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Three-Step Method for Lymphadenectomy in Gastric Cancer Surgery: A Single Institution Experience of 120 Patients
Three-Step Method for Lymphadenectomy in Gastric Cancer Surgery: A Single Institution Experience of 120 Patients Wu Wenguang, MM, Wang Xuefeng, MM, Zhang Zhiping, MM, Wu Xiangsong, MM, Wang Jianwei, MD, Li Songgang, PhD, Liu Yingbin, MD Gastric cancer is one of the most common malignancies and a leading cause of cancer death. Complete resection is still the only treatment to offer a cure for patients with gastric cancer. Lymphadenectomy is the most important part of curative resection, but lymphadenectomy is also very difficult in gastric cancer surgery. The aim of this study was to report our 3-step method for lymphadenectomy and clarify its safety and value in gastric cancer. STUDY DESIGN: A total of 120 consecutive patients underwent our 3-step method for lymphadenectomy at the Second Affiliated Hospital Zhejiang University College of Medicine between February 2006 and July 2007. The main surgical procedure was performed from right to left and from caudal to cranial. Clinical factors, surgical variables, postoperative morbidity, and hospital (30-day) mortality were analyzed retrospectively. RESULTS: Total gastrectomy was performed in 41 patients; combined adjacent organ resection was performed in 9 patients. The mean operation time was 201.8 minutes, and the mean blood loss was 376.7 mL. The median postoperative hospital stay was 14.9 ⫾ 4.3 days. A total of 3,569 lymph nodes (LNs) were removed and examined, and 2,879 were negative. More than 15 LNs were examined in all 120 patients. The median number of examined LNs was 29 (range 17 to 64; mean 29.7 ⫾ SD 9.6) per patient, and the median number of positive LNs was 5 (range 0 to 37; mean 5.8 ⫾ SD 7.1) per patient. The overall incidence of postoperative complications was 10.8%, and the rate of hospital death was 0%. The median follow-up period for those patients was 34.3 months (range 10 to 53 months), and the overall 3-year survival rate was 40.6%. CONCLUSIONS: The 3-step method for lymphadenectomy is easy to perform and is a safe and useful procedure for gastric cancer surgery. ( J Am Coll Surg 2011;212:200–208. © 2011 by the American College of Surgeons) BACKGROUND:
all group 1 and group 2 lymph nodes (LNs).3-6 Lymphadenectomy is the most important part of curative resection, but safe en bloc lymph node dissection is also the most difficult. Large Japanese and Eastern series have recently reported outstanding survival benefit and mortality rates of less than 1%;7-9 however, the Dutch and MRC randomized surgical trials comparing D1 and D2 resections for gastric cancer failed to prove any survival benefit for D2 resection.10,11 However, these trials were heavily criticized for unacceptably high surgical mortality and the poor quality of surgery in Western centers.12 It appears that the survival benefit of radical surgery may be offset completely by increased mortality, and the poor quality of surgery will deny some patients a chance of cure, or at least prolonged survival. The purpose of this study was to find a rational approach for lymphadenectomy and to simplify the surgery. We report our 3-step method for lymphadenectomy and clarify its safety and value in gastric cancer surgery.
Gastric cancer is one of the most common malignancies and a leading cause of cancer death.1,2 Complete resection is still the only treatment to offer a cure for patients with gastric cancer. D2 radical resection has been widely performed for advanced gastric cancer and requires removing Disclosure Information: Nothing to disclose. Received July 5, 2010; Revised September 8, 2010; Accepted September 10, 2010. From the Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (Wenguang, Jianwei, Yingbin); the Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China (Xuefeng, Songgang, Yingbin); the Department of General Surgery, Ningbo First Hospital, Ningbo, China (Zhiping); and the Department of Hepatobiliary Surgery, First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China (Xiangsong). Correspondence address: Liu Yingbin, PhD, MD, Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Rd, Shanghai, 200092 China.
© 2011 by the American College of Surgeons Published by Elsevier Inc.
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Abbreviations and Acronyms
LN ⫽ lymph node MLR ⫽ metastatic lymph node ratio PMOD ⫽ Peng’s multifunctional operative dissector
METHODS Patients
Between February 2006 and July 2007, a total of 137 gastric cancer patients with a curative intent were seen at the Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, China. One hundred twenty consecutive patients who underwent our 3-step method for lymphadenectomy were included in this study. The surgical procedure was defined as radical resection (R0) when no grossly visible tumor tissue remained after the resection and the resection margins were histologically negative. Nodal dissection of the en bloc surgical specimen was performed by surgeons in a standardized fashion (ie, according to the Japanese Research Society for Gastric Cancer [JRSGC] classification system) on the operating table in order to minimize stage migration. All primary tumors and node status were assessed by the same pathologist. Lymph node involvement was classified according to the 1997 International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) TNM classification (N0, no metastasis; N1, 1 to 6 metastatic lymph nodes; N2, 7 to 15 metastatic lymph nodes; N3, more than 15 metastatic lymph nodes).13 N ratio intervals were classified as follows: N ratio 0, 0%; N ratio 1, 1% to 9%; N ratio 2, 10% to 25%; and N ratio 3, more than 25%. The following independent variables were evaluated: sex, age, tumor site, type of surgical resection, grade, Borrmann macroscopic type, T stage (T1, mucosa or submucosa infiltration; T2, muscularis propria or subserosa infiltration; T3, serosa infiltration; or T4, extension to other structures), number of metastatic lymph nodes (TNM N0, N1, N2, or N3), M stage, and ratio between metastatic and examined lymph nodes. Surgical variables evaluated were operation time (minutes), blood loss (mL), and postoperative stay (days), and all data were expressed as means ⫾ standard deviations. The modified Clavien system has been applied to grade postoperative complications in our study. The median follow-up period for those patients was 34.3 months (range 10 to 53 months). For all analyses, statistical analyses and graphics were performed with the SPSS 13.0 statistical package for Windows (SPSS Inc). If the p value was less than 0.05, the results were considered statistically significant.
Figure 1. Peng’s multifunctional operative dissector, which combines 4 different functions: cutting, separating, aspirating, and coagulating.
Surgical procedure
We primarily used Peng’s multifunctional operative dissector (PMOD) (Fig. 1), which combines 4 different functions: cutting, separating, aspirating, and coagulating. Lymphadenectomy included 3 steps, and the main procedure started from right to left and from caudal to cranial (Figs 1 to 4). Step A
1. Gerota’s membrane and Kocher incision: The right Gerota’s membrane and perirenal fat were lifted to reveal the right renal blood vessels, the right testicular (ovarian) blood vessels and the beginning part of the right ureter on the left side. The right Gerota’s membrane and perirenal fat were elevated, and then a Kocher incision was performed to expose the duodenum, the head of the pancreas, and the inferior vena cava. The duodenum and the head of the pancreas were held upward to exclude previously undetected metastases. Then, an initial assessment of the resectability of the tumor and the extent of the operation was performed (Fig. 5). The origins of the superior mesenteric vein and artery were then found. At this point, we could exclude previously undetected metastases and define the extent and the difficulty of the operation, as we exposed the caudal part of the hepatoduodenal ligament and initiate omental bursa dissection from the hepatic to splenic flexures. 2. Dissection of the greater omentum and the anterior sheet of the mesocolon: The duodenal membrane was
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Figure 3. Step B. Figure 2. Step A.
the beginning point of this dissection after the Kocher incision was finished. Then, the greater omentum, the anterior sheet of the mesocolon, and the pancreatic capsule were dissected from right to left. The greater omentum was dissected from the transverse colon together with the anterior sheet of the mesocolon. The transverse colon was pulled caudally by the first assistant and the greater omentum was lifted by the left hand of the surgeon so that the surgeon could dissect the anterior sheet from the underlying tissue easily from the hepatic flexure to the splenic flexure using the PMOD in the right hand. At the middle of the colon, where the interstitial space between the anterior lobe and the posterior lobe of the mesocolon is narrow, we used the curettage and
Figure 4. Step C.
aspiration technique to develop this space by separating and pushing tissue aside, together with electrical coagulation and cutting. In this way, we could dissect the posterior lobe of the mesocolon more easily. Complete omentectomy and bursectomy are important for T3 and T4 tumors that may invade the lesser sac. While dissecting this sheet, the right accessory colic vein was found and followed cranially to the point where it joins Henle’s surgical trunk. The origin of the right gastroepiploic vein can then be identified, ligated, and divided at its origin (Fig. 6). Step B
After division of the duodenum, the serosa of the hepatoduodenal ligament was incised caudally toward the duodenum, and the right gastric artery was identified, ligated, and divided at its origin after the proper hepatic artery was
Figure 5. ➀Right renal vein. ➁Inferior vena cava. ➂Left renal vein. ➃Head of the pancreas.
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Figure 6. ➀Stump of the right accessory colic vein. ➁Right colic vein. ➂Middle colic vein. ➃Superior mesenteric vein.
found (Fig. 7). Tissue in the hepatoduodenal ligament was dissected along the proper hepatic artery from the liver toward the duodenum. We divided the right gastric artery at its origin first in this step to eliminate the possibility of damage and to obtain clear visualization. The lesser omentum was then divided just below the liver by electrical coagulation with the PMOD from the right side of the proper hepatic artery to the left side of the esophageal. This division was followed caudally along the lesser curvature if necessary. During this step, the space was narrow, and we used the PMOD to push the tissue aside and develop the space. This whole step was finished by the operator alone in order to obtain clear surgical visualization and minimize operation time (Fig. 8).
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Figure 7. ➀Stump of the right gastric artery. ➁Common bile duct. ➂Common hepatic artery. ➃Gastroduodenal artery.
Lymphadenectomy followed the main vessels. After division of the duodenum, dissection was performed from the
proper hepatic artery to the common hepatic artery and from the common hepatic artery to the left gastric artery, until the celiac artery was found. The proper hepatic artery was the starting point and most important part of this step (Fig. 9). Lymphadenectomy was performed along those main arteries, and the right gastroepiploic vein was identified, ligated, and divided at its origin. After this step, the origin of the splenic artery was found, and the dissection was performed along the splenic artery until the secondary branches of the splenic pedicle were found14 (Fig. 10). Several small vessels passing from behind the pancreas were coagulated in this step, and exposure of the secondary branches of the splenic pedicle reduced the rate of pancreatic leakage. If the tumor involved the upper or middle third of the stomach, this step of the dissection was performed to the left side of the cardia.
Figure 8. ➀Cardia. ➁Lesser curvature.
Figure 9. ➀Stump of left gastric artery. ➁Splenic artery. ➂Stump of posterior gastric artery. ➃Secondary branches of splenic pedicle. ➄Spleen. ➅Gastric.
Step C
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Figure 10. ➀Splenic artery. ➁Splenic vein. ➂Pancreas tail. ➃Secondary branches of splenic. ➄Spleen pedicle.
RESULTS A total of 137 patients who had histologically proven gastric cancer with a curative intent were enrolled in this study at the Second Affiliated Hospital Zhejiang University College of Medicine. Thirteen patients with early gastric cancer or more advanced disease were excluded before operation, and 4 patients were excluded because of peritoneal metastases. One-hundred twenty consecutive patients underwent our 3-step method for lymphadenectomy. The surgical decision-making process is shown in Figure 11. Clinicopathologic data of the 120 patients who underwent our 3-step method for lymphadenectomy are given in Table 1. Total gastrectomy was performed in 41 patients, and combined adjacent organ resection was performed in 9 patients (7.5%). The resected organs were the spleen (6
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patients), pancreas (1 patient), transverse colon (1 patient), and liver (1 patient). Surgical variables of the 120 patients are depicted in Table 2. The median operation time was 201.8 minutes, and the median blood loss was 376.7 mL. The median postoperative hospital stay was 14.9 ⫾ 4.3 days. Overall, a total of 3,569 LNs were removed and examined, and 2,879 were negative. More than 15 LNs were examined in each of the 120 patients. The median number of resected LNs was 29 (range 17 to 64; mean 29.7 ⫾ 9.6) per patient, and the median number of positive LNs was 5 (range 0 to 37; mean 5.8 ⫾ 7.1) per patient. The mean metastatic lymph node ratio (MLR) was 0.19 ⫾ 0.23. Figure 12A compares the MLR distribution among TNM staging system N categories. For N1 patients (49 patients), the distribution of the MLRs was as follows: N ratio 1, 18 patients (36.7%); N ratio 2, 29 patients (59.2%); and N ratio 3, 2 patients (4.1%). For N2 patients (23 patients), distribution of the MLRs was as follows: N ratio 2, 9 patients (39.1%); and N ratio 3, 14 patients (60.9%). Figures 12B and C show the number of metastatic lymph nodes and the ratio of metastatic lymph node distribution among the total number of resected nodes for each patient. The overall incidence of postoperative complications was 10.8% (13 of 120 patients). There were 7 (5.8%) patients in the Clavien grade I complications category, including 2 for wound infection, 2 for pleural effusion, 1 for diarrhea, 1 for lymphorrhea, and 1 for ileus. Another 5 (4.2%) patients were classified as having grade II complications, including 2 for anastomotic leakage and 3 for pneumonia. One (0.8%) man had grade IIIb complica-
Figure 11. The surgical decision-making process.
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Table 1. The Clinicopathologic Factors of the 120 Patients Factors
All Sex Female Male Age, y ⬍70 ⱖ70 Site Lower Middle Upper Diffuse Surgery Subtotal gastrectomy Total gastrectomy Extended total gastrectomy Grading Well differentiated (G1) Moderately differentiated (G2) Poorly differentiated (G3) Undifferentiated (G4) Borrmann macroscopic type I II III IV T stage T1 T2 T3 T4 Metastatic nodes, n N0 N1 N2 N3 M stage M0 M1
n
120
%
100
30 90
25.0 75.0
97 23
80.8 19.2
73 32 14 1
60.8 26.7 5.7 0.8
70 41 9
58.3 34.2 7.5
33 37 50 0
27.5 30.8 41.7 0.0
6 41 71 2
2.4 16.7 29.2 0.8
17 23 79 1
14.2 19.2 65.8 0.8
35 49 23 13
29.2 40.8 19.2 10.8
120 0
100.0 0.0
tions for abdominal abscess, and there were no grade IV or V complications. Survival curves with respect to pN category and MLR are shown in Figure 13. Considering pN staging, the 3-year survival rates were 97.1% for N0 stage, 75.0% for N1 stage, and 0% for N2/3 stage. While considering MLR, 3-year survival rates were 97.1% for N ratio 0, 88.9% for N ratio 1, 57.9% for N ratio 2, and 0% for N ratio 3. Survival curves ascended while the pN category and the MLR increased. The 3-year survival rates for patients in each MLR
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in N1 gastric cancer were, 88.9% for N ratio 1, 71.0% and 0% for N ratio 2. However, there was no significant difference between the subgroups in N2 gastric cancer patients (Fig. 14).
DISCUSSION Our method uses the PMOD that combines 4 different functions: cutting, separating, aspirating, and coagulating. We perform the curettage and aspiration technique,15-18 which saves operating time, reduces blood loss, and keeps the surgical field clear by eliminating the need to frequently change surgical instruments. Suction is maintained during the operation. Blood, the plume produced by electrical coagulation and tissue, are aspirated immediately, similar to the principle of no tumor. During the surgical dissection by the PMOD, the surgeon and the assistant must try to maintain tissue tension by pulling in opposite directions. When the PMOD meets the resistance of strong materials such as vessels or ducts, the “cutting or scraping” function stops, the bevel edge tip separates by pushing tissue aside and develops the space in the tissue, and the structure of vessels and ducts can be identified and isolated easily. This special function makes the PMOD more suitable for lymphadenectomy in gastric cancer surgery and greatly improves the quality of the operation. The operation time and the blood loss in our study were not higher than in previously reported data.19 This result highlights the major advantages of PMOD. The hepatorenal recess is not only the lowest part of the peritoneal cavity when the subject is supine, but is also the important exchange point between the lesser sac and the peritoneal cavity, which lies to the right side of the omental foramen. We believe that it is important to dissect the right Gerota’s membrane and perirenal fat to reduce the possibility of peritoneal metastasis, especially for T3 or T4 tumors. Then, along the Kocher incision, the duodenum, the head of the pancreas, and the inferior vena cava are exposed. This is the key procedure of the whole operation, not only for tumor detection but for surgical decision making. After this step, nearly all the lower third gastric cancer patients underwent a Billroth I type of anastomosis after gastrectomy in our practice. The Billroth I type of anastomosis is more physiologically sound because it preserves the continuity of the digestive tract with the duodenum, theoretically maintains autocrine and paraTable 2. Surgical Variables of the 120 Patients Operative factors
Median ⴞ SD
Range
Operation time, min Blood loss, mL Postoperative stay, d
201.8 ⫾ 39.0 376.7 ⫾ 196.9 14.9 ⫾ 4.3
120–300 100–1,500 9–30
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Figure 12. (A) The metastatic lymph node ratio (MLR) distribution among the TNM staging system N categories in 120 patients; (B and C) the number of metastatic lymph nodes and the ratio of metastatic lymph node distribution among the total number of resected nodes for each patient.
crine signaling and feedback mechanisms, and is associated with a lower rate of early postoperative complications. It is the first choice after distal gastrectomy.20-22 The postoperative complication rate in our study was low (10.8%), and a majority of our patients had a smooth recovery. Lymphadenectomy along the main vessels is very difficult in radical gastrectomy. A space was formed by loose connective tissue between the vessels and the vaginae vasorum. Liberation of these spaces can totally expose the whole course of vessels easily and safely. Only in this surgical plane can we perform true lymphadenectomy in radical gastrectomy, including removal of lymph nodes and also the entire fascia along the vessels. This also helps to reduce the probability of vessel injury and decreases operation time.
Studies show that the higher the number of resected nodes, the higher the number of metastatic lymph nodes.23 The current edition of the International Union Against Cancer staging manual recommends examining at least 15 LNs for adequate gastric cancer staging. A minimum of 15 nodes is required for an adequate assessment, but 25 are required for a precise evaluation.24 More than 15 LNs were examined in all 120 patients in our study, and the median total number of LNs examined was 29 per patient. The MLR, calculated by dividing the number of metastatic lymph nodes by the total number of lymph nodes, is an important prognostic factor.25-29 Many studies have shown that this parameter is less vulnerable to stage migration and reflects the efficacy of lymph node dissection.30-32 However, selection of the best cutoff values of metastatic lymph node
Figure 13. Survival curve according to (A) N stage and (B) the metastatic lymph node ratio, There were significant differences among the groups (p ⬍ 0.00;).
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Figure 14. Survival curve of patients with (A) pN1– 2, in relation to (B) metastatic lymph node ratio category.
ratio remains difficult. Some studies describe the best-fit cutoff values as 0%, 1% to 9%, 10% to 25%, and more than 25%, and the overall survival curves are significantly different between the different N ratio subgroups.31,33 In our study, the MLR is shown in Figure 12B, and the survival curve according to N stage and the metastatic lymph node ratio in Figure 13. There were significant differences among the groups. It is necessary to attempt to reduce the MLR to less than 10% for potentially curable patients, in order to achieve better therapeutic efficiency, and the rates of surgery-related complications and mortality must be maintained at a low level. The MLRs of all 120 patients in this study may be lower than in other literature. In our study, the N1 gastric cancer patients got more survival benefit than the N2 patients after D2 resection in the subgroup of MLR. But the further overall survival benefit of our 3-step method for lymphadenectomy in gastric cancer surgery needs to be studied over a longer period of time in multiple institutions.
CONCLUSIONS Our institutional experience of lymphadenectomy during gastric cancer surgery can be summarized as follows: Use of the PMOD and curettage and aspiration technique; 3-step en bloc lymphadenectomy; vessel skeletonization inside the vaginae vasorum; and surgery in the right surgical plane and space. We conclude that our 3-step method for lymphadenectomy is easy to perform, safe, and useful for gastric cancer surgery. Author Contributions Study conception and design: Yingbin, Wenguang, Xuefeng Acquisition of data: Wenguang, Zhiping, Xiangsong, Jianwei
Analysis and interpretation of data: Xuefeng, Wenguang, Songgang Drafting of manuscript: Wenguang, Xuefeng, Zhiping Critical revision: Wenguang, Xuefeng, Zhiping
REFERENCES 1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006;24:2137–2150. 2. Yao JC, Mansfield PF, Pisters PW, et al. Combined-modality therapy for gastric cancer. Semin Surg Oncol 2003;21:223–227. 3. Hartgrink HH, van de Velde CJ, Putter H, et al. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. J Clin Oncol 2004;22:2069–2077. 4. Di Martino N, Izzo G, Cosenza A, et al. [Total gastrectomy for gastric cancer: can the type of lymphadenectomy condition the long-term results?] Suppl Tumori 2005;4:S84–S85. 5. Volpe CM, Driscoll DL, Douglass HO Jr. Outcome of patients with proximal gastric cancer depends on extent of resection and number of resected lymph nodes. Ann Surg Oncol 2000;7:139–144. 6. Kulig J , Popiela T, Kolodziejczyk P, et al. Standard D2 versus extended D2(D2⫹) lymphadenectomy for gastric cancer: an interim safety analysis of a multicenter, randomized, clinical trial. Am J Surg 2007;193:10–15. 7. Maruyama K, Okabayashi S, Kinoshita T. Progress in gastric cancer surgery in Japan and its limits of radicality. World J Surg 1987;11:418–425. 8. Kodera Y, Sasako M, Yamamoto S, et al. Identification of risk factors for the development of complications following extended and superextended lymphadenectomies for gastric cancer. Br J Surg 2005;92:1103–1109. 9. Park DJ, Lee H-J, Kim H-H, et al. Predictors of operative morbidity and mortality in gastric cancer surgery. Br J Surg 2005; 92:1099–1102.
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10. Binenkamp JJ, Hermans J, Sasako M, van De velde, CJH for the Dutch Gastric Cancer Group. New Engl J Med 1999;340:908– 914. 11. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resection for gastric cancer: long-term results of the MRC randomized surgical trial. Br J Cancer 1999;79:1522– 1530. 12. Sasako M. Principles of surgical treatment for curable gastric cancer. J Clin Oncol 2003;23s:274s–275s. 13. Sobin LH, Wittekind CH. International Union Against Cancer (UICC). TNM Classification of Malignant Tumors, 5th ed. New York: John Wiley & Sons; 1997. 14. Liu YB, Kong Y, Wang XA, et al. Role of dissection of secondary branches of splenic pedicle in portal hypertension cases undergoing splenectomy. Chin Med J (Engl) 2008;121:2250–2253. 15. Di Carlo I. Peng’s Multifunctional Operational Dissector (PMOD) in Chirurgia Epatica, Edizioni Minerva Medica ,2007;34–35. 16. Peng SY, Li JT, Mou YP, et al. Different approaches to caudate lobectomy with “curettage and aspiration’’ technique using a special instrument PMOD: a report of 76 cases. World J Gastroenterol 2003;9:2169–2173. 17. Cai XJ, Liang L, Wang YF, et al. Laparoscopic hepatectomy by curettage and aspiration: a new technique. Chinese Med J 2007; 120:1773–1776. 18. Cai XJ, Yu H, Liang X, et al. Laparoscopic hepatectomy by curettage and aspiration-experiences of 62 cases. Surg Endosc Intervent Tech 2006;20:1531–1535. 19. Sasako M, Sano T, Yamamoto S, et al; Japan Clinical Oncology Group. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med 2008;359:453–462. 20. Sah BK, Chen M-M, Yan M, Zhu Z-G. Gastric cancer surgery: Billroth I or Billroth II for distal gastrectomy? BMC Cancer 2009,9:428. 21. Le Blanc-Louvry I, Ducrotté P, Peillon C, et al. Roux-en-Y limb motility after total or distal gastrectomy in symptomatic and asymptomatic patients. J Am Coll Surg 2000,190:408–417. 22. Le Blanc-Louvry I, Ducrotte P, Chayvialle JA, et al. Distal gastrectomy and Roux-Y limb in the rat: plasma motilin, pancreatic
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polypeptide concentrations, and duodenojejunal motility. Dig Dis Sci 2000,45:1525–1530. Liu C, Ping P, Lu Y, et al. Clinical implications of metastatic lymph node ratio in gastric cancer. BMC Cancer 2007;7:. De Manzoni G, Verlato G, Roviello F. The new TNM classification of lymph node metastasis minimizes stage migration problems in gastric cancer patients. Br J Cancer 2002;87:171– 174. Bando E, Yonemura Y, Taniguchi K, et al. Outcome of ratio of lymph node metastasis in gastric carcinoma. Ann Surg Oncol 2002,9:775–784. Saito H, Fukumoto Y, Osaki T, et al. Prognostic significance of level and number of lymph node metastases in patients with gastric cancer. AnnSurg Oncol 2007;14:1688–1693. Gunji Y, Suzuki T, Hori S, et al. Prognostic significance of the number of metastatic lymph nodes in early gastric cancer. Dig Surg 2003,20:148–153. Hyung WJ, Noh SH, Yoo CH, et al. Prognostic significance of metastatic lymph node ratio in T3 gastric cancer. World J Surg 2002;26:323–329. Celen O, Yildrim E, Berberoglu U. Prognostic impact of positive lymph node ratio in gastric carcinoma. J Surg Oncol 2007; 18:95–101. Bando E, Yonemura Y, Taniguchi K, et al. Outcome of ratio of lymph node metastasis in gastric carcinoma. Ann Surg Oncol 2002;9:775–784. Nitti D, Marchet A, Olivieri M, et al. Ratio between metastatic and examined lymph nodes is an independent prognostic factor after D2 resection for gastric cancer: analysis of a large European monoinstitutional experience. Ann Surg Oncol 2003;10:1077– 1085. Siewert JR, Böttcher K, Stein HJ, et al. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Study. Ann Surg 1998;228:449–461. Marchet A, Mocellin S, Ambrosi A, et al. The ratio between metastatic and examined lymph nodes(n ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy. Results from an Italian multicentric study in 1853 patients. Ann Surg 2007;245:543–553.
all group 1 and group 2 lymph nodes (LNs).3-6 Lymphadenectomy is the most important part of curative resection, but safe en bloc lymph node dissection is also the most difficult. Large Japanese and Eastern series have recently reported outstanding survival benefit and mortality rates of less than 1%;7-9 however, the Dutch and MRC randomized surgical trials comparing D1 and D2 resections for gastric cancer failed to prove any survival benefit for D2 resection.10,11 However, these trials were heavily criticized for unacceptably high surgical mortality and the poor quality of surgery in Western centers.12 It appears that the survival benefit of radical surgery may be offset completely by increased mortality, and the poor quality of surgery will deny some patients a chance of cure, or at least prolonged survival. The purpose of this study was to find a rational approach for lymphadenectomy and to simplify the surgery. We report our 3-step method for lymphadenectomy and clarify its safety and value in gastric cancer surgery.
Gastric cancer is one of the most common malignancies and a leading cause of cancer death.1,2 Complete resection is still the only treatment to offer a cure for patients with gastric cancer. D2 radical resection has been widely performed for advanced gastric cancer and requires removing Disclosure Information: Nothing to disclose. Received July 5, 2010; Revised September 8, 2010; Accepted September 10, 2010. From the Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (Wenguang, Jianwei, Yingbin); the Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China (Xuefeng, Songgang, Yingbin); the Department of General Surgery, Ningbo First Hospital, Ningbo, China (Zhiping); and the Department of Hepatobiliary Surgery, First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China (Xiangsong). Correspondence address: Liu Yingbin, PhD, MD, Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Rd, Shanghai, 200092 China.
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Abbreviations and Acronyms
LN ⫽ lymph node MLR ⫽ metastatic lymph node ratio PMOD ⫽ Peng’s multifunctional operative dissector
METHODS Patients
Between February 2006 and July 2007, a total of 137 gastric cancer patients with a curative intent were seen at the Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, China. One hundred twenty consecutive patients who underwent our 3-step method for lymphadenectomy were included in this study. The surgical procedure was defined as radical resection (R0) when no grossly visible tumor tissue remained after the resection and the resection margins were histologically negative. Nodal dissection of the en bloc surgical specimen was performed by surgeons in a standardized fashion (ie, according to the Japanese Research Society for Gastric Cancer [JRSGC] classification system) on the operating table in order to minimize stage migration. All primary tumors and node status were assessed by the same pathologist. Lymph node involvement was classified according to the 1997 International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) TNM classification (N0, no metastasis; N1, 1 to 6 metastatic lymph nodes; N2, 7 to 15 metastatic lymph nodes; N3, more than 15 metastatic lymph nodes).13 N ratio intervals were classified as follows: N ratio 0, 0%; N ratio 1, 1% to 9%; N ratio 2, 10% to 25%; and N ratio 3, more than 25%. The following independent variables were evaluated: sex, age, tumor site, type of surgical resection, grade, Borrmann macroscopic type, T stage (T1, mucosa or submucosa infiltration; T2, muscularis propria or subserosa infiltration; T3, serosa infiltration; or T4, extension to other structures), number of metastatic lymph nodes (TNM N0, N1, N2, or N3), M stage, and ratio between metastatic and examined lymph nodes. Surgical variables evaluated were operation time (minutes), blood loss (mL), and postoperative stay (days), and all data were expressed as means ⫾ standard deviations. The modified Clavien system has been applied to grade postoperative complications in our study. The median follow-up period for those patients was 34.3 months (range 10 to 53 months). For all analyses, statistical analyses and graphics were performed with the SPSS 13.0 statistical package for Windows (SPSS Inc). If the p value was less than 0.05, the results were considered statistically significant.
Figure 1. Peng’s multifunctional operative dissector, which combines 4 different functions: cutting, separating, aspirating, and coagulating.
Surgical procedure
We primarily used Peng’s multifunctional operative dissector (PMOD) (Fig. 1), which combines 4 different functions: cutting, separating, aspirating, and coagulating. Lymphadenectomy included 3 steps, and the main procedure started from right to left and from caudal to cranial (Figs 1 to 4). Step A
1. Gerota’s membrane and Kocher incision: The right Gerota’s membrane and perirenal fat were lifted to reveal the right renal blood vessels, the right testicular (ovarian) blood vessels and the beginning part of the right ureter on the left side. The right Gerota’s membrane and perirenal fat were elevated, and then a Kocher incision was performed to expose the duodenum, the head of the pancreas, and the inferior vena cava. The duodenum and the head of the pancreas were held upward to exclude previously undetected metastases. Then, an initial assessment of the resectability of the tumor and the extent of the operation was performed (Fig. 5). The origins of the superior mesenteric vein and artery were then found. At this point, we could exclude previously undetected metastases and define the extent and the difficulty of the operation, as we exposed the caudal part of the hepatoduodenal ligament and initiate omental bursa dissection from the hepatic to splenic flexures. 2. Dissection of the greater omentum and the anterior sheet of the mesocolon: The duodenal membrane was
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Figure 3. Step B. Figure 2. Step A.
the beginning point of this dissection after the Kocher incision was finished. Then, the greater omentum, the anterior sheet of the mesocolon, and the pancreatic capsule were dissected from right to left. The greater omentum was dissected from the transverse colon together with the anterior sheet of the mesocolon. The transverse colon was pulled caudally by the first assistant and the greater omentum was lifted by the left hand of the surgeon so that the surgeon could dissect the anterior sheet from the underlying tissue easily from the hepatic flexure to the splenic flexure using the PMOD in the right hand. At the middle of the colon, where the interstitial space between the anterior lobe and the posterior lobe of the mesocolon is narrow, we used the curettage and
Figure 4. Step C.
aspiration technique to develop this space by separating and pushing tissue aside, together with electrical coagulation and cutting. In this way, we could dissect the posterior lobe of the mesocolon more easily. Complete omentectomy and bursectomy are important for T3 and T4 tumors that may invade the lesser sac. While dissecting this sheet, the right accessory colic vein was found and followed cranially to the point where it joins Henle’s surgical trunk. The origin of the right gastroepiploic vein can then be identified, ligated, and divided at its origin (Fig. 6). Step B
After division of the duodenum, the serosa of the hepatoduodenal ligament was incised caudally toward the duodenum, and the right gastric artery was identified, ligated, and divided at its origin after the proper hepatic artery was
Figure 5. ➀Right renal vein. ➁Inferior vena cava. ➂Left renal vein. ➃Head of the pancreas.
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Figure 6. ➀Stump of the right accessory colic vein. ➁Right colic vein. ➂Middle colic vein. ➃Superior mesenteric vein.
found (Fig. 7). Tissue in the hepatoduodenal ligament was dissected along the proper hepatic artery from the liver toward the duodenum. We divided the right gastric artery at its origin first in this step to eliminate the possibility of damage and to obtain clear visualization. The lesser omentum was then divided just below the liver by electrical coagulation with the PMOD from the right side of the proper hepatic artery to the left side of the esophageal. This division was followed caudally along the lesser curvature if necessary. During this step, the space was narrow, and we used the PMOD to push the tissue aside and develop the space. This whole step was finished by the operator alone in order to obtain clear surgical visualization and minimize operation time (Fig. 8).
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Figure 7. ➀Stump of the right gastric artery. ➁Common bile duct. ➂Common hepatic artery. ➃Gastroduodenal artery.
Lymphadenectomy followed the main vessels. After division of the duodenum, dissection was performed from the
proper hepatic artery to the common hepatic artery and from the common hepatic artery to the left gastric artery, until the celiac artery was found. The proper hepatic artery was the starting point and most important part of this step (Fig. 9). Lymphadenectomy was performed along those main arteries, and the right gastroepiploic vein was identified, ligated, and divided at its origin. After this step, the origin of the splenic artery was found, and the dissection was performed along the splenic artery until the secondary branches of the splenic pedicle were found14 (Fig. 10). Several small vessels passing from behind the pancreas were coagulated in this step, and exposure of the secondary branches of the splenic pedicle reduced the rate of pancreatic leakage. If the tumor involved the upper or middle third of the stomach, this step of the dissection was performed to the left side of the cardia.
Figure 8. ➀Cardia. ➁Lesser curvature.
Figure 9. ➀Stump of left gastric artery. ➁Splenic artery. ➂Stump of posterior gastric artery. ➃Secondary branches of splenic pedicle. ➄Spleen. ➅Gastric.
Step C
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Figure 10. ➀Splenic artery. ➁Splenic vein. ➂Pancreas tail. ➃Secondary branches of splenic. ➄Spleen pedicle.
RESULTS A total of 137 patients who had histologically proven gastric cancer with a curative intent were enrolled in this study at the Second Affiliated Hospital Zhejiang University College of Medicine. Thirteen patients with early gastric cancer or more advanced disease were excluded before operation, and 4 patients were excluded because of peritoneal metastases. One-hundred twenty consecutive patients underwent our 3-step method for lymphadenectomy. The surgical decision-making process is shown in Figure 11. Clinicopathologic data of the 120 patients who underwent our 3-step method for lymphadenectomy are given in Table 1. Total gastrectomy was performed in 41 patients, and combined adjacent organ resection was performed in 9 patients (7.5%). The resected organs were the spleen (6
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patients), pancreas (1 patient), transverse colon (1 patient), and liver (1 patient). Surgical variables of the 120 patients are depicted in Table 2. The median operation time was 201.8 minutes, and the median blood loss was 376.7 mL. The median postoperative hospital stay was 14.9 ⫾ 4.3 days. Overall, a total of 3,569 LNs were removed and examined, and 2,879 were negative. More than 15 LNs were examined in each of the 120 patients. The median number of resected LNs was 29 (range 17 to 64; mean 29.7 ⫾ 9.6) per patient, and the median number of positive LNs was 5 (range 0 to 37; mean 5.8 ⫾ 7.1) per patient. The mean metastatic lymph node ratio (MLR) was 0.19 ⫾ 0.23. Figure 12A compares the MLR distribution among TNM staging system N categories. For N1 patients (49 patients), the distribution of the MLRs was as follows: N ratio 1, 18 patients (36.7%); N ratio 2, 29 patients (59.2%); and N ratio 3, 2 patients (4.1%). For N2 patients (23 patients), distribution of the MLRs was as follows: N ratio 2, 9 patients (39.1%); and N ratio 3, 14 patients (60.9%). Figures 12B and C show the number of metastatic lymph nodes and the ratio of metastatic lymph node distribution among the total number of resected nodes for each patient. The overall incidence of postoperative complications was 10.8% (13 of 120 patients). There were 7 (5.8%) patients in the Clavien grade I complications category, including 2 for wound infection, 2 for pleural effusion, 1 for diarrhea, 1 for lymphorrhea, and 1 for ileus. Another 5 (4.2%) patients were classified as having grade II complications, including 2 for anastomotic leakage and 3 for pneumonia. One (0.8%) man had grade IIIb complica-
Figure 11. The surgical decision-making process.
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Table 1. The Clinicopathologic Factors of the 120 Patients Factors
All Sex Female Male Age, y ⬍70 ⱖ70 Site Lower Middle Upper Diffuse Surgery Subtotal gastrectomy Total gastrectomy Extended total gastrectomy Grading Well differentiated (G1) Moderately differentiated (G2) Poorly differentiated (G3) Undifferentiated (G4) Borrmann macroscopic type I II III IV T stage T1 T2 T3 T4 Metastatic nodes, n N0 N1 N2 N3 M stage M0 M1
n
120
%
100
30 90
25.0 75.0
97 23
80.8 19.2
73 32 14 1
60.8 26.7 5.7 0.8
70 41 9
58.3 34.2 7.5
33 37 50 0
27.5 30.8 41.7 0.0
6 41 71 2
2.4 16.7 29.2 0.8
17 23 79 1
14.2 19.2 65.8 0.8
35 49 23 13
29.2 40.8 19.2 10.8
120 0
100.0 0.0
tions for abdominal abscess, and there were no grade IV or V complications. Survival curves with respect to pN category and MLR are shown in Figure 13. Considering pN staging, the 3-year survival rates were 97.1% for N0 stage, 75.0% for N1 stage, and 0% for N2/3 stage. While considering MLR, 3-year survival rates were 97.1% for N ratio 0, 88.9% for N ratio 1, 57.9% for N ratio 2, and 0% for N ratio 3. Survival curves ascended while the pN category and the MLR increased. The 3-year survival rates for patients in each MLR
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in N1 gastric cancer were, 88.9% for N ratio 1, 71.0% and 0% for N ratio 2. However, there was no significant difference between the subgroups in N2 gastric cancer patients (Fig. 14).
DISCUSSION Our method uses the PMOD that combines 4 different functions: cutting, separating, aspirating, and coagulating. We perform the curettage and aspiration technique,15-18 which saves operating time, reduces blood loss, and keeps the surgical field clear by eliminating the need to frequently change surgical instruments. Suction is maintained during the operation. Blood, the plume produced by electrical coagulation and tissue, are aspirated immediately, similar to the principle of no tumor. During the surgical dissection by the PMOD, the surgeon and the assistant must try to maintain tissue tension by pulling in opposite directions. When the PMOD meets the resistance of strong materials such as vessels or ducts, the “cutting or scraping” function stops, the bevel edge tip separates by pushing tissue aside and develops the space in the tissue, and the structure of vessels and ducts can be identified and isolated easily. This special function makes the PMOD more suitable for lymphadenectomy in gastric cancer surgery and greatly improves the quality of the operation. The operation time and the blood loss in our study were not higher than in previously reported data.19 This result highlights the major advantages of PMOD. The hepatorenal recess is not only the lowest part of the peritoneal cavity when the subject is supine, but is also the important exchange point between the lesser sac and the peritoneal cavity, which lies to the right side of the omental foramen. We believe that it is important to dissect the right Gerota’s membrane and perirenal fat to reduce the possibility of peritoneal metastasis, especially for T3 or T4 tumors. Then, along the Kocher incision, the duodenum, the head of the pancreas, and the inferior vena cava are exposed. This is the key procedure of the whole operation, not only for tumor detection but for surgical decision making. After this step, nearly all the lower third gastric cancer patients underwent a Billroth I type of anastomosis after gastrectomy in our practice. The Billroth I type of anastomosis is more physiologically sound because it preserves the continuity of the digestive tract with the duodenum, theoretically maintains autocrine and paraTable 2. Surgical Variables of the 120 Patients Operative factors
Median ⴞ SD
Range
Operation time, min Blood loss, mL Postoperative stay, d
201.8 ⫾ 39.0 376.7 ⫾ 196.9 14.9 ⫾ 4.3
120–300 100–1,500 9–30
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Figure 12. (A) The metastatic lymph node ratio (MLR) distribution among the TNM staging system N categories in 120 patients; (B and C) the number of metastatic lymph nodes and the ratio of metastatic lymph node distribution among the total number of resected nodes for each patient.
crine signaling and feedback mechanisms, and is associated with a lower rate of early postoperative complications. It is the first choice after distal gastrectomy.20-22 The postoperative complication rate in our study was low (10.8%), and a majority of our patients had a smooth recovery. Lymphadenectomy along the main vessels is very difficult in radical gastrectomy. A space was formed by loose connective tissue between the vessels and the vaginae vasorum. Liberation of these spaces can totally expose the whole course of vessels easily and safely. Only in this surgical plane can we perform true lymphadenectomy in radical gastrectomy, including removal of lymph nodes and also the entire fascia along the vessels. This also helps to reduce the probability of vessel injury and decreases operation time.
Studies show that the higher the number of resected nodes, the higher the number of metastatic lymph nodes.23 The current edition of the International Union Against Cancer staging manual recommends examining at least 15 LNs for adequate gastric cancer staging. A minimum of 15 nodes is required for an adequate assessment, but 25 are required for a precise evaluation.24 More than 15 LNs were examined in all 120 patients in our study, and the median total number of LNs examined was 29 per patient. The MLR, calculated by dividing the number of metastatic lymph nodes by the total number of lymph nodes, is an important prognostic factor.25-29 Many studies have shown that this parameter is less vulnerable to stage migration and reflects the efficacy of lymph node dissection.30-32 However, selection of the best cutoff values of metastatic lymph node
Figure 13. Survival curve according to (A) N stage and (B) the metastatic lymph node ratio, There were significant differences among the groups (p ⬍ 0.00;).
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Figure 14. Survival curve of patients with (A) pN1– 2, in relation to (B) metastatic lymph node ratio category.
ratio remains difficult. Some studies describe the best-fit cutoff values as 0%, 1% to 9%, 10% to 25%, and more than 25%, and the overall survival curves are significantly different between the different N ratio subgroups.31,33 In our study, the MLR is shown in Figure 12B, and the survival curve according to N stage and the metastatic lymph node ratio in Figure 13. There were significant differences among the groups. It is necessary to attempt to reduce the MLR to less than 10% for potentially curable patients, in order to achieve better therapeutic efficiency, and the rates of surgery-related complications and mortality must be maintained at a low level. The MLRs of all 120 patients in this study may be lower than in other literature. In our study, the N1 gastric cancer patients got more survival benefit than the N2 patients after D2 resection in the subgroup of MLR. But the further overall survival benefit of our 3-step method for lymphadenectomy in gastric cancer surgery needs to be studied over a longer period of time in multiple institutions.
CONCLUSIONS Our institutional experience of lymphadenectomy during gastric cancer surgery can be summarized as follows: Use of the PMOD and curettage and aspiration technique; 3-step en bloc lymphadenectomy; vessel skeletonization inside the vaginae vasorum; and surgery in the right surgical plane and space. We conclude that our 3-step method for lymphadenectomy is easy to perform, safe, and useful for gastric cancer surgery. Author Contributions Study conception and design: Yingbin, Wenguang, Xuefeng Acquisition of data: Wenguang, Zhiping, Xiangsong, Jianwei
Analysis and interpretation of data: Xuefeng, Wenguang, Songgang Drafting of manuscript: Wenguang, Xuefeng, Zhiping Critical revision: Wenguang, Xuefeng, Zhiping
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