【摘要】：研究背景及目的：近些年來(lái)內(nèi)鏡下治療技術(shù)發(fā)展迅速,內(nèi)鏡隧道技術(shù)的出現(xiàn)使得很多以前屬于外科手術(shù)或腔鏡手術(shù)治療的疾病進(jìn)入內(nèi)鏡治療范疇,其療效與外科手術(shù)無(wú)差異,并且還具有并發(fā)癥少,創(chuàng)傷小等優(yōu)勢(shì)。經(jīng)口內(nèi)鏡肌切開(kāi)術(shù)(peroral endoscopic myotomy, POEM)自2010年報(bào)道以來(lái),由于其良好的臨床治療效果,同時(shí)兼?zhèn)湎啾韧饪艸eller手術(shù)癥狀緩解率高,復(fù)發(fā)率低以及創(chuàng)傷小等優(yōu)點(diǎn),目前在世界范圍內(nèi)廣泛開(kāi)展。內(nèi)鏡黏膜下隧道法切除術(shù)(Submucosal tunnel endoscopic resection, STER)是在POEM的基礎(chǔ)上將內(nèi)鏡隧道技術(shù)拓展到消化道固有肌層病變的治療方面,并且療效確切,此手術(shù)方法在一定程度上優(yōu)于外科手術(shù)及胸腔鏡手術(shù)。為何內(nèi)鏡隧道技術(shù)擁有如此良好的療效同時(shí)又具備并發(fā)癥少等諸多優(yōu)勢(shì)呢?主要是因?yàn)閮?nèi)鏡隧道技術(shù)可以有效的防止在進(jìn)行固有肌層側(cè)病變或固有肌層以外病變的內(nèi)鏡手術(shù)時(shí)導(dǎo)致的消化管腔與管腔外腔隙相通,避免消化管腔內(nèi)的氣體、液體直接進(jìn)入消化管腔外組織間隙,以達(dá)到即治療病變又防止穿孔的目的。經(jīng)自然腔道內(nèi)鏡手術(shù)(natural orifice transluminal endoscopic surgery, NOTES)是一種基于人體自然腔道,如食管、胃、直腸、陰道等進(jìn)入體腔,應(yīng)用軟式內(nèi)鏡完成治療,而體表無(wú)手術(shù)切口的一種手術(shù)方式。但NOTES手術(shù)發(fā)展至今存在幾個(gè)瓶頸,首先是入口縫合困難,其次是消化道內(nèi)液體進(jìn)入腹腔造成感染,然后是軟式內(nèi)鏡進(jìn)入腹腔后無(wú)明確解剖定位容易迷失方向;以上問(wèn)題一直困繞著內(nèi)鏡學(xué)者,如果不能很好的解決這些問(wèn)題,NOTES技術(shù)的發(fā)展將會(huì)在很大程度上受到限制。聯(lián)合內(nèi)鏡隧道技術(shù)進(jìn)行NOTES手術(shù)將會(huì)解決封閉入口困難的問(wèn)題,僅需幾枚金屬夾即可完整封閉食管的人工入口：并且由于隧道入口位置較高(在食管中下段)可有效防止胃內(nèi)液體流入體腔,因此經(jīng)口經(jīng)食管隧道還具備降低腹腔感染發(fā)生率等其他優(yōu)勢(shì),同時(shí)通過(guò)術(shù)前定位及與體外解剖結(jié)構(gòu)的對(duì)比,能更了解內(nèi)鏡下腹腔解剖結(jié)構(gòu),可在一定程度上解決內(nèi)鏡進(jìn)入腹腔易迷失方向的問(wèn)題。腹腔鏡手術(shù)目前技術(shù)已十分成熟,但是胃后壁及腹主動(dòng)脈區(qū)域一直是腹腔鏡手術(shù)最困難的部位,而應(yīng)用消化內(nèi)鏡穿透胃后壁可直接抵達(dá)該區(qū)域,理論上手術(shù)操作更簡(jiǎn)單、直接,更易操作。本課題共四部分研究,第一章研究尋找一個(gè)最佳動(dòng)物手術(shù)體位和最佳內(nèi)鏡下建立隧道的方法;第二章我們研究了內(nèi)鏡在腹腔內(nèi)辨認(rèn)解剖結(jié)構(gòu)的情況;第三章研究了術(shù)中并發(fā)癥的發(fā)生及解決情況,第四章通過(guò)前幾章的研究結(jié)果應(yīng)用內(nèi)鏡隧道技術(shù)將內(nèi)鏡穿透賁門(mén)胃底后壁進(jìn)入腹腔進(jìn)行包括腹腔干旁神經(jīng)節(jié)毀損術(shù),部分肝切除術(shù),部分脾切除術(shù),后腹膜區(qū)域部分組織切除術(shù)以及早期胃癌ESD術(shù)后壁外淋巴結(jié)清掃等腹主動(dòng)脈區(qū)域相關(guān)疾病的內(nèi)鏡診療手術(shù)。本研究旨在證明經(jīng)口經(jīng)食管內(nèi)鏡隧道技術(shù)腹主動(dòng)脈周圍疾病診療手術(shù)是安全可行的,并可在未來(lái)應(yīng)用于臨床診療中。方法：第一章：①術(shù)前定位穿入點(diǎn)的研究：取6頭豬尸,分2組,每組3頭。第一組為無(wú)術(shù)前定位組,由食管后壁建立隧道至賁門(mén)下方2cm處,切開(kāi)固有肌層及漿膜層進(jìn)入腹腔;第二組為美蘭定位組,在賁門(mén)后壁黏膜下層注射1：2美蘭生理鹽水注射液定位,食管后壁建立隧道至賁門(mén)下方標(biāo)記處,切開(kāi)固有肌層及漿膜層進(jìn)入腹腔。對(duì)比以上2組中3例進(jìn)入腹腔后的結(jié)構(gòu)對(duì)比圖,并剖開(kāi)豬尸腹部對(duì)比,觀察每組間3例入路的差異,差異小者為優(yōu)。②入路方式的研究：取9頭豬尸,分3組,每組3頭。第一組,仰臥位內(nèi)鏡下于食管后壁建立黏膜下隧道至賁門(mén)下方2cm處,切開(kāi)固有肌層及漿膜層,進(jìn)入胃后腹腔,辨認(rèn)腹腔內(nèi)解剖結(jié)構(gòu);第二組,左側(cè)臥位于食管右側(cè)壁建立隧道至賁門(mén)胃底小彎側(cè),切開(kāi)固有肌層及漿膜層,由賁門(mén)小彎側(cè)進(jìn)入腹腔,辨認(rèn)腹腔內(nèi)解剖結(jié)構(gòu);第三組,仰臥右肩抬高位于食管右后壁建立隧道至賁門(mén)小彎側(cè)偏后壁,切開(kāi)固有肌層及漿膜層進(jìn)入腹腔,辨認(rèn)腹腔內(nèi)解剖結(jié)構(gòu)。以上三組通過(guò)體會(huì)各組內(nèi)鏡操作難易程度,內(nèi)鏡進(jìn)入腹腔辨認(rèn)解剖結(jié)構(gòu)后均剖開(kāi)豬尸腹部進(jìn)行對(duì)照確認(rèn)。以進(jìn)鏡困難程度小,進(jìn)入腹腔后損傷組織少即可完成相關(guān)手術(shù)的一組為優(yōu)。③肌切開(kāi)方式的研究：取6頭豬尸,分2組,每組3頭。第一組為橫行肌切開(kāi)組,在隧道末端用電刀橫切開(kāi)肌層,內(nèi)鏡進(jìn)入腹腔。第二組為縱行肌切開(kāi)組,在隧道末端縱形切開(kāi)肌層,內(nèi)鏡進(jìn)入腹腔。第三組為漸進(jìn)式縱行肌切開(kāi)組,由淺入深逐步切開(kāi)肌層,內(nèi)鏡進(jìn)入腹腔。對(duì)比三實(shí)驗(yàn)組肌切開(kāi)長(zhǎng)度,肌切開(kāi)后內(nèi)鏡視野暴露情況以及內(nèi)鏡進(jìn)入腹腔后鏡身自由度等。以肌切開(kāi)長(zhǎng)度短,壁外視野暴露好,肌層創(chuàng)傷小,鏡身自由度好的一組為優(yōu)。第二章：通過(guò)第一章得出的最佳入路在豬尸上模擬手術(shù),內(nèi)鏡進(jìn)入腹腔達(dá)腹主動(dòng)脈周圍后,觀察內(nèi)鏡下圖像,并剖開(kāi)豬尸腹腔辨認(rèn)解剖結(jié)構(gòu)后進(jìn)行對(duì)比,獲得良好的內(nèi)鏡圖像與解剖圖像對(duì)比,為后續(xù)活體動(dòng)物實(shí)驗(yàn)打下良好的實(shí)驗(yàn)基礎(chǔ)。第三章：并發(fā)癥的相關(guān)研究,①氣體相關(guān)并發(fā)癥的研究：實(shí)驗(yàn)分三組,無(wú)排氣組,氣腹機(jī)組和穿刺排氣組,選擇最佳入路內(nèi)鏡進(jìn)入腹腔,無(wú)排氣組內(nèi)鏡持續(xù)在腹腔內(nèi)送氣,氣腹機(jī)組將內(nèi)鏡連接氣腹機(jī)并調(diào)整PCO2維持12-15mmHg,穿刺排氣組內(nèi)鏡持續(xù)送氣,并在腹部用注射器針頭穿刺排氣,腹腔內(nèi)注氣時(shí)間90min,觀察術(shù)中實(shí)驗(yàn)豬的生命體征,如實(shí)驗(yàn)豬死亡記錄死亡時(shí)間。②實(shí)驗(yàn)分二組,無(wú)處理組和特殊處理組,2組實(shí)驗(yàn)豬分別于術(shù)前、術(shù)后24h、48h、72h及一周測(cè)體溫,采靜脈血化驗(yàn)血常規(guī),內(nèi)鏡術(shù)后觀察腹腔感染情況。3.一周后處死實(shí)驗(yàn)豬,腹部解剖觀察腹腔內(nèi)情況。第四章：選擇9頭實(shí)驗(yàn)豬,以最佳入路進(jìn)入實(shí)驗(yàn)豬腹腔,常規(guī)腹部穿刺排氣,模擬部分肝、脾組織切除術(shù),腹腔干旁神經(jīng)節(jié)毀損術(shù),胰腺尾部周圍的觀察及后腹膜區(qū)域部分組織切除術(shù),以及胃壁外淋巴結(jié)清掃術(shù)。術(shù)后禁食禁水,應(yīng)用抗生素,觀察實(shí)驗(yàn)豬生存情況,飼養(yǎng)3天后處死,解剖觀察腹腔內(nèi)情況。結(jié)果：第一章：①美蘭定位組3例入路幾乎相同,而無(wú)定位組入路則相對(duì)有較大差異。②采用仰臥右肩抬高位進(jìn)鏡,內(nèi)鏡由賁門(mén)右后壁進(jìn)入腹腔,此處胃壁外大血管及重要臟器少,不易造成誤傷,并且該體位下隧道入口不在最低位,胃內(nèi)液體不易進(jìn)入隧道導(dǎo)致腹腔污染。③橫形切開(kāi)肌層內(nèi)鏡視野較縱形切開(kāi)差,內(nèi)鏡自由度不佳,容易自動(dòng)翻轉(zhuǎn)鏡身；縱行全層切開(kāi)肌層雖可以保證直鏡身狀態(tài),內(nèi)鏡自由度好,但對(duì)消化道肌層損傷大,不利于術(shù)后愈合;漸進(jìn)式縱行切開(kāi)固有肌層內(nèi)鏡視野暴露好,逐層切斷固有肌層更有利于發(fā)現(xiàn)肌層及胃壁外的血管,進(jìn)入腹腔后內(nèi)鏡自由度更好,不易自動(dòng)翻轉(zhuǎn)鏡身,是最佳的肌切開(kāi)方式。第二章：通過(guò)多次實(shí)驗(yàn),獲得了一定的內(nèi)鏡下解剖位置知識(shí),為后續(xù)實(shí)驗(yàn)打下基礎(chǔ)。第三章：①氣體相關(guān)并發(fā)癥研究：內(nèi)鏡腹腔內(nèi)持續(xù)送氣,以一支或多支20ml注射針腹腔穿刺放氣可維持腹腔壓力相當(dāng)于氣腹機(jī)調(diào)控腹壓15mmHg,均可保證術(shù)中實(shí)驗(yàn)豬生命體征平穩(wěn);無(wú)排氣組實(shí)驗(yàn)豬在腹腔持續(xù)注氣一定程度后均死亡。②腹腔感染研究：通過(guò)對(duì)比2實(shí)驗(yàn)組的實(shí)驗(yàn)豬生存情況,術(shù)后白細(xì)胞計(jì)數(shù),處死后腹腔內(nèi)組織黏連和滲出等情況,特殊處理組的實(shí)驗(yàn)豬術(shù)后感染較無(wú)處理組輕,并且術(shù)后生存狀態(tài)良好。第四章：①模擬部分脾切除術(shù)實(shí)驗(yàn)豬術(shù)后死亡。②其余各模擬手術(shù)實(shí)驗(yàn)豬均安全、成功的實(shí)施各模擬手術(shù)。實(shí)驗(yàn)豬術(shù)后存活良好,三天后處死,除手術(shù)部位外其他部位無(wú)損傷破壞,但手術(shù)部分組織均有不同程度的黏連。③限于目前內(nèi)鏡器械,無(wú)法實(shí)施較大型的腹腔內(nèi)內(nèi)鏡治療。④食管建立隧道處由于瘢痕性修復(fù)無(wú)法再次應(yīng)用。結(jié)論：術(shù)前美蘭定位,仰臥右肩抬高位建立食管黏膜下隧道至賁門(mén)胃底側(cè)后壁美蘭定位處漸進(jìn)式縱行切開(kāi)固有肌層及漿膜層,內(nèi)鏡進(jìn)入腹腔并配合20ml注射器穿刺放氣,行部分肝組織切除術(shù)、腹腔干旁神經(jīng)節(jié)毀損術(shù)、后腹膜周圍組織切除術(shù)和胃壁外淋巴結(jié)清掃術(shù)等是安全可行的。
[Abstract]:Background and purpose: in recent years, endoscopic therapy has developed rapidly. The emergence of endoscopic tunnel technology has made many diseases which had previously been treated by surgical or endoscopic surgery into the scope of endoscopic treatment, with no difference in curative effect and surgery, and with less complications and less trauma. Endoscopic myotomy (peror Al endoscopic myotomy, POEM), since its report in 2010, has been widely used worldwide because of its good clinical therapeutic effects, high remission rate, low recurrence rate, and small trauma in surgical Heller surgery. Endoscopic submucosal tunneling (Submucosal tunnel endoscopic resection, STER) is widely carried out in the world. On the basis of POEM, endoscopic tunnel technology is extended to the treatment of the gastrointestinal myometrium, and the curative effect is accurate. This method is superior to surgery and thoracoscopy. Why endoscopy tunnel technology has such a good curative effect while having less hair and other advantages? Mainly because of endoscopy Tunnel technique can effectively prevent the interlacing of the digestive tube and the outer cavity caused by endoscopic surgery for pathological changes of the inherent muscularis lateral lesions or inherent muscularis, and avoid the gas in the digestive canal, and the liquid directly enters the outer space of the digestive canal to achieve the purpose of treating the lesions and preventing perforation. Natural orifice transluminal endoscopic surgery (NOTES) is a kind of operation method based on the natural cavity of human body, such as esophagus, stomach, rectum, vagina, etc., with soft endoscopy, without surgical incision. But there are several bottlenecks in the development of NOTES operation, first of all, the difficulty of the entrance suture is difficult, and the next is the difficulty of the entrance suture. In the digestive tract, the fluid enters the abdominal cavity to cause infection, and then the soft endoscope enters the abdominal cavity without clear anatomical location and is easy to lose direction; the above problems have been stranded by endoscopy scholars. If these problems can not be solved well, the development of NOTES technology will be limited to a large extent. Combined endoscopic tunnel technology for NOTES hands The operation will solve the difficult problem of closed entrance. Only a few metal clips can be used to complete the artificial entrance of the esophagus. And because the entrance of the tunnel is higher (in the middle and lower segment of the esophagus), the fluid inflow in the stomach can be prevented effectively. Comparing with the anatomical structure in vitro, it can better understand the anatomical structure of the abdominal cavity, and to some extent solve the problem that the endoscopy is easy to get lost in the abdominal cavity. The technique of laparoscopy is very mature, but the region of the posterior and abdominal aorta is the most difficult part of the laparoscopic operation, and the use of digestive endoscopy is penetrating. The posterior wall of the stomach can reach the area directly. In theory, the operation is simpler, direct and easier to operate. This topic is studied in four parts. The first chapter is to find a best method of animal operation and the best way to establish tunnel under the endoscope. In the second chapter, we studied the situation of the endoscopic identification of the anatomical structure in the abdominal cavity; the third chapter studied the operation. The fourth chapters use the results of the previous chapters to apply endoscopic tunnel technique to penetrate the posterior wall of the cardia and gastric fundus into the abdominal cavity, including paraplastic paraplastic ganglion lesion, partial hepatectomy, partial splenectomy, partial retroperitoneal resection, and early gastric carcinoma after ESD. The purpose of this study is to prove that transesophageal endoscopic tunnel technique is safe and feasible for the diagnosis and treatment of abdominal aorta diseases, and can be applied to clinical diagnosis and treatment in the future. Head. The first group was a non preoperative positioning group. The posterior wall of the esophagus was set up to the 2cm place below the cardia. The intraperitoneal muscle layer and serous layer were cut into the abdominal cavity. The second group was Milan location group, and 1:2 Milan saline injection was injected into the submucosa of the posterior wall of the cardia. The posterior wall of the esophagus was located to the marker below the cardia, and the intrinsic myometrium was cut and the myometrium was cut. The serous layer entered the abdominal cavity. Compared the structural contrast map of 3 cases into the abdominal cavity in the above 2 groups, and dissection of the abdominal contrast between the pigs and the pigs, and observed the difference between 3 cases in each group. The difference was excellent. The study of the way of entry: 9 pigs, 3 groups, 3 heads in each group. The first group, submucosa tunnel to the cardia under the posterior wall of the esophagus under the supine position, was set up under the supine position. In square 2cm, the intraperitoneal and serous layers were cut into the abdominal cavity to identify the intraperitoneal anatomy. In the second group, the left side of the esophagus was located on the right wall of the esophagus to establish the tunnel to the small side of the gastric fundus, and the intraperitoneal and serous layers were cut into the abdominal cavity to identify the intraperitoneal anatomy. The third group, the supine right shoulder elevation was located right in the right esophagus. The posterior wall established the tunnel to the posterior wall of the small flexural side of the cardia, incised the intraperitoneal and serous layer into the abdominal cavity to identify the intraperitoneal anatomy. The above three groups realized that the endoscopic operation was difficult and the endoscope entered the abdominal cavity to identify the abdominal anatomy. A group of fewer tissues could complete the operation. (3) the study of the operation of the surgery. (3) the study of myotomy: 6 pigs were taken, 2 groups, 3 heads in each group. The first group was the transverse myotomy group, the muscle layer was cut through the open muscle layer at the end of the tunnel, and the endoscopy entered the abdominal cavity. The second groups were longitudinal myotomy group, the myotomy at the end of the tunnel, and the endoscopy into the abdominal cavity. The third groups were in the abdominal cavity. In the progressive longitudinal muscle incision group, the myotomy length, the exposure of the endoscopic field after myotomy and the freedom of the endoscopy into the retroperitoneal mirror were compared between the three experimental groups, the length of the endoscopic field and the degree of freedom of the endoscopy into the retroperitoneal mirror. A group of second chapters with short length of myotomy, good exposure of the visual field, small trauma of the myometrium, and a good degree of freedom of the mirror body were compared. In the first chapter, the best way to simulate the operation on the porcine corpse, after the endoscope enters the abdominal aorta around the abdominal aorta, observe the image under the endoscope and dissection the anatomical structure of the porcine celiac to make a contrast, and get a good contrast between the endoscope image and the anatomical image, and make a good experimental basis for the following living animal experiment. Third chapters The study of complications: (1) the study of gas related complications: the experiment was divided into three groups: no exhaust group, pneumoperitoneum and puncture and exhaust group, the best endoscopy was selected to enter the abdominal cavity, the endoscopy without exhaust group was continued in the abdominal cavity, the pneumoperitoneum was connected to the pneumoperitoneum by endoscopy and the PCO2 was adjusted to maintain the 12-15mmHg, and the endoscopy of the puncture exhaust group was continuously delivered. Gas, puncture and exhaust in the abdomen with syringe needle and intraperitoneal injection of gas 90min, observe the life signs of the experimental pigs in the operation, such as the death time of the experimental pigs. The experiment is divided into two groups, no treatment group and special treatment group. The 2 groups of experimental pigs are before the operation, after the operation, 24h, 48h, 72h and one week to test the body temperature, the venous blood tests the blood routine, endoscopy A week after the operation, the abdominal infection was observed and the experimental pigs were killed and the abdominal anatomy was observed in the abdominal cavity. Fourth chapter fourth: select 9 experimental pigs to enter the experimental pig abdominal cavity with the best approach, routine abdominal puncture and exhaust, simulated partial liver, splenic resection, paraplastic paraplastic ganglion damage, the observation of the tail around the pancreas and the retroperitoneum area Partial tissue resection and dissection of gastric wall lymph node dissection. After operation, fasting and prohibiting water, using antibiotics to observe the survival of experimental pigs, 3 days after feeding, were sacrificed and observed in the abdominal cavity. Results: the first chapter: (1) 3 cases in the Meilan location group were almost the same, but there were relatively large differences without the orientation group. Secondly, the supine right shoulder was carried out. High position into the mirror, endoscope from the right posterior wall of the cardia into the abdominal cavity, the large blood vessels and important organs of the stomach wall are few, it is not easy to cause the injury, and the entrance of the tunnel is not at the lowest position, the fluid in the stomach is not easy to enter the tunnel to lead to the abdominal pollution. Although the whole layer of myotomy can guarantee the state of direct mirror body, the endoscopy has a good degree of freedom, but it has great damage to the myometrium of the digestive tract and is not conducive to the healing. The gradual longitudinal incision of the intrinsic myomeendoscopy is good, and the layer by layer is more beneficial to the discovery of the muscle layer and the blood vessels outside the stomach wall, and the degree of freedom of the endoscope is better after entering the abdominal cavity. It is not easy to automatically flip the mirror body, it is the best way of muscle incision. The second chapter: through several experiments, a certain knowledge of the anatomical position of the endoscope is obtained, and the foundation for the follow-up experiment is laid. Third chapters: (1) the study of gas related complications: endoscopy abdominal continuous gas delivery, abdominal puncture with one or more 20ml injection needles to maintain abdominal pressure The force equivalent to the pneumoperitoneum control abdominal pressure 15mmHg, can ensure the stable life signs of the experimental pigs in the operation, no exhaust group experimental pigs in the abdominal cavity after a certain degree of gas injection after a certain degree of death. 2. Abdominal infection study: by comparing the survival of the 2 experimental pigs, postoperative leukocyte count, the abdominal tissue adhesion and exudation after death, and other conditions, and other conditions. The infection of the experimental pigs in the treatment group was lighter than that in the non treatment group, and the survival state was good after the operation. Fourth chapters: (1) the simulated partial splenectomy experiment pigs died after operation. 2. The rest of the simulated operation pigs were safe and successful implementation of the simulated operation. The experimental pigs survived well after three days, and there were no other parts except the surgical site. Injury and destruction, but the operation part of the tissues have different degrees of adhesion. 3. Limited to the present endoscopic instruments, it is impossible to carry out a larger intraperitoneal endoscopy. (4) the esophagus building tunnel can not be used again because of scar repair. Conclusion: Milan location before operation, lying on the back of the right shoulder to establish the submucosal tunnel to the fundus of the gastric cardia The intraperitoneal and serous layer of wall Meilan location is gradually cut into the intraperitoneal cavity and the 20ml syringe is punctured and deflated. Partial liver resection, paraplastic paraplastic ganglion lesion, posterior peritoneum tissue resection and gastric parietal lymph node dissection are feasible.
【學(xué)位授予單位】：中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R543.1

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