APF is one of potential tumor-specific factors that can complicate partial nephrectomy (PN) and is associated with decreased progression-free survival in patients with localized renal cancer.6, 10, 14–16 Previous studies on the association of APF with clinical, radiological features, or perioperative outcomes are summarized in Table 5. Due to lack of objective criteria for APF, the incidence of APF varies greatly. Therefore, our study established objective criteria after multiple surgical videos were reviewed. In this study, the incidence of APF was 42.8%, which was between the documented incidence.6, 8, 10
Table 5 summary of previous studies on APF
Author Year
|
Patient
|
Surgery
|
APF grading
|
APF rate
|
Included factors
|
Significant variables
|
Bylund et al. (2013)
|
29
|
RPN, OPN or Laparoscopic cryoablation
|
Operative records
|
55.2%
|
Clinical, Imaging, Pathological, Outcome
|
Male gender, Tumor size, Stranding, Tumor >50% exophytic, Thickness of perinephric fat, OT
|
Zheng et al. (2014)
|
41
|
OPN
|
Time of perinephric fat dissection on
|
53.7%
|
Clinical, Imaging, Pathological, Outcome
|
Male gender, PnFSD
|
Davidiuk et al. (2014)
|
100
|
RPN
|
Described by Kim et al.
|
30%
|
Clinical, Imaging, Pathological, Outcome
|
Male gender, BMI, Posterolateral and Posterior perinephric fat, Stranding
|
Davidiuk et al. (2015)
|
100
|
RPN
|
Described by Kim et al.
|
30%
|
Outcome
|
|
Kobayashi et al. (2016)
|
47
|
LPN or RALPN
|
Operative records
|
14.9%
|
Clinical, Imaging, Outcome
|
OT, Hypertension, FSPA on CT
|
Martin et al. (2016)
|
86
|
OPN
|
Operative records
|
50.0%
|
Clinical, Imaging, Outcome
|
Age, MAPscore
|
Kocher et al. (2016)
|
245
|
LPN or RPN
|
Operative records
|
10.6%
|
Clinical, Imaging, Pathological, Outcome
|
Age, Male gender, Stranding, Posterior fat thickness, MAP score, Malignant renal histology, Operating time, EBL
|
Dariane et al. (2016)
|
125
|
RPN or OPN
|
Described by Kim et al.
|
40.8%
|
Clinical, Imaging, Pathological, Outcome, Histologically
|
OT, EBL,Male gender, Age, Waist circumference, Fat density on CT, MAP score , Larger adipocytes
|
Shintaro et al. (2017)
|
92
|
Laparoscopic donor nephrectomy
|
Intraoperative videos
|
55.4%
|
Clinical, Imaging, Outcome, IHC
|
Perinephric fat area, Stranding, sIL-6R, OT
|
Khene et al. (2017)
|
202
|
RPN
|
Operative records
|
39.6%
|
Clinical, Imaging, Outcome
|
Male gender, Obesity, Hypertension, MAP score, OT, EBL,Transfusion, Conversion to open surgery or radical nephrectomy
|
Most literatures have confirmed that APF is associated with advanced age and common in males,4–6, 8–10, 14 which is correspond with our study. Male patients have more perinephric fat, whereas women have more subcutaneous fat.12, 17 However, in the age, adipose tissue redistribute from subcutaneous to visceral and ectopic fat, especially along the kidneys, liver and bone marrow. Adipose tissue is an endocrine organ which produces hormones such as cytokines especially in tumor necrosis factor-a (TNFa) and interleukin (IL-6). They can increase with aging and excessive accumulation of fat.18 It was confirmed that APF group solely increased the expression of sIL-6R, suggesting that APF may be a pathological procedure caused by systemic chronic inflammation.11, 19–21 Therefore, both age and gender can affect the distribution of visceral and subcutaneous fat, and also be the risk factors of APF.
In addition, our study also confirmed hypertension is the risk factor of PFAD, as previous studies reported.22, 23 Immune system play an important role in the development of hypertension and renal immune cell infiltration has been demonstrated in both experimental and clinical hypertension.24 In SPF group, we first found that a large number of CD45 + immune cells accumulate in the renal cortex near renal capsule. There are also scattered immune cells, increased blood vessel distribution and thickening of the renal capsule near renal cortex. Hypertension may affect the adhesion of the renal capsule to the perinephric fat by inducing renal immune cell infiltration. Two patients with previous nephritis were in the SPF group, adding weight to the theory that chronic inflammation of the kidney can affect fat adhesion.11, 25, 26
Perinephric stranding and thickness of posterior perinephric fat are important radiological predictor for APF in this study. Perinephric stranding represents a chronic inflammatory reaction which is considered as an important factor for formation of APF. The posterior perinephric fat thickness represents excessive and dysfunctional adipose tissue. Based on the two variables, Mayo Adhesive Probability (MAP) Score was established to predict APF5, which has been validated in different surgical methods for renal cancer.6, 8, 10, 14, 23
However, predictive value for perinephric fat density is still controversial. Bylund et al4 found that the renal hilum level fat density had no significant effect on APF. Zheng et al9 pointed out that perinephric fat surface density can predict the difficulty of renal peritoneal fat separation. The above differences may be related to the measurement method of perinephric fat density. During surgery, we found that perinephric fat only adhered to the surface of the kidney and not to the posterior peritoneum or posterior abdominal wall, suggesting that the adhesion or inflammatory area may be closed to the kidney surface. So, we measure perinephric fat density in a high-density area adjacent to the renal capsule, we found that some patients with SPF had significantly increased perinephric fat HU value on enhanced CT. Our results suggest that perinephric fat density may be a complement to the MAP score.
Several authors considered that APF can increase the risk of OT and bleeding during PN.6, 10, 14 However, our results only find that drain output was associated with APF. The OT and intraoperative EBL may be more affected by surgeon's surgical experience and other reasons, such as location of the tumor, damage of variant renal blood vessels and adjacent organs, and suture cutting off the renal parenchyma. Senior surgeons can speed up the surgical process, reduce damage and intraoperative bleeding, suggesting that whether APF can affect the OT and EBL needs further verification.
In this study, we found another new layer of fascia on the lateral side of renal capsule in NPF group for the first time. This fascia was defined as extracapsular fascia. During PN, perinephric fat can be easily blunt dissected along the gap between renal capsule and extracapsular fascia. However, due to chronic inflammation for SPF group, extracapsular fascia was taken place by thickening and fusion of renal capsule with many vessels, which will cause decapsulation and increasing hemorrhage in the process of kidney mobilization.
In conclusion, APF is more prevalent in ageing and male populations, particularly those with hypertension. Radiological factors such as perinephric stranding, posterior perinephric fat thickness and perinephric fat density can be used to predict PFAD. APF was associated with drain output and accompanied by immune cells gathering in renal cortex near thickened renal capsule with many vessels.