Clinical and Endoscopic Characterization of Depressed Gastric Adenoma

• Introduction
• Patients and Methods
• Results
• Discussion
• References

Background and Study Aim: Depressed gastric adenoma remains poorly characterized because it is rare, and is infrequently detected by endoscopy. The aim of this study was to elucidate clinical and endoscopic characteristics of depressed adenoma of the stomach.
Patients and Methods: 95 consecutive patients who underwent endoscopic resection of gastric adenomas were studied. Gastric adenomas, diagnosed according to the Vienna classification, were endoscopically classified into two types: depressed and protruding adenomas. In order to clarify endoscopic features of gastric adenomas, we performed indigo carmine chromoendoscopy as well as magnifying endoscopy with narrow band imaging, which yields clear images of mucosal microvasculature.
Results: 12 % of 100 gastric adenomas resected from 95 patients were depressed adenomas. Age and gender were comparable between patients with each type. Depressed adenomas (15.9 ± 6.2 mm) were significantly larger in diameter than protruding adenomas (10.6 ± 8.0 mm) (P = 0.01). Half of depressed adenomas were reddish in color, whereas only 18 % of protruding adenomas were reddish. Magnifying endoscopy with narrow band imaging showed that 71 % of depressed adenomas had a regular ultrafine network pattern of mucosal microvasculature, which was not seen in protruding adenomas. Intramucosal carcinomas were more frequently found in depressed adenomas (25 %) than in protruding adenomas (4.5 %).
Conclusions: In comparison with protruding adenomas, depressed adenomas were rare and appeared endoscopically as large and reddish with a specific regular ultrafine network pattern of mucosal microvasculature. Depressed adenomas should be endoscopically resected because intramucosal carcinomas were found in a quarter of them.

Introduction

Gastric adenoma is a benign neoplastic growth characterized by localized proliferation of adenomatous epithelium with tubular and/or papillary structures [1] [2]. It predominantly occurs in Helicobacter pylori-infected gastric mucosa with atrophy and intestinal metaplasia [3] [4]. Previous studies have demonstrated that some gastric adenomas have evolved into adenocarcinomas [5] [6] [7], and the adenoma-carcinoma sequence has been postulated with regard to gastric carcinogenesis [8] [9] [10].

Most gastric adenomas protrude above the surrounding non-neoplastic mucosa, while a few have a depressed appearance and are classified as depressed gastric adenomas [11] [12] [13] [14]. Although it remains obscure whether the morphological difference between protruding and depressed types reflects a difference in biological and clinical behavior, in previous studies of surgically resected stomach, depressed adenomas were reported to have higher malignant potential than protruding adenomas. If depressed adenomas do possess high malignant potential, they should be resected as precancerous lesions in the adenoma-carcinoma sequence. However, depressed adenomas are rarely detected by endoscopy because of their morphological characteristics, and the detailed endoscopic features of depressed gastric adenomas have not been well defined. We therefore aimed to elucidate clinical and endoscopic characteristics of gastric depressed adenomas in patients with endoscopically resected adenomas of the stomach.

Patients and Methods

A total of 95 consecutive patients, with 100 gastric adenomas that were endoscopically resected at the Jikei University Hospital between January 2000 and January 2004, were enrolled in this study. All resected specimens were fixed in 10 % buffered formalin, and micrometric measurements were taken. Specimens were cut serially into 2-mm slices, embedded in paraffin blocks and then cut into 5-µm sections and stained with hematoxylin and eosin. Lesions diagnosed as mucosal low-grade neoplasms of category 3 according to the revised Vienna classification [15] were studied as gastric adenomas. If a part of a resected adenomatous lesion was pathologically diagnosed as noninvasive carcinoma of category 4.2 according to the revised Vienna classification, it was defined as carcinoma in adenoma.

Gastric adenomas were classified as protruding or depressed type based on their endoscopic appearance by indigo carmine chromoendoscopy with conventional endoscopes (GIF-Q230, GIF-XQ230, GIF-Q240, or GIF-XQ240; Olympus, Tokyo, Japan). A protruding adenoma was defined as an adenomatous lesion which projected above the surrounding non-neoplastic mucosa, and a depressed adenoma was defined as an adenomatous lesion which had clear pooling of indigo carmine and was depressed relative to the surrounding mucosa. A depressed lesion surrounded by a circumferential protrusion was classified as a depressed adenoma if a depression showed clear indigo carmine pooling more than 5 mm in maximal diameter. Location within the stomach was classified as lower (the antrum of the stomach), middle (from the angulus to the middle corpus), or upper portion (from the upper corpus to the fornix).

Magnifying endoscopy was performed using a video endoscope (GIF-Q240Z; Olympus) and a video processor consisting of a narrow band imaging (NBI) system (Olympus) [16] [17]. The NBI system used a lighting unit of frame sequential illumination with spectrally narrow band filters, for wavelengths 415 nm, 445 nm and 500 nm, while the standard lighting unit filters were for 445 nm (blue), 540 nm (green), and 620 nm (red) (Figure [1 a]). The absorption and scattering features of light, as well as penetration depth into tissue, depend on the wavelength (Figure [1 b]). Light of a shorter wavelength, such as blue, does not penetrate as deeply into the gastrointestinal tissue as light of a longer wavelength does. Therefore, optical information obtained with narrow band filters for shorter wavelengths is able to produce clearer images of surface structures. The spectral features used in the NBI system were optimized to yield clear images of superficial glandular structures and microvessels in the gastrointestinal mucosa.

The microvasculature on the surface of gastric adenomas was classified into three patterns: a normal pattern comparable with the microvascular structure of surrounding normal mucosa, a regular ultrafine network pattern, or an unclear pattern with no visible microvascular structure. In a regular ultrafine network pattern, the microvascular structures around gland pits form themselves into very fine and regular networks.

Statistical analysis. Quantitative data were summarized by the mean and standard deviation (SD), shown as mean ± SD. The data obtained were evaluated using the Student t test, Fisher’s exact test, or the chi-squared test with the Yates continuity correction. All P values were two-sided and assumed to be statistically significant at the level of 0.05 or smaller.

Results

Of 100 gastric adenomas, 12 % were classified as depressed adenomas and 88 % as protruding. Age and gender were comparable between patients with depressed adenomas and protruding adenomas (Table [1]). The maximum diameter of depressed adenomas (15.9 ± 6.2 mm) was significantly larger than that of protruding adenomas (10.6 ± 8.0 mm) (P = 0.01). The two subtypes demonstrated a difference in intragastric distribution. Depressed adenomas were predominantly located in the lower portion of the stomach and none was found in the upper portion, whereas protruding adenomas were predominantly located in the middle and lower portions of the stomach and 17 % of those were found in the proximal portion. Half of depressed adenomas were endoscopically reddish in color as compared with the surrounding non-neoplastic mucosa, while 18 % of protruding adenomas were reddish and the remainder were pale or similar in color to the surrounding mucosa.

Magnifying endoscopy with narrow band imaging was performed in 32 patients with 7 depressed and 25 protruding adenomas. A regular ultrafine network pattern of microvessels was demonstrated in 5 out of 7 depressed adenomas (71 %). In contrast, none of the tested protruding adenomas possessed a regular ultrafine network pattern of microvasculature. Representative endoscopic pictures of a depressed adenoma are shown in Figure [2].

Pathological examinations showed that noninvasive carcinomas were more frequently observed in depressed adenomas (4/12, 25 %) than in protruding adenomas (4/88, 4.5 %) (P = 0.036). Protruding adenomas with carcinomas (19.5 ± 7.6 mm) were significantly larger in diameter than protruding adenomas without carcinoma (10.1 ± 7.8 mm) (P = 0.008). If protruding adenomas were categorized into large (≥ 15 mm in diameter) and small ones (< 15 mm), noninvasive carcinomas more frequently coexisted in large ones (3/16, 18.8 %) than in small ones (1/81, 1.2 %). Noninvasive adenocarcinoma was not found in protruding adenomas smaller than 10 mm.

En bloc resection rates tended to be higher for depressed adenomas (100 %) than for protruding adenomas (76 %) (P = 0.066). Argon plasma coagulation or laser irradiation was subsequently applied to the margins of the ulcer left by endoscopic mucosal resection (EMR), to prevent local tumor recurrence in three of the depressed adenomas (25 %) and nine of the protruding adenomas (10 %). Local tumor recurrence was not found in any of the depressed adenomas and was found in one of the protruding adenomas (1.1 %); the recurrent lesion was successfully removed by EMR.

Discussion

To our knowledge, this is the first description, in the literature in English, of detailed endoscopic characteristics of depressed gastric adenomas. Depressed adenomas showed distinct endoscopic features in comparison with protruding adenomas: depressed adenomas were larger in size and more frequently reddish in color. Magnifying endoscopy with narrow band imaging demonstrated that three-quarters of depressed gastric adenomas had a specific regular ultrafine network pattern in the microvasculature, which was not observed in protruding adenomas nor in depressed types of superficial gastric carcinomas.

We have previously reported that magnifying endoscopy with narrow band imaging could be used to predict the histological characteristics of superficial depressed gastric carcinomas in relation to the pattern of microvasculature structure [18] [19]. Superficial depressed carcinomas that are well-differentiated adenocarcinomas (intestinal type of gastric carcinoma) display an irregular fine network pattern in their microvascular structure, whereas there is a corkscrew pattern in poorly differentiated adenocarcinomas (diffuse type of gastric carcinoma). In this study, we demonstrated that most depressed gastric adenomas displayed a regular ultrafine pattern, in which a network of microvessels was composed of small and regular circles and which differed from the irregular fine network pattern observed in depressed carcinomas consisting of well-differentiated adenocarcinoma. Thus, magnifying endoscopy with narrow band imaging is a powerful tool for discriminating between depressed gastric neoplasias. Because histological examinations of tiny biopsy samples occasionally provide only an indeterminate pathological diagnosis, magnifying endoscopy with narrow band imaging can provide additional information for the choice of treatment of superficial depressed neoplasias of the stomach.

Narrow band imaging is a new technology based on narrowing the bandwidth of spectral transmittance of the optical filters used in the frame sequential image method. Combined with magnifying endoscopy, narrow band imaging gives clearer images of superficial fine structures and microvessels in the gastrointestinal or bronchial mucosa that are accessible to flexible endoscopes. It has recently been shown that magnifying endoscopy with narrow band imaging is useful in the diagnosis of superficial gastric carcinomas [19], esophageal carcinomas [17], Barrett’s esophagus [20], and colorectal mucosal lesions [21]. Magnifying endoscopy with narrow band imaging provides informative endoscopic images which reflect histological findings, and could represent a possible method of optical pathology without tissue collection. However, the current design of the magnifying endoscopy and narrow band imaging system uses low light intensity and a shallow depth of focus to get constant clear magnified images of superficial structures. With further refinement the modality may show promise as a valid method of optical pathology.

In our series of endoscopically resected adenomas, 12 % were depressed, which is consistent with findings from previous studies of surgically resected stomachs [11] [12] [13] [14]. Depressed adenomas were predominantly located in the distal portion of the stomach, where intestinal metaplasia, a paraneoplastic alteration induced by H. pylori infection, was more prevalent. We found that none of the depressed adenomas and 15 % of the protruding adenomas were in the proximal portion of the stomach. The topographical difference between the two types might be a reflection of differences in tumorigenesis of protruding and depressed adenomas. However, further confirmation is required in a larger cohort.

Multi-step oncogenesis has been proposed as one pathway of gastric carcinogenesis [8] [9] [10]. Indeed, noninvasive carcinoma occasionally coexists in gastric adenoma, and noninvasive carcinoma itself demonstrates neoplastic progression to invasive carcinoma. Thus, gastric adenoma can be a stage of malignant transformation in gastric carcinogenesis [5] [7]. In this study, noninvasive carcinoma in adenoma was more frequently observed in depressed adenomas than in protruding adenomas, suggesting that depressed adenomas can have a higher potential for transformation into invasive carcinoma. While only 4.5 % of all protruding adenomas had carcinoma, 18 % of large protruding adenomas (≥ 15 mm) had noninvasive carcinoma. Noninvasive adenocarcinoma was not found in protruding adenomas smaller than 10 mm. Therefore, depressed gastric adenomas and large protruding adenomas (≥ 15 mm) should be endoscopically resected because of their potential for malignancy, and small protruding adenomas can be observed without resection.

Competing interests: None

References

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M. Kaise, M. D.

Department of Endoscopy · The Jikei University School of Medicine

3-25-8 Nishi-shinbashi · Minato-ku · Tokyo 105-8461 · Japan

Fax: +81-3-34594524

Email: kaise@jikei.ac.jp

References

• 1 Goldstein N S, Lewin K J. Gastric epithelial dysplasia and adenoma: historical review and histological criteria for grading.  Hum Pathol. 1997;  28 127-133
  CrossrefPubMedSearch in Google Scholar
• 2 Ming S C. Cellular and molecular pathology of gastric carcinoma and precursor lesions: a critical review.  Gastric Cancer. 1998;  1 31-50
  CrossrefPubMedSearch in Google Scholar
• 3 You W C, Zhang L, Gail M H. et al . Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors.  J Natl Cancer Inst. 2000;  92 1607-1612
  CrossrefPubMedSearch in Google Scholar
• 4 Komoto K, Haruma K, Kamada T. et al . Helicobacter pylori infection and gastric neoplasia: correlations with histological gastritis and tumor histology.  Am J Gastroenterol. 1998;  93 1271-1276
  CrossrefPubMedSearch in Google Scholar
• 5 Kamiya T, Morishita T, Asakura H. et al . Long-term follow-up study on gastric adenoma and its relation to gastric protruded carcinoma.  Cancer. 1982;  50 2496-2503
  PubMedSearch in Google Scholar
• 6 Correa P. Helicobacter pylori and gastric carcinogenesis.  Am J Surg Pathol. 1995;  19 (Suppl 1) S37-S43
  PubMedSearch in Google Scholar
• 7 Rugge M, Cassaro M, di Mario F. et al . The long term outcome of gastric non-invasive neoplasia.  Gut. 2003;  52 1111-1116
  CrossrefPubMedSearch in Google Scholar
• 8 Correa P. Human gastric carcinogenesis: a multistep and multifactorial process - First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention.  Cancer Res. 1992;  52 6735-6740
  PubMedSearch in Google Scholar
• 9 Meining A, Riedl B, Stolte M. Features of gastritis predisposing to gastric adenoma and early gastric cancer.  J Clin Pathol. 2002;  55 770-773
  CrossrefPubMedSearch in Google Scholar
• 10 Chang M S, Kim H S, Kim C W. et al . Epstein-Barr virus, p53 protein, and microsatellite instability in the adenoma-carcinoma sequence of the stomach.  Hum Pathol. 2002;  33 415-420
  CrossrefPubMedSearch in Google Scholar
• 11 Nakamura K, Sakaguchi H, Enjoji M. Depressed adenoma of the stomach.  Cancer. 1988;  62 2197-2202
  PubMedSearch in Google Scholar
• 12 Ito H, Yasui W, Yoshida K. et al . Depressed tubular adenoma of the stomach: pathological and immunohistochemical features.  Histopathology. 1990;  17 419-426
  PubMedSearch in Google Scholar
• 13 Xuan Z X, Ambe K, Enjoji M. Depressed adenoma of the stomach, revisited. Histologic, histochemical, and immunohistochemical profiles.  Cancer. 1991;  67 2382-2389
  CrossrefPubMedSearch in Google Scholar
• 14 Oya M, Yao T, Nakamura T. et al . Intestinal phenotypic expression of gastric depressed adenomas and the surrounding mucosa.  Gastric Cancer. 2003;  6 179-184
  CrossrefPubMedSearch in Google Scholar
• 15 Dixon M F. Gastrointestinal epithelial neoplasia: Vienna revisited.  Gut. 2002;  51 130-131
  CrossrefPubMedSearch in Google Scholar
• 16 Shibuya K, Hoshino H, Chiyo M. et al . High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer.  Thorax. 2003;  58 989-995
  CrossrefPubMedSearch in Google Scholar
• 17 Yoshida T, Inoue H, Usui S. et al . Narrow-band imaging system with magnifying endoscopy for superficial esophageal lesions.  Gastrointest Endosc. 2004;  59 288-295
  CrossrefPubMedSearch in Google Scholar
• 18 Tajiri H, Doi T, Endo H. et al . Routine endoscopy using a magnifying endoscope for gastric cancer diagnosis.  Endoscopy. 2002;  34 772-777
  Thieme ConnectPubMedSearch in Google Scholar
• 19 Nakayoshi T, Tajiri H, Matsuda K. et al . Magnifying endoscopy combined with narrow band imaging system for early gastric cancer.  Endoscopy. 2004;  36 1080-1084
  Thieme ConnectPubMedSearch in Google Scholar
• 20 Hamamoto Y, Endo T, Nosho K. et al . Usefulness of narrow-band imaging endoscopy for diagnosis of Barrett’s esophagus.  J Gastroenterol. 2004;  39 14-20
  CrossrefPubMedSearch in Google Scholar
• 21 Machida H, Sano Y, Hamamoto Y. et al . Narrow-band imaging in the diagnosis of colorectal mucosal lesions: a pilot study.  Endoscopy. 2004;  36 1094-1098
  Search in Google Scholar

M. Kaise, M. D.

Department of Endoscopy · The Jikei University School of Medicine

3-25-8 Nishi-shinbashi · Minato-ku · Tokyo 105-8461 · Japan

Fax: +81-3-34594524

Email: kaise@jikei.ac.jp