# Open Partial Nephrectomy in Renal Cancer:  A Feasible Gold Standard Technique in All Hospitals

Authors: J. M. Cozar; M. Tallada
Journal: Advances in Urology
 (2008)

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## Abstract

Introduction. Partial nephrectomy (PN) is playing an increasingly important role in localized renal cell carcinoma (RCC) as a true alternative to radical nephrectomy. With the greater experience and expertise of surgical teams, it has become an alternative to radical nephrectomy in young patients when the tumor diameter is 4 cm or less in almost all hospitals since cancer-specific survival outcomes are similar to those obtained with radical nephrectomy.
Materials and Methods. The authors comment on their own experience and review the literature, reporting current indications and outcomes including complications. The surgical technique of open partial nephrectomy is outlined.
Conclusions. Nowadays, open PN is the gold standard technique to treat small renal masses, and all nonablative techniques must pass the test of time to be compared to PN.  It is not ethical for patients to undergo radical surgery just because the urologists involved do not have adequate experience with PN. Patients should be involved in the final treatment decision and, when appropriate, referred to specialized centers with experience in open or laparoscopic partial nephrectomies.


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## Body

## 1. Introduction

In recent  years, the  surgical  treatment of renal cell carcinoma (RCC)
has developed towards conservative surgery of the renal parenchyma and the use
of minimally invasive techniques. The emerging conservative technique is open
partial nephrectomy (PN), which is
no longer an option reserved for patients with a single kidney or
bilateral renal tumors; it has become a viable alternative to radical
nephrectomy, and is considered the treatment of choice for selected patients
with a normal contralateral kidney [1, 2].The more frequent use of PN in renal
cancer treatment derives from a spectacular rise in the incidental diagnosis of
renal tumors in patients undergoing abdominal ultrasound or computed tomography (CT) for abdominal diseases.
This has markedly increased the detection of smaller, asymptomatic tumors than those observed when Robson proposed radical
nephrectomy as the technique of choice more than three decades ago [3].
Incidental tumors have a more favorable prognosis than clinically detected or
symptomatic tumors of a similar size and stage [4, 5].
The better health and longer life span of the general population and the
availability of radiological imaging techniques for closer screening and
follow-up programs are creating a favorable environment for the development of
conservative renal surgery. When PN is indicated, the decision to adopt an open or laparoscopic
(minimally invasive) approach depends on the benefits and risks to the patient
and the experience of the surgical team.This article
is devoted to open PN, providing an update on the indications, disease-free and disease-specific survival outcomes, benefits and risks, limitations and
technical aspects of the surgery, intra- and postoperative complications, and  post-treatment follow-up protocols. The aim is to describe the main
concepts to be considered in the decision-taking algorithm for an open PN in the treatment of RCC [6, 7].


## 2. Indications for Partial Nephrectomy

Indications can be classified as absolute, relative, or elective (Algorithm1), always basing the selection on the viability of
the technique and an optimal cancer  control [8].Algorithm 1:Indications for partial
nephrectomy.
(1) Absolute(i)
Single kidney(ii)
Bilateral renal tumor(iii)
Severe renal failure(2) Relative(i)
Abnormal contralateral kidney (nephropathy,nephrolithiasis, trauma, etc.)(ii)
Metabolic disease associated with renal failure(iii)
Genetic syndrome with tumor multifocality(e.g., VHL syndrome)(3) Elective(i)
Tumor <4 cm in young and healthy patients(ii)
Peripheral tumor(iii)
Tumor >4 cm (limit at 7 cm?)


### 2.1. Absolute Indications

Absolute indications relate to patients who would be
anatomically or functionally anephric if radical nephrectomy was performed.
They include the presence of only one kidney, synchronous bilateral renal cancer, and severe renal failure. It was proposed in the 1950’s that these patients
undergo conservative tumor excision to preserve maximum renal parenchyma and
allow the possibility of renal filtration with no need for dialysis. However, this proposal gained little acceptance among
urologists due to the high rate of complications observed after open PN. More recently, there has been a strong resurgence in the use of this technique as an
alternative to radical nephrectomy for the above-mentioned types of patients.
In the 1990’s, various studies
reported good survival outcomes and fewer complications with a conservative
approach.


### 2.2. Relative
Indications

These include conditions that might compromise the
future functioning of the contralateral kidney (without tumor), for example, moderate renal failure, nephrolithiasis, recurrent
pyelonephritis with parenchymal lesions, vesicoureteral reflux, and
congenital or acquired obstruction of the urinary tract, among others. A further relative indication would be the presence of disease
with  a potentially negative medium-term effect on renal function, for example, diabetes or hypertension. Other factors must be
taken into account in these patients, including their current age and age at onset of the disease, estimating the duration of its possible effect on renal function.


### 2.3. Elective
Indications

Partial nephrectomy has been proposed for small
peripheral renal tumors over the past few years. Being initially controversial, this indication has been supported by wide studies
showing similar outcomes to radical surgery in small (≤4 cm) renal tumors (Algorithm1). The age and general state of the patient are important in the selection
of candidates for PN, which is most beneficial for young and healthy patients. Some authors
have proposed to widen the indication for a conservative approach to include
larger tumors of up to 7 cm.
Thus, Fergany et al. at the
Cleveland Clinic reported similar five-year disease-free survival rates between
patients with tumors <4 cm and those with tumors of 4–7 cm [4].The greater longevity of the population and the
treatment of ever younger patients for incidentally detected tumors have drawn
attention to the long-term risks of renal failure or metachronous tumor
recurrence posed by PN treatment. Nevertheless, these risks should not
outweigh the benefits of this renal parenchyma-preserving surgery.


## 2.1. Absolute Indications

Absolute indications relate to patients who would be
anatomically or functionally anephric if radical nephrectomy was performed.
They include the presence of only one kidney, synchronous bilateral renal cancer, and severe renal failure. It was proposed in the 1950’s that these patients
undergo conservative tumor excision to preserve maximum renal parenchyma and
allow the possibility of renal filtration with no need for dialysis. However, this proposal gained little acceptance among
urologists due to the high rate of complications observed after open PN. More recently, there has been a strong resurgence in the use of this technique as an
alternative to radical nephrectomy for the above-mentioned types of patients.
In the 1990’s, various studies
reported good survival outcomes and fewer complications with a conservative
approach.


## 2.2. Relative
Indications

These include conditions that might compromise the
future functioning of the contralateral kidney (without tumor), for example, moderate renal failure, nephrolithiasis, recurrent
pyelonephritis with parenchymal lesions, vesicoureteral reflux, and
congenital or acquired obstruction of the urinary tract, among others. A further relative indication would be the presence of disease
with  a potentially negative medium-term effect on renal function, for example, diabetes or hypertension. Other factors must be
taken into account in these patients, including their current age and age at onset of the disease, estimating the duration of its possible effect on renal function.


## 2.3. Elective
Indications

Partial nephrectomy has been proposed for small
peripheral renal tumors over the past few years. Being initially controversial, this indication has been supported by wide studies
showing similar outcomes to radical surgery in small (≤4 cm) renal tumors (Algorithm1). The age and general state of the patient are important in the selection
of candidates for PN, which is most beneficial for young and healthy patients. Some authors
have proposed to widen the indication for a conservative approach to include
larger tumors of up to 7 cm.
Thus, Fergany et al. at the
Cleveland Clinic reported similar five-year disease-free survival rates between
patients with tumors <4 cm and those with tumors of 4–7 cm [4].The greater longevity of the population and the
treatment of ever younger patients for incidentally detected tumors have drawn
attention to the long-term risks of renal failure or metachronous tumor
recurrence posed by PN treatment. Nevertheless, these risks should not
outweigh the benefits of this renal parenchyma-preserving surgery.


## 3. Clinical Experience: Survival Outcomes

There is now considerable clinical experience in
patients with one of the above indications for PN, allowing careful analysis of patient outcomes and
evaluation of the prognostic factors that influence results.Studies of patients with small renal tumors at the
Memorial Sloan Kettering Cancer Center of UCLA, Mayo Clinic, and Cleveland Clinic
showed no significant differences in five-year survival rates (91–100%) between
those treated with open PN and those treated with
open radical nephrectomy (Figure1) [9–14]. Long-term follow-up studies have
corroborated these results. Thus, Lau et al. compared between patients treated with open PN (mean tumor size of 3.7 cm) and those treated with
radical nephrectomy (mean size of 3.3 cm), and found no significant differences
in overall survival, cancer-specific
survival, metastasis-free survival, or local recurrence-free survival at 5,
10, or 15 years [11]. These findings
validate the oncological efficacy of conservative versus radical renal surgery.Figure 1
Five-year survival: radical nephrectomy (RN) versus partial nephrectomy (PN).There have been no prospective randomized clinical
trials comparing the two techniques. Moreover, global results of the published studies cannot be grouped together because the
distribution of indication levels
(absolute, relative, or elective) is different in each study population. For this reason, outcomes of open PN are reported below in relation
to the type of indication.


### 3.1. Outcomes of Partial Nephrectomy with Absolute
Indication

In general terms, patient survival rates are lower  when the indication for surgery is absolute
rather than elective, influenced by
the higher age, the more advanced
stages, the larger tumor size, and the poorer health status of patients with an
absolute indication. Reports from the Cleveland and Mayo Clinics [4, 15] described disease-free survival rates after PN
of 81–88% at 5 years and 64–73% at 10 years, being relatively similar to disease-free survival rates described for radical
nephrectomy in tumors of the same size and stage. In 2007, Berdjis et al. studied 38 cases of open PN in
single kidney carried out between 1993 and 2003 [16]. After a mean follow-up of
41.7 months, they observed local
recurrence in four patients (including 3 with distant progression) and
metastatic progression in two. Tumor size was significantly larger in patients
with metastatic progression versus those without (6.2 cm versus 3.5 cm) and in patients with
subsequent renal failure versus those without (5.2 cm versus 3.3 cm).According to these authors, tumor size is the most significant prognostic factor for disease progression
followed by tumor stage (localized versus locally advanced), and larger tumor size is the main prognostic
factor for renal failure onset [16].


### 3.2. Results of
Partial Nephrectomy with Elective Indication

In the 1990’s,  numerous reports [5, 10, 11, 17–26] were published on a total of 572 patients
with normal contralateral kidney treated by open PN, having tumor sizes ranging from 2 to 4.3 cm (Table 1). A
survival rate of 90–100% was achieved
in these cases, with a local
recurrence rate of 0% in most series [10, 11, 18–20, 22, 23, 24, 25, 27], 1% in 2 series [5, 22], 3% in 2 series [12, 21], and 6-7% in 2 series [13, 26]. These outcomes opened up the way for open PN to become an
effective alternative to radical nephrectomy although higher rates of intra-
and postoperative complications were initially observed.Table 1
Conservative renal
surgery (partial nephrectomy);
five-year outcomes in patients with elective indication.
Author, yearNDisease-specific survivalLocal recurrenceMean tumor sizeMorgan, 199020100%0%3.1Selli, 19912090%0%3.5Provet, 199119100%0%2.6Steinbach, 19927294.4%2.7%NDMoll, 199398100%1%4Lerner, 19965492%5.6%4D'Armiento, 19971996%0%3.3Van Poppel, 19985198%0%3Herr, 19997097.5%1.5%3Hafez, 199945100%0%4Barbalias, 19994197.5%7.3%3.5Belldegrun, 199963100%3.2%4Published data establish 4 cm as the cut-off tumor size
for indication of this surgery, describing a shorter disease-free survival period in patients with larger
tumors. Studies report 95% five-year disease-free survival rates in patients
with a tumor <4 cm, comparable to the outcomes of radical nephrectomy
in tumors of a similar size (Table1).


### 3.3. Results of
Partial Nephrectomy in Patients with Von Hippel Lindau (VHL) Syndrome

The risk of local recurrence is very high in VHL patients
because of the multifocal nature of their malignant tumors; consequently their
disease-free survival is much lower in comparison to patients with incidental
or sporadic renal carcinoma.Out of nine VHL patients with bilateral renal
carcinoma studied by Novick and Campbell, seven had local recurrence and one died
from metastatic disease [2]. It is likely that most of these recurrences
represented a manifestation of a microscopic residual CCR that was not excised
during the NP [2].Walther et al.
[27] reported on 52 VHL patients with renal cancer treated at the National
Cancer Institute, finding that no
patient with tumors <3 cm developed metastatic disease. They therefore recommend waiting until this type
of tumor reaches 3 cm in order to reduce the need for surgery before onset of the multiple
recurrences observed during follow-up of these patients.The
effectiveness of PN as a valid alternative for the treatment of this disease
was demonstrated by a multicenter study in USA on the results of treating 65
patients with VHL and localized RCC (54 bilateral, 11 unilateral). PN was performed on 49 of these patients, with five-year and ten-year survival rates of 100% and 81%, respectively.  These
survival outcomes are similar to those obtained with radical nephrectomy, and they
support the role of PN in the treatment of this type of patient.In patients with advanced VHL and large multiple
bilateral tumors that require complete excision of both kidneys at first
surgery or after various interventions due to the post-PN growth of residual RCCs, renal transplant is an appropriate option to avoid
terminal kidney failure and the need for dialysis, especially in young patients with this genetic syndrome.


## 3.1. Outcomes of Partial Nephrectomy with Absolute
Indication

In general terms, patient survival rates are lower  when the indication for surgery is absolute
rather than elective, influenced by
the higher age, the more advanced
stages, the larger tumor size, and the poorer health status of patients with an
absolute indication. Reports from the Cleveland and Mayo Clinics [4, 15] described disease-free survival rates after PN
of 81–88% at 5 years and 64–73% at 10 years, being relatively similar to disease-free survival rates described for radical
nephrectomy in tumors of the same size and stage. In 2007, Berdjis et al. studied 38 cases of open PN in
single kidney carried out between 1993 and 2003 [16]. After a mean follow-up of
41.7 months, they observed local
recurrence in four patients (including 3 with distant progression) and
metastatic progression in two. Tumor size was significantly larger in patients
with metastatic progression versus those without (6.2 cm versus 3.5 cm) and in patients with
subsequent renal failure versus those without (5.2 cm versus 3.3 cm).According to these authors, tumor size is the most significant prognostic factor for disease progression
followed by tumor stage (localized versus locally advanced), and larger tumor size is the main prognostic
factor for renal failure onset [16].


## 3.2. Results of
Partial Nephrectomy with Elective Indication

In the 1990’s,  numerous reports [5, 10, 11, 17–26] were published on a total of 572 patients
with normal contralateral kidney treated by open PN, having tumor sizes ranging from 2 to 4.3 cm (Table 1). A
survival rate of 90–100% was achieved
in these cases, with a local
recurrence rate of 0% in most series [10, 11, 18–20, 22, 23, 24, 25, 27], 1% in 2 series [5, 22], 3% in 2 series [12, 21], and 6-7% in 2 series [13, 26]. These outcomes opened up the way for open PN to become an
effective alternative to radical nephrectomy although higher rates of intra-
and postoperative complications were initially observed.Table 1
Conservative renal
surgery (partial nephrectomy);
five-year outcomes in patients with elective indication.
Author, yearNDisease-specific survivalLocal recurrenceMean tumor sizeMorgan, 199020100%0%3.1Selli, 19912090%0%3.5Provet, 199119100%0%2.6Steinbach, 19927294.4%2.7%NDMoll, 199398100%1%4Lerner, 19965492%5.6%4D'Armiento, 19971996%0%3.3Van Poppel, 19985198%0%3Herr, 19997097.5%1.5%3Hafez, 199945100%0%4Barbalias, 19994197.5%7.3%3.5Belldegrun, 199963100%3.2%4Published data establish 4 cm as the cut-off tumor size
for indication of this surgery, describing a shorter disease-free survival period in patients with larger
tumors. Studies report 95% five-year disease-free survival rates in patients
with a tumor <4 cm, comparable to the outcomes of radical nephrectomy
in tumors of a similar size (Table1).


## 3.3. Results of
Partial Nephrectomy in Patients with Von Hippel Lindau (VHL) Syndrome

The risk of local recurrence is very high in VHL patients
because of the multifocal nature of their malignant tumors; consequently their
disease-free survival is much lower in comparison to patients with incidental
or sporadic renal carcinoma.Out of nine VHL patients with bilateral renal
carcinoma studied by Novick and Campbell, seven had local recurrence and one died
from metastatic disease [2]. It is likely that most of these recurrences
represented a manifestation of a microscopic residual CCR that was not excised
during the NP [2].Walther et al.
[27] reported on 52 VHL patients with renal cancer treated at the National
Cancer Institute, finding that no
patient with tumors <3 cm developed metastatic disease. They therefore recommend waiting until this type
of tumor reaches 3 cm in order to reduce the need for surgery before onset of the multiple
recurrences observed during follow-up of these patients.The
effectiveness of PN as a valid alternative for the treatment of this disease
was demonstrated by a multicenter study in USA on the results of treating 65
patients with VHL and localized RCC (54 bilateral, 11 unilateral). PN was performed on 49 of these patients, with five-year and ten-year survival rates of 100% and 81%, respectively.  These
survival outcomes are similar to those obtained with radical nephrectomy, and they
support the role of PN in the treatment of this type of patient.In patients with advanced VHL and large multiple
bilateral tumors that require complete excision of both kidneys at first
surgery or after various interventions due to the post-PN growth of residual RCCs, renal transplant is an appropriate option to avoid
terminal kidney failure and the need for dialysis, especially in young patients with this genetic syndrome.


## 4. Prognostic Factors for Tumor Recurrence after Partial Nephrectomy

In RCC, prognostic  factors for distant recurrence or metastatic progression after
radical nephrectomy are known to include the Fuhrman grade, size, and stage, as well as histological type of the tumor, the presence of positive lymph nodes, and ECOG performance status [2, 8]. Some of these factors, described below, are of special
interest in selecting candidates for PN.


### 4.1. Tumor Size >4 cm

Tumor size was found to be the most
significant predictor of the outcome in large series of PN patients [4, 11, 13, 25]. Tumor size independently predicts local recurrence and is the most important
criterion for the indication of a PN. The Cleveland Clinic series of 485 PNs, including 9% with elective indications, showed significant differences in five-year and ten-year survival rates between
patients with tumors smaller and larger than 4 cm, with a significant correlation between recurrence rate and tumor size. For this
reason, Barbalias et al. [25] proposed a
subclassification of stage T1 (tumors <7 cm and limited to renal parenchyma) into T1a
and T1b for tumor sizes of <4 cm and ≥4 cm, respectively.Lerner et al. [13] observed a 95% five-year
survival rate in PN patients with tumors <3 cm versus an 80% rate in
those with tumors >6 cm.
They also reported a significantly higher disease-free survival rate in
patients with tumors >4 cm after radical versus partial nephrectomy. More recently, various studies [9–14, 23] (Figure 2)
demonstrated equivalent cancer control rates between patients with tumors <4 cm and those with tumors of 4–7 cm after
electively indicated PN.Figure 2
Five-year disease-free survival by tumor size in patients undergoing partial nephrectomy.


### 4.2. Localization
of Tumor

It was classically thought that centrally localized
tumors carried a greater risk of metastasis at the time of disease
presentation. It was therefore considered that the risk of recurrence and/or
progression would be higher after partial versus radical nephrectomy in central
tumors. This idea was challenged by the results of a retrospective study by
D'Armiento et al. [23] on tumor localization as an independent risk factor. They
found no difference in cancer-free survival or recurrence between peripheral
tumors (not extending into the interior of the kidney) and central tumors
(infiltrating beyond the renal medulla). These authors concluded that PN is more complex in the case of central tumors,
but it is not associated with a worse recurrence or progression prognosis.


### 4.3. Multifocality

The incidence of small renal tumors
removed during radical nephrectomy for RCC or in necropsies ranges from 4 to
25% [27, 28]. As a consequence, many
urologists have argued against PN as a standard treatment for RCC, even when tumors are small, due to the high risk of multifocality. We need to know the factors that
increase the risk of multifocality to allow us to select PN when the risk of multifocality is low and radical nephrectomy when
the risk is high.The main factor signaling an increased risk of
multifocality is large tumor size, since 91% of multifocal tumors are associated with primary tumors >5 cm [29]. The second factor
is tumor stage (pT2 or higher). Thus, stage pT3a shows a 16.4% incidence of multifocality, with a mean distance between primary and secondary tumors of 26.4 mm [30]. Other factors
increasing the risk of multifocality cannot be known before surgery but only
after examination of the surgical specimen, including histological factors such as vascular infiltration and papillary or
mixed histological variants [27]. Knowledge of
factors carrying an elevated risk of multifocality alerts to the need for more
rigorous patient follow-up and inspection of the
whole defatted kidney to rule out satellite tumors during PN.With regard to the preoperative detection
of multifocal lesions by imaging techniques, only 22.9% of additional tumors subsequently observed in specimens after
radical nephrectomy had been detected by ultrasound or CT [31]. Intraoperative
ultrasound studies show a higher sensitivity, detecting up to 78% of multifocal tumors, which may be very useful when there are multifocality risk factors and a PN has
been proposed to the patient.


### 4.4. High Fuhrman Nuclear Grade and Symptomatic
Clinical Presentation

It was reported that recurrence-free survival after PN was not only significantly improved by smaller
tumor size (<4) but also by low Fuhrman grade and incidental clinical
presentation [4]. This finding was confirmed by Licht [32], who observed a significantly worse prognosis after
this surgery in symptomatic (83% five-year survival) versus incidental (94% five-year
survival) tumors.Moll et al. [5] and Ghavamian et al. [15] reported that
tumor stage and nuclear grade are significantly associated with RCC mortality.
These classic prognostic factors are valid for both radical and partial
nephrectomies, but a much more rigorous follow-up is required if partial
nephrectomy is selected and the pathology study reports grade
III disease.


### 4.5. Surgical
Margins

Conventional PN includes ≥1 cm margin of
healthy parenchyma, whereas this
margin is not left in tumor enucleation and there is a higher risk of surgical
margin involvement. Recent reports have shown similar rates of cancer control
between PN and enucleation, provided
that surgical margins in enucleation are examined by intraoperative biopsy of
the kidney bed.In a series of 44 patients treated  with PN
for tumors with a mean size of 3.2 cm and a mean surgical
margin of 2.5 mm, 93% had negative surgical margins and showed no
local recurrence after after a mean follow-up of 4 years [33]. In the Mayo
Clinic series, all partial
nephrectomies were carried out with margins ≥3 mm of healthy peritumoral renal
tissue, verified by intraoperative
biopsy of the kidney bed. Local five-year recurrence-free survival was 97% in a series of 130 patients [34].It can therefore be proposed that a margin
of 1-2 cm is not
necessary in PN, for which a few
millimeters (3–5 mm)
can be adequate as long as the intraoperative biopsy of the kidney bed is
negative.


## 4.1. Tumor Size >4 cm

Tumor size was found to be the most
significant predictor of the outcome in large series of PN patients [4, 11, 13, 25]. Tumor size independently predicts local recurrence and is the most important
criterion for the indication of a PN. The Cleveland Clinic series of 485 PNs, including 9% with elective indications, showed significant differences in five-year and ten-year survival rates between
patients with tumors smaller and larger than 4 cm, with a significant correlation between recurrence rate and tumor size. For this
reason, Barbalias et al. [25] proposed a
subclassification of stage T1 (tumors <7 cm and limited to renal parenchyma) into T1a
and T1b for tumor sizes of <4 cm and ≥4 cm, respectively.Lerner et al. [13] observed a 95% five-year
survival rate in PN patients with tumors <3 cm versus an 80% rate in
those with tumors >6 cm.
They also reported a significantly higher disease-free survival rate in
patients with tumors >4 cm after radical versus partial nephrectomy. More recently, various studies [9–14, 23] (Figure 2)
demonstrated equivalent cancer control rates between patients with tumors <4 cm and those with tumors of 4–7 cm after
electively indicated PN.Figure 2
Five-year disease-free survival by tumor size in patients undergoing partial nephrectomy.


## 4.2. Localization
of Tumor

It was classically thought that centrally localized
tumors carried a greater risk of metastasis at the time of disease
presentation. It was therefore considered that the risk of recurrence and/or
progression would be higher after partial versus radical nephrectomy in central
tumors. This idea was challenged by the results of a retrospective study by
D'Armiento et al. [23] on tumor localization as an independent risk factor. They
found no difference in cancer-free survival or recurrence between peripheral
tumors (not extending into the interior of the kidney) and central tumors
(infiltrating beyond the renal medulla). These authors concluded that PN is more complex in the case of central tumors,
but it is not associated with a worse recurrence or progression prognosis.


## 4.3. Multifocality

The incidence of small renal tumors
removed during radical nephrectomy for RCC or in necropsies ranges from 4 to
25% [27, 28]. As a consequence, many
urologists have argued against PN as a standard treatment for RCC, even when tumors are small, due to the high risk of multifocality. We need to know the factors that
increase the risk of multifocality to allow us to select PN when the risk of multifocality is low and radical nephrectomy when
the risk is high.The main factor signaling an increased risk of
multifocality is large tumor size, since 91% of multifocal tumors are associated with primary tumors >5 cm [29]. The second factor
is tumor stage (pT2 or higher). Thus, stage pT3a shows a 16.4% incidence of multifocality, with a mean distance between primary and secondary tumors of 26.4 mm [30]. Other factors
increasing the risk of multifocality cannot be known before surgery but only
after examination of the surgical specimen, including histological factors such as vascular infiltration and papillary or
mixed histological variants [27]. Knowledge of
factors carrying an elevated risk of multifocality alerts to the need for more
rigorous patient follow-up and inspection of the
whole defatted kidney to rule out satellite tumors during PN.With regard to the preoperative detection
of multifocal lesions by imaging techniques, only 22.9% of additional tumors subsequently observed in specimens after
radical nephrectomy had been detected by ultrasound or CT [31]. Intraoperative
ultrasound studies show a higher sensitivity, detecting up to 78% of multifocal tumors, which may be very useful when there are multifocality risk factors and a PN has
been proposed to the patient.


## 4.4. High Fuhrman Nuclear Grade and Symptomatic
Clinical Presentation

It was reported that recurrence-free survival after PN was not only significantly improved by smaller
tumor size (<4) but also by low Fuhrman grade and incidental clinical
presentation [4]. This finding was confirmed by Licht [32], who observed a significantly worse prognosis after
this surgery in symptomatic (83% five-year survival) versus incidental (94% five-year
survival) tumors.Moll et al. [5] and Ghavamian et al. [15] reported that
tumor stage and nuclear grade are significantly associated with RCC mortality.
These classic prognostic factors are valid for both radical and partial
nephrectomies, but a much more rigorous follow-up is required if partial
nephrectomy is selected and the pathology study reports grade
III disease.


## 4.5. Surgical
Margins

Conventional PN includes ≥1 cm margin of
healthy parenchyma, whereas this
margin is not left in tumor enucleation and there is a higher risk of surgical
margin involvement. Recent reports have shown similar rates of cancer control
between PN and enucleation, provided
that surgical margins in enucleation are examined by intraoperative biopsy of
the kidney bed.In a series of 44 patients treated  with PN
for tumors with a mean size of 3.2 cm and a mean surgical
margin of 2.5 mm, 93% had negative surgical margins and showed no
local recurrence after after a mean follow-up of 4 years [33]. In the Mayo
Clinic series, all partial
nephrectomies were carried out with margins ≥3 mm of healthy peritumoral renal
tissue, verified by intraoperative
biopsy of the kidney bed. Local five-year recurrence-free survival was 97% in a series of 130 patients [34].It can therefore be proposed that a margin
of 1-2 cm is not
necessary in PN, for which a few
millimeters (3–5 mm)
can be adequate as long as the intraoperative biopsy of the kidney bed is
negative.


## 5. Surgical Technique in Partial Nephrectomy

Surgical technique in PN has advanced over
recent years, offering improved
cancer control and anatomical-functional outcomes for the saved kidney.A flank incision approach is used, opening Gerota’s fascia and localizing the kidney and the tumor. A thorough
visual inspection is essential for adequate planning of the resection, especially if the tumor is near the hilum. It is
controversial whether renal ischemia is required for the resection. This
decision depends on the nature of the tumor and the skill of the surgeon. At
our center, where there is
considerable experience acquired over many years and excellent cancer control
and renal preservation outcomes have been obtained, the renal pedicle is identified and released, isolating
the main renal artery and vein with vessel-loops.If the tumor is small and the indication is elective, resection of the tumor then commences, allowing a safety margin of several millimeters of
healthy renal parenchyma. If there is no major bleeding as the resection
proceeds, total resection of the
tumor is completed without recourse to any type of renal ischemia. If there is
any doubt about the resection margins after removal of the tumor, an intraoperative biopsy of the bed is performed
and we proceed according to the results. Then, hemostasis of the tumor bed is started rapidly with single stitches of 4/0 vicryl at the main bleeding points using spray-coagulation on secondary vessels
with an electric scalpel, which
takes considerable time. To reduce this time, a technique modification was introduced at our centre one year ago, with the application of a fibrinogen hemostatic
patch (Tachosil, Nycomed Pharma, Austria) on the
resection surface after suturing the main bleeding vessels. This has shortened
the time for intervention and hemostasis to 15–20 minutes, and
improved the visual appearance (Figure3). We also leave the surgical bed open
after the resection, without using a
mattress stitch to draw the renal parenchyma together for better hemostasis.
The resection bed must be carefully inspected, and the opening of the urinary
passage (calyx or pelvis) must be avoided or, when necessary, repaired.Figure 3
Open partial nephrectomy for renal cell carcinoma of inferior pole satisfactory
hemostasis with application of a fibrinogen hemostatic patch (Tachosil, Nycomed
Pharma, Austria).When tumors are large but PN
is relatively or absolutely indicated, we prefer to clamp the renal artery to produce ischemia after administering
intravenous mannitol, keeping the renal vein patent to minimize the risk
of postoperative acute tubular necrosis. It may also be necessary to clamp the
renal artery in cases of central tumors that affect major vessels (e.g., arcuate arteries) or in cases of unexpected
bleeding that can only be controlled by ischemia. In these cases, it is very useful to have the renal pedicle prepared
in advance, allowing ischemia to be
produced within a few seconds and minimizing blood loss.Intraoperative ultrasonography
is not a standard procedure in our setting but can greatly assist in the
identification of other renal tumors when multifocality is suspected. Some
authors use intraoperative ultrasonography to demarcate intrarenal tumors and
to avoid damaging large vessels near the resection line or bed.Once hemostasis has been achieved, a careful examination is required to detect any
inadvertent opening of the urinary tract, thereby avoiding postoperative leaks or fistulas. If an opening is identified, it is closed using a resorbable suture. When an
opening is suspected but cannot be seen, an intrapelvic injection of methylene blue is required, leading some authors to previously insert a ureteral
stent in patients with central-located tumors. Fibrin sealants, as well as being hemostatic agents, can reinforce repair of the collecting system.
Gelfoam soaked with thrombin can be placed over the defect and then infiltrated
with Hemaseel fibrin sealant to close small defects of the urinary tract at the
level of the calyces.


## 6. Complications of Open Partial Nephrectomy

Open partial nephrectomy is more complex than radical
nephrectomy, and many authors place
limits on its use citing a higher risk of complications. Several decades ago, reports on open PN
described a greater risk of acute renal failure, urinary fistula, and hemorrhage of
the surgical bed, among other complications
[15, 22, 35, 36].The lower incidence of complications in the present
patient series can be attributed to the greater experience that urologists have
gained with this technique and the higher prevalence of incidental small
tumors. In 1994, Campbell et al. [35]
described complication rates after open PN of
37% for symptomatic tumors and of 22% for incidental tumors Table 2.Table 2
Complications after
open partial nephrectomy.
Author, year (Hospital)NAcute renal failure (%)Urinary fistula (%)Ghavamian, 2002 (Mayo
Clinic)6312.73.2Duque, 1998 (Brigham)6415.19.1Polascik, 1995 (Johns Hopkins)671.59Herr, 1994 (Memorial Sloan-KCC)4100Campbell, 1994 (Cleveland
Clinic)25912.717.3More recently, however, open
PN and radical nephrectomy have shown a similar complications’ rate, overall morbidity rate, hospital stay, blood losses, and frequency of acute renal failure [37, 38]. The
risk of acute renal failure after open PN ranges from
0 to 18% according to the series. Campbell et al. [35] reported a 13% incidence
of acute renal failure in 259 patients after open PN (for which only 10/259
patients [3.9%] had an elective indication). Risk factors for postoperative
acute renal failure were tumor size >7 cm, excision of more than half the renal parenchyma, and ischemia >60 minutes. In patients with PN, the renal parenchymal volume
loss correlates best with the renal function loss several months after surgery.
Estimates of volume loss may be useful for predicting postoperative renal
function when planning PN in patients with a solitary kidney [6, 7, 39].The risk of urinary fistula after open PN ranges from 1.8 to 21%, and is lower in patients
treated for a small incidental tumor with elective indication. Campbell et al.
[35] described an increased risk of urinary fistula in tumors >4 cm localized centrally or
near the hilum in surgery requiring reconstruction of the excretory tract.To summarize, complications of open PN appear to have been
reduced to levels found with open radical nephrectomy—thanks to the
greater experience of surgical teams with this technique. In the medium term, however, at 6–12 months, open PN patients have a significantly lower serum
creatinine level compared with laparoscopic radical nephrectomy patients [40]. This information must be explained to
patients when they are informed about the short-term and long-term risks of the
two approaches.


## 7. Follow-Up Guidelines after Open Partial Nephrectomy

Several clinical guidelines have been established for
the follow-up of patients after open PN, based on detailed analysis of reported tumor
recurrence patterns at specialized centers (e.g., Cleveland Clinic).Rates of local recurrence and metastatic
progression vary as a function of the tumor stage at surgery as follows:
T1N0M0: 0% local recurrence and 4.4% distant progression; T2N0M0: 2% and 5.3%, respectively; T3aN0M0: 8.2% and 11.5%,
respectively; T3bN0M0: 10.6% and 14.9%, respectively. Postoperative time
periods associated with a maximum incidence of local recurrence are between 6
and 24 months for T3 and T2 tumors and after 48 months for T1 tumors. Hence, the follow-up time and protocol are selected
according to the pathological stage at the time of the open PN.Novick and Campbell [2] proposed these follow-up guidelines.(1)
Patients with T1N0M0 tumors have annual anamnesis, physical examination, and serology, with no need for radiology during the first year. No
subsequent systematic diagnostic imaging studies are required due to the low
risk of  recurrence.(2)
Patients
with T2N0M0 tumors have
annual anamnesis, physical
examination, chest X-ray, and
abdominal CT scan, with abdominal
X-ray every 2 years.(3)
Patients
with T3N0M0 tumors have
anamnesis, physical examination, chest X-ray, and abdominal CT every 6 months for 3 years and then annually.In the long term, hyperfiltration can cause renal injury in these
patients, especially if there has
been >50% loss of nephrons, with
proteinuria, focal segmental
glomerulosclerosis, and progressive renal failure. Because proteinuria is
the first change in this disorder, 24-hour urine proteins should be determined annually in all patients with
suspicion of hyperfiltration due to loss of renal parenchyma.


## 8. When to Propose Open Partial Nephrectomy

Based on the
above reported data, clinical
studies (Mayo Clinic, Cleveland
Clinic, UCLA, etc.), and our own experience, we
can affirm, in common with other
authors [1, 2], that open PN is now the gold standard treatment for young and healthy patients
with incidentally detected small renal tumors (<4 cm). It also represents an
alternative to radical nephrectomy in single-kidney patients or those with
bilateral tumors.The presence of renal
failure, diseases that predispose
towards renal failure, or genetic syndromes associated with multifocality also shows
indications for open PN versus radical
nephrectomy since, in small tumors, there are no differences in disease-free survival, morbidity, or complication rates between the techniques.The current standard
surgical technique for partial nephrectomy is open partial nephrectomy. Only
certain highly specialized centers have gained sufficient experience with laparoscopic PN to minimize its risks and complications [40].
It remains a challenging technique, requiring a longer period of warm renal ischemia, vein closure, and the difficult
suturing of open vessels during tumor resection. In fact, the laparoscopic approach has been associated with a higher rate of
complications, even in the best
hands. Thus, Sharma et al. reported
intra- and postoperative complication rates of 5% and 11%, respectively, using laparoscopic PN, compared with 0% and 2%, respectively, using open PN [39].Although no
studies have been published to date on the long-term oncological effectiveness
of laparoscopic PN [1], preliminary data indicate that it does not differ from that
obtained with the open approach. In 2007, Gill et al. [41] reported three-year
cancer-specific survival rates of 99.3% in 771 patients treated with
laparoscopic partial nephrectomy and 99.2% in 1028 patients treated with open
partial nephrectomy. The same study confirmed a shorter surgery time (P < .0001),
hospital stay (P < .0001), and a lower blood loss (P < .0001)
with laparoscopic partial nephrectomy versus open partial nephrectomy, while intraoperative complication rates were
similar. Disadvantages of laparoscopic versus open partial nephrectomy were the
significantly longer ischemia time (P < .0001) and the more frequent
postoperative complications, especially urological disorders (P < .0001).Importantly, the laparoscopic approach is associated with a
reduction in postoperative pain and a shorter recovery period, posing surgeons and patients with a difficult
decision between open and laparoscopic partial nephrectomies for a small
incidentally detected renal tumor.Renal laparoscopy will
continue to develop, and urologists
will gain greater experience with the technique over time. Thus, outcomes published by Gill et al. in 2007 were superior
to those obtained by the same author in 2003 [41, 42]. It should be taken into
account that the study by Gill et al. comparing laparoscopic nephrectomy with open
partial nephrectomy [41, 43] was not a randomized clinical trial. In fact, most of the tumors selected for open partial
nephrectomy were >4 cm, and all of them were centrally localized single
tumors (size up to 7 cm)
with a malignant histology. These cases are technically more challenging and
carry a higher oncological risk, representing an important selection bias. There is a need for a randomized
clinical trial to be undertaken to assess the risks and benefits of each
approach. Nevertheless, there is an
evident trend towards a minimally invasive approach
to renal tumor treatment, and we can
expect laparoscopic PN to develop in the near future to a point where it can
replace open PN as a standard treatment for localized renal tumors.At our center, we have treated 35 patients by conservative
surgery of the renal parenchyma over the past 14 years (1993–2007), using open PN in 7 and
enucleation  in 28, with biopsies of
the renal bed when involvement of the surgical margin was suspected.
Indications were elective in 16 cases (45.5%), absolute in 11 (31.5%), and relative
in 8 (23%). Mean size of tumors was 3.6 cm (range of 1–9 cm), with peripheral localization in 22 patients (63%), mesorenal in 12 (34%), and multifocal (6 tumors) in 1 patient (3%). Applying  the technique described above in Section5, we have had no
intraoperative complications. Postoperative complications were renocutaneous
fistula (resolved by internal derivation
via ureteral catheter) and acute tubular necrosis (renal function
recovered after hemodialysis) in the same single-kidney patient. After a median
follow-up time of 69 months, we have
observed one local recurrence (3%), which was from enucleation and was
excised. Three patients died due to other causes and three were lost to the
follow-up after moving from the area. All followed-up patients are disease-free
and have creatinine levels similar to preoperative values.Based on this experience, our group considers conservative renal surgery to be an alternative to radical
surgery in tumors <4 cm or in larger tumors in single-kidney patients. Our selection of partial
nephrectomy or enucleation is based on tumor localization and size. Thus, we prefer enucleation in tumors in mesorenal
location because of its lower comorbidity versus PN. Our approach to peripheral
tumors depends on their size. We use enucleation for small tumors of 1–3 cm, but we
prefer partial nephrectomy for tumors ≥4 cm or when there is any suspicion of positive
margins.


## 9. Conclusions

Open PN has been
shown to be a safe and effective surgical technique in patients with a
localized renal tumor, including
patients with a normal contralateral kidney. We have gained experience with
this technique by applying it to patients with an absolute indication, and we are now increasingly able to recommend it
to patients with an elective indication, based on its good oncological outcomes and lower morbidity rates versus radical
nephrectomy. Moreover, the preservation of nephrons achieved with open partial nephrectomy reduces the
long-term risk of renal failure in these patients. These benefits outweigh any problems caused by the follow-up required
for these patients due to fears of local recurrence, which will undoubtedly be more effectively detected at an earlier stage with
new three-dimensional imaging techniques.Nowadays, open PN is the gold standard technique to treat small renal masses, and all nonablative techniques must
pass the test of time to be considered equally effective.It is not ethical for
patients to undergo radical surgery just because urologists involved do not
have adequate experience with PN or have concerns about their capacity to
manage its possible complications. Patients must be clearly informed about the
possibility of laparoscopic PN in specialized centers. Patients
should be involved in the final treatment decision and, when appropriate, referred to centers
with experience in open or laparoscopic partial nephrectomies.



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*Source: 916463-2008-08-26.xml*