bluuebunny/crossref_metadata_2025 huggingface dataset:
312. EFFICACY AND SAFETY OF NEOADJUVANT IMMUNOTHERAPY IN LOCALLY ADVANCED ESOPHAGEAL CANCER: A META-ANALYSIS OF CLINICAL TRIALS
Authors: Yang Xinyu , Sun Linyi , Tan Lijie
Published: September 2022

There recently have been great achievements in immunotherapy for locally advanced esophageal cancer (LAEC), but the efficacy and safety of neoadjuvant immunotherapy for LAEC have not been clearly demonstrated. This meta-analysis of clinical trials, based on the data available so far, aims to demonstrate the efficacy and safety of neoadjuvant immunotherapy for LAEC, to provide further treatment options for LAEC in the future, and obtain better survival benefits.

Original articles or Unpublished updated data of clinical trials describing the safety and efficacy of neoadjuvant immunotherapy in LAEC were researched from PubMed, Embase and Cochrane Library, ASCO, and ESMO. before April 25, 2022. The efficacy outcomes were pathological complete response (pCR) and major pathological response (MPR). The safety outcomes were treatment-related adverse events (TRAEs), and surgical resection rate. The risk differences and 95% confidence interval (CI) were calculated. Heterogeneity was determined by the χ2 test and I2 test. Subgroup analysis was performed based on pathology, immune checkpoints inhibitors and treatment modes.

A total of 351 patients from 16 clinical trials were included. The risk differences of pCR and MPR in neoadjuvant immunotherapy were 0.31 (95% CI: 0.26–0.35) and 0.61 (0.52–0.70), respectively. The incidences of all-grade TRAEs, grade ≥ 3 TRAEs, and surgical resection rate were 0.37 (0–0.77), 0.32 (0.18, 0.46), and 0.86 (0.82, 0.89), respectively. The better pCR and MPR in immunotherapy was shown in the immunotherapy combined with radio-chemotherapy, compared with immunotherapy combined with chemotherapy (pCR: 0.41 [0.31–0.51] vs. 0.28 [0.23–0.33]; MPR: 0.89 [0.74–1.03] vs. 0.61 [0.55, 0.68]). There were similar outcomes in other subgroups.

Neoadjuvant immunotherapy is effective and safe for LAEC.
325. THE ASSOCIATED RISK BETWEEN SINGLE NUCLEOTIDE POLYMORPHISMS OF AP1S1 AND ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN CHINESE POPULATION
Authors: Feng Su , Yong Fang , Jinjie Yu , Tian Jiang , Siyun Lin , Shaoyuan Zhang , Lu Lv , Tao Long , Huiwen Pan , Junqing Qi , Qiang Zhou , Weifeng Tang , Guowen Ding , Liming Wang , Lijie Tan , Jun Yin
Published: September 2022

The σ1A subunit of the adaptor protein 1 (AP1S1) participates in intracellular transport pathways, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case–control study, we investigated the genetic susceptibility to esophageal squamous cell carcinoma (ESCC) in relation to Single Nucleotide Polymorphisms (SNPs) of AP1S1 among Chinese population and made a preparation for the subsequent esophageal SNP risk model building.

A database containing a total of 1143 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P < 0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step.

AP1S1 rs77387752 C > T mutated homozygous TT was an independent risk factor for ESCC, while SNP rs4729666 C > T and rs35208462 C > T mutated heterozygote TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers. These three AP1S1 SNP sites could be incorporated into subsequent SNPs risk models for ESCC in specific populations.

AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers. These SNP sites might be added into the building of risk model and then the early diagnosis of ESCC. Besides, further mechanical exploration is required.

Table. Logistic regression analyses of associations between AP1S1 SNPs rs77387752 C > T, rs4729666 C > T, rs35208462 C > T and risk of ESCC.
336. IMPACT OF TIME TO SURGERY AFTER CHEMORADIOTHERAPY ON TUMOR REGRESSION AND SURVIVAL IN THE MULTICENTER RANDOMIZED CONTROLLED NEORES II TRIAL
Authors: Nilsson Klara , Klevebro Fredrik , Sunde Berit , Rouvelas Ioannis , Lindblad Mats , Szabo Eva , Halldestam Ingvar , Smedh Ulrika , Wallner Bengt , Johansson Jan , Borg David , Johnsen Gjermund , Aalin Eirik Kjus , Johannessen Hans-Olaf , von Döbeln Gabriella Alexandersson , Hjortland Geir Olav , Al-Haidari Ghazwan , Quaas Alexander , Wang Naining , Bartella Isabel , Bruns Christiane , Schröder Wolfgang , Nilsson Magnus
Published: September 2022

Time to surgery after termination of neoadjuvant chemoradiotherapy for esophageal cancer has traditionally been 4–6 weeks. Observational studies have suggested that delay of surgery for up to three months may lead to improved tumor regression and better outcomes. NeoRes II is the first randomized trial to address this in esophageal cancer. No difference in surgical morbidity or mortality between early and delayed surgery was reported in a previous publication from the trial.

A multicenter clinical trial with randomized 1:1 allocation of standard time to surgery of 4–6 weeks, or delay of surgery to 10–12 weeks, after termination of chemoradiotherapy. The primary endpoint was complete histological tumor regression in patients with adenocarcinoma. Secondary endpoints included tumor regression grade, tumor free resection margins and overall survival in all patients, and stratified by histological subtype.

In total 249 patients were randomized, 204 with adenocarcinoma and 45 with squamous cell carcinoma. There was no significant difference in histological complete response between adenocarcinoma patients allocated to standard time to surgery (20.6%) compared to delayed (25.6%) surgery (P = 0.18). Tumor free resection margin was achieved in 97.4% after standard time to surgery and 97.1% after delayed surgery (P = 1.0). The median follow-up time for survival was 51 months. Delayed time to surgery was associated with a 35% higher overall mortality, hazard ratio 1.35 (95% CI:0.94–1.95), (P = 0.11).

No significant difference in complete histological tumor regression or tumor free resection margins comparing standard and delayed time to surgery after chemoradiotherapy was observed. There was a non-significant trend towards inferior overall survival after delayed surgery, suggesting caution in delaying surgery for more than 6 weeks after neoadjuvant chemoradiotherapy.
343. THE RISK FACTORS OF HIATAL HERNIA IN ESOPHAGEAL CANCER PATIENTS WHO RECEIVED GASTRIC INTERPOSITION THROUGH POSTERIOR MEDIASTINAL ROUTE
Authors: Leow Osbert Qi Yao , Yeow Yun Jen , Yeow Kee Min , Gao Xing , Chao Yin Kai
Published: September 2022

Hiatal hernia (HH) after esophagectomy is becoming more relevant due to improvement in survival. The aims of this study were to define the incidence, risk factors of HH in patients who underwent esophagectomy and reconstructed with gastric tube via posterior mediastinal route.

We performed a monocentric retrospective study on 510 patients with esophageal cancer who underwent esophagectomy and reconstructed with the gastric substitute via posterior mediastinal route from 2007 to 2019. All postoperative computer tomography images were re-reviewed by two radiologists independently. The incidence of HH was estimated using Kalbfleisch and Prentice method and risk factors of HH were studied using the Fine and Gray competitive risk regression model by treating death as a competing event.

A total of 27 developed HH with the two-year cumulative incidence of 5.3%. The median time to diagnosis was 297 days. HH were symptomatic in 14 patients (52%) in whom five required emergent repair. Among the 22 patients who were treated non-operatively, progression of HH was found in 9. In the multivariable analysis, the risk factors for HH were: laparoscopic gastric tube harvest (HR = 5.756[1.07 ~ 31.2], p = 0.042) and the use of preoperative therapy (HR = 2.714[1.03 ~ 7.14], p = 0.043) were identified as independent factors associated with increased risk of HH.

HH represents a relevant surgical complication after esophagectomy and reconstructed with the gastric substitute via posterior mediastinal route. Especially in those who received preoperative therapy and using laparoscopic approach.
347. DEFINITIVE CHEMORADIOTHERAPY WITH DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL (DCF-RT) FOR ADVANCED CERVICAL ESOPHAGEAL CANCER
Authors: Okamoto Hiroshi , Taniyama Yusuke , Sato Chiaki , Ozawa Yohei , Ishida Hirotaka , Koseki Ken , Yamauchi Takuro , Kato Nobuhumi , Kamei Tokashi
Published: September 2022

Recently, the selection rate of definitive chemoradiotherapy (CRT) as a treatment option for cervical esophageal squamous cell carcinoma (ESCC) has increased to preserve the larynx. However, many things about the regimen, irradiation field, or which is better treatment have not been determined. We have started definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for advanced cervical esophageal squamous cell carcinoma.

We evaluated 20 advanced cervical ESCC patients (clinical stage II–IV, including T4b and/or M1 lymph node) in our department who received DCF-RT as the first-line treatment between December 2010 and August 2021.

16 males and 4 females. The pretreatment clinical stage included one stage II, five stage III, six stage IVa, and eight stage IVb cases (including 10 with T4b and 8 with M1 lymph node. Grade 3 or more adverse events included leucopenia (95%), neutropenia (90%), febrile neutropenia (55%). We attained CR in 17 patients (85%), SD in 2 patients, and PD in 1 patient. Of 17 patients with CR, 8 experienced recurrence and 9 continued exhibiting CR. Two patients who underwent salvage surgery. While the 2−/3-year overall survival rate was 60.2%/46.4%, the 2−/3-year recurrent-free survival rate was 51.4%/45.7%, respectively.

DCF-RT for advanced cervical ESCC could be completed by the careful administration, and although a strong blood toxicity might occur, a favorable prognosis can be obtained with larynx preservation. Further observations are warranted to establish the long-term prognosis, late complications of radiotherapy, and the significance of salvage surgery.
372. ASSESSMENT OF TUMOR REGRESSION GRADE IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER CHEMORADIOTHERAPY: COMPARISON OF 3 COMMONLY USED SCORING SYSTEMS
Authors: Huang Shih-han , Chao Yin-Kai , Wen Yu-Wen
Published: September 2022

Tumor regression grade (TRG) is a measure of histopathological response of cancer to neoadjuvant chemoradiotherapy (nCRT) and is associated with outcomes. Several TRG system are used in esophageal cancer: Becker (0%,1 ~ 10%,10 ~ 50%, >50% vital residual tumor cell [VRTC]), Chirieac (0%,1 ~ 50%, >50% VRTC) and Japan TRG (0%,1 ~ 33%,33 ~ 66%, >66% VRTC). Although these methods are generally accepted, currently there is no common standard.

We compared the application of three systems for assessment of TRG. Hematoxylin and eosin–stained slides from 482 resection specimens of esophageal squamous cell carcinoma following nCRT were independently reviewed by three pathologists.

Interobserver agreement was analyzed by kappa statistics. The prognostic strength of each TRG system was assessed using the concordance index.

Interobserver agreement for the Chirieac system showed the best kappa value (0.93) followed by the Becker (0.90) and JTRG (0.87) system. All three models predicted survival (P < 0.0001) independent of yp-stage in multivariate analysis. Concordance indices of the Chirieac, Becker and JTRG were: 0.627, 0.627 and 0.633, respectively (higher number = better prediction). When comparing with Chirieac system, the JTRG system more accurately predicted survival (p = 0.03) while the Becker system did not (p = 0.12).

Chirieac system is most reproducible for the evaluation of esophageal cancer response to nCRT. However, the JTRG system seemed to be more accurate in predicting survival.
375. PATTERNS OF RECURRENT DISEASE AFTER NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGEAL CANCER SURGERY WITH CURATIVE INTENT
Authors: Schuring Nannet , Stam WT , Plat VD , Kalff MC , Hulshof MCCM , van Laarhoven HWM , Derks S , van der Peet DL , van Berge Henegouwen MI , Daams F , Gisbertz SS
Published: September 2022

Recurrence is frequently observed in patients after esophageal cancer surgery and post-recurrence survival is dismal. Neoadjuvant chemoradiotherapy (nCRTx) followed by esophagectomy is the gold standard of care for resectable esophageal tumors in The Netherlands. This study investigated the recurrence patterns and survival in patients after nCRTx and esophagectomy.

This retrospective cohort study included data from a prospectively maintained database of patients with recurrent disease after nCRTx followed by esophagectomy in the Amsterdam UMC between 01-01-2010 and 31-12-2018. Post-recurrence treatment and survival were investigated for patients specified for tumor histology (adenocarcinoma [AC] or squamous cell carcinoma [SCC]) and by recurrence site (loco-regional, distant, or combined loco-regional and distant).

In total, 340 of the 803 patients included (42.3%) after nCRTx and esophagectomy developed a recurrent disease at a median of 49 and 51 weeks postoperatively, for patients with an AC or SCC, respectively. Fifty patients had loco-regional (14.7%, AC:11.2%/n = 31, SCC:32.2%/n = 19), 167 patients distant (49.1%, AC:52.3%/n = 145, SCC:33.9%/n = 20) and 122 patients had combined recurrences (35.9%, AC:36.5%/n = 101, SCC:33.9%/n = 20). Post-recurrence survival was superior for AC patients with loco-regional (33 weeks, 95%CI:7.3-58.7) compared to AC patients with distant (12 weeks, 95%CI 6.9-17.1) or combined recurrences (18 weeks, 95%CI:9.3-26.7). AC patients with loco-regional recurrences receiving curative intent treatment had the longest survival (87 weeks, 95%CI:6.9-167.4).

Most esophageal cancer recurrences after curatively intended treatment were located at distant or combined loco-regional and distant sites, with limited survival prospects. A subgroup of patients with loco-regional recurrence can be treated with curative intent and has prolonged survival. How to identify these patients needs to be investigated, as they may benefit from close postoperative surveillance.
390. ACUTE NUTRITIONAL AND FUNCTIONAL STATUS CHANGES IN PATIENTS UNDERGOING ESOPHAGECTOMY FOR CANCER
Authors: Lidoriki Irene , Syllaios Athanasios , Mylonas Konstantinos , Michalinos Adamantios , Gazouli Maria , Karavokyros Ioannis , Liakakos Theodoros , Schizas Dimitrios
Published: September 2022

Nutritional status of esophageal cancer patients who undergo esophagectomy is significantly exacerbated postoperatively. The aim of this study is to investigate changes in nutritional status and muscle function between preoperative period and the time of hospital discharge in cancer patients undergoing esophagectomy.

The study sample consisted of 70 patients with esophageal (n = 13) and gastroesophageal junction cancer (n = 57) who were admitted for surgery in our Department between September 2015 and February 2020. Out of them, 52 patients underwent Ivor-Lewis esophagectomy, while 18 patients underwent McKewon esophagectomy. The preoperative evaluation of nutritional status was based on Patient Generated Subjective Global Assessment (PG-SGA), while the preoperative assessment of muscle function was based on Handgrip Strength (HG). Weight loss and anthropometric measurements were also recorded. Patients’ follow-up was done at the time of hospital discharge.

Patients’ mean length of stay was 17.7 ± 12.5 days. Mean postoperative involuntary weight loss was 6% ± 3%. HG dominant hand was significantly lower at the time of discharge (−3.02 ± 3.80 kg, p < 0.001) compared to preoperative levels. Moreover, a significant change was observed for PG-SGA score (+2.61 ± 1.73) indicating greater rates of impaired nutritional status. There was a significant reduction in BMI (−3.7 ± 2.47 kg/m2, p < 0.001) and in arm circumference values (−0.8 ± 0.03 cm, p < 0.05), whereas no statistically significant alterations were observed in triceps skinfold measurements postoperatively (−0.007 ± 0.49, p = 0.368).

Esophageal cancer patients who undergo esophagectomy exhibit overt deterioration of nutritional and functional status during the postoperative course. Timely nutritional interventions are of great significance in order to avoid patients underfeeding and improve patients’ postoperative outcome.
405. TRANSTHORACIC VERSUS TRANSMEDIASTINAL ESOPHAGECTOMY FOR ESOPHAGEAL SQUAMOUS CELL CANCER: PROPENSITY SCORE-MATCHED COHORT ANALYSIS
Authors: Katsurahara Keita , Fujiwara Hitoshi , Shiozaki Atsushi , Konishi Hirotaka , Kubota Takeshi , Ohashi Takuma , Otsuji Eigo
Published: September 2022

Transthoracic esophagectomy (TTE) has been the standard procedure for esophageal squamous cell carcinoma (ESCC). In our institution, we performed transmediastinal esophagectomy (TME) as a radical operation for ESCC from 2013. In this study, we compared the short-term and long-term outcome of TME and conventional TTE using propensity score matching analysis.

We performed a retrospective cohort study including 223 patients who underwent esophagectomy with gastric tube reconstruction for ESCC between January 2009 and December 2017. Of these, 115 patents underwent TME and 108 patients underwent TTE. Propensity score was calculated using logistic regression analysis and one-to-one patient pairs were matched using propensity score matching.

72 patients in the TME group and TTE group were extracted by propensity score matching. The incidence of postoperative pneumonia was significantly lower in the TME group (9.7% vs 33.3%, P = 0.0004). Three-year overall survival rate was relatively better in the TME group than in the TTE group (75.0% vs 62.6%, P = 0.165). And Three-year recurrence-free survival rate also tended to be better in the TME group than in the TTE group (55.2% vs 48.5%, P = 0.373).

TME reduce postoperative pneumonia and may improve long-term prognosis in ESCC patients.
417. ROBOT-ASSISTED MINIMALLY INVASIVE ESOPHAGECTOMY WITH UPPER MEDIASTINAL LYMPHADENECTOMY
Authors: Tsunoda Shigeru , Nishigori Tatsuto , Hisamori Shigeo , Maekawa Hisatsugu , Hoshino Nobuaki , Hanada Keita , Yoshida Shinya , Nishiyama Kazuhiro , Obama Kazutaka
Published: September 2022

We started robot-assisted minimally invasive esophagectomy (RAMIE) in 2012 using da Vinci S. After the reimbursement in the national insurance system in 2018, RAMIE has been indicated as an institutional standard surgery simply depending on the da Vinci availability. Our early series of 45 RAMIEs showed significantly less postoperative morbidity (p = 0.03) mainly due to less pulmonary complication (p = 0.006) compared to conventional minimally invasive esophagectomy using propensity score matching (Ann Surg Oncol. 2020).

This study aims to retrospectively evaluate the feasibility of RAMIE and to demonstrate our standardized RAMIE with updated data.

Our surgical technique is as follows. A patient is placed in a prone position with both lung ventilation with 8-10 mmHg artificial pneumothorax. In the upper mediastinum, the thoracic duct is usually preserved unless there is tumor invasion. Then, the tracheoesophageal arteries flowing into the visceral sheath over the recurrent laryngeal nerve (RLN) are divided first and RLN is isolated laterally. Then, the lymphatic tissue is dissected from the trachea. This procedure is identical on both sides of RLN nodal dissection.

By January 2022, 89 RAMIEs (S: 6 cases and Xi: 83 cases) were performed. Thoracic operation time was 348 min and console time was 296 min. Intraoperative blood loss was 80 g and the number of harvested thoracic nodes is 23. There was no conversion from RAMIE to MIE nor to open procedure. Overall severe postoperative morbidity (Clavien-Dindo Grade 3 or higher) was 17% (15/89) and clinically relevant postoperative recurrent laryngeal nerve palsy (Clavien-Dindo Grade 2 or higher) was 10% (9/89). There was no postoperative mortality.

RAMIE was safe and feasible.
420. IDENTIFICATION AND CLASSIFICATION OF TUMOR CELLS IN PATIENTS WITH BARRETT’S CARCINOMA BY HYPERSPECTRAL IMAGING (HSI)
Authors: Maktabi Marianne , Wichmann Yannis , Köhler Hannes , Chalopin Claire , Jansen-Winkeln Boris , Gockel Ines , Thieme René
Published: September 2022

Hyperspectral imaging (HSI), as recently applied in medicine, is a novel technology combining imaging with spectroscopy. It might be used to identify, classify and discriminate malignant and non-malignant cells of histopathologic specimens. HSI allows the determination of a spectrum between the visual and near-infrared light (500-1000 nm).

After surgical resection, specimens (n = 96) of Barrett’s cancer were fixed in 4% formaldehyde and slices were conducted (3 μm), which were stained with hematoxylin and eosin (HE). Differences in the absorbance of squamous epithelium and esophageal adenocarcinoma (EAC) cells were determined at eosin’s and hematoxylin’s maximal absorption of 530 nm and 590 nm. A classification algorithm, which combines a multilayer perceptron (MLP) with a Gaussian filter and data reduction based on principal component analysis (PCA) was used for discrimination.

For the first time in literature, we were able to analyze esophageal adenocarcinoma, tumor stroma and squamous epithelium cells by HSI. For both, the squamous epithelium and the esophageal adenocarcinoma cells, the intragroup variances were quite low. A set of 20 specimens was used in a testing phase, which showed MLP by using reflectance data to provide the best results. Leave-one-patient-out-cross validation for all 96 specimens showed an accuracy of 77% with a sensitivity of 87% and a specificity of 72% for EAC determination and visualization.

Squamous epithelium and EAC cells show specific spectral alterations due to their HE-staining, when measured by HSI. However, the training algorithms need further validation to foster a semi-automatic decision-making process in histopathological tumor cell identification.
424. ROBOT-ASSISTED AND CONVENTIONAL MINIMALLY INVASIVE ESOPHAGECTOMY ARE ASSOCIATED WITH BETTER POSTOPERATIVE RESULTS COMPARED TO HYBRID AND OPEN TRANSTHORACIC ESOPHAGECTOMY
Authors: Tagkalos Evangelos , Van der Sluis Pieter C , Babic Benjamin , Berlth Felix , Lang Hauke , Grimminger Peter P
Published: September 2022

Currently 4 surgical techniques are performed for transthoracic esophagectomy (open esophagectomy (OE), hybrid esophagectomy (HE), conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE). Aim of this study was to compare these 4 different esophagectomy approaches regarding postoperative complications and short term oncologic outcomes.

Between 2008 and 2019, consecutive patients who underwent esophagectomy with gastric conduit reconstruction were included in this single center study. The primary outcome of this study was the incidence of postoperative complications. Overall 422 patients (OE (n = 107), HE (n = 101), MIE (n = 91) and RAMIE (n = 123)) were evaluated.

Uncomplicated postoperative course was observed in 27% (OE), 34% (HE), 53% (MIE), and 63% (RAMIE) of patients (p < 0.001). Pulmonary complications were observed in 57% (OE), 44% (HE), 28% (MIE), and 21% (RAMIE) of patients (p < 0.001). Cardiac complications were present in 25% (OE), 23% (HE), 9% (MIE), and 11% (RAMIE) of patients (p < 0.001). MIE and RAMIE were associated with fewer wound infections (p < 0.001). Median hospital stay was shorter for MIE and RAMIE went compared to OE and HE (p < 0.001). The lymph nodes yield differ significantly between the techniques (p < 0.001).

Total minimally invasive esophagectomy (MIE, RAMIE) was associated with a lower overall, pulmonary, cardiac and wound complication rate as well as a shorter hospital stay compared to open or hybrid approach (OE, HE). RAMIE resulted in higher lymph node harvest than MIE.
432. A CASE OF ADVANCED ESOPHAGEAL CARCINOSARCOMA DIAGNOSED LATE DUE TO SEVERE STENOSIS AFTER CHEMORADIOTHERAPY
Authors: Higashimoto Iku , Taniyama Yusuke , Sato Chiaki , Okamoto Hiroshi , Koseki Ken , Ozawa Yohei , Ishida Hirotaka , Kamei Takashi
Published: September 2022

Radiochemotherapy (CRT) is one of the curative treatment options next to surgery in the treatment of esophageal squamous cell carcinoma. However, CRT may cause esophageal stenosis or obstruction during the healing process. Therefore, in such cases, follow up of early recurrence detection becomes an issue for those patients.

We report a case of severe stenosis after CRT, in which recurrence could not detected until advanced cancer developed on the anal side of stenosis.

The case is a 73-year-old male. He was diagnosed with upper thoracic esophageal cancer (T4N2M0StageIVa) and had undergone radical chemoradiotherapy 5 years ago. The treatment effect achieved a complete response, but the primary tumor site caused severe esophageal stenosis. Therefore, biannual CT follow up had been done instead of endoscopic follow up. During follow-up, CT revealed a new neoplastic lesion in the lower thoracic esophagus, and endoscopy inserted through a gastrostomy revealed a bulky tumor on the anorectal side of the stenotic lesion. Biopsy revealed carcinosarcoma and robot-assisted thoracoscopic esophagectomy was performed.

Malignant neoplasms can be developed not only the same site of primary tumor after CRT. Especially in case of carcinosarcoma, detection would be delayed because of rapid growing. But when the severe esophageal stenosis occurred after CRT, the examination of anal side become difficult. Therefore, it is necessary to observe by frequent CT or PET examination, or endoscopy from gastrostomy for early detection of recurrence or newly malignant neoplasm.
435. A DIAGNOSTIC PITFALL; SMALL CELL CARCINOMA-LIKE FEATURES IN BASALOID SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS
Authors: Ishida Hirotaka , Kasajima Atsuko , Yamauchi Takuro , Kato Nobufumi , Koseki Ken , Ozawa Yohei , Okamoto Hiroshi , Sato Chiaki , Taniyama Yusuke , Fujishima Fumiyoshi , Kamei Takashi , Sasano Hironobu
Published: September 2022

Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to explore the pathological features of basaloid squamous cell carcinomas in biopsy specimens that mimic small cell carcinoma and to clarify their diagnostic and prognostic features. This study will contribute to draw attention to an important pitfall in pathology diagnosis in endoscopic biopsy specimens of the esophagus.

Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. A small cell carcinoma-like feature was defined as, when at least one of the three following findings was observed: 1) diffuse growth pattern, 2) nuclear molding and 3) nuclear crush artifact. Immunohistochemistry of synaptophysin, chromogranin A, CD56 (neuroendocrine markers) and p16 were performed in all cases.

Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24).

In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which may probably be caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is an only neuroendocrine marker expressed. p16 expression may be also detected in basaloid squamous cell carcinoma.
439. CAN THORACOSCOPIC ESOPHAGECTOMY IN CONVERSION SURGERY FOR LOCALLY ADVANCED UNRESECTABLE ESOPHAGEAL CANCER BE FEASIBLE?
Authors: Abe Tetsuya , Higaki Eiji , Fujieda Hironori
Published: September 2022

Conversion surgery (CS) after preoperative treatment has been reported to provide an improved prognosis for locally advanced unresectable esophageal cancer (LAUEC). The standard procedure of CS for LAUEC is transthoracic esophagectomy. However, few reports have been described on the safety and usefulness of conversion thoracoscopic esophagectomy.

We retrospectively analyzed the surgical outcomes of 26 patients who underwent transthoracic esophagectomy (open group) and 27 patients who underwent thoracoscopic esophagectomy (VATS group) between 2011 and 2019 after preoperative therapy for LAUEC.

Both groups had no significant differences in patient characteristics, excluding more females in VATS group. Median blood loss was significantly lower in VATS group. The two groups did not significantly differ in median operative time, R0 resection rate, any postoperative complications or hospital stay. No in-hospital deaths were observed in either group. The 3-year PFS rate was 62% in open group compared to 64% in VATS group, and the 3-year OS rate was 69% in the open chest group compared to 71% in the VATS group, which were comparable between the groups.

Thoracoscopic conversion surgery can be as safe and feasible as transthoracic thoracotomy in CS for LAUEC.
472. ROUTINE PLACEMENT OF FEEDING TUBES SHOULD BE AVOIDED IN ESOPHAGEAL CANCER PATIENTS UNDERGOING SURGERY
Authors: Shi Ge , Malthaner Richard , Nayak Rahul , Fortin Dalilah , Inculet Richard , Qiabi Mehdi
Published: September 2022

Perioperative nutritional optimization of patients undergoing esophagectomy for cancer is important as this population is prone to malnutrition associated with poor outcomes. Nutritional supplementation has been achieved via enteral nutrition through percutaneous feeding tubes such as gastrostomy tubes (G-tubes) and jejunostomy tubes (J-tubes). These are not benign and are associated with adverse events including infections, dislodgement, increased healthcare visits, among others. We aim to determine factors associated with adverse outcomes after feeding tube placement.

Patients who underwent esophagectomy for carcinoma and had at least one feeding tube placed from November, 2017 to October, 2021 at a single institution were retrospectively reviewed. Subgroup analyses were performed testing for revelant chracteristics. Wilcoxon rank sum test was used to analyze non-parametric continuous data, and Chi-Square and Fisher's exact test for categorical variables. Univeriate and multivariate logistical regression analyses were conducted evaluating outcomes of interests. The primary outcome was the overall rate of tube-related complications.

136 patients were included with 201 feeding tubes placed. The rate of adverse events related to feeding tubes was 39%. Of these, 11% were wound infections, 16% required procedural intervention, 11% visited the Emergency Department due to feeding tube-related complications. Smoking history was a significant risk factor for complications compared to never-smokers (44% vs. 24%, p=0.011). Females had increased complications compared to males (58% vs. 35%, p=0.010). Comorbid patients (Charlson Comorbidity Index 5-6) were more likely to suffer from tube-related complications (OR=4.47, p=0.038). There were no significant differences seen in complications rates comparing G- and J-tubes (32% vs. 43%, p=0.11).

There is significant morbidity related to feeding tubes. The risk profile of these tubes should be carefully discussed. Routine use of feeding tubes in esophagectomy patients should be avoided.
473. SAFETY AND USEFULNESS OF LARYNX- PRESERVING HIGH-LEVEL CERVICAL ANASTOMOSIS FOR CERVICAL ESOPHAGEAL CANCER
Authors: Fujieda Hironori , Abe Tetsuya , Higaki Eiji , Shimizu Yasuhiro
Published: September 2022

In cases of cervical esophageal cancer, total Pharyngo-Laryngo-Esophagectomy is often performed when the oral edge of the primary tumor is less than 2 cm from the esophageal entrance. In our hospital, we provide neo-adjuvant chemotherapy for cervical esophageal cancer and perform larynx-preserving esophagectomy whenever possible. The aim of this study was to evaluate the safety and efficacy of larynx- preserving high-level cervical anastomosis for cervical esophageal cancer.

41 patients underwent larynx- preserving esophagectomy for cervicothoracic esophageal cancer between January 2009 and September 2021 at our hospital were included. The distance from the oral edge of the primary tumor to the esophageal entrance was measured by esophagography and endoscopy. Patients with the distance of 2 cm or less were classified as the high cervical anastomosis group (H group: n=23), and patients with the distance of 2.1 cm or more were classified as the low cervical anastomosis group (L group: n=18). We compared the short-term and long-term results between the H and L groups.

There were no differences between H and L groups in terms of patient characteristics, such as clinical depth of tumor invasion, grading of lymph node metastasis, frequency neo-adjuvant chemotherapy. The incidence of postoperative complications was similar in the two groups such as pneumonia, anastomotic leakage, anastomotic stenosis, recurrent nerve palsy. In histopathological examination, the rate of positive proximal resection margin was significantly higher in H group. (34.8 vs 5.6%(P=0.028). 3-year recurrence-free survival rate and 3-year survival rate were similar in the two groups. The anastomotic recurrence rates did not differ between the two groups. (5.0 vs 5.9% (P=0.715))

In the H group, the rate of positive proximal resection margin was significantly higher. However, there was no difference in the anastomotic recurrence rate and the 3-year survival rate between the two groups. Therefore, we believe that larynx- preserving high-level cervical anastomosis is useful to maintain QOL in cervical esophageal cancer patients with the oral edge of the primary tumor is less than 2 cm from the esophageal entrance.
474. ESOPHAGEAL CANCER SURGERY AND ITS CHALLENGES: A STEP AHEAD WITH THE INTRODUCTION OF ROBOT-ASSISTED SURGERY
Authors: Noma Kazuhiro , Hashimoto Masashi , Maeda Naoaki , Tanabe Shunsuke , Shirakawa Yasuhiro , Fujiwara Toshiyoshi
Published: September 2022

We introduced robot-assisted thoracoscopic surgery for esophageal cancer surgery in 2018 and have performed 143 cases so far. Compared with thoracoscopic surgery, robot-assisted surgery is overwhelmingly more stable and precise, however there are concerns about the safety because there is no sensation from the forceps. Here, we will show a video of a standardized procedure utilizing the characteristics of da Vinci and its application to advanced cancer, and discuss the safe use of da Vinci.

We compared the short-term outcomes of pretreatment cStage ≤ II (n=40) and cStage ≥ III (n=53) in a total of 93 single-operator cases out of 143 da Vinci esophageal operations performed at our department since 2018.

For all patients, thoracoscopic time: mean 227 minutes, blood loss: 185 ml, recurrent nerve palsy: 15 patients (16.1%), postoperative hospital stay: 29.4 days, R0 surgery achievement rate: 96.8%. By stage (cStage ≤ II vs. ≥ III), thoracoscopic time: 211 vs. 240 minutes (p<0.05), blood loss: 171 vs. 195 ml (p=0.5), paralysis: 22.5 vs. 11.3% (p=0.17), postoperative hospital stay: 27.4 vs. 30.8 days (p=0.2). Although thoracoscopic time was significantly longer in the advanced cancer group, there was no difference in blood loss or hospital stay between the two groups, and paralysis was less common.

We focused on the effectiveness of robot-assisted thoracoscopic esophageal surgery for advanced cancer. Although robot-assisted surgery tends to take a relatively long time, we believe that it can be performed safely and effectively even for advanced cancer by careful surgical manipulation.
478. ENDOSCOPIC RESECTION OF A HUGE ESOPHAGEAL LIPOSARCOMA WITH LIGASURE INSTRUMENT
Authors: Su Ying-Chieh , Fong Yao , Chen Chao-Kun
Published: September 2022

Esophageal liposarcoma is a very rare pedunculated tumor of esophagus. It may cause progressive dysphagia due to mass effect and sudden death due to tumor suffocation. Surgical resection is challenging due to peduncle usually located at the superior esophageal sphincter region. We introduce a novel approach method that can transect the tumor peduncle safe and easy.

Review of the chart of Chimei Medical Center.

One 70 year old man with progressive dysphagia for 5 months and body weight loss over 8 KGs. A huge tip necrotic pedunculated tumor was found with endoscopy. Cut off the tumor peduncle with ligasure instrument under endoscopic guide was performed and the tumor was removed successfully. No tumor recurrence was found in 2 years.

Esophageal liposarcoma is a rare low grade malignancy of esophagus. Ligasure cut off the tumor peduncle can make a clear cut margin and avoid perforation or stenosis of esophagus.
480. OUTCOMES OF ADJUVANT LOCAL TREATMENT AFTER ESOPHAGEAL SURGERY WITH POSITIVE RESECTION MARGIN IN INTRATHORACIC ANASTOMOSIS
Authors: Son Jongbae , Jeon Yeong Jeong , Lee Junghee , Park Seong Yong , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Shim Young Mog
Published: September 2022

Esophageal cancer is aggressive diseases requiring surgery as an essential part of treatment. To achieve increased overall survival, complete resection (R0) is preferred. In some case, however, we encounter positive resection margin (R1).

Further resection will be required, but sometimes it is difficult to do additional procedure because of various reasons, especially the highest location of anastomosis.

Hypothesis of study is that R1 resection with adjuvant local therapy shows comparable result with R0 resection in intrathoracic anastomosis

From 2000 to 2017, total 2723 patients received the esophagectomy and mediastinal lymph node dissection for esophageal cancer. R0 resection was 1701, and R1 resection was 76 patients. Patients who received distal esophagectomy (n=56) and lack of information about adjuvant therapy (n=24) were excluded

Because of differences in some variables, we conducted 2:1 propensity score matching to reduce differences between groups.

Comparison of R1 resection group with adjuvant local therapy to R0 resection group is conducted

Overall survival (OS) and recurrence free survival (RFS) were estimated with Kaplan-Meier method.

76 patients were identified with R1 resection. Of those patients, 30 patients showed positive proximal resection margin from frozen section during surgery.

When compared to R0 resection group (including patients with adjuvant treatment), OS and RFS were statistically lower in R1 resection group (p=0.03 and 0.023, respectively)

When comparing R1 with adjuvant local treatment group to R0 resection group, there were no statistical differences in both OS and RFS.(p=0.13 and 0.22, respectively)

In R1 resection group, adjuvant local treatment group show favorable result compared to non-local treatment group, but there were no statistical differences in OS and RFS.(p=0.26 and 0.17, respectively)

R1 resection with proper adjuvant local treatment enable us to achieve comparable result with R0 resection group in intrathoracic anastomosis

When anastomosis is made at the highest level of thorax (i.e. thoracic inlet level), it is not easy to perform additional intrathoracic resection.

If it is difficult to do further resection when resection margin is positive, adjuvant local treatment after surgery can be one reasonable option to improve patient’s survival or minimize disease recurrence
487. THE OUTCOME OF NIVOLUMAB THERAPY FOR PLATINUM-RESISTANT UNRESECTABLE ADVANCED OR RECURRENT ESOPHAGEAL CANCER
Authors: Kanamori Kohei , Tajima Kohei , Yatabe Kentaro , Shoji Yoshiaki , Yamamoto Miho , Kazuno Akihito , Koyanagi Kazuo
Published: September 2022

In a phase III study, nivolumab treatment significantly prolonged survival compared with taxanes in patients with unresectable advanced or recurrent esophageal cancer who had become intolerant to first-line chemotherapy with 5-FU and platinum-based agents. We will report our experience and results of treatment with nivolumab at our hospital.

The subjects were 46 patients treated with nivolumab for unresectable advanced or recurrent esophageal cancer at our hospital from January 2019 to December 2021. Clinical factors and treatment effects were investigated.

The initial response was PR in 12 cases, SD in 18 cases, PD in 12 cases, and unevaluable in 4 cases. Median duration of nivolumab treatment was 3 months (1-18 months). Adverse effects grade 3 were found in 9 cases and grade 2 in 9 cases. Nivolumab was discontinued in 5 cases (10.8%) due to adverse effects.

Compared between cases who discontinued nivolumab within 2 months due to ineffectiveness or adverse effects and those who were able to continue for more than 2 months, overall survival was significantly prolonged in the latter group (median OS: 23.8 vs. 36.8 months, p=0.05).

In patients with unresectable advanced or recurrent esophageal cancer who responded to nivolumab, it was suggested that the drug may improve prognosis. The incidence of unsustainable adverse effects is relatively high, and it is important to control adverse effects.
496. THE OUTCOMES OF NIVOLUMAB FOR ESOPHAGEAL CANCER RECURRENT PATIENTS AFTER NAC-DCF THERAPY
Authors: Hashimoto Masashi , Noma Kazuhiro , Maeda Naoaki , Tanabe Shunsuke , Shirakawa Yasuhiro , Fujiwara Toshiyoshi
Published: September 2022

Cancer immune therapy is the most prominent topic in esophageal cancer. The attraction-3 trial showed that nivolumab was associated with a significant improvement in overall survival versus chemotherapy. This trial was well designed, including patients unresectable, after surgery, and after chemoradiotherapy. However, there are few reports limited to the recurrence after surgery. Here we report the outcome of Nivolumab for the recurrence after surgery with docetaxel, cisplatin, and 5-FU neoadjuvant chemotherapy (NAC-DCF).

The subjects were esophageal cancer recurrent patients after NAC-DCF, except for the cases performed only best supportive care, in Okayama University Hospital between January 2014 and October 2021, excepted the cases performed only best supportive care. We assessed their background characteristics, treatment details, immune-related adverse events (irAE), and overall survival (OS).

17 patients received therapies, including Nivolumab (Nivo). 41 patients received other chemotherapies (Control). There was no significant difference in gender (Nivo: male 88%, Control male 80%), age (Nivo: 68.1±8.9, Control: 65.1±5.6), and the period from surgery to recurrence (Nivo: 5.7±3.8 months, Control: 6.1±3.7 months). The Median overall survivals were 27±7.0 months and 18±2.5 months (P=0.055, Log Rank test). The major irAEs were reported in 4 cases (ACTH deficiency: 1 event, enterocolitis: 1 event, liver dysfunction: 2 events).

Nivolumab improved the outcomes of recurrent patients after NAC-DCF with a bit of tendency.
499. ICG GUIDED THORACIC DUCT CLIPPING FOR CHYLE LEAKS
Authors: Shukla Srijan , Thammineedi Subramanyeshwar Rao , Patnaik Sujit Chyau
Published: September 2022

Chylothorax and chyle leaks in neck are serious complications resulting from trauma or iatrogenic causes.

Early and accurate clipping of thoracic duct is potentially life saving.

ICG can be injected in groin node under USG guidance for fast visualisation and correct clipping of thoracic duct.

On table confirmation and documentation of no lymph flow beyond the clip is feasible.

2.5 mg indocyanine green in injected intranodal via ultrasound guidance.

Near infrared camera is utilised to view fluorescence imaging overlayed over thoracoscopic camera vision.

Groin intranodal injection of ICG yields brilliantly fluorescent illumination of thoracic duct which is especially useful in cases of chyle leaks.

Documentation of correct identification and post clipping termination of lymph flow beyond clip is feasible.

ICG intranodal injection yields excellent visualisation of thoracic duct which is useful in management of chyle leaks.
501. CONVERSATION WITH TISSUE IN UPPER MEDIASTINAL LYMPH NODE DISSECTION PROCEDURES FOR ESOPHAGEAL CANCER
Authors: Shirakawa Yasuhiro , Katsura Yuki , Hashimoto Masashi , Maeda Naoaki , Tanabe Shunsuke , Noma Kazuhiro , Fujiwara Toshiyoshi
Published: September 2022

Advances in the optical instrument for endoscopic surgery have enabled the anatomical recognition of minute membranes and layers previously invisible in open surgery. Those have allowed surgeons to take the benefits of conversing with the tissue. Furthermore, the recent introduction of robot-assisted surgery has made it possible to dissect with fidelity and safety according to the layers envisaged by the surgeon. Furthermore, we are increasingly having conversations with the tissues during the surgery.

Especially in the upper mediastinal lymph node dissection in esophageal cancer surgery, recognizing the delicate anatomy of the membranes and layers is an important technique. We have performed more than 600 thoracoscopic esophageal cancer surgeries in the prone position and more than 100 robot-assisted esophageal cancer surgeries. In our experience, we have tried to formulate the en bloc superior mediastinal lymph node dissection by applying the concept of microanatomy such as a visceral sheath, vascular sheath, and the meso-esophagus surrounded by a visceral sheath.

We have established a technique to detach the visceral sheath from the surrounding organs, release the trachea to reveal the meso-esophagus, and dissect the lymphatic chain in en-bloc while rescuing only the recurrent nerve. The spread of the visceral sheath is not symmetrical. On the left side, it is recognized as a firm membrane up to the aortic arch, but on the right side, it seems to disappear at the cervicothoracic border. This left-right difference is understandable considering the difference in the development of the primitive aortic arch on each side during fetal heart development.

In this study, we report on the technique and outcomes of upper mediastinal lymph node dissection based on the concept of the microanatomy of membranes and layers, which was developed through conversations with tissues in thoracoscopic esophageal cancer surgery, and its application to robot-assisted surgery.