Accuracy of dual-contrast gastrointestinal ultrasonography in predicting lymph node metastasis in older adults with gastric cancer

Abstract

BACKGROUND

Gastrointestinal dual-contrast ultrasonography (DCUS) is characterized by its high resolution, sensitivity, and specificity.

AIM

To determine the accuracy of DCUS in predicting lymph node metastasis in middle-aged and elderly patients with gastric cancer (GC).

METHODS

A total of 100 middle-aged and elderly patients with GC admitted to the Fourth Affiliated Hospital of Soochow University (Dushu Lake Hospital, Suzhou, China) between April 2022 and April 2024 were selected. The baseline data and lymph node metastasis status were collected. DCUS combined with intravenous contrast technology was used to calculate the enhancement time (ET), time to peak (TTP), and slope of the ascending branch wash-in rate (WIR). These indicators were used in assessing lymph node metastasis in patients with GC.

RESULTS

Among 100 middle-aged and elderly patients with GC, 35 (35.00%) had lymph node metastases. GC patients with lymph node metastasis had a higher proportion of stage II TNM classification and higher WIR values than those without lymph node metastasis. The ET and TTP values were lower in patients with lymph node metastases, and all differences were statistically significant (P < 0.05). The area under the curve values for ET, TTP, WIR, and combined diagnosis of GC lymph node metastasis using DCUS were all > 0.7. Optimal assessment was achieved when the cutoff values for ET, TTP, and WIR were set at 16.32 seconds, 10.67 seconds, and 7.02, respectively.

CONCLUSION

DCUS-mediated assessment of ET, TTP, and WIR can effectively predict and evaluate lymph node metastasis status in patients with GC, with higher sensitivity when used in combination.

Key Words: Gastrointestinal contrast ultrasound; Intravenous contrast; Middle-aged and elderly; Gastric cancer; Lymph node metastasis; Prediction

Core Tip: Accurate assessment of lymph node metastasis is crucial for middle-aged and elderly patients with gastric cancer (GC), and dual-contrast ultrasonography can effectively predict and evaluate lymph node metastasis status in GC patients.

INTRODUCTION

Gastric cancer (GC) is a prevalent malignant tumor associated with various factors, including genetics, environment, dietary habits, and lifestyle. It has a relatively high incidence rate in middle-aged and elderly populations. With the increasing aging of the global population, the diagnosis and treatment of GC have emerged as timely topics in clinical medicine[1,2]. Over the past several decades, research on GC has made remarkable progress; however, many questions remain unanswered. While various diagnostic methods are currently available including endoscopy, the accurate prediction of lymph node metastasis in patients with GC remains a significant challenge[3]. Lymph node metastasis is a critical factor affecting GC patient prognosis, and early and accurate prediction is essential for designing personalized treatment plans and improving patient outcomes[2,3]. Gastrointestinal contrast imaging is a novel diagnostic tool that provides a clear visualization of the morphological structure and functional status of the gastrointestinal tract, offering comprehensive information for GC diagnosis and staging[3-5]. Intravenous Sonazoid contrast imaging utilizes ultrasound technology for vascular imaging, enhancing blood vessel visibility by injecting contrast agents, thereby assisting physicians in the accurate assessment of tumor blood supply and surrounding tissue structure. The dual contrast ultrasound technique combines the advantages of Sonazoid IV contrast imaging and provides clinicians with new perspectives and methods. However, studies on the application of gastrointestinal dual-contrast ultrasonography (DCUS) to predict lymph node metastasis in GC are relatively limited. Although some studies have shown certain potential advantages, further validation and optimization are required. Therefore, in this study, we aimed to explore the accuracy of DCUS in predicting lymph node metastasis in middle-aged and elderly patients with GC, with the goal of providing more precise diagnostic evidence for clinical practice.

MATERIALS AND METHODS

General data

A total of 100 middle-aged and elderly patients with GC admitted to the Fourth Affiliated Hospital of Soochow University (Dushu Lake Hospital, Suzhou) and the Shanghai Jiao Tong University School of Medicine Suzhou Jiulong Hospital from April 2022 to April 2024 were included in the study, which was approved by the hospital's Ethics Committee. The inclusion criteria were as follows: (1) GC diagnosed based on postoperative histopathological examination; (2) Patient age > 40 years; (3) Estimated survival time of more than 6 months; (4) Suitable for gastrointestinal contrast ultrasonography and intravenous contrast indications; (5) Scheduled to undergo surgical treatment after DCUS; and (6) Provided informed consent. The exclusion criteria were as follows: (1) History of gastrointestinal surgery; (2) Received prior radiochemotherapy; (3) Other concurrent malignant tumors; and (4) Missing relevant clinical data. The sample size for this study was selected in accordance with stringent inclusion and exclusion criteria, encompassing all eligible patients from April 2020 to April 2024 for subsequent analysis.

Data collection

Detailed baseline data for each patient, including sex, age, body mass index, disease course, tumor stage, tumor location, and tumor size, were recorded through a medical record review, patient inquiry, and utilization of imaging materials.

Specific steps for gastrointestinal contrast ultrasonography

Patients fasted for > 8 hours and orally ingested 500 mL of prepared gastrointestinal contrast ultrasonography agent (Huzhou Dongya Medical Supplies Co., Ltd., Zhejiang; medical device registration number 20212060179) 5 minutes before the examination using a Siemens-SEQ1 color ultrasonography diagnostic device (registration number: National medical device registration import 20192060012) for gastrointestinal contrast ultrasonography. During the examination, the patient was adjusted to different positions, including supine, left and right lateral decubitus, and semi-sitting, with an appropriate amount of ultrasonography coupling agent applied. A probe was used to perform multi-plane scanning of the digestive tract from the cervical esophagus to the duodenum, with frequency and mechanical index set at 2-4 MHz and 0.07, respectively. After the basic contour structure of the stomach was clearly displayed, the thickness of the gastric wall, peristalsis, and the distribution of contrast agent in the gastric cavity were observed in detail. Representative images are shown in Figures 1 and 2.

Figure 1 Ultrasound images show changes in the gastric wall, including thickening of the mucosal layer and narrowing of the gastric cavity. A: The gastric cavity is well distended; B: With diffuse thickening of the mucosal layer in the antral; C: Body regions of the stomach, appearing rough and indistinct in local layers. The mucosal surface is uneven, with narrowing of the antral lumen.

Figure 2 Ultrasonographic findings in gastric cancer. A: The gastric wall layers are clearly defined, with circumferential thickening of the gastric wall in the antral and body regions, more pronounced in the antrum, narrowing of the antral lumen, an uneven mucosal surface, and partial interruption of the mucosa can be observed; B: Enlargement of the perigastric lymph nodes.

Specific steps for intravenous contrast

A channel was established in the patient's elbow vein, and sulfur hexafluoride microbubbles (Bracco Suisse SA, Switzerland; national drug approval number HJ20171213) were injected as a contrast agent. Then, 5 mL of physiological saline was used to flush the channel, and two regions of interest were selected outside the necrotic area, namely the lesion area and the surrounding normal gastric wall area, based on the gastrointestinal contrast ultrasonography examination. Based on workstation data and computational analysis, key parameters were obtained, including time to enhancement time (ET), time to peak (TTP), and wash-in rate (WIR).

Lymph node metastasis

After DCUS examination, all patients underwent radical surgery for GC within 2 weeks, and lymph node metastasis status was recorded.

Statistical analysis

All data collected in this study were processed using the SPSS version 26.0 statistical software. Categorical data are expressed as percentages (%) and were subjected to χ² testing. Normal distribution of continuous data was determined by the Shapiro-Wilk test; they are presented as mean ± SD and were analyzed using t-tests. Receiver operating characteristic curves were constructed for the ET, TTP, and WIR, and their combined diagnostic performance in predicting GC lymph node metastasis. The area under the curve (AUC) was calculated; an AUC > 0.90 indicated high diagnostic value, 0.7 < AUC ≤ 0.9 indicated moderate diagnostic value, and 0.5 < AUC ≤ 0.7 indicated poor diagnostic value. Statistical significance was set at P < 0.05.

RESULTS

Lymph node metastasis

Histopathological examination of the tissue collected during radical gastrectomy of the 100 middle-aged and elderly patients with GC demonstrated that 35 (35.00%) exhibited lymph node metastasis, whereas 65 (65.00%) did not.

Baseline data

There were no statistically significant differences in sex, age, body mass index, disease duration, or tumor diameter between GC patients with and without lymph node metastasis (P > 0.05). The proportion of patients with lymph node metastasis at TNM stage II was 28.57%, which was significantly higher than the 6.15% of those without lymph node metastasis (P < 0.05) (Table 1).

Table 1 General data (mean ± SD), n (%).

Data class	Lymph node metastasis (n = 35)	No metastasis (n = 65)	t/χ2	P value
Sex
Male	18 (51.43)	35 (53.85)	0.053	0.817
Female	17 (48.57)	30 (46.15)
Age (years)	56.24 ± 5.71	55.38 ± 5.43	0.742	0.461
Body mass index (kg/m2)	24.17 ± 1.15	24.09 ± 1.03	0.356	0.723
Duration of disease (years)	2.31 ± 0.46	2.24 ± 0.51	0.677	0.501
Tumor diameter (mm)	4.08 ± 0.75	3.97 ± 0.72	0.718	0.475
TNM staging
Phase I	25 (71.43)	61 (93.85)	9.496	0.002
Phase II	10 (28.57)	4 (6.15)

DCUS indices

The ET and TTP values of GC patients with lymph node metastasis were lower than those without lymph node metastasis, whereas the WIR value was higher, with all differences being statistically significant (P < 0.05; Table 2).

Table 2 Gastrointestinal dual-contrast ultrasonography examination indicators.

Group	n	ET (s)	TTP (s)	WIR
Lymph node metastasis	35	15.45 ± 4.37	8.16 ± 2.32	7.36 ± 1.97
No metastasis	65	22.08 ± 6.74	11.87 ± 4.28	6.17 ± 1.25
t	-	5.249	4.758	3.689
P value	-	< 0.001	< 0.001	< 0.001

ET: Enhancement time; TTP: Time to peak; WIR: Wash-in rate.

Value analysis of DCUS indices ET, TTP, WIR, and combined diagnosis for GC lymph node metastasis

The AUC values for ET, TTP, WIR, and combined diagnosis of GC lymph node metastasis using DCUS were all > 0.7, with the optimal assessment achieved when the cutoff values for ET, TTP, and WIR were set at 16.32 seconds, 10.67 seconds, and 7.02, respectively (Table 3).

Table 3 Efficacy analysis of gastrointestinal dual-contrast ultrasonography examination enhancement time, time to peak, wash-in rate, and combined diagnosis for gastric cancer lymph node metastasis.

Index	Sensitivity	Specificity	Youden index	AUC value	95%CI	Cut-off value
ET	0.615	0.807	0.421	0.792	0.708-0.891	16.32
TTP	0.930	0.569	0.495	0.776	0.684-0.867	10.67
WIR	0.725	0.961	0.676	0.751	0.604-0.904	7.02
Combined diagnosis	0.782	0.748	0.535	0.836	0.769-0.932	-

ET: Enhancement time; TTP: Time to peak; WIR: Wash-in rate; AUC: Area under the curve.

DISCUSSION

GC is a highly malignant gastrointestinal tumor with an increasing global incidence. It is particularly prevalent among middle-aged and elderly populations. Postoperative survival time in patients with GC is associated with various factors, including general physical condition, age, sex, lifestyle habits, psychological state, and postoperative treatment, and is closely related to the occurrence of lymph node metastasis. Studies have indicated that the 5-year survival rate for patients with GC without lymph node metastasis is approximately 40%-50%, whereas those with lymph node metastasis, it is only 0%-15%[6-8]. Therefore, employing safe and effective methods to accurately predict lymph node metastasis in middle-aged and elderly patients with GC is important for treatment planning and prognostic assessment.

Under normal physiological conditions, blood perfusion into the lymph node is typically at a relatively low level. This implies that in the absence of external interference, the internal blood flow within the lymph nodes is limited to meet their basic physiological needs. When tumor cells begin to invade and metastasize, there is a significant change in the hemodynamics within the lymph nodes, which is usually characterized by an increase in blood perfusion or a change in distribution patterns. Specifically, tumor cell invasion leads to the blood vessel dilation within lymph nodes, thereby increasing blood inflow[9]; their metabolic demands also prompt the generation of new vascular branches, further increasing blood perfusion[10]. Moreover, tumor cell invasion can alter blood flow distribution patterns within lymph nodes, causing the originally uniform blood flow to become uneven, even leading to localized blood stasis or vortex phenomena[11,12]. These changes not only reflect the presence and activity of tumor cells but also provide an important basis for clinical diagnosis and treatment. Gastrointestinal contrast ultrasonography is an advanced medical imaging technique that offers significant advantages, such as being non-invasive, easy to operate, and cost-effective compared to traditional computed tomography, magnetic resonance imaging (MRI), and other technologies[13,14]. Intravenous Sonazoid contrast technology is a widely applied medical imaging technique that leverages the properties of ultrasound to enhance image contrast and clarity using specific contrast agents. It allows for real-time observation of blood perfusion within the lymph nodes, clearly delineating the vascular distribution and blood flow status within these nodes[15,16]. By utilizing workstation data and computer analysis, this technology can provide detailed information on lymph node metastasis, capturing core indicators, such as ET, TTP, and WIR. These metrics are essential for evaluating tumor perfusion and determining tumor malignancy. They help physicians indirectly assess hemodynamic changes in lymph nodes and better understand the characteristics of both lesions and lymph nodes. In this study, GC patients with lymph node metastasis were more frequently classified as TNM stage II and showed significantly higher WIR values, along with lower ET and TTP values, compared to those without lymph node metastasis (P < 0.05). We believe that the WIR value reflects relative changes in blood perfusion within the lymph nodes, while ET and TTP represent the time required for the contrast agent to arrive and exit the lymph nodes, respectively. Changes in these indicators are closely associated with lymph node metastasis[17,18]. Therefore, DCUS can effectively predict lymph node metastasis in patients with GC through changes in these indicators, thereby providing important diagnostic information for clinical practice.

Additionally, the study results showed that the AUC values for ET, TTP, WIR, and the combined diagnosis of GC lymph node metastasis using DCUS were all > 0.7, with the optimal assessment achieved when the cutoff values for ET, TTP, and WIR were set at 16.32 seconds, 10.67 seconds, and 7.02, respectively. The AUC value is an important indicator of diagnostic efficacy[19,20]. In this study, the AUC values were all > 0.7, indicating that DCUS has a high diagnostic efficacy in predicting lymph node metastasis in patients with GC. In particular, the combined diagnostic AUC value reached 0.836, indicating that combining the three indicators of ET, TTP, and WIR for diagnosis can more comprehensively assess lymph node metastasis, providing a more accurate basis for clinical decision-making.

To further elucidate the significance of our findings, we conducted a detailed comparison of our results with those reported in literature. In recent years, numerous studies have explored the application of various imaging techniques to predict lymph node metastasis in GC. For instance, Wen et al[20] demonstrated that lymph node metastasis in GC patients is closely associated with TNM staging, which is consistent with our findings. Additionally, Riely et al[21] reported that the assessment of lymph node metastasis using multidetector computed tomography in patients with GC can achieve an AUC value of 0.854, which is comparable to the AUC value obtained from DCUS in our study. However, the unique strength of our study lies in the combined use of ET, TTP, and WIR for diagnosis, with a combined diagnostic AUC value of 0.836, which was higher than that of any single indicator. This indicates that the combined diagnostic approach has a significant advantage for evaluating lymph node metastasis in GC.

Moreover, a previous study demonstrated that quantitative dynamic contrast-enhanced MRI has high diagnostic value in assessing lymph node metastasis in patients with GC, with an AUC value close to our results[22,23]. This further corroborates the scientific validity and effectiveness of the proposed method. Nonetheless, the combined diagnostic approach in our study offers greater feasibility and operability in clinical applications, as DCUS is a non-invasive and convenient imaging technique that is well suited for widespread use in clinical practice.

In this study, DCUS revealed that patients with GC and lymph node metastasis exhibited higher TNM stage proportions, elevated WIR values, and reduced ET and TTP values, with a combined diagnostic AUC of 0.836, indicating the efficacy of this technique in predicting lymph node metastasis. These changes in indicators are closely associated with tumor cell invasiveness and increased metabolic activities, reflecting alterations in blood perfusion within lymph nodes. However, our study was limited by its single-center design and relatively small sample size, which may affect the generalizability of the results. Additionally, the absence of other imaging modalities as controls and the lack of long-term patient follow-up restricts the assessment of the indicators' long-term prognostic value. Variations in tumor biology, vascular structure, and metabolic activity among patients can influence the range of these indicators, and patient age, sex, and comorbidities may also impact diagnostic outcomes. Future research should adopt a multicenter, large-sample design, compare DCUS with other imaging techniques, and conduct long-term patient follow-ups to further validate its diagnostic and prognostic potential. Moreover, the development of more precise diagnostic models by integrating artificial intelligence and exploring the biological mechanisms underlying these indicators will provide stronger support for the diagnosis and treatment of GC.

CONCLUSION

DCUS can effectively predict and evaluate the lymph node metastasis status in patients with GC through assessment of ET, TTP, and WIR. The combination of all three values has higher diagnostic value, suggesting the potential for the application of this technique in clinical practice.