bluuebunny/crossref_metadata_2025 huggingface dataset:
387. REFUSING SURGERY AFTER NEOADJUVANT TREATMENT IN PATIENTS WITH ESOPHAGEAL CANCER: A PROPENSITY-SCORE MATCHED SURVIVAL ANALYSIS
Authors: Chi Chun-Ling , Gao Xing , Chao Yin-Kai
Published: September 2022

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the recommended treatment for patients with locally advanced esophageal cancer. However, not all patients who started nCRT will undergo esophagectomy and refusal is one of the main reasons. Although an active-surveillance strategy in patients with a clinically complete response after nCRT is increasingly implemented in clinical practice, the evidence is still immature and refusing surgery still comes with uncertain risk and outcomes.

We aimed to study survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) who underwent nCRT followed by surgery versus patients who refused surgery after nCRT. Two hundred thirty patients treated between 2012–2020 at Chang-Gung Memorial Hospital were assessed. To balance confounders that could interfere with patients’ decision, baseline characteristics, year of treatment, type of nCRT regimen, adverse events during nCRT, timing of response evaluation, and result of response evaluation (Figure 1) were subjected to propensity score matching (PSM). Thirty-three patients refused surgery and were matched with 66 (of 146) patients who underwent surgery.

Before PSM, the two groups had similar baseline characteristics. No significant differences were found in the choice of nCRT regimen nor the severity of adverse events during nCRT, except for the days between the end of nCRT and response evaluation, which was longer in the refusal group (31.7 ± 14.1 versus 37.4 ± 16.4, P = 0.047). Surprisingly, response evaluation results were also similar before PSM. Two patients refused surgery while having positive biopsies and 82% still had suspected nodal involvement on computerized or positron emission tomography scan. After PSM, 3-year overall survival was 59% versus 55% in the surgery and refusal group, respectively (P = 0.78).

Our findings suggest that patients who refused surgery have similar survival outcomes as patients receiving esophagectomy after nCRT. However, after refusal, 85% still received additional chemoradiotherapy, 52% had disease progression within 16 months and 12% received salvage surgery eventually. Refusing surgery based on patients’ values and belief does not necessarily lead to worse survival outcomes, but future clinical trials should focus on standardization of additional therapy and follow-up after refusal to avoid uncertain outcomes.
393. ENDOSCOPIC VACUUM THERAPY FOR PATIENTS WITH ESOPHAGEAL PERFORATION: A MULTI-CENTER RETROSPECTIVE COHORT STUDY
Authors: Luttikhold Joanna , Pattynama Lisanne MD , Seewald Stefan , Groth Stefan , Morell Bernhard , Ida Satoshi , Nilsson Magnus , Eshuis Wietse J , Pouw Roos E
Published: September 2022

Esophageal perforations are associated with high morbidity. Recently, endoscopic vacuum therapy (EVT) has been introduced as a novel treatment option for esophageal perforations. This technique has so far mainly been described for anastomotic leakage after upper gastrointestinal surgery. The aim of this study was to describe the initial experiences with EVT for treatment of esophageal perforations caused by Boerhaave syndrome or with an iatrogenic cause.

For this retrospective, multicenter cohort study, all patients primarily treated with EVT for an esophageal perforation at four hospitals in the Netherlands, Switzerland and Sweden between January 2018 and October 2021, were included. Data on patient characteristics, EVT and outcomes were analyzed. The primary endpoint was success rate of EVT, defined as closure of the defect, as assessed by endoscopy or CT-scan.

27 patients were included (Table 1). EVT succeeded in 24/27 patients (89%, 95%CI[71,98]) with 16/19 using EVT alone (84%, 95%CI[60,97]). In 8 patients an additional treatment modality was used. In 3 patients EVT failed: 2 (Boerhaave and unknown cause) deceased due to a pulmonary embolism and septic embolic stroke, and 1 (Boerhaave) underwent an additional esophagectomy. All had a ‘large’ perforation-size.

Median hospital stay was 18 days, with median 12 days EVT-duration and 1 sponge-exchange. Additional drainage was performed in 8 patients. EVT-associated complications occurred in 3 patients: 1 iatrogenic defect-expansion from the overtube and 2 hemorrhages, which spontaneously stopped.

EVT is a promising, possibly organ-preserving treatment for Boerhaave syndrome or iatrogenic esophageal perforation, with a success rate of 84–89%. More experience with the technique and indications for use will likely improve success rates in the future.
395. EXPRESSION OF MALAT1, MANCR, PSMA3-AS1 AND MIR-101 IN ESOPHAGEAL ADENOCARCINOMA PATIENTS: PRELIMINARY RESULTS OF A CASE–CONTROL STUDY
Authors: Syllaios Athanasios , Gazouli Maria , Sakellariou Stratigoula , Sougioultzis Stavros , Karavokyros Ioannis , Liakakos Theodoros , Schizas Dimitrios
Published: September 2022

Esophageal adenocarcinoma is a leading cause of cancer-related mortality. Ongoing research aims to elucidate the molecular mechanisms underlying the tumorigenesis and progression of esophageal adenocarcinoma and to identify novel therapeutic targets. The abnormal expression of lncRNAs and miRNAs may play an important role in various biological processes in cancer, including immune response, differentiation, angiogenesis, apoptosis, cell proliferation and autophagy.

A total of 50 patients who were operated for esophageal adenocarcinoma in our Department from January 2015 to December 2018, were enrolled in the study. Twenty-six healthy individuals that underwent upper gastrointestinal endoscopy were recruited as controls in the study. Total RNA was extracted from esophageal adenocarcinoma tumors, lymph nodes and healthy esophageal tissues using the reverse transcription and qRT-PCR. The expression of different lncRNAs (MALAT1, MANCR, PSMA3-AS1) and miRNA (miR-101) were determined by the 2-ΔΔct method and presented using Fold-Regulation.

MALAT1 expression was upregulated in esophageal adenocarcinoma tumors and positive lymph nodes compared to non-cancerous tissues (1.9 and 2.0 times higher than controls respectively). Higher expression of MANCR was also found in esophageal adenocarcinoma tissues and positive lymph nodes compared to controls (2.6 and 2.1 times respectively). MiR-101 was downregulated in esophageal adenocarcinoma tumors and positive lymph nodes compared to controls (16.0 and 7.8 times lower respectively). No significant difference was observed in PSMA3-AS1 expression between esophageal adenocarcinoma tumors or positive lymph nodes and relevant healthy tissues.

MALAT1 and MANCR are upregulated in esophageal adenocarcinoma patients while miR-101 is downregulated. Further research in lncRNAs, miRNAs and their interactions with oncogenic pathways may offer new options for the diagnosis, prognosis and therapy of esophageal adenocarcinoma patients.
396. LONG-TERM QUALITY OF LIFE AFTER MINIMALLY INVASIVE ESOPHAGECTOMY FOR ESOPHAGEAL CANCER: A SINGLE CENTER EXPERIENCE
Authors: Jones Amy , Conroy Molly , Barney Megan , Shettig Abigale , Crafts Trevor , Qureshi Alia , Wood Stephanie
Published: September 2022

Esophageal cancer typically requires multimodal treatment, with neoadjuvant chemotherapy and radiation followed by esophagectomy, which has helped improve the 5-year survival of this disease. Short-term quality of life (QOL) has been previously evaluated in patients who have undergone esophagectomy. As survival rates improve and patients are living longer after having multimodal therapy, there exists a need to better understand how long-term QOL is impacted after esophagectomy.

A single-center cross-sectional QOL study was performed on a cohort of patients who underwent esophagectomy for esophageal cancer (2010–2017) with a post-operative survival period of at least four years. Patients who met inclusion criteria were contacted by phone in 2021–2022 to complete the European Organisation for Research and Treatment of Cancer (EORTC) OES-30 and OES-18 questionnaires, after standardization of interviews via a telephone script. Descriptive statistics were performed.

One hundred and fifty-five patients met inclusion criteria, and 64 (41.3%) completed the QOL questionnaires. Mean age was 64 years, the majority were white (98.4%) men (82.3%), and 82% underwent preoperative chemoradiation treatment. All patients underwent a minimally invasive surgical approach. At the time of QOL surveillance, the mean time from operation was 6.9 years. The median global QOL score in this population was 79.2 (Max 100). The population had median reported severity scores for dysphagia (100), reflux (33.3) trouble eating (16.7), and pain (11.1) (Max 100). A median score of 0 was found for all other esophageal symptom categories.

In patients surviving at least four years from esophagectomy for esophageal cancer, symptom severity scored highest for dysphagia. Elevated severity scores were also seen in descending order for reflux, difficulty eating, and pain. Despite these continued symptoms, long-term overall QOL remained high for this population after esophagectomy.
399. CURRENT PRACTICE IN ANTIREFLUX AND HIATAL HERNIA SURGERY: EXPLORATION OF THE BELGIAN FIELD
Authors: Depypere Lieven , Van Veer Hans , Nafteux Philippe , Coosemans Willy
Published: September 2022

In Belgium no publicly available information exists on the spread, quality, results nor follow-up of antireflux and hiatal hernia surgery, in contrast to the recently centralized esophageal cancer surgery. However, in some countries a plea is rising to perform this benign esophageal surgery in high volume centers. The aim of this study was to create a snap shot of the current practice in Belgium.

An online questionnaire was distributed among all members of the Royal Belgian Society for Surgery in autumn 2021. A total of 33 questions spread over four sections were asked, covering demographics, current practice (case load, case mix, indications for surgery, preoperative workup, patient information, average length of stay, follow up, quality of life (QOL)), operative techniques (approach, type of procedure, crural reinforcement) and future thoughts (opinion on the future of antireflux and hiatal hernia surgery in Belgium).

Twenty-four surgeons completed the questionnaire.

Surgical indications are discussed multidisciplinary and based on guidelines in 67%. Workup includes endoscopy, pH-monitoring and manometry in 100%. Barium swallow, impedance and gastric emptying tests were added in respectively 83%, 42% and 13%. Symptom or QOL scores were used in 17%. 81% are performed as primary surgery, 18% redo surgery and 1% resections. Laparoscopic procedures are reported in 99%: Nissen(−Rosetti) 79%, Toupet/Lind 15%, partial gastrectomy 5% and Collis gastroplasty 1%. Discharge is planned on POD1 in 42% and on POD2 in 54%. 50% performs follow-up <1 year. Interest in further clinical research collaboration was expressed in 92%.

Antireflux and hiatal hernia surgery is not standardized in Belgium. There is an evident variety in clinical practice, but this questionnaire shows similarity amongst respondents regarding workup and surgical approach. Further research collaborations are possible in the future.
406. COMPARISON OF OUTCOMES BETWEEN SALVAGE OESOPHAGECTOMY AFTER DEFINITIVE CHEMORADIOTHERAPY WITH PLANNED OESOPHAGECTOMY AFTER NEOADJUVANT CHEMORADIOTHERAPY
Authors: Cooper Scott , Frankel Adam , Thomson Iain , Thomas Janine , Smithers Mark
Published: September 2022

Definitive chemoradiotherapy (dCRT) for oesophageal cancer is recommended in selected patients who are unfit for surgery, or where doctor and/or patient prefers to surgery. Salvage oesophagectomy after dCRT is reportedly a morbid procedure compared to oesophagectomy following neoadjuvant chemoradiotherapy (nCRT). If indications for dCRT expand, there will be a larger pool of patients requiring salvage oesophagectomy. We aimed to assess the post-operative clinical outcomes of patients who had dCRT compared with nCRT in our unit.

Data were obtained from a prospectively maintained database of patients receiving curative treatment for oesophageal cancer from January 2010 until February 2022. Patients receiving a salvage oesophagectomy after dCRT were compared to those receiving nCRT and planned oesophagectomy. An comparison of differences in group characteristics, post-operative outcomes and survival rates was made. Analysis was completed using t-test, chi-square, log rank and Kaplan–Meier methods.

216 patients had dCRT with 24 undergoing salvage oesophagectomy. 228 had nCRT followed by surgery. The salvage group had more SCC (47% versus 16%; p = 0.002), higher blood loss (434 versus 280 mL; p = 0.033) and more surgeon-rated technical problems (e.g. pleural adhesions or mediastinal fibrosis) (30% versus 11%; p = 0.010). Operative times were not significantly different (357 versus 330 minutes; p = 0.232). There was a trend towards higher complications in the dCRT group (83 versus 63%; p = 0.057). Operative mortality was 0% in both groups. As expected the median survival was worse in the dCRT group (26 versus 66 months; p = 0.040).

Patients selected to dCRT who require and are fit for salvage oesophagectomy have worse outcomes compared with those who have nCRT. However, this subgroup still have a modest potential for cancer survival. Our dataset adds to the existing literature and will help to counsel patients being considered for salvage oesophagectomy. The possible future increase in number of patients being offered dCRT makes improving the understanding of peri-operative and cancer-specific outcomes after salvage oesophagectomy a priority.
407. A STUDY OF OUTCOMES OF ESOPHAGEAL CANCER SURGERY FOR ELDERLY PATIENTS OVER 80 YEARS OF AGE
Authors: Shigeno Takashi , Fujita Takeo , Kajiyama Daisuke , Sato Kazuma , Fujiwara Naoto , Daiko Hiroyuki
Published: September 2022

According to the 2020 edition of the situation in Japan, the population aged 65 and over reached 35.89 million, accounting for 28.4% of the total population. Esophageal cancer is a common disease among the elderly, and it is expected that the number of encounters with elderly esophageal cancer patients will increase further in the future. We examined the outcomes of esophageal cancer surgery for elderly patients at our hospital.

Of 769 thoracic esophageal cancer resections performed at our hospital from 2015–2019, 53 (6.8%) patients aged 80 years or older were included.

The mean age was 82 (80–94) years, the male/female ratio was 45/8, tumor localization was Ut/Mt/Lt 5/23/25, and cStage (UICC 7th edition) was I/II/III/IV 12/8/30/3. The surgical technique was 1-stage resection/2-stage segmental resection/mediastinoscopy in 9/32/12 cases. Surgical complications were suture failure, recurrent nerve palsy, and pulmonary complications in 2/12/11 patients. The 3-year survival rate was 66.7%, and the 3-year recurrence-free survival rate was 62.1%. The 3-year survival rate was 66.7% and the 3-year recurrence-free survival rate was 62.1%.

Esophageal cancer surgery may be a treatment option for elderly patients who are able to tolerate surgery, even if they are over 80 years of age. Our hospital provides a multidisciplinary team intervention for patients over 70 years of age 3–4 weeks prior to surgery, during the perioperative period, and after discharge, which may be useful in reducing postoperative complications.
408. RISK FACTORS FOR PERMANENT RECURRENT LARYNGEAL NERVE PALSY AFTER MCKEOWN MINIMAL INVASIVE ESOPHAGECTOMY
Authors: Chao Yin-Kai , Kuo Chun-Ting
Published: September 2022

Recurrent laryngeal nerve (RLN) palsy, especially left side, is a common complication after 3-stage McKeown esophageal cancer surgery and is related to increased risk of respiratory complication. Although some risk factors have been identified on the development of RLN palsy, data on its long-term recovery and factors affecting the recovery was scarce. The present study aimed to assess these unresolved issues.

Patients who experienced left RLN palsy after McKeown minimally invasive esophagectomy (MIE) for esophageal carcinoma between 2008 and 2021 were selected from a prospective database. RLN palsy was defined based on postoperative fiberoptic laryngoscopy and was classified as permanent if recovery was not seen within 6 months. MIE was further classified as robot-assisted or conventional thoracoscopic approach.

Among the 85 patients who developed left RLN palsy after MIE, recovery was observed in 22 patients (i.e., permanent palsy rate: 75%). Multivariate logistic regression analysis revealed active smoker (unfavorable, OR [95%CI]:2.99 [1.06 ~ 8.41], p = 0.038) and the use of thoracoscopic approach (unfavorable, OR [95%CI]:3.52 [1.14 ~ 10.8], p = 0.028) as independent risk factors for permanent palsy. The permanent palsy rate was 33.3% in patients who were non- or ex-smoker and received robotic approach as opposed to 85.7% in those who were smokers and received conventional thoracoscopic appraoch (p < 0.001).

Among the patients who developed left RLN palsy after McKeown MIE, only one-fourth could be fully recovered. RLN palsy occurred in patients who were smoker and received thoracoscopic approach were less likely to have spontaneous recover and might be candidates for early intervention.
409. RECONSTRUCTION OF A SEGMENTAL OESOPHAGEAL DEFECT WITH A TUBED RADIAL ARTERY FOREARM FREE FLAP GUIDED BY 3-DIMENSIONAL MODELLING
Authors: Leggett Brandon , Bas Onur , Wiper Jonathan , Wagels Michael , Frankel Adam
Published: September 2022

Segmental defects of the oesophagus are rare but complex. If the patient survives the initial insult, reconstructive techniques most commonly involve gastric pull-up or colonic interposition (1) however alternative techniques such as free flap reconstruction can be utilised if the former are unsuitable (2). The surgical field often is quite hostile in these cases, making pre-operative visualisation and planning critical in achieving a successful outcome. We describe our approach after a surgical complication in a 49-year-old man.

cT3N2M0 GOJ adenocarcinoma, pre-operative FLOT4, three-stage oesophagectomy complicated by anastomotic leak and tracheo-gastric fistula. Cervical oesophagostomy and venting gastrostomy (via laparotomy) was performed (severe illness precluded one-lung ventilation). He improved and was discharged, but a persistent fistula from the gastric conduit to his trachea remained. Reconstruction was planned by a multidisciplinary team using detailed 3D modelling. Via right thoracotomy, the gastric conduit was reduced into the abdomen and the tracheal defect was repaired with an intercostal muscle flap. A retrosternal colonic interposition restored gastrointestinal continuity. The superior 2 cm infarcted and was replaced by a dual-paddled tubular radial forearm free flap.

This complex surgical situation demonstrates how 3D visualisation of a segmental oesophageal defect can be extremely helpful in pre-operative planning. In particular, the precise anatomical location of the gastro-tracheal fistula and its relationship to the bony landmarks and surrounding vascular anatomy were critical in considering surgical access and reconstruction options. Whilst the literature describes applications of 3D visualisation for surgical planning in alternative contexts, there is minimal information of its use in upper gastrointestinal reconstruction. The use of 3D modelling and printing within the surgical context has frequently been associated with reduced operating times and improved medical outcomes (3).

This case adds to the previously documented advantages of 3D modelling in surgical planning but applies them to an area not well covered in the literature. Additionally, it demonstrates the utility of an infrequently used technique (RAFF) for reconstructing a segmental oesophageal defect. Further research into quantifying the outcomes following the implementation of 3D modelling in visualisation and surgical planning would be useful in encouraging its integration into mainstream surgical practice.
414. SHORT-TERM CLINICAL EFFECT OF ROBOT-ASSISTED ESOPHAGECTOMY WITH THORACIC DUCT RESECTION
Authors: Li Chunguang , Li Bin , Yang Yang , Li Zhigang
Published: September 2022

Whether extended robot-assisted esophagectomy with thoracic duct resection (RAE-TDR) has a favorable impact on esophageal cancer patients remains not well defined. This study aimed to analyze safety and efficiency of RAE-TDR.

From January 2019 to July 2020, 73 consecutive patients with TD-resected and 127 consecutive patients with TD-preserved were enrolled, who received standard RAE McKeown surgery. Perioperative related indicators, RFS and OS at 1-year were compared between the two groups.

Morbidity of Clavien–Dindo classification grade ≥ II or III were similar (p > 0.05). The number of retrieved total lymph nodes and mediastinal nodes were significantly higher in the TD-resected group (29.0 ± 11.1 vs 25.1 ± 8.5, p = 0.006 and 2.3 ± 3.7 vs 1.7 ± 2.8, p = 0.002, respectively). Moreover, more metastatic TD-related lymph nodes were harvested in cT3–4 patients (2.3 ± 3.7 vs 1.7 ± 2.8，p = 0.21). The rate of LN recurrence and local recurrence were similar (6.8% vs 7.1%, p > 0.99 and 1.4% vs 2.4%, p > 0.99, respectively). OS and RFS at 1-year were equivalent regardless of the TD procedure in each stage (p > 0.05). However, Hematogenous metastasis in TD-resected group was significantly elevated (17.8% vs 7.9%, p = 0.034).

RAE-TDR may help to improve total and metastatic LNs harvest, especially for patients with advanced ESCC without increasing adverse events intra- and post-operation. However, RAE-TDR does not bring about a decrease in local recurrence rate within short-term follow-up. We are not sure whether the increase in distant metastasis rate in the RAE-TDR group is associated with relevant immune system damage. Therefore, non-selective RAE-TDR resection is not routinely recommended.
416. BIOMARKER IDENTIFICATION FOR CHEMOTHERAPY RESPONSE PREDICTION IN BARRETT’S CARCINOMA PATIENTS BY AN INFLAMMATORY-RELATED PLASMA PROTEIN PROFILING
Authors: Thieme René , Mehdorn Matthias , Netto Jeffrey , Schierle Katrin , Lordick Florian , Thiery Joachim , Gockel Ines
Published: September 2022

The prognosis of patients with advanced esophageal adenocarcinoma (EAC) is still poor, which is partly due to a limited chemotherapy response. About 50% of these patients, treated with neoadjuvant chemotherapy, are non-responder, which might by influenced by inflammation and immunological conditions.

EAC patients (n = 24) were characterized prospectively in a single center study for gender (female n = 4; male n = 20), age (median 64; range 43-77 years), TNM-classification, and pathological response rate (PRR) to neoadjuvant chemotherapy. PRR was assessed according to the Schneider classification (Grade 3 + 4 total + subtotal remissions were defined as good responders). A comprehensive high performance inflammation biomarker panel, including 92 inflammatory-related proteins, was conducted in plasma (OLINK, Uppsala, Sweden). Blood was taken before neoadjuvant chemotherapy induction (baseline) and after chemotherapy completion. EAC cell lines (OE33, OE19, SK-GT-4, FLO-1) were treated with the chemokine (C-X3-C motif) ligand 1 (CX3CL1) for 48 h.

Nineteen inflammatory-related proteins were altered significantly after neoadjuvant chemotherapy completion. The five most affected proteins were TNF, IFNγ, CX3CL1, FLT3L, and PD-L1. Pathway analyses revealed an activated IL10- and IL18-signalling pathway, after neoadjuvant chemotherapy. A PRR of 3 and 4 correlated significantly with higher baseline CX3CL1 values. CX3CL1 treatment led to decreased proliferation rates in two (OE19 and SK-GT-4) of the four investigated EAC cell lines by 25-50%. Values for GDNF were higher, while values for TRAIL and TNFRSR9 were lower in patients’ plasma with a good PRR after chemotherapy completion as compared to patients with a poor PRR.

Multiplex profiling of inflammatory-related biomarkers revealed an activated interleukin signaling, (IL10- and IL18 pathway) after neoadjuvant chemotherapy. Inflammatory plasma proteins as CX3CL1 could be an interesting candidate to predict PRR and to identify patients, who will benefit from neoadjuvant chemotherapy. However further prospective studies are needed to validate our first observations.
421. THE STAPLED ANASTOMOSIS IN ESOPHAGECTOMY: NO DIFFERENCES IN LEAKAGE AND STRICTURE-RATES BETWEEN THE 25 MM AND 28 MM CIRCULAR STAPLER
Authors: Tagkalos Evangelos , Uzun Eren , Berlth Felix , Lang Hauke , Van der Sluis Pieter C , Grimminger Peter P
Published: September 2022

For patients undergoing an Ivor Lewis esophagectomy with a circular stapled anastomosis, the optimal diameter of the used circular stapler to restore continuity is unknown. The aim of this study was to compare the 25 mm stapled versus the 28 mm stapled esophagogastric anastomosis after Ivor Lewis esophagectomy, focusing on anastomotic insufficiency and post- operative anastomotic strictures.

Between February 2008 and June 2019, 349 consecutive patients underwent Ivor Lewis esophagectomy with gastric conduit reconstruction and circular stapled anastomosis. Patient characteristics and postoperative results, such as anastomotic insufficiency rates, postoperative anastomotic stricture rates, time to anastomotic stricture rate, and the number of dilatations, were recorded in a prospective database and analyzed.

In 222 patients (64%), the 25 mm circular stapler was used. There were no differences in baseline characteristics. Anastomotic insufficiency rates were comparable between the 25 mm (12%) and the 28 mm groups (11%) (p = 0.751). There were no differences between postoperative anastomotic strictures in the 25 mm (14%) and the 28 mm groups (14%) (p = 0.863). Within patients with postoperative anastomotic strictures, a median number of 2 dilatations were observed in each group (p = 0.573) without differences in the time to first diagnosis (p = 0.412).

There were no differences in anastomotic insufficiency and postoperative anastomotic stricture rates between the 25 mm and the 28 mm circular stapled esophagogastric anastomosis after Ivor Lewis esophagectomy. Both the 25 mm and 28 mm stapler can be safely used to create a circular stapled esophagogastric anastomosis to restore continuity after esophagectomy.
427. CHARACTERIZATION OF THE CYTOSKELETON-ASSOCIATED PROTEIN 4 (CKAP4) IN A BARRETT’S ESOPHAGUS CELL CULTURE MODEL
Authors: Limberger Beate , Ludwig Alexandra , Lyros Orestis , Nowotny Robert , Gockel Ines , Thieme René
Published: September 2022

While the incidence of EAC is rapidly increasing, its prognosis remains poor, with a five-year survival rate of 20%. Consequently, the discovery of new molecular targets for an efficient characterization of EAC patients is necessary. CKAP4 has been attributed to be increased in various cancer entities and has a role in tumorigenesis. However, its role in EAC development and progression is widely unknown.

In a Barrett’s esophagus, in vitro cell culture model of BE and EAC, CKAP4 expression levels were verified with qPCR, western blot and FACS analysis. In OE33 and OE19 cells a knockdown of CKAP4-expression was done by siRNA for 48 h and 72 h. In siCKAP4 transfected cells FACS (apoptosis), western blot analysis, colony forming assay (CFA), transmigration, adhesion and proliferation assays, were performed. Using western blot, the impact of CKAP4-knockdown on the phosphorylation of Akt, MAP-Kinase, GSK3ß and ß-Catenin was investigated. Furthermore, DKK1-, Ki67- and p21-mRNA-expression was analyzed in siCKAP4 cells using qPCR.

CKAP4 was present in all cell lines of the Barrett’s sequence (squamous epithelium, metaplasia, dysplasia, and EAC). CKAP4 surface expression was significantly increased in OE33, OE19 and Flo-1 cells. The phosphorylation of Akt was decreased in OE19 cells only, whereas the phosphorylation of MAP-kinase was reduced in OE33 cells, suggesting a role of CKAP4 in tumor-associated proliferation. This was confirmed by decreased colonies in CFA in siCKAP4 cells. FACS analysis showed a significant increase in the amount of apoptotic cells after siCKAP4 transfection. SiCKAP4 led to an increased expression of adhesion molecules, suggesting an impact of CKAP4 in cell adhesion.

The role of CKAP4 is barely investigated in EAC at this time. Acting as a Dickkopf-1 (DKK1) receptor, the DKK1-CKAP4-axis might promote cell proliferation independently to the Wnt-pathway. Based on our current results, it can be assumed, that CKAP4 is important for EAC cell growth, proliferation and cell adhesion. Nevertheless, further characterization of CKAP4 is necessary, particularly focusing on the CKAP4-DKK1-axis to provide more evidence for its contribution in EAC development.
431. THORACOSCOPIC ESOPHAGEAL CANCER SURGERY IN THE LEFT LATERAL POSITION WITH EMPHASIS ON SAFETY AND RADICAL CURE
Authors: Sato Hiroshi , Miyawaki Yutaka , Lee Seigi , Sugita Hirofumi , Sakuramoto Shinichi
Published: September 2022

Compared with thoracoscopic esophagectomy in the prone position (PP), the conventional thoracoscopic esophagectomy in the left lateral position (LL) with artificial pneumothorax is slightly more difficult for dissection of the middle and lower mediastinum, but is superior to PP because the operation can be performed with good visual field in the upper mediastinum. The purpose of this study was to clarify the safety and curative potential of this technique.

We retrospectively reviewed 246 cases of thoracic esophageal cancer surgery from April 2012 to December 2018. Thoracoscopic surgery (group V) was performed in 154 patients and open right thoracotomy (group O) in 92 patients. When this procedure was judged to be feasible, it was started thoracoscopically, and when it was judged to be unfeasible, a small thoracotomy of about 10–15 cm was added to allow one hand to enter. Thoracoscopy not only reduces the invasiveness of the procedure, but also allows us to share the anatomy, and improves the maneuverability of esophageal transfer and ensures safety in emergency situations.

Postoperative complications with Clavien-Dindo classification II or higher were 40% in group O and 51% in group V. In group V, anastomotic leak was 15 (9.7%), vocal cord paralysis 34 (22%), pneumonia 17 (11%), SSI 16 (10%). The mean postoperative hospital stay was 20 days. 8 (8.7%) patients in the O group had anastomotic leak, 10 (11%) had vocal cord paralysis, 8 (8.7%) had pneumonia, 12 (7.8%) had SSI. The mean postoperative hospital stay was 28 days. Of 27 salvage procedures, 14 (52%) were performed thoracoscopically. Thoracoscopic surgery was completed in 10 cases and combined thoracotomy in 4 cases.

Short-term outcomes of thoracoscopic surgery show an increase in vocal cord paralysis compared to open surgery. The procedure does not improve infectious complications. This technique has the advantage of easy conversion to open thoracotomy, including in emergency situations, and is more advantageous in advanced cancer, and can be a curative and safe treatment for highly advanced cancer.
451. CLINICAL PATTERNS AND TREATMENT OUTCOMES OF OESOPHAGEAL PERFORATION—A TEN-YEAR RETROSPECTIVE ANALYSIS FROM A TERTIARY CENTER IN SOUTH INDIA
Authors: Sigamony Negine Paul Paul , Yacob Myla , Surendran Suraj , Chandran Sudhakar , John Anoop , Simon Ebby , Samarasam Inian
Published: September 2022

Oesophageal perforation is a rare, often life-threatening clinical condition with reported mortality rates of 18 to 25%. Early diagnosis is often challenging with many patients presenting late and in shock. Management is even more challenging with a myriad of options but no standard options or criteria. We aim to review our ten-year experience of managing oesophageal perforation and propose an algorithmic approach for managing this condition.

A retrospective review of patients diagnosed with oesophageal perforation from 2011 to 2020 was done. Oesophago-gastric anastomotic perforations and corrosive injuries were excluded. The data relevant for the study including Pittsburgh Severity Score (PSS) was collected from the hospital electronic medical records and strengthened using telephonic conversation.

Thirty-six patients (M: F-26:10, mean age: 48 years) were included. In 21 (58%) patients, the perforation was localized to the thoracic oesophagus. The commonest cause of perforation was Iatrogenic (n = 22, 61%), followed by spontaneous (n = 9, 25%). A severe PSS score (≥7) was associated with increased risk of operative intervention (76%) and mortality (18%). Eighteen patients (50%) required operative interventions wherein a primary repair was performed in seven (39%) patients, sepsis drainage in eight (44%) patients, and a diversion in one (6%) patient. Overall, eleven (31%) patients required a re-intervention, and the overall in-hospital mortality was 8.3%.

Early diagnosis and decision making using an algorithmic approach are critical in the management of oesophageal perforation. PSS score is a useful tool in assessing the severity of disease. A combined multidisciplinary approach involving therapeutic endoscopy, surgery, and critical care is essential. A minimally invasive surgical approach is a feasible option in selected group of patients.
456. THE PROGNOSTIC IMPACT OF TUMOR BUDDING IN ESOPHAGEAL ADENOCARCINOMA
Authors: Fiocca Roberto , Mastracci Luca , Lugaresi Marialuisa , Grillo Federica , D'Errico Antonietta , Malvi Deborah , Spaggiari Paola , Tomezzoli Anna , Albarello Luca , Ristimäki Ari , Bottiglieri Luca , Bonora Elena , Krishnadath Kausilia K , Rosati Riccardo , Romario Uberto Fumagalli , De Manzoni Giovanni , Räsänen Jari , Mattioli Sandro
Published: September 2022

In a previous study on esophageal adenocarcinoma (EAC) cases submitted to surgery (without neoadjuvant treatment), an algorithm (EACGSE classification) 1 based on morphologic distinctions provided significant prognostic impact. Tumor budding is a specific type of invasive growth pattern and was found to be an important prognostic parameter in gastrointestinal cancers. 2–3 We aimed to evaluate the prevalence of budding in glandular adenocarcinomas and its impact on survival.

The EAC cohort classified according to EACGSE 1 was included in the study: among the different histotypes, 215 cases, classified as well (WD) and poorly (PD) differentiated glandular adenocarcinomas, were considered. Tumor budding was defined as single cells or clusters of up to four cells at the invasive margin. Budding was grouped according to ITBCC 2 into Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (10 or more buds). Furthermore, the most prognostically relevant cut off for bud number in EAC was defined by ROC analysis. Cancer specific survival analyses were performed using the Kaplan–Meier method and Cox regression analyses.

Tumor budding was assessed in one hotspot (a field measuring 0.785 mm2) at the invasive front and ROC analysis identified 8 buds per field cut off as the most informative in relation to survival. By using this cut off, frequency of budding was higher in glandular PD (84/124,68%) cases than in WD ones (7/91,8%, p < 0.001). Budding was a strong negative predictor of survival both in univariate (p < 0.001) and multivariate analyses (p < 0.001) (Fig. 1). Using the 3 categories proposed by ITBCC, 2 budding was significantly related to survival in univariate analysis (p = 0.006) but lost significance in multivariate analysis.

Tumor budding showed a prognostically negative impact in glandular EACs. The 8 buds per field cut off appears to provide the best prognostic discriminant. Tumor budding assessment should be added to the identification of other prognostic factors already described in the same series (stage, histotype and vascular invasion). 1
457. STANDARDIZATION AND SHORT-TERM RESULTS OF ROBOT-ASSISTED THORACOSCOPIC ESOPHAGECTOMY
Authors: Koyanagi Kazuo , Kazuno Akihito , Yamamoto Miho , Higuchi Tadashi , Yatabe Kentaro , Kanamori Kohei , Tajima Kohei , Nakamura Kenji , Nabeshima Kazuhito , Ogimi Mika
Published: September 2022

Surgical cases of robot-assisted thoracoscopic esophagectomy (RAMIE) is increasing because of the advantages of robotic system. We introduced RAMIE in 2019 and standardized the surgical procedure. The usefulness of RAMIE was examined by classifying surgical cases into early and late periods and comparing the surgical results.

Fifty-four patients who underwent RAMIE were enrolled in the study. All patients underwent D2 or higher lymph node (LN) dissection, gastric tube reconstruction, and R0 surgery. The patients were divided into two groups, 26 cases in the first half up to December 2020 and 28 cases in the second half after January 2021. The patient background, surgical technique, and short-term results were compared. The tumor staging was based on the UICC 8th version.

Thoracic surgery time was 274 minutes, the chest bleeding volume was 30 mL, and the postoperative hospital stay was 19 days (median). In the late stage, patients with clinical thoracic LN metastasis (p = 0.01) and advanced stage (p = 0.006) were higher than those in the early period. There were significantly more cases of thoracic duct resection and D3 dissection in the late period (p = 0.02, p = 0.009). No differences in postoperative complications and intra-hospital death was observed, however the postoperative hospital stay was significantly shortened in the late period (p = 0.001).

Thorough mediastinal LN dissection by RAMIE could be safely performed by standardizing and improving the surgical procedures. RAMIE has several issues such as higher cost associated with equipment and longer operative time, but it is possible to perform precise procedures with solo surgery, and it is expected that cost reduction effects will be expected in terms of the number of participants in surgery and the length of hospital stay after surgery.
466. OUTCOME OF NIVOLUMAB FOR UNRESECTABLE ADVANCED OR RECURRENT ESOPHAGEAL CANCER IN OUR INSTITUTION
Authors: Tabuchi Satoshi , Takano Yuki , Ochiai Shigeto , Gunji Takahiro , Kobayashi Toshimichi , Suzumura Hirofumi , Shigoka Masatoshi , Chiba Naokazu , Hidaka Eiji , Kawachi Shigeyuki
Published: September 2022

In recent years, drug therapy for esophageal cancer has seen rapid progress, including immune checkpoint inhibitors. Guidelines for the treatment of esophageal cancer recommend nivolumab as second-line therapy. We report the results of nivolumab for unresectable advanced or recurrent esophageal cancer in our institution, including the cases that responded to the therapy.

We analyzed 12 patients (male: female = 10:2, median age: 67 years) treated with nivolumab for unresectable advanced or recurrent esophageal cancer between March 2020 and March 2022.

The status of treatment, response rate, adverse effects, and conversion rate to next line were analyzed for these patients.

The median follow-up period was 4.2 months, and the median number of treatment cycles was 5 (2-41). Response rate was 17%, and disease control rate was 42%. Adverse effects included one case (8%) of severe diarrhea, considered ir-AE. The patient was treated with steroids. The rate of conversion to next-line treatment was 17% (2 cases).

Nivolumab for esophageal cancer has a good prognosis in patients who respond to it. In addition, it is important to pay attention to ir-AE, perform imaging and physical examinations, and evaluate accurately and treat quickly.
476. SONIC HEDGEHOG POSITIVE EXPRESSION IS ASSOCIATED WITH PROGNOSIS AND THE RESPONSE OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA TO NEOADJUVANT CHEMOTHERAPY
Authors: Sun Haibo , Liu Xianben , Xing Wenqun , Feng Shaokang , Jiang Duo , Yan Sen , Ma Yaxing
Published: September 2022

Neoadjuvant therapy follow by surgery is the standard treatment mode for patients with locally advanced esophageal squamous cell carcinoma (ESCC). This research aimed to investigated the potential of sonic hedgehog (Shh), glioma-associated oncogene homolog1 (Gli1) and Phospho-S6 (p-S6) to predict the response of ESCC to neoadjuvant chemotherapy.

Firstly, the expressions of Shh, Gli1 and p-S6 in cancer tissues and normal tissues of 49 ESCC patients without neoadjuvant therapy were detected by immunohistochemistry. A total of 390 ESCC patients were included in the nest study, and 44 pairs of patients with or without neoadjuvant chemotherapy were matched after 1:1 propensity score matching to evaluate the effect of neoadjuvant chemotherapy on the expression of Shh, Gli1 and p-S6. The relationship between Shh, Gli1, and p-S6 expression and the outcomes of neoadjuvant chemotherapy was analyzed retrospectively.

The expressions of Shh (positive/negative: 25/24 vs. 0/49, P﹤0.001), Gli1 (24/25 vs. 0/49, P﹤0.001) and p-S6 (16/33 vs. 0/49, P﹤0.001) in cancer tissues were significantly higher than those in normal tissues. Neoadjuvant chemotherapy did not change the expression of Shh (24/20 vs. 23/21, P=0.109), Gli1 (23/21 vs. 21/23, P=0.839) and p-S6 (10/34 vs. 15/29, P=0.383) in ESCC cancer tissues. Among them, the positive expression of Shh was associated with poor tumor regression grade (TRG2-3/TRG1: 23/1 vs. 12/8, P=0.003) and poor 5-year survival rate (44.7% vs. 65.8%, P=0.041).

The expressions of Shh, Gli1 and p-S6 were increased significantly in ESCC and were not affected by neoadjuvant chemotherapy. Shh is a significant predictive indicator of ESCC response to neoadjuvant chemotherapy and prognosis.
477. TEXTBOOK OUTCOMES FOR OESOPHAGECTOMY: AN EVALUATION OF OESOPHAGECTOMY QUALITY PERFORMANCE INDICATORS AT A SINGLE HIGH-VOLUME AUSTRALIAN OESOPHAGOGASTRIC CENTRE
Authors: Wu M , McGregor R , Scott J , Smithers M , Frankel A , Barbour A , Thomson I
Published: September 2022

In 2017 the Dutch Upper-Gastrointestinal Audit Group (DUCA) proposed a ten-item composite measure for a “textbook outcome” after oesophagogastric resection. Utilising this composite measure, studies have shown associations between textbook outcomes and better conditional and overall survival. The aim of our study was to evaluate the applicability of this measure in the setting of an Australian oesophagogastric centre and to ascertain whether textbook outcome was associated with improved survival.

Data were obtained by retrospective analysis of a prospectively maintained database of oesophagogastric malignancies at a single oesophagogastric unit from 2013 to 2018. We used the DUCA group definition of textbook outcomes, encompassing resection radicality, resection margins, lymph node clearance, intra- and post-operative complications, length of stay, hospital and intensive care unit re-admissions, and post-operative mortality. Multivariable logistic regression analysis was conducted to assess association between patient factors and textbook outcome. Cox regression analysis was used to assess association between textbook outcome and survival. Post-operative complications were analysed in two separate groups (Clavien-Dindo ≥2 and Clavien-Dindo ≥3).

A total of 246 patients were analysed, with 50.8% achieving a textbook outcome when complications were defined as Clavien-Dindo ≥2 and 58.9% when using Clavien-Dindo ≥3. Patients with age <75 or a respiratory co-morbidity were less likely to achieve a textbook outcome. The 30-, 90-day and 1-year mortality rates were 1.6%, 2.4% and 15% respectively. There was no difference in survival between those who did versus those who did not have a textbook outcome when complications were defined as Clavien-Dindo ≥2. There was improved overall survival if complications were defined as Clavien-Dindo ≥3 (HR0.58, p=0.015).

Textbook outcome is a new multi-parameter metric that aims to better capture the quality of oesophageal cancer surgery compared to traditional volume-outcome relationships. We have demonstrated that it is applicable in our population, with the percentage of patients having a textbook outcome comparing favourably with published data. In our series, a textbook outcome was associated with improved overall survival when defining complications as Clavien-Dindo ≥3.
481. QUANTITATIVE ESTIMATION OF GASTRIC CONDUIT PERFUSION TO SELECT ESOPHAGECTOMY PATIENTS AT HIGH RISK OF IMPAIRED PERFUSION
Authors: Ishikawa Yoshitaka , Zhao Lili , Chang Andrew , Lin Jules , Orringer Mark , Lynch William , Lagisetty Kiran , Wakeam Elliot , Reddy Rishindra
Published: September 2022

Impaired gastric conduit perfusion is considered the most important factor of anastomotic leaks following esophagectomy. Gastric ischemic preconditioning (GIP) can improve conduit perfusion and may reduce anastomotic leaks; however, it remains unclear which patients could benefit from preconditioning. The aim of this study is to create a paradigm to select patients at high risk of impaired perfusion who may benefit from GIP.

Patients undergoing an esophagectomy with gastric conduit reconstruction and indocyanine green fluorescence angiography from July 2015 to December 2021 (Cohort 1), as well as all patients receiving an esophagectomy from 2003 to 2021 (Cohort 2) were reviewed. Analyzed variables for Cohort 1 included patient pre-operative demographics and ingress index (quantitative assessment of blood perfusion). Multiple linear regression model for conduit perfusion was used to select significant preoperative factors and to build a formula to estimate conduit perfusion. The formula was applied to Cohort 2 to estimate the percentage of patients who could receive GIP prior to esophagectomy.

349 patients were in Cohort 1, and 1965 in Cohort 2. There was a significant correlation with older age and low body mass index (BMI) and impaired conduit perfusion. Other factors, such as heart disease, diabetes, and prior chemoradiation did not correlate (Table). Using only two variables “age” and “BMI”, we determined how many could have poor conduit perfusion, defined as a low ingress index of <40 (the median value from the Cohort 1). When applying the formula to Cohort 2, we estimated that 26.7% (525) of patients would be at risk for low perfusion and for anastomotic leaks.

Using BMI and age, we are able to risk stratify patients who are likely to have low perfusion in their gastric conduits (Figure, higher risk in red). We feel that this group will be the most likely to benefit from pre-esophagectomy gastric ischemic conditioning.
486. ENDOSCOPIC VACUUM THERAPY FOR ANASTOMOTIC LEAKAGE AFTER ESOPHAGEAL RESECTION—A RETROSPECTIVE SINGLE-CENTER ANALYSIS
Authors: Herzberg Jonas , Strate Tim , Guraya Salman Yousuf , Honarpisheh Human
Published: September 2022

Esophagectomy still comes with a high rate of anastomotic leakage resulting in a persisting high postoperative mortality. Endoscopic vacuum therapy (EVT) is an upcoming technique for the treatment of anastomotic leakages. We aimed to evaluate our experience with the efficacy of EVT for anastomotic leakages after esophagectomy for cancer.

We retrospectively analyzed all 96 patients who had undergone Ivor-Lewis resection for esophageal malignancy from January 2015 until December 2021 for the need of EVT within the same hospital stay. Patients demographics, perioperative parameters, treatment efficacy and success were analyzed. Patient data were expressed as mean ± standard deviation.

We included fourteen patients treated with EVT following Ivor-Lewis resection for esophageal malignancy within the same hospital stay. 12 EVTs were due to anastomotic leakage whereas two procedures were performed prophylactically. We started the EVT 10.71 ± 8.04 days after surgery with a mean duration of 13.86 ± 7.39 days and a mean number of 4.36 ± 2.37 endoscopies per patient. Successful treatment was achieved in 10 patients (71.4%), one patient needed an esophageal stenting and an additional surgery for re-anastomosis was needed in 3 patients (21.4%).

EVT can prevent re-operation in a high proportion of patients with anastomotic leakage and therefore provides a good non-surgical option for these patients. The periinterventional risk and possible complications of repetitive endoscopies should be analyzed in larger studies.