Esophageal Squamous Cell Carcinoma Research Articles

1457P Tumor immune microenvironment subtypes of esophageal squamous cell carcinoma and their strong ability to predict the efficacy of neoadjuvant immunotherapy

1457P Tumor immune microenvironment subtypes of esophageal squamous cell carcinoma and their strong ability to predict the efficacy of neoadjuvant immunotherapy

739. SIGNIFICANCE OF COX2 INHIBITOR FOR ESOPHAGEAL CANCER FROM THE CLINICAL AND EXPERIMENTAL ESTIMATE

Abstract (Aims) We report experimental and clinical evidence that COX2 represent a potential molecular target for the treatment and prevention of esophageal cancer. (Methods) (A)Experiment: Thirty 8-week male wistar rats were exposed to duodenal content esophageal reflux. All animal underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. In ten rats the sham (Control). They were sacrified at 40th week. Their esophagi were examined for HE, COX2,PGE2, PCNA and total bile acids in the esophageal lumen was measured. (B)Clinical: The expression of COX2 was examined for 68 specimens of esophageal squamous cell carcinoma (SCC) and the correlation of COX2 expression with clinicopatholigic features was examined. (Results) (A) After 40 weeks of reflux, columnar dysplasia, squamous cell carcinoma and adenocarcinoma were found. Total bile acid in the esophageal lumen was significantly increased in the EDA group compared with the sham operated rats. PCNA LI and esophageal tissue PGE2 were higher in dysplastic and cancer tissue than that of control. Overexpression of COX2 was shown in dysplastic and cancer tissue. COX2 may play an important role in esophageal cancer by duodenal content reflux.(B) COX2 immunoreactivity was weak in 27(40%) and strong in 41(60%) of the carcinomas. The proportion of poorly differentiated SCC among tumors with a strong expression of COX2 (34%) was significantly higher than among tumors with a weak expression of COX2 (19%, p=0.02). The depth of tumors (p=0.004), lymph node metastasis (p=0.0009) and the stage of the tumors (p=0.001) were advanced significantly more progressively in ECCS with a strong COX2 expression. Moreover, survival was significantly reduced (p=0.02) among patients with strong COX2 expression when compared with the COX2 weak group. This study showed that strong expression of COX2 was correlated with tumor progression and poor differentiation in ESCC. (Conclusion) In this experimental study, we demonstrate that bile reflux of duodenal contents induce COX2 and increase prostaglandin synthesis in dysplastic and cancer tissue. Our study suggests that COX2 may play a role in esophageal carcinoma development and progression, COX2 inhibitors may be potential targets for the prevention or treatment of esophageal carcinoma.

Prophylactic endoscopic vacuum therapy for stricture prevention following wide-field endoscopic submucosal dissection of superficial esophageal cancer

Background and aimsEsophageal stricture (ES) is a severe adverse event following wide-field endoscopic submucosal dissection (ESD) of superficial esophageal carcinoma. This study evaluated the efficacy and safety of combining endoscopic vacuum therapy (EVT) and budesonide orodispersible tablet (BOT) in preventing post-ESD strictures. MethodsThis prospective case series included patients with superficial esophageal squamous cell carcinoma and adenocarcinoma who had wide-field ESD (≥75% circumference, resection length ≥50 mm). After ESD, EVT was applied immediately, followed by 8 weeks of BOT. The main outcome measurement was the incidence of post-ESD stricture. ResultsEleven patients underwent ESD. Of these, 81.8% had 75-99% circumference resected, and 18.2% had a circumferential resection. EVT remained in situ for a mean of 3.5 days. No esophageal strictures were observed by the final follow-up. There were no major adverse events related to EVT or BOT. ConclusionsThe prophylactic combination of EVT and BOT is a novel and promising strategy for reducing post-ESD strictures.

779. IMMUNE CHECKPOINT INHIBITOR WITH CHEMOTHERAPY (CISPLATIN+5FU) FOR ADVANCED ESOPHAGEAL CANCER

Abstract Background First-line chemotherapy for advanced esophageal carcinoma results in poor outcomes. Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma according to the KEYNOTE-590. We studied 17patients for the unresectable esophageal cancer and gastroesophageal junction adenocarcinoma cases treated with pembrolizumab and chemotherapy at our hospital between November 2023 and May 2024. Methods 17 patients with advanced carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis were enrolled in this study. pembrolizumab 200mg/m2 and CDDP 80 mg/m2 was administered on days 1 and 5-FU 800 mg/m2 was administered on days 1-5 intravenously 3corse in 3-week cycles. Results Back ground: Averaged Age 76 (55-86), male: female =16:1, location (Ce: Ut: mt: Lt: Jz =1:1:6:6:3), strength 71mm (30-120), Stage (IVA: IVB= 7:10), Pathology (SCC: AD= 16:1), Times (3 courses completed: uncompleted: ongoing=9:3:5), Response PR:SD:PD: unknown=6:1:2:8, Toxicity: iRAE: liver dysfunction: Febrile neutropenia=4:2:6, The incidence of Grade 3 or higher adverse events was 3/15. One toxicity-related death occurred. We performed conversive esophagectomy for 2 patients. After chemotherapy: operation: radiation: observation: death:=2:2:10:3 Conclusion and discussion Due to the small number of cases, it is unclear whether the treatment was safe in a single center. I would like to consider increasing the number of cases. We will show one toxicity-related death and two conversive operation.

448. PREOPERATIVE PEMBROLIZUMAB COMBINED WITH CHEMOTHERAPY FOR THORACIC ESCC WITH CERVICAL LYMPH NODE METASTASIS (PICC-1): A PROSPECTIVE, PHASE 2 STUDY

Abstract Background Thoracic esophageal squamous cell carcinoma patients with cervical lymph node metastasis have poor prognosis and less effective of first-line therapy. The PICC-1 study aimed to assess efficacy and safety of the pembrolizumab combined with chemotherapy for patients with cervical lymph node metastasis. Methods Preoperative therapy includes pembrolizumab, nab-paclitaxel and cisplatin every three weeks for 2 cycles. The surgery was performed 3-6 weeks after the completion of the preoperative neoadjuvant therapy. Three weeks after surgery, two periods of maintenance therapy were continued with pembrolizumab combined with chemotherapy. Then maintenance treatment was continued with pembrolizumab for a full year. The primary endpoint was the pathologic complete response (pCR) rate. The secondary endpoints included the R0 resection rate, the major pathological response (MPR), recurrence-free survival (RFS), overall survival (OS) and perioperative complications. Results As of December 31, 2023, 22 patients who met the criteria were enrolled. All 22 patients suffered from treatment-related AEs of any grade during the neoadjuvant treatment period. The majority of AEs were lymphopenia (72.7%), anemia (59.1%), neurotoxicity (77.3%), nausea/vomiting (77.3%) and leukopenia (40.9%). In 8 of the 22 patients (36.4%), grade III or higher AEs were observed. All the patients underwent thoraco-laparoscopic esophagectomy without intraoperative conversion to open surgery. R0 resection was achieved in 90.9% of patients (20/22). pCR and mPR were observed in 31.8% (7/22) and 13.6% (3/22) of the resected patients, respectively. No patient died postoperatively. Conclusions Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for thoracic esophageal squamous cell carcinoma patients with cervical lymph node metastasis. R0 resection was achieved in 90.9% of patients, and pCR was observed in 31.8% (7/22) of resected patients.

1417P Comparative efficacy and safety of tislelizumab versus anti-PD-1 treatments in second-line esophageal squamous cell carcinoma: Simulated treatment comparisons

1417P Comparative efficacy and safety of tislelizumab versus anti-PD-1 treatments in second-line esophageal squamous cell carcinoma: Simulated treatment comparisons

609. LONG-TERM OUTCOMES OF SALVAGE SURGERY AFTER PROTON BEAM THERAPY FOR ESOPHAGEAL SQUAMOUS CELL CANCER

Abstract Background Proton beam therapy (PBT) for esophageal cancer is a promising option for local control, reducing adverse events. The salvage surgery is sometimes performed for residual or recurrent lesion after PBT, however the long-term outcome has not been known for lack of previous reports. Methods Of 374 patients treated with radical PBT for squamous cell carcinoma of the thoracic esophagus at our institution from 2009 to 2018, we selected cases in which salvage surgery was performed. Salvage surgery was defined as surgical resection of recurrent primary tumor and/or lymph node metastases. The primary outcome was overall survival, and secondary outcomes and postoperative complications were investigated. Results Nineteen patients in whom salvage surgery was performed were included. Median age was 66 (55-80) years, male: female: 16:3, clinical stage at initial presentation was I:II:III = 3:6:10, and median time from PBT to relapse was 23.8 months. Esophagectomy were performed in 12 patients, and lymphadenectomy for recurrent lymph node were performed in 7 patients. During a median observation period of 26.5 months postoperatively, 14 cases were confirmed to have died of primary disease, and the median overall survival from salvage surgery was 38.3 months. 8/14 (57.1%) patients had Grade 3 or higher postoperative complications, and no operative mortality was observed. Conclusion We showed the long and short-term outcome of salvage surgery after PBT for esophageal squamous cell carcinoma. Although the risk of postoperative complications was high, some cases of long-term survival after salvage esophagectomy were observed.

214. THORACIC CAVITY/ CAGE RATIO IS PREDICTOR FOR SURGICAL DIFFICULTY OF MINIMALLY INVASIVE ESOPHAGECTOMY

Abstract Background Esophagectomy for esophageal cancer is highly invasive surgery. Minimally invasive esophagectomy (MIE) was introduced as a less invasive surgery, and conventional MIE (C-MIE) is being increasingly performed worldwide. Recently, robot-assisted MIE (RAMIE) was developed with the aim of further minimization of invasiveness, and is expected to spread in the future. When performing MIE, we sometimes experienced difficult cases. In this study, we aimed to clarify the factors related to surgical difficulty of MIE. Methods We evaluated 362 patients who underwent MIE (285 C-MIEs and 77 RAMIEs) for esophageal squamous cell carcinoma between April 2010 and February 2023. We used computed tomography to evaluate the occipitofrontal diameter of thoracic cavity and cage at brachiocephalic vein (BV), tracheal bifurcation (TB) and inferior right pulmonary vein (IRPV) levels, respectively. We calculated the thoracic cavity/cage ratio (TRRC) at each level. The cut-off values of TCCR at each level for thoracic procedure time were calculated using the receiver operating characteristic. Furthermore, total score consisted of four degrees (0,1,2,3) by the TCCR at three levels was calculated. We assessed clinicopathological and anatomical factors and determined the independent factors influencing the thoracic procedural time as parameter of difficulty in MIE. Results We divided the patients into C-MIE group and RAMIE group. Patients in each group were divided into two cohorts according to median thoracic procedure time (C-MIE: 307 and RAMIE: 409 minutes, respectively). In the C-MIE group, univariate analysis demonstrated that sex, body mass index (BMI), and the TCCR at BV, TB and IRPV levels were correlated with thoracic procedure time. The total TRRC score was also correlated with thoracic procedure time in univariate analysis. Next, multivariate analysis was done using sex, BMI, and the total TCCR score. Multivariate analyses demonstrated that BMI (p = 0.0005) and the total score (p = 0.0069) were independent factors for thoracic procedure time. In the RAMIE group, univariate analysis demonstrated that BMI and the TCCR at BV and TB levels were correlated with thoracic procedure time. Multivariate analyses demonstrated that the TCCR at TB level (p = 0.0187) was only independent factor for thoracic procedure time. Conclusions The TCCR and the total score based on it could be useful in assessing surgical difficulty of both C-MIE and RAMIE. C-MIE was affected by the diameter at all levels of the thoracic cavity due to restricted mobilities of thoracoscopic instruments. On the other hand, RAMIE’s articulated forceps prevent it from being affected by entire thoracic cavity. Consequently, only the TCCR at TB level, which is one of the most less flexible field, affects the difficulty in RAMIE.

1462P A pilot study of hypoxia as a potential resistance mechanism to PD-1 checkpoint blockade therapy in neoadjuvant treatment of esophageal squamous cell carcinoma (HYPERION)

1462P A pilot study of hypoxia as a potential resistance mechanism to PD-1 checkpoint blockade therapy in neoadjuvant treatment of esophageal squamous cell carcinoma (HYPERION)

Ten-Year Survivals of Right Thoracic vs Left Thoracic Approach for Esophageal Cancer

BackgroundEsophagectomy can be performed using various surgical techniques. The aim of this study was to understand the impact of surgery on long-term survival for esophageal cancer. MethodsBetween May 2010 and July 2012, 300 patients with esophageal cancer were randomly assigned to undergo esophagectomy with either a left or right thoracic approach. Disease-free survival (DFS) and overall survival (OS) were compared based on the per-protocol principle among 286 patients with esophageal squamous cell carcinoma determined by postoperative pathologic results (146 in the right and 140 in the left thoracic arms). ResultsThe median DFS was 92 months in the right thoracic arm and 41 months in the left thoracic arm (hazard ratio, 0.73; 95% CI, 0.54-0.99; P = .045), with a cumulative 10-year DFS of 47.6% and 37.5%, respectively. The median OS was 136 months in the right thoracic arm and 99 months in the left thoracic arm (hazard ratio, 0.75; 95% CI, 0.54-1.04; P = .081), with cumulative 10-year OS of 52.4% and 43.7%, respectively. DFS and OS were comparable between the 2 arms for patients without lymph node metastasis. Conversely, for patients with lymph node metastasis, 10-year DFS was 32.7% and 21.4%, respectively (P = .018), and 10-year OS of the right and left thoracic arms was 37.9% and 25.9%, respectively (P = .012). ConclusionsCompared with the left thoracic approach, patients who underwent esophagectomy through the right thoracic approach had better 10-year survival rates, and the survival benefit was significant for those with lymph node metastasis.

1446P Efficacy and safety of cadonilimab combined albumin-paclitaxel, cisplatin and fluorouracil (APF) in neoadjuvant therapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): Results from the CAPITAL trial

1446P Efficacy and safety of cadonilimab combined albumin-paclitaxel, cisplatin and fluorouracil (APF) in neoadjuvant therapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): Results from the CAPITAL trial

318. EFFICACY OF PROPHYLACTIC STEROID THERAPY OF INJECTION AND ADMINISTRATION AGAINST STRICTURE FOR SUBENTIRE CIRCUMFERENTIAL DEFECT AFTER ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION

Abstract Background Esophageal stricture is a major problem after endoscopic submucosal dissection (ESD) for large superficial esophageal squamous cell carcinomas (SESCC). Local triamcinolone injection (LTI) has been reported as the standard prophylactic treatment against stricture, however, it showed that its efficacy was insufficient for subentire circumferential mucosal defect after ESD in the subgroup analysis of randomized controlled trial (JCOG1217). On the other hand, the usefulness of oral prednisolone administration (OPA) has also been reported. Thus, we aimed to compare the efficacy of LTI with combination of LTI and OPA in patients with subentire circumferential mucosal defect after esophageal ESD. Methods This retrospective study enrolled the patients with mucosal defect after ESD larger than 7/8th circumference and not spreading entire who treated with LTI or combination of LTI and OPA between July 2010 to January 2020. Triamcinolone acetonide (50-100 mg) was injected into ulcer bed immediately after ESD, and oral prednisolone (30 mg daily, tapered gradually for 8 weeks) was administrated. We defined as an esophageal stricture in case the endoscope could not pass through the stricture, and then endoscopic balloon dilation (EBD) was required. We evaluated stricture-free survival (SFS), and the number and duration of EBD. Results A total of 42 patients in the LTI group and 26 in the combination group were enrolled. The median longitudinal extension of the lesions was 4.5 cm (range; 2-7) in the LTI group and 4 cm (2-7) in the combination group. Finally, 18 patients (42.9%) in the LTI group and 7 (26.9%) in the combination group developed esophageal stricture, and 12-week SFS was 64.3% and 76.9%. The median number and duration of required ESD were 6 (2-10) in the LTI group and 4 (2-9) in the combination group, and 88 days (15-288) and 66 days (22-176). Conclusion The steroid combination therapy of local triamcinolone injection and oral prednisolone administration showed the effective outcomes comparing with local triamcinolone injection alone for subentire circumferential mucosal defect after esophageal ESD. Thus, this combination therapy can be the most promising treatment and should be compared in the randomized controlled trail with large sample size.

291. CLINICAL OUTCOMES OF IMMUNOCHEMOTHERAPY FOR UNRESECTABLE OR RECURRENT ESOPHAGEAL SQUAMOUS CELL CARCIONOMA

Abstract Background/Aim KEYNOTE-590 and CheckMate 648 study showed significantly feasible clinical outcomes in patients with advanced esophageal carcinoma. Herein, we report our clinical results of immunochemotherapy for unresectable and recurrent esophageal squamous cell carcinoma. Patients and Methods 17 patients who received pembrolizumab plus 5-fluorouracil and cisplatin (IO+C) and 9 patients who received nivolumab plus ipilimumab (IO+IO) were enrolled. Results The median age of the IO+C group was 70 years, and all patients had unresectable disease. A median of 2 courses of treatment were performed, and the best overall response rate was 68.6% including CR in 2 patients, PR in 9 patients, SD in 4 patients, PD in 1 patient and NE in 1 patient. One-year progression-free survival rate (PFS) was 36.1% and one-year overall survival (OS) was 64.6%. Immune-related adverse events (irAE) included liver damage in 4 patients, skin damage in 4 patients, thyroid dysfunction in 2 patients and lung damage in 1 patient. The median age of the IO+IO group was 79 years, with 3 patients of unresectable disease and 6 patients of recurrence. A median of 2 courses of treatment were performed, and the best overall response rate was 71.4% including CR in 4 patients, PR in 1 patient, SD in 1 patient, PD in 1 patient, and NE in 2 patients. One-year PFS was 68.6% and one-year OS was 85.7%. irAE included liver damage in 3 patients, skin damage in 6 patients, thyroid dysfunction in 2 patients, rhabdomyolysis in 1 patient and hypopituitarism in 1 patient. Discussion/Conclusion Currently, in our institute, IO+C is the first choice for unresectable esophageal carcinoma, and IO+IO is selected for patients who are unresponsive or intolerant to FP, patients requiring outpatient treatment and patients with recurrent disease. Although long-term clinical outcomes will need to be examined, immunochemotherapy is very useful and it is necessary to examine the effective use of IO+C and IO+IO in the future.

235. A NOVEL TUMOR STAGING SYSTEM INCORPORATING CN STATUS FOR STRATIFYING EARLY STAGE ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS AFTER TRIMODAL THERAPY

Abstract Background This study aims to assess the prognostic significance of cN status in early-stage esophageal squamous cell carcinoma (ESCC) patients following neoadjuvant chemoradiotherapy (nCRT) and develop a novel staging model for personalized survival prediction. Methods Patients with ESCC who underwent nCRT and esophagectomy were included. The Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) were employed to evaluate the validity of various oncological staging systems. A reduction in AIC and BIC values indicates improved predictive capability and accuracy. Results We established a novel staging model by incorporating ypTNM stage and cN status, effectively stratifying ypI ESCC patients. Cox regression analysis showed that only cN status was an independent prognostic factor for both overall survival (p = 0.030) and disease-free survival (p = 0.019) in patients with stage ypI. The newly developed ypTNM-cN staging exhibited a superior alignment with overall survival trends compared to the AJCC 8th ypTNM staging, with a significantly lower AIC of 3143.014 versus 3149.950. This superiority was further supported by a BIC of 3146.605 compared to 3153.541. In terms of disease-free survival outcomes, the emerging ypTNM-cN staging, with AIC and BIC values of 3196.057 and 3199.648, respectively, outperformed the AJCC 8th ypTNM staging, which recorded values of 3203.853 and 3207.444. Conclusion We have devised a novel staging system based on ypTNM stage and cN status to accurately categorize patients with ypI stage. Our ypTNM-cN staging system offers valuable insights into the classification of ypI ESCC and demonstrates reliable classification efficacy for all ESCC patients following nCRT and surgery.

571. A PHASE I/II MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF INDUCTION IMMUNOCHEMOTHERAPY FOLLOWED BY CONCURRENT IMMUNO-CHEMORADIOTHERAPY IN UNRESECTABLE LA-ESCC

Abstract Background Despite advances in radiotherapy techniques, the prognosis for patients undergoing definite chemoradiotherapy remains suboptimal. There exists an urgent and unmet need to enhance the efficacy of concurrent chemoradiotherapy for patients with unresectable Locally Advanced Esophageal Squamous Cell Carcinoma (LA-ESCC). Immunotherapy, when combined with chemotherapy, has emerged as the established first-line treatment for advanced esophageal cancer. Significant tumor shrinkage and reduced tumor residual observed after induction immunotherapy might provide the potential to enhance locoregional control of radiotherapy as well as better protection of critical organs and circulating lymphocytes. Methods We conducted a multicenter, phase I/II study aiming to assess the efficacy and safety of induction immunochemotherapy followed by immuno-chemoradiotherapy (ICRT) for unresectable LA-ESCC (SCR-ESCC-002, NCT06173986) (Figure 1). Eligible patients will initiate treatment with 2-3 cycles of immunochemotherapy. Within 4 weeks after completing the induction treatment, patients without disease progression will proceed to receive concurrent radiotherapy (45-50Gy in 25 fractions), weekly chemotherapy, and PD-1 inhibitor on day1,22. Following immuno-chemoradiotherapy, patients will continue with immunotherapy maintenance until disease progression or unacceptable toxicity, for a maximum duration of one year. The study's dual primary endpoints are progression-free survival and treatment completion rate. Results As of January 2024, 13 eligible patients were enrolled in our trial, with median follow-up of 7.8 months. Due to tumor shrinkage of induction immunochemotherapy, radiation doses to normal tissues were significantly reduced, particularly for the lungs, heart, and vertebrae. All 13 patients completed the planned induction treatment and radiotherapy, with 8 completing more than 4 weekly chemotherapies. During ICRT, 10 of 13 patients experienced grade 3-4 adverse events. These included lymphopenia (69.23%), myelosuppression (46.15%), hepatitis (7.69%), esophagitis (7.69%), and pneumonitis (7.69%). Nine patients achieved a complete response, and 3 partial response 4 weeks after ICRT according to RECIST v1.1. Conclusion Decreased radiation volumes due to tumor regression brought by induction immunochemotherapy diminish the occurrence of non-hematological adverse events during ICRT. Preliminary analysis suggests that this therapeutic modality exhibits favorable safety profiles and yields a superior clinical complete response rate compared to definitive chemoradiotherapy alone. The trial is presently enrolling participants, and the confirmation of efficacy and survival outcomes necessitates larger sample sizes and extended follow-up durations.

449. CAN LARGE ANASTOMOTIC LEAKAGE AFTER ESOPHAGEAL SURGERY BE TREATED BY ENDOLUMINAL VACUUM-ASSISTED CLOSURE (EVAC THERAPY)?: A CASE REPORT

Abstract Background Anastomotic leakage after esophageal surgery is a deadly complication which approach is still under debate. The high morbimortality of the surgical approach has led to debate whether there are any alternative treatments. The appropriate strategy is based on many factors that include patient’s general conditions, size of anastomotic leakage and diagnosis delay. EVAC (Endoscopic vacuum assisted wound closure) is an emerging technique to treat these patients that can be placed either into the cavity or in the lumen under endoscopic guidance. It is then connected to a negative continuous pressure of 75-125mmhg and then reviewed after 3-4 days. Methods A 62-year-old man with esophageal squamous cell carcinoma underwent neoadjuvant chemoradiotherapy, followed by a minimally invasive Mckeown esophagectomy. On the fourth postoperative day, inflammatory indexes increased, and a CT scan showed an anastomotic leakage. It was decided to perform an endoscopy that showed that the leakage was about 70% of the anastomosis opening to a wound cavity of 5cm with necrotic tissue and fibrosis. Due to the clinical stability of the patient, it was decided to treat the anastomotic leakage conservatively by EVAC therapy. Results To start the EVAC therapy a polyurethane sponge was placed in the cavity via an overtube during the first endoscopy. The patient underwent a total of 14 EVAC sessions over 85 days. As we performed the sessions, healthy granulation tissue appeared leading the leakage and the cavity size to progressively improve. After the 13th session, the endoscopic evaluation showed a healed anastomosis. A CT scan with oral contrast was performed showing leak resolution. The patient started oral intake and was discharged after four days. Conclusions Treatment of anastomotic leakage after esophagectomy is still challenging and presenting high morbidity. The appropriate strategy needs to be individualized. Although surgical reintervention was the classical approach for these patients, new strategies have appeared like the EVAC. It is a promising option to improve the outcome of patients with transmural leakages who would otherwise require surgery. It has demonstrated that it is a reliable, safe and effective treatment.

425. PARACONDUIT HIATAL HERNIA FOLLOWING ESOPHAGECTOMY IN A PORTUGUESE TERTIARY CENTER

Abstract Background Esophageal Cancer is the seventh most common cancer worldwide with poor overall survival. As minimally invasive esophagectomy is becoming the new standard of care, an increased incidence of para-conduit hiatal hernias has been reported. Possible risk factors, other than those related to the operative approach have been suggested, such as location of the tumor. Histological type may also account for the increased incidence of hiatal hernias due to shift from esophageal squamous cell carcinomas to adenocarcinomas of the gastro-esophageal junction in Western world. We reviewed our center’s experience to determine whether the adoption of minimally invasive esophagectomy was associated with an increased incidence of para-conduit hernia. Methods A single-center, prospective database was used to retrospectively analyze consecutive patient who underwent esophagectomy between January 2007 and December 2023. Results Between January 2007 and December 2023, 497 patients were submitted to esophagectomy (Ivor-Lewis, McKeown or transhiatal) due to cancer (242 squamous cell carcinomas and 255 adenocarcinomas); 163 proximal esophageal cancers and 323 distal esophageal cancers. An hiatal hernia was diagnosed in 11 (2.21%) of 497 included patients submitted to esophagectomy; 5 (3.25%) after 154 totally minimally invasive esophagectomies, 3 (11.11%) after 27 hybrid esophagectomies and 3 (0.95%) after 316 open esophagectomies. The median days to diagnosis of hiatal hernia was 199 (6-3881) days. Surgical treatment consisted of cruroplasty in 1 patient, crurorrhaphy in 6 patients, reduction of herniated contents in 4 patients. The tumor was located proximally in 1 patient whereas the remaining 10 were at distal esophagus or at gastro-esophageal junction. Regarding pathologic evaluation, 2 were squamous cell carcinomas (0.82%) and 9 adenocarcinomas (3.53%). Conclusion In our experience, the adoption of minimally invasive esophagectomy has been associated with an increase of symptomatic para-conduit hernia, in line with the reports of recent meta-analyses. The prevalence of paraconduit hiatal hernia was also increased in adenocarcinomas, revealing the shift in the histological type in Western world. The true rate of herniation may be much higher, as our patients are not routinely submitted imaging diagnostic tests as part of their follow-up.

Neoadjuvant camrelizumab followed by concurrent camrelizumab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, phase II study.

Neoadjuvant therapy combining camrelizumab with chemotherapy has emerged as a promising approach for treating locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal strategy for integrating immunotherapy with chemotherapy remains to be fully defined. This single-arm phase II study aimed to evaluate the efficacy and safety of neoadjuvant therapy with camrelizumab induction followed by camrelizumab plus chemotherapy in locally advanced ESCC. Patients with clinical stage cT2-4N0M0 or cTxN1-3M0 ESCC were enrolled in the study. Patients received one dose of camrelizumab (200 mg) followed by docetaxel (75 mg/m2) and nedaplatin (75 mg/m2) plus camrelizumab (200 mg) every 3 weeks for two cycles, and then underwent surgery within 3-4 weeks. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints included the pathological complete response (pCR) rate, R0 resection rate, downstaging rate, disease-free survival (DFS), overall survival (OS), and safety. In total, 55 patients were enrolled in the study between 16 April 2020 and 30 October 2021. Of these 55 patients, 53 (96.4%) completed neoadjuvant therapy, and 48 (87.3%) underwent surgery. The MPR rate was 77.1% [37/48, 95% confidence interval (CI): 62.7-88.0%]. The pCR (ypT0N0) rate was 39.6% (19/48, 95% CI: 25.8-54.7%). All the patients had R0 resections. Primary tumor downstaging occurred in 44 (91.7%) patients, and nodal downstaging occurred in 19 (39.6%) patients. The 2-year DFS rate was 68.9% (95% CI: 53.0-80.4%), and the 2-year OS rate was 74.7% (95% CI: 60.2-84.6%). Grade ≥3 treatment-related adverse events (TRAEs) were observed in 7 (12.7%) patients. In conclusion, neoadjuvant camrelizumab followed by camrelizumab plus chemotherapy showed promising efficacy in treating locally advanced ESCC and had a manageable safety profile.

Prognostic prediction model for patients with pathological T1N0 stage esophageal squamous cell carcinoma undergone esophagectomy.

There is a shortage of reliable predictive models to provide valuable prognostic information for early esophageal squamous cell carcinoma (ESCC) without lymph node metastasis (LNM). We aimed to develop and validate a nomogram using the prognostic factors in T1N0 ESCC patients. Patients with pathological T1N0 ESCC who underwent esophagectomy between 2014 and 2021 at three institutes were reviewed. The prognostic factors were evaluated by Cox proportional hazards model and a nomogram was developed. Patients were divided into high- and low-risk groups based on cut-off value of total points in the nomogram. Overall survival (OS) was estimated by the Kaplan-Meier method and compared using the log-rank test. A total of 275 patients were included and split into training (n=180) and external validation (n=95) cohorts. In the training cohort, multivariable analysis showed that the surgical approach, T1 substage, and carcinoembryonic antigen (CEA) level were independent prognostic factors. The developed nomogram had relatively high performance, with the area under the receiver operating characteristic (ROC) curve (AUC) of 0.783, 0.711 and 0.612 for 1-, 3-, and 5-year OS, respectively. The calibration curves showed that the predicted probability was in good agreement with the actual probability. Forty-seven was determined as cut-off value of total points. High-risk group (n=148) showed a significant poor OS than low-risk group (n=127) (P<0.001). Left surgical approach, stage T1b, and higher CEA were associated with poorer prognosis in T1N0 ESCC patients. The nomogram demonstrated a good performance to predict the individual survival.

Patterns of regional lymph node metastasis predict postoperative overall survival and disease-free survival in locally advanced esophageal squamous cell carcinoma.

Lymph nodal characteristics are highly significant in predicting the survival of patients with esophageal squamous cell carcinoma (ESCC). However, there is currently a scarcity of studies examining their role in locally advanced ESCC. In the present study, we attempted to depict the patterns of regional lymph node metastasis and investigate their predictive potential in locally advanced ESCC. Patients with locally advanced ESCC underwent esophagectomy at the Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College were included. Kaplan-Meier curve was used to compare the survival differences between groups. Cox regression was constructed to screen the independent risk factors. A total of 439 patients were included. We identified 10% as the optimal cutoff value for positive lymph node ratio (PLNR) with X-tile software. Statistically significant differences were found in both overall survival (OS, P<0.001) and disease-free survival (DFS, P<0.001) among different PLNR groups. PLNR [hazard ratio (HR): 1.85, P<0.001] and metastatic lymph nodes along the left gastric artery (HR: 1.63, P=0.02) were the independent prognostic factors for OS. While PLNR (HR: 1.77, P<0.001) and metastatic total main bronchus lymph nodes (HR: 2.78, P=0.047) were the independent prognostic factors for DFS. We discovered that higher PLNR is associated with poorer OS and DFS of locally advanced ESCC. The lymph nodes along the left gastric artery and the total main bronchus lymph nodes were independent prognosticators for OS and DFS, respectively.