Current and Proposed Treatment Strategies for Siewert Type II Adenocarcinoma of the Esophagogastric Junction

BackgroundIncidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing in Japan as well as Western Country. However, there is no consensus on treatment strategy. The purpose of this study was to determine the optimal range of resection and lymph node dissection for Siewert type II AEG and to develop a strategy for treatment that includes adjuvant therapy to improve the survival rate. MethodsWe retrospectively investigate 88 cases of advanced AEG in patients who underwent surgery with lymph node dissection with 52 cases of superficial AEG, 23 of whom underwent endoscopic treatment (endoscopic mucosal resection [EMR] or endoscopic submucosal dissection [ESD]), and 29 of whom underwent surgery with lymph node dissection. Results The optimal lymph nodes to resect for advanced AEG were in the inferior mediastinum (No. 110), in the lesser curvature (Nos. 1, 3, 7), No. 2, and No 11. According to area of actual lymph node metastasis, lymphadenectomy of lymph nodes 1, 2, 3, 7, and 11 was sufficient to improve survival of patients with superficial AEG. If esophageal involvement was >40 mm, we performed esophagectomy through right thoracotomy. The 5-year overall survival rates were 88% for patients treated with ESD, 78% for those with superficial AEG who under-went surgery, and 24% for those with advanced AEG (p = 0.011). Despite of lymph node dissection, twenty-five patients experienced lymph node metastasis after operation in advanced AEG and there were many disseminations in advanced AEG. There were no differences in survival between patients who received postoperative adjuvant therapy with S-1 for advanced AEG and those who received surgery alone (p = 0.5192).ConclusionAlthough surgical procedures of superficial and locally advanced AEG are standardized, the role of adjuvant therapy for AEG is still controversial. We recommend nab-paclitaxel plus radiotherapy for advanced AEG as neoadjuvant therapy.

Transthoracic esophagectomy compared to transhiatal extended gastrectomy for adenocarcinoma of the esophagogastric junction: a multicenter retrospective cohort study

Optimal surgical treatment for Siewert type II esophagogastric junction adenocarcinoma is debated. The aim of this study was to compare transhiatal extended gastrectomy (TEG) and transthoracic esophagectomy (TTE). Patients with Siewert type II tumors who underwent a resection by TEG or TTE in two centers (Erasmus University Medical Center, Rotterdam, and University of Verona) between 2014 and 2019 were identified. To limit selection bias, patients were matched for baseline characteristics and compared with a multivariable logistic regression model. Some 159 patients treated by TEG (60 patients, 37.7%) or TTE (99 patients, 62.3%) were included. Patients in the TEG group were older, had less tumor invasion of the esophagus, and were more often excluded from neoadjuvant therapy. Post-operative morbidity was comparable (P = 0.88), while 90-day mortality was higher after TEG (90-day mortality 10.0% in TEG group vs. 2.0% in TTE group P = 0.01). R0 resection was achieved in 83.3% of patients after TEG and in 97.9% after TTE (P < 0.01), with the proximal resection margin involved in 16.6% of patients after TEG versus 0 in TTE group (P < 0.01). The 3-year overall survival was comparable (TEG: 36.5%, TTE: 48.4%, P = 0.12). At multivariable analysis, (y)pT category was an independent risk factor for 3-year recurrence. After matching, TEG was still associated with an increased risk of incomplete tumor resection (P = 0.03) and proximal margin involvement (P < 0.01), while there were no differences in post-operative morbidity (P = 0.56) and mortality (P = 0.31). Our data suggest that patients with Siewert type II tumors treated by TEG are exposed to a higher risk of positive proximal resection margin compared to TTE.

Surgical and oncological outcome after extended lymph node dissection for carcinoma of the stomach and the esophagogastric junction; a retrospective analysis from experienced single center.

IntroductionGastric cancer remains the fourth leading cause of cancer-related death in Europe, while the proportion of the adenocarcinomas of the esophagogastric junction has risen by more than one third over recent years. In 2018, 14,700 new cases of gastric cancer were estimated in Germany, while the 5-year relative survival rate is reported to be 33% for women and 30% for men; in the U.S.A. was reported almost the same rate with 31% 5-year survival.Material and methodsBetween 2001 and 2014, 590 patients with a diagnosis of gastric cancer underwent surgery in our institution, including 120 Siewert type II/III carcinomas of the esophagogastric junction. All patients underwent distal resection of the stomach, gastrectomy or total gastrectomy combined with transhiatal distal esophageal resection. All operations included D2-D3 lymph node dissection. Data was recorded by the cancer registry of the department of surgery and analyzed retrospectively.ResultsThe patients were classified according to the TNM (UICC 2010) and Lauren classification. 29% of the patients underwent primary surgery and 31% received neo-adjuvant therapy. The median number of harvested lymph nodes was 33 for patients diagnosed with gastric cancer, and 29 for esophagogastric adenocarcinomas, respectively. The anastomotic leak rate was 3%. In this study, the 5-year overall survival rate was 51% concerning gastric carcinomas, 44% for Siewert type II and 47% for Siewert III cancers carcinomas of the esophagogastric junction.ConclusionsIncreased survival with low complication rates were achieved after individualized and multimodal treatment concepts combined with consistently applied extended lymphadenectomy.

Survival Benefit of Pyloric Lymph Node Dissection for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction Based on Tumor Diameter: A Large Cohort Study

BackgroundIt is unclear whether the dissection of pyloric lymph nodes (PLNs, No. 5 and No. 6 lymph nodes) is necessary for adenocarcinoma of the esophagogastric junction (AEG) with a tumor diameter >4 cm based on current guidelines. This study aimed at evaluating whether pyloric node lymphadenectomy is essential for patients with Siewert type II/III AEG according to different tumor diameters.MethodsThis study included 300 patients on whom transabdominal total gastrectomy was performed for Siewert type II/III AEG at a high-volume center in China from January 2006 to December 2015. The index of estimated benefit from lymph node dissection (IEBLD) was used to analyze the priority of pyloric lymphadenectomy.ResultsIn Siewert type II AEG, the 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were similar between patients with PLN-positive cancer and patients of stage III AEG without PLN metastasis (23.1% vs. 30.6%, p = 0.505; 23.1% vs. 27.1%, p = 0.678). However, in Siewert type III AEG, the OS and the DFS of patients with PLN-positive cancer were significantly lower than that of patients with stage III without PLN metastasis (7.9% vs. 27.8%, p = 0.021; 0 vs. 26.8%, p = 0.005). According to the IEBLD, the dissection of PLNs did not appear to be beneficial in either Siewert type II AEG or type III AEG, whereas a stratified analysis revealed that PLN dissection yielded a high therapeutic benefit for Siewert type II AEG with tumor diameters >4 cm.ConclusionWe recommended that the PLNs be dissected in Siewert type II AEG when a tumor diameter is >4 cm. Total gastrectomy should be optional for Siewert type II AEG with a tumor diameter >4 cm and Siewert type III AEG.

Current and Proposed Treatment Strategies for Siewert Type II Adenocarcinoma of the Esophagogastric Junction

BackgroundIncidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing in Japan as well as Western Country. However, there is no consensus on treatment strategy. The purpose of this study was to determine the optimal range of resection and lymph node dissection for Siewert type II AEG and to develop a strategy for treatment that includes adjuvant therapy to improve the survival rate. MethodsWe retrospectively investigate 88 cases of advanced AEG in patients who underwent surgery with lymph node dissection with 52 cases of superficial AEG, 23 of whom underwent endoscopic treatment (endoscopic mucosal resection [EMR] or endoscopic submucosal dissection [ESD]), and 29 of whom underwent surgery with lymph node dissection. ResultsThe optimal lymph nodes to resect for advanced AEG were in the inferior mediastinum (No. 110), in the lesser curvature (Nos. 1, 3, 7), No. 2, and No 11. According to area of actual lymph node metastasis, lymphadenectomy of lymph nodes 1, 2, 3, 7, and 11 was sufficient to improve survival of patients with superficial AEG. If esophageal involvement was >40 mm, we performed esophagectomy through right thoracotomy. The 5-year overall survival rates were 88% for patients treated with ESD, 78% for those with superficial AEG who under-went surgery, and 24% for those with advanced AEG (p = 0.011). Despite of lymph node dissection, twenty-five patients experienced lymph node metastasis after operation in advanced AEG and there were many disseminations in advanced AEG. There were no differences in survival between patients who received postoperative adjuvant therapy with S-1 for advanced AEG and those who received surgery alone (p = 0.5192).Conclusion Although surgical procedures of superficial and locally advanced AEG are standardized, the role of adjuvant therapy for AEG is still controversial. We recommend nab-paclitaxel plus radiotherapy for advanced AEG as neoadjuvant therapy.

Long-Term Efficacy of Neoadjuvant Concurrent Chemoradiotherapy for Potentially Resectable Advanced Siewert Type II and III Adenocarcinomas of the Esophagogastric Junction

BackgroundReports have shown that neoadjuvant concurrent chemoradiotherapy (nCRT) increases the R0 resection rate for patients with Siewert type II or III adenocarcinoma of the gastroesophageal junction (AEG). However, the long-term efficacy of nCRT for AEG patients remains unclear. In this multicenter study, we investigated the long-term results of AEG patients treated with nCRT.MethodsA total of 149 patients with potentially resectable advanced AEG (T3/4, Nany, M0) were randomly divided into two groups: the nCRT-treated group (treated group) (n = 76) and the surgery group (control group) (n = 73). The primary endpoint was disease-free survival (DFS), and the secondary outcome indexes included the R0 resection rate, HER-2 expression, tumor regression grade (TRG), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events.ResultsIn the treated group, the overall therapeutic efficacy rate was 40.8%, and the pathological complete response (pCR) rate was 16.9%. The rates of patients who underwent R0 resection in the treated and control groups were 97.0% and 87.7%, respectively (p < 0.05). The toxic effects were mainly graded 1–2 in the treated group. The median DFS times in the treated and control groups were 33 and 27 months, respectively (p = 0.08), whereas the median OS times were 39 and 30 months, respectively (p = 0.01). The median DFS times of patients with positive and negative HER-2 expression in the treated group were 13 and 43 months, respectively (p = 0.01), and the median OS times were 27 and 41 months, respectively (p = 0.01).ConclusionSurgery after nCRT improved the efficacy of treatment for AEG patients and thus provided a better prognosis.Clinical Trial RegistrationThe trial is registered with ClinicalTrials.gov (number NCT01962246).

Short-Term Clinical Efficacy of Neoadjuvant Chemotherapy Combined With Laparoscopic Gastrectomy for Locally Advanced Siewert Type II and III Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Propensity Score-Matched Study

BackgroundLaparoscopic gastrectomy (LG) has been increasingly used for the treatment of locally advanced Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). However, whether LG can achieve the same short-term efficacy in the treatment of patients who receive neoadjuvant chemotherapy (NACT) remains controversial. Thus, the aim of this study was to investigate the clinical outcomes of NACT combined with LG for Siewert type II and III AEG.MethodsThis retrospective study identified patients with locally advanced Siewert type II and III AEG diagnosed between May 2011 and October 2020 using the clinical tumor-node-metastasis (cTNM) staging system. The short-term outcomes were compared between the matched groups using a 1:3 propensity score matching (PSM) method, which was performed to reduce bias in patient selection.ResultsAfter PSM, 164 patients were selected, including 41 in the NACT group and 123 in the LG group. The baseline characteristics were similar between the two groups. Compared with the LG group, the NACT group exhibit a smaller tumor size and significantly less advanced pathological tumor classification and nodal classification stages. The time to first flatus of the NACT group was significantly shorter, but the hospital stay was significantly longer than that of the LG group. The NACT group showed similar overall (29.3% vs 25.2%, P=0.683), systemic (24.4% vs 21.1%, P=0.663), local (12.2% vs 9.8%, P=0.767), minor (19.5% vs 19.5%, P=1.000) and major (9.8% vs 5.7%, P=0.470) complications as the LG group. Subgroup analyses showed no significant differences in most stratified parameters. Operation time≥ 300 minutes was identified as an independent risk factor for overall complications. Age≥ 60 years was identified as an independent risk factor for major complications.ConclusionNACT combined with LG for AEG does not increase the risk of postoperative morbidity and mortality compared with LG.