Curettage and aspiration in splenic hilar lymph node dissection for spleen-preserving radical D2 gastrectomy

D2 radical gastrectomy is the standard procedure for gastric cancer in the middle or upper part of the stomach. According to the latest Japanese treatment guidelines for gastric cancer, dissection of the splenic hilar lymph nodes is required during the radical treatment for this condition. This study reports a D2 radical total gastrectomy employing the curettage and dissection techniques, in which the resection of the anterior lobe of transverse mesocolon, vascular denudation and splenic hilar lymph node dissection were successfully completed.Key Words: Gastric cancer, gastrectomy, lymph node dissection, curettage and dissection     

A rare complication of D3 dissection for gastric carcinoma: chyloperitoneum

Background Chyloperitoneum is the accumulation of lymphatic fluid in the peritoneal cavity. Although uncommon, it has been reported after retroperitoneal lymph node dissection. But the incidence of this complication after radical gastrectomy is unknown. In the present study, we analyzed our patients who underwent D3 dissection for gastric carcinoma and developed chyloperitoneum.Methods Between June 1999 and June 2002, a total of 134 patients with gastric cancer underwent radical lymph node dissection, performed according to the Japanese Research Society for Gastric Cancer guidelines, as the standard procedure for gastric cancer treatment. Of these patients, 34 underwent D3 lymphadenectomy, and chyloperitoneum was detected in 4 of them.Results There were three male patients and one female patient. All patients were in stage III according to the International Union Against Cancer (UICC)-TNM classification. In three patient, chyle leakage was noticed during the surgery, and surgical ligation of the duct was performed. Abdominal distension developed in one patient 7 days after the surgery, and chylous ascites was diagnosed. This patient was success-fully treated with fasting and total parenteral nutrition, within 2 weeks.Conclusion The incidence of chyloperitoneum is not low, and may increase with more aggressive surgery. Surgeons should be aware of this complication after retroperitoneal lymph node dissection, and injured lymphatics must be controlled and ligated intraoperatively.Presented as an abstract at the 12th World Congress of the International Association of Surgeons and Gastroenterologists, Istanbul, 2002.     

Laparoscopic D2 lymph node dissection for advanced gastric cancer located in the middle or lower third portion of the stomach

The standard lymph node dissection for advanced gastric cancer is a D2 dissection, performed in accordance with the new Japanese classification of gastric carcinoma (13th edition). Although laparoscopic D2 dissections according to the General rules for gastric cancer study (12th edition) have been reported, no studies have reported laparoscopic D2 dissections according to the revised classification for advanced gastric cancers located in the middle or lower portions of the stomach. The lack of such studies is due to the perceived technical difficulty of the procedure. However, we successfully performed this novel procedure in five patients with advanced gastric cancer located in the middle or lower portions of the stomach. In fact, this surgical procedure is technically feasible and safe. Received: January 31, 2000 / Accepted: May 11, 2000     

Survival results of a multicentre phase II study to evaluate D2 gastrectomy for gastric cancer

Curative resection is the treatment of choice for potentially curable gastric cancer. Two major Western studies in the 1990s failed to show a benefit from D2 dissection. They showed extremely high postoperative mortality after D2 dissection, and were criticised for the potential inadequacy of the pretrial training in the new technique of D2 dissection, prior to the phase III studies being initiated. The inclusion of pancreatectomy and splenectomy in D2 dissection was associated with increased morbidity and mortality. Following these results, we started a phase II trial to evaluate the safety and efficacy of pancreas-preserving D2 dissection. The results of this trial regarding the safety of pancreas preserving D2 dissection were published in 1998. In this paper, we present the survival results of this phase II trial to confirm the rationale of carrying out a phase III study comparing D1 vs D2 dissection for curable gastric cancer.Italian patients with histologically proven gastric adenocarcinoma were registered in the Italian Gastric Cancer Study Group Multicenter trial. The study was carried out based on the General Rules of the Japanese Research Society for Gastric Cancer. A strict quality control system was achieved by a supervising surgeon of the reference centre who had stayed at the National Cancer Center Hospital, Tokyo, to learn the standard D2 gastrectomy and the postoperative management. The standard procedure entailed removal of the first and second tier lymph nodes. During total gastrectomy, the pancreas was preserved according to the Maruyama technique. Complete follow-up was available to death or 5 years in 100% of patients and the median follow-up time was 4.38 years.Out of 297 consecutive patients registered, 191 patients were enrolled in the study between May 1994 and December 1996. The overall morbidity rate was 20.9%. The postoperative in-hospital mortality was 3.1%. The overall 5-year survival rate among all eligible patients was 55%. Survival was strictly related to stage, depth of wall invasion, lymph node involvement and type of gastrectomy (distal vs total).Our results suggest a survival benefit for pancreas-preserving D2 dissection in Italian patients with gastric cancer if performed in experienced centres. A phase III trial among exclusively experienced centres is urgently needed.     

A case of small undifferentiated intramucosal gastric cancer with lymph node metastasis

Early gastric cancer (EGC) has a favorable prognosis after surgical gastrectomy. For intramucosal EGC with little risk of lymph node metastasis, endoscopic mucosal resection (EMR) is an accepted treatment method. Herein we document a noteworthy case of small undifferentiated gastric cancer with nodal metastasis. A 60-year-old Japanese woman underwent gastrectomy with D2 lymph node dissection for the treatment of EGC in the lower gastric body. Histological examination revealed that signet-ring cell carcinoma was located in approximately one-third of the superficial portion of the mucosal layer, with a tumor size of 13 mm. No lymphatic invasion, venous invasion, or fibrosis was observed in the submucosal layer. This case had nodal metastasis and was finally diagnosed as stage IB (T1N1M0) according to the Japanese Classification of Gastric Carcinoma (JCGC). The patient is alive without recurrence 6 years after treatment.     

Involvement of three or more lymph nodes predicts poor prognosis in submucosal gastric carcinoma

BACKGROUND: Multivariate analyses has shown that the status of lymph node metastasis and the depth of tumor penetration through the gastric wall are the most important prognostic factors in patients with advanced gastric carcinoma after curative operation. A clinicopathological study was carried out to clarify a simple and optimal prognostic indicator for early gastric cancer. METHODS: Retrospective analyses of 982 patients with early gastric cancer (562 with mucosal [M] and 420 with submucosal [SM] tumor) treated by gastrectomy with D2 lymph node dissection were performed. RESULTS: The incidence of lymph node metastasis from M and SM tumors was 2.5% (14/562) and 20.2% (85/420), respectively. There were no apparent prognostic indicators in patients with M tumors. In patients with SM tumors, the cancer-specific 5-year survival of those with lymph node metastasis was significantly lower than that of those without such metastasis (77.6% vs 98.2%; P < 0.001). An sharp decrease in survival was seen between patients with two positive nodes and those with three positive nodes, and the cancer-specific 5-year survival rate of patients with three or more metastatic lymph nodes was significantly lower than that of those with one or two nodes (P < 0.001; univariate analysis). Multivariate analysis revealed that the involvement of three or more lymph nodes was the sole independent prognostic determinant (P = 0.016); the level of nodal metastasis was not an independent prognostic factor (P = 0.384). All patients with N2 lymph node echelons (according to the Japanese Research Society for Gastric Cancer classification of the draining lymph nodes of the stomach) in the group with one or two positive nodes survived for more than 5 years. CONCLUSION: The sole independent prognostic factor in SM gastric cancer is the involvement of three or more metastatic lymph nodes. We suggest that this simple prognostic indicator for the follow-up of early gastric cancer, and this could lead to potentially effective adjuvant chemotherapy.     

术中淋巴结示踪定位技术对进展期胃癌淋巴清扫指导作用的研究

目的探讨术中淋巴结示踪定位技术对进展期胃癌淋巴清扫的指导作用。方法术中肿瘤周围注射第三代淋巴结示踪剂——纳米炭混悬液,在D2根治术的基础上以黑染淋巴结为导向进行个体化清扫。统计清扫淋巴结的数目及淋巴结转移情况、黑染情况,并观察不良反应及并发症的发生。结果本组平均每例清扫淋巴结（35.1±13.4）枚,其中阳性淋巴结（6.9±2.5）枚;淋巴结黑染率为52.7%,黑染淋巴结中发生转移的阳性率（27.6%）,高于未黑染淋巴结（10.8%）,差异有统计学意义（χ2=6.034,P=0.016）;本组发生1例输入襻梗阻。结论进展期胃癌在D2根治术的基础上以术中淋巴显影技术为指导进行个体化清扫,能增加淋巴结清扫的彻底程度,并可提高清扫转移淋巴结的效率,但肿瘤进展程度会影响淋巴显影效果。     

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。      

Possible candidates for splenic hilar nodal dissection among patients with upper advanced gastric cancer without invasion of the greater curvature

Gastric Cancer - Spleen preserving D2 total gastrectomy without dissection of the splenic hilar nodes (#10) is a standard operation for upper advanced gastric cancer without invasion of the greater...     

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     

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.     

Body mass index determines the success of lymph node dissection and predicts the outcome of gastric carcinoma patients

We tried to determine the role of the body mass index (BMI) on the extent of lymph node dissection in gastric cancer surgery. Seven hundred and eighty-seven patients with gastric carcinoma were reviewed. Ninety-two (11%) patients exceeded the upper limit of the optimum BMI. Significantly fewer lymph nodes were removed following D2 (p = 0.002) and >/=D3 (p = 0.023) dissections, and the lymph node ratio was significantly (p = 0.0383) higher in overweight patients. The recurrence-free survival was significantly (p = 0.0297) shorter in T2/T3 cases with high BMI, and BMI (relative risk 1.85) became an independent prognostic factor in multivariate analysis. Higher BMI hampers regional lymph node dissection in gastric cancer patients and became an independent predictor of disease recurrences in T2/T3 gastric cancers.     

Improved survival after resectable non-cardia gastric cancer in the Netherlands: The importance of surgical training and quality control

Background

In the Netherlands, standardised limited D1 and extended D2 lymph node dissections in the treatment of resectable gastric cancer were introduced nationwide within the framework of the Dutch D1–D2 Gastric Cancer Trial between 1989 and 1993. In a population-based study, we evaluated whether the survival of patients with resectable gastric cancer improved over time on a regional level.

Methods

We compared 5-year overall and relative survival of patients with curatively resected non-cardia gastric cancer in the regional cancer registry of the Comprehensive Cancer Centre West in the Netherlands before the Dutch D1–D2 trial (1986 to mid 1989; n = 273), during the trial period (mid 1989 to mid 1993; n = 255), and after the trial (mid 1993 to 1999; n = 219), adjusting for prognostic variables.

Results

Unadjusted survival was highest in the post-trial period: 5-year overall and relative survival were 42% and 52%, respectively, compared to 34% and 41% in the pre-trial period, and 39% and 46% in the trial period (p = 0.31 and p = 0.06, respectively). After adjustment for age, gender, tumour site, pT-stage, nodal status and hospital volume, the effect of period on survival was more apparent (p = 0.009). Compared to the pre-trial period, the hazard ratio was 0.83 (95% confidence interval, 0.68–1.02) for the trial period, and 0.72 (0.58–0.89) after the trial. Less than 1% of the patients received adjuvant therapy.

Conclusion

Survival of patients with curatively resected non-cardia gastric cancer has improved. Standardisation and surgical training in D1 and D2 lymph node dissection are the most likely explanation for this improvement.     

Prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in patients with advanced gastric cancer

BACKGROUND AND OBJECTIVES: To determine the prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in gastric cancer patients. METHODS: We retrospectively reviewed 777 advanced gastric cancer patients who had undergone curative gastrectomy at our hospital. RESULTS: The n ratio was significantly greater in cases with a large tumor, undifferentiated tumor, lymphatic vessel invasion, or blood vessel invasion. Furthermore, the n ratio was significantly correlated with the depth of invasion, level of lymph node metastasis, and number of lymph node metastases. The prognosis for gastric cancer patients correlated well with the n ratio. Multivariate analysis indicated that the n ratio, but not the number of lymph node metastases, was an independent prognostic indicator. Moreover, the n ratio was an independent prognostic factor in N1, N2, and N3 patients defined by the Japanese Classification of Gastric Cancer (JCGC). CONCLUSIONS: The n ratio is useful for evaluating the status of lymph node metastasis in gastric cancer. Therefore, the addition of the n ratio to the N (nodal) category defined by the JCGC may be a useful strategy in the N-staging classification of gastric cancer.     

Spleen-preserving splenic lymph node dissection in radical total gastrectomy

Radical gastrectomy has been recognized as the standard surgical treatment for advanced gastric cancer, and essentially applied in a wide variety of clinical settings. The thoroughness of lymph node dissection is an important prognostic factor for patients with advanced gastric cancer. Splenic lymph node dissection is required during D2 radical gastrectomy for upper stomach cancer. This is often accompanied by removal of the spleen in the past few decades. A growing number of investigators believe, however, that the spleen plays an important role as an immune organ, and thus they encourage the application of a spleen-preserving method for splenic hilum lymph node dissection.Key Words: Gastric cancer, D2 radical resection, lymph node dissection, splenic hilumAccording to the Japanese Gastric Cancer Treatment Guidelines, the splenic hilar lymph nodes (No. 10) are the station 2 lymph nodes in gastric cancer of the upper and middle stomach (cardia, fundus, and gastric body). In a typical D2 gastrectomy, this group must be dissected. In order to achieve a thorough dissection, there has been controversy as to whether the spleen is preserved or removed.In April 2013, a 51-year-old female patient visited our department due to “upper abdominal swelling with nausea and vomiting for more than a month”. Gastroscopy and endoscopic ultrasound showed a mucosal nodular bulge at the gastric body and the fundus. The diagnosis was stomach cancer. Pathology suggested diffuse-type, poor cohesive cancer (gastric body), HP (–). Abdominal CT showed that the tumor was located at the junction of the gastric body and fundus, invading through the serosa and into the pancreatic capsule, with lymph node metastases. The cTNM staging was T4aN2M0. With adequate preoperative preparation, we performed spleen-preserving D2 radical total gastrectomy (Video 1) for the patient.Open in a separate windowVideo 1Spleen-preserving splenic lymph node dissection in radical total gastrectomyFollowing the routine procedures for D2 resection, we removed the anterior lobe of transverse mesocolon, and separated the pancreatic capsule. After the Kocher incision was made, we found lymph nodes around the inferior vena cava, so dissection of the station 16 was conducted, followed by dissection of the station 13 posterior to the pancreatic head.The gastrosplenic ligament was cut, and the spleen hilum was resected. The station 10 lymph nodes were dissected. It is much easier to resect the spleen than preserving it. Iatrogenic splenic injury can often occur during gastrectomy, especially when dissecting the lymph nodes around the splenic artery, fat and connective tissue around the spleen, and denuding the splenic artery, which is associated with a high risk of injury to the spleen and blood vessels. In this case, when major bleeding was present due to splenic vascular injury, we use 5-0 proline suture to close the vascular wounds effectively. The lesion was transected 3 cm above the cardia, and the specimen was removed. Roux-en-y esophagojejunal anastomosis was conducted.Ikeguchi and coworkers (1) reported that splenectomy was needed in advanced gastric cancer complicated by serosal invasion and local lymph node metastases. The rate of metastases to splenic hilar lymph nodes was 20.19%, and failure to dissect the lymph nodes was associated with poor prognosis, while the prognosis in patients undergoing successful dissection was comparable to those without metastasis. Zhang et al. (2) studied 108 cases with gastric cancer and the cardia and fundus to compare the prognoses with and without splenectomy. The 5-year survival rates were 38.17% in the spleen-preserving group, and 16.19% in the splenectomy group (P=0.1008), suggesting a worse prognosis in those undergoing splenectomy. Therefore, the spleen should be preserved as long as it is unaffected by the lesion.The length of operation was 153 minutes, with an estimated blood volume of 80 mL. According to the staging criteria described in the seventh edition of AJCC, the postoperative pathologic stage was T4aN3M0 (IIIc). Liquid diet was started from the 4th day after surgery, and the patient was discharged on the 8th day. No evidence of complications or tumor recurrence and metastasis has been found in the ongoing follow-up.     

胃癌患者淋巴结转移组数与预后相关性分析

  目的  探讨淋巴结转移组数与胃癌患者预后的关系。  方法  将中山大学肿瘤防治中心胃胰科2000年1月至2010年9月间1 009例行胃癌根治术、淋巴结检取超过15枚的患者纳入本研究。淋巴结分组采用日本第13版胃癌处理规约的定义。应用Log rank检验和Cox回归分析探讨淋巴结转移组数(n group, Ng)与预后的相关性。  结果  将淋巴结转移组数分为5组:无淋巴结转移(Ng0)、1组淋巴结转移(Ng1)、2组淋巴结转移(Ng2)、3~5组淋巴结转移(Ng3)、6组及以上淋巴结转移(Ng4), 3年生存率分别为91.6%、84.7%、72.0%、59.6%、43.0%, 5年生存率分别为89.9%、82.4%、66.9%、54.6%、38.3%, 各组间3、5年生存率均有统计学意义(P<0.05)。胃癌患者Ng越高, 5年生存率越低, Ng是胃癌的独立预后因素。  结论  Ng是对于现行UICC N分期的良好补充。      

Nodal abdominal spread in adenocarcinoma of the cardia. Results of a multicenter prospective study

Background. Precise knowledge of the abdominal nodal spread of cardia adenocarcinoma in relation to the depth of invasion of the tumor and its longitudinal extension may be very important for the surgeon as a guide in choosing the type of resection and lymphadenectomy. Methods. The frequency of node metastases in each abdominal station of the first and second tier was prospectively studied in 101 patients with type II and III cardia cancer (defined as approved by the consensus conference held during the second International Gastric Cancer Conference in Munich in April, 1997) who underwent total gastrectomy with D2 lymphadenectomy during the period January 1994 to April 1998. Lymph nodes were retrieved immediately after operation by the surgeon and assigned to the appropriate station according to the classification of the Japanese Research Society for Gastric Cancer. Results. In early gastric cancer, of both type II and type III, lymph node involvement was limited to the perigastric nodes of the upper half of the stomach and to the lymph node station of the celiac trunk. In advanced cancers, whether of type II or type III, there was a fairly high frequency of metastases to the perigastric nodes of the lower half of the stomach; there was also high frequency of metastases at N2 stations, without differences in frequency between pT2 and pT3 tumors (staged according to the classification of the Japanese Research Society for Gastric Cancer). Conclusions. The results of our study provide evidence for the need to perform a total gastrectomy with D2 lymphadenectomy in all patients with advanced cardia cancer type II or type III. In early cancers, a less extensive resection (proximal gastrectomy) with D2 lymphadenectomy may be indicated. Received for publication on Jul. 15, 1998; accepted on Oct. 22, 1998     

淋巴导航技术在胃癌微创手术中的研究进展

规范化D2淋巴结清扫与手术后标本精细分拣淋巴结相结合可以提高胃癌患者生存并达到精准分期的目的。随着不同淋巴示踪剂的广泛应用,个体化淋巴导航正在成为胃癌微创手术中新的技术突破。淋巴结示踪技术是提高术中淋巴结清扫质量以及纠正术后病理分期偏倚的重要手段。本文将就此技术的应用现状及进展作一综述。     

Complete histological response in gastric cancer stage IV after neoadjuvant chemotherapy including S-1 combined with CDDP--report of a case

A 60-year-old man complaining of black stool, body weight loss, and anemia, was examined and diagnosed with advanced gastric cancer (M, type 3, por 2, cT3, cN3, cH0, cP0, cM0, cStage IV). A poor prognosis was predicted, yet we tried neoadjuvant chemotherapy (NAC) expecting downstaging of the tumor. Considering the efficacy and safety, we chose S-1+CDDP as the NAC regimen. S-1 (120 mg/day) was administered orally for 21 days, followed by CDDP (75 mg/body) div on day 8. Distal partial gastrectomy and lymph node dissection (D2) were performed, with Billroth I reconstruction. Histological examination of the resected stomach and lymph nodes revealed no residual cancer cells, suggesting complete histological remission (grade 3) according to the Japanese classification of gastric carcinoma.     

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。