Surg Endosc DOI 10.1007/s00464-013-3336-2
and Other Interventional Techniques
Safety and patient satisfaction of early diet after endoscopic submucosal dissection for gastric epithelial neoplasia: a prospective, randomized study Sunyong Kim • Kyung Seok Cheoi • Hyun Jik Lee • Choong Nam Shim Hyun Soo Chung • Hyuk Lee • Sung Kwan Shin • Sang Kil Lee • Yong Chan Lee • Jun Chul Park
•
Received: 15 July 2013 / Accepted: 10 November 2013 Ó Springer Science+Business Media New York 2013
Abstract Background Endoscopic submucosal dissection (ESD) is a standard treatment for gastric neoplasia limited to the mucosa without lymph node metastasis. However, there are neither standardized guidelines nor studies on the best time to start oral intake after ESD. The aim of this study was to compare patient satisfaction, safety, length of hospital stay, and economic feasibility between an early post-ESD diet and the conventional immediate fasting protocol. Methods A total of 130 patients with 156 gastric epithelial neoplasias who underwent ESD by a single expert endoscopist were consecutively and prospectively enrolled. Enrolled patients were randomized to an early diet group or a control group. The early diet group started meals as a clear liquid diet on day 0, and a soft diet and general diet in sequence on day 1. The fasting group was fasted for 2 days. Patients in both groups underwent second-look endoscopy within 2 days following ESD and follow-up endoscopy after 2 months. Results In the course of the study, ten patients were excluded. The total number of patients in the early diet group and control group was 63 and 57, respectively. Mean age was 62 years (±9.4). There were no significant differences in clinicopathologic conditions or endoscopic results such as procedure time or size of lesions between
Sunyong Kim and Kyung Seok Cheoi have contributed equally to this study, and should be considered to be co-first authors. S. Kim K. S. Cheoi H. J. Lee C. N. Shim H. S. Chung H. Lee S. K. Shin S. K. Lee Y. C. Lee J. C. Park (&) Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea e-mail: [email protected]
the two groups. There were no significant differences in abdominal pain score, rate of post-ESD bleeding or healing rate of ESD-induced ulcer between the two groups. However, the early diet protocol led to significantly higher patient satisfaction (p = 0.001), lower hospital costs (p \ 0.001), and shorter hospital stay (p \ 0.001) than the conventional fasting protocol. Conclusions An early post-ESD diet protocol provides higher patient satisfaction, is more cost effective, decreases hospital stay, and does not influence complication rates such as post-ESD bleeding, abdominal pain, or ulcer healing compared with the conventional fasting protocol. Keywords Endoscopic submucosal dissection Early diet Safety of ESD Post-ESD bleeding
Gastric cancer is one of the most common causes of malignancy and cancer-related deaths worldwide, with a particularly high incidence in Asian countries [1]. Currently, the priority consideration with regard to therapeutic modality involves endoscopic resection techniques such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) with very low risk of node metastasis [2]. In particular, ESD allows en bloc resection of the lesion through dissection of the mucosa and submucosa surrounding the lesion, irrespective of lesion size. Compared with surgical resection, ESD is a less invasive treatment option that preserves most of the gastric mucosa, requires a shorter hospital stay, and therefore is associated with lower costs. Accordingly, ESD is now widely accepted as the optimal endoscopic treatment for early gastric neoplasias [3]. However, to date, optimal strategies regarding when to start oral feeding after ESD have not yet been established.
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Patients are typically fasted for 24 h after the procedure, followed by clear liquid on the second day, and a soft diet on day 3 and for the following 3 days [3, 4]. This prolongation of the fasting period could result in reduced quality of life and increased medical costs for patients due to prolonged hospital stay, which could require more medical resources. Thus, this prospective randomized trial aimed to investigate whether an early post-ESD diet was associated with any complications of ESD, including postESD bleeding, delayed healing of artificial ulcers, or more severe abdominal pain. In addition, the present study investigated medical expenses, length of hospital stay, and patient satisfaction based on diet start time.
Materials and methods Study population and design From February 2011 to February 2012, a total of 130 consecutive patients with 156 gastric epithelial neoplasias, including EGC and gastric adenoma, with histologic evidence who underwent ESD by one expert endoscopist were enrolled in this prospective randomized study at Yonsei University Severance Hospital. Exclusion criteria included age under 20 years; a high risk of bleeding, including the use of antiplatelet agents such as aspirin, clopidogrel, and glycoprotein IIb/IIIa antagonists, anticoagulation with warfarin or low-molecular-weight heparin; and inability or unwillingness to consent to the study. Cases in which a complete procedure was not possible due to severe fibrosis or perforation were also excluded from the present study. ESD was indicated for possible node-negative EGC according to the criteria of Gotoda [3] and the Japanese Gastric Cancer Association [5], which are as follows: (i) differentiated adenocarcinoma, intramucosal cancer, without ulcer findings, irrespective of tumor size; (ii) differentiated adenocarcinoma, intramucosal cancer, with ulcer findings, B30 mm in size; (iii) differentiated adenocarcinoma, minute submucosal penetration (SM1, 500-lm penetration into submucosa), without ulcer findings, B30 mm in size; and (iv) undifferentiated intramucosal cancer, without ulcer findings, B20 mm in size. In cases of gastric adenoma, ESD was also performed if there was a
chance of foci of malignancy or if the patient strongly desired the procedure. Patients in the early diet group started oral intake in the evening of the day of ESD treatment with a clear liquid diet. The clear liquid diet in our study comprised 300 mL wellmilled rice gruel and 100 mL clear beef soup, which provided 170 kilocalories. Subsequently, the diet was advanced to a soft diet in the morning of post-ESD day 1, and then a general diet was commenced and maintained from the afternoon of post-ESD day 1 until discharge. Patients in the control group were fasted for 2 days from the day of the procedure, started a soft diet on the morning of the second day after the procedure, and then began a general diet that afternoon (Table 1). Patients were randomly assigned to the early diet group or the control group after the ESD procedure by a research nurse who was not involved in the ESD procedure using a random, computer-generated sequence. The ESD operator and anyone involved in the procedure were excluded from the randomization. The institutional review board of the hospital approved the study protocol. All enrolled patients provided signed informed consent before participation in the trial. ESD methods The patients were sedated by an anesthesiologist with a continuous intravenous infusion of propofol just before the procedure, and oxygen saturation and electrocardiograms were monitored. ESD was performed with a standard single accessory channel endoscope (GIF-H260Z or H260J Olympus Optical Co., Ltd., Tokyo, Japan) attached to a transparent hood. Marking dots were made using argon plasma coagulation along the circumference of the target lesion. A mixture of hypertonic saline solution, indigocarmine, and diluted epinephrine (1:10,000) was injected into the submucosal layer using a 21-gauge needle to lift the lesion off the muscle layer. A circumferential incision was made outside the marking dots with an insulationtipped (IT) knife (KD-610L, Olympus Optical Co. Ltd, Tokyo, Japan). Subsequent submucosal dissection of the lesion was performed with an IT knife or dual knife (KD-650L, Olympus Optical Co. Ltd., Tokyo, Japan) until complete removal was achieved. Endoscopic hemostasis was performed with a hemoclip or hemostatic forcep whenever bleeding or exposed vessels were observed.
Table 1 Diet protocols of the early diet group and control group during the trial Group
Day 1
Day 0 (ESD)
Day 1
Day 2
Early diet
Admission
NPO ? CLD (supper only)
SD ? GD ? GD
GD (breakfast and discharge)
Control
Admission
NPO
NPO
SD ? GD ? GD
CLD clear liquid diet, ESD endoscopic submucosal dissection, GD general diet, NPO nil per os, SD soft diet
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Day 3
GD (breakfast and discharge)
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Definitions and outcome measures En bloc resection was defined as resection in a single piece as opposed to the resection of multiple pieces. The complete resection of en bloc-resected tumors was defined by negative lateral and vertical margins on histologic examination. The complete resection of piecemeal-resected tumors was defined as the removal of the tumors in their entirety and sufficient tumor-free margins after reconstruction of all pieces. Procedure time was defined as the time from marking to complete removal, including the time required for hemostasis. Post-ESD bleeding was defined as clinical evidence of bleeding after ESD, as represented by hematemesis, melena, or hematochezia after normalization of stool color, or a decrease in hemoglobin levels of C2.0 g/dL, after consecutive stable hemoglobin level and/ or active bleeding confirmed by endoscopic evaluation. Bleeding within 2 days was considered to be early bleeding. All suspected bleeding cases were confirmed by emergency endoscopy. Delayed bleeding was defined as clinical evidence of bleeding found 2 or more days after ESD. A diagnosis of perforation required direct endoscopic observation of mesenteric fat or the presence of free air on abdominal radiography or computed tomography (CT). Histologic evaluation and assessment of resection efficacy All resected specimens were systematically sectioned at 2-mm intervals, centered on the part of the lesion closest to the margin and the site of the deepest invasion. Histological assessment was based on the Vienna classification [6]. Final pathologic diagnoses were classified as low-grade dysplasia, high-grade dysplasia, differentiated EGC, or undifferentiated EGC. Medication Patients in both groups received intravenous administration of 40 mg pantoprazole on the day of ESD. From the first day after ESD, patients in both groups received 30 mg oral lansoprazole once a day and took the same discharge medication for 8 weeks. Non-steroidal anti-inflammatory agents or tramadol were used if patients complained of severe post-ESD pain. Follow-up Second-look endoscopy was performed within 3 days of ESD as scheduled. During second-look endoscopy, the artificial ulcer was meticulously examined. The bleeding site was treated with electrical coagulation when either
spurting hemorrhage (Forrest Ia), oozing hemorrhage (Forrest Ib), or a visible vessel (Forrest IIa) was noted [7]. Most of the patients in the early diet group were discharged on day 2 post-ESD with early toleration of oral intake, while patients in the control group were usually discharged on day 3 post-ESD, unless they showed any signs or symptoms of complications (i.e., significant changes in vital signs, persistent abdominal pain, tarry stools, pneumonia, or unexplained fever). Hemoglobin levels were checked daily during the hospitalization period. Physical examination, history taking, and laboratory analysis, including hemoglobin level, were performed at our outpatient clinic at 2 weeks and 2 months to assess delayed bleeding. Follow-up esophagogastroduodenoscopy (EGD) was performed 2 months after ESD to evaluate the status of post-ESD ulcer. Questionnaires Patients in both groups completed a questionnaire that assessed (i) abdominal pain score between 1 and 4 (1 = none, 2 = mild pain, 3 = moderate pain, 4 = severe pain) on the day before ESD and 48 h after ESD and (ii) overall satisfaction score between 1 and 7 (1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied) with their diet protocol 48 h after ESD. Statistical analysis Clinicopathological factors were analyzed separately for all early diet group patients and control group patients. Abdominal pain, overall satisfaction, duration of hospitalization, and medical expenses were evaluated in relation to each of the diet protocols. Statistical analyses were conducted for patients in the early diet group versus the control group. p values for baseline characteristics were calculated using t tests for continuous variables and Pearson’s Chi squared test or Fisher’s exact test for categorical variables. A p value of \0.05 was considered to indicate statistical significance. Statistical analyses were performed with SPSS software version 12.0 (SPSS Inc., Chicago, IL, USA). Sample size determination Sample size was calculated based on the assumption that early diet protocol would not be inferior to conventional early fasting protocol in terms of post-ESD bleeding rate if the lower limit of the 95 % confidence interval (CI) for the difference did not exceed 10 %. We assumed that the postESD bleeding rates were 3.8 %, based on data from the
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ESD registry of our institute. Assuming a 10 % drop-out rate, 63 patients would be needed per group to prove the overall equivalent post-ESD bleeding rate using a 5 % significance level and a statistical power of 80 %.
Results Study population A total of 130 patients with 156 lesions were enrolled in this study, and ten of these patients were withdrawn from the study. One patient who underwent gastric perforation during the ESD, two patients who had a gastrectomy during the research period, and seven patients who were lost to follow-up after ESD were withdrawn, as shown in Fig. 1. Finally, a total of 120 patients (86 men, 34 women; median age 62 years, range 33–86) were investigated. Endoscopic and pathologic results of ESD The total number in the early diet group and control group was 63 and 57 patients, respectively. The clinicopathologic characteristics of the patients are summarized in Table 2. In the total study population, the mean age was 61.8 ± 9.4 years, and 71.7 % of the patients were male. There were no statistically significant differences in age and gender between groups. The proportion of endoscopic location of the tumors was higher in the lower one-third at 68.3 and 66.7 % in the early diet group and control group,
Fig. 1 Flow chart representing patient inclusion and exclusion in this study. ESD endoscopic submucosal dissection
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respectively (p = 0.733). Mean tumor and resected specimen size were not different between the two groups, and were 13.1 ± 10.3 mm and 43.5 ± 19.3 mm in the early diet group and 15.0 ± 12.1 mm and 42.0 ± 15.8 in control group (p = 0.348, p = 0.641, respectively). Pathologic diagnosis revealed malignancy in 57 cases (27 cases in the early diet group, 30 cases in the control group) and dysplasia in 63 cases (36 cases in the early diet group, 27 cases in the control group). Pathologic results were not significantly different between the two groups. All gastric lesions were treated by en bloc resection (100 %) and the majority by complete resection (94.3 % in all, 93.7 % in the early diet group and 94.7 % in the control group). The mean operation time was not significantly different between groups (52.9 min in the early diet group and 61.8 min in the control group, p = 0.200). In addition to these results, there were no significant differences in other demographics or clinicopathologic characteristics such as comorbidities, the presence of ulcers, or the multiplicity of neoplastic lesions between groups (Table 2). Findings of second-look and 2-month follow-up EGD between early diet and control groups There were no significant differences in the healing status of post-ESD ulcer between the two groups, as presented in Table 3. The hemoglobin levels of both groups were slightly decreased at the 2-week post-ESD follow-up laboratory test
Surg Endosc Table 2 The clinicopathologic characteristics of the study population
Variable
All patients (N = 120)
Early diet group (N = 63)
Control group (N = 57)
Age, years [mean ± SD (range)]
61.8 ± 9.4 (33–86)
62.5 ± 8.8 (36–80)
61.1 ± 10.1 (33–86)
Male
86 (71.7 %)
44 (69.8 %)
42 (73.7 %)
Female
34 (28.3 %)
19 (30.2 %)
15 (26.3 %)
Gender
p value 0.434 0.641
Comorbidity DM
18 (15.0 %)
11 (17.5 %)
7 (12.3 %)
0.427
Hypertension Cardiac disease
7 (5.8 %) 7 (5.8 %)
20 (31.7 %) 5 (7.9 %)
18 (31.6 %) 2 (3.5 %)
0.984 0.301
Renal disease
7 (5.8 %)
0 (0 %)
2 (3.5 %)
0.134
10 (8.3 %)
4 (6.3 %)
6 (10.5 %)
Location of lesion Upper
0.733
Middle
29 (24.2 %)
16 (25.4 %)
13 (22.8 %)
Lower
81 (67.5 %)
43 (68.3 %)
38 (66.7 %)
Single
99
52
47
Synchronous
21
11
10
Ulcer present
18 (15.0 %)
8 (12.7 %)
10 (17.5 %)
0.458
Pathologic lesion size of ESD, mm Specimen size of ESD, mm
14.0 ± 11.2
13.1 ± 10.3
15.0 ± 12.1
0.348
42.7 ± 17.7
43.5 ± 19.3
42.0 ± 15.8
0.641
46 (38.3 %)
26 (41.3 %)
20 (35.1 %)
Multiplicity of lesion
0.867
Pathologic findings Low-grade dysplasia
0.446
High-grade dysplasia
17 (14.2 %)
10 (15.9 %)
7 (12.3 %)
Differentiated cancer
52 (43.3 %)
26 (41.3 %)
26 (45.6 %)
Undifferentiated cancer
5 (4.2 %)
1 (1.6 %)
4 (7.0 %)
120 (100 %)
63 (100 %)
57 (100 %)
[0.999
En bloc resection Curability Complete resection
113 (94.3 %)
59 (93.7 %)
54 (94.7 %)
[0.999
Incomplete resection
7 (5.7 %)
4 (6.3 %)
4 (5.3 %)
[0.999
Lateral margin, positive
4 (3.3 %)
2 (3.2 %)
2 (3.5 %)
0.919
Basal margin, positive
3 (2.5 %)
2 (3.2 %)
1 (1.8 %)
0.619
Margin involvement
Procedure time (min) Data are presented as n (%) or mean ± SD (range)
Dissection time
48.8 ± 34.3 (8–160)
45.4 ± 30.6 (8–140)
54.2 ± 40.5 (11–160)
0.179
ESD endoscopic submucosal dissection, DM diabetes mellitus, SD standard deviation
Total procedure time
57.1 ± 37.9 (10–200)
52.9 ± 32.9 (10–154)
61.8 ± 42.0 (13–200)
0.200
compared with that of the day of ESD. The mean decrease in hemoglobin level was 0.58 ± 0.96 g/dL in the early diet group and 0.47 ± 0.69 g/dL in the control group (p = 0.494). The decrement of follow-up hemoglobin level did not show statistical significance. Second-look EGD was performed in 109 patients among the enrolled 120 patients, as 11 patients refused. There were no significant differences in ulcer stage, the presence of bleeding stigmata, the need for prophylactic hemostasis, or post-ESD ulcer size. Follow-up EGD after 2 months was performed in 104 patients, and 16 patients refused EGD follow-up. There were also no
significant differences in ulcer stage, presence of bleeding stigmata, or post-ESD ulcer size (Table 3). Early post-ESD bleeding did not occur in either group, while delayed bleeding occurred in 5 of 120 patients (4.17 %). There were no significant differences in delayed bleeding rates between the early diet group and control group (Table 3; 4.8 vs. 3.5 %). The first and last bleeding case occurred on the 8th (control group) and 55th (control group) day after ESD treatment, respectively. All five cases of delayed ESD bleeding were controlled by endoscopic hemostasis such as electrocoagulation, epinephrine–hypertonic saline mixture
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Surg Endosc Table 3 Analysis of initial and follow-up hemoglobin levels, findings of follow-up EGD and bleeding complications between early diet and control group Variable
Early diet group
Control group
p value
Hemoglobin (g/dL) Admission
13.7 ± 1.3
13.7 ± 1.5
0.921
F/U after 2 weeks Gap (F/U–admission)
13.3 ± 1.6 0.58 ± 0.96
13.4 ± 1.5 0.47 ± 0.69
0.708 0.494
Second-look EGD Ulcer stage
0.693
A1
38 (64.4 %)
34 (68.0 %)
A2
21 (35.6 %)
16 (32.0 %)
Stigmata
0.161
Present
14 (23.7 %)
18 (36.0 %)
Absent
45 (76.3 %)
32 (64.0 %)
Prophylactic hemostasis Present Absent Mean ulcer size, mm
0.41 13 (22.0 %)
10 (20.0 %)
46 (78.0 %)
40 (80.0 %)
Maximal length
53.6 ± 20.8
56.0 ± 23.4
0.577
Minimal length
43.0 ± 18.7
46.0 ± 18.9
0.396
Follow-up EGD after 2 months Ulcer stage
0.862
A2
0 (0 %)
H1
1 (2.0 %)
1 (1.9 %)
H2
14 (27.5 %)
16 (30.2 %)
S1
33 (64.7 %)
33 (62.3 %)
S2
3 (5.9 %)
2 (3.8 %)
Stigmata Present Absent
1 (1.9 %)
0.324 0 (0 %)
1 (1.9 %)
51 (100 %)
52 (98.1 %)
13.6 ± 8.3
13.3 ± 7.0
0.810
Early bleeding
0 (0 %)
0 (0 %)
NS
Delayed bleeding
3 (4.8 %)
2 (3.5 %)
0.732
Ulcer size, mm Post-ESD bleeding
Data are presented as n (%) or mean ± SD EGD esophagogastroduodenoscopy, ESD endoscopic submucosal dissection, F/U follow-up
injection or hemoclipping. Blood transfusion was not required for any of the five patients. Abdominal pain and overall satisfaction for ESD treatment The abdominal pain and overall satisfaction scores during hospitalization for ESD are summarized in Fig. 2. The abdominal pain score of the early diet group and control group at the time of admission was increased after ESD
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treatment. However, there were no significant differences in the increment of abdominal pain score before and after ESD between the two groups. The early diet group reported significantly higher patient satisfaction compared with the control group (5.0 vs. 4.1, p = 0.001). The duration of hospitalization and medical expenses for ESD treatment Medical expenses and length of hospital stay were analyzed between the two groups among 116 patients, excluding four patients who were transferred to other departments for their other problems. The discharge of several patients in both groups was delayed for 1 or 2 days by mild fever, abdominal discomfort, or general weakness. The early diet group had a significantly shorter hospital stay (4.3 vs. 5.2 days, p \ 0.001) and lower total hospital expenses (US$2,554.4 vs. US$2,939.8, p \ 0.001) compared with the control group (Table 4).
Discussion This prospective randomized controlled study demonstrates that early diet protocol after ESD for gastric epithelial neoplasia increased the satisfaction of patients without affecting complication rates, including post-ESD bleeding, the healing rate of post-ESD ulcers, and abdominal pain, compared with a conventional fasting protocol. Furthermore, an early diet protocol can decrease the expense and period of hospitalization compared with a conventional fasting protocol. To the best of our knowledge, this study is the first to evaluate the clinical impact of early post-ESD diet protocol on patient comfort and satisfaction. It was found to minimize length of hospitalization, which decreased medical expenses. The endoscopic technique for EGC has been further developed since the first EMR technique was reported in 1984 [8]. ESD is a widely used therapeutic procedure that preserves the stomach and allows for en bloc resection [9–13]. Thus, ESD is now widely accepted as the optimal endoscopic treatment for early gastric neoplasias, especially in Asian countries where the incidence of gastric neoplasias is high [3]. Nevertheless, the optimal timing to start oral feeding after ESD has not yet been established. Patients are typically fasted for 24 h after the procedure, followed by a clear liquid diet on the second day, and a soft diet on day 3, which may continue for another 3 days [3, 4]. However, these diet strategies are not based on concrete evidence, but rather rely solely on experience. Several studies have examined the issue of early oral feeding and early enteral nutrition in the gastrointestinal surgical field. In gastrointestinal surgery, 2–5 days of fasting
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Fig. 2 A Diagram of the abdominal pain scale of both groups before and after ESD treatment. Admission, p = 0.625; 48 h post-ESD, p = 0.187; increment, p = 0.295. B Overall satisfaction score of both
groups after ESD, p = 0.001. Data are expressed as mean ± SD. ESD endoscopic submucosal dissection
Table 4 Analysis of hospitalization period, total medical expenses and patient-medical expenses between early diet and control group
there have been no studies concerning diet strategies in the field of therapeutic endoscopy, unlike in the field of surgery. To maximize these advantages of ESD treatment over gastric surgery, the present study demonstrated that an early postESD diet protocol could result in patients’ earlier tolerance of oral intake, resulting in more comfortable nourishment, shorter hospitalization, and lower healthcare costs. Earlier toleration of oral intake might reduce the use of parenteral nutrition, and moreover, oral intake could enable patients to be nourished more effectively and discharged earlier, thus leading to a decrease in medical costs for ESD treatment. A significant reduction in medical expenses might stem from not only a decrease in hospitalized days, but also reduced use of parenteral nutrition, creating a virtuous circle. The early diet protocol may have some safety concerns, especially for post-ESD bleeding, delayed ulcer healing rate, and abdominal pain. Our results demonstrate that an early diet strategy after ESD did not worsen abdominal pain, and did not affect post-ESD bleeding rates or delay the healing rate of ESD-induced artificial ulcers. In our study, it was assumed that many of the patients might have had baseline abdominal discomfort or pain before the ESD procedure, because upper endoscopy might have been performed in search of the cause of their gastrointestinal problems, except in the case of healthy screenees. Therefore, it is appropriate to compare not only abdominal pain, but also the increment of abdominal pain after ESD, even if abdominal pain was mild or absent before the procedure. Post-ESD abdominal pain is probably caused by ulcer defects or electrical thermal burns inflicted during dissection or coagulation, from the submucosal layer to the serosa [24].
Early diet group (N = 61) Hospitalization period (days)
4.3 ± 0.6
Total medical expenses (US$)
2,554.4 ± 374.7
Control group (N = 55)
p value
5.2 ± 1.1
\0.001
2,939.8 ± 497.2 \0.001
has been thought necessary due to postoperative atonic bowel [14]. However, recent reports have supported the view that early oral feeding after gastric cancer surgery is safe, with no evidence of increased morbidity, and could result in a faster recovery of bowel function and a shorter hospitalization [15, 16]. Several studies have also reported that strategies for pain relief, stress reduction, early mobilization, and early oral feeding lead to faster recovery or reduced hospital stay in colon surgery [17, 18]. Experimental data has shown that immediate postoperative enteral nutrition improves wound healing related to the integrity of intestinal anastomosis, muscle function, insulin resistance, and moreover, reduces sepsis [19]. In addition, early enteral nutritional support may more effectively activate normal digestive reflexes, which play a crucial role in intestinal recovery after gastrointestinal surgery, than a strategy of bowel rest and intravenous nutrition [20]. Early oral feeding compared with parenteral nutrition might have both nutritional and immunological merits thanks to improved protein kinetics and preservation of the immune system, leading to improved wound healing and resistance to infection [21–23]. ESD is less invasive and requires a shorter hospital stay and lower medical expenses than surgical treatment. However,
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In addition, post-ESD abdominal discomfort and intolerance to oral diet can be caused by post-procedural transient gastric ileus. In the case of gastrointestinal surgery, postoperative ileus arises from multifactorial causes, including surgical trauma, local inflammatory reactions, anesthetic agents, hyperactivity of the sympathetic nervous system, and opioid use in the postoperative period [25]. In particular, postoperative gastric ileus typically improves within 24–48 h, while peristalsis in the colon may not return until 72 h after surgery [25]. ESD treatment for gastric epithelial neoplasia may also be accompanied by gastric mucosal trauma, local inflammatory reactions, sedative administration, and hyperactivity of the sympathetic nervous system, but opioids are not used during the procedure. The ESD procedure is generally shorter in duration than gastrointestinal surgery and the mucosal trauma, local tissue reaction, and the amount of sedatives used are minimal compared with those of gastric surgery. This supports the conclusion that ESD treatment might not require as long a fasting period during postoperative care. In terms of gastric ulcer, early feeding has been investigated in several studies. In one study by Khoshbaten et al. [26], there was no significant difference between the early diet group (oral diet from day 1) and the control group (nil by mouth for 3 days) according to the re-bleeding rate and the need for blood transfusion; therefore, early oral feeding was thought to enable earlier discharge and decrease treatment costs. In another two studies by de Ledinghen et al. [27, 28], there were no significant associations between re-bleeding and early oral feeding. These results are in agreement with those of our study, which established that ESD-induced artificial ulcers neither bled more frequently nor healed at a slower rate in the early diet group. There are several limitations to the present study. First, this was a single-center study with a small study population. Second, all ESD procedures were performed by a single experienced endoscopist. Even with these limitations, this is the first evidence to support the adoption of an early oral diet protocol for ESD of gastric epithelial neoplasias. Another randomized control study will be necessary in the future to reliably evaluate the safety and effectiveness of the diet protocol with a larger, multicenter study population. In conclusion, an early post-ESD diet protocol provides higher patient satisfaction, is more cost effective, decreases hospital stay, and does not influence complication rates such as post-ESD bleeding, abdominal pain, or ulcer healing compared with the conventional fasting protocol. Our study supports the recommendation that a long period of post-ESD fasting might not be necessary. Disclosures Drs. Sunyong Kim, Kyung Seok Cheoi, Hyun Jik Lee, Choong Nam Shim, Hyun Soo Chung, Hyuk Lee, Sung Kwan Shin,
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Sang Kil Lee, Yong Chan Lee, and Jun Chul Park have no conflicts of interest or financial ties to disclose.
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24. Kiriyama S, Oda I, Nishimoto F, Mashimo Y, Ikehara H, Gotoda T (2009) Pilot study to assess the safety of local lidocaine injections during endoscopic submucosal dissection for early gastric cancer. Gastric Cancer 12:142–147 25. Maron DJ, Fry RD (2008) New therapies in the treatment of postoperative ileus after gastrointestinal surgery. Am J Ther 15:59–65 26. Khoshbaten M, Ghaffarifar S, Jabbar Imani A, Shahnazi T (2013) Effects of early oral feeding on relapse and symptoms of upper gastrointestinal bleeding in peptic ulcer disease. Dig Endosc 25:125–129 27. de Ledinghen V, Beau P, Mannant PR, Ripault MP, Borderie C, Silvain C, Morichau-Beauchant M (1998) When should patients with bleeding peptic ulcer resume oral intake? A randomized controlled study. Gastroenterol Clin Biol 22:282–285 28. de Ledinghen V, Beau P, Mannant PR, Borderie C, Ripault MP, Silvain C, Beauchant M (1997) Early feeding or enteral nutrition in patients with cirrhosis after bleeding from esophageal varices? A randomized controlled study. Dig Dis Sci 42:536–541
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and Other Interventional Techniques
Safety and patient satisfaction of early diet after endoscopic submucosal dissection for gastric epithelial neoplasia: a prospective, randomized study Sunyong Kim • Kyung Seok Cheoi • Hyun Jik Lee • Choong Nam Shim Hyun Soo Chung • Hyuk Lee • Sung Kwan Shin • Sang Kil Lee • Yong Chan Lee • Jun Chul Park
•
Received: 15 July 2013 / Accepted: 10 November 2013 Ó Springer Science+Business Media New York 2013
Abstract Background Endoscopic submucosal dissection (ESD) is a standard treatment for gastric neoplasia limited to the mucosa without lymph node metastasis. However, there are neither standardized guidelines nor studies on the best time to start oral intake after ESD. The aim of this study was to compare patient satisfaction, safety, length of hospital stay, and economic feasibility between an early post-ESD diet and the conventional immediate fasting protocol. Methods A total of 130 patients with 156 gastric epithelial neoplasias who underwent ESD by a single expert endoscopist were consecutively and prospectively enrolled. Enrolled patients were randomized to an early diet group or a control group. The early diet group started meals as a clear liquid diet on day 0, and a soft diet and general diet in sequence on day 1. The fasting group was fasted for 2 days. Patients in both groups underwent second-look endoscopy within 2 days following ESD and follow-up endoscopy after 2 months. Results In the course of the study, ten patients were excluded. The total number of patients in the early diet group and control group was 63 and 57, respectively. Mean age was 62 years (±9.4). There were no significant differences in clinicopathologic conditions or endoscopic results such as procedure time or size of lesions between
Sunyong Kim and Kyung Seok Cheoi have contributed equally to this study, and should be considered to be co-first authors. S. Kim K. S. Cheoi H. J. Lee C. N. Shim H. S. Chung H. Lee S. K. Shin S. K. Lee Y. C. Lee J. C. Park (&) Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea e-mail: [email protected]
the two groups. There were no significant differences in abdominal pain score, rate of post-ESD bleeding or healing rate of ESD-induced ulcer between the two groups. However, the early diet protocol led to significantly higher patient satisfaction (p = 0.001), lower hospital costs (p \ 0.001), and shorter hospital stay (p \ 0.001) than the conventional fasting protocol. Conclusions An early post-ESD diet protocol provides higher patient satisfaction, is more cost effective, decreases hospital stay, and does not influence complication rates such as post-ESD bleeding, abdominal pain, or ulcer healing compared with the conventional fasting protocol. Keywords Endoscopic submucosal dissection Early diet Safety of ESD Post-ESD bleeding
Gastric cancer is one of the most common causes of malignancy and cancer-related deaths worldwide, with a particularly high incidence in Asian countries [1]. Currently, the priority consideration with regard to therapeutic modality involves endoscopic resection techniques such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) with very low risk of node metastasis [2]. In particular, ESD allows en bloc resection of the lesion through dissection of the mucosa and submucosa surrounding the lesion, irrespective of lesion size. Compared with surgical resection, ESD is a less invasive treatment option that preserves most of the gastric mucosa, requires a shorter hospital stay, and therefore is associated with lower costs. Accordingly, ESD is now widely accepted as the optimal endoscopic treatment for early gastric neoplasias [3]. However, to date, optimal strategies regarding when to start oral feeding after ESD have not yet been established.
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Patients are typically fasted for 24 h after the procedure, followed by clear liquid on the second day, and a soft diet on day 3 and for the following 3 days [3, 4]. This prolongation of the fasting period could result in reduced quality of life and increased medical costs for patients due to prolonged hospital stay, which could require more medical resources. Thus, this prospective randomized trial aimed to investigate whether an early post-ESD diet was associated with any complications of ESD, including postESD bleeding, delayed healing of artificial ulcers, or more severe abdominal pain. In addition, the present study investigated medical expenses, length of hospital stay, and patient satisfaction based on diet start time.
Materials and methods Study population and design From February 2011 to February 2012, a total of 130 consecutive patients with 156 gastric epithelial neoplasias, including EGC and gastric adenoma, with histologic evidence who underwent ESD by one expert endoscopist were enrolled in this prospective randomized study at Yonsei University Severance Hospital. Exclusion criteria included age under 20 years; a high risk of bleeding, including the use of antiplatelet agents such as aspirin, clopidogrel, and glycoprotein IIb/IIIa antagonists, anticoagulation with warfarin or low-molecular-weight heparin; and inability or unwillingness to consent to the study. Cases in which a complete procedure was not possible due to severe fibrosis or perforation were also excluded from the present study. ESD was indicated for possible node-negative EGC according to the criteria of Gotoda [3] and the Japanese Gastric Cancer Association [5], which are as follows: (i) differentiated adenocarcinoma, intramucosal cancer, without ulcer findings, irrespective of tumor size; (ii) differentiated adenocarcinoma, intramucosal cancer, with ulcer findings, B30 mm in size; (iii) differentiated adenocarcinoma, minute submucosal penetration (SM1, 500-lm penetration into submucosa), without ulcer findings, B30 mm in size; and (iv) undifferentiated intramucosal cancer, without ulcer findings, B20 mm in size. In cases of gastric adenoma, ESD was also performed if there was a
chance of foci of malignancy or if the patient strongly desired the procedure. Patients in the early diet group started oral intake in the evening of the day of ESD treatment with a clear liquid diet. The clear liquid diet in our study comprised 300 mL wellmilled rice gruel and 100 mL clear beef soup, which provided 170 kilocalories. Subsequently, the diet was advanced to a soft diet in the morning of post-ESD day 1, and then a general diet was commenced and maintained from the afternoon of post-ESD day 1 until discharge. Patients in the control group were fasted for 2 days from the day of the procedure, started a soft diet on the morning of the second day after the procedure, and then began a general diet that afternoon (Table 1). Patients were randomly assigned to the early diet group or the control group after the ESD procedure by a research nurse who was not involved in the ESD procedure using a random, computer-generated sequence. The ESD operator and anyone involved in the procedure were excluded from the randomization. The institutional review board of the hospital approved the study protocol. All enrolled patients provided signed informed consent before participation in the trial. ESD methods The patients were sedated by an anesthesiologist with a continuous intravenous infusion of propofol just before the procedure, and oxygen saturation and electrocardiograms were monitored. ESD was performed with a standard single accessory channel endoscope (GIF-H260Z or H260J Olympus Optical Co., Ltd., Tokyo, Japan) attached to a transparent hood. Marking dots were made using argon plasma coagulation along the circumference of the target lesion. A mixture of hypertonic saline solution, indigocarmine, and diluted epinephrine (1:10,000) was injected into the submucosal layer using a 21-gauge needle to lift the lesion off the muscle layer. A circumferential incision was made outside the marking dots with an insulationtipped (IT) knife (KD-610L, Olympus Optical Co. Ltd, Tokyo, Japan). Subsequent submucosal dissection of the lesion was performed with an IT knife or dual knife (KD-650L, Olympus Optical Co. Ltd., Tokyo, Japan) until complete removal was achieved. Endoscopic hemostasis was performed with a hemoclip or hemostatic forcep whenever bleeding or exposed vessels were observed.
Table 1 Diet protocols of the early diet group and control group during the trial Group
Day 1
Day 0 (ESD)
Day 1
Day 2
Early diet
Admission
NPO ? CLD (supper only)
SD ? GD ? GD
GD (breakfast and discharge)
Control
Admission
NPO
NPO
SD ? GD ? GD
CLD clear liquid diet, ESD endoscopic submucosal dissection, GD general diet, NPO nil per os, SD soft diet
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Day 3
GD (breakfast and discharge)
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Definitions and outcome measures En bloc resection was defined as resection in a single piece as opposed to the resection of multiple pieces. The complete resection of en bloc-resected tumors was defined by negative lateral and vertical margins on histologic examination. The complete resection of piecemeal-resected tumors was defined as the removal of the tumors in their entirety and sufficient tumor-free margins after reconstruction of all pieces. Procedure time was defined as the time from marking to complete removal, including the time required for hemostasis. Post-ESD bleeding was defined as clinical evidence of bleeding after ESD, as represented by hematemesis, melena, or hematochezia after normalization of stool color, or a decrease in hemoglobin levels of C2.0 g/dL, after consecutive stable hemoglobin level and/ or active bleeding confirmed by endoscopic evaluation. Bleeding within 2 days was considered to be early bleeding. All suspected bleeding cases were confirmed by emergency endoscopy. Delayed bleeding was defined as clinical evidence of bleeding found 2 or more days after ESD. A diagnosis of perforation required direct endoscopic observation of mesenteric fat or the presence of free air on abdominal radiography or computed tomography (CT). Histologic evaluation and assessment of resection efficacy All resected specimens were systematically sectioned at 2-mm intervals, centered on the part of the lesion closest to the margin and the site of the deepest invasion. Histological assessment was based on the Vienna classification [6]. Final pathologic diagnoses were classified as low-grade dysplasia, high-grade dysplasia, differentiated EGC, or undifferentiated EGC. Medication Patients in both groups received intravenous administration of 40 mg pantoprazole on the day of ESD. From the first day after ESD, patients in both groups received 30 mg oral lansoprazole once a day and took the same discharge medication for 8 weeks. Non-steroidal anti-inflammatory agents or tramadol were used if patients complained of severe post-ESD pain. Follow-up Second-look endoscopy was performed within 3 days of ESD as scheduled. During second-look endoscopy, the artificial ulcer was meticulously examined. The bleeding site was treated with electrical coagulation when either
spurting hemorrhage (Forrest Ia), oozing hemorrhage (Forrest Ib), or a visible vessel (Forrest IIa) was noted [7]. Most of the patients in the early diet group were discharged on day 2 post-ESD with early toleration of oral intake, while patients in the control group were usually discharged on day 3 post-ESD, unless they showed any signs or symptoms of complications (i.e., significant changes in vital signs, persistent abdominal pain, tarry stools, pneumonia, or unexplained fever). Hemoglobin levels were checked daily during the hospitalization period. Physical examination, history taking, and laboratory analysis, including hemoglobin level, were performed at our outpatient clinic at 2 weeks and 2 months to assess delayed bleeding. Follow-up esophagogastroduodenoscopy (EGD) was performed 2 months after ESD to evaluate the status of post-ESD ulcer. Questionnaires Patients in both groups completed a questionnaire that assessed (i) abdominal pain score between 1 and 4 (1 = none, 2 = mild pain, 3 = moderate pain, 4 = severe pain) on the day before ESD and 48 h after ESD and (ii) overall satisfaction score between 1 and 7 (1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied) with their diet protocol 48 h after ESD. Statistical analysis Clinicopathological factors were analyzed separately for all early diet group patients and control group patients. Abdominal pain, overall satisfaction, duration of hospitalization, and medical expenses were evaluated in relation to each of the diet protocols. Statistical analyses were conducted for patients in the early diet group versus the control group. p values for baseline characteristics were calculated using t tests for continuous variables and Pearson’s Chi squared test or Fisher’s exact test for categorical variables. A p value of \0.05 was considered to indicate statistical significance. Statistical analyses were performed with SPSS software version 12.0 (SPSS Inc., Chicago, IL, USA). Sample size determination Sample size was calculated based on the assumption that early diet protocol would not be inferior to conventional early fasting protocol in terms of post-ESD bleeding rate if the lower limit of the 95 % confidence interval (CI) for the difference did not exceed 10 %. We assumed that the postESD bleeding rates were 3.8 %, based on data from the
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ESD registry of our institute. Assuming a 10 % drop-out rate, 63 patients would be needed per group to prove the overall equivalent post-ESD bleeding rate using a 5 % significance level and a statistical power of 80 %.
Results Study population A total of 130 patients with 156 lesions were enrolled in this study, and ten of these patients were withdrawn from the study. One patient who underwent gastric perforation during the ESD, two patients who had a gastrectomy during the research period, and seven patients who were lost to follow-up after ESD were withdrawn, as shown in Fig. 1. Finally, a total of 120 patients (86 men, 34 women; median age 62 years, range 33–86) were investigated. Endoscopic and pathologic results of ESD The total number in the early diet group and control group was 63 and 57 patients, respectively. The clinicopathologic characteristics of the patients are summarized in Table 2. In the total study population, the mean age was 61.8 ± 9.4 years, and 71.7 % of the patients were male. There were no statistically significant differences in age and gender between groups. The proportion of endoscopic location of the tumors was higher in the lower one-third at 68.3 and 66.7 % in the early diet group and control group,
Fig. 1 Flow chart representing patient inclusion and exclusion in this study. ESD endoscopic submucosal dissection
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respectively (p = 0.733). Mean tumor and resected specimen size were not different between the two groups, and were 13.1 ± 10.3 mm and 43.5 ± 19.3 mm in the early diet group and 15.0 ± 12.1 mm and 42.0 ± 15.8 in control group (p = 0.348, p = 0.641, respectively). Pathologic diagnosis revealed malignancy in 57 cases (27 cases in the early diet group, 30 cases in the control group) and dysplasia in 63 cases (36 cases in the early diet group, 27 cases in the control group). Pathologic results were not significantly different between the two groups. All gastric lesions were treated by en bloc resection (100 %) and the majority by complete resection (94.3 % in all, 93.7 % in the early diet group and 94.7 % in the control group). The mean operation time was not significantly different between groups (52.9 min in the early diet group and 61.8 min in the control group, p = 0.200). In addition to these results, there were no significant differences in other demographics or clinicopathologic characteristics such as comorbidities, the presence of ulcers, or the multiplicity of neoplastic lesions between groups (Table 2). Findings of second-look and 2-month follow-up EGD between early diet and control groups There were no significant differences in the healing status of post-ESD ulcer between the two groups, as presented in Table 3. The hemoglobin levels of both groups were slightly decreased at the 2-week post-ESD follow-up laboratory test
Surg Endosc Table 2 The clinicopathologic characteristics of the study population
Variable
All patients (N = 120)
Early diet group (N = 63)
Control group (N = 57)
Age, years [mean ± SD (range)]
61.8 ± 9.4 (33–86)
62.5 ± 8.8 (36–80)
61.1 ± 10.1 (33–86)
Male
86 (71.7 %)
44 (69.8 %)
42 (73.7 %)
Female
34 (28.3 %)
19 (30.2 %)
15 (26.3 %)
Gender
p value 0.434 0.641
Comorbidity DM
18 (15.0 %)
11 (17.5 %)
7 (12.3 %)
0.427
Hypertension Cardiac disease
7 (5.8 %) 7 (5.8 %)
20 (31.7 %) 5 (7.9 %)
18 (31.6 %) 2 (3.5 %)
0.984 0.301
Renal disease
7 (5.8 %)
0 (0 %)
2 (3.5 %)
0.134
10 (8.3 %)
4 (6.3 %)
6 (10.5 %)
Location of lesion Upper
0.733
Middle
29 (24.2 %)
16 (25.4 %)
13 (22.8 %)
Lower
81 (67.5 %)
43 (68.3 %)
38 (66.7 %)
Single
99
52
47
Synchronous
21
11
10
Ulcer present
18 (15.0 %)
8 (12.7 %)
10 (17.5 %)
0.458
Pathologic lesion size of ESD, mm Specimen size of ESD, mm
14.0 ± 11.2
13.1 ± 10.3
15.0 ± 12.1
0.348
42.7 ± 17.7
43.5 ± 19.3
42.0 ± 15.8
0.641
46 (38.3 %)
26 (41.3 %)
20 (35.1 %)
Multiplicity of lesion
0.867
Pathologic findings Low-grade dysplasia
0.446
High-grade dysplasia
17 (14.2 %)
10 (15.9 %)
7 (12.3 %)
Differentiated cancer
52 (43.3 %)
26 (41.3 %)
26 (45.6 %)
Undifferentiated cancer
5 (4.2 %)
1 (1.6 %)
4 (7.0 %)
120 (100 %)
63 (100 %)
57 (100 %)
[0.999
En bloc resection Curability Complete resection
113 (94.3 %)
59 (93.7 %)
54 (94.7 %)
[0.999
Incomplete resection
7 (5.7 %)
4 (6.3 %)
4 (5.3 %)
[0.999
Lateral margin, positive
4 (3.3 %)
2 (3.2 %)
2 (3.5 %)
0.919
Basal margin, positive
3 (2.5 %)
2 (3.2 %)
1 (1.8 %)
0.619
Margin involvement
Procedure time (min) Data are presented as n (%) or mean ± SD (range)
Dissection time
48.8 ± 34.3 (8–160)
45.4 ± 30.6 (8–140)
54.2 ± 40.5 (11–160)
0.179
ESD endoscopic submucosal dissection, DM diabetes mellitus, SD standard deviation
Total procedure time
57.1 ± 37.9 (10–200)
52.9 ± 32.9 (10–154)
61.8 ± 42.0 (13–200)
0.200
compared with that of the day of ESD. The mean decrease in hemoglobin level was 0.58 ± 0.96 g/dL in the early diet group and 0.47 ± 0.69 g/dL in the control group (p = 0.494). The decrement of follow-up hemoglobin level did not show statistical significance. Second-look EGD was performed in 109 patients among the enrolled 120 patients, as 11 patients refused. There were no significant differences in ulcer stage, the presence of bleeding stigmata, the need for prophylactic hemostasis, or post-ESD ulcer size. Follow-up EGD after 2 months was performed in 104 patients, and 16 patients refused EGD follow-up. There were also no
significant differences in ulcer stage, presence of bleeding stigmata, or post-ESD ulcer size (Table 3). Early post-ESD bleeding did not occur in either group, while delayed bleeding occurred in 5 of 120 patients (4.17 %). There were no significant differences in delayed bleeding rates between the early diet group and control group (Table 3; 4.8 vs. 3.5 %). The first and last bleeding case occurred on the 8th (control group) and 55th (control group) day after ESD treatment, respectively. All five cases of delayed ESD bleeding were controlled by endoscopic hemostasis such as electrocoagulation, epinephrine–hypertonic saline mixture
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Surg Endosc Table 3 Analysis of initial and follow-up hemoglobin levels, findings of follow-up EGD and bleeding complications between early diet and control group Variable
Early diet group
Control group
p value
Hemoglobin (g/dL) Admission
13.7 ± 1.3
13.7 ± 1.5
0.921
F/U after 2 weeks Gap (F/U–admission)
13.3 ± 1.6 0.58 ± 0.96
13.4 ± 1.5 0.47 ± 0.69
0.708 0.494
Second-look EGD Ulcer stage
0.693
A1
38 (64.4 %)
34 (68.0 %)
A2
21 (35.6 %)
16 (32.0 %)
Stigmata
0.161
Present
14 (23.7 %)
18 (36.0 %)
Absent
45 (76.3 %)
32 (64.0 %)
Prophylactic hemostasis Present Absent Mean ulcer size, mm
0.41 13 (22.0 %)
10 (20.0 %)
46 (78.0 %)
40 (80.0 %)
Maximal length
53.6 ± 20.8
56.0 ± 23.4
0.577
Minimal length
43.0 ± 18.7
46.0 ± 18.9
0.396
Follow-up EGD after 2 months Ulcer stage
0.862
A2
0 (0 %)
H1
1 (2.0 %)
1 (1.9 %)
H2
14 (27.5 %)
16 (30.2 %)
S1
33 (64.7 %)
33 (62.3 %)
S2
3 (5.9 %)
2 (3.8 %)
Stigmata Present Absent
1 (1.9 %)
0.324 0 (0 %)
1 (1.9 %)
51 (100 %)
52 (98.1 %)
13.6 ± 8.3
13.3 ± 7.0
0.810
Early bleeding
0 (0 %)
0 (0 %)
NS
Delayed bleeding
3 (4.8 %)
2 (3.5 %)
0.732
Ulcer size, mm Post-ESD bleeding
Data are presented as n (%) or mean ± SD EGD esophagogastroduodenoscopy, ESD endoscopic submucosal dissection, F/U follow-up
injection or hemoclipping. Blood transfusion was not required for any of the five patients. Abdominal pain and overall satisfaction for ESD treatment The abdominal pain and overall satisfaction scores during hospitalization for ESD are summarized in Fig. 2. The abdominal pain score of the early diet group and control group at the time of admission was increased after ESD
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treatment. However, there were no significant differences in the increment of abdominal pain score before and after ESD between the two groups. The early diet group reported significantly higher patient satisfaction compared with the control group (5.0 vs. 4.1, p = 0.001). The duration of hospitalization and medical expenses for ESD treatment Medical expenses and length of hospital stay were analyzed between the two groups among 116 patients, excluding four patients who were transferred to other departments for their other problems. The discharge of several patients in both groups was delayed for 1 or 2 days by mild fever, abdominal discomfort, or general weakness. The early diet group had a significantly shorter hospital stay (4.3 vs. 5.2 days, p \ 0.001) and lower total hospital expenses (US$2,554.4 vs. US$2,939.8, p \ 0.001) compared with the control group (Table 4).
Discussion This prospective randomized controlled study demonstrates that early diet protocol after ESD for gastric epithelial neoplasia increased the satisfaction of patients without affecting complication rates, including post-ESD bleeding, the healing rate of post-ESD ulcers, and abdominal pain, compared with a conventional fasting protocol. Furthermore, an early diet protocol can decrease the expense and period of hospitalization compared with a conventional fasting protocol. To the best of our knowledge, this study is the first to evaluate the clinical impact of early post-ESD diet protocol on patient comfort and satisfaction. It was found to minimize length of hospitalization, which decreased medical expenses. The endoscopic technique for EGC has been further developed since the first EMR technique was reported in 1984 [8]. ESD is a widely used therapeutic procedure that preserves the stomach and allows for en bloc resection [9–13]. Thus, ESD is now widely accepted as the optimal endoscopic treatment for early gastric neoplasias, especially in Asian countries where the incidence of gastric neoplasias is high [3]. Nevertheless, the optimal timing to start oral feeding after ESD has not yet been established. Patients are typically fasted for 24 h after the procedure, followed by a clear liquid diet on the second day, and a soft diet on day 3, which may continue for another 3 days [3, 4]. However, these diet strategies are not based on concrete evidence, but rather rely solely on experience. Several studies have examined the issue of early oral feeding and early enteral nutrition in the gastrointestinal surgical field. In gastrointestinal surgery, 2–5 days of fasting
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Fig. 2 A Diagram of the abdominal pain scale of both groups before and after ESD treatment. Admission, p = 0.625; 48 h post-ESD, p = 0.187; increment, p = 0.295. B Overall satisfaction score of both
groups after ESD, p = 0.001. Data are expressed as mean ± SD. ESD endoscopic submucosal dissection
Table 4 Analysis of hospitalization period, total medical expenses and patient-medical expenses between early diet and control group
there have been no studies concerning diet strategies in the field of therapeutic endoscopy, unlike in the field of surgery. To maximize these advantages of ESD treatment over gastric surgery, the present study demonstrated that an early postESD diet protocol could result in patients’ earlier tolerance of oral intake, resulting in more comfortable nourishment, shorter hospitalization, and lower healthcare costs. Earlier toleration of oral intake might reduce the use of parenteral nutrition, and moreover, oral intake could enable patients to be nourished more effectively and discharged earlier, thus leading to a decrease in medical costs for ESD treatment. A significant reduction in medical expenses might stem from not only a decrease in hospitalized days, but also reduced use of parenteral nutrition, creating a virtuous circle. The early diet protocol may have some safety concerns, especially for post-ESD bleeding, delayed ulcer healing rate, and abdominal pain. Our results demonstrate that an early diet strategy after ESD did not worsen abdominal pain, and did not affect post-ESD bleeding rates or delay the healing rate of ESD-induced artificial ulcers. In our study, it was assumed that many of the patients might have had baseline abdominal discomfort or pain before the ESD procedure, because upper endoscopy might have been performed in search of the cause of their gastrointestinal problems, except in the case of healthy screenees. Therefore, it is appropriate to compare not only abdominal pain, but also the increment of abdominal pain after ESD, even if abdominal pain was mild or absent before the procedure. Post-ESD abdominal pain is probably caused by ulcer defects or electrical thermal burns inflicted during dissection or coagulation, from the submucosal layer to the serosa [24].
Early diet group (N = 61) Hospitalization period (days)
4.3 ± 0.6
Total medical expenses (US$)
2,554.4 ± 374.7
Control group (N = 55)
p value
5.2 ± 1.1
\0.001
2,939.8 ± 497.2 \0.001
has been thought necessary due to postoperative atonic bowel [14]. However, recent reports have supported the view that early oral feeding after gastric cancer surgery is safe, with no evidence of increased morbidity, and could result in a faster recovery of bowel function and a shorter hospitalization [15, 16]. Several studies have also reported that strategies for pain relief, stress reduction, early mobilization, and early oral feeding lead to faster recovery or reduced hospital stay in colon surgery [17, 18]. Experimental data has shown that immediate postoperative enteral nutrition improves wound healing related to the integrity of intestinal anastomosis, muscle function, insulin resistance, and moreover, reduces sepsis [19]. In addition, early enteral nutritional support may more effectively activate normal digestive reflexes, which play a crucial role in intestinal recovery after gastrointestinal surgery, than a strategy of bowel rest and intravenous nutrition [20]. Early oral feeding compared with parenteral nutrition might have both nutritional and immunological merits thanks to improved protein kinetics and preservation of the immune system, leading to improved wound healing and resistance to infection [21–23]. ESD is less invasive and requires a shorter hospital stay and lower medical expenses than surgical treatment. However,
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In addition, post-ESD abdominal discomfort and intolerance to oral diet can be caused by post-procedural transient gastric ileus. In the case of gastrointestinal surgery, postoperative ileus arises from multifactorial causes, including surgical trauma, local inflammatory reactions, anesthetic agents, hyperactivity of the sympathetic nervous system, and opioid use in the postoperative period [25]. In particular, postoperative gastric ileus typically improves within 24–48 h, while peristalsis in the colon may not return until 72 h after surgery [25]. ESD treatment for gastric epithelial neoplasia may also be accompanied by gastric mucosal trauma, local inflammatory reactions, sedative administration, and hyperactivity of the sympathetic nervous system, but opioids are not used during the procedure. The ESD procedure is generally shorter in duration than gastrointestinal surgery and the mucosal trauma, local tissue reaction, and the amount of sedatives used are minimal compared with those of gastric surgery. This supports the conclusion that ESD treatment might not require as long a fasting period during postoperative care. In terms of gastric ulcer, early feeding has been investigated in several studies. In one study by Khoshbaten et al. [26], there was no significant difference between the early diet group (oral diet from day 1) and the control group (nil by mouth for 3 days) according to the re-bleeding rate and the need for blood transfusion; therefore, early oral feeding was thought to enable earlier discharge and decrease treatment costs. In another two studies by de Ledinghen et al. [27, 28], there were no significant associations between re-bleeding and early oral feeding. These results are in agreement with those of our study, which established that ESD-induced artificial ulcers neither bled more frequently nor healed at a slower rate in the early diet group. There are several limitations to the present study. First, this was a single-center study with a small study population. Second, all ESD procedures were performed by a single experienced endoscopist. Even with these limitations, this is the first evidence to support the adoption of an early oral diet protocol for ESD of gastric epithelial neoplasias. Another randomized control study will be necessary in the future to reliably evaluate the safety and effectiveness of the diet protocol with a larger, multicenter study population. In conclusion, an early post-ESD diet protocol provides higher patient satisfaction, is more cost effective, decreases hospital stay, and does not influence complication rates such as post-ESD bleeding, abdominal pain, or ulcer healing compared with the conventional fasting protocol. Our study supports the recommendation that a long period of post-ESD fasting might not be necessary. Disclosures Drs. Sunyong Kim, Kyung Seok Cheoi, Hyun Jik Lee, Choong Nam Shim, Hyun Soo Chung, Hyuk Lee, Sung Kwan Shin,
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Sang Kil Lee, Yong Chan Lee, and Jun Chul Park have no conflicts of interest or financial ties to disclose.
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