Case presentation

The patient sought medical attention at the outpatient clinic due to experiencing epigastric discomfort persisting for a duration of 20 days. Subsequent gastroscopy conducted at the outpatient clinic revealed the presence of circumferential thickening in the gastric antrum and encroachment of the duodenal bulb across the pyloric ring. Additionally, biopsy of the intragastric lesion indicated the presence of high-grade intraepithelial neoplasia. Upon admission, the patient reported postprandial bloating and discomfort, accompanied by a loss of appetite. However, there were no reports of nausea, vomiting, or weight loss. Abdominal examination did not reveal any signs of abdominal pain, and the remainder of the physical examination yielded no noteworthy findings. The patient presented with a documented history of hypertension spanning three years, effectively managed through standardized medication. No additional gastrointestinal symptoms were reported. Laboratory tests, including admission blood routine, biochemical routine, and gastrointestinal tumor markers, did not reveal any abnormalities. Furthermore, the serum antibody test for Helicobacter pylori yielded a negative result.

Following that, a meticulous examination of the upper gastrointestinal endoscopy was conducted, revealing the thickening of the distal gastric sinus and pyloric ring, accompanied by an unevenly elevated surface (type 0-I and 0-IIa) (Figures 1a,1b). Notably, no ulceration or erosion was observed. Further assessment through Narrow-Band Imaging Magnification Endoscopy (NBIME) demonstrated that the gastric sinus exhibited a background of atrophic mucosa, while the overall mucosa of the lesion displayed a distinct “tea browness color”. Additionally, irregular widening of the ducts, covered by White Opaque Substance (WOS) (Figures 1c,1d). During the endoscopic insufflation test, the lesion demonstrated softness and displayed normal functionality of the pyloric ring. The lesion extended into the duodenal bulb, where it exhibited a characteristic flat and elevated appearance (type 0-IIa) with a distinct boundary, resembling the morphology of a Laterally Spreading Tumor (LST) in the colon (Figure 2e). Magnification observation using NBI revealed that a significant portion of the lesion’s surface was extensively attached with WOS. The glandular ducts exhibited Irregular Microvascular Pattern (IMVP) and Irregular Microsurface Pattern (IMSP), while the blood vessels displayed varying thickness and disorganized alignment (Figures 2f,2h). However, the level of disorganization observed was comparatively lower than that observed in the gastric sinus lesions. Regrettably, the unavailability of indigo carmine staining and ultrasonic endoscopy hindered their utilization in this study due to material constraints in the endoscopy department. The abdominal CT scan revealed a marginal thickening of the gastric sinus, with no evidence of distant metastasis or enlarged perigastric lymph nodes. Multiple biopsies were obtained from intragastric and duodenal lesions, indicating high-grade intraepithelial neoplasia in the gastric sinus, low-grade intraepithelial neoplasia in the duodenum, and focal high-grade neoplasia.

Treatment programs

Following a Multidisciplinary Team (MDT) evaluation encompassing gastrointestinal surgery, gastroenterology, imaging and pathology departments, a unanimous consensus was reached indicating a high likelihood of EGC for the lesion under consideration. However, due to the lesion’s extensive size and circumferential growth involving the pylorus and duodenum, endoscopic treatment posed significant challenges, with potential complications such as stenosis and perforation difficult to avoid after Endoscopic Submucosal Dissection (ESD). Consequently, surgical intervention emerged as the preferred treatment option. Subsequently, the patient underwent laparoscopic-assisted major gastrectomy with B-II anastomosis and D2 lymph node dissection. Following the postoperative pathological examination of the tumor, it was determined that the gastric sinus lesion exhibited characteristics of highly differentiated adenocarcinoma, while the duodenal lesion displayed primarily low-grade intraepithelial neoplasia. The lesion measured approximately 6.5 cm x 4.6 cm and was confined to the mucosal muscular layer, with cancer cells extending to the duodenum. The distance from the anal side to the pyloric ring was 2.6 cm (Figure 3), and the margins were devoid of cancer cells. Notably, there was no evidence of lymph or venous invasion, nor any metastasis to peripheral lymph nodes. Based on these findings, the tumor was classified as pT1aN0M0 Ia stage.The surgical specimen revealed the presence of High-Grade Intraepithelial Neoplasia (HGIN) with localized moderately differentiated adenocarcinoma(Figures 4a-4f).Immunostains suggests that the lesion as a whole is strongly positive for Muc5ac and partially positive for CDX2 (Figures 4g,4h). P53 exhibited weak staining (1+) in 30% of cells, and the Ki-67 proliferation index was measured at 60%. Following surgical intervention, the patient experienced a successful recovery and was discharged from the hospital after 11 days. Subsequently, during a 13-month followup period, the patient remained in a stable condition without any signs of recurrence.

Discussion

The etiology of gastric cancer is influenced by a combination of genetic predisposition and environmental factors [2]. ECG patients are usually asymptomatic. In the case, the patient with early gastric cancer exhibited peripheral growth in the distal gastric sinus and pyloric ring, only resulting in discomfort such as abdominal bloating rather than the typical symptoms associated with malignant tumors in the distal stomach. This highlights the significance of utilizing endoscopy for the early diagnosis of gastric cancer. Advanced gastric cancer in the antrum has been found to occasionally invade the pyloric ring and duodenum, with a majority of cases demonstrating submucosal vertical invasion. The occurrence of ECG invading the duodenum while being confined to the mucosa is extremely rare. Namikawa T et al. [3] examined reports from the Japanese Centra database spanning 33 years after 1975, identifying 13 similar cases. The average tumor diameter was measured at 6.3 cm, with the mean length of duodenal infiltration recorded at 0.9 cm (ranging from 0.2 to 3.8 cm). Based on the Japanese pathologic staging system for early gastric cancer, the predominant tumor types observed in these cases were Tub (differentiated) and Sig (signet ring) tumors. Our case aligns with Tub1 classification, as confirmed by immunohistochemistry indicating gastric type gastric cancer. Furthermore, the extent of duodenal invasion in our case exceeded the mean diameter reported in existing literature. A comprehensive search of the Medline database spanning the past two decades yielded a mere four pertinent reports [3-5]. In contrast, this case was extensively documented, presenting a series of consecutive magnified endoscopic and histopathologic images that effectively illustrate not only the macroscopic morphological alterations of the lesion, but also offer a comprehensive Magnifying Endoscopy (NBI-ME) perspective of the flat and depressed regions within the lesion.

The clinical definition of the boundary between the stomach and duodenum poses challenges due to its lack of clear demarcation [6]. In practice, the pyloric ring is commonly employed as a reference point to distinguish between the two anatomical structures. However, this demarcation is better characterized as a region of pyloric annulus, as the criteria for delineating this line are not as stringent as those applied to the boundary between the stomach and esophagus in clinical settings. From a clinicopathological perspective, the commencement of Brunner’s gland is frequently employed as the demarcation boundary between the stomach and the duodenum [7]. The prevalence of malignant neoplasms at the gastroduodenal junction in clinical settings is considerably lower compared to those occurring at the esophagogastric junction. Is there a correlation between the distinctive structure of the pyloric region and the recurrence of Early Gastric Cancer (EGC)? A Japanese scholar [8] reported a case that EGC recurrenced in the pyloric region, occurring eight months after Endoscopic Mucosal Resection (EMR). The recurrence was accompanied by extensive infiltration in the duodenal mucosa, leading to the suspicion that the disruption of the microstructure of the gastroduodenal mucosa caused by EMR facilitated the invasion of cancer cells into the duodenal mucosa. This prompts the question of whether there exists a barrier between the mucosa and submucosa of the gastroduodenum that hinders the progression of gastric tumors towards the distal end? Scholars [1] have noted that Brunner’s glands can remain unaffected even when cancer cells directly infiltrate the duodenal mucosa. Therefore, it can be hypothesized that Brunner’s glands may potentially impede the advancement of gastric cancer cells from the gastric mucosa to the duodenum. Brunner’s glands, situated in the submucosa of the duodenum [9], serve the purpose of producing an alkaline fluid that counteracts gastric acid. Additionally, these glands secrete various substances such as epidermal growth factor, trefoil peptides, bactericidal factors, proteinase inhibitors, and surfaceactive lipids. These components effectively bind to the mucus layer, safeguarding it and the underlying mucosa from degradation caused by gastric acid, pancreatic enzymes, and other surfactants present in the area. However, the medical community has not provided detailed elucidation on the potential involvement of Brunner’s gland in tumor suppression. From a molecular pathology standpoint, it has been proposed that the demarcation between gastric and duodenal regions lies in the expression boundary of SOX2 and CDX2 [10]. Additionally, abnormal CDX2 expression in the stomach is believed to be associated with intestinal metaplasia, which in turn is closely linked to the development of intestinal-type gastric cancer. This provides evidence, in part, for the molecular expression boundary theory. It is worthwhile to investigate the presence of crucial proteins in the duodenum that possess the ability to impede tumorigenesis.

The utilization of endoscopic techniques has become increasingly prominent in the management of gastric and duodenal early cancers [11]. As per the sixth edition of the Japanese Guidelines for the Treatment of Gastric Cancer [12], intramucosal carcinoma exceeding a diameter of 2 cm (cT1a), differentiated carcinomas, and UL0 are regarded as definitive indications for endoscopic intervention. However, in the case of lesions situated in specific regions, such as sizable Early Gastric Cancers (EGCs) found in the pylorus, cardia, and duodenum, while Endoscopic Submucosal Dissection (ESD) is theoretically viable as a treatment option, it necessitates a surgeon with advanced proficiency in this intricate technique, as well as thorough readiness to manage potential postoperative gastrointestinal perforation and stenosis. Nakayama et al. [13]reviewed 24 cases of invasion of the duodenum in Japan and found that duodenal infiltration was detectable preoperatively in only 4 cases. Their findings revealed that preoperative detection of duodenal infiltration was only possible in four cases. Consequently, when dealing EGCs located in close proximity to the pylorus, it is crucial to thoroughly evaluate lesion margins prior to endoscopic treatment and exercise caution when selecting the appropriate resection method. The presence of a tubular structure in the pyloric region poses additional challenges to endoscopic treatment, necessitating a careful assessment of the risk of positive margins before opting for EMR treatment. ESD mitigates the likelihood of margin positivity; however, it is imperative to conduct the procedure subsequent to magnification endoscopy for the purpose of accurately delineating the tumor boundary. In this case, the decision to opt for laparoscopic-assisted surgery instead of ESD treatment was based on a thorough assessment of the tumor’s location and dimensions. Furthermore, Laparoscopic Endoscopic Cooperative Surgery (LECS) [14] has been documented as an investigative therapeutic alternative for specific sites of EGC, offering superior preservation of healthy tissues and organs compared to standalone surgery. In summary, it is imperative to thoroughly assess lesions in the pyloric region prior to surgery in order to determine the potential risk of duodenal invasion, irrespective of the stage.

Conclusion

In summary, further investigation of additional cases is warranted to enhance our understanding of the underlying mechanism of early gastric cancer with duodenal invasion. Our study has revealed that early gastric cancers situated in the gastric antrum, particularly in the prepyloric region, possess the ability to directly infiltrate the duodenal mucosal layer.

Declarations

Acknowledgements: This work was completely supported by Weifang People’s Hospital.

Author’s contributions: Guangxu Zhu, and Hao Fu conjectured the study and reviewed the paper; Guangxu Zhu, and Shengjie Zhou analyzed the data and wrote the draft; Hao Fu, and Aifeng Pan selected the patients and collected the data.

Funding: Funding program: The Scientific Research Project of Weifang Health Commission

(WFWSJK-2021-028), Medical and Health Science Technology Development Program in Shandong Province (202104080159, 202204010313), Natural Science Foundation of Shandong Province (ZR2022LSW005), Science Technology Development Program in Weifang City (2021YX007),

Availability of data and materials: All data generated or analysed during this study are included in this published article.

Ethics approval and consent to participate: Not applicable.

Consent for publication: Not applicable.

Competing interests: The authors declare that they have no competing interests.

References

1. Kakeji Y, Tsujitani S, Baba H, Moriguchi S, Mori M, et al. Clinicopathologic features and prognostic significance of duodenal invasion in patients with distal gastric carcinoma. Cancer. 1991; 68(2): 380-4.
2. Matsuda A, Kato S, Furuya M, Shimizu Y, Okino T, et al. Multiple early gastric cancer with duodenal invasion. World J Surg Oncol. 2007; 5: 125.
3. Namikawa T, Kobayashi M, Kitagawa H, Okabayashi T, Dabanaka K, et al. Early gastric cancer with widespread duodenal invasion within the mucosa. Dig Endosc. 2010; 22(3): 223-7.
4. Khan S, Zhu LP, Zhang Y, Chen X, Wang BM. Laterally spreading tumour of the distal stomach: A case report. BMC Cancer. 2018; 18(1): 502.
5. Matsuda A, Kato S, Furuya M, Shimizu Y, Okino T, et al. Multiple early gastric cancer with duodenal invasion. World J Surg Oncol. 2007; 5: 125.
6. Li X, Udager AM, Hu C, Qiao XT, Richards N, et al. Dynamic patterning at the pylorus: Formation of an epithelial intestine-stomach boundary in late fetal life. Dev Dyn. 2009; 238(12): 3205-17.
7. Krause WJ. Brunner’s glands: A structural, histochemical and pathological profile. Prog Histochem Cytochem. 2000; 35(4): 259-367.
8. Ishikawa M, Kitayama J, Fujii S, Ishigami H, Kaizaki S, et al. Recurrent intramucosal gastric carcinoma with extensive invasion to duodenal mucosa after endoscopic mucosal resection: A case report. Am Surg. 2005; 71(4): 366-8.
9. Goldner B, Stabile BE. Duodenal adenocarcinoma: Why the extreme rarity of duodenal bulb primary tumors? Am Surg. 2014; 80(10): 956-9.
10. San Roman AK, Shivdasani RA. Boundaries, junctions and transitions in the gastrointestinal tract. Exp Cell Res. 2011; 317(19): 2711-8.
11. Yamada T, Sugiyama H, Ochi D, Akutsu D, Suzuki H, et al. Risk factors for submucosal and lymphovascular invasion in gastric cancer looking indicative for endoscopic submucosal dissection. Gastric Cancer. 2014; 17(4): 692-6.
12. Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric Cancer. 2023; 26(1): 1-25.
13. Nakayama Y, Kadowaki K, Hirata K, Higure A, Nagata N, et al. A case report of early gastric cancer with duodenal extension. Jpn J Gastroenterol Surg. 2004; 37: 506-511.
14. Hiki N, Nunobe S. Laparoscopic endoscopic cooperative surgery (LECS) for the gastrointestinal tract: Updated indications. Ann Gastroenterol Surg. 2019; 3(3): 239-246.