Malignant Gastric Disease Research Articles

Gastric Stump Cancer

Purpose: Gastric stump cancer is defined as a cancer that develops in the stomach after a resection in cases of non-malignant or malignant gastric disease. The interval between the gastrectomy and the detection of gastric stump cancer must be over 5 years. Since duodenogastric reflux gastritis is a precancerous condition and one of the most important factors inducing gastric stump cancer, we compared the bile-acid content of gastric juice between gastric stump cancer patients and controls. Materials and Methods: To evaluate retrospectively the surgical treatment of patients with gastric stump cancer, we reviewed the cases histories of 1016 stomach cancer patients who had been operated on at the Department of General Surgery, Kosin University Gospel Hospital, between 1995 and 1998. The gastric juice was collected during the operations on the gastric stump cancer patients by using a needle puncture of the fundus of the stomach and during the endoscopic examinations of the control subjects. The samples were analyzed for various bile acids (gas chromatography/mass spectrometry). Results: The 6 gastric stump cancer cases accounted for of all gastric cancer patients; 5 patients were first operated on for a peptic ulcer and the remaining one for an adenocarcinoma of the stomach. All of the cases were men. The reconstruction method after the initial gastrectomy was a Billroth II in all cases. The sites of the gastric stump cancer were the anastomotic sitein 2 patients, the upper body in 2, the fundus in 1 and the cardia in 1. The operative methods were 3 total gastrectomies, 2 subtotal gastrectomies with Roux en Y anastomosis, and 1 partial gastrectomy with lymph node dissection and had a curative intention in all patients. All of the patients were still surviving at the time of this report. The gastric juices of 4 gastric stump patients showed significantly higher contents of cholic acid () compared to the gastric juices of 35 control subjects ()(p). Chenodeoxycholic acid and lithocholic acid were not significantly different. Conclusion: The gastric juice of gastric stump cancer patients contained a significantly higher cholic acid content. At the time of the initial gastrectomy, an operative method that prevents duodenogastric reflux may prevent or minimize the development of gastric stump cancer, and more aggressive surgical treatment may improve survival.

Evolution of Helicobacter pylori: the role of recombination

Helicobacter pylori is one of the most common pathogenic bacteria infecting humans. It is estimated that more than half of the human population is chronically colonized with this bacterium, which invariably causes a chronic inflammatory response of the stomach known as type B gastritis. Type B gastritis is asymptomatic in most patients but leads to ulceration of the stomach or the duodenum in ∼10% of those infected. H. pylori infection is also a risk factor for malignant gastric diseases, including carcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT). H. pylori has long been known to exhibit considerable genetic diversity. Molecular typing methods, such as restriction patterns of genomic DNA, random amplified polymorphic DNA (RAPD), pulsed-field gel electrophoresis or nucleotide sequencing of single genes, show that almost all H. pylori isolates from unrelated patients are unique and no clonal relationships have been observed1–4. The origin of this diversity has been attributed to several mechanisms, including an elevated mutation rate, impaired DNA repair mechanisms and frequent recombination (for an extensive review, see Ref. 5). Recent molecular genetic, population genetic and genomic studies have quantified the extent of H. pylori diversity and elucidated some of the underlying mechanisms.

New model of colon interposition following distal gastrectomy in rats.

An interposed colon segment has been clinically used as a gastric substitute following an esophagogastric resection for benign or malignant esophageal and gastric cardia disease. The purpose of this study is to establish a rat model of colonic interposition following distal gastrectomy and to investigate its serial mucosal changes. About 80% of the glandular stomach was resected, and a 3-cm segment of the transverse colon interposed isoperistaltically between the remnant stomach and duodenum. Epithelial proliferation and aberrant crypt foci in the interposed colon segment were investigated serially. Crypt lengths in the interposed colon increased significantly (P < 0.05) compared to the remnant colon. The number of goblet cells per crypt per 1 mm in the interposed colon also decreased significantly (P < 0.05) compared to the remnant colon. A PCNA labeling index (LI) of the remnant colon was almost 30%. A PCNA LI in the interposed colon at 4, 8, and 12 months after surgery was 30.8%, 31.8%, and 47.8%, respectively. The PCNA LI in the interposed colon increased significantly (P < 0.05) 12 months after surgery compared to the remnant colon at 4, 8, and 12 months after surgery. Aberrant crypt foci were not detected in the interposed colon segment. In conclusion, we established a rat model of colonic interposition following distal gastrectomy. The interposed colon mucosa adapted well. Long-term mucosal changes of the interposed colon segment should now be studied.

Immunoblot technique to visualise serum pepsinogen A isozymogen patterns.

Pepsinogen A (PGA) isozymogen patterns in urine and gastric mucosa can be visualised in non-denatured polyacrylamide gel electrophoresis by showing proteolytic activity after the conversion of pepsinogen into pepsin by acid. This method is not suitable for visualising PGA patterns in serum due to low PGA concentrations. To obtain a more sensitive visualisation method an immunoblotting technique was developed. PGA isozymogen patterns from urine and sonified gastric mucosa specimens obtained by immunoblotting were identical with those obtained by activity staining. The immunostaining method was at least 50 times more sensitive. PGA isozymogen patterns could be visualised in serum. Preliminary results suggest that the PGA patterns in serum and gastric mucosa are identical. As an association has been found between the genetically determined PGA isozymogen patterns in gastric mucosa and gastric malignancies in man, immunoblotting of PGA isozymogens in serum may provide a screening tool for subjects at risk of malignant gastric disease.

O6-Methylguanine-DNA transmethylase activity in extracts of human gastric mucosa.

In view of the possible involvement of N-nitroso compounds in the etiology of gastric carcinoma in man, we have examined the abilities of extracts of human gastric mucosa for the removal from DNA of O6-methylguanine, the primary precarcinogenic lesion induced in DNA by methylating carcinogenic N-nitroso compounds. We find that all 20 specimens examined (including 14 non-neoplastic and 6 neoplastic) possess significant activity, removing on average 0.73 +/- 0.06 (s.e.m.) pmol O6-methylguanine per mg protein in the extract. This activity, which has the characteristics of an O6-methylguanine-DNA-transmethylase, while exhibiting wide interindividual variations, shows no significant differences between the groups of normal and of neoplastic tissues or between the groups of non-neoplastic tissues obtained from individuals with benign or with malignant gastric disease. It is estimated that the average O6-methylguanine-removing capacity of the cells of normal gastric mucosa (calculated as 166 000 +/- 26 000 (s.e.m.) molecules per cell) greatly exceeds the extent of DNA damage likely to be caused by gastric-juice N-nitroso compounds.

Carcinoembryonic antigen in endoscopic brush specimens from benign and malignant gastric lesions

The measurement of carcinoembryonic antigen (CEA) in serum and endoscopic brush specimens was evaluated for the differential diagnosis of malignant and nonmalignant gastric disease. Brush specimens were studied from 33 patients with gastric cancer and 36 patients with benign gastric lesions or apparently normal gastric mucosa. Demonstrable CEA immunoreactivity was found by radioimmunoassay in brush specimens from 24/33 cancer patients (73%) and from 23/36 patients with benign lesions (64%). Patients with CEA+ tissue in the immunoperoxidase test had somewhat higher CEA concentrations in the brush specimens than cases with CEA- biopsy tissue, although overlap was considerable. Thirty-five per cent of cancer patients had both a positive tissue CEA reaction and a CEA/DNA ratio greater than 10 ng/micrograms, whilst patients with benign lesions had only 15% of positives by these criteria (0.01 greater than P greater than 0.001). The serum CEA concentration was above the upper normal level of 5 ng/ml in 2/39 patients, both of whom had gastric cancer. The CEA immunoreactive material from benign and malignant lesions eluted in gel filtration on Sephadex G-200 in the same volume as CEA purified from liver metastases of cancer of the colon, showing that a glycoprotein sharing immunological and physicochemical properties with CEA is present both in malignant and nonmalignant lesions of the gastric mucosa, and that there is considerable overlapping in the amount of CEA. The estimation of CEA in gastric-brush specimens is therefore of limited value in the differential diagnosis of benign and malignant gastric lesions.

GASTRIC CANCER: QUO VADIMUS?

The majority of nonmalignant gastric ulcers are satisfactorily controlled by simple antrectomy or antrectomy combined with wedge excision. In a recent issue of the<i>Archives of Surgery</i>, Eisenberg and Woodward¹have expressed serious concern for the 80% to 90% of patients who undergo unnecessarily extensive resective procedures. Fortunately, diagnostic acumen has evolved to the point where the differentiation between benign and malignant gastric disease should impose little difficulty. Several studies have demonstrated that, while the individual use of standard diagnostic techniques—x-ray, cytology, and gastroscopy—has an accuracy yield of 60% to 80%, by the combined use of all three techniques, from 94% to 99% of lesions can be properly characterized preoperatively. On this basis, ill-advised radical surgery for the nonmalignant ulcer can be minimized. As a by-product of these observations, analysis of currently available data has brought into sharper focus the inadequacy of surgical management of stomach cancer. It is