Surgical Strategies for Lymphocele Prevention in Minimally Invasive Radical Prostatectomy and Lymph Node Dissection: A Systematic Review

Abstract

Purpose:

Pelvic lymph node dissection is an important step during robotic radical prostatectomy. The collection of lymphatic fluid (lymphocele) is the most common complication with potentially severe impact; therefore, different strategies have been proposed to reduce its incidence.

Materials and Methods:

In this systematic review, EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials were searched for articles including the following interventions: transperitoneal vs extraperitoneal approach, any reconfiguration of the peritoneum, the use of pelvic drains, and the use of different sealing techniques and sealing agents. The outcome evaluated was the incidence of symptomatic lymphocele. Randomized, nonrandomized, and/or retrospective studies were included.

Results:

Twelve studies were included (including one ongoing randomized clinical trial). Because of heterogeneity of included studies, no meta-analysis was performed. No significant impact was reported by different sealing techniques and agents or by surgical approach. Three retrospective, nonrandomized studies showed a potential benefit of peritoneal reconfiguration to maximize the peritoneal surface of reabsorption.

Conclusion:

Lymphocele formation is a multistep and multifactorial event; high-quality literature analyzing risk factors and preventive measures is rather scarce. Peritoneal reconfiguration could represent a reasonable option that deserves further evaluation; no other preventive measure is supported by current evidence.

Background

Extended pelvic lymph node dissection (PLND) at the time of radical prostatectomy is a procedure with controversial survival benefit, but with pivotal role in providing staging and prognostic information.¹ European Urology Association (EAU) guidelines recommend performing an extended PLND (intended as removing lymphatic tissue covering the external iliac vessels, in the obturator fossa and both medially and laterally to the internal iliac artery) when the estimate risk of lymph node (LN) metastasis is at least 5%.²

Description of the Condition

Lymphocele can be defined as a collection of lymphatic fluid without an epithelial lining.³ It is usually a surgical complication after the disruption of lymphatic vessels. Although lymphocele after radical prostatectomy seems directly attributable to PLND,⁴ its true incidence is difficult to estimate because most lymphoceles occur asymptomatically and there is no standard screening procedure after prostatectomy. When considering symptomatic lymphocele, incidence has been reported between 0% and 8%.⁵

A lymphocele can become symptomatic because of superinfection of the lymphatic fluid (causing pain, fever, and/or sepsis) or because of the compression on adjacent structures; the latter event can result in abdominal discomfort or venous drainage impairment leading to lower limb edema, deep venous thrombosis, and/or pulmonary embolism. Lymphocele, even when asymptomatic, might also affect radiation therapy planning.⁶

Lymphocele is the most frequent complication after radical prostatectomy⁵ and many potential risk factors have already been reviewed by Lee and Kane⁷: many of them are indeed nonmodifiable elements such as patient age,⁸ comorbidities,⁹ surgeon experience,¹⁰ and LN involvement.^11,12

This literature strongly supports the idea that the extent of PLND should not be guided by the aim of preventing lymphocele formation, but rather by the purpose of improving oncologic outcomes. In addition, studies comparing lymphocele incidence in extended vs standard templates showed controversial results regarding the theoretical increasing risk of lymphocele with extended dissection.^8,4,13

Similar considerations can be made regarding the role of prophylactic anticoagulation (LMWH, low molecular weight heparin) where guidelines already defined its role in the setting of minimally invasive radical prostatectomy¹⁴ and the expected benefits deep venous thrombosis/pulmonary embolism reduction should outweigh the potential increased risk of lymphocele.^15
–17

In this systematic review, we aim to analyze intraoperative strategies that can be applied at the time of minimally invasive procedure to reduce the risk of symptomatic lymphocele.

Description of the Interventions

Transperitoneal vs extraperitoneal approach

Experiences from open radical prostatectomy suggest that there could be a benefit from transperitoneal approach because of the wider surface for lymphatic fluid reabsorption offered by the peritoneum.^12,18 Porpiglia and colleagues and Chung and colleagues found lower incidences of symptomatic lymphocele in the transperitoneal approach compared to the extraperitoneal, although methodological considerations impaired the inclusion of these studies in our analysis.^19,20 The rationale and benefit of peritoneal fenestration are confirmed also in a recent meta-analysis in the setting of kidney transplantation.²¹

Peritoneum reconfiguration

With the same rationale noted above, it was observed that even when the transperitoneal approach is used, the incidence of lymphoceles is still significant⁵ and this is thought to be caused by the early adherence of the perivesical fat to the lymph node dissection (LND) bed when the pneumoperitoneum is released, thus jeopardizing the potential advantages originating from the peritoneum opening.²² Some authors have then investigated the efficacy of interventions aimed to delay the spontaneous closure of the peritoneal wall.

Pelvic drains

Pelvic drains are used to ensure drainage of blood, urine, and lymph from the surgical bed. With the diffusion of minimally invasive techniques, where magnification of the image facilitates accurate suturing and detection of urine and blood spillage, there is a debate on whether drainage can be safely omitted,^23,24 but other studies show that in the setting of retropubic radical prostatectomy (RRP), higher lymphocele rates were found when drains were removed early or completely omitted compared to 7 days of drainage.¹² A large retrospective series of patients undergoing PLND at the time of either RRP or laparoscopic radical prostatectomy (LRP) reported, in the multivariate analysis, that symptomatic lymphocele was associated with the number of nodes removed and use of LMWH, but not with the number drains placed (1 vs 2).¹⁷

A Cochrane review updated in 2014 found that drainage of surgical field after PLND performed for gynecological cancer was not effective in preventing lymphocele and, in particular, when the peritoneum was left open, the presence of drain was even associated to an increased risk.²⁵

Ligation techniques and hemostatic agents

It is intuitive that meticulous dissection and ligation of lymphatic vessels are mandatory to reduce the risk of lymphocele. Various agents and techniques to facilitate this aim are available and currently used at surgeon's discretion. Fibrin sealants are widely used to maximize hemostasis based on their interaction on coagulation cascade. Some of these agents have been investigated to assess their ability to prevent lymphocele formation with a mechanism thought to be attributable to the mechanical compression with a lymphostatic effect or a direct effect of the presence of coagulation cascade components in the lymphatic fluid. A meta-analysis of randomized controlled trials including patients who underwent LND for gynecological malignancies found no differences in overall and symptomatic lymphocele rates in groups where fibrin collagen agents were used vs standard technique (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.36–1.05, p = 0.08 and OR 0.59, 95% CI 0.26–1.35, p = 0.22, respectively), but showed a decreased duration and volume of lymphatic drainage.²⁶ Inguinal LND is a procedure known by urologists for penile cancer, but it is also performed for melanoma: in this setting, a recent meta-analysis showed no improvement in terms of duration of drain placement, total drained volume, and wound-related complication with the use of tissue sealants.²⁷

Methods

Methods and results of this review are presented after the PRISMA guidelines.²⁸

Randomized clinical trials (RCTs), cohort studies, and case control studies were considered. Cross-sectional studies and case reports were excluded because of their statistical inadequacy for an accurate statistical assessment of risk factors and outcomes. Participants were patients who underwent pelvic lymphadenectomy with any template as part of their surgical treatment for prostate cancer performed with a robot-assisted or laparoscopic technique. At least 7 postoperative days of follow-up were considered reasonable for detecting lymphocele. Authors evaluated all the interventions that can be performed at the time of operation to prevent lymphocele formation, including the extraperitoneal vs transperitoneal approach, any reconfiguration of the peritoneum, the use of pelvic drains, or the use of any ligation technique or hemostatic agent. Outcomes evaluated were the incidence of significant lymphocele intended as any lymphocele of diameter 3 cm or greater or any symptomatic lymphocele. Expecting different definitions for symptomatic lymphocele, inclusion criteria were met when the study methodology clearly described abdominal or pelvic symptoms related to lymphocele or DVT-related symptoms (including Clavien-Dino grade I or greater), or any required intervention, including antibiotic treatment, surgical, or percutaneous drainage.

A comprehensive search of terms (prostate cancer, prostatectomy, lymphocele, pelvic lymphadenectomy, and complications) in EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials from 1980 up to January 31, 2019, was performed. All languages were included in the primary selection. Other sources of literature were not considered in this study.

Two authors (G.M. and A.M.) undertook the study selection screening the titles and abstracts of articles found in the search and discarding those that did not meet the eligibility criteria. Full-text copies of the eligible articles were obtained. Both review authors independently assessed whether the studies met the inclusion criteria, with disagreements resolved by discussion. For each included study, information regarding the location of the study, methods of the study, the participants (age range and eligibility criteria), the nature of the interventions, and data relating to the outcomes specified above was collected.

Risk of bias for RCTs was assessed through the Cochrane Collaboration tools²⁹ and summarized in Figure 1. For nonrandomized study, bias was assessed through the Newcastle-Ottawa Scale³⁰ and summarized in Table 1.

FIG. 1.

Risk of bias assessment for randomized studies.

Table 1.

Risk of Bias Assessment for Non-Randomized Studies

Author	Selection	Comparability	Outcome
Dal Moro	^****		^**
Horovitz	^****	^**	^***
Lebeis	^****		^**
Stolzenburg	^***		^**
Stolzenburg	^***	^**	^**
Waldert	^****		^**

,^**** scale indicates ^* = very low, ^**** = high.

Extracted data were judged by authors to be inappropriate for pooled analysis because of low quality and heterogeneity of the studies; thus, no meta-analysis was performed.

Results

After removing duplicates, 220 studies were evaluated and after screening of abstracts and titles, 56 full-text articles were obtained; 44 of them did not meet the inclusion criteria, leaving 12 studies (including 1 ongoing randomized trial) in the final analysis.

The study selection process is summarized in Figure 2 showing the PRISMA flow chart.

FIG. 2.

PRISMA flowchart of study selection.

Characteristics of included studies are shown in Table 2.

Table 2.

Characteristics of Included Studies

Author	Study period	Methods	N participants (pairs in matched design)	Surgical technique	Extent of LND	LMWH prophylaxis	Drain	Peritoneum reconfiguration	Ligation techniques	Other agents	Primary outcome
Buelens	2013–2016	RCT	100	Robotic, transperitoneal	Extended	Yes	Yes	n.d.	Metallic clips	Tachosil^a	Lymphocele volume on 1 week, 1 month, 3 months
Chenam	2012–2016	RCT	189	Robotic, transperitoneal	Limited or extended	None	Yes vs no^a	n.d.	Weck clips	None	Complications at 90 days
Dal Moro	n.d.	Cohort	371	Robotic, transperitoneal	Limited or extended	Yes	Yes	Yes^a	n.d.	n.d.	Symptomatic lymphocele
Gilbert	n.d.	RCT	88	Robotic, transperitoneal	Limited or extended	Yes	No	Not closed	Hem-o-Lock	Arista AH^™,a	Lymphocele detection at 3 months
Grande	2012–2015	RCT	220	Robotic, approach n.d.	Extended	n.d.	n.d.	n.d.	Clips vs bipolar^a	n.d.	Lymphocele at 10 and 30 days
Horovitz	2003–2016	Cohort, propensity matched	671	Robotic, transperitoneal vs extraperitoneal^a	Extended	Yes	n.d.	n.d.	Hem-o-Lock	n.d.	Symptomatic lymphocele
Lebeis	n.d.	Cohort	154	Robotic, transperitoneal	Limited or extended	Yes	Yes	Yes^a	Hem-o-Lock	n.d.	Symptomatic lymphocele
Stolzenburg	2006–2007	Cohort	100	Laparoscopic, extraperitoneal	Extended	n.d.	n.d.	Yes^a	n.d.	n.d.	Complications up to 90 days
Stolzenburg	2010–2017	Cohort	193	Laparoscopic or robotic, transperitoneal	Extended	n.d.	Yes	Yes^a	Clips	n.d.	Symptomatic and asymptomatic lymphocele up to 90 days
Waldert	2008–2009	Cohort	142	Laparoscopic, extraperitoneal	Limited	Yes	Yes	n.d.	n.d.	FloSeal^a	Symptomatic lymphocele
Yasumizu	2010–2011	RCT	120	Laparoscopic, extraperitoneal	Limited	n.d.	Yes	n.d.	VSD^a	n.d.	Lymphocele detection at 1 month

Intervention investigated in the study.

LMWH = low molecular weight heparin; LND = lymph node dissection; n.d. = no information available; RCT = randomized clinical trial; VSD = vessel-sealing device.

Effects of the interventions

Transperitoneal vs extraperitoneal

A large (n = 671 pairs), propensity-matched approach and prospectively maintained cohort of patients undergoing robotic PLND either with extraperitoneal robotic radical prostatectomy (eRARP) or transperitoneal robotic radical prostatectomy (tRARP) approach were compared in terms of rates of symptomatic lymphocele³¹; patients on the tRARP group had higher T stage (p = 0.0015), and higher incidence of N+ disease (p = 0.0002) and number of LN removed (p < 0.0001). No difference in symptomatic lymphocele was found between the groups (eRARP 19/671 [2.83%] vs tRARP 10/671 [1.49%], p = 0.09). Notably, the tRARP group had more LNs removed and incidence of pN1 disease. When controlling for N stage and LN removed, logistic regression showed a nonsignificant trend for higher lymphocele rates in eRARP when controlling for LN count (p = 0.071), pathological N stage (p = 0.111), or both combined (p = 0.085) on symptomatic lymphocele rates.

Peritoneum reconfiguration

Stolzenburg and colleagues in 2008 performed bilateral peritoneal fenestration at the end of extraperitoneal radical prostatectomy with lymphadenectomy in 50 patients and compared them to 50 patients where the peritoneum was left intact, looking at lymphocele detection at 8 and 30 days on US examination. Significant differences (p < 0.001) were found in the fenestration group (3 lymphocele found, all of them asymptomatic) and 16 were found in the control group (7 out of 16 were symptomatic). No differences in terms of pain, inflammation, and bowel function were reported.³²

Three studies report peritoneal reconstruction as an intervention to prevent lymphocele formation during tRARP:

- Lebeis and coworkers analyzed the rates of lymphocele detection on 77 consecutive patients who underwent a peritoneal interposition flap (“created by rotating and advancing the peritoneum around the lateral surface of the ipsilateral bladder to the dependent portion of the pelvis and fixing it to the bladder itself”). They were compared retrospectively to 77 patients who underwent standard procedure without this reconfiguration. Authors reported no lymphocele in the group with peritoneal flap and 9 (11.6%) lymphoceles in the comparison group (p = 0.0033) with a mean detection time of 30.4 days (range 6–72). Every patients with lymphocele experienced symptoms.²²

- Dal Moro and Zattoni performed a variation of the aforementioned technique (P.L.E.A.T.—preventing lymphocele ensuring absorption transperitoneally—Fig. 3) on 176 patients and compared the rates of symptomatic lymphocele to 195 patients who underwent no peritoneal reconfiguration. Results showed significantly higher rates (p = 0.039) of symptomatic lymphocele in the control group (9/195—4.1%) vs the “P.L.E.A.T.” group (1/176—0.6%) with calculated median detection time of 32 days (range 11–145); the P.L.E.A.T. cohort was characterized by higher pathologic staging and higher number of LNs removed.³³

- Stolzenburg and associates in 2018 evaluated US diagnosis of both symptomatic and asymptomatic lymphocele at 8, 28, and 90 days in 193 patients who underwent a reconfiguration with a four-point peritoneal flap fixation (4PPFF) compared to matched controls where no reconfiguration was performed. They reported a significant difference in the incidence of symptomatic lymphocele: two patients (1.03%) in the 4PPFF group vs nine patients (4.6%) without 4PPFF (p = 0.0322). Asymptomatic lymphocele incidence was also lower in the 4PPFF group (p = 0.0058).³⁴

Results from the undergoing triple-blind RCT using a “Peritoneal Iliac Flap” are eagerly awaited (NCT03567525) to provide higher quality evidence on this topic.

FIG. 3.

P.L.E.A.T. reconfiguration (original drawing by the author). P.L.E.A.T. = preventing lymphocele ensuring absorption transperitoneally.

Pelvic drains

A single-center randomized noninferiority trial (noninferiority margin set at 10%) was performed by Chenam and colleagues in 2018. Patients were assigned to pelvic drainage (PD) or nondrainage after robotic-assisted radical prostatectomy (RARP). Five patients were excluded because of anastomotic leakage or inadequate hemostasis. The study did not reach the target accrual number; however, after adjustment for the type I error level, authors found no statistically significant difference in 90-day complication rate and symptomatic lymphocele rate (2/92 [2.2%] in the nondrainage cohort and 3/97 [4.1%] in the PD cohort, p = 0.7).³⁵

Sealing techniques and sealing agents

In the setting of LRP, different instruments can be used to achieve efficient hemostasis and facilitate LND. Yasumizu and coworkers evaluated one of them looking at lymphocele rates in patients undergoing limited LND during e-LRP with conventional technique (ultrasonic cutting and coagulating system—SonoSurg) or using a vessel sealing device (EnSeal). At 90 days, CT scan detected lymphocele in 35/60 patients in the conventional technique groups compared to 28/60 (p = 0.201); only one lymphocele was symptomatic from the first group. In this study, authors calculated a mean size of 1335 mm²; when the presence of a collection >1500 mm² was established as an outcome, the use of vessel sealing device was the only outcome predictor on the multivariate analysis (p < 0.01).³⁶ An RCT performed by Grande and colleagues evaluated the rate of lymphocele detection and symptomatic lymphocele at 10 and 90 days after RARP and PNLD in 110 patients in whom titanium clips were used during LND and 110 patients in whom LND was performed with bipolar energy only. Results showed no difference between groups in terms of symptomatic lymphocele (6/110 in the titanium clips groups vs 5/110 in the bipolar energy group; p = 0.7). Similarly, no difference was found in lymphocele detection rates (p = 0.9).³⁷

In the setting of laparoscopic extraperitoneal LND for prostate cancer, Waldert evaluated, in a small cohort, bilateral application of 2.5 cc Floseal^® (a hemostatic matrix containing human derivated thrombin; Baxter Healthcare, Deerfield, IL) after LND, and 1/32 (3.1%) symptomatic lymphoceles were detected in the Floseal group compared to 16/110 (14.5%) in the control group (p = 0.149). In this study, timing of imaging was defined by patient symptoms and was not reported³⁸; the small numbers probably limited the statistical validity of the study.

A randomized trial evaluated the impact of the use of Arista AH^™ (hemostatic powder that acts through Microporous Polysaccharide Hemospheres; Davol, Inc.) applied only on one side of the PLND bed compared to the other side in 88 patients undergoing RARP. A CT scan at 3 months was performed in every patient and fluid collections of 3 cm or greater were considered lymphocele. Five of them (5.7%) occurred on the Arista AH side and nine (10.2%) on the untreated side (p = 0.248). None of the lymphocele was symptomatic and no statistical difference was found in average lymphocele size (p = 0.441).³⁹

More recently, a randomized controlled trial by Buelens and colleagues evaluated lymphocele formation and volume at 1 week, and 1 and 3 months after operation in patients undergoing transperitoneal robot-assisted extended PNLD for staging before external beam radiation therapy (n = 50) or during RP (n = 50). Twenty-five patients were randomized to bilateral placement of TachoSil (hemostatic sponge made of horse collagen and human thrombin; Nycomed-Takeda Austria GmbH) above the external iliac vessels. Symptomatic lymphoceles were evaluated as a secondary endpoint. Patient undergoing PNLD only were older, and had a worse ASA score and a more advanced clinical T stage; their procedures, other than shorter operative time and blood loss, included higher number of LN removed and higher N+ stage. Symptomatic lymphoceles were detected in 13 patients (26%) in both TachoSil and control group (p = 0.85) without differences regarding the surgical procedure (p = 0.39).⁴⁰

Discussion

The overall incidence of symptomatic lymphocele in the included studies is consistent with other reports⁵ and, even if relatively low, should be taken in account as it can lead to relevant complications that make efforts and costs of these procedures vain.

Only one study evaluating tRARP vs eRARP met the inclusion criteria and was included in our review, reporting no significant differences between the two techniques.³¹ Notably, the raw incidence of lymphocele was almost twice in the eRARP group, with higher number nodes removed and positive nodes in the tRARP group. These results should then be taken cautiously; in fact, PLND in eRARP may be more technically challenging, and in this study, it was performed in patients with lower risk of nodal disease, by a single experienced surgeon. Given the increasing need of performing extended PLNDs the most promising, low-quality evidence comes from techniques that enhance the peritoneal surface of reabsorption. The techniques described in the setting of extraperitoneal³² or transperitoneal^22,33,34 approaches are cheap, safe, and quick; however, evidence from RCTs is awaited to confirm these results.

The rationale for drain placement goes further than preventing lymphocele, and although the well-conducted study by Chenam and colleagues³⁵ suggests that pelvic drains can be safely omitted, this conclusion may not be used to make any recommendation or generalized to larger cohort of patients and different surgical experiences. In particular, this study is limited to a single-center experience and designed to detect overall complications, and results are based on an interim analysis attributable to poor accrual. Overall, in most of the studies analyzed, drains were left in place until drainage volume was <100 cc/24 hour, and this usually happens in the first postoperative days; this strategy can be helpful in detecting rare, but severe, events like anastomotic disruption and hemorrhage, probably without affecting morbidity, but may not be sufficient to control lymphatic leakage.¹²

None of the included studies was able to show improvement in lymphocele prevention with any of the techniques described; some trends toward improvement were shown by Gilbert and colleagues³⁹ and Waldert and colleagues,³⁸ but none of them reached significant levels, mainly with concerns related to the small sample size in relationship to the incidence of the disease. In general, the use of hemostatic agents or clips remains questionable, particularly when considering costs implicated with it.

Reported results must be read in light of the risk of bias present in the studies. Six of the included studies are retrospective and nonrandomized. Direct comparison between studies results is difficult because of potential confounding interventions in the same group (e.g., different extent of PLND) and many other potential confounders that were not reported in the articles. The outcome of symptomatic lymphocele was assessed at different times and with different techniques. The only group of comparable interventions was that of peritoneal reconfiguration, but because of the retrospective nature of the study and the absence of information on potential confounder, was not judged to be amenable to meta-analysis. All studies in this setting show some benefit in peritoneal reconfiguration, but results are to be read in light of the high risk of bias and thus prospective and randomized studies are eagerly awaited.

Despite the reported limitations, this review provides a summary of the most updated available evidence that could help the surgeon in its intraoperative evaluations and guide future research.

Conclusion

Symptomatic lymphocele is the most common complication after RARP. Maximizing peritoneal surface of reabsorption could help preventing its formation and, even though supported only by nonrandomized data, could be a quick and inexpensive option, and deserves further evaluation in prospective randomized setting. Current literature does not support the use of particular sealing techniques or agents. Further evidence is needed to draw meaningful conclusions about other approaches for lymphocele prevention.

Footnotes

Authors' Contributions

G.M.: project development, data collection, data analysis, and article writing. A.M.: project development, data collection, data analysis, and article writing. N.Z.: article editing and critical revision. M.E.A.: article editing and critical revision. F.Z.: critical revision of the article for important intellectual content and supervision. R.J.K.: critical revision of the article for important intellectual content and supervision. F.D.M.: critical revision of the article for important intellectual content and supervision.

Author Disclosure Statement

None of the authors has any relevant disclosures, and none of the authors has any financial or non-financial interests that may be relevant to the submitted work.

Funding Information

No funding was received for this article.

Abbreviations Used

References

Fossati

, Willemse

, Van den Broeck

, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: A systematic review. Eur Urol, 2017; 72:84–109.

Mottet

, Bellmunt

, Bolla

, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol, 2017; 71:618–629.

Metcalf

, Peel

. Lymphocele. Ann R Coll Surg Engl, 1993; 75:387–392.

Liss

, Palazzi

, Stroup

, Jabaji

, Raheem

, Kane

. Outcomes and complications of pelvic lymph node dissection during robotic-assisted radical prostatectomy. World J Urol, 2013; 31:481–488.

Ploussard

, Briganti

, de la Taille

, et al. Pelvic lymph node dissection during robot-assisted radical prostatectomy: Efficacy, limitations, and complications-a systematic review of the literature. Eur Urol, 2014; 65:7–16.

Jereczek-Fossa

, Colangione

, Fodor

, et al. Radiotherapy in prostate cancer patients with pelvic lymphocele after surgery: Clinical and dosimetric data of 30 patients. Clin Genitourin Cancer, 2015; 13:e223–e228.

Lee

, Kane

. How to minimize lymphoceles and treat clinically symptomatic lymphoceles after radical prostatectomy. Curr Urol Rep, 2014; 15:445.

Capitanio

, Pellucchi

, Gallina

, et al. How can we predict lymphorrhoea and clinically significant lymphocoeles after radical prostatectomy and pelvic lymphadenectomy? Clinical implications. BJU Int, 2011; 107:1095–1101.

Keskin

, Argun

, Obek

, Tufek

, Tuna

, Mourmouris

, Erdogan

, Kural

. The incidence and sequela of lymphocele formation after robot-assisted extended pelvic lymph node dissection. BJU Int, 2016; 118:127–131.

10.

, Gold

, Pashos

, Mehta

, Litwin

. Role of surgeon volume in radical prostatectomy outcomes. J Clin Oncol, 2003; 21:401–405.

11.

Orvieto

, Coelho

, Chauhan

, Palmer

, Rocco

, Patel

. Incidence of lymphoceles after robot-assisted pelvic lymph node dissection. BJU Int, 2011; 108:1185–1190.

12.

Danuser

, Di Pierro

, Stucki

, Mattei

. Extended pelvic lymphadenectomy and various radical prostatectomy techniques: Is pelvic drainage necessary?. BJU Int, 2013; 111:963–969.

13.

Yuh

, Ruel

, Mejia

, Novara

, Wilson

. Standardized comparison of robot-assisted limited and extended pelvic lymphadenectomy for prostate cancer. BJU Int, 2013; 112:81–88.

14.

Tikkinen

KAO

, Cartwright

, Gould

, Naspro

, Novara

, Sandset

, Violette

, Guyatt

. EAU guidelines on thromboprophylaxis in urological surgery 2018. In: European Association of Urology Guidelines. 2018 Edition, vol. presented at the EAU Annual Congress Copenhagen 2018. Arnhem, The Netherlands: European Association of Urology Guidelines Office, 2018.

15.

Koch

, Smith

Jr . Low molecular weight heparin and radical prostatectomy: A prospective analysis of safety and side effects. Prostate Cancer Prostatic Dis, 1997; 1:101–104.

16.

Naselli

, Andreatta

, Introini

, Fontana

, Puppo

. Predictors of symptomatic lymphocele after lymph node excision and radical prostatectomy. Urology, 2010; 75:630–635.

17.

Gotto

, Yunis

, Guillonneau

, Touijer

, Eastham

, Scardino

, Rabbani

. Predictors of symptomatic lymphocele after radical prostatectomy and bilateral pelvic lymph node dissection. Int J Urol, 2011; 18:291–296.

18.

Kowalczyk

, Levy

, Caplan

, Lipsitz

, Yu

, Gu

, Hu

. Temporal national trends of minimally invasive and retropubic radical prostatectomy outcomes from 2003 to 2007: Results from the 100% Medicare sample. Eur Urol, 2012; 61:803–809.

19.

Porpiglia

, Terrone

, Tarabuzzi

, et al. Transperitoneal versus extraperitoneal laparoscopic radical prostatectomy: Experience of a single center. Urology, 2006; 68:376–380.

20.

Chung

, Kim

, Ham

, Yu

, Chae

, Chung

, Choi

. Comparison of oncological results, functional outcomes, and complications for transperitoneal versus extraperitoneal robot-assisted radical prostatectomy: A single surgeon's experience. J Endourol, 2011; 25:787–792.

21.

Mihaljevic

, Heger

, Abbasi Dezfouli

, Golriz

, Mehrabi

. Prophylaxis of lymphocele formation after kidney transplantation via peritoneal fenestration: A systematic review. Transplant Int, 2017; 30:543–555.

22.

Lebeis

, Canes

, Sorcini

, Moinzadeh

. Novel technique prevents lymphoceles after transperitoneal robotic-assisted pelvic lymph node dissection: peritoneal flap interposition. Urology, 2015; 85:1505–1509.

23.

Musser

, Assel

, Guglielmetti

, Pathak

, Silberstein

, Sjoberg

, Bernstein

, Laudone

. Impact of routine use of surgical drains on incidence of complications with robot-assisted radical prostatectomy. J Endourol, 2014; 28:1333–1337.

24.

Sharma

, Kim

, Mohler

. Routine pelvic drainage not required after open or robotic radical prostatectomy. Urology, 2007; 69:330–333.

25.

Charoenkwan

, Kietpeerakool

. Retroperitoneal drainage versus no drainage after pelvic lymphadenectomy for the prevention of lymphocyst formation in women with gynaecological malignancies. Cochrane Database Syst Rev, 2017; 6:CD007387.

26.

Prodromidou

, Iavazzo

, Fotiou

, Psomiadou

, Drakou

, Vorgias

, Kalinoglou

. The application of fibrin sealant for the prevention of lymphocele after lymphadenectomy in patients with gynecological malignancies: A systematic review and meta-analysis of randomized controlled trials. Gynecol Oncol, 2019; 153:201–208.

27.

Gerken

ALH

, Dobroschke

, Reissfelder

, et al. Tissue sealants for the prevention of lymphoceles after radical inguinal lymph node dissection in patients with melanoma: A systematic review and individual patient data meta-analysis. J Surg Oncol 2019. J Surg Oncol, 2019; 113:728–736.

28.

Moher

, Liberati

, Tetzlaff

, Altman

. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med, 2009; 151:264–269, w264.

29.

Higgins

JPT

, Altman

, Gøtzsche

, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 2011; 343:d5928.

30.

Wells

, Shea

, O'Connel

, Peterson

, Welch

, Losos

, Tugwell

. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed September 18, 2019 ).

31.

Horovitz

, Lu

, Feng

, Messing

, Joseph

. Rate of symptomatic lymphocele formation after extraperitoneal vs transperitoneal robot-assisted radical prostatectomy and bilateral pelvic lymphadenectomy. J Endourol, 2017; 31:1037–1043.

32.

Stolzenburg

, Wasserscheid

, Rabenalt

, et al. Reduction in incidence of lymphocele following extraperitoneal radical prostatectomy and pelvic lymph node dissection by bilateral peritoneal fenestration. World J Urol, 2008; 26:581–586.

33.

Dal Moro

, Zattoni

. P.L.E.A.T.-Preventing lymphocele ensuring absorption transperitoneally: A robotic technique. Urology, 2017; 110:244–247.

34.

Stolzenburg

J-U

, Arthanareeswaran

VKA

, Dietel

, et al. Four-point peritoneal flap fixation in preventing lymphocele formation following radical prostatectomy. Eur Urol Oncol, 2018; 1:443–448.

35.

Chenam

, Yuh

, Zhumkhawala

, et al. Prospective randomised non-inferiority trial of pelvic drain placement vs no pelvic drain placement after robot-assisted radical prostatectomy. BJU Int, 2018; 121:357–364.

36.

Yasumizu

, Miyajima

, Maeda

, Takeda

, Hasegawa

, Kosaka

, Kikuchi

, Oya

. How can lymphocele development be prevented after laparoscopic radical prostatectomy?. J Endourol, 2013; 27:447–451.

37.

Grande

, Di Pierro

, Mordasini

, Ferrari

, Wurnschimmel

, Danuser

, Mattei

. Prospective randomized trial comparing titanium clips to bipolar coagulation in sealing lymphatic vessels during pelvic lymph node dissection at the time of robot-assisted radical prostatectomy. Eur Urol, 2017; 71:155–158.

38.

Waldert

, Remzi

, Klatte

, Klingler

. FloSeal reduces the incidence of lymphoceles after lymphadenectomies in laparoscopic and robot-assisted extraperitoneal radical prostatectomy. J Endourol, 2011; 25:969–973.

39.

Gilbert

, Angell

, Abaza

. Evaluation of absorbable hemostatic powder for prevention of lymphoceles following robotic prostatectomy with lymphadenectomy. Urology, 2016; 98:75–80.

40.

Buelens

, Van Praet

, Poelaert

, Van Huele

, Decaestecker

, Lumen

. Prospective randomized controlled trial exploring the effect of TachoSil on lymphocele formation after extended pelvic lymph node dissection in prostate cancer. Urology, 2018; 118:134–140.