| BackgroundAEG is defined as an adenocarcinoma in which the tumor invades or exceeds the EGJ.The incidence of AEG has been gradually increasing worldwide for the past 40 years.Reports from the National Cancer Center of Japan showed that the proportion of AEG in gastric cancer increased from 2.3% in the mid-20 th century to 10.3% in the early 21 st century.Similarly,a study from China showed that the proportion of AEG in gastric cancer increased from 22.3% in 1988 to 35.7% in 2012.Due to its unique anatomical site and poor long-term prognosis,AEG is regarded as a class of specific diseases different from gastric cancer and esophageal cancer.At present,the main classifications for AEG are the Siewert classification and the Nishi classification.The Nishi classification is widely used in Japan while the Siewert classification is accepted internationally.Siewert,a German scholar,first classified AEG into three types based on the location of the tumor center relative to EGJ in 1987.Siewert type I is that the tumor invades the EGJ and the center of the tumor is located 1-5 cm above the EGJ.Siewert type II is that the tumor invades the EGJ and the center of the tumor is located 1 cm above the EGJ to 2 cm below the EGJ.Siewert type III is that the tumor invades the EGJ and the center of the tumor is located 2-5 cm below the EGJ.Due to the special anatomical location of the AEG at the junction of the esophagus and stomach,the surgical option is controversial due to Siewert type II.Currently,domestic and international expert consensus recommends a transthoracic approach for Siewert I AEG,which is mainly performed by thoracic surgeons,and a transhiatal approach for Siewert III AEG,which is mainly performed by abdominal surgeons.The JCOG9502 trial from Japan recommended a transhiatal approach for Siewert Ⅱ/Ⅲ AEG with esophageal invasion <3 cm.Therefore,our study focuses on Siewert Ⅱ/Ⅲ AEG.In recent years,laparoscopic gastrectomy has been increasingly used in clinical practice because of its characteristics of less trauma,less bleeding,and faster recovery.Laparoscopic distal gastrectomy was first reported by Kitano in 1994.Subsequently,minimally invasive surgery,represented by laparoscopic surgery,has flourished worldwide.High-quality RCT studies have confirmed the safety and efficacy of laparoscopic gastrectomy for early and advanced gastric cancer.However,laparoscopic gastrectomy is predominantly performed for distal gastric cancer,while proximal gastric cancer,especially AEG,is rare.Some technical difficulties limit the use of laparoscopic surgery for Siewert type Ⅱ/Ⅲ AEG,such as the complex topographic anatomy,the narrow surgical space,and the higher than usual anastomotic level of the esophageal jejunostomy.The current related studies are mainly Japanese and Korean,and the cases are mostly focused on T1-3 cases,while the cases of T4 a stage are fewer,and there is also a lack of reports of long-term survival outcomes,so whether laparoscopic surgery is safe for Siewert Ⅱ/Ⅲ AGE with serosa-invasive needs further investigation.Robotic gastrectomy was first reported by Hashizume in 2002.Robotic surgery is known for the advantages of high-definition 3D vision,operational flexibility,filtered tremor,and multi-angle joint movement.However,robotic surgery has been used mostly in distal gastric cancer,and very few studies have been reported in AEG.Whether robotic surgery is safe for Siewert Ⅱ/Ⅲ AEGs also remains uncertain.Minimally invasive surgery has been widely reported in the literature as being less invasive,causing less bleeding,and promoting faster recovery.Then,minimizing the extent of surgical resection can likewise reduce patient trauma for faster recovery.A key component of surgical resection extent is the extent of lymph node dissection.Therefore,another concern for Siewert Ⅱ/Ⅲ AEG is the optimal extent of abdominal lymph node dissection.The 5th edition of the Japanese gastric cancer guidelines has updated the extent of lymph node dissection for AEG,and proximal gastrectomy can be considered for AEG with tumor length diameter ≤4 cm.It should be noted that the extent of AEG proximal gastrectomy is based on the extent of lymph node dissection,especially the value of dissection of lymph node metastasis in No.5 and No.6.The classification of AEG in Japan is mostly based on the Nishi classification,which includes some esophageal squamous carcinomas and limits the tumor length to less than 4 cm,while the extent of lymph node dissection for AEG with a tumor length >4 cm is not described.Unlike countries such as Japan and Korea,where early-stage AEG patients predominate,80% of AEG patients in China are already diagnosed at an advanced stage at the time of consultation,and most of the tumor diameter is over 4 cm.Therefore,the applicability of the 5th edition of Japanese gastric cancer treatment guidelines to China is controversial.The 2018 edition of the Chinese Expert Consensus on Surgical Treatment of Adenocarcinoma of the Esophagogastric Junction summarized the current hot spots and controversies regarding the surgical treatment of AEG,including the safety of minimally invasive surgical approaches for Siewert Ⅱ/Ⅲ AEG and the extent of lymph node dissection and.Therefore,to address these concerns and controversies,this study aims to investigate the clinical efficacy of different minimally invasive surgical treatment modalities for Siewert Ⅱ/Ⅲ AEG and to provide a theoretical basis for clinical selection of more minimally invasive and less invasive treatment modalities.Part one Clinical outcome of laparoscopic gastrectomy versus open gastrectomy for serosa-invasive(p T4a)Siewert Ⅱ/Ⅲ AEGsPurposeTo investigate the surgical safety and long-term oncological prognosis of laparoscopic gastrectomy(LG)for patients with p T4 a Siewert Ⅱ/Ⅲ AEG.MethodsPatients with p T4 a Siewert Ⅱ/Ⅲ AEG who underwent LG or open gastrectomy(OG)at our center from January 2004 to September 2015 were retrospectively collected and analyzed.To minimize confounding bias,a 1:1 matched PSM analysis was used.The primary endpoint was 5-year OS,and the secondary endpoints were 5-year DFS and postoperative complications.ResultsAfter PSM,the operative time was significantly longer in the LG group than in the OG group(316.9 vs 256 min,P=0.000);the estimated blood loss was significantly less in the LG group than in the OG group(255.4 vs 361.3 ml,P=0.006);the time to first flatus was significantly shorter in the LG group than in the OG group(3.7 vs 4.2 d,P=0.002);the time to start fluid diet was significantly shorter in the LG group than in the OG group(4.2 vs 4.9 d,P=0.000);the incision length was significantly shorter in the LG group than in the OG group(7.3 vs 18.0 cm,P=0.000).There was no significant difference in the overall complication rate and severe complication rate(Clavien-Dindo ≥grade IIIa)between the LG and OG groups for patients with p T4 a Siewert type Ⅱ/Ⅲ AEG(20.4% vs 25.8%,P=0.385;4.4% vs6.5%,P=0.516).In addition,there was no significant difference in 5-year OS and 5-year Disease-free Survival(DFS)between the LG and OG groups for patients with p T4 a Siewert type Ⅱ/Ⅲ AEG(35.4% vs 32.1%,P=0.541;34.1% vs 31.0%,P=0.523).There was no difference in the recurrence rate between the LG and OG groups during the 5-year follow-up period(38.7% vs.37.6%,P=0.880).The results of the Cox proportional hazards model showed that Siewert type and p N stage were independent risk factors for 5-year OS,whereas surgical type was not an independent risk factor for prognosis.ConclusionsIn patients with p T4 a Siewert type Ⅱ/Ⅲ AEG,LG achieves similar long-term oncologic outcomes as OG,and its short-term surgical outcomes are superior to those of OG.Part two Long-term and surgical outcomes of robotic gastrectomy and laparoscopic gastrectomy for Siewert type Ⅱ/Ⅲ AEGs: a 1:2 propensity score matching analysisPurposeTo explore the surgical safety and long-term oncologic outcome of robotic gastrectomy(RG)for patients with Siewert type Ⅱ/Ⅲ AEG.MethodsWe retrospectively collected and analyzed data from patients with Siewert Ⅱ/Ⅲ AEG who had RG or LG at our center between January 2005 and September 2016.A 1:2 matched PSM analysis was performed to minimize confounding bias.The primary endpoint was 5-year OS,and the secondary endpoints were 5-year DFS and postoperative complications.ResultsAfter PSM,the RG group had less estimated blood loss(144.8 vs 171.7 ml,P=0.004),shorter time to first flatus(3.5 vs 3.9 d,P=0.005),shorter time to first ambulation(2.6 vs 2.9d,P=0.004),and shorter time to remove the drainage tube(6.2 vs 7.1 d,P=0.002)compared to the LG group.The RG group also retrieved significantly higher abdominal lymph nodes than the LG group(34.2 vs.30.3,P=0.002),with the preponderance of their dissection lymph nodes distributed in the suprapancreatic area.The RG and LG groups of Siewert type Ⅱ/Ⅲ AEG were similar in overall postoperative complication rate and severe complication rate(Clavien-Dindo ≥grade IIIa)(20.7% vs 25.0%,P=0.457;7.3% vs 6.7%,P=0.859).Similarly,there was no significant difference in the recurrence rate between the RG and LG groups of Siewert type Ⅱ/Ⅲ AEG during the 5-year follow-up period(26.8% vs.28.7%,P=0.763).The results of the Cox proportional hazards model showed that histological type and p N stage were independent risk factors for 5-year OS.Postoperative adjuvant chemotherapy was an independent protective factor for prognosis.However,the surgical type was not a risk factor for 5-year OS.ConclusionsRobotic surgery is safe and feasible for Siewert Ⅱ/Ⅲ AEG and superior to laparoscopic surgery in terms of short-term postoperative outcomes,and both surgical types are comparable in terms of long-term oncologic outcomes.Part three The optimal extent of abdominal lymph node dissection based on tumor diameter for patients with Siewert type Ⅱ/Ⅲ AEGPurposeTo investigate the characteristics and long-term oncological prognosis of abdominal lymph node metastasis of Siewert Ⅱ/Ⅲ AEGs under different tumor diameters and to explore the pattern of lymph node metastasis in No.5 and No.6 lymph nodes(PLNs)and the value of clearance.MethodsBaseline clinicopathological characteristics of patients with Siewert Ⅱ/Ⅲ AEG who underwent total gastrectomy at our center from January 2006 to December 2015 were collected and analyzed retrospectively.Patients with Siewert Ⅱ/Ⅲ were grouped according to whether the tumor diameter was greater than 4 cm,and the number of lymph nodes cleared in No.1 to 12,the metastasis status,and the 5-year Overall Survival(OS)of patients with lymph node metastasis in each station were analyzed.The primary endpoints were IEBLD values of lymph nodes in each station.ResultsIn patients with Siewert Ⅱ/Ⅲ AEG,high lymph node clearance values were obtained for No.1,2,3,7,8,9,and 11 lymph nodes(IEBLD ≥3),while low lymph node clearance values were obtained for No.4,5,6,and 12 lymph nodes away from the esophagogastric junction(IEBLD <3).The value of No.10 lymph node dissection was high in patients with Siewert III AEG but low in patients with Siewert II AEG.Subsequently,a subgroup analysis based on different tumor diameters(≤4 cm and >4 cm)showed that lymph node dissection in No.1,2,3,7,8,9,and 11 was still of high value in patients with Siewert Ⅱ/Ⅲ AEG,regardless of tumor diameter.Similarly,regardless of tumor diameter,the value of lymph node dissection was low in No.4,10,and 12 in patients with Siewert II AEG and in No.12 in patients with Siewert III AEG.Interestingly,the value of lymph node dissection was high in No.5 and 6 in patients with Siewert type II AEG with a tumor diameter >4 cm.In contrast,the value of lymph node dissection in No.5 and 6 was low in patients with Siewert type III AEG with a tumor diameter >4 cm.Similarly,in patients with a tumor diameter >4 cm of Siewert type III AEG,the value of lymph node dissection was high in No.4 and 10.The results of the Cox proportional hazards model showed that tumor diameter,p N stage,and PLNs status were independent risk factors for prognosis,while postoperative adjuvant chemotherapy was an independent protective factor for prognosis.ConclusionsFor patients with Siewert II AEG and a tumor diameter ≤4 cm,PLNs should not be dissected and proximal gastrectomy should be adopted,while for patients with Siewert II AEG and a tumor diameter >4 cm,PLNs should be dissected and total gastrectomy is recommended. |
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