bluuebunny/crossref_metadata_2025 huggingface dataset:
526. COMPARISON OF CANCER CACHEXIA DEFINITIONS AND THEIR ASSOCIATION WITH OVERALL SURVIVAL IN PATIENTS WITH INCURABLE OESOPHAGOGASTRIC CANCER
Authors: Brown Leo , Yule Michael , Soupashi Maria , Laird Barry , Wigmore Stephen , Skipworth Richard
Published: September 2024

Background

Cancer cachexia is highly prevalent in oesophagogastric cancer, particularly amongst patients with advanced stage disease. However, classifications for cachexia remain heterogenous within the existing literature. The aim of this study is to compare prognostication using the Fearon et al. consensus definition to the Global Leadership Initiative on Malnutrition (GLIM) criteria, in patients with incurable oesophagogastric cancer.

Methods

Consecutive patients with newly diagnosed incurable oesophagogastric cancer between 2019-2020 were identified from a prospectively maintained regional database. Data were collected regarding demographics, clinicopathological details, patient-reported involuntary weight loss and body mass index. CT body composition analysis was performed using staging scans and neutrophil-lymphocyte-ratio was retrieved as a marker of inflammation at the time of diagnosis. These data allowed comparison based on Fearon and GLIM classifications for cachexia. The primary outcome of interest was overall survival.

Results

Overall, 330 patients (66.9% male, median 74 years) were diagnosed with incurable oesophageal (70.6%) or gastric cancer (29.4%) during the study period. Of these 65.5% (n=216) met the Fearon definition of cachexia at diagnosis, while 64.8% (n=214) could be diagnosed based on the GLIM criteria. Both diagnostic criteria were met by 148 patients (47.9%). Clinicopathological characteristics were all broadly comparable between cachectic and non-cachectic groups based on both classifications. Worse overall survival was seen in cachectic patients using Fearon (median: 118 vs. 228 days) and GLIM (median: 114 vs. 245 days) diagnostic criteria (both p<0.001). Following adjustment for known confounders, cachexia diagnosed based on the GLIM criteria (HR 1.60 (95%CI: 1.25-2.05), p<0.001) was more strongly associated with adverse survival than that diagnosed using the Fearon criteria (HR: 1.44 (95%CI: 1.13-1.84), p=0.003)).

Conclusion

Cancer cachexia is strongly associated with worse survival in patients with incurable oesophagogastric cancer. Diagnosis based on the GLIM criteria appears to have the greatest prognostic effect.
536. TUMOR-INFORMED “LIQUID BIOPSY” FOR ESOPHAGEAL ADENOCARCINOMA FROM MATCHED CANCER ORGANOID CULTURE
Authors: Rispoli Thaiane , Shathasivam Premalatha , Aiyar Niharikaa , Allen Jonathan , Alisson Frances , Bach Yvonne , Dakpo Eugenia , Sundby Adam , Wilson Gavin , Yeung Jonathan
Published: September 2024

Background

The absence of recurrent mutations in esophageal adenocarcinoma (EAC) poses a challenge in detecting circulating tumor DNA (ctDNA) in plasma and may hinder the advancement of liquid biopsy methods. To address this, we cultured patient-derived EAC organoids (PDOs), speculating that they could serve as a guide for identifying ctDNA in the patient's blood samples. This approach aims to leverage organoids as a potential tool to overcome the complexity of identifying ctDNA in EAC, offering a promising avenue for refining liquid biopsy strategies in clinical practice.

Methods

PDOs were generated from EAC tumor tissue in Matrigel domes and expanded in suspension culture. To isolate mononucleosomes (147 bp), chromatin from PDOs was extracted and digested with micrococcal nuclease (MNase). Fragments larger than 147 bp were removed through size selection. MNase-sequencing was performed to generate a mutation map with preferential coverage of nucleosome-protected DNA for each sample. Matched whole genome sequencing of the tumor for each respective PDO sample was used as a control. Primers were designed for the identified mutations in nucleosome-protected DNA and used to amplify patient cfDNA for sequencing.

Results

DNA from five different PDOs were collected and MNase digested. MNase concentration and digestion time were optimized for each sample. MNase digestion produced mononucleosomes of approximately 147 bp for all samples. MNase-sequencing identified 24 mutations in peaks (mononucleosomes) in 24 genes, including known oncogenes. Among these were 16 missense, 2 frameshift, and 1 nonsense mutations, and 5 mutations in splice regions. To date, amplicons of expected size were detected by PCR for six genes using either total PDO DNA or normal cell-free DNA, confirming the detectability of these genes. PCR amplification using patient ctDNA and next-generation sequencing is ongoing.

Conclusion

These findings show that we are able to isolate and detect somatic mutations in nucleosomes from different PDOs, allowing us to generate a nucleosome SNV map for each sample. Preliminary data indicate these regions can be PCR amplified from normal cfDNA. Amplification and sequence verification of mutated regions from corresponding patient blood ctDNA is ongoing. The mapping of patient-specific variants will enable the development of targeted personalized PCR panels, aiding in recurrence prediction and enhancing drug screening accuracy. This advancement holds promise for early cancer detection and improving prognoses for individuals with EAC by addressing gaps in recurrence prediction.
537. ASSESSING THE EFFECT OF HIATAL HERNIA SIZE ON PERIOPERATIVE OUTCOMES AND HOSPITAL READMISSION RATES AFTER PRIMARY REPAIR
Authors: Latorre-Rodriguez Andres R , Rajan Ajay , Mittal Sumeet K
Published: September 2024

Background

Minimally invasive hiatal hernia (HH) repair remains the gold standard for correcting mechanical defects due to its safety and favorable clinical outcomes (i.e., relief of patient symptoms). However, several operative factors, including the HH size, may negatively impact the postoperative course. We aimed to determine if an increase in HH size was related to an increased risk of perioperative complications or hospital readmissions.

Methods

After IRB approval, we performed a retrospective analysis using a prospectively maintained database containing demographic, perioperative, and clinical data from all patients who underwent HH repair by a single experienced foregut surgeon between September 2016 and July 2023. Four groups were defined based on the proportion of stomach at the thoracic cavity determined during the surgery: A (small HH: <25%), B (moderate HH: 25-49%), C (large HH: 50-74%), and D (intrathoracic stomach [ITS]: ≥75%). Non-parametric tests were used to assess differences between the groups, and logistic regressions were used to determine the relevant odds ratios (OR).

Results

A total of 391 patients who underwent primary HH repair met the inclusion criteria (73.7% women; mean age 64.4±12.5 years; mean BMI 28.9±4.9 kg/m2). The distribution of groups was: A (n=160, 40.9%), B (n=63, 16.1%), C (n=64, 16.4%), and D (n=104, 26.6%). Patients presenting with ITS (group D) were older, had longer operative duration, greater blood loss (p<.001), and a significantly increased risk of presenting with early postoperative complications (OR 2.78 [CI95: 1.52-5.06]) and being admitted to the ICU (OR 12.35 [CI95: 3.41-44.71]).

Conclusion

The HH size, defined by the proportion of the stomach at the thoracic cavity, is associated with an increased risk of early postoperative complications and ICU admission; moreover, a trend toward higher 30- and 90-day hospital readmission rates was noted. This factor may be a consequence of the progressive nature of the disease; hence, it should be considered when choosing between continued medical observation and surgical treatment of patients presenting with asymptomatic HH. An early intervention may reduce the risk of postoperative comorbidity.
539. ASSOCIATION BETWEEN WAITING PERIOD FOR RADICAL SURGERY AND POSTOPERATIVE RELAPSE IN CLINICAL STAGE I ESOPHAGEAL CANCER
Authors: Miyawaki Yutaka , Sato Hiroshi , Lee Seigi , Kobayashi Ryota , Takabatake Kazuya , Toriumi Tetsuro , Ehara Gen , Hirano Yasumitsu , Okamoto Kojun , Koyama Isamu , Sakuramoto Shinichi
Published: September 2024

Background

Esophagectomy with locolegional lymphanedectomy based on potential lymph node metastatic risk is the current standard treatment for clinical Stage I thoracic esophageal cancer. Local excision by endoscopic submucosal dissection (ESD) is the standard treatment for clinical Stage 0, however surgery is considered as an additional treatment for pathological T1b cases due to potential metastatic risk. Cases of additional resection after ESD are those pathologically demonstrated to have a high risk of metastasis based on tumor depth and vascular invasion, etc. Compared to cases of surgery for clinical Stage I, many of these cases have a high risk of metastasis, and therefore a poor prognosis is generally expected. Addionally, the prolonged waiting time between initial diagnosis and radical surgery due to ESD may be a factor in poor prognosis, but there is currently no consensus on the risk. Therefore, we conducted a study to clarify the effect of waiting period before surgery (WP) on the risk of recurrence in clinical Stage I esophageal cancer surgery.

Methods

We retrospectively evaluated the association between WP and 3-year postoperative recurrence-free survival (3y-RFS) in 65 patients who underwent primary esophagectomy and gastric tube reconstruction for clinical Stage I esophageal cancer and 22 patients who underwent additional resection after ESD at our hospital.

Results

The WP of 87 patients was 2.12 ± 1.43 months (mean± SD), and 13 patients had postoperative recurrence (3y-RFS 85.1%). A 2-arm comparison of short or long WP with a cutoff value of 2.83 months (mean+0.5 SD) showed no clear association with 3y-RFS (100% vs 81.4%, p=0.071). A strong correlation was shown between WP and ESD (r=0.647, p<0.01). WP was 1.69±1.20 months (mean± SD) in 65 patients who underwent surgery as initial treatment, and 12 patients had postoperative recurrence (3y-RFS 81.5%). A 2-arm comparison of short or long WP with a cutoff value of 2.29 months (mean+0.5 SD) suggested an association with 3y-RFS (85.7% vs 55.6%, p=0.018).

Conclusion

Although this is a single-center, retrospective study of a small number of cases and only a univariate study due to the small number of events, it suggests that a longer waiting period before surgery may be a risk factor for postoperative recurrence.
541. THE PHOENIX-HH SCORE: A TOOL TO PREDICT ADMISSION TO THE ICU AFTER HIATAL HERNIA REPAIR
Authors: Latorre-Rodriguez Andres R , Rajan Ajay , Bremner Ross M , Mittal Sumeet K
Published: September 2024

Background

Minimally invasive hiatal hernia (HH) repair is usually a safe procedure with low morbidity; however, a subset of patients may require intensive care unit (ICU) admission. To date, no specific and validated tool is available to predict the risk of ICU admission after HH repair. Although multiple tools to predict the risk of admission to the ICU after major surgical procedures have been reported, most of them are complex and require laboratory parameters. We propose a novel and quick intraoperative score that is useful for assessing unexpected ICU admission and tailoring patient management during HH repair.

Methods

A development cohort was established using a prospectively maintained database containing demographic, clinical, and surgical information of consecutive patients who underwent HH repair between September 2016 and July 2023. Clinical expertise and multiple logistic regressions were employed to select adequate demographic or surgical predictors to create an intuitive risk score (PHOENIX-HH). Further, a specific scoring system for each included variable was designated, and the total score (a scale from 0 to 9 points) was assessed for accuracy using the area under the receiver operating characteristic curve (AUC-ROC).

Results

The development cohort was formed by 391 patients who underwent primary HH repair (73.7% women; mean age 64.4±12.5 years; mean BMI 28.9±4.9 kg/m2). The mean AUC in the development cohort was 0.845 (95%CI: 0.756-0.934), and when defining a cut-off of ≥6 points, 12 of 15 patients who required ICU admission were identified using the proposed score (sensitivity, 80% [95%CI: 51.9-95.7%]; specificity, 80.1% [95%CI: 75.7-84%]; positive likelihood ratio, 4.0 [95%CI: 2.9-5.6]; negative predictive value, 99.0% [95%CI: 97.3-99.6%]).

Conclusion

The strongest predictor for unexpected ICU admission and postoperative complications following HH repair was the HH size (defined as the percentage of intrathoracic stomach); hence, the incorporation of this variable and other preoperative and intraoperative factors into a scoring system led to the development of the PHOENIX-HH score. This tool may allow early identification of patients who may require admission to the ICU after the surgery. Future validation using an external cohort is highly desirable.
549. CLINICAL IMPLICATIONS OF SELECTIVE RIGHT PARATRACHEAL LYMPH NODE DISSECTION IN PATIENTS WITH EARLY-STAGE ESOPHAGEAL CANCER: PROPENSITY-SCORE MATCHED ANAYLSIS
Authors: Kwon Yelee , Yun Jae Kwang , Kim Hyeong Ryul , Kim Yong-Hee , Jeong Jae Hwa
Published: September 2024

Background

The optimal extent of lymph node dissection in esophageal squamous cell carcinoma (Sqcc) still remains a topic of debate without specifying the lymph node stations. This study aimed to evaluate the clinical impact of selective right paratracheal lymph node (RtPTLN) dissection in patients with esophageal squamous cell carcinoma (SQCC).

Methods

We included the patients who underwent curative surgery for clinical stage I esophageal SQCC (cT1N0) at our institution between January 2010 and December 2021. Patients who underwent neoadjuvant therapy were excluded.

A total of 1,484 patients underwent surgery for esophageal cancer at our institution during the study period. Among these, 658 patients (mean age 63.1±7.7 years, 46 [7.0%] women) were identified, categorized into RtPTLN+ (dissection performed, n = 88) and RtPTLN- (no dissection, n = 570) groups. The RtPTLN+/- groups were matched in a 1:3 ratio using propensity scores.

Results

Median follow-up was 48.8 (24.2–85.2, interquartile) months. Five-year overall survival (OS, RtPTLN+ vs. RtPTLN-, 75.8% vs. 79.0%, P = 0.38) and recurrence-free survival (RFS, 70.0% vs. 72.5%, P = 0.55) rates showed no significant differences.

Propensity-score matching yielded 313 patients: RtPTLN+ (n = 83) and RtPTLN- (n = 230). OS and RFS rates did not significantly differ between RtPTLN+ and RtPTLN- groups (OS: 77.2% vs. 79.9%, P = 0.57; RFS: 72.1% vs. 74.7%, P = 0.79) after adjustment (Figure). Multivariate analysis confirmed that RtPTLN dissection was not a significant predictor for OS or RFS (Table).

Conclusion

In this propensity-score matched analysis, there was no significant difference in OS and RFS between patients with and without RtPTLN dissection. These findings discreetly suggest that the routine RtPTLN dissection may not be necessary, and selective dissection could be considered acceptable.
552. COMPARING ROBOTIC ESOPHAGECTOMY TO VIDEO-ASSISTED THORACOSCOPIC ESOPHAGECTOMY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA: RESULTS FROM THE REVATE RANDOMIZED CLINICAL TRIAL
Authors: Chao Yin-Kai , Li Zhi-Gang , Jiang Hongjing , Chiu Chen-Hung , Li Bin , Shang Xiaobin
Published: September 2024

Background

The treatment of esophageal squamous cell carcinoma (ESCC) includes dissecting lymph nodes along the recurrent laryngeal nerve (RLN), which is oncologically important but is technical demanding. Vocal cord palsy as a result from RLN injury, carries significant morbidities. This randomized clinical trial (RCT) compared the efficacy and safety of robotic esophagectomy (RE) and video-assisted thoracoscopic esophagectomy (VATE) for performing RLN lymph node dissection (LND)

Methods

We conducted a multicenter RCT(NCT03713749) from November 2018 to March 2022, enrolling patients with ESCC who required McKeown esophagectomy. The primary endpoint was to determine the success rate of left RLN LND. Success was defined as the removal of lymph nodes confirmed by pathology, without causing permanent nerve palsy (duration > 6 months). Secondary endpoints encompassed perioperative and oncological outcomes.

Results

The per-protocol analysis included data from 203 patients (RE group: n=103; VATE group: n=100). The primary endpoint was achieved in 88.3% of the RE group and 69% of the VATE group (p<0.001). Additionally, the RE group had a higher mediastinal lymph node harvest (16 [12−22] versus 14 [10−20], p=0.04), shorter thoracic operating time (110 [89−137] min versus 124[103.5−154] min, p=0.004), and earlier drainage removal (4 [3−7] days versus 6 [4−9] days, p=0.007) compared to the VATE group. The two study arms exhibited comparable complication rates with no recorded in-hospital deaths in either group.

Conclusion

This multicenter trial demonstrates the effectiveness of RE in enhancing the feasibility and safety of RLN LND in ESCC. Additionally, RE leads to an improved mediastinal lymphadenectomy, shorter operating times, and earlier removal of drainage.
556. PREDICTORS OF EARLY RECURRENCE AFTER OESOPHAGECTOMY AND NEOADJUVANT FLOT
Authors: Dayanamby Abbienaya , Chmelo Jakub , Phillips Alexander W
Published: September 2024

Background

FLOT, a novel type of perioperative chemotherapy, has led to improved survival after surgery for oesophageal adenocarcinoma. Yet, rates of cancer recurrence remain high. There is limited research on predictors for early recurrence (ER) in patients receiving FLOT. The aim of this study was to investigate ER and survival rates and identify risk factors of ER.

Methods

Patients who underwent neoadjuvant FLOT and oesophagectomy for oesophageal and oesophagogastric junction adenocarcinomas at a single high-volume centre between August 2018 and January 2023 were evaluated for ER, defined as disease present within one year of surgery. Multivariable logistic regression was conducted to identify risk factors for ER. Patients who died in-hospital or within 90 days of surgery and those with positive longitudinal margin were excluded.

Results

145 patients were included. 139 (95.9%) and 63 (43.4%) patients fully completed neoadjuvant and adjuvant FLOT. 44 patients (30.3%) developed recurrence and 22 patients (15.2%) had ER in the follow up period. Distant, local or mixed type of recurrence was found in 32, 6 and 6 patients respectively. The estimated recurrence free survival and overall survival at one, two and three years were 81.4%, 66.9%, 52.0% and 89.0%, 73.7%, 65.5% respectively. The estimated median survival after recurrence was 4.9 months. In multivariable analysis ypN3 status was identified to be an independent predictor of ER (OR 13.769, 95%CI 1.358-139.573, p=0.026).

Conclusions

This study confirms that ER after neoadjuvant FLOT is common. Patients with a high pathological nodal stage are particularly at risk. It is possible that some patients with ER might have undetected metastases prior to surgery and some do not respond well to neoadjuvant treatment. Identifying chemotherapy non-responders is an important area for future research. These results might be beneficial for prognostication and tailoring follow up care, such as regular surveillance imaging, treatment, and frequency of reviews.
559. SURGICAL PROCEDURE AND CLINICAL OUTCOME OF TRANSMEDIASTINAL ESOPHAGECTOMY FOR ESOPHAGEAL CANCER
Authors: Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Nishibeppu Keiji , Ohashi Takuma , Shimizu Hiroki , Arita Tomohiro , Yamamoto Yusuke , Morimura Ryo , Kuriu Yoshiaki , Ikoma Hisashi , Kubota Takeshi , Otsuji Eigo
Published: September 2024

Background

We started performing esophagectomy by a laparoscopic transhiatal approach in 2009, and 577 patients had undergone to date. Furthermore, we started performing single-port mediastinoscopic cervical approach in 2014, and developed a technique for total mediastinal lymph node dissection (390 patients).

Methods

The upper and middle mediastinal lymph node dissection including lymph nodes along the left recurrent laryngeal nerve, using a left cervical approach, was performed with a single-port mediastinoscopic technique. This approach with pneumomediastinum by AirSeal System improved the visibility and handling in the deep mediastinum around the aortic arch. We recently performed intraoperative monitoring of the recurrent laryngeal nerve using Nerve Integrity Monitor system. For dissection of upper and middle mediastinal lymph nodes, the left recurrent laryngeal nerve was sometimes compressed by the shaft of the sealing device or the retractor. We used continuous monitoring with the Automatic Periodic Stimulation electrode for the left recurrent laryngeal nerve, and immediately recognized dangerous procedures. Frequency of recurrent laryngeal nerve palsy was dramatically reduced to half by the introduction of Nerve Integrity Monitor system. Furthermore, to understand the anatomy of bilateral bronchial arteries, we performed 3-dimensional computed tomography angiography preoperatively, which was crucial to avoid intraoperative bleeding.

Results

The outcome of patients performed transmediastinal radical esophagectomy was compared with those performed the right thoracotomy by using propensity score matching. The operative time, the operative bleeding, and postoperative respiratory complications were significantly decreased by transmediastinal radical esophagectomy.

Conclusion

Our surgical procedure resulted in a good surgical view, safe en-bloc mediastinal lymph node dissection, and the decrease of postoperative respiratory complications.

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563. CURRENT AND PROPOSED TREATMENT STRATEGIES FOR LOCALLY ADVANCED ESOPHAGEAL ADENOCARCINOMA OF THE ESOPHAGOGASTRIC JUNCTION
Authors: Narumiya Kosuke , Kudo Kenji , Toyoshima Yukinori , Ide Hiroko , Osugi Harushi , Okamura Yukiyasu
Published: September 2024

Background

The optimal treatment strategy for locally advanced esophageal adenocarcinoma of the esophagogastric junction (AEG) is still unclear, and no consensus exists whether to treat it as an esophageal cancer or as a gastric cancer, which would include adjuvant therapy. The purpose of this study was to determine the optimal lymph node dissection, considering lymph node metastases and to develop a strategy for treatment that includes adjuvant therapy to improve the survival rate.

Methods

The patients were selected from a retrospective study by the Department of Surgery, Institute of Gastroenterological Surgery, Tokyo Women’s Medical University, that was conducted from 1990 to 2019. We studied 88 cases of advanced AEG in patients who underwent surgery with lymph node dissection. We retrospectively investigated the patient characteristics, pathological findings, surgical procedures, optimum extent of lymph node dissection, location of metastatic lymph nodes, recurrence pattern, and survival curves.

Results

Positivity for H. pylori was 29.8%. Barrett esophagus was found in 33%. Barrett esophagus was low. The calculated index for each nodal station was in stations 1, 2, 3, 7, 11 and 110 for 3-year survival and in stations 1, 2, 3 and 7 for 5-year survival. The proportion with undifferentiated histological type was high. The surgical approach underwent lower esophagectomy + proximal gastrectomy. Double-tract reconstruction was performed in 45%. Adjuvant (postoperative) chemotherapy was given to 51% patients. Preoperative (neoadjuvant) chemoradiotherapy was 17%. The 5-year overall survival rates were 24%.

Conclusion

We found that the optimal lymph node resection consists of the inferior mediastinum (No. 110), the lesser curvature (Nos. 1, 3, 7), No. 2, and No 11. When esophageal involvement was > 40 mm, we performed esophagectomy including upper thoracic lymph nodes. We were not satisfied with the result of surgical treatment including lymph node dissection alone in advanced AEG. We will recommend nab-paclitaxel combined with radiotherapy for advanced AEG to improve the survival rate.
569. PROGNOSTIC VALUE OF T CELL PHENOTYPES AND PD-L1 EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Toyozumi Takeshi , Hu Jie , Murakami Kentaro , Uesato Masaya , Nakano Akira , Kurata Yoshihiro , Hayano Koichi , Matsumoto Yasunori , Otsuka Ryota , Arasawa Takahiro , Takahishi Yumiko , Matsubara Hisahiro
Published: September 2024

Backgrounds

The tumor microenvironment (TME) is a complex niche for tumor cells and immune cells to survive. Tumor-infiltrating lymphocytes (CD8+ T cells, FoxP3+ Tregs…etc), one of the main components of TME, are key factors in the host-tumor immune response, and the exact immune response in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression of PD-L1 and TILs phenotypes in ESCC, their interactions and clinical significance.

Methods

Surgical specimens from 126 ESCC patients who underwent curative surgery between January 2001 and April 2017. We performed immunophenotyping of CD4, CD8, CD25, FOXP3 and PD-L1 within the tumor using immunohistochemistry and multiple immunofluorescence immunolabeling. PD-L1 was detected to expressed on tumor cells (PD-L1 TC) and tumor-infiltrating immune cells (PD-L1 TIIC), and PD-L1 TC affect biologic behavior. The calculation of overall survival (OS) and recurrence-free survival (RFS) were made using Kaplan-Meier analysis, and Cox regression model was used to analyze the correlation between survival and prognosis.

Results

CD8, FoxP3 and PD-L1 expression were positive in 40 (31.7%), 55 (43.7%) and 35 (27.8%) ESCC patient, respectively. CD8 and FoxP3 positive were associated with prolonged OS (p=0.0028, p=0.0324, respectively) and RFS (p=0.0019, p=0.0628, respectively). The overall survival rate in the PD-L1 positive group was statistically lower than that in the negative group (p=0.0402). Furthermore, the combination of CD8/PD-L1 and CD8/Foxp3 was able to more clearly classify and predict prognostic groups of ESCC. Considering the Treg phenotype, the presence of triple positive cell infiltration with Foxp3, CD4, and CD25 was strongly associated with poor prognosis of ESCC (p=0.0349). Cox proportional hazard model suggested that tumor depth, CD8+ infiltration and PD-L1 expression were significantly correlated with overall survival. CD8+ infiltration and PD-L1 expression were revealed to be independent prognostic factors.

Conclusion

CD8 and PD-L1 expression are independent prognostic and predictive factors for ESCC. And it is necessary to elucidate the immune mechanism comprehensively and thoroughly in the insight of multidimensional, multi-molecular and to provide therapeutic strategies for immunotherapy of ESCC.
572. TECHNICAL DETAIL AND SHORT-TERM OUTCOMES OF ROBOT-ASSISTED CERVICAL ESOPHAGECTOMY (RACE) WITH BILATERAL CERVICAL APPROACH FOR ESOPHAGEAL CANCER
Authors: Fujita Takeo , Fujiwara Naoto , Sato Kazuma , Kajiyama Daisuke , Shigeno Takashi , Daiko Hiroyuki
Published: September 2024

Background

The transcervical mediastinoscopic esophagectomy is a relative new technique that has gradually demonstrated because of its ease of dissection along the organ sheath and its less invasive nature. However, the conventional cervical approach to mediastinoscopy has been reported to have a relatively high rate of recurrent nerve palsy due to interference in the mediastinum caused by the straight forceps.

The robot-assisted transcervical esophagectomy (RACE) approach is novel procedure expected to reduce these interferences and improve maneuverability around the recurrent nerve. In this report, we describe a surgical technique and short-term outcome of RACE.

Methods

In this study, we included 26 RACE cases performed between Feb 2023 to Feb 2024.

Principally, our hospital performs transcervical esophagectomy mainly on patients who are difficult to approach by transthoracic approach due to history of thoracic diseases, etc.

In our department, transcervical esophagectomy is usually performed via a bilateral cervical approach, starting from the right neck and continuing to the left neck, and RACE is performed using the da Vinci Xi via a bilateral cervical approach as well. Recently, we have been shortening the operation time by performing simultaneous cervical and abdominal operations without muscle relaxation using NIM.

Results

Patient background: mean age 74.5, male to female ratio 22:4, cStage I/II/III/IV: 13/3/9/1, NAC: 46.1%, more than 80% had some history of pulmonary disease/systemic history.

All patients underwent RACE via bilateral cervical approach, and no intraoperative complications or thoracoscopic conversion were observed. Postoperative complications (CD Grade≥1) included recurrent nerve palsy in 15.6% and respiratory complications in 7.6%. In addition, the recent operation with simultaneous cervical/abdominal NIM and no muscle relaxant has significantly shortened the average total operative time to 4 hours and 40 minutes.

Conclusion

Robot-assisted Cervical Esophagectomy (RACE) is a relatively safe procedure that offers a natural anatomic approach, fewer respiratory complications, and a significant reduction in operative time due to simultaneous neck and abdominal manipulation. With the advancement of robotics and devices, RACE is expected to become more effective and more widely used in the future.
573. SHORT- AND LONG-TERM RESULTS OF RAMIE IN BORDERLINE CT3 /T4B ESOPHAGEAL CANCER AT INITIAL DIAGNOSIS: COMPARISON WITH CONVENTIONAL MIE
Authors: Fujita Takeo , Fujiwara Naoto , Sato Kazuma , Kajiyama Daisuke , Shigeno Takashi , Daiko Hiroyuki
Published: September 2024

Background

Conversion esophagectomy in patients with locally advanced esophageal cancer, initially deemed unresectable, but which has responded to prior therapy, remains unclear. Recently, the utility of RAMIE for locally advanced esophageal cancer has come under discussion. In this study, we first analyzed the short- and long-term outcomes of RAMIE, then investigated the outcomes of conversion RAMIE in cT3br/T4b patients, and compared them with those of conversion using conventional MIE.

Methods

Between January 2020 and August 2023, thirty-three patients with locally advanced esophageal cancer initially diagnosed as cT3br/T4b, who underwent RAMIE after prior treatment, were analyzed, and short-term and long-term postoperative outcomes were evaluated. Additionally, these 33 patients who underwent RAMIE for cT3br/T4b were compared to 48 patients with initial cT3br/T4b who underwent conventional MIE during the same period.

Results

The mean age of RAMIE patients with cT3br/T4b was 63.2 years, with a male-to-female ratio of 26:7, and a clinical stage III/IV distribution of 12/21. Nearly all patients received preoperative treatment with induction chemotherapy (e.g., induction-DCF) or definitive chemoradiation. Among these patients, three underwent R1 or R2 resection. Surgical complications included pneumonia in 18.1% of cases, recurrent nerve palsy in 12.1% (excluding complicated resection cases), and anastomotic leakage in 7.4%. Regarding long-term survival, the 3-year overall survival (3yOS) was 66.2%, and the 3-year disease-free survival (3yDFS) was 48.7% in patients who underwent RAMIE with initial cT3br/T4b.

In the 48 patients who underwent esophagectomy with conventional MIE after pretreatment with cT4br/T4b status, the 3yOS was 52.7%, and the 3yDFS was 40.3%. These survival results for conventional MIE were lower than those for patients who underwent RAMIE (p=0.02).

Conclusion

The short- and long-term outcomes of RAMIE, including cases of T3br/T4 were described, and they were deemed acceptable. Regarding recurrence, local/regional disease control was considered relatively good.
579. DUPILUMAB IMPROVES ENDOSCOPIC FEATURES OF EOSINOPHILIC OESOPHAGITIS IN CHILDREN WITH EOSINOPHILIC OESOPHAGITIS: 52-WEEK ANALYSIS OF THE EOE KIDS STUDY
Authors: Schlag Christoph , Hirano Ikuo , Schroeder Shauna , Chehade Mirna , Menard-Katcher Calies , Hundal Navneet Virk , Liu Ruiqi , Abdulai Raolat , Maloney Jennifer , Glotfelty Lila , Radin Allen
Published: September 2024

Introduction

Eosinophilic oesophagitis (EoE) is a chronic type 2 inflammatory disease. Dupilumab, a fully human monoclonal antibody that blocks drivers of type 2 inflammation, is approved in the USA for EoE patients aged ≥1 year, weighing ≥15 kg, and in the EU for adult and adolescent EoE patients aged ≥12 years, weighing ≥40 kg. The EoE-Endoscopic Reference Score (EREFS) is a validated tool for assessing oesophageal features of EoE, with subscores for inflammation and remodelling. This study assessed the impact of dupilumab on EREFS in children aged 1–<12 years with active EoE in the phase 3 EoE KIDS trial.

Methods

In Part A, 102 patients (mean [SD] age: 7.1 [3.05] years) were randomised 2:2:1:1 to receive weight-tiered dupilumab higher-exposure (HE) or lower-exposure, or placebo (two groups) for 16 weeks. In Part B, all patients received dupilumab at their preassigned dupilumab regimen for a further 36 weeks. This analysis focused on the dupilumab HE and placebo groups. EREFS were scored centrally by reviewers blinded to both treatment allocation and time point. Absolute change from baseline in EREFS total score (0−18), and EREFS inflammation (0−10) and remodelling (0−8) subscores were assessed at Weeks 16 and 52.

Results

A total of 37 and 34 patients received dupilumab HE and placebo, respectively; baseline mean EREFS scores were similar across treatment groups (6.8 vs 7.3) with EREFS inflammation subscores higher than remodelling subscores (6.0 vs 0.9 in the total population). EREFS total score was significantly reduced at Week 16 with dupilumab HE versus placebo (LS mean difference -3.8 [95% CI: -4.9, -2.6], P<0.0001), with improvement sustained through Week 52 in the dupilumab HE group (figure). Similar improvements were observed for EREFS inflammation subscore. Assessment of changes in remodelling was limited by low prevalence of fibrostenotic features in young children.

Conclusion

Dupilumab HE led to significant improvement in EREFS total score at Week 16 versus placebo, which was sustained through Week 52. Dupilumab HE also improved EREFS inflammation subscore.
582. LOW EXPRESSION OF FRG1 PROMOTES MIGRATION AND INVASION IN ESOPHAGEAL CANCER
Authors: Zeng Ya , Su Xi , Zhou Tongfang , Wang Yunfeng , Jia Jingyi , Gao Jie , Deng Yuezhen , Fu Xiaolong , Cai Xuwei
Published: September 2024

Purpose

Distant metastasis is the primary cause of mortality among patients with esophageal cancer. Although FRG1 is known to play a role in the metastasis of various cancers, its specific function in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. In this study, we aimed to explore the role and potential molecular mechanism of FRG1 in the metastasis of ESCC.

Methods

Whole-exome sequencing was performed in ESCC patients who experienced distant metastasis (DM group) and those without metastasis within two years (non-DM group). Bioinformatics analysis and Immunohistochemistry (IHC) validation were conducted. In vitro, FRG1-overexpressed ESCC cell lines were established with lentivirus and validated by western blots. The wound-healing assay, transwell migration and invasion assay were performed in esophageal cancer cell lines. Additionally, RNA sequencing was conducted in ESCC cells to identify potential pathways involved.

Results

Mutations in FRG1 were more frequently observed in DM group compared to those in non-DM group. IHC revealed that the expression of FRG1 in DM group was significantly lower than non-DM group. In vitro, our results showed that ESCC cells with low FRG1 expression exhibited enhanced migration and invasion capabilities. Conversely, overexpression of FRG1 inhibited migration and invasion in ESCC cells. Mechanistically, RNA sequencing analysis showed a total of 93 differential expression genes between FRG1-overexpressed cells and the negative control. Notably, most differential genes were mainly enriched in the PPAR pathway and tyrosine metabolism pathway.

Conclusion

Our findings suggest that low FRG1 expression in patients may be indicative of rapid distant metastasis. The significant impact of FRG1's abnormal expression on the migration and invasion of ESCC cells highlights its potential as a therapeutic target for treating esophageal squamous cell carcinoma.
586. VALUE OF PEPSIN IN SALIVA TO ASSESS THE POSTOPERATIVE OUTCOME OF PATIENTS WITH GERD
Authors: Weitzendorfer Michael , Wallner Eva Johanna , Rabl Charlotte , Emmanuel Klaus , Koch Oliver Owen
Published: September 2024

Background

The aim of this study was to evaluate the value of salivary pepsin to assess the outcome of surgical treatment of patients with gastroesophageal reflux (GERD).

Methods

Forty-five consecutive patients with GERD despite proton pump inhibitor treatment received laparoscopic anti-reflux surgery (LARS). 24-hour esophageal pH-monitoring (MII-pH) and esophageal manometry (HRM) data were documented preoperatively and at 3-month follow-up. Clinical symptoms were rated with the Gastrointestinal Quality of Life Index (GIQLI) and gastrointestinal symptoms were evaluated by a standardized symptom checklist (SCL), assessing the severity and intensitiy of 14 different symptoms. Simultaneous to MII-pH the collection of 3 saliva samples per patient was performed. Treatment failure was defined as improvement of GIQLI and SCL of < 10 points, despite showing a normal DeMeester score.

Results

At baseline, all patients showed a pathological MII-pH measurement. Furthermore, all patients showed postoperatively a normal DeMeester score (mean 7.10 ± 4.56). Ten patients were defined as treatment failures with a change of pepsin concentration from a mean value of 198.73 ng/mL to 186.00 ng/mL (p>0.05). In patients defined as treatment success, mean pepsin value decreased from 205.83 ng/mL to 85.24 ng/mL (p<0.001).

Conclusion

Salivary pepsin could be a marker for treatment success after LARS. However, larger studies are required to reach firm conclusions.
587. PD-L1 EXPRESSION AND CD8+ TUMOR-INFILTRATING LYMPHOCYTES CHANGES AFTER PREOPERATIVE CHEMORADIOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Kim Hak Jae , Kim Byoung Hyuck , Lee Clinical Fellow Tae Hoon
Published: September 2024

Background

Neoadjuvant chemoradiotherapy (nCRT) has been established as a standard treatment for locally advanced esophageal squamous cell carcinoma (SqCC), but there are still insufficient research advances on the incorporation of immunologic agents. The aim of this study was to explore immune microenvironment changes before and after nCRT.

Methods

A total of 101 patients who underwent nCRT followed by radical surgery for esophageal SqCC in a single institution between 2005 and 2021 were analyzed. Pre-nCRT endoscopic biopsy and post-nCRT surgical specimen were evaluated using tissue microarray. Immunohistochemical staining for CD3, CD8, and PD-L1 were performed. Tumor-infiltrating lymphocytes (TIL) density were independently evaluated by blinded pathologist (total number of 2+ to 3+ cells/total area (mm2)).

Results

Compared to pre-nCRT biopsy, PD-L1 expression (8.7% vs. 14.0%, p<0.001) and TIL density (259.1 vs. 566.9, p<0.001) were significantly increased in surgical specimen after nCRT. When divided into groups according to nCRT response, post-nCRT TIL density (p=0.341), fold changes of TIL density (p=0.749), and PD-L1 expression (p=0.642) were not significantly different between ypCR (n=23) and non-ypCR group (n=78). In ypT0 group (n=36), post-nCRT TIL density was marginally higher than that of non-ypT0 group (404 vs. 259, p = 0.050).

Conclusion

Irrespective of clinical responses, PD-L1 expression and TIL density were both increased after nCRT. Our results could help the development of combination strategy of immunologic drugs and seek the possibility of an organ-saving strategy that will contribute to improving quality of life of patients.
603. GASTROINTESTINAL SYMPTOMS, AND SYMPTOMS OF DELAYED GASTRIC CONDUIT EMPTYING, ONE YEAR AFTER DIAGNOSIS OF CANCER IN THE ESOPHAGUS
Authors: Konradsson Magnus , Klevebro Fredrik , Nilsson Magnus
Published: September 2024

Background

Improved survival after esophagectomy for esophageal cancer emphasises persistent symptoms related to the surgically altered anatomy. The Swedish national registry of esophageal and gastric cancer collects patient reported EORTC questionnaires OG25 and C30 12 months after diagnosis. These questionnaires adress gastrointestinal symptoms and specifically symptoms of delayed gastric conduit emptying (DGCE) according to diagnostic criteria defined in an international Delphi consensus. The aim of this study is to describe gastrointestinal symptoms, and symptoms of DGCE in a large cohort of patients, 12 months after diagnosis and esophagectomy for cancer with correlation to potential risk factors for DGCE.

Methods

Data for all cases that underwent esophagectomy with gastric conduit reconstruction during 2009-2018 was analysed. Baseline data was compared between responders and non-responders to the EORTC questionnaires to address responder bias. Frequency and severity of gastrointestinal symptoms was documented. An algorithm was created to identify cases reporting symptoms consistent with DGCE according to the symptom based part of the diagnostic criteria. Odds-ratios and 95% confidence intervals were calculated for univariate analysis for correlation to baseline data and risk factors and logistic regression used for multivariable analysis, using STATA v 16.1.

Results

Totally 484 (51,2%) responded the questionnaires. Responders were similar to non-pesponders regarding age, sex and ASA score. Early satiety was most commonly reported (44%), followed by concerns of low body weight, long time completing meals, enjoying meals and appetite. 147 patients (30.4%) reported symptoms compatible with DGCE. Patients with DGCE had a mean score of 3.79 (CI=3.57-4.0) for overall health compared to 5,13 (CI=5.0-5.26) non-DGCE patients. DGCE symptom patients had a mean score of 3.77 (CI=3.54-4.01) for overall quality of life compared to 5,22 (CI=5.08-5.36) for non-DGCE patients.

Conclusion

Almost one third of patients who had an esophagectomy with a gastric conduit reconstruction for esophageal cancer had symptoms compatible with DGCE after one year. Patients reporting symptoms of DGCE rated markedly lower for overall quality of life and overall health compared to patients without DGCE symptoms. This this study suggests that DGCE is a major quantitative and qualitative problem after esophagectomy.
605. MITOCHONDRIAL METABOLISM IN UPPER GI ADENOCARCINOMA DETERMINES PATIENT SURVIVAL
Authors: Shang Ersong , Smith Anna , Reynolds Martin , Matly Amna , Edwards Joanne , Phillips Alexander W , Greaves Laura
Published: September 2024

Background

Mitochondrial oxidative phosphorylation (OXPHOS) is responsible for meeting the vast majority of cellular energy demands. Ever since the description of aerobic glycolysis by Warburg in 1927, it has been recognised that cancers have dysfunctional metabolism. Clinically, this Warburg effect is the basis of FDG-PET imaging, increased FDG uptake represents increased tumour glycolysis and translates to worse upper GI adenocarcinoma outcomes. The cause of OXPHOS disruption in upper GI adenocarcinoma is poorly understood, its impact on potential therapeutic strategies is yet to be explored. This is particularly pertinent in upper GI adenocarcinomas as despite recent improvements, 5-year survival remains alarmingly low.

Method

Oesophageal and gastric adenocarcinoma samples collected in the UK from 175 patients (89 oesophageal adenocarcinoma, 86 gastric adenocarcinoma, 131 male, 44 female, median age=65, IQR=12) who underwent radical resection with curative intent between 1995 and 2009. Quantitative immunofluorescence were used to determine expressions of OXPHOS Complex I and IV at a single cell level. Patients were divided into high vs. low expressors of Complex I and IV using K-means clustering to allow for subsequent subgroup analysis.

Result

Survival analysis demonstrated significantly worse outcomes for low expressors as compared to high expressors of Complex I at 5 years post-op (5-year survival probability low expressors=0.440, 95%CI=0.358-0.539, high expressors=0.629, 95%CI=0.515-0.769, P-value=0.048). Similarly comparison of Complex IV expression also demonstrates disadvantageous survival for Complex IV low expressors (5-year survival probability low expressors=0.432, 95%CI=0.346-0.538, high expressors=0.603, 95%CI=0.499-0.729, P-value=0.042).

The low expressors of Complex I and IV encompassed significantly more Stage III disease as per AJCC 7th edition.

The low vs. high expression Complex I and IV groups are similarly matched for baseline patient characteristics.

Conclusion

These results demonstrate reduced capacity to carry out OXPHOS in oesophageal and gastric adenocarcinoma is characteristic of more advanced cancer and results in worse patient outcomes. Further work is needed to determine if OXPHOS status impacts on neo-adjuvant therapy response and how to exploit OXPHOS deficiency therapeutically in oesophageal and gastric adenocarcinomas.

The limitations of this preliminary work include small sample size and tissue derived from historic patients over a long period of time, during which treatment and outcomes for upper GI cancer have significantly changed.
609. LONG-TERM OUTCOMES OF SALVAGE SURGERY AFTER PROTON BEAM THERAPY FOR ESOPHAGEAL SQUAMOUS CELL CANCER
Authors: Toshiyama Satoshi , Honda Michitaka , Yamamoto Ryuya , Kawamura Hidetaka , Takagawa Yoshiaki , Murakami Masao , Teranishi Yasushi
Published: September 2024

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.