Contemporary Management of Chylous Ascites after Retroperitoneal Surgery: Development of an Evidence-Based Treatment Algorithm
2022; Lippincott Williams & Wilkins; Volume: 208; Issue: 1 Linguagem: Inglês
10.1097/ju.0000000000002494
ISSN1527-3792
AutoresKyle Rose, Heather L. Huelster, Erica Roberts, Brandon J. Manley, Scott M. Gilbert, Wade J. Sexton,
Tópico(s)Abdominal Trauma and Injuries
ResumoYou have accessJournal of UrologyReview Articles1 Jul 2022Contemporary Management of Chylous Ascites after Retroperitoneal Surgery: Development of an Evidence-Based Treatment Algorithm Kyle M. Rose, Heather L. Huelster, Erica C. Roberts, Brandon J. Manley, Scott M. Gilbert, and Wade J. Sexton Kyle M. RoseKyle M. Rose *Correspondence: H. Lee Moffitt Cancer Center, 12902 USF Magnolia Dr., Tampa, Florida , 33612 telephone: 813-745-8000; FAX: 813-449-6882; E-mail Address: [email protected] https://orcid.org/0000-0001-7728-1144 Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida , Heather L. HuelsterHeather L. Huelster Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida , Erica C. RobertsErica C. Roberts Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida , Brandon J. ManleyBrandon J. Manley Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida , Scott M. GilbertScott M. Gilbert Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida , and Wade J. SextonWade J. Sexton Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida View All Author Informationhttps://doi.org/10.1097/JU.0000000000002494AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: Chylous ascites (CA) is an uncommon complication that occurs from traumatic disruption of lymphatic channels after retroperitoneal surgery. The purpose of this study was to generate an evidence-based management strategy for CA by reviewing the current literature and available treatment modalities. Materials and Methods: A MEDLINE® literature review was performed for "chylous ascites." Individual patient data were extracted from case series and reports to create an efficacy analysis. Treatment modality, drain output, time to escalation of care and time to resolution were recorded. The efficacy analysis was utilized to generate a data-driven treatment algorithm. Results: The literature review yielded 1,953 articles, from which 146 studies contributed data for 523 patients. The efficacy analysis included 245 patients, 168 (69%) of whom were managed successfully with conservative management (CM), at a median time to resolution of 11 days. Forty-eight patients underwent lymphangiography±embolization after CM, with a success rate of 85%. Thirty-one (12%) patients underwent surgical exploration. When treating CA, the patients who underwent stepwise management with CM followed by lymphangiography if CM failed experienced a resolution rate of 96.7%. An evidence-based treatment algorithm was created to guide treatment selection and duration of therapy before escalating to additional forms of therapy. Conclusions: In this report, we describe the largest conglomeration of iatrogenic CA cases from a literature review (523 cases) and efficacy analysis (245 cases), and created the first evidence-based treatment algorithm for this condition. Treatment success is substantial when using a stepwise combination of CM followed by lymphangiography±embolization. Abbreviations and Acronyms CA chylous ascites CM conservative management INL intranodal lymphangiography IPD individual patient data MCT medium chain triglyceride NPO nil per os PVS peritoneovenous shunting TPN total parenteral nutrition Chylous ascites (CA) is an uncommon but troubling complication that is due to traumatic disruption of lymphatic channels during retroperitoneal surgery.1 The incidence of CA has been reported as high as 7% after complex oncologic abdominal surgery,2 1%–9% following retroperitoneal lymph node dissection3–6 and 1%–5% following laparoscopic nephrectomy.7,8 The clinical consequences of CA include malnourishment, dehydration, hypoalbuminemia and leukopenia due to volume depletion. However rare, this complication may linger for weeks to months, prolonging surgical morbidity and delaying recovery from surgery. This poses a particular problem by delaying patient recovery and the administration of systemic or adjuvant therapies in the setting of malignancy. Treatment algorithms for CA have been proposed by multiple authors,1,3,4,9–11 most of which have been derived from case series and based on cases managed at tertiary referral centers. Although the low incidence of CA precludes generation of high-level evidence, advances in management strategies over the last several decades have resulted in a significant shift in the treatment approach of complicated CA cases. For example, reports of successful management using percutaneous and ablative procedures in contemporary series have fundamentally changed how refractory CA is now managed. Thus, an updated and data-driven treatment algorithm that reflects current options and approaches for managing postoperative CA is needed. We aim to review and update current treatment modalities in the existing CA literature, compare treatment efficacies in iatrogenic CA following retroperitoneal surgery and design an evidence-based algorithm that will aid the retroperitoneal surgeon in managing CA. We believe that by standardizing the treatment of CA, we can decrease morbidity and hasten recovery. Materials and Methods Literature Review We performed a MEDLINE® literature review for "chylous ascites" to establish a current landscape in the existing literature of English-language publications. Internal review board approval was not necessary, given the public availability of the articles used. Full-text articles were then screened by 2 independent authors (KMR, ECR). Disagreement regarding inclusion/exclusion was settled by a third author (HLH). Articles that were evaluated for full-text eligibility required iatrogenic CA following retroperitoneal operations. This included retroperitoneal surgery such as retroperitoneal lymph node dissection, nephrectomy, adrenalectomy, vascular surgery and intra-abdominal anterior spinal surgery. In colorectal surgery, CA may occur because of mesenteric excision and disruption of mesenteric lymphatics. For this reason, we excluded iatrogenic CA cases following colorectal surgery unless a retroperitoneal lymphadenectomy was specifically described. Articles were required to describe the diagnostic confirmation of CA via paracentesis or ascites analysis.9,10 Data Extraction After finalizing articles included in the analysis, granular data were extracted from each publication regarding treatment and efficacy by individual patient data (IPD). Drain output, time to escalation of care and time to resolution of CA were recorded. Patients with complete information reported in drainage amount, treatment modality and duration of therapy were included in the efficacy analysis to generate an evidence-based treatment algorithm. Patients without granular data on time to resolution or escalation of care after each management step described were excluded from the efficacy analysis. Data Organization and Analysis A preliminary analysis identified significant variability in first-step noninvasive management by authors, precluding a stepwise analysis of conservative management (CM). Therefore, patients who underwent a combination of dietary changes, pharmacotherapy, total parenteral nutrition (TPN) and peritoneal drainage were grouped together under CM, and the discrete elements of this aggregate were individually recorded. We defined peritoneal drainage as the requirement of paracentesis beyond the initial diagnostic paracentesis, placement of a percutaneous drain or continuation of a surgical drain for more than 7 days postoperatively. We defined treatment success as the resolution of CA as described by authors or the removal of drains. Unpaired t-tests were used to determine significance between group means. Categorical variables were compared using the chi-squared test. Results Literature Review The initial MEDLINE search yielded 1,953 articles. Figure 1 details the flow diagram showing the inclusion and exclusion of reports. Table 1 outlines the 146 studies included in the final literature review. Studies regarding CA management and outcomes originated from 29 different countries and compiled 523 patients. The supplementary Appendix and supplementary Table list studies included in the literature review and studies along with patients included in the efficacy analysis, respectively (https://www.jurology.com). Figure 1. Flow diagram displays the results of the systematic literature review. A total of 146 studies were included in the final literature review, comprising 523 patients. Table 1. Publications and patients included in the literature review and efficacy analysis, based on surgical subspecialty Literature Review Efficacy Analysis Total Studies/Patients No. Studies (%) No. Pts (%) No. Studies (%) No. Pts (%) Total 146 523 85 245 Urological surgery 72 (49) 213 (41) 40 (47) 62 (25) Gynecologic surgery 33 (23) 197 (37) 21 (25) 146 (60) Vascular surgery 26 (18) 37 (7) 14 (16) 18 (7) Neurosurgery 5 (3) 9 (2) 3 (4) 4 (2) General surgery 4 (3) 4 (1) 3 (4) 3 (1) Colorectal surgery 2 (1) 2 (1) 2 (2) 2 (1) Multidisciplinary 4 (3) 61 (11) 2 (2) 10 (4) Elements of CM Dietary Interventions The aim of dietary interventions in the management of CA is to minimize enterolymphatic flow by augmenting the elements of enteric intake. The initiation of a low-fat diet is typically the first step in management of patients with CA. Although there are no previous clinical trials that compare the efficacy of standard vs low fat diet in CA, the increased rate of lymphatic flow in the cisterna chyli after a fatty meal from 1 ml/kg/hour to 200 ml/kg/hour encourages the utilization of this noninvasive strategy.3,12 A low-fat diet can be augmented with the addition of medium chain triglycerides (MCTs). Long chain triglycerides are converted into monoglycerides and free fatty acids, which are transported via intestinal lymphatics to the cisterna chyli and thus exacerbate chylous leaks (Fig. 2).13 In contrast, MCTs are transported as free fatty acids and glycerol through the portal vein, bypassing the enterolymphatic circulation. Depending on the degree of chylous output per day, some surgeons elect to limit enteral feeding to a clear liquid diet or nil per os (NPO). TPN is typically initiated in the setting of prolonged NPO or liquid diet states, or in patients at high risk for malnutrition. Finally, if dietary or conservative measures are successful, a low-fat diet is typically continued for several weeks postoperatively, although the ideal duration is unknown. Figure 2. Anatomical model of retroperitoneal lymphatic drainage. Illustration demonstrates the antegrade flow of lymph and chyle into the cisterna chyli from the lumbar trunks and mesenteric lymphatic trunk, respectively. These serve as important landmarks during lymphangiography or surgical exploration, and key maneuvers are described to assist in leak identification. TPN TPN consists of intravenous delivery of nutritional products to patients who cannot tolerate or have a contraindication to enteral feeding. TPN is commonly used in the management of CA and serves as a method to minimize gut stimulation and production of chyle. There are several complications which should be considered prior to the initiation of TPN. Advanced intravenous access is required, often in the form of a peripherally inserted central catheter, which carries the potential of pneumothorax, bleeding, venous thrombosis and air embolism.14 From a metabolic standpoint, adverse effects include hyperglycemia, electrolyte abnormalities, refeeding syndrome, Wernicke's encephalopathy and hepatic dysfunction.14 Compared to enteral feeding, infectious and septic complications have occurred more frequently with TPN, which may be due to hyperglycemia.15,16 The effect of TPN on CA resolution is difficult to interpret, given that reports are retrospective and have inherent selection biases that may drive patients with higher CA output to TPN. Solmaz et al described that patients treated with TPN demonstrated a slower resolution of CA.5 Similarly, Tulunay and colleagues noted that surgical therapy was required for CA management more often in the TPN vs the enteral group.17 Nevertheless, utilizing a multidisciplinary team of physicians, nutritionists and pharmacists to administer and manage TPN has been shown to reduce complications and the total cost of therapy.18 Pharmacotherapy Multiple medication regimens have been described in the treatment of iatrogenic CA. The majority of studies have utilized somatostatin or octreotide to decrease creation of chyle. Somatostatin, a hormone produced by the gastrointestinal system, acts to inhibit splanchnic intestinal peptides such as glucagon.9 Ultimately, this decreases portal pressure and enterohepatic lymphatic flow, thereby decreasing chyle leakage. Somatostatin has a relatively short half-life of 1–3 minutes, requiring continuous intravenous injection beginning at 100 μg/24 hours.19 Octreotide is a synthetic analogue of somatostatin with a longer half-life, which enables subcutaneous administration, with an initial dose of 100 μg 3 times daily, but can be increased up to 200 μg 3 times daily depending on response to therapy.5,11,20 Pan et al retrospectively compared these 2 agents vs dietary measures alone and noted that pharmacotherapy reduced the time to clinical success (4.4 vs 11.6 days), time to resume oral intake (8.8 vs 16.4 days) and time to drain removal (12.0 vs 18.6 days).20 The use of diuretics has also been described, which may partially alleviate the peripheral edema resulting from hypoalbuminemia.21–24 Peritoneal Drainage The method of ascites drainage is dependent on the timing of postoperative diagnosis, the existing drains in place at diagnosis and the chylous output volume. Patients may develop CA during the immediate post-surgical hospitalization, in which case many have existing surgical drains already in place. In these events, continuous bulb suction can be used to monitor daily output. In contrast, patients may present between 1 and 4 weeks postoperatively with abdominal distension, which requires diagnostic and therapeutic paracentesis. Following the initial paracentesis, the decision to continue intermittent paracentesis vs placement of an indwelling intraperitoneal drainage catheter is both physician and patient dependent, influenced by a patient's clinical course. An option with an indwelling catheter is the integration of a valve mechanism for intermittent drainage (eg PleurX®) instead of continuous gravity or suction drainage. This allows for intermittent abdominal drainage as abdominal distension occurs. Intermittent drainage might minimize the creation of a negative pressure circuit that could promote continuous lymphatic leakage and excessive volume loss. However, no current efficacy data exist to favor one type of drainage over another. Percutaneous Lymphangiography and Embolization Lymphangiography with or without embolization is typically used in the management of CA when patients fail CM.25–30 Contemporary series describe intranodal lymphangiography (INL), which uses ultrasound-guided percutaneous access to the inguinal lymph nodes to enable antegrade lymphangiography.25,26,28 Once lymphatic leakage is identified via INL, the closest upstream lymph node that provides afferent flow is identified, punctured and embolized.27,30 Originally, pedal lymphangiography was used to identify lymphatic channels and guide ablation,29 but this technique is time-consuming, is difficult to duplicate and shows no differences in success rates compared to INL.26,30 Limitations of INL include the difficult to treat lymphatic injuries at the level of the cisterna chyli and cephalad.26 Retrograde lymphangiography has been described in several reports and is often used when antegrade identification of lymphatic leakage is unsuccessful.28,31–35 Lymphostasis may also be achieved by percutaneously accessing the lymphopseudoaneurysm, then sealing with endovascular coils and glue mixture.27 Lymphangiography is typically performed with ethiodized oil (eg Lipiodol®), which creates an inflammatory reaction at the sites of extravasation and the soft tissue adjacent to the retained agent.29 In some cases, infusion of ethiodized oil alone is both diagnostic and therapeutic, while others have utilized embolization agents during lymphangiography. Two reviews of the literature revealed that in patients undergoing lymphangiography with or without embolization, lymphangiography with ethiodized oil alone was successful in 55%–67%, vs 70%–89% in those who also underwent embolization.25,28 Commonly used embolization agents include butyl cyanoacrylate, doxycycline and coils.26–28,30,36,37 Majdalany et al described a stepwise lymphangiographic approach in their multi-institutional series.28 The authors describe an initial bi-inguinal INL with ethiodized oil to identify lymphatic flow into the pelvis and retroperitoneum. Glue embolization was then performed in patients with extravasation identified at the pelvic sidewall or below an accessible retroperitoneal vessel. When retroperitoneal lymphatics were identified, percutaneous transabdominal lymphatic access was achieved, followed by embolization with butyl cyanoacrylate glue and ethiodized oil. In patients who did not demonstrate a leak on lymphangiography, but in whom there was high clinical suspicion, retrograde thoracic duct access was established, followed by balloon occlusion and retrograde lymphangiography and sclerotherapy. Peritoneovenous Shunting (PVS) PVS has been frequently used for ascites of cirrhotic and malignant origin, and transfers intraperitoneal fluid to the venous system. PVS has been described in refractory CA cases specifically.2–4,21 A series of 20 patients with CA was described by Yarmohammadi and colleagues.21 In this study, ascites resolved in 90% of patients, ultimately leading to shunt removal at an average of 162 days post-insertion. Complications associated with shunting occurred in 40%, including pulmonary embolism, superior vena cava thrombosis, subclinical disseminated intravascular coagulopathy and shunt occlusion requiring revision.21 More serious side effects have been reported, including peritonitis and sepsis.2,4 In the MD Anderson experience with CA, all 5 patients who underwent PVS had shunt malfunction, 4 of whom required revision.4 Surgical Management Surgical therapy is typically reserved as a final but definitive step in the management of CA. Lymphaticovenular anastomosis is a microsurgical technique that bypasses the retroperitoneal lymphatics and redirects lymphatic flow to the venous system. This can be accomplished in the lower extremity or in the retroperitoneal space by anastomosing lymphatic channels to the gonadal vein.38,39 The most reported surgical method to definitively treat CA is surgical exploration and ligation via laparoscopy or laparotomy. Injection of the lower extremity with blue dye may help assist in identifying chylous leakage from the lumbar trunk in the retroperitoneum.40–42 In contrast, several techniques may be used to examine the lymphatic drainage from the intestines and mesentery (Fig. 2). These include performing INL during laparotomy43 and intraoperative injection of blue dye into the small bowel mesentary.44 Several authors describe enteral regimens prior to reoperation to help localize chylous leakage from the enterolymphatic channels, such as high-fat oral boluses.45–48 Examples of these include Intralipid®,45 milk,48 dyed cream46 and peanut oil.47 A typical strategy is administration of approximately 200 ml of these agents 6 hours prior to exploration, although intraoperative nasogastric tube administration has also been described.46 Surgical methods may vary between open and laparoscopic approaches, depending on the index surgery and surgeon skill set. Following ligation, surgeons may supplement lymphostasis with hemostatic agents during reoperations, including oxidized cellulose49 and fibrin glue.43 One potential disadvantage in laparoscopic ligation is the concealment of lymphatic leaks by the pressure of the pneumoperitoneum. In our review, surgery was unsuccessful in controlling CA in only 1 case that was then managed with 5 cycles of external beam radiation.50 Efficacy Analysis Efficacy data were available for 245 patients from 85 studies (Table 2, and the supplementary Figure and Table, https://www.jurology.com). CM was utilized in all patients initially and was successful in resolving CA in 168 (69%). Table 2 demonstrates the frequencies of therapies used and underscores the variability among CM elements. There was a significant difference between the successful CM and nonsuccessful CM groups in the time to resolution vs escalation of care (median 11 vs 22 days, p <0.01). TPN was more commonly utilized in the successful vs nonsuccessful group (54% vs 36%, p=0.02), but the remaining elements of CM were similar between the 2 groups. Table 2. Management of iatrogenic CA within efficacy analysis cohort Successful Not Successful p Value CM (245 pts): No. outcome of all CM therapies combined (%) 168 (68.5) 77 (31.4) Median days to resolution vs escalation (IQR) 11 (8–16) 22 (14–42) 750 ml/day). These thresholds were selected to capture the patients at the upper range demonstrated for both days to resolution in the successfully managed CM patients and the daily drain output for patients who required additional therapies. Drain output was described if patients have relative improvement in daily output within 21 days but output remains >750 ml/day. If drainage remains elevated 7–10 days following lymphangiography, repeat lymphangiography with embolization is appropriate and has been successful in several reports.25,26,28,30 Lastly, surgical exploration remains the final step in management. Reoperation should be a shared decision between the surgeon and patient. However, the timing of reoperation is critical to prevent further complications and to maximize the likelihood of CA resolution. The intense inflammatory reaction and tissue friability that occur in postoperative weeks 2–6 can make reoperation more difficult and predispose to further complications. Five patients in the efficacy analysis were managed with surgery after an incomplete trial of CM (<21 days). This may reflect patient and surgeon preference, or the availability of interventional radiologist expertise. In the absence of patient and surgeon factors that require immediate resolution of CA by surgical therapy, CM should be initiated in all patients, followed by lymphangiography. Although the treatment algorithm above represents the only evidence-based management of CA to date, there are several intangible patient factors that may guide treatment selection. For this reason, surgeons should consider social, institutional and occupational factors when selecting treatment of CA, especially the aspects of CM. Limitations of our efficacy analysis and treatment algorithm include the exclusion of CA series if data were presented as a central tendency measurement, such as a mean or median to represent the entire case series, rather than IPD. These studies were included in the descriptive literature review but excluded from the efficacy analysis.3,4,7,21 Given that most authors presented IPD with time to escalation or resolution, we chose this method of comparison, rather than a meta-analysis. This may represent a selection bias, but allowed for inclusion of far more patients than the sum of the excluded studies. Regardless, the results of this analysis should be interpreted with the possibility of selection and publication bias. Second, the significant heterogeneity among CM would not permit for a stepwise analysis within conservative treatment. For this reason, the elements of CM cannot be compared for efficacy in a meaningful way. Lastly, our literature review, although thorough, did not include study registration or review of bias, which are utilized in systematic reviews and meta-analyses. Despite these limitations, this report represents the first evidence-based guideline in the management of CA. Future investigations should include multicenter prospective registries to evaluate the utilization of CM elements and provide more insight into the selection of these treatments. Due to the rarity of CA incidence after retroperitoneal surgery and the technical demands of retroperitoneal dissection in most cases producing CA, we recommend that advanced treatment of CA be focused to tertiary care centers that have access to the interventional radiology techniques noted above. Conclusions Iatrogenic CA is an uncommon complication after retroperitoneal surgery with substantial variability in published management strategies. We generated the first evidence-based treatment algorithm which encompasses various retroperitoneal dissection procedures across several surgical subspecialties. Current management of CA is largely based on tertiary care center experiences or cases series. Our review suggests that previously published reports utilized CM for extended periods of time, potentially increasing patient morbidity associated with unsuccessful treatment. Alternatively, some patients were advanced to reoperation without an adequate trial of conservative measures. 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Ethics Statement: In lieu of a formal ethics committee, the principles of the Helsinki Declaration were followed. © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 208Issue 1July 2022Page: 53-61Supplementary Materials PEER REVIEW REPORT Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.Keywordslymphretroperitoneal spacelymph node excisionlymphatic vesselschylous ascitesMetricsAuthor Information Kyle M. Rose Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida *Correspondence: H. Lee Moffitt Cancer Center, 12902 USF Magnolia Dr., Tampa, Florida , 33612 telephone: 813-745-8000; FAX: 813-449-6882; E-mail Address: [email protected] More articles by this author Heather L. Huelster Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Erica C. Roberts Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Brandon J. Manley Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Scott M. Gilbert Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Wade J. Sexton Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Expand All Support: None. Conflict of Interest: Erica C. Roberts: Merck, Department of Defense, Kidney Cancer Association. Wade J. Sexton: Urogen; expert testimony. Ethics Statement: In lieu of a formal ethics committee, the principles of the Helsinki Declaration were followed. Advertisement Advertisement PDF downloadLoading ...
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