whereas the management of localized renal cell carcinoma ( rcc ) has evolved toward minimally invasive and nephron - sparing surgery , the treatment of endophytic renal tumors has remained problematic .
these tumors typically require precise intracorporeal suturing and complex reconstruction , with the added time constraints imposed by renal ischemia .
even open partial nephrectomy is acknowledged to be technically demanding in this situation , with increased complication rates compared with procedures for tumors in peripheral locations .
in addition , serial studies of laparoscopic partial nephrectomy ( lpn ) report higher postoperative complication rates , which result in more ischemic time and longer hospital stays for endophytic tumors [ 2 - 4 ] . with the increasing application of minimally invasive surgery ,
several energy - based tissue ablation technologies including cryoablation and radiofrequency ablation are being investigated . in these procedures ,
tissue is destroyed in situ , thereby avoiding the complications induced by renal ischemia and surgical excision .
although energy - based ablation may injure the collecting system , clinical and preclinical studies on cryoablation have demonstrated the ability of this technique to manage tumors located almost within the collecting system without compromising the integrity of the underlying structure [ 5 - 7 ] .
in addition , the laparoscopic approach allows the surgeon to position the cryoprobe by using intraoperative ultrasonography more precisely and to move adjacent organs away from the ablation site .
if the surgical and oncological outcomes support the feasibility and efficacy of laparoscopic cryoablation ( lrc ) for endophytic renal tumors , and safety can be maintained during the surgical procedure , this method may provide an alternative nephron - sparing surgery for selected patients . to determine this
, we evaluated the intermediate - term outcome of lrc in patients with endophytic rcc .
from june 2005 to may 2009 , lrc was performed on 45 renal tumors in 39 patients at our institution .
indications for lrc included the presence of a localized , solid enhancing renal mass smaller than 4 cm in a patient at high risk for partial nephrectomy or older than 70 years of age .
high operative risk in our institution was defined as an american society of anesthesiology ( asa ) physical status score of over 3 . among these inclusion criteria for lrc ,
absolute indications included bilateral tumors and a patient with a solitary kidney or renal insufficiency .
a patient with normal contralateral renal function but poor operability was defined as an elective indication .
all patients underwent a preoperative radiologic evaluation with contrast - enhanced computed tomography ( ct ) or magnetic resonance imaging ( mri ) in the case of renal insufficiency to delineate the parameters of the renal lesion , including location , size , depth , and position relative to hilar vessels and the collecting system .
all patients who underwent lrc in our institution were registered prospectively in a specific database that included all important information about tumor and patient characteristics including operative time , blood loss , hospital stay , pathology findings , and occurrence of complications .
this allowed us to collect and analyze the data of the patients retrospectively , depending on the location of the tumor and pathologic findings .
three attending urologists reviewed the preoperative imaging studies for each patient to categorize the renal mass depending on tumor position .
an endophytic location of a tumor in this study was defined as less than 40% of the lesion extending off the surface of the kidney ( fig .
1 ) , as originally described by finley et al . among all patients who underwent lrc , 15 tumors from 14 patients who were confirmed as having rcc by intraoperative needle biopsy and
patients were initially evaluated at 1 month and 3 months , then every 3 months during the first year .
follow - up evaluations involved a medical history update , physical examination , blood pressure measurement , contrast - enhanced ct or mri , chest radiography , measurement of serum electrolytes , liver function tests , and renal function tests .
a lack of enhancement on ct or mri along with stable or decreased tumor size were considered signs of successful treatment .
recurrence was defined as increasing tumor size or lack of tumor shrinkage , with image enhancement .
all lrc procedures were conducted by a single surgeon with use of nearly identical technique . for the laparoscopic procedure ,
a standard technique using three ports was performed . in general , tumors anterior to a horizontal line within the coronal plane through the renal hilum were approached transperitoneally , and tumors posterior to this line were approached retroperitoneally .
real - time intraoperative ultrasonography ( ious : aloka dynaview ii , americanlab , miami , fl , usa ) was used in all cases to identify the lesion and to determine the degree of the ice ball extension .
the kidney was mobilized and the gerota 's fascia was opened to facilitate identification of the tumor .
up to two needle biopsies were taken from the tumor before the insertion of a cryoprobe .
then 1.47 mm cryoprobes ( icerod , oncura , plymouth meeting , pa , usa ) were inserted , each of which induced a -40 isothermal lesion 14.5x34 mm in diameter and radiating from the ablation probe . before insertion into the kidney , the proper number and positions of the cryoprobes
temperature probes were then inserted into the deep margins of the tumor . in all cases ,
a double - freeze cycle was applied , with an intervening thawing process . at the base of a lesion in proximity to the collecting system ,
the extent of the ice ball was identified by ious as a complete loss of echogenic lesion in the circumferential area of the base .
hemostasis was achieved by filling the probe tract with fibrin glue ( baxter , deerfield , il ) and surgicel ( johnson & johnson , irvine , ca , usa ) after the second thaw allowed the safe removal of the cryoprobe .
all data were analyzed with the statistical package for the social sciences , version 13 ( spss inc , usa ) .
statistical comparison of pre- and postoperative values was performed with paired t - tests , with differences considered statistically significant if p<0.05 .
from june 2005 to may 2009 , lrc was performed on 45 renal tumors in 39 patients at our institution .
indications for lrc included the presence of a localized , solid enhancing renal mass smaller than 4 cm in a patient at high risk for partial nephrectomy or older than 70 years of age .
high operative risk in our institution was defined as an american society of anesthesiology ( asa ) physical status score of over 3 . among these inclusion criteria for lrc ,
absolute indications included bilateral tumors and a patient with a solitary kidney or renal insufficiency .
a patient with normal contralateral renal function but poor operability was defined as an elective indication .
all patients underwent a preoperative radiologic evaluation with contrast - enhanced computed tomography ( ct ) or magnetic resonance imaging ( mri ) in the case of renal insufficiency to delineate the parameters of the renal lesion , including location , size , depth , and position relative to hilar vessels and the collecting system .
all patients who underwent lrc in our institution were registered prospectively in a specific database that included all important information about tumor and patient characteristics including operative time , blood loss , hospital stay , pathology findings , and occurrence of complications .
this allowed us to collect and analyze the data of the patients retrospectively , depending on the location of the tumor and pathologic findings .
three attending urologists reviewed the preoperative imaging studies for each patient to categorize the renal mass depending on tumor position .
an endophytic location of a tumor in this study was defined as less than 40% of the lesion extending off the surface of the kidney ( fig .
1 ) , as originally described by finley et al . among all patients who underwent lrc , 15 tumors from 14 patients who were confirmed as having rcc by intraoperative needle biopsy and
patients were initially evaluated at 1 month and 3 months , then every 3 months during the first year .
follow - up evaluations involved a medical history update , physical examination , blood pressure measurement , contrast - enhanced ct or mri , chest radiography , measurement of serum electrolytes , liver function tests , and renal function tests .
a lack of enhancement on ct or mri along with stable or decreased tumor size were considered signs of successful treatment .
recurrence was defined as increasing tumor size or lack of tumor shrinkage , with image enhancement .
all lrc procedures were conducted by a single surgeon with use of nearly identical technique . for the laparoscopic procedure , a standard technique using three ports was performed . in general , tumors anterior to a horizontal line within the coronal plane through the renal hilum were approached transperitoneally , and tumors posterior to this line were approached retroperitoneally .
real - time intraoperative ultrasonography ( ious : aloka dynaview ii , americanlab , miami , fl , usa ) was used in all cases to identify the lesion and to determine the degree of the ice ball extension .
the kidney was mobilized and the gerota 's fascia was opened to facilitate identification of the tumor . the fat overlying the tumor was placed aside and later retrieved for pathology examination .
up to two needle biopsies were taken from the tumor before the insertion of a cryoprobe .
then 1.47 mm cryoprobes ( icerod , oncura , plymouth meeting , pa , usa ) were inserted , each of which induced a -40 isothermal lesion 14.5x34 mm in diameter and radiating from the ablation probe . before insertion into the kidney , the proper number and positions of the cryoprobes
temperature probes were then inserted into the deep margins of the tumor . in all cases ,
a double - freeze cycle was applied , with an intervening thawing process . at the base of a lesion in proximity to the collecting system ,
the extent of the ice ball was identified by ious as a complete loss of echogenic lesion in the circumferential area of the base .
hemostasis was achieved by filling the probe tract with fibrin glue ( baxter , deerfield , il ) and surgicel ( johnson & johnson , irvine , ca , usa ) after the second thaw allowed the safe removal of the cryoprobe .
all data were analyzed with the statistical package for the social sciences , version 13 ( spss inc , usa ) .
statistical comparison of pre- and postoperative values was performed with paired t - tests , with differences considered statistically significant if p<0.05 .
among 45 renal tumors treated with lrc in our institution , 17 ( 37.8% ) were defined as endophytic tumors . among them , 15 tumors from 14 patients were confirmed as rccs and were exclusively enrolled in this series .
five tumors were centrally located , which was defined as being completely surrounded by normal parenchyma , with no visual clue regarding the location of the tumor on laparoscopy .
one patient had a hilar tumor , which was defined as a tumor positioned medially within 5 mm of the renal artery or vein .
the mean ( range ) age of the 14 enrolled patients was 61.4 years ( range , 43 - 75 years ) old .
four patients ( 28.6% ) were over 70 years old , and their mean age was 72.8 years ( range , 70 - 75 years ) old with a mean asa physical status score of 2.3 ( range , 1 - 3 ) .
the mean asa physical status score of the whole patient group was 2.9 ( range , 1 - 4 ) , and 85.7% ( 12/14 ) of patients had an asa physical status score over 3 .
the indications for nephron - sparing surgery included a bilateral tumor in 2 patients , solitary kidney tumors in 3 patients , and chronic renal failure in 1 patient .
the mean tumor size was 2.8 cm ( range , 1.7 - 3.7 cm ) and the mean operating time was 169.7 minutes ( range , 110 - 220 minutes ) .
the mean time of the first freeze cycle was 7.9 minutes , and the mean of the second freeze cycle was 7.4 minutes . in the case of five central tumors , more fat tissue overlying the kidney
was removed to achieve an adequate image for monitoring the position of the cryoprobe tip . in the case of a hilar tumor ,
the major renal vessels , ureter , and renal pelvis were displaced from the ice ball with vascular loops , and rolled gauze was placed into the renal hilum . in all patients ,
multiple cryoprobes were used , and the mean number of cryoprobes needed was 3.2 ( range , 2 - 5 ) .
the mean blood loss , measured as the amount in the suction device , was 99.5 ml ( range , 40 - 150 ml ) .
no major complications , including open surgical conversion and nephrectomy due to bleeding , occurred in any patient .
the serum creatinine and hemoglobin levels checked 7 days after surgery showed no significant differences compared with preoperative levels .
the average preoperative and postoperative creatinine levels were 1.31 mg / dl and 1.43 mg / dl , respectively ( p=0.13 ) .
the average preoperative and postoperative hemoglobin levels were 13.94 g / dl and 13.21 g / dl , respectively ( p=0.57 ) .
one patient who had a previous subtotal gastrectomy for early gastric adenocarcinoma needed a postoperative transfusion due to a low preoperative baseline hemoglobin level ( 8.4 g / dl ) .
the mean hospital stay was 4.1 days ( range , 3 - 8 days ) , and during this stay , no one experienced clinical signs or symptoms of collecting system injuries , including flank pain , fever , and leukocytosis . in the pathologic examination ,
all of the patients showed common clear cell carcinoma , rcc , except for two patients with papillary type 1 .
the mean follow - up was 32.6 months ( range , 12 - 51 months ) .
follow - up imaging studies revealed no evidence of hydronephrosis , and all patients remained asymptomatic .
a 2.2 cm sized central tumor was in direct contact with the collecting system , as shown by the enhancing portion in the deep peripheral area of the cryoablated site in an initial follow - up ct taken 1 month after lrc . due to his high anesthesiologic risk from myocardial infarction , which required vascular stenting 3 times , and the anterior location of the tumor , which disturbs deployment of the probes for other minimally invasive ablative techniques including radiofrequency ablation , this patient is currently under active surveillance . follow - up images showed no increase in the enhancing lesion or distant metastasis for 24 months after the initial lrc .
except for this patient , all other patients have remained free of recurrence or metastasis as shown by the periodic radiologic workups .
the mean size of these properly treated lesions was 2.750.72 cm , 2.960.42 cm , 2.710.26 cm , 2.430.19 cm , 2.240.21 cm , 1.260.31 cm , and 1.080.34 cm before surgery , and at 1 month , 3 months , 6 months , 9 months , 12 months , and 24 months , respectively ( fig . 2 , 3 ) .
because small renal tumors emerge incidentally during imaging for various indications , questions persist about the best way to treat endophytic tumors with a minimally invasive technique .
although 3- , 5- , and 10-year - old data encourage the use of renal cryoablation , especially for tumors in peripheral locations [ 14 - 16 ] , extending these findings to endophytic tumors is still under debate . because of the proximity to the renal vasculature and the collecting system ,
the cryoablation of an intraparenchymal endophytic tumor can potentially be disturbed by natural heat sinks , including the blood and urine . actually , wright et al reported two cases of treatment failure , both in endophytic tumors ( i.e. , completely intrarenal lesions ) , among 35 lrc lesions during an 18-month follow - up . in the multivariate analysis in their study ,
in contrast to this , hurby et al reported the successful treatment by lrc in all 11 patients with tumors located within 5 mm of the renal vasculature during 11.3 months of follow - up . considering the technical difficulty of lpn in endophytic and hilar lesions , nisbet et al formulated an algorithm on the basis of published series outcomes that recommended lrc for endophytic and lpn for exophytic and mesophytic lesions .
our results provide additional evidence for the efficacy of lrc for the treatment of endophytic tumors . with intermediate - term follow - up , whereas 1 among 15 rcc lesions was managed improperly with lrc , the other lesions have remained free of recurrence or metastasis .
although we studied a small number of patients , the treatment failure rate of 6.7% in our series agrees with the positive margin rate of 1 - 7.4% in partial nephrectomy .
this result provides us with technical clues for successful ablation in cases of endophytic lesions .
we usually planned the position of the cryoprobe tip on the basis of the preoperative imaging , including ct or mri . in our series ,
the skin insertion site of each probe , the depth of insertion of the cryoprobe into the tumor in the operative filed , and the number of cryoprobes were decided on preoperatively on the basis of the shape , location , and diameter of the tumor .
the ious image is also valuable , especially in guiding the location of the cryoprobe for endophytic tumors , because laparoscopic visual cues alone do not permit precise localization of cryoprobe tips , leaving ious as the only mode of real - time imaging .
however , the image during freezing is distorted by several factors , including artifacts at the leading edge of the ice ball and inability to monitor the periphery of the mass , as noted by badger et al . in our lrc experience with endophytic tumors , the capacity of ious to monitor ice ball expansion
is limited , especially for endophytic intraparenchymal tumors , because the collecting system itself behaves as an anechoic lesion . to inflict lethal freezing injury throughout the tumor volume
while sparing normal healthy tissues , the targeted lesion should be located within the lethal area of cryoablation , and a temperature below -40 is usually required to effectively destroy malignant renal tissue .
unfortunately , no tool currently available can precisely define the three - dimensional configuration of this critical isothermal surface during cryoablation .
thus , we surmise that the use of multiple cryoprobes is more practical than focusing on the accuracy of the cryoprobe itself for conducting lrc for an endophytic lesion . hypothetically
, this approach might increase freezing efficiency by extending the coldest isothermal line , as compared with a single probe , and the distribution of the probes across the tumor might also compensate for an asymmetric tumor shape . particularly for an intraparenchymal tumor , the use of multiple cryoprobes may have the additional advantage of evading the natural heat sink effect , a barrier intrinsic in low - temperature - based ablation .
one challenge a surgeon faces in a partial nephrectomy , whether open or laparoscopic , on a patient with an endophytic renal tumor is reconstruction of the collecting system .
cryoablation averts this challenge , but not the risk of injury to the collecting system , with resultant urine leakage , particularly for endophytic and deep lesions . however , recent reports on renal cryoablation support the tolerance of the collecting system to the radiographic ice ball formed in the procedure . targeted renal pelvic cryoablation resulted in no urinary extravasations from a total of 15 lesions in a swine model . in a clinical setting
, six patients with intraparenchymal tumors who were treated by percutaneous cryoablation revealed no clinical evidence of ureteral sequelae . in a comparison of 11 lrc and 12 lpn procedures for hilar tumors that were defined
as located within 5 mm of the renal vasculature , the lrc group experienced no complications , whereas the complication rate of the lpn group was 50% , with urine leakage being the most significant complication .
similarly , in our series of 14 patients with endophytic tumors , none showed clinical or radiological evidence of collecting system injury during the minimum follow - up of 28 months .
these studies together support the safety of the cryoablative ice ball for the underlying structure of the kidney .
we still recognize several limitation of this series , including this being the experience of a single institution for a relatively small number of cases .
the noncomparative , retrospective study design may also limit the application of our findings . obviously , to establish the effectiveness of a new technique , prospective studies must be conducted to compare the new technique with conventional methods . however , it deserves notice that our patient criteria for lrc included high risk for anesthesia with severe co - morbidity or relatively old age , leaving lrc as the last surgical treatment option .
still , the application of cryoablation to renal tumors is currently in the investigational stage , despite the promising reported clinical outcomes .
therefore , although our data showed the intermediate - term oncologic efficacy of lrc , longer follow - up with larger scale series is still needed before ablative technologies can be established as a valid alternative option for the treatment of renal tumors and before their indication can be expanded to endophytic renal tumors .
in this series with an intermediate - term follow - up , lrc for small endophytic tumors showed acceptable oncological and surgical outcomes without adverse effects in the collecting system . these results also emphasize that careful preoperative design of the layout of the cryoprobes and the use of multiple cryoprobes should be given special consideration , especially in endophytic cases .
however , further studies with longer term follow - up and larger patient groups are needed to establish the position of ablative technologies in the treatment of renal tumors and to extend their application to renal tumors in endophytic locations .
 purposeto evaluate the efficacy and safety of laparoscopic renal cryoablation ( lrc ) of small endophytic renal cell carcinoma , for which surgical treatment is technically difficult.materials and methodswe enrolled patients with endophytic tumors from a prospectively collected database of 45 renal tumors in 39 patients who had undergone lrc from june 2005 to may 2009 . 
 an endophytic tumor was defined as less than 40% of the lesion extending off the surface of the kidney . 
 we evaluated surgical and oncological outcomes.resultsamong the treated tumors , 17 tumors ( 37.8% ) were defined as endophytic tumors and 15 tumors from 14 patients were confirmed as renal cell carcinoma ( rcc ) in the pathologic examination of the tissue biopsy that was conducted at the time of lrc . 
 the mean american society of anesthesiologists ( asa ) score of the whole patient group was 2.9 ( range , 1 - 4 ) , and 85.7% ( 12/14 ) of the patients had an asa physical status score over 3 . 
 the mean tumor size was 2.8 cm ( range , 1.7 - 3.7 cm ) . 
 the layout of the cryoprobe was carefully planned preoperatively on the basis of radiologic evaluation in all tumors . 
 multiple cryoprobes ( mean , 3.2 ; range , 2 - 5 ) were used . 
 no major complications , including open surgical conversion and nephrectomy due to bleeding , occurred . no patient experienced clinical symptoms of collecting system injuries . during the mean follow - up of 32.6 months ( range , 12 - 51 months ) , radiologic evidence of tumor recurrence was found in one patient ( 6.7% for rcc ) . with the exception of this patient , all other patients have remained free of recurrence or metastasis , as determined by periodic radiologic workups.conclusionsin this series of patients with intermediate - term follow - up , lrc for endophytic renal cell carcinoma showed acceptable oncological and surgical outcomes without sequelae in the collecting system . 