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304 Challenging Concepts in Urological Surgery
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Figure 31.4 Post- reconstructive procedure X- ray of the kidneys, ureters, and bladder showing bilateral
ureteric stents lying within the configuration of the anastomosis with bilateral nephrostomies in situ.
drainage with the bilateral ureteric stents in situ (Figure 31.4) as part of the reconstruction. His baseline creatinine level and eGFR were 147 μmol/ L and 47 mL/ min/ 1.73 m2
respectively at the time of operation.
A bilateral nephrostogram was performed within 6 weeks of the reconstructive
surgical procedure (March 2017) which showed no evidence of obstruction with
free drainage of contrast (Figure 31.5). Both nephrostomies and ureteric stents
were removed and renal function remained stable (creatinine 157 μmol/ L and eGFR
42 mL/ min/ 1.73 m2).
Figure 31.5 Post- reconstruction nephrostograms showing the configuration of procedure with bilateral
stents and nephrostomies in situ. Visualization of the ileal segment from the left renal pelvis to the right
renal pelvis and contrast moving down to the ileal chimney to the augmented bladder.
Clinical tip Anastomoses
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The complications of anastomoses involving bowel and urinary tracts are well recognized and it
has significant impact on the outcome of the procedure. The numbers of anastomoses are usually
high in reconstructive procedures. Therefore, performing a minimum number of anastomoses while
using small bowel (ileum) as a continuous segment joining the left renal pelvis, right renal pelvis,
and with the previous ileal chimney (three anastomoses) reduces the chance of anastomotic- related
complications. The importance of planning reconstructive surgical procedure (such as using of bowel
segment and number of anastomotic sites) is crucial.
Clinical tip Mobilization of the ileal segment
The selected segment of the ileum needs to be mobilized under the inferior mesenteric artery
following mobilization of both small bowel and large bowel, similar to a standard retroperitoneal
lymph node dissection procedure. However the ileal segment can also be mobilized through a
mesentery window, but in our case, it was done through the formal method to reduce the tension on
the mesentery and also to make the ileal segment become isoperistaltic. It has significant relation to
the early recovery of the post operative period, reduce morbidity and eventually the outcome of the
procedure.
Clinical tip Metabolic complications
One of the common long term complications of reconstructive procedure is malabsorption
syndrome due to using a significant length of bowel segment. It is necessary to monitor the serum
biochemical level regularly to rule out any biochemical abnormalities such as serum bicarbonate,
serum vitamin B12 and serum folate level. Low serum bicarbonate level is one of most common
abnormalities and requires regular sodium bicarbonate supplementation. Therefore lifelong follow
up after the reconstructive procedure is essential to monitor and treatment of the biochemical
abnormalities.
305Case 31 Management of ketamine-induced bilateral upper urinary tract injury
Outcome and follow- up
The patient’s baseline creatinine level (157– 220 μmol/ L) and eGFR (38– 46 mL/ min/
1.73 m2) remained stable at a follow- up of 34 months.
The MAG3 renogram in July 2017 showed sluggish flow on the left side (due to the sur-
gical configuration) with no obvious obstruction in the right side and the USS in December
2017 demonstrated stable left hydronephrosis with mild fullness of the right renal pelvis.
He was under regular urology follow- up every 3 months for the first year and cur-
rently, every 6 months to monitor his renal function along with USS surveillance for
hydronephrosis. Furthermore, he is now on regular sodium bicarbonate supplementation therapy for his low serum bicarbonate level.
In addition, he is under regular follow- up with the renal physician team for chronic
kidney disease as part of a multidisciplinary and holistic management approach to
manage this rare catastrophic clinical condition involving the entire urinary tract following chronic ketamine abuse.
Expert comment Multidisciplinary team involvement and education of the patient
Multidisciplinary team involvement is essential (such as renal medicine, urology, psychiatry, and social
support) for the holistic management of the patient with chronic ketamine abuse. The importance
of patient’s education and appropriate information regarding potential disease progression or
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complication should be discussed in a specialized clinic. This group of patient should be under regular
follow up and ensure about abstinence from ketamine abuse by providing adequate social and
mental support. They also need lifelong follow up which will help to monitor the disease progression
and involvement of multidisciplinary team earlier for planning of further management prior to the
development of catastrophic consequence.
Discussion
The incidence of ketamine- associated urinary tract injury (cystitis and upper tract involvement) is a complex and challenging syndrome.
It needs a patient- centred approach including consideration of the patient’s psychosocial issues and co- morbidities, and long- term abstinence of ketamine is essential for
treatment to be successful.
There are various treatment modalities and the use of intravesical agents such as
dimethylsulfoxide and hyaluronic acid (Cystistat®) is also common. But no medical
management shows any significant success if there is evidence of continued ketamine
8
abuse.
Medical management relies on symptomatic control with combinations of anticholinergic, antibiotic, steroid, and non- steroidal anti- inflammatory drugs.
Disease progression or failed medical management leads to consideration of surgical
management such as hydrodistension, urinary diversion, augmentation cystoplasty,
autotransplantation, and pyelovesicostomy.
It has been reported that ureteric transmural inflammation and ulceration leads to
stricture and hydronephrosis.13 Ureteric stenting is the most common form of management of obstructive uropathy prior to extensive surgical intervention.
Small bowel interposition is commonly used for ureteric reconstruction in case of
extensive ureteric injuries and the common complications of small bowel interposition
as part of reconstruction are metabolic abnormalities, mucus production, and renal
dysfunction. Furthermore, the risk of small bowel syndrome with formation of renal
stones, dehydration, and malabsorption syndrome is higher if the patient has had prior
small bowel resection.
8
9
10,11
12
Evidence base Ketamine abuse and hydronephrosis
Ketamine induced cystitis (frequency, urgency, nocturia, dysuria and suprapubic pain) is the most
common urological presentation due to direct toxic effects of ketamine and its metabolites. However,
toxic effects of ketamine in the upper urinary tract are becoming a well- recognized clinical condition
leading to development of hydronephrosis or obstructive uropathy. Chu et al. reported 30 out of 59
patients (51%) presenting with lower urinary tract symptoms due to ketamine abuse had unilateral or
bilateral hydronephrosis on renal USS.9 However. Tam et al. reported 8.1% had hydronephrosis in a
cohort of 160 patients.
Evidence base Risk factors for hydronephrosis
Most of these patients in Chu et al.9 case series were found to have hydronephrosis and hyroureter
down to the level of vesico- ureteric junctions on intravenous urogram implying upper tract
involvement was due to long term decrease in bladder compliance however in Yee et al. series ureteric
obstruction was found in some patient and level of obstruction varied from vesicoureteric junction to
the pelvic- ureteric junction. Yee et al. reported that age, full blood count, serum creatinine level, and
14
abnormal serum liver enzyme profile were associated with the risk of hydronephrosis. The resolution
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of hydronephrosis was noted in some patients following abstinence of ketamine usage but require
further study to confirm. However, permanent toxicity to the upper urinary tract is still of concern with
long- term ketamine abuse.
Learning point Pathological changes
Gross pathological changes of the urinary tract include contracted bladder, thickening of the bladder
wall, adhesion to the peritoneum, dilatation of ureters, and thickening of the ureteric wall.
Endoscopic pathological changes are erythematous bladder mucosa (bleeds easily), ulceration of
bladder mucosa and laceration on hydrodistension, swelling, and oedematous mucosa of the ureter.
Microscopic pathological changes are denuded urothelium, formation of granulation tissue with
infiltration by mast cells, eosinophils, lymphocytes, and plasma cells, fibrinoid necrosis of arterioles,
focal calcification, muscle hypertrophy, collagen accumulation, thickening of ureteric wall, and ureteric
mucosal infiltration by inflammatory cells and eosinophils.
15
16– 19
Here, we report our case of ketamine- induced complete bilateral upper urinary tract
obstruction / uropathy involving both renal pelvises managed with ileal segmental
anastomoses. The ileal segment passes from the left renal pelvis to the right renal
pelvis and was anastomosed to the previous ileal chimney (roux- en- Y configuration).
It ensures normal flow of urine following failed augmentation cystoplasty and medical
management. This case highlights the multidisciplinary management of renal dysfunction and biochemical abnormalities and demonstrates the challenging surgical
treatment following devastating effects of bilateral upper urinary tract involvement
due to chronic ketamine usage that developed following augmentation cystoplasty. It
also helps us to develop awareness regarding ketamine effects throughout the entire
urinary tract (lower and upper urinary tract). In this case, we report 34 months of
surgical outcome of the complex surgical management of ketamine- induced bilateral
upper urinary tract obstruction and the necessity of involvement of a multidisciplinary
team (renal medicine, urology) for lifelong follow- up.
307Case 31 Management of ketamine-induced bilateral upper urinary tract injury
Conclusion
The surgical management of ketamine- induced bilateral upper urinary tract injury is
complex and needs a holistic approach for lifelong follow- up. However, surgical intervention is based on local expertise and tailed to the individual patient. To the best of
our knowledge, this is the first case reported using iso- peristaltic ileal segmental anastomosis involving both renal pelvis with continuation of the ileal segment to the previous ileal chimney of the clam ileocystoplasty procedure with 34 months of follow- up.
A final word from the expert
Ketamine- induced urinary tract injury is increasing because of its popularity as a common
recreational street drug among the younger generation. It has catastrophic consequences
due to its devastating effects on the urinary tract and it needs lifelong multidisciplinary
team management. Abstinence of using ketamine is the most important step of reducing
308 Challenging Concepts in Urological Surgery
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the progression of the disease; however, permanent toxicity still remains high in chronic
ketamine abuse.
The management of the ketamine- induced lower urinary tract injury includes management
of symptoms (medical management) and surgical intervention (failed medical management).
However, upper urinary tract injury needs surgical intervention such as ureteric stenting and ileal
interposition of the ureter if hydronephrosis develops due to benign ureteric stricture following
chronic ketamine abuse.
The maintenance of potency is important during consideration of extensive surgical
management of the younger patient; therefore, the option of cystectomy may not be popular
among this group of patients. The importance of increasing bladder capacity to improve the
bladder compliance is essential in case of a small non- compliant bladder. However, extensive
upper urinary tract damage may occur despite cessation of using ketamine and ultimately leads
to a bespoke solution to be formulated.
There are currently no guidelines available regarding management of ketamine- induced
upper urinary tract injury. Therefore, careful patient selection, planning of surgical intervention,
discussion in a multidisciplinary team meeting, holistic approach including the patient’s
education of the disease process with their involvement in the management plan, involvement
of other specialities (such as renal medicine), and lifelong follow- up are essential for the optimal
management of ketamine- induced upper urinary tract injury.
References
1. Lankenau SE, Sanders B. Patterns of ketamine use among young injection drug users. J
Psychoactive Drugs. 2007;39(1):21– 29.
2. Walter M, Li S, Demenescu LR. Multistage drug effects of ketamine in the treatment of
major depression. Eur Arch Psychiatry Clin Neurosci. 2014;264(Suppl 1):S55– 65.
3. Wan LB, Levitch CF, Perez AM, et al. Ketamine safety and tolerability in clinical trials for
treatment- resistant depression. J Clin Psychiatry. 2015;76(3):247– 252.
4. Best SR. Combined ketamine/ transcranial magnetic stimulation treatment of severe depression in bipolar I disorder. J ECT. 2014;30(4):e50– e51.
5. Kalsi SS, Wood DM, Dargan PI. The epidemiology and patterns of acute and chronic toxicity
associated with recreational ketamine use. Emerg Health Threats J. 2011;4:7107.
6. Forster JA, Harrison SC. Ketamine uropathy: rising to the challenges of a new condition.
BJU Int. 2012;109(9):1277– 1278.
7. Shahani R, Streutker C, Dickson B. Ketamine- associated ulcerative cystitis a new clinical
entity. Urology. 2007;69(5):810– 812.
8. Lai Y, Wu S, Ni L. Ketamine- associated urinary tract dysfunction: an under recognized clinical entity. Urol Int. 2012;89(1):93– 96.
9. Chu PSK, Ma WK, Wong SCW. The destruction of the lower urinary tract by ketamine
abuse: a new syndrome? BJU Int. 2008;102(11):1616– 1622.
10. Ng CF, Chiu PKF, Li ML. Clinical outcomes of augmentation cystoplasty in patients suffering
from ketamine- related bladder contractures. Int Urol Nephrol. 2013;45(5):1245– 1251.
11. Misra S, Chetwood A, Coker C. Ketamine cystitis: practical considerations in management.
Scand J Urol. 2014;48(5):482– 488.
12. Raison NT, O’Brien T, Game D, Olsburgh J. Autotransplantation for the management of
ketamine ureteritis. BMJ Case Rep. 2015;2015:bcr2014207652.
13. Hopcroft SA, Cottrell AM, Mason K, et al. Ureteric intestinal metaplasia in association with
chronic recreational ketamine abuse. J Clin Pathol. 2011;64(6):551– 552.
14. Tam YH, Ng CF, Pang KK, et al. One stop clinic for ketamine- associated uropathy: report on
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service delivery model, patients’ characteristics and non- invasive investigations at baseline
by a cross- sectional study in a prospective cohort of 318 teenagers and young adults. BJU
Int. 2014;114(5):754– 760.
15. Yee CH, Teoh JY, Lai PT, et al. The risk of upper urinary tract involvement in patients with
ketamine associated uropathy. Int Neurourol J. 2017;21(2):128– 132.
16. Jhang JF, Hsu YH, Kuo HC. Possible pathophysiology of ketamine- related cystitis and associated treatment strategies. Int J Urol. 2015;22(9):816– 825.
17. Chung SD, Wang CC, Kuo HC. Augmentation enterocystoplasty is effective in relieving refractory ketamine- related bladder. Neurourol Urodyn. 2014;33(8):1207– 1211.
18. Chu PS, Kwok SC, Lam KM, et al. ‘Street ketamine’- associated bladder dysfunction: a report
of ten cases. Hong Kong Med J. 2007;3(4):311– 313.
19. Huang LK, Wang JH, Shen SH, Lin AT, Chang CY. Evaluation of the extent of ketamineinduced uropathy: the role of CT urography. Postgrad Med J. 2014;90(1062):185– 190.
309Case 31 Management of ketamine-induced bilateral upper urinary tract injury
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CASE
Vesicovaginal fistula
Sachin Malde
Expert commentary Arun Sahai
Case history
A 48- year- old lady was referred to our centre with a history of vaginal leak 2 months
post laparoscopic total hysterectomy and bilateral salpingo- oophorectomy. The
gynaecological surgery was performed for potential malignancy based on blood
tests and imaging but her final histology was benign. The patient reported urinary
leak from the vagina day 1 post surgery. She was managed with a urinary catheter at the referring hospital. Despite this she continued to have a vaginal leak.
The local urology team were asked to review the patient and a cystoscopy and bilateral retrograde studies were performed, which revealed evidence of some suture
material in the bladder above the trigone, and above and medial to the left ureteric
orifice with no evidence of ureteric injury. The suture material was removed endoscopically and a catheter was left for a further 2 weeks. A cystogram performed at
that time suggested a vesicovaginal fistula (VVF) and the patient was referred to
our centre.
On review in our clinic, the patient was noted to have a background of mixed
connective tissue disorder, autoimmune arthritis requiring steroids, type 1 diabetes,
coeliac disease, depression, and had two previous Caesarean sections. The patient
reported worsening of urinary incontinence and vaginal leak despite the indwelling
urethral catheter and so this was removed just prior to our first review.
Prior to the hysterectomy the patient did not complain of bothersome lower
urinary tract symptoms or incontinence. She was clearly distressed with her symptoms and a number of investigations were organized including midstream specimen
of urine, urea and electrolytes, cystoscopy plus examination under anaesthetic/
methylene blue test/ retrograde studies, and an up- to- date computed tomography
intravenous urogram. At cystoscopy, a clear VVF was demonstrated (Figure 32.1).
This was assessed both intravesically with the cystoscope and vaginally. A wellformed 1 cm × 0.5 cm fistula was seen approximately 1 cm above and medial to the
left ureteric orifice. Bilateral retrograde studies were performed which were normal
and she was noted to have a good capacity bladder. The rest of her bladder was
unremarkable. The computed tomography intravenous urogram revealed normal
upper tracts and no evidence of pelvic collection. The midstream specimen of urine
was clear and her renal function normal.
Expert comment Urgent
referrals
If a VVF is suspected early, urgent
referral to a specialist is required
for diagnosis, as early repair is
feasible if identified typically within
the first week. After this time,
oedema, inflammation, potential
tissue necrosis, and infection
make successful repair of the VVF
challenging. Expert opinion would
suggest that if a VVF is identified
later than this time, the optimal
time for repair would be after
3 months and some may argue at
6 months.
Learning point Aetiology
of VVF
● Obstetric trauma, for
example, prolonged labour
(commonest in low- resourced/
underdeveloped world).
● Other obstetric causes include
Caesarean section, forceps
delivery, and uterine rupture.
● Pelvic surgery, for example,
hysterectomy (commonest
in developed/ well- resourced
world); others include benign
and malignant colorectal,
gynaecological, and urological
surgery.
● Pelvic radiation.
● Advanced pelvic malignancy.
● Foreign body.
● Trauma— pelvic fracture, sexual.
● Congenital.
312 Challenging Concepts in Urological Surgery
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Clinical tip Removing
urethral catheters prior to
surgical repair
The catheter will cause an
inflammatory reaction on the
posterior wall of the bladder and
often will involve the bladder base,
which is often the site of the VVF.
In our view, removing the catheter
in advance of the planned repair
will allow the catheter reaction to
settle, optimizing the chances of a
successful repair. Furthermore, the
patient will often find the catheter
uncomfortable and, as in this
case, it usually does not prevent
vaginal leak.
Figure 32.1 Cystoscopic view of a VVF with sensor guidewire placed through it.
Clinical tip Cystoscopy and examination under anaesthetic
Always perform your own evaluation of the urinary incontinence. At cystoscopy and examination under
anaesthetic, it is important to assess the location and size of the fistula and the quality of the tissue
planned for repair. There may be more than one VVF! Retrograde studies should be performed routinely
to assess for ureteric involvement and ureterovaginal fistula or ureteric injury. Furthermore, one must
decide whether the VVF can be repaired through the vaginal or abdominal route or in select cases where
the tissue quality is so poor a further delay and re- evaluation or urinary diversion may be required. In
cases of uncertainty, attempt to place a small catheter or Fogarty balloon catheter through the VVF with
the tubing exiting through the vagina. Then place gentle traction onto the tubing to see if this helps with
bringing the VVF into the field of view to allow vaginal repair. In our opinion, the vaginal route of repair
is preferable and will allow a quicker postoperative recovery. In cases where the VVF cannot be easily
identified and doubt remains about the diagnosis, a methylene blue test should be performed.
Learning point Methylene blue test
This involves placing three appropriately sized swabs into the vagina sequentially to fill the upper,
mid, and lower (closest to the introitus) portions of the vaginal length. Ensure the vagina is dry prior
to inserting the three swabs. Methylene blue is then instilled into the bladder via a catheter (at least
200 mL) and the catheter removed. The dye is left in the bladder for at least 15 minutes. The swabs
can then be removed. Blue staining on the upper swab indicates a VVF. Blue staining on the lower
swab indicates either a urethrovaginal fistula or contamination of the dye from urethral leak into the
introitus (careful removal of the catheter is required and also caution to not over- distend the bladder
with dye). Finally, a wet upper swab that has no dye suggests a ureterovaginal fistula. If all swabs are
dry with no staining there is unlikely to be a VVF.
Learning point Abdominal route for VVF repair
The abdominal route for VVF repair is required if the VVF is thought to be inaccessible per vagina,
the ureter is involved or at risk of compromise from vaginal repair, or simultaneous augmentation
cystoplasty is required. In such cases, the abdominal route is preferred. Ureteric reimplantation can
be performed at the same time if required or planned. In abdominal cases of repair, typically the
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posterior bladder is bivalved to the fistula site and using sharp dissection the plane between the
bladder and vagina separated and developed. The vagina is then closed and the greater omentum
or peritoneum mobilized and used as an interposition graft over the repair site before closing the
bladder.
Expert comment Advanced pelvic malignancy and radiotherapy
In cases of advanced pelvic malignancy and/ or as a result of cancer treatment such as radiotherapy
as a cause of VVF, repair may not be possible if the tissue quality is too poor. In a wide radiotherapy
field, there may be concomitant problems such as ureteric stricture(s), enteritis/ proctitis, and the
environment may be too hostile to allow healing and repair. In selected cases where oncologically it is
appropriate, a urinary diversion procedure should be considered, such as an ileal conduit.
A week later the patient underwent elective vaginal repair of the fistula with
Martius fat pad interposition. In brief, she was positioned in a supine Trendelenburg
position with her legs in lithotomy. A 6- French (Fr) ureteric catheter was fed up the
left ureter in order to help protect and identify any ureteric injury during VVF repair
and was secured to a 14 Fr urethral catheter draining the bladder. A lone star retractor
was set up to help facilitate retraction of tissues. An 8 Fr catheter was utilized to catheterize the fistula with the tubing being exteriorized through the vagina. This helped
to bring the VVF into the surgical field and be more accessible. In addition, 2/ 0 Vicryl®
stay sutures were utilized either side of the VVF and tacked to the lone star retractor to
bring the VVF into the field of view. The fistula was sharply circumscribed and a plane
developed between the bladder and vaginal walls. Stay sutures were again employed
to facilitate retraction of the dissected edge of the vaginal tissue. The bladder defect
was exposed with a 0.5 cm margin all around and was closed with interrupted 3/ 0
polydioxanone sutures and was leak tested to be watertight. As there was a distinct
lack of good- quality pubocervical fascia to close over the bladder as a second layer, a
Martius fat pad was harvested from the right on its inferior pedicle and tunnelled into
the fistula repair site with the use of a Statinsky clamp. The fat pad was laid over the
repair and fixed to the fascia with three 2/ 0 Vicryl® sutures beyond the repair site. A
suction drain was placed in a dependent position in the labial wound and the subcutaneous tissue closed with 2/ 0 Vicryl®. The labial skin was then closed with 3/ 0 Vicryl®
Rapide and vaginal skin with 3/ 0 Vicryl®. A vaginal pack was left in situ overnight. She
went on to make an unremarkable recovery and was discharged on postoperative day
3 with her catheter in situ. She then had a cystogram 3 weeks later, which showed no
demonstrable leak from the bladder. Her catheter was removed. She had follow- up at
3 and 12 months and was discharged with no evidence of any vaginal leak.
313Case 32 Vesicovaginal fistula
Clinical tip Martius fat pad
Have a low threshold for the use of a Martius fat pad. It is important when repairing a VVF that there
is a three- layer closure with non- overlying suture lines. Typically, the bladder, pubocervical fascia, and
vaginal skin can make up the three layers and are closed at differing levels, for example, horizontal
closure of the bladder and vertical closure of the pubocervical fascia and then lateral closure of
the vaginal skin to prevent overlying suture lines (a risk for a recurrent VVF). However, often the
defect, radiotherapy) or the surgeon feels the tissue quality is poor, and so an interposition fat pad
should be used. In our hands the Martius fat pad is an excellent choice.
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