Postoperative Chylous Ascites in Gynecological Malignancies: Two Case Reports and a Literature Review

Aim To explore the potential factors that influence the presentation and recovery of postoperative chylous ascites (CA) in gynecological malignancies. Methods We reported two cases of postoperative CA following gynecological surgery and reviewed the clinical features of 140 patients from 16 relevant papers. Patients' clinicopathological characteristics, surgical approach, and management were summarized. The onset and resolution times of postoperative CA in different groups were analyzed separately. Results The two patients in our report had recovery after conservative treatments. According to the literature review, the median time of onset of postoperative CA was 5 days (range, 0–75 days) after surgery. The median resolution time was 9 days (range, 2–90 days). Among patients, 87.14% of them had lymphadenectomy during gynecological surgeries, while 92.86% of the patients had resolution after conservative treatments. Conclusions Lymphadenectomy during surgery may be relevant to the postoperative CA. Conservative management could be the initial choice for postoperative CA treatment.


Introduction
Chylous ascites (CA) is a rare condition caused by disruption of the lymphatic system, with the accumulation of milky triglyceride-rich chyle in the peritoneal cavity.Multiple etiologies have been reported, including traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic, or cardiogenic.In 1992, the incidence of CA at a large university-based hospital over a two-decade period was reported to be approximately 1 in 20,000 admissions [1].Te rate has likely increased in recent years due to improved survival rates among patients with cancer, extensive surgical interventions, as well as advances in laparoscopic surgery and transplantation [2].
Te symptoms of CA are nonspecifc.Te most typical feature is abdominal distention (81%), followed by indigestion, nausea, and vomiting [3].Te severity depends on the amount of ascitic fuid and its accumulation rate, as well as the patient's health condition.Serious cases of peritonitis and ileus have also been reported.In some cases, deterioration with environmental disturbances and immunological dysfunctions have also been reported [3,4].
Treatment strategies for postoperative CA are broadly divided into two categories, namely, conservative management (dietary restriction and medical therapy) and surgery [4].Conservative management, which aims to reduce the production of chyle and promote closure of the fstula, is successful in most cases [5].Surgical intervention is usually performed following unsuccessful conservative management [6].
Postoperative CA is infrequent after gynecological surgery.Most available studies are case reports.Experience in the prevention, diagnosis, and treatment of postoperative CA is lacking.Here, we described two cases of postoperative CA following gynecological surgeries and reviewed the relevant articles on patients with gynecological malignancies and postoperative CA.Tis study aimed to describe the clinical features of CA after gynecological surgery and to determine the potential factors associated with its prognosis.
1.1.Case 1. Te frst case was a 14-year-old girl with a large pelvic mass.A large complex mass in the abdominal cavity was observed on ultrasonography, and a plain MRI scan confrmed a 31 cm × 25 cm × 16 cm cystic-solid mass with calcifcation and composed of fat, enwrapped with the omentum.Several serum tumor markers were increased.In particular, CA125 was 202.84 U/mL and CA19-9 was 98.61 U/mL.Te alpha-fetoprotein (AFP) level was 262.04 ng/mL.Te patient was subsequently admitted to our hospital for surgical treatment, and open surgery was performed immediately.A 30 cm × 25 cm × 16 cm mass, weighing 7.5 kg, was removed.Te mass originated from the right ovary and densely adhered to the peritoneum and intestine.Te common iliac and para-aortic lymph nodes were unusually enlarged and fused into one large mass of approximately 15 cm × 8 cm × 7 cm, which was adhered to the aorta and inferior vena cava.A Müllerian anomaly was also observed with a small rudimentary horn of the uterus in the right pelvic cavity.During surgery, the ovarian mass along with the right fallopian tube, enlarged lymph nodes, and the right rudimentary horn of the uterus were carefully removed.Grossly, the solid mass consisted of separate cysts with necrotic and hemorrhagic contents.Small amounts of hair and yellow fat were also observed inside the mass.Te microscopic appearance and immunohistochemical results confrmed that the mass consisted of two major parts: a yolk sac tumor and a mature teratoma, both originated from ovarian germ cells.After surgery, the abdominal drainage was normal.A clean yellow liquid (approximately 350-400 mL per day in the frst three days) was drained.In addition to an intravenous infusion, the patient was also provided with soft digestible food to eat.On postoperative day 4, drainage increased to 500 mL per day and the color changed to milky white.Te drained fuid was analyzed: red blood cell count, 1.7 × 10 9 /L; white blood cell count, 1.5 × 10 7 /L; cholesterol, 1.65 mmol/L; total protein, 0.178 g/L; albumin, 0.06 g/L; triglycerides, 4.44 mmol/L; amylase, 50 U/L; and cultures were negative.Te patient was only slightly hypodynamic.Food was restricted once CA was diagnosed, but water was taken at will.Parenteral nutrition (PTN) was provided through peripheral vein infusion to guarantee daily nutrients and calories (25 kcal/kg plus 10% extra calories per day).One compound nutrient formulation containing 885 mL of 11% glucose, 300 mL of essential amino acids (34 g), and 255 mL of 20% intralipid solution supplied 1000 kcal.Moreover, 1000 mL of 10% glucose solution supplied 400 kcal and 500 mL of 8.5% compound amino acid solution supplied 42.5 g amino acids.Te daily drainage volume and appearance are shown in Figure 1(a).Fat-free semi-liquid food was given from day 11 and then changed to low-fat soft food on day 14.Te patient resumed her normal diet on day 15 postsurgery.Te drainage tube was removed on day 15.Subsequently, the patient began chemotherapy.To date, the patient has received six cycles of bleomycin, etoposide, and platinum (BEP) chemotherapy and is still being followed.

Case 2.
Te second patient was a 55-year-old woman who underwent supracervical hysterectomy for a uterine tumor 4 years ago.Histopathological examination revealed that the tumor was low-grade endometrial stromal sarcoma.Te patient refused further treatment until relapse occurred.Irregular vaginal bleeding persisted for 10 days.A mass, measuring 5 cm × 4 cm × 4 cm, was fxed to the residual cervix and palpated through a bimanual examination.Open surgery was performed to remove the mass, along with the residual cervix and bilateral ovaries.Te resection of the parametrium was the same as that for radical hysterectomy.Tumor emboli in the small veins were found in the cardinal ligaments, sacral ligaments, and parametrium tissues.Pelvic and para-aortic lymphadenectomy was not performed because it would not have benefted the patient owing to the extensive metastatic tumor embolus.Te fnal histopathological results confrmed the relapse of low-grade endometrial stromal sarcoma.Abdominal drainage was normal.A clean yellow liquid (approximately 220 mL-240 mL per day in the frst three days) was drained.Te drainage tube was removed on day 3 postsurgery.On day 9, a milky-white discharge from the patient's vaginal cuf when she sat up was detected.Te uric acid, urea, and creatinine levels were 204 μmol/L, 3.50 mmol/L, and 52 μmol/L in the blood; 165 μmol/L, 3.40 mmol/L, and 50 μmol/L in the discharge; and 1190 μmol/L, 53.60 mmol/L, and 10854 μmol/L in the urine.Based on these results, the diagnosis of urinary fstula was excluded.Te biochemistry of the drained fuid was also tested: red blood cell count, 0.9 × 10 9 /L; white blood cell count, 1.1 × 10 7 /L; cholesterol, 1.45 mmol/L; total protein, 0.16 g/L; albumin, 0.04 g/L; triglycerides, 4.21 mmol/L; amylase, 47 U/L; and cultures were negative.Treatment for this patient was similar to the frst case.Food was restricted once CA was diagnosed.Nutrition was guaranteed through parenteral feeds via a peripheral vein.Te patient was also provided with low-fat soft food to eat.Te discharge decreased from day 12 and totally resolved on day 15.Te patient's daily discharge and the conservative management plan are summarized in Figure 1(b).After systematic evaluation by a gynecological oncologist, the patient was administered letrozole for therapy.

Literature Review
We conducted a literature review to evaluate the risk of CA after gynecological surgery.We searched the following databases: PubMed, Embase, and the Cochrane Library.All relevant peer-reviewed articles with the keywords, "chylous ascites," "gynecological surgery," "chylous ascites," and "gynecological malignancies" were considered.Time or language limitations were not included.Te type of paper was also not limited.
Te onset of postoperative CA started 0-75 days after surgery, with a median of 5 days.Te median resolution time was 9 days (range, 2-90 days).For conservative management, nearly a third of the patients (39 patients, 27.86%) were given a high-protein, low-fat, medium-chain triglyceride (MCT)-based diet.More than half of the patients (73 patients, 52.14%) received total parenteral nutrition (TPN), and 13 patients (9.29%) received both management strategies in sequence.Among the patients who received TPN, 21 received somatostatin as supplemental treatment.Finally, 10 patients underwent surgery to correct lymph leakage due to unsuccessful conservative management.
Te patients were divided into diferent groups according to the primary site of disease, surgical approach, lymphadenectomy, lymph node status, conservative management, surgical treatment, and drug therapy.We analyzed the onset and resolution times of CA in these diferent groups.Only patients with specifc grouping information and onset or resolution time were included in this analysis.Te median onset and resolution times in each group are listed in Table 3.  Obstetrics and Gynecology International      Obstetrics and Gynecology International  Obstetrics and Gynecology International

Discussion
Chylous ascites is an infrequent postoperative complication.Among patients with gynecological malignancies, the prevalence ranges from 0.17% to 9% [14][15][16][19][20][21].Notably, numerous cases may be subclinical or may resolve spontaneously; thus, estimating the true prevalence is diffcult.Moreover, most published studies are single-center studies.Terefore, the sample size, selection bias, and surgical procedure diferences may all contribute to a diferent incidence rate.In Zhao's study, the prevalence rate was 0.9% in 997 patients who underwent laparoscopic surgery [19].In contrast, the prevalence was 9% in Solmaz et al.'s study, which included 399 patients who underwent either open or laparoscopic surgery [20].Moreover, the placement of a drainage tube was associated with a higher prevalence.In some studies, a peritoneal drainage tube was not routinely placed during surgery, which may have led to not identifying mild CA, resulting in a relatively lower incidence [14][15][16]21].
Diagnosis is made based on the milky ascitic fuid, which contains triglycerides >200 mg/dL [5].Te ascitic fuid is often detected using an abdominal drainage tube or from paracentesis.
Intraoperative cisterna chili injury and retroperitoneal lymphatic gland dissection are believed to be the most common causes of CA [5].Normally, a small amount of lymphatic leakage caused by lymphadenectomy resolves spontaneously without any symptoms.Injury to the cisterna chili or major lymphatic channels can result in the accumulation of lymphatic fuid in the abdominal cavity and lead to symptoms, such as distention, nutrient imbalance, and infection [5].Cisterna chili receives fatty chyle from the intestine, and thus, its injury results in the accumulation of white or straw-colored lymphatic fuid in the abdominal cavity.Tis is a distinct clinical feature.Radiotherapy following surgery may also be associated with CA.Baiocchi  [12].Tis is probably due to radiation fbrosis of the lymphatic vessels in the small bowel, leading to occlusion and extravasation of the chylous fuid [23].Lymphatic spread is one of the most common patterns of tumor dissemination in gynecological malignancies.According to the National Comprehensive Cancer Network (NCCN), bilateral pelvic lymph node dissection (PLND) and para-aortic lymph node dissection (PALND) are part of the surgical treatment of advanced gynecological malignancies [24][25][26].Te number of lymph nodes removed has been reported to be related to the incidence of CA.In the THIEL study, patients with CA had a higher mean number of removed lymph nodes than those who had not developed CA (51.9 vs. 40.0,p � 0.002) [21].In Tulunay's study, the median number of removed para-aortic lymph nodes (PALN) was 26 (range, 8-54) in patients with CA and 17 (range, 1-76) in patients without CA [16].Tey suggested that the number of harvested PALN, other than the pelvic lymph nodes, was relevant to the development of CA, which was also consistent with Solmaz's fndings.Solmaz et al. recommended an optimal cutof value of >14 harvested PALNs in the prediction of CA, calculated using the receiver operating characteristic (ROC) curve analysis [20].Te dissection of para-aortic lymph nodes usually includes the region from the bifurcation of the aorta to the superior mesenteric artery or the renal veins and is more likely to damage the central lymphatics than the dissection of pelvic lymph nodes.Te frst patient in our study had a large paraaortic lymph node that was dissected using an ultrasonic device.Termal injury to the surrounding tissues or even central lymphatics may be responsible for postoperative CA.In the second patient, the intra-abdominal adhesions resulting from the previous surgery were extremely severe, and the normal anatomical structure was severely damaged.Lymphatic vessels may have been injured, even though no lymph nodes were removed.
Te surgical approach (laparoscopy and open surgery) may also be associated with postoperative CA.Divergent lymphatic vessel sealing approaches, harvesting techniques, diferences in intra-abdominal pressure, and accessible lymph node regions may have been responsible for this discrepancy.Zhao et al. analyzed 997 patients who underwent laparoscopic lymphadenectomy and reported that only 9 patients (0.9%) developed CA [19].Tis was a relatively low prevalence, but there was no control data for open surgery in their study to draw comparisons.In the THIEL study, 20 of 28 patients with CA (71.4%) had laparoscopic treatment.Tis was signifcantly more than those who underwent open surgery (8/28; 28.6%) (p < 0.0001) [21].However, no other studies have compared the prevalence of CA after two diferent approaches, thus it remains As ascitic fuids contain abundant metabolites of longchain triglycerides, food restriction aimed to largely reduce the production of chyle [2,27].Tus, a high-protein and low-fat diet with MCT is recommended in practice [28].If they do not respond well to MCT, patients are asked to fast and rely on total parenteral nutrition (TPN) [29].In a large retrospective study, the efectiveness of TPN in patients with postoperative CA was 100% [30].Te MCT diet provided essential nutrients and was more accepted by the patients.However, summarized from 36 articles, Weniger et al. suggested TPN as the priority selection for patients who had chylous leakage of more than 200 mL/day.Te MCT diet is a more suitable option for patients with chylous leakage of less than 200 mL/day or when TPN is contraindicated [30].In one retrospective study, an enteral nutrition (EN) + MCT plan was reported as superior to TPN alone or MCT alone in terms of the curative efectiveness and cost of treating CA [31].
As for medical therapy, somatostatin, a peptide hormone that suppresses the secretion of numerous gastrointestinal hormones and gastric emptying when working together with TPN or MCT, contributes to relieve the symptoms of CA [31,32].Octreotide, a somatostatin analog, has also been demonstrated to be efective in refractory postoperative CA by relieving portal hypertension and reducing the triglyceride levels in ascites [18,33].In a small retrospective clinical analysis, octreotide plus TPN worked better than TPN alone in eliminating CA [34].Tus, octreotide should be considered if TPN is administered to patients.According to a retrospective study, the application of somatostatin or its analog octreotide improved symptoms and shorten hospital stays [31].
Surgical intervention is usually performed if conservative management fails.Te fstula could be ligated once located via lymphangiography or lymphoscintigraphy before surgery or identifed during surgery [35,36].Less radical approaches, such as abdominal paracentesis, transjugular intrahepatic portosystemic shunt, and peritoneovenous shunts, are also alternatives [5].Paracentesis promptly relieves distention and can help make a diagnosis, but repeated performance may lead to nutrient loss, hypoproteinemia, and increased risk of bacterial peritonitis [37].Successes of lymphatic embolization following lymphangiography have also been widely reported [38,39].Lymphatic embolization could be achieved through diferent percutaneous approaches with diferent liquid embolic agents or balloons to stop the leakage.Normally, the resolution time in patients who underwent surgical treatment was longer than that in patients who underwent conservative management because surgery was not the frst-line choice for patients.Tis was observed in our analysis, where the resolution time was 41 days in the surgical group and 9 days in the conservative group.
Generally, the prognosis of postoperative CA is better than that of nonoperative CA.In our analysis, the median time for resolution was 9 days, with a wide range of 2 to 90 days.Specifcally, in Solmaz et al.'s study, the median time (5 days, 2-12 days) was the shortest [20].However, the longest resolution time was reported by Boran, who reported a patient who had CA lasting for 90 days after para-aortic lymph node dissection [8].Tis patient sequentially received TPN + somatostatin, repeated paracentesis, MCT + somatostatin, and underwent surgery to thoroughly correct the CA.Encouragingly, conservative management works well in patients with CA following gynecological surgeries, with a success rate of 100% in certain studies [15,19,20].In our analysis, 92.86% of patients had a good prognosis after conservative management.

Conclusions
Te current study consists of two parts.First, we reported two cases of postoperative CA caused by gynecological surgeries and described our experience with successful conservative treatment.Ten, we reviewed 16 studies that included 140 patients with postoperative CA.Lymphadenectomy during surgery may be relevant to the occurrence of postoperative CA.Once diagnosed, conservative management could be the initial choice for postoperative CA treatment, and most patients could get resolution from it.

Figure 1 :
Figure 1: Te postoperative conservative management and the daily drainage/discharge volume for patients in case 1 (a) and case 2 (b).TPN: total parenteral nutrition.

Table 1 :
Clinicopathological characteristics, surgical information, and management of patients with chylous ascites.

Table 2 :
Summary of patients' clinicopathological characteristics, surgical approach, and management.

Table 3 :
Te median onset and resolution time in each group.and Gynecology International inconclusive if one approach is superior to the other in preventing postoperative CA.In our analysis, laparoscopic patients had a shorter onset time than open surgery patients (3.5 days vs. 5 days), but the two groups had a similar resolution time (9 days vs. 8 days), suggesting that laparoscopic patients may receive an earlier diagnosis and treatment.Tis in turn, may have resulted in a shorter hospital stay and lower medical costs.