Case Report
Factors Associated with Peritumoral Adhesions during Nephrectomy after Renal Mass Biopsy
Kyo Chul Koo, Won Sik Jang, Dong Hyuk Kang and Won Sik Ham*
Department of Urology, Yonsei University College of Medicine, Korea
*Corresponding author: Won Sik Ham, Departments of Urology and Urological Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Korea
Published: 19 Oct, 2016
Cite this article as: Koo KC, Jang WS, Kang DH, Ham WS.
Factors Associated with Peritumoral
Adhesions during Nephrectomy after
Renal Mass Biopsy. Clin Oncol. 2016;
1: 1117.
Abstract
Objectives: To analyze factors associated with peritumoral adhesions (PTAs) during nephrectomy
performed after Renal Mass Biopsy (RMB).
Methods: From January 2009 to September 2013, 80 patients underwent Radical Nephrectomy (RN)
or Partial Nephrectomy (PN) following RMB for renal masses that were ambiguous for malignancy
on preoperative computed tomography imaging. Patients whose final pathology revealed urothelial
carcinoma were excluded. PTAs were prospectively categorized as grade I (from no to moderate)
and II (severe) by the operating surgeon immediately after surgery. Multivariate logistic regression
analysis was performed to analyze factors associated with PTA.
Results: Among the 80 patients, 60 (75%) were diagnosed as renal cell carcinoma (RCC) and 20
(25%) as benign tumors. The benign tumors included 10 (12.5%) angiomyolipomas, 5 (6.3%)
oncocytomas, and 5 (6.3%) leiomyomas. Patients with grade II PTAs had a higher estimated blood
loss. There was no conversion to RN in 30 patients treated by PN for RCC; however, of the 20 patients
with benign tumors, 10 (50.0%) underwent unplanned conversion to RN. Among the 10 patients
who underwent PN for benign tumors, 5 (50.0%) experienced postoperative pseudoaneurysms.
Multivariate analysis revealed a younger age (p=0.039), higher Body Mass Index (BMI) (p=0.013),
benign pathology (p=0.001), and more numbers of biopsy cores (p=0.045) as independent predictors
for grade II PTAs.
Conclusions: Compared to patients with RCC, younger patients with benign renal tumors were
more likely to have severe PTAs during nephrectomy following RMB, especially those with a high
BMI. Therefore, surgical treatment should be carefully planned for these patients.
Keywords: Biopsy; Needle; Nephrectomy; Tissue adhesions
Introduction
Thin-slice renal Computed Tomography (CT) remains the single most important radiographic
tool for delineating the nature of a renal mass. However, in 10-20% of solid renal masses, CT
findings are indeterminate, and pathological ambiguity intensifies, especially for small renal masses
[1,2]. To predict the nature of these pathologically ambiguous masses, a Renal Mass Biopsy (RMB)
can be performed to identify candidates for extirpative treatment.
Historically, RMB has been reserved for a limited number of indications, such as clinical findings
suggestive of renal abscess, lymphoma, or metastatic carcinoma to the kidney [3]. Furthermore,
RMB has been primarily reserved for patients with disseminated metastases or unresectable
masses because of concerns of false-negatives, complications, and risk of tract seeding. However,
contemporary series have shown that RMB is indeed a safe and accurate diagnostic technique, with
a 94% overall accuracy and a minor complication rate of less than 5% (with subclinical bleeding
being the most common complication) [4]. In accordance with evidence that it is a safe procedure
with minimal complications, the role of RMB has expanded, and more nephrectomies are now
being performed following RMB [5,6]. However, the presence of unexpected peritumoral adhesions
(PTAs) during nephrectomy after RMB is a comorbid condition that has not been accounted for
in contemporary studies, although PTAs are known to be a potential risk factor for perioperative
morbidity.
Adhesions commonly occur following invasive procedures and pose a tremendous burden on
the subsequent surgical therapy. In prostate cancer, several reports have noted the relationship
between prostate biopsy and radical prostatectomy [7-12]. However, there is a paucity of literature
regarding the incidence and the severity of PTAs following RMB
and their impact on the subsequent renal surgery. Indeed, PTAs
may lead to significant surgical morbidity, especially in the setting of
Partial Nephrectomy (PN). To the best of our knowledge, our study
represents the first to analyze the factors associated with PTAs in
patients who have undergone RMB prior to nephrectomy.
Table 1
Methods
Patients
We retrospectively reviewed a prospective database of 80 patients
who underwent Radical Nephrectomy (RN) or PN between January
2009 and September 2013 following RMB for renal masses that were
ambiguous for malignancy on preoperative CT imaging. Patients
whose final pathology revealed urothelial carcinoma were excluded
from the study because of disparities in the approach and extent of
the surgical field compared to nephrectomy. Patients with previous
intra-abdominal or renal surgery or known intra-abdominal or
urinary tract infection were excluded.
Ultrasonography-guided percutaneous RMB was performed by a
single uro-radiologist using an 18-gauge core biopsy needle according
to the previously reported method [13]. The number of RMB cores
was determined by the uro-radiologist, depending on the size and
location of the tumor.
Patients diagnosed with Renal Cell Carcinoma (RCC) according
to the results of the RMB underwent RN or PN by either open or
laparoscopic methods, based on the discretion of the surgeon (YDC,
WSH). For patients diagnosed with benign tumors by RMB, in whom
surgery was indicated for persistent pain, hematuria, or patients’
desire, PN via an open or laparoscopic approach was recommended.
Clinicopathological data were collected, including the patients’
age, Body Mass Index (BMI), and sex, and the surgical pathology. Data
regarding the number of biopsy cores and the time interval between
RMB and surgery were also collected. Postoperative complications
were classified according to the Clavien-Dindo surgical complications
classification [14]. The study was carried out in lieu of a formal ethics
committee, followed by the principles of the Helsinki Declaration.
CT data interpretation
Preoperative CT images obtained using a 64-slice detector
(Sensation 64, Siemens, Erlangen, Germany) were retrospectively
reviewed by a single uro-radiologist who was blinded to the surgical
and pathological outcomes. The tumors were classified according
to the RENAL nephrometry score based on axial and coronal
reconstructed images [15].
Classification of adhesions
PTAs were prospectively identified and graded by each
surgeon immediately after surgery. The surgeon was blinded to any
confirmatory pathological results. The degree of PTA was classified
according to the scoring system of Evans, et al. [16]. This system uses
the following criteria: 0=no adhesions, 1=filmy adhesions separating
spontaneously, 2=firm adhesions separated by traction, and 3=dense
adhesions requiring sharp dissection. For statistical analysis, degrees
0 to 2 were classified as grade I, and degree 3 as grade II.
Statistical analysis
Baseline characteristics of patients and tumors were compared
according to the severity of PTA using descriptive statistics. The
Mann-Whitney U-test and the Fisher’s exact test were used to compare
continuous and categorical variables, respectively. Univariate and
multivariate logistic regression analysis was performed to analyze
the factors predicting grade II PTA: age, BMI, RENAL nephrometry
score, number of biopsy cores, time interval between biopsy and
nephrectomy, and tumor pathology (which was dichotomized
as benign or malignant). All tests were two-sided, with statistical
significance set at p <0.05. The statistical analyses were performed
using SPSS version 20 (SPSS Inc., Chicago, IL, USA).
Table 2
Table 3
Table 3
Univariate and multivariate regression analyses of prognostic factors of grade II peritumoral adhesions.
Results
Among the 80 patients, 60 (75%) were diagnosed with RCC
and 20 (25%) were diagnosed with benign tumors. The benign
tumors including the following: 10 (50.0%) angiomyolipoma
(AML), 5 (25.0%) oncocytoma, and 5 (25.0%) leiomyoma. Patients’
characteristics according to the severity of PTA are presented in
Table 1. Patients with grade II adhesions were younger (p=0.001) and
had a higher BMI (p=0.015) than those with grade I adhesions. All
patients with grade II adhesions underwent open surgery (p=0.001).
However, patients with grade I and II adhesions had similar tumor size
(p=0.346), RENAL nephrometry scores (p=0.512), and time interval
since RMB (p=0.148). Patients diagnosed with RCC underwent
nephrectomy according to the surgeon’s discretion (RN, 30 patients;
PN, 30 patients), among which 5 (8.3%) patients exhibited grade II
adhesions. Patients with RCCs had less severe adhesions than those
with benign tumors, especially oncocytomas or AMLs (p <0.001).
Perioperative outcomes according to the severity of PTAs are
presented in Table 2. The presence of grade II adhesions was associated
with higher Estimated Blood Loss (EBL) (p <0.001); however, the
operative time was comparable for those with grade I and II PTAs,
possibly due to a higher rate of open surgery performed for patients
who had grade II PTAs. In patients treated by PN for RCC, none
required conversion to RN. By contrast, among the 20 patients with
benign tumors diagnosed by RMB in whom PN was planned for
persistent pain, hematuria, or patients’ desire, 10 (50.0%) underwent
unplanned conversion to RN. The conversion to RN rates of patients
with benign tumors did not differ between the grade I and II PTA
groups. All five patients with grade I PTAs who required conversion
to RN underwent surgery via a laparoscopic approach. Conversion to
RN was required for the five patients with grade II PTAs, even though
all patients underwent surgery via an open approach. Although there
were no grade IV and V Clavien-Dindo complications in any patients,
5 of the 10 patients who underwent PN for benign tumors experienced
grade IIIa complications; postoperative pseudo aneurysms.
When we analyzed the factors predicting grade II PTAs during
nephrectomy after RMB (Table 3), younger age (p=0.002), higher
BMI (p=0.018), and benign pathology (p <0.001) were significant
predictors for grade II adhesions on univariate analysis. Younger
age (p=0.039), higher BMI (p=0.001), benign pathology (p <0.001),
and more numbers of biopsy cores were significant predictors on
multivariate analysis.
Discussion
An adhesion occurs when two tissues that normally move freely
past each other are attached via a fibrous bridge [17]. Although the
exact mechanism that shifts the normal healing process after renal
injury to PTA formation remains unclear, the fibrinolytic system,
extracellular matrix deposition and remodeling, and inflammation
are generally accepted interrelated processes that are involved in the
subsequent transition of persistent fibrinoid adhesions to permanent
fibrous tissue [18,19]. The presence of adhesions during surgery due
to previous violation of the tissue, such as during needle biopsy,
may result in a longer operative time and increased complications,
both immediately and for up to 10 years [20]. Therefore, predicting
their presence and degree may considerably aid urological surgeons
in selecting the appropriate surgical plane and modality, and in
counseling patients about the potential risks of surgery.
For prostate cancer, essentially all prostatectomies are performed
after a confirmative prostate biopsy. Therefore, numerous reports
exist regarding the effect of preoperative prostate biopsies on
perioperative outcomes [7-12]. However, preoperative RMB has only
recently increased in frequency, as a consequence of the exponential
increase in the incidence of small renal masses, recognition of the
heterogeneity of the biological aggressiveness of renal masses, and
awareness of the improved accuracy and safety profile of RMB
[2,4,6]. There have heretofore been no reports regarding PTAs and
perioperative outcomes of nephrectomy after RMB. In our study,
we sought to evaluate the preoperative factors predicting PTA
during nephrectomy after RMB using our prospective database of 80
consecutive patients who underwent RN or PN after RMB for renal
masses that were ambiguous for malignancy.
As predicted, patients with grade II PTAs had a higher EBL. These
patients were also expected to have longer operative times; however,
all underwent open surgery, unlike those patients with grade I PTAs
whose surgery was performed via either the open or laparoscopic
approach. This observation may account for the comparable operative
times between the grade I and II PTA groups. Moreover, there was no
difference in the rate of conversion to RN for benign tumors between
the two groups. Therefore, considering that patients with grade
II PTAs were performed by the open approach, we presume that a
subset of patients with grade I PTAs may have avoided conversion to
RN if a laparoscopic approach had not been performed.
In contrast to our expectations, the RENAL nephrometry score,
and time interval from biopsy were not significant predictors for
grade II PTAs. Rather, patients with grade II adhesions were younger
and had a higher BMI than those with grade I adhesions. Moreover,
malignant tumors were associated with less severe adhesions than
benign tumors, especially oncocytomas and AMLs. On multivariate
analysis, a younger age, higher BMI, the presence of benign tumors,
and more numbers of biopsy cores were significant predictors for
grade II PTAs. Considering that hemorrhage and extension into
perirenal fat may occur in up to one third of renal oncocytomas
[21], and that AML is the most common renal tumor associated
with spontaneous peritumoral hemorrhage [22], it can be assumed
that PTAs may intensify with RMB by worsening of peritumoral
hemorrhage. To date, the explanation for the correlation between
young age, high BMI and PTA is less clear. However, it has been
reported that adhesion formation is a normal part of wound healing,
with a number of factors then differentiating between resolution and
pathological adhesion formation and should be considered as highly
cellular, vascularized and dynamic structures under the influence
of complex signalling pathways.(new references 1, 2 add) And it is
known that the perirenal fat can be firmly attached to the kidney in
patients with metabolic syndrome (new reference 3 add) like our
result that BMI was found to be a significant independent predictor
of the severity of adhesions. Therefore, younger patients with high
BMI may have rapid wound healing, but pathological adhesion
formation compared to older patients with normal BMI. Moreover, it
is possible that a narrower surgical field in patients with higher BMI
may have increased the difficulty of surgery and thereby influenced
the surgeon’s subjective assessment of PTA severity.
We acknowledge several limitations to our findings. First, our
data were retrospectively collected from surgery performed by
two surgeons, thus the results are prone to selection bias. Second,
although the adhesion scores were evaluated by surgeons blinded
to the pathological results, adhesion scoring systems are prone to
subjectivity and inter-observer variation. Moreover, the final results
may differ depending on the types of adhesion scoring system and
the surgical approach used. To ensure consistency in the assessment
and avoid bias, it would have been better to have one single surgeon
assess and grade the severity of adhesions on video-recorded
procedures. Third, as mentioned earlier, there can be correlation
between firm perirenal fat attachment and metabolic syndrome.
Therefore, although the information on the concomitant presence of
hypertension and diabetes mellitus should be also accounted for in
the analysis, unfortunately, our prospective database did not include
these in formations.
Our study showed that PTAs following RMB in patients diagnosed
with RCC were generally not severe, irrespective of the patient or
tumor characteristics. By contrast, younger patients diagnosed
with oncocytoma or AML were frequently noted to have severe
PTAs, especially those patients with a high BMI. Therefore, surgical
treatment should be carefully planned in patients with benign mass
characteristics who undergo nephrectomy after RMB.
References
- Heuer R, Gill IS, Guazzoni G, Kirkali Z, Marberger M, Richie JP, et al. A critical analysis of the actual role of minimally invasive surgery and active surveillance for kidney cancer. Eur Urol. 2010; 57: 223-232.
- Vasudevan A, Davies RJ, Shannon BA, Cohen RJ. Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy. BJU Int. 2006; 97: 946-949.
- Sahni VA, Silverman SG. Biopsy of renal masses: when and why. Cancer Imaging. 2009; 6: 44-55.
- Schmidbauer J, Remzi M, Memarsadeghi M, Haitel A, Klingler HC, Katzenbeisser D, et al. Diagnostic accuracy of computed tomography-guided percutaneous biopsy of renal masses. Eur Urol. 2008; 53: 1003-1011.
- Londoño DC, Wuerstle MC, Thomas AA, Salazar LE, Hsu JW, Danial T, et al. Accuracy and implications of percutaneous renal biopsy in the management of renal masses. Perm J. 2013; 17: 4-7.
- Ordon M, Landman J. Renal mass biopsy: "just do it". J. Urol. 2013; 190: 1638-1640.
- Choi H, Ko YH, Kang SG, Park HS, Cheon J, Patel VR. Biopsy related prostate status does not affect on the clinicopathological outcome of robotic assisted laparoscopic radical prostatectomy. Cancer Res Treat. 2009; 41: 205-210.
- Lee DK, Allareddy V, O'Donnell MA, Williams RD, Konety BR. Does the interval between prostate biopsy and radical prostatectomy affect the immediate postoperative outcome? BJU Int. 2006; 97: 48-50.
- Martin GL, Nunez RN, Humphreys MD, Martin AD, Ferrigni RG, Andrews PE, et al. Interval from prostate biopsy to robot-assisted radical prostatectomy: effects on perioperative outcomes. BJU Int. 2009; 104: 1734-1737.
- Kim IS, Na W, Nam JS. Interval from Prostate Biopsy to Robot-Assisted Laparoscopic Radical Prostatectomy (RALP): Effects on Surgical Difficulties. Korean J Urol. 2011; 52: 664-668.
- Shah JB, McKiernan JM, Elkin EP, Carroll PR, Meng MV. Prostate biopsy patterns in the CaPSURE database: evolution with time and impact on outcome after prostatectomy. J Urol. 2008; 179: 136-140.
- Eggener SE, Yossepowitch O, Serio AM, Vickers AJ, Scardino PT, Eastham JA. Radical prostatectomy shortly after prostate biopsy does not affect operative difficulty or efficacy. Urology. 2007; 69: 1128-1133.
- Lee SW, Lee MH, Yang HJ. Experience of ultrasonography-guided percutaneous core biopsy for renal masses. Korean J Urol. 2013; 54: 660-665.
- Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009; 250: 187-196.
- Kutikov A, Uzzo RG. The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol. 2009; 182: 844-853.
- Evans DM, McAree K, Guyton DP, Hawkins N, Stakleff K. Dose dependency and wound healing aspects of the use of tissue plasminogen activator in the prevention of intra-abdominal adhesions. Am J Surg. 1993; 165: 229-232.
- Ward BC, Panitch A. Abdominal adhesions: current and novel therapies. J. Surg. Res. 2011; 165: 91-111.
- Pismensky SV, Kalzhanov ZR, Eliseeva MY, Kosmas IP, Mynbaev OA. Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation. BMC Surg. 2011; 14: 11-30.
- Tokgöz H, Bektaş S, Hancı V, Erol B, Akduman B, Karakaya K, et al. Postoperative adhesions after application of topical hemostatic agents: outcomes in a rat partial nephrectomy model. Urology. 2011; 78: 970. 9-14.
- Hellebrekers BW, Kooistra T. Pathogenesis of postoperative adhesion formation. Br. J. Surg. 2011; 98: 1503-1516.
- Perez-Ordonez B, Hamed G, Campbell S, Erlandson RA, Russo P, Gaudin PB, et al. Renal oncocytoma: a clinicopathologic study of 70 cases. Am. J. Surg. Pathol. 1997; 21: 871-83.
- Zhang JQ, Fielding JR, Zou KH. Etiology of spontaneous perirenal hemorrhage: a meta-analysis. J. Urol. 2002; 167: 1593-1596.