Survival outcomes after sentinel node navigation surgery for early gastric cancer

Abstract Aim This study evaluated the prognosis after sentinel node navigation surgery (SNNS) for early gastric cancer. Methods For 100 patients who underwent SNNS (between August 13, 2003 and December 17, 2018) at our hospital, the survival outcomes were investigated. Results (a) SN were detected with a diagnostic accuracy of 0.98. (b) Of seven patients who had positive SN metastasis, three underwent standard gastrectomy with D2 lymph node dissection. Among them, one patient died of recurrence (bone) and the other two patients were alive 4.5 and 14.7 years after surgery. The remaining four patients with positive SN who underwent diminished gastrectomy with lymphatic basin dissection at their request are alive 2.8, 6.0, 6.9 and 10.8 years after surgery without recurrence. (c) No patients who underwent diminished gastrectomy died of gastric cancer after surgery. (d) In the period following diminished gastrectomy, one patient underwent total gastrectomy and five patients underwent endoscopic submucosal dissection, and they survived for longer than 5 years. (e) As a result of SNNS, the gastric cancer‐specific cumulative 5‐year survival rate was 98.5%. Conclusions Diminished gastrectomy during SNNS resulted in a satisfactory prognosis. However, regular follow‐up after surgery is needed to detect secondary cancer of the remaining stomach.

the postoperative QOL of patients who underwent function-preserving gastrectomy with SN mapping are currently ongoing (UMIN 000014401).
The standard operative procedure for early gastric cancer (T1) is wide-extent gastrectomy with lymph node dissection D1/D1+ for N0 or D2 for N(+). Here, we examined whether the prognosis of patients after SNNS in our series was comparable with that after standard gastrectomy. Three patients had undergone prior endoscopic submucosal dissection (ESD) for early gastric cancer at another hospital and came to our hospital for SNNS.

| PATIENTS AND ME THODS
Eligibility criteria for SNNS and diminished gastrectomy were gastric cancer patients with a tumor size of 40 mm or less and a preoperative diagnosis of T1, N0, and M0. Information stated for informed consent included that SNNS is not recognized as a standard procedure for gastric cancer and that if a frozen SN section is positive, the recommended treatment is standard gastrectomy (wide-extent distal gastrectomy [WDG] or total gastrectomy [TG] with D2 lymph node dissection). Patients with heart disease, pulmonary disease, liver or renal disease, asthma, or allergic history were excluded.
All patients underwent open laparotomy, except for two patients who underwent laparoscopy. A total of 1 mL of Patent Blue (2.5%) (Wako Pure Chemical Industries) was injected endoscopically into the submucosal layer at four sites around the gastric cancer lesion.
Approximately 5-15 minutes later, the stained nodes (sentinel lymph nodes, SN) around the stomach were resected. SN were immediately submitted for frozen sectioning.
In principle, diminished gastrectomy is performed including the main tumor with 2 cm of the surrounding gastric wall as a safety margin. Four types of diminished gastrectomy during SNNS with lymphatic basin dissection were performed: (a) 1/2 distal gastrectomy (1/2DG), in which the approximate distal half of the whole stomach is resected while preserving the hepatic and celiac branches of the vagus nerve; (b) pylorus-preserving gastrectomy (PPG), in which the distal part of the stomach is resected while retaining 3-5 cm (average 4 cm) of the pyloric cuff and preserving the hepatic, pyloric, and celiac branches of the vagus nerve; (c) segmental gastrectomy (SG), in which the annular part of the middle or upper part of the stomach is transected while preserving the hepatic, pyloric, and celiac branches of the vagus nerve; and (d) local resection (LR), in which the gastric wall is locally resected, including the cancerous lesion with a 2-cm safety margin endoscopically marked by clips before the operation, while preserving the hepatic, pyloric, and celiac branches of the vagus nerve.
After surgery, the remaining stomach after SNNS was routinely assessed by endoscopy every year after surgery. The endpoint of this study was the survival outcomes after SNNS. The terminology used in the present study was mainly in accordance with the "Japanese classification of gastric carcinoma 3rd English edition" 7 or "Japanese gastric cancer treatment guidelines 2014 (ver. 4)". 8

| Statistical analysis
All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University), which is a graphical user interface for R (The R Foundation for Statistical Computing). More precisely, it is a modified version of R commander designed to add statistical functions frequently used in biostatistics. 9 Overall survival curves and gastric cancer-specific survival curves were calculated and plotted using the Kaplan-Meier method. In general, P values < .05 by one-way analysis of variance were considered significant.  (Table 1) The clinicopathological factors during SNNS are shown in Table 1.

| Clinicopathological features during SNNS and accuracy of SN
The lymphatic flow with SN was simply separated into three groups: lymphatic flow to the lesser curvature side, lymphatic flow to the greater curvature side, and lymphatic flow to both sides.
Lymphatic basin dissection was performed according to the range of lymphatic flow that was clearly observed when selecting SN.
Dissected lymph node stations in gastrectomy are presented in Table 1. For 87 patients with SN in the lesser curvature side, the following lymph node dissections were performed as a precau-  Table 1).
The mean number of SN was 3.

| Characteristics of seven patients with positive SN metastasis and prognosis (Table 2)
In true positive SN patients with a median follow-up period of

| Patients who underwent surgical or endoscopic treatment after diminished gastrectomy (Table 3)
Six patients underwent surgical or endoscopic treatment after di- All patients with diminished gastrectomy in this study underwent eradication of Helicobacter pylori before or after surgery, except patient No. 2 who refused eradication until the first ESD.

| Overall survival rate and gastric cancer-specific survival rate of the patients who underwent SNNS
In this SN series with a mean follow-up period of 6.7 years, one patient with positive SN metastasis who underwent standard gastrectomy (D2) died of bone metastasis. One patient died of pancreatic cancer. Five patients died of other benign disease, and one patient died from an accident. As a result, for the patients who underwent SNNS, the overall 5-year survival rate was 89.6% ( Figure 1) and the gastric cancer-specific 5-year survival rate was 98.5% ( Figure 2).
Among 97 patients who underwent diminished gastrectomy, although four patients with lymph node metastasis were included, no patient died or developed recurrence in this series (gastric cancer-specific survival rate of 100% with a mean follow-up period of 5.8 years). The accuracy of SN was not a main subject of this study because it should be investigated in patients who underwent D2 lymph node dissection. However, the diagnostic accuracy (0.98) in the present study was comparable with that in previous studies. 10 Regarding the retrieval of SN, 11  As stated above, we previously reported the QOL after different types of diminished gastrectomy (1/2DG, PPG, SG, and LR) in comparison with standard gastrectomy (TG and WDG) by postgastrectomy syndrome assessment scale-45. 5,16 As a result, TG was the poorest, 1/2DG, PPG, and SG were better than WDG, and LR was slightly better than 1/2DG, PPG, and SG. In this previous series, all diminished gastrectomies except for approximately half of the 1/2DG procedures were carried out during SNNS.

| D ISCUSS I ON
Diminished gastrectomy can be applied in many early gastric cancer cases more safely and broadly by incorporating SNNS, which may improve the QOL of the patients in the future. LR with lymphatic basin resection by SNNS may be the most powerful operative procedure to improve the postoperative QOL if curability is confirmed.
This retrospective cohort study of SNNS has some limitations.
First, the number of SNNS patients was relatively small. Second, all patients in this study underwent SNNS by a single surgeon who conducted the local multi-center trial for assessment of the feasibility of SNNS. 3 Thus, the standard use of SNNS is unclear.
In conclusion, diminished gastrectomy during SNNS resulted in a satisfactory prognosis. However, regular follow-up after surgery is needed to detect secondary cancer of the remaining stomach.

ACK N OWLED G EM ENT
We are grateful to Dr. Hiroshi Toyoda (Department of Pathology, Okayama Kyoritsu Hospital, Okayama, Japan) for his contribution to the pathological diagnoses of gastric cancer at our hospital, including frozen sections of lymph nodes.

D I SCLOS U R E
Conflict of Interest: The authors declare they have no conflicts of interest.