10.1245/s10434-006-9190-x
Annals of Surgical Oncology 14:1312-1319 (2007)
© 2007 Society of Surgical Oncology
Spleen Preservation in Radical Surgery for Gastric Cardia Cancer
Chang-Hua Zhang,
Wen-Hua Zhan,
Yu-Long He,
Chuang-qi Chen,
Mei-Jin Huang and
Shi-Rong Cai1
Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong Province, People’s Republic of China
Correspondence: Address correspondence and reprint requests to: Yu-Long He; Department of Gastrointestinopancreatic Surgery of the First Affiliated Hospital of Sun Yat-Sen, University, 58 Zhongshan 2nd Road, Guangzhou, 510080 Guangdong Province, People’s Republic of China; E-mail: ylh{at}medmail.com.cn
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ABSTRACT
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Background: In gastric cardia cancer (GCC), the spleen is usually removed when the tumor is resected. This allows thorough lymph node dissection in the splenic hilus. However, the long-term effect of splenectomy on patient survival is controversial. The purpose of this study was to investigate the effect of spleen preservation on survival following radical resection for gastric cardia cancer.
Methods: We reviewed the records of 116 GCC patients (Siewert types II and III) who underwent radical resection with D2 or D3 lymphadenectomy between July 1994 and December 2003. Survival status was ascertained in December 2004 and data from 108 patients were analysed. Of these 108 patients, 38 underwent splenectomy and 70 had splenic preservation. Clinicopathological features and prognostic data of the splenectomy(+) and splenectomy(–) groups were compared.
Results: Seventy-four patients (68.5%) had lymph node involvement; 18 (16.7%) had involvement of nodes in the splenic hilus. Postoperative morbidity in the two groups was similar. Overall 5-year survival was higher in the splenectomy(–) group than the splenectomy(+) group (38.7% versus 16.9%, P =.008). Multivariate regression indicated that tumor invasion (P =.009) and lymph node metastasis (P = .001) were independent prognostic factors – they predicted decreased survival – with or without splenectomy. Although splenectomy was be associated with lower survival, it was not an independent prognostic factor (P =.085).
Conclusions: Splenectomy does not improve survival of patients who undergo curative resection for gastric cardia cancer. Thus, the spleen should be preserved in patients without direct cancer invasion of the spleen.
Key Words: Gastric cardia cancer • Spleen-preserving • Lymphadenectomy • Survival
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INTRODUCTION
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Preservation of the spleen is feasible with extended lymph node dissection in the splenic hilus, and it might improve survival after radical surgery for gastric cardia cancer. Prognostic factors were analysed for 116 patients with gastric cardia carcinoma who underwent radical resections with or without splenectomy.
Although the incidence of gastric carcinoma is decreasing throughout the world, there has been an increase in malignant tumors localized to the proximal stomach, particularly at the level of the gastric cardia.1–3 The only effective treatment for gastric cardia carcinoma is resection, and surgical advances have made it possible to safely perform combined resections of the spleen, liver, and pancreas with esophagogastric resection. Splenectomy is the most commonly performed simultaneous operation with radical resection of gastric cardia carcinoma, and its purpose is to remove metastatic lymph nodes when there is invasion of the splenic hilus or artery.4 Some reports state that average survival of patients who undergo curative gastrectomy with splenectomy and extended lymph node dissection for gastric cardia carcinoma is longer than that of patients who undergo only gastrectomy.5–7 However, other authors have suggested that patients who undergo only gastrectomy have a better prognosis.8–10 And a number of studies have demonstrated that patients undergoing gastrectomy with simultaneous splenectomy for gastric cardia carcinoma have a higher morbidity rate than patients undergoing only gastrectomy.9,11,12 Thus, the long-term effect of splenectomy on survival is still controversial. The purpose of our study was to investigate the effect of splenic preservation on survival of patients undergoing radical resection for gastric cardia cancer.
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PATIENTS AND METHODS
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Patient Population and Classification
We reviewed the records of 116 patients with gastric cardia carcinoma who underwent radical resections in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Sun Yet-san University from July 1994 to December 2003. All underwent a radical en bloc resection with extended lymph node dissection (D2 or D3). The histological classification was based on the review of histopathology reports of surgical specimens from all patients included in the study. The classification of the location of the adenocarcinomas was based on the Siewert definitions.2 Of the 116 patients, 73 (62.9%) had type II tumors and 43 (37.1%) had type III. The assignment was purely morphological and topographical and based on the findings of contrast radiography, endoscopy, computed tomography, and intraoperative findings.
Surgical Approach
The choice of surgical approach was based on the tumor type and the goal of achieving complete macroscopic and microscopic tumor resection. In general, extended total gastrectomy with transhiatal resection of the distal esophagus was performed in patients with type III tumors. In patients with type II tumors, an attempt was usually made to achieve radical resection by means of total gastrectomy associated with a transhiatal resection of the distal esophagus, at least 5 cm above the tumor, and reconstruction with esophagojejunostomy. If the success of radical tumor resection appeared unlikely, based on the intraoperative findings, an extended esophagectomy by thoracoabdominal incision was performed.
An abdominal D2 lymph node dissection was routinely performed. The mediastinal lymphadenectomy comprised en bloc and vascularized removal of all lymphatic tissue in lower posterior mediastinum and the periesophageal and parabronchial lymph nodes. Dissection of the hepatoduodenal, the left retroperitoneal para-aortic, and left renal hilus nodes was performed only in patients who had enlarged nodes in these areas on preoperative or intraoperative staging (Fig. 1
). Before 1999, splenectomy was routinely performed in patients with enlarged nodes in the splenic hilus to remove these lymph nodes. In the years following, spleen and pancreas combined resection were only performed when they were suspected to be directly infiltrated or involved by metastasis.
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FIG. 1. En bloc and vascularized lymph node dissection in the hepatoduodenal ligament and around the celiac artery.
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Grouping of Patients
Forty-two (36%) of the 116 patients underwent simultaneously splenectomy. In the splenectomy(+) group, 4 patients were excluded from the analyses: 2 because of death due to coronary infarction; 2 were lost to follow-up. In the splenectomy(–) group, 4 patients lost to follow-up were excluded from the analysis. Therefore, 38 and 70 patients from the splenectomy(+) and splenectomy(–) groups, respectively, were included in the final analysis.
The age and sex of the patients as well as the location, macroscopic type, histological grade (G), stage, and depth of the invasion (T) of the tumor, histological lymph node (N) metastasis, and type of operation were retrieved from the patients’ records. Stage of gastric carcinoma was determined according to the TNM Classification of Malignant Tumors established by The International Union Against Cancer.13 Tumor histology and the location of regional lymph nodes were described according to the Japanese classification of gastric carcinoma.14 The survival status of patients was ascertained in December 2004. The maximum follow-up period was 71 months in the splenectomy(+) group and 104 months in the splenectomy(–) group.
Statistical Analysis
In analysing survival time, the Statistical Package for the Social Sciences (SPSS 13.0, LEAD Technologies Inc., USA) was used. Survival curves and overall five–year survival rates were established according to the Kaplan–Meier method and compared using the log rank test. P < .05 was considered statistically significant. Prognostic factors were analysed with a Cox proportionate hazard regression analysis using a stepwise procedure. Multivariate 
2 and P values were used to characterize the independence of these factors; the relative risk was used to quantify the relationship between survival time and each independent factor.
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RESULTS
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The clinicopathological features of the 38 patients in the splenectomy(+) group and the 70 patients in the splenectomy(–) group are shown in Table 1. Table 2 shows histopathological findings of their tumors. Of the 108 patients, 74 (68.5%) patients had regional lymph node metastasis, 16.7% (18/108) had nodal involvement in the splenic hilus, and 15.7% (17/ 108) had involvement along the splenic artery. Two patients had pancreatic invasion and no spleen was involved. Although the splenectomy(+) group had a higher lymph node metastatic rate in the splenic hilus than the splenectomy(–) group, there were no significant differences between them (23.7% versus 12.9%). Using bivariate analysis, the only significant difference was in the extent of gastric resection (P = 0.012) between the two groups.
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TABLE 1. Clinicopathological findings of patients with gastric cardia carcinoma who underwent curative gastric resection with or without splenectomy
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TABLE 2. Histopathological findings of gastric cardia carcinoma for patients who underwent curative gastric resection with or without splenectomy
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A stepwise multiple proportional hazards regression was carried out to identify independent predictors of survival. Several variables – tumor infiltration, lymph node involvement, simultaneously splenectomy, Siewert’s classification, macroscopic appearance, extent of gastric resection, extent of lymphadenectomy, histologic type, differentiation degree, sex, and age – were tested for significance. Using Cox regression, the only variables found to independently predict survival were depth of tumor invasion (P =.009) and lymph node involvement (P =.001). The odds ratio (OR) was 2.373 for tumor infiltration and 2.269 for histological lymph node metastasis. In multivariate analysis, preservation of spleen improved survival but was not an independent prognostic factor (P =.085).
The 5-year-survival rates in the splenectomy(+) and splenectomy(–) groups were 16.9% and 38.7%, respectively. In the splenectomy(+) group, the mean survival period was 21.8 months and the median survival period was 18.9 months. In the splenectomy(–) group, the mean survival period was 28.6 months and the median survival period was 21.9 months. Survival in the splenectomy (+) and (–) groups were compared by the Kaplan-Meier and log-rank tests, and showed significant differences (P =.008) (Fig. 2). According to strata analysis adjusted for histological lymph node metastasis, there were significant differences between the splenectomy (+) and (–) groups (P =.028) (Fig. 3). The Kaplan-Meier and log-rank tests were also used to assess tumor infiltration and lymph node metastasis and their effects on survival were determined by multivariate analysis. The 5-year survival rates for patients with T1, T2, and T3 disease were 100%, 52%, and 20.1%, respectively (Fig. 4). The corresponding rates for patients with N0, N1, and N2 disease were 55.3 %, 21.7%, and 0%, respectively (Fig. 5).
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FIG. 2. According to the Kaplan-Meier and log-rank methods, there were significant differences in the survival curves of patients who underwent curative gastrectomy with splenectomy and those who underwent curative gastrectomy without splenectomy. (P =.0079).
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FIG. 3. According to the Kaplan-Meier and log-rank methods, there were significant differences in the survival curves of patients who underwent curative gastrectomy with splenectomy and those who underwent curative gastrectomy without splenectomy adjusted for histological lymph node metastasis (P =.0284).
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FIG. 4. According to the Kaplan-Meier and log-rank methods, there were survival differences among tumor infiltration (T) subgroups of patients who underwent splenectomy and those who did not.
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FIG. 5. According to the Kaplan-Meier and log-rank methods, there were survival differences among N subgroups of patients who underwent splenectomy and those who did not.
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Postoperative complications developed in 17 (15.7%) of the 108 patients (Table 3) including 1 patient who died of bleeding on the seventh postoperative day. No significant difference was found in postoperative morbidity for curative gastrectomy with or without splenectomy (18.4% versus 14%, 2 = 0.318, P =.573).
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DISCUSSION
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The incidence of proximal gastric cancers has increased.1–3 This is primarily due to an increase in the rate of adenocarcinoma of the distal oesophagus.1,2 In addition, there is a shift in the location of gastric tumors from the distal portion of the stomach to the proximal stomach and the gastric cardia.3 Despite a rising incidence, the survival rate for gastric cardia cancer has remained relatively unchanged over the past 30 years and the only effective treatment for gastric cardia carcinoma is resection.11,15 Radical skeletonizing esophagectomy including extended excision of the lymph nodes and soft tissues around the esophagus and stomach provides a chance of long-term survival to a substantial percentage of adenocarcinoma patients who are eligible for a major surgical procedure.11,15,16 Fortner et al.17 suggested that the objectives of surgical treatment of adenocarcinoma of the gastric cardia included: (1) removal of tumor and prevention or relief of obstruction of the esophagus, (2) obtaining tumor-free margins around the primary neoplasm, and (3) removal of those regional lymph nodes that are likely to be involved due to local metastasis. Since an R0 resection represents a critical prognostic factor, it appears that lymphadenectomy of regional nodes must be radical. In our institute, a radical resection for gastric cardia tumors of Siewert’s type II and III must include a standard D2 vascularized lymphadenectomy.
The spleen is rarely a target of direct invasion by gastric cardia cancers, but sometimes tumor metastases are found in the lymph nodes close to the splenic hilus and splenic artery. Lymphograms have shown that lymphatics from the upper left part of the stomach drain into the splenic hilar nodes and travel to the nodes around the celiac trunk through the splenic artery.18 About 10% of patients undergoing curative gastrectomy with splenectomy have metastatic nodes in the splenic hilus.8 For this reason, removal of the splenic hilus lymph nodes in the curative treatment of gastric cardia cancer is widely accepted and splenectomy is routinely performed simultaneously with radical esophagogastrectomy to remove these lymph nodes.4,6 Among the 108 patients, 18 patients (16.7%) had involvement of nodes at the splenic hilus and 17 patients (15.7%) had involvement of nodes along the splenic artery, but none had infiltration of the spleen or had metastases involved.
Some reports have stated that the survival of patients who undergo curative gastrectomy with splenectomy and extended lymph node dissection for gastric cardia carcinoma is longer than that of patients who undergo only gastrectomy.5–7 However, other authors have suggested that patients who undergo only gastrectomy have a better prognosis.8–10 Wanebo et al.19 suggested that elective splenectomy be avoided in patients with stage II and III gastric cancer. Erturk et al.20 concluded that simultaneous splenectomy had no effect on the survival of patients with gastric carcinoma who underwent curative resection, and it was not a prognostic factor. Using bivariate analysis, we found a significant difference only between the extent of resection in patients undergoing curative gastrectomy with or without splenectomy (P =.012). Although the splenectomy(+) group had a higher metastatic rate at the splenic hilar nodes (23.7%) than the splenectomy(–) group (12.9%), there were no significant differences. As expected, depth of tumor invasion, lymph node involvement, and simultaneous splenectomy were significant negative predictors of survival in the univariate analysis. According to the Kaplan-Meier and log-rank methods and strata analysis adjusted for histological lymph node metastasis, we also found that splenectomy had a negative effect on the survival of patients with curative resection for gastric cardia cancers because the 5-year survival rate in the splenectomy(–) group was significantly higher than that in the splenectomy(+) group. We also found that splenectomy and certain other factors were not independent predictors of survival according to the Cox regression model of proportional hazards. In contrast, the only variables found to independently predict survival were depth of tumor invasion and lymph node metastasis. Therefore, by itself, simultaneous splenectomy is not a positive prognostic factor and does not improve survival.
Indeed, simultaneous splenectomy may have a negative impact on the survival of patients with curative resection for gastric cardia cancers. For it is not an innocent procedure and may cause increased morbidity and even mortality.12,21 On the one hand, the spleen is a sophisticated filter having both blood cell monitoring and management functions and important immune functions. It accounts for 25 per cent of the total lymphoid tissue mass and removes bacterial antigens, neoplastic cells, and foreign bodies from the blood. It also produces opsonins and antibodies against infectious agents. Moreover, it is the mutual activity center of T and B lymphocytes. When the spleen is removed, these functions are lost and postoperative complications are more frequently encountered such as sepsis, wound infection, hemorrhage, subphrenic abscess, and portal vein and mesenteric thrombosis. Yoshizumi et al.22 provided evidence to suggest that gastrectomy with lymph node dissection at the splenic hilus without splenectomy could decrease postoperative morbidity. Although there was no significant difference in the complication rates between our splenectomy (–) and (+) groups, the incidence was slightly higher in the splenectomy(+) group. On the other hand, the role of the spleen in tumor immunology is still controversial. Experimental evidence suggests that destruction of malignant cells in the spleen limits the incidence of clinically apparent metastases.23
Prior to 1999 in our institute, splenectomy was routinely performed simultaneously with gastrectomy in patients with enlarged nodes at the splenic hilus for radical resection. However, the results have not been favorable, and therefore spleen and pancreas combined resection are now only performed when they are suspected to be directly infiltrated or involved by metastasis on preoperative or intraoperative staging, even in patients with enlarged nodes at the splenic hilus. Spleen-preserving lymphadenectomy at the splenic hilus is feasible. First, palpation is carried out to detect any inflammatory adhesions to the spleen that might cause a capsular tear and troublesome bleeding if not carefully divided. Then, the spleen is mobilized by dividing its posterior ligamentous attachments, which may contain blood vessels requiring control by electrocauterization or ligation. When the spleen is mobilized from the posterior parietal peritoneum in a medial direction, even outside the abdominal cavity, greatly facilitates lymph node dissection (Fig. 6). The splenic vessels are thus exposed and all associated node-bearing tissue in this area may be removed en bloc. Occasionally, it may be necessary to ligate some branches of the splenic vessels. But, more important, the procedure should be performed only by a senior expert in experienced centers because postoperative splenic bleeding may be fatal.
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FIG. 6. The spleen was mobilized outside the abdominal cavity from the posterior parietal peritoneum for lymph node dissection in the splenic hilus.
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In conclusion, our retrospective study shows that simultaneous splenectomy does not improve survival for patients with gastric cardia carcinoma who undergo curative resection and indeed may have a negative effect on survival. These results convince us that an R0 resection should be performed for all patients with gastric cardia carcinoma and spleen should be preserved except where there is direct invasion by the cancer.
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FOOTNOTES
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Supported by the Project of 211 from Chinese Education Ministry, No.98087.
Received for publication March 6, 2006.
Accepted for publication July 13, 2006.
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ABSTRACT
INTRODUCTION
