Pathological appearance of the stomach after endoscopic mucosal resection for early gastric cancer

BACKGROUND: The pathological findings of the resected stomach after endoscopic mucosal resection (EMR) for early gastric cancer were reviewed. EMR was indicated when a lesion consisting of well or moderately differentiated adenocarcinoma had a diameter of less than 2 cm. METHODS: Of 39 patients with early gastric cancer were treated with EMR between 1990 and 1995, 11 required additional surgery. RESULTS: Malignant tissue in the gastric wall was completely removed in four patients, while cancer cells remained in the mucosa adjacent to the scar in five and infiltrated into the submucosa in two. Most of these residual cancers were characterized by a lesion with a diameter exceeding 15 mm and by the location in the body or cardia of the stomach. Lymph node metastases were observed in one patient whose carcinoma invaded the deeper submucosal layer. Assessment of the depth of entire invasion from the endoscopically-resected specimen was correct for six of 11 patients. CONCLUSION: Gastric carcinomas to be resected by EMR should be smaller, especially if located in the body or cardia. Accurate diagnosis of the width and depth of invasion is indispensable before proceeding to EMR. Surgery may be the treatment of choice when there is submucosal invasion.     

Body mass index and the risk of cancers of the gastric cardia and distal stomach in Shanghai, China

The divergent incidence patterns of gastric cardia and distal stomach cancers suggest different etiologies. Although obesity has recently been linked to cardia cancer in Western populations, its association with distal stomach cancer remains unclear. This study examined the relation of anthropometric measurements to risk by subsites of stomach cancer in a Chinese population. We identified 1124 population-based cases of stomach cancer, ages 20-69 years, newly diagnosed between December 1988 and November 1989 in Shanghai, China. Controls (n = 1451) were randomly selected from permanent Shanghai residents and frequency-matched to cases by age and sex. Information on demographic characteristics, height and weight, diet, smoking, and other exposures was obtained by trained interviewers in person. The body mass index (BMI) was calculated as weight in kilograms divided by height in square meters and categorized into quartiles based on the distribution among controls. Odds ratios and 95% confidence intervals were estimated using logistic regression models, simultaneously adjusting for age, education, income, cigarette smoking (men only), alcohol drinking (men only), intake of total calories, and chronic gastric diseases. For gastric cardia cancer, the odds ratios among men were 1.4, 1.5, and 3.0 in the second, third, and fourth quartiles of usual BMI (P for trend, < 0.01). Among women, elevated risks also were associated with excess weight, but the gradient in risk was not smooth. Risk patterns for usual body weight, maximum BMI, and minimum BMI were similar to those found for usual BMI. For distal stomach cancer, no association with usual BMI was observed among men, but a slightly elevated risk was seen among women. Our observations in China support recent findings in Western populations that obesity contributes to the risk of gastric cardia cancer, especially among men.     

Two cases of gastric involvement of esophageal cancer: intramural metastasis and intramural lymph node metastasis

Cases of esophageal cancer with intramural metastasis to the stomach and esophageal cancer with metastasis to an intramural lymph node of the stomach are herein reported. The former patient was a 52 year-old male. Squamous cell carcinoma (SCC) of the lower esophagus with an intramural metastasis located at the gastric cardia and a small leiomyoma at the fornix were resected. The latter patient was a 70 year-old female. SCC of the lower esophagus and an intramural lymph node metastasis located at the anterior wall of the gastric cardia were resected. The patient died nevertheless of multiple liver metastases. These gastric involvements were detectable by endoscopy before surgery. The clinicopathological features of these esophageal cancers were characterized; the sites were the lower part of the esophagus, and extreme lymphatic and vascular invasions were shown histologically. The gastric tumors were located in the upper third of the stomach, and the findings revealed submucosal tumors. It is therefore important to discriminate other gastric tumors, and to resect them simultaneously with esophageal cancer when a gastric tube has been used for reconstruction after esophagectomy.     

Distribution and frequency of gastric cancer at the para-cardiac region and fornix

To clarify the distribution and frequency of gastric cancer in the upper third of the stomach, especially in the para-cardiac region and fornix, we reviewed 634 lesions of all gastric cancers in any location in the University Hospital of Tsukuba University from April 1985 to March 1992. The para-cardiac region was defined as a circular area of 6 cm in diameter around the cardia. We found 56 lesions (8.8%) in the para-cardiac region, almost all of which were concentrated in the distal half of the para-cardiac region, and only three of which (0.47%) were in the fornix. Cancer in the upper third of the stomach tended to occur predominantly in aged male patients, and histologically most of them were classified as having differentiated adenocarcinoma. Since the percentage of advanced cancer at the para-cardiac region was much higher than at any other location, we should be careful to obtain double-contrast images of sufficient quality during the upper gastrointestinal examinations and not to overlook subtle changes in this region during the interpretation of films.     

Risk of esophageal and gastric adenocarcinomas in relation to use of calcium channel blockers, asthma drugs, and other medications that promote gastroesophageal reflux

Incidence of adenocarcinomas of the esophagus and gastric cardia has risen dramatically over the past 2 decades in the U. S., for reasons that are not yet clear. A number of common medications (e.g., calcium channel blockers, tricyclic antidepressants, and certain asthma medications) promote gastroesophageal reflux by relaxing the lower esophageal sphincter (LES). Reflux is thought to increase cancer risk by promoting cellular proliferation, and by exposing the esophageal epithelium to potentially genotoxic gastric and intestinal contents. Recent studies have suggested that calcium channel blockers may also increase cancer risk by inhibiting apoptosis. Using personal interview data from a multicenter, population-based case-control study conducted between 1993 and 1995 in three areas of the U. S., we evaluated whether the use of LES-relaxing drugs was associated with increased risk of adenocarcinomas of the esophagus and gastric cardia. Cases of esophageal adenocarcinoma (n = 293) and gastric cardia adenocarcinoma (n = 261) were compared with general population controls (n = 695). Information on additional case groups of esophageal squamous cell carcinoma (n = 221) and noncardia gastric cancer (n = 368) were also available for comparison. Overall, 27.4% of controls had used one or more of these drugs for at least 6 months, compared with 30.2% of esophageal adenocarcinoma and 23.8% of gastric cardia adenocarcinoma cases. The adjusted odds ratios (ORs) for ever use were 1.0 [95% confidence interval (CI) = 0.7-1.5] and 0.8 (95% CI = 0.5-1.1), respectively. There was little evidence of increasing risk with increasing duration of use of all LES-relaxing drugs together. We found an increased risk of esophageal adenocarcinoma among persons reporting use of asthma drugs containing theophylline (OR = 2.5; 95% CI = 1.1-5.6) or beta agonists (OR = 1.7; 95% CI = 0.8-3.8). Risks were higher among long-term users (>5 years) of these drugs (OR = 3.1; 95% CI = 0.9-10.3 and OR = 2.3; 95% CI = 0.8-7.0, respectively). In contrast, there was no evidence that the use of calcium channel blockers or other specific groups of drugs increased the risk of any of the cancers studied. These results provide reassuring evidence that the increases in incidence of adenocarcinomas of the esophagus and gastric cardia are not likely to be related to the use of LES-relaxing drugs as a group, or calcium channel blockers in particular, but they do suggest that persons treated for long-standing asthma may be at increased risk of esophageal adenocarcinoma.     

NMR spectroscopy of human post mortem cerebrospinal fluid: distinction of Alzheimer''s disease from control using pattern recognition and statistics

Mutations of ras oncogenes in 37 human stomach cancers and 13 adenomas were investigated with regard to the histological phenotypes using polymerase chain reaction (PCR), allele-specific oligonucleotide hybridization and/or direct sequencing of the PCR products. The ras mutation was found only in one case (2.7%), the histology of which was poorly differentiated adenocarcinoma. We found no mutation in stomach adenomas. The mutation consisted of a guanine-to-adenine transition in the first base of codon 13 of c-Ki-ras which replaced wild-type glycine with serine, indicating that a putative glycine-to-aspartic acid change is not necessarily the critical event for c-Ki-ras gene activation in codon 13. These results further confirm the infrequency of ras mutation in stomach tumors and also suggest that ras mutations are not specific to the differentiated type of stomach cancer.     

Results of treatment of cancer of the cardia

Cancer of the cardia is traditionally discussed with cardiac cancer of the lower portion of the esophagus and upper gastric cancer invading the esophagus, and the specific characteristics of cancer of the cardia have never been clearly defined. We reviewed the outcome of 172 patients with adenocarcinoma of the cardia who had undergone radical surgery between 1949 and 1994 in the Division of Gastrointestinal Surgery of the Cancer Institute Hospital. The centers of the tumors were located within 2 cm above and below the boundary between the esophagus and the stomach, and their longitudinal diameter was less than 8 cm. We divided the patients into an early period (1949-1979; n = 79) and a late period (1980-1994; n = 93), and focused on the historical transition. There were no differences in patient gender or histology between the two periods. However, the late period was associated with fewer cases of esophageal invasion and shorter longitudinal diameter, as the age of the population advanced. The number of advanced cancers such as the localized and infiltrative type had decreased, and early cancer and early clinical stage had become more common, but despite the fact that the number of early cancers had increased, extended dissection, such as thoracic and paraaortic lymph node dissection, was performed more frequently. By clinical stage, the long-term outcome markedly improved in Stage I patient in the late period, and tended to improve in Stage II and III patients. This appears to have been attributable to the prevention of micrometastasis by extended dissection, although the number of early cancers is another major potential cause. There were no differences in the outcome of Stage IV patients between the two periods, and further advances in multimodality therapy must be awaited. The range of resection is basically proximal gastrectomy, and if there are adequate indications, the prognosis is favorable. In view of the status of lymphatic flow and lymph node metastasis, and long-term results, lateroaortic lymph node dissection is important. Since the number of early cancer patients has been increasing, if intraabdominal recurrence is prevented, intrathoracic lymph node dissection will contribute greatly to the outcome of such patients.     

Functional and evolutionary implications of natural variation in clock genes

Stomach cancer remains the second leading cancer in incidence in Shanghai, China, despite its decline over the past 2 decades. To clarify risk factors for this common malignancy, we conducted a population-based case-control study in Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20-69) newly diagnosed in 1988-1989 and 1,451 controls randomly selected among Shanghai residents. Usual adult dietary intake was assessed using a comprehensive food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Risks of stomach cancer were inversely associated with high consumption of several food groups, including fresh vegetables and fruits, poultry, eggs, plant oil, and some nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast, risks increased with increasing consumption of dietary carbohydrates, with odds ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1-2.1) and 1.9 (95% CI 1.3-2.9) in the highest quartile of intake among men (p for trend=0.02) and women (p=0.0007), respectively. Similar increases in risk were associated with frequent intake of noodles and bread in both men (p=0.07) and women (p=0.05) after further adjustment for fiber consumption. In addition, elevated risks were associated with frequent consumption of preserved, salty or fried foods, and hot soup/porridge, and with irregular meals, speed eating and binge eating. No major differences in risk were seen according to subsite (cardia vs. non-cardia). Our findings add to the evidence that diet plays a major role in stomach cancer risk and suggest the need for further evaluation of risks associated with carbohydrates and starchy foods as well as the mechanisms involved.     

Brachytherapy and breast cancer

The study compares, in true adenocarcinoma of the cardia and in adenocarcinoma in Barrett's esophagus, the prevalence of early cancers and their outcome in those patients suitable for resection surgery. From 1980 to 1993, 26 of 350 (7.4%) resected adenocarcinomas of the esophago-gastric junction were pathologically staged as early cancer or pT1. The prevalence of early cancer was 3.7% (11/294) for true cancer of the cardia and 27% (15/56) for cancer in Barrett's esophagus (P < 0.001). Ten of the 15 latter cancers were diagnosed during endoscopic surveillance for benign Barrett's esophagus. Among early cancers, there were four mucosal and 22 submucosal tumours; of the latter, eight had lymph node metastasis and seven neoplastic permeation of lympho-hematic vessels. The most frequently used surgical procedure was esophago-gastric resection and gastric pull-up. Postoperative morbidity was 15.4%, and hospital mortality 3.8%. Excluding postoperative deaths, the overall 5-year survival rate was 79% for early cancer of the cardia and 83% for early cancer in Barrett's esophagus (log rank test = 0.0214, P = 0.88). Overall, the survival rate was 100% in the absence of lymph node metastasis and 43% in the presence of node metastasis (log rank test = 15.811, P = 0.0001). Only one of five patients with both node metastasis and vessel infiltration survived longer than 5 years. In conclusion, the prevalence of early cancer was significantly greater for cancer in Barrett's esophagus than for true cancer of the cardia. Prognosis of the two types of tumour after resection surgery was the same and depended on lymph node status and neoplastic permeation of lympho-hematic vessels.     

Experimental gastric cancer (author's transl)

Methods have been established to produce gastric cancer in rats and dogs by administration of N-methyl-N'-nitro-N-nitrosoguanidine or of the ethyl derivate. The agent is administered in drinking water or by a pellet diet soaked in the carcinogen. Histologically well differentiated and poorly differentiated types of adenocarcinoma and signet-ring cell tumors are induced in several months with greath reliability. Metastases were observed in both rats and dogs with gastric carcinoma. The carcinogenic effect could be enhanced by surface active agents, sodium chloride, iodoacetamide, insertion of plastic beads into the stomach and gastroenteroanastomosis. Follow-up studies by radiologic, endoscopic and bioptic examinations are possible in the dog. There are similarities in these experimental tumors to those in man and thus they provide means for the investigation of histogenesis, prevention, and chemotherapy of gastric cancer. An adenocarcinoma of the glandular stomach of a Wistar rat was successively transplanted to new born rats of the same strain.     

Advanced glycation endproducts are associated with Hirano bodies in Alzheimer''s disease

Green tea is now an acknowledged cancer preventive in Japan. This paper discusses several important features of (-)-epigallocatechin gallate (EGCG), the main constituent of green tea and tea polyphenols. EGCG and other tea polyphenols inhibited growth of human lung cancer cell line, PC-9 cells with G2/M arrest. 3H-EGCG administered by p.o. intubation into mouse stomach revealed that small amounts of 3H-activity were found in various organs where EGCG and green tea extract had previously demonstrated their anticarcinogenic effects, such as skin, stomach, duodenum, colon, liver, lung and pancreas. Cancer onset of patients who had consumed over 10 cups of green tea per day was 8.7 years later among females and 3.0 years later among males, compared with patients who had consumed under three cups per day. The mechanisms of action of EGCG were briefly discussed with regard to inhibition of tumor necrosis factor-alpha (TNF-alpha) release.     

Adenocarcinoma in the middle third of the stomach--an evaluation for the prognostic significance of clinicopathological features

BACKGROUND/AIMS: The prognosis of patients with gastric adenocarcinoma varies with the location of the tumor. Adenocarcinoma in the middle third of the stomach has been claimed to have a better outcome than those in other locations. However, there is still very limited information specifically regarding the prognostic factors which influence the survival time of patients with adenocarcinoma in the middle third of the stomach. This retrospective study was designed with the aim to evaluate and uncover the possible significant clinicopathological parameters for adenocarcinoma in the middle third of the stomach. METHODOLOGY: Between 1986 and 1992, 363 patients underwent gastric resection for primary gastric adenocarcinoma at this hospital. Fifty-two (14.3%) of these patients were included in this study and they all met the following criteria: 1) tumor primarily located in the middle third of the stomach without distant metastases or peritoneal seeding, 2) undergoing curative resection and 3) undergoing R2 nodal dissection, at least. The clinicopathological findings were obtained by detailed review of the medical records and the histologic slides. All surviving patients were also contacted and their current conditions were recorded. RESULTS: The overall 5-year survival rate (Kaplan-Meier method) was 42.5%. In univariate survival analysis by Kaplan-Meier method and long-rank test, serosal invasion (p < 0.01), lymph node metastasis (p < 0.01) and lymphatic involvement (p < 0.01) had an individual prognostic significance. When a multivariate analysis using Cox proportional hazards regression was performed, serosal invasion (P < 0.01) and lymphatic involvement (p < 0.05) appeared as the only two independent prognostic factors regarding long-term survival. When these 52 patients were categorized into patients with early gastric cancer (n = 10) and patients with advanced gastric cancer (n = 42), there was a significant difference (p < 0.01) between the survival rates (90.0% vs. 29.1%). When these tumors were further categorized into early gastric cancer (n = 10), early simulating advanced gastric cancer (n = 14) and Borrmann type advanced gastric cancer (n = 28), there were significant differences (P < 0.01 and P < 0.01, respectively) in 5-year overall survival rates between early gastric cancer (90.0%) and Borrmann type advanced gastric cancer (18.9%), also between early simulating advanced gastric cancer (52.5%) and Borrmann type advanced gastric cancer (18.9%). UICC stage also had significant influence (P < 0.01) on the survival rates. CONCLUSIONS: Serosal invasion and lymphatic involvement are the significant, independent prognostic factors in predicting the survival rate of patients with adenocarcinoma in the middle third of the stomach. Since more advanced stage tumors usually carry a poorer prognosis, early detection is of extreme importance for improving the survival rate.     

A case of esophageal cancer required jejunal reconstruction because of a gastric ulcer scar

Recently, with increase of number of esophagectomy for esophageal cancer, the cases having the lesion in the organs for esophageal substitute have been increasing. The case of esophageal cancer, required reconstruction using the pedicled jejunum, because of impaired submucosal blood perfusion of the stomach caused by a ulcer scar, was reported. The patient was a 72-year-old female, with the ulcerative and infiltrative cancer lesion in the anterior wall of the mid-thoracic esophagus. Barium swallow revealed shortening of the lesser curvature and indentation of the greater curvature of the stomach. Endoscopy showed the lesion occupying anterior two thirds of the esophageal wall circumferentialy from 30 to 34 cm from the incisor tooth. The lineal scar of ulcer on the lesser curvature of the body of the stomach was also found. Following esophagectomy through right thoracotomy, the stomach was mobilized for reconstruction by dividing left gastric artery and short gastric artery, but the stomach oral to the ulcer scar became ischemic and bleeding was not found at the tip of the stomach. Therefore, reconstruction was performed using the pedicled jejunum through antesternal route. The gastric cardia is rich in the vascular network in the submucosal layer. The ulcer or ulcer scar of this region can cause ischemia in the tip of the gastric tube for esophageal substitute. Care should be taken to detect the ulcer lesion at the stomach preoperatively. In the case with the ulcer lesion blood supply to the tip of the gastric tube should be critically evaluated.     

Evaluation of high-resolution CT and MR cisternography in the diagnosis of cerebrospinal fluid fistula

BACKGROUND & AIMS: Whether inflammation of the cardia indicates gastroesophageal reflux disease (GERD) and/or is a manifestation of pangastritis caused by Helicobacter pylori infection is unknown. The aim of this study was to evaluate the relationship between cardia inflammation, H. pylori infection, and cardia intestinal metaplasia in patients with and without GERD. METHODS: Patients with GERD were compared with controls undergoing endoscopy for a variety of other conditions. Endoscopic biopsy specimens from the distal esophagus and cardia, fundus, and antrum were evaluated for inflammation, H. pylori infection, and intestinal metaplasia. RESULTS: Neither the prevalence of H. pylori infection (controls, 48%; GERD, 41%) nor cardia inflammation (controls, 41%; GERD, 40%) differed between groups. All 11 controls and 22 of 23 patients with GERD (96%) and cardia inflammation had H. pylori infection. Esophagitis was more common among GERD patients (33%) than controls (7%; P = 0.01). Cardia intestinal metaplasia was more common among controls (22%) than GERD patients (3%; P = 0.01); all had cardia inflammation, 7 had H. pylori infection, and 6 had metaplasia elsewhere in the stomach. CONCLUSIONS: The prevalence of cardia inflammation is similar in patients with and without GERD and is associated with H. pylori infection (P < 0.001). Cardia intestinal metaplasia is associated with H. pylori-related cardia inflammation (P = 0.01) and intestinal metaplasia elsewhere in the stomach, indicating that it is distinct from Barrett's esophagus.     

Laparoscopic surgery for early gastric cancer--its advantage and pitfall

We have successfully treated 50 patients with early gastric cancer by using two different laparoscopic procedures since March 1992. which are laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 33) and laparoscopic intragastric mucosal resection (n = 17). The indication is as follows; (A) mucosal cancer, (B) < 25 mm, if the lesion is protruded type, (C) < 15 mm and Ul(-), if the lesion is depressive type. The advantages of these methods are; 1) minimally invasiveness. 2) sufficient surgical margin, 3) feasibility of detailed histology, 4) feasibility of perigastric lymph node dissection. In contrast, there are several problems to be solved, which are; 1) preoperative diagnostic accuracy of the depth of cancer invasion, 2) possibility of reoperation because of sm invasion or lymphatic or venous invasion in final histology, 3) possibility of postoperative stenosis after laparoscopic intragastric mucosal resection for the lesion near the cardia, 4) incidence of metachronous multiple gastric cancer.     

Enhanced expression of cytochrome P450 in stomach cancer

The cytochromes P450 have a central role in the oxidative activation and detoxification of a wide range of xenobiotics, including many carcinogens and several anti-cancer drugs. Thus the cytochrome P450 enzyme system has important roles in both tumour development and influencing the response of tumours to chemotherapy. Stomach cancer is one of the commonest tumours of the alimentary tract and environmental factors, including dietary factors, have been implicated in the development of this tumour. This type of tumour has a poor prognosis and responds poorly to current therapies. In this study, the presence and cellular localization of several major forms of P450, CYP1A, CYP2E1 and CYP3A have been investigated in stomach cancer and compared with their expression in normal stomach. There was enhanced expression of CYP1A and CYP3A in stomach cancer with CYP1A present in 51% and CYP3A present in 28% of cases. In contrast, no P450 was identified in normal stomach. The presence of CYP1A and CYP3A in stomach cancer provides further evidence for the enhanced expression of specific forms of cytochrome P450 in tumours and may be important therapeutically for the development of anti-cancer drugs that are activated by these forms of P450.     

Prevention of gastric cancer: Helicobacter--eradication and immunization]

Adenocarcinoma of the stomach (excluding carcinoma of the cardia) has been established as a consequence of gastric infection with Helicobacter pylori (H.p.). The specific role of H.p. in the pathogenesis is unknown so far; yet, several other factors are involved in the development of the neoplasia. Since-in contrast to the wide prevalence of the infection-only very few persons will develop gastric carcinomas, prophylaxis by H.p. eradication is not advisable. This may change after a vaccination has become available; however, studies on the characterization of efficient vaccines are still under investigation. Thus, H.p. eradication treatment may, if at all, be used as prophylaxis for gastric carcinoma only in clinical studies and in subjects at a high risk for this tumour.     

Adenocarcinoma of the stomach: radiological and pathological correlation of effects of treatment with fast neutrons

During the past six years 40 patients have been treated with fast neutrons for inoperable adenocarcinoma of the stomach. A number of these patients have been studied in detail both radiologically and pathologically with regard to the effects of fast neutrons on both the tumour and normal stomach. After treatment there was a constant reduction in size of the stomach capacity when compared with a control group and the motility of the stomach was lost. Mucosal changes, which were noted radiologically, appeared to be dose related. Histologically most of the tumour was destroyed. Small clumps of cells were, however, found in all except one of the patients but only in areas of the stomach which had not received the standard dose. Marked fibrosis occurred and it is our impression that the amount of fibrosis is in excess of that seen with other forms of radiotherapy.     

Laparoscopic surgery for early gastric cancer--its advantages and pitfalls]

We have successfully established two different laparoscopic procedures for early gastric cancer since March 1992, which are laparoscopic wedge resection of the stomach using a lesion-lifting method and laparoscopic intragastric mucosal resection. The indication is as follows; (A) mucosal cancer, (B) < 25 mm, if the lesion is elevated type, (C) < 15 mm and Ul (-), if the lesion is depressive type. The advantages of these methods are; 1) minimally invasiveness, 2) sufficient surgical margin, 3) feasibility of detailed histology, 4) feasivility of perigastric lymph node dissection. In contrast, there are several problems to be solved, which are; 1) preoperative diagnostic accuracy of the depth of cancer invasion, 2) possibility of reoperation because of sm invasion or lymphatic or venous invasion in final histology, 3) possibility of postoperative stenosis after laparoscopic intragastric mucosal resection for the lesion near the cardia, 4) incidence of metachronous multiple gastric cancer. In conclusion, if the indication is properly selected, these laparoscopic procedures are curative and minimally invasive treatment for early gastric cancer.