Showing papers in "Gastric Cancer in 2000"

Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers

Abstract: Background. The presence of lymph node metastasis (LNM) is the most important prognostic factor for patients with early gastric cancer (EGC). A D2 gastrectomy has been the gold standard treatment. Strict criteria for endoscopic mucosal resection have been widely accepted in Japan. There are some trials aimed at expanding the indications for local treatment, although there has not been a comprehensive review of the risk of LNM with the lesions of EGC. Methods. We investigated 5265 patients who had undergone gastrectomy with lymph node dissection for EGC at the National Cancer Center Hospital and the Cancer Institute Hospital. Nine clinicopathological factors were assessed for their possible association with LNM. Results. None of the 1230 well differentiated intramucosal cancers of less than 30 mm diameter regardless of ulceration findings, were associated with metastases (95% confidence interval [CI], 0–0.3%). None of the 929 lesions without ulceration were associated with nodal metastases (95% CI, 0–0.4%) regardless of tumor size. Similarly to findings for intramucosal cancers, for submucosal lesions, there was a significant correlation between tumor size larger than 30 mm and lymphatic-vascular involvement with an increased risk of LNM. None of the 145 differentiated adenocarcinomas of less than 30-mm-diameter without lymphatic or venous permeation were associated with LNM, provided that the lesion had invaded less than 500 μm into the submucosa (95% CI, 0–2.5%). Conclusion. Based on our large series of cases, we have been able to clarify the risks associated with EGC and to propose expansion of the criteria for local treatment. However, accurate histological evaluation of the resected specimens is essential to avoid recurrence for such EGCs that should be cured.

Screening for gastric cancer in Japan

Abstract: In Japan, mass screening for gastric cancer with photofluorography was initiated in 1960. At present, over 6 million people are screened annually. The sensitivity and specificity of photofluorography are 70%–90% and 80%–90%, respectively. The 5-year survival rate is 15%–30% better in screen-detected cancers than in symptom-diagnosed cases. Although no randomized controlled trials have been reported, cohort and case-control studies generally showed a decreased risk of mortality from gastric cancer in the screened subjects. The summary odds ratio (95% confidence interval) of three case-control studies for ever screened versus never screened subjects was 0.39 (0.29–0.52) for men and 0.50 (0.34–0.72) for women. Substantial evidence indicates that the Japanese screening program with photofluorography is effective in reducing the mortality from gastric cancer. The measurement of serum pepsinogens has recently drawn attention as an alternative to photofluorography, given its lower cost and simplicity. Some studies have suggested a comparable accuracy for the two methods. However, these investigations may have overestimated the relative sensitivity of serum pepsinogen testing compared with photofluorography, because serum pepsinogen testing was conducted as prevalent screening, while photofluorography was done as incident screening. Furthermore, no studies have directly examined whether the screening with serum pepsinogens reduced gastric cancer mortality. Therefore, at present, evidence is insufficient to determine the benefit of this program.

Laparoscopic D2 lymph node dissection for advanced gastric cancer located in the middle or lower third portion of the stomach.

Abstract: The standard lymph node dissection for advanced gastric cancer is a D2 dissection, performed in accordance with the new Japanese classification of gastric carcinoma (13th edition). Although laparoscopic D2 dissections according to the General rules for gastric cancer study (12th edition) have been reported, no studies have reported laparoscopic D2 dissections according to the revised classification for advanced gastric cancers located in the middle or lower portions of the stomach. The lack of such studies is due to the perceived technical difficulty of the procedure. However, we successfully performed this novel procedure in five patients with advanced gastric cancer located in the middle or lower portions of the stomach. In fact, this surgical procedure is technically feasible and safe.

Evaluation of serum CEA and CA19-9 levels as prognostic factors in patients with gastric cancer.

Abstract: BACKGROUND: This clinicopathological study evaluated the utility of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as predictors of locoregional recurrence and long-term disease-free survival in patients with gastric cancer.METHODS: During the period January 1989 to December 1994, 485 patients with primary gastric cancer were evaluated. Gastrectomies were performed in 434 patients. Prognostic factors were analyzed by the Kaplan-Meier method and multivariate analysis, using Cox regression.RESULTS: Elevated serum CEA and CA19-9 levels were observed in 92 of the 485 patients (19.0%), and in 95 of the 435 patients (21.8%), respectively, and both markers were elevated in 29 of these 435 patients (6.7%). Elevated serum CEA and CA19-9 levels correlated well with lymph node metastasis, lymphatic invasion, vessel invasion, stage grouping, depth of invasion, and curability. Patients with elevated serum CEA levels were at significantly higher risk of having all recurrence factors than were those with normal serum CEA levels. Patients with elevated serum CA19-9 levels were at significantly higher risk of having peritoneal metastases and distant metastases than were those with normal serum CA19-9 levels. A significant difference in the cumulative survival curves of patients was demonstrated between those with elevated and those with normal serum CEA or CA19-9 levels, even for patients at the same disease stage (stage III). Patients with elevated levels of both markers had a significantly worse prognosis than patients in whom the levels of both markers were normal. In patients who underwent gastrectomy, elevated serum CEA levels either preoperatively or within 3 weeks after gastrectomy were associated with significantly worse prognosis than were normal levels. When the cutoff level of serum CEA was increased to 10 ng/ml, serum CEA, age, lymph node metastasis, and surgical stage grouping were selected as independent prognostic factors by multivariate analysis of 14 prognostic factors, using Cox regression.CONCLUSION: Serum CEA and CA19-9 levels provide additional prognostic information in patients with primary gastric cancer. In particular, an elevated serum CEA level provides additional prognostic information and is a useful indicator of curability in patients who undergo gastrectomy. Serum CEA level is an independent prognostic factor in patients with primary gastric cancer.

Effect of fat volume on postoperative complications and survival rate after D2 dissection for gastric cancer.

Abstract: BACKGROUND: D2 lymph node dissection in gastric cancer is controversial in Western countries because of the relatively high complication and mortality rates. The purpose of this study was to clarify the effects of fat volume on operation factors, postoperative complications, and survival in gastric cancer surgery.METHODS: We studied 293 consecutive patients who had undergone distal gastrectomy with D2 dissection for gastric cancer at our hospital between 1990 and 1997. The patients were classified into three groups according to their body mass index (BMI; kg/m(2)). We analyzed differences in the operation time, the amount of blood loss, the postoperative complications and the survival rate among the three groups.RESULTS: Group A patients had a BMI of less than 20 ( n = 61), group B had a BMI of 20-25 ( n = 178), and group C had a BMI of more than 25 ( n = 54). There were significant differences in operation time (group A, 206 +/- 66 min; group B, 226 +/- 61 min; group C, 252 +/- 61 min; P < 0.05), blood loss (group A, 417 +/- 282 ml; group B, 501 +/- 295 ml; group C, 605 +/- 333 ml; P < 0.05), and postoperative complications (group A, 3.3%; group B, 5.6%; group C, 22.0%). There were significant differences in postoperative complications between groups A and C, and between groups B and C. However, the difference between groups A and B was not significant, and no significant difference in survival rate was seen among the three groups.CONCLUSION: Fat volume definitely increases the postoperative complications. Accordingly, the high rate of postoperative complications of D2 surgery in Western countries may be related to the patients' relative obesity.

Decreasing complication rates with stapled esophagojejunostomy following a learning curve

Abstract: BACKGROUND: Recently, two reports of clinical trials on gastric cancer surgery have reported high mortality following extended lymph node dissection. In these reports, anastomotic leakage at the esophagojejunostomy was observed in approximately 10% of patients, with high mortality. These data highlight the importance of avoiding this complication. In this article, we report the use of a stapler to achieve a safe anastomosis, with low incidences of leakage and postoperative stenosis. METHODS: From January 1985 to December 1997, we performed 1234 esophagojejunal anastomoses at the National Cancer Center Hospital. Records of the 1234 patients were reviewed to evaluate changes in anastomotic techniques and changes in the incidence of anastomotic leakage. In this series, 588 stapled anastomoses were carried out between 1992 and 1997. These were evaluated to calculate the incidence of leakage and stenosis, with special reference to the use of supplementary sutures around the stapled anastomosis. Statistical analysis was performed by the chi2 test. RESULTS: This series showed an overall increase in the use of staplers to form the esophagojejunal anastomosis, and a decrease in the incidence of leakage. In 1995, all anastomoses were stapled, with a leakage rate of less than 1.0%. In the last 6 years of the series (1992-1997), the leakage rate was 1.0% and the incidence of postoperative stenosis was 1.2%. The results were not improved by supplementary sutures around the stapled anastomosis. CONCLUSION: These data show that a stapled esophagojejunal anastomosis without supplementary sutures is a safe way to create a esophagojejunal anastomosis, with results superior to those with hand suturing. We believe the stapled anastomosis should become the "gold standard" for esophagojejunal anastomosis.

Papillary adenocarcinoma of the stomach.

Abstract: Background. Papillary gastric carcinoma (PGC) is a rare histologic entity among gastric adenocarcinomas. The aim of this study was to clarify the clinicopathologic characteristics of PGC, including the survival rate, recurrence pattern, and factors influencing the prognosis of patients with PGC.

Role of MMP-7 in the formation of peritoneal dissemination in gastric cancer

Abstract: BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is an important matrix-degrading enzyme that has a large role in the invasion and metastasis of cancer. To discover the mechanism of the formation of peritoneal dissemination in gastric cancer, we studied the mRNA and protein expression of MMP-7 in primary gastric cancers and peritoneal dissemination.METHODS: MMP-7 expression in primary gastric cancers (136 patients) was studied by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and the results were compared with chinicopathological parameters.RESULTS: MMP-7 mRNA was expressed in 28 (53%) of 53 primary gastric cancers, but not in normal gastric mucosa, fibroblasts, or mesothelial cells. An immunohistochemical method demonstrated that MMP-7 immunoreactivity was found on the cell membrane and cytoplasm of cancer cells. Among 136 primary tumors, 70 (53%) tumors overexpressed MMP-7, and MMP-7 tissue status had significant positive correlation with serosal involvement, lymph node metastasis, poor differentiation of cancer, and peritoneal dissemination. Patients with MMP-7-positive tumor had significantly poorer survival and more frequently died of peritoneal recurrence than did those with MMP-7-negative tumors. All 6 examined peritoneal disseminations expressed MMP-7 mRNA, and 13 of 14 peritoneal disseminations showed immunoreactivity to anti-human MMP-7 monoclonal antibody. Logistic regression analysis showed that MMP-7 immunohistological status was an independent risk factor for peritoneal dissemination, and patients with MMP-7 mRNA-positive tumors had a 9.9-fold higher relative risk for peritoneal metastasis.CONCLUSION: These results strongly suggest that MMP-7 may have a large role in the formation of peritoneal dissemination in gastric cancer, and that clonal selection of cancer cells with MMP-7 overexpression may occur during the invasion of intraperitoneal free cancer cells from the peritoneal surface into the subperitoneal tissue. MMP-7 tissue status in the primary tumor may be a good indicator of peritoneal dissemination.

Prognostic factors in stage IV gastric cancer: univariate and multivariate analyses

Abstract: BACKGROUND: The prognosis of stage IV gastric cancer is poor with the 5-year survival rate still being about 10%.METHODS: We classified 130 patients with stage IV gastric cancer into four groups: peritoneal metastasis, liver metastasis, lymph node metastasis, and multiple factor groups, according to the factors that determined stage IV in each patient and compared survival in the four groups. We also performed univariate and multivariate analyses of various prognostic clinicopathological factors. The 5-year survival rate in the patients with stage IV gastric cancer was 7.4%.RESULTS: No significant differences were observed in survival among the four groups. Univariate analysis showed significant differences in survival among the categories of lymphatic invasion ( P = 0.0045), venous invasion ( P = 0.0024), peritoneal metastasis ( P = 0.0019), postoperative chemotherapy ( P = 0.0385), curability ( P = 0.0001), and lymph node dissection ( P = 0.0001). In the curability B group, survival was prolonged in the postoperative chemotherapy group. Multivariate analysis revealed the highest relative hazard (RH) for lymph node dissection (RH, 2.261), followed, in descending order, by curability (RH, 1.905), peritoneal metastasis (RH, 1.896), lymphatic invasion (RH, 1.736), and venous invasion (RH, 1.481).CONCLUSION: As prognostic factors in stage IV gastric cancer, the tumor factors of peritoneal metastasis and vessel invasion, and the treatment factors of curability and lymph node dissection may be important, and active treatment appears to improve survival.

Prognostic factors in patients with advanced gastric cancer with macroscopic invasion to adjacent organs treated with radical surgery.

Abstract: BACKGROUND: The prognosis of patients with gastric cancer with invasion to adjacent organs is poor. The prognostic factors of patients with advanced gastric cancer with macroscopic invasion to adjacent organs (T4) who were treated with radical surgery was determined in the present study.METHODS: A total of 86 consecutive patients with advanced gastric cancer who underwent radical (potentially curable) gastrectomy with combined resection of other organs for macroscopic invasion to adjacent organs during surgery, were investigated. The organs invaded macroscopically were the pancreas in 43 patients, mesocolon in 29, liver in 7, transverse colon in 5, adrenal gland in 3, spleen in 1, diaphragm in 1, and other organs in 5. The prognostic factors were evaluated by univariate and multivariate analysis.RESULTS: The cumulative 5-year survival rate of the patients treated by radical surgery with the combined resection of invaded organs was 35.0%. Multivariate analysis demonstrated that location of the tumor, lymph node metastasis, histological depth of invasion, and extent of lymph node dissection were significant prognostic factors in advanced gastric cancer patients treated by radical surgery with combined resection of adjacent organs for macroscopic invasion.CONCLUSION: For patients with macroscopic T4 gastric cancer located in the middle- or lower-third of the stomach, aggressive resection of invaded adjacent organs with extended lymph node dissection should be performed to improve long-term outcome.

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with bone metastasis.

Abstract: BACKGROUND: Patients with bone metastasis of gastric cancer occasionally experience disseminated intravascular coagulation (DIC), with a very poor prognosis.METHODS: We treated 18 gastric cancer patients with bone metastasis with sequential methotrexate and 5-fluorouracil (sequential MTX/5-FU therapy). The treatment schedule comprised weekly administration of methotrexate (MTX; 100 mg/m(2), i.v. bolus) followed by 5-fluorouracil (5-FU; 600 mg/m(2), i.v. bolus) after an interval of 3 h. Calcium leucovorin (10 mg/m(2), p.o. or i.v.) was administered six times, every 6 h starting 24 h after the administration of MTX.RESULTS: In 11 patients with measurable metastatic lesions, the response rate was 64% (7/11). Nine patients (50%) had DIC before the initiation of chemotherapy, and 8 of them (89%) recovered from it. Two of these 9 patients (22%) survived for more than 1 year. The median survival times for all patients and for the 9 with DIC were 186 and 113 days, respectively. Grade 4 leukopenia was observed in 3 patients (17%). No treatment-related deaths occurred.CONCLUSION: Sequential MTX/5-FU therapy may have palliative potential and may be a feasible treatment for gastric cancer patients with bone metastasis with or without DIC.

Significance of and problems in adopting response evaluation criteria in solid tumor RECIST for assessing anticancer effects of advanced gastric cancer.

Abstract: BACKGROUND: The response evaluation criteria in solid tumor (RECIST) exclude the use of barium meal studies. This will deeply affect the Japanese criteria for evaluating the response in the primary lesion of gastric cancer.METHODS: Of 280 patients with gastric cancer enrolled in a Japan Clinical Oncology Group (JCOG) phase III study, 255 had been assessed for response by the WHO and/or Japanese criteria. We selected these 255 patients as our subjects and reassessed their response outcomes by RECIST.RESULTS: Of the 255 patients, 32 (13%) had no evaluable lesion other than the primary site, and 171 (67%) had some measurable lesion defined by the WHO criteria. Because the lesions in 129 of these 171 patients were 20 mm or more in size, only 51% of the 255 subjects were eligible for assessment of the target lesion by RECIST. In 162 of the 171 patients who had a lesion of 10 mm or more, response rates by the old and new criteria were nearly equal, in spite of the different methods of measurement. The response rate in the primary lesions assessed by the Japanese criteria was lowest among all the groups examined.CONCLUSION: The RECIST is simple and good for clinical practice. Nevertheless, the recommendation of 20 mm or more for target lesions, which may restrict the number of eligible patients, could be replaced by a size of 10 mm or more. Because the Japanese evaluation criteria are rigid and do not inflate the response rate, they can be used, as additional criteria for assessing the quality of response, when the RECIST is used.

Micrometastasis in lymph nodes of mucosal gastric cancer.

Abstract: Background. Endoscopic mucosal resection is frequently used in the treatment of mucosal gastric cancer. Micrometastasis in the lymph nodes of mucosal gastric cancer remains unclear. Methods. We examined 2526 lymph nodes from 84 patients with mucosal gastric cancer. Two consecutive sections were prepared, for simultaneous staining with hematoxylin and eosin and immunostaining with CAM 5.2 monoclonal antibody against cytokeratin (CK), respectively. A clinicopathological comparison was made between patients with and without lymph node involvement. Results. Lymph node involvement was detected in 45 of 2526 (1.8%) lymph nodes. The incidence of nodal involvement was significantly increased, from 1.2% (1/84 patients) with hematoxylin and eosin staining, to 19% (16/84 patients) with CK immunostaining. Although no significant difference was found, micrometastasis to lymph nodes was more frequently detected in tumors larger than 1.0 cm (15/72 patients, 21%) than in those less than or equal to 1.0 cm (1/12 patients; 8%, P = 0.307). However, discrete CK-positive cancer cells or clusters of CK-positive cancer cells were detected only in tumors larger than 2 cm. Conclusion. Because mucosal gastric cancer of more than 1.0 cm in superficial diameter may indicate a risk of micrometastasis to lymph nodes, endoscopic mucosal resection is not recommended for these patients.

Surgically treated Cronkhite-Canada syndrome associated with gastric cancer.

Abstract: Cronkhite-Canada syndrome is generally accepted to be a benign disorder, with 374 reported cases to the present. Worldwide, there have been 18 previously reported cases of Cronkhite-Canada syndrome associated with gastric cancer. In this report we describe a case of a 52-year-old man with the clinical features of Cronkhite-Canada syndrome combined with gastric cancer. Although the gastric tumor was located at the antrum of the stomach, we performed a total gastrectomy because of the edematous swelling and high risk of malignancy in the remnant stomach. As Cronkhite-Canada syndrome may be a premalignant condition for gastric cancer, as well as for colorectal cancer, we suggest periodic examination of the stomach, colon, and rectum for patients with Cronkhite-Canada syndrome.

Advanced gastric glandular-endocrine cell carcinoma with 1-year survival after gastrectomy.

Abstract: Primary gastric endocrine cell carcinoma (ECC) is extremely rare. In general, when it is advanced, gastric ECC causes extensive ulceration (type 2) and invades or metastasizes to other organs, frequently to the liver and sometimes to the lungs or bones, and carries a poor prognosis. We herein report a 67-year-old man with advanced gastric ECC of extensive-polypoid shape (type 1) but without distant metastasis, who underwent total gastrectomy and treatment with oral tegafur-uracil (UFT), and showed no sign of recurrence 1 year later.

The role of growth patterns, according to Kodama's classification, and lymph node status, as important prognostic factors in early gastric cancer: analysis of 412 cases

Abstract: BACKGROUND: During the 1970s, a special type of Gastric Cancer with excellent prognosis (early gastric cancer; EGC) was identified by the Japanese Research Society for Gastric Cancer. EGC has been defined as a tumor which invades the mucosa and/or submucosa, regardless of the lymph node status. Using this definition, we identified an initial phase of tumor development which could be treated both endoscopically and surgically.METHODS: We examined 412 EGC patients, recruited between 1976 and 1999, with an average follow-up of 9 years. All tumors were classified according to the macroscopic and microscopic criteria proposed by the Japanese Society of Gastroenterological Endoscopy (JSGE) and Lauren, respectively. The infiltrative growth pattern was evaluated according to Kodama's classification. Only tumor-related death was considered as an end-point of interest for the survival analysis.RESULTS: Submucosal tumors ( P = 0.008), Pen A (see definition below) type disease ( P = 0.0001), and lymph node-positive cancers ( P = 0.0002) were significant prognostic factors on univariate analysis. Moreover, bivariate analysis showed that the worst prognosis, in terms of survival, was for patients with nodal involvment, submucosal invasion, and node-positive and Pen-A type cancer. The abbreviation Pen, penetrating, indicates a lesion with a diameter of less than 4 cm, which invades the submucosa diffusely. Pen A type EGC represents a subgroup of tumors which infiltrates the submucosa extensively, with nodular masses, causing the complete destruction of the muscularis mucosae.CONCLUSION: In our series, Pen A type was an important prognostic factor (hazard ratio; HR, 8.32; 95% confidence interval [CI], 3.49-19.86. For this reason, we believe it is important to evaluate the infiltration into the wall in all patients with EGC, paying particular attention to the growth pattern of the neoplasm. Moreover, submucosal Pen A type tumors had a considerably worse prognosis and this finding was reinforced when lymph node metastases coexisted. We suggest, therefore, that surgical treatment with at least a D2 lymphadenectomy is performed in all these patients, as the lesions must be considered to be advanced, no longer being EGC.

Clinical significance of disordered beta-catenin expression pattern in human gastric cancers.

Abstract: BACKGROUND: Beta-catenin plays two distinct roles, in intercellular adhesion by E-cadherin, and in transcriptional activation via TCF/LEF. Theoretically, the former role is tumor-suppressive, while the latter is oncogenic. We investigated the involvement of beta-catenin in the histogenesis and clinical outcome of gastric cancers.METHODS: The expression pattern of beta-catenin was evaluated in stomach and lymph nodes from 82 patients with gastric cancer by immunohistochemistry and Western blot. Its association with E-cadherin expression and clinicopathological factors, including histological type and postoperative survival, was examined.RESULTS: Beta-catenin expression was classified into two patterns, normal (23.2%; 19 patients) and disordered (76.8%; 63 patients), the latter being subclassified as overexpressed (7.3%; 6 patients) and reduced (69.5%; 57 patients). A disordered beta-catenin expression pattern was significantly correlated with diffuse type adenocarcinoma and deep tumor infiltration ( P = 0.0154), but was not associated with lymph node metastasis ( P = 0.7877). E-cadherin was always expressed at the cell membrane, and disordered beta-catenin expression was significantly associated with reduced E-cadherin expression ( P < 0.0001). On univariate analysis, the beta-catenin pattern, as well as depth of invasion and lymph node metastasis, was associated with postoperative prognosis; however, only lymph node metastasis was an independent prognostic factor on multivariate analysis. Interestingly, different disordered patterns of beta-catenin expression, both overexpressed and reduced, were associated with E-cadherin reduction and poorer postoperative survival.CONCLUSION: Although disordered patterns of beta-catenin expression varied in gastric cancers, they were consistently associated with cancer progression.

Gastric cancer recognized by metastasis to the ureter.

Abstract: Although ureteral obstruction is rarely noted in patients with gastric cancer at an advanced stage or at autopsy, the condition caused by authentic ureteral metastasis of gastric cancer is extremely rare. We experienced a case of gastric cancer in a 51-year-old woman who showed bilateral ureteral metastasis. The patient initially complained of right flank pain, caused by right ureteral obstruction, and was referred to our hospital, where she underwent a right nephroureterectomy, with suspicion of primary ureteral neoplasm. Histopathological examination of the resected specimen showed that metastatic growth of adenocarcinoma in the ureteral wall had caused the obstruction, and the subsequent extensive search for the primary lesion revealed asymptomatic gastric cancer. Soon after the nephroureterectomy, the patient developed left hydronephrosis, possibly caused by left ureteral metastasis, and a left percutaneous nephrostomy was performed. She then received chemotherapeutic reagents. However, she finally developed peritoneal carcinomatosis, and died of the disease about 1 year after the onset of the disease. In this report, we also review true ureteral metastasis from the stomach, and discuss the clinicopathologic features.

Gastritis cystica polyposa associated with a gastric stump carcinoma, with special reference to cell kinetics and p53 gene aberrations.

Abstract: We report a case of gastritis cystica polyposa (GCP) that developed in association with a small stump carcinoma. The patient had had distal gastrectomy for peptic ulcer 33 years prior to the present illness. Total gastrectomy was carried out for the stump carcinoma of the remnant stomach, followed by Roux-en-Y anastomosis. Histological examination revealed that the cancer was associated with a GCP lesion in its neighborhood. The resected stomach was subjected to a cell kinetics study and p53 gene analysis, as GCPs are thought to have a high potential for carcinogenesis. The GCP mucosae, as well cancer tissues and remnant mucosae obtained from the same specimens, were investigated and compared. We found that cell kinetics, as measured by a Ki-67 labeling index count, was more accelerated in the GCP than in the remnant mucosa, and that p53 gene aberrations, including both mutations and deletions, took place in the GCP lesion. As the p53 gene is considered to be recessive, in principle, its tumor suppressive activity is lost only when gene aberration, either mutation or deletion, occurs concurrently or successively in both alleles. It was of interest to us that a benign lesion such as GCP had, in this instance, already developed both gene aberrations, strongly suggesting a precancerous nature for this disease.

Long-term results for patients with unresectable gastric cancer who received chemotherapy in the Japan Clinical Oncology Group (JCOG) trials

Abstract: Background. Despite recent developments in chemotherapeutic trials, the long-term results of chemotherapy remain to be clarified. We evaluated the impact of chemotherapy on long-term survival in patients with unresectable gastric cancer. Methods. Between 1985 and 1991, a total of 363 patients with gastric cancer were enrolled into a single randomized phase II study and into three series of phase II studies of the Japan Clinical Oncology Group. The chemotherapy regimens consisted of tegafur + mitomycin C (FTM), uracil-tegafur + mitomycin C (UFTM), 5′deoxy-flurorouridine + cisplatin (5′P), etoposide + doxorubicin + cisplatin (EAP), and 5-fluorouracil + cisplatin (FP). After a review of the 363 patients' case records, 226 patients who fulfilled the criteria of having "unresectable" factors prior to chemotherapy became the subjects for this analysis. Of the 226 patients, 50 were in the FTM regimen group, 39, in the UFTM; 49, in the 5′P; 42, in the EAP; and 46, in the FP group. Survival was updated continually. Results. Of the 226 patients, 22 (10%) survived longer than 2 years, and 8 (4%) have survived longer than 5 years. The 8 5-year survivors consisted of 6 patients who had para-aortic node metastases alone as an "unresectable factor", 1 who had para-aortic and cervical node metastases, and the remaining patient who had liver metastasis alone. Twenty-nine patients with para-aortic node metastasis alone had a significantly longer survival than the other 197 patients (P < 0.001). Conclusion. Systemic chemotherapy may offer some hope of achieving long-term survival in patients with unresectable gastric cancer, particularly when the patient has metastasis only to para-aortic nodes.

Gastric cancer with extragastric lymph node metastasis: multivariate prognostic study.

Abstract: BACKGROUND: Although many authors have investigated the prognostic factors of gastric cancer, there are few comprehensive studies on the prognosis of patients with extensive lymph node metastasis. The aim of this study was to clarify the prognostic factors of gastric cancer with extragastric lymph node metastasis, using multivariate analysis.METHODS: The study population consisted of 121 patients who had undergone radical gastrectomy and extended lymph node dissection (D2, D3) for gastric cancer with extragastric lymph node metastasis. We examined 18 clinicopathologic factors, including the type of gastrectomy, tumor size, depth of wall invasion, status of lymph node metastasis, and stage of disease. Survival rates were analyzed by the Kaplan-Meier and Mantel-Cox methods, and multivariate analysis was done using the Cox proportional hazards model.RESULTS: The overall 5-year survival rate was 32%, and the 5-year survival rate after curative gastrectomy was 37%. Overall survival rate was associated with the type of gastrectomy, stage of disease, operative curability, tumor size, depth of wall invasion, and anatomical distribution of positive nodes, whereas the survival rate after curative gastrectomy was correlated with the type of gastrectomy, stage of disease, tumor size, gross type, and depth of wall invasion. Independent prognostic factors were operative curability and depth of wall invasion, and survival after curative gastrectomy was influenced only by the depth of wall invasion (mucosa and submucosa [T1], muscularis and subserosa [T2] vs serosa [T3]).CONCLUSION: In patients with gastric cancer with extragastric lymph node metastasis, independent prognostic factors after gastrectomy were operative curability and depth of wall invasion. Long-term survival can be achieved when the patients have no serosal invasion (T1, T2) and are treated by curative gastrectomy.

Extensive liver metastasis of gastric cancer effectively treated by hepatic arterial infusion of 5-fluorouracil/cisplatin.

Abstract: Most gastric cancer patients with jaundice caused by extensive liver metastasis show no tumor shrinkage response to systemic chemotherapy, while often showing severe adverse reactions. Their prognosis is very poor. We experienced two patients for whom hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) and cisplatin through an implantable port was effective for treating extensive liver metastasis. One patient had jaundice (serum bilirubin level before HAI therapy, 12.4 mg/dl) caused by metachronous liver metastasis, and prior systemic chemotherapy with 5-FU and irinotecan had not been effective. The other patient had gastric cancer with synchronous liver metastasis and also exhibited jaundice (serum bilirubin level before HAI therapy, 11.8 mg/dl). Both patients were treated with HAI of cisplatin, 20 mg/m(2) for 30 min on day 1, and continuous intraarterial infusion of 5-FU, 300 mg/m(2), from day 1 to day 4 every week. Their metastatic liver tumors were significantly reduced in volume and the jaundice disappeared. They survived for 30 and 27 weeks, respectively. A pharmacokinetic study conducted during the period of partial remission revealed that the extraction ratios of 5-FU and cisplatin in the liver were 0.89 and 0.024, respectively, suggesting a favorable first-pass effect of 5-FU. Although our findings here suggest that the successful local control of liver metastasis could improve the deteriorated condition and prolong the survival in some patients with far advanced cancer, it is essential to pay much attention to possible adverse effects during the treatment.

Influence of perioperative blood transfusion on the prognosis of patients with gastric cancer receiving anticancer chemotherapy.

Abstract: Background The deleterious effect of blood transfusions on survival has been reported in patients with cancers of various organs However, it remains unclear whether there is any adverse effect of blood transfusion when the patients are administered anticancer drugs after surgery for gastric cancers

Expression of transforming growth factor β (TGF-β) may contribute, in part, to the variations in histogenesis and the prevalence of peritoneal dissemination in human gastric carcinoma

Abstract: Background. Alterations in the activity of transforming growth factor β (TGF-β) in humans have been implicated in fibrosis, immunosuppression, development of cancer, and other disorders. Scirrhous gastric carcinoma is characterized by cancer cells that infiltrate rapidly in the stroma with extensive growth of fibroblasts and fibrous tissue. Hence, the majority of studies examining the role of TGF-β in gastric carcinoma have focused on scirrhous carcinoma. Methods. We undertook a retrospective immunohistochemical study of gastric carcinoma in order to characterize TGF-β expression in malignant gastric lesions and to determine whether TGF-β expression was related to disease progression. Results. TGF-β expression in scirrhous gastric carcinomas was significantly higher than that in nonscirrhous gastric carcinomas. In patients with advanced gastric carcinoma with surgically curative resection, TGF-β expression was significantly higher in those patients who developed peritoneal recurrence after surgery than in those who did not develop such recurrence. Patients with TGF-β expression-positive tumors had significantly poorer survival than did those with TGF-β expression-negative tumors (P = 0.017). In addition, multivariate Cox proportional hazard model analysis showed that TGF-β immunohistochemical status was an independent prognostic factor (P = 0.0031). Conclusion. These data suggest that TGF-β may contribute, in part, to the variations in histogenesis and to the prevalence of peritoneal dissemination in gastric carcinoma.

Benign gastric carcinoid tumor with hypergastrinemia followed up for 12 years.

Abstract: Gastric carcinoid tumors associated with chronic atrophic gastritis type A have been reported to show good prognosis, because invasion and metastasis are rare. We report a case of gastric carcinoid tumor associated with hypergastrinemia that showed no malignant changes for 12 years. A 15-year-old man with abdominal discomfort underwent endoscopic examination. A polypoid lesion was detected on the atrophic mucosa of the fundus, and was diagnosed as a carcinoid tumor. Serological examination revealed a high level of anti-parietal-cell antibody, suggesting that the patient had chronic atrophic gastritis type A. The tumor was treated by endoscopic mucosal resection. Follow-up examinations were performed for 12 years, but showed no recurrence. This case confirms that gastric carcinoid tumors associated with chronic atrophic gastritis type A may have a good prognosis.

Relationship between interleukin-1-alpha concentration in tumors and cell growth in gastric cancer, determined using flow cytometry.

Abstract: Background. Interleukin-1-alpha (IL-1α) produced by tumor cells stimulates the proliferation or the growth of several cancer cell lines. The aim of this study was to clarify the relationship between growth activity evaluated by DNA analysis and the concentration of tumor-derived IL-1α in gastric cancers in clinical cases. Methods. We measured the concentration of IL-1α in homogenized tumor samples obtained from 49 patients with gastric cancer, using an enzyme-linked immunosorbent assay, and we analyzed the cellular DNA content of paraffin-embedded tumor sections using flow cytometry. Results. Both the IL-1α concentration and the percentage of S-phase fraction were significantly correlated with liver metastasis, histologic type, pattern of tumor infiltration, quantity of stroma, and venous invasion. A good correlation was found between IL-1α concentration in tumors and the percentage of S-phase fraction ( R = 0.604, P < 0.0001). Conclusion. IL-1α may be related to the stimulation of cell growth of gastric cancer in clinical cases.

Prediction of recurrence after curative resection of gastric carcinoma invading the muscularis propria: a multivariate analysis.

Abstract: Background. In Japan, the incidence of gastric cancer invading the muscularis propria is about 10% of all patients with gastric cancer undergoing surgical resection. Although many prognostic factors for early gastric cancer and advanced gastric cancer have been identified, there are few reports concerning prognostic factors for gastric cancer invading the muscularis propria, and the characteristics of recurrence are not well understood. Methods. We retrospectively analyzed data on 167 patients with gastric cancer that had invaded the muscularis propria. All patients had undergone curative resection. Results. Recurrences were evident in 37 patients (22.2%). Based on our univariate analysis, the recurrence was associated with lymph node metastases. Multivariate analysis showed that independent risk factors for recurrence were lymph node metastases and location of tumor in the upper or lower one-third of the stomach. With respect to the pattern of recurrence, 17 (46.0%) were secondary to hematogenous recurrence, 8 (21.6%) to peritoneal dissemination, and 6 (16.2%) to a local recurrence in the remnant stomach and in regional lymph nodes. Most deaths occurred during the second year after surgery, and approximately two-thirds of all patients (64.8%) died within 3 years after surgery. Conclusion. In patients with the risk factors of lymph node metastases and tumor in the upper or lower one-third of the stomach, lymph node dissection and postoperative adjuvant therapy are vital to try to prevent recurrences, especially during the first 2 years after surgery.

Five-year survivor with liver metastasis from gastric cancer successfully treated with systemic chemotherapy

Abstract: We report a patient with liver metastasis from gastric cancer who has achieved a 5-year survival after systemic chemotherapy. The patient was diagnosed with advanced gastric cancer and received a total gastrectomy in August 1991, followed by adjuvant chemotherapy. Liver and lymph node metastases were detected in April 1994, and systemic chemotherapy with a combination of etoposide, doxorubicin, and cisplatin was initiated. Although the liver metastasis completely disappeared, lymph node metastasis at the falciform ligament of the liver and around the portal fissure remained after six courses of this therapy. A second type of chemotherapy, a combination of 5-fluorouracil and methotrexate, was then administered, 12 times, from December 1994 to May 1995, during which time no disease progression was observed. After surgery for the metastatic lymph nodes in August 1995, no progression was observed until December 1998, when a tumor thrombus was detected in the portal vein. Combination chemotherapy of irinotecan and cisplatin was initiated in January 1999. Although tumor regression was achieved after two courses of this, the disease continued to progress after five courses. In July 1999, a fourth type of chemotherapy, using 1 M tegafur-0.4 M gimestat-1 M otastat potassium (S-1), was initiated, and size reduction of the tumor thrombus was achieved; this therapy has continued to the time of submission of this report.

Advanced gastric carcinoma successfully treated with TS-1 as neoadjuvant chemotherapy

Abstract: We report a patient with advanced gastric carcinoma successfully treated with the novel oral fluoropyrimidine anticancer drug TS-1 as neoadjuvant chemotherapy. The patient was a 76-year-old man who had gastric cancer clinically diagnosed as N2T4, invading the pancreas, the duodenum, and the transverse colon. He was treated as an outpatient with TS-1, 120 mg, administered orally every day for 28 days, followed by 14 days' rest, as one course. Two courses resulted in a marked reduction of the tumor without severe toxicity. Subsequently, the patient underwent curative surgery consisting of distal gastrectomy with D2 lymph node dissection. No surgical complications were observed. On microscopic examination, a few tumor cells were detected in the ulcer scar of the resected stomach and in the regional lymph nodes. Our report is the first to demonstrate the advantages of TS-1 as neoadjuvant chemotherapy for the treatment of advanced gastric carcinoma.

Meeting report of the 72nd Japanese Gastric Cancer Congress.

Abstract: surgical techniques. In this session, reconstruction methods after gastrectomy were discussed. K. Nakamura, Tokai University, evaluated the survival rates in patients who had undergone various reconstructive procedures after distal and total gastrectomy. They reported that higher 5-year survival rates were observed in patients who had undergone gastroduodenostomy and jejunal interposition, allowing food to pass through the duodenum, than in those who had undergone gastroor esophagojejunostomy. They suggested that reconstruction enabling food to pass through the duodenum should be performed irrespective of the disease stage. Y. Nakane, Kansai Medical University, reported that reconstruction with a jejunal pouch after total gastrectomy was effective in the prevention of the small stomach syndrome, but that long-term emptying disorders were observed in some patients after Roux-en-Y anastomosis with a jejunal pouch. H. Kashimura, Jikei University, reported that the ileocolon interposition was superior to the Roux-en-Y method after total gastrectomy because less reflux esophagitis and more food intake occurred at each meal. K. Yamaguchi, Sapporo Medical University, evaluated jejunal pouch interposition after proximal gastrectomy both clinically and experimentally. They performed jejunal pouch interposition or esophagogastrostomy in beagles and showed that the former was superior to the latter in terms of changes in gastrointestinal hormones, maintenance of body weight, and emptying of the residual stomach. They concluded that jejunal pouch interposition should be considered after proximal gastrectomy. S. Kinami, Kanazawa University, evaluated jejunal pouch interposition after distal gastrectomy. As compared with the Billroth I method, the incidences of dumping syndrome, bile reflux and inflammation of the remnant stomach, and Helicobacter pylori infection were all low. The 73rd Congress of the Japanese Gastric Cancer Association (JGCA) was held at Kanazawa City, March 1–3, 2001, and attended by 1350 participants. A total of 517 papers were presented. In addition to free papers and poster presentations, a variety of gastric cancer topics ranging from molecular biology to frontline surgical techniques were discussed at two special symposia, four regular symposia, two video symposia, four panel discussions, four workshops, and four debate sessions. An open educational session entitled “Basic principles of diagnosis and treatment for gastric cancer” was organized for the first time at the 73rd JGCA congress, and the meeting hall was unexpectedly packed to overflowing with young attendees. The JGCA completed the first edition of the Guideline for Gastric Cancer Treatment just before the congress, and a special forum was held for the editorial members to present the principal points. This guideline is expected to serve as the standard not only in clinical practice but also for clinical trials in the future. Discussions of some of the main topics of the congress are summarized below by a chairperson of the session.