Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2016; 8(4): 410-415
Published online Apr 15, 2016. doi: 10.4251/wjgo.v8.i4.410
Clinicopathological features of patients with middle third gastric carcinoma
Jin Hong Kim, Jae Kyoon Joo, Seong Yeob Ryu, Ho Gun Kim, Jae Hyuk Lee, Dong Yi Kim
Jin Hong Kim, Jae Kyoon Joo, Seong Yeob Ryu, Ho Gun Kim, Dong Yi Kim, Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju 501-757, South Korea
Jae Hyuk Lee, Department of Pathology, Chonnam National University Medical School, Gwangju 501-757, South Korea
Author contributions: Kim JH performed the research and wrote the paper; Joo JK and Kim HG designed the research; Ryu SY contributed to the analysis; Lee JH provided clinical advice and performed the research; Kim DY conceived this research and supervised the report.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Chonnam National University Hospital.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dong Yi Kim, MD, Professor, Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Hakdong, Donggu, Gwangju 501-757, South Korea. dockim@jnu.ac.kr
Telephone: +82-62-2206450 Fax: +82-62-2271635
Received: January 5, 2016
Peer-review started: January 5, 2016
First decision: January 30, 2016
Revised: February 22, 2016
Accepted: March 14, 2016
Article in press: March 16, 2016
Published online: April 15, 2016

Abstract

AIM: To compared the prognosis of middle third gastric carcinoma (MGC) patients with those of patients with proximal/distal gastric carcinoma (PGC/DGC).

METHODS: Of 3299 patients diagnosed with gastric carcinoma who underwent surgery at our hospital over a 15-year period, 919 (27.9%) were diagnosed with MGC. For each patient, the following information was obtained from hospital records: Age, sex, tumor size, depth of invasion, histologic type, nodal involvement, extent of lymph node dissection, hepatic metastasis, peritoneal dissemination, stage at initial diagnosis, operative type, curability, and survival rate.

RESULTS: T1 category tumors were more common in patients with MGC than in patients with PGC (P < 0.001). Tumor stage (stage I), N category (N0), and T category (T1) significantly influenced the 5-year survival rates for patients with curatively resected tumors. A multivariate analysis showed that age, tumor size, serosal invasion, lymph node metastasis, and curability were significant predictors of survival in patients with MGC. The survival rate for MGC patients was similar to that for PGC/DGC patients (52.8% vs 44.4%/51.4%, P = 0.1138). The 5-year survival rate for MGC patients with curative resection was higher than that for MGC patients with non-curative resection (62.9% vs 8.7%, P < 0.001).

CONCLUSION: These results indicate that tumor location did not affect the prognosis. Curative resection is important for improving the prognosis of patients with MGC.

Key Words: Middle third gastric carcinoma, Prognosis, Curative resection

Core tip: The clinicopathological features of the patients with middle third gastric carcinoma (MGC) were reviewed retrospectively. Tumor location did not affect the prognosis. When the MGC group was divided into patients with or without curative resection, the survival rates were higher for patients with curative resection. Therefore, curative resection is important for improving the prognosis of patients with MGC.



INTRODUCTION

Although the incidence of gastric carcinoma is declining, it remains one of the leading causes of death from malignant tumors worldwide and advanced gastric carcinoma patients still have unfavorable prognoses[1]. Generally, the prognosis of patients with middle third gastric carcinoma (MGC) is better than that of patients with proximal or distal third gastric carcinoma (PGC/DGC)[2]; however, few studies have described the follow-up of patients with MGC. Therefore, it is important to analyze the prognostic factors in patients with MGC. We compared the clinicopathological features and outcomes of MGC with those of more proximally or distally located gastric carcinomas.

MATERIALS AND METHODS
Patients

Between 1987 and 2004, 3299 patients with gastric carcinoma were admitted to the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, South Korea. Of these, 919 (27.9%) had MGC. The clinicopathological features of the patients with MGC were reviewed retrospectively. Patients with carcinomas involving the entire stomach were excluded. Following the Japanese classification of gastric carcinoma outlined by the Japanese Research Society for Gastric Cancer[3], the location of each tumor was described as the proximal, middle, or distal third of the stomach. The following information about each patient was obtained from hospital records: Age, sex, tumor size, depth of invasion, histologic type, nodal involvement, extent of lymph node dissection, hepatic metastasis, peritoneal dissemination, stage at initial diagnosis, operative type, curability, and survival rate.

Statistical analysis

The survival rates of the patients were calculated using the Kaplan-Meier method, and the relative prognostic importance of the parameters was investigated using the Cox proportional hazards model. The χ2 test was used to evaluate the statistical significance of differences, and P values less than 0.05 were considered significant.

RESULTS

Of the 3299 patients diagnosed with gastric carcinoma who underwent surgery at our hospital over a 17-year period, 919 (27.9%) were diagnosed with MGC. Table 1 describes the clinicopathological features of these 919 patients and the 2312 patients with PGC/DGC. There was a significant difference in the mean age of the patients with MGC (55.8 years) compared to the patients with DGC (57.6 years) (P < 0.001). Of the 919 patients with MGC, 602 (65.5%) were male and 317 (34.5%) were female. There were more males than females in each group, but there was no significant difference in the sex ratio of each group. Carcinomas in the middle third of the stomach were smaller than were carcinomas in the proximal third of the stomach (4.2 cm vs 4.7 cm), and the difference in mean tumor size was significant (P < 0.001).

Table 1 Clinicopathologic findings of middle, proximal and distal third gastric carcinoma patients.
VariablesMGC (n = 919) (%)PGC (n = 312) (%)DGC (n = 2000) (%)P value
Age (mean, yr)55.8 ± 11.755.8 ± 12.557.6 ± 10.7< 0.001
Gender0.277
Male602 (65.5)219 (70.2)1327 (66.4)
Female317 (34.5)93 (29.8)673 (33.6)
Tumor size (mean, cm)4.2 ± 2.84.7 ± 2.63.7 ± 2.3< 0.001
Depth of invasion< 0.001
T1296 (32.2)41 (13.1)648 (32.4)
T2112 (12.2)45 (14.4)307 (15.4)
T3410 (44.6)177 (56.8)844 (42.2)
T4101 (11.0)49 (15.7)201 (10.0)
Histologic type< 0.001
Differentiated324 (35.3)108 (34.6)941 (47.1)
Undifferentiated595 (64.7)204 (65.4)1059 (52.9)
Lymph node dissection0.018
< D2215 (23.4)51 (16.3)475 (23.7)
≥ D2704 (76.6)261 (83.7)1525 (76.3)
Lymph node metastasis0.045
N (-)561 (61.1)125 (40.1)1217 (60.9)
N (+)358 (38.9)187 (59.9)783 (39.1)
Operative type< 0.001
Total gastrectomy297 (32.3)267 (85.6)75 (3.8)
Others622 (67.7)45 (14.4)1925 (96.2)
Hepatic metastasis0.068
H (-)899 (97.8)300 (96.2)1914 (95.7)
H (+)20 (2.2)12 (3.8)86 (4.3)
Peritoneal dissemination0.556
P (-)838 (91.2)282 (90.4)1829 (91.4)
P (+)81 (8.8)30 (9.6)171 (8.6)
Stage< 0.001
I356 (38.7)71 (22.7)840 (42.0)
II167 (18.2)66 (21.2)322 (16.1)
III223 (24.3)109 (34.9)432 (21.6)
IV173 (18.8)66 (21.2)406 (20.3)
Curability0.796
Curative764 (83.1)254 (81.4)1658 (82.9)
Non-curative155 (16.9)58 (18.6)342 (17.1)

Using the pTNM system, 296 patients with MGC were classified as pT1, 112 as pT2, 410 as pT3, and 101 as pT4. T1 tumors were more common in patients with MGC than in patients with PGC (32.2% vs 13.1%, P < 0.001). Using the grade of anaplasia, 324 (35.3%) of the MGC tumors were differentiated and 595 (64.7%) were undifferentiated adenocarcinomas. Of the patients with MGC, 561 (61.1%) had no lymph node metastases (pN0) and 358 (38.9%) had lymph node metastases. Lymph node metastasis was less common in patients with MGC than in patients with PGC (P < 0.05).

Hepatic metastases from MGC were found in 20 patients (2.2%), and peritoneal dissemination was present in 81 patients (8.8%). No significant differences were found in the frequency of hepatic metastasis or peritoneal dissemination among the groups. Of the patients with MGC, 396 (43.1%) were classified as either stage III or IV at the initial diagnosis. In MGC patients, 55.6% of the tumors extended to the serosa or adjacent organs (pT3 and pT4), while 72.5% of the PGCs extended beyond the serosa.

Compared with its use in MGC/DGC, total gastrectomy was performed significantly more frequently for the treatment of PGC (85.6% of cases, P < 0.001). The curative resection rate for patients with MGC was 83.1%, similar to that for patients with PGC/DGC (81.4%/82.9%, P > 0.05).

The clinicopathological variables tested in our univariate analysis are shown in Table 2. Factors influencing the 5-year survival rate were patient age, sex, tumor size, depth of invasion, histologic type, presence of hepatic metastasis, lymph node invasion, extent of lymph node dissection, and stage at initial diagnosis. When corrected for depth of invasion, tumor stage, and lymph node invasion in the two groups, tumor stage (stage I), N category (N0), and T category (T1) significantly influenced the 5-year survival rates for patients with curatively resected tumors (Table 3). A multivariate analysis showed that age, tumor size, serosal invasion, lymph node metastasis, and operative curability were significant predictors of survival for patients with MGC (Table 4). Figure 1 shows the patient survival rate according to tumor location. The 5-year survival rate for patients with MGC (52.8%) was higher than that for patients with PGC/DGC (44.4%/51.4%), but not significantly (P > 0.05). When the MGC group was divided into patients with or without curative resection, the respective 5-year survival rates were 62.9% and 8.7% (P < 0.001) (Figure 2). There were no significant differences in the survival rates among MGC, PGC, and DGC when the patients were divided into early and advanced gastric carcinoma (Figures 3 and 4).

Figure 1
Figure 1 Survival curves for middle third gastric carcinoma, proximal third gastric carcinoma and distal third gastric carcinoma. 5-year survival rate: MGC = 52.8%, PGC = 44.4%, DGC = 51.4%; = 0.1138. MGC: Middle third gastric carcinoma; PGC: Proximal third gastric carcinoma; DGC: Distal third gastric carcinoma.
Table 2 Univariate analysis of prognostic factors in middle third gastric carcinoma patients.
VariablesNo. of patients5-yr survival rateP value
Age0.0057
< 6568856.0
≥ 6523140.0
Gender0.0161
Male60248.9
Female31759.9
Tumor size (cm)< 0.001
< 561668.5
≥ 530328.0
Depth of invasion< 0.001
T129688.3
T211275.9
T341037.8
T410115.4
Histologic type0.0294
Differentiated32462.8
Undifferentiated59548.2
Hepatic metastasis< 0.001
(-)89953.7
(+)2010.8
Operative type0.4327
Total29752.4
Others62263.6
Lymph node invasion< 0.001
N (-)56177.5
N (+)35832.7
Lymph node dissection< 0.001
< D221518.3
≥ D270460.0
Stage< 0.001
I35687.5
II16762.5
III22335.2
IV17314.7
Figure 2
Figure 2 Survival curves for middle third gastric carcinoma according to curability. Five-year survival rate: curative = 62.9%, non-curative = 8.7%; P < 0.001.
Table 3 Influence of T category, and N category on the 5-year survival rate of patients with middle third gastric carcinoma surgically treated with curative intent.
VariablesPGC (n = 254) (%)MGC (n = 764) (%)P value
Depth of invasion
T177.688.80.0477
T276.076.10.7534
T344.645.10.9900
T417.316.80.1698
Lymph node metastasis
N072.379.90.0270
N142.749.60.6285
N233.431.00.6933
Stage
I77.287.90.0420
II68.463.20.5566
III33.736.30.5823
IV17.621.80.3635
Figure 3
Figure 3 Survival curves of early middle third gastric carcinoma, proximal third gastric carcinoma and distal third gastric carcinoma. MGC = 87.8%, PGC = 77.9%, DGC = 89.5%; P = 0.0936. MGC: Middle third gastric carcinoma; PGC: Proximal third gastric carcinoma; DGC: Distal third gastric carcinoma.
Table 4 Multivariate analysis of survival for middle third gastric carcinoma patients.
VariablesRisk ratio95%CIP value
Age (< 65 vs≥ 65)1.781.24-2.550.002
Tumor size (mm) (< 50 vs≥ 50)1.511.03-2.210.036
Serosal invasion (negative vs positive)2.461.45-4.150.001
Lymph node metastasis (negative vs positive)2.481.59-3.870.000
Curability (curative vs non-curative)3.462.29-5.23< 0.001
Figure 4
Figure 4 Survival curves of advanced middle third gastric carcinoma, proximal third gastric carcinoma and distal third gastric carcinoma. MGC = 40.8%, PGC = 40.6%, DGC = 39.1%; P = 0.7586. MGC: Middle third gastric carcinoma; PGC: Proximal third gastric carcinoma; DGC: Distal third gastric carcinoma.
DISCUSSION

The prognosis of gastric carcinoma varies with tumor location[4-6]. Although MGCs are reported to have relatively better outcomes than carcinomas in other parts of the stomach[2], there is limited information on the prognostic factors for MGC. Therefore, we compared the clinicopathological features and prognosis of MGC patients with those of patients with PGC/DGC.

Investigators have discussed various prognostic factors for MGC. Serosal invasion, lymph node metastasis, and lymphatic involvement were found to have significant correlations with prognosis in univariate analyses, and serosal invasion and lymphatic involvement were independent prognostic factors in a multivariate analysis[7]. Other authors have reported similar findings[8,9]. An anterior location was clearly an independent prognostic factor for patients with MGC based on a multivariate analysis. It has been postulated that tumors in the anterior wall metastasize more easily to the peritoneum compared with tumors elsewhere because there are no organs on the abdominal side of the anterior wall[5]. This explanation seems reasonable, although others do not agree[7]. In this study, we found that age, tumor size, serosal invasion, lymph node metastasis, and curability were independent predictors of survival in patients with MGC in a multivariate analysis.

The operation type for patients with MGC is controversial. One prospective randomized trial conducted in Italy stated that distal gastrectomy was sufficient for treating tumors located in the middle third of the stomach if a cancer-free microscopic margin could be achieved[10]. However, that study included a relatively small number of MGCs. Therefore, many surgeons still recommend total gastrectomy for MGC because they are concerned about the possibility of local recurrence due to the short proximal resection margin and less extensive lymph node dissection in distal gastrectomy[11,12]. In a separate report, distal gastrectomy was performed in only 39.3% of patients with a middle third advanced gastric carcinoma for the same reasons, although the authors stated that the type of gastric resection and length of the proximal resection margin did not affect the long-term prognosis. They also reported that distal gastrectomy was sufficient to achieve a tumor-free resection margin in many cases[13]. Other authors have reported that if curative surgery can be performed, the long-term prognosis of patients with MGC is not affected by the extent of gastric resection, and a distal gastrectomy is feasible[14-16]. When determining the type of operation for MGC, we also stress tumor-free resection. The statistical analysis in this study showed that operation type was not a prognostic factor.

Generally, the prognosis of patients with MGC is better than that of patients with PGC/DGC[2]; the present study showed that tumor location did not affect the prognosis. We thought that the possible reason was due to similar curative resection rates. A significant difference in survival between patients with early and advanced gastric carcinomas has been reported[7]. We also found a significant difference in survival rates between patients with early (87.8%) and advanced (40.8%) gastric carcinomas. The survival rate for patients with MGC was 52.8%, and the cumulative survival rate for patients with MGC was slightly better than that for patients with PGC/DGC. When the MGC group was divided into patients with or without curative resection, the respective 5-year survival rates were 62.9% and 8.7%. Furthermore, we evaluated the relationship between the survival of patients with gastric carcinoma after curative resection and the depth of invasion. There was no significant difference in cumulative survival between the groups when the depth of invasion was that of T2-T4 tumors.

In patients with MGC, as the tumors progress the lymph nodes around the splenic artery and hilum are also frequently involved[5]. Several studies have reported that the incidence of lymph node metastasis is 9.7%-20% along the splenic artery and 9.2%-17% at the splenic hilum in advanced PGC and MGC[17-19]. In our department, splenectomy is not routine for patients with advanced MGC. However, we perform a splenectomy when the tumor invades the spleen directly or when metastasis to the splenic hilar lymph nodes or lymph nodes around the splenic artery is suspected.

Regarding adjuvant chemotherapy, we administered postoperative chemotherapy to select patients according to the pathologic findings instead of tumor location. Since the chemotherapeutic regimen varied during the study period, we did not analyze the effect of postoperative adjuvant chemotherapy.

In conclusion, our results show that tumor location did not affect the prognosis of MGC. When the MGC group was divided into patients with or without curative resection, the survival rates were higher for patients with curative resection. Therefore, curative resection is important for improving the prognosis of patients with MGC.

COMMENTS
Background

The prognosis of patients with middle third gastric carcinoma (MGC) is better than that of patients with proximal or distal third gastric carcinoma; however, few studies have described the follow-up of patients with MGC.

Research frontiers

The prognosis of gastric carcinoma varies with tumor location. Although MGCs are reported to have relatively better outcomes than carcinomas in other parts of the stomach, there is limited information on the prognostic factors for MGC.

Innovations and breakthroughs

The authors did not find any difference in survival rates according to the tumor location. When the MGC group was divided into patients with or without curative resection, the survival rates were higher for patients with curative resection.

Applications

The study shows the importance of curative resection in patients with MGC.

Terminology

The stomach is anatomically divided into three portions: The upper (U), middle (M), and lower (L) parts. If more than one portion is involved, all involved portions should be described in order of degree of involvement, the first indicating the portion in which the bulk of the tumor is situated.

Peer-review

These authors provided an overall review of the middle third gastric cancer. These authors described several clinico pathological parameters of MGC compared to PGC/DGC. In this article, authors also demonstrated the significant difference between curative resection is one of the prognostic factors for MGC. It is interesting and acceptable for publication.

Footnotes

P- Reviewer: Chen JN, Hsu LS S- Editor: Qi Y L- Editor: A E- Editor: Lu YJ

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