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1.  Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma 
To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC).
Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using χ2 test. Survival was analyzed using the Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression model (backward, stepwise).
A total of 181 patients with gastric cancer (74 MGC, 107 SRCC) were included. MGC, when compared with SRCC, was featured by senile patients, stage III and IV, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion (P<0.05). The overall 5-year survival rate showed no difference between the two groups (48.8% vs. 44.8%, P>0.05). However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age <60 years, negative distant metastasis, and tumor localized at upper third stomach (P<0.05). Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group.
While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.
PMCID: PMC3555291  PMID: 23372339
Mucinous gastric carcinoma; signet-ring cell carcinoma; clinicopathology; prognosis
2.  Comparison of patients by family history with gastric and non-gastric cancer 
AIM: To compare the gastric cancer (GC) patients by their family history with gastric and non-GC.
METHODS: Positive family histories within second-degree relatives and clinicopathological features were obtained for 256 patients.
RESULTS: Of the 256 probands, 112 (76 male, 36 female) were incorporated into familial GC (FGC) group: at least two GC members; 144 (98 male, 46 female) were included in the non-FGC group (relatives only affected with non-GCs). Of 399 tumors in relatives (181 from FGC against 212 from non-FGC), GC was the most frequent, followed by esophageal, hepatocellular, and colorectal cancer. Nasopharyngeal cancer was next to lung cancer but prior to breast and urogenital cancers. Most affected members aggregated within first-degree relatives (FGC: 66 siblings, 48 fathers, 31 mothers, four offspring; non-FGC: 56 fathers, 55 siblings, 43 mothers, and 15 offspring). The ratio of males to females in affected first-degree relatives was usually higher in male probands. Paternal history of GC was a slight risk for GC in males (OR = 1.19, 95% CI: 0.53-2.69), while risk of GC by maternal history of non-GCs was increased in females (OR = 0.46, 95% CI: 0.22-0.97). Diffuse-GC was the major histological type in all subgroups. Difference in tumor sites between the two groups was derived from an excess of upper sites in non-FGC female probands.
CONCLUSION: Distribution of associated non-GCs in a family history of GC may vary with geographic areas. GC may have different genetic and/or environmental etiology in different families, and a certain subtype may be inherited in a female-influenced fashion.
PMCID: PMC2691497  PMID: 19496196
Gastric cancer; Family history; Familial gastric cancer; Familial predisposition; Female-influenced fashion
3.  Effect of extramucin pools in gastric cancer patients 
Mucinous gastric adenocarcinoma (MGC) is defined by the World Health Organization as a gastric adenocarcinoma with >50% extracellular mucin pools within the tumors. In this study, we attempted to analyze the clinicopathologic features of patients pathologically diagnosed as gastric cancer with lower than 50% tumor volume of extracellular mucin pool adenocarcinoma (LEMPC). We compared MGC versus nonmucinous gastric adenocarcinoma (NMGC). We were used in abbreviations LEMPC for NMGC including extracellular mucin pool.
Files of 995 patients with gastric cancer NMGC (n = 935), MGC (n = 20), LEMPC (n = 40) who underwent curative resection at Pusan National University Yangsan Hospital from December 2008 to December 2013 were retrospectively analyzed. All pathologic reports after curative resection and evaluated clinicopathologic features were reviewed to identify the effect of extracellular mucin pools in gastric cancer.
Compared with the NMGC patients, the clinicopathological features of MGC patients were as follows: more frequent open surgery, larger tumor size, more advanced T stage and N stage, more positive lymph node metastasis, and perineural invasion. LEMPC patients showed similar features compared with NMGC patients. MGC and LEMPC patients showed similar clinicopathological features, except T stage and lymph node metastasis.
LEMPC can be thought of as a previous step of MGC. It is reasonable to consider LEMPC patients in the diagnostic criteria of MGC, and to adequately treat.
PMCID: PMC4644906  PMID: 26576405
Mucinous adenocarcinoma; Stomach; Neoplasms
4.  Characteristics and prognosis of mucinous gastric carcinoma 
Mucinous gastric carcinoma (MGC) is a rare histological subtype of undifferentiated gastric carcinoma, accounting for ~2.6–6.6% of all gastric cancer cases. The clinicopathological characteristics and prognosis of MGC are controversial. The present study aimed to determine the clinicopathological characteristics and prognosis of patients with MGC. We retrospectively compared the characteristics and postoperative survival of 70 patients with MGC and 2,492 non-MGC (NMGC) cases who underwent surgical resection between 1990 and 2010. MGC was characterised by larger tumor size, macroscopic Borrmann type 2 and 3, T4 invasion of the gastric wall, positive N2 and N3 lymph node metastasis, positive lymphatic vessel invasion, positive venous invasion, peritoneal metastasis and advanced tumor stage III and IV. The prognosis of MGC patients was worse compared to that of NMGC patients, as the former group consisted of more advanced-stage cases. When patients with similar disease stages were compared, the incidence of peritoneal metastasis was significantly higher among MGC patients. However, hepatic metastasis was found significantly more often in NMGC patients. Otherwise, the prognosis of MGC and NMGC patients with similar disease stages was not significantly different. Therefore, our findings indicated that, although MGC is more rare and mostly detected at an advanced stage, the diagnosis of the mucinous histological subtype was not an independent prognostic factor.
PMCID: PMC4251105  PMID: 25469268
gastric cancer; mucinous gastric carcinoma
5.  Clinicopathologic characteristics of serosa-positive gastric carcinoma in elderly patients 
The relationship between the prognosis and the age of patients with gastric carcinoma is controversial. This study examined the clinicopathologic features of elderly gastric carcinoma patients with serosal invasion.
We reviewed the hospital records of 136 elderly gastric carcinoma patients with serosal invasion retrospectively to compare the clinicopathologic findings in the elderly (aged > 70 years) and young (aged < 36 years).
The 5-year survival rates of elderly and young patients with curative resection did not differ statistically (33.9% vs. 43.3%; P = 0.318). Multivariate analysis showed that two factors were independent, statistically significant parameters associated with survival: histologic type (risk ratio, 1.805; 95% confidence interval [CI], 1.041 to 3.132; P < 0.05) and operative curability (risk ratio, 2.506; 95% CI, 1.371 to 4.581; P < 0.01).
This study demonstrated that elderly gastric carcinoma patients with serosal invasion do not have a worse prognosis than young patients. The important prognostic factor was whether the patients underwent curative resection.
PMCID: PMC3204556  PMID: 22066096
Gastric carcinoma; Serosal invasion; Elderly; Prognosis; Age
6.  Prognostic prediction in gastric cancer patients without serosal invasion: comparative study between UICC 7th edition and JCGS 13th edition N-classification systems 
T-stage and N-stage have been proven to be the most important factors influencing survival in gastric cancer patients, and have been accepted for use in the Japanese Classification of Gastric Carcinoma (JCGC) and the Union International Cancer Control (UICC-TNM) staging systems. The purpose of this study was to compare the prognostic values of the different N classification systems in gastric cancer patients without serosal invasion.
We retrospectively compared the clinicopathological results of 1,115 patients with primary gastric cancer who underwent curative gastric resection.
Serosal invasion was identified in 212 of 1,115 patients (19.0%), and it was associated with lymph node metastasis according to the JCGC13th (P<0.001) and TNM7th (P<0.001) systems. The 5-year survival rate for the serosal invasion-negative patients (78.2%) was significantly higher than that for the serosal invasion-positive patients (31.1%) (P<0.001). Multivariate Cox regression survival analysis showed that depth of invasion (P=0.013), 13th JCGC PN stage (P<0.001), and 7th TNM PN stage (P<0.001) were independent prognostic factors for serosal invasion-negative gastric cancer patients.
The prognosis of gastric cancer patients with serosal invasion is very poor. Both the 13th JCGC and 7th TNM N-staging systems were able to accurately estimate the prognosis of gastric cancer patients, but the 7th TNM system was simpler and easier to use.
PMCID: PMC4220259  PMID: 25400426
Gastric cancer; serosal invasion; depth of invasion; lymph node metastasis
7.  Factors predicting survival in patients with proximal gastric carcinoma involving the esophagus 
AIM: To investigate the clinicopathologic features which predict surgical overall survival in patients with proximal gastric carcinoma involving the esophagus (PGCE).
METHODS: Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009. Each retrieved pathology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were selected as PGCE. Each tumor was re-staged, following the guidelines on esophageal adenocarcinoma, according to the 7th edition of the American Joint Commission on Cancer Staging Manual. All histology slides were studied along with the pathology report for a retrospective analysis of 13 clinicopathologic features, i.e., age, gender, Helicobacter pylori (H. pylori) infection, surgical modality, Siewert type, tumor Bormann’s type, size, differentiation, histology type, surgical margin, lymphovascular and perineural invasion, and pathologic stage in relation to survival after surgical resection. Prognostic factors for overall survival were assessed with uni- and multi-variate analyses.
RESULTS: Patients’ mean age was 65 years (range: 47-90 years). The male: female ratio was 3.3. The 1-, 3- and 5-year overall survival rates were 87%, 61% and 32%, respectively. By univariate analysis, age, male gender, H. pylori, tumor Bormann’s type, size, histology type, surgical modality, positive surgical margin, lymphovascular invasion, and pT stage were not predictive for overall survival; in contrast, perineural invasion (P = 0.003), poor differentiation (P = 0.0003), > 15 total lymph nodes retrieved (P = 0.008), positive lymph nodes (P = 0.001), and distant metastasis (P = 0.005) predicted poor post-operative overall survival. Celiac axis nodal metastasis was associated with significantly worse overall survival (P = 0.007). By multivariate analysis, ≥ 16 positive nodes (P = 0.018), lymph node ratio > 0.2 (P = 0.003), and overall pathologic stage (P = 0.002) were independent predictors for poor overall survival after resection.
CONCLUSION: Patients with PGCE showed worse overall survival in elderly, high nodal burden and advanced pathologic stage. This cancer may be more accurately staged as gastric, than esophageal, cancer.
PMCID: PMC3400864  PMID: 22826627
Cancer; Esophagus; Gastroesophageal junction; Staging; Stomach
8.  Prognosis of gastric cancer patients with node-negative metastasis following curative resection: Outcomes of the survival and recurrence 
The purpose of the present study was to provide valuable prognostic information on lymph node-negative gastric cancer patients following curative resection.
Data from 112 lymph node-negative gastric cancer patients who underwent curative resection were reviewed to identify the independent factors of overall survival and recurrence.
The five-year survival rate of lymph node-negative gastric cancer patients was 85.7%, and recurrence was identified in 25 patients after curative surgery. The five-year survival rate of lymph node-negative gastric cancer patients was higher than that of lymph node-positive gastric cancer patients (P<0.001). Recurrence in lymph node-negative gastric cancer patients was less than that of lymph node-positive gastric cancer patients (P=0.001). The median survival after recurrence of lymph node-negative gastric cancer patients was longer than that of lymph node-positive gastric cancer patients (P=0.021). Using multivariate analyses, the following results were determined for lymph node-negative gastric cancer patients: sex, operative type and the presence of serosal involvement were independent factors of overall survival; and lymphadenectomy, number of dissected nodes and the presence of serosal involvement were independent factors of recurrence.
The prognosis of lymph node-negative gastric cancer patients was better than that of lymph node-positive gastric cancer patients. Male sex, subtotal gastrectomy and nonserosal involvement should be considered to be the favourable predictors of postoperative long-term survival of lymph node-negative gastric cancer patients. Conversely, limited lymphadenectomy, few dissected nodes and serosal involvement should be considered to be risk factors of postoperative recurrence of lymph node-negative gastric cancer patients.
PMCID: PMC2661304  PMID: 18925308
Gastric cancer; Lymph node metastasis; Multivariate analysis; Overall survival
9.  Prognosis of early mucinous gastric carcinoma 
Little is known about the clinicopathological features of early mucinous gastric carcinoma (MGC). The purpose of this study was to compare the clinicopathological features and prognosis between patients with early MGC and those with early nonmucinous gastric carcinoma (NMGC).
We reviewed the records of 2,732 patients diagnosed with gastric carcinoma who were treated surgically. There were 14 patients (0.5%) with early MGC and 958 with early NMGC.
Early MGC patients had a higher prevalence of elevated type (71.4%) compared with early NMGC patients (29.5%). More early MGC patients had submucosal carcinoma, compared with early NMGC patients (78.6% vs. 64.1%). The overall 5-year survival of the patients with early MGC was 97.2% as compared with 92.7% for the patients with early NMGC (P < 0.01). The statistically significant prognostic parameters influencing the 5-year survival rate according to Cox's proportional hazard regression model were: age (risk ratio, 2.22; 95% confidence interval [CI], 1.62-3.04; P < 0.01); sex (risk ratio, 1.97; 95% CI, 1.42-2.73; P < 0.01); and lymph node metastases (risk ratio, 1.88; 95% CI, 1.28-2.77; P < 0.01).
Patients with early MGC had a better prognosis than those with early NMGC. Mucinous histology itself appears not to be an independent prognostic factor. Therefore, early detection is important for improving the prognosis for patients with gastric carcinoma regardless of tumor histology.
PMCID: PMC4091442  PMID: 25025020
Gastric neoplasm; Mucinous; Prognosis; Tumor histology
10.  Borrmann’s type IV gastric cancer: clinicopathologic analysis  
Canadian Journal of Surgery  1999;42(5):371-376.
To determine whether there is a specific pattern of clinicopathological features that could distinguish Borrmann’s type IV gastric cancer from other types of gastric cancer.
A retrospective study of patients with advanced gastric cancer treated between 1985 and 1995.
The Department of Surgery, Sendai National Hospital, a 716-bed teaching hospital.
The clinicopathologic features of 88 patients with Borrmann’s type IV carcinoma of the stomach were reviewed from the database of gastric cancer. The results were compared with those of 309 patients with other types of gastric carcinoma.
Main outcome measures
Gender, age, tumour size, depth of invasion, histologic type, cancer–stromal relationship, histologic growth pattern, nodal involvement, lymphatic and vascular invasion, type of operation, cause of death and 5-year survival.
Women were afflicted as commonly as men in the Borrmann’s type IV group. These patients tended to be younger and to have larger tumours involving the entire stomach than patients with other types of cancer. Histologic type was commonly diffuse and scirrhous, and serosal invasion was prominent with infiltrative growth. Nodal involvement and lymphatic invasion were more common in patients with Borrmann’s type IV than in those with other types of gastric cancer. The disease was advanced in most instances and a total gastrectomy was performed in 55% of the patients. The survival rate of patients with Borrmann’s type IV tumour was lower than for patients with other types of gastric cancer ( p < 0.005, log-rank test).
In Borrmann’s type IV gastric cancer, early detection and curative resection are crucial to extend the patient’s survival. Aggressive postoperative chemotherapy is recommended when a noncurative resection is performed.
PMCID: PMC3788904  PMID: 10526523
11.  Plant-Derived MINA-05 Inhibits Human Prostate Cancer Proliferation In Vitro and Lymph Node Spread In Vivo1 
Neoplasia (New York, N.Y.)  2007;9(4):322-331.
Few treatment options exist for metastatic prostate cancer (PC) that becomes hormone refractory (HRPC). In vitro, plant-derived MINA-05 caused dose-dependent decreases in cell numbers in HRPC cell lines LNCaP-C4-2B and PC-3, and in androgen-sensitive LNCaP-FGC, DuCaP, and LAPC-4, by WST-1 assay. MINA-05 pretreatment significantly decreased clonogenic survival in agar and on plastic at 1 x and 2 x IC50 for PC-3 (P < .05 and P < .001, respectively), and at ½ x, 1 x, and 2 x IC50 for LNCaP-FGC cells (P < .001). MINA-05 also induced G2M arrest of LNCaP-FGC and PC-3 cells (by flow cytometry) and caused some apoptosis in LNCaP-FGC (sub-G1 peak on flow, expression of activated caspase-3) but not in PC-3 cells. Western blotting indicated that these cell cycle changes were associated with decreased levels of regulatory proteins cyclin B1 and cdc25C. MINA-05 given daily by gavage for 39 days did not diminish primary orthotopic PC-3 growth in nude mice, but decreased the extent of lymph node invasion at higher doses. We conclude that MINA-05 induces G2M arrest, inhibits cell growth, reduces PC cell regrowth in vitro, and reduces lymph node invasion after orthotopic PC-3 cell implantation in vivo. It has potential as an adjuvant treatment for patients with PC.
PMCID: PMC1854853  PMID: 17460776
Prostate cancer; G2M block; MINA-05 herbal treatment; lymph node metastases; clonogenic assays
12.  A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor 
PLoS ONE  2014;9(12):e115613.
Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma.
Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma.
The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93–24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05–34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13–10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma.
Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.
PMCID: PMC4281150  PMID: 25551773
13.  Impact of Intraoperative Macroscopic Diagnosis of Serosal Invasion in Pathological Subserosal (pT3) Gastric Cancer 
Journal of Gastric Cancer  2014;14(4):252-258.
The macroscopic diagnosis of tumor invasion through the serosa during surgery is not always distinct in patients with gastric cancer. The prognostic impact of the difference between macroscopic findings and pathological diagnosis of serosal invasion is not fully elucidated and needs to be re-evaluated.
Materials and Methods
A total of 370 patients with locally advanced pT2 to pT4a gastric cancer who underwent curative surgery were enrolled in this study. Among them, 155 patients with pT3 were divided into three groups according to the intraoperative macroscopic diagnosis of serosal invasion, as follows: serosa exposure (SE)(-) (no invasion, 72 patients), SE(±) (ambiguous, 47 patients), and SE(+) (definite invasion, 36 patients), and the clinicopathological features, surgical outcomes, and disease-free survival (DFS) were analyzed.
A comparison of the 5-year DFS between pT3_SE(-) and pT2 groups and between pT3_SE(+) and pT4a groups revealed that the differences were not statistically significant. In addition, in a subgroup analysis of pT3 patients, the 5-year DFS was 75.1% in SE(-), 68.5% in SE(±), and 39.4% in SE(+) patients (P<0.05). In a multivariate analysis to evaluate risk factors for tumor recurrence, macroscopic diagnosis (hazard ratio [HR], SE(-) : SE(±) : SE(+)=1 : 1.01 : 2.45, P=0.019) and lymph node metastasis (HR, N0 : N1 : N2 : N3=1 : 1.45 : 2.20 : 9.82, P<0.001) were independent risk factors for recurrence.
Gross inspection of serosal invasion by the surgeon had a strong impact on tumor recurrence in gastric cancer patients. Consequently, the gross appearance of serosal invasion should be considered as a factor for predicting patients' prognosis.
PMCID: PMC4286904  PMID: 25580357
Stomach neoplasms; Prognosis; Neoplasm staging
14.  Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer 
AIM: To investigate human epidermal growth factor receptor 2 (HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.
METHODS: One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study. HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) analysis on formalin-fixed paraffin-embedded gastric cancer samples from all patients. For scoring, Hofmann’s HER2 gastric cancer scoring system was adopted. All cases showing IHC3+ or FISH positivity were defined as HER2 positive. Patient clinicopathological data and survival information were collected. Finally, χ2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including; gender, age, tumor location, Lauren classification, differentiation, TNM staging, depth of invasion, lymph node metastases and distant metastasis. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.
RESULTS: According to Hofmann’s HER2 gastric cancer scoring criteria, 31 cases (15.74%) were identified as HER2 gene amplified and 19 cases (9.64%) were scored as strongly positive for HER2 membrane staining (3+), 25 cases (12.69%) were moderately positive (2+) and 153 cases (77.66%) were HER2 negative (0/1+). The concordance rate between IHC and FISH analyses was 88.83% (175/197). Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression, with 24 of these cases being eligible for Herceptin treatment according to United States recommendations, and 29 of these cases eligible according to EU recommendations. Highly consistent results were detected between IHC3+, IHC0/1 and FISH (73.68% and 95.42%), but low consistency was observed between IHC2+ and FISH (40.00%). The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively (28.57% vs 13.43%, P = 0.0103; 37.25% vs 11.64%, P < 0.0001), but were not correlated with gender, age, tumor location or TNM stage, depth of invasion, lymph node metastases and distant metastasis. In poorly-differentiated gastric cancer patients, those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis (26.47% vs 7.14%, P = 0.0021). This association was not present in those patients with well-differentiated gastric cancer (28.57% vs 43.33%, P = 0.2832). Within our patient cohort, 26 cases were lost to follow-up. The median survival time for the remaining 171 patients was 18 mo. The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively. Overall survival was not significantly different between HER2-positive and negative groups (χ2 = 0.9157, P = 0.3386), but in patients presenting well-differentiated tumors, the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group (P = 0.0123). In contrast, patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2. Furthermore, the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender, age, tumor location, TNM classification, lymph node metastases and distant metastasis.
CONCLUSION: Patients with intestinal type gastric cancer (GC), well-differentiated GC and poorly-differentiated GC without lymph node metastasis, may all represent suitable candidates for targeted therapy using Herceptin.
PMCID: PMC3627881  PMID: 23599643
Gastric cancer; Human epidermal growth factor receptor 2; Gene amplification; Protein expression; Clinicopathological characteristics
15.  Expression of Rab25 correlates with the invasion and metastasis of gastric cancer 
The objective of this study was to determine the expression of the important vesicle trafficking-regulating factor Rab25 in human gastric cancer tissues, to analyze the correlation between Rab25 protein expression with gastric cancer occurrence and development, and to discuss the correlation of Rab25 protein expression with gastric cancer cell metastasis. The overall aim was to provide experimental evidence that can be used to design future biological treatments of human gastric cancer. Human gastric cancer tissue and the adjacent normal gastric tissue were surgically removed, and immunohistochemistry and Western blotting were used to detect Rab25 protein expression. The correlation between Rab25 protein expression with the development and pathological characteristics of gastric cancer was analyzed. Using RNAi, Rab25 expression was reduced in the gastric cancer cell line MGC80-3, and the changes in MGC80-3 cell invasiveness were then monitored. Immunohistochemistry showed that the Rab25 protein expression rates were 78.21% and 23.08% in gastric carcinoma and the adjacent normal gastric tissue, respectively. Immunohistochemistry and Western blot results showed that Rab25 protein expression in gastric cancer was significantly higher than in adjacent normal gastric tissues (P<0.01). Less differentiated gastric cancer cells had higher expression of Rab25 protein (P<0.01). Gastric carcinomas from patients with a late pathological stage (III-IV) had significantly higher Rab25 protein expression than early stage (I-II) patients (P<0.01). Gastric carcinomas from patients with lymph node metastasis had significantly higher Rab25 protein expression than lymph node metastasis-free patients (P<0.01). Gastric carcinomas from patients with distant metastases had significantly higher Rab25 protein expression than the distant metastasis-negative patients (P<0.01). Rab25 protein expression in gastric cancer was not affected by the patients, sex, age, or tumor size (P>0.05). MGC80-3 cells transfected with Rab25 siRNA had significantly lower Rab25 protein expression (P<0.01) and a significantly lower number of cells that passed through a Transwell chamber compared with non-transfected controls and the transfected control group (P<0.01). Rab25 protein expression is associated with the development of gastric cancer. siRNA knockdown of Rab25 protein expression in MGC80-3 gastric cancer cells reduced MGC80-3 cell invasiveness and provided experimental evidence for potential future biological treatment strategies of human gastric cancer.
PMCID: PMC3626988  PMID: 23592900
Rab25; human gastric cancer; immunohistochemistry; Western blot; siRNA; invasion
16.  Extent of Serosal Changes Predicts Peritoneal Recurrence and Poor Prognosis After Curative Surgery for Gastric Cancer 
Medicine  2015;94(42):e1750.
To investigate whether the width of gastric serosal lesions in advanced gastric cancer patients have a predictive value for peritoneal recurrence and the 5-year survival rate.
A total of 1109 patients with advanced noncardia primary gastric adenocarcinoma, who underwent curative gastrectomy between January 1997 and December 2007, were included. Data about tumor size, longitudinal tumor location, resection type, serum albumin concentration, lymphatic/venous invasion, lymph node metastasis status, lesion size, histological and Borrmann type of tumor, as well as the recurrence rate and width of the gastric serosal lesions were collected and analyzed.
The peritoneal recurrence rate in patients with gastric serosal lesions ≤3 cm was lower than in patients with gastric serosal lesions >3 cm. Multivariate analyses of the 5-year survival rate variables for all patients revealed significant correlations with serum albumin concentrations (HR 1.382, P = 0.002, 95% CI 1.123–1.701), width of serosa changes (HR 1.377, P = 0.020, 95% CI 1.053–1.802), depth of invasion (HR 1.529, P < 0.001, 95% CI 1.288–1.814), and lymph node metastasis (HR 1.551, P < 0.001, 95% CI 1.420–1.694), whereas for recurrent patients only serum albumin concentrations (HR 2.000, P < 0.001, 95% CI 1.425–2.805), width of serosa changes (HR 1.867, P = 0.002, 95% CI 1.248–2.793), and lymph node metastasis (HR 1.521, P < 0.001, 95% CI 1.249–1.852) correlated with the 5-year survival rate.
Gastric serosal lesions >3 cm may indicate a high risk for peritoneal recurrence and serve as additional indicators for preventive postoperative adjuvant chemotherapies in patients with advanced gastric cancer.
PMCID: PMC4620790  PMID: 26496292
17.  Clinicopathological Characteristics of Alpha-Fetoprotein-Producing Gastric Cancer 
Journal of Gastric Cancer  2011;11(1):23-30.
α-fetoprotein (AFP)-producing gastric cancer is a rare tumor with high rates of liver metastasis and a poor prognosis. Many studies have been performed but there have been no comprehensive investigations of the clinicopathological and prognosis.
Materials and Methods
Six hundred ninety four patients with gastric cancer who underwent a curative gastric resection in Hanyang University Hospital from February 2001 to December 2008 were evaluated retrospectively after excluding active or chronic hepatits, liver cirrhosis and preoperative distant metastasis. Among them, thirty five patients had an elevated serum level of AFP (>7 ng/ml) preoperatively. The clinicopathological features of AFP-producing gastric cancer were analyzed.
There was poorer differentiation, a higher incidence of lymph node metastasis, more marked lymphatic and vascular invasion in the AFP-positive group than in the AFP-negative group. The 5-year survival rate of the AFP-positive group was significantly poorer than that in the AFP-negative group (66% vs. 80%, P=0.002). A significantly higher incidence of liver metastasis was observed in the AFP-positive group than in the AFP-negative group (14.3% vs. 3.6%, P=0.002) with a shorter median time period from the operation to the metachronous liver metastasis (3.7 months vs. 14.1 months, P=0.043). Multivariate survival analysis revealed the depth of invasion, degree of lymph node metastasis and AFP-positivity to be the independent prognostic factors.
AFP-producing gastric cancers have an aggressive behavior with a high metastatic potential to the liver. In addition, their clinicopathological features are quite different from the more common AFP-negative gastric cancer.
PMCID: PMC3204474  PMID: 22076198
Stomach neoplasms; Alpha-fetoproteins; Liver metastasis; Prognosis
18.  Clinicopathologic characteristics of gastric carcinoma in elderly patients: A comparison with young patients 
AIM: To examine the clinicopathologic features of elderly patients with gastric carcinoma and to investigate the relationship between prognosis and age.
METHODS: We reviewed the hospital records of 2014 patients with gastric carcinoma retrospectively to compare the clinicopathologic findings in elderly (age >70 years) and young (age <36 years) patients during the period from 1986 to 2000 in a tertiary referral center in Gwangju, Korea. Overall survival was the main outcome measure.
RESULTS: Of the 2014 patients, 194 (9.6%) were in the elderly group and 137 (6.8%) were in the young group. The elderly and young patients had similar distributions with respect to depth of invasion, nodal involvement, hepatic metastasis, peritoneal dissemination, tumor stage at the initial diagnosis, and type of surgery. Synchronous multiple carcinomas were found in 14/194 (7.2%) of the elderly group and 4/137 (2.9%) of the young group (P<0.05). Using the Borrmann classification, type IV was more frequent in the young patients than in the elderly patients (P<0.05). Significantly more elderly patients had a well or moderately differentiated histology, and more young patients had a poorly differentiated histology and signet ring cell carcinoma (P<0.001). The 5-year survival rates of elderly and young patients did not differ statistically (52.8% vs 46.5%, P = 0.5290). Multivariate analysis showed that the histologic type, nodal involvement and operative curability were significant prognostic factors, and age itself was not an independent prognostic factor of survival for elderly gastric carcinoma patients.
CONCLUSION: Elderly patients with gastric carcinoma do not have a worse prognosis than young patients. The important prognostic factor is whether the patients undergo a curative resection.
PMCID: PMC4205377  PMID: 15609390
Gastric carcinomas; Prognosis; Age; Surgery
19.  Effect of complication grade on survival following curative gastrectomy for carcinoma 
AIM: To elucidate the potential impact of the grade of complications on long-term survival of gastric cancer patients after curative surgery.
METHODS: A total of 751 gastric cancer patients who underwent curative gastrectomy between January 2002 and December 2006 in our center were enrolled in this study. Patients were divided into four groups: no complications, Grade I, Grade II and Grade III complications, according to the following classification systems: T92 (Toronto 1992 or Clavien), Accordion Classification, and Revised Accordion Classification. Clinicopathological features were compared among the four groups and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of complications of each grade on survival.
RESULTS: Significant differences were found among the four groups in age, sex, other diseases (including hypertension, diabetes and chronic obstructive pulmonary disease), body mass index (BMI), intraoperative blood loss, tumor location, extranodal metastasis, lymph node metastasis, tumor-node-metastasis (TNM) stage, and chemotherapy. Overall survival (OS) was significantly influenced by the complication grade. The 5-year OS rates were 43.0%, 42.5%, 25.5% and 9.6% for no complications, and Grade I, Grade II and Grade III complications, respectively (P < 0.001). Age, tumor size, intraoperative blood loss, lymph node metastasis, TNM stage and complication grade were independent prognostic factors in multivariate analysis. With stratified analysis, lymph node metastasis, tumor size, and intraoperative blood loss were independent prognostic factors for Grade I complications (P < 0.001, P = 0.031, P = 0.030). Age and lymph node metastasis were found to be independent prognostic factors for OS of gastric cancer patients with Grade II complications (P = 0.034, P = 0.001). Intraoperative blood loss, TNM stage, and chemotherapy were independent prognostic factors for OS of gastric cancer patients with Grade III complications (P = 0.003, P = 0.005, P < 0.001). There were significant differences among patients with Grade I, Grade II and Grade III complications in TNM stage II and III cancer (P < 0.001, P = 0.001).
CONCLUSION: Complication grade may be an independent prognostic factor for gastric cancer following curative resection. Treatment of complications can improve the long-term outcome of gastric cancer patients.
PMCID: PMC4081699  PMID: 25009399
Gastric cancer; Complication grade; Gastrectomy; Overall survival; Prognosis
20.  Tumor budding as a risk factor of lymph node metastasis in submucosal invasive T1 colorectal carcinoma: a retrospective study 
BMC Surgery  2012;12:16.
This study was designed to identify risk factors for lymph node metastasis of early stage colorectal cancer, which was confirmed to a carcinoma that invaded the submucosa after radical resection.
In total, 55 patients revealing submucosal invasive colorectal carcinoma on pathology who underwent curative radical resection at the Department of Surgery, St. Vincent’s Hospital, The Catholic University of Korea from January 2007 to September 2010 were evaluated retrospectively. Tumor size, depth of submucosal invasion, histologic grade, lymphovascular invasion, tumor budding, and microacinar structure were reviewed by a single pathologist. Student t-test for continuous variables and Chi-square test for categorical variables were used for comparing the clinicopathological features between two groups (whether lymph node involvement existed or not). Continuous variables are expressed as the mean ± standard error while statistical significance is accepted at P < 0.05.
The mean age of 55 patients (34 males and 21 females) was 61.2 ± 9.6 years (range, 43–83). Histologically, eight (14.5%) patients had metastatic lymph node. In the univariate analysis, tumor budding (P = 0.047) was the only factor that was significantly associated with lymph node metastasis. Also, the tumor budding had a sensitivity of 83.3%, a specificity of 60.5%, and a negative predictive value of 0.958 for lymph node metastasis in submucosal invasive T1 colorectal cancer.
The tumor budding seems to have a high sensitivity (83.3%), acceptable specificity (60.5%), and a high negative predictive value (0.958). A close examination of pathologic finding including tumor budding should be performed in order to manage early CRC properly.
PMCID: PMC3469500  PMID: 22866826
Lymph node metastasis; T1 colorectal cancer; Tumor budding
21.  An analysis of 13 patients with perforated gastric carcinoma: A surgeon's nightmare? 
Background and Objectives
Perforation is a rare complication of gastric carcinoma and generally not diagnosed preoperatively. To clarify the clinicopathologic characteristics of patients with this condition we reviewed 13 cases of gastric cancer perforation who required emergency surgery.
A total of 13 patients with gastric cancer perforation were retrospectively reviewed. The clinicopathological features including tumor stage and survival and also the type of treatment were analyzed and compared to literature data.
There were 13 patients (10 males and 3 females) with a mean age of 59.0 ± 9.56 years. The incidence of perforated gastric cancer was 9.6% among gastric carcinoma and 4.2% of all gastric perforation cases. The perforation was more frequently in stage III–IV (2–10), but one case of stage II (T3N0M0) gastric cancer was also observed. None of the patients had curative resection or radical lymph-node dissection. Six (46%) patients were treated by palliative, local surgery. Emergency gastrectomy were performed in 7 (54%) patients. Overall 30-day mortality rate was % 46. The overall survival time was 128.2 ± 184.8 days for all patients, it was 52.8 ± 52.9 days for locally treated group, and 192.9 ± 235.4 days for patients who underwent resectional surgery. The difference between the treatment groups was not significant
Perforation usually occurs in advanced stages of gastric cancer. These patients had a poor prognosis because of the presence of advanced cancer.
PMCID: PMC2397385  PMID: 18471321
22.  Lymph node metastasis in gastric cardiac adenocarcinoma in male patients 
AIM: To reveal the clinicopathological features and risk factors for lymph node metastases in gastric cardiac adenocarcinoma of male patients.
METHODS: We retrospective reviewed a total of 146 male and female patients with gastric cardiac adenocarcinoma who had undergone curative gastrectomy with lymphadenectomy in the Department of Surgery, Xin Hua Hospital and Rui Jin Hospital of Shanghai Jiaotong University Medical School between November 2001 and May 2012. Both the surgical procedure and extent of lymph node dissection were based on the recommendations of Japanese gastric cancer treatment guidelines. Univariate and multivariate analyses of lymph node metastases and the clinicopathological features were undertaken.
RESULTS: The rate of lymph node metastases in male patients with gastric cardiac adenocarcinoma was 72.1%. Univariate analysis showed an obvious correlation between lymph node metastases and tumor size, gross appearance, differentiation, pathological tumor depth, and lymphatic invasion in male patients. Multivariate logistic regression analysis revealed that tumor differentiation and pathological tumor depth were the independent risk factors for lymph node metastases in male patients. There was an obvious relationship between lymph node metastases and tumor size, gross appearance, differentiation, pathological tumor depth, lymphatic invasion at pN1 and pN2, and nerve invasion at pN3 in male patients. There were no significant differences in clinicopathological features or lymph node metastases between female and male patients.
CONCLUSION: Tumor differentiation and tumor depth were risk factors for lymph node metastases in male patients with gastric cardiac adenocarcinoma and should be considered when choosing surgery.
PMCID: PMC3787356  PMID: 24115823
Gastric neoplasm; Lymph node metastasis; Risk factors; Gastrectomy; Lymphadenectomy
23.  Gastric cancer: predictors of recurrence when lymph-node dissection is inadequate 
The TNM classification (sixth edition) requires at least 15 lymph nodes to be examined to allow an accurate staging. However, in our environment, only 20% of patients have the recommended minimum of 15 nodes removed.
To evaluate clinicopathological predictors of recurrence in patients with gastric cancer undergoing radical resection with an inadequate number of lymph nodes examined.
101 patients were included in this retrospective cohort. We evaluated age, gender, tumoral location, Borrmann type, Lauren histotype, type of gastrectomy, grade, invasion depth of tumor, lymph node involvement, ratio between metastatic and total number of excised lymph nodes keeping 20% as the cutoff value (LNR) and adjuvant treatment. The association between these variables and recurrence was investigated by using univariate methods and multivariate logistic regression analysis.
Median (range) age was 63 years (44-85). 63% males, 37% females. Median follow-up time for the whole patients population was 36 months (10-104). Median number of lymph nodes retrieved was 6 (0-14). Recurrence: 50 of 101 cases (49,6%); 41 hematogeneus dissemination, 9 locoregional recurrences. The following factors were found to be correlated with the recurrence risk: tumoral location, invasion depth of tumor, lymph node involvement and LNR. A multivariate analysis revealed that depth of invasion [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.03-7.58, P = 0.04] and LNR (OR 2.34, 95% CI 1.05-5.21, P = 0.03) were independent risk factors for recurrences of gastric cancer. Median time to recurrence: 16 months (2-50). 82% of recurrences occurred within the first two years after surgical treatment. The estimated cumulative risk of recurrence at five years: 61% in the whole patients population, with serosal invasion and LNR > and < 20% was 82% and 44%, without serosal invasion 73% and 39% respectively.
Invasion depth of tumor and LNR were independent predictors of recurrence in gastric cancer after potentially curative resection with an inadequate number of lymph nodes examined.
PMCID: PMC2753311  PMID: 19761613
24.  Prognostic factors of T4 gastric cancer patients undergoing potentially curative resection 
AIM: To investigate the prognostic factors of T4 gastric cancer patients without distant metastasis who could undergo potentially curative resection.
METHODS: We retrospectively analyzed the clinical data of 71 consecutive patients diagnosed with T4 gastric cancer and who underwent curative gastrectomy at our institutions. The clinicopathological factors that could be associated with overall survival were evaluated. The cumulative survival was determined by the Kaplan-Meier method, and univariate comparisons between the groups were performed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model and a step-wise procedure.
RESULTS: The study patients comprised 53 men (74.6%) and 18 women (25.4%) aged 39-89 years (mean, 68.9 years). Nineteen patients (26.8%) had postoperative morbidity: pancreatic fistula developed in 6 patients (8.5%) and was the most frequent complication, followed by anastomosis stricture in 5 patients (7.0%). During the follow-up period, 28 patients (39.4%) died because of gastric cancer recurrence, and 3 (4.2%) died because of another disease or accident. For all patients, the estimated overall survival was 34.1% at 5 years. Univariate analyses identified the following statistically significant prognostic factors in T4 gastric cancer patients who underwent potentially curative resection: peritoneal washing cytology (P < 0.01), number of metastatic lymph nodes (P < 0.05), and venous invasion (P < 0.05). In multivariate analyses, only peritoneal washing cytology was identified as an independent prognostic factor (HR = 3.62, 95% CI = 1.37-9.57) for long-term survival.
CONCLUSION: Positive peritoneal washing cytology was the only independent poor prognostic factor for T4 gastric cancer patients who could be treated with potentially curative resection.
PMCID: PMC3063911  PMID: 21448423
Gastric cancer; T4; Prognostic factors; Peritoneal cytology; Venous invasion
25.  Prognostic Factors for Advanced Gastric Cancer: Stage-stratified Analysis of Patients who Underwent Curative Resection 
Advanced gastric cancer patients have a poorer prognosis as compared to the patients with early gastric cancer. This study was conducted to define the prognostic factors for advanced gastric cancer.
Materials and Methods
606 patients with advanced gastric cancer who underwent curative gastric resection at our hospital were retrospectively examined. The patients were divided into two groups: group 1 was comprised of patients with a survival time <5 years, and group 2 patients had a survival time ≥5 years. We compared clinicopathological characteristics of the two groups by performing univariate and multivariate analysis. We also investigated the prognostic factors according to the stage.
On univariate analysis, 7 factors (age, tumor size, Borrmann type, resection type, distal resection margin, depth of invasion and lymph node status) were found to be different, and multivariate analysis revealed that patient age, depth of invasion and lymph node metastasis were the only significantly differences between the two groups. On the other hand, age and the Borrmann type for stage I b patients, age and the number of retrieved lymph nodes for stage II patients, tumor size for stage III patients, and the type of resection for stage IV patients were found to be the independent prognostic factors.
The age of patients had prognostic value in the early stages of advanced gastric cancers such as stage I b or II. The number greater than 20 retrieved lymph nodes affected the survival, particularly for the patients with stage II disease, and the tumor size was a significant prognostic factor for patients with stage III disease. Therefore, physicians are advised to pay special attention to lymph node dissection for those patients with stage II or III disease.
PMCID: PMC2741652  PMID: 19771253
Stomach neoplasms; Prognostic factor

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