Effects of extended lymphadenectomy and postoperative chemotherapy on node-negative gastric cancer

AIM:To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis.METHODS:Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected,from January 2002 to December 2006,were analyzed retrospectively.Patients with pT4 stage or distant metastasis were excluded.We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features,such as age,tumor size,tumor location and depth of invasion.At the same time,the relationship between postoperative chemotherapy and the5-year survival rate among different subgroups were also analyzed.RESULTS:The overall 5-year survival rate of the entire cohort was 63.7%.The 5-year survival rate was poor in those patients who were:(1)more than 65 years old;(2)with tumor size larger than 4 cm;(3)with tumor located in the upper portion of the stomach;and(4)with pT3 tumor.The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor(P=0.019),but not in other subgroups.Moreover,there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups(P>0.05).CONCLUSION:For gastric cancer patients without lymph node metastasis,extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor.However,there was no evidence of a survival benefit from postoperative chemotherapy alone.

Systematic review of D2 lymphadenectomy versus D2 with para-aortic nodal dissection for advanced gastric cancer

AIM:To evaluate the feasibility and therapeutic effects of para-aortic nodal dissection (PAND) for advanced gastric cancer.METHODS:Randomized controlled trials (RCTs) and non-randomized studies comparing D2 + PAND with D2 lymphadenectomy were identified using a predefined search strategy.Five-year overall survival rate,post-operative mortality,and wound degree of surgery between the two operations were compared by using the methods provided by the Cochrane Handbook for Systematic Reviews of Interventions.RESULTS:Four RCTs (1120 patients) and 4 nonrandomized studies (901 patients) were identif ied.Metaanalysis showed that there was no signif icant difference between these two groups in 5-year overall survival rate [risk ratio (RR) 1.04 (95% CI:0.93-1.16) for RCTs and 0.96 (95% CI:0.83-1.10) for non-randomized studies] and post-operative mortality [RR 0.99 (95% CI:0.44-2.24) for RCTs and 2.06 (95% CI:0.69-6.15) for non-randomized studies].There was a significant difference between these two groups in wound degree of surgery,operation time was significantly longer [weighted mean difference (WMD) 195.32 min (95% CI:114.59-276.05) for RCTs and 126.07 min (95% CI:22.09-230.04) for non-randomized studies] and blood loss was signif icantly greater [WMD 301 mL (95% CI:151.55-450.45) for RCTs and 302.86 mL (95% CI:127.89-477.84) for non-randomized studies] in D2 + PAND.CONCLUSION:D2 + PAND can be performed as safely as standard D2 resection without increasing post-operative mortality but fail to benefit overall survival in patients with advanced gastric cancer.

Satisfactory surgical outcome of T2 gastric cancer after modified D2 lymphadenectomy

Objective： Though D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer （GC）, the modified D2 （D 1＋7, 8a and 9） lymphadenectomy may be more suitable than D2 dissection for T2 stage GC. The purpose of this study is to elucidate whether the surgical outcome of modified D2 lymphadenectomy was comparable to that of standard D2 dissection in T2 stage GC patients. Methods： A retrospective cohort study with 77 cases and 77 controls matched for baseline characteristics was conducted. Patients were categorized into two groups according to the extent of lymphadenectomy： the modified D2 group （roD2） and the standard D2 group （D2）. Surgical outcome and recurrence date were compared between the two groups. Results： The 5-year overall survival （OS） rate was 71.4% for patients accepted mD2 lymphadenectomy and 70.1% for those accepted standard D2, respectively, and the difference was not statistically significant. Multivariate survival analysis revealed that curability, tumor size, TNM stage and postoperative complications were independently prognostic factors for T2 stage GC patients. Patients in the mD2 group tended to have less intraoperative blood loss （P=0.001） and shorter operation time （P〈0.001） than those in the D2 group. While there were no significant differences in recurrence rate and types, especially lymph node recurrence, between the two groups. Conclusions： The surgical outcome of mD2 lymphadenectomy was equal to that of standard D2, and the use of mD2 instead of standard D2 can be a better option for T2 stage GC.

Totally Laparoscopic Total Gastrectomy with D2 Lymphadenectomy for Advanced Gastric Cancer

Introductions: Gastrectomy, which is the standard surgical procedure for gastric cancer, has gradually come to be performed laparoscopically. Laparoscopic distal gastrectomy (LDG) has been adopted gradually and performed for advanced gastric cancer. However, laparoscopic total gastrectomy (LTG) has not been as widely accepted as LDG due to technical difficulties, especially with reconstruction and proper D2 lymphadenectomy. The purpose of the current study was to determine the utility of TLTG with concomitant splenectomy and D2 lymphadenectomy (TLTGS) for advanced gastric cancer (AGC). Materials and Methods: Between January 2006 and May 2014, 10 consecutive patients who underwent TLTGS for AGC and 76 patients who underwent TLTG with D1 lymphadenectomy were included in this study. These two groups were compared in terms of perioperative results, with assessment of intraoperative and postoperative outcomes. Results: There were no significant differences in patients’ characteristics between the two groups. Operative time was longer in the TLTGS group than in the TLTG group. However, the rate of patients with postoperative complications including major complications was not different between the groups, and no patient in the TLTGS group had anastomotic leakage or pancreatic fistula. Conclusions: In the short-term, TLTGS had good postoperative outcomes and was useful and acceptable for AGC.

Improved Survival after Implementation of Multidisciplinary Team Meetings,Perioperative Chemotherapy,Extended Lymphnode Dissection and Laparoscopic Surgery in the Treatment of Advanced Gastric Cancer

Aims: The treatment of gastric cancer has changed in the western countries during the last decade. This includes multidisciplinary team (MDT) meetings, perioperative chemotherapy, extended lymph node dissection, and laparoscopic surgery, all of which were gradually implemented at our department from 2008. The aim of the present study was to determine the effect of these changes on morbidity and survival. Material and Methods: 185 patients with gastric cancer were operated with curative intent from 2000 until 2016 in this retrospective, observational, follow-up study;83 before implementation of modern principles in 2008 (period 1) and 102 were treated after 2008 (period 2). Results: The resection rate (94% vs 92.8%) and mortality rates (4.8% vs 2.9%) did not differ between the two periods. In period 2, 48 patients (47.1%), received neoadjuvant chemotherapy. In 36 patients (35.3%), laparoscopic surgery with D2 lymphadenectomy was performed. There was a significantly higher yield in the number of lymph nodes in period 2 compared to period 1 (14 vs 8, p pparent between laparoscopic and open surgery in the second period (32 vs 10, p The five-year survival rate was significantly improved after the change in treatment principles with an estimated improvement from 30% to 40% between the periods (p = 0.033). Conclusion: The combined effect of MDT meetings, neoadjuvant chemotherapy, extended lymphnode dissection and laparoscopy has improved the prognosis of gastric cancer patients.

Evaluation of rational extent lymphadenectomy for local advanced gastric cancer

Based upon studies from randomized clinical trials, the extended （D2） lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes （PAN） in JCOG9501, the clinical benefit of D2＋ para-aortic nodal dissection （PAND） for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.l I nodes has been controversial, and however, the final results from the randomized trial ofJCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as MI stage in the current version of the Japanese classification. We propose that D2~No.14v and ＋No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients.

A decade in gastric cancer curative surgery:Evidence of progress(1999-2009)

To investigate the progress in evidence-based surgical treatment of non-metastatic gastric cancer,we re- viewed the last ten years'literature.The data used in this review were identified by searches made on MED-LINE,Current Contents,PubMed,and other references taken from relevant original articles(on prospective and retrospective studies)concerning gastric cancer surgery.Only papers published in English between January 1999 and December 2009 were selected.Data from ongoing studies were obtained in December 2009, from the trials registry of the United States National Institutes of Health(http://www.clinicaltrial.gov).The citations list was presented according to evidence based relevance(i.e.,randomized controlled trials,pro- spective studies,retrospective series).In the last ten years,many challenges have been faced relating to the extension of gastric resection and nodal dissection as well as surgical timing,but we found only limited evidence,regardless of latitude of study.The ongoing phase-Ⅲ trials may provide answers that will be valid for the coming decades,and which may bring definitive answers for the currently unresolved questions.

^(18)F-FDG PET-CT在阴茎鳞状细胞癌个体化手术治疗中的价值初探

目的:探讨^(18)F-FDG PET-CT检查对阴茎鳞状细胞癌个体化手术治疗的指导价值。方法:7例确诊阴茎鳞状细胞癌患者,术前行^(18)F-FDG PET-CT检查,均无远处脏器转移,但发现区域淋巴结转移;7例患者共计14侧区域淋巴结,均行双侧腹股沟淋巴结清扫术,其中1例因^(18)F-FDG PET-CT检查提示单侧腹股沟淋巴结阳性数目5枚,伴盆腔淋巴结转移,故同期行单侧盆腔淋巴结清扫术。结果:术前^(18)F-FDG PET-CT检查与术后淋巴结病理学检查结果对比:敏感性87.5%,特异性100%。结论:^(18)F-FDG PET-CT检查对诊断阴茎鳞状细胞癌淋巴结转移有良好的敏感性和特异性,对阴茎鳞状细胞癌个体化手术治疗有指导价值,尤其是术前预判淋巴结转移数目及盆腔淋巴结转移,从而确定区域淋巴结清扫范围方面价值重大。

Gastric cancer: Current status of lymph node dissection

D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.

Factors associated with early recurrence after curative surgery for gastric cancer

AIM: To characterize patterns of gastric cancer recurrence and patient survival and to identify predictors of early recurrence after surgery.METHODS: Clinicopathological data for 417 consecutive patients who underwent curative resection for gastric cancer were retrospectively analyzed. Tumor and node status was reclassified according to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis classification for carcinoma of the stomach. Survival data came from both the patients' follow-up records and telephone followups.Recurrent gastric cancer was diagnosed based on clinical imaging, gastroscopy with biopsy, and/or cytological examination of ascites, or intraoperative findings in patients who underwent reoperation.Predictors of early recurrence were compared in patients with pT1 and pT2-4a stage tumors. Pearson's χ 2 test and Fisher's exact test were used to compare differences between categorical variables. Survival curves were constructed using the Kaplan-Meier method and compared via the log-rank test. Variables identified as potentially important for early recurrence using univariate analysis were determined by multivariate logistic regression analysis.RESULTS: Of 417 gastric cancer patients, 80(19.2%)were diagnosed with early gastric cancer and the remaining 337(80.8%) were diagnosed with locally advanced gastric cancer. After a median follow-up period of 56 mo, 194 patients(46.5%) experiencedrecurrence. The mean time from curative surgery to recurrence in these 194 patients was 24 ± 18 mo(range, 1-84 mo). Additionally, of these 194 patients,129(66.5%) experienced recurrence within 2 years after surgery. There was no significant difference in recurrence patterns between early and late recurrence(P < 0.05 each). For pT1 stage gastric cancer, tumor size(P = 0.011) and pN stage(P = 0.048) were associated with early recurrence of gastric tumors.Patient age, pT stage, pN stage, Lauren histotype,lymphovascular invasion, intraoperative chemotherapy,and postoperative chemotherapy were independent predictors of early recurrence in patients with pT2-4a stage gastric cancer(P < 0.05 each).CONCLUSION: Age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy are independent factors influencing early recurrence of pT2-4a stage gastric cancer.

Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials(RCTs) comparing NAC followed by surgery(NAC + S) with surgery alone(SA) for gastric cancer(GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association(JGCA) performed in both arms, disease-specific(DSS) and disease-free survival(DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment. RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S(n = 1089) with SA(n = 973) published in the period from January 1993-March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node(LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. Inthe third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the "Study Treatment" protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction(EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients' populations are even higher than the survival rates reported after NAC followed by incomplete surgery.CONCLUSION NAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicinerelated demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended(D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.

Advancements and challenges in treating advanced gastric cancer in the West

Gastric cancer is a leading cause of cancer incidence and death worldwide.Patients with advanced gastric cancer benefit from a multi-modality treatment regimen.Sound oncologic resection with negative margins and complete lymphadenectomy plays a crucial role in long-term survival for patients with resectable disease.The utilization of minimally invasive techniques for gastric cancer has been slowly increasing and is proving to be both technically and oncologically safe.Perioperative chemotherapy is the current standard of care for advanced gastric cancer.A variety of chemotherapy regimens have been used with the combination of docetaxel,oxaliplatin,5-fluorouracil,and leucovorin being the current recommendation given its superior ability to induce a complete pathologic response and prolong survival.The use of radiation has been more controversial with its optimal place in the treatment sequence being unclear.There are current ongoing studies assessing the impact of radiation as an adjunct or in place of chemotherapy.Targeted treatments(e.g.,trastuzumab for human epidermal growth factor receptor 2 positive tumors and pembrolizumab for programmed death-ligand 1 positive tumors)are showing promise and are part of a continued emphasis on individualized care.Intraperitoneal chemotherapy may also play a role in preventing peritoneal recurrences for patients with high risk lesions.The treatment of patients with advanced gastric cancer in the West continues to advance and improve with a better understanding of optimal treatment sequences and the utilization of personalized treatment regimens.

Lymph node,peritoneal and bone marrow micrometastases in gastric cancer:Their clinical significance

The 7th TNM classification clearly states that micro-metastases detected by morphological techniques(HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease(pN1mi or M1),while patients in whom micrometas-tases are detected by non-morphological techniques(e.g.,ow cytometry,reverse-transcriptase polymerase chain reaction) should still be classif ied as N0 or M0.In gastric cancer patients,micrometastases have been de-tected in lymph nodes,the peritoneal cavity and bone marrow.However,the clinical implications and/or their prognostic signif icance are still a matter of debate.Cur-rent literature suggests that lymph node micrometasta-ses should be encountered for the loco-regional staging of the disease,while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes.Peritoneal fluid cytology ex-amination should be obligatorily performed in pT3 or pT4 tumors.A positive cytology classif ies gastric cancer patients as stage Ⅳ.Although a curative resection is not precluded,these patients face an overall dismal prognosis.Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further.Gas-tric cancer cells are detected with high incidence in the bone marrow.However,the published results make comparison of data between groups almost impossible due to severe methodological problems.If these meth-odological problems are overcome in the future,specif ic target therapies may be designed for specif ic groups of patients.

Dynamics of a D’Alembert wave and a soliton molecule for an extended BLMP equation

The D’Alembert solution of the wave motion equation is an important basic formula in linear partial differential theory.The study of the D’Alembert wave is worthy of deep consideration in nonlinear partial differential systems.In this paper,we construct a(2+1)-dimensional extended Boiti-Leon-Manna-Pempinelli(eBLMP)equation which fails to pass the Painleve property.The D’Alembert-type wave of the eBLMP equation is still obtained by introducing one arbitrary function of the traveling-wave variable.The multi-solitary wave which should satisfy the velocity resonance condition is obtained by solving the Hirota bilinear form of the eBLMP equation.The dynamics of the three-soliton molecule,the three-kink soliton molecule,the soliton molecule bound by an asymmetry soliton and a one-soliton,and the interaction between the half periodic wave and a kink soliton molecule from the eBLMP equation are investigated by selecting appropriate parameters.

基于扩展卡尔曼滤波的高转速修正引信滚转角测量方法

针对二维弹道修正技术中采用双旋稳定弹总体设计方案的修正引信在全弹道范围内的旋转特点,提出了一种基于扩展卡尔曼滤波的高转速修正引信滚转角测量方法。以某双旋稳定迫弹为仿真平台,建立了7自由度（DOF）外弹道仿真模型分析修正引信的旋转特性,完成了滚转角与弹载陀螺输出之间的解析关系推导并验证其正确性;在引入陀螺固有系统误差、测量误差以及北斗卫星定位测量误差后,基于扩展卡尔曼滤波估计方法对修正引信滚转角进行实时测量,仿真结果表明：采用该方法1 s内就可以实现滚转角解算快速收敛,全弹道滚转角解算绝对误差不大于6°,在弹道10~40 s段解算绝对误差不大于2°;通过炮射试验的采集数据进行验证,以15~35 s弹道段为例,滚转角解算绝对误差不大于10°,绝对误差的均值为3.9°,可以满足修正系统的滚转角测量精度要求。

基于扩展卡尔曼滤波的转速补偿滚转角测量算法

针对二维弹道修正引信全弹道转速变化范围较大的旋转特点,提出了一种基于扩展卡尔曼滤波的转速补偿滚转角测量算法。首先以某双旋稳定迫弹为仿真平台,分别在高速和低速时变转速条件下对引入转速补偿的EKF滚转角测量算法进行了验证。仿真结果表明,高转速条件下全弹道滚转角解算绝对误差不大于5°,低转速条件下解算绝对误差全弹道不大于2.5°,且均能快速收敛。而后又基于MEMS三轴转台进行了实验室滚转角测量精度验证,结果表明,在修正引信转速自30 r/s至1 r/s范围动态变化过程中,滚转角解算绝对误差不超过4°。

端羧基聚乳酸的扩链、改性及其性能

以丙交酯为原料、辛酸亚锡为催化剂、丁二酸酐为改性剂,采用梯度升温法,在150℃、0.098MPa条件下采用直接熔融缩聚法合成端羧基聚乳酸共聚物P（LA/SA）,接着用2,2-（1,3-亚苯基）-二噁唑啉（1,3-PBO）对其进行扩链,按n（丙交酯）/n（1,3-PBO）=1/2.4加入1,3-PBO,反应1h制得聚酰胺酯（PEA）,最后将高岭土与PEA在150℃、减压条件下熔融复合改性。采用GPC、FTIR、~1H NMR、DSC、SEM等手段对聚合物的结构进行表征和性能测试,结果表明,与P（LA/SA）相比,扩链产物PEA相对分子质量大幅度提高,重均相对分子质量高达24万,玻璃化转变温度T_g高于PLA和P（LA/SA）,改性后复合材料的热稳定性能提高,结晶度降低。

基于传统的CMOS工艺延伸漏极NMOS功率管研究

延伸漏极N型MOS(EDNMOS)是基于传统低成本CMOS工艺设计制造,用N-well作为NMOS漏极漂移区,以提高其击穿电压。用二维器件模拟软件Medici[1]对该器件进行模拟分析,结果表明有效地提高了NMOS管击穿电压。实验结果表明采用这种结构能使低压CMOS工艺输出功率管耐压提高到电源电压的2.5倍,样管在5 V栅压下输出的电流可达到750 mA。作为开关管工作,对于1 000 pF容性负载,其工作电流在550 mA时,工作频率可达500 KHz。

Chylorrhea complicating D2＋a gastrectomy： review of the literature and clarification of terminology apropos one case

Lymphatic complications leading to retention,accumulation or drainage of peritoneal fluid are frequently encountered following extended or superextended lymphadenectomy for gastric cancer.1 The vast majority of these drainages usually subsides spontaneously, but in some instances they can persist for long period of time causing significant morbidity.However, the classification,

基于扩展卡尔曼滤波的二维弹道修正弹制导算法研究

为解决固定鸭舵二维弹道修正弹闭环制导问题,首先基于固定鸭舵修正组件的工作特性,建立含有控制量的运动方程组,利用扩展卡尔曼滤波对一段有控状态的弹道进行估计得到当前状态值,并外推得到预测的无控落点,根据预测落点与目标落点的偏差,给出修正组件滚转角控制指令。仿真实验结果表明,该算法有效地减小了卫导测量噪声对当前状态估计的影响,显著减小了落点散布,圆概率误差减小至28 m。