A CASE OF DIFFUSE‐TYPE EARLY GASTRIC CANCER WITH NODULAR GASTRITIS

A 39‐year‐old woman was referred to Osaka Police Hospital and admitted for surgical treatment of gastric cancer. Barium upper gastrointestinal study and endoscopic examination showed a 3.0 × 3.0 cm depressed lesion in the greater curvature of the middle corpus. An unusual miliary pattern resembling ‘goose flesh’ was observed endoscopically in the antrum. Biopsy specimens from the tumor showed poorly differentiated adenocarcinoma, and specimens from the antrum showed many lymphoid follicles with a germinal center. Rapid urease test and histological tests (Giemsa stain) for Helicobacter pylori were both positive. Early gastric cancer with nodular gastritis (NG) was diagnosed and a partial gastrectomy was performed. Histological examination of the resected specimen showed a stage I tumor consisting mainly of signet‐ring cell carcinoma restricted to the mucosa. Postoperatively H. pylori eradication therapy was performed and proved to be successful. One year after eradication therapy, endoscopy with biopsy showed no recurrence of gastric cancer and the remarkable regression of antral NG.     

SMALL EARLY GASTRIC CANCER OCCURRING IN A YOUNG WOMAN WITH NODULAR GASTRITIS

We found a small gastric cancer in a 25‐year‐old woman with nodular gastritis. Endoscopically, the cancer was identified as a whitish area in the gastric antrum. There was also a miliary pattern in the gastric antrum and corpus. In addition, serology and histology revealed the patient to have been infected by Helicobacter pylori. Histological examination of the resected stomach showed that the cancer was poorly differentiated adenocarcinoma with signet‐ring cell restricted to the mucosal layer. In the surrounding mucosa, there were chronic inflammatory cell infiltrates and enlarged lymphoid follicles with germinal centers. Our case suggests that nodular gastritis may be at a high risk for the development of gastric cancer of poorly differentiated type.     

Advanced gastric cancer associated with nodular gastritis in a young patient

A 20-year-old female underwent an endoscopy for epigastralgia that revealed many small, elevated nodules in the antrum that were diagnosed as nodular gastritis. The endoscopy also showed an ulcerative lesion with an uneven round wall at the greater curvature of the middle corpus. Biopsy of the ulcerative lesion yielded a diagnosis of poorly differentiated adenocarcinoma. A distal gastrectomy was performed on the basis of a diagnosis of gastric cancer associated with nodular gastritis. The intraoperative findings revealed serosal invasion of the gastric cancer and the patient tested positive for peritoneal cytology. The pathological findings revealed poorly differentiated adenocarcinoma showing invasive growth with fibrosis on the corpus and large and superficial lymphoid follicles on the miliary nodules at the antrum. The patient was positive for Helicobacter pylori infection by both the serum Helicobacter pylori antibody and histopathological findings.     

A Case of Poorly Differentiated Early Adenocarcinoma of the Stomach Forming a Protruded Type Lesion

Abstract: A case of poorly differentiated adenocarcinoma (undifferentiated type by Nakamura, diffuse type by Lauren) of the stomach infiltrating the submucosa and forming a protruded type lesion is reported. A 60-year-old man underwent endoscopic examination, which revealed a protruded type lesion with a nodular configuration and shallow ulceration accompanied by slough along the greater curvature of the upper gastric body, which was proved to be poorly differentiated adenocarcinoma by endoscopic biopsy. The patient underwent radical surgery, consisting of total gastrectomy with pancreato-splenectomy. Macroscopic observation of the resected specimen revealed a protruded type lesion, measuring 30 mm in diameter, in the fundus along the greater curvature. The surface of the lesion had an irregular and nodular configuration with erythema and superficial erosions. Although, in the setting of early gastric cancer, poorly differentiated adenocarcinomas are usually macroscopically depressed or ulcerated type, this case presented a protruded type lesion (polypoid type). We report this unusual case because of its extremely important implications in the discussion of gastric cancer therapy.     

Differentiated adenocarcinoma with a gastric phenotype in the stomach: difficulties in clinical and pathological diagnoses

Differentiated-type adenocarcinoma with gastric phenotype of the stomach is rare and is difficult to diagnose both clinically and pathologically. We report a case of differentiated-type adenocarcinoma with a gastric phenotype in the stomach. A 60-year-old Japanese female was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed a granular elevated lesion in the lower body near the lesser curvature and a depressed lesion on the antrum. A biopsy specimen showed benign atrophic mucosa in a granulated lesion and moderately differentiated adenocarcinoma in the depressed lesion. The patient underwent laparoscopy-assisted distal gastrectomy with lymph node dissection. The postoperative course was uneventful. Histological examination of the resected tissue confirmed well-differentiated adenocarcinoma in the granulated lesion and moderately differentiated adenocarcinoma in the depressed lesion, without lymph node metastasis. Both lesions were confined to the mucosa. Since mucin immunohistochemistry revealed MUC5AC-positive staining in the granulated lesion, the final diagnosis was differentiated-type adenocarcinoma with gastric phenotype in the stomach. Despite the high malignant potential, the clinical and pathological diagnoses of gastric-type differentiated adenocarcinoma are often difficult. Mucin immunohistochemistry together with hematoxylin and eosin (HE) staining may be helpful in the pathological diagnosis of this rare disease.     

EARLY GASTRIC CANCER WITH WIDESPREAD DUODENAL INVASION WITHIN THE MUCOSA

We report a rare case of early gastric cancer confined to the mucosal layer with extensive duodenal invasion, curatively removed with distal gastrectomy. An 84‐year‐old Japanese woman was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed an irregular nodulated lesion measuring 6.5 x 5.5 cm in the gastric antrum and an aggregation of small nodules in the duodenal bulb. A biopsy specimen showed well‐differentiated adenocarcinoma. The patient underwent distal gastrectomy with partial resection of the duodenal region containing the tumor and regional lymph node dissection, with no complication. Histological examination of the resected tissue confirmed well‐differentiated adenocarcinoma limited to the mucosal layer and without lymph node metastasis. The cancer extended into the duodenum as far as 38 mm distant from the pyloric ring, and the resected margins were free of cancer cells. Gastric cancer located adjacent to the pyloric ring thus has the potential for duodenal invasion, even when tumor invasion is confined to the mucosal layer. In such cases, care should be taken during examinations to detect duodenal invasion, and the distal surgical margin must be negative given sufficient duodenal resection.     

Synchronous occurrence of early neuroendocrine carcinoma and tubular adenocarcinoma in the stomach

This report describes a patient with early neuroendocrine carcinoma (NEC) and tubular adenocarcinoma in the stomach. A 74-year-old Japanese male experienced epigastralgia. Endoscopic examination revealed two small lesions; one was an elevated lesion with ulceration at the posterior wall of the pre-pylorus and the other was a depressed lesion at the greater curvature of the antrum. Pathological diagnosis of the biopsies indicated poorly differentiated adenocarcinoma from the lesion on the pre-pylorus and well differentiated adenocarcinoma from the lesion on the antrum. He was referred to the surgical outpatient clinic with early double cancer of the stomach. A distal partial gastrectomy with lymph node dissection was performed. A histopathological examination revealed NEC at the lesion on the pre-pylorus and well differentiated tubular adenocarcinoma at the lesion on the antrum. These two lesions were completely separate from each other. Therefore, this case is thought to demonstrate the synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.     

Rapidly growing early gastric cancer with microsatellite instability

A 77-year-old man underwent gastrointestinal endoscopy that revealed a small flat elevated lesion in the gastric antrum. Endoscopically, we assessed the tumor as intramucosal cancer or adenoma, and biopsy specimens were diagnosed as showing borderline malignancy. At the second examination, performed 6 months later, the elevated lesion had grown, showing remarkable changes in its appearance, and a diagnosis of adenocarcinoma was confirmed pathologically. The patient underwent distal gastrectomy about 8 months after the first examination, and the tumor in the resected specimens showed a moderately differentiated adenocarcinoma invading through the entire submucosal layer, with metastasis to a regional lymph node. Microsatellite analysis of this early gastric cancer disclosed mutations in all six markers examined, indicating high-level microsatellite instability (MSI-H). The tumor also showed frameshift mutations of TGFβRII and BAX genes, as well as hypermethylation of the hMLH1 promoter. These results suggest that a deficiency of the mismatch repair system played a critical role in the progression of this cancer. Received: August 13, 2001 / Accepted: January 25, 2002 Reprint requests to: K. Yamashita Present address: The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA     

NODULAR GASTRITIS AND GASTRIC CANCER

Nodular gastritis is defined as antral gastritis usually characterized endoscopically by a miliary pattern resembling gooseflesh and pathologically by prominent lymphoid follicles and infiltration of mononuclear cells. This physiological phenomenon was once considered particular to young women. Recent studies have shown that nodular gastritis is strongly associated with Helicobacter pylori infection and may be associated with gastric cancer. Reported cases of gastric cancer with nodular gastritis showed some features in common: all gastric cancers were diagnosed histologically as the diffuse‐type, and all were located in the corpus with Helicobacter pylori infection. Because nodular gastritis may be a risk factor for diffuse‐type gastric cancer, Helicobacter pylori may need to be eradicated to prevent gastric cancer in patients with nodular gastritis.     

A case of collagenous gastritis resembling nodular gastritis in endoscopic appearance

A 25-year-old Japanese female was referred to our clinic for the investigation of moderate iron-deficiency anemia and epigastralgia. Endoscopic examination showed diffuse mucosal nodules in the gastric body resembling nodular gastritis, but this pattern was not observed in the antrum. Histology of the gastric biopsies taken from the gastric body showed mild atrophic mucosa with chronic active inflammation. Some of the biopsy specimens showed deposition of patchy, band-like subepithelial collagen. Four years later, the patient showed no clinical symptoms and signs. A follow-up endoscopic examination showed similar findings, which mimicked pseudopolyposis or a cobblestone-like appearance. The biopsy specimens from the depressed mucosa between the nodules revealed a thickened subepithelial collagen band with no improvement, which led to a diagnosis of collagenous gastritis. Treatment with oral administration of proton-pump inhibitors and histamine-2-receptor antagonists had proved ineffective. To make a correct diagnosis of collagenous gastritis, we should determine the characteristic endoscopic findings and take biopsies from the depressed mucosa between the nodules.     

Predicting histologic findings from endoscopic appearance of early gastric cancer.

In 156 cases of depressed early gastric cancer in the antrum or corpus, the differences between differentiated and undifferentiated carcinoma were studied by comparing the histological diagnosis of the resected specimens and their endoscopic appearance. We reached the following conclusions: (a) Younger patients more often had undifferentiated carcinoma (mean age: 59.8 years) than differentiated carcinoma (mean age: 77.2 years). (b) One hundred and twenty-five of 156 cases were limited to the mucosa and 29 cases were limited to the submucosa. (c) Undifferentiated gastric cancers more often invaded beyond the mucosa even when the tumor was small than did differentiated tumors. (d) Many differentiated tumors showed a smooth depressed surface, erythema at the edge of the cancer, and tapering of the gastric rugae. (e) In undifferentiated lesions the depressed tumor surface had a varied appearance, with various sized granules and nodules, as well as fading of the mucosal color and fusion of the rugae. It is important at endoscopy to consider not only whether a lesion is benign or a malignant, but also to consider its histological type. In particular, it is vital to detect small, undifferentiated gastric cancers as early as possible.     

Correlation between serum pepsinogen levels and gastric mucosal histological findings before and after Helicobacter pylori eradication therapy

Background: Helicobacter pylori causes chronic gastritis and is also associated with many other gastrointestinal diseases. The incidence of gastric cancer is thought to vary according to the degree and topography of chronic gastritis. Histological findings of specimens obtained at endoscopy are therefore important. In the present study, we investigated the correlation between these histological findings and serum pepsinogen (PG) levels. Methods: Helicobacter pylori eradication therapy was conducted in 100 H. pylori‐positive patients. Endoscopies were performed prior to, and 2 months after, eradication therapy; gastric mucosal biopsies were taken from the antrum and corpus. Helicobacter pylori infection was diagnosed using the rapid urease test, culture and histology. Using the Updated Sydney System, histological findings of inflammation, activity, atrophy and intestinal metaplasia were each graded. Blood was taken on the same two occasions for determination of serum levels of PG I and II. Results: Levels of PG I were highest in association with antrum‐predominant gastritis (APG), followed in order by pangastritis (PAN) and corpus‐predominant gastritis (CPG), with a significant difference between APG and CPG. No correlations were seen between PG II levels and gastritis topography. Examination of the relationship between PG levels and histological findings revealed significant correlations between PG I levels after eradication atrophy and intestinal metaplasia in the gastric corpus. No significant correlations were seen between PG II levels and before or after eradication histological findings. Conclusion: Our results indicate that serum PG levels may be a useful indicator of before‐eradication gastritis topography and after‐eradication gastric atrophy in the gastric corpus.     

Conversion surgery after S-1 plus oxaliplatin combination chemotherapy for advanced gastric cancer with multiple liver metastases

Conversion therapy for gastric cancer is a new therapeutic concept. We report a case of a patient with advanced gastric cancer who underwent conversion surgery due to a remarkable regression of multiple liver metastases following chemotherapy. A 71-year-old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy (EGD) revealed an irregular, nodular, ulcerated lesion in the lower third of the stomach. Analysis of biopsy specimens revealed a poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) showed multiple liver mass lesions. The patient was clinically diagnosed with advanced gastric cancer with liver metastases and received S-1 plus oxaliplatin chemotherapy. After 6 cycles of chemotherapy, CT and magnetic resonance imaging showed complete resolution of the liver metastases, and EGD detected mucosal irregularities only. Since there was no evidence of further metastatic lesions in other organs, the patient underwent distal gastrectomy with D2 lymphadenectomy. The gross appearance of the surgically resected specimen showed a slightly elevated tumor measuring 4.5?×?3.5 cm. Pathological examination confirmed the diagnosis of a moderately differentiated gastric adenocarcinoma invading the muscularis propria with no lymph node metastases. The postoperative course was uneventful. The patient has continued to receive S-1 and oxaliplatin chemotherapy, and there has been no evidence of recurrence for 3 months following the operation. We propose that conversion therapy might be an effective treatment for patients with advanced gastric cancer; however, further studies and assessments are needed to confirm and establish this treatment strategy.     

Endoscopic mucosal resection for early adenocarcinoma arising in Barrett's esophagus

A 58‐year‐old man was diagnosed to have an esophageal adenocarcinoma arising in Barrett's esophagus by screening examination at the previous hospital. Endoscopically, a slightly reddish elevated lesion with a central depressed component was detected in the Barrett's epithelium. Endoscopic ultrasonography showed the thickness of the second layer of the esophagus and no enlarged lymph node. Histological examination of a biopsy specimen revealed well or moderately differentiated adenocarcinoma. From these findings, the lesion was diagnosed as a mucosal esophageal cancer, type IIa + IIc, arising in Barrett's esophagus. As he refused operation, the lesion was resected endoscopically with his informed consent. Histologically, the resected specimens showed moderately differentiated adenocarcinoma arising in Barrett's esophagus. The adenocarcinoma had invaded the superficial muscularis mucosa, but was limited to the deep one with no vessel invasion. Barrett's esophagus often has a double muscularis mucosa. Connective tissues containing vascular and lymphatic vessels exist between them. However, one consideration is whether the existence of vessels between the double muscularis mucosa and the presence of vessel invasion are risk factors for metastasis. In order for a definitive indication for endoscopic mucosal resection, the frequency of lymph node and distant metastasis in cases of early Barrett's cancer needs to be investigated.     

Histological features of nodular gastritis and its endoscopic classification

OBJECTIVES: To clarify the histological features and endoscopic classifications of nodular gastritis (NG). METHODS: Overall 40 996 patients who had undergone an upper gastrointestinal endoscopy were enrolled. NG is defined as a uniform and diffuse protrusion from the antrum to angulus, which has two types at endoscopy: nodular (N) and granular (G). Three biopsy specimens were taken from the antrum, angulus and corpus. The histological features were evaluated using the updated Sydney System (USS). The topography of gastritis (antrum‐predominant, pangastritis or corpus‐predominant) and the prevalence of lymphoid follicles were also investigated. RESULTS: Overall 89 patients (0.22%) were diagnosed with NG, which tended to decrease in prevalence over age and predominantly affected women. All the patients were Helicobacter pylori‐positive. Among these, 65 patients underwent biopsy. Activity and inflammation were mostly moderate or severe, while intestinal metaplasia and atrophy were mostly absent at all three sites. Pangastritis was the most frequent (72%) type of gastritis. Lymphoid follicles were found in 69% at the antrum, 65% at the angulus and 51% at the corpus. There were no significant differences between N and G types in clinical features, USS scores, topography of gastritis, and prevalence of lymphoid follicles. CONCLUSIONS: Atrophy and intestinal metaplasia are rare but activity and chronic inflammation are severe at the antrum, angulus and corpus in NG. Pangastritis is the commonest type of gastritis. Lymphoid follicles affect everything up to the upper corpus, contrary to endoscopic protrusion found only at angulus. There was no correlation with pathological features between N and G types.     

GASTRIC ADENOCARCINOMA OF FUNDIC GLAND TYPE (CHIEF CELL PREDOMINANT TYPE) TREATED WITH ENDOSCOPIC ASPIRATION MUCOSECTOMY

Upper endoscopy screening in an asymptomatic 56‐year‐old man showed a small, yellowish elevated lesion with a central depression on the posterior wall in the gastric cardia. Biopsy specimens from this lesion were suspicious of carcinoid tumor. We suspected this lesion to be a sporadic gastric carcinoid tumor with a diameter of 5 mm, limited to the mucosal layer. We then performed an endoscopic aspiration mucosectomy with a cap‐fitted endoscope. Microscopically, the lesion obtained from the resected specimen was minimally invasive to the submucosa and showed highly differentiated columnar cells in irregularly anastomosing glands. Immunohistology was positive for pepsinogen‐I, and MUC6, partially positive for H⁺/K⁺‐ATPase, and negative for MUC5AC. In addition, it was positive for synaptophysin and CD56, and negative for chromogranin A. We finally diagnosed the patient as having gastric adenocarcinoma of fundic gland type (chief cell predominant type) with minimal invasion (100 µm) to the submucosa. Surveillance endoscopy with biopsy specimens and abdominal computed tomography at 1 year revealed no evidence of tumor recurrence. We herein report this rare case of gastric adenocarcinoma of fundic gland type (chief cell predominant type).     

Gastric Mucosa Epithelial Cell Kinetics Are Differentiated by Anatomic Site and Helicobacter Pylori Infection

Changes in epithelial cell turnover related to Helicobacter pylori infection may contribute to gastric cancer development. The response of different anatomic sites of the gastric mucosa to H. pylori is not known. We studied apoptosis and cell proliferation at the grater and lesser curvature of the antrum and corpus, the fundus, and the cardia from 9 H. pylori gastritis patients and 11 H. pylori-negative controls with normal histology. Proliferation was highest at the major curve of the antrum and lowest at the fundus, and apoptosis was highest at the cardia and lowest at the major curve of the antrum in both H. pylori gastritis and normal mucosa. Proliferation was significantly higher at all anatomic sites, while apoptosis was significantly lower only at the major and lesser curve of the corpus in H. pylori gastritis compared with normal controls. Our data suggest that gastric mucosa epithelial cell kinetics is differentiated by the anatomic site and H. pylori infection.     

A Case of Early Gastric Cancer Manifesting as a Submucosal Tumor

Abstract: Gastric cancer manifesting as a submucosal tumor (SMT) is not common. A gastric barium meal and endoscopic studies performed on a 49-year-old male with epigastric pain, revealed an elevated lesion with bridging folds and central depression on the posterior wall of the lower body. An endoscopic ultrasonography (EUS) revealed a hypoechoic mass lesion within the submucosal layer. Due to an increase in the size of the tumor and its central depression during the subsequent year and a half, the patient was admitted for closer examination. Endoscopic biopsy material from the deeper layer, obtained by mucosal resection, revealed a poorly differentiated adenocarcinoma. Microscopic examination of the resected stomach showed a poorly differentiated adenocarcinoma within the submucosal layer, with considerable lymphocyte infiltration. Immunohistological examination disclosed marked T cell infiltration adjacent to the cancer cells. We suggest that considerable lymphocyte infiltration, particularly T cells, may have some role in the protective reaction against cancer cells. Our case was diagnosed as being cancer 18 months after the first endoscopic study. The biopsy material taken from the depression at the time of the first examination showed benign findings and a EUS revealed typical SMT. In the case of SMT shown by EUS to be a hypoechoic mass lesion in the submucosal layer, it is recommended that biopsy material be obtained from the deeper layer using methods available such as artificial ulcer formation.     

Eosinophilic gastroduodenitis showing nodular lesions in the gastric antrum and duodenal bulb

A 32‐year‐old female was admitted to Osaka National Hospital for remarkable anemia. She had a history of food allergy for the past 6 years. Laboratory examinations revealed remarkable iron de?ciency anemia and protein‐losing gastroenteropathy. On upper gastrointestinal endoscopy, multiple nodular lesions resembling verrucous gastritis were observed in the gastric antrum and the duodenal bulb. Marked mucosal eosinophilic in?ltration was seen in the biopsy specimens. Small intestine and colon were normal by X‐ray examination and colonoscopy, respectively. She was diagnosed as eosinophilic gastritis. Her symptoms, laboratory data and endoscopic ?ndings improved by regulation of food intake and administration of steroid. Rare endoscopic appearance of eosinophilic gastritis probably has strong correlation with food allergy.     

Comparative Classification and Grading of Helicobacter pylori Gastritis in Patients with Gastric Cancer and Patients with Functional Dyspepsia

Background: It has previously been shown that corpus-dominant grade and activity of Helicobacter pylori gastritis in combination with intestinal metaplasia in the antrum or corpus are risk markers for the development of stomach cancer. If one point is scored for each of these three parameters, a gastric cancer risk index is obtained that permits prediction of the risk of gastric cancer developing on the soil of H. pylori gastritis. The aim of the present study was to evaluate the accuracy of the gastric cancer risk index based on a large number of patients compared with dyspeptic controls. Methods: In 415 biopsied patients with gastric carcinoma, biopsy specimens taken from the antrum and corpus were investigated retrospectively. From this group of patients, 244 patients positive for H. pylori were compared with 244 sex- and age-matched H. pylori -infected patients with functional dyspepsia. Results: H. pylori gastritis was detected in 395 carcinoma patients (95.2%). The 244 sex- and age-matched patients significantly more frequently had corpus-dominant H. pylori gastritis (compared with NUD controls). The incidence of intestinal metaplasia was also significantly increased. For a gastric cancer risk index score of 3 points (i.e. corpus pronounced grade and activity of gastritis, and intestinal metaplasia in antrum or corpus), a sensitivity of 93% and a specificity of 85% for the presence of gastric carcinoma can be calculated. Conclusion: Using the proposed risk index, the topographic grading of H. pylori gastritis in the antrum and corpus enables the diagnosis of a 'risk gastritis' to be made.