Safety and Efficacy of Sutureless Zero Ischemia Laparoscopic Tumor Enucleation for T1 Stage Renal Carcinoma
Conditions: Carcinoma, Renal Cell, Kidney Neoplasms
Sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine

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Safety and efficiency of 
laparoscopic unassisted 
zero-ischemia enucleation for stage 
T1 renal carcinoma 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DATE：February 10, 2023 

                                                                  Version Date：February 10, 2023                    
 
1. Research Background 
Renal cell carcinoma(RCC) is a common tumor of the urinary 
system, accounting for 4.1% of all malignant tumors. 1 According to the 
latest GLOBOCAN data, in 2021, there are 71,676 new cases and 
15,259 deaths of kidney cancer in the United States and 77,410 new 
cases and 46,345 deaths in China. The incidence of kidney cancer in 
China has increased at an average annual rate of 6.5% over the past 20 
years and has surpassed bladder cancer in the number of deaths related 
to urological tumors, ranking first. Since renal ultrasound is a routine 
medical examination for people over 40 years old in China, most of the 
patients are in the early stage of limited renal cancer when they are 
diagnosed.  
In the current guidelines, nephron sparing surgery(NSS) is the 
preferred treatment for early-stage limited kidney cancer. NSS includes 
partial nephrectomy(PN) and tumor enucleation(TE). Unlike PN, TE is a 
surgical procedure that bluntly separates the tumor along the natural 
cutting plane between the pseudocapsule and healthy parenchyma, 
completely removing the tumor tissue while maximizing the preservation 
of normal kidney tissue. However, most surgeons currently perform 
partial nephrectomy. The reason for this phenomenon is first, the 
problem of concept. most surgeons doubt whether TE can clean up 
tumor tissue. on the other hand, enucleation requires surgeons to have a 
better understanding of the anatomical relationship around the tumor 
and accurately separate the tumor envelope and normal kidney tissue, 
and its surgical difficulty is higher than that of traditional PN.  
Our team has conducted a clinical meta-analysis on these two 
procedures, and the results showed that TE has the advantages of less 
trauma, faster postoperative recovery, and better protection of renal 
function than PN, without increasing the risk of tumor recurrence.  

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Minervini et al. analyzed the pseudocapsule integrity of 304 specimens 
after TE, founding that 51% of the specimens had an intact 
pseudocapsule 
and 
49% 
had 
infiltrating 
tumor 
cells 
on 
the 
pseudocapsule. but all specimens had negative cut margins and there is 
no statistical difference in 5-year progression-free survival. thus they 
concluded that enucleation for renal cancer is a safe surgical procedure. 
In the past 10 years, our team has performed more than 500 kidney 
cancer enucleations without any positive margins and no patient has 
experienced in local recurrence. In addition, traditional PN requires 
temporary blockage of the renal artery to achieve a relatively bloodless 
operating environment to ensure the safety of tumor removal. But 
prolonged warm ischemia is bound to affect the function of normal 
kidney tissue. Therefore reducing thermal ischemia time up to zero 
ischemia time has become a quest for surgeons. The combination of 
zero-ischemia technique on the basis of kidney cancer enucleation is a 
field that has rarely been touched. 
Therefore reducing thermal ischemia time up to zero ischemia time 
has become a quest for surgeons. Clinically, the combination of 
zero-ischemia technique on the basis of kidney cancer enucleation is a 
field that has rarely been touched. In the last 3 years, our team has 
performed nearly 100 cases of zero-ischemic renal tumor enucleation, 
and this procedure can maximize the protection of renal parenchyma 
and renal function under the premise of ensuring tumor safety. In 
conclusion, if zero ischemia enucleation can be applied and popularized 
to limited renal cancer surgery, it will benefit a large number of patients 
and improve the prognosis. 
 
 
 

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2. Research objectives  
    Main objective: the efficacy (rate of change in renal function GFR, 
overall survival OS, tumor-free survival TFS, progression-free survival 
PFS, etc.) and safety (positive incision margin rate, intraoperative blood 
loss, postoperative complication rate, etc.) of unassisted zero-ischemia 
enucleation in the surgical treatment of patients with early stage (T1) 
renal cancer. 
Secondary 
objectives: 
differences 
between 
unassisted 
zero 
ischemic enucleation of renal cancer and partial nephrectomy with 
clamping of the hilum in the surgical management of patients with renal 
cancer and the role of the modified ABC score in the assessment of 
renal cancer. 
 
 
3.Study content and design 
    This study aims to evaluate the effectiveness and safety of the 
surgery by using renal cancer patients who met the inclusion criteria.  
Summarizing the preoperative, perioperative, and postoperative data, 
and 
evaluating 
the 
operative 
time, 
intraoperative 
bleeding, 
postoperative hospitalization days, postoperative complication rate, 
postoperative short-term, intermediate, and long-term renal function 
indexes, overall survival, tumor-free survival, progression-free survival 
and postoperative renal cancer recurrence rate of the patients. 
Statistical software is used to describe the characteristics of patient 
data. T-test, rank sum test, multi-factor regression, and cox regression 
are used to investigate the effects of each factor on the treatment 
outcome and prognosis of patients undergoing zero-ischemic renal 
enucleation, to describe whether there are differences in the safety and 
efficacy of zero ischemic renal enucleation compared with traditional 

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partial nephrectomy for the treatment of stage T1 renal carcinoma. 
This study used a retrospective research trial design to include 73 
patients who underwent zero-ischemic enucleation and 73 patients who 
underwent traditional partial nephrectomy from 2014 to 2022, for a total 
of 146 patients. The formula for calculating the sample size is as follows. 
 
 
Figure 1. Estimated sample size calculation 
 
note：Zα、Zβare the quartiles under standard normal distribution. 
p1: Expected morbidity in the exposed group. 
p0: Expected incidence in the control group. 
q1: q1=1- p1. 
q0: q0=1- p0. 
 
 
4.Study population  
4.1 Inclusion criteria 
1. The age is between 18 and 80 years old. 
2. Stage T1a or T1b according to the 8th edition of the AJCC  
TNM staging of kidney cancer, 2017.  
3.The patients who underwent PN or TE between 2014 and 2022. 
 
4.2 Exclusion criteria 
1. With severe active infection or serious cardiac, hepatic, renal 
and hematopoietic diseases; and other physical conditions that make 
them unsuitable for the test in question (as judged by the 
investigator). 
2. The patient has no measurable or evaluable lesions. 
3. The tumor is close to the collecting system, touching the renal 
artery or renal vein, and other anatomical conditions that are not 

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suitable for nephrectomy. 
4.History 
of 
organ 
transplantation 
or 
need 
for 
long-term 
adrenocorticotropic hormone therapy; hypothyroidism, adrenal or 
pituitary function that cannot be controlled with hormone replacement 
therapy alone, type I diabetes, psoriasis or vitiligo requiring systemic 
treatment, etc.  
5. The presence of active infection requiring systemic therapy. The 
presence of human immunodeficiency virus (HIV) infection (known to 
be HIV antibody positive). The presence of active HBV or HCV 
infection (HBsAg positive individuals, or HBcAb positive but HBsAg 
negative individuals who require additional DNA quantification and 
whose results do not exceed the upper limit of normal values in the 
study center laboratory can participate in this study. Previous HCV 
infected patients with negative HCV RNA test results during the 
screening period can participate in this study).   
6. Have a history of kidney surgery or any inflammatory kidney 
surgery, have kidney cancer associated with the urinary collection 
system, and have other kidney diseases (including kidney stones and 
glomerulonephritis). 
 
5. Experimental program  
5.1 The patients are screened according to the inclusion and 
exclusion criteria. Then the patients are divided into two groups 
according to whether they underwent zero-ischemic  
enucleation 
or 
partial 
nephrectomy, 
with 
the 
zero-ischemic 
enucleation group as the test group and the partial nephrectomy 
group 
as 
the 
control 
group. 
Describing 
the 
preoperative 
conditions(age, sex, Anatomy of tumor, RENAL score, ABC score, 
preoperative renal function), the perioperative conditions(operation 
time, 
intraoperative 
bleeding, 
perioperative 
complications, 
negative/positive specimen margins, postoperative renal function 
changes, postoperative hospitalization days), and the postoperative 
condition(follow-up renal function, tumor recurrence rate, overall 
survival, tumor-free survival, progression-free survival).  
5.2 The data of the two groups are corrected for baseline and 
screened so that there is no statistical difference in the number of 
patients, gender age, tumor anatomy, renal function and other 
preoperative conditions between the two groups (t-test/rank sum test 
p > 0.05).  
5.3 The zero ischemic renal enucleation group is grouped 
according to RENAL score, ABC score and other scoring criteria.  
Different preoperative tumor score groupings are used as exposure 

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factors, and the percentage decrease of postoperative renal function 
compared with preoperative, perioperative complication rate and 
postoperative survival rate are used as outcome variables to analyze 
the 
association 
between 
exposure 
factors 
and 
outcome, 
to 
investigate the association of different factors on the surgical 
outcome of zero ischemic renal enucleation.  
5.4 Using zero-ischemic nephrectomy or partial nephrectomy with 
clamping of the renal hilum as the exposure factor. T-test/rank sum 
test and one-way regression are used to compare the efficacy 
indexes such as negative/positive tumor margins, postoperative and 
follow-up renal function, survival rate, and safety indexes such as 
perioperative complication rate and intraoperative bleeding between 
the two groups to investigate whether there is a statistical difference 
in their treatment safety and efficacy. Then we investigated whether 
there are statistical differences and correlations between the safety 
and efficacy of the treatment, and whether there are statistical 
differences in survival outcomes between the two groups by 
multifactorial cox regression. 
 
 
 
 
 
Figure 2. Experimental flow 
 
6. Data management and statistical analysis  
6.1 Statistical Software 
Data statistics are processed by biostatisticians using the 
statistical software SPSS 20.0. 
6.2 Data description 
The measurement data are described as mean standard 
Comparison of 
test group and 
control group 
Describe the 
data of 
subjects 
 
Baseline 
correction 
Intra-group 
comparison of 
test group 

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deviation (x 士s), median, maximum, minimum, and quartiles, and the 
count data are expressed as percentages (%). 
6.3 Statistics 
Data entry: Enter the age, gender, kidney cancer stage and 
prognosis follow-up of the subjects.  
Data management: The data are presented by number, and all 
personnel except the initial data entry personnel do not have access 
to the subjects' initial information (including subjects' personal 
information such as subjects' names, addresses, occupations and 
other sensitive information). There is no direct contact between the 
data entry personnel and the subjects, and all privacy of the subjects 
is protected from disclosure.  
All hypothesis tests are two-sided, and differences are 
considered statistically significant at P < 0.05. Baseline data are 
evaluated for comparability between groups, and two-tailed statistical 
tests are performed at the a=5% level. The chi-square test or Fisher's 
exact probability method is used for comparison between groups for 
count 
data, 
the 
t-test 
for 
comparison 
between 
groups 
for 
measurement data, and the rank sum test for comparison between 
groups for nonparametric variables.  
 
7. Informed consent  
Previous case information is used for this study and a  
waiver of informed consent is requested.