bluuebunny/crossref_metadata_2025 huggingface dataset:
320. EFFICACY OF LAPAROSCOPIC FUNDOPLICATION IN PATIENTS WITH CHRONIC COUGH AND GASTRO-OESOPHAGEAL REFLUX
Authors: Frankel Adam , Ong Hock Soo , Nathanson Lesley , Smithers B Mark , Martin Ian , Gotley David
Published: September 2022

The outcome of anti-reflux surgery in patients with cough suspected to be induced by gastro-oesophageal reflux disease is frequently uncertain. The aims of this study were to assess the efficacy of laparoscopic fundoplication (LF) for controlling cough in a patient population suffering chronic cough when alternative aetiologies (e.g. asthma) had been excluded and pathologic gastro-oesophageal reflux had been confirmed on ambulatory pH monitoring, and to identify predictors of response.

From a prospective database of 1,598 patients who had undergone laparoscopic fundoplication, 66 (4%) had a principal presenting symptom of chronic cough as well as objective evidence of gastro-oesophageal reflux disease (GORD). Patients completed questionnaires for GORD symptoms (modified DeMeester score) and severity of cough (visual analog scale) both before and after LF, and had pre-operative gastroscopy and 24-hour pH monitoring before operation. Patients were considered to have responded to LF if they had no cough or the cough had improved by 50% or more after operation.

Follow-up data was available for 66/66 patients (100%), with a median follow-up time of 43 months (range 14–104 months) after operation. Cough was relieved in 40/66 (61%), while typical GORD symptoms (heartburn, regurgitation) was relieved in 44/49 (90%). The presence of typical GORD symptoms, oesophagitis, or pH study variables did not predict the response of the cough to LF. At 1 year, 67% of patients were satisfied with the results of their surgery, 20% were not and 13% were unsure. For comparison, the 1430/1598 patients in the database with no laryngopharyngeal symptoms had a satisfaction rate of 94%.

Based on our study and available literature, it appears there are no reliable pre-operative clinical predictors of a satisfactory response of cough to LF. This probably reflects a current inability to obtain an accurate aetiological diagnosis of chronic cough, even in the presence of known abnormal gastro-oesophageal reflux disease. Regardless, in a well-chosen cohort of patients with chronic cough, LF can yield good patient satisfaction rates, albeit less than for patients with typical GORD symptoms.
323. CLINICAL CHARACTERISTICS OF HIATAL HERNIA WITH ANEMIA AND SIGNIFICANCE OF SURGICAL REPAIR
Authors: Nakanishi Yasutaka , Hata Hiroaki , Suenaga Takahiro , Moriyama Masaaki , Degawa Kanako , Kojima Hiroya , Kanbe Hiroyuki , Miki Akimori , Nakanishi Hiroki , Yamaoka Ryoya , Matsusue Ryo , Narita Masato , Otani Tetsushi , Yamaguchi Takashi
Published: September 2022

Most patients with hiatal hernia (HH) are asymptomatic. However, HH may provoke severe gastroesophageal reflex, anorexia, and anemia. Therefore, therapeutic indication and approach are controversial especially for elderly and frail patients. So, we investigated clinical features of HH with anemia and treatment outcome of surgical repair.

From Jan. 2010 to Sep. 2021, 97 patients diagnosed HH by upper gastrointestinal scope and/or computed tomography and were taken blood test at the same time. Patients with malignant disease and after gastrectomy were excluded in this research. We examined the correlation between anemia and clinical characteristics (symptoms, physical and morphological factors) retrospectively. Similarly, hemoglobin(HGB) status after surgical repair were investigated.

HGB of 21 cases (21.6%) represented less than 10 g/dl at the time of diagnosis. Elderly (p = 0.0007), disorders of the spine (kyphosis and scoliosis) (p = 0.006), typeIV hiatal hernia (p = 0.02), GERD (Grade ≥ A) (p = 0.07) were correlated with anemic cases of HH, which were consistent with clinical characteristic of giant hiatal hernia (GHH).

In GHH (47 cases) with more than 30% stomach bulges into mediastinum, HGB of 17 cases (36%) represented less than 8 g/dl, and 9 cases (19%) were required blood transfusion. Six cases (13%) of GHH underwent surgical repair, and no exacerbation of anemia was observed after surgery.

Elderly, kyphosis/scoliosis, and GHH were represented as the features of HH with anemia. Severe anemia is common symptom in GHH cases, and surgical repair might improve anemia in operable cases.
324. CLINICAL OUTCOME OF CURATIVE SURGERY AND DEFINITIVE CHEMORADIOTHERAPY FOR PATIENTS WITH RESECTABLE CERVICAL ESOPHAGEAL CANCER
Authors: Inoue Masazumi , Tsubosa Yasuhiro , Haneda Ryoma , Mayanagi Syuhei , Ishii Kenjiro
Published: September 2022

Esophagectomy and definitive chemoradiotherapy are standard initial treatment modality for resectable cervical esophageal cancer. We compared the treatment results of both treatment methods and examined treatment strategies for resectable cervical esophageal cancer.

Patients who were treated for resectable cervical esophageal cancer at our hospital from January 2003 to March 2017 were divided into surgery group and chemoradiation therapy group (CRT group) for the initial treatment. The treatment results were compared retrospectively.

Of all 51 patients, 20 patients received surgery and 31 received CRT. In surgery group, 16 cases lost their laryngeal function by surgery. Recurrence was observed in 7 cases, of which only 1 case was local. In CRT group, 26 cases (83.9%) achieved complete response, of which 13 cases relapsed. 5-year laryngeal-preserving survival rate was 56.2% in CRT group, and 72.3% for non-stenotic patients. There was no significant difference in 5-year survival rate between two groups (surgery, 62.2%; CRT, 66.1; p = 0.648). In stenotic cases, 5-year survival rate was better in surgery group (surgery, 75 0.0%; CRT, 25.0%; p = 0.033).

The local control of the primary lesion and the prognosis in the stenotic cases were better in the surgery group. On the other hand, the 5-year laryngeal-preserving survival rate of the CRT group was high in non-stenotic cases. These results can be an important factor in choosing initial treatment for resectable cervical esophageal cancer.
326. REDUCTION OF ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY WITH RETROSTERNAL GASTRIC TUBE RECONSTRUCTION
Authors: Okumura Tomoyuki , Miwa Takeshi , Numata Yoshihisa , Watanabe Toru , Hirano Katsuhisa , Igarashi Takamichi , Tanaka Haruyoshi , Hashimoto Isaya , Shibuya Kazuto , Hojo Shozo , Yoshioka Isaku , Fujii Tsutomu
Published: September 2022

Anastomotic leakage (AL) after esophagectomy is one of the major complications after esophagectomy.

The aim of this study was to evaluate anastomotic procedure to reduce AL after esophagectomy with retrosternal gastric pull up.

A total of 157 consecutive patients underwent thoracoscopic esophagectomy followed by retrosternal reconstruction with gastric tube in our hospital between January 2008 and December 2021. The anastomotic procedure was revised at January 2016. After cervical esophagogastric anastomosis using circular stapler, gastric tube was pulled down to linearize and place the anastomotic site below the suprasternal notch (SN). The sternum tracheal distance (STD) and the level of esophagogastric anastomosis (LEA) were measured using CT image.

In comparison between the former (-December 2015, 65 cases) and later (January 2016-, 92 cases) group, AL was significantly reduced from 11/65 (16.9%) to 0/92 (0%) cases (p < 0.001). LEA was significantly lower in the later group than former group (2.7 mm below SN vs 25 mm above SN; p < 0.001). No difference was observed in the clinicopathological characteristics. In comparison between the cases with and without AL (11/146 cases), significant difference was seen in BMI (average 24.4/21.6, p<0.01) and LEA (average 23.5/8.0 mm, p = 0.02). Multivariate analysis revealed that BMI (21.5>, p = 0.02) and LEA (0>, p < 0.01) were the independent factors associated to AL.

Surgical procedure which avoids excessive compression on the gastric tube at the thoracic inlet may take an important role in reduction of AL.
328. MOLECULAR SUBTYPING OF ESOPHAGEAL ADENOCARCINOMA BY NON-NEGATIVE MATRIX FACTORIZATION OF LASER CAPTURE MICRODISSECTED RNA-SEQ SAMPLES
Authors: Wilson Gavin , Mathew Elizabath , Shibahara Yukiko , Allison Frances , Bach Yvonne , Allen Jonathan , Kalimuthu Sangeetha N , Elimova Elena , Darling Gail , Yeung Jonathan
Published: September 2022

Previous attempts to construct prognostic molecular subtypes for esophageal adenocarcinoma (EAC) using gene expression profiling has met with little success when compared to adenocarcinomas from other disease sites. We hypothesized that this is in part due to the low tumour cellularity obtained from EAC biopsy and resection specimens, which obscures the tumour-intrinsic gene expression signals due to normal cell contamination.

We systematically collected biopsies from pre-treatment, post-induction, and metastatic EAC tumors. Laser capture microdissection (LCM) was utilized to enrich for tumour cells for whole transcriptome sequencing (RNA-seq) (N = 54). We utilized non-negative matrix factorization (NMF) with 7 components to identify common gene expression programs across our samples.

After applying NMF to our samples, we identified 4 tumour-intrinsic components and 3 tumour-extrinsic components (including immune infiltrate and normal esophagus). These components validated on TCGA EAC and esophageal squamous cell carcinoma RNA-seq, single cell RNA-seq from EAC organoids, and the cancer cell line encyclopedia. Moreover, we observed that these tumour-intrinsic gene expression programs were preserved in EAC samples metastatic to other organ sites such as liver and lymph nodes. We observed that most tumours expressed more than one tumour component and that approximately 25% of our samples had low tumour signals despite LCM enrichment.

We used LCM to enrich for tumour signal in EAC gene expression profiling data and identified 4 tumour-intrinsic gene expression programs that validate across multiple datasets. We have currently conducting survival analysis on our data and TCGA data to further validate the prognostic potential of our tumour signatures.
329. IMPROVED TUMOUR PURITY AND PLOIDY ESTIMATION FROM LASER CAPTURE MICRODISSECTED ESOPHAGEAL ADENOCARCINOMA SAMPLES
Authors: Wilson Gavin , Mathew Elizabath , Shibahara Yukiko , Allison Frances , Bach Yvonne , Allen Jonathan , Akhter Akhi , Shathasivam Premalatha , Kalimuthu Sangeetha N , Elimova Elena , Darling Gail , Yeung Jonathan
Published: September 2022

Large scale sequencing efforts by The Cancer Genome Atlas (TCGA), among others, have generated detailed genomic data for esophageal adenocarcinoma. However, samples with low cancer purity (i.e. high amounts of normal DNA) will limit accurate inference of copy number aberrations, a genomic hallmark of esophageal adenocarcinoma. This consequently restricts more advanced analysis such as quantifying intratumor heterogeneity or inferring tumor evolution.

We have systematically collected biopsies from pre-treatment and post-induction esophageal adenocarcinoma tumors. Laser capture microdissection (LCM) was utilized to enrich for tumor cells for whole genome sequencing. Matching blood was utilized as germline control. Cancer purity and ploidy was estimated using a developed method tailored to the high genomic instability observed in EAC samples. This method uses both sequencing depth and minor allele frequencies to infer ploidy and purity. The esophageal adenocarcinoma dataset from TCGA were used as comparison.

We achieved significantly higher tumor cellularity in surgical resection specimens (n = 8) compared to TCGA (71%+/−11 vs. 58%+/−18). Interestingly, tumor cellularity from biopsy specimens (n = 25) remained similar to TCGA despite LCM (65%+/−13), which is likely due to TCGA only using surgical resections that were pre-selected to have at least 60% cellularity, while we applied no histopathological cellular constraints on our samples. Estimated ploidy was similar between biopsy of primary tumors and surgical resection specimens compared to TCGA (2.67+/−0.58, 2.72+/−0.70, 2.64+/−0.75). There was a trend towards higher ploidy (3.07+/− 0.13) in metastatic biopsies (n = 3) but additional specimens are required.

Laser capture microdissection of post-induction esophageal adenocarcinoma surgical resection specimens has resulted in significantly higher tumor purity in whole genome sequencing data. This will allow for improved inferences of phylogenetic trees between pre- and post- induction samples and quantification of subclonal copy number aberrations or intratumor heterogeneity.
334. DEFINITION OF SEVERE BENIGN OESOPHAGEAL STRICTURES AND IDENTIFICATION OF ASSOCIATED RISK FACTORS
Authors: Elbe Peter , Boytsova Anna , Lindblad Mats , Klevebro Fredrik , Vujasinovic Miroslav
Published: September 2022

Benign oesophageal strictures (BES) are often easily treated but around 30% progress into recurrent or refractory benign oesophageal strictures (RBES), that need repetitive dilatations. Difficulties of RBES have been widely discussed in the literature, but there is not a well-established consensus regarding the definition of RBES. In this study we wanted to develop a simple definition in relation to aetiology and number of dilatation sessions per stricture.

A retrospective study on 242 BES-patients treated with endoscopic dilatation was performed. The primary endpoint was need of further dilatation per procedure, based on total number of dilatation sessions performed and stricture ethology. Univariate and multivariable regression analysis were performed to assess risk factors for RBES.

Among 242 patients, 76 had RBES. The need of further dilatation increases with 13% at fifth dilation session and keeps a continuous mean value at 81%. Investigating some aetiologies separately, the point where need increases does vary. The risk of having RBES decreased for distal (Odds Ratio (OR) 0,25 (Confidence interval (CI) 95% 0,09-0,65)) and middle (OR 0,35 (CI 95% 0,13-0,88)) location of the stricture compared to proximal strictures.

We propose that a stricture can be defined as RBES when reaching the fifth dilatation session. At that point we also suggest that clinicians should consider additional treatment, in addition to dilatation, in order to resolve the stricture.
342. GENOMIC ANALYSIS OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN OESOPHAGEAL ADENOCARCINOMA
Authors: Breininger Stella P , Izadi Fereshteh , Sharpe Ben , Secrier Maria , Gibson Jane , Walker Robert , Rahman Saqib , Devonshire Ginny , Lloyd Megan , Walters Zoë , Fitzgerald Rebecca , Rose-Zerilli Matthew , Underwood Tim
Published: September 2022

Oesophageal adenocarcinoma (OAC) is the ninth most common cancer worldwide, with a mortality of >500,000 deaths yearly. Neoadjuvant chemotherapy (NAC) followed by surgery is the standard of care (SOC) for locally advanced OAC. Although almost all patients receive chemotherapy as SOC, but <20% respond and benefit from chemotherapy before surgery. The OAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance.

To identify associations between genomic events and response to NAC in OAC, a comparative genomic analysis was performed in 65 patients using whole-genome sequencing. We defined response to NAC using Mandard Tumour Regression Grade TRG), with responders classified as TRG1–2 (n = 27) and non-responders classified as TRG4–5 (n = 38).

We report a higher non-synonymous mutation burden in responders (median 2.08/Mb vs 1.70/Mb, P = 0.036) and elevated copy number variation (CNV) in non-responders (282 vs 136/patient, P < 0.001). We identified CNVs unique to each group, with cell cycle (CDKN2A, CCND1), c-Myc (MYC), RTK/PIK3 (KRAS, EGFR) and gastrointestinal differentiation (GATA6) pathway genes being specifically altered in non-responders. Of particular interest was the identification of the Neuron Navigator-3 (NAV3), a known tumour suppressor downstream of EGFR, which was mutated exclusively in 22% of non-responders.

Our work characterises genetic features and mutations that are uniquely associated with response to NAC. We envision a treatment pipeline that incorporates driver mutation profiling in OAC, combining response prediction with targeted therapies to enhance response to NAC and improve survival outcomes.
345. CAMRELIZUMAB AS ADJUVANT THERAPY IN RESECTED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A PHASE 2 TRIAL
Authors: Meng Xiangrui , Shan Zhengzheg , Xu Mengli , Lu Yao , Guan Lulu , Chen Yu , Wang Huike , Yang Yuanyuan , Chi Yanyan , Yang Yalan , Fan Qingxia , Wang Feng
Published: September 2022

CheckMate 577 has confirmed that adjuvant immunotherapy significantly prolongs disease-free survival (DFS) in patients with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy. However, adjuvant therapy for patients with different neoadjuvant therapies needs to be explored. Therefore, this study was designed to investigate the efficacy and safety of camrelizumab as adjuvant therapy in patients with resected (R0) esophageal squamous cell carcinoma (ESCC).

This is an ongoing, non-randomized, open-label, phase 2 trial (NCT04533490) in China. ESCC patients (stage cT1b-T4aN0M0/cT1-T4aN + M0) aged 18–75 years with ECOG performance status of 0–1 was planned to be enrolled in cohort A (n = 42, with 6–12 weeks of neoadjuvant therapy) and cohort B (n = 43, without neoadjuvant therapy). Following R0 resection, adjuvant camrelizumab (200 mg Q2W) was given until tumor recurrence, metastasis, intolerable toxicity, or the completion of 12-month treatment. The primary endpoint was DFS. Secondary endpoints included overall survival, recurrence rate, 1/3/5-year DFS rates, and safety.

At data cutoff (Apr 21, 2022), 17 patients were enrolled, with a median age of 65 years; 9 (53%) patients were males, and 12 (71%) had ECOG performance status of 0. There were 15 patients in cohort A (14 with neoadjuvant immunochemotherapy, and 1 with neoadjuvant chemotherapy) and 2 in cohort B. With a median follow-up of 5.5 months, DFS was not reached. A total of 14 (82.3%) patients had treatment-related adverse events, which were all grade 1–2. The most common events were reactive cutaneous capillary endothelial proliferation (11 [65%]), adrenal cortical insufficiency (3 [18%]), and interstitial pneumonia (2 [12%]).

Adjuvant camrelizumab showed acceptable safety profile in patients with resected (R0) ESCC who mainly received neoadjuvant immunochemotherapy, and the efficacy was worth expecting. The study enrollment is ongoing, and further survival and safety data will be reported in the future.
351. SUPERIOR MEDIASTINAL DISSECTION DURING MINIMALLY INVASIVE ESOPHAGECTOMY FOR ESOPHAGEAL CANCER—A MULTICENTER PROPENSITY SCORE MATCHED (PSM) ANALYSIS
Authors: Yip Hon Chi , Lam Dennis Chin Tou , So Rain Choi Kwan , Fung Michelle Hei Wai , Ng Stephen Ka Kei , Chan Shannon Melissa , Teoh Anthony Yuen Bun , Ng Enders Kwok Wai , Chiu Philip Wai Yan
Published: September 2022

Minimally invasive esophagectomy (MIE) is currently the preferred approach of surgery for esophageal cancer. Systematic superior mediastinal lymphadendectomy along bilateral recurrent laryngeal nerve is enhanced by the magnified view in thoracoscopy, and is increasingly performed to achieve complete nodal dissection. Both participating centers began MIE with systematic superior mediastinal dissection in recent 5 years. In the current study, we aim to compare the short- and medium-term outcomes of MIE with or without superior mediastinal dissection.

Consecutive patients who received MIE for esophageal cancers from 2004 to 2021 were recruited, data were collected from a prospectively maintained database. Patients were divided into ‘systematic superior mediastinal dissection’ and ‘control’ groups, and propensity score matching was performed with age, tumor location, tumor stage and neoadjuvant therapy. Total 157 patients were recruited, 67 (42.7%) in the extended superior mediastinal dissection group. After PSM, 48 patients were identified in each group. Short term surgical outcomes as well as medium term survival results were compared.

Operative time was significantly longer with extended superior mediastinal dissection. Higher number of lymph nodes were yielded in total and from the superior mediastinum. Recurrent laryngeal nerve palsy developed in 52.1% and 43.8% of the MIE with or without extended dissection respectively, but significantly fewer palsies required intervention in the extended dissection group. Higher rate of anastomotic leakage was observed in the extended dissection group, but there was no difference in the overall severe adverse event (> = Grade III: 31.3% vs 35.4%). There was no statistical difference in the survival, but a trend towards improved 2 year disease-free survival was observed.

Minimally invasive esophagectomy with systematic superior mediastinal dissection achieved a higher lymph node yield and a trend towards improved disease free survival. The overall adverse event rate was similar with conventional dissection. While better cancer staging could be achieved with extended dissection, further research is required to confirm the oncological benefit of extended dissection.
352. ENDOSCOPIC SCORING SYSTEM FOR ACHALASIA PRE AND POST LOWER ESOPHAGEAL SPHINCTER INTERVENTION: THE DELAYED ESOPHAGEAL CLEARANCE IN ACHALASIA (DECA) SCORE
Authors: Ellison Ashton , Nguyen Anh D , Podgaetz Eitan , “Shan" Reddy Chanakyaram , Souza Rhonda F , Spechler Stuart J , Konda Vani JA
Published: September 2022

While esophageal high-resolution manometry (HRM) is the gold standard test to diagnose achalasia, endoscopy findings can demonstrate impaired esophageal clearance. Presently, there is no standardized method to describe the severity of these findings. We developed a novel scoring system, the Delayed Esophageal Clearance in Achalasia (DECA) score, to describe achalasia findings on endoscopy. In this study, we seek to demonstrate that DECA scores, an objective marker of esophageal clearance, improve after peroral endoscopic myotomy (POEM).

We reviewed the Baylor Scott and White Center for Esophageal Diseases patient database for patients who had both HRM and endoscopy performed between December 2020 and April 2021. Each patient had a DECA endoscopic score calculated based on four endoscopic findings at the time of endoscopy (Table 1). The medical records of patients who underwent a POEM with pre- and post- DECA scores between December 2020 to November 2021 were also reviewed. Patients with suspected or known achalasia were on a 1–5 day liquid diet prior to their endoscopic procedure.

Among 254 patients in our database, 165 patients had no prior foregut surgery. Of the 165 surgical-naïve patients, 72 had an abnormal EGJ complex (EGJOO = 58, achalasia type 1 = 2, type 2 = 7, and type 3 = 5) with a mean DECA score of 5.9 (SD 2.4) in those with achalasia and 2.2 (SD 1.6) in EGJOO. There were 17 patients who underwent a POEM with a mean pre-POEM DECA score of 8.7 (SD 2.2) and a mean post-POEM DECA score of 3.2 (SD 2.2). The reduction in DECA score after POEM was statistically significant (p = <0.001).

The DECA scoring system can be easily calculated at the time of endoscopy and allows for a standardized language in describing achalasia endoscopic finding especially in the pre- and post-treatment endoscopic assessment. In our study, we found a statistically significant difference in DECA score in patients pre and post POEM intervention.
354. THE PARADIGM OF INACCURACIES IN STAGING EARLY OESOPHAGEAL ADENOCARCINOMA
Authors: Reyhani Arasteh , Gimson Eliza , Baker Cara , Kelly Mark , Maisey Nick , Meenan John , Subesinghe Manil , Hill Mark , Lagergren Jesper , Gossage James , Zeki Sebastian , Dunn Jason , Davies Andrew
Published: September 2022

The clinical value of multiple staging investigations for high-grade dysplasia (HGD) or early adenocarcinoma of the oesophagus (EOC) is unclear.

A single centre prospective cohort of patients treated for EOC between 2000 and 2019 was analysed. This coincided with a transition period from oesophagectomy to endoscopic mucosal resection (EMR) as the treatment of choice for early cancers. All patients were staged with computed tomography (CT), endoscopic ultrasound (EUS), and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)-CT. The aim of this study was to assess the accuracy of these investigations and impact on clinical management.

297 patients with HGD or EOC were included (EMRn = 184; oesophagectomy n = 113 [preceded by EMRn = 23]). Staging patterns for both groups were similar throughout staging modalities (CT, EUS, PET-CT), showing low overall accuracy. In the EMR group, over-staging that might have changed management occurred in 10 patients (3.6%)for T-staging (T2) and 14 patients (5.0%)for positive lymph node-staging (LNM). In the oesophagectomy alone group LNM identified following surgery was rare (8.9%) and staging sensitivity for these surgically treated patients was low (CT 12.5%, EUS 12.5%, PET-CT 0.0%). Overall, PET-CT and EUS changed decision-making in less than 1%of patients with a clear CT and low risk histology criteria on EMR specimen.

Staging accuracy is low in EOC and the addition of EUS and PET-CT does not change patient decision making significantly. Histology obtained from EMR specimens contain important predicting factors that do change patient management, proving to be an excellent staging tool rather than imaging techniques, hence, EUS and PET-CT should only be used selectively in patients being assessed for EOC.
361. EARLY RECURRENCE PATTERNS AFTER ESOPHAGECTOMY FOR ESOPHAGEAL CANCER IN PATIENTS UNDERGOING CROSS NEOADJUVANT THERAPY
Authors: Liu Zhonghe , Li Chunguang , Liu Zhichao , Liu Jun , Li Hongxuan , Li Bin , Hua Rong , Pan Jie , Shao Jincheng , Zhu Li , Li Zhigang
Published: September 2022

Chemoradiotherapy (CROSS regimen) has been regarded as standard preoperative treatment for patients with locally advanced esophageal cancer, but some patients still developed early recurrence after such intensive therapy. The present study aimed to determine the factors associated with early recurrence for patients with ESCC treated by CROSS therapy within 6 months.

Patients were identified from single institution from 2019 to 2021. All patients with locally advanced ESCC who underwent CROSS regimen NCRT and following R0 esophagectomy were reviewed.

Total 115 patients were included. 19 patients (16.52%) recurred within 6 months post-surgery. 8 patients (6.96%) had local-regional recurrence with most common location was cervical lymphnodes; 11 patients (9.56%) had distant recurrence and most often occured in lung. In univariate analysis: BMI before CROSS (p = 0.03), tumor size regression (p = 0.03), ypN≧1 (p = 0.002) and neck metastases (p = 0.01) were significantly associated with local-regional recurrence. In multivariate analysis: ypN≧1 (HR = 9.08, p = 0.05) was only independent covariate. For distant recurrence, tumor size regression (p = 0.02), ypN≧1 (p < 0.0001) and TRG3/4 (p = 0.01) were risk factors in univariate analysis, ypN≧1 (HR = 15.60, p = 0.01) was also independent covariate in multivariate analysis.

For patients after CROSS neoadjuvant therapy, if there are still positive lymph nodes in clinical evaluation, M staging should be performed more carefully to avoid ineffective surgery with early postoperative distant recurrence.
366. SURGERY VERSUS NON-SURGICAL TREATMENT FOR THORACIC ESOPHAGEAL CANCER IN PATIENTS OLDER THAN 70 YEARS: A RETROSPECTIVE ANALYSIS OF 749 CASES
Authors: Li Kexun , Leng Xue Feng , Du Kunyi , Liu Kun , He Wenwu , Wang Qifeng , Luo Xi , Wang Chenghao , Wang Kangning , Liu Guangyuan , Wei Xing , Li Haojun , Zhou Qiang , Li Zhiyu , Jiang Longlin , Zheng Kai , Li Changding , Mao Tianqin , Du Kunyi , Fang Qiang , Xiao WenGuang , Han Yongtao , Peng Lin
Published: September 2022

The highest incidence of esophageal cancer is in East Asia, but as for advanced age people, there are also many non-tumor factors affecting overall survival (OS), such as cardiovascular and cerebrovascular diseases. Our purpose is to determine whether the older patients after esophagectomy had better OS than those treated with non-surgical treatment.

Data were obtained from the Sichuan Cancer Hospital & Institute Esophageal Cancer Case Management Database (SCH-ECCM Database) and Department of Radiation Oncology Database. We retrospective analyzed esophageal cancer patients older than 70 years who underwent esophagectomy or radiotherapy/chemotherapy from Jan. 2009 to Dec. 2017. The patients were divided into two groups: surgery group (S group), and non-surgery group (NS group). Outcome measures depend on OS.

After 60.6 months of median follow-up time, 749 patients were included. 532 of 749 patients (71.0%) underwent surgery, 217 of 749 patients (39.0%) underwent non-surgical treatment including radiotherapy and/or chemotherapy. In the S group, the median OS of was 39.7 months (95% CI 33.7–45.7), while the NS group was only 24.0 months (95% CI 19.6–28.4). The OS at 1, 3, and 5 years were 84%, 52%, and 39% in the S group, respectively. In the NS group, the OS rates at 1, 3, and 5 years were 72%, 32%, and 29%, respectively (HR 0.69, 95% CI 0.561–0.846, P<0.0001).

Esophageal cancer patients older than 70 years who underwent esophagectomy had significantly better OS than those who underwent non-surgical treatment based on radiotherapy and/or chemotherapy.
368. EARLY DELAYED GASTRIC EMPTYING AFTER ESOPHAGECTOMY: VALIDATION OF THE INTERNATIONAL EXPERT CONSENSUS DEFINITION (MIE GROUP)
Authors: Abdelrahman Mohamed , Fu Kathryn , Tham Ji , Emslie Katy , Ariyarathenam Arun , Berrisford Richard , Humphreys Lee , Sanders Grant , Wheatley Tim , Chan David
Published: September 2022

Early delayed gastric emptying (DGE) affects up to 37% of patients after esophagectomy. An international expert consensus (IEC) agreed on a diagnostic criteria in 2020. The degree of adoption of this definition worldwide is unknown and how it compares to well established definitions locally with subtle yet significant differences. The aim of this study was to compare the IEC definition of early DGE to the definition at the University.

All patients who underwent esophagectomy for cancer at UHP between April 2019–August 2020 were analysed. The IEC definition was applied retrospectively and the rates of DGE were compared between the two criteria.

One hundred consecutive patients [74 Male (74%), median age (range) 68 (45–83 years)] were analysed. The rates of early DGE according to the IEC and UHP definitions were 20% and 28% respectively (p = 0.246). Eight patients had anastomotic leak, 6 of whom had DGE. Pneumonia was diagnosed in 28 patients (8 and 6 in the IEC and UHP groups respectively). Twenty-nine patients (29%) had pyloric balloon dilatation (PBD). Seventeen patients in the index admission and twelve at later date. Of the 17 patients 9 were in the IEC group and 11 in the UHP group.

The UHP definition does seem to match the MIE consensus definition and is not inferior. The dynamic process of DGE does support the policy our unit has to continue monitoring patients with chest radiographs. This not only identifies DGE early and modify management but also allows assessment of conduit after the patient starts eating.

Definition of Early Delayed Gastric Emptying post Esophagectomy.pdf (could not be inserted).
370. EXTERNAL VALIDATION OF A NOMOGRAM PREDICTING CONDITIONAL SURVIVAL AFTER CURATIVE TREATMENT OF ESOPHAGEAL CANCER
Authors: Schuring Nannet , Donlon NE , Hagens ERC , Donohoe CMD , van Berge Henegouwen MI , Reynolds JV , Gisbertz SS
Published: September 2022

To predict 5-year overall survival for esophageal cancer patients after neoadjuvant treatment followed by esophagectomy, recently a conditional survival nomogram was developed. This nomogram includes cN-stage, ypT-stage, ypN-stage, cardiac comorbidity, chyle leakage and pulmonary complications as independent predictors of survival. The aim of this study was to externally validate the conditional survival nomogram in a cohort of patients from another European high volume esophageal cancer center.

We included consecutive patients with a resectable (cT1-4a, N0–3, M0) adeno- or squamous cell esophageal carcinoma between January 2004 and January 2016 who received neoadjuvant treatment followed by an esophagectomy in a tertiary referral center for esophageal cancer. Standard prognostic factors and nomogram specific data were collected. The discriminative ability of the nomogram for the prediction of 5-year overall survival was quantified by Harrell’s C-statistics, directly after surgery and given survival for 1, 2, 3 and 4 years already survived. Calibration of the conditional survival nomogram was visualized by plotting actual 5 years survival against predicted probabilities.

296 patients were included. The median overall survival was 48.1 months (95%CI:37.5–58.7). The probability to achieve 5-year overall survival directly after surgery was 45% and increased to 57%, 68%, 78% and 89% for each additional year survived. Prediction of 5-year overall survival differed from the observed survival with a calibration slope of 0.54, 0.55, 0.59, 0.73 and 1.09, directly after surgery and given 1, 2, 3, and 4 years already survived, respectively. The discriminative ability of the nomogram for 5-year survival was moderate with a C-statistics of 0.65, compared to a value of 0.70 in the original study.

This study externally validated a model for conditional survival after neoadjuvant chemoradiotherapy and surgery for esophageal cancer. The proposed nomogram had a moderate predictive discrimination and accuracy for the derivation cohort, and therefore it should be updated for or used with caution in external cohorts for the prediction of conditional 5-year survival.
371. MAPPING OF LYMPH NODE METASTASIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AT ESOPHAGOGASTRIC JUNCTION: A RETROSPECTIVE SURGICAL STUDY COHORT
Authors: Jiang Chao , Liu Zhichao , Li Chunguang , Sun Yifeng , Guo Xufeng , Hua Rong , He Yi , Yang Yang , Zhang Jie , Wei Jinzhi , Li Zhigang
Published: September 2022

The aim of this study was to determine the optional extent of lymph node dissection of the squamous cell carcinoma (SCC) at the esophagogastric junction (EGJ) based on the incidence of metastasis in a retrospective single-center study.

Patients with SCC involving and within 5 cm of the esophagogastric junction (EGJ) who underwent McKeown esophagectomy without preoperative treatment were reviewed in a prospectively maintained database at a single institution from 2015 to 2021. Lymph nodes stations was based on the definitions from the Japan Esophageal Society, and lymph nodes were further classified according to the metastatic incidence rate, as follows: Category-1 (strongly recommended for dissection), rate of more than 10%; Category-2 (weakly recommended for dissection), rate of from 5% to 10%; and Category-3 (not recommended for dissection), rate of less than 5%.

Sixty-one patients were identified. T stage was pT1 (n = 9), pT2 (n = 11), pT3 (n = 40), and pT4 (n = 1). For all patients, category-1 nodes were predominantly abdominal stations (1, 2, 3, 7) and lower mediastinal stations (110); category-2 nodes were upper-middle mediastinal stations (105,106recR,107,108); station 106recL was category-3 with a metastasis rate of 4.92%. More nodal metastases were observed in cases with upper-margin exceeding EGJ >3 cm, and station 106recL was upgraded to category-2. For pT1 SCC, category-1 was focused on station 111, with no nodal metastasis in upper-middle mediastinal. For pT2 and pT3 SCC, cervical, thoracic, and abdominal lymph node metastases were found.

Radical total mediastinal lymph node dissection is as important as abdominal dissection for SCC at EGJ, but lymph node dissection around the left recurrent laryngeal nerve appears to be exempt in T1 patients.
377. NEOADJUVANT CARBOPLATIN/PACLITAXEL VERSUS 5-FLUOROURACIL/CISPLATIN IN COMBINATION WITH RADIOTHERAPY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A MULTICENTER COMPARATIVE STUDY
Authors: Gao Xing , Tsai PingChung , Chuang KaiHao , Pai ChuPin , Hsu PoKuei , Lee ShauHsuan , Lu HungI , van Lanschot Joseph Jan-Baptist , Chao YinKai
Published: September 2022

Treatment options for esophageal cancer (EC) have rapidly expanded from surgery alone to multimodal approaches comprising surgery, chemotherapy or radiotherapy. High-quality evidence from clinical trials indicated that both carboplatin/paclitaxel (CROSS) and cisplatin/5-fluorouracil (PF) regimens are significantly effective at improving survival. However, the most beneficial neoadjuvant chemoradiotherapy (nCRT) combination for esophageal squamous cell carcinoma (ESCC) in Asia still remains uncertain. In this study we compared neoadjuvant CROSS versus PF regimen in combination with 41.4-50.4Gy of radiotherapy.

Patients with ESCC were enrolled from three asian medical centers and stratified according to their nCRT regimen, i.e., CROSS+41.4-45Gy (CROSS) versus PF + 45Gy (PF4500) versus PF + 50.4Gy (PF5040). Propensity score analyses with stratification by inverse probability of treatment weighting (IPTW) was applied for nine baseline variables: gender, age, Charlson’s comorbidity index, clinical T and N stages, clinical stage, tumor length, tumor level and year of nCRT. Primary and secondary endpoints included overall survival (OS) and treatment-related complications. Compared to CROSS, patients who received PF regimens were expected to achieve comparable OS albeit more treatment-related complications.

Before IPTW, 334 patients were included (CROSS, n = 124 versus PF4500, n = 105 versus PF5040, n = 105). The lowest chemotherapy completion rate was observed in the PF5040 group (76.2% versus 89.4% in CROSS and 92% in the PF4500 group). Compared with CROSS, both PF groups showed more severe weight loss during nCRT and a higher frequency of post-esophagectomy anastomotic leaks. PF5040 had the significantly highest pCR rate (45.3%). CROSS conferred a significant OS benefit over PF4500 (hazard ratio [HR] =1.30, 95% CI = 1.05-1.62) and similar survival compared with PF5040 (HR = 1.17, 95% CI = 0.94-1.45). The same trends were found upon analysing recurrence free survival. (Figure).

Prior investigations reporting on the safety and efficacy of CROSS are mainly conducted in western populations, generally consisting adenocarcinoma, limiting the generalisability of these findings to Asian patients with ESCC. In our study, the CROSS regimen conferred a significant survival benefit over PF4500 and similar survival figures compared with PF5040. Considering the lower incidences of severe weight loss and post-esophagectomy anastomotic leaks, CROSS represents a safe and effective neoadjuvant treatment in Asian patients with ESCC.
379. ENLIGHTENMENT OF THE VENOUS ANATOMY OF THE ESOPHAGUS—AN ANOMALY CAPTURED UNDER MEDIASTINOSCOPY
Authors: Nakabayashi Rumi , Suzuki Akihiro , Yokoi Tadao , Miyachi Yosuke , Taketa Takashi , Matsubara Taketo , Shimada Gen , Kaido Toshimi
Published: September 2022

Distant organ metastasis often occurs early in the course of esophageal cancer development and is associated with a poor prognosis. The modes of metastasis include hematological and lymphatic routes. Although in the literature the venous outflow of the esophagus is described to occur through the esophageal vein into the azygous vein, which subsequently joins the superior vena cava, the detained anatomy of the venous and lymphatic systems of the esophagus remains to be further investigated.

We aimed to elucidate the regional anatomy of the venous system surrounding the esophagus via mediastinoscopic esophagectomy. Between January 2021 to January 2022, six patients with early esophageal cancer without apparent distant metastasis underwent minimally invasive esophagectomy and posterior mediastinal reconstruction with mediastinoscopy in our hospital. Detailed anatomy was captured and the spatial relationship between the esophageal vein and its draining vein was assessed intraoperatively and thoroughly reviewed postoperatively for any anomalies.

A venous anomaly was seen in one out of six patients where the esophageal vein drained into the left pulmonary vein rather than into the azygous vein. This anomaly was not detectable on the preoperative CT images. Hemostasis of the esophageal vein was achieved without major hemorrhage or injury to surrounding tissues. The esophageal specimen showed a localized ulcerative lesion in the midthoracic esophagus that was consistent with moderately differentiated squamous cell carcinoma, pT3N0M0 pStage IIB, with v1 and ly1 invasion. The patient will remain under surveillance for recurrence.

Direct venous drainage into the systemic circulation may attribute to its high rates of distant metastasis in esophageal cancer. This mechanism supports the higher prevalence of metastasis to the liver over the lung, and relatively high rates of bone and brain metastases. Close attention should be paid when performing esophagectomy as injuries to the esophageal vein and inadequate hemastasis may result in catastrophic bleeding when a direct connection with the systemic circulation is present.
380. UTILITY OF PET/CT FOR LYMPH NODE METASTASIS DETECTION IN PT1 EARLY ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Xu Jia-qi , Lin Si-yun , Li Quan-Lin , Zhou Ping-Hong , Tan Li-Jie
Published: September 2022

Nodal staging for early esophageal squamous cell carcinoma (ESCC) was mandatory to decide therapy strategy. Utility of preoperative Positron Emission Tomography/Computed Tomography (PET/CT) for lymph node metastasis (LNM) detection in early ESCC was evaluated in the study.

186 consecutive patients with pathologically confirmed T1 tumors undergoing preoperative PET/CT at Zhongshan Hospital between 2015 August to 2020 December were retrospectively enrolled. Clinical characteristics and PET/CT results were collected and compared between patients with or without LNM. A PET integrated risk score model for prediction of LNM was established and validated. Survivals were compared between high risk group and low risk group by Log Rank test.

40 out of 186 patients were diagnosed with LNM on PET-CT. PET/CT alone for LNM detection was with a 53.3% sensitivity, 84.65% specificity, and 90.4% negative predictive value. Tumor size >2.5 cm (P = 0.015), tumor depth (P = 0.012), LVI (P < 0.001), differentiation (P = 0.066) and PET LN (+) (P < 0.001) were included in the prediction model for LNM. The AUC of ROC in derivation cohort and validation cohort was 0.860 and 0.846 respectively. High risk group scoring >3 points showed poorer 5-year recurrence free survival (62.6% VS. 74.7%, P = 0.046) and similar overall survival (87.6% VS. 86.9%, P = 0.942) as compared to low risk group.

PET/CT for LNM detection in early ESCC was of 53.3% sensitivity and 84.65% specificity. PET integrated risk score model for LNM was of fair property with 0.860 AUC and was predictive of recurrence.
382. PREDICTION OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC) RISK BY ASSESSING EPIGENETIC AND GENETIC FIELD DEFECTS
Authors: Kishino Takayoshi , Yakashita Satoshi , Lee Yi-Chia , Wu Ming-Shiang , Okano Keiichi , Ushijima Toshikazu
Published: September 2022

Field defects are important for human carcinogenesis. Such field defects are formed by accumulation of epigenetic and genetic alterations. Here, we aimed to predict cancer risk of ESCC by assessing epigenetic and genetic field defects.

First, we focused on epigenetic field defects. Genome-wide methylation analyses were performed using the esophageal mucosae, and methylation risk markers were isolated. Methylation levels of the isolated candidate genomic regions were measured by quantitative methylation-specific PCR (qMSP).

Second, we focused on genetic field defect. However, measurement of such point mutations has been very difficult in human DNA samples, because of their very low frequencies. We established a novel method to the such rare mutations at the 10–6 per bp level in non-cancerous mucosae: the 100-copy method.

Both epigenetic and genetic alterations were accumulated in a stepwise manner according to the risk level of the esophageal mucosae. The odds ratio to distinguish patients with ESCC (high-risk group) from healthy individuals exposed to risk factors, namely, alcohol drinking, betel quid chewing, and cigarette smoking (ABC) (intermediate-risk group), were 10.9 (AUC:0.787) by assessment of epigenetic alterations and 18.2 (AUC:0.791) by assessment of genetic alterations.

Integration of genetic and epigenetic markers could predict the ESCC risk more precisely [Yamashita, PNAS, 115:1328, 2018].
385. OUTCOME FOLLOWING MINIMAL INVASIVE VERSUS OPEN ESOPHAGECTOMY FOR ESOPHAGEAL CARCINOMA PATIENTS WITH LIVER CIRRHOSIS: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Lin Yi-yu , Chiu Chien-Hung , Tsai Chun-Yi , Chao Yin-Kai
Published: September 2022

Although minimally invasive esophagectomy (MIE) has advanced into a safe and effective alternative to open esophagectomy (OE), its utility in cirrhotic esophageal cancer (EC) patients remained unknown. This study analyzed the perioperative outcomes of MIE for EC with LC compared with open esophagectomy (OE).

We retrospectively reviewed the clinical charts of patients treated with esophagectomy for EC who had a concomitant diagnosis of LC. Of the 74 patients identified from our records, 43 underwent MIE and 31 OE. The two treatment groups underwent propensity scores (PS) matching using a logistic model that included the following covariates: type of preoperative therapy, Charlson comorbidity index, Child-Pugh class, and elective versus emergency surgery.

Following PS matching, the MIE and OE groups consisted of 40 and 20 patients, respectively. Patients treated with MIE less frequently showed severe pneumonia (7.5% versus 30%, respectively, p = 0.049) and had a shorter length of stay (median: 16 versus 22 days, respectively, p = 0.009), albeit at the expense of a longer operating time (median: 465.5 versus 403 min, respectively, p = 0.015). Compared with OE, MIE was associated with a lower in-hospital mortality (25% versus 2.5%, respectively, p = 0.013). Moreover, MIE did not compromise the quality of resected specimens with similar R0 resection rate.

EC patients with LC showed more favorable mortality figures and lower rates of severe pneumonia after MIE compared with those who underwent OE. MIE may serve as a safe and feasible alternative for selected EC patients with LC.
386. SURGICAL SHORT-OUTCOMES IN ELDERLY PATIENTS WITH ESOPHAGEAL CANCER IN OUR INSTITUTION
Authors: Ishida Yoshinori , Kono Syugo , Hojo Yudai , Nakao Eiichiro , Nakamura Tatsuro , Kurahashi Yasunori , Shinohara Hisashi
Published: September 2022

With aging, patients with esophageal cancer would have several comobidity and decline of physiological function. It is difficult to fit the standerd treatment to the elderly patients with esopageal camcer. We review the data of elderly patients who underwent operation for esopageal cancer in our institution to evaluate the safety of surgery in this partucular population.

During January 2017 and December 2021, twenty three patients over 75-year-old underwent the operation with right thoracotomy, that is McKeown’s or Ivor-Lewis operation, for esophageal cancer or esophago-gastric junction cancer in our institution.

We retrospectively analyzed their preoperative assessment, concurrent disorders, surgical techniques used, postoperative course, and complications.

Average age of the patients was 79.5 years, and over 80 year-old patients were nine. Preoperative chemotherapy was done in 12 cases. Only 3 patients underwent esophagectomy with right thoracotomy and three-field lymph node dissection.

Postoperative complications occurred in 17 patients (74%). Mortality was one cases, because of severe respiratory failure. Anastomotic leakage was observed in nine patients. As other complications over Grade II in Clavien-Dindo (CD) classification, anastomotic stricture was 4, pneumonia was 3 cases. Recurrent nerve paralysis was observed in 6 patients in Grade I in CD classification.

It is difficult to decide treatment for esophageal cancer only at age. In elderly cases, it would require more ingenuity for anastomosis after esophagectomy.