Omeprazole-cisapride combination for gastroparesis following radical gastrectomy for gastric cancer: An efficacy and safety analysis

Abstract

BACKGROUND

The management of gastroparesis (GP) following radical gastrectomy (RGE) for gastric cancer (GC) remains challenging, and treatment optimization is needed because current therapeutic approaches have limited efficacy.

AIM

To investigate the clinical efficacy and safety of omeprazole (OME) combined with cisapride (CIS) in the treatment of GP after RGE in patients with GC.

METHODS

A total of 198 patients with post-RGE GP were retrospectively enrolled from September 2020 to September 2025. Patients were grouped according to treatment regimen: 92 patients receiving OME constituted the control group, and 106 patients receiving OME plus CIS comprised the research group. Outcomes included clinical efficacy, symptom improvement assessed using the GP Cardinal Symptom Index, gastrointestinal function recovery (time to bowel sound recovery, nasogastric tube removal, and resumption of a normal diet), gastrointestinal hormone levels (gastrin and motilin), and safety (diarrhea, abdominal pain, headache/dizziness, palpitations, and nausea). Factors influencing treatment efficacy were subsequently evaluated.

RESULTS

The research group showed a significantly higher total effective rate than the control group. Following treatment, GP Cardinal Symptom Index scores across all domains were lower, the time to bowel sound recovery, nasogastric tube removal, and normal diet resumption was shorter, and gastrin and motilin levels were higher in patients receiving the combination therapy. The incidence of total adverse reactions was comparable between the two groups. Tumor-node-metastasis staging, baseline motilin level, and treatment regimen were independent factors affecting treatment efficacy.

CONCLUSION

OME combined with CIS is effective for treating GP after RGE for GC without increasing the overall incidence of adverse reactions. Additionally, stage IIB-III disease, baseline motilin < 309 mg/L, and treatment with OME alone are associated with an increased risk of treatment inefficacy.

Key Words: Omeprazole; Cisapride; Radical gastrectomy; Gastroparesis; Effect; Safety

Core Tip: This retrospective study evaluated the clinical efficacy and safety of omeprazole (OME) combined with cisapride in patients with gastroparesis following radical gastrectomy for gastric cancer. The combination regimen was more effective than OME alone without increasing the overall incidence of adverse reactions. It also demonstrated clinical advantages in promoting symptom relief, accelerating gastrointestinal function recovery, and actively regulating gastrointestinal hormones. Patients with stage IIB-III disease, baseline motilin < 309 mg/L, and treatment with OME alone were at increased risk of treatment inefficacy.

INTRODUCTION

Gastric cancer (GC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related mortality, with a higher incidence in males than females[1]. In 2020 alone, more than one million new GC cases and approximately 770000 GC-related deaths were reported globally[2]. Given that GC directly affects the gastrointestinal (GI) system, surgical resection remains the primary treatment modality[3]. Radical gastrectomy (RGE), a commonly performed surgical procedure for GC, can impose substantial physiologically stress, suppress systemic immune function, and induce intestinal mucosal ischemia and hypoxia, thereby increasing the risk of postoperative complications[4]. Gastroparesis (GP), a common and clinically challenging complication post-RGE, is characterized by non-mechanical delayed gastric emptying[5]. Factors such as advanced age, smoking history, pylorochesis, Roux-en-Y anastomosis, and intraoperative blood transfusion have been associated with an increased risk of post-RGE GP[6,7]. Current treatment options for GP include pharmacotherapy, diet modification, botulinum toxin injection, gastric electrical stimulation combined with pyloroplasty, and peroral endoscopic myotomy; however, their therapeutic efficacy remains insufficient[8]. Therefore, optimizing treatment strategies to improves outcomes in patients with GP following RGE for GC remains clinically necessary.

Omeprazole (OME), a proton pump inhibitor, has a rapid onset of action, good antioxidant properties, and strong acid-suppressive activity, with established safety and tolerability in acid-related digestive disorders[9]. It has also been used in patients with proton pump inhibitor-resistant non-erosive reflux disease, where it can ameliorate gastroesophageal reflux and delayed gastric emptying[10]. Additionally, OME has demonstrated benefits in promoting GI digestive function in patients with functional dyspepsia[11]. Cisapride (CIS), a gastroprokinetic agent, effectively improves gastric emptying in patients with diabetic GP while maintaining acceptable overall safety[12]. In a retrospective study of pediatric patients with intestinal failure who did not respond to first-line prokinetic therapy, CIS significantly improved enteral nutrition progression within three months, increasing the enteral nutrition progression rate from 0.14% to 0.69% per day and the enteral nutrition percentage from 23.9% to 79.4%[13]. Given the limited evidence regarding efficacy and safety of the OME-CIS combination in patients with GP post-RGE, this study aimed to evaluate the clinical benefits of this combination therapy and provide evidence for optimizing treatment in this patient population.

MATERIALS AND METHODS

Case selection

Inclusion criteria were as follows: GC confirmed via postoperative pathology[14]; treatment with RGE followed by the development of postoperative GP[15]; age 18-80 years; absence of postoperative acid-base imbalance or electrolyte disorders based on blood gas and biochemical testing; no history of mental illness; and complete medical records. Exclusion criteria included the following: Severe diabetes mellitus or mechanical intestinal obstruction; concomitant malignancies, acute or chronic infectious diseases, or severe disease of vital organs (e.g., liver or kidneys); neurological disorders such as epilepsy; allergy to study medications; use of opioids, calcium channel blockers, or anticholinergic drugs in the previous three months; poor compliance; or inability to follow medical instructions and cooperate with treatment. A retrospective analysis was conducted on 198 eligible patients with post-RGE GP treated at our center from September 2020 to September 2025. Among them, 92 patients receiving OME alone were assigned to the control group, whereas 106 patients receiving OME plus CIS were assigned to the research group. Baseline characteristics were comparable between the groups, with no statistically significant differences observed (P > 0.05).

Intervening methods

The controls received OME enteric-coated capsules orally at a dose of 20 mg once daily. In addition to the same OME regimen, patients in the research group received CIS tablets orally at 10 mg three times daily. Both groups completed a 21-day treatment course.

Data collection and outcome measures

Clinical efficacy: Clinical efficacy was assessed after 21 days of treatment. Cure was defined as complete resolution of related symptoms (nausea, vomiting, upper abdominal distension, persistent hiccups, and loss of appetite), anal gas passage within 24 hours, gastric juice volume during GI decompression < 50 mL, bowel sounds occurring 3-5 times/minute, and once daily defecation. Marked effectiveness was defined as significant symptom relief, anal gas passage within 48 hours, gastric juice volume during GI decompression < 250 mL, bowel sounds occurring 1-2 times/minute, and either once daily or irregular defecation. Effectiveness was defined as partial symptom improvement, anal gas passage within 72 hours, gastric juice volume during GI decompression < 500 mL, bowel sounds occurring 0-2 times/minute, and defecation that was once daily, irregular, or absent. Ineffectiveness was defined as unchanged or worsened symptoms, no anal gas passage or defecation for > 72 hours, and gastric juice volume during GI decompression > 500 mL. The total effective rate was calculated as the proportion of patients classified as cured, markedly effective, or effective[16].

Symptom improvement: Before treatment and after 21 days of treatment, patients completed the simplified GP Cardinal Symptom Index (GCSI) to assess symptom severity[17]. Evaluated domains included nausea and vomiting, abdominal distension, inability to eat a normal amount of food, inappetence, and severe postprandial fullness. Symptoms were self-rated using a 6-point Likert scale ranging from 0 to 5, in which 0 indicated asymptomatic, 1 indicated very mild, 2 indicated mild, 3 indicated moderate, 4 indicated severe, and 5 indicated very severe symptoms.

GI function recovery: The time to bowel sound recovery, nasogastric tube removal, and resumption of a normal diet during treatment was recorded.

GI function indices: Before treatment and after 21 days of treatment, fasting venous blood samples (5 mL) were collected. Serum was isolated via centrifugation and cryopreserved for analysis. Serum gastrin and motilin levels were quantified using radioimmunoassay.

Safety: Adverse events occurring during treatment, including diarrhea, abdominal pain, headache/dizziness, palpitations, and nausea, were recorded, and the incidence rate was calculated.

Statistical analysis

The normality of continuous variables was assessed using the Shapiro-Wilk test. Normally distributed data are presented as mean ± SD and were analyzed using the independent samples t-test for between-group comparisons and the paired t-test for within-group pre- vs post-intervention comparisons. Non-normally distributed data are presented as median (interquartile range) and were analyzed using the Mann-Whitney U test for between-group comparisons and the Wilcoxon signed-rank test for within-group comparisons. Categorical variables are presented as n (%) and were compared using the χ² test. Factors influencing treatment efficacy were evaluated using univariate analysis followed by multivariable binary logistic regression. Statistical analyses were performed using SPSS 24.0, and P < 0.05 was considered statistically significant.

RESULTS

General patient information

As presented in Table 1, no significant differences were observed between the two groups regarding sex, age, body mass index, anesthesia mode, surgical technique, tumor-node-metastasis (TNM) stage, or surgical duration (P > 0.05), indicating good baseline comparability.

Table 1 General patient information, n (%)/mean ± SD.

Data	Control group (n = 92)	Research group (n = 106)	χ2/t	P value
Sex			0.604	0.437
Male	47 (51.09)	60 (56.60)
Female	45 (48.91)	46 (43.40)
Age (years)	55.86 ± 6.22	56.60 ± 8.42	0.694	0.488
Body mass index (kg/m2)	22.90 ± 2.29	22.79 ± 2.38	0.330	0.742
Mode of anesthesia			2.214	0.137
General anesthesia	38 (41.30)	55 (51.89)
Epidural anesthesia	54 (58.70)	51 (48.11)
Surgical technique			1.409	0.494
Gastroduodenostomy	36 (39.13)	42 (39.62)
Gastrojejunostomy	27 (29.35)	24 (22.64)
Roux-en-Y anastomosis	29 (31.52)	40 (37.74)
TNM staging			1.164	0.281
I-IIA	28 (30.43)	40 (37.74)
IIB-III	64 (69.57)	66 (62.26)
Surgical duration (hours)			1.901	0.168
< 4	37 (40.22)	53 (50.00)
≥ 4	55 (59.78)	53 (50.00)

TNM: Tumor-node-metastasis.

Clinical efficacy comparison

As shown in Table 2, the numbers of markedly effective, effective, and ineffective cases in the control group were 36, 32, and 24, respectively, compared with 55, 40, and 11 in the research group. The total effective rate was significantly higher in the research group than in the control group (89.62% vs 73.91%; P = 0.004).

Table 2 Clinical efficacy comparison, n (%).

Efficacy	Control group (n = 92)	Research group (n = 106)	χ2	P value
Marked effectiveness	36 (39.13)	55 (51.89)
Effectiveness	32 (34.78)	40 (37.74)
Ineffectiveness	24 (26.09)	11 (10.38)
Overall effectiveness	68 (73.91)	95 (89.62)	8.353	0.004

Symptom improvement across groups

As presented in Table 3, baseline GCSI scores were comparable between the two groups across all domains (P > 0.05). Following treatment, GCSI scores decreased to varying degrees in both groups. However, post-treatment scores for all GCSI domains were significantly lower in the research group than in the control group (P < 0.05).

Table 3 Symptom improvement across groups, median (interquartile range).

GCSI	Control group (n = 92)	Research group (n = 106)	Z	P value
Nausea and vomiting (points)
Before intervention	2.00 (1.00, 3.00)	2.00 (1.00, 4.00)	-1.405	0.160
After intervention	2.00 (1.00, 2.00)	1.00 (1.00, 2.00)	-3.868	< 0.001
Stomach distension (points)
Before intervention	2.00 (1.00, 3.00)	2.00 (1.75, 3.00)	-0.538	0.591
After intervention	1.00 (1.00, 2.00)	1.00 (0.00, 1.00)	-5.929	< 0.001
Inability to eat a normal amount of food (points)
Before intervention	3.00 (2.00, 4.00)	3.00 (2.00, 4.00)	-1.257	0.209
After intervention	3.00 (2.00, 3.75)	2.00 (1.75, 3.00)	-2.096	0.036
Inappetence (points)
Before intervention	2.00 (2.00, 3.00)	2.00 (2.00, 3.00)	-0.172	0.863
After intervention	1.00 (1.00, 2.00)	1.00 (1.00, 2.00)	-2.192	0.028
Severe postprandial fullness (points)
Before intervention	2.00 (1.00, 2.00)	2.00 (2.00, 2.00)	-1.533	0.125
After intervention	1.00 (1.00, 2.00)	1.00 (0.75, 1.00)	-3.761	< 0.001

GCSI: Gastroparesis Cardinal Symptom Index.

Time to GI function recovery in two groups

As shown in Figure 1, the time to bowel sound recovery was 7.85 ± 2.80 days in the control group and 5.94 ± 2.06 days in the research group. The time to nasogastric tube removal was 10.14 ± 3.68 days and 7.68 ± 3.00 days, respectively, whereas the time to resumption of a normal diet was 13.52 ± 3.98 days and 10.21 ± 2.95 days, respectively. These findings indicate that patients in the research group experienced significantly faster bowel sound recovery, earlier accelerated nasogastric tube removal, and quicker return to a normal diet than controls (P < 0.01).

Figure 1 Recovery time of gastrointestinal function. A: Comparison of the time to bowel sound recovery between control and research groups; B: Inter-group comparison of nasogastric tube removal time; C: Inter-group comparison of normal diet resumption time. ^bP < 0.01 vs control group.

GI function indices

As shown in Figure 2, baseline gastrin levels were 89.93 ± 10.26 ng/L in the control group and 86.93 ± 12.71 ng/L in the research group, increasing to 99.49 ± 11.68 ng/L and 116.72 ± 14.81 ng/L, respectively, after treatment. Baseline motilin levels were 312.76 ± 37.24 mg/L in the control group and 307.42 ± 34.23 mg/L in the research group, increasing to 429.24 ± 46.99 mg/L and 501.16 ± 55.45 mg/L, respectively, after treatment. No significant between-group differences were observed in baseline gastrin or motilin levels (P > 0.05). Both indices increased significantly after treatment in each group (P < 0.05), with significantly greater increases observed in the research group (P < 0.05).

Figure 2 Gastrointestinal function indexes of the two groups. A: Comparative gastrin assessment; B: Comparative motilin evaluation. ^aP < 0.05, ^bP < 0.01 vs the pre-interventional level within the group, ^cP < 0.05 vs control group at the identical time point.

Safety profile comparison

As summarized in Table 4, no significant difference was identified between the two groups in the overall incidence of adverse reactions, including diarrhea, abdominal pain, headache/dizziness, palpitations, and nausea (P > 0.05).

Table 4 Safety of two groups, n (%).

Adverse reactions	Control group (n = 92)	Research group (n = 106)	χ2	P value
Diarrhea	1 (1.09)	4 (3.77)
Abdominal pain	2 (2.17)	2 (1.89)
Headache/dizziness	3 (3.26)	4 (3.77)
Palpitations	1 (1.09)	3 (2.83)
Nausea	3 (3.26)	2 (1.89)
Total	10 (10.87)	15 (14.15)	0.481	0.488

Analysis of factors influencing treatment efficacy

Univariate analysis (Table 5) revealed that age, TNM stage, surgical duration, baseline gastrin level, baseline motilin level, and treatment regimen were significantly associated with treatment efficacy (P < 0.05). No significant associations were observed for the remaining variables (P > 0.05).

Table 5 Univariate analysis, n (%).

Data	Ineffective group (n = 35)	Effective group (n = 163)	χ2	P value
Sex			0.117	0.733
Male (n = 107)	18 (51.43)	89 (54.60)
Female (n = 91)	17 (48.57)	74 (45.40)
Age (years)			4.888	0.027
< 56 (n = 90)	10 (28.57)	80 (49.08)
≥ 56 (n = 108)	25 (71.43)	83 (50.92)
Body mass index (kg/m2)			0.075	0.784
< 23 (n = 89)	15 (42.86)	74 (45.40)
≥ 23 (n = 109)	20 (57.14)	89 (54.60)
Anesthesia mode			0.027	0.870
General anesthesia (n = 93)	16 (45.71)	77 (47.24)
Epidural anesthesia (n = 105)	19 (54.29)	86 (52.76)
Surgical modality			1.720	0.423
Gastroduodenostomy (n = 78)	16 (45.71)	62 (38.04)
Gastrojejunostomy (n = 51)	6 (17.14)	45 (27.61)
Roux-en-Y anastomosis (n = 69)	13 (37.14)	56 (34.36)
TNM staging			7.586	0.006
I-IIA (n = 68)	5 (14.29)	63 (38.65)
IIB-III (n = 130)	30 (85.71)	100 (61.35)
Surgical duration (hours)			4.888	0.027
< 4 (n = 90)	10 (28.57)	80 (49.08)
≥ 4 (n = 108)	25 (71.43)	83 (50.92)
Baseline nausea and vomiting (points)			0.090	0.764
< 2 (n = 55)	9 (25.71)	46 (28.22)
≥ 2 (n = 143)	26 (74.29)	117 (71.78)
Baseline stomach distension (points)			1.282	0.258
< 2 (n = 55)	7 (20.00)	48 (29.45)
≥ 2 (n = 143)	28 (80.00)	115 (70.55)
Baseline inability to eat a normal amount of food (points)			0.011	0.916
< 3 (n = 72)	13 (37.14)	59 (36.20)
≥ 3 (n = 126)	22 (62.86)	104 (63.80)
Baseline inappetence (points)			1.601	0.206
< 2 (n = 46)	11 (31.43)	35 (21.47)
≥ 2 (n = 152)	24 (68.57)	128 (78.53)
Baseline severe postprandial fullness (points)			0.024	0.877
< 2 (n = 53)	9 (25.71)	44 (26.99)
≥ 2 (n = 145)	26 (74.29)	119 (73.01)
Baseline gastrin (ng/L)			5.357	0.021
< 88 (n = 95)	23 (65.71)	72 (44.17)
≥ 88 (n = 103)	12 (34.29)	91 (55.83)
Baseline motilin (mg/L)			10.886	0.001
< 309 (n = 97)	26 (74.29)	71 (43.56)
≥ 309 (n = 101)	9 (25.71)	92 (56.44)
Therapeutic regimen			8.353	0.004
Omeprazole (n = 92)	24 (68.57)	68 (41.72)
Omeprazole + cisapride (n = 106)	11 (31.43)	95 (58.28)

TNM: Tumor-node-metastasis.

Further multivariate analysis (Table 6) showed that TNM stage, baseline motilin level, and treatment regimen were independent predictors of treatment ineffectiveness. Specifically, compared with stage I-IIA disease, stage IIB-III disease was associated an approximately 3.9-fold higher risk of ineffective treatment. A baseline motilin level ≥ 309 mg/L was associated with an approximately 74.7% lower risk of treatment failure than a baseline motilin level < 309 mg/L. Additionally, OME-CIS combination therapy reduced the risk of treatment ineffectiveness risk by approximately 69.0% compared with OME monotherapy.

Table 6 Multivariate analysis.

Variable	β	SE	Wald	P value	OR	95%CI
Age (years)	0.716	0.446	2.573	0.109	2.046	0.853-4.909
TNM staging	1.367	0.545	6.292	0.012	3.922	1.348-11.408
Surgical duration (hours)	0.747	0.451	2.741	0.098	2.110	0.872-5.106
Baseline gastrin (ng/L)	-0.796	0.433	3.385	0.066	0.451	0.193-1.053
Baseline motilin (mg/L)	-1.374	0.456	9.063	0.003	0.253	0.104-0.619
Therapeutic regimen	-1.172	0.449	6.801	0.009	0.310	0.128-0.747

OR: Odds ratio; CI: Confidence interval; TNM: Tumor-node-metastasis.

DISCUSSION

GP is a common manifestation of GI motility disorders, primarily characterized by symptoms such as nausea, vomiting, abdominal distension, early satiety, postprandial fullness, and epigastric discomfort or pain[18]. As a common post-RGE complication, GP can significantly delay postoperative recovery, highlighting the importance of timely and effective intervention to facilitate patient rehabilitation[19].

In this study, OME combined with CIS demonstrated superior overall efficacy in patients with post-RGE GP, suggesting that the combination regimen is more effective in alleviating clinical symptoms and promoting GI function recovery. OME, a weakly alkaline proton pump inhibitor, accumulates selectively within the acidic secretory tubules of gastric parietal cells, where it becomes protonated and irreversibly binds to H⁺/K⁺-ATPase, thereby inhibiting gastric acid secretion, improving the intragastric environment, enhancing gastric mobility, and alleviating postoperative GP[20,21]. CIS selectively promotes acetylcholine release from myenteric postganglionic fibers, enhances GI cholinergic neurotransmission, coordinates GI peristalsis, accelerates gastric emptying, and reduces food retention and reflux[22]. The superior efficacy of the combination therapy may therefore result from the complementary mechanisms of the two drugs, which act synergistically through different pathways. The combination regimen also yielded greater improvements in GP-related symptoms, as reflected by significantly lower GCSI scores across all evaluated domains. This benefit may be attributable to OME-mediated inhibition of gastric acid secretion, which reduces gastric mucosal irritation and relieves symptoms such as nausea and vomiting. Meanwhile, CIS promotes gastric emptying by enhancing coordinated antroduodenal propulsive activity, thereby improving postprandial fullness, early satiety, and abdominal bloating. Through the combined effects of gastric acid suppression and enhanced GI motility, OME plus CIS may provide more comprehensive symptom relief than OME alone.

Regarding GI functional recovery, OME plus CIS significantly shortened the time to bowel sound recovery, nasogastric tube removal, and resumption of a normal diet. CIS promotes acetylcholine release from the myenteric plexus, enhancing the contractility and coordination of GI smooth muscles and accelerating recovery of GI peristalsis, which may contribute to earlier restoration of bowel sounds. Its prokinetic activity may also complement the effects of OME, facilitating gastric emptying function, thereby significantly shortening the time for gastric tube removal and resumption of normal eating. Further evaluation of GI function indices showed significant increases in gastrin and motilin levels following the combination therapy. This finding may be related to CIS-mediated enhancement of GI motility and neural reflexes, which can stimulate antral G-cell secretion of gastrin and potentially promote motilin release from enterochromaffin cells, thereby supporting GI functional recovery. The marked increases in gastrin and motilin levels observed after OME-CIS intervention may therefore partly explain its beneficial effects on GI functional recovery. Safety evaluation revealed no statistically significant difference in the overall incidence of adverse reactions, including diarrhea, abdominal pain, headache/dizziness, palpitations, and nausea, between the OME-CIS and OME-only groups. This may be because the two drugs do not introduce additional toxicological pathways or clinically significant drug-drug interactions when used together. Their mechanisms of action differ significantly, with CIS-induced adverse reactions primarily attributed to its prokinetic activity and OME acting mainly through the inhibition of gastric acid secretion; therefore, no synergistic amplification of toxicity would be expected[23,24]. Furthermore, OME exerts only weak inhibition of CYP3A4 compared with agents such as ketoconazole and is insufficient to increase CIS plasma concentrations to toxic levels[25]. Analysis of factors associated with treatment efficacy identified TNM stage, baseline motilin level, and treatment regimen as independent predictors of treatment inefficacy. Specifically, stage IIB-III, baseline motilin < 309 mg/L, and OME monotherapy were associated with an increased risk of treatment inefficacy. Patients with stage IIB-III disease often undergo more extensive surgical procedures and experience greater damage to the vagus nerve and gastric anatomy, which may hinder recovery of gastric motility. Similarly, baseline motilin < 309 mg/L suggests impaired endogenous GI motility, limiting the therapeutic response. Although OME effectively suppresses gastric acid secretion, it does not alleviate motility disorders, which may explain the increased risk of treatment inefficacy associated with monotherapy. Collectively, these findings suggest that OME combined with CIS may be particularly advantageous for high-risk patients with stage IIB-III disease and baseline motilin < 309 mg/L.

Several previous studies have also explored strategies for optimizing GP management. For example, Jing et al[26] reported that perioperative administration of omega-3 (ω-3) polyunsaturated fatty acid fish oil emulsion in patients with GC undergoing Roux-en-Y reconstruction effectively reduced GP risk and improved surgical outcomes. Qin and Xie[27] found that nutritional support combined with comprehensive nursing significantly enhanced GI function, accelerated symptom relief, and regulated GI hormone levels in patients with GP. Additionally, Yin and Chen[28] suggested that noninvasive electrical neuromodulation, including transcutaneous and percutaneous auricular vagal nerve stimulation, provides certain clinical benefits and acceptable safety in patients with drug-refractory GP, ameliorating GI symptoms and dyskinesia.

Several limitations of this study should be acknowledged. First, as a retrospective study, treatment allocation was not randomized, and the influence of unknown or unmeasured confounding factors cannot be excluded. Prospective controlled studies are needed to further validate the findings and improve their generalizability. Second, the absence of mechanistic investigations limits understanding the observed therapeutic effects; future experimental studies are warranted to clarify the underlying mechanisms of OME-CIS therapy. Finally, long-term follow-up data were unavailable. Future studies incorporating follow-up periods of up to three years may help clarify the long-term efficacy and prognostic implications of combination therapy.

CONCLUSION

In summary, OME combined with CIS demonstrates definite therapeutic efficacy in patients with post-RGE GP. Compared with OME alone, the combination therapy further improves overall effectiveness, relieves clinical symptoms, accelerates GI functional recovery, and regulates GI hormone levels without significantly increasing the incidence of adverse reactions. Additionally, stage IIB-III disease, baseline motilin < 309 mg/L, and OME monotherapy are associated with an increased risk of treatment inefficacy.