Prognostic Factor In Gastric Carcinoma Research Articles

Early Onset Gastric Cancer No Longer Presents as an Advanced Disease with Ominous Prognosis

Background: This study aimed to characterize the clinicopathological features and prognosis of early onset gastric carcinomas (EOGCs) in a sample of young Portuguese adults. Material and Methods: A subset of 415 patients submitted to gastric resection was divided into 2 groups: A – patients aged 45 years or less (n = 108), and B – patients older than 45 years (n = 307). The groups were compared for several clinicopathological features and the survival of the patients was analyzed by uni- and multivariate analysis. Results: The surgical resection rate was higher in young patients, in whom tumors more frequently displayed an ulcerative shape (p < 0.001) and diffuse/isolated cell-type histology (p < 0.001). In the elderly, the rate of vascular invasion was significantly higher (p = 0.002). Overall, the survival of young patients was higher than in the elderly (p < 0.001). Survival curves were higher in young patients, except for pT4 and pM1 cases. In the multivariate survival analysis, age (p < 0.001), depth of tumor invasion (p < 0.001), nodal status (p < 0.001), vascular invasion (p = 0.011) and distant metastases (p = 0.007) emerged as independent prognostic factors for gastric carcinoma. Conclusion: Young gastric cancer patients no longer present with more advanced disease than the elderly and, overall, survival is better in young patients.

Prognostic factors of gastric carcinoma

Gastric carcinoma is the second most common cancer in the world. Adenocarcinoma of the stomach has a rate of incidence of 21% in men and 9% in women in Navarra and represents the fifth most common. The incidence of gastric cancer has decreased during the last decades. Although the causes of this decline are unknown, adenocarcinoma of the stomach appears to be related to the environment factors. Several specific patiens conditions appear to be associated with an increased risk of gastric cancer: age, socio-economic status and the weight loss. Multiple factors associated with the tumor include histologic type, tumor invasion of the gastric wall, lymph nodes involvement, tumor markers (CEA; Ca 19.9...), biologic factors as gen p53 mutations, the urokynase-type plasminogen activator system and the angiogenesis. Another prognostic factors have been correlated with the type treatment: total or subtotal gastrectomy, the extent of lymphadenectomy or the adjuvant treatment with chemoradiation. Although the majority of patients are diagnosed at a locally advanced or metastasis disease, the identification of prognostic factors has attracted particular interest to select different treatment modalities in an attempt to increase tumor response and survival.

Co-expression of keratinocyte growth factor and K-sam is an independent prognostic factor in gastric carcinoma

Keratinocyte growth factor (KGF) from gastric fibroblasts have been reported to stimulate proliferation of scirrhous gastric cancer cells with K-samII amplification in a paracrine manner. The aim of this study was to evaluate the clinical significance of the co-expression of K-sam and KGF in gastric carcinomas. A total of 136 primary gastric tumors were investigated by staining with antibodies against K-sam and KGF. K-sam expression on cancer cells and KGF expression on fibroblasts was estimated. The relationship between the K-sam and/or KGF expression and the clinicopathological characteristics were analyzed. K-sam expression was positive in 42 (31%) of 136 gastric carcinomas. K-sam expression was positively correlated with scirrhous cancer (p<0.001), diffuse type (p=0.031), invasion depth (p=0.018) and infiltration type (p<0.001). Prognosis of K-sam positive patients was significantly poorer than that of K-sam negative patients (p<0.001). The prognosis of patients with both K-sam and KGF positive tumors was significantly worse in comparison to either negative tumors (p<0.001). In 94 patients with a curative resection, a multivariate analysis revealed the co-expression of K-sam and KGF to be an independent prognostic factor (p=0.029). In conclusion, the co-expression of K-sam and KGF in gastric cancer might be a useful prognostic factor.

Identification of genes epigenetically silenced by CpG methylation in human gastric carcinoma

To identify novel methylation-silenced genes in gastric cancer, we carried out a genome-wide search for genes that are up-regulated after treatment with the demethylating agent, 5-aza-2′-deoxycytidine (5Aza-dC). When three gastric cancer cell lines (SNU-1,-601, and -719) were treated with 5Aza-dC, 143 genes were found to be upregulated by twofold or more using oligonucleotide microarrays. Six of these genes, i.e. TFPI2, GPX3, GPX1, IGFBP6, IRF7 and DMRT1, showed promoter hypermethylation in one or more gastric cancer cell lines, but were unmethylated in normal gastric mucosa by bisulphite sequencing and methylation-specific PCR analysis. The following percentages of these genes were found to be aberrantly methylated in gastric cancer samples; TFPI2 (80.9%), GPX3 (30.1%), DMRT1 (46.9%), GPX1 (16.7%), IGFBP6 (22.6%) and IRF7 (32.1%). Interestingly, the survival of patients possessing methylated alleles of TFPI2 (123/152, 80.9%) was poorer than that of patients with unmethylated alleles (p=0.023). Multivariate analysis confirmed that TFPI2 methylation is a significant and independent prognostic factor in gastric carcinoma. Furthermore, altered TFPI2 expression, as demonstrated by immunohistochemistry in 566 consecutive gastric cancer tissues, was found to be significantly associated with sex (p=0.003), WHO classification (p<0.001), and a mixed subtype by Lauren’s classification (p<0.001). Thus, the present study identified several novel genes, which were methylated in gastric cancer and among them, methylation of TFPI2 was an unfavourable prognostic marker.

The overexpression of c-met as a prognostic indicator for gastric carcinoma compared to p53 and p21 nuclear accumulation

The purpose of this study was to clarify the relationship of the immunohistochemical expression of c-met, p53 and p21 with clinicopathological parameters and prognosis in gastric carcinomas. We analyzed specimens from 114 gastric cancer patients (median age 64 years, range: 33-86) who underwent gastrectomy with lymphadenectomy. Specimens were categorized according to the tumor differentiation, based on UICC, WHO, Laurén, Ming and Goseki classifications. Specimens were examined immunohistochemically with antibodies against c-met, p53 and p21. The expression was evaluated semiquantitatively and correlated with the clinicopathological parameters. The c-met staining pattern was positive in 73.7%. P53 and p21 were positive in 86.8 and 67.5%, respectively. No significant correlation between c-met or p21 expression and the clinicopathological parameters was seen. A significant increase of p53 expression was observed in stage pT3 and -4. The overexpression of c-met and p53 was significantly associated with a poor prognosis in the univariate survival analysis. In the multivariate analysis this impact was maintained for c-met. P21 proved to be a significant prognostic factor in the multivariate analysis. Our data suggest that the overexpression of c-met and p21 may represent independent prognostic factors in gastric carcinoma.

Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas

To investigate the pathobiological behaviors of gastric mixed-type (MT) carcinomas and gastric carcinogenesis, the clinicopathological characteristics of MT carcinomas were analyzed and compared with intestinal-type (IT) and diffuse-type (DT) carcinomas. The expression of Ki-67, caspase-3, p53, fragile histine triad (FHIT), maspin, extracellular matrix metalloproteinase inducer (EMMPRIN), vascular growth factor (VEGF), MUC-2, 4, 5AC and 6, CD44, E-cadherin, β-catenin, and phosphorylated glycogen synthase kinase 3β-ser9 (P-GSK3β-ser9) was examined on tissue microarrays using immunohistochemistry. It was found that MT carcinomas exhibited large size, deep invasion, frequent local invasion, and lymph node metastasis in comparison with IT and DT carcinomas (p < 0.05). All the markers except MUC-5AC showed higher expression in IT than DT carcinomas (p < 0.05). The expression of maspin, EMMPRIN, VEGF, MUC-4, and membrane E-cadherin was stronger in MT intestinal than diffuse component (p < 0.05). Immunoreactivities to Ki-67, EMMPRIN, and VEGF were weaker in IT carcinoma than in the MT intestinal portion (p < 0.05), while the opposite was true for CD44, MUC-2, and MUC-6 (p < 0.05). The MT diffuse component displayed a higher expression of FHIT, VEGF, and P-GSK3β-ser9 than DT carcinoma (p < 0.05). The accumulative survival rate of the IT carcinoma patients was higher than the other types (p < 0.05). The invasive depth, venous invasion, lymph node, peritoneal or liver metastasis, and Lauren's classification were independent prognostic factors for gastric carcinomas (p < 0.05). These findings suggested that MT carcinomas were also indicated to be more aggressive than IT and DT carcinomas. Significant differences were observed in the proliferation, apoptosis, angiogenesis, mucin secretion, and cell adhesion between IT and DT carcinomas, whereas only a few of these characteristics showed differences between the MT intestinal and diffuse parts, thus suggesting that both the MT components might originate from the stem cells with similar genetic traits, but follow different histogenic pathways.

Large Metastatic Lymph Node Size, Especially More Than 2 cm: Independent Predictor of Poor Prognosis in Node‐Positive Gastric Carcinoma

The presence of metastatic lymph nodes (MLNs) is the most important prognostic factor for gastric carcinoma, with the number of MLNs thought to be predictive of the prognosis. However, there have been long-standing debates on how to classify node-positive patients into prognostic groups appropriately. Recent findings in patients with colon and esophageal cancer have suggested that MLN size, more than MLN number, is an important prognostic factor; but less is known about the impact of MLN size on the prognosis of patients with gastric carcinoma. We therefore assessed the prognostic impact of large MLNs, especially those>or=2 cm, in patients with gastric carcinoma. A total of 1190 patients who underwent curative resection for gastric carcinoma between 2001 and 2003 and had lymph node metastases were divided into two groups according to the size of the largest MLN:>or=2 cm (n=51) vs. <2 cm (n=1139). Clinicopathologic data, including tumor recurrence and survival, were reviewed retrospectively. The median follow-up for living patients was 47 months (range 30-80 months). Age, sex ratio, type of surgery, and histologic classification did not correlate with MLN size. The depth of invasion did correlate with MLN size (T1-2 vs. T3-4, p=0.045) but not with the number of MLNs (N stage, p=0.311). The two groups showed similar distribution of stage according to the UICC/AJCC TNM staging system. Disease-free survival (34% vs. 53%, p<0.001) and overall survival (40% vs. 63%, p=0.011) were significantly worse in the large MLN group. Univariate analysis with the log-rank test showed that MLN>or=2 cm, type of surgery, T stage, N stage, and histologic classification had a significant impact on overall survival. Multivariate analysis with the Cox proportional hazard model showed that MLN>or=2 cm was an independent prognostic factor (hazard ratio 1.76, p=0.006), along with T stage and N stage. MLN>or=2 cm is an independent additional predictor of poor prognosis in patients with node-positive gastric carcinoma.

Serum Albumin as a Significant Prognostic Factor for Patients with Gastric Carcinoma

The definition of prognostic factors in gastric carcinoma (GC) remains controversial. The potential of serum albumin as a prognostic factor for GC is emphasized because the technique to measure it is simple as well as being cheap and widely available. Our aim was to define the prognostic role of serum albumin in GC. A cohort treated from January 1987 to December 2002 was studied. Relevant clinical, pathological and therapeutic variables were recorded. Kaplan-Meier and Cox's methods were used to define prognostic factors associated with cancer-related survival. One thousand and twenty-three patients were included. Serum albumin did impact survival, showing a dose-response effect. This effect was present after adjustment for other prognostic factors, including Tumor-Node-Metastasis (TNM) stage, surgical resection and type of lymphadenectomy. In multivariate analysis, TNM stage [Stage Ia and Ib Hazard Ratio [HR] 1, Stage II HR 1.6 (95% confidence interval [CI], 0.56-4.7), Stage IIIa HR 4.4 (95% CI 1.7-11.3), Stage IIIb HR 5.6 (95% CI 2.6-17.2), Stage IV HR 6.8 (95% CI 2.7-17.5), high albumin HR 1, medium albumin HR 1.2 (95% CI 0.8-1.7), low albumin HR 1.2 (95% CI 0.8-1.8), very low albumin HR 1.8 (95% CI 1.3-2.6), D2 dissection HR 1, D1 dissection HR 1.9 (95% CI 1.3-2.97), and no resection HR 3.7 (95% CI 2.4-5.7)] were the most significant prognostic factors associated to survival (model P = 0.00001). Pretherapeutic serum albumin level is a significant prognostic factor, which should be evaluated along with other well-defined prognostic factors in decisions concerning therapy for GC.

Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas

Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a key role in responses to hypoxia and expression of HIF-1alpha downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF-1alpha expression in gastric carcinoma. We examined HIF-1alpha, vascular endothelial growth factor (VEGF), and insulin-like growth factor-2 (IGF-2) expression patterns immunohistochemically in 126 specimens of gastric carcinoma. CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density (MVD) within tumors and correlations between HIF-1alpha expression, clinicopathological features, and survival were examined. HIF-1alpha expression correlated with tumor size (P<0.005), depth of invasion (P=0.018), VEGF expression (P=0.03), and intra-tumor MVD (P<0.005). IGF-2 expression was more prevalent in HIF-1alpha positive than in HIF-1alpha negative tumors and the 5-year survival rate was 58.4% for HIF-1alpha positive patients and 81.5% for HIF-1alpha negative patients (P=0.009). HIF-1alpha expression is an independent prognostic factor in gastric carcinoma (P=0.032). Overexpression of HIF-1alpha in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients.

Expression of Hepatoma-Derived Growth Factor Is Correlated with Lymph Node Metastasis and Prognosis of Gastric Carcinoma

Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined. HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1. One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival. HDGF expression level was shown to be a prognostic factor for gastric carcinoma.

Prognostic Factors in Gastric Carcinoma with Peritoneal Dissemination

Objective: The prognosis for gastric carcinoma patients with peritoneal dissemination is very poor. We evaluated the survival benefit of resection and intravenous chemotherapy in these patients.Material and methods: We reviewed the hospital records of 348 gastric carcinoma patients with peritoneal dissemination seen during the period from 1986 to 2000.Results: Based on the grade of anaplasia, 76 (21.8%) were differentiated and 272 (78.2%) were undifferentiated. In the univariate analyses, the factors influencing the 5-year survival rate were histologic type, resection, and intravenous chemotherapy. Using Cox’s proportional hazard regression model, two factors were independent, statistically significant prognostic parameters: resection (risk ratio, 1.48; 95% confidence interval, 0.90-2.46; p<0.05) and intravenous chemotherapy (risk ratio, 1.68; 95% confidence interval 1.15-2.47; p < 0.01). The 5-year survival rate was higher for patients who had intravenous chemotherapy (3.6%) than for patients who did not (2.4%), and also higher for patients who underwent resection (4.8%) than for patients who did not (0%; p < 0.001).Conclusion: The results highlight the improved survivorship of gastric carcinoma patients with peritoneal dissemination who had resection and received intravenous chemotherapy, compared with those who did not. Although curative resection cannot be performed in this group of patients, we recommend performing resection and subsequent intravenous chemotherapy.

Epidemiology and long term survival of gastric carcinoma in the French district of Finistère between 1984 and 1995

The aims of this study were to evaluate trends in incidence, clinical characteristics, treatment regimen and prognosis of gastric carcinoma in the area of Finistere (France) during a 12-year period. Between 1984 and 1995, the Finistere Registry of GastroIntestinal Tract Tumors listed 2 139 patients with gastric carcinoma in a population of 838 627 inhabitants. Curative resection and operative mortality were analyzed by logistic regression. Prognostic factors were determined using the Kaplan-Meier method and the Cox model. When comparing the second period (1990-1995) to the first period (1984-1989) we observed: a) a decrease of standardized incidence (13.2 vs. 15.6/100 000 inhabitants/year in males and 5.4 vs. 7.0/100 000 inhabitants/year in females); b) a significant increase of linitis plastica (21.4% vs. 10.9%) and infiltrative tumors (53.1 vs. 31.2%) (P<0.0001); c) no variation in tumor stage at diagnosis; d) a significant increase in curative resection (65.7% vs. 45.0%; P<0.0001); e) no variation in operative mortality; f) the absence of improvement of survival rate; the latter was 29% at 2 years, 19% at 5 years and 11% at 10 years during the second period. Multivariate analysis showed that the main prognostic factors of gastric carcinoma were age, tumor stage and the type of surgical procedure. This study showed a decrease in the incidence of gastric carcinoma over time and an increase of linitis plasticia and infiltrative forms. Despite improvement in management of patients, the global prognosis of gastric carcinoma did not improve significantly over a 12-year period of observation.

Prognostic effect of CD55SC-1 in gastric carcinoma (GC) and survival after treatment with the monoclonal antibody SC-1

4067 Background: SC-1 is a human monoclonal IgM antibody that targets CD55SC-1, a cell surface receptor specifically expressed on human GC cells, inducing apoptotic cell death and tumor cell regression in nude mice with no toxicity. The aim of this study was to examine whether CD55SC-1 expression is a prognostic tool in GC, and whether SC-1 confers a survival benefit in GC patients. Methods: Retrospective data from 126 CD55SC-1 positive and negative GC surgery-only patients from 1990–1997 was used to determine the prognostic ability of CD55SC-1. In an open-label, non-randomized study between 1997–2001, 51 CD55SC-1 positive GC patients received a single i.v. infusion of 10–30mg SC-1 24–48 hours before curative surgical (R0) resection. Data were compared to 19 CD55SC-1 negative GC patients who received only curative surgery between 1997–2001. Results: In the retrospective analysis, median survival of CD55SC-1 negative R0 patients was better than untreated CD55SC-1 positive R0 patients (93 months vs. 27 months); better UICC staging is associated with CD55SC-1 negative patients who are more associated with longer survival than CD55SC-1 positive patients (Cox proportional hazards, HR=2). In R0 resected patients after 1997, treatment with SC-1 increased survival at 2 years (77%) compared to CD55SC-1 negative untreated patients (63%). Conclusions: CD55SC-1 may be a prognostic factor in GC; an imbalance in UICC stage between CD55SC-1 positive and negative patients requires further data to confirm the prognostic ability of CD55SC-1, and may also indicate that CD55SC-1positive tumors are more aggressive. Treatment of CD55SC-1 positive GC patients with SC-1 increased 2-year survival compared to CD55SC-1 negative untreated patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration H3 Pharma, Inc.; OncoMab GmbH OncoMab GmbH OncoMab GmbH

Prognostic effect of CD55SC-1 in gastric carcinoma (GC) and survival after treatment with the monoclonal antibody SC-1

4067 Background: SC-1 is a human monoclonal IgM antibody that targets CD55SC-1, a cell surface receptor specifically expressed on human GC cells, inducing apoptotic cell death and tumor cell regression in nude mice with no toxicity. The aim of this study was to examine whether CD55SC-1 expression is a prognostic tool in GC, and whether SC-1 confers a survival benefit in GC patients. Methods: Retrospective data from 126 CD55SC-1 positive and negative GC surgery-only patients from 1990–1997 was used to determine the prognostic ability of CD55SC-1. In an open-label, non-randomized study between 1997–2001, 51 CD55SC-1 positive GC patients received a single i.v. infusion of 10–30mg SC-1 24–48 hours before curative surgical (R0) resection. Data were compared to 19 CD55SC-1 negative GC patients who received only curative surgery between 1997–2001. Results: In the retrospective analysis, median survival of CD55SC-1 negative R0 patients was better than untreated CD55SC-1 positive R0 patients (93 months vs. 27 months); better UICC staging is associated with CD55SC-1 negative patients who are more associated with longer survival than CD55SC-1 positive patients (Cox proportional hazards, HR=2). In R0 resected patients after 1997, treatment with SC-1 increased survival at 2 years (77%) compared to CD55SC-1 negative untreated patients (63%). Conclusions: CD55SC-1 may be a prognostic factor in GC; an imbalance in UICC stage between CD55SC-1 positive and negative patients requires further data to confirm the prognostic ability of CD55SC-1, and may also indicate that CD55SC-1positive tumors are more aggressive. Treatment of CD55SC-1 positive GC patients with SC-1 increased 2-year survival compared to CD55SC-1 negative untreated patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration H3 Pharma, Inc.; OncoMab GmbH OncoMab GmbH OncoMab GmbH

Correlation of tumor-positive ratio and number of perigastric lymph nodes with prognosis of patients with surgically-removed gastric carcinoma.

To evaluate the tumor-positive ratio and number of perigastric lymph nodes as prognostic factors of gastric carcinoma in surgically-treated patients. The postoperative survival of 169 patients with gastric cancer who were performed D2 curative gastrectomy was analyzed with regard to its lymph node metastasis ratio and number. Meanwhile correlation of tumor-positive ratio and number of perigastric lymph nodes with pathological parameters of these patients was studied. The overall 5-year survival rate of all the patients studied was 29.6%. The 5-year cumulative survival rate in patients with 1%-20% and more than 20% of tumor-positive lymph nodes was 70.6% and 12.0% respectively, and 46.6% and 17.4% in those with 1-5 and more than 5 of tumor-positive lymph nodes respectively, which were significantly decreased with the increment of involved lymph nodes assessed by either numbers or ratio (P<0.05). Multiple stepwise regression analysis showed that both the positive ratio and number of tumor-involved lymph nodes were sensitive prognostic factors in these surgically-treated patients, which were also significantly correlated with tumor size and depth of submucosal invasion (P<0.05). Tumor-positive ratio and number of perigastric lymph nodes are associated with cancer progression and five-year survival rate, and may serve as valuable prognostic factors of gastric cancer in surgically-treated patients.

Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma.

To investigate the role of cyclooxygenase-2(COX-2) and vascular endothelial growth factor (VEGF) in the development of gastric carcinoma and correlation between expression of COX-2 and VEGF and clinicopathologic features in tissues from patients with gastric carcinoma. 281 patients with gastric carcinoma who underwent surgical resection between 1990 and 1999 at the First Affiliated Hospital, Anhui Medical University, PRC, were followed up. Expression of COX-2 and VEGF was investigated retrospectively in 232 gastric carcinoma tissues and 60 noncancerous specimens by using immunohistochemistry. The 5-year survival rates of early gastric carcinoma (EGC) and advanced gastric carcinoma (AGC) were 93.4 % and 59.0 %, respectively. Survival time was highly correlated with lymph node metastasis, vascular invasion, depth of invasion and treatment with chemotherapy. Compared with paired noncancerous tissues, expression of COX-2 and VEGF and microvessel density (MVD) value in carcinoma tissue were significantly higher. The MVD value was much higher in COX-2-positive group and VEGF-positive group than that in COX-2-negative group and VEGF-negative group. Expression of COX-2 and VEGF, as well as MVD value were highly correlated with lymph node metastasis and vascular invasion. The 5-year survival rate of patients with expression of COX-2 or VEGF was significantly lower than that of patients without COX-2 or VEGF expression. Multivariate analysis revealed that VEGF overexpression, lymph node metastasis, COX-2 overexpression, depth of invasion and vascular invasion were all independent prognostic factors of gastric carcinoma. Overexpression of COX-2 and VEGF in patients with gastric carcinoma can enhance the possibility of invasion and metastasis, implicating a poor prognosis. They may serve as the fairly good prognostic factors to indicate biologic behaviors of gastric carcinoma.

Extended lymph node dissection in gastric carcinoma: where do we stand after the Dutch and British randomized trials?

Despite declining incidence in Western Europe and the United States, gastric carcinoma remains the second most common cause of cancer death worldwide with over 600,000 deaths per year. The curative treatment of gastric carcinoma remains primarily surgical. But developments in surgery have been slowed in the West by the large percentage of patients presenting with advanced cancers. In the meanwhile, some developments have taken place in Japan, in which early-stage cancers are more frequently encountered, caused in part by nationwide mass screening. Depth of tumor invasion (T categories), lymph node metastases (N categories), and the presence of distant metastases (M categories) represent three essential prognostic factors for gastric carcinoma, incorporated as key components in major stage classifications. Of these, the presence of distant metastasis indicates that the patient has a systemic disease and precludes the possibilities of curative surgical treatment. This does not necessarily apply to the lymph node metastases, because a surgical technique is available whereby the regional lymph nodes are dissected en bloc with the primary lesion. This resection technique might lead to a cure of the patients with node metastases, provided the metastases were limited to within the margin of dissection. The extent of lymph node dissection has long been debated because the Japanese proposed that it is a possible factor in improved survival, following initial attempts at anatomically “more thorough” operations by McNeer and colleagues performed in the 1950s. Theoretically, removal of a wider range of lymph nodes by extended lymph node dissection increases the chance for cure. In effect, such resection might be irrelevant and even harmful in terms of increased morbidity and mortality if the cancer had developed into a systemic disease. This review concentrates on current controversies over the extended lymph node dissection for gastric carcinoma, and offers an optimal management approach in view of the results of recent clinical trials.

C-erb B-2 expression is associated with tumor location and venous invasion and influences survival of patients with gastric carcinoma.

The HER-2/neu gene or c-erb B-2, localized on chromosome 17q, belongs to a family of tyrosine kinase receptors and shares extensive homology with the epidermal growth factor receptor. c-erb B-2 gene amplification and protein overexpression have been reported in several human cancers. The prognostic value of this genetic alteration in gastric carcinoma is far from being established. In the present study, formalin-fixed, paraffin-embedded gastric carcinoma tissues from 157 patients were evaluated for c-erb B-2 overexpression, by immunohistochemistry using a polyclonal antibody. c-erb B-2 expression was evaluated according to clinical and pathological parameters, and to the survival of the patients. Our results show that: (1). c-erb B-2 was overexpressed in 15.3% of gastric carcinoma cases; (2). c-erb B-2 overexpression was significantly more frequent in cardia (23.8%) and fundus/body (25.0%) carcinomas than in antrum (7.2%) carcinomas; (3). c-erb B-2 overexpression was significantly associated with venous invasion; (4). c-erb B-2 is a prognostic factor for gastric carcinoma.

Evaluation of Intraoperative Intraperitoneal Cytology for Advanced Gastric Carcinoma

Objective: We evaluated intraperitoneal cytology during surgery as a significant predictor of survival and tried to establish strategies for preventing peritoneal carcinomatosis. Methods: The study included 236 patients with gastric carcinoma macroscopically invading the serosa who underwent intraperitoneal cytological examination during surgery. In the 215 resected patients, the relationship between cytological positivity for cancer cells and various clinicopathologic features was analyzed. Additionally, postoperative survival was assessed in relation to the positivity of intraoperative cytology. Results: Cancer cells were positive [Cy(+)] in 78 (33.1%) of 236 patients who underwent cytological examinations. Among 73 patients with peritoneal metastases, 53 patients (72.6%) were Cy(+), as were 25 (15.3%) of the 163 patients without peritoneal metastases. Multivariate analysis indicated that peritoneal metastasis (p = 0.0001) and the depth of tumor invasion (p = 0.0069) were significant factors correlated with Cy(+). Among patients with curative surgery, the 5-year survival rate of the Cy(+) group was 22.2%, which was worse (p = 0.0004) compared with that of the Cy(–) group (60.9%). Among Cy(+) patients, the survival rate of the group treated with intraperitoneal administration of mitomycin C (MMC) and OK-432 was better (p = 0.0108) than that of the historical control group. Conclusion: These results suggest that intraperitoneal cytological examination can be a significant prognostic factor for gastric carcinoma with serosal invasion. In addition, dissemination of cancer cells in the peritoneum may be controlled by intraperitoneal immunochemotherapy with MMC and OK-432.

Is Borrmann type IV gastric carcinoma a surgical disease? An old problem revisited with reference to the result of peritoneal washing cytology.

Borrmann type IV gastric carcinoma (B-4) remains a disease with poor prognosis despite an aggressive surgical approach. Cytology examination of the peritoneal washes is an established prognostic factor for gastric carcinoma in general, and may be useful for identifying adequate treatment strategy for B-4. Pathologic data from 70 patients with B-4 who underwent laparotomy and peritoneal washing cytology during the recent 6 years were retrieved from a prospective computer database and reviewed. Prognostic significance of the cytology examination along with other known clinicopathologic variables was evaluated by univariate and multivariate analyses. Long-term survivors were observed only among the patients who were treated with curative R0 resection. Prognosis of the patients with positive cytology and no other residual disease (R1) was extremely poor and was equivalent to that of the patients undergoing noncurative R2 resection. No difference in survival, either, was observed between the patients treated by R2 resection and those who did not undergo resection. Multivariate analysis identified cytology examination as an independent prognostic factor. Peritoneal washing cytology plays an important role in staging B4. Positive cytology findings as well as other evidence of disseminated disease may indicate that gastrectomy should be avoided.