腹腔镜辅助下胃癌全胃切除及其联合脏器切除的临床研究
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摘要
胃癌在世界范围内发病率和死亡率居于恶性肿瘤的第二位,是东南亚地区发病率最高的胃肠道恶性肿瘤。胃癌根治术可选择传统开腹术和腹腔镜辅助的胃癌根治术。进展期胃癌是指浸润到粘膜下层,进入肌层或已穿过肌层达浆膜者。胃癌D2根治术仍被认为是治疗进展期胃癌的金标准。胃癌标准的D2根治术是指,肿瘤在没有远处转移的前提下,切除近端或远端胃的2/3或全胃,并清扫肿瘤生长部位相应的第1站和第2站区域淋巴结的手术。
胃癌切除范围根据手术方式而定,包括以下几种术式：①远端胃切除适应于胃远端癌,次全胃切除后,能满足近端切缘至少距肿瘤5cm以上；②近端胃切除适用于肿块<3cm癌灶,更大的肿瘤可能需要全胃切除；③全胃切除适用于弥漫型胃癌、胃近端和中部癌、胃远端癌侵犯胃体、胃多发癌。已有前瞻性研究发现,对于近端胃癌早期病例接受全胃切除或近端胃切除术后5年生存率无显著差别,但Ⅲ期和Ⅳ期行近端胃大部分切除会降低术后生存率,且术后常伴有返流性食管炎影响患者术后生活质量。日本胃癌诊治规范明确指出,对于可切除的近端胃原则上应施行全胃切除术,T1期胃癌可考虑行近端胃切除,但必须保留1/2的胃。可见对进展期近端胃癌行根治性全胃切除已趋向共识。
得益于微创技术的迅猛发展,目前腹腔镜治疗进展期胃癌已被广泛认可。腹腔镜技术治疗胃癌根据手术部位以及淋巴结清扫范围的不同,存在不同的分类方法。按手术部位的不同,可分为腹腔镜下远端胃大部切除术、腹腔镜下近端胃大部切除术和腹腔镜下全胃切除术,甚至有报道运用于腹腔镜下联合脏器切除术；按淋巴结清扫范围,可分为腹腔镜下胃癌D1根治术、腹腔镜下胃癌D2根治术,甚至运用于腹腔镜下胃癌D3根治术。
随着腹腔镜技术在临床中的应用,腹腔镜手术治疗胃癌已成为胃肠外科发展的一种趋势,并且取得了良好的临床效果,有取代传统开腹手术之势。已有临床研究表明,腹腔镜辅助全胃切除术是安全和可行的。但很少有临床研究将腹腔镜辅助全胃切除术和传统的开腹全胃切除术进行临床疗效等比较。由于操作技术的困难,使得腹腔镜辅助胃癌全胃切除术还不是一个胃肠外科医生普遍接受的方法。
我们探讨腹腔镜辅助下根治性D2全胃切除术与传统开腹手术治疗胃癌的近期临床疗效及机体血清学变化特点。临床疗效包括手术时间,术中出血量,术后排气时间,术后住院时间,淋巴结淋巴结清扫数,术后并发症,术后肿瘤复发率等方面。机体血清学变化是指外周血CRP、CEA、CA199、CA125水平的变化。采用了回顾性分析的方法。回顾性分析我院同一手术团队2011年3月至2013年3月施行216例根治性D2全胃切除术患者的临床资料。严格纳入标准。两组临床资料具有可比性。腹腔镜组的手术方法：采用腹腔镜辅助下根治性D2全胃切除术。采用腹腔镜辅助下根治性D2全胃切除术。参照2010年第3版日本胃癌治疗指南进行D2淋巴结清扫术。用超声刀沿横结肠边缘游离并暴露大网膜,于横结肠边缘用超声刀沿无血管区切断大网膜,向左横结肠脾曲,向右至胃网膜右动脉根部,按照自下而上、先大弯后小弯的顺序进行淋巴结清扫。具体清扫顺序是：No.6、No.4d (幽门下区)→No.7、No.9、No.11p(胰腺上方区)→No.8a、No.12a、No.5(胰腺上方区)→No.3、No.1(胃小弯区)→No.4sb(脾门区)→No.10、No.lld(脾门区)→No.2(贲门左区)。在剑突下做一长度为6cm的正中线纵行切口,放置切口保护器,取出已游离的胃,于腔内用管状吻合器行食管空肠吻合、空肠输出输入襻侧吻合(食管空肠Roux-en-Y吻合)。吻合口旁常规放置引流管。开腹组采用常规开腹胃癌根治性D2全胃切除术。对两组的术中、术后情况、淋巴结清扫数目、术后并发症及术后肿瘤复发率等进行比较,分析两种手术方式的临床疗效。其中术中情况包括手术时间、术中出血量等；术后情况包括术后肠道功能恢复时间(表现为术后排气时间),术后住院时间等；术后住院时间与出院标准有关。待肛门排气、胃管拔除且消化道造影示排空良好开始进食；先流质饮食,逐渐过渡到半流质饮食,出院标准为患者进半流质及馒头正常、排便正常且各项抽血指标基本正常。术后淋巴结清扫数根据术后病理计数所得。术后并发症包括肺部感染、肠梗阻、腹腔感染、吻合口漏、吻合口出血、吻合口狭窄、胰漏、淋巴漏、切口感染及皮下气肿等。两组患者随访1-26个月,平均14个月,观察肿瘤复发情况。对患者机体血清学变化特点进行观察,观察两组手术前及术后第30天清晨血清C反应蛋白(CRP)、癌胚抗原(CEA)、CA99、CA125水平。采用免疫比浊法检测血清CRP水平。采用电化学发光分析法检测血清CEA、CA199、CA125水平。比较不同手术方式对患者上述血清学指标的变化的影响。
两组患者均顺利完成手术,腹腔镜组中无一例中转剖腹。临床疗效方面比较：与开腹手术组比较,腹腔镜组手术时间延长(P<0.01),术中出血量和住院时间明显减少(P均<0.01),术后排气时间早(P<0.01),术后并发症发生率低(P<0.05)。在淋巴结清扫数方面,两组无明显差异(P>0.05)。
病变、手术等任何损伤均可导致机体应激反应的发生。血清CRP可反映组织损伤程度。胃癌的机体炎症反应程度、组织损伤深度及范围较良性病变明显。CRP在术后24小时达到高峰,之后逐渐下降,术后1月CRP水平则反映癌肿清除后机体炎症反应及病变情况。我们研究发现,两组术后均可降低患者术后1月血清CRP,但观察组较对照组降低更明显(P<0.01)。肿瘤标志物是指从临床应用角度,在组织、血浆或胃液中能检测到有关生化物质基础达到一定时揭示肿瘤的存在信息。CEA在健康人血中水平甚微,最早用于内胚层恶性肿瘤胃肠癌的诊断,CEA水平的高低与胃癌肿瘤大小、局部浸润、淋巴结或者其他部位转移、预后有关。CAL199是一种粘蛋白型的糖类蛋白肿瘤标志物,主要用于检测胰腺癌和消化道肿瘤,其在胃癌中也有一定的阳性检出率。CA125也是胃癌的一种肿瘤标志物。CA199、CA125、CA724、CEA均为肿瘤相关抗原,但均为非肿瘤特异性抗原,一种肿瘤标志物可出现于多种肿瘤中,一种肿瘤亦可出现多种肿瘤标志物。本研究显示,两组均可降低血清CEA、CA199、CA125水平。有研究发现,进展期胃癌化疗后CEA、CA199和CA125的水平显著下降,我们的研究发现胃癌术后血清中3项指标均显著下降,提示动态观察血清中这3项指标的变化可以评价胃癌术后的疗效及判断预后。
随着腹腔镜技术的发展及腔镜器械的不断改进与更新,腹腔镜治疗早期胃癌及相对早期的进展期胃癌均能取得较好的近期疗效,且能达到与开腹手术相同的根治效果。腹腔镜手术的微创优势及其手术临床效果是在保证根治的前提下实现的。近年来,我国的腹腔镜下胃癌手术技术蓬勃发展,但至今腹腔镜下联合脏器切除的进展期胃癌根治术在世界范围内仍然未广泛展开,主要是因为以下几点：①对腹腔镜胃癌根治联合脏器切除的手术指征的争议；②联合脏器切除加大手术难度及手术时间,考验手术团队对术中可能出现突发情况的处理与应对,及对术后可能出现胰漏、腹腔内大出血等并发症的观察与处理；③手术后远期疗效的争议。我们通过回顾性分析我科2012年6月至2013年10月进行的11例腹腔镜胃癌根治术联合脏器切除术的病例的临床资料。探讨腹腔镜胃癌根治联合脏器切除的病例选择、开展时机及手术的可行性。结果示手术时间为(252.14±41.25)min,术中出血(366.43±153.21)ml,术后住院时间(13.27±2.58)d。术后发生肺部感染3例,胰漏2例,均经通畅引流治疗痊愈。无吻合口漏及腹腔内出血病例。无死亡病例。随访至今无肿瘤复发或转移。
结论：1.在拥有熟练的腹腔镜操作技术及较强的临床解剖理念前提下,腹腔镜辅助下根治性D2全胃切除术治疗胃体上段、胃底贲门癌是安全可行的。腹腔镜辅助下根治性D2全胃切除术具有微创优势,术中出血量少,术后恢复快,术后并发症少等优点,能够有效切除癌组织,同时能够有效进行淋巴清扫,更能取得良好的临床近期疗效。胃癌患者血清CRP在手术治疗1月较术前下降,腹腔镜手术能更好减低组织损伤。CEA、CA199、CA125是常见的肿瘤标志物。胃癌患者血清CEA、CA199、CA125在手术治疗1月较术前下降。腹腔镜辅助下根治性D2全胃切除术的远期疗效尚待高质量、大样本的多中心、前瞻性随机对照研究的开展来进一步论证。2.腹腔镜胃癌根治术联合脏器切除在选择合适的病例的情况下,正确的解剖理念的引导下,在积累较多腹腔镜辅助下根治性D2切除术的经验基础上开展是安全可行的,可进行尝试与探索。
The morbidity and mortality of gastric cancer worldwide is in the second position of malignant tumor. Gastric cancer is of the highest incidence in malignant tumor of gastrointestinal tract in Southeast Asia. There are two methods for the radical surgery of gastric cancer:the conventional open surgery and laparoscopy-assisted radical gastrectomy. Advanced gastric cancer refers to tumor cell infiltrating into the submucosa, muscularis or serosa through muscularis. Radical D2resection of gastric cancer is still considered the gold standard for the treatment of advanced gastric cancer. The standard radical D2resection of gastric cancer means to resection of proximal2/3stomach in proximate or distal position, or full stomach, and clearance of the first and second station lymph node corresponding to tumor position, in the premise of no distant metastasis.
The resection range in Gastric cancer operation is set according to the operation modes. There are three modes at least:(1) the distal gastrectomy, suitable for distal gastric cancer, gastric tumor occurred after subtotal gastrectomy, requires the proximal resection margin away from the tumor more than at least5cm;(2) proximal gastric resection, suitable for proximate gastric tumor<3cm, while larger tumors may need total gastrectomy;(3) total gastrectomy, suitable for gastric cancer of diffuse infiltration type, gastric cancer in proximal and middle position, distal gastric cancer infiltrating the gastric body and multiple gastric carcinoma. There was a prospective study of5years survival rate after proximal gastrectomy or total gastrectomy for early proximal gastric cancer. The rate of5years survival had no significant difference between two procedures. However, if the proximal gastric cancer of III and IV stage received proximal subtotal gastrectomy, postoperative survival rate can reduce, and reflux esophagitis often occurred which affect postoperative quality of life. The Japan standard of Diagnosis and treatment of gastric cancer points out clearly that resectable proximal gastric cancer should be performed total gastrectomy in principle. Although proximal gastric cancer in T1stage may be considered for proximal gastrectomy, half stomach must be retained. Thus, radical total gastrectomy has become consensus for advanced proximal gastric cancer.
Benefited from the rapid development of minimally invasive techniques, the laparoscopic treatment for advanced gastric cancer has been widely recognized. The classification of laparoscopic technique in the treatment of gastric cancer is different according to the operation site and the extent of lymph node dissection. According to the operation site, laparoscopic technique can be divided into laparoscopic distal gastrectomy, laparoscopic proximal gastrectomy and laparoscopic total gastrectomy, even laparoscopic gastrectomy combined organ resection (which was already reported). According to the extent of lymph node dissection, laparoscopic technique can be divided into laparoscopic radical D1resection for gastric cancer, laparoscopic radical D2resection for gastric cancer, even laparoscopic D3radical gastrectomy for gastric cancer.
With the application of laparoscopic technique in the clinical treatment, laparoscopic operation for gastric cancer has become a trend in the development of gastrointestinal surgery, and achieved good clinical results, to replace the traditional open operation. Clinical studies already show that laparoscopic assisted total gastrectomy is safe and feasible. But few clinical study of curative effect comparison in laparoscopic assisted total gastrectomy and the traditional open total gastrectomy is conducted. Due to technical difficulties, the method of laparoscopic assisted total gastrectomy for gastric cancer is still not generally accepted by gastrointestinal surgeon.
We investigated the curative effect of short term and the serological changes between laparoscopic assisted radical D2gastrectomy and traditional open operation in treatment of gastric cancer. The clinical outcomes included operation time, intraoperative blood loss, postoperative exhaust time, postoperative hospital stay, number of lymph node removed, postoperative complications, recurrence rate etc.. The serological change refered to changes of peripheral blood CRP, CEA, CA199, CA125level. The retrospective analysis method was used. From March2011to March2013,216patients received radical D2total gastrectomy, in which118patients underwent laparoscopic surgery (observation group) while98patients underwent open surgery (control group). The intraoperative and postoperative situation and number of lymph node removed between two groups were compared. C-reactive protein (CRP), CEA, CA99and CA125of peripheral blood were assayed preoperatively and on the30th day postoperatively. The rate of cancer recurrence between two groups was compared. The cases were selected according to strict entering standard. The clinical data of the two groups was of comparability. Operation procedure of the laparoscopic group was laparoscopic assisted radical D2total gastrectomy. D2Lymphadenectomy was conducted according to Japanese gastric cancer treatment guidelines of the third Edition in2010. Make dissociation along the transverse colon and expose the greater omentum with ultrasonic knife. Cut off the greater omentum along the avascular area using ultrasonic knife. Make dissociation to the site of splenic flexure of colon on the left, and gastroepiploic artery root on the right. The order of lymph node clearance was conducted according to the greater curvature side first and then the lesser curvature side, down to up. Specific order of lymph node clearance was:No.6, No.4d (pyloric region), No.7, No.9, No.11p (pancreatic anodic region)→No.8a, No.12a, No.5(pancreatic anodic region)→No.3, No.1(the lesser curvature of the stomach area)→No.4sb (splenic hilum area) and No.10, No.11d (splenic hilum area)→No.2(cardiac left area). Open abdomen through a length of6cm longitudinal midline incision under xiphoid bone, and place incision protector, remove the dissociative stomach, conduct esophagojejunostomy with tubular anastomat in the cavity, side anastomosis between input ansa and output anasa (Roux-en-Y esophagojejunostomy). The drainage tube was placed beside the anastomosis routinely. The procedure for open group was conventional laparotomy radical D2total gastrectomy for gastric cancer. The intraoperative and postoperative situation and number of lymph node removed between two groups were compared. The postoperative complications and the rate of cancer recurrence were also compared. Analyze the clinical effect of two kinds of operation mode. The intraoperative conditions included operation time, intraoperative blood loss and so on. The postoperative conditions included the time of recovery of intestinal function after operation (performance as the postoperative exhaust time), postoperative hospital stay and so on. The postoperative hospital stay was related to the discharge standard. We defined discharge standard as follow:the patient can eat semi-liquid food and bread normally, with normal defecation and the normal blood index. The number of postoperative lymph node yielded according to the postoperative pathological counting. The Postoperative complications included pulmonary infection, intestinal obstruction, abdominal infection, anastomotic leakage, anastomotic hemorrhage, anastomotic stenosis, pancreatic leakage, lymphatic leakage, infection of incision and subcutaneous emphysema etc.. The patients in two groups were followed up for126months (average14months), to observe the tumor recurrence. The characteristics of serum changes of patients were observed. Observe the serum level of C reactions protein (CRP), CEA, CA99, CA125on preoperative morning and the morning of the thirtieth day preoperatively in two groups. CRP was detected by immunoturbidimetry. CEA, CA199, CA125were detected by electrochemical luminescence analysis. Analyze the effect of different operation methods on above-mentioned serum markers.
The patients in two groups were completed the operation successfully, and no case was converted to laparotomy in laparoscopic group. Comparison of clinical efficacy:Compared with open surgery group, laparoscopic group had longer operation time (P<0.01), less intraoperative blood loss and postoperative hospital stay (both P<0.01), earlier time of the first postoperative flatus (P<0.01) and lower rate of postoperative complication (P<0.05). The number of lymph node removed between two groups was no significantly different (P>0.05). Compared with the preoperative period, the levels of CRP, CEA and CA199in both groups were decreased on the30th day postoperatively (P<0.01). The postoperative CRP, CEA and CA199were significantly lower in the laparoscopic group than those in the open operation group (P<0.01). The level of CA125in both groups was decreased on the30th day postoperatively (P<0.01). The postoperative CA125was no significantly different between two groups (P>0.05).There were no significant differences in postoperative cancer recurrence and postoperative survival between two groups (P>0.05)
Any injury such as pathological change, operation, can cause the body's stress response. Serum CRP can reflect the degree of tissue injury. The degree of inflammatory reaction, depth and range of tissue damage in gastric cancer is more obvious than those in gastric benign lesion. The serum CRP reaches peak level in24hours after operation, and then decreases gradually. The level of CRP in one month postoperatively reflects body's inflammatory reaction and lesion after removal of the tumour. Through our study, We found that the serum CRP in one month postoperatively in two groups was reduced, compared to preoperative CRP, but it decreased more significantly in the observation group than in the control group (P<0.01).
Tumor markers are some biochemical materials in tissue, plasma or gastric juice which can be detected and reveal the information of tumour existence. The level of CEA is related to tumor size, local invasion, metastasis of lymph node or other parts, and prognosis. CA199is a kind of tumor markers which belongs to mucin type carbohydrate protein, mainly used for detection of pancreatic cancer and gastrointestinal cancer. It can be showed positive detection rate in gastric cancer at certain range. CA125is also a tumor marker for gastric cancer. CA199, CA125, CA724, CEA were tumor associated antigen, but were not tumor specific antigen. One tumor marker can occur in a variety of tumors. One kind of tumor can take on a variety of tumor markers. This study shows that, the level of serum CEA, CA199, CA125in the two groups both descend in one month postoperatively. According to some study, the level of CEA, CA199and CA125descended significantly in advanced gastric cancer after chemotherapy. In our study, we found that these three indexes of serum in gastric cancer were significantly decreased after operation, suggesting that dynamic observation of changes of these3indicators in serum can be used for evaluating curative effect of gastric surgery and judging prognosis of gastric cancer.
With the development of laparoscopic technique and continuous improvement and renewal of laparoscopic instrument, laparoscopic treatment for early gastric cancer and advanced gastric cancer in relatively early stage can obtain better curative effect in the near future, and achieve the same radical effect as open operation. The advantage of minimally invasive and clinical effect of laparoscopic operation is guaranteed by the premise of the radical resection. In recent years, the technique of laparoscopic gastric cancer operation has been developed vigorously in our country, but so far laparoscopic radical gastrectomy combined with organ resection is still not widely carried out in the world, mainly because of the followings:①Controversy of operation indications with laparoscopic radical gastrectomy combined organ resection;②Combined organ resection increases the difficulty of the operation and operation time. It tests operation team rigorously for the ability of dealing with emergencies occurred in operation process and the observation and treatment of postoperative complications such as pancreatic leakage, hemorrhea in abdominal cavity.③Controversy of postoperative curative effect in long term. From June2012to October2013,11patients with advanced gastric cancer received laparoscopic radical gastrectomy combined with organ resection in our department. The clinical data of these cases was analyzed retrospectively. The study was to explore the case choice, the occasion of carrying out and the feasibility of laparoscopic radical gastrectomy combined with organ resection for patients with advanced gastric cancer. Results are as follows:The mean operation time, blood loss, postoperative hospital stay were (252.14±41.25) minutes,(366.43±153.21)ml,(13.27±2.58) days respectively. After surgery,3patients were complicated by pulmonary infection. Two patients were complicated by pancreatic juice leakage and were cured with drainage. No anastomotic leakage, abdominal bleeding or mortality was observed. Followed up to now, there was no tumor recurrence or metastasis in these cases.
Conclusion:1. In the premise of proficient laparoscopic operation and strong clinical anatomical concept, laparoscopic assisted radical D2gastrectomy treating cancer in upper site of stomach body, fundus and cardia of stomach is safe and feasible. Laparoscopic assisted radical D2gastrectomy have the advantages of minimal invasion, less intraoperative bleeding, faster postoperative recovery, less postoperative complications and so on, and can excise the cancerous tissue effectively and also carry out the clearance of lymph node effectively. It can obtain good clinical curative effect in the short term. The serum CRP in one month postoperatively was reduced in gastric tumour patients, compared to preoperative CRP, but laparoscopic operation can reduce tissue injury preferably. CEA, CA199, CA125are common tumor markers. The level of CEA, CA199and CA125in gastric cancer patients was decreased in one month after the operation treatment. Long term effect of laparoscopic assisted radical D2gastrectomy need to be further demonstrated by carrying out prospective randomized study of high quality, large sample and multicenter.
2. Laparoscopic radical gastrectomy combined with organ resection is safe and feasible in selected cases for doctors who have sufficient clinical experience of laparoscope-assisted radical D2total gastrectomy, guided by correct anatomic idea. This technique can be tried and explored.
胃癌切除范围根据手术方式而定,包括以下几种术式：①远端胃切除适应于胃远端癌,次全胃切除后,能满足近端切缘至少距肿瘤5cm以上；②近端胃切除适用于肿块<3cm癌灶,更大的肿瘤可能需要全胃切除；③全胃切除适用于弥漫型胃癌、胃近端和中部癌、胃远端癌侵犯胃体、胃多发癌。已有前瞻性研究发现,对于近端胃癌早期病例接受全胃切除或近端胃切除术后5年生存率无显著差别,但Ⅲ期和Ⅳ期行近端胃大部分切除会降低术后生存率,且术后常伴有返流性食管炎影响患者术后生活质量。日本胃癌诊治规范明确指出,对于可切除的近端胃原则上应施行全胃切除术,T1期胃癌可考虑行近端胃切除,但必须保留1/2的胃。可见对进展期近端胃癌行根治性全胃切除已趋向共识。
得益于微创技术的迅猛发展,目前腹腔镜治疗进展期胃癌已被广泛认可。腹腔镜技术治疗胃癌根据手术部位以及淋巴结清扫范围的不同,存在不同的分类方法。按手术部位的不同,可分为腹腔镜下远端胃大部切除术、腹腔镜下近端胃大部切除术和腹腔镜下全胃切除术,甚至有报道运用于腹腔镜下联合脏器切除术；按淋巴结清扫范围,可分为腹腔镜下胃癌D1根治术、腹腔镜下胃癌D2根治术,甚至运用于腹腔镜下胃癌D3根治术。
随着腹腔镜技术在临床中的应用,腹腔镜手术治疗胃癌已成为胃肠外科发展的一种趋势,并且取得了良好的临床效果,有取代传统开腹手术之势。已有临床研究表明,腹腔镜辅助全胃切除术是安全和可行的。但很少有临床研究将腹腔镜辅助全胃切除术和传统的开腹全胃切除术进行临床疗效等比较。由于操作技术的困难,使得腹腔镜辅助胃癌全胃切除术还不是一个胃肠外科医生普遍接受的方法。
我们探讨腹腔镜辅助下根治性D2全胃切除术与传统开腹手术治疗胃癌的近期临床疗效及机体血清学变化特点。临床疗效包括手术时间,术中出血量,术后排气时间,术后住院时间,淋巴结淋巴结清扫数,术后并发症,术后肿瘤复发率等方面。机体血清学变化是指外周血CRP、CEA、CA199、CA125水平的变化。采用了回顾性分析的方法。回顾性分析我院同一手术团队2011年3月至2013年3月施行216例根治性D2全胃切除术患者的临床资料。严格纳入标准。两组临床资料具有可比性。腹腔镜组的手术方法：采用腹腔镜辅助下根治性D2全胃切除术。采用腹腔镜辅助下根治性D2全胃切除术。参照2010年第3版日本胃癌治疗指南进行D2淋巴结清扫术。用超声刀沿横结肠边缘游离并暴露大网膜,于横结肠边缘用超声刀沿无血管区切断大网膜,向左横结肠脾曲,向右至胃网膜右动脉根部,按照自下而上、先大弯后小弯的顺序进行淋巴结清扫。具体清扫顺序是：No.6、No.4d (幽门下区)→No.7、No.9、No.11p(胰腺上方区)→No.8a、No.12a、No.5(胰腺上方区)→No.3、No.1(胃小弯区)→No.4sb(脾门区)→No.10、No.lld(脾门区)→No.2(贲门左区)。在剑突下做一长度为6cm的正中线纵行切口,放置切口保护器,取出已游离的胃,于腔内用管状吻合器行食管空肠吻合、空肠输出输入襻侧吻合(食管空肠Roux-en-Y吻合)。吻合口旁常规放置引流管。开腹组采用常规开腹胃癌根治性D2全胃切除术。对两组的术中、术后情况、淋巴结清扫数目、术后并发症及术后肿瘤复发率等进行比较,分析两种手术方式的临床疗效。其中术中情况包括手术时间、术中出血量等；术后情况包括术后肠道功能恢复时间(表现为术后排气时间),术后住院时间等；术后住院时间与出院标准有关。待肛门排气、胃管拔除且消化道造影示排空良好开始进食；先流质饮食,逐渐过渡到半流质饮食,出院标准为患者进半流质及馒头正常、排便正常且各项抽血指标基本正常。术后淋巴结清扫数根据术后病理计数所得。术后并发症包括肺部感染、肠梗阻、腹腔感染、吻合口漏、吻合口出血、吻合口狭窄、胰漏、淋巴漏、切口感染及皮下气肿等。两组患者随访1-26个月,平均14个月,观察肿瘤复发情况。对患者机体血清学变化特点进行观察,观察两组手术前及术后第30天清晨血清C反应蛋白(CRP)、癌胚抗原(CEA)、CA99、CA125水平。采用免疫比浊法检测血清CRP水平。采用电化学发光分析法检测血清CEA、CA199、CA125水平。比较不同手术方式对患者上述血清学指标的变化的影响。
两组患者均顺利完成手术,腹腔镜组中无一例中转剖腹。临床疗效方面比较：与开腹手术组比较,腹腔镜组手术时间延长(P<0.01),术中出血量和住院时间明显减少(P均<0.01),术后排气时间早(P<0.01),术后并发症发生率低(P<0.05)。在淋巴结清扫数方面,两组无明显差异(P>0.05)。
病变、手术等任何损伤均可导致机体应激反应的发生。血清CRP可反映组织损伤程度。胃癌的机体炎症反应程度、组织损伤深度及范围较良性病变明显。CRP在术后24小时达到高峰,之后逐渐下降,术后1月CRP水平则反映癌肿清除后机体炎症反应及病变情况。我们研究发现,两组术后均可降低患者术后1月血清CRP,但观察组较对照组降低更明显(P<0.01)。肿瘤标志物是指从临床应用角度,在组织、血浆或胃液中能检测到有关生化物质基础达到一定时揭示肿瘤的存在信息。CEA在健康人血中水平甚微,最早用于内胚层恶性肿瘤胃肠癌的诊断,CEA水平的高低与胃癌肿瘤大小、局部浸润、淋巴结或者其他部位转移、预后有关。CAL199是一种粘蛋白型的糖类蛋白肿瘤标志物,主要用于检测胰腺癌和消化道肿瘤,其在胃癌中也有一定的阳性检出率。CA125也是胃癌的一种肿瘤标志物。CA199、CA125、CA724、CEA均为肿瘤相关抗原,但均为非肿瘤特异性抗原,一种肿瘤标志物可出现于多种肿瘤中,一种肿瘤亦可出现多种肿瘤标志物。本研究显示,两组均可降低血清CEA、CA199、CA125水平。有研究发现,进展期胃癌化疗后CEA、CA199和CA125的水平显著下降,我们的研究发现胃癌术后血清中3项指标均显著下降,提示动态观察血清中这3项指标的变化可以评价胃癌术后的疗效及判断预后。
随着腹腔镜技术的发展及腔镜器械的不断改进与更新,腹腔镜治疗早期胃癌及相对早期的进展期胃癌均能取得较好的近期疗效,且能达到与开腹手术相同的根治效果。腹腔镜手术的微创优势及其手术临床效果是在保证根治的前提下实现的。近年来,我国的腹腔镜下胃癌手术技术蓬勃发展,但至今腹腔镜下联合脏器切除的进展期胃癌根治术在世界范围内仍然未广泛展开,主要是因为以下几点：①对腹腔镜胃癌根治联合脏器切除的手术指征的争议；②联合脏器切除加大手术难度及手术时间,考验手术团队对术中可能出现突发情况的处理与应对,及对术后可能出现胰漏、腹腔内大出血等并发症的观察与处理；③手术后远期疗效的争议。我们通过回顾性分析我科2012年6月至2013年10月进行的11例腹腔镜胃癌根治术联合脏器切除术的病例的临床资料。探讨腹腔镜胃癌根治联合脏器切除的病例选择、开展时机及手术的可行性。结果示手术时间为(252.14±41.25)min,术中出血(366.43±153.21)ml,术后住院时间(13.27±2.58)d。术后发生肺部感染3例,胰漏2例,均经通畅引流治疗痊愈。无吻合口漏及腹腔内出血病例。无死亡病例。随访至今无肿瘤复发或转移。
结论：1.在拥有熟练的腹腔镜操作技术及较强的临床解剖理念前提下,腹腔镜辅助下根治性D2全胃切除术治疗胃体上段、胃底贲门癌是安全可行的。腹腔镜辅助下根治性D2全胃切除术具有微创优势,术中出血量少,术后恢复快,术后并发症少等优点,能够有效切除癌组织,同时能够有效进行淋巴清扫,更能取得良好的临床近期疗效。胃癌患者血清CRP在手术治疗1月较术前下降,腹腔镜手术能更好减低组织损伤。CEA、CA199、CA125是常见的肿瘤标志物。胃癌患者血清CEA、CA199、CA125在手术治疗1月较术前下降。腹腔镜辅助下根治性D2全胃切除术的远期疗效尚待高质量、大样本的多中心、前瞻性随机对照研究的开展来进一步论证。2.腹腔镜胃癌根治术联合脏器切除在选择合适的病例的情况下,正确的解剖理念的引导下,在积累较多腹腔镜辅助下根治性D2切除术的经验基础上开展是安全可行的,可进行尝试与探索。
The morbidity and mortality of gastric cancer worldwide is in the second position of malignant tumor. Gastric cancer is of the highest incidence in malignant tumor of gastrointestinal tract in Southeast Asia. There are two methods for the radical surgery of gastric cancer:the conventional open surgery and laparoscopy-assisted radical gastrectomy. Advanced gastric cancer refers to tumor cell infiltrating into the submucosa, muscularis or serosa through muscularis. Radical D2resection of gastric cancer is still considered the gold standard for the treatment of advanced gastric cancer. The standard radical D2resection of gastric cancer means to resection of proximal2/3stomach in proximate or distal position, or full stomach, and clearance of the first and second station lymph node corresponding to tumor position, in the premise of no distant metastasis.
The resection range in Gastric cancer operation is set according to the operation modes. There are three modes at least:(1) the distal gastrectomy, suitable for distal gastric cancer, gastric tumor occurred after subtotal gastrectomy, requires the proximal resection margin away from the tumor more than at least5cm;(2) proximal gastric resection, suitable for proximate gastric tumor<3cm, while larger tumors may need total gastrectomy;(3) total gastrectomy, suitable for gastric cancer of diffuse infiltration type, gastric cancer in proximal and middle position, distal gastric cancer infiltrating the gastric body and multiple gastric carcinoma. There was a prospective study of5years survival rate after proximal gastrectomy or total gastrectomy for early proximal gastric cancer. The rate of5years survival had no significant difference between two procedures. However, if the proximal gastric cancer of III and IV stage received proximal subtotal gastrectomy, postoperative survival rate can reduce, and reflux esophagitis often occurred which affect postoperative quality of life. The Japan standard of Diagnosis and treatment of gastric cancer points out clearly that resectable proximal gastric cancer should be performed total gastrectomy in principle. Although proximal gastric cancer in T1stage may be considered for proximal gastrectomy, half stomach must be retained. Thus, radical total gastrectomy has become consensus for advanced proximal gastric cancer.
Benefited from the rapid development of minimally invasive techniques, the laparoscopic treatment for advanced gastric cancer has been widely recognized. The classification of laparoscopic technique in the treatment of gastric cancer is different according to the operation site and the extent of lymph node dissection. According to the operation site, laparoscopic technique can be divided into laparoscopic distal gastrectomy, laparoscopic proximal gastrectomy and laparoscopic total gastrectomy, even laparoscopic gastrectomy combined organ resection (which was already reported). According to the extent of lymph node dissection, laparoscopic technique can be divided into laparoscopic radical D1resection for gastric cancer, laparoscopic radical D2resection for gastric cancer, even laparoscopic D3radical gastrectomy for gastric cancer.
With the application of laparoscopic technique in the clinical treatment, laparoscopic operation for gastric cancer has become a trend in the development of gastrointestinal surgery, and achieved good clinical results, to replace the traditional open operation. Clinical studies already show that laparoscopic assisted total gastrectomy is safe and feasible. But few clinical study of curative effect comparison in laparoscopic assisted total gastrectomy and the traditional open total gastrectomy is conducted. Due to technical difficulties, the method of laparoscopic assisted total gastrectomy for gastric cancer is still not generally accepted by gastrointestinal surgeon.
We investigated the curative effect of short term and the serological changes between laparoscopic assisted radical D2gastrectomy and traditional open operation in treatment of gastric cancer. The clinical outcomes included operation time, intraoperative blood loss, postoperative exhaust time, postoperative hospital stay, number of lymph node removed, postoperative complications, recurrence rate etc.. The serological change refered to changes of peripheral blood CRP, CEA, CA199, CA125level. The retrospective analysis method was used. From March2011to March2013,216patients received radical D2total gastrectomy, in which118patients underwent laparoscopic surgery (observation group) while98patients underwent open surgery (control group). The intraoperative and postoperative situation and number of lymph node removed between two groups were compared. C-reactive protein (CRP), CEA, CA99and CA125of peripheral blood were assayed preoperatively and on the30th day postoperatively. The rate of cancer recurrence between two groups was compared. The cases were selected according to strict entering standard. The clinical data of the two groups was of comparability. Operation procedure of the laparoscopic group was laparoscopic assisted radical D2total gastrectomy. D2Lymphadenectomy was conducted according to Japanese gastric cancer treatment guidelines of the third Edition in2010. Make dissociation along the transverse colon and expose the greater omentum with ultrasonic knife. Cut off the greater omentum along the avascular area using ultrasonic knife. Make dissociation to the site of splenic flexure of colon on the left, and gastroepiploic artery root on the right. The order of lymph node clearance was conducted according to the greater curvature side first and then the lesser curvature side, down to up. Specific order of lymph node clearance was:No.6, No.4d (pyloric region), No.7, No.9, No.11p (pancreatic anodic region)→No.8a, No.12a, No.5(pancreatic anodic region)→No.3, No.1(the lesser curvature of the stomach area)→No.4sb (splenic hilum area) and No.10, No.11d (splenic hilum area)→No.2(cardiac left area). Open abdomen through a length of6cm longitudinal midline incision under xiphoid bone, and place incision protector, remove the dissociative stomach, conduct esophagojejunostomy with tubular anastomat in the cavity, side anastomosis between input ansa and output anasa (Roux-en-Y esophagojejunostomy). The drainage tube was placed beside the anastomosis routinely. The procedure for open group was conventional laparotomy radical D2total gastrectomy for gastric cancer. The intraoperative and postoperative situation and number of lymph node removed between two groups were compared. The postoperative complications and the rate of cancer recurrence were also compared. Analyze the clinical effect of two kinds of operation mode. The intraoperative conditions included operation time, intraoperative blood loss and so on. The postoperative conditions included the time of recovery of intestinal function after operation (performance as the postoperative exhaust time), postoperative hospital stay and so on. The postoperative hospital stay was related to the discharge standard. We defined discharge standard as follow:the patient can eat semi-liquid food and bread normally, with normal defecation and the normal blood index. The number of postoperative lymph node yielded according to the postoperative pathological counting. The Postoperative complications included pulmonary infection, intestinal obstruction, abdominal infection, anastomotic leakage, anastomotic hemorrhage, anastomotic stenosis, pancreatic leakage, lymphatic leakage, infection of incision and subcutaneous emphysema etc.. The patients in two groups were followed up for126months (average14months), to observe the tumor recurrence. The characteristics of serum changes of patients were observed. Observe the serum level of C reactions protein (CRP), CEA, CA99, CA125on preoperative morning and the morning of the thirtieth day preoperatively in two groups. CRP was detected by immunoturbidimetry. CEA, CA199, CA125were detected by electrochemical luminescence analysis. Analyze the effect of different operation methods on above-mentioned serum markers.
The patients in two groups were completed the operation successfully, and no case was converted to laparotomy in laparoscopic group. Comparison of clinical efficacy:Compared with open surgery group, laparoscopic group had longer operation time (P<0.01), less intraoperative blood loss and postoperative hospital stay (both P<0.01), earlier time of the first postoperative flatus (P<0.01) and lower rate of postoperative complication (P<0.05). The number of lymph node removed between two groups was no significantly different (P>0.05). Compared with the preoperative period, the levels of CRP, CEA and CA199in both groups were decreased on the30th day postoperatively (P<0.01). The postoperative CRP, CEA and CA199were significantly lower in the laparoscopic group than those in the open operation group (P<0.01). The level of CA125in both groups was decreased on the30th day postoperatively (P<0.01). The postoperative CA125was no significantly different between two groups (P>0.05).There were no significant differences in postoperative cancer recurrence and postoperative survival between two groups (P>0.05)
Any injury such as pathological change, operation, can cause the body's stress response. Serum CRP can reflect the degree of tissue injury. The degree of inflammatory reaction, depth and range of tissue damage in gastric cancer is more obvious than those in gastric benign lesion. The serum CRP reaches peak level in24hours after operation, and then decreases gradually. The level of CRP in one month postoperatively reflects body's inflammatory reaction and lesion after removal of the tumour. Through our study, We found that the serum CRP in one month postoperatively in two groups was reduced, compared to preoperative CRP, but it decreased more significantly in the observation group than in the control group (P<0.01).
Tumor markers are some biochemical materials in tissue, plasma or gastric juice which can be detected and reveal the information of tumour existence. The level of CEA is related to tumor size, local invasion, metastasis of lymph node or other parts, and prognosis. CA199is a kind of tumor markers which belongs to mucin type carbohydrate protein, mainly used for detection of pancreatic cancer and gastrointestinal cancer. It can be showed positive detection rate in gastric cancer at certain range. CA125is also a tumor marker for gastric cancer. CA199, CA125, CA724, CEA were tumor associated antigen, but were not tumor specific antigen. One tumor marker can occur in a variety of tumors. One kind of tumor can take on a variety of tumor markers. This study shows that, the level of serum CEA, CA199, CA125in the two groups both descend in one month postoperatively. According to some study, the level of CEA, CA199and CA125descended significantly in advanced gastric cancer after chemotherapy. In our study, we found that these three indexes of serum in gastric cancer were significantly decreased after operation, suggesting that dynamic observation of changes of these3indicators in serum can be used for evaluating curative effect of gastric surgery and judging prognosis of gastric cancer.
With the development of laparoscopic technique and continuous improvement and renewal of laparoscopic instrument, laparoscopic treatment for early gastric cancer and advanced gastric cancer in relatively early stage can obtain better curative effect in the near future, and achieve the same radical effect as open operation. The advantage of minimally invasive and clinical effect of laparoscopic operation is guaranteed by the premise of the radical resection. In recent years, the technique of laparoscopic gastric cancer operation has been developed vigorously in our country, but so far laparoscopic radical gastrectomy combined with organ resection is still not widely carried out in the world, mainly because of the followings:①Controversy of operation indications with laparoscopic radical gastrectomy combined organ resection;②Combined organ resection increases the difficulty of the operation and operation time. It tests operation team rigorously for the ability of dealing with emergencies occurred in operation process and the observation and treatment of postoperative complications such as pancreatic leakage, hemorrhea in abdominal cavity.③Controversy of postoperative curative effect in long term. From June2012to October2013,11patients with advanced gastric cancer received laparoscopic radical gastrectomy combined with organ resection in our department. The clinical data of these cases was analyzed retrospectively. The study was to explore the case choice, the occasion of carrying out and the feasibility of laparoscopic radical gastrectomy combined with organ resection for patients with advanced gastric cancer. Results are as follows:The mean operation time, blood loss, postoperative hospital stay were (252.14±41.25) minutes,(366.43±153.21)ml,(13.27±2.58) days respectively. After surgery,3patients were complicated by pulmonary infection. Two patients were complicated by pancreatic juice leakage and were cured with drainage. No anastomotic leakage, abdominal bleeding or mortality was observed. Followed up to now, there was no tumor recurrence or metastasis in these cases.
Conclusion:1. In the premise of proficient laparoscopic operation and strong clinical anatomical concept, laparoscopic assisted radical D2gastrectomy treating cancer in upper site of stomach body, fundus and cardia of stomach is safe and feasible. Laparoscopic assisted radical D2gastrectomy have the advantages of minimal invasion, less intraoperative bleeding, faster postoperative recovery, less postoperative complications and so on, and can excise the cancerous tissue effectively and also carry out the clearance of lymph node effectively. It can obtain good clinical curative effect in the short term. The serum CRP in one month postoperatively was reduced in gastric tumour patients, compared to preoperative CRP, but laparoscopic operation can reduce tissue injury preferably. CEA, CA199, CA125are common tumor markers. The level of CEA, CA199and CA125in gastric cancer patients was decreased in one month after the operation treatment. Long term effect of laparoscopic assisted radical D2gastrectomy need to be further demonstrated by carrying out prospective randomized study of high quality, large sample and multicenter.
2. Laparoscopic radical gastrectomy combined with organ resection is safe and feasible in selected cases for doctors who have sufficient clinical experience of laparoscope-assisted radical D2total gastrectomy, guided by correct anatomic idea. This technique can be tried and explored.
引文
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