Early drainage removal in the management of lymphatic leakage after robotic pelvic lymph node dissection

Abstract

Background: Radical prostatectomy (RP) and radical cystectomy (RC) with concurrent pelvic lymph node dissection (PLND) are considered as the curative surgical treatment options for localized prostate cancer (PC) or muscle-invasive bladder cancer (BC). Regarding lymphatic leakage management after PLND, there is no standard of care, with different therapeutic approaches having been reported with varying success rates.

Methods: Seventy patients underwent pelvic lymphadenectomy during robotic RP and RC with postoperative pelvic drainage volume more than 50 mL/day before the removal of drainage tube, were retrospectively evaluated in this study between August 2015 and June 2023. If the pelvic drainage volume on postoperative Day 2 was more than 50 mL/day, a drainage fluid creatinine was routinely tested to rule out urine leakage. We removed the drainage if the patient had no significant abdominal free fluid collection, no abdominal distension or pain, no fever, and no abdominal tenderness. After 1-day observation of the vital signs and abdominal symptoms, the patient was discharged and followed-up in clinic for 2 weeks after surgery.

Results: Forty-one cases underwent the early drainage removal even if the pelvic drainage volume was more than 50 mL/day. Among these forty-one cases, twenty-five drainage tubes were removed when drainage volume was more than 100 mL/day. All the forty-one cases with pelvic drainage volume greater than 50 mL/day were successfully managed with the early drainage removal. No paracentesis or drainage placement was required. No re-admission occured during the follow-up period.

Conclusion: It is safe to manage the high-volume pelvic lymphatic leakage by early clamping of the drainage tube, ultrasonography assessment of no significant residual fluid in the abdominal and pelvic cavity, and then the early removal of the drainage tube.

Keywords

bladder cancer / lymphatic leakage / pelvic drainage / pelvic lymph node dissection / prostate cancer / robotic surgery

1 INTRODUCTION

Radical prostatectomy (RP) and radical cystectomy (RC) with concurrent pelvic lymph node dissection are considered as the curative surgical treatment options for localized prostate cancer (PC) or muscle-invasive bladder cancer (BC). They are the most frequently performed urological pelvic surgical interventions[1,2]. Although the extent is debatable, pelvic lymphadenectomy (PLND) is the most accurate and reliable staging procedure for detecting lymph node invasion and may add treatment value in high-risk PC and muscle-invasive BC[3,4].

However, it is not a complication-free procedure. One of the common PLND complications is the lymphatic leakage, which increased proportionally with respect to the extent of PLND and the number of lymph nodes removed[5,6]. Intraoperative lymphatic system trauma results in postoperative lymphatic leakage, which includes lymphatic ascites, lymphorrhea, lymphatic fistula, and lymphocele[7]. The incidence of lymphatic leakage is 4.3% (lymphorrhea) in robotic RP and 9% (lymphocele) in robotic RC[6,8].

The pelvic drainage may contain residual fluid used during irrigation, postoperative inflammatory exudate, peritoneal fluid, and lymphatic fluid. Often the surgeon must face a difficult decision about the timing of drain removal, with persistent high drainage volume more than 50 mL/day. Prolonged drainage time may cause dehydration, nutritional deficiency, immunologic dysfunction, increase risk of pelvic infection, and prolong hospital stay.

Even though the value of PLND in staging and treatment of PC and BC has been well established, the prolonged pelvic drainage could impair patients in both health and psychological aspects and surgeon's willingness to preform PLND.

It is based on our understanding that the open lymphatic fluid is drained freely into the abdominal cavity through the open lymphatic ducts and is reabsorbed by the peritoneum, we have developed a clinical technique for early pelvic drainage removal in patients with a pelvic drainage volume greater than 50 mL/day after PLND.

The aim of this study was to evaluate the safety and efficacy of early drainage removal in the management of high-volume pelvic lymphatic leakage after transperitoneal PLND.

2 MATERIALS AND METHODS

2.1 Patients

Patients diagnosed with PC and BC who met the criteria of European Urological Association (EAU) guidelines for RP and RC and accepted robotic transperitoneal RP or RC and concurrent PLND[1,2].

Seventy patients underwent PLND during robotic RP and RC for PC and BC in Beijing United Family Hospital (Beijing, China) between August 2015 and June 2023. Forty-one (41/70, 58.6%) patients with postoperative pelvic drainage volume more than 50 mL/day before the removal of drainage tube were retrospectively evaluated in this study. Twenty-nine patients removed drainage when postoperative pelvic drainage volume less than 50 mL/day before the removal were excluded from this study.

This study was retrospective and all treatments were performed in accordance with standard postoperative treatment protocols as indicated in the ethics statement, and no additional investigations were performed except the data assessment.

2.2 Robotic PLNDs

For PC, the standard robotic PLND included obturator and external iliac lymph node dissection, while the extended PLND included obturator, external, and internal iliac lymph node dissection[9]. For BC, the standard robotic PLND included obturator, internal iliac, external iliac lymph node dissection, while the extended PLND included the standard PLND, and the region of common iliac vessels, the aortic bifurcation, the presacral lymph node dissection[10].

Routinely, on the completion of surgery, an F18 pelvic drainage tube connected to a gravity drainage bag was placed into pelvic cavity, and the drainage volume was recorded every 24 hours.

All the robotic PLNDs were completed by one senior urologist with the da Vinci Si Surgical System (Intuitive Surgical Inc., USA).

2.3 Postoperative management

Perioperatively, patients were cared for following enhanced recovery after surgery (ERAS) protocols[11]. The patient was encouraged to do voluntary mobilization and to start to eat and drink as tolerated immediately after surgery.

The diagnosis of postoperative persistent high-volume lymphatic leakage was made with the following criteria: (1) continuous discharge of clear fluid from the pelvic drainage tube after surgery; (2) drainage volume exceeding 50 mL/day; and (3) exclusion of urinary leakage[12].

In this cohort of patients, if the pelvic drainage volume on postoperative Day 2 was more than 50mL/day, a drainage fluid creatinine was routinely tested to rule out urine leakage, which was defined as an elevated drain fluid creatinine-to-serum creatinine ratio (DCSCR) of more than 1.12[13]. After urine leakage was ruled out, the drainage tube was clamped. The abdominal ultrasonography was then performed the day after to check if there was a significant abdominal residual fluid, which was defined as the ultrasonography revealing the presence of more than 2-cm free fluid collection in abdomen and/or pelvic area[14]. We removed the drainage tube if patient presented with no remarkable abdominal free fluid collection, no abdominal distension or pain, no fever, and no abdominal tenderness. Patients were discharged when they met the criteria of stable vital signs, ability to ambulate, tolerance of regular diet, controlled pain with oral pain killer, and absence of drainage. After 1-day observation of the vital signs and abdominal symptoms, the patient was discharged and followed up in clinic for 2 weeks after surgery.

No food restriction or low-fat medium-chain triglycerides supplements were added, and no somatostatin treatment was applied in this group of patients.

In clinic follow-up, the patients were asked if there were abdominal bloating, pain, and fever. If there was a concern of above symptoms, an ultrasonography or a CT scan was performed. Postoperative complication data one year after surgery were recorded.

2.4 Data collection

For each case, we retrospectively collected the demographic data, body mass index (BMI), American Society of Anesthesiologists (ASA) score, Charlson's comorbidity index, clinical TNM stage, and basic laboratory tests.

Perioperative data were collected as well. Intraoperative variables included the operation time, estimated blood loss, and extent of PLND (standard vs. extended). Postoperative data included the postoperative complications classified with the Clavien-Dindo classification system, comprehensive complication index (CCI), postoperative drainage volume before tube clamp, abdominal distension, pain, and fever after tube clamp, days of drainage placement, length of hospital stay, complications after discharge, and re-admission.

Pathological data included pathology stage according to the TNM classification, the number of lymph nodes removed, and positive lymph node numbers.

2.5 Statistical methods

All statistical analyses were performed using the SPSS 26.0 software (IBM Co., USA). Data were summarized using descriptive statistics. Mean (standard deviations [SD]) and median (interquartile range [IQR]) were used to report continuous variables, and frequencies and proportions were applied for categorical variables. A Mann–Whitney U test was used to compare the differences between two independent samples. p < 0.05 was considered statistically significant.

3 RESULTS

A total of forty-one patients were enrolled in this study. The demographics and perioperative characteristics are listed in Table 1.

Of the forty-one cases, twenty-five cases (61.0%) had the drainage tube removed when the drainage volume was more than 100 mL/day (median, 163.0 mL/day; IQR: 121.5, 206.5). The other sixteen cases had drainage less than 100 mL/day (median, 63.5 mL/day; IQR: 56.2, 84.5). There were twenty-nine patients with pT2, and eight patients with pT3 of PC. There were three patients with pT2 of BC, and one patient with T4 BC.

The intraoperative and postoperative results are shown in Table 2.

All forty-one cases with pelvic drainage volume of more than 50 mL/day were successfully managed with early drain removal. There were two patients who complained of abdominal distension and pain after drainage tube clamping. After re-opening of the tube, the patients' abdominal pain were relieved. Then the drainage tube were clamped again on the second day and then removed on the following day. No paracentesis or drainage placement was required. During the follow-up period of 31 days, there were no re-admissions because of high-volume of lymphatic leakage. One month after surgery, no patients complained of abdominal distension, pain, or fever.

One patient underwent robotic RC with extended PLND, during which 49 lymph nodes were removed. He had drainage tube clamped on Day 9, with a pelvic drainage volume of 1400 mL/day. On Day 10, there was 150-mL/day leakage through the drainage site along the tube, but the ultrasonography did not show significant free fluid in the abdominal or pelvic cavity, and the patient had no abdominal pain or distention. The drainage tube was successfully removed on Day 11, and the patient recovered uneventfully.

Of the extended PLND cases, there were 10/13 (76.9%) cases in which the drainage tube was removed when the drainage volume was more than 100 mL/day. Meanwhile, for the standard PLND cases, only 15 out of 28 (53.6%) cases had the drainage tube removed when the drainage volume was more than 100 mL/day. Of the PC patients, the mean pelvic lymphatic leakage volume before tube clamp in extended PLND cases and in standard PLND cases were 150 mL/day (IQR: 108, 244) and 101 mL/day (IQR: 68, 179), respectively (p = 0.034). The mean pelvic lymphatic leakage volume before tube clamp in pT3 PC patients and in pT2 PC patients were 156 mL/day (IQR: 80, 382) and 101 mL/day (IQR: 76, 151), respectively (p = 0.111). On the day of tube clamp, BC patients who underwent PLND had a high pelvic lymphatic leakage volume (mean, 592 mL/day).

There were 5/41 (12.2%) cases who developed complications after surgery during a mean follow-up of 40 weeks. One patient had mild urine leakage with a DCSCR of 50.3 at Day 2 after surgery and the drain was removed uneventfully at Day 4 after the surgery. One BC patient had postoperative ileus, graded as Clavien-Dindo level I, CCI 8.7, and this resolved with conservative treatment. One case (2.4%) was diagnosed with asymptomatic unilateral lymphoceles 4 months after surgery. No surgical intervention was needed for this patient. One case developed distal urethral stenosis 1 year after surgery and underwent urethral sound dilation and the stenosis subsequently resolved. This complication was classified as a Clavien-Dindo level IIIa, CCI 26.2. There were three cases with complications classified as Clavien-Dindo level I, CCI 8.7.

4 DISCUSSION

Pelvic surgical procedures may cause injury of lymphatic ducts unexpectedly during PLND in cancer treatment and will lead to iatrogenic lymphatic leakage. The use of pelvic drains after PLND is controversial, but it is common to place a pelvic drain for the purpose of observing secondary bleeding, lymphatic leakage, urine leakage, and bowel fistula[7,15,16]. Techniques such as the transperineal approach or peritonectomy during extraperineal robotic RP have been studied for prevention of lymphatic leakage[16]. But the incidence of lymphatic leakage after PLND remains as high as 5%–15% of cases[17]. And it is even higher in extended PLND cases as shown in our study.

Lymphatic circulation drains proteins, lipids, and interstitial fluid back to the systemic circulation, and it plays an important role in regulating the immune responses by both cellular and humoral mechanisms[18]. In the presence of lymphatic leakage, the loss of fluid, triglyceride, lymphocyte, and immunoglobulin may lead to dehydration, nutritional deficiency, and immunologic dysfunction, as well as pain, infection and prolonged hospital stay (about 12.4–20.4 days) mainly due to the persistent high-volume drainage[7].

Regarding lymphatic leakage management, there is no standard of care, with different therapeutic approaches having been reported with varying success rates. Careful intraoperative ligation of the lymphatics, instillation of fibrin sealant, and placement of closed suction drains are used to prevent lymphatic leakage. Shao had shown in their study that lymphatic leakage was a self-limiting complication, the lymphatic leakage may heal within 2–3 weeks without further intervention as lymphatic fluid could be absorbed by the peritoneum[5]. Thus, clinical management modalities have been mainly focused on conservative treatment and watchful waiting[19]. The traditional way of dealing with a persistent high volume (more than 50 mL/day) drainage was to keep the drainage tube till the drainage volume decreased to lower than 50 mL/day[20]. However, it is unclear if this is the best way to manage the high-volume lymphatic leakage by leaving the drain for an extended period, or on the contrary, the lower intra-abdominal pressure produced by the gravity drain may have potentially perpetuated an otherwise small lymph leak, leading to a persistent lymphatic leakage[7].

Usually, the conservative treatment also includes diet control (high protein, low fat, medium-chain triglyceride diet), fasting and total parenteral nutrition, administration of drugs (somatostatin, octreotide, vasoconstrictor pancreatic lipase inhibitor, diuretics, traditional Chinese herb medicine), paracentesis and sclerotherapy[7]. Some authors suggested that if the drainage volume is greater than 1000–1500 mL/day for more than 5 days during conservative treatment, surgical interventions should also be considered to avoid metabolic complications[21]. These approaches have not proven to be completely successful and require long time drain placement. In some cases, this can be for more than 2 weeks, and some patients have to be discharged with the pelvic drainage tube, which causes inconvenience, discomfort, risk of infection, and patient anxiety[3,22].

As presented in this study, our management of persistent high-volume lymphatic leakage is to remove the drain in the early postoperative period. Based on our results, it is safe and effective to use early drainage removal in the management of high-volume lymphatic leakage after PLND. We did not wait for the spontaneous healing but actively managed patients by early clamping of the drainage tube, ultrasonography assessment of no significant residual fluid in the abdominal and pelvic cavity, and then the drain removal. In our series, all patients with pelvic drainage more than 50 mL/day were successfully managed. There was one BC case who underwent extended PLND and had pelvic drainage volume greater than 1400 mL/day, who was successfully managed with this technique as well. This technique shortens patient's recovery period, length of hospital stay, and expedites their return to normal life and work without food restriction and the need for extra medication treatment.

The mechanism of this result is not clearly understood. The absorptive feature of the peritoneal surface allows lymphatic fluid to re-enter into the circulation. We also assume that the closed abdominal cavity has created increased intra-abdominal pressure to the natural level, which may block the lymphatic leakage and facilitate the closure of damaged lymph vessels and recovery. This may be true as Castillo et al. reported in their series that there were three cases with free fluid in the abdominal cavity. These cases were identified on CT scans on postoperative Day 5–7 after patients complained of abdominal distention and pain. Subsequently they were diagnosed with high-output lymphatic leakage. All these three cases were conservatively managed with watchful waiting without paracentesis and drainage placement. All patient's abdominal distention and pain relieved spontaneously[23]. Further research is recommended, including an in vitro and in vivo study to explore the mechanism further.

Lymphatic leakage is not negligible when patients undergo PLND, even in high-volume urological surgeons. Exposure of patients to the risk of lymphatic leakage should be balanced with the proven benefit of PLND for accurate nodal staging and improved oncological control in highly selected patients. Prevention of lymphatic leakage begins with an elegant surgical approach in which surgeons should be extremely careful in ligating or sealing all the open ends of the lymphatic vessels with effective instruments. Recently randomized trail found significant advantages for patients who received bilateral peritoneal interposition flaps as an adjunct to RARP with PLND with regard to lymphoceles[24]. However, if postoperative lymphatic leakage occurs, it can be cautiously and conservatively managed in a short period of time with the technique presented in this study and usually patients will recover uneventfully.

We reported a safe and effective way to tackle the high-volume pelvic lymphatic leakage postrobotic PLDN. There is no need for food restriction and octreotide treatment. This will shorten the drainage time and the hospital stay, fasten the recovery, and improve patient's experience. The surgeon will be more confident to perform the PLND to achieve the goals of staging and better cancer control.

The limits of this study were that this was a single center, retrospective, and small case number study. All these underpowered the conclusion of this study. A well-designed, multicenter, large-scale, prospective study is needed to extend and verify our findings.

Lymphatic leakage is a common postoperative complication after PLND. It is safe to treat the high-volume pelvic lymphatic leakage by early clamping the drainage tube, ultrasonography reassurance of no significant residual fluid in abdominal and pelvic cavity, and then the early removal of the drainage tube.

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