Sentinel Node Navigation Surgery:
Application to Minimally Invasive and Function-Preserving Surgery for Early Gastric Cancer
Yoshihide Otani1, Yuko Kitagawa1, Toshiharu Furukawa1,
Masashi Yoshida1, Yoshiro Saikawa1, Tetsuro Kubota1, Makio Mukai2, Kaori Kameyama2, Hirofumi Fujii3, Atsushi Kubo3, Koichiro Kumai4, and Masaki Kitajima1
Introduction
Lymphadenectomy in radical gastrectomy for gastric cancer has been generally accepted as a standard technique in many countries. Although gastrectomy with prophylactic lymph node dissection is the standard surgical procedure, the survival benefit of gastrectomy with D2 lymphadenectomy remains controversial [1,2]. Deter- mination of the extent of lymph node dissection required in patients with gastric cancer on the basis of actual node involvement is important because minimalization of dissection may be associated with reduced postoperative morbidity and mortality rates and increased postoperative quality of life (QOL). The development of novel diagnostic procedures for lymph node involvement is therefore crucial to accurate lymph node staging.
The recent increase in the detection rate of T1 gastric cancers in Japan and other countries has highlighted the importance of patients’ postoperative QOL. The accu- rate diagnostic exclusion of cases with lymph node involvement is an essential pre- condition to the acceptance and use of modified lymphadenectomy such as D0 or D1 for T1 cancers.
What Is the Sentinel Node?
The word “sentinel” is an old military word used to describe a soldier standing as a guard at the entrance of a castle or military base (Fig. 1). The sentinel node (SN) is the first lymph node (LN) encountered by the lymphatic flow as it drains from the primary lesion. SNs are detectable intraoperatively by the injection of a suitable dye or radioac- tive tracer (Fig. 2). A negative result for metastasis in the SN predicts the absence of the metastases in the other regional lymph nodes. The validity of the SN hypothesis
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1Department of Surgery,2Department of Pathology, and 3Department of Radiology,4Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
e-mail: otaniy@sc.itc.keio.ac.jp
has been demonstrated in various solid tumors including breast cancers [3,4], malig- nant melanoma [5], penile cancers [6], and gastrointestinal (GI) cancers [7,8].
Feasibility of Sentinel Node Navigation in Gastric Cancer Surgery
Despite the fact that lymphatic drainage from the GI tract is multidirectional and vari- able, recent reports from our group and other groups indicate that SN mapping and the detection of metastasis is feasible (Tables 1, 2) [8–32]. Here we introduce the actual methodology of SN navigation surgery and its possible application not only to mini- mally invasive but also to function-preserving surgery for early gastric cancer.
Endoscopic and Laparoscopic Surgery as a Minimally Invasive Procedure
From the standpoint of minimizing both the invasiveness of the procedure itself and posttreatment loss of gastric volume, endoscopic treatment is superior to other gastric cancer surgeries. Recent progress in endoscopic techniques has enabled the en bloc resection of larger mucosal areas than before, a procedure termed endoscopic sub- mucosal dissection (ESD) (see chapter by M. Fujishiro). The benefit of endoscopic mucosal resection (EMR) can be fully achieved through precise histological exami- nation using resected specimens, so an en bloc resection is always preferable.
Laparoscopic surgery was first introduced into gastric surgery more than a decade ago [33–36] (see chapter by S. Kitano). Since then, the minimal invasiveness of this method has been evidenced in many studies, using a variety of parameters such as postoperative pain, length of postoperative hospital stay, and so on [37,38].
Sentinel Node Hypothesis Sentinel Node:
First draining node from the primary lesion
A negative metastasis in the sentinel node predicts
the absence of the tumor metastasis in the other regional lymph nodes
Fig. 1. Definition of sentinel node and sen- tinel node hypothesis
Function-Preserving Gastric Surgery and Its Expected Benefit
Postgastrectomy disturbances such as dumping syndrome, alkaline reflux esopha- gogastritis, cholecystolithiasis, and reduced food intake from a small gastric volume are unpleasant sequelae in patients undergoing gastrectomy. These conditions lead to body weight loss and malnutrition and may be associated with carcinogenesis in the remnant stomach. A number of methods are now available to minimize or prevent Table 1. Summary of sentinel node studies in gastric cancer
Author No. of patients Study Year Journal Ref. No.
Kitagawa et al. 36 R 2000 Surg Clin N Am 8
Tsioulias et al. 6 D 2000 Arch Surg 9
Hiratsuka et al. 74 D 2001 Surgery 10
Aikou et al. 18 R, D 2001 Ann Surg Oncol 11
Kitagawa et al. 106 R 2001 Ann Surg Oncol 12
Ichikura et al. 62 D 2002 World J Surg 13
Kitagawa et al. 145 R 2002 Br J Surg 14
Hundley et al. 14 D 2002 Am Surg 15
Carlini et al. 40 D 2002 J Exp Clin Cancer Res 16
Hayashi et al. 31 R, D 2003 J Am Col Surg 17
Yasuda et al. 21 R 2003 Jpn J Clin Oncol 18
Gretschel et al. 15 R 2003 Chirurg 19
Miwa et al. 211 D 2003 Br J Surg 20
Tonouchi et al. 17 R, D 2003 Dig Surg 21
Levine et al. 12 D 2003 J Gastrointest Surg 22
Simsa et al. 22 D 2003 Acta Chir Belg 23
Ajisaka and Miwa 35 D 2003 Br J Surg 24
Ishigami et al. 27 R 2003 J Gastrointest Surg 25
Uenosono et al. 36 R 2003 Cancer Lett 26
Shiozawa et al. 22 D 2003 Hepatogastroenterology 27
Ryu et al. 71 D 2003 Eur J Surg Oncol 28
Song et al. 27 D 2004 Am J Surg 29
Karube et al. 41 R, D 2004 J Surg Oncol 30
Nimura et al. 84 D 2004 Br J Surg 31
Kim et al. 46 R 2004 Ann Surg 32
R, radioactive tracer labeling; D, dye labeling
Table 2. Results of sentinel node (SN) biopsy for gastric cancer in Keio University Hospital
Detection rate 97% (262/270)
Number of SN 4.1
Sensitivity 92% (34/37)
Accuracy 99% (259/262)
Source: Keio University Hospital (Jan. 1999–Feb. 2004)
these problems. The reduction of resection volume provided by the recently intro- duced segmental gastrectomy with lymphadenectomy preserves gastric volume and improves QOL in patients with early gastric cancer. Preservation of pylorus function, as a means of avoiding dumping syndrome and duodenal fluid regurgitation, is a current topic of interest among gastric surgeons [39–45]. Further, vagus-sparing gas- trectomy involves preservation of the hepatic and celiac branches of the vagus nerve, with the expectation that this will be beneficial in reducing postgastrectomy distur- bances as compared with conventional distal gastrectomy.
Treatment Strategy for Early Gastric Carcinoma with Intraoperative Sentinel Node Biopsy
If the SN can be intraoperatively confirmed as negative for metastasis, resection of the cancer lesion with modified LN dissection such as D0, D1+ a, and D1 + b is accept- able. Our treatment protocol under these conditions is shown in Fig. 3. Indications for laparoscopy-assisted segmental gastrectomy for gastric cancer in our institute include the following: (a) T1 (M, SM1), N0, (b) lack of indications for regular EMR, and (c) cancer located in the middle or lower third of the stomach, more than 4 cm from the pyloric ring [46].
Laparoscopy-Assisted Vagus-Sparing Segmental Gastrectomy (LAVSSG) under SN Navigation
We have introduced a novel method of laparoscopy-assisted surgery for early gastric cancer [46] (Fig. 4). For intraoperative SN detection, radiolabeled particles (tech- netium-99m-radiolabeled tin colloid) are endoscopically injected into the submucosal layer of the lesion 6 h before surgery.
The laparoscopic procedure is done with the patient in the modified lithotomy posi- tion. After laparoscopic survey of the abdomen, the gastrocolic ligament is divided 4cm distal to the epiploic arcade toward the lower pole of the spleen using Ligasure (Valleylab, Boulder, CO, USA). The roots of the left gastroepiploic vessels are exposed and divided using double clips at their origin. The lymph nodes (no. 4sb) along with the left gastroepiploic vessels are dissected from the greater curvature using Ligasure.
After division of LN station no. 4d, the root of the right gastroepiploic vein is exposed and secured with double clips and the right gastroepiploic artery is divided at its origin, preserving the infrapyloric artery (Fig. 5).
SN sampling (pathological examination) Mets (-) Mets (+)
Operation over Standard treatment (gastrectomy with D2 LN dissection)
EMR / Wedge resection / Segmental gastrectomy Fig. 3. Strategy for the treatment of early gastric cancer under sentinel node navigation. EMR, endoscopic mucosae resection; LN, lymph node
The innervations to the liver (hepatic branch), pylorus (pyloric branch), and small intestine (celiac branch) are preserved (see Fig. 4). The suprapyloric lymph nodes, no.
5, located only on the left side of the vessels, are sampled using the LCS. To preserve vagal nerve innervation of the pylorus, the hepatoduodenal ligament should be kept intact. The gastrohepatic ligament is divided toward the abdominal esophagus to remove the lymph nodes along the lesser curvature. With exposure of the right crus and anterodorsal side of the abdominal esophagus, the white wirelike vagus nerve can be identified under laparoscopic magnified view. The posterior trunk is then isolated with a right-angle clamp and retracted with a vessel loop toward the right side. The stomach is then transected 4 cm proximal to the pylorus using an endoscopic stapling device (60 mm, Endo GIA-II; US Surgical, Norwalk, CT, USA). The lymph nodes along the common hepatic artery, no. 8a, are dissected toward the celiac axis using LCS.
Lymph nodes no. 9 and 11p along the common hepatic artery and splenic artery are removed by LCS, exposing the left gastric artery and celiac axis. The celiac branch of the vagus nerve runs down along the lesser curvature to the celiac ganglion together with a branch of the left gastric artery. Retraction of the celiac branch using a vessel loop toward the right side facilitates this procedure (see Fig. 5). Finally, the celiac branch of the posterior vagal trunk is divided from the root of the left gastric artery, which is divided with double clips, thereby keeping the celiac branch and celiac gan- glion intact. An en bloc vagus nerve-sparing LN dissection is then completed.
The stomach with perigastric lymph nodes is exteriosed through a midline incisi- son measuring 5 cm and divided with an ILA 100 stapler (US Surgical). The small abdominal wound is covered with Lap Disc (Ethicon, Cincinnati, OH, USA) and the pneumoperitoneum is established again, confirming the absence of radiolabeled sen-
Anterior trunk Posterior trunk
Hepatic branch Celiac branch
Celiac Plexus Antral branch
Post. gastric branch
Ant. gastric branch
4 cm
Fig. 4. Surgical anatomy of vagus-sparing segmental gastrectomy (VSSG)
tinel nodes among residual lymph nodes in the upper abdominal cavity. On a back table, the resected specimen is carefully investigated, and radiolabeled lymph nodes identified with a handheld gamma probe are taken for intraoperative pathological examination (Fig. 6). The gastrogastric anastomosis is created manually with an inter- rupted layer-to-layer suture. A tube drain is inserted from the right lower trocar wound and placed through the foramen of Winslow, and the abdominal wound is closed. In the case illustrated here, the patient was discharged uneventfully 10 days postoperatively. Postoperative pathological examination revealed that the lesion was mucosal cancer with a negative surgical margin, and no positive lymph nodes were detected including sentinel nodes. On gastroscopy and barium meal 1 year after surgery, gastritis was less obvious than is seen with regular Billroth I anastomosis.
Occasionally, peristalsis was observed in the remnant stomach from the oral side to the pyloric ring (Fig. 7).
Unanswered Questions in SN Navigation in Gastric Cancer Surgery
Before SN navigation surgery in gastric cancer treatment can be broadly applied, the following issues require elucidation:
1. Should the tracer be radioactive particles or dye?
2. Should the SN be sampled by pinpoint pickup of the lymph node or lymphatic basin dissection?
3. Should the detection of cancer cells be done using hematoxilin and eosin, immuno- histochemistry, or the polymerase chain reaction?
Two nation-wide prospective studies are now examining these issues, one by the Japanese Society of Sentinel Node Navigation Surgery (http://web.sc.itc.keio.
ac.jp/surgery/snns/) and the second by the Japan Clinical Oncology Group (http://www.jcog.jp/).
Conclusion
The SN concept in gastric cancer treatment appears ready to assume several impor- tant roles in the individualization of treatment in patients with gastric cancer, espe- cially early gastric cancer. The coming decade is likely to see broad general acceptance of minimally invasive and function-preserving surgery based on the sensitive pre- diction of LN metastasis by SN biopsy.
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Fig. 2. Laparoscopic detection of sentinel nodes in gastric cancer. Sentinel nodes (lymph node station of no. 4d) are visible after intraoperative injection of blue dye into the submucosal layer under the mucosal cancer lesion
LGA
CHA SA GDA
Celiac branch of vagus nerve
RGV
Fig. 5. Preservation of the celiac branch of the vagus nerve. The celiac branch of the posterior trunk is separated from the left gastric artery. Retraction of the celiac branch using a vessel loop toward the right side facilitates this procedure. CHA, common hepatic artery; LGA, left gastric artery; SA, splenic artery; GDA, gastroduodenal artery; RGV, stump of right gastric vein
Color Plates
Fig. 7. Findings of endoscopy 1 year after laparoscopic-assisted VSSG (LAVSSG). Mucosal inflammation, which is commonly observed in the residual stomach of Billroth I anastomosis, is not obvious after pylorus preserving (segmental) gastrectomy. Also, peristalsis can be observed in the residual stomach
Fig. 6. Detection of radioactive lymph node in the resected specimen on the back table using handheld gamma probe
