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Objective:To investigate the influencing factors and regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 185 Siewert type Ⅱ and Ⅲ AEG patients in two medical centers (113 cases in Changzhi People's Hospital Affiliated to Changzhi Medical College and 72 cases in Heji Hospital Affiliated to Changzhi Medical College) from January 2017 to January 2022 were collected. There were 143 males and 42 females, aged (64±8)years. Patients underwent radical resection of AEG combined with inferior mediastinal lymph node dissection. Observation indicators: (1) clinicopathological charac-teristics of Siewert type Ⅱ and Ⅲ AEG patients; (2) analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG; (3) regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparsion between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. Results:(1) Clinicopathological characteristics of Siewert type Ⅱ and Ⅲ AEG patients. Pathologic staging as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ, degree of tumor invasion as stage T1, T2, T3 and T4, length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were found in 30, 61, 75, 7, 3, 41, 79, 50, 101, 46, 18, 8 cases of the Siewert type Ⅱ and Ⅲ AEG patients without inferior mediastinal lymph node metastasis, respectively, versus 0, 2, 10, 0, 0, 0, 5, 7, 4, 3, 2, 3 cases of the Siewert type Ⅱ and Ⅲ AEG patients with inferior mediastinal lymph node metastasis, showing a significant differences between them ( Z=?2.21, ?2.49, ?2.22, P<0.05). (2) Analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Results of univariate analysis showed that pathological staging, depth of tumor invasion and length of esophageal invasion were related factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=2.48, 3.26, 2.03, 95% confidence intervals as 1.02?6.01, 1.21?8.80, 1.18?3.51, P<0.05). Results of multivariate analysis showed that depth of tumor invasion and length of esophageal invasion were independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=4.01, 2.26, 95% confidence interval as 1.35?11.96, 1.26?4.06, P<0.05). The inferior mediastinal lymph node metastasis probability of AEG patients with the length of esophageal invasion >3 cm and ≤4 cm was 9.47 times that of AEG patients with the length of esophageal invasion ≤1 cm. (3) Regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The number of inferior mediastinal lymph nodes including No.110, No.111 and No.112 dissected in 185 patients of Siewert type Ⅱ and Ⅲ AEG were 127, 50 and 27. The number of lymph nodes dissected and the number of metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 69, 4, 42, 4, 4, 1, 12, 4 and 23, 0, 17, 0, 7, 2, 3, 0, respectively. There were significant differences in metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm ( χ2=8.45, 7.30, P<0.05). Of the 185 patients of Siewert type Ⅱ and Ⅲ AEG, the ratio of cases with inferior mediastinal lymph nodes metastasis was 6.49%(12/185). The ratio of inferior mediastinal lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 3.81%(4/105), 6.12%(3/49), 10.00%(2/20), 27.27%(3/11), respectively. The ratio of No.110 lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 2.86%(3/105), 6.12%(3/49), 5.00%(1/20), 27.27%(3/11), respectively, showing a significant difference among them ( χ2=8.26, P<0.05). Conclusions:Depth of tumor invasion and length of esophageal invasion are independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The rate of inferior mediastinal lymph node metastasis increases with the increase of the length of esophageal invasion.
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With the continuous update and improvement of minimally invasive techni-ques, laparoscopic and robotic surgeries have increased significantly for the surgical treatment of adenocarcinoma of esophagogastric junction (AEG). Due to the anatomical particularity and biolo-gical characteristics of Siewert type Ⅱ AEG, surgical approach, the range of resection, lymph node dissection and digestive tract reconstruction cannot be unified at present, which is also the contro-versy between gastrointestinal surgery and thoracic surgery. Laparoscopic minimally invasive techni-que may be more conducive to lower mediastinal lymph node dissection. Laparoscopic surgery of AEG after neoadjuvant chemotherapy is safe and feasible. Robotic surgery may be the direction of minimally invasive surgery in the future. The authors mainly investigate strategies of minimally invasive surgery for the surgical treatment of AEG, and look forward to more clinical trials on Siewert type Ⅱ AEG surgery to guide surgical treatment.
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Objective:To investigate the application value of self-pulling and latter transection (SPLT) technique in double anti-reflux double-tract reconstruction of totally laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 103 patients with Siewert type Ⅱ adenocarcinoma of esophagogastric junction in clinical stage Ⅰ-Ⅱ who were admitted to Shanxi Cancer Hospital from January 2018 to January 2020 were collected. There were 65 males and 38 females, aged from 45 to 79 years, with a median age of 59 years. Of 103 patients, 49 cases undergoing totally laparoscopic proximal gastrectomy with double-tract reconstruction of SPLT were assigned into the SPLT group, 54 cases undergoing totally laparoscopic proximal gastrectomy with conventional double-tract reconstruction were assigned into the traditional group. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone inter-view to detect postoperative reflux esophagitis of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and the t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and the Wilcoxon test was used for comparison between groups. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Intraoperative situations: the operation time, digestive tract reconstruction time, volume of intraoperative blood loss, the number of inferior mediastinal lymph nodes dissected, cases with auxiliary incisions for the SPLT group were (261±48)minutes, (26±4)minutes, (114±42)mL, 8.0(6.5,9.5), 1, respectively. The above indicators were (244±42)minutes, (30±6)minutes, (118±46)mL, 5.5(4.0,8.0), 9 for the traditional group, respectively. There were significant differences in the digestive tract reconstruction time, the number of inferior mediastinal lymph nodes dissected and cases with auxiliary incisions between the two groups ( t=-3.34, Z=-4.05, χ2=4.72, P<0.05). There was no significant difference in the operation time or volume of intraoperative blood loss between the two groups ( t=1.87, -0.47, P>0.05). (2) Postoperative situations: duration of postopera-tive hospital stay and cases with postoperative complications were (11.5±2.7)days and 4 for the SPLT group, versus (12.5±4.3)days and 9 for the traditional group, showing no significant difference between the two groups ( t=-1.47, χ2=1.68, P>0.05). There were 13 of 103 patients with postopera-tive complications, including 5 cases of left pleural effusion, 4 cases of anastomotic leakage, 2 cases of mild pneumonia, 1 case of incision infection, 1 case of chylous leakage. Four patients had anasto-motic leakage at the esophagojejunostomy, the abdominal esophagus of whom was invaded by more than 1 cm. During the operation, mediastinal drainage tubes were placed through the abdominal wall. The 4 patients were cured after enteral and parenteral nutrition support and adequate drainage, and the remaining patients with complications were cured after symptomatic treatment. (3) Follow-up: of 49 patients in the SPLT group, 43 cases were followed up for (18±4)months. During the follow-up, 1 case showed reflux esophagitis by gastroscopy, with the incidence of 2.33%(1/43). Of 54 patients in the traditional group, 53 cases were followed up for (17±4)months. During the follow-up, 4 cases showed reflux esophagitis by gastroscopy, with the incidence of 7.55%(4/53). There was no significant difference in the incidence of reflux esophagitis between the two groups ( χ2=0.47, P>0.05). Conclusions:SPLT technology is feasible for double anti-reflux double-tract reconstruction of proximal gastrectomy. Compared with traditional double-tract reconstruction of totally laparos-copic proximal gastrectomy, SPLT technology can reduce the auxiliary incisions, increase the number of lower mediastinal lymph nodes dissected, and shorten the digestive tract reconstruction time.
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Objective:To investigate the clinical efficacy of proximal gastrectomy and total gastrectomy in the treatment of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 170 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to Guangdong Provincial People′s Hospital from January 2010 to December 2018 were collected. There were 125 males and 45 females, aged from 30 to 85 years, with a median age of 64 years. Of the 170 patients, 82 cases undergoing proximal gastrectomy were allocated into the proximal gastrectomy group and 88 cases undergoing total gastrectomy were allocated into the total gastrectomy group. Observation indica-tors: (1) surgical and postoperative situations; (2) follow-up and survival; (3) analysis of prognostic factors. Follow-up was conducted using telephone interview and outpatient examination to detect survival of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan-Meier method was used to draw survival curves, and Log-Rank test was used for survival analysis. COX proportional hazard model was used for univariate and multivariate analyses. Variables with P<0.1 in univariate analysis were included for multivariate analysis. Results:(1) Surgical and postoperative situations. Cases with surgical approach as transthoracic or thoraco-abdominal approach, transabdominal approach, the operation time, cases with volume of intra-operative blood loss ≤100 mL or >100 mL, cases with length of proximal margin ≤1.5 cm or >1.5 cm, cases with radical surgery outcome as R 0, R 1, R 2, the number of lymph nodes harvest, cases with anastomotic leakage, cases with anastomotic stricture, cases with incision infection, cases with pleural infection or effusion, cases with abdominal infection or ascites were 61, 21, (211±18)minutes, 46, 36, 44, 38, 73, 6, 3, 15(9,22), 5, 2, 2, 4, 2 in the proximal gastrectomy group, respec-tively. The above indicators were 12, 76, (263±15)minutes, 27, 61, 45, 43, 82, 4, 2, 23(18,32), 4, 1, 3, 1, 4 in the total gastrectomy group, respectively. There were significant differences in the surgical approach, operation time, volume of intraoperative blood loss and the number of lymph nodes harvest between the two groups ( χ2=63.94, t=-25.50, χ2=11.19, Z=-5.62, P<0.05). There was no significant difference in the length of proximal margin or radical surgery outcome between the two groups ( χ2=0.11, Z=-0.95, P>0.05) and there was no significant difference in the anastomotic leakage, anastomotic stricture, incision infection, pleural infection or effusion, abdominal infection or ascites between the two groups ( P>0.05). (2) Follow-up and survival. All the 170 patients were followed up for 89(64,106)months. Of the 170 patients, the 5-year overall survival rates were 43.8% and 35.5% of the Siewert type Ⅱ and Ⅲ AEG patients, respectively, showing no significant difference between them ( χ2=0.87, P>0.05). Of the patients with Siewert type Ⅱ AEG, the 5-year overall survival rates were 41.7% and 54.3% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=1.05, P>0.05). Of the patients with Siewert type Ⅲ AEG, the 5-year overall survival rates were 31.3% and 37.5% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=0.33, P>0.05). The 5-year overall survival rates were 39.0% and 44.2% in the proximal gastrectomy group and the total gastrectomy group, respectively, showing no significant difference between the two groups ( χ2=0.63, P>0.05). Of the patients in TNM stage Ⅰ, stage Ⅱ, stage Ⅲ, the 5-year overall survival rates were 65.3%, 36.3%, 27.1% in the proximal gastrectomy group, versus 83.3%, 48.0%, 39.7% in the total gastrectomy group, showing no signifi-cant difference between the two groups ( χ2=0.02, 1.50, 1.21, P>0.05). (3) Analysis of prognostic factors. Results of univariate analysis showed that pathological N staging, degree of tumor differen-tiation and radical surgery outcome were related factors influencing prognosis of AEG patients ( hazard ratio=1.71, 1.70, 2.85, 95% confidence interval as 1.16-2.60, 1.15-2.50, 1.58-5.14, P<0.05). Results of multivariate analysis showed that pathological N staging and radical surgery outcome were independent factors influencing prognosis of AEG patients ( hazard ratio=1.55, 2.18, 95% confidence interval as 1.05-2.31, 1.18-4.02, P<0.05). Conclusions:There is no significant difference in the prognosis of Siewert type Ⅱ and Ⅲ AEG patients undergoing proximal gastrectomy or total gastrectomy. Proximal gastrectomy can be used for the treatment of advanced Siewert type Ⅱ and Ⅲ AEG.
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There are high burden of disease including a high incidence, relatively high proportion of late stage when diagnosed and poor overall prognosis in China regarding to the diagnosis and treatment of gastric cancer. Surgery remains as the major treatment for gastric cancer. Based on the latest guidelines, endoscopic surgery or gastrectomy is performed for early gastric cancer, and the standard surgery for locally advanced gastric cancer is D2 lymphadenectomy. Besides, this article will discuss about other research hotspots, such as expansion of lymph node dissection in selected patients, construction methods of adenocarcinoma of esophagogastric junction, especially Siewert type Ⅱ, minimally invasive techniques (laparoscopic gastrectomy and robotic gastrectomy), the surgical treatment for elderly patients with gastric cancer will be discussed also.
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@#Surgery is an accepted standard in the treatment of adenocarcinoma of esophagogastric junction (AEG), but the efficacy of surgery alone for locally advanced AEG is limited. In-depth studies concerning combined therapy for AEG have been carried out worldwide, including neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), perioperative chemotherapy (pCT), postoperative chemoradiotherapy, etc. Significantly, the contribution of nCRT and pCT to improving the prognosis of locally advanced AEG patients has been shed light on. Compared with that, multimodality treatment for AEG patients is not well established in China. An attempt was thus made to take an overview of the evidence-based research advance regarding integrated therapy of AEG.
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Objective:To investigate the application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy (nCRT) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The perspec-tive randomized control study was conducted. The clinicopathological data of 90 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent nCRT in the Fourth Hospital of Hebei Medical University from February 2012 to December 2018 were selected. Patient were divided into two groups with 1:1 according to random number table. Patients undergoing nCRT combined with individualized full-course nutritional intervention were allocated into experimental group, and patients undergoing nCRT combined with common nutritional intervention were allocated into control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period; (3) efficacy evaluation and adverse effects of nCRT; (4) surgical and recovery situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement date with skewed distribution were represented as M ( P25, P75) or M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Grouping situations of the enrolled patients: a total of 90 patients were selected for eligibility. There were 77 males and 13 females, aged from 26 to 74 years, with a median age of 62 years. Of 90 patients, there were 45 cases in the experimental group and 45 cases in the control group. (2) Changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period: ① during the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the body mass was (67±10)kg, (66±9)kg, (67±10)kg, (68±10)kg, (70±10)kg for the experi-mental group, respectively, and (65±9)kg, (59±8)kg, (62±8)kg, (64±8)kg, (66±9)kg for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the body mass ( χ2=195.010, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of body mass changing between the two groups ( F=93.974, 60.638, 4.144, P<0.05). ② During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the total protein was (66±4)g/L, (65±4)g/L, (65±4)g/L, (68±4)g/L, (71±5)g/L for the experimental group, respectively, and (65±4)g/L, (62±5)g/L, (63±5)g/L, (65±5)g/L, (67±6)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the total protein ( χ2=652.524, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of total protein changing between the two groups ( F=672.507, 6.424, 5.057, P<0.05). ③ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the albumin was (40±3)g/L, (38±4)g/L, (38±4)g/L, (39±4)g/L, (40±4)g/L for the experimental group, respectively, and (39±4)g/L, (35±5)g/L, (36±4)g/L, (36±4)g/L, (37±5)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the albumin ( χ2=289.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of albumin changing between the two groups ( F=4 210.683, 5.013, 7.330, P<0.05). ④ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the prealbumin was (228±41)mg/L, (222±56)mg/L, (223±47)mg/L, (227±46)mg/L, (233±53)mg/L for the experimental group, respectively, and (202±49)mg/L, (174±68)mg/L, (179±54)mg/L, (185±51)mg/L, (193±57)mg/L for the control group. The multi-variate test was conducted based on the mauchly's test of sphericity for the prealbumin ( χ2=297.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of prealbumin changing between the two groups ( F=871.545, 6.111, 14.426, P<0.05). ⑤ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the hemoglobin was (124±14)g/L, (121±14)g/L, (125±13)g/L, (127±13)g/L, (128±13)g/L for the experimental group, respectively, and (121±18)g/L, (114±14)g/L, (116±14)g/L, (117±16)g/L, (118±22)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the hemoglobin ( χ2=257.560, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of hemoglobin changing between the two groups ( F=2 533.553, 4.142, 4.985, P<0.05). ⑥ During the nCRT treatment (week 3, week 6) and the preopera-tive waiting period (week 9, week 12, week 15), the patient-generated subjective global assessment (PG-SGA) score was 4.4±1.2,6.3±1.4, 5.5±1.4, 4.3±1.4, 3.4±1.7 for the experimental group, respec-tively, and 4.9±1.2, 7.4±1.7, 7.3±1.6, 6.3±1.4, 6.0±1.5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the PG-SGA score ( χ2=289.543, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of PG-SGA score changing between the two groups ( F=648.583, 41.906, 26.098, P<0.05). ⑦ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the quality of life questionnaire of stomach (QLQ-ST022) score was 13±3, 16±6, 16±4, 14±4, 12±5 for the experimental group, respectively, and 15±4, 21±6, 20±4, 17±4, 15±5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the QLQ-STO22 ( χ2=279.865, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of QLQ-STO22 changing between the two groups ( F=710.238, 7.261, 16.794, P<0.05). (3) Efficacy evaluation and adverse effects of nCRT: there were 25 patients and 20 cases of the experimental group with partial response and stable disease, showing the objective response rate and disease control rate as 55.6%(25/45)and 100.0%(45/45). There were 18 patients and 27 cases of the control group with partial response and stable disease, showing the objective response rate and disease control rate as 40.0%(18/45)and 100.0%(45/45). There was no significant difference in the nCRT efficacy between the two groups ( P>0.05). Cases with leukopenia, neutropenia, anemia, nausea, and loss of appetite were 27, 25, 19, 30, 34 for the experimental group, versus 37, 34, 29, 39, 42 for the control group, showing significant differences between the two groups ( χ2=5.409, 3.986, 4.464, 5.031, 5.414, P<0.05). (4) Surgical and recovery situations: patients of the experimental group underwent surgeries successfully. Two patients of the control group diagnosed with peritoneal metastasis after laparoscopic exploration underwent conversion therapy and no surgery, the other 43 patients underwent surgeries. The time to postoperative gastric tube removal, time to postopera-tive drainage tube removal, time to postoperative first flatus, time to postoperative first defecation, duration of postoperative hospital stay were 2.0 days (1.5 days, 3.0 days), 6.0 days (5.0 days,11.0 days), 2.0 days (1.5 days, 2.5 days), 2.0 days (1.5 days, 2.5 days), 7.0 days (6.0 days,14.0 days) for the experimental group, versus 3.0 days (2.0 days,4.0 days), 7.0 days (5.5 days,14.0 days), 2.0 days (1.5 days,3.0 days), 3.0 days (2.0 days,3.5 days), 8.0 days (6.0 days, 17.0 days) for the control group, showing significant differences between the two groups ( Z=-3.477, -4.398, -3.068, -5.786, -3.395, P<0.05). Conclusion:For AEG patients undergoing nCRT, the individualized full-course nutrition intervention involving nutritionists is beneficial to improve the nutritional status, reduce adverse reactions, and improve the quality of life of the patients, promote postoperative short-term recovery. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT01962246.
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Due to the unique position and biological behaviors of adenocarcinoma of esophagogastric junction (AEG), the pattern of treatment has gradually changed from surgery alone leading by surgeons to comprehensive treatment by multidisciplinary teams including thoracic surgeons, oncologists, radiotherapy physicians, anesthetists and so on. The development of laparoscopic surgery makes the jointed operation possible by laparoscopy and thoracoscopy. The concept of enhanced recovery after surgery could further promote minimally invasive surgery in AEG. Meanwhile, with the continuous innovation of neoadjuvant chemotherapy, popularization of neoadjuvant radiotherapy and bold attempt of targeted therapy and immunotherapy, the resection rate, pathologic release rate and long-term survival of AEG have already achieved inspiring effects.
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Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.
Subject(s)
Humans , Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/administration & dosage , Chemoradiotherapy, Adjuvant , Esophagogastric Junction/surgery , Gastrectomy , Lymph Node Excision , Neoadjuvant Therapy , Neoplasm Staging , Oxaliplatin/administration & dosage , Prognosis , Prospective Studies , Retrospective Studies , Stomach Neoplasms/therapyABSTRACT
The prognosis of gastroesophageal junction cancer is relatively poor given its special location and biological behavior. Surgery is the main treatment for adenocarcinoma of esophagogastric junction (AEG), but there is no consensus on the surgical method in different Siewert types. Based on the NCCN guideline and large-scale study results, this review believes that thoracogastroesophageal gastrectomy may benefit patients with Siewert type. In contrast, for patients with Siewert III, partial or total gastrectomy is recommended. However, for Siewert Ⅱ patients, for surgical method we should consider tumor stage, tumor size, distance from the distal end to the junction of the stomach and esophagus, and other factors. No matter which surgical method is selected, R0 resection and thorough lymph node dissection are the most important factors affecting the prognosis. In addition, perioperative chemoradiotherapy or chemotherapy following surgery and adjuvant chemotherapy can benefit some patients at local regional advanced stage. For patients at advanced stage, targeted therapy and immunotherapy are an option of treatment.
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@#Objective To compare and analyze the short-term efficacy of different surgical methods for Siewert type Ⅰ and type Ⅱ esophagogastric junction carcinoma. Methods We selected 82 patients who accepted radical resection of esophagogastric junction carcinoma from March 2015 to March 2018 in our department, including 53 males and 29 females, aged 48-72 (61±6) years. The patients were divided into four groups according to the surgical method: a left thoracotomy group (n=14), a laparoscopic left small thoracotomy group (n=33), a thoracoscopic Ivor-Lewis group (n=17), and a thoracoscopic McKeown group (n=18). Their clinical characteristics, operative situations, postoperative complications and survival rate were analyzed. Results Among the four groups, the left thoracotomy group cost the shortest operation time, followed by laparoscopic left small thoracotomy group, thoracoscopic McKeown group and thoracoscopic Ivor-Lewis group. The thoracoscopic McKeown group/laparoscopic left small thoracotomy group had the least bleeding. The fewest lymph nodes were dissected in the left thoracotomy group and the most in the thoracoscopic McKeown group. The laparoscopic left small thoracotomy group had the lowest total complication rate and the incidence of pneumonia and arrhythmia among the four groups (P<0.05). There was no significant difference in survival rate among the four groups (P>0.05). Conclusion For Siewert type Ⅰ and type Ⅱ esophagogastric junction carcinoma, thoracoscopy combined with laparoscopic radical resection is safe and reliable. Laparoscopic left small thoracotomy has the advantages of minimal invasiveness and complete lymph node dissection, especially for the patients with poor cardiopulmonary function, which will significantly shorten operation time and reduce postoperative complications, so it is worth to be popularized.
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Adenocarcinoma of esophagogastric junction (AEG) has a special anatomical position. In clinical practice, there are many overplays among thoracic surgeons, gastrointestinal surgeons, gastroenterologists and oncologists. In recent years, AEG has attracted more and more clinical attention with its increasing incidence. It has a tendency to be gradually separated from esophageal cancer and gastric cancer and be defined as a new special type of tumor. At present, there are still many controversies in the definition, classification, TNM staging, surgical approach, extent of resection, lymph node dissection, digestive tract reconstruction and neoadjuvant therapy of AEG. Meanwhile many problems still need to be solved, which is in a stage of gradual improvement and standardization. This article mainly reviews the important research progress in the field of AEG in 2019, summarizes the current clinical hotspots of AEG, especially the surgical treatment hotspots and the current application status of related new technologies, and aims the future development. We suggest that communication and cooperation among multiple disciplines should be strengthened. Through more clinical researches, basic experimental researches, and innovation and application of new technologies, personalized and accurate diagnosis and treatment will be carried out for patients with different conditions to ultimately achieve the common goal of maximizing the benefits of patients.
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The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing worldwide, which attracts great attention among medical professionals because of its anatomical location and unique biological behavior. Although some consensus has been reached regarding the pathogenesis and classification of AEG, there remain debates about its surgical treatment, including the surgical route, scope of gastrectomy, range of lymph node dissection, and digestive tract reconstruction. These debates limit the exploration and development of AEG treatment and make it difficult to standardize the diagnosis and treatment of AEG. This study reviews the relevant literature on AEG in recent years and comprehensively discusses the current consensus and controversy regarding the treatment of AEG with the aim to provide a more reasonable and effective method for its clinical diagnosis and treatment.
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The incidence of adenocarcinoma of esophagogastric junction (AEG) is increasing,but its treatment strategy is still controversial.Surgery is the main strategy of multidisciplinary treatment.Siewert classification and TNM staging play a decisive role in the choice of operative approach,clinical decision and prognosis.Perioperative chemoradiotherapy plays an important role in the multidisciplinary treatment of AEG,and more researches support neoadjuvant therapy in patients with AEG.What's more,targeted therapy has become an integral part of multidisciplinary treatment of AEG with the constantly emergence of targeted drugs.In addition,the particularity of AEG determines that its treatment requires multidisciplinary cooperation,and the multidisciplinary team is expected to improve the prognosis of AEG patients.
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Objective To explore the application value of carbon nanoparticle labeled lymph node staining in radical resection of adenocarcinoma of esophagogastric junction with preoperative chemoradiotherapy.Methods The retrospective cohort study was conducted.The clinicopathological data of 56 patients with adenocarcinoma of esophagogastric junction who underwent preoperative chemoradiotherapy in the Peking University Cancer Hospital from January 2014 to November 2017 were collected.There were 52 males and 4 females,aged from 22 to 76 years,with an average age of 62 years.Among 56 patients undergoing total gastrectomy and D2 lymphadenectomy,17 using carbon nanoparticle lymph node staining and 39 using traditional lymph node sorting were respectively allocated into observation group and control group.Observation indicators:(1) treatment situations;(2) detection of lymph nodes;(3) perioperative complications;(4) follow-up.Followup using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis up to May 2019.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was evaluated by the independent sample t test.Measurement data with skewed distribution were represented as M (range),and comparison between groups was evaluated by the Mann-Whitney U test.Count data were described as absolute numbers,and comparison between groups was analyzed using the chi-square test or Fisher exact propability.Comparison of ordinal data was analyzed using the nonparametric rank sum test.Results (1) Treatment situations:patients in both groups were successfully treated with concurrent chemoradiotherapy based on intensity modulated radiotherapy before operation.Radical gastrectomy with D2 lymphadenectomy was successfully performed after chemoradiotherapy,and Roux-en-Y esophagojejunostomy was used to reconstruct the digestive tract during operation.The operation time and volume of intraoperative blood loss were respectively (217± 58)minutes and (112±60)mL in the observation group,and (235±65) minutes and (119±77)mL in the control group,with no statistically significant difference between the two groups (t =1.017,0.341,P＞0.05).(2) Detection of lymph nodes:the average number of harvested lymph nodes,average number of radiation target lymph nodes,and average number of peritarget lymph nodes were respectively 32± 10,21±8,and 7±4 in the observation group,and 22±7,16±5,5±3 in the control group,with statistically significant differences between the two groups (t=4.138,2.881,2.401,P＜0.05).The median number of positive lymph nodes harvested,median number of positive radiation target lymph nodes,and median number of positive peritarget lymph nodes were respectively 0 (range,0-2),0 (range,0-2),and 0 (range,0-0) in the observation group,and 0 (range,0-7),0 (range,0-3),and 0 (range,0-1) in the control group,showing no statistically significant difference between the two groups (Z=1.305,1.101,0.660,P ＞ 0.05).(3) Perioperative complications:6 and 18 patients in the observation group and the control group had complications,respectively,with no statistically significant difference between the two groups (x2=0.570,P＞0.05).Patients with complications were improved after drug treatment and local treatment without second operation.No local or systemic adverse reactions caused by carbon nanoparticles was observed during and after operation in the observation group.(4) Follow-up:56 patients were followed up for 5-65 months,with a median follow-up time of 32 months.There were 14 and 6 patients in the observation group and the control group with tumor recurrence or metastasis,respectively,showing no significant difference between the two groups (x2 =0.002,P＞0.05).Conclusion Carbon nanoparticle labeled lymph node staining in radical resection of adenocarcinoma of esophagogastric junction with preoperative chemoradiotherapy can increase the number of harvested lymph nodes.
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Objective To investigate the safety and feasibility of totally laparoscopic transabdominalhiatal approach in the treatment of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 11 patients with Siewert type Ⅱ AEG who were admitted to Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine from May 2017 to July 2018 were collected.There were 8 males and 3 females,aged 56-72 years,with an average age of 63 years.Patients underwent radical resection of AEG by totally laparoscopic transabdominalhiatal approach.Observation indicators:(1) surgical situations and postoperative recovery;(2) postoperative pathological examination;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative adjuvant chemotherapy,complications,food intake,anastomosis patency,tumor recurrence and metastasis,and survival up to December 2018.Measurement data with normal distribution were presented as Mean±SD,measurement data with skewed distribution were presented as M (range),and count data were represented as absolute number or percentage.Results (1) Surgical situations and postoperative recovery:all the patients underwent totally laparoscopic radical resection of Siewert type Ⅱ AEG by transabdominal-hiatal approach,without conversion to open surgery or perioperative death.Of the 11 patients,8 underwent total gastrectony including 3 combined with splenic hilar lymph node dissection and 3 underwent proximal gastrectomy with double-tract reconstruction.Operation time,time of superior overlap esophagojejunostomy,volume of intraoperative blood loss,time for initial out-of-bed activities,time to first flatus,time to initial liquid diet intake,time of drainage tube removal were respectively (245± 39)minutes,(60± 12) minutes,(75±23) mL,(24± 8) hours,(2.4± 0.5) days,(3.5 ± 0.8) days,(8.2 ± 1.3) days respectively.There was no serious complication including postoperative hemorrhage,anatomotic fistula or death.Three patients had left pleural effusion,and were cured after thoracic drainage.The duration of postoperative hospital stay was (11.0±3.0) days.(2) Postoperative pathological examination:all the 11 patients had negative upper surgical margin.The length of proximal margin,tumor diameter,total number of lymph lodes harvested,and number of lower mediastinal lymph lodes harvested were (2.1 ±0.2) cm,(2.6±0.9) cm,(36.0±4.0)/case and (2.3± 0.8)/case.Pathological examination showed adenocarcinoma in all the 11 patients.pTNM staging:2 cases were in stage Ⅰ B,4 cases in stage Ⅱ A,3 cases in stage Ⅱ B and 2 cases in stage Ⅲ A.(3) Follow-up and survival situations:11 patients were follow-up for 6-19 months,with a median time of 9 months.Chemotherapy regimeus were formulated according to the pathological examination.Nine patients received postoperative adjuvant chemotherapy,and 2 in stage Ⅱ B received no postoperative adjuvant chemotherapy.During the follow-up,11 patients had no obvious reflux symptom or choking feeling,and the anastomosis was patent as evaluated by oral contrast agent and gastroscopy.There was no tumor recurrence and metastasis or death in the 11 patients.Conclusion Totally laparoscopic transabdominal-hiatal approach applied in the radical resection is safe and feasible for the treatment of Siewert type Ⅱ AEG,with good short-term outcomes.
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Objective To investigate the pattern of lymph node metastasis and analyze prognostic factors of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods The retrospective case-control study was conducted.The clinicopathological data of 368 patients with Siewert type Ⅱ AEG who were admitted to Tianjin Medical University Cancer Institute and Hospital from June 2010 and November 2015 were collected.There were 323 males and 45 females,aged from 35 to 80 years,with an average age of 64 years.Of 368 patients,209 underwent left transthoracic surgery,1 12 underwent thoracoabdominal surgery,and 47 underwent Ivor-Lewis surgery.Observation indicators:(1) total lymph node metastasis and metastasis of various lymph node stations;(2) follow-up and survival;(3) prognostic factors analysis;(4) influencing factors affecting thoracic lymph node metastasis.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients up to November 2018.Measurement data with skewed distribution were represented as M (range).Count data were represented as absolute number or percentage.The survival time and rate were calculated using the Kaplan-Meier method.The univariate and multivariate analyses were done by the COX proportional hazard model.Results (1) Total lymph node metastasis and metastasis of various lymph node stations:the total lymph node metastasis rate was 66.58％ (245/368) in 368 patients.The metastasis rates of abdominal lymph nodes,thoracic lymph nodes,lower mediastinal lymph nodes,and upper mediastinal lymph nodes were 65.49％ (241/368),12.77％ (47/368),12.23％ (45/368),and 1.09％ (4/368),respectively.The order of metastasis rate of various lymph node stations from high to low was 51.99％(170/237) of No.7 left gastric artery,34.23％(89/260) of No.1 right paracardial region,33.88％ (83/245) of No.2 left paracardial region,28.91％ (85/294) of No.3 lesser curvature,27.10％(29/107) of No.1 1 splenic artery,19.75％(16/81) of No.9 celiac trunk,15.25％(36/236) of No.E8Lo lower paraesophageal region,11.94％ (16/134) of No.4 greater curvature,11.76％ (6/51) of No.E8M middle paraesophageal region,11.1 1％(10/90) of No.8 common hepatic artery,4.65％(4/86) of No.E9L left inferior pulmonary ligament and 3.39％ (2/59) of No.E7 subcarinal region.(2) Follow-up and survival:of the 368 patients,309 were followed up for 1-103 months,with a median follow-up time of 38 months.The survival time of 309 patients was 0.7-101.9 months,and the median survival time was 35.9 months.During the followup,the postoperative l-,2-,3-year overall survival rates were 85.9％,68.6％,and 58.7％,respectively.(3) Prognostic factors analysis.Results of univariate analysis showed that tumor differentiation degree,presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,tumor diameter,and length of esophageal invasion were associated factors affecting prognosis of patients (x2 =8.776,26.582,46.057,18.679,22.460,9.158,P＜0.05).Results of multivariate analysis showed that presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter were independent influencing factors for prognosis of patients [odds ratio (OR) =1.699,1.271,1.422,1.238,95％ confidence interval:1.102-2.621,1.019-1.481,1.090-1.856,0.971-1.481,P＜0.05].(4) Influencing factors affecting thoracic lymph node metastasis:results of univariate analysis showed that tumor diameter,length of esophageal invasion,number of lymph lodes harvested in thorax were related factors for thoracic lymph node metastasis (x2 =5.129,43.140,10.605,P＜0.05).Results of multivariate analysis showed that length of esophageal invasion ≥2 cm,number of lymph lodes harvested in thorax ≥ 4 were independent risk factors for thoracic lymph node metastasis (OR =6.321,1.097,95％ confidence interval:2.982-13.398,1.026-1.173,P＜0.05).Conclusion Lymph node metastasis of Siewert type Ⅱ AEG spreads two regions,mainly at abdominal lymph nodes,followed by the thoracic lymph nodes.Presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter are independent influencing factors for prognosis of patients.Presence of thoracic lymph node metastasis indicates poor prognosis of patients.Length of esophageal invasion ≥ 2 cm and number of lymph lodes harvested in thorax ≥4 are independent risk factors for thoracic lymph node metastasis.
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In recent years,the incidence of gastric cancer has been decreasing year by year in the world,but the incidence of adenocarcinoma of esophagogastric junction (AEG) has shown a significant upward trend,especially in western countries such as Europe and America.The prognosis of AEG is poor,therefore,it is extremely necessary to establish AEG's best diagnosis and treatment strategies to improve the long-term outcome of AEG.Nowadays,the most commonly used AEG classification is the Siewert classification proposed by German scholars in 1987,which is based on the anatomical features of the esophagogastric junction.It provides guidance for the choice of surgical methods.Compared with European and American countries,Siewert type Ⅱ or type Ⅲ are more common in Asian countries,and are mainly treated as the proximal gastric cancer.Compared with gastric tumors in other areas,AEG has obvious differences and specialities in anatomy,physiology and pathology,and there is still much controversy in the field of surgical and comprehensive treatment.
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Surgical approaches for adenocarcinoma of esophagogastric junction have become controversial issues in recent years,including complete resection of tumors,negative proximal margin,complete lymph node dissection,safety of digestive tract reconstruction and reduction of perioperative complications.JCOG9502 trial in Japan is a well-known clinical trial on the surgical approach for adenocarcinoma of esophagogastric junction,which provides evidence-based medicine results for the transabdominal or transthoracic approach.However,due to the differences between the left and right thoracic approaches,the choice of a reasonable surgical approach has also become the focus of discussion between eastern and western scholars.With the development of minimally invasive surgery,it is possible to perform the operations combining laparoscopy and thoracoscopy in the future.
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Adenocarcinoma of esophagogastric junction (AEG) refers to the tumor invading the esophagogastric junction and Siewert type is the most practical classification at present.There are many surgical controversies about AEG,mainly focusing on Siewert Ⅱ type.In this paper,definition and classification of AEG,epidemiological characteristics,pathological TNM staging,rules of lymph node metastasis and dissection,esophageal resection margin,gastric resection scope,surgical approach and other issues are investigated combined with recent highquality evidence.