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Innovative surgical techniques for gastric cancer treatment
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Medical Center of Leipzig, Germany
Gastric cancer is one of the 5 most common cancers in Europe, with an incidence of 4.6% and a mortality rate of 6.5% in men and a mortality rate of 5.6% in women1. Between 1998 and 2010, Germany had among the highest age-standardized incidences of gastric cancer (highest in women, third highest in men)2.
Current standards for surgery in gastric cancer treatment
The recommended therapy for more proximal tumours is total (en bloc) gastrectomy, to guarantee an appropriate proximal resection margin.
Pylorus-preserving gastrectomy may be appropriate, depending on the Siewert type of oesophagogastric junction (AEG). Siewert type II and III AEGs have a similar index of estimated benefit of lymph node dissection at all lymph node stations except the lower perigastric lymph nodes. Total gastrectomy is therefore the standard of care for Siewert type III AEG, and recent data from Japan suggest that preservation of the distal part of the stomach may be acceptable in Siewert type II AEG3.
Distal gastrectomy results in a better nutritional status and quality of life than is obtained with total gastrectomy, but survival is similar whether the gastrectomy is total or distal. The success of distal gastrectomy, however, may depend on achievement of a disease-free proximal resection margin4,5. The German S3 and Japanese Gastric Cancer Association (JGCA) criteria for surgical margins differ (Table 1)6,7.
As long as the resection margin is clear, the length of the proximal resection margin has no prognostic impact: proximal margin length is not associated with local recurrence or overall survival, and N+ patients with positive margins may not benefit from extended re-excision8,9.
Tumours at the oesophagogastric junction present a problem in that the resection margin is circumferential.
The standard procedure is a D2 lymphadenectomy (Fig. 1). The JGCA has classified lymphadenectomy according to the lymph node stations dissected (Fig. 2):7
- LAD I (stations 1–6)
- LAD II (stations 7–12)
- LAD III (stations 13–16)
In the German S3 guidelines6, D2 lymphadenectomy, defined as resection of regional lymph nodes of compartments 1 and 2, is standard for surgery of curative intent, and D2 lymphadenectomy without splenectomy or distal pancreatectomy should include resection and histological examination of at least 25 locoregional lymph nodes. The NCCN guidelines state that removal of an adequate number of lymph nodes (> 15) is beneficial for staging purposes10.
In a Japanese trial, no survival advantage was obtained for patients who underwent prophylactic para-aortic nodal dissection (PAND) (in 263 versus 260 patients, the 5 year overall survival rates were 69.2% and 70.3%, respectively)11.
Roux-en-Y reconstruction is a crucial reconstruction technique, particularly for oesophago-jejunostomy (Fig. 3).
Latest innovative techniques
Sentinel lymph node mapping
In advanced gastric cancer patients undergoing radical gastrectomy, secondary sentinel lymph node (SSLN) tracing provides surgeons with important information about the terminal status of lymph node metastasis and a scientific basis for individual lymphadenectomy14.
The SSLN technique was examined in 247 patients with gastric angle cancer and metastasis in group 3 lymph nodes who were randomized to undergo methylthioninium chloride injection into group 3 lymph nodes before resection (group A, n = 138) and individual lymphadenectomies performed on the basis of biopsy results from traced SSLNs (group B). SSLNs were identified in 82.6% of patients, of whom 78.9% had existing metastases in SSLNs. In group B, 109 patients underwent standard D2 radical gastrectomy.
The postoperative survival rates were significantly higher for patients in group A than for those in group B (P < 0.05) (Fig. 4)14.
Fig. 4. Overall survival in group A and group B. (Li Z, Jiang H, Song M, et al. J Zhejiang Univ Sci B 2015;16:897-903. Image at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642870/
Laparoscopic and robotic gastrectomy
Whether gastrectomy is performed laparoscopically or robotically, the extent of resection is the same as that obtained with open surgery and classified according to AEG type (Fig. 5).
Outcomes after laparoscopic and open subtotal gastrectomy have been compared by meta-analysis (Table 2).
In a meta-analysis of laparoscopic versus open D2 gastrectomy, there was no significant difference in 5-year disease-free survival (Fig. 6a) or 5-year overall survival (Fig. 6b), but laparoscopic D2 gastrectomy was considered safe and effective and to offer some advantages over open D2 gastrectomy for the treatment of locally advanced gastric cancer16.
Fig. 6. Five-year (a) disease-free and (b) overall survival after laparoscopic or open D2 gastrectomy. (Zou Z-H, Zhao L-Y, Mou T-Y, et al. World J Gastroenterol. 2014;20:16750-64. Image at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248223
In a case-control study of 2,041 consecutive laparoscopic gastrectomies, however, 3-year disease-free and overall survival rates were significantly higher with laparoscopic than with open surgery (Table 3)17.
Outcomes of laparoscopic and open gastrectomy in advanced gastric cancer are currently being evaluated in three multicentre, prospective, randomized, controlled studies from Asia:
- KLASS 02 (NCT01456598): Korean Laparoscopic Gastrointestinal Surgery Study (phase 3)
- JLSSG 0901 (CUMIN-CTR000003420): Japanese Laparoscopic Gastric Surgery Study (phase 2–3)
- CLASS 01 (NCT01609309): Chinese Laparoscopic Gastrointestinal Surgery Study (phase 3)
The inclusion criteria, planned enrolment, and aims of these studies are summarized in Table 4.
Robotic D2 gastrectomy in gastric cancer maintains respect of oncological principles and has been assessed in several studies (Tables 5 and 6)18.
Outcomes of robotic, laparoscopic, and open gastrectomy (data on robotic and laparoscopic gastrectomy from Asia) have been examined by meta-analysis of 12 studies (8,493 patients), with the following results:
- Intraoperative blood loss: robotic = laparoscopic < open
- Duration of surgery: robotic > laparoscopic ≈ open
- Number of lymph nodes: robotic = laparoscopic = open
- Morbidity and mortality: robotic = laparoscopic = open
No differences were found between total gastrectomy and distal gastrectomy19.
Optimizing surgical outcomes by multimodal therapy
The algorithm for the management of gastric cancer includes multimodal therapy to optimize surgical outcomes (Fig. 7)13.
Patients with advanced gastric cancer (cT3/4, N+) undergo CT, EUS, staging laparoscopy, or PET-CT to determine their suitability for gastrectomy. In those for whom R0 resection is probable, perioperative therapy with gastrectomy is advocated; in those for whom R0 resection is unlikely, gastrectomy may follow neoadjuvant therapy.
Several randomized trials have assessed outcomes of surgery with and without neoadjuvant or perioperative chemotherapy (Table 7) and of adjuvant chemotherapy or radiochemotherapy in resected gastric cancer (Table 8).
The role of neoadjuvant radiochemotherapy in gastric cancer is under evaluation (Fig. 8).
1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374-403.
2. Robert Koch Institute, Association of Population-based Cancer Registries in Germany. Cancer in Germany 2009/2010. 2014. Available from www.krebsdaten.de/Krebs/EN/Content/Publications/Cancer_in_Germany/cancer_chapters_2009_2010/cancer_germany_2009_2010.pdf?__blob=publicationFile. Accessed 26 April 2016.
3. Goto H, Tokunaga M, Miki Y, et al. The optimal extent of lymph node dissection for adenocarcinoma of the esophagogastric junction differs between Siewert type II and Siewert type III patients. Gastric Cancer 2015; 18(2): 375–81.
4. Bozzetti F, Marubini E, Bonfanti G, et al. Total versus subtotal gastrectomy: surgical morbidity and mortality rates in a multicenter Italian randomized trial. The Italian Gastrointestinal Tumor Study Group. Ann Surg 1997;226:613-20.
5. Bozzetti F, Marubini E, Bonfanti G, Miceli R, Piano C, Gennari L. Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Ann Surg 1999;230:170-8.
6. Moehler M, Al-Batran S-E, Andus T, et al. [German S3-guideline “Diagnosis and treatment of esophagogastric cancer”]. Z Für Gastroenterol 2011;49:461-531.
7. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc 2011;14:101-12.
8. Jang Y-J, Park M-S, Kim J-H, et al. Advanced gastric cancer in the middle one-third of the stomach: Should surgeons perform total gastrectomy? J Surg Oncol 2010;101:451-6.
9. Postlewait LM, Squires MH, Kooby DA, et al. The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative. J Surg Oncol 2015;112:203-7.
10. National Comprehensive Cancer Network. NCCN guidelines version 1.2016: Gastric cancer. 2016. Available from www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Accessed 26 April 2016.
11. Sasako M, Sano T, Yamamoto S, et al. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med 2008;359:453-62.
12. Waddell T, Verheij M, Allum W, et al. Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol ESMO 2013;24 Suppl 6:vi57-63.
13. Waddell T, Verheij M, Allum W, et al. Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 2014;40:584-91.
14. Li Z, Jiang H, Song M, Xu L, Xia D, Liu Q. Secondary sentinel lymph node tracing technique: a new method for tracing lymph nodes in radical gastrectomy for advanced gastric cancer. J Zhejiang Univ Sci B 2015;16:897-903.
15. Son T, Kwon IG, Hyung WJ. Minimally invasive surgery for gastric cancer treatment: current status and future perspectives. Gut Liver 2014;8:229-36.
16. Zou Z-H, Zhao L-Y, Mou T-Y, et al. Laparoscopic vs open D2 gastrectomy for locally advanced gastric cancer: a meta-analysis. World J Gastroenterol 2014;20:16750-64.
17. Lin J-X, Huang C-M, Zheng C-H, et al. Surgical outcomes of 2041 consecutive laparoscopic gastrectomy procedures for gastric cancer: a large-scale case control study. PloS One 2015;10:e0114948.
18. Baek S-J, Lee D-W, Park S-S, Kim S-H. Current status of robot-assisted gastric surgery. World J Gastrointest Oncol 2011;3:137-43.
19. Zong L, Seto Y, Aikou S, Takahashi T. Efficacy evaluation of subtotal and total gastrectomies in robotic surgery for gastric cancer compared with that in open and laparoscopic resections: a meta-analysis. PloS One 2014;9:e103312.