- Email: [email protected]
A Simple Method Minimizes Chylothorax after Minimally Invasive Esophagectomy
A Simple Method Minimizes Chylothorax after Minimally Invasive Esophagectomy Yaxing Shen, MD, Mingxiang Feng, MD, Muhammad Asim Khan, MBBS, Hao Wang, MD, Lijie Tan, MD, Qun Wang, MD Postoperative chylothorax is a rare, but potentially fatal complication after esophagectomy. Preventive measures aimed at decreasing the incidence of chyle leakage after minimally invasive esophagectomy (MIE) could potentially reduce the high postoperative mortality associated with this complication. However, previous techniques are traumatic and time consuming. We present a simple method in the prophylaxis of chylothorax after MIE. STUDY DESIGN: A total of 344 consecutive esophageal cancer patients who underwent 3-stage MIE between June 2006 and July 2012 were included. Of these, 178 patients were given preoperative milk orally 6 hours before surgery (Group Mþ), and 166 underwent MIE without preoperative milk and served as controls (Group M). Patient demographics were retrospectively collected. The incidences of intraoperative thoracic duct identification and postoperative chylothorax were recorded and statistically compared between the 2 groups. RESULTS: In this cohort, the 2 groups were comparable in clinical features including age, sex, tumor location, histologic type, and TNM stage. No patient was converted to open thoracotomy. During the thoracoscopic stage, a higher incidence of duct identification (95.5% vs 12.7%, p < 0.001) and a lower incidence of duct ligation (6.74% vs 13.25%, p ¼ 0.039) were recorded in Group Mþ. Postoperatively, a total of 10 cases of chylothorax (2.91%) were observed. The incidence of chylothorax was significantly lower in Group Mþ than in Group M (0.56% vs 5.42%, p ¼ 0.018). CONCLUSIONS: Preoperative oral administration of milk facilitates visualization of the thoracic duct and minimizes the risk of iatrogenic injury to the thoracic duct during thoracoscopic esophagectomy. It is a simple and safe method for preventing chyle leakage after MIE. A randomized and controlled trial is required to confirm these findings. (J Am Coll Surg 2014;218: 108e112. 2014 by the American College of Surgeons)
BACKGROUND:
remains high.4,5 Therefore, a preventive method is required to deal with chyle leakage after esophagectomy. Previously, thoracic duct ligation was reported to be effective in the prophylaxis of chylothorax.6-8 In a recent study, the incidence of chylothorax fell from 10% to 1.5% when prophylactic thoracic duct mass ligation was performed.9 However, the sample size of the study was relatively small, and the effect of the learning curve might contribute to the high incidence of chylothorax in the controls. Secondly, as a traumatic procedure, prophylactic ligation may cause extra injury to adjacent structures such as the intercostal vessels and the azygous vein, which would make MIE more invasive. In this study, we hypothesized that improved visualization of the thoracic duct would minimize inadvertent injury to the duct and decrease the incidence of postoperative chylothorax. Based on our 7-year experience performing MIE, we herein report our simple method and examine its efficacy in a retrospective study.
During surgical resection of esophageal cancer, the thoracic duct is vulnerable to iatrogenic injury, which will lead to postoperative chyle leakage.1,2 Recently, promising results from minimally invasive esophagectomy (MIE) were shown in decreasing pulmonary complications.3 However, the incidence of chylothorax in MIE is comparable to that in open chest approaches, and the recorded mortality rate CME questions for this article available at http://jacscme.facs.org Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, Editor-in-Chief, has nothing to disclose. Received July 19, 2013; Revised September 23, 2013; Accepted September 24, 2013. From the Division of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China (Shen, Feng, H Wang, Tan, Q Wang) and University College Hospital, London, United Kingdom (Khan). Correspondence address: Lijie Tan, MD, 180 Fenglin Rd, Division of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. email: [email protected]
ª 2014 by the American College of Surgeons Published by Elsevier Inc.
108
ISSN 1072-7515/13/$36.00 http://dx.doi.org/10.1016/j.jamcollsurg.2013.09.014
Shen et al
Vol. 218, No. 1, January 2014
METHODS A total of 344 consecutive patients underwent 3-stage MIE at our institution between June 2006 and July 2012 and were enrolled in this study. Tumor lesions were clinically staged using endoscopy, tissue biopsy, abdominal-thoracic CT, and endoscopic ultrasound. Inclusion criteria for MIE were: clinically staged T1-3N0M0 tumors; no previous history of cancer; no previous history of neck or chest surgery; and an American Society of Anesthesiologists (ASA) score of I to III. All operations were performed under the direction of the same senior consultant over the same time period. Patients who met inclusion criteria were assigned to 2 surgical groups. Preoperative milk was given to only 1 surgical group (Group Mþ), who received 500 mL of whole milk orally 6 hours before MIE. The other surgical group underwent MIE without preoperative milk and served as controls (Group M). All patients fasted for at least 6 hours before surgery. Patient demographics are summarized in Table 1. The hospital ethics committee approved the study. All patients gave their written informed consent before the operation after receiving careful explanation of the goals of the study. Table 1.
Clinical Characteristics
Characteristic
Age, mean, y Sex, M:F Location, U; M; L, n Neoadjuvant therapy Histology, SC; AD; othersx Stage, T1;T2;T3;T4jj Thoracic duct visualization Thoracic duct ligation Blood loss, mL Blood transfusion Thoracic stage duration, min Length of stay, d
Group Mþ (n ¼ 178)
Group M (n ¼ 166)
62.2 8.3 128:50 31; 123; 24 7
60.3 9.1 130:36 26; 120; 20 9
0.740* 0.171y 0.810y 0.512y
167;8;3 42; 50; 81; 5
155;7;4 33; 54; 77; 2
0.941z 0.543z
170 12 158 70 0
21 37 163 67 0
<0.001y <0.001y 0.328{ –
87 29 8.9 3.3
102 35 10.1 4.2
0.054* 0.427{
p Value
Group Mþ patients received preoperative milk; Group M- patients did not. values indicate standard deviation. *Student’s t-test. y Chi-square test. z Fisher’s exact test. x Others: 3 cases of small cell carcinoma in both groups and 1 case of carcinoma sarcomatode in Group Mþ. jj Including 7 cases of T4b, and 1 case of T4 (in Group Mþ), which was invasive to the thoracic duct, and the patient had resection of thoracic duct during MIE. { Mann-Whitney test. AD, adenocarcinoma; L, lower; M, middle; SC, squamous cancer; U, upper.
Preoperative Milk Minimizes Chylothorax
109
Operative procedures All patients received a combination of epidural and general anesthesia before the operation and were provided with patient-controlled analgesia postoperatively. Patients were intubated with a left-sided, double-lumen endotracheal tube to accomplish selective deflation of the right lung during the thoracic phase of the thoracic esophagectomy, and they were switched to double-lung ventilation during the abdominal and cervical stages. The MIE consisted of 3 stages: the thoracic, the abdominal, and the cervical stages. Thoracic stage The thoracic stage included esophageal mobilization and mediastinal lymphadenectomy. An observation port was placed at the seventh intercostal space along the midaxillary line, and another10-mm port was placed at the ninth intercostal space in the mid-scapular line. Two 5-mm ports were placed at the third intercostal space along the midaxillary line and just inferior to the tip of the scapula, respectively. An artificial CO2 pneumothorax was achieved at a pressure of 8 mmHg. After thoracoscopic exploration, the azygous vein was double-ligated by Hem-o-Lok (Teleflex) and then divided, after mobilization of the thoracic esophagus, which progressed from the tumor inspection site to the thoracic inlet cranially, and to the hiatus caudally. Identification of the thoracic duct was confirmed if the vessel was visible without any additional dissection. One of 3 methods was used when handling the thoracic duct: ligation, dissection, or preservation; the method was selected according to the operative findings. During the surgical resection, the thoracic duct was ligated only if it were deemed inadvertently injured, or divided if it were involved in the tumor process. Otherwise, the duct was preserved. Mediastinal lymphadenectomy was performed along the bilateral recurrent laryngeal nerves, together with the subcarinal and paraesophageal lymph node stations. The procedure was completed by placing an intercostal drain and closing the thoracic ports. Abdominal and cervical stages The abdominal and cervical stages were carried out as previously described.10 Jejunostomy was performed on all patients in order to provide enteral nutrition (usually begun on the second postoperative day). The operation concluded with closure of the cervical and abdominal incisions in layers. Data collection and statistical analysis Clinical data, including patient demographics and operative features of all patients, were collected from the clinical database at our institution. Postoperative chylothorax was
110
Shen et al
J Am Coll Surg
Preoperative Milk Minimizes Chylothorax
suspected when chylous drainage from the chest tube exceeded 400 mL. The diagnosis was then verified with laboratory confirmation of elevated triglycerides (>110 mL/dL) or positive Sudan III stain in the setting of sustained drainage. Clinical features of patients with postoperative chylothorax, their associated treatments, and their overall outcomes were also recorded. All data were tabulated using Microsoft Excel for further analysis. Statistical analysis was undertaken using SPSS software (version 17.0). Variables were compared using the Mann-Whitney test, the Student’s t -test, and chi-square test. A 2-sided p value less than 0.05 was considered statistically significant.
RESULTS Patient demographics There was a male predominance in our cohort of 258 men and 86 women. The mean age at time of surgery was 61.0 5.3 years (SD). There was no significant difference in age (p ¼ 0.740) or sex (p ¼ 0.171) between Group Mþ and Group M. According to the UICC (Union for International Cancer Control) esophageal cancer TNM staging system (7th Edition, 2010), there were 75 cases of pT1 (21.80%), 104 cases of pT2 (30.23%), 158 cases of pT3 (45.93%), and 7 cases of pT4 (2.03%) in our study. The depth of tumor invasion was similar between the 2 groups (p ¼ 0.543). There was no significant difference in tumor location (p ¼ 0.810) or histologic subtype (p ¼ 0.941) between the 2 groups (Table 1). Operative features All patients underwent thoracoscopic esophagectomy without conversion to open thoracotomy. During surgery, the thoracic duct was visually identified (Fig. 1) in 191 of 344 patients (170 patients in Group Mþ vs 21 patients in Group M). A significantly higher rate of thoracic duct identification was recorded in Group Mþ compared with Group M (95.51% vs 12.65%, p < 0.001). Accidental injury requiring thoracic duct ligation was noted in 6.74% of patients in Group Mþ vs 13.25% of patients in Group M (p ¼ 0.039). One patient in Group Mþ was found to have tumor invasion to the thoracic duct, and the patient had resection of the thoracic duct during MIE. No significant differences were found in the length of hospital stay, volume of blood loss, or number of blood transfusions between the 2 groups. Operative features are listed in Table 1. Morbidity and mortality No patients died during the operation in either group (Table 2). Complications were observed in 152
Figure 1. Identification of the thoracic duct during thoracoscopic esophagectomy. The thoracic duct (TD) was prominent after preoperative oral administration of milk. AA, aortic artery; Az, azygous vein; E, esophagus; B, left main bronchus.
patients (39.89% in Group Mþ vs 48.80% in Group M, p ¼ 0.096). In Group M, 1 patient developed a gastric conduit leak on the eighth postoperative day and died 2 weeks later because of septic shock and multiorgan failure. No significant difference in 30-day mortality was noted between the 2 groups. Management and outcome of chylothorax There were 10 cases of chylothorax in this study, and the incidence of postoperative chylothorax was significantly lower in Group Mþ compared with Group M (0.56% vs 5.42%, respectively; p ¼ 0.018). All 10 cases of chylothorax failed in thoracic duct identification during the operation, and 3 patients with postoperative Table 2. Mortality and Morbidity Variable
Mortality Morbidity Chylothoraxz Cervical anastomotic leak Gastric conduit failure Respiratory complications Hoarsenessx Delayed gastric emptying Bleedingjj
Group Mþ (n ¼ 178)
Group M (n ¼ 166)
p Value
0 71 1 37 2 18 9 3 1
1 81 9 41 1 17 11 2 0
0.972* 0.096y 0.018* 0.387y 0.952* 0.969y 0.534* 0.937* 0.972*
Group Mþ patients received preoperative milk; Group M- patients did not. *Fisher’s exact test. y Chi-square test. z A total of 3 patients required reoperation and religation of thoracic duct due to chylothorax (0% in Group Mþ vs 1.22% in Group M, p ¼ 0.371). x Including temporary and permanent recurrent laryngeal nerve palsy. jj Bleeding requiring reoperation.
Shen et al
Vol. 218, No. 1, January 2014
chylothorax had undergone intraoperative thoracic duct ligation (0% in Group Mþ vs 1.81% in Group M, p ¼ 0.222). Conservative chylothorax treatment consisted of intrapleural drainage via chest tube, total parenteral nutrition, and pleurodesis (50% hypertonic glucose injected into the thoracic cavity). Patients in whom conservative treatment was not successful underwent reoperation. In this study, 4 patients were treated conservatively and 6 patients (all from Group M, Table 3) required reoperation due to persistent chyle leakage despite conservative treatment for at least 5 days. The incidence of reoperation for chylothorax was lower in Group Mþ compared with Group M (0% vs 3.61%, p ¼ 0.032). Thoracoscopic exploration was performed on all patients who underwent reoperation, and milk was given intraoperatively via nasal-gastric tube to facilitate identification of the thoracic duct. The injuries were identified and ligated under thoracoscopy, and chyle leakage resolved within 24 hours of reoperation in all patients. One patient developed a thoracic cavity infection 6 months after discharge (from Group M, Table 3). The patient recovered without sequelae after reoperation for thoracic debridement.
DISCUSSION As the most common subtype in the East, esophageal squamous cell cancer is more commonly located in the mid-upper thoracic esophagus,11 and the close relationship of the thoracic duct to the thoracic esophagus makes iatrogenic injury more frequent during operation. In a recent study from Shah and associates,12 squamous histology was identified as an independent predictor of chylothorax after esophagectomy, and it follows that patients from the East are at higher risk of chylothorax Table 3. Pt. no.
1 2 3 4 5 6 7 8 9 10
Preoperative Milk Minimizes Chylothorax
111
compared with their western counterparts. In the surgical resection of esophageal squamous cell cancer, we introduced preoperative milk 6 hours before surgery and observed a higher rate of intraoperative thoracic duct identification and a lower incidence of postoperative chylothorax, which suggested preoperative milk as an effective method in the prevention of chyle leakage. Previously, researchers successfully used 50 mL of cream administered orally 3 hours before open esophagectomy to reduce the incidence of chylothorax.13 The success of this method for identifying the thoracic duct during minimally invasive surgery remains uncertain. Inspired by this idea, oral preoperative milk was given 6 hours before MIE and the thoracic duct was observed as a bright white vessel under thoracoscopy (Fig. 1). The presence of fat facilitated visualization of the thoracic duct, which had subsequently widened in diameter to 2 to 3 mm compared with the usual 1 to 2 mm.14 The change in size and appearance of the thoracic duct, as well as the magnified view afforded by thoracoscopy, improved identification of thoracic duct during MIE. Given the improvements on duct visualization, preoperative milk was effective in preventing chylothorax in this study. First, preoperative milk administration minimized intraoperative thoracic duct ligation due to incidental injury (6.74% of Group Mþ patients vs 13.25% of Group M), which saved the time of ligation and assured continuity of the operation. Second, even when thoracic duct injury occurred during the surgery, chylous fluid would be suggestive in bright white due to preoperative milk, and ligation could be easily performed to stop the chyle leakage at the injury site, which saved patients from potential chylothorax. Because milk had been administered 6 hours before surgery, the improvements in identification would not interfere with the operation,
Clinical Features of Patients with Postoperative Chylothorax Group
Age, y
Sex
Location
Histology
M M Mþ M M M M M M M
60 58 63 58 62 57 70 56 61 70
M M M F M F M F M M
M U M M M M U M M U
SC SC SC SC AD SC SC SC SC SC
Thoracic duct* Identification Ligation
e e e e e þ e e e e
e þ e þ e e e þ e e
Treatment
Outcomes
Reoperation Reoperation Pleurodesis Reoperation Pleurodesis Pleurodesis Reoperation Reoperation Reoperation Pleurodesis
Survival Survival Survival Survival Survival Survival Survival Survival Survival Survivaly
Group Mþ patients received preoperative milk; Group M- patients did not. *Identification and injury to the thoracic duct recorded during MIE. y This patient developed infection 6 months after discharge and recovered without sequelae after reoperation for thoracic debridement. AD, adenocarcinoma; M, middle; MIE, minimally invasive esophagectomy; SC, squamous cancer; U, upper.
112
Shen et al
J Am Coll Surg
Preoperative Milk Minimizes Chylothorax
making administration of preoperative milk a simple method to prevent chylothorax after MIE. To prevent the chyle leakage, prophylactic ligation of the thoracic duct is favored during esophagectomy. In a recent study, chyle leakage decreased from 2.1% to 1.2% when intraoperative thoracic duct ligation was performed on all patients operated on for esophageal cancer,14 which means that less than 1% of patients benefit from prophylactic ligation. In addition, the long-term effect of thoracic duct ligation on esophageal cancer patients remains uncertain. Because poor nutritional status is commonly noted in these patients,15 ligation of the thoracic duct may interfere with absorption of fats and other nutrients,16 which leads to the safety concerns regarding this procedure. Reoperation due to chylothorax was observed in 6 patients in Group M; 3 of these had a history of duct ligation during the original MIE. These results suggested that 3 of 21 ligations (14.29%) had failed during thoracoscopic esophagectomy. Although thoracic duct ligation has been proven effective,14 it does not completely eliminate the occurrence of chylothorax because there is considerable variation in duct anatomy, and some injury might be missed during the operation.9 On the other hand, preoperative milk minimized the incidence of reoperation in Group Mþ, which made MIE a safer procedure because reoperation for chylothorax carries high mortality when patients are nutritionally and immunologically depleted.7 We believe that identification and preservation of the thoracic duct using milk is a safe method for prevention of chylothorax after MIE. In our study, thoracic ligation was performed in 6.74% of Group Mþ patients compared with 13.25% in Group M. The lower incidence of ligation in Group Mþ could be explained by improvement in duct visualization during MIE because thoracic duct leakage appeared bright white. In Group M, the chyle leakage was often observed as transparent liquid under thoracoscopy, and in some cases might be falsely positive without intraoperative laboratory testing. Therefore, more ligations were performed if indefinite thoracic duct injury was suspected.
CONCLUSIONS Although this study has limitations, including its retrospective design and lack of randomized controls, preoperative administration of milk has shown simplicity and safety in minimizing chylothorax after MIE. Further study based on larger samples is required to confirm this finding. Author Contributions Study conception and design: Shen Acquisition of data: Feng, H Wang
Analysis and interpretation of data: Khan Drafting of manuscript: Shen Critical revision: Tan, Q Wang REFERENCES 1. Bolger C, Walsh TN, Tanner WA, et al. Chylothorax after oesophagectomy. Br J Surg 1991;78:587e588. 2. Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007;32: 362e369. 3. Biere SS, van Berge Henegouwen MI, Maas KW, et al. Minimally invasive vs open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 2012;379:1887e1892. 4. Lagarde SM, Omloo JM, de Jong K, et al. Incidence and management of chyle leakage after esophagectomy. Ann Thorac Surg 2005;80:449e454. 5. Kranzfelder M, Gertler R, Hapfelmeier A, et al. Chylothorax after esophagectomy for cancer: impact of the surgical approach and neoadjuvant treatment: systematic review and institutional analysis. Surg Endosc 2013;27:3530e3538. 6. Rao DV, Chava SP, Sahni P, et al. Thoracic duct injury during esophagectomy: 20 years’ experience at a tertiary care center in a developing country. Dis Esophagus 2004;17:141e145. 7. Merigliano S, Molena D, Ruol A, et al. Chylothorax complicating esophagectomy for cancer: a plea for early thoracic duct ligation. J Thorac Cardiovasc Surg 2000;119:453e457. 8. Cagol M, Ruol A, Castoro C, et al. Prophylactic thoracic duct mass ligation prevents chylothorax after transthoracic esophagectomy for cancer. World J Surg 2009;33:1684e1686. 9. Guo W, Zhao YP, Jiang YG, et al. Prevention of postoperative chylothorax with thoracic duct ligation during video-assisted thoracoscopic esophagectomy for cancer. Surg Endosc 2012; 26:1332e1336. 10. Luketich JD, Alvelo-Rivera M, Buenaventura PO, et al. Minimally invasive esophagectomy: outcomes in 222 patients. Ann Surg 2003;238:486e494. 11. He Z, Zhao Y, Guo C, et al. Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey. Br J Cancer 2010;103:1085e1088. 12. Shah RD, Luketich JD, Schuchert MJ, et al. Postesophagectomy chylothorax: Incidence, risk factors, and outcomes. Ann Thorac Surg 2012;93:897e904. 13. Shackcloth MJ, Poullis M, Lu J, et al. Preventing of chylothorax after oesophagectomy by routine preoperative administration of oral cream. Eur J Cardiothorac Surg 2001;20: 1035e1036. 14. Lai FC, Chen L, Tu YR, et al. Prevention of chylothorax complicating extensive esophageal resection by mass ligation of thoracic duct: a random control study. Ann Thorac Surg 2011;91:1770e1774. 15. Ouattara M, D’Journo XB, Loundou A, et al. Body mass index kinetics and risk factors of malnutrition one year after radical oesophagectomy for cancer. Eur J Cardiothorac Surg 2012;41: 1088e1093. 16. Aiko S, Yoshizumi Y, Matsuyama T, et al. Influences of thoracic duct blockage on early enteral nutrition for patients who underwent esophageal cancer surgery. Jpn J Thorac Cardiovasc Surg 2003;51:263e271.
BACKGROUND:
remains high.4,5 Therefore, a preventive method is required to deal with chyle leakage after esophagectomy. Previously, thoracic duct ligation was reported to be effective in the prophylaxis of chylothorax.6-8 In a recent study, the incidence of chylothorax fell from 10% to 1.5% when prophylactic thoracic duct mass ligation was performed.9 However, the sample size of the study was relatively small, and the effect of the learning curve might contribute to the high incidence of chylothorax in the controls. Secondly, as a traumatic procedure, prophylactic ligation may cause extra injury to adjacent structures such as the intercostal vessels and the azygous vein, which would make MIE more invasive. In this study, we hypothesized that improved visualization of the thoracic duct would minimize inadvertent injury to the duct and decrease the incidence of postoperative chylothorax. Based on our 7-year experience performing MIE, we herein report our simple method and examine its efficacy in a retrospective study.
During surgical resection of esophageal cancer, the thoracic duct is vulnerable to iatrogenic injury, which will lead to postoperative chyle leakage.1,2 Recently, promising results from minimally invasive esophagectomy (MIE) were shown in decreasing pulmonary complications.3 However, the incidence of chylothorax in MIE is comparable to that in open chest approaches, and the recorded mortality rate CME questions for this article available at http://jacscme.facs.org Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, Editor-in-Chief, has nothing to disclose. Received July 19, 2013; Revised September 23, 2013; Accepted September 24, 2013. From the Division of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China (Shen, Feng, H Wang, Tan, Q Wang) and University College Hospital, London, United Kingdom (Khan). Correspondence address: Lijie Tan, MD, 180 Fenglin Rd, Division of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. email: [email protected]
ª 2014 by the American College of Surgeons Published by Elsevier Inc.
108
ISSN 1072-7515/13/$36.00 http://dx.doi.org/10.1016/j.jamcollsurg.2013.09.014
Shen et al
Vol. 218, No. 1, January 2014
METHODS A total of 344 consecutive patients underwent 3-stage MIE at our institution between June 2006 and July 2012 and were enrolled in this study. Tumor lesions were clinically staged using endoscopy, tissue biopsy, abdominal-thoracic CT, and endoscopic ultrasound. Inclusion criteria for MIE were: clinically staged T1-3N0M0 tumors; no previous history of cancer; no previous history of neck or chest surgery; and an American Society of Anesthesiologists (ASA) score of I to III. All operations were performed under the direction of the same senior consultant over the same time period. Patients who met inclusion criteria were assigned to 2 surgical groups. Preoperative milk was given to only 1 surgical group (Group Mþ), who received 500 mL of whole milk orally 6 hours before MIE. The other surgical group underwent MIE without preoperative milk and served as controls (Group M). All patients fasted for at least 6 hours before surgery. Patient demographics are summarized in Table 1. The hospital ethics committee approved the study. All patients gave their written informed consent before the operation after receiving careful explanation of the goals of the study. Table 1.
Clinical Characteristics
Characteristic
Age, mean, y Sex, M:F Location, U; M; L, n Neoadjuvant therapy Histology, SC; AD; othersx Stage, T1;T2;T3;T4jj Thoracic duct visualization Thoracic duct ligation Blood loss, mL Blood transfusion Thoracic stage duration, min Length of stay, d
Group Mþ (n ¼ 178)
Group M (n ¼ 166)
62.2 8.3 128:50 31; 123; 24 7
60.3 9.1 130:36 26; 120; 20 9
0.740* 0.171y 0.810y 0.512y
167;8;3 42; 50; 81; 5
155;7;4 33; 54; 77; 2
0.941z 0.543z
170 12 158 70 0
21 37 163 67 0
<0.001y <0.001y 0.328{ –
87 29 8.9 3.3
102 35 10.1 4.2
0.054* 0.427{
p Value
Group Mþ patients received preoperative milk; Group M- patients did not. values indicate standard deviation. *Student’s t-test. y Chi-square test. z Fisher’s exact test. x Others: 3 cases of small cell carcinoma in both groups and 1 case of carcinoma sarcomatode in Group Mþ. jj Including 7 cases of T4b, and 1 case of T4 (in Group Mþ), which was invasive to the thoracic duct, and the patient had resection of thoracic duct during MIE. { Mann-Whitney test. AD, adenocarcinoma; L, lower; M, middle; SC, squamous cancer; U, upper.
Preoperative Milk Minimizes Chylothorax
109
Operative procedures All patients received a combination of epidural and general anesthesia before the operation and were provided with patient-controlled analgesia postoperatively. Patients were intubated with a left-sided, double-lumen endotracheal tube to accomplish selective deflation of the right lung during the thoracic phase of the thoracic esophagectomy, and they were switched to double-lung ventilation during the abdominal and cervical stages. The MIE consisted of 3 stages: the thoracic, the abdominal, and the cervical stages. Thoracic stage The thoracic stage included esophageal mobilization and mediastinal lymphadenectomy. An observation port was placed at the seventh intercostal space along the midaxillary line, and another10-mm port was placed at the ninth intercostal space in the mid-scapular line. Two 5-mm ports were placed at the third intercostal space along the midaxillary line and just inferior to the tip of the scapula, respectively. An artificial CO2 pneumothorax was achieved at a pressure of 8 mmHg. After thoracoscopic exploration, the azygous vein was double-ligated by Hem-o-Lok (Teleflex) and then divided, after mobilization of the thoracic esophagus, which progressed from the tumor inspection site to the thoracic inlet cranially, and to the hiatus caudally. Identification of the thoracic duct was confirmed if the vessel was visible without any additional dissection. One of 3 methods was used when handling the thoracic duct: ligation, dissection, or preservation; the method was selected according to the operative findings. During the surgical resection, the thoracic duct was ligated only if it were deemed inadvertently injured, or divided if it were involved in the tumor process. Otherwise, the duct was preserved. Mediastinal lymphadenectomy was performed along the bilateral recurrent laryngeal nerves, together with the subcarinal and paraesophageal lymph node stations. The procedure was completed by placing an intercostal drain and closing the thoracic ports. Abdominal and cervical stages The abdominal and cervical stages were carried out as previously described.10 Jejunostomy was performed on all patients in order to provide enteral nutrition (usually begun on the second postoperative day). The operation concluded with closure of the cervical and abdominal incisions in layers. Data collection and statistical analysis Clinical data, including patient demographics and operative features of all patients, were collected from the clinical database at our institution. Postoperative chylothorax was
110
Shen et al
J Am Coll Surg
Preoperative Milk Minimizes Chylothorax
suspected when chylous drainage from the chest tube exceeded 400 mL. The diagnosis was then verified with laboratory confirmation of elevated triglycerides (>110 mL/dL) or positive Sudan III stain in the setting of sustained drainage. Clinical features of patients with postoperative chylothorax, their associated treatments, and their overall outcomes were also recorded. All data were tabulated using Microsoft Excel for further analysis. Statistical analysis was undertaken using SPSS software (version 17.0). Variables were compared using the Mann-Whitney test, the Student’s t -test, and chi-square test. A 2-sided p value less than 0.05 was considered statistically significant.
RESULTS Patient demographics There was a male predominance in our cohort of 258 men and 86 women. The mean age at time of surgery was 61.0 5.3 years (SD). There was no significant difference in age (p ¼ 0.740) or sex (p ¼ 0.171) between Group Mþ and Group M. According to the UICC (Union for International Cancer Control) esophageal cancer TNM staging system (7th Edition, 2010), there were 75 cases of pT1 (21.80%), 104 cases of pT2 (30.23%), 158 cases of pT3 (45.93%), and 7 cases of pT4 (2.03%) in our study. The depth of tumor invasion was similar between the 2 groups (p ¼ 0.543). There was no significant difference in tumor location (p ¼ 0.810) or histologic subtype (p ¼ 0.941) between the 2 groups (Table 1). Operative features All patients underwent thoracoscopic esophagectomy without conversion to open thoracotomy. During surgery, the thoracic duct was visually identified (Fig. 1) in 191 of 344 patients (170 patients in Group Mþ vs 21 patients in Group M). A significantly higher rate of thoracic duct identification was recorded in Group Mþ compared with Group M (95.51% vs 12.65%, p < 0.001). Accidental injury requiring thoracic duct ligation was noted in 6.74% of patients in Group Mþ vs 13.25% of patients in Group M (p ¼ 0.039). One patient in Group Mþ was found to have tumor invasion to the thoracic duct, and the patient had resection of the thoracic duct during MIE. No significant differences were found in the length of hospital stay, volume of blood loss, or number of blood transfusions between the 2 groups. Operative features are listed in Table 1. Morbidity and mortality No patients died during the operation in either group (Table 2). Complications were observed in 152
Figure 1. Identification of the thoracic duct during thoracoscopic esophagectomy. The thoracic duct (TD) was prominent after preoperative oral administration of milk. AA, aortic artery; Az, azygous vein; E, esophagus; B, left main bronchus.
patients (39.89% in Group Mþ vs 48.80% in Group M, p ¼ 0.096). In Group M, 1 patient developed a gastric conduit leak on the eighth postoperative day and died 2 weeks later because of septic shock and multiorgan failure. No significant difference in 30-day mortality was noted between the 2 groups. Management and outcome of chylothorax There were 10 cases of chylothorax in this study, and the incidence of postoperative chylothorax was significantly lower in Group Mþ compared with Group M (0.56% vs 5.42%, respectively; p ¼ 0.018). All 10 cases of chylothorax failed in thoracic duct identification during the operation, and 3 patients with postoperative Table 2. Mortality and Morbidity Variable
Mortality Morbidity Chylothoraxz Cervical anastomotic leak Gastric conduit failure Respiratory complications Hoarsenessx Delayed gastric emptying Bleedingjj
Group Mþ (n ¼ 178)
Group M (n ¼ 166)
p Value
0 71 1 37 2 18 9 3 1
1 81 9 41 1 17 11 2 0
0.972* 0.096y 0.018* 0.387y 0.952* 0.969y 0.534* 0.937* 0.972*
Group Mþ patients received preoperative milk; Group M- patients did not. *Fisher’s exact test. y Chi-square test. z A total of 3 patients required reoperation and religation of thoracic duct due to chylothorax (0% in Group Mþ vs 1.22% in Group M, p ¼ 0.371). x Including temporary and permanent recurrent laryngeal nerve palsy. jj Bleeding requiring reoperation.
Shen et al
Vol. 218, No. 1, January 2014
chylothorax had undergone intraoperative thoracic duct ligation (0% in Group Mþ vs 1.81% in Group M, p ¼ 0.222). Conservative chylothorax treatment consisted of intrapleural drainage via chest tube, total parenteral nutrition, and pleurodesis (50% hypertonic glucose injected into the thoracic cavity). Patients in whom conservative treatment was not successful underwent reoperation. In this study, 4 patients were treated conservatively and 6 patients (all from Group M, Table 3) required reoperation due to persistent chyle leakage despite conservative treatment for at least 5 days. The incidence of reoperation for chylothorax was lower in Group Mþ compared with Group M (0% vs 3.61%, p ¼ 0.032). Thoracoscopic exploration was performed on all patients who underwent reoperation, and milk was given intraoperatively via nasal-gastric tube to facilitate identification of the thoracic duct. The injuries were identified and ligated under thoracoscopy, and chyle leakage resolved within 24 hours of reoperation in all patients. One patient developed a thoracic cavity infection 6 months after discharge (from Group M, Table 3). The patient recovered without sequelae after reoperation for thoracic debridement.
DISCUSSION As the most common subtype in the East, esophageal squamous cell cancer is more commonly located in the mid-upper thoracic esophagus,11 and the close relationship of the thoracic duct to the thoracic esophagus makes iatrogenic injury more frequent during operation. In a recent study from Shah and associates,12 squamous histology was identified as an independent predictor of chylothorax after esophagectomy, and it follows that patients from the East are at higher risk of chylothorax Table 3. Pt. no.
1 2 3 4 5 6 7 8 9 10
Preoperative Milk Minimizes Chylothorax
111
compared with their western counterparts. In the surgical resection of esophageal squamous cell cancer, we introduced preoperative milk 6 hours before surgery and observed a higher rate of intraoperative thoracic duct identification and a lower incidence of postoperative chylothorax, which suggested preoperative milk as an effective method in the prevention of chyle leakage. Previously, researchers successfully used 50 mL of cream administered orally 3 hours before open esophagectomy to reduce the incidence of chylothorax.13 The success of this method for identifying the thoracic duct during minimally invasive surgery remains uncertain. Inspired by this idea, oral preoperative milk was given 6 hours before MIE and the thoracic duct was observed as a bright white vessel under thoracoscopy (Fig. 1). The presence of fat facilitated visualization of the thoracic duct, which had subsequently widened in diameter to 2 to 3 mm compared with the usual 1 to 2 mm.14 The change in size and appearance of the thoracic duct, as well as the magnified view afforded by thoracoscopy, improved identification of thoracic duct during MIE. Given the improvements on duct visualization, preoperative milk was effective in preventing chylothorax in this study. First, preoperative milk administration minimized intraoperative thoracic duct ligation due to incidental injury (6.74% of Group Mþ patients vs 13.25% of Group M), which saved the time of ligation and assured continuity of the operation. Second, even when thoracic duct injury occurred during the surgery, chylous fluid would be suggestive in bright white due to preoperative milk, and ligation could be easily performed to stop the chyle leakage at the injury site, which saved patients from potential chylothorax. Because milk had been administered 6 hours before surgery, the improvements in identification would not interfere with the operation,
Clinical Features of Patients with Postoperative Chylothorax Group
Age, y
Sex
Location
Histology
M M Mþ M M M M M M M
60 58 63 58 62 57 70 56 61 70
M M M F M F M F M M
M U M M M M U M M U
SC SC SC SC AD SC SC SC SC SC
Thoracic duct* Identification Ligation
e e e e e þ e e e e
e þ e þ e e e þ e e
Treatment
Outcomes
Reoperation Reoperation Pleurodesis Reoperation Pleurodesis Pleurodesis Reoperation Reoperation Reoperation Pleurodesis
Survival Survival Survival Survival Survival Survival Survival Survival Survival Survivaly
Group Mþ patients received preoperative milk; Group M- patients did not. *Identification and injury to the thoracic duct recorded during MIE. y This patient developed infection 6 months after discharge and recovered without sequelae after reoperation for thoracic debridement. AD, adenocarcinoma; M, middle; MIE, minimally invasive esophagectomy; SC, squamous cancer; U, upper.
112
Shen et al
J Am Coll Surg
Preoperative Milk Minimizes Chylothorax
making administration of preoperative milk a simple method to prevent chylothorax after MIE. To prevent the chyle leakage, prophylactic ligation of the thoracic duct is favored during esophagectomy. In a recent study, chyle leakage decreased from 2.1% to 1.2% when intraoperative thoracic duct ligation was performed on all patients operated on for esophageal cancer,14 which means that less than 1% of patients benefit from prophylactic ligation. In addition, the long-term effect of thoracic duct ligation on esophageal cancer patients remains uncertain. Because poor nutritional status is commonly noted in these patients,15 ligation of the thoracic duct may interfere with absorption of fats and other nutrients,16 which leads to the safety concerns regarding this procedure. Reoperation due to chylothorax was observed in 6 patients in Group M; 3 of these had a history of duct ligation during the original MIE. These results suggested that 3 of 21 ligations (14.29%) had failed during thoracoscopic esophagectomy. Although thoracic duct ligation has been proven effective,14 it does not completely eliminate the occurrence of chylothorax because there is considerable variation in duct anatomy, and some injury might be missed during the operation.9 On the other hand, preoperative milk minimized the incidence of reoperation in Group Mþ, which made MIE a safer procedure because reoperation for chylothorax carries high mortality when patients are nutritionally and immunologically depleted.7 We believe that identification and preservation of the thoracic duct using milk is a safe method for prevention of chylothorax after MIE. In our study, thoracic ligation was performed in 6.74% of Group Mþ patients compared with 13.25% in Group M. The lower incidence of ligation in Group Mþ could be explained by improvement in duct visualization during MIE because thoracic duct leakage appeared bright white. In Group M, the chyle leakage was often observed as transparent liquid under thoracoscopy, and in some cases might be falsely positive without intraoperative laboratory testing. Therefore, more ligations were performed if indefinite thoracic duct injury was suspected.
CONCLUSIONS Although this study has limitations, including its retrospective design and lack of randomized controls, preoperative administration of milk has shown simplicity and safety in minimizing chylothorax after MIE. Further study based on larger samples is required to confirm this finding. Author Contributions Study conception and design: Shen Acquisition of data: Feng, H Wang
Analysis and interpretation of data: Khan Drafting of manuscript: Shen Critical revision: Tan, Q Wang REFERENCES 1. Bolger C, Walsh TN, Tanner WA, et al. Chylothorax after oesophagectomy. Br J Surg 1991;78:587e588. 2. Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007;32: 362e369. 3. Biere SS, van Berge Henegouwen MI, Maas KW, et al. Minimally invasive vs open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 2012;379:1887e1892. 4. Lagarde SM, Omloo JM, de Jong K, et al. Incidence and management of chyle leakage after esophagectomy. Ann Thorac Surg 2005;80:449e454. 5. Kranzfelder M, Gertler R, Hapfelmeier A, et al. Chylothorax after esophagectomy for cancer: impact of the surgical approach and neoadjuvant treatment: systematic review and institutional analysis. Surg Endosc 2013;27:3530e3538. 6. Rao DV, Chava SP, Sahni P, et al. Thoracic duct injury during esophagectomy: 20 years’ experience at a tertiary care center in a developing country. Dis Esophagus 2004;17:141e145. 7. Merigliano S, Molena D, Ruol A, et al. Chylothorax complicating esophagectomy for cancer: a plea for early thoracic duct ligation. J Thorac Cardiovasc Surg 2000;119:453e457. 8. Cagol M, Ruol A, Castoro C, et al. Prophylactic thoracic duct mass ligation prevents chylothorax after transthoracic esophagectomy for cancer. World J Surg 2009;33:1684e1686. 9. Guo W, Zhao YP, Jiang YG, et al. Prevention of postoperative chylothorax with thoracic duct ligation during video-assisted thoracoscopic esophagectomy for cancer. Surg Endosc 2012; 26:1332e1336. 10. Luketich JD, Alvelo-Rivera M, Buenaventura PO, et al. Minimally invasive esophagectomy: outcomes in 222 patients. Ann Surg 2003;238:486e494. 11. He Z, Zhao Y, Guo C, et al. Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey. Br J Cancer 2010;103:1085e1088. 12. Shah RD, Luketich JD, Schuchert MJ, et al. Postesophagectomy chylothorax: Incidence, risk factors, and outcomes. Ann Thorac Surg 2012;93:897e904. 13. Shackcloth MJ, Poullis M, Lu J, et al. Preventing of chylothorax after oesophagectomy by routine preoperative administration of oral cream. Eur J Cardiothorac Surg 2001;20: 1035e1036. 14. Lai FC, Chen L, Tu YR, et al. Prevention of chylothorax complicating extensive esophageal resection by mass ligation of thoracic duct: a random control study. Ann Thorac Surg 2011;91:1770e1774. 15. Ouattara M, D’Journo XB, Loundou A, et al. Body mass index kinetics and risk factors of malnutrition one year after radical oesophagectomy for cancer. Eur J Cardiothorac Surg 2012;41: 1088e1093. 16. Aiko S, Yoshizumi Y, Matsuyama T, et al. Influences of thoracic duct blockage on early enteral nutrition for patients who underwent esophageal cancer surgery. Jpn J Thorac Cardiovasc Surg 2003;51:263e271.