Jin-Pok Kim

Nutritional Status of Gastric Cancer Patients after Total Gastrectomy

Abstract. A number of causes of malnutrition after total gastrectomy have been proposed. The purpose of this study was to assess nutritional status and to determine the cause of malnutrition after total gastrectomy. We studied 20 gastric cancer patients who had undergone total gastrectomy and immmunochemotherapy and 6 normal controls. Nutritional status was assessed by dietary history, anthropometric methods, and serologic measurements. Malabsorption tests included the fecal fat excretion test, d-xylose absorption test, glucose tolerance test, vitamin B 12 absorption test using dual isotopes, bacterial culture of jejunal aspirates, and jejunal biopsy. Weight loss was compared to the preoperative status in all patients (average 15%: 59.0 ± 9.9 vs. 50.2 ± 7.8 kg, preoperatively vs. postoperatively). Average daily calorie intake was 1586.2 kcal, which is lower than the normal intake of Korean adults (1838 kcal). Malnutrition of skeletal and visceral protein was not found. There was, however, severe fat malnutrition and a deficit of body fat. Postoperatively the body mass index was considerably lower than that preoperatively (22.2 ± 0.4 vs. 18.9 ± 0.4 kg/m 2 ; preoperatively vs. postoperatively). With malabsorption tests, the daily excreted amount of fecal fat was 28.6 ± 3.4 g (mean ± SD) in patients and 6.9 ± 0.2 g in controls. There was no significant malabsorption of carbohydrates. In 64.3% (9/14) of patients, vitamin B 12 absorption was abnormal; and the serum concentration of vitamin B 12 , which was significantly related to malabsorption of this vitamin, was lower than normal in 73.7% (14/19). Bacterial overgrowth was not found, and there were no abnormal histologic findings in the jejunal mucosa. These results suggest that poor oral intake and fat malabsorption following total gastrectomy cause malnutrition and that fat malabsorption may be related to relative pancreatic insufficiency.

Establishment and characterization of human gastric carcinoma cell lines

We report 8 newly established gastric‐carcinoma cell lines (SNU‐216, 484, 520, 601, 620, 638, 668, 719) from Korean patients. Morphologic study was carried out using light and electron microscopes. CEA, αFP, and CA 19‐9 and TPA in supernatant and in cell lysate were measured by radioimmunoassay. p53 and c‐Ki‐ras gene mutations were screened and confirmed by sequencing. The cell lines, derived from tumors with moderate differentiation, grew as a diffuse monolayer, and those from tumors with poor differentiation and minimal desmoplasia grew exclusively as non‐adherent. Out of the 8 gastric‐cancer cell lines, 5 had detectable levels of CEA both in supernatant and in cell lysate; there was no expression or secretion of αFP in these cells; 4 cell lines showed high levels of CA 19‐9 in cell pellets. All cell lines except SNU‐484 had high concentrations of TPA both in cell lysate and in supernatants. p53 mutation was found in 6 cell lines (75%): 2 (SNU‐216 and SNU‐668) had mutations in exon 6, and other 3 in exon 8. The c‐Ki‐ras mutation was found in 2 cell lines (25%), SNU‐601 and SNU‐668. The former showed GGT‐to‐GAT transition mutation at codon 12, while the latter showed CAA‐to‐AAA transversion mutation at codon 61. DNA profiles using restriction endonuclease Hinfl and polymorphic DNA probes ChdTC‐15 and ChdTC‐114 showed different unique patterns; which suggests that these cell lines are unique and not cross‐contaminated. We believe that the newly characterized gastric‐cancer cell lines presented in this paper will provide a useful in vitro model for studies related to human gastric cancer. Int. J. Cancer, 70:0–0, 1997.

Lymph node metastasis as a significant prognostic factor in early gastric cancer: Analysis of 1,136 early gastric cancers

AbstractBackground: Gastric cancer is the most frquent cancer and the leading cause of death from cancer in Korea. Early gastric cancer has been defined as a gastric carcinoma confined to mucosa or submucosa, regardless of lymph node status, and has an excellent prognosis with a >90% 5-year survival rate. From 1974 to 1992, we encountered 7,606 cases of gastric cancer and performed 6,928 gastric resections. Among them, 1,136 cases were early gastric cancer (14.9% of all gastric cancer cases and 16.4% of resected gastric cancer cases). Methods: A retrospective analysis of 1,136 cases of early gastric cancer was performed to evaluate the prognostic significance of clinicopathologic features (sex, age, tumor location, gross type, histologic type, depth of invasion, status of lymph node metastasis, resection type). Lymph node metastasis was classified into three groups: N(n=0) for no lymph node metastasis; N(n=1−3) for one to three lymph node metastases; and N(n>3) for more than three lymph node metastases. All patients received radical total or subtotal gastrectomy with lymph node dissection. Results: In univariate and multivariate analysis of these nine factors, the only statistically significant prognostic factor was regional lymph node metastasis (p<0.001). The others had no statistically significant association with prognosis. Lymph node metastasis was present in 178 cases (15.7%). The factors associated with the lymph node metastasis were depth of invasion and gross type [protruding type (e.g., types I, IIa)]. One hundred twenty-five of these patients had one to three lymph node metastases, and 53 cases had more than three lymph node metastases. The difference in 5-year survival rates among these groups was statistically significant: 94.5% for N(n=0), 88.3% for N(n=1−3), and 77.3% for N(n>3). Conclusion: We propose that for early gastric cancer, lymph node dissection is necessary in addition to gastric resection, at least in patients with a high risk of lymph node metastasis.

Risk of gastric cancer among Korean familial adenomatous polyposis patients : report of three cases

Gastric cancer has been recognized as an extracolonic manifestation in patients with familial adenomatous polyposis (FAP). In Korea, gastric cancer is the most common malignant neoplasm. In a recent survey, we collected data from 72 Korean patients with FAP. Among them, three (4.2 percent) were found to have associated gastric cancer. This incidence of gastric cancer in our series is much higher than the previous reports from Japan and other countries. The expected cumulative incidence of gastric cancer among these 72 patients was 0.44, which gives the standardized incidence ratio of 6.9 (95 percent CI, 1.4–20.1). This difference in incidence of gastric cancer was statistically significant (P< 0.05), which implies that patients with FAP are at significantly higher risk of developing gastric cancer compared with the general population in Korea. These findings confirm an increased risk of gastric cancer in FAP patients, even in a region where gastric cancer is highly prevalent.

Prognostic significance of Bcl-2 and p53 expression in gastric cancer

Background and aimsApoptosis regulates cell death and influences cell proliferation and therefore may play an important role in development or growth of various malignant tumors. The Bcl-2 and p53 are closely linked in the regulation of apoptosis. We investigated the prognostic significance of Bcl-2 and p53 expression in patients with gastric cancer.Patients and methodsImmunohistochemistry was used to study Bcl-2 and p53 expression in 308 consecutive patients with gastric cancer.ResultsBcl-2 expression was positive in 39 patients (12.7%) and showed a significant negative correlation with depth of invasion and lymph node metastasis. p53 expression was observed in 105 patients (34.1%) and was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and intestinal type. Patients with Bcl-2+ tumors showed a trend to better 5-year survival rate (81%) than those with Bcl-2− negative tumors (71%). The 5-year survival rate in p53 positive cases (60%) was significantly lower than that in p53-negative cases (78%). In addition, p53 expression showed a significantly poorer prognosis in both diffuse and intestinal types. In multivariate analysis restricted to patients with R0 resection p53 expression was an independent prognostic factor (relative risk: 2.063). In combined assessment of p53 and Bcl-2 expression the group with p53+/Bcl-2− tumors showed significantly worse 5-year survival (57%) than the other groups, while best survival was seen in the group with p53+/Bcl-2+ tumors (100%).Conclusionp53 expression is an unfavorable prognostic factor in gastric cancer. Bcl-2 expression may have possible prognostic value when combined with p53 expression.

Co-carcinogenic effects of several Korean foods on gastric cancer induced by N-methyl-N′-nitro-N-nitrosoguanidine in rats

In study I, 48 ACI and Fisher inbred rats were given MNNG 100 μg/ml, with or without 1 per cent or 3 per cent red pepper diet; in study II, 164 Sprague-Dawley rats given MNNG 100 μg/ml, with or without 5 per cent or 10 per cent NaCl; in study III, 181 Wistar rats given MNNG 83 μg/ml with or without maejoo 10 gm per cent/diet; in study IV, 78 Wistar rats given MNNG 83 μg/ml with or without ginseng extract 150 μg/ml; in study V, 120 Wistar rats given MNNG 83 μg/ml with or without retinyl palmitate 150,000 IU/kg. Except for study II (28 weeks), all rats were fed the diets for 37 weeks and were examined at 38 weeks or 40 weeks. In study I, tumor incidence in rats fed a red pepper diet and MNNG solution were 57 per cent (ACI rats, 1 per cent red pepper) and 63 per cent (Fisher rats, 1 per cent or 3 per cent red pepper) which were higher than control group (44 per cent, 43 per cent); in study II, gastric cancer, 61.9 per cent (10 per cent NaCl-MNNG), 27.3 per cent (control); in study III, gastric cancer, 14.8 per cent (maejoo-MNNG), 24 per cent (control); in study IV, malignant tumor of gastroduodenum, 3.4 per cent (ginseng-MNNG), 32.1 per cent (control); in study V, forestomach papilloma, 10.7 per cent (retinoid-MNNG), 29.4 per cent (control), and cancer in duodenum and small intestine, 50.0 per cent (retinoid-MNNG), 17.6 per cent (control). Thus, gastric carcinogenesis was enhanced by red pepper and a high salt diet, was inhibited by a maejoo and ginseng diet and was not effected by vitamin A.

Is the new UICC staging system of gastric cancer reasonable? (Comparison of 5-year survival rate of gastric cancer by old and new UICC stage classification)

In the new UICC TNM system for gastric cancer approved in 1985, a T1 lesion with lymph node (LN) metastasis is classified as stage, Ib; in the old TNM system this was classified as stage III. This is contradictory to a general rule of the UICC TNM system, whereby cancer with LN metastasis is classified as stage II or III. Two thousand and sixty-three patients with less than T4 gastric cancer who were treated at Seoul National University Hospital from 1970 to 1986 were analysed for significant prognostic factors. Survival curves were subsequently analysed according to the number of LN metastases and the depth of invasion. As a result of multivariate study for clinical and pathological features such as age, tumour location, gross appearance, histological type, depth of tumour invasion and regional lymph node metastasis, we confirmed that only two factors--regional lymph node metastasis and depth of gastric wall invasion--are significant. We showed that when the LN variable is classified according to the number of LN metastases (0 group, 1-3 group, > 3 group) like the UICC TNM classification of colorectal cancer, the survival curves are similar to those reported by the Japanese Research Society for Gastric Cancer. The authors propose the modification of the UICC TNM classification system according to depth of invasion and the number of LN metastases, whereby a T1 lesion with LN metastasis is classified as stage IIa instead of stage 1b.

Effect of multiple invasive foci on breast cancer outcomes according to the molecular subtypes: a report from the Korean Breast Cancer Society

BACKGROUND In this study, the prognostic impact of the presence of the multifocal or multicentric tumor (MMT) and its association with molecular subtypes were investigated. PATIENTS AND METHODS We investigated the breast cancer metastasis and survival in patients with multifocal or multicentric invasive foci in the same breast. The study population includes 2882 patients in the Seoul National University Hospital Breast Care Center (SNUHBCC) dataset and 41 179 patients in Korean Breast Cancer Registry (KBCR) dataset. RESULTS From SNUHBCC dataset, we observed a significant role of MMT in developing distant metastasis and death when the tumors were triple-negative subtype. This subtype-specific prognostic importance of MMT in overall survival was also seen in KBCR dataset (HR, 1.32; 95% CI, 1.02-1.69). In tumors <2 cm, the hazard ratios (HRs) for node metastasis and death were similar along the tumor size change in triple-negative subtype, while other subtypes showed a stepwise increment, suggesting the biologic importance of small invasive foci in this subtype. CONCLUSIONS Our results demonstrate the prognostic importance of MMT in patients with triple-negative breast cancers. Small additional invasive foci in triple-negative breast cancer patients should be considered as clinically relevant tumor deposits.

Overexpression of the 67 kD Laminin Receptor Correlates with the Progression of Gastric Carcinoma

This retrospective study was designed to investigate the relationship between overexpression of the 67 kD laminin receptor (67LR) using immunohistochemistry, and several clinicopathological parameters including overall survival in human gastric adenocarcinoma. We stained paraffin-embedded sections of 93 resected primary gastric adenocarcinomas using a polyclonal antibody specific for the 67LR as well as monoclonal antibodies for p53 protein, epidermal growth factor receptor, proliferating cell nuclear antigen, carcinoembryonic antigen and chromagranin. The results showed statistically significant correlations between overexpression of the 67LR and types of early or advanced gastric carcinoma (p < 0.001), depth of invasion (p < 0.001), WHO histopathologic classification (p < 0.001), stage (p = 0.001), expression of p53 protein (p = 0.019), expression of epidermal growth factor receptor (p < 0.001) and proliferating cell nuclear antigen labeling index (p = 0.002). A lower proportion of signet ring cells revealed a higher percentage of overexpression of 67LR in both early (p < 0.002) and advanced (p < 0.001) gastric carcinomas. Intestinal type adenocarcinoma (according to Laurens classification) revealed a higher percentage of overexpression of the 67LR than the diffuse type in both early (p = 0.057) and advanced (p < 0.001) gastric carcinomas. The correlations between overexpression of the 67LR and lymph node metastasis were statistically significant (p < 0.07). Although the overexpression of the 67LR tended to correlate with lower survival rates, the correlation was not statistically significant due to the limited sample size. Our data revealed that overexpression of the 67LR is correlated with the progression of gastric carcinoma. The expression of the 67LR may be important as one of the steps which determines invasiveness during the progression of cancer.

Gastric cancer in Korea: experience at the Seoul National University Hospital

Gastric cancer is the most common cancer in Korea and constitutes 24.2% of all malignancies, 29.6% of male tumors, and 17.8% of female tumors [1]. The annual incidence is 69.1 per 100,000 in males and 29.5 per 100,000 in females. The prognosis for gastric carcinoma continues to be unfavorable in this country. The annual death rates are 38.8 per 100,000 for male and 23.9 per 100,000 for female. Surgery can result in cures or longer disease free survivals in only a small number of patients, since most gastric carcinomas are diagnosed when the tumor is at an advanced stage. More than 50% of all patients with newly diagnosed gastric carcinoma at the Seoul National University Hospital (SNUH) had an unresectable, locally advanced disease, and/or distant metastases (Figure 1). While response rates in gastric cancer patients treated with a combination chemotherapy regimen are somewhat better than for colorectal cancer, complete responses are generally uncommon. Thus far, the only treatment that results in a significant cure of gastric cancer is surgery. As the result of surgery depends upon the stage of disease, only early detection has been the best method to cure gastric cancer up to now. In this chapter, we intend to summarize the biologic and pathologic characteristics of gastric cancer, data of detection with radiologic and endoscopic measures, and the results of surgical treatment and chemotherapy regimens utilized at SNUH.