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.

Pembrolizumab (Keytruda)

CADTH recommends that Keytruda should be reimbursed by public drug plans for the treatment of esophageal or human epidermal growth factor receptor 2 (HER2)-negative esophagogastric junction (EGJ) cancer that cannot be removed by surgery or is metastatic, if certain conditions are met. Keytruda should only be covered to treat adult patients who have not received previous treatment for advanced or metastatic esophageal or EGJ cancer and who have good performance status. Keytruda should only be reimbursed if prescribed in combination with platinum and fluoropyrimidine–based chemotherapy and given by a clinician who is experienced in treating cancer. The price of Keytruda must be lowered to be cost-effective and affordable.

Endoscopic Versus Surgical Therapy for Early Esophagogastric Junction Adenocarcinoma Based on Lymph Node Metastasis Risk: A Population-Based Analysis

BackgroundIn this study, we aimed to compare the prognosis and lymph node metastasis (LNM) risk in patients with early-stage esophagogastric junction (EGJ) adenocarcinoma after endoscopic treatment (ET) or radical surgery.MethodsWe collected data from eligible patients based on the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Logistic regression analysis was used to determine independent predictors of LNM (examination of at least 16 lymph nodes). Cox regression analysis and propensity score-matched (PSM) analysis were subsequently utilized to compare the overall survival (OS) and cancer-specific survival (CSS) of patients treated with ET or radical surgery.ResultsIn total, 3708 patients were identified. Among them, 856 patients had greater than or equal to 16 examined lymph nodes (LNs) (LNE≥16). The LNM rates were 18.8% in all patients 8.3% in T1a patients and 24.6% in T1b patients. Independent predictors of LNM were submucosal invasion, tumor size ≥3cm and decreasing differentiation (P<0.05). The LNM rate decreased to approximately 5.3% in T1b tumors with well differentiation and tumor size <3cm. However, the LNM incidence increased to 17.9% or 33.3% in T1a tumors with poor differentiation or with both tumor size≥3cm and poor differentiation. Cox regression analysis demonstrated CSS was not significantly different in early-stage EGJ adenocarcinoma patients undergoing ET and those treated with radical surgery (HR= 1.004, P=0.974), which were robustly validated after PSM analysis. Moreover, subgroup analysis stratified by T1a and T1b showed similar results.ConclusionsThe findings of this study indicated ET as an alternative to radical surgery in early EGJ adenocarcinoma.

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.

Assessment of esophagogastric junction morphology by dynamic real-time MRI: comparison of imaging features to high-resolution manometry

Purpose To assess the esophagogastric junction (EGJ) on real-time MRI and compare imaging parameters to EGJ morphology on high-resolution manometry (HRM). Methods A total of 105 of 117 eligible patients who underwent real-time MRI and high-resolution manometry for GERD-like symptoms between 2015 and 2018 at a single center were retrospectively evaluated (male n = 57; female n = 48; mean age 52.5 ± 15.4 years). Real-time MRI was performed at a median investigation time of 15 min (1 frame/40 ms). On HRM, EGJ morphology was assessed according to the Chicago classification of esophageal motility disorders. Real-time MRI was performed at 3 T using highly undersampled radial fast low-angle shot acquisitions with NLINV image reconstruction. A 10 mL pineapple juice bolus served as oral contrast agent at supine position. Real-time MRI films of the EGJ were acquired during swallowing events and during Valsalva maneuver. Anatomic and functional MRI parameters were compared to EGJ morphology on HRM. Results On HRM, n = 42 patients presented with EGJ type I (40.0%), n = 33 with EGJ type II (31.4%), and n = 30 with EGJ type III (28.6%). On real-time MRI, hiatal hernia was more common in patients with EGJ type III (66.7%) than in patients with EGJ type I (26.2%) and EGJ type II (30.3%; p < 0.001). Sliding hiatal hernia was more frequent in patients with EGJ type II (33.3%) than in patients with EGJ type III (16.7%) and EGJ type I (7.1%; p = 0.017). The mean esophagus–fundus angle of patients was 85 ± 31° at rest and increased to 101 ± 36° during Valsalva maneuver. Conclusion Real-time MRI is a non-invasive imaging method for assessment of the esophagogastric junction. Real-time MRI can visualize dynamic changes of the EGJ during swallowing events.