Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial.

PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.     

Lymph node dissection for gastric cancer.

Complete tumor removal with margins of clearance at the resection lines must be the aim of today's surgical treatment of gastric cancer, and this must be applied even in lymph node dissection. But, over the last few decades, the extent and impact of lymphadenectomy remains controversial. Whereas Japanese centers advocate extensive lymph node dissection as the base of their excellent results, many Western surgeons, supported by actual randomized trials, believe that the potential benefit of such procedures cannot outweigh the risk of increased postoperative morbidity and mortality. However, if lymphadenectomy is restricted to the removal of nodes only, it does not influence the operative risk. Further, the lymph node ratio and number of lymph nodes involved are relevant prognostic parameters. Survival improvement can be achieved in a moderate degree of metastatic involvement of the nodes (pN0,1). Therefore, systematic lymph node dissection should be an integral part of the curative resection sought. Limited or no lymphadenectomy might be indicated in noncurative surgery or in special types of mucosal early gastric cancer, respectively.     

Evolution of gastric surger y techniques and outcomes

Surgical management of gastric cancer improves survival. However, for some time, surgeons have had diverse opin-ions about the extent of gastrectomy. Researchers have conducted many clinical studies, making slow but steady progress in determining the optimal surgical approach. The extent of lymph node dissection has been one of the major issues in surgery for gastric cancer. Many trials demonstrated that D2 dissection resulted in greater morbidity and mortality than D1 dissection. However, long-term outcomes demonstrated that D2 dissection resulted in longer survival than D1 dissection. In 2004, the Japan Clinical Oncology Group reported a pivotal trial which was performed to determine whether para-aortic lymph node dissection combined with D2 dissection was superior to D2 dissec-tion alone and found no beneift of the additional surgery. Gastrectomy with pancreatectomy, splenectomy, and bursectomy was initially recommended as part of the D2 dissection. Now, pancreas-preserving total gastrectomy with D2 dissection is standard, and ongoing trials are addressing the role of splenectomy. Furthermore, the feasibility and safety of laparoscopic gastrectomy are well established. Survival and quality of life are increasingly recognized as the most important endpoints. In this review, we present perspectives on surgical techniques and important trials of these techniques in gastric cancer patients.     

Laparoscopic pancreas- and spleen-preserving D2 lymph node dissection in advanced (cT2) upper-third gastric cancer

BACKGROUND AND OBJECTIVES: Although the laparoscopic assisted total gastrectomy (LATG) has been performed in upper gastric cancer, dissection of lymph nodes No. 10 and 11d without resection of the distal pancreas and the spleen has been hard to accomplish, because of the possibilities of injury to splenic vessels and parenchyma of the spleen or pancreas. Herein, we present successful results in laparoscopic pancreas- and spleen-preserving D2 lymph node dissection in advanced upper gastric cancer. METHODS: Between March 2004 and May 2007, 18 clinical T2 patients who underwent LATG with D2 lymph node dissection for upper gastric cancer were enrolled. RESULTS: We used the technique of encircling and pulling the splenic artery with umbilical tape and that helped us complete dissection of lymph nodes No. 10 and 11d without distal pancreatectomy or splenectomy. The mean operative time was 370 min without any perioperative complications or conversion to an open procedure. CONCLUSIONS: Laparoscopic extended lymph node dissection without pancreatectomy or splenectomy can be adapted to the patients with clinical T2 upper gastric cancer. The techniques like taping of the splenic artery can be a useful tip for surgeons who wish to perform laparoscopic complete D2 lymph node dissection in advanced upper gastric cancer.     

Extended lymph node dissection in gastrointestinal cancer

We reviewed the literature concerning the effect of extended lymph node dissection on survival in patients with gastrointestinal cancer. Most retrospective and/or prospective nonrandomized comparative studies have claimed that extended lymph node dissection significantly improves survival rate in patients with esophageal cancer, gastric cancer, and colorectal cancer. However, it is difficult to interpret these results since specialized care provided in trials may itself improve survival. In gastric cancer, several prospective randomized trials have failed to demonstrate a survival advantage of extended dissection, while there are few well-done prospective randomized trials in esophageal or colorectal cancer. Therefore, the therapeutic value of extended lymph node dissection remains to be determined in gastrointestinal cancer. Randomized prospective studies within the bounds of the ethical treatment of patients can and should be done. J. Surg. Oncol. 1997;65:57-65. © 1997 Wiley-Liss, Inc.     

D2 Lymphadenectomy in Gastric Cancer Surgery

Gastric cancer is one of the most common causes of cancer death worldwide. Surgery is the most widely utilized treatment for resectable gastric cancer. Evidence indicates that lymph node involvement and depth of invasion of the primary tumor are the most important prognostic factors for gastric cancer patients. Therefore, lymph node clearance is deemed a key procedure in gastric cancer surgery for the prognostic value to patients. Although the appropriate lymphadenectomy during gastrectomy for cancer still remains controversial, extended lymph node dissection (D2 lymphadenectomy) should be recommended in high volume hospitals.     

D2 lymphadenectomy in gastric cancer surgery

Gastric cancer is one of the most common causes of cancer death worldwide. Surgery is the most widely utilized treatment for resectable gastric cancer. Evidence indicates that lymph node involvement and depth of invasion of the primary tumor are the most important prognostic factors for gastric cancer patients. Therefore, lymph node clearance is deemed a key procedure in gastric cancer surgery for the prognostic value to patients. Although the appropriate lymphadenectomy during gastrectomy for cancer still remains controversial, extended lymph node dissection （D2 lymphadenectomy） should be recommended in high volume hospitals.     

Indications for EMR/ESD in cases of early gastric cancer: relationship between histological type,depth of wall invasion,and lymph node metastasis

Background Limited surgery by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for gastric cancer is frequently performed in many institutions. These techniques do preserve gastric function and maintain a high quality of life but may compromise survival. The treatment strategy for early tumors should therefore be based on a complete cure, and limited surgery must thus have clear indications. Methods D2 gastric resection was performed in 278 early gastric adenocarcinomas, and a retrospective histological review of the specimens was made. The extended indications for EMR or ESD, according to the Japanese Gastric Cancer Association Treatment guidelines for gastric cancer in Japan, were also assessed. Results Of the 278 early gastric cancers, 115 were mucosal (M) cancers without ulcer. No lymph node metastases were seen in these specimens. Six of the 41 specimens of M cancer with ulcers had lymph node metastases at the N1 level only. One of these had lymph node metastases from a tumor measuring less than 3 cm in size. Twenty-eight of 122 submucosal cancers had lymph node metastases (23%). Twenty of these were SM1 tumors and 5 had lymph node metastases; 4 of these 5 had lymph node metastases despite the absence of vascular invasion. Conclusion Three cases had lymph node metastases that met the extended criteria for EMR/ESD. EMR and/or ESD should be limited to M cancers without ulcer or differentiated-type M cancer with ulcers smaller than 2 cm. When the depth of tumor invasion is deeper than M, then a gastric resection with lymph node dissection is necessary.     

Sentinel lymph node detection for gastric cancer: Promise or pitfall?

At present, optimal surgery for gastric cancer is still under debate, especially the extent of lymph node dissection. Gastrectomy with D1/D2 lymphadenectomy is standard treatment for resectable advanced gastric cancer. However, in early gastric cancer without lymph node metastasis, gastrectomy with D1/D2 lymphadenectomy may not be unnecessary, which could increases morbidity and mortality and reduces the quality of life (QOL). Therefore, the concept of sentinel lymph node could be applied in gastric cancer. But due to the complexity of gastric lymphatic drainage, there are still many issues under debate, such as suitable tracers, the method of mapping and collecting and the oncologic safety of sentinel node navigation surgery (SNNS). In addition, skip metastasis and unreliability of intraoperative pathological diagnosis are two main reasons for false negative cases. In this review, we summarize the current status and controversy of sentinel lymph node detection in gastric cancer, attempting to help with practical application. Further, we hold opinion that we should be cautious about performing sentinel lymph node detection in gastric cancer before an accurate and effective method occurs.     

进展期远端胃癌行扩大淋巴结清扫术的研究进展

淋巴结清扫范围一直是胃癌外科的热点问题。D2根治术作为进展期胃癌标准手术已达成共识,然而扩大淋巴结清扫的价值依然存在争议。进展期远端胃癌第14v组淋巴结转移率较高,D2+14v组淋巴结清扫有可能改善第6组淋巴结明显转移患者预后;尽管胃癌腹主动脉旁淋巴结转移视为M1,但D2+16a2/b1淋巴结清扫对局限性第16组淋巴结转移患者可能获益;而D2+13组淋巴结清扫有可能提高伴有十二指肠浸润胃癌患者生存率。本文旨在探讨扩大淋巴结清扫在胃癌中的价值,以期为临床提供依据,现就进展期远端胃癌扩大淋巴结清扫的研究进展进行综述。      

Management of lymph node metastases in breast cancer and gastric cancer

The management of regional lymph node metastases in breast cancer and gastric cancer is reviewed. Regional lymph node metastasis is a critical prognostic factor in these diseases, but there is an apparent discrepancy in the efficacy of regional lymph node dissection between them. A number of prospective randomized clinical trials have demonstrated that regional lymph node dissection improves the regional control of breast cancer, but does not improve the survival. On the other hand, only retrospective or prospective comparative studies have shown that extended lymph node dissection significantly improves the survival in gastric cancer. Although the discrepancy in the regional lymph node dissection between breast and gastric cancers has been explained by differences in their biological behaviors, caution must still be exercised in drawing conclusions from these nonrandomized studies. © 1995 Wiley-Liss, Inc.     

Application of minimally invasive treatment for early gastric cancer

BACKGROUND AND OBJECTIVES: Although various types of minimally invasive treatment have emerged as the best front-line therapies for early gastric cancer (EGC), there have been no established indications that these attempts are applicable. The purpose of this study was to propose indications for the application of minimally invasive therapy for EGC. METHODS: A total of 566 patients with EGC who had undergone gastrectomy with D2 or more extended lymphadenectomy, from July 1993 to December 1997 were retrospectively analyzed. The risk factors that determine lymph node metastasis were investigated by univariate and multivariate analysis. RESULTS: The rate of lymph node metastasis was 11.8% for all EGC, 3.4% for mucosal cancer, and 21.0% for submucosal cancer. Lymph node metastasis was associated with submucosal invasion, larger tumor size, undifferentiated histology, and the presence of lymphatic or blood vessel invasion (LBVI) by univariate and multivariate analyses. When LBVI was absent, there was no lymph node metastasis if the tumor was smaller than 2.5 cm with differentiated histology, and smaller than 1.5 cm with undifferentiated histology, regardless of depth of invasion. Extra-perigastric lymph node metastases were noted in patients with submucosal tumors that have LBVI while none of mucosal cancer showed extra-perigastric lymph node metastases. CONCLUSIONS: Minimally invasive treatment can be possibly applied for patients with EGC using these four independent risk factors for lymph node metastasis in EGC. For mucosal cancers, EMR is indicated for EGCs without lymph node involvement based on tumor size and histology. When we found LBVI by pathologic examination after EMR, gastrectomy with D1 lymph node dissection is mandatory. For submucosal cancers, patients with small tumors could be treated with laparoscopic wedge resection without lymph node dissection. However, patients with larger sized tumors or tumors with LBVI should be treated with extended (D2) lymph node dissection.     

Prognostic factors for patients with node‐negative gastric cancer: Can extended lymph node dissection have a survival benefit?

BACKGROUND AND OBJECTIVES: For the patients with node-negative gastric cancer, there is no agreement on which clinicopathological factors influence the final results except T stage. The aim of this study was to investigate the prognostic factors, and to reveal whether the extent of lymph node dissection is associated with survival benefit for these patients. METHODS: Clinicopathological data of 506 patients with node-negative gastric cancer were studied. We divided the patients into D1 and D2 groups and carried out univariate and multivariate survival analyses. RESULTS: On the univariate analysis, the factors influencing survival were age, tumor size, Borrmann type, resection type, and the T stage. However, multivariate analysis with the Cox proportional hazard model disclosed age and the T stage to be significant variables. The extent of lymphadenectomy was revealed to be the independent prognostic factors for survival only for the patients with T3 stage. CONCLUSIONS: For the patients with clinically node-negative gastric cancer, an extended D2 lymph node dissection for the patients with T1 and T2 stage has no survival benefits. Although it might have some benefit for T3 stage by multivariate analysis, we should ascertain its value through a large randomized prospective study.     

Comparison of complications after D2 and D3 dissection for gastric cancer.

BACKGROUND: D3 dissection is accepted as having higher rates of mortality and morbidity than D2 dissection. In this study, we aimed to evaluate the mortality and morbidity rates of D3 dissection in our department and to compare these with mortality and morbidity after D2 dissection. PATIENTS AND METHODS: All patients who underwent radical gastric resection with lymph node dissection for gastric adenocarcinoma between June 1999 and June 2002 were evaluated. Clinicopathologic features of the tumour, the resection and lymphadenectomy, the postoperative mortality and morbidity were analysed. RESULTS: There were 359 patients admitted for the treatment of gastric cancer. One hundred twenty four underwent palliative resection and 134 underwent resection with curative intent. Of 34/134 patients, underwent gastric resection with D3 dissection, and 100 underwent D2 dissection. The overall operative mortality rate of D2 and D3 dissections was 1 and 8.8%, respectively (p<0.05). The relaparotomy rate was almost doubled in D3 dissection group (11.8% vs. 6%) but this difference was not statistically significant. D3 dissection was also associated with an increase in morbidity (35.3% vs. 10%, p<0.05). CONCLUSIONS: This study indicates that D3 dissection can be performed with reasonable safety. It may be a useful alternative procedure in advanced cases for which additional risks of surgical morbidity and mortality are felt to be outweighed by potential benefits to patients.     

Comments to young surgeons concerning laparoscopic spleen- preserving D2 lymph node dissection for advanced gastric cancer on the upper body

Qualified radical gastrectomy with lymph node dissection is very important to the prognosis of patients with gastric cancer. Now D2 lymph node dissection is standard procedure for gastric cancer surgery, and spleen hilar lymph node dissection is mandatory for gastric cancer in upper body. Because the anatomy of vessels in this area is very complicated, D2 lymph node dissection is technical challenging not only for open gastrectomy but also for laparoscopic one. Adapting a new technique is important to all surgeons, but we surgeons should always consider a patient＇s safety as the most important factor during surgery and that efforts should be based on scientific rationale with oncologic principles. I hope that the recent report by Huang et al. about laparoscopic spleen preserving hilar lymph node dissection would be helpful to young surgeons who will perform laparoscpic total gastrectomy for gastric cancer.     

Time trends of surgical treatment and the prognosis for Japanese patients with gastric cancer

The incidence of gastric cancer is much higher in Japan than in other countries even though diagnostics and treatments of such patients have improved. The objective of this study was to present an overview of the past, present and future of surgical treatment for our patients with gastric cancer. We analysed data on 2152 Japanese men and women with gastric cancer who underwent surgical resection from 1965 to 1995 at Kyushu University in Fukuoka, Japan, based on a univariate and the multivariate analysis. We focused on time trends of surgical treatment and the postoperative outcome. Over the years, there have been favourable changes in the numbers of patients with early gastric cancer. In all cases of gastric cancer, the rate of 18% in the first six year period (group 1) was 57% in the last 5 year period (group 6). Size of the tumour was smaller, well-differentiated tumour tissue was more common, and lymphatic involvement was less frequent. Lymph node metastasis, liver metastasis and peritoneal dissemination all decreased. Extensive lymph node dissection was more frequently done and the rate of curative resection (curability A and B) increased. With increases in identifying the early stage of cancer and better perioperative care, mortality rates 30 days after the surgery greatly decreased. Multivariate analysis revealed that the 10 factors of depth of invasion, lymph node metastasis, lymph node dissection, tumour size, liver metastasis, peritoneal dissemination, lymphatic invasion, vascular invasion, lesion in the whole stomach and lesion in the middle stomach were independent factors for determining the prognosis. Detection of the tumour in an early stage, standardized surgical treatment, including routine lymph node dissection, close follow-up schedules and better perioperative management are expected to increase survival time for patients with this malignancy.     

胃癌各组淋巴结的转移特点及其在实施合理根治术中的指导意义

目的 总结胃癌1～16组淋巴结转移的规律,探讨其对实施合理胃癌根治手术的指导意义.方法 收集因胃癌行全胃切除术的73例患者的临床病理资料,淋巴结分组按照只本胃癌学会胃癌处理规约第13版进行,共分为16组,比较患者淋巴结转移率和转移度的差异.结果 淋巴结转移率由低到高排列为第15、13、16、14v、12、10、9、11、8、2.6、7、5、1、4、3组,其中第15组淋巴结的转移率为1.4%,第3组淋巴结的转移率为65.8%,差异有显著的统计学意义(P＜0.01).淋巴结转移度由低到高排列为第13、16、1、7、6、5、12、4、11、8.2、15、9、3、10、14v组,其中第13组淋巴结的转移度为10.7%,第14v组淋巴结的转移度为56.3%,差异亦有显著的统计学意义(P＜0.01).结论 胃癌全胃切除术时,对淋巴结转移率高的区域必须实施清扫;对转移度高的区域要实施完整清扫.第3组淋巴结活检阴性是缩小手术的绝对指征;第14v组淋巴结活榆阴件是缩小手术的相对指征,而活检阳性是扩大手术的相对指征;第13和16组淋巴结活检阳性是姑息于术的绝对指征,而活检阴性、同时第14v组淋巴结活检阳性则是扩大手术的绝对指征.     

Neoadjuvant chemotherapy followed by surgery in gastric cancer patients with extensive lymph node metastasis

Gastric cancer with extensive lymph node metastasis (ELM) is usually considered unresectable and is associated with poor outcomes. Cases with clinical enlargement of the para-aortic lymph nodes and/or bulky lymph node enlargement around the celiac artery and its branches are generally dealt with as ELM. A standard treatment for gastric cancer with ELM has yet to be determined. Two phase II studies of neoadjuvant chemotherapy followed by surgery showed that neoadjuvant chemotherapy with S-1 plus cisplatin followed by surgical resection with extended lymph node dissection could represent a treatment option for gastric cancer with ELM. However, many clinical questions remain unresolved, including the criteria for diagnosing ELM, optimal regime, number of courses and extent of lymph node dissection.     

A systematic review of spleen and pancreas preservation in extended lymphadenectomy for gastric cancer

Background

The overall prognosis and survival of patients with advanced gastric cancer are generally poor. Extended lymphadenectomy is recommended for patients with advanced gastric cancer; however, splenectomy and distal pancreatectomy performed with an extended lymph node dissection may be associated with increased morbidity and mortality.

Method

Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 31 December 2009. Studies on gastric carcinoma investigating extended lymphadenectomy with splenectomy and/or pancreaticosplenectomy that reported data on surgical outcomes or survival were selected.

Results

Forty studies were included in this review. Decreased complication rates were demonstrated with spleen preservation in two prospective studies and three retrospective studies, and with pancreas preservation in five retrospective studies. No randomized controlled trial showed survival benefit or detriment for preservation of spleen or pancreas in extended lymphadenectomy. Improved survival was demonstrated with spleen preservation in two prospective and eight retrospective studies, and with pancreas preservation in one prospective and four retrospective studies.

Conclusions

Preservation of the spleen and pancreas during extended lymphadenectomy for gastric cancer decreases complications with no clear evidence of improvement or detriment to overall survival.

     

New trends in surgery for gastric cancer in Japan

Although standard radical gastrectomy for gastric cancer, including lymph node dissection of compartments I and II, has been commonly utilized in Japan, new trends in gastric cancer surgery recently have been developed. In the treatment of early gastric cancer, endoscopic and limited surgeries have become more prevalent, whereas for advanced gastric cancer, super extended radical gastrectomy (SERG) and aggressive adjuvant therapy have been applied. Limited surgery includes wedge resection of the stomach, pylorus-preserving gastrectomy, vagus-preserving gastrectomy, and proximal gastrectomy. The purpose of these more limited techniques is usually to improve quality of life after surgery. Since Takahashi's lymph node staining method using fine activated carbon particles (CH40) made possible systematic para-aortic lymph node dissection, SERG has increased in popularity. The survival rate of patients with para-aortic lymph node metastases who underwent SERG was higher than that of patients who underwent extended radical gastrectomy. © 1994 Wiley-Liss, Inc.