Treatment Of Esophageal Cancer Research Articles

The evolution of anastomotic techniques in robot-assisted Ivor Lewis esophagectomy

Radical esophagectomy is the cornerstone in the treatment of esophageal cancer combined with perioperative therapies, whereas patients diagnosed at an early stage may be candidates for endoscopic resection. Minimally invasive procedures aim to improve the postoperative complications and reduce overall morbidity. The short and long-term results of the incorporation of robot-assisted esophagectomy in specialised centres worldwide have been encouraging. The Ivor Lewis technique has become the preferable approach, reaching up to 61% of the minimally invasive reconstructions in the Western World; however, the percentage of anastomotic leaks remains problematic. Throughout the last decade, a few modifications of the anastomotic technique have been proposed in an effort to improve the surgical results of the robot-assisted approach. This review presents the evolving robotic techniques of performing the esophagogastric anastomosis. An overview of the available approaches will be discussed with a focus on the intrathoracic anastomosis.

Chinese Guidelines on Perioperative Management of Resectable Esophageal Cancer (2023 edition)

The standardization of surgical treatment has become indispensable in the overall outcome of esophageal cancer care in China, but there is a notable deficiency of clinical guidelines regarding esophageal surgery. The Chinese National Cancer Center organized esophageal surgery experts from the Chinese Association of Thoracic Surgeons (CATS), Chinese Society for Thoracic and Cardiovascular Surgery (CSTCVS), and Chinese Society for Disease of the Esophagus (CSDE) to develop and establish the Chinese Guidelines on Perioperative Management of Resectable Esophageal Cancer (2023 edition). This guideline comprehensively covers all aspects of surgical treatment for esophageal cancer, including conceptual clarification, preoperative diagnosis, clinical staging, indications for surgery, multidisciplinary comprehensive treatment, surgical treatment modalities, and perioperative management. A total of 39 critical clinical questions are categorized into six domains above. This guideline follows the globally accepted approach for developing recommendations and takes into account the most recent research evidence as well as China's unique national circumstances. Its main aim is to serve as a comprehensive resource for standardizing the diagnosis and surgical treatment of esophageal cancer in China, with the ultimate goal of substantially improving the overall outcomes.

Inhibition of the interaction between Hippo/YAP and Akt signaling with ursolic acid and 3'3-diindolylmethane suppresses esophageal cancer tumorigenesis.

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

Identification of hub genes and microRNAs with prognostic values in esophageal cancer by integrated analysis

Esophageal cancer (EC) is the eighth most common cancer in the world, and the sixth most common cause of cancer-related mortality. The aim of the present study was to identify cell and molecular mechanisms involved in EC, and to provide the potential targets for diagnosis and treatment. Here, a microarray dataset (GSE20347) was screened to find differentially expressed genes (DEGs). Different bioinformatic methods were used to analyze the identified DEGs. The up-regulated DEGs were significantly involved in different biological processes and pathways including extracellular matrix organization and ECM-receptor interaction. FN1, CDK1, AURKA, TOP2A, FOXM1, BIRC5, CDC6, UBE2C, TTK, and TPX2 were identified as the most important genes among the up-regulated DEGs. Our analysis showed that has-miR-29a-3p, has-miR-29b-3p, has-miR-29c-3p, and has-miR-767–5p had the largest number of common targets among the up-regulated DEGs. These findings strengthen the understanding of EC development and progression, as well as representing potential markers for EC diagnosis and treatment.

Assessment of a collaborative treatment model for trimodal management of esophageal cancer.

Patients with esophageal cancer often receive care in a collaborative (multi-institutional) treatment model as opposed to a single institutional model. The effect of a collaborative model on the quality of trimodality therapy and survival is unknown. The National Cancer Database (NCDB) was used to identify patients receiving neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy for esophageal cancer between 2012-2017. Patients who received neoadjuvant therapy and surgery at a single institution were compared to those that received collaborative treatment across multiple institutions. Outcomes included adherence to guideline recommended multiagent chemotherapy, receipt of 41.4-50.4 Gy of radiation, R0 resection, pathologic complete response (pCR), and 5-year survival. Sociodemographics, comorbidities, and tumor characteristics were assessed in bivariate and multivariable analysis. Among 8,396 patients identified, 39% received treatment at a single institution, while 61% received collaborative treatment. Median travel distance to the site of esophagectomy was two times greater for patients receiving collaborative treatment (30 vs. 15 miles; P<0.001). Patients in the collaborative cohort were less likely to receive guideline-recommended multiagent chemotherapy (85% vs. 96%; P<0.001) and 41.4-50.4 Gy of radiation (89% vs. 91%; P=0.01). R0 resection rates were similar (94.4% vs. 93.7%; P=0.17). Patients who received collaborative treatment had an increased rate of pCR (24% vs. 22%; P=0.02). Overall, 90-day and 5-year survival were 92.9% and 42.6% respectively and did not differ significantly between the two groups. Collaborative trimodality treatment of esophageal cancer is a common and reasonable practice model, which may alleviate patient travel burden with only a modest impact on the quality of CRT, pCR, 90-day survival, and 5-year survival.

373. THE PROGNOSTIC IMPACT OF TIME DELAYS IN OESOPHAGEAL CANCER SURGERY: 10-YEAR EXPERIENCE OF A HIGH-VOLUME CENTRE

Abstract Background Over the last twenty years, treatment of oesophageal cancer has changed towards a multimodal approach to achieve better clinical outcomes. Detailed staging paradigms and neoadjuvant treatment have resulted in a longer time period before oesophagectomy, but literature on the prognostic impact of longer waiting times is scarce in this field. The aim of this study was to determine whether hospital (HD) or time to surgery (TTSD) delays adversely impact patient outcomes. Methods All patients who underwent oesophagectomy for oesophageal cancer between January 2009 and February 2020 at the Royal Infirmary of Edinburgh (RIE) were identified from a prospectively maintained database. Two different time delays were considered. Hospital delay, defined as the time between date of diagnosis and start of treatment (i.e. neoadjuvant chemotherapy or straight to surgery). Time to surgery delay (time between the end of neoadjuvant regimen and surgery). The primary endpoint was to investigate whether hospital or time to surgery delay affected overall survival (OS). Secondary endpoints anaylsed whether hospital or time to surgery delays affected post-operative complication rate, 30 day mortality, or disease-free survival (DFS). Results A total of 512 patients were included for analysis over the 10 year study period. ‘Delayed treatment’ (DT) was calculated as greater than the median ‘hospital delay’, which was 56 days. ‘Early treatment’ (ET) was therefore defined as &amp;lt;56 days. Similarly, median time to surgery was 35 days, and delay in time to surgery (DTTS) was defined as ≥35 days. Kaplan–Meier survival analysis and the log rank tests did not find any significant difference in OS, DFS, post-operative complications, or 30 day mortality with either time delay. Further multivariate analyses showed that hospital and time to surgery delay, were not independent prognostic variables. Conclusion In our study group a hospital delay longer than 8 weeks did not impact on OS, DFS, or post-operative complications. Moreover, a time to surgery delay over 5 weeks appears safe, and did not impact overall survival.

152. SINTILIMAB PLUS CISPLATIN AND PACLITAXEL INDUCTION TREATMENT FOR BORDERLINE RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A PHASE II CLINICAL TRIAL

Abstract Background An increasing number of clinical studies focus on investigating the use of immunotherapy in the treatment of esophageal cancer. This phase II trial (NEOCRTEC-2001 clinical trial) aimed to assess the safety and efficacy of sintilimab in combination with cisplatin and paclitaxel induction immunochemotherapy followed by surgery for locally advanced borderline-resectable esophageal squamous cell carcinoma (BR-ESCC). Methods Patients with primary tumor or bulky lymph nodes that might invade nearby organs were eligible. Treatment started with 2–4 cycles of induction immunochemotherapy, followed by surgery if the tumor was assessed resectable, or by radical concurrent chemoradiotherapy if unresectable. The primary endpoint was pathologically proven complete resection (R0) rate. The secondary end points included pathological complete response (pCR) rate, overall survival (OS), progression-free survival (PFS), adverse events and postoperative complication. Results From September 2020 to now, a total of 34 patients were enrolled. After immunochemotherapy, 21 patients (61.8%) received surgery and 13 (38.2%) did not. All patients underwent McKeown procedure, and median operation time was 295 minutes (range 201–489 minutes). All patients received esophageal reconstruction using gastric tube, and underwent cervical anastomosis. An average of 46.6 lymph nodes were dissected, and positive lymph nodes were observed in 5 of the 21 patients. R0 resection was confirmed in 20 patients (58.8%). One patient underwent R2 resection because of tumor invasion of the aorta. Pathologic complete response was confirmed in 6 patients (6/34, 17.6%), while 5 patients (5/34, 14.7%) had few or no regressive changes (TRG3). Conclusion The treatment strategy of induction immunochemotherapy followed by surgery is promising for patients with locally advanced borderline-resectable esophageal squamous cell carcinoma. The whole results of pathologic response and prognostic value are awaited with interest.

Transarterial infusion chemotherapy for advanced esophageal cancer with airway stenosis.

This study aimed to investigate the safety and efficacy of transarterial infusion chemotherapy for the treatment of esophageal cancer with airway stenosis. Data of patients with advanced esophageal cancer complicated with airway stenosis treated with transarterial infusion chemotherapy were retrospectively analyzed. Dyspnea, clinical efficacy and adverse reactions were evaluated. Of these patients, 27 had grade II preoperative dyspnea, and 31 had grade III preoperative dyspnea, 26 had grade I postoperative dyspnea, 25 had grade II postoperative dyspnea, and 7 had grade III postoperative dyspnea. Among 3 patients with left main bronchial stenosis and atelectasis, 2 had complete remission after transarterial infusion chemotherapy, and 1 demonstrated partial remission. After treatment, complete response, partial response, and stable disease were observed in 7, 34, and 17 cases, respectively. Total objective effective rate and disease control rate were 70.6% (41/58) and 100.0%, respectively. During follow up, 24 patients died of organ failure, and 17 patients died of tumor-related respiratory failure. Seven patients died of gastrointestinal bleeding, 1 patient died of myocardial infarction, and 9 patients survived. Transarterial infusion chemotherapy is safe and effective for the treatment of advanced esophageal cancer with airway stenosis.

309. SURGICAL TREATMENT FOR THE RECURRENT SITE OF ESOPHAGEAL CANCER AFTER ESOPHAGECTOMY

Abstract Background Although the outcome of patients with recurrent esophageal cancer following radical esophagectomy is extremely poor, long-term survival can be achieved with multimodal therapy, including surgical resection of the recurrent lesion. Developing a treatment strategy is a critical issue; therefore, we examined the indications and optimal timing for surgical treatment in patients with recurrence. Methods A total of 184 patients with recurrent esophageal cancer after radical esophagectomy were studied between 2001 and 2015, with a focus on surgical resection. Results The first recurrence site was the lymph nodes (124 cases; 67%) [neck (35; 19%), mediastinum (82; 45%), abdomen (35; 19%)], lung (36; 20%), liver (32; 17%), pleura (18; 10%), bone (13; 7%), etc. Second-line treatment following recurrence was surgery (8 cases), chemoradiotherapy (89 cases), chemotherapy (64 cases), and best supportive care (23 cases). Patients with single organ or solitary recurrence and recurrence more than 8 months after surgery had better prognoses. All the surgical cases had single-site recurrence (lung-3, cervical lymph nodes-3, colon-1, and brain-1). Good prognosis was expected for the patients with lung or cervical lymph node recurrence. Conclusion Surgical treatment for recurrent esophageal cancer following radical esophagectomy was considered beneficial for the recurrence of cervical lymph node or lung metastasis of solitary lesions at least 8 months after esophagectomy. Immune checkpoint inhibitors have recently been indicated for esophageal cancer and expected for improving prognosis, and the role of surgery in multidisciplinary treatment for metastatic recurrence needs repeated investigation.

148. COMPARISON OF EARLY POSTOPERATIVE OUTCOME BETWEEN OPEN AND MINIMALLY INVASIVE TRANSTHORACIC ESOPHAGECTOMY FOR ESOPHAGEAL CANCER: A RETROSPECTIVE STUDY

Abstract Background Esophagectomy is a highly invasive surgical procedure for esophageal cancer, with open thoracotomy associated with a significant risk of pulmonary complications. Minimally invasive techniques, such as minimally invasive esophagectomy (MIE), are expected to reduce these complications and enhance postoperative recovery. This study aimed to compare the early postoperative outcomes of patients who underwent open esophagectomy versus MIE. Methods We conducted a retrospective study using a single-center database from January 1, 2010, to February 28, 2023, including patients aged 18–90 years with a resectable lesion of the esophagus or esophagogastric junction who underwent either open transthoracic esophagectomy or MIE (thoracoscopic/robotic-assisted). Patient data, surgical procedures, interventions, and early outcomes (within 30 days of operation) were collected and analyzed. The study included a total of 76 patients, with 50 patients in open esophagectomy group and 26 patients in MIE group. The primary outcome was the incidence of pulmonary complications during the hospital stay, and logistic regression was used for data analysis. Results The overall incidence of pulmonary complications was 37 cases (74%) in the open esophagectomy group and 14 cases (53.8%) in the MIE group, with the incidence of pulmonary infection occurring in 19 cases (38%) and 8 cases (30.8%), respectively. Perioperative mortality was 1 cases (2%) in the open esophagectomy group and 0 cases (0%) in the MIE group. After adjusting for age, sex, BMI, smoking, COPD, and operative time, the open esophagectomy group had a 4.29 times higher risk of pulmonary complications than the MIE group (odds ratio 4.29, 95% confidence interval 1.30–14.16; p = 0.017). Conclusion Our study demonstrates that MIE is associated with a lower incidence of pulmonary complications, reduced blood loss, and shorter ICU stays compared to open esophagectomy. Rates of anastomosis leakage, vocal cord paralysis, and hospital stays were comparable. These findings support the feasibility and safety of MIE, potentially improving surgical outcomes and enhancing postoperative recovery for the treatment of esophageal cancer.

415. STEP-BY-STEP APPROACH TO CERVICAL LYMPHADENECTOMY IN ESOPHAGEAL CANCER

Abstract https://drive.google.com/file/d/1sByes2_wNgSmb8DW9BjNQknjN7HCXtf1/view Background Cervical lymphadenectomy is an essential component of the treatment of esophageal cancer. Over the last six years, our upper gastrointestinal unit has carried out 180 esophagectomies, with 20% of them involving 3-field lymph node dissection. According to our unit’s protocol, the procedure is indicated for the following conditions: supraclavicular lymph node metastases, upper thoracic esophageal cancer, and recurrent nerve lymph node metastasis. We aim to present a step-by-step approach to cervical lymphadenectomy. Methods Our upper gastrointestinal unit has implemented several learning protocols that aim to design the most efficient and effective training environment. The primary objective is to enhance the learning process and surgical performance while maintaining quality standards. One of the essential components of this learning environment is video coaching, which provides a powerful tool for demonstrating and deconstructing surgical procedures. In recognition of the importance of cervical lymphadenectomy, we have developed a video that is incorporated into our unit’s existing curriculum. Results As an essential component of our comprehensive teaching protocol, we have included a video demonstrating the systematic approach to cervical lymphadenectomy. It offers a clear and concise overview of the anatomical landmarks that must be identified during the procedure, as well as the steps involved and the main pitfalls that must be avoided. Conclusion Our unit is committed to a phased and systematized approach to learning based on steps through the deconstruction of complex procedures. The unit’s structured teaching protocol allows the acquisition of competencies that enable the performance of cervical lymphadenectomy in an effective and efficient way, without compromising patient safety. We believe that our step-by-step approach to cervical lymphadenectomy will be a valuable resource for healthcare professionals working in our upper gastrointestinal unit.

416. FEASIBILITY STUDY ON THE INTRA-OPERATIVE USE OF IMPEDANCE PLANIMETRY (ENDOFLIP) TO ASSESS PYLORIC FUNCTION DURING ESOPHAGECTOMY

Abstract Background Esophagectomy remains the cornerstone of curative treatment of esophageal cancer. Despite this, the optimal management of the pylorus remains unclear. In open surgery, a pyloroplasty, pyloromyotomy or finger fracture of the pylorus has been standard. In minimally invasive surgery, pyloric procedures are frequently excluded. Approximately 16% of patients will subsequently require endoscopic dilation of their pylorus due to issues with conduit function. Conversely, those with a pyloric procedure have significantly higher rates of dumping. The aim of this feasibility study is to determine whether intra-operative impedance planimetry (EndoFLIP) assessment of the pylorus may help identify those who will benefit from an up-front pyloric procedure. Methods 20 consecutive patients undergoing esophagectomy for esophageal cancer were consented and enrolled. At the conclusion of the operative procedure, when assessing the anastomosis and conduit endoscopically, the EndoFLIP catheter was passed with the endoscope. Diameter of the pyloric lumen and distensibility index (DI) were recorded for a range of balloon pressures. Results There were significant variations in lumen diameter and DI between patients. Mean lumen diameter with 30 mL balloon volume is 8.3 mm (5.1–11.3), with 40 mL balloon volume is 12.5 mm (11.6–13.8), and with 50 mL balloon volume is 14.9 mm (13.9–15.9). Mean DI at 30 mL is 5.77 (1.35–13.5), at 40 mL is 8.64 (4.59–17.0) and at 50 mL is 12.7 (3.56–38.0). Conclusion EndoFLIP assessment of pyloric function is feasible during esophagectomy. There are significant variations in pyloric measurements between patients. This may allow personalised management of the pylorus for patients undergoing minimally invasive esophagectomy.

279. ENDOSCOPIC RENDEZVOUS TECHNIQUE FOR RECANALIZATION OF COMPLETE ESOPHAGEAL OBLITERATION

Abstract Background Radiation-induced esophageal stricture is a common late complication following radiation treatment for esophageal cancer or head and neck cancer. Currently, treatments for esophageal stricture are typically minimally invasive, as opposed to surgical reconstruction. However, this condition can significantly impact a patient’s quality of life during treatment including multiple sessions of dilatation, prolonged use of a nasogastric tube or gastrostomy status. In severe cases, complete esophageal obliteration can occur. The patients’ symptoms experienced are more severe than those in ordinary cases, marking endoscopic interventions more challenging and having a higher failure rate. This case report aims to demonstrate the use of the rendezvous technique in endoscopic treatment for the recanalization of the esophagus. Methods A 61-year-old female presented with dysphagia for two years. The patient had a history of hypopharyngeal cancer and underwent concurrent chemoradiation. During surveillance, the patient’s symptoms had worsened, and she was unable to eat or even swallow her own saliva. Endoscopic findings had shown complete esophageal obliteration, and a gastrostomy was performed. An endoscopic intervention was planned to use a two-team approach involving antegrade and retrograde endoscopy. The obstruction part was located at the upper thoracic esophagus using both endoscopes and esophagography. A retrograde guidewire was cannulated from the distal esophagus under fluoroscopic guidance. The guidewire position was checked from multidimensional fluoroscopic views to avoid false tract cannulation. Once the guidewire was nearly passed through the esophageal fibrotic septum, a stricturoplasty was performed from the antegrade endoscope. The guidewire was retrieved from the antegrade endoscope out of the oral cavity, and the esophagus was dilated with Savary-Gilliard dilators and a CRE balloon. A nasogastric tube was placed under direct endoscopic view. Results The procedure was successful, and the patency to the esophageal lumen was achieved. The patient’s symptoms improved, there was a decrease in saliva pooling. The patient was scheduled for serial dilatation of the esophagus to maintain luminal patency. Conclusion Endoscopic rendezvous technique is a safe therapeutic option for short-segment complete esophageal obliteration. Despite the complex procedure and multidisciplinary approach required, this technique can recanalize the esophageal lumen and avoid the need for surgical reconstruction.

261. THE PROGNOSTIC IMPACT OF PRE-OPERATIVE NUTRITIONAL INDICATORS OF THE PATIENTS WITH ESOPHAGEAL CANCER

Abstract Background Esophagectomy with or without concurrent chemoradiotherapy had been the treatment of choice for the patients with clinically operable esophageal cancer. In addition to the standard TNM status of the disease, it is unknown about whether pre-operative nutrition indicators, inclusive of hemoglobin value and albumin level before treatment, will have impact on post-operative survival outcome of these patients. Methods This is a retrospective study from a single medical center. We retrospectively reviewed and analyze the survival impact of various pre-operative nutritional indicators of esophageal cancer patients who received esophagectomy. Pre-operative indicators included age, gender, receiving concurrent chemoradiotherapy or not, alcohol, betel nuts and cigarette usage or not, lung function test, Hemoglobin value, Albumin level and white blood cell level. The survival impact of these parameters was evaluated with univariate as well as multi-variate analysis. Results Our study had totally retrospectively reviewed 1213 patients, which received esophagectomy between 1996 to 2022. Ratio of Male to Female is 1112 to 111, and 325 patients are older than 65 years old. Before operation, 746 among 1213 patients had received concurrent chemoradiotherapy. In univariate analysis, we found that Pre-operative Hemoglobin value (cut-off point 11.9) and Albumin level (cut-off point 4.1) had statistically significant difference on overall survival, with increased risk of mortality by the presence of lower level of Hb and albumin with P-value &amp;lt;0.001. The survival difference persisted after adjusted with TNM status under multi-variate analysis. Conclusion Our study showed that Pre-operative Hemoglobin value and Albumin level can be a significant prognosis factor of esophageal cancer patients who received esophagectomy. This significant result highlight the importance of nutritional status in caring the patients of esophageal cancer and suggested the possibility of improvement of survival by intervention of malnutrition during the course of treatment for esophageal cancer.

463. THE IMPACT OF PATHOLOGICAL TUMOR RESPONSE FOLLOWING NEOADJUVANT CHEMOTHERAPY AND CHEMORADIOTHERAPY FOR ESOPHAGEAL ADENOCARCINOMA. A RETROSPECTIVE MULTICENTER COHORT STUDY

Abstract Background Two multimodal strategies are available for the treatment of esophageal cancer: neoadjuvant chemotherapy (CT) and chemoradiotherapy (CTRT). The higher rate of pathological complete response (pCR) after CTRT is an argument to support this treatment. However, previous studies have failed to demonstrate a survival benefit of CTRT for adenocarcinoma (ADC) and the correlation between pathological tumor response (pTR) and survival is unclear. Methods This multicenter retrospective cohort study included data from 2 high-volume centers. Only patients with ADC who underwent CT or CTRT and surgery between 2012 and 2019 were included. The correlation between pTR and survival after both treatments was evaluated using Kaplan–Meier analysis. The 5-year overall (OS) and disease-free survivals (DFS) of patients showing pCR after the 2 treatments were compared. pTR was assessed using the Mandard tumor regression grade (TRG). Results Overall, 424 patients were included, 236 received CT and 188 CTRT. The incidence of pCR was 12.7% in the CT group and 26.1% after CTRT (p = 0.0005). At 5-years the OS rate after CT was 85.6% for TRG1 patients, 75.5% for TRG2, 57% for TRG3 and 42% for TRG4–5 (p = 0.004). After CTRT it was 72.8% for TRG1, 60.8% for TRG2, 39% for TRG3 and 27% for TRG4–5 (p = 0.0003) (figure 1). The OS of patients with pCR was not significantly different after CT and CTRT (p = 0.65). The 5-years DFS of pCR patients was higher in the CT group (86% vs. 70%, p = 0.05). Conclusion Despite a lower rate of pCR, both OS and, especially, DFS of pCR patients were improved after CT compared to CTRT. TRG showed to be significantly associated with survival in both treatment groups. The effectiveness of long-term disease control after CT and CTRT should be further analyzed in ADC.

33. QUALITY PERFORMANCE INDICATORS FOR THE SURGICAL TREATMENT OF OESOPHAGEAL CANCER- A SYSTEMATIC REVIEW

Abstract Background A systematic review was undertaken to identify existing quality performance indicators (QPI) for the surgical treatment of oesophageal cancer (OC) with the aim of defining a set of QPIs that can be used in accreditation and allowing comparison of treatment and outcomes across jurisdictions, and provide a basis to develop quality improvement programs. These QPIs capture key components of patient care that are fundamental to the overall outcomes. Methods A systematic literature review was conducted by searching MEDLINE, PubMed, EMBASE, and SCOPUS with all literature available until the date of 1st March 2022 included. Search terms utilised were Quality of health care OR Quality improvement OR Quality control OR Quality indicators OR Benchmark, AND Oesophagectomy OR Esophagectomy OR Oesophageal neoplasm OR Esophageal Neoplasm OR Adenocarcinoma OR Squamous Cell Cancer OR Oesophageal resection OR Esophageal Resection OR Oesophageal cancer OR Esophageal Cancer OR Ivor Lewis OR Oesophageal Surgery OR Esophageal Surgery. Results Twenty-five articles were included in the final analysis. The selected studies included editorials, retrospective review, prospective review, expert guidelines and consensus. For OC QPIs, process measures included multi-disciplinary meetings, access to perioperative multimodal diagnostic pathways, and surgical metrics (margin negative resections and adequate lymphadenectomy). Outcome measures included the RO resection rate, reoperation, readmission rate, and length of hospital stay. Conclusions This systematic review summarises QPIs for the surgical management of OC. The data from this review will form the basis of a project to develop internationally agreed QPIs for OC resections.

Clinical implications of dose to functional lung volumes in the trimodality treatment of esophageal cancer

Background Trimodality treatment, i.e., neoadjuvant chemoradiotherapy (nCRT) followed by surgery, for locally advanced esophageal cancer (EC) improves overall survival but also increases the risk of postoperative pulmonary complications. Here, we tried to identify a relation between dose to functional lung volumes (FLV) as determined by 4D-CT scans in EC patients and treatment-related lung toxicity. Materials and methods All patients with EC undergoing trimodality treatment between 2017 and 2022 in UZ Leuven and scanned with 4D-CT-simulation were selected. FLVs were determined based on Jacobian determinants of deformable image registration between maximum inspiration and expiration phases. Dose/volume parameters of the anatomical lung volume (ALV) and FLV were compared between patients with versus without postoperative pulmonary complications. Results of pre- and post-nCRT pulmonary function tests (PFTs) were collected and compared in relation to radiation dose. Results Twelve out of 51 EC patients developed postoperative pulmonary complications. ALV was smaller while FLV10Gy and FLV20Gy were larger in patients with complications (respectively 3141 ± 858mL vs 3601 ± 635mL, p = 0.025; 360 ± 216mL vs 264 ± 139mL, p = 0.038; 166 ± 106mL vs 118 ± 63mL, p = 0.030). No differences in ALV dose-volume parameters were detected. Baseline FEV1 and TLC were significantly lower in patients with complications (respectively 90 ± 17%pred vs 102 ± 20%pred, p = 0.033 and 93 ± 17%pred vs 110 ± 13%pred, p = 0.001), though no other PFTs were significantly different between both groups. DLCO was the only PFT that had a meaningful decrease after nCRT (85 ± 17%pred vs 68 ± 15%pred, p < 0.001) but was not related to dose to ALV/FLV. Conclusion Small ALV and increasing FLV exposed to intermediate (10 to 20 Gy) dose are associated to postoperative pulmonary complications. Changes of DLCO occur during nCRT but do not seem to be related to radiation dose to ALV or FLV. This information could attribute towards toxicity risk prediction and reduction strategies for EC.

Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.

Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.

Results of robot-assisted minimally invasive esophagectomy in 111 consecutive patients: an Asia cohort study

BackgroundRobot-assisted minimally invasive esophagectomy (RAMIE) is becoming increasingly popular as a treatment for esophageal cancer. The purpose of this study was to use the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA) to perform 111 consecutive cases of radical esophageal cancer and report the perioperative data of surgery and postoperative complications and short-term oncological outcomes.MethodsWe retrospectively analyzed 111 patients who underwent RAMIE conducted at Fujian Medical University Union Hospital from August 2016 to January 2021. Each patient’s characteristics, clinicopathological stage, postoperative pathological stage, surgery outcome, postoperative recovery, and short-term oncological outcomes were analyzed.ResultsOf the 111 patients who underwent RAMIE, 77 were male and 34 were female, and the mean age was 62.1 ± 8.8 years. Twenty-seven patients (24.3%) received preoperative neoadjuvant therapies, the most popular of which was preoperative induction chemotherapy in 16 cases (14.4%), followed by preoperative induction radiotherapy in 8 cases (7.2%) and preoperative induction chemotherapy plus immunization in 3 cases (2.7%). The vast majority of patients (110/111, 99.1%) underwent radical resection, with a mean intraoperative bleeding amount of 99.9 ± 68.4 mL and a mean operative time of 271.9 ± 70.0 min. The mean total number of lymph nodes removed was 40.9 ± 16.7, including 21.8 ± 9.0 thoracic lymph nodes. Fifty-five (49.6%) patients had lymph node metastases, including 17 (15.3%) with lymph node metastases in the left recurrent laryngeal nerve, 24 (21.6%) with lymph node metastases in the right recurrent laryngeal nerve, and 7 (6.3%) with lymph node metastases in the bilateral recurrent laryngeal nerve. The positive rate of left recurrent nerve lymph nodes was 4.77%, and he positive rate of right recurrent nerve lymph nodes was 8.38%. The main postoperative complications included pulmonary infection in 24 cases (21.6%), celiac disease in 3 cases (2.7%), tracheoesophageal fistula in 1 case (0.9%), anastomotic fistula in 3 cases (2.7%), postoperative cardiac arrhythmias in 11 cases (9.9%), VTE in 3 cases (2.7%), and pleural effusion (requiring postoperative tube drainage) in 13 cases (11.7%). Additionally, 2 cases of postoperative pneumothorax (1.8%), 1 case of poor incision healing (0.9%), 1 case of incomplete bowel obstruction (0.9%), 1 case of neck hematoma (0.9%), and 1 case of postoperative admission to the intensive care unit (0.9%) occurred. The median length of stay was 10.9 ± 6.1 days, and there were no cases of perioperative death.ConclusionsRobotic esophageal cancer radical surgery is safe and feasible. The surgeon can be proficient in thoracic robotic surgery and mediastinal lymph node dissection and achieve high levels of perioperative safety and short-term efficacy.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.