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- Subjects and Methods
- Conflict of Interest
Since 1976 when Fernstorm and Johannson  introduced percutaneous renal stone management, the urological community has focused its efforts on improving percutaneous nephrolithotomy (PCNL) techniques in terms of morbidity. To this end, several alternative approaches have been established, including tubeless PCNL [2, 3]. The concept behind tubeless PCNL is to spare patients the postoperative percutaneous nephrostomy tube drainage that has been associated with substantial postoperative pain and morbidity [4-6].
While several studies in humans have shown that the use of absorbable haemostatic sealants may be safe, feasible and a useful adjunct for a safer tubeless PCNL, the precise effect of these haemostatic agents on renal histology is still not clear [7-10]. Haemostatic sealant use during PCNL remains an ‘off-label’ use of haemostatics and so no guidelines exist to elucidate which sealant is indicated and which is not. Currently, almost the entire range of haemostatic agents has been used in the clinical setting. Nevertheless, concerns regarding a potential negative impact on renal tissue stem from the fact that such haemostatic agents may have varying degrees of bio-absorbability, antigenicity, anaphylactic/hypersensitivity reactions and risk of inducing adverse reactions such as fever, granuloma, abscess or foreign body reaction.
In an attempt to address this issue we examined the mid-term effects of various common haemostatic sealants in the drainage and histology of porcine renal units, using an in vivo totally tubeless PCNL model.
- Top of page
- Subjects and Methods
- Conflict of Interest
The lack of postoperative drainage is considered to be a disadvantage of the tubeless PCNL technique, mainly with regard to potential delayed bleeding. Application of haemostatic agents in the nephrostomy tract after the procedure has been proposed as a useful adjunct to tubeless PCNL, inducing immediate haemostasis and thus eliminating the need for postoperative drainage. Fibrin glue, gelatin matrix and oxidized cellulose application are haemostatic sealants that have already been evaluated in several clinical studies [8-14]. Nevertheless, the exact effect of these haemostatic agents on the renal drainage and histology is still not clear.
Several experimental studies question the safety of this haemostatic sealant application, mainly focusing on the potential of such materials to occlude urinary drainage. Uribe et al. , in an in vitro experimental setting evaluated the mixing of several haemostatic agents with urine. Fibrin glue and oxidized regenerated cellulose maintained a solid form when initially mixed with urine and then assumed to a semisolid gelatinous state, which remained in the same form during the 5 days of observation. Polyethylene glycol formed a solid clot, that did not dissolve after 5 days. Only the gelatin matrix formed a fine particulate suspension. In addition, Kim et al.  examined the effect of direct injection of various haemostatic agents in the porcine collecting system through a nephrostomy tube. A risk of obstruction in >50% of applied cases that did not resolve over a 5-day period was reported. In the present study, drainage occlusion was observed in only 5% of cases where a haemostatic sealant was used (1 out of 20 renal units). The difference between the two studies can be attributed to the fact that, in the present experimental setting, haemostatic agents were not purposely injected inside the collecting system. Yet, the single case of obstruction, which was observed in one case of Tachosil® application, as well as the presence of clot inside the renal pelvis in two cases in the Helisorb® group, show that the danger of occlusion existed for all renal units but was avoided in the majority of cases. Consequently, the present study verifies that haemostatic agent application during tubeless PCNL presents a risk for urinary drainage obstruction and, therefore, measures to avoid the insertion of such materials to the collecting system (e.g. sealing the collecting system with a balloon catheter) are recommended.
Histological data from the present study show that haemostatic agent application after percutaneous nephrostomy is not harmless for the kidney. All three examined agents induced an inflammatory reaction in the renal units (Table 2). It is worth mentioning that renal histological lesions were identified not only around the nephrostomy tract but, to a lesser degree, to parenchymal areas located away (>1 cm) from the site of penetration as well. It remains to be investigated whether a possible renal inflammatory reaction was responsible for the increased pain (resolved 1 month postoperatively) observed after haemostatic sealant application, as reported in a prospective randomized study comparing tubeless Floseal® closure with fascial stitch or Cope loop nephrostomy tube placement after PCNL .
Table 2. Main renal histopathological findings
| ||Site of application (no. of renal units)||Main renal histopathological findings||Comments|
|Control||None (4)||No significant lesions|| |
|Helisorb®||Tract and kidney (4)||Chronic tubulointerstitial nephritis, chronic urothelial inflammation, urothelial hyperplasia.||Clot inside renal pelvis and upper ureter in two cases without drainage occlusion.|
|Tract only (4)||Mild urothelial hyperplasia in the renal pelvis.|| |
|Tachosil®||Tract and kidney (4)||Moderated chronic inflammatory infiltrates and focal fibrosis of the renal cortex and medulla.||One case of drainage occlusion/significant histological deterioration in the particular case.|
|Tract only (4)||No significant lesions.|| |
|Floseal®||Tract and kidney (4)||Moderate chronic inflammatory infiltrates and focal fibrosis of the renal cortex and medulla.|| |
|Tract only (4)||No significant lesions.|| |
Owing to the limited number of animals, reliable statistical analysis of the histological data was not possible and thus, the present study failed to demonstrate any superiority of one haemostatic sealant over the others in terms of induced histological reaction. Nevertheless, it was evident that the solid form of the Tachosil® sponge and the gel form of Floseal® were superior to the powdered form of Helisorb®. In the case of Helisorb®, renal reaction was observed even in cases where the agent was not applied inside the renal parenchyma, but was injected in the s.c. part of the nephrostomy tract only. In addition, clot formation inside the renal pelvis in two cases of parenchymal application was an indication that some amount of substance may have slipped inside the collecting system. By contrast, Tachosil® and Floseal® placement was more accurate and signs of relocation from tract to kidney were not observed. Finally, tubeless PCNL without sealant application in this experimental series was associated with no morbidity (urinoma or clot formation) and the fewest histopathological changes. Based on the latter, it might be safer to perform tubeless PCNL without the use of any sealants in properly selected cases.
A limitation of the present study is that differences between porcine and human kidney reaction to the examined haemostatic sealants might exist. Moreover, potential functional deterioration of the examined renal units was not evaluated (porcine renal scintigraphy was not available and biochemical markers are unreliable for examining unilateral functional deterioration). Thus, further studies in other experimental models are needed to reinforce the conclusions of this work. In addition, the rationale of extending the follow-up period to 40 days after the procedure, was based on the maximum period of housing allowed by our animal care unit. Nevertheless, inflammatory reactions seen in the post mortem specimens could potentially subside after a longer period, which is quite possible given that particular haemostatic sealants have been traced in the nephrostomy tract even after 30 days postoperatively . Consequently, given that the time for absorption of fish origin collagen, human fibrinogen and thrombin as well as bovine-derived gelatin matrix components of the applied haemostatic sealants is unknown for the porcine organism, the relatively short duration of this trial should also be considered to be a limitation.
Furthermore, particular aspects of our model, including suturing of the nephrostomy incision and overdilatation of the nephrostomy tract could induce a tissue reaction which, in turn, could complicate the interpretation of our histological data. Suturing of the nephrostomy site itself could induce local inflammation. Nevertheless, given that the particular part of the procedure was identical for all groups, and histological analysis did not reveal significant inflammatory reaction at tissues located near to the suturing site we consider the impact on our results of suturing to be small. Additionally, nephrostomy tract dilatation by up to 30 F in the relatively small kidney of porcine experimental subjects can be considered an overdilatation which might be a contributing factor to the histological findings of the study. Such dilatation was required to imitate exactly our clinical practice in humans, allow nephroscope insertion and ease the Tachosil® folded sponge application which was relatively thick. Nevertheless, the effect of overdilatation was equal in all nephrostomy tracts and consequently its impact on the observed histological differences between study groups should be considered minimal. Finally, owing to the lack of adequate statistical power of the study, further investigation is required so as to define which haemostatic sealant is superior to the others in terms of inducing the least histological reaction to the injected renal units.
In conclusion, data from the present study indicate that haemostatic agent application in the nephrostomy tract is associated with a risk of renal drainage occlusion and measures to prevent the injection of these agents into the collecting system should be recommended. Moreover, taking into consideration all limitations related to an experimental study, it was revealed that haemostatic agents induce an inflammatory reaction to the injected renal units. While none of the studied haemostatics was proven superior to the others, solid and gel sealants were more accurately placed in the nephrostomy tract and showed no signs of relocation. Further investigation into the effects of each haemostatic sealant in the kidney is recommended before this tool can be regularly adopted for use during tubeless PCNL in humans.