Advanced Esophagogastric Junction Adenocarcinoma Research Articles

Combination of immune checkpoint inhibitors and radiotherapy in locally advanced esophagogastric junction adenocarcinoma: A review

AbstractEsophagogastric adenocarcinoma (EGJ‐AC) poses a significant global health burden, characterized by high incidence rates and poor prognosis. Despite advancements in treatment modalities, including surgery, chemotherapy, and radiation therapy (RT), locally advanced EGJ‐AC management remains challenging. Various preclinical and clinical studies have provided insights into the synergistic effects of combining immune checkpoint inhibitors (ICIs) with RT, further supporting the combination therapy in EGJ‐AC. Immunotherapy, particularly ICIs, has emerged as a promising therapeutic approach in various malignancies, including EGJ‐AC. This narrative review aims to critically examine the rationale behind combining ICIs with standard treatment modalities, including RT or chemoradiotherapy, in the preoperative setting for locally advanced EGJ‐AC. A comprehensive literature search identified eight phase 2 randomized clinical trials evaluating the safety profile and oncologic outcomes of adding ICI agents to neoadjuvant chemoradiotherapy in this population. The results of enrolled trials show that the combination of ICIs with standard treatment modalities is a promising approach for improving survival and pathological response in patients with locally advanced EGJ‐AC. This combination treatment was associated with mostly grade 1–2 immune‐related toxicities, indicating its safety and tolerability. There were higher rates of complete or major pathologic responses compared to historical controls. Further studies, including large‐scale randomized controlled trials, are needed to address remaining questions regarding the efficacy, safety, and long‐term outcomes of combination therapy in this population.

245. ESOPHAGECTOMY AFTER NEOADJUVANT CHEMOTHERAPY WITH AN INDICATION FOR CONVERSION SURGERY FOR HIGHLY ADVANCED ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA

Abstract Background There is currently no strong evidence for preoperative chemotherapy for advanced esophagogastric junction adenocarcinoma. Furthermore, no curative treatment strategy has been established for advanced junction adenocarcinoma, including Stage IV disease, with no indication for conversion surgery. Subjects and Methods In this study, we retrospectively reviewed nine patients with highly advanced esophagogastric junctional adenocarcinoma, including Stage IV adenocarcinoma, who underwent systemic chemotherapy followed by planned resection at our hospital. Results The participants included 6 males and 3 females, with median age of 64 (range: 45–72) years. Pretreatment stages III, IVA, and IVB, categorized based on UICC TNM classification (esophageal adenocarcinoma), were observed in 1, 4, and 4 cases, respectively, with 1 case of (#104) subclavian lymph node metastases, 1 case of (#16) abdominal para-aortic lymph node metastases, and 2 cases of liver metastases, including multiple lesions. All patients received S-1 plus oxaliplatin (SOX) therapy as preoperative chemotherapy (2–40 courses). Although we observed one patient with unresectable abdomen malingnancies, the others underwent R0 resection, six underwent esophagectomy (with three total gastrectomy and one liver resection), and two open (+ continuous right thoracotomy) lower esophagectomy + total gastrectomy. Pathological stages I, II, III, and IV were observed in two, one, four, and one patients, respectively. Postoperatively, stereotactic irradiation, chemotherapy, and immune checkpoint inhibitors were administered to the patients to treat recurrent brain and liver metastases, and the 1-year survival rate was found to be 71.4% with a median observation period of 17 (range: 0–61) months. Among them, downstage and pN0 cases were relatively promising. Conclusion Even in highly advanced cases, cases with promising prognoses with multidisciplinary treatment, including surgery, were observed. We hope that large-scale clinical trials, such as JCOG2203, will help clarifying the significance of this approach, and advancements in chemotherapy regimens are expected.

473P Perioperative safety and oncologic feasibility of proximal gastrectomy in Siewert II/III locally advanced adenocarcinoma of esophagogastric junction: An inverse propensity-weighted study

473P Perioperative safety and oncologic feasibility of proximal gastrectomy in Siewert II/III locally advanced adenocarcinoma of esophagogastric junction: An inverse propensity-weighted study

Computed tomography-based nomogram of Siewert type II/III adenocarcinoma of esophagogastric junction to predict response to docetaxel, oxaliplatin and S-1.

Neoadjuvant chemotherapy (NAC) has become the standard care for advanced adenocarcinoma of esophagogastric junction (AEG), although a part of the patients cannot benefit from NAC. There are no models based on baseline computed tomography (CT) to predict response of Siewert type II or III AEG to NAC with docetaxel, oxaliplatin and S-1 (DOS). To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS. One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS, and were randomly and consecutively assigned to the training cohort (TC) (n = 94) and the validation cohort (VC) (n = 34). Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors (version 1.1) criteria. Possible prognostic factors associated with responses after DOS treatment including Siewert classification, gross tumor volume (GTV), and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age. Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS. A nomogram was established based on independent factors to predict the response. The predictive performance of the nomogram was evaluated by Concordance index (C-index), calibration and receiver operating characteristics curve in the TC and VC. Univariate analysis showed that Siewert type (52/55 vs 29/39, P = 0.005), pretherapeutic cT stage (57/62 vs 24/32, P = 0.028), GTV (47.3 ± 27.4 vs 73.2 ± 54.3, P = 0.040) were significantly associated with response to DOS in the TC. Multivariate analysis of the TC also showed that the pretherapeutic cT stage, GTV and Siewert type were independent predictive factors related to response to DOS (odds ratio = 4.631, 1.027 and 7.639, respectively; all P < 0.05). The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC (C-index: 0.838 and 0.824), with area under the receiver operating characteristic curve of 0.838 and 0.824, respectively. The calibration curves showed that the practical and predicted response to DOS effectively coincided. A novel nomogram developed with pretherapeutic cT stage, GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.

Real-world comparison of treatment outcomes between advanced esophagogastric junction adenocarcinoma and gastric adenocarcinoma.

267 Background: The characteristics of esophagogastric junction adenocarcinoma (EGJA) differ from those of gastric adenocarcinoma (GA). Although chemotherapy for advanced GA has been adapted for advanced EGJA, its efficacy remains unknown. This study aims to elucidate the effectiveness of chemotherapy for advanced EGJA in real-world practice. Methods: This retrospective study compared treatment outcomes between advanced GA and EGJA in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy, including platinum agents, as first-line treatment at our hospital between 2010 and 2020. Patients with non-curative resection factors limited to positive peritoneal cytology, or those who relapsed during adjuvant chemotherapy or within 6 months after its completion, were excluded. Results: Out of the total 825 patients, 765 had GA and 60 had EGJA. The baseline characteristics of the GA and EGJA groups were as follows, respectively: median age 65.0 and 59.5 years (p = 0.02); PS 0, 35.9% and 33.3%; PS 1, 57.5% and 65.0%; PS 2, 6.5% and 1.7% (p = 0.28); HER2 positive, 16.1% and 26.7% (p = 0.06); diffuse histology, 52.7% and 26.7% (p &lt; 0.01); lymph node metastasis, 74.0% and 93.3% (p &lt; 0.01); peritoneal metastasis, 66.4% and 25.0% (p &lt; 0.01); liver metastasis, 26.4% and 40.0% (p = 0.03); lung metastasis, 6.5% and 16.7% (p &lt; 0.01). The proportions of fluoropyrimidine, taxanes, and irinotecan in all treatment lines did not differ between the two groups (fluoropyrimidine, 99.7% vs. 100%; taxanes, 70.1% vs. 73.3%; irinotecan, 23.0% vs. 23.3%). However, the EGJA group used ramucirumab, trastuzumab, and immune checkpoint inhibitors (ICIs) significantly more frequently than the GA group (ramucirumab, 27.8% vs. 43.3%, p = 0.02; trastuzumab, 15.4% vs. 26.7%, p = 0.03; ICIs, 21.0% vs. 41.7%, p &lt; 0.01). Overall survival did not differ between the two groups (median, 14.8 months vs. 18.5 months, HR 0.80; 95% CI, 0.59-1.10, p = 0.17). Moreover, multivariate analysis revealed that EGJA and GA had a comparable prognosis (HR 1.23; 95% CI, 0.87-1.72, p = 0.24). HER2 positivity was a favorable prognostic factor in multivariate analysis, whereas diffuse histology, poor PS, lymph node metastasis, liver metastasis, and the presence of peritoneal metastasis were poor prognostic factors. There was no difference in time-to-treatment failure between the two groups for first-line (median, 6.1 vs. 4.9 months, HR 0.96; 95% CI, 0.73-1.28, p = 0.80), second-line (median, 2.9 vs. 3.5 months, HR 0.99; 95% CI, 0.73-1.34, p = 0.93), and third-line treatment (median, 1.9 vs. 2.7 months, HR 0.78; 95% CI, 0.53-1.13, p = 0.62). Conclusions: In real-world practice, the efficacy of chemotherapy for advanced EGJA was comparable to that for advanced GA.

Proximal incisal edge length and recent clinical observation of Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma

Objective: To investigate the clinical effect of the radical resection with a proximal incisal edge length of 20-25 mm and 30-35 mm in Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma, to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm. Methods: A retrospective cohort study method was used. The clinical data of 166 patients with Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma who underwent total gastrectomy from January 2017 to August 2020 in the Department of Gastrointestinal Surgery, Heji Hospital Affiliated to Changzhi Medical College were retrospectively collected. According to the proximal incisal edge length, the patients were divided into two groups: the proximal incisal edge length of 20-25 mm group (69 cases) and 30-35 mm group (97 cases). The perioperative conditions and the 6-month follow-up after the operation were compared between the two groups. Results: There was no statistically significant difference in baseline information between the patients in the two groups (P>0.05). The operations of both groups were completed. The intraoperative operation time of the proximal incisal edge length of 20-25 mm group was shorter than that in the proximal incisal edge length of 30-35 mm group ((172±24)and(206±27)min, P<0.001). There were no significant differences in the amount of intraoperative blood loss, the treatment of the diaphragm during the operation and the positive rate of intraoperative freezing of the upper incisal edge between the patients in the two groups (all P>0.05). And there was no significant differences in the first exhaust time, gastric tube removal time, first feeding time and hospital stay after the operation of the two groups (all P>0.05). There was no significant differences in the incidence of anastomotic leakage, anastomotic stenosis, reflux esophagitis and intestinal obstruction after the operation between the patients in the two groups (all P>0.05). And there was no anastomotic leakage case among the 69 cases in the proximal incisal edge length of 20-25 mm group. Postoperative pathological treatment showed no significant differences in the vascular tumor thrombus and nerve infiltration between the two groups (both P>0.05). During the 6-month follow-up, there was no death or tumor recurrence in the two groups, and there was no significant difference in body weight loss at 6 months after the operation between the two groups (P=0.178). Conclusion: When radical resection of Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma is performed, it is feasible to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm under the premise of ensuring R0 resection. The operation time is shortened. Due to the shortening the incisal edge distance, the anastomotic tension is decreased, and the incidence of postoperative anastomotic leakage is also reduced.

Five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction

Objective: Surgical operation is the main treatment for advanced adenocarcinoma of esophagogastric junction (AEG). Due to its special anatomic location and unique lymph node reflux mode, the surgical treatment of Siewert II AEG is controversial. Lower mediastinal lymph node dissection is one of the most controversial points and a standard technique has not yet been established. This study is aim to explore the safety and feasibility of five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection for Siewert type II AEG. Methods: A descriptive case series study was conducted. The intraoperative and postoperative data of 25 patients with Siewert type II AEG who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection in Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2019 to April 2021 were retrospectively analyzed. Five-step maneuver was as follows: In the first step, the subcardiac sac was exposed; the right pulmonary ligament lymph nodes and the anterior thoracic paraaortic lymph nodes were dissected cranial to inferior pericardium, left to left edge of thoracic aorta. In the second step, the left diaphragm was opened, and a 12 mm trocar was placed through the 6-7 rib in the left anterior axillary line. The supra-diaphragmatic nodes were dissected through the thoracic operation hole. In the third step, the left inferior pulmonary ligament was severed. The anterior fascia of thoracic aorta was incised to join the anterior space of thoracic aorta formed in the first step and then the lymphatic tissue was dissected upward until the exposure of left inferior pulmonary vein. In the fourth step, the posterior pericardium was denuded retrogradely from ventral side to oral side to the level of left inferior pulmonary vein, right to right pleura, and then the right pulmonary ligament lymph nodes were completely removed. In the fifth step, the esophagus was denuded, and the esophagus was transected 5 cm above the tumor using a linear stapler to complete the dissection of lower thoracic paraesophageal lymph nodes. Results: Operations were successfully completed in 25 patients without conversion, intra-operative complication and perioperative death. Total gastrectomy was performed in 19 cases and proximal gastrectomy in 6 cases. The mean operative time was (268.7±85.6) minutes, the mean estimated blood loss was (90.4±44.2) ml, the mean time of lower mediastinal lymph node dissection was (38.6±10.3) minutes, and the mean harvested number of lower mediastinal lymph node was 5.9±2.9. The length of esophageal invasion was >2 cm in 7 cases and ≤ 2 cm in 18 cases. Eight patients (33.0%) had lower mediastinal lymph node metastasis, including 3 cases with esophageal invasion >2 cm and 5 cases with esophageal invasion ≤ 2 cm. The mean time to postoperative first flatus was (5.5±3.1) days. The average time of postoperative thoracic drainage was (5.9±2.9) days. The mean hospital stay was (9.7±3.1) days. Two patients (8.0%) developed postoperative grade IIIa complications according to the Clavien-Dindo classification, including 1 case of pancreatic fistula and 1 case of pleural effusion, both of whom were cured by puncture drainage. Conclusions: Five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph nodes dissection for Siewert type II AEG is safe and feasible. Which can ensure sufficient lower mediastinal lymph node dissection to the level of left inferior pulmonary vein.

Survival Benefit of Neoadjuvant Chemotherapy for Locally Advanced Adenocarcinoma of Esophagogastric Junction.

Adenocarcinoma of the esophagogastric junction (AEG) is refractory even when curative resection is followed by adjuvant chemotherapy. This study evaluated the efficacy of neoadjuvant chemotherapy (NAC) using an oral fluoropyrimidine-platinum regimen for AEG. Out of 35 patients with locally advanced AEG who underwent curative resection, 21 who underwent surgery first and 14 who received NAC were retrospectively compared in terms of survival. The NAC regimens comprised of S-1 or capecitabine plus oxaliplatin or cisplatin; trastuzumab was added to six borderline resectable cases. The downstaging rate was 50% and the pathological response rate including complete response (29%) was 50%. The three-year relapse-free survival in the NAC group was significantly superior than the surgery-first group (78% vs. 22%, p=0.011). The NAC group had a significantly longer median survival time than the surgery-first group (NR vs. 29 months, p=0.032). NAC using an oral fluoropyrimidine-platinum regimen may provide survival benefit in AEG.

Neoadjuvant chemoradiotherapy improves survival in locally advanced adenocarcinoma of esophagogastric junction compared with neoadjuvant chemotherapy: a propensity score matching analysis

BackgroundTo analyze whether neoadjuvant chemoradiotherapy (nCRT) could improve the survival for patients with adenocarcinoma of the esophagogastric junction compared with neoadjuvant chemotherapy (nCT). Both neoadjuvant chemotherapy alone and chemoradiotherapy before surgery have been shown to improve overall long-term survival for patients with adenocarcinoma in the esophagus or esophagogastric junction compared to surgery alone. It remains controversial whether nCRT is superior to nCT.Methods170 Patients with locally advanced (cT3-4NxM0) Siewert II and III adenocarcinoma of the esophagogastric junction (AEG) were treated with neoadjuvant chemotherapy consisting of capecitabine plus oxaliplatin with or without concurrent radiotherapy in the Fourth Hospital of Hebei Medical University. Intensity-modulated radiation therapy (IMRT) was used and delivered in 5 daily fractions of 1.8 Gy per week for 5 weeks (total dose of PTV: 45 Gy). 120 Patients were included in the propensity score matching (PSM) analysis to compare the effects of nCRT with nCT on survival.ResultsWith a median follow-up of 41.2 months for patients alive after propensity score matching analysis, the 1- and 3-year OS were 84.8%, 55.0% in nCRT group and 78.3%, 38.3% in nCT group (P = 0.040; HR = 1.65, 95% CI 1.02–2.69). The 1- and 3-year PFS were 84.9%, 49.2% in nCRT group and 68.3%, 29.0% in nCT group (P = 0.010; HR = 1.80, 95% CI 1.14–2.85). The pathological complete response (pCR) was 17.0% in nCRT group and 1.9% in nCT group (P = 0.030). No significant difference was observed in postoperative complications between the two groups.ConclusionThe nCRT confers a better survival with improved R0 resection rate and pCR rate compared with nCT for the patients with locally advanced AEG.

A Case of Photodynamic Therapy for Advanced Adenocarcinoma of Esophagogastric Junction

Photodynamic therapy (PDT) is a new minimally invasive technique for the treatment of tumors. Compared with traditional treatments such as surgery, radiotherapy and chemotherapy, PDT has the advantages of targeted killing of primary and recurrent tumor cells, less damage to surrounding normal tissue, less complications and high repetition rate. The purpose of this study was to investigate the short-term efficacy and adverse reactions of photodynamic therapy in advanced elderly patients with esophageal-gastric junction adenocarcinoma without surgical indications. A patient with advanced adenocarcinoma of esophagus and fundus was treated with photodynamic therapy under gastroscope. Intravenous drip of Cipofen (hematoporphyrin injection 150mg / 0.9% saline 250ml) for 1 hour to keep the patient away from light.48 hours after administration, photodynamic therapy was performed with "Leimai" PDT630-A photodynamic therapy apparatus, 3cm columnar optical fiber, laser treatment wavelength of 630nm, transmission efficiency of 0.70, output power of 1.4W, irradiation at the lower segment of the esophagus and cardia for 150s. The curative effect was evaluated by comparing gastroscopy before and after photodynamic therapy. Before treatment, there were proliferative lesions in the lower part of esophagus and cardia, erosion and necrosis on the surface, stricture of esophageal cavity, huge ulcer near gastric fundus, filthy moss and dam-like hyperplasia and eminence of surrounding mucosa. After treatment, the local mucosa at the entrance of cardia became white and there was no bleeding. Within four days after treatment, the symptoms of nausea and vomiting disappeared; the adverse reaction of retrosternal discomfort began to occur on the second day after operation, and the adverse reaction was not improved after photodynamic therapy. Photodynamic therapy has a significant short-term effect on advanced elderly patients with adenocarcinoma of the esophagogastric junction, which can significantly alleviate the clinical symptoms and relieve the pain of the patients. However, the adverse reactions can not be ignored. Therefore, photodynamic targeting therapy for tumor needs to be further studied. It is believed that with the continuous development of high-performance photosensitizers and new generation lasers, and the continuous progress of endoscopy and image guidance technology, photodynamic therapy will become an important adjuvant or palliative treatment for tumor prevention and treatment.

Priority of lymph node dissection for advanced esophagogastric junction adenocarcinoma with the tumor center located below the esophagogastric junction.

To clarify the priority of lymph node dissection (LND) in advanced Siewert type II and III AEG, in which the center of the tumor is located below the esophagogastric junction (EGJ).Data in 395 patients with advanced Siewert type II or III AEG was analyzed retrospectively. The index of estimated benefit from LND (IEBLD) was used to evaluate the efficacy of LND for each nodal station.The mean number of dissected LNs did not differ significantly between patients with type II and III AEG, nor did the mean number of retrieved LNs at each station significantly differ between the 2 groups. According to the IEBLD, the dissection of parahiatal LNs (No.19 and 20) and LNs along the distal portion of the stomach (No.5, 6, and 12a) seemed unlikely to be beneficial, whereas the dissection of Nos.1–3, 7, 9 and 11p yielded high therapeutic benefit (IEBLD>3.0) in both groups. The IEBLDs of No.4d, 8a, and 10 were much higher in type III than in type II AEG cases. No.10 LND may improve survival for type III AEG cases (IEBLD = 2.9), especially for subgroups with primary tumors invading the serosa layer, undifferentiated cancers, macroscopic type 3–4 tumors and tumors ≥50 mm in size (all IEBLDs > 4.0).For advanced AEG located below the EGJ, the dissection of paracardial LNs, lesser curvature LNs, and LNs around the celiac axis would promote higher survival benefits regardless of the Siewert subtype. Patients with type III AEG, especially those with serosa-invasive tumors, undifferentiated tumors, macroscopic type 3–4 tumors and tumors ≥50 mm in size may obtain relatively higher survival benefits from No. 10 lymphadenectomy.

Effect of Radical Surgery for Advanced Adenocarcinoma of Esophagogastric Junction on Perioperative Cellular Cell Immunity

Background: To investigate the perioperative peripheral blood levels of CD4+CD25+ regulatory T cells, programed cell death 1 (PD-1), and lymphocyte activation gene 3 (LAG-3) in patients with advanced Siewert type II adenocarcinoma of esophagogastric junction (AEG). Methods: Patients (n = 102) with advanced Siewert type II AEG underwent open total gastrectomy/proximal gastrectomy with a transhiatal resection of the distal esophagus and lymphadenectomy of the lower mediastinum and the abdominal D2 compartment. Flow cytometry was used to detect CD4+CD25+ T cells, PD-1 and LAG-3 expression on both CD4+ and CD8+ T cells in the peripheral blood of the Siewert type II AEG patients prior to surgery and on postoperative day (POD) 1, 3, 7, and 9. Results: The proportion of CD4+CD25+ T cells rapidly decreased on POD 1, then gradually increased and peaked at POD 7. The proportion of CD4+PD-1+ T cells significantly increased after surgery, reaching a maximum on POD 1, and remained significantly elevated on POD 3 compared to the preoperative day. The proportion of CD8+ PD-1+ and CD4+LAG-3+ T cells gradually increased after surgery and reached a peak at POD 7. The change in proportion of CD8+LAG-3+ T cells in the peripheral venous blood lymphocytes after surgery was not statistically significant. Conclusion: The change in the CD4+PD-1+ T lymphocyte ratio may likely reflect the cellular immunity status of the perioperative period.

A Case of Pathologic Complete Response with Neoadjuvant Biweekly-DCF Therapy and following Laparoscopic Transhiatal Extended Total Gastrectomy for Advanced Esophagogastric Junction Adenocarcinoma

A Case of Pathologic Complete Response with Neoadjuvant Biweekly-DCF Therapy and following Laparoscopic Transhiatal Extended Total Gastrectomy for Advanced Esophagogastric Junction Adenocarcinoma

Survival analysis of preoperative involved-field irradiation with concurrent chemotherapy for patients with Siewert′s type II and III adenocarcinoma of esophagogastric junction

Objective To analyze the clinical efficacy, toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy (a total of 45 Gy in 25 fractions, 5 times weekly). After 6-8 weeks, they underwent surgical resection. After the surgery, patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status, TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0 resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia, thrombocytopenia and neutropenia was 78%, 47% and 44%, respectively. In terms of gastrointestinal reactions, the incidence of nausea, vomiting and loss of appetite was 62%, 24% and 71%, respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer, 1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-, 2-and 3-year progression-free survival (PFS) rates were 90%, 70% and 67%, respectively. The 1-, 2-and 3-year overall survival rates were 95%, 80% and 75%, respectively. The 1-, 2-and 3-year local control rates were 95%, 84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert type Ⅱ and Ⅲ locally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery. Key words: Adenocarcinoma of esophagogastric junction/radiotherapy; Adenocarcinoma of esophagogastric junction/chemotherapy; Prognosis; Drug tolerance

Neoadjuvant Radiochemotherapy for Patients with Locally Advanced Esophagogastric Junction Adenocarcinoma.

neoadjuvant RCT influence on early and long term postoperative outcomes in patients with locally advanced esophagogastric junction adenocarcinomas. Sixty two patients with locally advanced esophagogastric junction adenocarcinomas were treated at the Center of Excellence in Esophageal Surgery at St. Mary Hospital between 2010-2017. According to the Siewert classification, the group comprised of type I - 11 patients, type II - 18 patients and type III - 33 patients. Only 17 patients received preoperative RCT. The surgical treatment for the 62 resected patients was: abdominal extended gastrectomy - 40 patients, Ivor-Lewis - 13 patients, McKeown esophagogastrectomy (3 incisions) - 5 patients and transhiatal esophagectomy - 4 patients. Results: Postoperative morbidity was 46.77% and was mainly represented by fistulas in 17 patients and pulmonary complications such as pleurisy,pneumonia and ARDS in 12 patients. Fistula occurred in 15 cases: grade 1 - 2 patients, grade 2 - 10 patients, grade 3 - 5 patients. Postoperative mortality was 4.8% (p_value = 0.017980 Fisher's Exact Test). Downstaging was observed in 7 patients. I did not encounter statistically significant differences in long term survival. Conclusions: Neoadjuvant RCT had no impact on postoperative morbidity, but statistically influenced postoperative mortality.

606 Short-term efficacy of OXA plus GOPC combined with endostar and preoperative concurrent radiotherapy in patients with locally advanced adenocarcinoma of esophagogastric junction

adenosine deaminase (to degrade extracellular adenosine) or the antiCD73 antibody TY/23 also significantly reduced radiation-induced lung fibrosis. Conclusions: Our data demonstrate that CD73 plays an active role in the pathogenesis of radiation-induced lung fibrosis driving progressive accumulation of adenosine and pathological tissue remodeling and suggest new routes for therapeutic intervention. No conflict of interest.

Management of Dysphagia in Esophageal Adenocarcinoma Patients Undergoing Neoadjuvant Chemotherapy: Can Invasive Tube Feeding be Avoided?

Neoadjuvant chemotherapy is an accepted standard for locally advanced esophagogastric junction adenocarcinoma. However, the dysphagia frequently associated with this condition may interfere with patient tolerance of this treatment. In many centers, invasive tube feeding, placed either endoscopically, radiographically, or surgically, is used to address this issue, but it can cause significant morbidity. We sought to determine if an approach of goal-directed dietary counseling and appropriately timed neoadjuvant chemotherapy could obviate the need for invasive tube feeding. Patients with locally advanced (cT3 or N+) esophageal and esophagogastric junction adenocarcinoma undergoing neoadjuvant TCF [Taxotere, cisplatin 5-fluorouracil (5-FU)], ECF (epirubicin, cisplatin, 5-FU), or FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) at the McGill University Health Center from March 2007 to September 2012 were identified from a prospective database. All received individualized goal-directed dietary counseling, were monitored for signs/symptoms of malnutrition with serial (baseline/presurgery) body mass index, albumin, and completed serial symptom scores (dysphagia), and quality-of-life questionnaires (Functional Assessment in Cancer Therapy with the esophageal subset, FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant chemotherapy and the need for invasive tube feeding. Of 130 patients undergoing neoadjuvant chemotherapy, 78 had severe dysphagia (defined as dysphagia score ≥2 on a 5-point Likert scale), most of whom received TCF (91 %). Overall dysphagia scores improved in 75 (96 %) of 78 patients from a dysphagia score of 3-0, most of which improved after the first cycle of therapy. This was associated with an increase in quality of life (FACT-E scores 117 ± 23 to 140 ± 20). With maintenance of weight (70 ± 22 to 69 ± 24 kg), body mass index (24.5 ± 8 to 23.9 ± 7 kg/m(2)), and serum albumin (40 ± 5 to 37 ± 4 g/L). Only one patient required a stent, and none required jejunostomy or gastrostomy. Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.

Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma-a pilot study.

To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

Risk factors of vagus nerve invasion in patients with advanced adenocarcinoma of esophagogastric junction

Objective To investigate the risk factors of vagus nerve invasion of advanced adenocarcinoma of esophagogastric junction (AEG).Methods The specimens from 98 patients with advanced AEG who underwent radical total gastrectomy and esophagogastric Roux-en-Y anastomosis from January 2011 to August 2012 at the First Affiliated Hospital of Anhui Medical University were collected.Serial section cutting was done and the upper and bottom incisional edges of every section were marked.The specimens were stained by hematoxylin-eosin solution,S-100 and CK immunohistochemistry.Vagus nerve invasion could be affirmed if cancer cells were observed in the peripheral space of vagus nerve and vagus nerve parenchyma or cancer cells infiltrated along the peripheral space of vagus nerve.Relationship between nerve invasion and clinicopathological factors was analyzed using chi-square test or Fisher exact probability.Factors related to vagus nerve invasion were analyzed using one-way analysis of variance and multi-factor logistic regression analysis.Results The incidence of vagus nerve invasion was 28.6％ (28/98),and the tumor only invaded the vagus nerve which had the same altitude as the upper incisional edge.The results of one-way analysis of variance showed that Siewert classification,intravascular cancer emboli,lymph node metastasis,the degree of lymph node metastasis,clinical staging,the degree of tumor differentiation were correlated with the vagus nerve invasion (x2 =14.156,14.552,5.454,10.706,6.919,14.767,P ＜ 0.05).The results of multi-factor logistic regression analysis showed that Siewert classification,intravascular cancer emboli and degree of tumor differentiation were the independent influencing factors of vague nerve invasion (OR =3.667,10.368,0.249,P ＜ 0.05).Conclusion Vagus nerve invasion is correlated with Siewert classification,intravascular cancer emboli and degree of tumor differentiation.The range of vagus nerve invasion is restricted under the upper incisional edge of tumor section. Key words: Carcinoma of esophagogastric junction; Vagus nerve ; Neural invasion