the basis of
the tissue samples, despite clear proliferation activation of the
epithelium.
Based on the histological findings the neoplasm was identified as a
mucosal polyp.
FOLLOW UP
The horse was medicated with flunixin-meglumin3(1.1mg/kg bwt, iv) for 3 days postoperatively.
24 hours after surgery a cystoscopy was performed, to check the
resection site. The swelling of the mucosa in the ureteral orifice had
regressed and via ureteroscopy the base of the polyp could be located
and was unchanged to the preoperative view. The idea of removal of the
remnant of the stalk in the ureter using laser surgery via ureteroscopy
was abandoned due to the risk of injury to the ureteral mucosa.
Post-operatively the patient remained asymptomatic and was discharged
from the clinic three days later.
Follow-up cystoscopy 5 months later showed the urethra, bladder, and
right ureter with no signs of inflammation. The remnant of the stalk
within the ureter was unchanged without any surrounding inflammatory
reaction (Fig. 4). In transrectal ultrasonography the right ureter was
still dilated (maximum 1.8 centimetres) in the caudal 10 cm.
Transabdominal ultrasonography showed both kidneys from normal shape and
size. According to the owner, all clinical signs resolved.
Urine analysis, including fractional electrolyte excretion and
GGT/Creatinine ratio, were in the physiological range.
DISCUSSION
Causes of hematuria in the gelding may be found in various sections of
the urogenitaltract, e.g. urethra, bladder, ureter, kidney or
bulbourethral glands. A distinction must be made between hematuria,
haemoglobinuria and myoglobinuria. Frequently, centrifugation of the
urine is helpful, since erythrocytes will form a sediment, leaving a
clear supernatant, whereas myoglobin and haemoglobin will not
(Schumacher 2007, Schumacher & Schumacher 2017, Rosales et al. 2017,
Ingelfinger 2021). The basic investigation includes a detailed history
with clinical examination and laboratory tests in the form of bloodwork
and urinalysis (inflammation parameters, renal retention values)
together with renal / bladder ultrasonography, urethroscopy and
cystoscopy (Cercone 2022). Further investigations like biopsy,
ureteroscopy, laparoscopy or contrast studies can be performed if
necessary (Schumacher et al. 2010, Cercone 2022). In foals it is
possible to visualize ureters, bladder and urethra in (contrast)
radiography and computed tomography (Cercone 2022). In adult horses
these investigations are less accurate due to their body size (Cercone
2022).
Common causes of hematuria are cystitis, urethritis, pyelonephritis,
urethral rent, urolithiasis, idiopathic haematuria, renal and vesicular
neoplasia, intoxication, administration of nonsteroidal
anti-inflammatory drugs, cantharidin toxicosis, exercise induced
hematuria or vascular anomalies (Glass et al. 2016, Larsdotter et al.
2009, Savage 2008, Schumacher & Schumacher 2017, Barton et al. 2019).
The timing of bleeding during urination may indicate the anatomical area
from which the bleeding originates (Schumacher & Schumacher 2017).
Diagnosis of a ureteral fibroepithelial polyp is a unique challenge due
to their variable size, shape and the inability to visualize it. If the
full size of the polyp cannot be seen via endoscopy, ultrasonography
including colour Doppler examination might help with further
investigation (Reichle et al. 2003). In human literature abdominal
radiographs, computerized tomography and magnetic resonance imaging with
or without contrast are described to visualize the shape of ureteral
masses, but are often unreliable (Kumar et al. 2022). Anterograde or
retrograde ureteropyelography can be used to reveal a filling defect
that might indicate the presence of a polyp or other obstruction (Lam et
al. 2003, Reichle et al. 2003, Li et al. 2015). In equine a retrograde
pyelogram might be only possible in foals and small horses.
Differential considerations for ureteral masses include malignant tumor,
e.g.transitional cell carcinomas, ureteric carcinomas, and benign tumors
e.g. granulomas, leiomyomas, hemangiomas, blood clots or radiolucent
calculi (Williams et al. 2002, Lam et al. 2003). Distinguishing a polyp
on clinical and imaging findings may be difficult, and a definitive
diagnosis is based on the pathological findings.
In this specific case it can be imagined that initially the polyp was
inside the ureter, causing intermittent occlusion. During time the stalk
lengthened due to ureteral peristalsis and the pressure of the urine.
The proliferated mass was moved caudally to the bladder. At the moment
it entered the bladder cavity it could be visualised. Whereas the polyp
in our case was visualized by endoscopy having had retracted in the
ureter, it was hypothesized that during earlier examination the polyp
could only occasionally be seen extending through the orifice and could
have been missed during endoscopy.
Due the size of the polyp moving forwards and backwards, sometimes
occluding the ureteral lumen, a hydroureter developed. This could be
detected by transrectal examination as well as transrectal
ultrasonography. The dilatation of the ureter can be the consequence of
intermittent occlusion or by vesicoureteral reflux. In human, children
with urinary tract infections tend to develop vesicoureteral reflux
which can cause chronic renal failure and hydronephrosis (Greenbaum &
Mesrobian 2006). In most patients it resolves spontaneously, except for
higher grade reflux (Edwards et al. 1977).
In the history of this patient two years ago the obstruction caused
hydronephrosis. Antimicrobial treatment resulted in regression of the
clinical signs. It is probable that the polyp showed secondary swelling
due to microbiological infection at this time. Whereas the polyp was not
resected recurrence of the problem occurred.
Fibroepithelial polyps might have several causes such as trauma,
obstruction, inflammation, chronic irritation from calculi or allergies
(Kara et al. 2010, Ludwig et al. 2015).
Jones et al. (1994) described a case of a 4-month-old foal with a
history of hematuria and clinically unilateral hydronephrosis and
hydroureter following occlusion of the ureter by polyps. The polyps were
considered to be congenital, but the etiopathogenesis was not known.
In this case, the polyp was considered to be secondary to a ureteral
calculi obstruction with consequent ureteral mucosal proliferation.
Physical irritation caused by the ureteral calculus might have induced
mucosal oedema and epithelial proliferation leading to the development
of the mucosal polyps. At the moment of presentation, no calculi were
found although sediment covered the urinary bladder and urinalysis
showed formations of calcium carbonates and calcium oxalate
monohydrates. Therefore, it seems likely that there is a connection with
increased crystalluria and fibroepithelial polyps. It seems necessary to
exclude the possibility of ureteral calculi to better assess the
prognosis for the patient and to choose the method of surgical
therapy.
The proteinuria in this case might be caused by the inflammation of the
soft tissue in the area of the polyp. Other causes for proteinuria in
horses include renal insult, inflammation in other regions or exercise
(Savage 2008). Delayed surgical intervention may finally affect renal
function and even hydronephrosis with consequently clinical signs like
pain, fever, and persistent urinary tract infections (Ludwig et al
2015). At the moment of referral, no sign of hydronephrosis was present
and only the caudal 10 cm of the ureter showed a hydroureter and no
explanation could be given for the occurrence of the hydronephrosis
diagnosed earlier and it was difficult to confirm the diagnosis as
obstructive hydronephrosis caused by ureteral polyps 2 years ago.
Current practice in human medicine is to endoscopically resect the
ureteral tumor using electrocautery (Abdessater et al. 2019), holmium
(12 cases) or thulium laser (Sheng et al. 2016) and a temporary stent
can be placed to prevent constriction (Sun et al. 2021, Kumar et al.
2022, Buckland & Blatt 2023). If the size of the polyp is too large and
the entire lumen of the ureter is blocked or the polyp is located far
cranial in the ureter or in the renal pelvis percutaneous resection is
performed (Lam et al. 2003). When malignancy is suspected or
percutaneous resection is not possible, laparoscopy following
nephroureterectomy is recommended (Lam et al. 2003, Kijvikai et al.
2007).
In this case the authors opted for transendoscopic resection, because
the polyp was easily accessible within the ureteral orifice and the
peri- and postoperative risks were the lowest.
If the polyp is not accessible endoscopically because of intraureteral
retraction and inability of inserting the endoscope, balloon dilation of
the ureteral orifice as well as the caudal part of the ureter might be
an option to increase the size of the ureter so that the endoscope can
be inserted (Kara et al. 2010). Otherwise, laparoscopic ureterotomy to
resect the polyp might be optional being aware that the dilated ureter
is retroperitoneally as described in human (Gao et al. 2021).
After resection the tumor was flushed out of the bladder, alternatively
a stone retrieval basket advanced through the scope’s working port could
have been used. The mass is then captured in the net and withdrawn from
the bladder together with the endoscope. Grasping the tumor with an
endoscopic forceps was another option.
In addition, if the polyps are removed ureterscopically, close follow-up
is recommended because of possible recurrence, especially in case of an
incomplete excision (Williams et al. 2002). In human recurrence is rare
(Ludwig et al 2015). Whereas human ureteral polyps have a fibrous
pedicle covered with normal transitional epithelium (Tsuzuki & Epstein
2005), we considered to have excised enough material. Resection of the
base may pose potential risks, causing irritation of the ureteral mucosa
with subsequent ureteral stricture.
Although the tumor is benign, still close follow up is recommended. In
human in rare cases, fibroepithelial polyps can develop into malignant
transitional cell carcinomas. Therefore, a histopathological
investigation of each resected polyp should be performed, to better
asses the follow-up treatment and the long-term prognosis for the
patient (Min et al. 2012, Xu et al. 2013).