INTRODUCTION
Standard gastrectomy is defined in the Japanese gastric cancer treatment guidelines as the resection of at least two-thirds of the stomach with a D2 lymph node dissection. Modified surgery (limited surgery) is defined as a reduced extent of gastric resection and/or lymphadenectomy compared to standard surgery and includes optional procedures that preserve the bursa, omentum, pylorus, and vagal nerve[1]. This modified surgery was started for early gastric cancer (EGC) cases with favorable prognoses to reduce their surgical invasiveness, and it has overlapped with the indications for laparoscopic gastrectomy, which is regarded as one form of minimally invasive surgery; in fact, modified surgery has often been performed laparoscopically[2,3]. On the other hand, new concepts such as function-preserving surgery (FPS) that preserves gastric function, which has been sacrificed in gastric cancer surgery, were generated from the perspective of patients’ postoperative quality of life (QOL)[4,5]. Namely, an operation that is performed with the intent of achieving a better postoperative condition is thought to be FPS. Although modified surgery is apt to be used synonymously for FPS, modified surgery is not always function-preserving, and FPS does not always involve a modified procedure. However, because FPS has been derived from modified surgery, most FPS methods are currently considered modified surgery. These issues are reviewed, while providing a historical perspective.
HISTORY OF FPS
In Japan, there used to be many gastroduodenal ulcer patients, and surgery was the most effective and certain therapy until the appearance of H2-blockers[6-9]. Therefore, it was necessary to analyze gastric physiological motor function[10,11], control of the autonomic nervous system[12], and the dynamics of acid secretion and hormonal secretion[13,14], and to investigate how these changed after gastrectomy[15-17]. The incidence rate of gastric cancer was similarly high, and too much attention was paid to the ability of surgery to cure gastric cancer, so that less attention was paid to FPS in gastric cancer, though it was studied for gastroduodenal ulcer. In particular, there was much research on the relationship between the vagus nerve and acid secretion[18]. Maki et al[19] developed pylorus-preserving gastrectomy (PPG) for gastric ulcer in 1967. They found that pyloric motor function changed according to the distance of the transection line from the pyloric ring in canine experiments, and they advocated that the transection line should be placed 1.5 cm proximal to the pyloric ring. Meanwhile, the definition of EGC was investigated[1,20] from the 1960s. Then, from the 1970s, histopathological investigations of EGC were carried out in an active manner[21-23], and the validity of modified surgery was confirmed under specific indications[24-26]. Because the number of operations for gastroduodenal ulcer decreased after the development of H2-blockers, and the number of EGC patients simultaneously increased, modified surgery for EGC was gradually started. In the late 1980s, PPG for EGC in the middle third of the stomach had come to be performed[27]. Thereafter, many kinds of function-preserving gastrectomies (FPGs) came to be performed and studied in other fields of gastric cancer[28-33]. During the same period of time, endoscopists took the initiative to start endoscopic mucosal resection (EMR) for EGC, and endoscopic submucosal dissection (ESD) was developed with improved instruments and techniques. Originally, radicality and QOL conflicted with each other, but FPS tried to improve postoperative QOL while maintaining radicality. After modified surgery began, the ability of FPS to preserve gastric function and physical condition was studied.
PYLORUS-PRESERVING GASTRECTOMY
Maki et al[19] decided that pylorus-preserving gastrectomy (PPG) was indicated for gastric benign disease when the distal transection line could be made 1.5 cm proximal to the pyloric ring, and the therapeutic purpose could be achieved through resection of 1/2 to 2/3 of the stomach (Figure 1). It was initially expected that PPG would decrease dumping symptoms compared to the Billroth I method, with the later advantages of reservoir function and prevention of regurgitation of bile juice[28]. However, meal stasis was common, so that the kinetics of gastric emptying were studied, and the length of the pyloric cuff was gradually elongated[34,35]. Suprapyloric lymph node dissection has come to be omitted to preserve the pyloric branch of the vagal nerve and right gastric vessels[34]. Furthermore, there has been a tendency to preserve the infrapyloric vessels[36]. Thus, from the balance between radicality and functional preservation, PPG has become a procedure that preserves the upper third of the stomach and a 3 to 4-cm pyloric cuff for cN0, cT1 gastric cancer, and it preserves the hepatic branch, pyloric branch, and celiac branch as much as possible[1]. As a result, in a large-scale postgastrectomy syndrome assessment study, Fujita et al[37] reported that better postoperative QOL was observed in PPG, including a lower incidence of diarrhea, dumping symptoms, and frequency of additional meals compared to the Billroth I procedure. Furthermore, Namikawa et al[38] reported that the size of the proximal gastric remnant significantly affected the change in body weight, scores for dissatisfaction at meals, and the dissatisfaction for daily life subscale, and preservation of a sufficient proximal gastric remnant is recommended when using PPG as FPS.
Figure 1 Pylorus-preserving gastrectomy.
PROXIMAL GASTRECTOMY
Proximal gastrectomy (PG) began as modified surgery for gastric cancer, and Papachristou and Fortner[39] reported that PG for adenocarcinoma of the cardia was curative only in cases of stage I and II disease (Figure 2). It turned out that the incidence rate of lymph node metastases for EGC in the upper third of the stomach was low[29], and proximal gastrectomy is currently performed for cN0, cT1 tumors where more than half of the distal stomach can be preserved[1]. Furthermore, the hepatic branch, pyloric branch, and celiac branch of the vagal nerve are preserved as much as possible. The reconstructive procedures need to be considered: jejunal interposition (Figure 2A), double tract (Figure 2B), and esophagogastrostomy (Figure 2C and D). The first two methods involve reconstruction with 8-15 cm of interposed jejunum between the esophagus and the remnant stomach to prevent reflux esophagitis and to observe the remnant stomach for follow-up of neoplastic tumor[40-42]. The third method involves reconstruction by fundoplication, wrapping the remnant stomach around the circumference of the esophagus[43] (Figure 2C) by double-flap technique, embedding the lower edge of the esophagus to the gastric submucosal layer, etc[44] (Figure 2D). For each reconstruction, QOL has been evaluated. Takiguchi et al[45] reported that PG was better than total gastrectomy in terms of weight loss, necessity of additional meals, diarrhea, and dumping symptoms in a multi-institutional study. Especially in esophagogastrostomy after PG, Inada et al[46] reported that diarrhea scores and the necessity for additional meals were lower in the group with more than three-quarters of a remnant stomach compared to patients with a remnant stomach two-thirds the preoperative size. Procedures to prevent gastroesophageal reflux and the use of a pyloric bougie were considered effective ways to reduce the deterioration of QOL.
Figure 2 Proximal gastrectomy.
A: Jejunal interposition; B: Double tract method; C: Esophagogastrostomy with fundoplication; D: Esophagogastrostomy with double flap technique.
JEJUNAL POUCH INTERPOSITION
To increase the smaller gastric capacity after gastrectomy, distal gastrectomy[30] (Figure 3A), PG[31] (Figure 3B), and total gastrectomy[47] (Figure 3C and D) with an interposed jejunal pouch were performed throughout Japan[48]. Because this procedure was intended to recover the gastric reservoir function that was taken away by gastrectomy and to prevent the occurrence of reflux esophagitis, jejunal pouch interposition (JPI) was thought to be FPS. On the other hand, JPI was often added to the conventional operation (standard gastrectomy), so that it was not often a modified operation. However, Fukuhara[49] reported that, when jejunojejunostomy was performed, disappearance of systemic intestinal peristalsis due to the division of circular muscle resulted in the occurrence of meal stasis in the jejunal pouch. Mochiki et al[50] reported that the interposed jejunum with a pouch showed motor abnormalities. Katsube et al[51] reported a case with severe dilatation of the jejunal pouch and reflux esophagitis. Finally, Namikawa et al[52] reported that the better short-term QOL of JPI than of Roux-en-Y reconstruction decreases with time. As a result, the number of institutes performing surgery with JPI has been decreasing.
Figure 3 Jejunal pouch interposition.
A: Distal gastrectomy with jejunal pouch interposition; B: Proximal gastrectomy with jejunal pouch interposition; C: Total gastrectomy with upper jejunal pouch interposition; D: Total gastrectomy with lower jejunal pouch interposition.
SEGMENTAL GASTRECTOMY AND LOCAL GASTRECTOMY
Segmental gastrectomy (SG) is defined as a relatively small circumferential gastric resection preserving the cardia and pylorus, excluding PPG (Figure 4). Local gastrectomy (LG) is defined as a non-circumferential gastric resection (Figure 5)[1]. If these operative procedures could achieve radicality, they might be the ultimate FPS. Although some institutes have performed these operations under strict indications[32,53], systemic lymph node dissection cannot be performed. Therefore, in order to assure radicality in these operations, the number of institutes that perform these operations using sentinel node navigation has been increasing[54]. In the original concept of sentinel node navigation surgery (SNNS), detected sentinel nodes were histologically examined intraoperatively, and if no lymph node metastasis was detected, further lymphadenectomy was omitted[55]. The feasibility and accuracy of diagnosis using sentinel node biopsy in T1 gastric cancer were evaluated in a multicenter trial (JCOG0302)[56]. The primary endpoint was to determine the proportion of false negatives, which was defined as the number of patients with negative stained nodes by frozen section divided by those with positive stained nodes and/or positive non-stained nodes by paraffin section. It was found that the proportion of false negatives was much higher (14%) than expected (10%), and further accrual was suspended at semiannual monitoring. Thereafter, several clinical studies of lymphatic basin dissection, which is a selective lymphadenectomy to dissect stained areas, so-called lymphatic basins, containing lymph nodes and lymphatic vessels stained with dye or a radioisotope or both used as a tracer for sentinel node mapping in EGC, were conducted[57].
Figure 4 Segmental gastrectomy.
Figure 5 Local gastrectomy.
FUSION OF LAPAROSCOPIC SURGERY AND FUNCTION-PRESERVING SURGERY
FPS was concurrent with the beginning of laparoscopic gastrectomy and interest shifted to minimally invasive surgery. For this reason, the number of institutes where PPG[58,59] or PG[41,42] is performed using the laparoscopic approach has been increasing. Of course, if the efficacy of SNNS could be proven, it was thought that SG and LG would become the FPS performed under the laparoscopic approach. However, laparoscopic surgery is a kind of approach that is thoroughly minimally invasive surgery, not FPS.
ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION
Generally, it may be thought that endoscopic resection is not a surgical procedure, namely FPG. However, as the techniques and instruments of endoscopic resection have developed, and its indications have expanded, the borderline between usual surgical operations and recent endoscopic resection has become unclear. Therefore, endoscopic resection was treated as an FPS in this article.
Endoscopic resection was developed as the endoscopic resection method for tumors of the colon by Rosenberg et al[60] and Deyhle et al[61] in Western countries. In Japan, there was a report of its use for gastric cancer by Hirao et al[62]. The indication for endoscopic resection was based on investigation of a large number of EGC cases who underwent open gastrectomy[63]. Endoscopic mucosal resection (EMR) for selected intramucosal EGC cases, for which the possibility of lymph node metastasis is almost zero, has been widely accepted as a curative therapeutic strategy. The accepted indications for EMR are: (1) well differentiated elevated lesions less than 20 mm in size; and (2) small (≤ 10 mm), depressed, well-differentiated tumors without ulceration[1]. From further investigation of many EGC cases and the development of instruments for tissue detachment and dissection, EMR has been evolving to endoscopic submucosal dissection (ESD)[64,65]. Currently, tumors indicated for endoscopic resection as an investigational treatment (expanded indication) are as follows: tumors clinically diagnosed as T1a and: (1) of differentiated type, UL(-), but > 2 cm in diameter; (2) of differentiated-type, UL(+), and ≤ 3 cm in diameter; and (3) of undifferentiated-type, UL(-), and ≤ 2 cm in diameter[1]. After non-curative resection by EMR or ESD, additional surgical treatment should be performed; in fact, it can be said that surgical treatment could be easily added. Gastric mucosal resection as intra-gastric surgery had been performed using laparoscopic instruments through the abdominal and gastric walls[66] and seemed to be replaced by endoscopic resection. Although the indication is restricted, endoscopic resection can be said to be the ultimate FPS with respect to reduction of invasiveness and maintenance of QOL.
EVALUATION OF FUNCTION-PRESERVING GASTRECTOMY
Given the view that function-preserving gastrectomy (FPG) preserves the autonomic nerves and maintains physiological gastrointestinal hormonal secretion, we evaluated the postoperative physical conditions of patients who had undergone various kinds of operating methods incorporating three elements: (1) reduction of the extent of gastrectomy; (2) preservation of the pylorus; and (3) preservation of the vagal nerve[67]. It was found that the operating methods incorporating more than two elements maintained postoperative function and QOL. In fact, PPG and PG are thought to be the ideal methods to fulfill all elements. Saito et al[68] discussed PPG and PG as FPG, and they described their oncological safety under the rigid indications and their several advantages with respect to postoperative QOL. Furthermore, in order to investigate the most important of these 3 elements, the following studies were performed. The functional outcomes of EGC patients treated by laparoscopic distal gastrectomy were compared with respect to size of the remnant stomach (1/2 vs 1/3) and the type of reconstruction (Billroth I vs Roux-en-Y). It was found that patients actually benefited from 1/2 gastrectomy rather than the typical 2/3 gastrectomy, irrespective of reconstruction method[69]. Similar results were seen in the investigation of advanced gastric cancer patients; better functional outcomes were observed in patients with a large remnant stomach (1/3) compared to a small one (1/5), regardless of the reconstruction[70] (Figure 6). However, a large remnant stomach sometimes shows gastric stasis, so that appropriate selection of the reconstruction method with smooth gastric emptying is needed, such as avoiding the Roux-en-Y reconstruction[69]. Furthermore, we compared functional outcomes between different types of reconstructions (jejunal interposition method, double tract method) following open or laparoscopic 1/2- or 2/3-PG for gastric cancer. Better functional outcomes were observed in patients with a large remnant stomach and with easy flow of food into the remnant stomach regardless of whether they underwent open or laparoscopic procedures[71]. In laparoscopic 1/2-PG with as much vagal nerve preservation as possible, the postoperative/preoperative body weight ratio was significantly higher in the jejunal interposition group in which all meals passed through the remnant stomach than in the double tract group[41,71]. Figure 6 shows the comparison of the postoperative/preoperative body weight ratio between the open distal gastrectomy without preservation of the vagal nerve group and the laparoscopic PG with preservation of the vagal nerve group. Of the above mentioned three elements, we think that reduction of the extent of gastrectomy and passage through the stomach are the most important, although the proof for preservation of the vagal nerve is difficult. Therefore, we should try to reduce the extent of gastrectomy if curability of the gastric cancer can be achieved. However, Miwa et al[72] stated that FPG carries the risk of metachronous gastric cancer. In fact, since 1995, 160 EGC patients with negative sentinel nodes underwent FPG, which consisted of local resection, SG, and limited distal gastrectomy. Of these 160 patients, 5 developed metachronous gastric cancer. The incidence of metachronous gastric cancer at 5 years after surgery was 2.8%, which was less than that for EMR and almost the same as that for conventional D2 distal gastrectomy[73]. Consequently, if we could preserve a wider residual stomach as in FPG, we should pay attention to the development of metachronous gastric cancer. Specifically, regular follow-up with endoscopic examination is needed. Furthermore, for the surgeon, especially following PG, it is most important to select the reconstruction method that is appropriate for observation of the remnant stomach through endoscopy. Of course, eradication of Helicobacter pylori should be considered.
Figure 6 Postoperative to preoperative body weight ratio according to the size of the gastric remnant and the type of reconstruction following open distal and laparoscopic proximal gastrectomy including total gastrectomy.
1/3B1: Distal 2/3-gastrectomy with Billroth I reconstruction; 1/3RY: Distal 2/3-gastrectomy with Roux-en-Y reconstruction; 1/5RY: Distal 4/5-gastrectomy with Roux-en-Y reconstruction; TG: Open total gastrectomy with Roux-en-Y reconstruction; L1/2DT: Laparoscopic 1/2-proximal gastrectomy with double tract reconstruction; L1/2JIP: Laparoscopic 1/2-proximal gastrectomy with jejunal interposition reconstruction; LTG: Laparoscopic total gastrectomy with Roux-en-Y reconstruction.
Although the above mentioned 3 elements should be considered in FPG, further randomized, clinical trials are needed to identify the most important element.
CONCLUSION
Current surgical FPGs are thought to include PPG, PG, JPI, SG, and LG. Of these operations, the procedures that include systemic lymph node dissection and three important elements (reduction of the extent of gastrectomy, preservation of the pylorus, and preservation of the vagal nerve) are thought to be PPG and PG. Recently, the number of institutes that perform these operations with laparoscopic approaches has been increasing. Furthermore, with diagnostic examinations such as SNNS, SG and LG will become conventional as FPS in the near future.
Manuscript source: Invited manuscript
P- Reviewer: Komatsu S, Lianos GD, Yang MH S- Editor: Qi Y L- Editor: A E- Editor: Wang CH
