This study found that only 63 of 3427 patients who underwent radical hysterectomy and pelvic lymph node dissection for cervical cancer were diagnosed with postoperative lymphatic leakage, corresponding to an incidence rate of 1.8%. Furthermore, the condition manifested as persistent abdominal drainage in 66.7% of cases, chylous ascites in 19.0% of cases, and vaginal drainage in 14.3% of cases. The time from surgery to onset of postoperative lymphatic leakage ranged from 4–21 days, and all cases resolved in a median 10 days (range, 3–56 days) after conservative treatment. Notably, two cycles of neoadjuvant chemotherapy, a decrease in hemoglobin level of ≥ 20 g/L after surgery and postoperative albumin level < 35 g/L were significantly associated with postoperative lymphatic leakage. Our findings show that postoperative lymphatic leakage is an uncommon complication of lymphadenectomy for cervical cancer and may be managed with conservative treatments. Since postoperative anemia and postoperative hypoproteinemia are risk factors for postoperative lymphatic leakage, attention should be made to meeting the nutritional needs of patients after surgery for cervical cancer.
Lymphatic leakage is an uncommon surgical complication. Prior studies of patients who underwent lymph node dissection for gynecological malignancies have reported incidences of postoperative lymphatic leakage varying from 0.17–4.0% [10–14]. The incidence of postoperative lymphatic leakage in the present study was 1.8%, which is comparable to that reported previously.
The occurrence of lymphatic leakage after surgery for cervical cancer likely results from damage to the lymphatic vessels. The extent of lymph node dissection is closely related to the occurrence of lymph leakage. In the present study, univariate analysis indicated that a significantly larger number of lymph nodes was dissected in the case group (patients diagnosed with postoperative lymphatic leakage) than in the control group. In agreement with our findings, other studies have also reported that a greater range of surgical dissection is associated with an increased risk of lymphatic leakage [15, 17–19]. However, there was no significant difference between the case group and control group in surgical method used (laparoscopic or open), in contrast to the findings of Perez-Medina et al. [20]. The characteristics of lymphatic leakage vary according to its location and the components of its lymphatic fluid. In particular, the fluid is clear or pale-yellow in color when lymphatic leakage occurs in the pelvic cavity but is milky when lymphatic vessels of the digestive tract are damaged due to the triglyceride-rich content.
An important finding of the present study was that although preoperative hemoglobin levels were similar between the case and control groups, a decrease in hemoglobin level of ≥ 20 g/L after surgery was independently associated with increased odds of lymphatic leakage. This is consistent with a previous univariate analysis that chylous ascites may be associated with the duration of surgery and intraoperative blood loss [21]. Although further research is needed to confirm our observations, we consider that the timely correction of postoperative anemia may decrease the risk of lymphatic leakage after surgery.
Our analysis also found that a lower postoperative albumin level was independently associated with lymphatic leakage. Furthermore, other studies have found that lower BMI may be a risk factor for lymphatic leakage [22, 23], implying that nutritional deficiency may enhance the risk of lymphatic leakage after an operation. We consider that the association between hypoproteinemia and postoperative lymphatic leakage may involve a decrease in the fluid pressure in the abdominal and pelvic cavities. Thus, we suggest that the provision of adequate nutrition to correct disturbances in plasma protein levels may reduce the risk of lymphatic leakage after surgery. Interestingly, the preoperative albumin level in the case group was slightly higher than that in the control group. We speculate that more attention may have been paid to perioperative nutrition (e.g., administration of protein supplements) in patients identified as having preoperative hypoproteinemia, which limited the decrease in their albumin levels after surgery. Although additional research is needed to fully characterize the relations of preoperative/postoperative albumin levels with lymphatic leakage, it is important that adequate perioperative nutrition be provided to all patients.
NACT and/or neoadjuvant radiotherapy can reduce the clinical stage of a tumor and make the tumor resectable. A notable finding of this study was that the use of two cycles of NACT was associated with increased odds of lymphatic leakage, in agreement with a previous report [22]. One possible reason for this is that the patients who received NACT would likely have had more advanced cancers and thus greater tumor invasion into local tissues, resulting in surgery that was more difficult and longer in duration, which in turn caused increased intraoperative damage to lymphatic vessels. Chemotherapy can also lead to hepatic dysfunction, immune dysfunction and poor nutritional status [24], leading to anemia and hypoproteinemia, and this may increase the risk of postoperative lymphatic fistula.
In the univariate analysis, postoperative pelvic infection was considered as a possible risk factor for lymphatic leakage after surgery. Postoperative pelvic infection may lead to changes in the micro-environment of the abdominal cavity, aggravating tissue edema and lowering the body protein level. However, collinearity with albumin level prevented this factor being entered into the multivariate analysis, so further research is needed to explore whether pelvic infection is related to lymphatic leakage.
Lymphatic leakage is usually managed conservatively, and the vast majority of cases resolve after the use of such therapies [17]. The available conservative treatments include routine placement of an indwelling drainage tube and provision of a low-fat diet supplemented with medium-chain triglycerides [25] with or without enteral nutrition or total parenteral nutrition. In addition, somatostatin has a good effect in patients with a large amount of transudate. Treatment should be individualized and adjusted to the severity of the lymphatic leakage and its consequences [26]. Although not all patients show recovery after fasting and somatostatin treatment, the initiation of a low-fat and high-protein diet for more than ten days usually achieves a curative effect through tissue self-repair. Lymphangiography is useful for detecting lymphatic leakage occurring after lymph node dissection, and lymphatic embolization is regarded as a new option in the treatment of lymphatic leakage [27, 28].
This study has some limitations. First, since this was a retrospective analysis, the results may be prone to selection bias and information bias. Second, the generalizability of the findings is not known because all patients were from a single institution. Third, the sample size was small, so the study may have been underpowered to detect some real differences between groups. Fourth, collinearity prevented the inclusion of some parameters in the multivariate analysis, so their possible effects on the risk of lymphatic leakage could not be evaluated. Fifth, other unknown confounding factors may have influenced the results. Multicenter, large-scale, prospective studies are needed to extend our observations.
In conclusion, postoperative lymphatic leakage is a rare complication of radical hysterectomy and pelvic node resection for cervical cancer. However, cases of postoperative lymphatic leakage can be managed successfully with conservative treatments. Since postoperative anemia and postoperative hypoproteinemia are risk factors for postsurgical lymphatic leakage, attention should be paid to actively correcting anemia and meeting the nutritional needs of patients after surgery for cervical cancer.