j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 3 ( 2 0 1 5 ) 1 9 0 e1 9 5
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Long-term outcomes of laparoscopic gastrectomy for gastric cancer Hirofumi Sugita, MD, PhD,a,* Kazuyuki Kojima, MD, PhD,b Mikito Inokuchi, MD, PhD,a and Keiji Kato, MD, PhDa a b
Department of Gastric Surgery, Tokyo Medical and Dental University, Tokyo, Japan Center for Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo, Japan
article info
abstract
Article history:
Background: Laparoscopic gastrectomy (LG) has been established as a procedure for the
Received 17 March 2014
treatment of gastric cancer. However, there have been few reports on the long-term out-
Received in revised form
comes of LG for gastric cancer. The aim of this study is to investigate the long-term out-
29 June 2014
comes of LG for gastric cancer.
Accepted 18 July 2014
Methods: A total of 278 consecutive patients who underwent LG in our unit between January
Available online 30 July 2014
1999 and December 2006 were included in this study. Survival, recurrence, and late gastrointestinal complications were analyzed.
Keywords:
Results: The median follow-up period was 73.7 mo (6e165 mo). Distal gastrectomy was
Laparoscopic gastrectomy
performed in 229 patients, total gastrectomy in 23 patients, proximal gastrectomy in 15
Gastric cancer
patients, and pylorus-preserving gastrectomy in 11 patients. Five-year overall and disease-
Oncological outcome
specific survival rates were 91% and 99% for stage IA, 75% and 91% for stage IB, 72% and 88%
Postoperative complication
for stage II, and 40% and 50% for stage III, respectively. Recurrences were detected in 15
Recurrence
(5.4%) patients, including 5 distant lymph node, 5 peritoneal, 4 hematogenous, and 1 locoregional recurrences. Bowel obstruction occurred in 4 (1.4%) patients, and gallstones developed in 37 (15%) patients. Conclusions: This follow-up investigation suggested that LG for gastric cancer is a feasible procedure from the standpoint of long-term oncological outcome and postoperative complications. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Since first reported by Kitano et al. in 1994 [1], laparoscopicassisted distal gastrectomy for gastric cancer has been established as a minimally invasive procedure. Technological advances, increased surgical experience, and improved techniques have promoted the use of laparoscopic gastrectomy (LG), which has been shown to be safe for patients with early gastric cancer [2,3]. LG has several advantages, including less blood loss, less postoperative pain, faster recovery, and better
short-term quality of life than open gastrectomy (OG) [4e8]. Although many reports have indicated the feasibility of LG with respect to short-term surgical outcomes, the role of LG has remained controversial because studies of long-term outcomes of LG have been insufficient [7,9e13]. Some previous reports of long-term outcomes included patients with short-term follow-up, and the median follow-up periods were 5 y or until death. Postoperative follow-up included clinical, laboratory, and imaging (ultrasonography or computed tomography) examinations performed every 6e12 mo in patients with stage I disease and every 3e6 mo in those with stage II or more advanced disease. Endoscopy was performed annually in most patients. Adjuvant chemotherapy treatment was not used in this series. A late complication was defined as a complication that occurred more than a month after surgery. Recurrence was diagnosed based on physical examinations, laboratory tests, endoscopy, computed tomography, and ultrasonography. The recurrence pattern was classified into the following four categories: locoregional, hematogenous, peritoneal, and distant lymph nodes [18]. Locoregional recurrence included tumor in adjacent organs, including in the anastomosis, gastric stump, or regional lymph nodes. Hematogenous recurrence included recurrence in the liver, lung, bone, brain, or other distant site. Peritoneal recurrence was defined as peritoneal seeding. Recurrence in distant lymph nodes was defined as involving the extra-regional lymph nodes of the stomach.
Indications and surgical procedures 2.4.
The type of gastric resection was determined according to tumor location. Proximal gastrectomy (PG) is indicated for lesions of early gastric cancer in the upper third of the stomach with no evidence of lymph node metastasis. Total gastrectomy (TG) is indicated for multiple lesions for which the distal stomach cannot be preserved. Pylorus-preserving gastrectomy (PPG) is indicated for lesions of the body of the stomach limited to the submucosa, 4 cm from the pylorus. The procedure for laparoscopic distal gastrectomy (LDG) has been described previously [16]. The extent of lymph node dissection was classified as D1, D1þ, or D2 in accordance with the treatment guidelines of the Japanese Gastric Cancer
Fig. 1 e Flowchart showing follow-up results of 278 patients with median follow-up of 73.7 mo.
Statistical analysis
Survival rates were estimated by the KaplaneMeier method. All analyses were performed using a statistical software package (SPSS version 11.0.5; SPSS Inc, Chicago, IL).
3.
Results
The data of 278 patients who underwent LG from January 1999eDecember 2006 were used in this study. The median follow-up period was 73.7 mo (Fig. 1). The patients’ clinicopathologic characteristics are presented in Table 1. Their median age was 63 y (range, 27e92 y). The ratio of males to females was 71:29. LDG was performed for 229 patients, TG for 23 patients, PG for 15 patients, and PPG for 11 patients. Lymph node dissection was classified as D1 in 1 patient, D1þ in 210 patients, and D2 in 67 patients. The median number of retrieved lymph nodes was 27 (range 10e70). Tumor depth was T1a in 115 patients, T1b in 113 patients, T2 in 24 patients, T3 in 18 patients, and T4a in 8 patients. Nodal status was N0 in 237 patients, N1 in 27 patients, N2 in 7 patients, and N3 in 7 patients. Stage IA was found in 211 patients (75.9%), IB in 32 patients (11.5%), IIA in 10 patients (3.6%), IIB in 15 patients (5.4%), IIIA in 5 patients (1.8%), IIIB in 2 patients (0.7%), and IIIC in 3 patients (1.1%). Fifteen patients (5.4%) experienced recurrence. The recurrence rate was 1.8% (4/228) in patients with early cancer and 22% (11/50) in those with advanced cancer. The median recurrence period was 14.3 mo (range 3e62 mo). The recurrence pattern was distant lymph node in 5 patients, peritoneal in 5 patients, hematogenous in 4 patients, and locoregional in
192
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Table 1 e Patients’ characteristics. Sex, n (%) Male Female Age (y) Median (range) BMI (kg/m2) Median (range) Type of resection, n (%) DG PPG PG TG Extent of lymph node dissection, n (%)* D1 D1þ D2 Tumor size (mm) Median (range) Number of dissected LNs Median (range) Histologic type, n (%) Differentiated Undifferentiated Depth of tumor, n (%)y T1a T1b T2 T3 T4a Lymph node metastasis, n (%)y N0 N1 N2 N3 Stage, n (%)y IA IB IIA IIB IIIA IIIB IIIC
Table 2 e Recurrence pattern according to depth and lymph node metastasis. 196 (70.5) 82 (29.5) 63 (27e92) 22.7 (15.6e36.4) 229 11 15 23
(82.4) (4.0) (5.4) (8.2)
1 (0.3) 210 (75.5) 67 (24.2) 35 (27e92) 27 (0e70) 177 (63.7) 101 (36.3) 115 113 24 18 8
(41.4) (40.6) (8.6) (6.5) (2.9)
237 27 7 7
(85.3) (9.7) (2.5) (2.5)
211 32 10 15 5 2 3
(75.9) (11.5) (3.6) (5.4) (1.8) (0.7) (1.1)
BMI ¼ body mass index; LN ¼ distant lymph nodes. * Gastric cancer treatment guidelines for doctor’s reference. y Japanese classification of gastric carcinoma, 14th edition.
1 patient. Locoregional recurrence was identified at the anastomosis site (Table 2). Remnant gastric cancer was considered heterochronous multiple cancers; thus, four remnant gastric cancers were excluded from the recurrences in this study. Late gastrointestinal complications occurred in 8 patients. Bowel obstruction occurred in 4 patients after LDG, but in no patients after TG, PG, and PPG. Cholecystitis occurred in 3 patients, and an incisional hernia occurred in 1 patient. Gallstones developed in 36 patients (14.5%), excluding patients who had undergone cholecystectomy before gastrectomy (Table 3). The hepatic branch of the vagus nerve was preserved in all patients, and the celiac branch of the vagus nerve was preserved in almost 60%. A total of 48 patients were dead at the time of analysis. The causes of death were 15 postoperative recurrences and 33 due to
T1a T1b T2 T3 T4a
N0
N1
H, LN LN, H
Loco LN, H
N2
N3 LN
P
H LN, P
P
H ¼ hematogenous; L ¼ locoregional; LN ¼ distant lymph nodes; P ¼ peritoneal.
other diseases. Causes of death other than gastric cancer were as follows: 9 other primary cancer, 7 pulmonary disease, 4 cardiovascular disease, 1 remnant gastric cancer, and 12 unknown. The 5-y overall survival rate (OS) was 85.6%. According to stage, 5-y OS was 91.0% in stage IA, 75.0% in stage IB, 72.0% in stage II, and 40.0% in stage III. The 5-y disease-specific survival rate (DSS) was 95.3%. The 5y DSS was 99.1% in stage IA, 90.6% in stage IB, 88.0% in stage II, and 50.0% in stage III. (Fig. 2) According to tumor depth, 5-y DSS was 100% in T1a, 96.5% in T1b, 91.7% in T2, 83.3% in T3, and 50.0% in T4a. According to lymph node metastasis, 5-y DSS was 97.5% in N0, 88.9% in N1, 85.7% in N2, and 28.6% in N3 (Fig. 3).
4.
Discussion
The 5-y DSS (95.3%) was completely satisfactory in comparison with previous reports and supported the oncological efficacy of LG [19,20]. On the other hand, the 5-y OS was lower than that reported by Lee et al., at 94.2% for stage IA, 87.4% for stage IB, 80.8% for stage IIA, and 69.6% for stage IIB. The main reason for the difference is that the follow-up period in the present study was longer than that in other reports that included short-term follow-up patients. Thus, the death rate due to other diseases, 11.9% in the present study, was higher than that reported by others (2.8% by Pak et al. [20] and 3.6% by Lee et al. [19]). In the present study, the postoperative recurrence rate was 5.4%. Limited to early cancer, the recurrence rate was 1.8%, the same as in other reports [18,21]. Fujiwara et al. [10] reported that early-stage cancers could recur rather late after surgery. In the present study, the median recurrence interval was 14.3 mo, but among 15 recurrence cases, 3 (20.0%) were diagnosed over 3 y after surgery, at 37, 50, and 62 mo, respectively. Feng et al. [22] reported that the recurrence peak
Table 3 e Late gastrointestinal complications. n (%) Ileus Incisional hernia Cholecystitis* Gallstone formation* *
Excluding patients who had undergone cholecystectomy.
4 1 3 36
(1.4) (0.4) (1.2) (14.6)
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193
Fig. 2 e Overall and disease-specific survivals by tumor stage.
rose to its maximum at 1.5 y after surgery, followed by a decline until 7.5 y after surgery. A long and careful follow-up may be needed after surgery for gastric cancer. The recurrence pattern in the present study was not that different from that previously reported [18,20]. There were five peritoneal recurrences in advanced cases. A previous report suggested that pneumoperitoneum was the cause of dissemination and port-site metastasis [23]. In the present study, there were no cases of port-site metastasis, and the rate of peritoneal recurrence was not as high as in some other reports [24,25]. Only 50 advanced gastric cancer cases were included in the present study; thus, the sample size was too small for a detailed analysis. A randomized, controlled trial of LG versus OG for advanced gastric cancer will clarify whether laparoscopic surgery is associated with peritoneal recurrence.
Ileus seemed to be less frequent than in another study of open surgery [26]. Several articles reported that adhesive bowel obstruction was less common after laparoscopic than after open surgery [27,28]. On the other hand, our previous report suggested that the possibility of an internal hernia was higher after laparoscopic Roux-en-Y reconstruction, such as Petersen hernia, than after open surgery because of fewer adhesions [29]. To prevent this hernia, we close Petersen space using a nonabsorbable running suture (Ethibond; Ethicon Endo-Surgery Inc, Blue Ash, OH). In the present study, the incidence of gallstones did not differ according to whether the celiac branch of the vagus nerve was preserved or removed. This result might be explained by the following factors. Not only the hepatic
Fig. 3 e Disease-specific survival by tumor depth and lymph node metastasis.
194
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branches of the vagus nerve regulate gallbladder function, but the retroperitoneal sympathetic and parasympathetic nerves are also involved. The part of the nerve plexus along the common hepatic artery or the celiac artery might be damaged by ultrasonically activated devices used for lymph node dissection of the number 8a or number 9 lymph nodes [30e33]. No patient in this study had symptomatic cholecystitis or received surgical treatment for gallstones after gastric surgery. In contrast, a previous study reported that cholecystitis developed in 27% of patients with gallstones after OG, and 46% of these patients underwent surgical treatment [32]. The present study suggests that LG for gastric cancer, especially early cancer, is a feasible procedure from the standpoint of long-term oncological outcome and postoperative complications. We expect that the present result will be confirmed by prospective, randomized trials, and the indications for LG will be expanded in the future.
Acknowledgment Authors’ contributions: H.S. was responsible for drafting and writing the article, and analyzing the patient data. Ka.K., M.I., and Ke.K. collected the data.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in the article.
references
[1] Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy assisted Billroth I gastrectomy. Surg Laparosc Endosc 1994; 4:146. [2] Lee JH, Kim YW, Ryu KW, et al. A phase-II clinical trial of laparoscopy-assisted distal gastrectomy with D2 lymph node dissection for gastric cancer patients. Ann Surg Oncol 2007; 14:3148. [3] Katai H, Sasako M, Fukuda H, et al. Safety and feasibility of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: a multicenter phase II trial (JCOG 0703). Gastric Cancer 2010;13:238. [4] Kim Y, Baik YH, Yun YH, et al. Improved quality of life outcomes after laparoscopy assisted distal gastrectomy for early gastric cancer: results of a prospective randomized clinical trial. Ann Surg 2008;248:721. [5] Kim MC, Kim W, Kim HH, et al. Risk factors associated with complication following laparoscopy-assisted gastrectomy for gastric cancer: a large-scale Korean multicenter study. Ann Surg Oncol 2008;15:2692. [6] Lee JH, Han HS. A prospective randomized study comparing open vs laparoscopy-assisted distal gastrectomy in early gastric cancer: early results. Surg Endosc 2005;19:168. [7] Memon MA, Khan S, Yunus RN, Barr R, Memon B. Metaanalysis of laparoscopic and open distal gastrectomy for gastric carcinoma. Surg Endosc 2008;22:1781.
[8] Huscher CG, Mingoli A, Sgarzini G, et al. Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: five-year results of a randomized prospective trial. Ann Surg 2005;241: 2132. [9] Volz J, Kster S, Spacek Z, Paweletz N. The influence of pneumoperitoneum used in laparoscopic surgery on an intraabdominal tumor growth. Cancer 1999;86:770. [10] Fujiwara M, Kodera Y, Kasai Y, et al. Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection for early gastric carcinoma: a review of 43 cases. J Am Coll Surg 2003;196:75. [11] Curet MJ. Port site metastases. Am J Surg 2004;187:705. [12] Kitano S, Shiraishi N, Uyama I, Sugihara K, Tanigawa N. Japanese Laparoscopic Surgery Study Group. A multicenter study on oncologic outcome of laparoscopic gastrectomy for early cancer in Japan. Ann Surg 2007;245:68. [13] Kim HI, Hyung WJ, Lee CR, et al. Intraoperative portable abdominal radiograph for tumor localization: a simple and accurate method for laparoscopic gastrectomy. Surg Endosc 2011;25:958. [14] Sano T, Sasako M, Kinoshita T, Maruyama K. Recurrence of early gastric cancer. Follow-up of 1475 patients and review of the Japanese literature. Cancer 1993;72:3174. [15] Kwon HY, Hyung WJ, Lee JH, Lee SK, Noh SH. Outcomes of laparoscopic gastrectomy after endoscopic treatment for gastric cancer: a comparison with open gastrectomy. J Gastric Cancer 2013;13:51. [16] Kojima K, Yamada H, Inokuchi M, Kawano T, Sugihara K. A comparison of Roux-en-Y and Billroth-I reconstruction after laparoscopy-assisted distal gastrectomy. Ann Surg 2008;247:962. [17] Japanese Gastric Cancer Association. Gastric cancer treatment guidelines for doctor’s reference. 3 ed. Tokyo: Kanehara; 2010 (in Japanese). [18] Song J, Lee HJ, Cho GS, et al. Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) Group. Recurrence following laparoscopy-assisted gastrectomy for gastric cancer: a multicenter retrospective analysis of 1,417 patients. Ann Surg Oncol 2010;17:1777. [19] Lee SW, Nomura E, Bouras G, Tokuhara T, Tsunemi S, Tanigawa N. Long-term oncologic outcomes from laparoscopic gastrectomy for gastric cancer: a single-center experience of 601 consecutive resections. J Am Coll Surg 2010;211:33. [20] Pak KH, Hyung WJ, Son T, et al. Long-term oncologic outcomes of 714 consecutive laparoscopic gastrectomies for gastric cancer: results from the 7-year experience of a single institute. Surg Endosc 2012;26:130. [21] Kim KH, Kim MC, Jung GJ, Kim HH. Long-term outcomes and feasibility with laparoscopy-assisted gastrectomy for gastric cancer. J Gastric Cancer 2012;12:18. [22] Feng XY, Chen YB, Wang W, et al. Time-varying pattern of recurrence risk for gastric cancer patients. Med Oncol 2013; 30:514. [23] Lee YJ, Ha WS, Park ST, Choi SK, Hong SC. Port-site recurrence after laparoscopy-assisted gastrectomy: report of the first case. J Laparoendosc Adv Surg Tech A 2007;17:455. [24] Roukos DH, Lorenz M, Karakostas K, Paraschou P, Batsis C, Kappas AM. Pathological serosa and node-based classification accurately predicts gastric cancer recurrence risk and outcome, and determines potential and limitation of a Japanese-style extensive surgery for Western patients: a prospective with quality control 10-year follow-up study. Br J Cancer 2001;84:1602. [25] Sasako M. Principles of surgical treatment for curable gastric cancer. J Clin Oncol 2003;21:274. [26] Sugimachi K, Korenaga D, Tomikawa M, et al. Factors influencing the development of small intestinal obstruction
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 3 ( 2 0 1 5 ) 1 9 0 e1 9 5
following gastrectomy for early gastric cancer. Hepatogastroenterology 2008;55:496. [27] Gutt CN, Oniu T, Schemmer P, Mehrabi A, Buchler MW. Fewer adhesions induced by laparoscopic surgery? Surg Endosc 2004;18:898. [28] Dowson HM, Bong JJ, Lovell DP, Worthington TR, Karanjia ND, Rockall TA. Reduced adhesion formation following laparoscopic versus open colorectal surgery. Br J Surg 2008;95:909. [29] Kojima K, Inokuchi M, Kato K, Kazuo M, Sugihara K. Petersen’s hernia after laparoscopic distal gastrectomy with Roux-en-Y reconstruction for gastric cancer. Gastric Cancer 2013;17:146 [Epub ahead of print].
195
[30] Inokuchi M, Kojima K, Yamada H, Kato K, Hayashi M, Motoyama K. Sugihara long-term outcomes of Roux-en-Y and Billroth-I reconstruction after laparoscopic distal gastrectomy. Gastric Cancer 2012;61:430. [31] Fukagawa T, Katai H, Saka M, Morita S, Sano T, Sasako M. Gallstone formation after gastric cancer surgery. J Gastrointest Surg 2009;13:886. [32] Akatsu T, Yoshida M, Kubota T, et al. Gallstone disease after extended (D2) lymph node dissection for gastric cancer. Word J Surg 2005;29:182. [33] Rehnberg O, Haglund U. Gallstone disease following antrectomy and gastroduodenostomy with or without vagotomy. Ann Surg 1985;201:172.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Long-term outcomes of laparoscopic gastrectomy for gastric cancer Hirofumi Sugita, MD, PhD,a,* Kazuyuki Kojima, MD, PhD,b Mikito Inokuchi, MD, PhD,a and Keiji Kato, MD, PhDa a b
Department of Gastric Surgery, Tokyo Medical and Dental University, Tokyo, Japan Center for Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo, Japan
article info
abstract
Article history:
Background: Laparoscopic gastrectomy (LG) has been established as a procedure for the
Received 17 March 2014
treatment of gastric cancer. However, there have been few reports on the long-term out-
Received in revised form
comes of LG for gastric cancer. The aim of this study is to investigate the long-term out-
29 June 2014
comes of LG for gastric cancer.
Accepted 18 July 2014
Methods: A total of 278 consecutive patients who underwent LG in our unit between January
Available online 30 July 2014
1999 and December 2006 were included in this study. Survival, recurrence, and late gastrointestinal complications were analyzed.
Keywords:
Results: The median follow-up period was 73.7 mo (6e165 mo). Distal gastrectomy was
Laparoscopic gastrectomy
performed in 229 patients, total gastrectomy in 23 patients, proximal gastrectomy in 15
Gastric cancer
patients, and pylorus-preserving gastrectomy in 11 patients. Five-year overall and disease-
Oncological outcome
specific survival rates were 91% and 99% for stage IA, 75% and 91% for stage IB, 72% and 88%
Postoperative complication
for stage II, and 40% and 50% for stage III, respectively. Recurrences were detected in 15
Recurrence
(5.4%) patients, including 5 distant lymph node, 5 peritoneal, 4 hematogenous, and 1 locoregional recurrences. Bowel obstruction occurred in 4 (1.4%) patients, and gallstones developed in 37 (15%) patients. Conclusions: This follow-up investigation suggested that LG for gastric cancer is a feasible procedure from the standpoint of long-term oncological outcome and postoperative complications. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Since first reported by Kitano et al. in 1994 [1], laparoscopicassisted distal gastrectomy for gastric cancer has been established as a minimally invasive procedure. Technological advances, increased surgical experience, and improved techniques have promoted the use of laparoscopic gastrectomy (LG), which has been shown to be safe for patients with early gastric cancer [2,3]. LG has several advantages, including less blood loss, less postoperative pain, faster recovery, and better
short-term quality of life than open gastrectomy (OG) [4e8]. Although many reports have indicated the feasibility of LG with respect to short-term surgical outcomes, the role of LG has remained controversial because studies of long-term outcomes of LG have been insufficient [7,9e13]. Some previous reports of long-term outcomes included patients with short-term follow-up, and the median follow-up periods were 5 y or until death. Postoperative follow-up included clinical, laboratory, and imaging (ultrasonography or computed tomography) examinations performed every 6e12 mo in patients with stage I disease and every 3e6 mo in those with stage II or more advanced disease. Endoscopy was performed annually in most patients. Adjuvant chemotherapy treatment was not used in this series. A late complication was defined as a complication that occurred more than a month after surgery. Recurrence was diagnosed based on physical examinations, laboratory tests, endoscopy, computed tomography, and ultrasonography. The recurrence pattern was classified into the following four categories: locoregional, hematogenous, peritoneal, and distant lymph nodes [18]. Locoregional recurrence included tumor in adjacent organs, including in the anastomosis, gastric stump, or regional lymph nodes. Hematogenous recurrence included recurrence in the liver, lung, bone, brain, or other distant site. Peritoneal recurrence was defined as peritoneal seeding. Recurrence in distant lymph nodes was defined as involving the extra-regional lymph nodes of the stomach.
Indications and surgical procedures 2.4.
The type of gastric resection was determined according to tumor location. Proximal gastrectomy (PG) is indicated for lesions of early gastric cancer in the upper third of the stomach with no evidence of lymph node metastasis. Total gastrectomy (TG) is indicated for multiple lesions for which the distal stomach cannot be preserved. Pylorus-preserving gastrectomy (PPG) is indicated for lesions of the body of the stomach limited to the submucosa, 4 cm from the pylorus. The procedure for laparoscopic distal gastrectomy (LDG) has been described previously [16]. The extent of lymph node dissection was classified as D1, D1þ, or D2 in accordance with the treatment guidelines of the Japanese Gastric Cancer
Fig. 1 e Flowchart showing follow-up results of 278 patients with median follow-up of 73.7 mo.
Statistical analysis
Survival rates were estimated by the KaplaneMeier method. All analyses were performed using a statistical software package (SPSS version 11.0.5; SPSS Inc, Chicago, IL).
3.
Results
The data of 278 patients who underwent LG from January 1999eDecember 2006 were used in this study. The median follow-up period was 73.7 mo (Fig. 1). The patients’ clinicopathologic characteristics are presented in Table 1. Their median age was 63 y (range, 27e92 y). The ratio of males to females was 71:29. LDG was performed for 229 patients, TG for 23 patients, PG for 15 patients, and PPG for 11 patients. Lymph node dissection was classified as D1 in 1 patient, D1þ in 210 patients, and D2 in 67 patients. The median number of retrieved lymph nodes was 27 (range 10e70). Tumor depth was T1a in 115 patients, T1b in 113 patients, T2 in 24 patients, T3 in 18 patients, and T4a in 8 patients. Nodal status was N0 in 237 patients, N1 in 27 patients, N2 in 7 patients, and N3 in 7 patients. Stage IA was found in 211 patients (75.9%), IB in 32 patients (11.5%), IIA in 10 patients (3.6%), IIB in 15 patients (5.4%), IIIA in 5 patients (1.8%), IIIB in 2 patients (0.7%), and IIIC in 3 patients (1.1%). Fifteen patients (5.4%) experienced recurrence. The recurrence rate was 1.8% (4/228) in patients with early cancer and 22% (11/50) in those with advanced cancer. The median recurrence period was 14.3 mo (range 3e62 mo). The recurrence pattern was distant lymph node in 5 patients, peritoneal in 5 patients, hematogenous in 4 patients, and locoregional in
192
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Table 1 e Patients’ characteristics. Sex, n (%) Male Female Age (y) Median (range) BMI (kg/m2) Median (range) Type of resection, n (%) DG PPG PG TG Extent of lymph node dissection, n (%)* D1 D1þ D2 Tumor size (mm) Median (range) Number of dissected LNs Median (range) Histologic type, n (%) Differentiated Undifferentiated Depth of tumor, n (%)y T1a T1b T2 T3 T4a Lymph node metastasis, n (%)y N0 N1 N2 N3 Stage, n (%)y IA IB IIA IIB IIIA IIIB IIIC
Table 2 e Recurrence pattern according to depth and lymph node metastasis. 196 (70.5) 82 (29.5) 63 (27e92) 22.7 (15.6e36.4) 229 11 15 23
(82.4) (4.0) (5.4) (8.2)
1 (0.3) 210 (75.5) 67 (24.2) 35 (27e92) 27 (0e70) 177 (63.7) 101 (36.3) 115 113 24 18 8
(41.4) (40.6) (8.6) (6.5) (2.9)
237 27 7 7
(85.3) (9.7) (2.5) (2.5)
211 32 10 15 5 2 3
(75.9) (11.5) (3.6) (5.4) (1.8) (0.7) (1.1)
BMI ¼ body mass index; LN ¼ distant lymph nodes. * Gastric cancer treatment guidelines for doctor’s reference. y Japanese classification of gastric carcinoma, 14th edition.
1 patient. Locoregional recurrence was identified at the anastomosis site (Table 2). Remnant gastric cancer was considered heterochronous multiple cancers; thus, four remnant gastric cancers were excluded from the recurrences in this study. Late gastrointestinal complications occurred in 8 patients. Bowel obstruction occurred in 4 patients after LDG, but in no patients after TG, PG, and PPG. Cholecystitis occurred in 3 patients, and an incisional hernia occurred in 1 patient. Gallstones developed in 36 patients (14.5%), excluding patients who had undergone cholecystectomy before gastrectomy (Table 3). The hepatic branch of the vagus nerve was preserved in all patients, and the celiac branch of the vagus nerve was preserved in almost 60%. A total of 48 patients were dead at the time of analysis. The causes of death were 15 postoperative recurrences and 33 due to
T1a T1b T2 T3 T4a
N0
N1
H, LN LN, H
Loco LN, H
N2
N3 LN
P
H LN, P
P
H ¼ hematogenous; L ¼ locoregional; LN ¼ distant lymph nodes; P ¼ peritoneal.
other diseases. Causes of death other than gastric cancer were as follows: 9 other primary cancer, 7 pulmonary disease, 4 cardiovascular disease, 1 remnant gastric cancer, and 12 unknown. The 5-y overall survival rate (OS) was 85.6%. According to stage, 5-y OS was 91.0% in stage IA, 75.0% in stage IB, 72.0% in stage II, and 40.0% in stage III. The 5-y disease-specific survival rate (DSS) was 95.3%. The 5y DSS was 99.1% in stage IA, 90.6% in stage IB, 88.0% in stage II, and 50.0% in stage III. (Fig. 2) According to tumor depth, 5-y DSS was 100% in T1a, 96.5% in T1b, 91.7% in T2, 83.3% in T3, and 50.0% in T4a. According to lymph node metastasis, 5-y DSS was 97.5% in N0, 88.9% in N1, 85.7% in N2, and 28.6% in N3 (Fig. 3).
4.
Discussion
The 5-y DSS (95.3%) was completely satisfactory in comparison with previous reports and supported the oncological efficacy of LG [19,20]. On the other hand, the 5-y OS was lower than that reported by Lee et al., at 94.2% for stage IA, 87.4% for stage IB, 80.8% for stage IIA, and 69.6% for stage IIB. The main reason for the difference is that the follow-up period in the present study was longer than that in other reports that included short-term follow-up patients. Thus, the death rate due to other diseases, 11.9% in the present study, was higher than that reported by others (2.8% by Pak et al. [20] and 3.6% by Lee et al. [19]). In the present study, the postoperative recurrence rate was 5.4%. Limited to early cancer, the recurrence rate was 1.8%, the same as in other reports [18,21]. Fujiwara et al. [10] reported that early-stage cancers could recur rather late after surgery. In the present study, the median recurrence interval was 14.3 mo, but among 15 recurrence cases, 3 (20.0%) were diagnosed over 3 y after surgery, at 37, 50, and 62 mo, respectively. Feng et al. [22] reported that the recurrence peak
Table 3 e Late gastrointestinal complications. n (%) Ileus Incisional hernia Cholecystitis* Gallstone formation* *
Excluding patients who had undergone cholecystectomy.
4 1 3 36
(1.4) (0.4) (1.2) (14.6)
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 3 ( 2 0 1 5 ) 1 9 0 e1 9 5
193
Fig. 2 e Overall and disease-specific survivals by tumor stage.
rose to its maximum at 1.5 y after surgery, followed by a decline until 7.5 y after surgery. A long and careful follow-up may be needed after surgery for gastric cancer. The recurrence pattern in the present study was not that different from that previously reported [18,20]. There were five peritoneal recurrences in advanced cases. A previous report suggested that pneumoperitoneum was the cause of dissemination and port-site metastasis [23]. In the present study, there were no cases of port-site metastasis, and the rate of peritoneal recurrence was not as high as in some other reports [24,25]. Only 50 advanced gastric cancer cases were included in the present study; thus, the sample size was too small for a detailed analysis. A randomized, controlled trial of LG versus OG for advanced gastric cancer will clarify whether laparoscopic surgery is associated with peritoneal recurrence.
Ileus seemed to be less frequent than in another study of open surgery [26]. Several articles reported that adhesive bowel obstruction was less common after laparoscopic than after open surgery [27,28]. On the other hand, our previous report suggested that the possibility of an internal hernia was higher after laparoscopic Roux-en-Y reconstruction, such as Petersen hernia, than after open surgery because of fewer adhesions [29]. To prevent this hernia, we close Petersen space using a nonabsorbable running suture (Ethibond; Ethicon Endo-Surgery Inc, Blue Ash, OH). In the present study, the incidence of gallstones did not differ according to whether the celiac branch of the vagus nerve was preserved or removed. This result might be explained by the following factors. Not only the hepatic
Fig. 3 e Disease-specific survival by tumor depth and lymph node metastasis.
194
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 3 ( 2 0 1 5 ) 1 9 0 e1 9 5
branches of the vagus nerve regulate gallbladder function, but the retroperitoneal sympathetic and parasympathetic nerves are also involved. The part of the nerve plexus along the common hepatic artery or the celiac artery might be damaged by ultrasonically activated devices used for lymph node dissection of the number 8a or number 9 lymph nodes [30e33]. No patient in this study had symptomatic cholecystitis or received surgical treatment for gallstones after gastric surgery. In contrast, a previous study reported that cholecystitis developed in 27% of patients with gallstones after OG, and 46% of these patients underwent surgical treatment [32]. The present study suggests that LG for gastric cancer, especially early cancer, is a feasible procedure from the standpoint of long-term oncological outcome and postoperative complications. We expect that the present result will be confirmed by prospective, randomized trials, and the indications for LG will be expanded in the future.
Acknowledgment Authors’ contributions: H.S. was responsible for drafting and writing the article, and analyzing the patient data. Ka.K., M.I., and Ke.K. collected the data.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in the article.
references
[1] Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy assisted Billroth I gastrectomy. Surg Laparosc Endosc 1994; 4:146. [2] Lee JH, Kim YW, Ryu KW, et al. A phase-II clinical trial of laparoscopy-assisted distal gastrectomy with D2 lymph node dissection for gastric cancer patients. Ann Surg Oncol 2007; 14:3148. [3] Katai H, Sasako M, Fukuda H, et al. Safety and feasibility of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: a multicenter phase II trial (JCOG 0703). Gastric Cancer 2010;13:238. [4] Kim Y, Baik YH, Yun YH, et al. Improved quality of life outcomes after laparoscopy assisted distal gastrectomy for early gastric cancer: results of a prospective randomized clinical trial. Ann Surg 2008;248:721. [5] Kim MC, Kim W, Kim HH, et al. Risk factors associated with complication following laparoscopy-assisted gastrectomy for gastric cancer: a large-scale Korean multicenter study. Ann Surg Oncol 2008;15:2692. [6] Lee JH, Han HS. A prospective randomized study comparing open vs laparoscopy-assisted distal gastrectomy in early gastric cancer: early results. Surg Endosc 2005;19:168. [7] Memon MA, Khan S, Yunus RN, Barr R, Memon B. Metaanalysis of laparoscopic and open distal gastrectomy for gastric carcinoma. Surg Endosc 2008;22:1781.
[8] Huscher CG, Mingoli A, Sgarzini G, et al. Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: five-year results of a randomized prospective trial. Ann Surg 2005;241: 2132. [9] Volz J, Kster S, Spacek Z, Paweletz N. The influence of pneumoperitoneum used in laparoscopic surgery on an intraabdominal tumor growth. Cancer 1999;86:770. [10] Fujiwara M, Kodera Y, Kasai Y, et al. Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection for early gastric carcinoma: a review of 43 cases. J Am Coll Surg 2003;196:75. [11] Curet MJ. Port site metastases. Am J Surg 2004;187:705. [12] Kitano S, Shiraishi N, Uyama I, Sugihara K, Tanigawa N. Japanese Laparoscopic Surgery Study Group. A multicenter study on oncologic outcome of laparoscopic gastrectomy for early cancer in Japan. Ann Surg 2007;245:68. [13] Kim HI, Hyung WJ, Lee CR, et al. Intraoperative portable abdominal radiograph for tumor localization: a simple and accurate method for laparoscopic gastrectomy. Surg Endosc 2011;25:958. [14] Sano T, Sasako M, Kinoshita T, Maruyama K. Recurrence of early gastric cancer. Follow-up of 1475 patients and review of the Japanese literature. Cancer 1993;72:3174. [15] Kwon HY, Hyung WJ, Lee JH, Lee SK, Noh SH. Outcomes of laparoscopic gastrectomy after endoscopic treatment for gastric cancer: a comparison with open gastrectomy. J Gastric Cancer 2013;13:51. [16] Kojima K, Yamada H, Inokuchi M, Kawano T, Sugihara K. A comparison of Roux-en-Y and Billroth-I reconstruction after laparoscopy-assisted distal gastrectomy. Ann Surg 2008;247:962. [17] Japanese Gastric Cancer Association. Gastric cancer treatment guidelines for doctor’s reference. 3 ed. Tokyo: Kanehara; 2010 (in Japanese). [18] Song J, Lee HJ, Cho GS, et al. Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) Group. Recurrence following laparoscopy-assisted gastrectomy for gastric cancer: a multicenter retrospective analysis of 1,417 patients. Ann Surg Oncol 2010;17:1777. [19] Lee SW, Nomura E, Bouras G, Tokuhara T, Tsunemi S, Tanigawa N. Long-term oncologic outcomes from laparoscopic gastrectomy for gastric cancer: a single-center experience of 601 consecutive resections. J Am Coll Surg 2010;211:33. [20] Pak KH, Hyung WJ, Son T, et al. Long-term oncologic outcomes of 714 consecutive laparoscopic gastrectomies for gastric cancer: results from the 7-year experience of a single institute. Surg Endosc 2012;26:130. [21] Kim KH, Kim MC, Jung GJ, Kim HH. Long-term outcomes and feasibility with laparoscopy-assisted gastrectomy for gastric cancer. J Gastric Cancer 2012;12:18. [22] Feng XY, Chen YB, Wang W, et al. Time-varying pattern of recurrence risk for gastric cancer patients. Med Oncol 2013; 30:514. [23] Lee YJ, Ha WS, Park ST, Choi SK, Hong SC. Port-site recurrence after laparoscopy-assisted gastrectomy: report of the first case. J Laparoendosc Adv Surg Tech A 2007;17:455. [24] Roukos DH, Lorenz M, Karakostas K, Paraschou P, Batsis C, Kappas AM. Pathological serosa and node-based classification accurately predicts gastric cancer recurrence risk and outcome, and determines potential and limitation of a Japanese-style extensive surgery for Western patients: a prospective with quality control 10-year follow-up study. Br J Cancer 2001;84:1602. [25] Sasako M. Principles of surgical treatment for curable gastric cancer. J Clin Oncol 2003;21:274. [26] Sugimachi K, Korenaga D, Tomikawa M, et al. Factors influencing the development of small intestinal obstruction
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 3 ( 2 0 1 5 ) 1 9 0 e1 9 5
following gastrectomy for early gastric cancer. Hepatogastroenterology 2008;55:496. [27] Gutt CN, Oniu T, Schemmer P, Mehrabi A, Buchler MW. Fewer adhesions induced by laparoscopic surgery? Surg Endosc 2004;18:898. [28] Dowson HM, Bong JJ, Lovell DP, Worthington TR, Karanjia ND, Rockall TA. Reduced adhesion formation following laparoscopic versus open colorectal surgery. Br J Surg 2008;95:909. [29] Kojima K, Inokuchi M, Kato K, Kazuo M, Sugihara K. Petersen’s hernia after laparoscopic distal gastrectomy with Roux-en-Y reconstruction for gastric cancer. Gastric Cancer 2013;17:146 [Epub ahead of print].
195
[30] Inokuchi M, Kojima K, Yamada H, Kato K, Hayashi M, Motoyama K. Sugihara long-term outcomes of Roux-en-Y and Billroth-I reconstruction after laparoscopic distal gastrectomy. Gastric Cancer 2012;61:430. [31] Fukagawa T, Katai H, Saka M, Morita S, Sano T, Sasako M. Gallstone formation after gastric cancer surgery. J Gastrointest Surg 2009;13:886. [32] Akatsu T, Yoshida M, Kubota T, et al. Gallstone disease after extended (D2) lymph node dissection for gastric cancer. Word J Surg 2005;29:182. [33] Rehnberg O, Haglund U. Gallstone disease following antrectomy and gastroduodenostomy with or without vagotomy. Ann Surg 1985;201:172.
