Introduction

With the increasing proportion of early gastric cancer (EGC) and the excellent survival outcomes after treatment, surgeons are now paying attention to postoperative quality of life (QOL) to be as important as survival for these patients [1, 2]. Function-preserving surgery is a surgical approach which meets such trend. Pylorus-preserving gastrectomy (PPG) is a good example of function-preserving surgeries to reduce the surgical extent without compromising oncologic safety. PPG was firstly introduced by Maki et al. in 1967 for the treatment of peptic ulcers [3] and then was applied in gastric cancer in Japan and Korea. EGC located in the middle part of the stomach would be indicated, and with preserved pylorus, less postgastrectomy symptom or sequelae are expected.

Indication

For PPG, to preserve pyloric branch of the vagus nerve, lymph node (LN) dissection around hepatic artery proper and right gastric artery is not done. Therefore, an important factor that should be considered before performing a PPG is the possibility of metastasis to LN station 5 around right gastric artery, and any case which can have LN metastasis in this area should not be indicated for PPG. In a study of the current status of PPG in Japan among 144 institutions, dissection of LN station 5 was not performed in 36.8% (53/144) and was partially performed in 56.2% (81/144) [4]. Our group had reported two important studies regarding the indication of PPG. Kong et al. analyzed the safety of lymph node station 5 and 6 in PPG using 1802 gastric cancer cohort [5]. In this study, if the tumor was located more than 5 cm from the pylorus, the metastasis rate of station 5 was 0% and 0.9% in T1a and in T1b, respectively. Similarly, the metastasis rate of station 6 was 0% and 1.8% in T1a and in T1b. Also, Yoo et al. reported the median and mean Maruyama index (MI, sum of the percentage of undissected lymph node station) of PPG as 0 and 0.8, respectively [6]. Both studies provided the background data of the oncologic safety of PPG and concluded PPG is safe for EGC located more than 5 cm from the pylorus.

Because the probability of LN metastasis increases as the depth of the lesion increases, the depth of invasion should also be evaluated [5, 7]. For these reasons, PPG should only be considered only for patients with a cT1N0M0 gastric cancer. According to the Japanese gastric cancer treatment guidelines, PPG is indicated for the treatment of cT1N0M0 gastric cancers in the middle-third of the stomach, at least 4 cm away from the pylorus [8].

Surgical Techniques (Figs. 16.1, 16.2, 16.3, and 16.4 and Video)

The standard technique for PPG includes the preservation of the infra-pyloric vessels and the hepatic branch of the vagus nerve for the preservation of the pylorus functionally as well as structurally [4]. There are three types in accordance with the origin of the infra-pyloric artery, and the ligation points of the right gastroepiploic artery are different according to the anatomical type. According to a study by Haruta et al., the infra-pyloric artery originates from the anterior superior pancreaticoduodenal artery in 64.2% of cases (distal type), the right gastroepiploic artery in 23.1% of cases (caudal type), or the gastroduodenal artery in 12.7% of cases (proximal type) [9]. During LN dissection of station 6, the right gastroepiploic artery is ligated at its root in the distal or proximal types. In the caudal-type cases, the right gastroepiploic artery is ligated at a location distal to the origin of the infra-pyloric artery [4, 5, 10, 11]. The hepatic branch of the vagus nerve that innervates the pylorus usually follows the course of the supra-pyloric LNs (LN station 5) and should be preserved to maintain the motility of the pylorus. Most surgeons prefer to preserve the vagus nerve, rather than dissect supra-pyloric LN during PPG [7, 12,13,14], although surgeons commonly tried to completely dissect the supra-pyloric LNs in the early years of PPG [15].

Fig. 16.1
figure 1

(a, b) Preserving infra-pyloric vessels but lymph node around #6 station has been dissected

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Fig. 16.2
figure 2

Dissection of LN #8

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Fig. 16.3
figure 3

Dissected LN #8, #7, #1, and #3. In this case, there was a replacing left hepatic artery from left gastric artery

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Fig. 16.4
figure 4

Gastro-gastroanastomosis

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Because an insufficient antral cuff length may lead to postoperative gastric stasis, a representative complication of PPG, the distance from the lesion to the pylorus needs to be carefully considered. When surgeons maintained an antral cuff length of 1.5 cm in the initial period of PPG, the incidence of postoperative delayed gastric emptying (DGE) was reported to range of 23–40% [12, 16, 17]. The relationship between the length of the antral segment and the incidence of DGE was investigated by Nakane et al. reporting an incidence rate of DGE of 35% (7/20) among patients with an antral cuff of 1.5 cm, compared to only 10% (1/10) among patients with an antral cuff of 2.5 cm, 1 year after PPG [18]. Nunobe et al. reported an incidence rate of DGE of 6–8% among 90 patients after PPG in whom vagus innervation and blood flow to the pylorus were preserved with 3 cm of antral cuff length [7]. As more studies on the PPG, the length of the antral cuff has tended to be longer. Considering a sufficient distal resection margin of >1 cm for EGC, current guidelines indicate that a minimum distance of 4.0 cm should be maintained between the side of the lesion to the pylorus. However, the optimal length for the antral cuff remains to be clarified.

Nowadays, pylorus-preserving gastrectomy (LAPPG) is commonly performed laparoscopically because patients who undergo PPG are diagnosed with EGC. Although the operation time is longer in LAPPG than in open PPG due to additional setting of laparoscopic surgery, LAPPG provides several benefits over PPG, such as reduced intraoperative blood loss and postoperative pain and a faster recovery [7, 15, 19].

For anastomosis, both extra- and intracorporeal methods can be performed for anastomosis in LAPPG. For the extracorporeal method, a hand-sewn anastomosis is usually applied. It generally requires an about 5 cm upper midline incision after laparoscopic dissection is finished (just before resection of the stomach). The distal part of the stomach is retracted through the incision and resected first. For the proximal side, after confirming the proximal margin by palpating a hemostatic clip applied preoperatively, lesser curvature side is resected by 10 cm linear stapler, and greater curvature side is anastomosed to antral cuff by continuous interlocking where hand-sewn gastro-gastrostomy is performed (or by interrupted Gambee suture). Intracorporeal anastomosis methods using linear staplers have recently been introduced. For the intracorporeal anastomosis, transection of the stomach in the sagittal direction (posterior to anterior direction), rather than in the transverse direction (greater curvature to lesser curvature direction), can facilitate the alignment of the linear staplers [20, 21]. After resection of the distal and proximal parts of the stomach, each arm of a 60 mm linear stapler is inserted into distal and proximal gastric remnants through the gastrostomy on the greater curvature side corner. The stapler has to be fired between the posterior walls on either side, and then the remaining gastrostomy can be closed using further staplers. [20, 21]

Robot-assisted pylorus-preserving gastrectomy (RAPPG) may provide another treatment option for EGC in the middle-third of the stomach considering benefits of robotic surgery including a three-dimensional and highly magnified imaging, a steady fixed camera, and an absence of a surgeon’s tremors [22]. Han DS et al. reported that there was no significant difference in complication rates between the robot-assisted PPG and laparoscopic PPG groups. The mean number of examined lymph nodes (33.4 vs. 36.5; P = 0.153) and the mean number of lymph nodes at each station were not different between the two groups. RAPPG can be a safe treatment option for middle-third early gastric cancer in terms of surgical complications and oncologic outcomes. However, RAPPG has no benefit over LAPPG in this study [23]. In this study, the energy device was ultrasonic device in RAPPG group; future robotic device such as articulating energy device may improve the result. The benefits of RAPPG over LAPPG from patients’ perspective remain controversial.

Oncologic Safety

Preservation of the vessel and nerves to maintain pyloric function may result in insufficient LN dissection at LN stations 5, 6, and 12a. An insufficient LN dissection would compromise the curative potential of radical gastrectomy in the treatment of gastric cancer. According to the Japanese gastric cancer treatment guidelines, D1+ lymphadenectomy should be performed in patients with a cT1N0 cancer [8]. LN dissection of station 6 with infra-pyloric artery preservation is a relatively easy technique, and LN station 12a is considered to be beyond the D1+ level in patients with cT1N0M0. However, LN station 5 is considered to be D1 level. In PPG, dissection of LN station 5 is not routinely performed in order to preserve function of the hepatic branch of the vagus nerve and, hence, of pyloric function. This could result in an incomplete D1 LN dissection, which is a concern regarding the oncologic safety of the procedure.

Sasako et al. used a new index (estimated by multiplying the incidence of metastasis and the 5-year survival rate of patients having metastasis to LN station 5) to evaluate the therapeutic value of LN dissection for gastric cancer, reporting a low index of 0.8 among patients with a cancer in the middle-third of the stomach [24]. The probability of metastasis to LN station 5 with an EGC localize to the middle-third of the stomach was also evaluated. Kodera et al. [25] reported the rate of metastasis rate to LN station 5 to be <5%, and Kone et al. [5] reported a rate of 4.2%. In both of these studies, however, most patients with metastasis to LN station 5 were ultimately confirmed as having ≥T2 cancer after surgeries, whereas the metastasis rates to LN station 5 were very low among patients with T1 cancer. Furthermore, Hiki et al. [26] and Nunobe et al. [7] reported supra-pyloric LN metastasis rates of 0.2% and 0.5%, respectively, among patients with T1 cancer located in the middle-third of the stomach.

In terms of long-term outcomes of PPG, Hiki et al. reported a 5-year survival rate of 98% among patients who underwent PPG for a cT1N0 gastric cancer without any case of recurrence [27]. Morita et al. reported a 5-year survival rate of 96.3%, with five cases of recurrence, among patients who underwent PPG for EGC [28]. Suh et al. reported a 3-year recurrence-free survival rate of 98.2% for LAPPG for EGC, which is comparable with the rate for LADG [14].

Advantages and Pitfalls

Compared to DG, PPG provides several benefits including a lower incidence of dumping syndrome, bile reflux, and gallstone formation, and better nutritional advantages, which is associated with a relatively small postoperative change in body weight [11, 14, 31,32,31]. Our group reported that PPG had fewer subjective postprandial symptoms, less bile reflux than distal gastrectomy [11]. Our group also reported that patients who underwent LAPPG had a better nutritional status, as compared with those who underwent LADG, including a smaller decrease in serum protein levels, serum albumin levels, and abdominal fat [14].

Gastric stasis is an annoying complication of PPG which makes surgeons to hesitate to perform PPG despite of many advantages. While the incidence of gastric stasis was as high as 40% during initial experiences with PPG [32], recent studies have reported the incidence of such complications after PPG of 6.2–10.3% [7, 14, 19, 28, 33, 34]. This value is still considered to be high, given that the rate of these complications after DG is about 1.0% [35]. Although the pathophysiologic mechanism of gastric stasis after PPG has not yet been fully defined, anastomotic edema and neurologic dysfunction, secondary to intraoperative damage, are known to be contributing factors [13, 32, 33]. Gastric stasis can be easily diagnosed based on a combination of symptoms, such as postprandial epigastric fullness or indigestion, with diagnosis confirmed by simple imaging, such as radiography or an upper gastrointestinal series [36]. Patients who developed gastric stasis after PPG may improve via conservative management and radiological interventions, such as balloon dilatation or stent insertion [23, 34, 36].

KLASS-04 Study: A Multicenter Prospective Randomized Controlled Trial

Currently, the comparison of the surgical, oncological, and patient-reported outcomes between LAPPG and LADG for the treatment of the middle-third of the stomach has only been evaluated in a few studies. Most of these studies were retrospective in nature, including data from a limited number of patients at a single center. To support the application of LAPPG in clinical practice, a comparative analysis of the short- and long-term outcomes of prospective randomized data is essential. In order to confirm whether the postoperative quality of life and nutritional status are better, and whether survival is comparable between LAPPG and LADG, the KLASS group has initiated a multicenter RCT (KLASS-04 study; NCT No.02595086) to compare LAPPG and LADG for the treatment of EGC located in the middle-third of the stomach.

A total of 256 patients, diagnosed with a cT1N0M0 primary gastric adenocarcinoma located in the middle-third of the stomach by EUS or CT, will be enrolled (128 patients in each group) (Table 16.1). The primary end point is the incidence of dumping syndrome, assessed using the Sigstad score (≥7 for dumping syndrome) at 1 year after surgery. The secondary end points are the 3-year relapse-free survival and overall survival; the 30-day operative morbidity and mortality; changes in body weight and fat volume on abdominal CT; postoperative changes in hemoglobin, protein, albumin, and prealbumin levels; symptoms and quality of life measurement using the JSGIS-Q, EORTC C30, and STO22; the incidence of gallstones; and the gross and microscopic findings on gastroscopy.

Table 16.1 Indications and contraindications for KLASS-04 study
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