Quality control of lymph node dissection in the Dutch randomized trial of D1 and D2 lymph node dissection for gastric cancer

Background. Variability among surgeons and reduced protocol adherence threaten the conduct and outcome of surgical multicenter trials. We introduced, in the Dutch Gastric Cancer Trial of D1 and D2 (extended) lymph node dissection for gastric cancer, a novel way of managing instruction, quality control, and evaluation of protocol adherence. Methods. Of 1078 patients entered in the Dutch trial, 711 patients with potentially curative resections were evaluated. Numbers and locations of lymph nodes detected at pathological investigation were compared according to the guidelines of the Japanese Research Society for the Study of Gastric Carcer. Non-compliance indicated inadequate removal of lymph node stations, whereas contamination indicated that lymph nodes were detected outside the intended level of dissection. Protocol adherence during the course of the trial, and the impact on complications, hospital mortality, and survival were evaluated. Results. Major non-compliance was noted in 15.3% of D1 and 25.9% of D2 patients. Contamination was present in 22.9% of D1 and 23.5% of D2 patients, and was limited to one or two lymph node stations only. Intensification of quality control resulted in only a marginal improvement in protocol adherence and in the number of lymph nodes detected. There was no association between protocol adherence and the occurrence of complications or long term survival. Conclusions. Contamination proved an important parameter to substantiate protocol adherence by the surgeon, whereas non-compliance had a multifactorial cause. Non-adherence to the protocol did not lead to increased hospital morbidity and mortality, but also had no impact on long term survival. Received for publication on Aug. 17, 1998; accepted on Nov. 12, 1998     

腹腔镜胃癌根治术淋巴结清扫手术入路的合理选择

腹腔镜技术在胃癌根治术中的应用已有较长时间,但是由于胃的解剖层面复杂、血供丰富、腹腔镜手术器械操作等特殊性,使腹腔镜胃癌淋巴结清扫的难度较大,技术要求较高。合理的手术入路是腹腔镜胃癌淋巴结清扫术成功的开始,也是手术顺利进行的前提。术者在熟知胃癌淋巴结引流及解剖特点的基础上,根据患者的体位、术者的站位、淋巴结清扫顺序等,不同的区域,如幽门下区、胰腺上缘区和脾门区中选择不同的手术入路,以保证安全、彻底的胃周淋巴结清扫。本文介绍本课题组在腹腔镜胃癌根治术中不同区域淋巴结清扫时的手术入路选择,以期为开展腹腔镜胃癌手术的外科医师提供参考。      

Gastroesophageal carcinoma: individualized surgical therapy

During the twentieth century, surgical management of gastroesophageal carcinoma was developed by an establishment of standard procedures with lymph node dissection according to the metastatic distribution. The "fear" of invisible micrometastasis caused surgeons to perform more aggressive resection with lymphadenectomy to control the disease locally. Although several promising results of extensive lymph node dissection have been reported, the prognostic benefits of extensive surgery have not been proven by prospective randomized trials. A novel technology to detect micrometastasis without extensive surgical resection is required to gastroesophageal carcinoma. The lymphatic mapping technique is one of the attractive candidates for a novel tool to approach this issue.     

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.     

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.     

Clinical trials of surgical treatment of malignant diseases

The Dutch Gastric Cancer Study Group Trial was the first clinical phase III trial to be carried out in the field of cancer surgery. In spite of the excellent quality of the trial, it was heavily criticized for the poor quality of the treatment itself. Actually, the hospital mortality after the new surgical treatment (D2 lymph node dissection for gastric cancer) was unacceptably high. In surgical trials, special attention should be paid to quality issues specific to surgery. The first and the most important issue is the quality of treatment given. Reproducibility, homogeneity, and verifiability are the greatest problems in surgical trials. There are also some patient factors. If the patient is old, or fragile, or obese, the results of the surgical treatment can easily be affected by these factors. The surgeon can also be a prognostic factor, especially in complicated procedures or those requiring experience and training. Experience, including postoperative care, and dexterity affect the results. If surgeons do not know how to manage complications, mortality becomes very high. Because blinding is impossible in surgical trials, the treatment may easily be affected by personal preference or prejudice. To minimize the influence of these hampering factors, the procedures should be defined in as detailed a way as possible. If pretrial training or a feasibility study (phase II) is needed, it should be carried out properly for the patients’ sake. An excellent design and excellent statistical analysis cannot lead to meaningful results if the quality of treatment is poor. Nonsense in, nonsense out.The ASCO-JSCO Joint Symposium was held in Kyoto, Japan, on October 29, 2004.     

Current status and challenges in sentinel node navigation surgery for early gastric cancer

As an optimal surgical procedure to accurately evaluate lymph node (LN) metastasis during surgery with minimal surgical resection, we have been developing sentinel node (SN) biopsy for early gastric cancer since the 1990s. Twelve institutions from the Japanese Society of Sentinel Node Navigation Surgery (SNNS), including Keio University Hospital, conducted a multicenter prospective trial to validate the SN concept using the dual-tracer method with blue dye and a radioisotope. According to the results, 397 patients were included in the final analysis, and the overall accuracy in detecting LN metastasis using SN biopsy was 99% (383 of 387). Based on the validation study, we are targeting cT1N0 with a primary tumor of ≤4 cm in diameter as an indication for SN biopsy for gastric cancer. We are currently running a multicenter nonrandomized phase III trial to assess the safety and efficacy of SN navigation surgery. The Korean group has reported the result of a multicenter randomized phase III trial. Since meticulous gastric cancer in the remnant stomach was rescued by subsequent gastrectomy, the disease-specific survival was comparable between the two techniques, implying that SN navigation surgery can be an alternative to standard gastrectomy. With the development of SN biopsy procedure and treatment modalities, the application of SN biopsy will be expanded to achieve an individualized minimally invasive surgery.     

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.     

The role of surgery in the current treatment of gastric carcinoma

Surgery currently is the only curative option in the treatment of gastric cancer. For early gastric cancer, an endoscopic mucosal resection (EMR) is adequate for intramucosal cancer less than 2?cm in diameter without ulcer. For early cancers ineligible for EMR, limited surgical operation (proximal gastrectomy, segmental resection, and pylorus-preserving distal gastrectomy) can be recommended to reduce surgical risk and achieve improvements in quality of life without decreasing survival. Subtotal/total gastrectomy plus D2 lymph node dissection is the standard surgery for advanced gastric cancer in Japan. Pancreas-preserving total gastrectomy is recommended due to the reduced risk of pancreatic fistula and postoperative diabetes. Regarding extended surgery, results of a phase III study to evaluate the role of paraaortic node dissection will be analyzed in a few years' time after the accrual of more than 500 patients in a Japan Clinical Oncology Group (JCOG) study. For scirrhous gastric cancer, left upper abdominal exenteration appears to be associated with improved survival and should be tested in another controlled trial.     

New concepts in axillary management of breast cancer

In the last decades, surgical treatment of breast cancer has evolved from more extensive procedures like radical mastectomy to less invasive breast conserving surgery. Similarly, surgical management of axilla has enormously changed from routine axillary dissection to sentinel lymph node biopsy. Traditional surgical approach to the axilla in case of sentinel lymph node negativity is to avoid completion axillary dissection. However, surgeons even avoid performing axillary dissection in selected patients with positive sentinel lymph node in clinical practice depending on the recent randomized controlled studies supporting this concept. All of the recent changes in the management of positive axilla necessitate surgeons to refresh their knowledge on this challenging topic.     

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.     

Sentinel node biopsy or limited oriented axillary dissection (LOAD) in early breast cancer.

AIMS: The value of the sentinel node biopsy technique is recognised by the majority of surgical teams as an alternative to conventional axillary lymph node dissection for the treatment of small breast cancers. Secondary procedures are necessary when lymph node invasion not detected by frozen section examination is discovered post-operatively. In order to avoid or limit these reoperations, our sentinel node biopsy technique has gradually been transformed into limited oriented axillary dissection (LOAD), which avoids secondary procedures in the majority of patients. PATIENTS AND METHODS: Three hundred and eighty two patients were operated on by the same surgeon, using the patent blue sentinel node identification technique. This technique failed in nine patients, seven of whom were obese. Only one lymph node was removed in 75 patients, two in 88 patients, 3-5 in 174 patients and more than five lymph nodes were removed in the remaining patients. Eighty-eight percent of patients had no lymph node invasion on intraoperative and post-operative examination. RESULTS: Only seven patients were reoperated by secondary conventional lymph node dissection and there was residual cancer in only one patient. CONCLUSION: The oriented limited axillary dissection technique, combined with frozen section histological examination, avoids the usually unnecessary secondary operations in small breast cancers, in which axillary lymph node invasion rarely exceeds more than two nodes. This technique requires surgeons experienced in axillary surgery and conventional sentinel lymph node biopsy. It needs to be validated on a larger scale by a multicentre randomized prospective trial comparing LOAD to conventional axillary lymph node dissection.     

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。      

Controversies in surgical treatment of gastric cancer

Conservative surgery is performed for patients with early gastric cancer, according to the guideline proposed from Japanese Gastric Cancer Society. There are many kinds of operations, such as ordinary open surgery, laparoscopic-assisted gastrectomy, laparoscopic intragastric surgery, pyrolus preserving gastrectomy, hand-assisted laparoscopic surgery. Indications of the operations are various, but it is necessary to have standard indication for each procedure. Standard operation for advanced gastric cancer in Japan is D2 gastrectomy. Surgeons in Eastern world believed that D1 + alpha or D1 + adjuvant radio-chemotherapy are the standard treatments, because of high incidence of mortality and morbidity after D2 dissection. In Japan, D4 dissection has been performed for patients with nodal involvement, and the validity of D4 dissection is now studied by two randomized trials. Combined resection for T4 tumor is believed to be mandatory. However, the validity of pancreato-splenectomy to yield a complete clearance of No. 10 or No. 11 lymph node station is in controversial, because of high incidence of the postoperative development of pancreatic fistula, anastomotic insufficiency and abscess. There was no prospective study to confirm the effect of omentectomy. Patients with advanced gastric cancer showing a serosal invasion-diameter less than 2.5 cm have less risk of peritoneal recurrence. It may be valuable to perform randomized controlled study consisting of omentum-preserving gastrectomy and gastrectomy with omentectomy. Prognosis of patients with peritoneal dissemination was improved by intraperitoneal chomo hyporthormia and peritonectomy, and prospective studies should be done to compare the effects of systemic chemotherapy and regional chemotherapy combined with peritonectomy. Furthermore, effects of neoadjuvant chemotherapy with cytoreduction with R0 resection should be confirmed by prospective studies.     

Randomized clinical trial of D2 and extended paraaortic lymphadenectomy in patients with gastric cancer

Background The survival of patients with advanced gastric cancer after D2 dissection is still poor. Asian surgeons have proposed a more radical lymph node dissection, designated as D4 dissection, where paraaortic lymph nodes are removed in combination with D2 dissection. To evaluate the survival benefit of D4 dissection, a multi-institutional randomized trial of D2 vs D4 gastrectomy was conducted. Methods Patients enrolled in the study had potentially curable gastric adenocarcinoma at an advanced stage. Patients were randomized to undergo either D2 or D4 gastrectomy. Results Two hundred and ninety-three patients were registered and 269 patients were eligible; 135 patients were allocated to the D2 group and 134 to the D4 group. Five-year survival was 52.6% after D2 surgery and 55.0% after D4 gastrectomy. There was no significant difference in survival between the D2 and D4 groups (χ² = 0.064; P = 0.801). Hospital deaths occurred in 1 patients (0.7%) in the D2 group and 5 in the D4 group D4 gastrectomy is a more risky surgery than D2 dissection. Seven patients (5.2%) in the D2 and 15 (11.2%) in the D4 group died of causes other than gastric cancer recurrence. Sixty-three patients (46.7%) in the D2 group and 52 (38.8%) in the D4 group had disease recurrence. Conclusion Prophylactic D4 dissection is not recommended for patients with potentially curable advanced gastric cancer.     

Single-institute prospective trial of laparoscopy-assisted distal gastrectomy with systemic lymph node dissection for early gastric carcinoma

Background  

Laparoscopy-assisted gastrectomy (LAG) is an advanced surgery that requires the mastery of complex surgical skills. We evaluate the feasibility of LAG with systemic lymph node dissection when participating surgeons have sufficient knowledge and experience to conduct open surgery for gastric cancer and basic laparoscopic skills.     

On the road to standardization of D2 lymph node dissection in a European population of patients with gastric cancer

The amount of lymph node dissection (LD) required during surgical treatment of gastric cancer surgery has been quite controversial. In the 1970s and 1980s, Japanese surgeons developed a doctrine of aggressive preventive gastric cancer surgery that was based on extended (D2) LD volumes. The West has relatively lower incidence rates of gastric cancer, and in Europe and the United States the most common LD volume was D0-1. This eventually caused a scientific conflict between the Eastern and Western schools of surgical thought: Japanese surgeons determinedly used D2 LD in surgical practice, whereas European surgeons insisted on repetitive clinical trials in the European patient population. Today, however, one can observe the results of this complex evolution of views. The D2 LD is regarded as an unambiguous standard of gastric cancer surgical treatment in specialized European centers. Such a consensus of the Eastern and Western surgical schools became possible due to the longstanding scientific and practical search for methods that would help improve the results of gastric cancer surgeries using evidence-based medicine. Today, we can claim that D2 LD could improve the prognosis in European populations of patients with gastric cancer, but only when the surgical quality of LD execution is adequate.     

The role of lymphadenectomy in esophageal cancer

The role of lymph node dissection for resectable esophageal carcinoma has remained controversial, addressed by two contradictory groups of surgeons: the more conservative ones considering esophageal carcinoma with lymph node metastasis to be a systematic disease and the others, supporters of extended lymph node dissection, viewing the metastatic disease phenomenon in sequential manner. In favor of extended lymphadenectomy that allows better postoperative staging, there are also the consistent event of skipping metastasis and the high rate of micrometastasis found mostly with immunohistochemical testing. The discussed concept of sentinel lymph node evaluation does not seem a feasible approach to esophageal cancer. Although there are not undoubted results that three-field resection may offer a survival benefit, before these techniques can be widely adopted, we need more experience and randomized studies to substantiate the benefit of such radical surgery.     

乳腺癌前哨淋巴结活检研究进展

近年来,乳腺癌的发病率越来越高,乳腺癌治疗方式也在不断改进,但手术仍然是早期乳腺癌治疗的主要手段。对于早期乳腺癌,前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）是一种安全、精确的手术方式,已逐渐替代腋窝淋巴结清扫术（axillary lymph node dissection,ALND）成为早期乳腺癌治疗的标准术式。随着研究的深入,SLNB的应用范围更广,术后生活质量显著改善,但其操作尚需要进一步统一规范。在前哨淋巴结微转移、宏转移、前哨淋巴结活检阳性的老年患者以及新辅助化疗的前哨淋巴结活检等方面尚未达成共识,还需要更多大型多中心前瞻性的随机试验来进一步论证。     

局部进展期胃癌合理淋巴结清扫范围再探讨*

基于随机对照临床研究结果，D 2 淋巴结清扫在全球范围被推荐为标准胃癌术式。但是针对不同分期病例的精准淋巴结清扫范围仍存在争议。淋巴结清扫数目以及淋巴结外软组织转移与患者的预后密切相关。近端非大弯侧胃癌是否切脾以彻底清扫No.10淋巴结，仍等待JCOG0110研究的最终结论。No.14组淋巴结在新版日本胃癌指南中划归为M 1，但是对于No.6 组淋巴结转移和十二指肠受累的病例而言，D 2 +No. 14v 可能会使患者获益。JCOG9501研究由于入组病例仅包括T 2b-3，N 1- 2（ⅡB-ⅢA）病例，因此其结果不能证明T 3 和/ 或N 3 病例是否能从D 2+PAND中获益，而这组病例在中国以及除日韩以外的国家非常多见。