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154 Challenging Concepts in Urological Surgery
https://t.me/med1917
24. Martignoni G, Pea M, Rigaud G, et al. Renal angiomyolipoma with epithelioid sarcomatous
transformation and metastases: demonstration of the same genetic defects in the primary
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25. Espinosa M, Roldan- Romero JM, Duran I, et al. Advanced sporadic renal epithelioid
angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation. BMC Cancer. 2018;18(1):561.
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with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic
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27. Kenerson H, Folpe AL, Takayama TK, Yeung RS. Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol.
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28. Kawaguchi K, Oda Y, Nakanishi K, et al. Malignant transformation of renal
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29. Li W, Guo L, Bi X, Ma J, Zheng S. Immunohistochemistry of p53 and Ki- 67 and
p53 mutation analysis in renal epithelioid angiomyolipoma. Int J Clin Exp Pathol.
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30. Bukowski RM. Natural history and therapy of metastatic renal cell carcinoma: the role of
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16
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CASE
Upper urinary tract
urothelial carcinoma
Richard Nobrega
Expert commentary Mark Sullivan
Case history
A 74- year- old gentleman presents to his district general hospital as a 2- week wait
with visible haematuria. His flexible cystoscopy was normal, and his renal function revealed an estimated glomerular filtration rate of 49 mL/ min with a serum
creatinine of 126 μmol/ L. A computed tomography urogram (CTU) revealed bilateral ureteric filling defects: a right ureteric lesion at L4/ L5 and left ureteric
lesion at L3/ L4 with a long stricture distally. His right kidney was hydronephrotic
(Figure 16.1).
Subsequent cystoscopy was undertaken under general anaesthesia demonstrating
a normal bladder. Retrograde study on the right showed dense ureteric filling defects
and an impassable right ureter with both rigid and flexible ureteroscopy. A left
retrograde study confirmed the computed tomography (CT) findings of a distal ureteric stricture with more proximal filling defects. Cytology was aspirated and the
left ureter was subsequently perforated on attempting rigid ureteroscopy; biopsy
was unsuccessful and a JJ stent left in situ. Cytology showed atypical cells only.
The patient was then referred to our tertiary centre upper tract MDT for further
management given the high index of suspicion for bilateral upper tract urothelial
carcinomas (UTUC). The right side was thought likely to be a high- grade invasive
tumour while on the left, possibly superficial disease proximal to a long benign
distal ureteric stricture.
Figure 16.1 (a) CTU of case study patient with bilateral UTUC showing dilated right kidney. (b) Blue
arrow shows irregular, thickened distal right ureter radiologically suspicious for high- grade disease.
(c) A dilated distal left ureter just above the stricture indicated by the green arrow and filling defects
within the left proximal and mid ureter shown by the blue arrow also suspicious for TCC.
156 Challenging Concepts in Urological Surgery
CTU = c
*All these f
**Any of these factors need to be present.
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Learning point Incidence, clinical presentation, and diagnosis of UTUC
UTUCs are malignant lesions that arise from the lining of the proximal urinary tract from the renal
pelvis to the distal ureter. Non- urothelial cancers are rare at <5%. The incidence of UTUC is slowly
Learning point
Pre- intervention risk stratification
and management of UTUC
The EAU guidelines on UTUC
stratify UTUC into low risk and
high risk based on a variety of
pre- intervention features including
tumour size, cytology, ureteric
biopsy, CTU, and previous radical
cystectomy for bladder cancer
(Figure 16.2). The subsequent
management of UTUC is based
on this risk stratification, with
high- risk disease being managed
with radical nephroureterectomy
(RNU) with or without template
lymphadenectomy (Figure 16.3).
rising but it remains a rare tumour when compared with bladder cancers, which are ten times more
common.
The European Association of Urology (EAU) guidelines suggest that 60% of upper tract tumours are
invasive at diagnosis compared with 15– 25% of bladder tumours.
cancer where approximately 30% are invasive at diagnosis.5 UTUC is twice as common in men
compared with women and peak incidence in patients aged 70– 90 years.
The most common presentation of UTUC is painless visible or non- visible haematuria. In 17% of cases
it is associated with a synchronous bladder tumour.7 Recurrence in the bladder occurs in 24– 47% of
UTUC patients
gold- standard investigation for UTUC, and as per Figures 16.2 and 16.3 shown from current EAU
guidance, it forms part of the pre- intervention risk stratification and management algorithm.14 The
European Society of Urogenital Radiology (ESUR) also advocates CTU.15 Positive urine cytology is
highly suggestive of UTUC in the presence of a normal cystoscopy although it has a high specificity
and low sensitivity with a high false- negative rate in low- grade tumours.
1,2
8– 10
compared with 2– 6% recurrence in the contralateral upper tract.
Low-risk UTUC*
Unifocal disease
•
Tumour size <2 cm
•
Low-grade cytology
•
Low-grade URS biopsy
•
No invasive aspect on CTU-urography
•
omputed tomography urography; URS = ureteroscopy; UTUC = upper urinary tract urothelial carcinoma.
actors need to be present.
UTUC
3,4
This compares with bladder
6
11– 13
CTU is the
16
High-risk UTUC**
Hydronephrosis
•
Tumour size >2 cm
•
High-grade cytology
•
High-grade URS biopsy
•
Multifocal disease
•
Previous radical cystectomy for high-
•
grade bladder cancer
Variant histology
•
Expert comment The need
for rigid/ flexible ureteroscopy?
If you have convincing CTU
findings for invasive transitional
cell carcinoma (TCC) as in this case
and your retrograde study confirms
this, obtaining positive cytology is
more valuable than pursuing with a
difficult ureteroscopy and causing
a perforation and having to leave a
stent without taking any biopsies.
Stents tend to cause periureteric
inflammation and can make
nephroureterectomy more difficult.
There is also a theoretical risk of
tumour seeding on perforation.
Figure 16.2 Pre- intervention risk stratification of UTUC.
Adapted from EAU 2020 UTUC guidelines with permission (www.uroweb.org/ guideline).
157Case 16 Upper urinary tract urothelial carcinoma
*In patients with solitary kidne
y, consider a more conservative approach.
CTU = c
omputed tomography urography; RNU = radical nephroureterectomy;
UTUC = upper urinary tract urothelial carcinoma.
UTUC
Low-risk UTUC
Diagnostic evaluation:
CTU, urinary cytology, cystoscopy
± Flexible ureteroscopy with biopsies
Kidney-sparing surgery:
flexible ureteroscopy or
segmental resection
or percutaneous approach
High-risk UTUC*
RNU ± template lymphadenectomy
± perioperative platinum-based
combination chemotherapy
Open
(prefer open in cT3, cN+)
Laparoscopic
Recurrence
Close and stringent follow-up
Single postoperative dose of intravesical
chemotherapy
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Evidence base Ureteroscopy
before RNU and dissemination
Does ureteroscopy before
RNU cause dissemination?
A meta- analysis of eight studies
(N = 3975) showed a cancerspecific survival hazard ratio of
0.76 (95% confidence interval
0.59– 0.99; p = 0.04) (in favour of
ureteroscopy). Overall survival,
recurrence- free survival, and
metastasis- free survival were all
equivalent.
17
Figure 16.3 Proposed flowchart for the management of UTUC.
Adapted from EAU 2020 UTUC guidelines with permission (www.uroweb.org/ guideline).
The patient is otherwise fit with a history of hypertension and benign prostate enlargement. His regular medications are codeine, finasteride, lactulose, and amlodipine.
Unfortunately, preoperatively the patient developed shortness of breath and a CT pulmonary angiogram showed a pulmonary embolus necessitating anticoagulation with
treatment dose low- molecular- weight heparin (dalteparin). After further preoperative assessment and echocardiography he was deemed fit for surgery and bridged
perioperatively as per local haematology advice.
This patient with suspected bilateral UTUC was discussed at our tertiary multidisciplinary team meeting and a decision made for Open bilateral nephroureterectomies
via midline laparotomy and ex vivo bench surgery under cold ischaemia for both kidneys with the intent of autotransplantation of the more favourable kidney with renal
pelvis free of TCC and viable ureter for bladder reimplantation.
Expert comment Management of bilateral high- grade UTUC
UTUC is rare in itself, with bilateral high- grade disease even more so. Given the paucity of published
management on these cases with most evidence being low level, there is no established treatment
protocol. Midline laparotomy and bilateral nephroureterectomies is a viable option in a patient with
high- grade, invasive bilateral disease involving the renal pelvis and proximal ureters. Other options
would be to consider nephroureterectomy on the side of high- grade/ invasive disease and either
renal autotransplantation, ileal interposition or if feasible a Boari flap if on the contralateral side, the
renal pelvis with or without the upper ureter is free of invasive tumour. With a distal invasive ureteric
tumour, a distal ureterectomy and reimplantation can be considered.
158 Challenging Concepts in Urological Surgery
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Expert comment Nephron- sparing surgery in bilateral UTUC
The challenge in this situation is for patients to recognise that with nephron- sparing surgery, there
may be an increased risk of recurrence in the remaining renal unit(s), but they may accept this, if
it is the only options of maintaining adequate renal function and stay off dialysis. One also should
consider at this point the ease of endoscopic access to the remaining renal unit for surveillance and/ or
endoscopic ablation of recurrences. If there was high- grade disease on one side, and the contralateral
ureter had low- grade disease only, an endoscopic approach could be taken with the low- grade
disease initially and RNU on the contralateral side. Close 3- monthly endoscopic surveillance with
or without laser ablation would be the mainstay of treatment to the remaining kidney and ureter
containing low- grade disease.
Via midline laparotomy, the right RNU was undertaken first. After the bladder cuff
was taken, the renal pedicle was dealt with in a surgical manner consistent with live
related donor nephrectomy in order to preserve vessel length and minimize warm ischaemic time. Ex vivo bench surgery under cold ischaemia demonstrated a strictured
and thickened right ureter macroscopically suspicious for high- grade TCC up to the
renal pelvis. This was set aside as the least likely favourable kidney for autotransplantation. The left RNU was then performed in a similar fashion and the specimen
inspected macroscopically ex vivo under cold ischaemia. The distal ureter seemed
involved by only a benign stricture only, with superficial- looking TCC in the middle
ureter; the very most proximal ureter and renal pelvis were free of disease on flexible
renoscopy and were thus separated from the ureteric TCC under cold ischaemia. The
vessels were prepared as for renal transplantation. Renal autotransplantation was performed in the right iliac fossa in an ordinary extraperitoneal fashion with single renal
artery and vein anastomosed to the external iliac vessels and direct ureterovesical
reimplantation performed.
Clinical tip Technical elements of autotransplantation
The kidney should only be devascularized once it and the entire ureter have been dissected free,
irrespective of the method of excision at the bladder end, in so doing keeping warm ischaemia to
a minimal. Once out, the kidney is perfused with transplant medium (e.g. Soltran) and put on ice.
Bench surgery starts with sharp dissection of the fat off the kidney to expose the pedicle and collecting
system. The ureter is inspected macroscopically and a flexible ureterorenoscope used to identify
tumour burden. In the case of bilateral disease, this can help identify the kidney best preserved
for autotransplantation. The ureter is excised as far proximally as is required and a final flexible
ureterorenoscopy performed to check all macroscopic disease has been removed. The bench surgery
can usually be performed in 30– 45 minutes, not that dissimilar to standard bench surgery times for
preparing a donor nephrectomy.
Evidence base Autotransplantation
Renal autotransplantation is a rare, safe, and effective surgical procedure for the treatment of complex
urological conditions. It was first reported by J.D. Hardy in 1963 when he repaired a high ureteric
injury following aortic surgery by reimplanting the repaired kidney into the ipsilateral iliac fossa.
The longest follow- up on patients with renal autotransplants was reported by Holmäng and
Johansson in 2005.19 Their study was conducted on 23 patients with urothelial carcinoma in the
upper urinary tract, operated with resection and autotransplantation then followed for 7– 20 years.
Nine of these patients had either bilateral UTUC or disease in a single kidney. Of these nine, two
survived without needing dialysis or having recurrences for 127 and 238 months, respectively. Three
patients required haemodialysis 0– 3 times weekly for 27, 85, and 108 months, respectively. Three
18
patients with low- grade disease developed invasive recurrences in the autotransplanted kidney
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after 16, 27, and 90 months, respectively, and later died from the disease. One patient died in an
accident after 14 months.
Expert comment Autotransplantation
Renal pelvic resection, ureterectomy, and renal autotransplantation with direct pyelo- or
ureterocystostomy implies increased radicality and safety in the conservative treatment of patients
with urothelial tumours of the upper urinary tract. The technique also simplifies follow- up. If a
recurrence is diagnosed, it can often be treated by the transurethral route. The procedure should be
considered as an alternative in the treatment of patients with bilateral tumours of the ureter and/ or
renal pelvis and in patients with a ureteric and/ or pelvic tumour within a solitary kidney.20 It should be
noted that both Pettersson’s and Holmäng’s groups only advocate autotransplantation in the context
of UTUC in a solitary kidney or bilateral disease.21 This is due to the significant surgical morbidity and
mortality of an autotransplant and the risk of recurrence in the preserved renal unit when compared
to a RNU in a patient who has a normal contralateral kidney.
The patient in this case study had their catheter removed after a cystogram at 14
days (Figure 16.4). Rigid cystoscopy at 8 weeks allowed removal of JJ stent from the
renovesical anastomosis. Inspection of the bladder at this time and biopsy of the transplant ureteric orifice and flexible renoscopy of the autotransplant was normal. Final
histology showed:
● Right: G3T1 TCC + carcinoma in situ, clear margins
● Left: low- grade TCC mid ureter, no carcinoma in situ, clear margins.
159Case 16 Upper urinary tract urothelial carcinoma
Clinical tip Post- RNU
mitomycin C
All patients should receive a single
course of intravesical 40 mg
mitomycin C post RNU. Logistically,
the best way to give this is for
the patient to come back to a
specialist nurse clinic or urology
triage the day of their postoperative
cystogram (day 10– 14), at which
point mitomycin C can be given
if there is no leak. The evidence
for this is laid out in the ODMIT- C
22
trial.
Figure 16.4 Cystogram post bilateral RNU and renal autotransplantation. Check cystogram 2 weeks post
bilateral RNU and autotransplant demonstrating no leak and non- dilated well- opacified pelvicalyceal system
of autotransplanted kidney. Metal clips are at the site of the vascular anastomosis with the external iliac vessels.
Evidence base Benign
disease following RNU
In a Korean series in 2014 in which
244 patients underwent RNU
without biopsy over 6 years, seven
patients had (2.9%) benign disease
(five in the ureter, two in the renal
23
pelvis).
160 Challenging Concepts in Urological Surgery
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Learning point Five- year disease- specific survival rates by tumour stage in UTUC
The UTUC 5- year disease- specific survival rates stratified by tumour stage range from 100% in pTa/
carcinoma in situ to <5% in pT4 disease (Table 16.1).
There are subtle differences in managing UTUC between the EAU guidelines and what is practised in
the UK. Moon et al.25 summarized what we practice in the UK and made a comparison with the EAU
guidelines (Table 16.2).
Table 16.1 Disease- specific 5- year survival rates
by tumour stage in UTUC
Stage Disease- specific 5- year survival
rates by tumour stage (%)
pTa/ CIS 100
pT1 91.7
pT2 72.6
pT3 40.5
pT4 <5.0
CIS, carcinoma in situ.
Adapted from Craig et al. Prognostic factors, recurrence, and
survival in transitional cell carcinoma of the upper urinary
tract: a 30- year experience in 252 patients. Urology, Volume 52,
Issue 4, 594– 601.
Table 16.2 A comparison of the major differences between the EAU guidance and UK
practice
24
EAU UK practice
Low risk UUT- TCC should be offered
kidney- sparing surgery
Invasive or large tumours are a
contraindication to laparoscopic NU
Lymphadenectomy is recommended for
invasive UUT- UC
Neoadjuvant chemotherapy is optional Neoadjuvant chemotherapy is not offered
Annual CT- IVU for all stages of disease Annual CT for high- risk tumours only (pT1 and
Routine use of urine cytology in follow- up Urine cytology is not offered as routine follow- up
CT, computed tomography; CT- IVU, computed tomography intravenous urography; NU, nephroureterectomy;
UUT- TCC, upper urinary tract transitional cell carcinoma.
Adapted from Moon et al. Urothelial carcinomas of the upper urinary tract – how does UK practice compare with
European guidelines: is there a difference? Journal of Clinical Urology 2018;11(2):139– 143.
In the presence of a normal contralateral kidney
NU remains the current standard of care for the
majority cases of UUT- UC
Laparoscopic NU is the most common surgical
option for UUT- UC and significant numbers of
patients will have invasive disease
Lymph node dissection is not performed routinely
above)
A final word from the expert
Bilateral simultaneous nephroureterectomy and nephroureterectomy of a single kidney as
radical treatment for high- grade urothelial carcinoma of the upper tract is relatively rare.
However, surgical techniques to deal with the oncological burden while avoiding the rendering
of a patient anephric should be considered. With an ageing population and patients rightly
valuing quality of life, bearing in mind the potential burden of dialysis on our patients is
important. It should be noted that to be listed for a renal transplant in the UK, patients have to
https://t.me/med1917
be cancer- free for 5 years. Given that 50% of patients with UTUC will have a bladder recurrence,
once patients are anephric it is likely they may never receive a transplant as they will at some
point have a de novo bladder cancer while on surveillance and thus be removed from, or never
reach, the transplant waiting list. This case demonstrates that careful multidisciplinary team
planning and joint working with our nephrology and transplant colleagues can allow us to
offer and perform nephron- sparing surgery under cold ischaemia in selected cases of UTUC
bilaterally or in a solitary kidney in patients who would otherwise become anephric and require
renal replacement therapy. Autotransplantation for upper tract TCC from our institution has
followed five patients from 2004 to 2019, with a mean 3- year follow- up and shows a cancerspecific survival of 100%: 100% of patients are recurrence- free and 100% of patients are dialysis
free. These patients are highly selected, require a very careful informed discussion of recurrence
risk, and need meticulous intensive follow- up utilizing cytology, CTU, and ureteroscopy.
161Case 16 Upper urinary tract urothelial carcinoma
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SECTION 7
Penile cancer
Case 17 Localized penile cancer
Case 18 Advanced and metastatic penile cancer
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