Upper urinary tract - Urothelial cell carcinoma

Upper Urinary Tract
Urothelial Cell Carcinomas
-Surgical Management
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1

Moderators:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2

Introduction
Treatment impact on outcomes ?
Relatively low frequency of Lesions
Lack of prospective randomized trials
Open vs. Laparoscopic
Radical Nephroureterectomy
Open vs. Retrograde endoscopic vs.
Percutaneous Renal sparing tumor ablation
3
Dept of Urology, GRH and KMC, Chennai.

Treatment - General Considerations
•RNU with excision of the bladder cuff -- Gold
standard
•Most tumors are not large or bulky. Laparoscopic
surgery is ideal at least for renal part.
•Various combinations of laparoscopic and open
techniques are employed for distal ureterectomy.
4

•Low grade non invasive upper tract tumors are
managed initially by ablative renal-sparing surgery.
• Retrograde ureteroscopy and ureteropyeloscopy --
Tumor size, number, and access allow complete
tumor ablation.
•Percutaneous antegrade tumor ablation --
Anatomy and tumor not allowing complete
ablation through a retrograde approach.
Treatment - General Considerations
5

T- Primary Tumour
TX -- Primary tumour cannot be assessed
T0 -- No evidence of primary tumour
T a -- Non-invasive papillary carcinoma
T is -- Carcinoma in situ
T1 -- Tumour invades subepithelial
connective tissue
T2 -- Tumour invades muscle
T3 -- Renal pelvis - Tumour invades beyond
muscularis in to peripelvic fat or renal parenchyma
Ureter -- Tumour invades beyond muscularis in to
periureteric fat
T4 -- Tumour invades adjacent organs or through the kidney
in to perinephric fat
Tumour Node Metastasis (TNM) staging
6

N - Regional Lymph nodes
NX -- Regional lymph nodes cannot be assessed
N0 -- No regional lymph node metastasis
N1 -- Metastasis in a single lymph node 2 cm or
less in the greatest dimension
N2 -- Metastasis in a single lymph node more than
2 cm but not more than 5 cm in the greatest
dimension or multiple lymph nodes, none more
than 5 cm in greatest dimension
N3 -- Metastasis in a lymph node more than 5 cm
in greatest dimension
M - Distant Metastasis
M0 -- No distant metastasis
M1 -- Distant metastasis
Tumour Node Metastasis (TNM) staging
7

World Health Organization (WHO) classification of 1973
Three Grades -- G1, G2, and G3 .
2004 WHO classification ---
Three Groups of Noninvasive tumours
▪ Papillary urothelial neoplasia of low malignant potential
▪ Low - grade carcinomas
▪ High- grade carcinomas.
There are almost no tumours of low malignant
potential in the upper urinary tract.
Tumour grade
8

Centrally located well /
moderately differentiated tumor
in the renal pelvis
Poorly differentiated urothelial
renal pelvis tumor invading renal
parenchyma 9

Prognostic Factors
Age → Independent prognostic factor --
Older age at the time of RNU is associated with
decreased cancer specific survival
Gender → No longer considered an independent
prognostic factor .
Tumour stage and grade
Muscle wall invasiveness -- Very poor prognosis.
5-yr specific survival is < 50% for pT2 /pT3 and
< 10% for pT4 .
Lymphovascular invasion
Present in approximately 20% of UUT-UCCs and
an independent predictor of survival. 10

Tumour location
No longer a prognostic impact for tumour
location (i.e., Ureteral vs Pyelocaliceal tumours)
when adjusted for tumour stage
Other factors
Extensive tumour necrosis( > 10% of the tumour area )
Tumour architecture (e.g., Papillary vs Sessile )
Sessile growth pattern -- Worse outcome .
The Presence of concomitant CIS
11

Microsatellite instabilities (MSIs) -- Loss of
heterozygosity at chr. 9p21
Mutation of tumor suppressor genes:
TP53 (chr.17p), Retinoblastoma gene (RB) chr.13q,
and CDKN2C , CDKN2A (chr. 9)
E –cadherin , Hypoxia inducible factor (HIF)-1α and
Telomerase RNA component .
None of the markers has been externally validated
Molecular markers
12

TREATMENT
13

RNU with excision of the bladder cuff --
Gold standard regardless of the location
Recommended for
• Large, high - grade, invasive tumors
• Medium grade, non invasive tumors
( large, multifocal, or rapidly recurring
despite maximal
efforts at conservative surgery.)
Must comply with oncologic principles
Preventing tumour seeding by avoiding entry
Localised
Disease
Radical Nephroureterectomy
14

SURGICAL APPROACHES
Flank Torque Position
Thoracoabdominal incision over the 11th or 12th rib.
Extrapleural, Extraperitoneal
Middle and anterior portions of the skin incision angle down
toward the pelvis rather than in a subcostal direction
SINGLE INCISION THORACOABDOMINAL APPROACH
15

SURGICAL APPROACHES
Supine with a small roll placed behind the rib
cage on the affected side.
Single long midline incision and intraperitoneal exposure.
Upper anterior subcostal incision and Lower quadrant
Gibson incision or Lower midline or Pfannenstiel incision 16

17

Not infrequent site of metastasis for urothelial tumor.
Traditionally, ipsilateral adrenal gland included.
One may omit adrenalectomy if
•Gland appears normal on preoperative imaging
•Grossly normal at the time of surgery
•Disease seems localized within the renal pelvis.
ADRENALECTOMY ?
However, adrenalectomy is prudent for maximal control if
locally advanced disease is discovered.
18

Therapeutic interest and allows for optimal staging .
Unnecessary in cases of Ta-T1 UUT-UCCs
Retrieval 2.2% in pT1 & 16% in pT2-4 tumours .
Lymphadenectomy in pN+ allows for reduction of the
tumour burden – Guide adjuvant treatments .
Anatomic sites of lymphadenectomy not defined.
(Ipsilateral renal hilar nodes and adjacent para-aortic or paracaval nodes )
No trial so far has shown its direct impact on survival .
Role of lymphadenectomy
19

The entire distal ureter, including the intramural
portion and the ureteral orifice, has to be removed.
Approach considerations -- Tumor location, potential
for seeding, patient factors, and personal experience.
No study has shown a clear advantage of any single technique
Laparoscopic approach -- Maintenance of a “closed
system” is important
Management of Distal Ureter and Bladder Cuff
20

Traditional Open Distal Ureterectomy
Transvesical Approach
Intravesical and
extravesical dissection
Anterior cystotomy
1 cm of bladder
mucosa is included
circumferentially around
the ureteral orifice.
21

Traditional Open Distal Ureterectomy
Extravesical Approach
Need for a cystotomy is
avoided.
The ureter is tented up,
and the bladder mucosa is
divided between clamps.
Avoid contralateral injury
from excessive traction.
22

Transurethral Resection of the Ureteral Orifice
Pluck technique-
Reserved for proximal,
low-grade tumors.
The entire orifice and
intramural ureter are
resected transurethrally
until the extravesical
fat is seen.
Beginning or at the
end of the procedure.
23

Intussusception (Stripping) Technique
Ureteral catheter placed
at the beginning of the
procedure.
Ureteral catheter secured
to the proximal end of
the distal ureter.
Ureter is intussuscepted
in to the bladder with
retrograde traction.
Resectoscope used to
excise the attached orifice. 24

Transvesical Ligation and Detachment Technique
Two laparoscopic
ports are placed
transvesically.
The ureteral orifice is
tented up; a loop is
placed around the
orifice.
Collins knife
facilitates the
dissection to the
extravesical space.
25

Laparoscopic RNU
Performed by Transperitoneal, Retroperitoneal
and Hand assisted approaches.
Significant decrease in morbidity.
Two distinct portions of the procedure:
Nephrectomy
Excision of the distal ureter with intact specimen
extraction for accurate staging.
Incision strategically placed for both extraction of
the specimen and dissection of the distal ureter.
26

Modified lateral decubitus position with
the ipsilateral flank rotated up 15 degrees.
Laparoscopic RNU
27

Laparoscopic RNU
Upper midline and lateral trocars -- Dissection of the kidney
and the proximal half of the ureter.
Lower midline and lateral trocars -- Dissection of the distal
ureter.
28

Safety not yet achieved final proof .
Equivalent oncologic results between laparoscopic
RNU and open surgery.
Superior to open surgery only with regard to
functional outcomes .
Retroperitoneal metastatic dissemination and
Dissemination along the trocar pathway
( when large tumours were manipulated in a
pneumoperitoneal environment )
Laparoscopic RNU
29

• Entering the urinary tract should be avoided.
• Direct contact of the instruments with tumour
avoided.
• Morcellation of the tumour should be avoided,
and an endobag is necessary to extract
the tumour.
• Invasive, large (T3/T4 and/or N+/M+), or
multifocal tumours are contraindications .
LAP RNU Precautions
30

Preservation of the upper urinary renal unit . Avoid
morbidity associated with open radical surgery
Conservative Surgery
INDICATIONS
Imperative cases --Renal insufficiency,
Solitary functional kidney
Synchronous bilateral tumors
or
In elective cases (i.e., contralateral kidney is
functional ) for low-grade, low-stage tumours.
31

Conservative Surgery
Open Nephron Sparing Surgery for Renal Pelvis Tumors:
OPTIONS : Pyelotomy and Tumor Resection
Partial Nephrectomy
Preoperative arteriography -- Not routinely obtained.
Helpful before rare hypervascular tumors.
Tumor recurrence
• Reported overall risk 7% to 60%
• Risk increases with tumor stage
<10% for Gr.1 to 28% to 60% for Gr. 2 & 3
• Reflects the inherent multifocal atypia and
field change of the renal pelvis
32

Treatment of low and high risk tumours of the
distal ureter.
Failure rate higher when attempted for
Iliac and lumbar ureter
Pyelocaliceal tumours .
Ensure that the area of tissue around the tumour
is not invaded.
Conservative Surgery – OPTIONS
Open Segmental Resection
33

✓Low volume ureteral and renal tumors.
✓ Larger tumors of the upper ureter or kidney
✓ Tumors not adequately manipulated in a retrograde
approach because of location (e.g., lower pole calyx) or
previous urinary diversion.
Multifocal involvement →
Endoscopic Treatment
34

• A flexible rather than a rigid ureteroscope,
with pliers (pluck) for biopsies
•Tumor is first sampled and then ablated by
electrocautery or laser energy sources.
Holmium : yttrium-aluminum-garnet and Neodymium : yttrium-aluminum-garnet.
•A complete resection is advocated.
• Patient is informed of the need for closer,
more stringent surveillance.
Ureteroscopy
35

36

Low grade tumours in the lower caliceal system
that are inaccessible or difficult to manage by
ureteroscopy.
Main advantage—Ability to use larger instruments
that can remove a large volume of tumor
• Theoretical risk of seeding exists in the puncture
tract and in perforations
• Progressively abandoned due to availability of
recent ureteroscopes with distal tip deflection.
Percutaneous access
37

Tumors in peripheral calyces --
Direct puncture as far distally
in the calyx as possible.
Tumors in the renal pelvis and
upper ureter --
Upper or Middle calyx
puncture.
Tumors in the lower calyx --
Lower calyx puncture
Nephrostomy tract puncture sites
38

Percutaneous
removal of TCC
•Debulking by forceps
to its base.
•Resection by standard
resectoscope .
Holmium or
Neodymium laser
•Standard nephroscope
•Flexible cystoscope
39

Regardless of approach, a nephrostomy tube is left
in place.
To ensure complete tumor removal
3 to 5 days later to allow adequate healing.
Visualise the tumor resection site
Residual tumor -- Removed.
No tumor -- Base sampled and treated by cautery
Nephroureterectomy is indicated if the pathologic
examination shows high -grade or invasive disease.
40

Instillation of bacillus Calmette-Guérin or mitomycin C
(After complete eradication of the tumour)
By Percutaneous nephrostomy via a three-valve
system open at 20 cm
OR
Through a ureteric catheter.
Adjuvant Topical Agents
MMC
RESECTED SITE
COPE
41

Chemotherapy
• Platinum based chemotherapy -- CISCA Regimen &
MVAC Regimen , Gemcitabine , Paclitaxel
•Adjuvant chemotherapy
Recurrence free rate -- 50% .
Minimal impact on survival .
Advanced
Disease
Nephroureterectomy
No benefits of RNU in metastatic (M+) disease,
As a Palliative option
Radiation therapy
•Adjuvant radiotherapy may improve local control .
•Combination with cisplatin, it may result in a longer
disease-free and overall survival . 42

Mandatory to detect
Metachronous bladder tumours (in all cases )
Local recurrence, and distant metastases
(in the case of invasive tumours).
Reported recurrence rate within the bladder
15% to 50% .
Ipsilateral upper urinary tract requires careful
follow up ( During conservative treatment.)
Follow-up
43

After RNU ( At least 5 yr)
Noninvasive tumour
Cystoscopy / Urinary cytology at 3 mo and then yearly.
MDCTU every year
Invasive tumour
Cystoscopy / Urinary cytology at 3 mo and then yearly.
MDCTU every 6 mo over 2 yrs and then yearly
Guidelines for follow up of UUT -UCC
patients
( after initial treatment)
44

After conservative management ( At least 5 yr)
Urinary cytology and MDCTU at 3 mo, 6 mo, and
then yearly
Cystoscopy, Ureteroscopy and cytology in situ at
3 mo, 6 mo, and then every 6 mo over 2 yr,
and then yearly.
Guidelines for follow up of UUT -UCC
patients
( after initial treatment)
45

Algorithm for the management of upper-tract TCC
46

47

Wilms tumor, or Nephroblastoma, -- Most common
Primary malignant renal tumor of childhood.
Current management now emphasizes
Reducing the morbidity of treatment for low-
risk patients
&
Reserving more intensive treatment for high
risk patients.
Emergent operation -- Not necessary unless there
is evidence of active bleeding or tumor rupture.
48

NWTSG -- National Wilms Tumor Study Group
COG -- Children’s Oncology Group
SIOP -- International Society of Pediatric Oncology
UKCCSG -- United Kingdom Children’s Cancer Study Group
Multiple Randomized Clinical Trials
To determine the appropriate role for each of
the therapeutic modalities available.
Patients are stratified in to different treatment
groups based on stage and pathology.
Goals: To decrease the intensity of therapy for
most patients in an effort to prevent late
sequelae of treatment.
49

Staging System of the Children's Oncology Group
Stage
I Tumor limited to the kidney
Tumor completely excised.
Renal capsule is intact and the tumor was not
ruptured prior to removal. No residual tumor.
II Tumor beyond the kidney, but is completely
resected.
Extrarenal vessels may contain tumor thrombus
or infiltrated by tumor.
50

Staging System of the Children's Oncology Group
III Residual non hematogenous tumor confined to
the abdomen:
Lymph node involvement, any tumor spillage,
rupture or biopsy, Peritoneal implants, tumor
beyond surgical margin either grossly or
microscopically, or tumor not completely removed.
IV Hematogenous metastases to lung, liver, bone,
brain, etc.
V Bilateral renal involvement at diagnosis
51

Prognostic Factors
 Cytokines = Vascular endothelial growth factor (VEGF)
 Tumor size
 Histology
 Lymph node metastases
Lesser ability to stratify
patients for treatment.
 Chromosomal Abnormalities
LOH for a portion of chromosome 16q and /or , chr. 1p
High telomerase Activity
 DNA Content
Aneuploidy - High in anaplastic tumors
52

▪Planning for renal-sparing surgery
▪Tumor extension into IVC above the hepatic veins
▪Inoperable tumors
▪Bilateral wilms tumor
Preoperative Chemotherapy
(COG Recommendations)
On the COG Wilms’ tumor protocols, treatment is
dependent on surgical and pathologic staging
following immediate nephrectomy.
53

▪ Initial therapy --
( Transperitoneal approach )
▪ Thorough exploration of the abdominal cavity
▪ Exploration of the contralateral kidney is no
longer mandatory
▪ Selective sampling of suspicious nodes – local
tumor staging.
▪ Formal RPLND is not recommended
Treatment - Surgical Considerations
54

Complete removal of the tumor without
contamination of the operative field.
Risk factors for local tumor recurrence
( Shamberger and colleagues (1999))
▪ Tumor spillage
▪ Unfavorable histology
▪ Incomplete tumor removal
▪ Absence of any lymph node sampling.
Treatment Surgical Considerations
55

Surgical Complications -- 11% .
Most common -- Hemorrhage and Small
bowel obstruction .
Lower rate of complications when
nephrectomy is performed after preoperative
chemotherapy ( SIOP )
56

Vena caval involvement (4%)
Below the level of the hepatic veins:
• Caval thrombus -- Cavotomy after proximal and
distal vascular control
• Adherent thrombus -- Fogarty or Foley balloon
catheter.
Thrombus extends above the level of the hepatic veins:
Preoperative chemotherapy can shrink the tumor
and thrombus, facilitating complete removal.
Vascular Extension
57

Inoperable Tumors.
Pre treatment with Chemotherapy
Repeat imaging -- 6 weeks of
chemotherapy.
Progressive Disease – Treatment
with Different
chemotherapeutic regimen
Adequate shrinkage of
the tumor -- Definitive
resection
58

Tumour Response to Chemotherapy
59

Tumor response is assessed
after 6 weeks with CT or MRI.
Bilateral Wilms' Tumors
Tumors not responding to
therapy -- Bilateral open
Biopsy to determine histology.
Tumors amenable to renal-
sparing procedures can
proceed with surgery.
Additional chemotherapy ( based on biopsy findings)
All patients should proceed to surgical resection within 12
weeks of starting therapy.
No initial radical nephrectomy. Preoperative chemotherapy for 6 weeks
60

Poor Response to chemotherapy
61

Removing the kidney with too extensive tumor
Second look Procedure
RENAL SPARING PROCEDURE
Partial nephrectomy or wedge excision
(Complete tumor resection with
negative margins )
Radical Nephrectomy
Rarely required when both tumors fail to respond
to chemotherapy and radiation therapy.
Bilateral nephrectomy and dialysis
62

Most Wilms' tumors are too large at diagnosis
Tumors detected during screening have small lesion
After preoperative chemotherapy, Partial nephrectomy
can be performed in 10% to 15% of patients.
Frozen sections to confirm a negative margin and
also to evaluate the histology.
Partial Nephrectomy for Unilateral Tumors.
Concerns :
Increased risk for local recurrence after Partial nephrectomy.
Additional chemotherapy required . 63

Stage II focal anaplasia or Stage III favorable
histology and focal anaplasia
• Nephrectomy
• Abdominal Radiation (1000 cGy)
• Vincristine, Actinomycin D, and Doxorubicin
(24 wks)
Postoperative chemotherapy and radiotherapy
Stage I favorable histology and unfavorable histology
or
Stage II favorable histology
• Nephrectomy
• Postoperative Vincristine and Actinomycin D
(18 wks)
64

Stage II to stage IV Diffuse anaplasia
• Nephrectomy
• Abdominal irradiation
• Whole lung irradiation for stage IV
• Vincristine, Actinomycin D, Doxorubicin,
Etoposide, and Cyclophosphamide ( 24 weeks)
Postoperative chemotherapy and radiotherapy
Stage IV Favorable histology or Focal anaplasia
• Nephrectomy
• Abdominal irradiation according to local stage
• Bilateral pulmonary irradiation (1200 cGy)
• Vincristine, Actinomycin D, and Doxorubicin
65

Late effects of treatment
Second Malignant Neoplasms (SMNs).
Cumulative incidence is 1.6% ( after 15 years)
Leukemia or Lymphoma
Radiation and Doxorubicin
Congestive heart failure
Doxurubicin , Whole Lung Irradiation
Growth disturbances
Spinal irradiation-- Severe reduction in spinal growth
Chemotherapeutic agents -- Direct effect on chondrocytes
66

Hormonal dysfunction and / or infertility.
Gonadal radiation in males – Temporary azoospermia
and hyogonadism.
Abdominal radiation in females -- Ovarian failure(12%)
Impairment of renal function
Irradiation,
Nephrotoxic chemotherapeutic agents
or
Hyperfiltration of the remaining nephrons.
Late effects of treatment
67

68

Upper urinary tract - Urothelial cell carcinoma

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Upper urinary tract - Urothelial cell carcinoma

Similar to Upper urinary tract - Urothelial cell carcinoma (20)

More from GovtRoyapettahHospit

More from GovtRoyapettahHospit (20)

Recently uploaded

Recently uploaded (20)

Upper urinary tract - Urothelial cell carcinoma