Abstract

Objective

Gastric cancer is the fifth most prevalent cancer and the third leading cause of cancer-related deaths. After gastric cancer surgery, 1.99% of patients developed chylous leaks after dissections of D1 and D2 and 6.3% after dissections of D3 and D4. The milky discharge from the abdominal drains following enteral feeding indicates chylous leak. After cancer surgery, diagnosis and treatment of chylous leaks are crucial. This study aimed to guide the treatment of chylous leaks.

Methods

A total of 213 patients (147 men, 66 women) underwent D2 lymph node dissection after total or subtotal gastric resection. Age, gender, tumor location, type of surgery, number of resected lymph nodes, metastatic lymph nodes, day of lymphatic discharge, diagnosis of chylous leak, treatment, morbidity, mortality, fistula closure, and length of hospital stay were evaluated.

Results

The mean number of lymph nodes removed during surgery was 39 (16-87). Thirteen patients developed chylous leaks, with an average detection time of 5 days (3-7). At the outset of the study, total parenteral nutrition was administered to patients with chylous leaks. The patients were then given a low-fat diet with medium-chain triglycerides (MCT).

Conclusion

The Tg was 230-3497 mg/dL in our study. The chylous leak group had more lymph nodes dissected than the non-chylous leak group, but the difference was not statistically significant. Chylous leaks are associated with preoperative anemia, hypoalbuminemia, and lymph node resection. After drain output dropped below 300 cc/day, a middle-chain triglyceride diet was administered. None of our patients underwent surgery due to chylous leaks, and we can confidently state that patients with chylous leaks can be followed up with the MCT diet.

Introduction

Gastric cancer is the fifth most commonly diagnosed malignancy and the third leading cause of cancer-related deaths worldwide⁽¹⁾. Gastric resection with D2 lymphadenectomy is a standard surgical procedure for gastric cancer patients^{(2, 3)}.

Developing surgical techniques and more aggressive dissections improved the survival of patients with gastric cancer. In addition to this improvement in survival, complications related to these interventions have increased over the past 20 years⁽⁴⁾.

After gastric cancer surgery, chylous leaks can be seen in 1.99% of patients after D1 and D2 dissection and 6.3% after D3 and D4 dissection^{(5, 6)}. The cytoskeleton is lymphatic fluid and is rich in triglyceride (Tg) and lymphocytes. A chylous leak is usually encountered after enteral feeding as a milky discharge from the abdominal drains, which is sterile and rich in Tg. Tg levels are set as ≥110 mg/dL by some authors and ≥200 mg/dL by others, to name it chylous fluid^{(7, 8)}. Diagnosis and management of chylous leaks after cancer surgery are essential^{(9, 10)}.

Lymphatic damage and lymph fluid pressure > abdominal pressure are prerequisites for chylous leakage. Cisterna chyli, which drains intestinal and celiac lymph nodes, is located on the right side of the aorta at the level of L1-L2. Variations in the anatomy may be a reason for the injury, with normal anatomy found only in 50% of patients⁽¹¹⁾. After abdominal cancer surgery, it is observed in approximately 1.1% of cases and can also be observed after donor nephrectomy, abdominal aortic surgery, and trauma other than cancer patients^(12-14).

Materials and Methods

Ethical approval was obtained from University of Health Sciences Türkiye, Prof. Dr. Cemil Taşcıoğlu City Hospital Ethical Committee (number: 2022/30, date: 14.02.2022). All interventions were performed by surgeons experienced in gastric cancer surgery. A total of 213 patients (147 men, 66 women) underwent D2 lymph node dissection after total or subtotal gastric resection. Energy devices are used for the ligation of small vessels and lymphatic vessels. When a large lymph vessel is encountered, it is either ligated with a suture or hemoclip. Patients were analyzed according to age, sex, body mass index (BMI), tumor location, type of surgery, number of resected lymph nodes, metastatic lymph nodes, day of lymphatic discharge, diagnosis of the chylous leak, type of treatment, morbidity, mortality, day of fistula closure, and duration of hospital stay. Data of patients who underwent surgery between January 2011 and September 2021 at University of Health Sciences Türkiye, Prof. Dr. Cemil Taşcıoğlu City Hospital in the Gastrointestinal Surgery Department were retrospectively analyzed. Detailed consent was not obtained from the patients because it was a retrospective study and no interventional procedure was performed. A total of 207 patients were enrolled in the study. One hundred and forty-two 142 were male (68.6%), and 65 were (31.4%) female. The mean age of the patients was 60.9 (29-94). All patients underwent D2 lymph node dissection after either total or subtotal gastric resection. A total of 137 patients (66.2%) underwent total gastrectomy, and 70 (33.8%) underwent subtotal gastrectomy with D2 dissection. The mean BMI of the patients was 26.09 kg/m² (18-43). Tumor localization was in the cardia in 58 (28%), in the corpus in 72 (34.8%), in the antrum in 73 (35.3%), and diffuse in 4 (1.9%). The mean number of lymph nodes harvested during surgery was 39 (16-87). Among all patients, 76 had no lymph node metastasis and 131 had lymph node metastasis (Table 1).

Statistical Analysis

Descriptive statistics of continuous variables were reported as mean ± standard deviation or median (min-max) depending on the data distribution. The normality distribution of the data was evaluated using the Kolmogorov-Smirnov test. Mann-Whitney U test was used to compare non-normally distributed data. Relationships or proportion comparisons between categorical variables were performed using the chi-square test or Fisher’s exact test. The statistical significance level was set as p<0.05.

Results

Total gastrectomy was performed in 140 patients and subtotal gastrectomy in 73 patients. Of the total gastrectomy group, 11 (7.9%) patients, and of the subtotal gastrectomy group, 2 (6.1%) patients had a chylous leak without statistical significance (p=0.22). Patients were given a liquid diet on postoperative day 1. We have 13 patients with chylous leaks. Of the leak group, four were in the N0 group, three in the N1, one in the N2, and 5 in the N3 group. The mean time to leak detection was the 5^th (3-7) postoperative day. Routine drain amylase and Tg tests were not performed. When milky white discharge from abdominal drains was detected with high Tg levels, chylous leaks were considered. Biochemical analysis of drain fluid revealed Tg levels between 230 and 3.497 (mean: 843.5). We did not use lymphoscintigraphy for either the diagnosis or treatment of chylous leaks. After detecting chylous leaks, total parenteral nutrition (TPN) was introduced at the beginning of the study; with increasing experience, patients were started on a low-fat diet with medium-chain Tg (MCT). Six patients received TPN and seven received an MCT diet. None of the patients underwent surgery due to chylous leak. All patients recovered with TPN and MCT diet treatment. None of the patients in the MCT arm switched to TPN. Complications related to chylous leak were evaluated according to Clavien-Dindo (CD) classification⁽¹⁵⁾. Nine patients had CD 2 complications, and four patients had CD 1 complications (Table 2).

Discussion

The number of patients with gastric cancer who undergo radical surgery with aggressive lymph node dissection is increasing. As the number of harvested lymph node increases, the chylous leak also increases with more aggressive surgery, presenting a challenging clinical entity⁽⁵⁾. The standard method of tumor surgery is to remove the tumor with adequate margins and extend lymphadenectomy. For gastric cancers, subtotal or total gastrectomy with D2 resection is the preferred surgical intervention for potentially curable cT2-T4 and cT1N+ tumors. D2 lymphadenectomy should be performed whenever the possibility of nodal involvement can not be dismissed. In addition to the positive effects of extended lymph node dissection, it is associated with an increased risk of complications. The incidence of chylous leaks after major abdominal surgeries varies between 0.17% and 1.1%^{(16, 17)}. It is as high as 7.4% after retroperitoneal and esophageal cytoreductive surgeries^{(12, 17)}. Chylous fluid, chyliform or pseudochylous fluid, and lymphorrhea explain the nature of fluid from abdominal drains. Lymphorrhea is yellow in color, isosmotic to interstitial fluid, and has nearly equal Tg levels with serum due to injury to prenodal ducts. It occurs in approximately 7.4% of patients after abdominal oncologic surgery. The criteria to name it a chylous leak are a milky appearance, a sterile and odorless character with increased Tg level 2≥ two times of serum Tg level or Tg >200 mg/dL. The risk of chylous leaks increases in proximally located tumors. In our study, there were four tumors in the cardia, six in the corpus, two in the antrum, and one diffuse tumor in the chylous leak group. The lowest Tg level was 230 mg/dL, and the highest was 3.497 mg/dL. We obtained a chylous leak ratio of 6.1%, which is compatible with the literature.

Assumpcao et al.⁽¹⁸⁾ determined that after pancreatic surgery of 3.532 patients, postoperative chylous ascites were associated with the number of resected lymph nodes after pancreatic surgery in 3.532 patients. The number of dissected lymph nodes was higher than average (>39) in the chylous leak group, without statistical significance.

All complications were less than CD 3 in our study. No mortality was observed. Most patients recovered after MCT diet intake. The shortest hospitalization period after the detection of the chylous leak was 2 days, whereas the longest was 30 days (mean: 10.3 days). After a decrease in drain discharge below 300 cc/day, if the patient had no symptoms, the drain was withdrawn, and the patient was discharged with the recommendation of a middle-chain Tg diet. Regardless of whether the patients had complaints, they were called for control on the post-op 14^th day. If not diagnosed earlier and managed properly, morbidity and mortality can occur.

Preoperative anemia, hypoalbuminemia, and the number and extent of resected lymph nodes are associated with a chylous leak⁽¹⁹⁾. Patients’ BMI with the chylous leak was lower than the mean BMI of all patients (24.07 vs. 26.09). This result was statistically significant (p=0.03). The mean Hgb level was 12.5 (9.4-16) and the albumin level was 3.04 (2.2-4.3) in the chylous leak group. The relationship between preoperative hemoglobin and albumin levels and chylous leakage was not significant. Manipulation of the para-aortic area and early enteral feeding were identified as independent risk factors for chylous leaks, as described by Kuboki et al.⁽¹¹⁾ before. Patients were started on a liquid diet on postoperative day 1. Previously, after cessation of oral intake, we were administering TPN with somatostatin. TPN administration has its own vascular and infectious complications. We began administering the MCT diet to these patients after they gained more experience. Our study found no complications following MCT feeding in patients with chylous leaks.

Study Limitations

The patient number in our study is not high enough to make thorough suggestions. This is a limitation of our study.

Conclusion

Surgery may be considered in cases of a chylous leak volume of more than 1000 mL/day for 5 days and a persistent leak for two weeks, but none of our patients were operated on due to a chylous leak. After all, we can confidently state that patients with chylous leaks can be followed up with the MCT diet.

The number of patients in our study was not high enough to prompt thorough suggestions. This is a limitation of our study.