World J Surg DOI 10.1007/s00268-014-2660-6
Assessment of Motor Function of the Remnant Stomach by 13C Breath Test With Special Reference to Gastric Local Resection Masahiko Kawamura • Koji Nakada • Hideo Konishi • Taizo Iwasaki Keishiro Murakami • Norio Mitsumori • Nobuyoshi Hanyu • Nobuo Omura • Katsuhiko Yanaga
•
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Background Indications for gastric local resection (LR) include gastrointestinal stromal tumors, neuroendocrine tumors, and early gastric cancer. LR is expected to preserve physiological function and ameliorate postgastrectomy syndrome. Methods Gastric emptying was assessed by the 13C-acetate breath test in 20 healthy volunteers (HVs) and 60 gastrectomized patients [distal gastrectomy with Billroth I reconstruction (DGBI) in 26 patients, LR in 34 patients]. For the 13C breath test, 100 mg of 13C-acetate sodium salt was mixed in a test meal. Breath samples were collected before intake and during the next 3 h. We compared the gastric reservoir capacity using the gastric retention rate at 5 min (RR5) and gastric emptying by the half emptying time (T). Patients completed a questionnaire survey about their symptoms, dietary intake, body weight, and restriction of activities of daily living [reflecting quality of life (QOL)]. Results The RR5 values for the HV, LR, and DGBI groups were 93.7, 90.0, and 45.3* %, respectively (*compared to HV and LR, p \ 0.0001). The T values were 23.3, 20.2, and 5.9* min, respectively. Dietary intake and body weight change were significantly more reduced in the DGBI group than the LR group (p \ 0.05). Subgroup analysis indicated that the reservoir capacity in those with LR at the lesser curvature was more disturbed than that in patients with LR at
M. Kawamura (&) K. Nakada H. Konishi T. Iwasaki K. Murakami N. Mitsumori N. Hanyu N. Omura K. Yanaga Department of Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan e-mail: [email protected]
the greater curvature. The questionnaire showed no differences in those patients’ QOL. Conclusions Because the reservoir capacity, the gastric emptying and QOL were maintained, LR is an option for selected patients with early gastric cancer.
Introduction Gastric local resection (LR) is increasingly performed for diseases such as GIST, NET, and early gastric cancer. With the widespread use and improvements in endoscopy, gastric cancer is now diagnosed at an early stage in Japan [1, 2]. In the past, conventional gastrectomy, such as distal gastrectomy with Billroth I reconstruction (DGBI), had been performed for early gastric cancer. However, the optimal extent of gastric resection and lymph node (LN) dissection was reconsidered, and function-preserving gastrectomy, such as pylorus-preserving gastrectomy and proximal gastrectomy, was introduced as the standard option for T1N0 early gastric cancer in the latest guideline for treatment of gastric cancer in Japan [3]. Endoscopic procedures are also carried out for early gastric cancer. Currently, well-differentiated intramucosal cancers B2 cm in diameter (T1a) are deemed suitable for endoscopic therapy [4, 5]. The incidence of LN metastasis in early gastric cancer is 2–4 % for intramucosal cancer and 13–20 % for submucosal cancer [6–9]. The indication for endoscopic submucosal resection (ESD) was expanded to include submucosal cancer without LN metastasis and poorly differentiated mucosal cancer. However, the long-term prognosis following expansion of indications for ESD has not been clarified [3]. Meanwhile, LR may ensure a sufficient margin in lateral and horizontal directions compared to ESD, and it retains a larger amount of residual stomach than that in conventional gastrectomy or
123
World J Surg Table 1 Patients’ characteristics Parameter
HV group
Table 2 Patients’ characteristics (LR subgroups)
(n = 26)
DGBI group (n = 26)
LR group
Parameter
LRGC group (n = 20)
LRLC group (n = 14)
(n = 34)
Sex (M/F)
16/4
19/7
23/11
Sex (M/F)
12/8
11/3
Age (years)
29.5 ± 6.9
66.0 ± 8.8
64.6 ± 10.3
Age (years)
65.4 ± 10.2
63.5 ± 10.5
Location (U/M/L)
5/14/1
Location (U/M/L) Resection size (mm)
– –
0/11/5 –
6/26/2 57.0 ± 16.4
Resection size (mm)
1/12/1
60.5 ± 15.1
52.1 ± 16.9
Carcinoma
–
26
17
9
8
GIST
–
–
17
11 20/0 (100 %)a
6 6/8 (43 %)a
–
0/26 (0 %)a
26/8 (76 %)a
Postop. period (months)
39.1 ± 29.4
46.9 ± 44.9
Surgical approach (open/laparoscopic)
1/19
1/13
Primary disease (no.)
Primary disease (no.)
Latarjet branch preserved (yes/no)
Carcinoma
Postop. period (months)
–
37 ± 91.4
42.3 ± 36.8
Surgical approach (open/laparoscopic)
–
16/10
2/32
GIST Latarjet branch preserved (yes/no)
Results are given as the mean ± SD or the number of subjects unless otherwise stated
Results are given as the mean ± SD or the number of subjects unless otherwise stated
LRGC local resection at greater curvature, LRLC local resection at lesser curvature, Postop. postoperative
HV healthy volunteer, DGBI distal gastrectomy with Billroth I reconstruction, LR gastric local resection, U upper third of the stomach, M middle third of the stomach, L lower third of the stomach, GIST gastrointestinal stromal tumor
a
a
Percentage of ‘‘yes’’
function-preserving gastrectomy. Therefore, well-maintained physiologic gastric function is expected after LR, which may reduce disabilities following gastric surgery. It is therefore hoped that LR can contribute to improving the patient’s quality of life (QOL). However, the superiority of LR regarding motility of the remnant stomach and QOL has not been verified. This study was carried out to clarify this issue.
Materials and methods The subjects consisted of 60 patients who had undergone gastrectomy at least 1 year previously. Among them, 26 patients underwent DGBI and 34 underwent LR. Of the LR patients, 14 had lesions in the lesser curvature (LRLC), and 20 had lesions in the greater curvature (LRGC) (Tables 1, 2). All DGBIs were performed for gastric cancer (stages IA and IB). The extent of LN dissection for DGBI was D1? or D2 according to the Japanese Gastric Cancer Classification. LR was carried out for GIST or early gastric cancer, for which informed consent for sentinel node navigation surgery (SNNS) was obtained. In patients who underwent LR for early gastric cancer with SNNS, indocyanine green was locally injected into the submucosa around the tumor using intraoperative endoscopy. When only one lymphatic basin was found upon laparoscopic observation using infrared spectrophotometry, the regional LNs were dissected and were subsequently confirmed to be metastasis-free by intraoperative pathology examination. LR was carried out
123
Percentage of ‘‘yes’’
ensuring a 2-cm margin from the edge of the tumor [10]. The Latarjet branch was resected during LRLC for early gastric cancer but was preserved during LRLC for gastric GIST and during LRGC (Table 2). This study was carried out after obtaining written informed consent from the gastrectomized patients and HVs. The ethics committee of the Jikei University School of Medicine approved the study. Evaluation of gastric motility using the breath test
13
C-acetate
The gastric emptying study using the 13C-acetate breath test was performed in 26 patients with DGBI, 34 patients with LR, and 20 healthy volunteers [11]. The test meal was 200 kcal/200 ml liquid meal (Racol; Otsuka Pharmaceutical, Tokyo, Japan) mixed with 100 mg of 13C-acetate sodium salt. Expiratory samples were obtained before intake and at 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 135, 150, 165, and 180 min after intake. The 13 CO2/12CO2 ratio in the expiratory samples was determined using infrared spectrophotometry (UBiT-IR 300; Otsuka Electronics, Tokyo, Japan). Wagner–Nelson analysis was carried out on the obtained data [11]. The gastric retention rate at each time point was calculated quantitatively. Gastric reservoir capacity was evaluated by determining the retention rate at 5 min (RR5) after ingestion. Gastric emptying was evaluated using the half-emptying time (T). The RR5, T, and gastric emptying curve were compared among the groups. The LR subgroups were analyzed according to the resection site (LRGC or LRLC) to investigate its influence.
World J Surg Table 3 Comparison of gastric motility and living status among the DGBI, LR, and HV groups Parameter
HV group (n = 20
DGBI group (n = 26)
LR group (n = 34)
p
RR5 (%)
93.7 ± 5.7
45.3 ± 28.6
90.1 ± 7.2
\0.0001* (DGBI vs. HV, LR)
T (min)
23.3 ± 4.9
5.94 ± 4.0
20.2 ± 8.6
\0.0001* (DGBI vs. HV, LR)
Meal-related distress (yes/no)a
–
14/12 (54 %)
6/28 (18 %)
0.0008**
Diarrhea (yes/no)a
–
8/18 (31 %)
7/27 (21 %)
0.158**
Dumping (yes/no)a
–
17/9 (65 %)
7/27 (21 %)
0.002**
Restricted ADL (yes/no)a
–
12/14 (46 %)
4/30 (12 %)
0.002**
Food intake (%)b Change in body weight (%)c
– –
64.6 ± 1.7 -9.3 ± 0.07
84.8 ± 1.3 -2.7 ± 0.06
\0.0001*** 0.0002***
Results are given as the mean ± SD or the number of subjects unless otherwise stated RR5 retention rate at 5 min, T half emptying time, ADL activities of daily living *Bonferroni/Dunn; **v2-test; ***t-test a
Percentage of ‘‘yes’’
b
Percentage of preoperative food intake
c
Percentage difference from preoperative body weight
Table 4 Comparison of gastric motility and ADL status between LRLC and LRGC Parameter
LRGC group (n = 20)
p
RR5 (%)
85.8 ± 8.3
93.1 ± 4.2
0.003*
T (min)
17.5 ± 4.6
22 ± 10.1
0.136*
Meal-related distress (yes/no)a
3/11 (21 %)
3/17 (15 %)
0.628**
Diarrhea (yes/no)a
3/11 (21 %)
4/16 (20 %)
0.678**
Dumping (yes/no)a
3/11 (21 %)
4/16 (20 %)
0.919**
Restricted ADL (yes/no)a
2/12 (14 %)
2/18 (10 %)
0.703**
83.9 ± 1.3
85.5 ± 1.4
0.938*
-4.73 ± 0.06
-1.09 ± 0.05
0.081*
Food intake (%) Fig. 1 Comparison of gastric emptying curve among patients who underwent distal gastrectomy with Billroth I reconstruction (DGBI), gastric local resection (LR), and healthy volunteers (HV). Significant acceleration of gastric emptying was observed in the DGBI group compared to that in the HV or LR group (*p \ 0.05 vs. HV and LR). Gastric emptying after LR was similar to that in HVs except for 20 min (?p \ 0.05 vs. HV)
LRLC group (n = 14)
b
Change in body weight (%)c
Results are given as the mean ± SD or the number of subjects unless otherwise stated *t-test; **v2-test a
Percentage of ‘‘yes’’
b
Percentage against preoperative food intake
c
Percentage difference from preoperative body weight
Questionnaire
Statistical analysis
All patients who underwent the 13C-acetate breath test to assess remnant gastric motility were asked to answer questions on a questionnaire that addressed postoperative symptoms and living status. The questionnaire included the existence of symptoms (meal-related distress, diarrhea, dumping), ingestion amount per meal, frequency of meals per day, change in body weight, and restricted activities of daily living (ADL), which reflects QOL. Dumping included early and late dumping symptoms, such as cold sweat, palpitation, dizziness, unconsciousness, and headache.
A statistical analysis was conducted using the t test, v2 test, or analysis of variance followed by the Tukey–Kramer test. Results Gastric emptying study by
13
C breath test
There were a significant decrease in RR5 and a shorter T in patients undergone DGBI compared to the HV and LR
123
World J Surg
Fig. 2 Comparison of gastric emptying curves between local resection at the lesser curvature (LRLC) and that at the greater curvature (LRGC). In gastric emptying curve, initial gastric emptying (RR5) was significantly accelerated in the LRLC group, with no differences observed thereafter
groups (p \ 0.05). Significant acceleration of gastric emptying was observed in the DGBI group compared with that in the HV and LR groups (p \ 0.05 each). The RR5, T, and gastric emptying curves for the LR group were comparable to those for the HV group (Table 3; Fig. 1). Although the reservoir function of the remnant stomach (RR5) was significantly reduced in the LRLC subgroup, no differences were observed in gastric emptying (T) between the LRLC and LRGC subgroups (Table 4). Initial gastric emptying (RR5) was significantly accelerated in the LRLC subgroup. No differences were observed between the two groups thereafter (Fig. 2). Questionnaire All patients responded to the questionnaires. The incidences of meal-related distress and dumping symptoms were significantly higher in the DGBI group. The amount of food intake per meal was prominently reduced after DGBI to an average 65 % of the preoperative intake but was well maintained after LR at an average of 85 %, which was significantly better than that after DGBI (p \ 0.05). Weight loss after LR was 2.7 %, which was significantly less than that after DGBI (9.3 %) (p \ 0.05). Significantly more patients in the DGBI group than in the LR group complained of restricted ADL (p \ 0.05) (Table 3). Analysis showed that in a comparison of the LRGC and LRLC subgroups, no differences were observed in regard to symptoms, the amount of food intake per meal, change in body weight, or QOL (Table 4).
Discussion Disabilities have frequently been observed following gastrectomy including reduced dietary intake, weight loss,
123
dumping, and other gastrointestinal symptoms [12], which may result in impaired QOL. The reduced reservoir function and accelerated emptying of the remnant stomach may be the cause of these problems following gastrectomy. The usefulness of pylorus-preserving gastrectomy to attenuate rapid gastric emptying and creation of a substitute stomach by making a jejunal pouch to compensate for the reduced gastric reservoir capacity have been reported [13–16]. When LR is performed for the treatment of GIST, NET, or limited cases of early cancer, the extent of resection is minimized unless curability is jeopardized. Therefore, improved postoperative QOL is anticipated. However, there is little information on living status after LR (e.g., s dietary intake, changes in body weight, restricted ADL), and motor function of the remnant stomach has not been well investigated. Our results indicated that patients’ QOL and remnant gastric motility were well maintained in the LR group compared to those in the DGBI group. Kitaoka et al. [17], was the first to report the use of LR for treating early gastric cancer. Maintenance of curability and QOL are essential to introducing LR for early gastric cancer clinically. During LR, intraoperative SNNS can confirm the absence of LN metastasis, thereby enhancing curability. Thus, by introducing SNNS into the protocol, the indications for LR may be expanded as an alternative to function-preserving gastrectomy. Although there have been sporadic reports on local recurrence without SNNS following LR for early gastric cancer, local recurrence can be controlled. Hence, curability may be enhanced by concomitant use of SNNS and by establishing a fixed adaptive criterion [1, 18–20]. There are some technical difficulties when applying LR to tumors near the esophagogastric junction or the pylorus. This is because of the risk of stricture, deformity, or dysfunction caused by the procedure. Hence, an insufficient surgical margin is a possible drawback with LR. In recent years, laparoscopic and endoscopic cooperative surgery has been developed [21, 22]. With these techniques, an appropriate margin is marked under intraoperative endoscopy, and the lesion is excised as a whole layer of the gastric wall. The gastric defect is then closed by suturing it laparoscopically. Because of this technical development, LR may be safely performed with a reliable margin without functional disabilities even for lesions close to the esophagogastric junction or the pylorus. Thus, the indications for LR can now be further expanded. As a gastric emptying test, the radioisotope method has served as the gold standard. However, this method cannot avoid radiation exposure, requires special facilities such as a gamma camera and a radiation-controlled area, and is expensive. In this study, we evaluated the postoperative gastric motility using the 13C-acetate breath test, which was proposed in 1993 by Ghoos et al. and has been widely used
World J Surg
to investigate the abnormal gastric emptying that accompanies various digestive disorders. In recent years, it has also been used to evaluate remnant gastric emptying following gastrectomy [23–25]. The 13C-breath test has several advantages, including noninvasiveness, simplicity, safety, and cost efficiency. Regarding the credibility and quantitative evaluation compared to the radioisotope method, Sanaka et al. reported that the 13C-breath test is comparable to the radioisotope method for evaluating quantitative gastric emptying by applying the Wagner– Nelson analysis to the obtained data [26, 27]. In this study, we first applied Wagner–Nelson analysis to the 13C-breath test in the clinical setting to evaluate postoperative gastric motility quantitatively. The 13C-breath test with Wagner– Nelson analysis enables evaluation of the reservoir capacity of the remnant stomach in addition to the gastric emptying rate. Therefore, this method is clinically useful for detecting various digestive disorders and postoperative disturbances in gastric motility. Our study showed excellent QOL after LR. It approximated that of the HV group and was significantly better than that of the DGBI group. The patients were able to eat a sufficient amount of their meals, their weight loss was attenuated, and restricted ADL and symptoms were rare. In addition, the motility of the remnant stomach after LR was similar to that of the HV group. These aspects promise a better QOL to patients after LR. The vagal nerve is a main control of gastric motility. Denervation of the proximal stomach impairs receptive relaxation, which could result in reduced gastric volume after meals. Also, denervation of the distal stomach impairs peristalsis of the antrum, thereby causing delayed gastric emptying [28, 29]. During LR for an early gastric cancer located on the lesser curvature side, the vagal input is excised by regional lymphadenectomy. Therefore, impaired motility of the remnant stomach is a concern. In this study, although the reservoir function of the remnant stomach was significantly reduced in the LRLC subgroup, there were no differences in gastric emptying or in the patients’ QOL between the LRLC and LRGC subgroups. Furthermore, we compared gastric motility after LRLC with or without preservation of the Latarjet branch. There were no differences in gastric motility between the two groups (data not shown). The fact that most of the stomach, pylorus, and cardia are preserved after both LRGC and LRLC may partly explain the well-maintained gastric motility after LR despite the tumor site. Therefore, LR could be securely applied for lesions at any site. The limitation of this study was that the HVs were younger than the patients in either the DGBI or LR group. This difference may have caused some problems with our results as there have been some reports that gastric emptying tends to be slow in elderly subjects [30, 31].
Conclusions LR was superior to DGBI with regard to patients’ postoperative QOL and motility of the remnant stomach. Therefore, LR could be an optimal treatment for patients with early gastric cancer unless curability is jeoparadized. Acknowledgments This study was supported by a grant from MEXT (Ministry of Education, Culture, Sports, Science and Technology)-Supported Program for the Strategic Research Foundation at Private Universities, (2011–2013). The authors thank all the patients whose cooperation made this study possible. Conflict of interest
None.
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24. Katsube T, Konno S, Murayama M et al (2007) Gastric emptying after pylorus-preserving gastrectomy: assessment using the 13Cacetic acid breath test. Hepatogastroenterology 54:639–642 25. Barden B, Adams S, Duan LIP et al (1995) The accuracy reflects gastric emptying of liquids and semisolid test meal. Gastroenterology 108:1048–1055 26. Sanaka M, Nakada K, Nosaka C et al (2007) The Wagner–Nelson method makes the 13C-breath test comparable to radioscintigraphy in measuring gastric emptying of a solid/liquid mixed meal in humans. Clin Exp Pharmacol Physiol 34:641–644 27. Sanaka M, Urita Y, Sugimoto M et al (2006) Comparison between gastric scintigraphy and the 13C-acetate breath test with Wagner–Nelson analysis in humans. Clin Exp Pharmacol Physiol 33:1239–1243 28. Nomura E, Isozaki H, Fujii K et al (2003) Postoperative evaluation of function-preserving gastrectomy for early gastric cancer. Hepatogastroenterology 50:2246–2250 29. Grundy D, Scratched T (1984) The role of the vagus and sympathetic nerves in the control of gastric motility. In: Akkermans LMK, Johnson AG, Read NW (eds) Gastric and gastroduodenal motility. Praeger, New York, pp 21–33 30. Horowitz M, Maddern GJ, Chatterton BE et al (1984) Changes in gastric emptying rates with age. Clin Sci 67:213–218 31. Moore JG, Tweedy C, Christian PE et al (1983) Effect of age on gastric emptying of liquid-solid meals in man. Dig Dis Sci 28:340–344
Assessment of Motor Function of the Remnant Stomach by 13C Breath Test With Special Reference to Gastric Local Resection Masahiko Kawamura • Koji Nakada • Hideo Konishi • Taizo Iwasaki Keishiro Murakami • Norio Mitsumori • Nobuyoshi Hanyu • Nobuo Omura • Katsuhiko Yanaga
•
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Background Indications for gastric local resection (LR) include gastrointestinal stromal tumors, neuroendocrine tumors, and early gastric cancer. LR is expected to preserve physiological function and ameliorate postgastrectomy syndrome. Methods Gastric emptying was assessed by the 13C-acetate breath test in 20 healthy volunteers (HVs) and 60 gastrectomized patients [distal gastrectomy with Billroth I reconstruction (DGBI) in 26 patients, LR in 34 patients]. For the 13C breath test, 100 mg of 13C-acetate sodium salt was mixed in a test meal. Breath samples were collected before intake and during the next 3 h. We compared the gastric reservoir capacity using the gastric retention rate at 5 min (RR5) and gastric emptying by the half emptying time (T). Patients completed a questionnaire survey about their symptoms, dietary intake, body weight, and restriction of activities of daily living [reflecting quality of life (QOL)]. Results The RR5 values for the HV, LR, and DGBI groups were 93.7, 90.0, and 45.3* %, respectively (*compared to HV and LR, p \ 0.0001). The T values were 23.3, 20.2, and 5.9* min, respectively. Dietary intake and body weight change were significantly more reduced in the DGBI group than the LR group (p \ 0.05). Subgroup analysis indicated that the reservoir capacity in those with LR at the lesser curvature was more disturbed than that in patients with LR at
M. Kawamura (&) K. Nakada H. Konishi T. Iwasaki K. Murakami N. Mitsumori N. Hanyu N. Omura K. Yanaga Department of Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan e-mail: [email protected]
the greater curvature. The questionnaire showed no differences in those patients’ QOL. Conclusions Because the reservoir capacity, the gastric emptying and QOL were maintained, LR is an option for selected patients with early gastric cancer.
Introduction Gastric local resection (LR) is increasingly performed for diseases such as GIST, NET, and early gastric cancer. With the widespread use and improvements in endoscopy, gastric cancer is now diagnosed at an early stage in Japan [1, 2]. In the past, conventional gastrectomy, such as distal gastrectomy with Billroth I reconstruction (DGBI), had been performed for early gastric cancer. However, the optimal extent of gastric resection and lymph node (LN) dissection was reconsidered, and function-preserving gastrectomy, such as pylorus-preserving gastrectomy and proximal gastrectomy, was introduced as the standard option for T1N0 early gastric cancer in the latest guideline for treatment of gastric cancer in Japan [3]. Endoscopic procedures are also carried out for early gastric cancer. Currently, well-differentiated intramucosal cancers B2 cm in diameter (T1a) are deemed suitable for endoscopic therapy [4, 5]. The incidence of LN metastasis in early gastric cancer is 2–4 % for intramucosal cancer and 13–20 % for submucosal cancer [6–9]. The indication for endoscopic submucosal resection (ESD) was expanded to include submucosal cancer without LN metastasis and poorly differentiated mucosal cancer. However, the long-term prognosis following expansion of indications for ESD has not been clarified [3]. Meanwhile, LR may ensure a sufficient margin in lateral and horizontal directions compared to ESD, and it retains a larger amount of residual stomach than that in conventional gastrectomy or
123
World J Surg Table 1 Patients’ characteristics Parameter
HV group
Table 2 Patients’ characteristics (LR subgroups)
(n = 26)
DGBI group (n = 26)
LR group
Parameter
LRGC group (n = 20)
LRLC group (n = 14)
(n = 34)
Sex (M/F)
16/4
19/7
23/11
Sex (M/F)
12/8
11/3
Age (years)
29.5 ± 6.9
66.0 ± 8.8
64.6 ± 10.3
Age (years)
65.4 ± 10.2
63.5 ± 10.5
Location (U/M/L)
5/14/1
Location (U/M/L) Resection size (mm)
– –
0/11/5 –
6/26/2 57.0 ± 16.4
Resection size (mm)
1/12/1
60.5 ± 15.1
52.1 ± 16.9
Carcinoma
–
26
17
9
8
GIST
–
–
17
11 20/0 (100 %)a
6 6/8 (43 %)a
–
0/26 (0 %)a
26/8 (76 %)a
Postop. period (months)
39.1 ± 29.4
46.9 ± 44.9
Surgical approach (open/laparoscopic)
1/19
1/13
Primary disease (no.)
Primary disease (no.)
Latarjet branch preserved (yes/no)
Carcinoma
Postop. period (months)
–
37 ± 91.4
42.3 ± 36.8
Surgical approach (open/laparoscopic)
–
16/10
2/32
GIST Latarjet branch preserved (yes/no)
Results are given as the mean ± SD or the number of subjects unless otherwise stated
Results are given as the mean ± SD or the number of subjects unless otherwise stated
LRGC local resection at greater curvature, LRLC local resection at lesser curvature, Postop. postoperative
HV healthy volunteer, DGBI distal gastrectomy with Billroth I reconstruction, LR gastric local resection, U upper third of the stomach, M middle third of the stomach, L lower third of the stomach, GIST gastrointestinal stromal tumor
a
a
Percentage of ‘‘yes’’
function-preserving gastrectomy. Therefore, well-maintained physiologic gastric function is expected after LR, which may reduce disabilities following gastric surgery. It is therefore hoped that LR can contribute to improving the patient’s quality of life (QOL). However, the superiority of LR regarding motility of the remnant stomach and QOL has not been verified. This study was carried out to clarify this issue.
Materials and methods The subjects consisted of 60 patients who had undergone gastrectomy at least 1 year previously. Among them, 26 patients underwent DGBI and 34 underwent LR. Of the LR patients, 14 had lesions in the lesser curvature (LRLC), and 20 had lesions in the greater curvature (LRGC) (Tables 1, 2). All DGBIs were performed for gastric cancer (stages IA and IB). The extent of LN dissection for DGBI was D1? or D2 according to the Japanese Gastric Cancer Classification. LR was carried out for GIST or early gastric cancer, for which informed consent for sentinel node navigation surgery (SNNS) was obtained. In patients who underwent LR for early gastric cancer with SNNS, indocyanine green was locally injected into the submucosa around the tumor using intraoperative endoscopy. When only one lymphatic basin was found upon laparoscopic observation using infrared spectrophotometry, the regional LNs were dissected and were subsequently confirmed to be metastasis-free by intraoperative pathology examination. LR was carried out
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Percentage of ‘‘yes’’
ensuring a 2-cm margin from the edge of the tumor [10]. The Latarjet branch was resected during LRLC for early gastric cancer but was preserved during LRLC for gastric GIST and during LRGC (Table 2). This study was carried out after obtaining written informed consent from the gastrectomized patients and HVs. The ethics committee of the Jikei University School of Medicine approved the study. Evaluation of gastric motility using the breath test
13
C-acetate
The gastric emptying study using the 13C-acetate breath test was performed in 26 patients with DGBI, 34 patients with LR, and 20 healthy volunteers [11]. The test meal was 200 kcal/200 ml liquid meal (Racol; Otsuka Pharmaceutical, Tokyo, Japan) mixed with 100 mg of 13C-acetate sodium salt. Expiratory samples were obtained before intake and at 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 135, 150, 165, and 180 min after intake. The 13 CO2/12CO2 ratio in the expiratory samples was determined using infrared spectrophotometry (UBiT-IR 300; Otsuka Electronics, Tokyo, Japan). Wagner–Nelson analysis was carried out on the obtained data [11]. The gastric retention rate at each time point was calculated quantitatively. Gastric reservoir capacity was evaluated by determining the retention rate at 5 min (RR5) after ingestion. Gastric emptying was evaluated using the half-emptying time (T). The RR5, T, and gastric emptying curve were compared among the groups. The LR subgroups were analyzed according to the resection site (LRGC or LRLC) to investigate its influence.
World J Surg Table 3 Comparison of gastric motility and living status among the DGBI, LR, and HV groups Parameter
HV group (n = 20
DGBI group (n = 26)
LR group (n = 34)
p
RR5 (%)
93.7 ± 5.7
45.3 ± 28.6
90.1 ± 7.2
\0.0001* (DGBI vs. HV, LR)
T (min)
23.3 ± 4.9
5.94 ± 4.0
20.2 ± 8.6
\0.0001* (DGBI vs. HV, LR)
Meal-related distress (yes/no)a
–
14/12 (54 %)
6/28 (18 %)
0.0008**
Diarrhea (yes/no)a
–
8/18 (31 %)
7/27 (21 %)
0.158**
Dumping (yes/no)a
–
17/9 (65 %)
7/27 (21 %)
0.002**
Restricted ADL (yes/no)a
–
12/14 (46 %)
4/30 (12 %)
0.002**
Food intake (%)b Change in body weight (%)c
– –
64.6 ± 1.7 -9.3 ± 0.07
84.8 ± 1.3 -2.7 ± 0.06
\0.0001*** 0.0002***
Results are given as the mean ± SD or the number of subjects unless otherwise stated RR5 retention rate at 5 min, T half emptying time, ADL activities of daily living *Bonferroni/Dunn; **v2-test; ***t-test a
Percentage of ‘‘yes’’
b
Percentage of preoperative food intake
c
Percentage difference from preoperative body weight
Table 4 Comparison of gastric motility and ADL status between LRLC and LRGC Parameter
LRGC group (n = 20)
p
RR5 (%)
85.8 ± 8.3
93.1 ± 4.2
0.003*
T (min)
17.5 ± 4.6
22 ± 10.1
0.136*
Meal-related distress (yes/no)a
3/11 (21 %)
3/17 (15 %)
0.628**
Diarrhea (yes/no)a
3/11 (21 %)
4/16 (20 %)
0.678**
Dumping (yes/no)a
3/11 (21 %)
4/16 (20 %)
0.919**
Restricted ADL (yes/no)a
2/12 (14 %)
2/18 (10 %)
0.703**
83.9 ± 1.3
85.5 ± 1.4
0.938*
-4.73 ± 0.06
-1.09 ± 0.05
0.081*
Food intake (%) Fig. 1 Comparison of gastric emptying curve among patients who underwent distal gastrectomy with Billroth I reconstruction (DGBI), gastric local resection (LR), and healthy volunteers (HV). Significant acceleration of gastric emptying was observed in the DGBI group compared to that in the HV or LR group (*p \ 0.05 vs. HV and LR). Gastric emptying after LR was similar to that in HVs except for 20 min (?p \ 0.05 vs. HV)
LRLC group (n = 14)
b
Change in body weight (%)c
Results are given as the mean ± SD or the number of subjects unless otherwise stated *t-test; **v2-test a
Percentage of ‘‘yes’’
b
Percentage against preoperative food intake
c
Percentage difference from preoperative body weight
Questionnaire
Statistical analysis
All patients who underwent the 13C-acetate breath test to assess remnant gastric motility were asked to answer questions on a questionnaire that addressed postoperative symptoms and living status. The questionnaire included the existence of symptoms (meal-related distress, diarrhea, dumping), ingestion amount per meal, frequency of meals per day, change in body weight, and restricted activities of daily living (ADL), which reflects QOL. Dumping included early and late dumping symptoms, such as cold sweat, palpitation, dizziness, unconsciousness, and headache.
A statistical analysis was conducted using the t test, v2 test, or analysis of variance followed by the Tukey–Kramer test. Results Gastric emptying study by
13
C breath test
There were a significant decrease in RR5 and a shorter T in patients undergone DGBI compared to the HV and LR
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Fig. 2 Comparison of gastric emptying curves between local resection at the lesser curvature (LRLC) and that at the greater curvature (LRGC). In gastric emptying curve, initial gastric emptying (RR5) was significantly accelerated in the LRLC group, with no differences observed thereafter
groups (p \ 0.05). Significant acceleration of gastric emptying was observed in the DGBI group compared with that in the HV and LR groups (p \ 0.05 each). The RR5, T, and gastric emptying curves for the LR group were comparable to those for the HV group (Table 3; Fig. 1). Although the reservoir function of the remnant stomach (RR5) was significantly reduced in the LRLC subgroup, no differences were observed in gastric emptying (T) between the LRLC and LRGC subgroups (Table 4). Initial gastric emptying (RR5) was significantly accelerated in the LRLC subgroup. No differences were observed between the two groups thereafter (Fig. 2). Questionnaire All patients responded to the questionnaires. The incidences of meal-related distress and dumping symptoms were significantly higher in the DGBI group. The amount of food intake per meal was prominently reduced after DGBI to an average 65 % of the preoperative intake but was well maintained after LR at an average of 85 %, which was significantly better than that after DGBI (p \ 0.05). Weight loss after LR was 2.7 %, which was significantly less than that after DGBI (9.3 %) (p \ 0.05). Significantly more patients in the DGBI group than in the LR group complained of restricted ADL (p \ 0.05) (Table 3). Analysis showed that in a comparison of the LRGC and LRLC subgroups, no differences were observed in regard to symptoms, the amount of food intake per meal, change in body weight, or QOL (Table 4).
Discussion Disabilities have frequently been observed following gastrectomy including reduced dietary intake, weight loss,
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dumping, and other gastrointestinal symptoms [12], which may result in impaired QOL. The reduced reservoir function and accelerated emptying of the remnant stomach may be the cause of these problems following gastrectomy. The usefulness of pylorus-preserving gastrectomy to attenuate rapid gastric emptying and creation of a substitute stomach by making a jejunal pouch to compensate for the reduced gastric reservoir capacity have been reported [13–16]. When LR is performed for the treatment of GIST, NET, or limited cases of early cancer, the extent of resection is minimized unless curability is jeopardized. Therefore, improved postoperative QOL is anticipated. However, there is little information on living status after LR (e.g., s dietary intake, changes in body weight, restricted ADL), and motor function of the remnant stomach has not been well investigated. Our results indicated that patients’ QOL and remnant gastric motility were well maintained in the LR group compared to those in the DGBI group. Kitaoka et al. [17], was the first to report the use of LR for treating early gastric cancer. Maintenance of curability and QOL are essential to introducing LR for early gastric cancer clinically. During LR, intraoperative SNNS can confirm the absence of LN metastasis, thereby enhancing curability. Thus, by introducing SNNS into the protocol, the indications for LR may be expanded as an alternative to function-preserving gastrectomy. Although there have been sporadic reports on local recurrence without SNNS following LR for early gastric cancer, local recurrence can be controlled. Hence, curability may be enhanced by concomitant use of SNNS and by establishing a fixed adaptive criterion [1, 18–20]. There are some technical difficulties when applying LR to tumors near the esophagogastric junction or the pylorus. This is because of the risk of stricture, deformity, or dysfunction caused by the procedure. Hence, an insufficient surgical margin is a possible drawback with LR. In recent years, laparoscopic and endoscopic cooperative surgery has been developed [21, 22]. With these techniques, an appropriate margin is marked under intraoperative endoscopy, and the lesion is excised as a whole layer of the gastric wall. The gastric defect is then closed by suturing it laparoscopically. Because of this technical development, LR may be safely performed with a reliable margin without functional disabilities even for lesions close to the esophagogastric junction or the pylorus. Thus, the indications for LR can now be further expanded. As a gastric emptying test, the radioisotope method has served as the gold standard. However, this method cannot avoid radiation exposure, requires special facilities such as a gamma camera and a radiation-controlled area, and is expensive. In this study, we evaluated the postoperative gastric motility using the 13C-acetate breath test, which was proposed in 1993 by Ghoos et al. and has been widely used
World J Surg
to investigate the abnormal gastric emptying that accompanies various digestive disorders. In recent years, it has also been used to evaluate remnant gastric emptying following gastrectomy [23–25]. The 13C-breath test has several advantages, including noninvasiveness, simplicity, safety, and cost efficiency. Regarding the credibility and quantitative evaluation compared to the radioisotope method, Sanaka et al. reported that the 13C-breath test is comparable to the radioisotope method for evaluating quantitative gastric emptying by applying the Wagner– Nelson analysis to the obtained data [26, 27]. In this study, we first applied Wagner–Nelson analysis to the 13C-breath test in the clinical setting to evaluate postoperative gastric motility quantitatively. The 13C-breath test with Wagner– Nelson analysis enables evaluation of the reservoir capacity of the remnant stomach in addition to the gastric emptying rate. Therefore, this method is clinically useful for detecting various digestive disorders and postoperative disturbances in gastric motility. Our study showed excellent QOL after LR. It approximated that of the HV group and was significantly better than that of the DGBI group. The patients were able to eat a sufficient amount of their meals, their weight loss was attenuated, and restricted ADL and symptoms were rare. In addition, the motility of the remnant stomach after LR was similar to that of the HV group. These aspects promise a better QOL to patients after LR. The vagal nerve is a main control of gastric motility. Denervation of the proximal stomach impairs receptive relaxation, which could result in reduced gastric volume after meals. Also, denervation of the distal stomach impairs peristalsis of the antrum, thereby causing delayed gastric emptying [28, 29]. During LR for an early gastric cancer located on the lesser curvature side, the vagal input is excised by regional lymphadenectomy. Therefore, impaired motility of the remnant stomach is a concern. In this study, although the reservoir function of the remnant stomach was significantly reduced in the LRLC subgroup, there were no differences in gastric emptying or in the patients’ QOL between the LRLC and LRGC subgroups. Furthermore, we compared gastric motility after LRLC with or without preservation of the Latarjet branch. There were no differences in gastric motility between the two groups (data not shown). The fact that most of the stomach, pylorus, and cardia are preserved after both LRGC and LRLC may partly explain the well-maintained gastric motility after LR despite the tumor site. Therefore, LR could be securely applied for lesions at any site. The limitation of this study was that the HVs were younger than the patients in either the DGBI or LR group. This difference may have caused some problems with our results as there have been some reports that gastric emptying tends to be slow in elderly subjects [30, 31].
Conclusions LR was superior to DGBI with regard to patients’ postoperative QOL and motility of the remnant stomach. Therefore, LR could be an optimal treatment for patients with early gastric cancer unless curability is jeoparadized. Acknowledgments This study was supported by a grant from MEXT (Ministry of Education, Culture, Sports, Science and Technology)-Supported Program for the Strategic Research Foundation at Private Universities, (2011–2013). The authors thank all the patients whose cooperation made this study possible. Conflict of interest
None.
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