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Chapter21:Stenting, brachytherapy, and photodynamic therapy
in 1cm, and EBRT with a conformal technique and dose of
48
50Gy.
Brachytherapy, while prolonging stent patency, can be a
means of achieving longer patient survival times and improving quality of life. For preventing reocclusion, brachytherapy
could be used as a solitary source of radiation therapy. In
a prospective, non-randomized study, Chen et al. applied
HDR brachytherapy aer insertion of a self-expandable
metal stent. Signicantly longer stent patency duration was
achieved in patients undergoing brachytherapy (12.6 vs.
8.3months), but extended survival did not reach a statistically signicant level.49 Longer-term patency of metal stents
was achieved also by Park etal. when applying only external radiotherapy in a dose of 45–50 Gy. While they used
both covered and uncovered metal stents, subgroup analysis showed no dierence in patency rate for these two types
of stent. For the radiation therapy group and non-radiation
group, respectively, median overall patency of uncovered
stents was 17.7 and 9.6months and patency of covered stents
was 12.2 and 7.2months.
50
Despite the importance of brachytherapy and PDT in
prolonging patient survival and symptom palliation, these
techniques remain demanding in terms of the organization of
care and markedly extended hospitalization times that they
entail. Local ablation techniques such as endoluminal radiofrequency ablation with simple and one-time application
are potentially useful in palliating endoluminal tumors, preventing early ingrowth of the tumors through the stent mesh,
and even helping to resolve stent obstruction. ere are still
no randomized, prospective studies for these applications,
however.
51
Extrahepatic biliary cancer remains a complex medical
problem. Its predominantly hilar location, inltration, and longitudinal spread along the bile ducts, as well as the occlusion
of vascular bundles, frequently make it dicult or impossible
to achieve R0 resection. Chemotherapy or combinations of
chemoradiation therapy can prolong survival, but their results
are still far from satisfactory. Survival times can be inuenced
by optimal drainage, brachytherapy, PDT, or other ablation
treatments. In view of its morphological diversity, relatively
low incidence, and high patient age, it is very dicult to create a suciently homogeneous set of patients to demonstrate
the eectiveness of the individual therapeutic methods or
combinations. It seems that in highly selected patient groups
very good prognoses can be achieved, while in some patients
all therapeutic methods either fail or cannot be fully used due
to the patient’s status or to the unavailability of the necessary
technology.
References
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15. Inal M, Aksungur E, Akgul E, Oguz M, Seydaoglu G.
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16. Huibregtse K, Cheng J, Coene PP, Fockens P, Tytgat GN.
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Section V:Extrahepatic biliarycancer
18. Lammer J, Klein GE, Kleinert R, Hausegger K, Einspieler R.
Obstructive jaundice:use of expandable metal endoprosthesis
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19. Lameris JS, Stoker J, Nijs HG, Zonderland HM, Terpstra
OT, van Blankenstein M, etal. Malignant biliary
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20. Brountzos EN, Ptochis N, Panagiotou I, Malagari K, Tzavara C,
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21. Karnabatidis D, Spiliopoulos S, Katsakiori P, Romanos O,
Katsanos K, Siablis D. Percutaneous trans-hepatic bilateral
biliary stenting in Bismuth IV malignant obstruction. World J
Hepatol 2013; 5 (3):114–119.
22. Schima W, Prokesch R, Osterreicher C, urnher S, Fugger R,
Scho R, etal. Biliary Wallstent endoprosthesis in malignant
hilar obstruction:long-term results with regard to the type of
obstruction. Clin Radiol 1997; 52 (3):213–219.
23. Lee MJ, Dawson SL, Mueller PR, Hahn PF, Saini S, Lu DS, etal.
Failed metallic biliary stents:causes and management of delayed
complications. Clin Radiol 1994; 49 (12):857–862.
24. Rossi P, Bezzi M, Rossi M, Adam A, Chetty N, Roddie ME, etal.
Metallic stents in malignant biliary obstruction:results of a
multicenter European study of 240 patients. J Vasc Interv Radiol
1994; 5 (2):279–285.
25. Becker CD, Glattli A, Maibach R, Baer HU. Percutaneous
palliation of malignant obstructive jaundice with the Wallstent
endoprosthesis:follow-up and reintervention in patients with
hilar and non-hilar obstruction. J Vasc Interv Radiol 1993; 4
(5):597–604.
26. Krokidis M, Fanelli F, Orgera G, Bezzi M, Passariello R,
Hatzidakis A. Percutaneous treatment of malignant jaundice
due to extrahepatic cholangiocarcinoma:covered Viabil stent
versus uncovered Wallstents. Cardiovasc Intervent Radiol 2010;
33 (1):97–106.
27. Krokidis M, Fanelli F, Orgera G, Tsetis D, Mouzas I,
Bezzi M, etal. Percutaneous palliation of pancreatic head
cancer:randomized comparison of ePTFE/FEP-covered versus
uncovered nitinol biliary stents. Cardiovasc Intervent Radiol
2011; 34 (2):352–361.
28. Ito K, Ogawa T, Horaguchi J, Koshita S, Fujita N. Reintervention
for occluded biliary metal stent for patients with malignant
distal biliary stricture. Dig Endosc 2013; 25 Suppl 2:126–131.
29. Ortner MA. Photodynamic therapy in cholangiocarcinomas.
Best Pract Res Clin Gastroenterol 2004; 18 (1):147–154.
30. Talreja JP, Degaetani M, Ellen K, Schmitt T, Gaidhane
M, Kahaleh M. Photodynamic therapy in unresectable
cholangiocarcinoma:not for the uncommitted. Clin Endosc
2013; 46 (4):390–394.
31. Cosgrove ND, Al-Osaimi AM, Sano HK, Morris MM, Read
PW, Cox DG, etal. Photodynamic therapy provides local
control of cholangiocarcinoma in patients awaiting liver
transplantation. Am J Transplant 2014; 14 (2): 466–471.
32. Zoepf T, Jakobs R, Arnold JC, Apel D, Riemann JF. Palliation
of nonresectable bile duct cancer:improved survival aer
photodynamic therapy. Am J Gastroenterol 2005; 100
(11):2426–2430.
33. Ortner ME, Caca K, Berr F, Liebetruth J, Mansmann U, Huster
D, etal. Successful photodynamic therapy for nonresectable
cholangiocarcinoma:a randomized prospective study.
Gastroenterology 2003; 125 (5):1355–1363.
34. Leggett CL, Gorospe EC, Murad MH, Montori VM, Baron
TH, Wang KK. Photodynamic therapy for unresectable
cholangiocarcinoma:a comparative eectiveness systematic
review and meta-analyses. Photodiagnosis Photodyn er 2012; 9
(3):189–195.
35. Cheon YK, Lee TY, Lee SM, Yoon JY, Shim CS. Longterm
outcome of photodynamic therapy compared with
biliary stenting alone in patients with advanced hilar
cholangiocarcinoma. HPB (Oxford) 2012; 14 (3):185–193.
36. Matull WR, Dhar DK, Ayaru L, Sandanayake NS, Chapman
MH, Dias A, etal. R0 but not R1/R2 resection is associated with
better survival than palliative photodynamic therapy in biliary
tract cancer. Liver Int 2011; 31 (1):99–107.
37. Witzigmann H, Berr F, Ringel U, Caca K, Uhlmann
D, Schoppmeyer K, etal. Surgical and palliative
management and outcome in 184 patients with hilar
cholangiocarcinoma:palliative photodynamic therapy plus
stenting is comparable to r1/r2 resection. Ann Surg 2006; 244
(2):230–239.
38. Kahaleh M, Mishra R, Shami VM, Northup PG, Berg CL,
Bashlor P, etal. Unresectable cholangiocarcinoma:comparison
of survival in biliary stenting alone versus stenting with
photodynamic therapy. Clin Gastroenterol Hepatol 2008; 6
(3):290–297.
39. Lee TY, Cheon YK, Shim CS. Current status of photodynamic
therapy for bile duct cancer. Clin Endosc 2013; 46 (1):38–44.
40. Milano MT, Chmura SJ, Garofalo MC, Rash C, Roeske JC,
Connell PP, etal. Intensity-modulated radiotherapy in treatment
of pancreatic and bile duct malignancies:toxicity and clinical
outcome. Int J Radiat Oncol Biol Phys 2004; 59 (2):445–453.
41. Fletcher MS, Brinkley D, Dawson JL, Nunnerley H, Wheeler
PG, Williams R. Treatment of high bile duct carcinoma by
internal radiotherapy with iridium-192 wire. Lancet 1981; 2
(8239):172–174.
42. Mayo-Smith WW, Dawson SL, Mauceri T, Mueller PR.
Attenuation eects of biliary endoprostheses on therapeutic
radiation. Radiology 1996; 199 (2):571–572.
43. Alden ME, Mohiuddin M. e impact of radiation dose in
combined external beam and intraluminal Ir-192 brachytherapy
for bile duct cancer. Int J Radiat Oncol Biol Phys 1994; 28
(4):945–951.
44. Takamura A, Saito H, Kamada T, Hiramatsu K, Takeuchi
S, Hasegawa M, etal. Intraluminal low-dose-rate 192Ir
brachytherapy combined with external beam radiotherapy
and biliary stenting for unresectable extrahepatic bile duct
carcinoma. Int J Radiat Oncol Biol Phys 2003; 57 (5):1357–1365.
45. Shin HS, Seong J, Kim WC, Lee HS, Moon SR, Lee IJ, etal.
Combination of external beam irradiation and high-dose-rate
intraluminal brachytherapy for inoperable carcinoma of the
extrahepatic bile ducts. Int J Radiat Oncol Biol Phys 2003; 57
(1):105–112.
46. Chan SY, Poon RT, Ng KK, Liu CL, Chan RT, Fan ST. Long-term
survival aer intraluminal brachytherapy for inoperable hilar
cholangiocarcinoma:a case report. World J Gastroenterol 2005;
11 (20):3161–3164.
200
Chapter21:Stenting, brachytherapy, and photodynamic therapy
47. Shinohara ET, Guo M, Mitra N, Metz JM. Brachytherapy in the
treatment of cholangiocarcinoma. Int J Radiat Oncol Biol Phys
2010; 78 (3):722–728.
48. Valek V, Kysela P, Kala Z, Kiss I, Tomasek J, Petera J.
Brachytherapy and percutaneous stenting in the treatment of
cholangiocarcinoma:a prospective randomised study. Eur J
Radiol 2007; 62 (2):175–179.
49. Chen Y, Wang XL, Yan ZP, Cheng JM, Wang JH, Gong GQ,
etal. HDR-192Ir intraluminal brachytherapy in treatment of
50. Park S, Park JY, Bang S, Park SW, Chung JB, Song SY.
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malignant pancreatobiliary obstructions. Gut Liver 2013; 7
(4):480–485.
51. Dolak W, Schreiber F, Schwaighofer H, Gschwantler
M, Plieschnegger W, Ziachehabi A, etal. Endoscopic
radiofrequency ablation for malignant biliary obstruction:a
nationwide retrospective study of 84 consecutive applications.
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malignant obstructive jaundice. World J Gastroenterol 2004; 10
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201
Section VI
Organ-specific cancers – renal cell carcinoma
Chapter
Management of small renalmasses
22
Mansi A. Saksena, Debra A. Gervais, Michael C. Soulen, and Peter R. Mueller
Approximately 61,560 new cases of renal cell carcinoma (RCC)
were estimated to be diagnosed in the USA in 2015, with 14,080
cancer-related deaths attributed to cancers of the kidneys and
the renal pelvis.1 More than one-half of these patients were
diagnosed incidentally on cross-sectional imaging performed
for non-related conditions.2 Increased incidental detection of
small renal masses as well as advances in surgical techniques
have led to development of nephron-sparing procedures for
treatment in order to preserve renal function. Over the past
decade, the options for the treatment of RCC have evolved to
include radical nephrectomy as well as partial nephrectomy,
laparoscopic nephrectomy and, in selected cases, percutaneous
radiofrequency ablation (RFA), microwave ablation (MWA),
and cryotherapy. Each therapy has unique clinical applications
and benets. is article illustrates various treatment modalities used in the therapy of RCC, with special emphasis on percutaneous ablative techniques.
Clinical overview
RCC accounts for 85% of all renal tumors and is slightly more
common in men than in women (1.6:1.0).2 Symptomatic RCC
usually presents with a triad of ank pain, hematuria, and a palpable abdominal mass. Hematuria, either gross or microscopic,
in any patient usually warrants evaluation by a computed
tomographic (CT) scan. Other non-specic symptoms include
weight loss, anemia, or fatigue. However, almost one-half of
patients are asymptomatic at diagnosis and have incidentally
detected tumors on cross-sectional imaging. Certain genetic
syndromes such as von Hippel–Lindau (VHL) disease increase
the incidence of RCC (accounting for approximately 2% of
cases of RCC). Other risk factors include smoking, hypertension, obesity, and end-stage renal disease resulting in dialysis.
Clear-cell RCC is the most common histological subtype
and is associated with VHL syndrome and end-stage renal
disease (Table22.1). Other inherited forms include familial
clear-cell RCC. Papillary RCC, when sporadic, has a prominent male preponderance and is associated with almost 90%
5-year survival rates prior to metastatic spread. Papillary
RCC has a lesser incidence of metastases than clear-cell but,
when metastatic, is harder to treat. Papillary RCC is also seen
in end-stage renal disease and in several familial syndromes.
Other less common cell types include chromophobe RCC and
collecting-ductRCC.
One-quarter of patients with RCC have metastatic disease
at diagnosis and have a poor 5-year survival rate.2 is underscores the importance of a robust initial metastatic workup,
which should include a chest X-ray and abdomen CT scan,
with bone scan being optional to evaluate for bone metastases
if needed. Ahead CT scan may be obtained in case the patient
demonstrates any neurological symptoms. Moreover, one-third
of patients undergoing treatment develop metastatic disease
on follow-up. Hence, the goal is to develop eective surgical
or ablative therapies, bearing in mind that, for some patients,
multiple treatments may be indicated.
e presence of multiple renal masses usually suggests a
genetic predisposition, and patients are screened for various
hereditary syndromes. Conditions such as VHL have unique
extrarenal manifestations. Patients with these genetic syndromes are closely monitored with either contrast-enhanced
CT or magnetic resonance imaging (MRI). In these patients,
small masses are usually low-grade and can occasionally be
monitored with surgical or ablative therapy initiated for any
mass as tumors enlarge.
3,4
e exact size at which therapy is
generally initiated for a particular tumor in VHL patients is
generally accepted to be 3cm
3,4
for surgical resection based on
the low metastatic potential of small RCC. However, for percutaneous ablative therapies, some have advocated treating
smaller tumors, starting at 2.5–3cm.
5,6,7
Staging
Like most cancers, the prognosis of RCC is largely dependent
on the stage of disease. e tumor–node–metastasis (TNM)
classication is a commonly used staging system wherein stage
Idisease is associated with a 95% 5-year survival rate, whereas
survival in stage IV disease is 20% (Figure22.1; Table22.2).
2
Diagnosis
Any enhancing renal mass on a CT study of the abdomen is generally considered to be RCC unless proven otherwise. Ninety
percent of masses greater than 3cm are RCC and warrant surgical resection. However, 25% of small renal masses (< 3cm in
size) are benign in nature.2 us, some physicians prefer biopsy
Interventional Oncology, Second Edition, ed. Jean-François H. Geschwind and Michael C. Soulen. Published by Cambridge University Press.
©Cambridge University Press2016
203
Section VI:Renal cell carcinoma
Aorta
Table 22.1 Incidence of various histological types of sporadic renal cell
carcinoma
2
Histological appearance Incidence (%)
Conventional 75
Papillary 12
Chromophobe 4
Oncocytoma 4
Collecting duct <1
Unclassified 3–5
Table 22.2 Tumor–node–metastasis (TNM) staging of renal cell
carcinoma
Primary tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 7 cm or less, limited to the kidney
T2 Tumor more than 7 cm, limited to the kidney
T3 Tumor extension into major veins, adrenal gland or surrounding
tissue, but limited within the Gerota’s fascia
T3a – Tumor invades the adrenal gland or surrounding tissue
T3b – Tumor grossly extends into the renal vein or vena cava
Inferior
vena cava
Adrenal Gland
T4 Tumor extends beyond Gerota’s fascia
Regional lymph nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional node metastasis
Gerota’s
fascia
N1 Metastasis in a single regional lymph node
N2 Metastasis in more than one regional lymph node
Distant metastasis (M)
MX Presence of metastasis cannot be assessed
M0 No distant metastasis present
Lymph
Nodes
M1 Distant metastasis present
3–4cm may be amenable to nephron-sparing partial nephrec-
Kidney
tomy. e clinical indications for nephron-sparing surgery or
partial nephrectomy include patient factors such as
6,8,9
:
• bilateral or multifocaltumors
• RCC in a solitarykidney
• poor function of the unaectedkidney
• signicant comorbidities such as chronic renal failure or
Stage I
Stage II
Stage III
Stage IV
Figure 22.1 Diagrammatic representation of staging of renal cell carcinoma.
(Adapted from Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med
2005; 353: 2477–2490, with permission.2)
conrmation prior to resection in order to avoid performing a
nephrectomy for benign disease.
Treatment options
Surgery
Stage IRCC is curable by complete resection and patients who
have no contraindication to surgery generally undergo resection. e historical standard, radical nephrectomy, involves
en-bloc resection of the kidney along with the ipsilateral
adrenal gland, Gerota’s fascia, and regional lymph nodes.
Radical nephrectomy can be either open or laparoscopic, with
decreased postoperative pain and earlier recovery being the
advantages of a laparoscopic procedure. Masses smaller than
hypertension.
Additional tumor-related factors include a tumor less than 4cm
in size and polar lesions. ese tumor features are not absolute
but make partial nephrectomy technically less dicult.
Partial nephrectomy, which can also be performed laparoscopically, does bear the burden of a 3–6% rate of local recurrence, a result similar to radical nephrectomy.10 Given similar
recurrence and survival rates, partial nephrectomy has become
an acceptable alternative to radical nephrectomy.
Percutaneous techniques
Small renal masses are increasingly being detected, particularly
in patients with signicant comorbid conditions. ese patients
are usually not ideal surgical candidates and can be treated by
various minimally invasive therapies – namely, percutaneous RFA, MWA, and cryoablation.
shown promising early results and that in turn has generated
enthusiasm for their application. Although other technologies
such as high-intensity focused ultrasound and irreversible electroporation have been proposed, percutaneous RFA and cryoablation are the most widely available and the most extensively
evaluated and will be reviewed in this chapter.
11,12
ese techniques have
204
Chapter22:Management of small renalmasses
Radiofrequency ablation
Background
RFA of a tumor involves the delivery of an electrical current via
needle electrodes to create high tissue temperatures and cause
cell death. Cell death occurs at temperatures higher than 45°C,
with complete tumor necrosis being achieved at 60–100°C.13
e needle electrode placed within a tumor is connected to
a RF generator, and the circuit is completed by placement of
grounding pads on the patient’s thighs, which are also connected to the generator. As an electrical current is applied in
this circuit, it causes ion agitation at the electrode tip, leading
to an increase in tissue temperatures. e maximal diameter
of a zone of ablation created by a 17-gauge needle electrode
in liver experiments is 1.6cm. e limitation in the size of the
zone of ablation created by an electrode tip is caused by vaporization and carbonization of tissue as temperatures rise above
100°C.13 is leads to an increase in tissue impedance to the
ow of electrical current. Hence, most recent technical innovations in RFA technology are aimed at achieving larger burns–
that is, increasing the maximal diameter of the zone of ablation
created by an electrode. Such innovations include the develop-
Microwave ablation
Background
Similar to RFA, MWA causes rapid oscillation of water molecules to induce tissue heating. Unlike RFA, MWA is independent of tissue impedance and causes more rapid heating to
higher temperatures than RFA. Larger ablation zones can be
created within a few minutes with relative resistance to heat
25
sinks.
Histology
In an in-vivo porcine model, ablated lesions could be divided
into three zones: carbonization zone, coagulation zone, and
inammatory reaction zone.
e ablation zone enlarged with increasing power and time.
When combined with two needles, the maximum diameter of
the ablated lesions signicantly increased. Pathological results
indicated that renal tissues of the carbonization zone were
necrotic. Coagulative necrosis was observed in the coagulation zone. No skipped areas were noted in any ablation zone.
Interstitial small blood vessels were congested with inltrated
inammatorycells.
26
ment of multitined electrodes, cluster arrangement of multiple
electrodes, pulsing of the electrical current, internal cooling of
the electrode, and interstitial saline infusion.
14,15,16,17
Histology of RFA
Normal porcine kidneys and ablation treatment of VX2 tumors
implanted in rabbit kidneys are the primary animal tumor models utilized for determining the immediate and short-term histopathological renal changes brought about by RFA. Immediately
aer an RFA treatment, the zone of ablation has been found to
be gray–white in VX2 rabbit tumors and well-circumscribed
yellowish white in normal porcine kidneys.
18,19
Minimal hemorrhage may be seen at the electrode insertion site. Microscopically,
treated cells demonstrate loss of cell border integrity, nuclear
chromatin blurring, interstitial hemorrhage, and cytoplasmic
eosinophilia.18 By the third day posttreatment, cellular nuclei
become pyknotic and lysed, suggestive of coagulative necrosis.
Early broblastic inltration and inammation are seen at the
boundary between the region of treatment and normal renal
parenchyma. By 14 days posttreatment, as nuclear degeneration is completed, four zones are identied from the center to
the periphery:namely, central necrosis, inammatory inltrate,
hemorrhage and brosis, and regeneration. Complete architectural distortion within the zone of necrosis is identied by
the 30th day, and the necrotic focus is resorbed approximately
90 days aer treatment.18 Initial studies in humans revealed
similar results,
20,21
but the claim of complete tumor necrosis was
soon challenged as Michaels etal. reported incomplete tumor
necrosis in 17 tumors treated prior to nephrectomy.22 is and
other studies suered from limitations pertaining to technique
and technology available at that time.23 For example, in the study
by Michaels etal., only one ablation was performed per tumor
without repositioning the electrode for overlapping ablations.
e importance of meticulous technique with close attention
to performing multiple ablations for adequate coverage of the
entire tumor has since been promoted.
8,24
Cryoablation
Background
Cryoablation operates on the conversion of high-pressure argon
gas to cold low-pressure liquid by using the Joule–ompson
eect.27 e system comprises a computer workstation, a gas
distribution apparatus, and needle-like cryoprobes. Cryoprobes
are equipped with a thermocouple, which is used to monitor
tissue temperature during both freezing and thawing. Renal
cryoablation can be performed via open, laparoscopic, or
percutaneous approaches.
has the advantage of allowing visualization of the ice ball by
imaging. is provides for intraprocedural monitoring and
rough prediction of regions of cryonecrosis. is may prevent
unwanted damage to normal structures and facilitate eective
coverage of tumor tissue. Repetitive freeze–thaw cycles are
used during cryoablation, with temperatures reaching a nadir
of–130°C during the freeze. Temperatures at the edge of the ice
ball are about 0°C and are considered non-lethal.
Histology of cryoablation
Cryoablation achieves cell death by direct cryothermic and
indirect ischemic cell injury. ese two synergistic mechanisms are sequential, with direct cytotoxicity secondary to
intracellular ice crystal formation occurring during the freeze
phase and indirect ischemic injury due to local tissue microvasculature occlusion occurring during the thaw phase.
threshold temperature at which irreversible cell death occurs
is between –19.4°C and –40°C.34 Although such temperatures are easily achieved in the center of the ice ball, the temperature at the periphery is 0°C, and hence the ice ball must
extend approximately 3.1mm beyond the tumor margins to
achieve complete treatment.35 Adouble freeze–thaw cycle has
been found to increase the region of cryonecrosis compared
with a single freeze–thaw cycle.36 Histological examination
28,29,30,31
Percutaneous cryoablation
32,33
e
205
Section VI:Renal cell carcinoma
of cryoablated tissue demonstrates signs of cell death such as
vascular congestion, nuclear pyknosis, mitochondrial damage
and coagulative necrosis, with central zones demonstrating
complete cell death and transitional zones, incomplete cellular
injury at the periphery.
33
Indications for percutaneous ablation
Patient factors
Until robust 10-year survival and disease-free survival rates
are available, percutaneous ablation is limited to treatment of
patients who are not ideal candidates for other well-established
treatments such as nephrectomy. ese include the following
conditions:
• elderly patients (less than 10-year life expectancy)
• multiple renal tumors, as in a VHL patient
• solitarykidney
• limited renal function
• comorbid conditions precluding surgery
• refusal of surgery.
Additionally, ablation is generally reserved for patients with
greater than 1-year life expectancy, as a small RCC is unlikely
to cause clinically signicant morbidity before 1year.
Tumor-specific factors
Tumor location and size are primary considerations when
assessing a lesion for percutaneous ablation. As stated earlier, smaller tumors are more amenable to complete ablation.
Although dierent reports use various size limits to dene an
ablatable RCC, the range of a small tumor is 1.5–4cm.
,39,40,41,42
Gervais etal. have shown that complete tumor necro-
5,6,11,37,38
sis at imaging can be achieved for tumors 4cm or smaller.
In addition to size, tumor location plays a signicant role in
the suitability of a lesion for ablation. For thermal ablation,
an exophytic lesion surrounded by perirenal fat is ideal, as the
insulation aorded by perirenal fat allows for achievement
and maintenance of higher temperatures. Astudy by Gervais
etal. demonstrated less complete necrosis in centrally located
tumors.9 is can be attributed to a heat-sink eect seen in
tumors close to large hilar vessels. Blood ow in large vessels
causes a perfusion-mediated cooling of tumor tissue, limiting
the temperatures that can be achieved and hence inhibiting
complete ablation. In addition, the rate of complications may
be higher for more central tumors.
Preablation imaging
Adequate preablation imaging provides vital information about
the margins and extent of the tumor, which allows for eective
treatment planning. Preablation imaging can be performed
by contrast-enhanced CT or MRI regardless of the method of
percutaneous ablation being used. Additionally, pretreatment
images serve as a baseline for future evaluation on follow-up.
Adjunctive procedures
A biopsy is usually performed prior to percutaneous ablation
as the tumor is le in situ, unlike surgical resection, wherein
specimens undergo pathological evaluation. In case of benign
disease, one may not treat and, if treated, the follow-up may
dier. e biopsy can be performed either on the same day as
the ablation or tissue diagnosis may be obtained some time
prior to ablation.
24
Technique
Anesthesia
Most patients can undergo RFA under conscious sedation as
an outpatient procedure.9 Some patients may require an overnight admission. Monitored anesthesia care is usually reserved
for those who do not meet institutional criteria for sedation
or have failed sedation, although some operators prefer to perform all RFA or MWA with the aid of an anesthesiologist.
Cryoablation is far less painful than RFA, but takes longer
to perform and requires breath holding for adequate intraprocedural imaging. Some practitioners prefer anesthesia for
cryoablation; however, it can be performed under conscious
sedation as well and is an excellent alternative for patients too
frail for anesthesia.
Modality for guidance
Cryoablation or RFA can be performed using ultrasound, CT,
or MRI guidance. e ease of tumor visualization, availability of imaging equipment, and operator experience usually
dictate the choice of modality. Ultrasound provides real-time
visualization as the needle electrode is placed in the tumor
for either technique. e disadvantage of ultrasound is that,
as thermal ablation is performed, tumors are oen rendered
highly echogenic due to formation of bubbles of water vapor
or ice ball formation. is makes tumor visualization for
electrode repositioning to perform overlapping treatments
9,24
particularly challenging. CT allows for adequate preprocedure planning and intraprocedure electrode repositioning
as it produces consistent, easily reproducible images. Neither
unenhanced CT nor ultrasound allows for intraprocedure precise delineation of the exact zone of ablation. MRI aords this
luxury by providing accurate monitoring of treatment eects
during an ablation as the ice ball formed during cryoablation
has a very short T2 relaxation time and is seen as a region
of signal void on T2-weighted images. Limited interventional
MRI units, MRI-compatible thermal ablation equipment, and
patient-monitoring equipment preclude widespread use of
MRI guidance. Additionally, patients with a history of active
ischemic heart disease cannot undergo MRI-guided cryoablation as the magnetic eld of an MRI scanner precludes electrocardiographic monitoring during the procedure.
Radiofrequency ablation
Once adequate anesthesia and patient position are set up, the
needle is placed within the tumor under image guidance. e
value of overlapping ablations is well recognized, and multiple
ablations involving repositioning the needle between sequential ablations are usually performed, with the ablation plan to
cover the entire tumor. us, overlapping ablations are performed based on tumor size and geometry (Figure22.2). RF
electrodes allow the option of track ablation upon electrode
removal. is is performed by slow removal during application
206
Chapter22:Management of small renalmasses
A
C
E
B
D
F
Figure 22.2 A 78-year-old woman with
incidental detection of a right renal mass.
(A) Axial section from a contrast-enhanced
computed tomography (CT) scan
performed prior to radiofrequency
ablation (RFA) shows a 3-cm exophytic
mass (arrow) in the middle pole of the
right kidney. This mass was found to
be renal cell carcinoma after biopsy.
(B–E) Axial CT images at RFA with the
patient in right lateral decubitus position
demonstrate multiple placements of
a needle electrode (arrow) in order to
perform overlapping ablations. Multiple
treatments are often essential to ensure
treatment of all regions of the tumor. The
patient recovered uneventfully. (F) Axial
image from a contrast-enhanced CT scan
performed 1 month after the ablation
demonstrates an abnormal region of
residual enhancement (arrow) along the
medial margin of the ablated tumor. This
appearance is consistent with residual
disease. (G) Patient underwent re-ablation
of the residual portion of the tumor. Axial
CT image obtained at the second ablation
demonstrates needle electrode (arrow)
within the region of residual disease seen
on prior image. (H) Axial image from a
contrast-enhanced CT scan performed
1 month after the second ablation
demonstrates expected postablation
stranding in the region of treatment
(arrow). There is no evidence of residual
disease. No abnormal enhancement was
seen on follow-up studies performed 3
and 6 months after the second ablation
(not shown).
G
H
of current to cauterize any small bleeding vessels and to minimize the likelihood of track seeding. Once the tumor is satisfactorily covered, the patient undergoes routine postprocedure
care depending on the type of anesthesiaused.
Microwave ablation
Similar to RFA, MWA entails placement of one or more applicators in or bracketing the tumor to achieve a complete ablation zone with adequate margin, depending upon the treatment
207
Section VI:Renal cell carcinoma
scheme of the particular device used. Track ablation can also be
performed if needed.
Cryoablation
Unlike most RF systems, multiple cryoprobes can be used at
one ablation. Typically, one cryoprobe generates an ice ball that
is 2cm in the short axis.27 Tumors that measure 2–3cm can be
treated with two or three cryoprobes, whereas larger tumors
require four or ve probes.12 us, the treatment plan is determined by tumor size and geometry, and the number of cryoprobes is selected. Multiple (two or three) freeze–thaw cycles
involving a 15-minute freeze and a 10-minute thaw can be used,
with temperatures reaching up to–130°C.
12,43
Intraprocedural
ice ball monitoring by CT or MRI can allow rough prediction
of the region of cryonecrosis. If the ice ball does not encompass
the entire tumor and a 3.1-mm margin of tissue beyond the
tumor, additional cryoprobes can be placed.
Historically, cryoprobe size required open surgical
exposure for placement.
43,44,45
Advancements in cryoprobe
technology have made probes small enough for percutaneous placement, enabling cryoablation to compete with
percutaneousRFA.
12
Adjacent structures
During thermal ablation, tissue injury may extend to adjacent
normal organs such as the ureters or bowel. When planning
ablation, note the position of nearby structures to minimize
risk. Techniques such as change in patient position and hydrodissection can be used to displace contiguous structures and
protect them from thermal injury.46 Hydrodissection involves
instillation of sterile 5% dextrose (for RFA) or normal saline
(for MWA and cryoablation) in the tissue planes between the
tumor and any adjacent organ, such as bowel (Figure22.3).
is separates the tumor from nearby organs and allows ablation to be performed safely. Other agents such as carbon dioxide may also be used for organ separation.
47,48
Alternatively,
laparoscopic exposure may allow retraction of bowel or ureter
for safe ablation.
5
Postprocedure follow-up
Because ablated tumor is le in situ, no histopathological information is available to assess the adequacy of treatment. Imaging, therefore, is the mainstay of follow-up both
for initial assessment of ecacy and for monitoring for local
progression aer ablation. Tumor regions that do not demonstrate any enhancement on follow-up CT or MRI are considered to be regions of complete necrosis, whereas residual foci
of enhancement are interpreted to represent residual disease
(Figure22.2).49 Residual disease can undergo retreatment by
percutaneous ablation, assuming it remains within the limits of
suitable size and location.
e initial postablation scan is generally performed between
1 and 5 weeks, depending on operator preference.
9,38,39,40,41
If no
viable tumor is seen on the rst follow-up study, repeat imaging can be performed at 3months, followed by 6months and
1year. If no new or residual disease is detected, the patient can
then undergo long-term annual follow-up. In most cases, a
small non-enhancing mass is persistently seen at the ablation
site. e zone of ablation is known to regress more aer cryoablation than aer RFA. However, the keystone of diagnosing
residual disease remains enhancement.
Clinical ecacy
As available RF equipment has improved, so have the results
(Table22.3). Earlier studies reported inferior treatment rates
(79%),50 probably attributable to weaker generators, which
failed to achieve adequate treatment temperatures. Later studies using 150–200-W generators have shown 88–100% successful treatment rates in tumors 2.5–4cm in size.
2,50,51,52
Larger tumors (>3cm) have predictably been harder to
5,8,24,38,39,40,41,4
treat. McDougal etal. followed 16 patients treated with renal
RFA for 4years and found renal RFA of lesions less than 5cm
in diameter to be comparable to surgery.7 Although renal RFA
has been established as an eective therapy for small renal
masses in non-surgical candidates, 5–10-year survival data
are currently lacking. Once sucient cohorts of postablation
patients are available to assess 5-year survival, percutaneous
ablation outcomes can be compared to surgical standards of
resection.
ree-year follow-up data on laparoscopic renal cryoablation are encouraging, with a 3-year cancer-specic survival
rate of 98% in 56 patients with a mean tumor size of 2.3cm.53
However, percutaneous renal cryoablation is relatively newer,
and there is a scarcity of ecacy data in the literature. In an
initial report by Shingleton et al., 22 tumors in 20 patients
were treated, with a mean tumor size of 3cm. Only one patient
required retreatment at a mean follow-up of 9.1 months.45
Astudy of 23 patients by Silverman etal. reported complete
ablation in 24 of 26 tumors, with only one patient needing
retreatment.12 ese studies are limited by lack of long-term
follow-up and small sample size. Larger trials with long-term
follow-up are needed before accurate ecacy of cryoablation
can be determined.
Early and intermediate outcomes aer MWA are encouraging. Moreland et al. reported early outcomes on 55
biopsy-proven tumors 0.5–4.0cm treated with percutaneous
MWA with no local recurrence or metastasis at a median
follow-up of 8 months.54 Yu et al. reported on 49 RCCs
0.6–7.7cm (mean 3.0cm) with initial technical eectiveness
in 48/49 (98%). At 3 years the local control rate was 92%,
cancer-specic survival rate 100%, and overall survival 98%
with no metastases.55 Two surgical series comparing MWA to
open radical or partial nephrectomy reported equivalent oncologic outcomes at 3–5years.
56,57
Complications
Compared with resection, percutaneous ablative techniques
are relatively safe, with a lower rate of major complications.
e most common minor complication is pain or paresthesia
related to the probe insertion site58 (Table22.3). Other minor
complications include self-limited paresthesias, transient
hematuria, and subcapsular hematomas (Figure22.4).
Hemorrhage necessitating blood transfusion or ureteral
stent placement is the most common major complication and is
58
208