A phase II study of preoperative chemotherapy with S-1 plus cisplatin followed by D2/D3 gastrectomy for clinically serosa-positive gastric cancer (JACCRO GC-01 study).

AIMS: Clinically serosa-positive (T3-4) gastric cancer has a poor prognosis. This phase II trial explored the feasibility and safety of preoperative chemotherapy followed by D2 or D3 gastrectomy in this type of gastric cancer. METHODS: Patients with T3-4 gastric cancer received one course of S-1 (80mg/m(2) daily for 3 weeks) and cisplatin (60mg/m(2) on day 8) chemotherapy and then underwent D2 or D3 gastrectomy with curative intent. Primary endpoint was toxicities. RESULTS: Of 50 patients enrolled, 49 were eligible and received the treatment protocol. Chemotherapy-related toxicities were mild; grade 3 neutropenia in 2 patients, anorexia in 3, and nausea in 2, and no grade 4 toxicities. Clinical response was achieved in 13 of 34 evaluable patients. Of the 49 patients, 39 underwent D2 or D3 dissection. There was no surgical mortality. Operative morbidity occurred in 5 of 49 patients, including pancreatic fistula in 1 and abdominal abscess in 2. CONCLUSION: This multi-modality treatment seems to be feasible and safe for T3-4 gastric cancer.

Spontaneous complete regression of a rectal cancer.

We report a unique case of a biopsy-proven rectal cancer exhibiting spontaneous complete regression in an extremely short period of 3 months. An 80-year-old man visited our hospital because of a positive fecal occult blood test. Colonoscopy showed a sessile polyp, about 25 mm in diameter, in the middle part of the rectum. Instead of endoscopic resection, two endoscopic biopsies were taken for histological evaluation, as an invasive cancer was endoscopically suspected.Well-differentiated invasive adenocarcinoma was revealed, and thus surgical resection was planned. At the second colonoscopy for endoscopic tattooing before surgery, the polyp was found to have unexpectedly developed into a flat lesion. Furthermore, the surgically removed specimen showed that the flat lesion had transformed to a depressed lesion, and surprisingly, no cancerous tissue was detected histologically.

Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy.

BACKGROUND: We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis. AIM: To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach. METHODS: Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3-5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed. RESULTS: After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group. CONCLUSIONS: Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.

Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection.

Polymorphonuclear neutrophils (PMNs) are crucial for the outcome of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis. We compared PMNs and inflammatory cytokines in the lungs and blood from susceptible BALB/c and resistant C3H/HeN mice 1 and 2 days after intratracheal challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs and the sera and the percentage of PMNs was increased in the blood. However, 2 days after challenge the concentration of G-CSF and MIP-2 was higher in the lungs and sera of BALB/c mice. CD11b expression was higher on the PMNs of the C3H/HeN mice. The expression of CD62L on PMNs of both strains of mice was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the persistent chemotactic gradient provided by MIP-2 in the lungs.

Diagnostic performance of light-induced fluorescence endoscopy for gastric neoplasms.

BACKGROUND AND STUDY AIM: Malignant tumors generate autofluorescent patterns that differ from those of normal tissue. However, whether autofluorescent diagnosis could be genuinely useful in screening for gastric neoplasms has not been well investigated in clinical practice. Accordingly, we retrospectively studied our experience with this diagnostic technique for various gastric lesions and assessed its diagnostic utility. PATIENTS AND METHODS: Autofluorescence diagnosis of 109 gastric lesions in 79 patients was done, without knowledge of the diagnosis by conventional white light endoscopy, retrospectively and independently by three endoscopists with 6 years', two years' and no experience of the technique. After examination of the interobserver bias in the assessment of autofluorescent pseudocolor in light-induced fluorescence endoscopy (LIFE), the relationship between pseudocolor and characteristics of gastric lesions (including histology, macroscopic type, and depth of invasion) were investigated. RESULTS: The kappa statistic for agreement in pseudocolor diagnosis between the three endoscopists was 0.71. The assessment of pseudocolor by all of the observers was in agreement in 67 of the total of 109 lesions (61.5 %). Experience with the LIFE technique did not improve the accuracy of pseudocolor determination. All of the cancers, 87.5 % of the adenomas, and 50.9 % of the benign lesions were recognized as having an abnormal autofluorescent image. None of the gastric cancers and 49.1 % of the benign lesions were evaluated as having a normal autofluorescence image. The histopathological and macroscopic types of tumors and their depths of invasion were not reflected in the autofluorescence diagnosis. CONCLUSIONS: LIFE provided a sensitivity of 96.4 % and specificity of 49.1 %, suggesting that this technique has limited clinical utility, regardless of the merits of acceptable interobserver bias and lack of necessity for experience with this technique.

Inhibition of proliferation of gastric epithelial cells by a cyclooxygenase 2 inhibitor, JTE522, is also mediated by a PGE2-independent pathway.

BACKGROUND: Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes for prostaglandin synthesis from arachidonic acid. Although it is known that inhibition of cyclooxygenase activity delays ulcer healing, the regulatory relationship between COX-2 and its metabolites in gastric epithelial cell proliferation is not well known. AIM: To investigate whether COX-2 has an effect on gastric mucosal cell proliferation and further studied whether such effect is mediated only by prostaglandin E2 (PGE2), a representative metabolite of arachidonates in the gastric mucosa. METHODS: Artificial wounds of defined area size were created on complete monolayer cell sheets of isolated rat gastric epithelial cells and rat gastric cell line RGM1 under the addition of arachidonic acid or a COX-2 selective inhibitor, JTE522. Repair of wounds was assessed by monitoring wound size, with cell proliferation detected using 5-bromodeoxyuridine staining. Quantity of secreted PGE2 was measured by enzyme immunoassay. RESULTS: Stimulation of foetal calf serum increased the expression of COX-2 protein and inhibition of COX-2 retarded wound healing with reduction of cell proliferation. Arachidonic acid increased PGE2 production and accelerated restoration. Combination of JTE522 and arachidonic acid resulted in a marked retardation of wound healing compared to the control, but JTE522 did not completely suppress the increase in cellular PGE2 content following the addition of arachidonate. CONCLUSIONS: The difference in the effects of JTE522 on PGE2 production and on wound healing suggest that the involvement of COX-2 in gastric epithelial cell proliferation is not mediated solely by PGE2.

Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response.

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.

[Significance of radical recurrent tumor resection for recurrent gastric cancer as assessed by prognosis].

To evaluate the relationship between radical surgery of recurrent tumor and prognosis in cases of recurrent gastric cancer, we analyzed data on 202 patients with relapsed gastric cancer, focusing on surgical recurrent tumor removal. In our series, 18 of the 202 patients underwent radical recurrent tumor resection. Resected tumors were located in the ovarium (n = 4), colorectum (n = 3), liver (n = 3), lymph node (n = 2), locoregional stoma (n = 2), and peritoneum, adrenal gland, brain, and lung (n = 1 each). No surgery-related mortality occurred. One patient remains alive over 5 years after hepatectomy without recurrence, and 17 died within 3 years: 7 patients from primary recurrence and 10 from multiple modes of recurrence. Median survival after recurrence (MSTAR) in the 18 radical surgery patients was 14 months, against 5 months in those treated palliatively (p = 0.0001). MSTAR for the ovary and the liver were 30 months and 15 months in the radical surgery cases, and 2.5 months for the ovary and 5 months for the liver in the palliative cases. Significant differences were thus seen between radical and palliative cases in the ovary (p = 0.010) and in the liver (p = 0.036). Median survival after gastrectomy was 45 months in the radical surgery cases, and 28 months in the palliative cases (p = 0.024). In postoperative gastric cancer follow-up, early detection of recurrence and radical surgery may well benefit patients with relapse, especially in the liver and ovary, in terms of survival.

Should scirrhous gastric carcinoma be treated surgically? Clinical experiences with 233 cases and a retrospective analysis of prognosticators.

BACKGROUND/AIMS: The prognosis of patients with scirrhous gastric carcinoma has been poorest. METHODOLOGY: To clarify the role of surgical treatment, 233 patients with a primary scirrhous gastric carcinoma were retrospectively analyzed. RESULTS: Of the 233 patients, 182 underwent surgical resection, while the other 51 did not. The median survival time of those with unresectable tumors was 88.0 +/- 15.3 days and that of those who underwent resection was 380.0 +/- 41.8 days. In the 182 patients who underwent resection, multivariate analysis revealed four significant factors; lymphatic invasion, serosal invasion, curability, and lymph node dissection. Of these, curability was the most significant. The median survival time of patients whose tumor were curatively resected was 727.0 +/- 116.3 days, significantly longer than 272 +/- 34.9 days for those whose resection ended noncuratively. In 65 patients whose tumor was curatively resected, subset analyses of factors by multivariate analyses revealed an absence of serosal invasion as the single significant prognosticator. The 5-year survival rate was 55.6% in patients with scirrhous cancer without serosal invasion. CONCLUSIONS: For patients with scirrhous gastric carcinoma, palliative resection should not be attempted for poor outcome. However, if curative resection seems feasible, radical surgery would be justified, especially for tumors without serosal exposure.

[Significance of laparoscopy for response assessment of chemotherapy in gastric cancer].

UNLABELLED: We performed laparoscopy before and after chemotherapy in two patients with relapsed and advanced gastric cancer, whose major metastatic sites had been diagnosed as being in the peritoneum. A change in tumor responses when assessed by laparoscopy was found. Case 1: A 63-year-old man presented with an umbilical metastasis and suspected peritoneal metastases after gastrectomy. Laparoscopy revealed peritoneal metastases before chemotherapy. After one course of chemotherapy the umbilical tumor disappeared (CR). Laparoscopy after two courses of chemotherapy revealed increasing peritoneal metastases (PD). The overall response was PD. Case 2: A 67-year-old woman was referred to our hospital with a diagnosis of type 4 gastric cancer. Staging laparoscopy revealed massive lymph node metastases and the patient was positive in peritoneal washing cytology. After four courses of chemotherapy, the primary tumor and the metastatic lymph nodes had decreased in size (PR). In contrast, laparoscopy revealed increasing peritoneal metastases (PD). The overall response was PD. CONCLUSION: In patients with peritoneal and other modes of metastasis, tumor response to chemotherapy may be misjudged by conventional imaging alone. Intraperitoneal examination by laparoscopy provides accurate information, including the tumor response to chemotherapy.

Cyclooxygenase-2 downregulates inducible nitric oxide synthase in rat intestinal epithelial cells.

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression has been demonstrated in inflamed intestinal mucosa. Although regulation of COX-2 and iNOS expression has been studied extensively, the interplay between these two enzymes remains unclear. Because they play crucial roles in inflammation and/or carcinogenesis, we investigated whether COX-2 regulates iNOS expression and evaluated the effects of COX-2 inhibitor and arachidonic acid (AA) on iNOS induction. The COX-2 gene coding region was stably transfected into rat intestinal epithelial cells (RIE sense cells). After interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) administration, iNOS and COX-2 expression was evaluated by Western blotting. PGE(2) was measured by the enzyme immunoassay (EIA) method. Expression of IFN response factor-1, phosphorylated extracellular signal-related kinase-1 and -2, and Ikappa-Balpha was evaluated. Activator protein-1 and nuclear factor-kappaB (NF-kappaB) were examined by gel mobility shift assay; a supershift assay was performed to identify the NF-kappaB complex components. JTE-522 or AA was added before IFN-gamma and LPS administration, and effects on iNOS and PGE(2) induction were evaluated by Western blotting or EIA. iNOS protein and mRNA expression was inhibited in RIE sense cells. Although NF-kappaB activation was suppressed and Ikappa-Balpha protein was more stable, respectively, in RIE sense cells, no difference was noted in other transcription factors. JTE-522 increased iNOS protein expression in RIE cells. We conclude that COX-2 suppressed iNOS expression in RIE cells through suppression of NF-kappaB by stabilizing Ikappa-Balpha.

[Myasthenia gravis is improved temporarily at postburn period].

A 62-year-old woman with a 25-year history of myasthenia gravis (MG) was admitted to our hospital due to burn injury over 20-25% of the total body surface area. Five months before admission, the serum concentration of acetylcholine receptor (AchR) antibodies was 80.9 nmol.l-1 (normal range < 0.3 nmol.l-1). Anticholinesterase agents had been administered for MG, but were discontinued six days after admission due to muscarinic side effects, but no symptoms of MG appeared. Thirteen days after admission, the AchR antibody titer was 21.2 nmol.l-1. Free skin grafting was performed under general anesthesia without any event. About 80 days after admission, weakness of extraocular muscles appeared. Positive tensilon test and the characteristic electromyographic findings revealed deterioration of MG, and anticholinesterase agents were resumed. Ten months after admission, the AchR antibody titer was 50.4 nmol.l-1. The mechanism of the temporary improvement of MG symptoms does not appear to be explained by the diffuse immunosuppression after burn. At a postburn period, nicotinic AchRs at the neuromuscular junction are known to be temporarily induced. This up-regulation may have caused the temporary improvement in this patient.

Intratumoral concentrations of tissue inhibitor of matrix metalloproteinase 1 in patients with gastric carcinoma a new biomartker for invasion and its impact on survival.

BACKGROUND: Previously, the authors clarified that the plasma concentration of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) in patients with gastric carcinoma was a significant predictor of tumor invasiveness and metastasis. METHODS: To further clarify the clinical significance of TIMP-1, the authors used an enzyme-linked immunoassay to assess TIMP-1 protein concentrations in samples of tumor tissue from 86 patients who underwent primary resection for gastric carcinoma. Concentrations in samples of normal gastric mucosa from 73 of these patients also were assessed. RESULTS: Tissue TIMP-1 concentrations were significantly greater in gastric tumors than in normal gastric mucosa and were associated significantly with a variety of pathologic factors, including macroscopic type, depth of tumor invasion in the gastric wall, presence of lymphatic vessel invasion, pattern of tumor infiltration into the surrounding tissue, and disease stage. Significantly greater TIMP-1 concentrations were found in tumors that were exposed to the serosal surface compared with tumors that were limited to the submucosal layer. TIMP-1 protein was significantly greater in tumors with lymphatic vessel invasion, an infiltrative pattern into the surrounding tissue (INF-gamma), and in tumors from patients with Stage III disease. Survival was significantly poorer in patients with TIMP-1 concentrations > or = 10.0 ng/mg total protein. When patients were stratified by disease stage, survival was significantly different in patients with Stage III disease. Multivariate analysis demonstrated that intratumoral concentrations of TIMP-1 were the most significant independent factor for survival. CONCLUSIONS: These findings suggest that the intratumoral concentration of TIMP-1 protein may be a good indicator of tumor aggressiveness and can serve as a significant independent predictor of survival in patients with gastric carcinoma.

A new technique: light-induced fluorescence endoscopy in combination with pharmacoendoscopy.

BACKGROUND: Most cancers and adenomas of the GI tract are easily detected by light-induced fluorescence endoscopy (LIFE-GI). However, some tumors are poorly visualized by using this technique. To investigate whether the spraying of noradrenaline on the lesion provides better visualization of the boundaries of neoplasms, the conventional and LIFE-GI endoscopic observations were made before and after spraying of nonadrenaline. METHODS: Seven patients with gastric cancers were studied. After a conventional fiberscopic examination, a LIFE-GI procedure was performed, and then 20 mL of 0.02% noradrenaline solution was sprayed on the lesion. RESULTS: The normal mucosa became paler than the tumor after spraying noradrenaline, thereby clarifying the tumor boundary in the LIFE-GI image. CONCLUSIONS: The combined use of pharmacoendoscopy with LIFE-GI is useful in the detection of gastric malignant tumors because it enhances the boundaries of these lesions.

Clinicopathologic differences between early gastric remnant cancer and early primary gastric cancer in the upper third of the stomach.

BACKGROUND/AIMS: This study was designed to clarify the clinicopathologic characteristics and survival in early gastric remnant cancer and compare with early primary cancer in the upper third of the stomach. METHODOLOGY: Twenty-five patients with early gastric remnant cancer, who underwent resection at Kanagawa Cancer Center and First Department of Surgery, Yokohama City University between 1974 and 1996 were evaluated in this study. Various clinicopathologic characteristics, such as age, sex, symptoms, size of tumor, depth of invasion, lymph node metastasis, cell differentiation, and survival were investigated and early gastric remnant cancer was compared with early primary cancer in the upper third of the stomach. RESULTS: According to the macroscopic type, protruded type such as I or II type accounted for a great majority in early gastric remnant cancer, while II c depressed type was common in early primary cancer in the upper third of the stomach, comprising 64.2% of all cases. Pathological examination disclosed that well-differentiated carcinoma and mucosal carcinoma were more frequently observed in early gastric remnant cancer than in early primary cancer in the upper-third of the stomach. The 5-year survival rate was 83.5% for early primary cancer in the upper-third of the stomach. In contrast, no patients experienced recurrence after operation for early gastric remnant cancer. CONCLUSIONS: From the view point of clinicopathological evaluation, gastric remnant cancer is a special from of gastric cancer. A follow-up program is important in order to detect early gastric remnant cancer. A low incidence of lymph node metastasis suggests that endoscopic mucosal resection of the tumor or limited operation could be performed under strict indication.

Walker-Warburg syndrome is genetically distinct from Fukuyama type congenital muscular dystrophy.

A female patient who fulfilled the diagnostic criteria of Walker-Warburg syndrome had muscle biopsy finding of muscular dystrophy. There was normal expression of merosin (laminin alpha2 chain) and dystrophin and only slightly reduced dystrophin-associated glycoprotein expression. On genetic analysis, she had no specific haplotype, the common mutation of 3kb insertion, or point mutations in the Fukuyama-type congenital muscular dystrophy gene, suggesting that the two diseases are not genetically identical.

Effect of age on the relationship between gastric cancer and Helicobacter pylori. Tokyo Research Group of Prevention for Gastric Cancer.

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10-year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20 - 29, 14.5 for those aged 30 - 39, 9.1 for those aged 40 - 49, 3.5 for those aged 50 - 59, and 1.5 for those aged 60 - 69 (trend in odds ratios: P < 0.01). However, there was no such age-dependent trend for early diffuse-type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P = 0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age-class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age-dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age-independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and / or irreversible damage to gastric mucosa in childhood or the teenage years.

Prognostic value of tissue inhibitor of matrix metalloproteinase-1 in plasma of patients with gastric cancer.

Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma has been reported to be related to disease progression in patients with gastric cancer. However, the prognostic significance of plasma TIMP-1 concentrations has not been clarified. Concentrations of TIMP-1 protein were measured by enzyme-linked immuno-sorbent assay in plasma samples of 147 preoperative patients who subsequently underwent gastric resection, and prognosis was compared. The cut-off value of plasma TIMP-1 concentrations was defined as 112.5 ng/ml, referring to the TIMP-1 levels in patients with intramucosal gastric cancer. Twenty-nine out of 147 patients had higher plasma TIMP-1 levels than the cut off value. When the patients were divided into those with elevated values and those with normal TIMP-1, such parameters as age, serosal invasion, metastases to lymph nodes, peritoneum, and liver, lymphatic invasion, curability, and stage were significantly different between the two. By univariate analysis of the factors affecting survival, macroscopic type, histology, serosal invasion, metastasis to lymph node, peritoneum, and liver, vessel invasions, curability, and plasma TIMP-1 were significant. However, multivariate analysis revealed that TIMP-1 was the only significant factor. In patients with gastric cancer, plasma TIMP-1 seem to be an independent and most powerful prognosticator for the survival.

Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma.

We examined plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 54 patients with gastric carcinoma. Postoperative survival was significantly poorer in patients with plasma VEGF levels more than 10.0 pg/ml at the time of surgery. By an univariate analysis of the factors affecting survival, serosal invasion, lymph node metastasis, peritoneal dissemination, lymphatic vessel invasion, curability, and VEGF proteins were significant. By a multivariate analysis only VEGF levels and curability remained significant. Patients with recurrent disease, including liver metastasis, had significantly higher plasma VEGF concentrations than those with resectable primary tumors. VEGF, not bFGF, may serve as an independent prognosticator and a sensitive indicator for liver recurrence in patients with gastric carcinoma.