bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of elevated embryonic incubation temperature on the temperature preference of juvenile lake (Coregonus clupeaformis) and round whitefish (Prosopium cylindraceum)
Authors: Harman Adam , Mahoney Hannah , Thompson William Andrew , Fuzzen Meghan L M , Aggarwal Bhuvan , Laframboise Lisa , Boreham Douglas R , Manzon Richard G , Somers Christopher M , Wilson Joanna Y
Published: August 2023

Anthropogenic impacts can lead to increased temperatures in freshwater environments through thermal effluent and climate change. Thermal preference of aquatic organisms can be modulated by abiotic and biotic factors including environmental temperature. Whether increased temperature during embryogenesis can lead to long-term alterations in thermal preference has not been explicitly tested in native freshwater species. Lake (Coregonus clupeaformis) and round (Prosopium cylindraceum) whitefish were incubated at natural and elevated temperatures until hatching, following which, all groups were moved to common garden conditions (15°C) during the post-hatching stage. Temperature preference was determined at 8 months (Lake whitefish only) and 12 months of age (both species) using a shuttle box system. Round whitefish preferred a cooler temperature when incubated at 2 and 6°C compared with 0.5°C. Lake whitefish had similar temperature preferences regardless of age, weight and incubation temperature. These results reveal that temperature preference in freshwater fish can be programmed during early development, and that round whitefish may be more sensitive to incubation temperature. This study highlights the effects that small increases in temperature caused by anthropogenic impacts may have on cold-adapted freshwater fish.
27. OPLAH PROTEIN EXPRESSION STRATIFIES THE PROGNOSIS OF PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS
Authors: Shimizu Dai , Kanda Mitsuro , Nakanishi Koki , Kurimoto Keisuke , Umeda Shinichi , Takami Hideki , Inokawa Yoshikuni , Hattori Norifumi , Hayashi Masamichi , Sato Yusuke , Tanaka Chie , Nakayama Goro , Fujiwara Michitaka , Kodera Yasuhiro
Published: August 2023

Background

Squamous cell carcinoma (SCC) is one of the major subtypes of esophageal carcinoma, and accounts for up to 90% of esophageal carcinoma cases in eastern Asia and eastern and southern Africa and 50% in Western countries. The 5-year overall survival rate of ESCC patients who undergo curative treatment remains below 40%. The elucidation of molecular biomarkers could be of clinical importance both as prognostic factors besides the established clinical staging and as potential targets for treatment. We aimed to detect and validate the prognosticators of esophageal squamous cell carcinoma in patients who underwent radical esophagectomy.

Methods

We identified OPLAH as one of the differentially expressed genes between esophageal squamous cell carcinoma (ESCC) tissue and normal esophageal mucosa whose expression changes were significantly associated with a patient prognosis using The Cancer Genome Atlas data. The OPLAH protein expression in ESCC tissue and serum OPLAH protein concentrations were evaluated and analyzed for their association with clinicopathological factors.

Results

OPLAH mRNA was significantly overexpressed in ESCC tissue compared to normal esophageal mucosa, and patients with high OPLAH mRNA expression had a significantly poorer prognosis according to The Cancer Genome Atlas data. The high staining intensity of OPLAH protein in ESCC tissue clearly stratified patient prognosis. According to the multivariable analysis, high OPLAH protein expression was an independent prognostic factor for survival after surgery. Pre-neoadjuvant chemotherapy serum OPLAH protein concentrations were significantly associated with clinical tumor depth and node positivity and, consequently, with advanced clinical stage. The serum OPLAH protein concentration was significantly decreased by neoadjuvant chemotherapy.

Conclusions

OPLAH may serve as a useful prognosticator for ESCC patients.
46. THORACOSCOPIC REPAIR OF IATROGENIC INJURY TO THE THORACIC AORTA DURING MINIMALLY INVASIVE ESOPHAGECTOMY
Authors: Tan Jeremy , Chan Weng Hoong , Lee Zhen Jin , Lim Eugene , Chng Jack Kian
Published: August 2023

Description of video:

Background

We present the case of a 75-year-old male patient with locally advanced Siewert Type 2 gastroesophageal adenocarcinoma post neoadjuvant chemotherapy. Inadvertent through-and-through piercing of the lower thoracic aorta with the tip of an energy device just above the diaphragm was sustained during the thoracoscopic esophageal dissection phase of the three-field minimally-invasive McKeown approach.

Methods

The procedure proceed thoracoscopically. The lower thoracic aorta was dissected and mobilized proximally and distally, and clamped on both ends with the introduction of Debakey clamps directly through separate small incisions in the chest wall. Primary repair of both anterior and posterior defects was then performed with monofilament non-absorbable sutures. Total clamp time was 30 minutes (in 15-minute intervals).

Results

Post-repair, perfusion status to the distal viscera and lower limbs were verified and intact. The rest of the operation then proceeded uneventfully. A Computed Tomography scan of the thoracic aorta on postoperative day 14 showed a patent thoracic aorta with no intraluminal narrowing or thrombosis.

Conclusion

Thoracoscopic repair of aortic injury sustained during the thoracoscopic dissection phase of a minimally invasive esophagectomy can be performed safely in well-selected, haemodynamically stable patients.

Drpbox link to video: https://www.dropbox.com/s/xbwt6ge23iywr3m/aorta3mus1.mp4?dl=0.
47. PERORAL ENDOSCOPIC MYOTOMY VS HELLER MYOTOMY WITH FUNDOPLICATION IN OUR CENTER
Authors: Muranami Yuto , Sato Chiaki , Taniyama Yusuke , Okamoto Hiroshi , Ozawa Yohei , Ishida Hirotaka , Koseki Ken , Kanabuchi Sawa , Fusegawa Kazuki , Kamei Takashi
Published: August 2023

Heller myotomy with fundoplication (HF) is one of the established treatments for esophageal achalasia. However, the less invasive Peroral endoscopic myotomy (POEM) is rapidly spreading. Several papers report short-term efficacy and safety of POEM is as well as HF, but GERD is more frequent after POEM. Moreover, the long-term outcome is still unknown.

This is a single center retrospective study. In our center, HF was carried out for 59 patients between 1999 and 2014. Among them, 58 cases underwent laparoscopic procedure, 52 were with Dor fundoplication and 7 were with Toupet. From 2015 we performed POEM for 224 patients until Dec 2022.

For POEM, grade of dilatation was lower (I/II/III=POEM;76/131/17, HF;6/44/9, p < 0.001) and esophageal myotomy length was longer (8.5 ± 3.4 cm vs 5.7 ± 0.8 cm, P < 0.001). Median IRP and Eckardt score decreased for them (24.3 ± 13.0 to 7.8 ± 4.8 mmHg/5.37 ± 2.09 to 0.54 ± 0.84). HF improved their LES pressure (40.2 ± 20.3 to 18.0 ± 7.1 mmHg, p < 0.001). Postoperative LA grade B GERD was more often for POEM (26.9% vs 4.7%, p < 0.001), however grade C or D were comparable. All of them were controlled by PPIs, except one POEM patient considering further treatment. For HF, median follow-up period was longer (78 vs 19 mo), however, additional treatment was more necessary (6.8% vs 1.3%, p = 0.033).

Postoperative grade B GERD was more common for POEM, but almost all of them were controlled by PPIs. POEM was less likely to require additional treatment, though follow-up time was relatively short. Further observation and re-evaluation are warranted.
135. IMPACT OF GENDER, RACE AND AGE OF ONSET ON THE PHENOTYPE AND COMORBIDITIES OF PEDIATRIC EOSINOPHILIC ESOPHAGITIS
Authors: Mckeown Kyle , Pritchett Justin , Carlisle Annette , Lieberman Jay , Xi Dong
Published: August 2023

Eosinophilic esophagitis (EoE) is recognized as chronic immunologic disorder of the esophagus resulting in esophageal inflammation by the accumulation of eosinophils in the epithelium. Several risk factors are thought to be associated with the development of EoE, but because of its complex underlying mechanisms of disease, there is little clarity in regards to the different symptoms experienced, pathological findings and associated comorbidities including atopic and allergic disorders between different gender, race and age of onset.

This study utilized a retrospective chart review on the patients seen by a multidisciplinary EoE clinic from January 2020 to December 2022. Subjects were diagnosed with EoE, and retrospectively assessed for eosinophilic counts on the initial distal and proximal esophageal biopsies, and previously specified symptoms and comorbidities. The differences of eosinophilic counts, associated symptoms and comorbidities between gender (male or female), race (White or non-White) and age of onset (≤ 6 years old is defined as early onset, or > 6 years old is defined as regular onset in this study), were statistically analyzed by t-test or Chi-Square. P < 0.05 is considered as significant.

Ninety patients were included in this study, of whom 72% are male (M) while 28% are female (F), and 68% are White (W) while 32% are non-White (NW). Age of onset ranges from 1 year to 17 years, with 44% being early onset while 56% being regular onset. We found females and White race were significantly more likely to report dysphagia. Non-White patients were found to have higher incidence of vomiting, asthma than White. Significant higher incidence of vomiting, and eosinophilic counts was found in early onset (EO) patients (distal: 56, proximal: 50) compared to regular onset (RO) (distal: 39, proximal: 39), while no significant difference was found between different gender and race.

Our retrospective study demonstrated that there are significant differences between different gender, race and age of onset for pediatric EoE in regard to the severity of eosinophilic inflammation, gastrointestinal symptoms and associated comorbidities. These findings could provide some guidance to clinicians in identifying proper diagnosis and developing appropriate treatment to achieve the best outcome.
150. PATTERN OF LYMPH NODE RECURRENCE AFTER NEOADJUVANT CHEMORADIOTHERAPY AND MODIFIED EN BLOC ESOPHAGECTOMY
Authors: Hsu Po-kuei
Published: August 2023

Background

Esophageal cancer is an aggressive malignancy with high incidence of lymph node metastasis and recurrence rate even after neoadjuvant treatment and radical resection. Previous study has shown that modified en bloc esophagectomy (mEBE) improves survival for esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). In this study, we aim to investigate the pattern of lymph node recurrence after nCRT+mEBE.

Methods

The data of patients who received nCRT followed by curative surgical resection for ESCC were retrospectively reviewed. The mEBE includes ‘mesophagus’ dissection and bilateral recurrent laryngeal nerve node dissection, whereas conventional esophagectomy (CE) only requires periesophageal tissues dissection that were close to the esophagus. The pattern of recurrence, especially lymph node recurrence (cervical, upper mediastinum, infra-carina, and abdominal), were compared between CE and mEBE, with stratification according to pathological stage (ypT0N0 or not.)

Results

A total of 221 (CE, n = 181; mEBE, n = 40) patients were included. Mediastinal lymph node recurrence was noted in 16.0% and 7.5% of patients after CE and mEBE, respectively (p = 0.166). In ypT0N0 patients who received CE, 6.0% had upper mediastinum recurrence, whereas no mediastinal recurrence was noted after mEBE (p = 0.329). In non-ypT0N0 stage patients who received CE, 15.3% and 8.2% had upper mediastinum and infra-carina recurrences, compared to 12.0% and 0% after mEBE (p = 0.283). There cervical/abdominal recurrences were noted in 6.6%/7.2% and 15.0%/5.0% after CE and mEBE, respectively (p = 0.080/0.618).

Conclusion

Although there was no significant difference in lymph node recurrence pattern between mEBE and CE, we observed that (1) 6% of ypT0N0 patients developed mediastinal lymph node recurrence after CE, implying the possibility of understaging after CE; (2) no patients developed infra-carina lymph node recurrence after mEBE, suggesting the necessity of mesoesophagus dissection, and (3) high incidence of cervical lymph node recurrence even after mEBE, indicating that cervical dissection should be considered in selected patients.
152. SINTILIMAB PLUS CISPLATIN AND PACLITAXEL INDUCTION TREATMENT FOR BORDERLINE RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A PHASE II CLINICAL TRIAL
Authors: Wu Jia-Di , Wang Zhi-Qiang , Zhao Ze-Rui , Li Qiao-Qiao , Wu Jia-Di , Li Zhi-Chao , Li Yu-Hong
Published: August 2023

Background

An increasing number of clinical studies focus on investigating the use of immunotherapy in the treatment of esophageal cancer. This phase II trial (NEOCRTEC-2001 clinical trial) aimed to assess the safety and efficacy of sintilimab in combination with cisplatin and paclitaxel induction immunochemotherapy followed by surgery for locally advanced borderline-resectable esophageal squamous cell carcinoma (BR-ESCC).

Methods

Patients with primary tumor or bulky lymph nodes that might invade nearby organs were eligible. Treatment started with 2–4 cycles of induction immunochemotherapy, followed by surgery if the tumor was assessed resectable, or by radical concurrent chemoradiotherapy if unresectable. The primary endpoint was pathologically proven complete resection (R0) rate. The secondary end points included pathological complete response (pCR) rate, overall survival (OS), progression-free survival (PFS), adverse events and postoperative complication.

Results

From September 2020 to now, a total of 34 patients were enrolled. After immunochemotherapy, 21 patients (61.8%) received surgery and 13 (38.2%) did not. All patients underwent McKeown procedure, and median operation time was 295 minutes (range 201–489 minutes). All patients received esophageal reconstruction using gastric tube, and underwent cervical anastomosis. An average of 46.6 lymph nodes were dissected, and positive lymph nodes were observed in 5 of the 21 patients. R0 resection was confirmed in 20 patients (58.8%). One patient underwent R2 resection because of tumor invasion of the aorta. Pathologic complete response was confirmed in 6 patients (6/34, 17.6%), while 5 patients (5/34, 14.7%) had few or no regressive changes (TRG3).

Conclusion

The treatment strategy of induction immunochemotherapy followed by surgery is promising for patients with locally advanced borderline-resectable esophageal squamous cell carcinoma. The whole results of pathologic response and prognostic value are awaited with interest.
177. BULKY LYMPHADENOPATHY IN ESOPHAGEAL CANCER: ASSESSING PATHOLOGICAL AND SURVIVAL OUTCOMES AFTER TREATMENT WITH CURATIVE INTENT
Authors: Tankel James , Nevo Yenothan , Najmeh Sara , Spicer Jonathan , Mueller Carmen , Ferri Lorenzo , Cools-Lartigue Jonathan
Published: August 2023

Aim

Whilst pre-treatment bulky regional lymphadenopathy is associated with poor survival outcomes in gastric adenocarcinoma, the impact this may have on survival in the setting of esophageal adenocarcinoma has not been described. The aim of this study was to explore the relationship between bulky regional lymphadenopathy found at diagnosis and survival outcomes in patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy and en bloc esophagogastrectomy.

Methods

A single center, retrospective review of a prospectively maintained upper GI cancer surgical database was performed between 01/2012 and 12/2020. Patients with adenocarcinoma of the esophagus/esophagogastric junction (cT2–3, Nany, M0) treated with neoadjuvant docetaxel based chemotherapy and transthoracic en bloc esophagogastrectomy were identified. Pretreatment CT scans were reviewed and patients stratified according to whether bulky periesophageal or periceliac lymph nodes were present. This was defined as periceliac or periesophageal lymphadenopathy >2 cm in its long axis. Once stratified by the presence of bulky lymphadenopathy, overall survival (OS) was compared and a Cox multivariate regression model calculated.

Results

Of the 975 patients identified, 225 met the inclusion criteria. cT3/4 and cN+ was found in 169/225 (75%) and 154/225 (73%) respectively. Forty-eight patients (21%) were allocated to the bulky lymphadenopathy group. Among them, ypT status was similar, ypN3 disease more common (18/48,38% vs 39/177,20%, p = 0.025) with a trend towards pathological complete response (5/48,10% vs 7/177,4%, p = 0.086). OS was worse among patients with bulky regional lymphadenopathy (32.6 vs 50 months, p = 0.012). Along with poor differentiation (HR 1.8,95% CI 1.0–2.9, p = 0.034) and ypN+ (HR 1.9,95% CI 1.1–3.6, p = 0.032), bulky lymphadenopathy was independently associated with an increased risk of death (HR 1.7,1.0–2.9,p = 0.048).

Conclusion

Pre-treatment bulky regional lymphadenopathy is a poor prognostic sign despite multimodal treatment with docetaxel based systemic neoadjuvant therapy and en bloc resection. Identification of alternative treatment strategies may help improve survival outcomes among this specific group of patients.
184. INTRATHORACIC SIDE-OVERLAP ESOPHAGOGASTROSTOMY DURING MINIMALLY INVASIVE ESOPHAGECTOMY FOR ESOPHAGOGASTRIC JUNCTION CANCER
Authors: Shoji Yoshiaki , Koyanagi Kazuo , Kanamori Kohei , Tajima Kohei , Ogimi Mika , Ninomiya Yamato , Yamamoto Miho , Kazuno Akihito , Nabeshima Kazuhito , Nishi Takayuki , Mori Masaki
Published: August 2023

Backgrounds

Surgical algorithm for esophagogastric junction cancer have been proposed according to the results of a recent prospective study. However, reconstruction method has yet to be standardized. Esophagogastrostomy is often performed for esophagogastric junction cancer with esophageal invasion, although, it has been related to frequent and severe complications. Recently, we have introduced IntraThoracic Side-overlap EsophagoGastrostomy (ITS-EG), an eazy and novel intrathoracic anastomotic method with reflux prevention mechanism during minimally invasive esophagectomy for esophagogastric junction cancer.

Methods

We retrospectively reviewed patient backgrounds and surgical/short term outcomes for the patient who underwent ITS-EG during minimally invasive esophagectomy for esophagogastric junction cancer between February 2018 to April 2023 at our institute.

Results

The study cohort included ten patients, with a median age of 67 (55–77) years. All tumors were classified as Siewert type II, and the median esophageal invasion length was 32 (11.8–40) cm. After extended proximal gastrectomy, patients underwent either thoracoscopic (five patients) or robot-assisted (five patients) minimally invasive esophagectomy followed by ITS-EG. ITS-EG consist of overlap anastomosis utilizing surgical stapler, and reflux prevention mechanism owing to the creation of pseudo-fornix and a slit-shaped anastomosis. The initial case suffered anastomotic leakage, however, recovered by conservative measures. All the other patients had an uneventful recovery without reflux esophagitis nor anastomotic stricture.

Conclusion

ITS-EG is an easy and safe esophagogastric anastomosis with reflux prevention mechanism during minimally invasive esophagectomy, and may be considered for esophagogastric junction cancers with esophageal invasion. Further accumulation of cases is needed to demonstrate the safety and efficacy of ITS-EG. Surgical procedure for ITS-EG would be presented by video.
191. CIRCULATING TUMOR DNA (CTDNA) ANALYSIS FOR DETECTION OF RESIDUAL DISEASE AFTER NEOADJUVANT CHEMORADIOTHERAPY (NCRT) FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC)
Authors: Liu Zhichao , Yang Yang , Liu Jun , Fu Xiaolong , Chen Songan , Li Xi , Xiang Jianxing , Zhu Mingjun , Li Zhigang
Published: August 2023

Background

High pathological complete response (pCR) rates were observed in ESCC patients after nCRT. A ‘Watch and Wait’ strategy has been proposed for patients with clinical complete response (cCR) after nCRT. However, clinical assessments (e.g. endoscopic biopsy) may misclassify non-pCR as cCR. In this study, we investigate the value of two kinds of ctDNA analysis strategies in predicting tumor response and residual disease after nCRT in ESCC, including personalized panel and tumor-naïve fixed panel (TNFP) analyses.

Methods

This is a side study of preSINO trial (NCT03937362). After nCRT completion, patients underwent clinical response evaluations (CREs) before planned surgery. CRE-1 was 4–6 weeks after nCRT. CRE-2 was 10–12 weeks after nCRT for patients without histological evidence of residual tumor at CRE-1. Individual tumors and matched white blood cells prior to nCRT (B0) were whole-exome sequenced for somatic mutations selection. Serial plasma samples were analyzed by brPROPHET personalized panel and 168-gene TNFP respectively at three timepoints: B0, CRE-1, CRE-2. We correlated ctDNA status with pCR and major locoregional residual disease (MLRD) (>10% residual cancer or any residual nodal disease).

Results

A total of 55 ESCC patients who received per-protocol treatments underwent ctDNA detection. The pCR rate was 27% (15/55). 98.38% of variants selected for brPROPHET panel design were private to a specific patient, only 3.1% of variants were included in the TNFP (Fig. A-B). ctDNA positive rates of brPROPHET were significantly higher than TNFP assay at three timepoints (Fig. C). Importantly, the brPROPHET achieved higher sensitivity than TNFP in predicting non-pCR and MLRD owing to its ability to detect extremely low ctDNA fractions (Fig. D). Moreover, combining brPROPHET with CREs could further improve the sensitivity (Fig. E).

Conclusion

Personalized ctDNA analysis exhibited superior sensitivity and predictive performance than TNFP assay. What’s more, personalized ctDNA analysis can supplement the clinical assessment to decrease the false negative rate in identifying patients with residual disease after nCRT, and might become useful in the ‘Watch and Wait’ strategy for the management of ESCC.
194. INTENSIVE SURVEILLANCE INCREASES SALVAGE SURGERY AND SURVIVAL RATES FOR ESOPHAGEAL CANCER
Authors: Walsh Thomas , Abdulrahman Rand , Abdulrahman Maan , Shamiya Khalid Adnan , Al-Khusaibi Mohamed , Picket Lianne , Monaghan Orla , O’Neill Brian , Grogan Liam , Sorensen Jan
Published: August 2023

Background

Following curative treatment there are no international follow-up guidelines, with most relying on symptoms for reinvestigation. This may delay diagnosis and impair survival. We hypothesized that intense surveillance would detect recurrent disease at a salvageable stage: and this study compared the outcome for patients undergoing salvage surgery for recurrent disease identified on intense surveillance with survival of patients that had undergone curative treatment for locoregionally advanced disease and didn’t require salvage surgery.

Patients and Methods: A prospective database of esophageal carcinoma patients treated with curative intent was interrogated for patients with recurrent or new cancers amenable to salvage surgery. Surveillance consisted of 3-monthly endoscopy and 6-monthly CT scanning for 3 years, 6-monthly endoscopy and yearly CT scanning to 5 years, and endoscopy yearly with imaging as desired thereafter. Once new or recurrence cancer was diagnosed patients were restaged and, if suitable, underwent salvage surgery. Their outcome was compared with patients undergoing chemoradiotherapy plus or minus resection for locoregionally advanced disease.

Results

Of 205 patients treated with curative intent, 24 (11.7%) patients underwent salvage surgery for locoregional, metastatic or second primary tumours. They had a median survival of 48.4 months and a 3-year survival of 54.6%. This compares to 157 patients with locoregionally advanced disease not requiring salvage surgery, who had a median survival of 45.6 months and a 3-year survival of 44%, which was statistically insignificant between the groups (p = 0.975).

Conclusions

In this hypothesis-generating study an intensive surveillance strategy identified a cohort of patients (almost 12%) with recurrence disease or new primary cancers amenable to salvage surgery and with outcomes non-inferior to patients without recurrence. As most were asymptomatic, it is unlikely that curative intervention would have been as successful without surveillance. It is suggested that surveillance guidelines be updated to standardize interval endoscopy/imaging as for other GI malignancies.
197. FIBROSING MEDIASTINITIS CAUSING CONCOMITANT FOCAL STRICTURE AND TRACTION DIVERTICULA OF THE ESOPHAGUS
Authors: Dickerson Austin , Ford Kenneth , Nguyen Anh D
Published: August 2023

Background

Fibrosing mediastinitis, also known as mediastinal fibrosis or sclerosing mediastinitis, is a rare condition caused by an excessive fibrosing reaction of the mediastinum. The clinical presentation of fibrosing mediastinitis varies based on the mediastinal structures involved, which can include the great vessels, airway, thoracic duct, phrenic nerve, or esophagus. We present a unique case of a patient with fibrosing mediastinitis causing dysphagia due to esophageal involvement with both focal esophageal stricture and multiple traction diverticula.

Case Report: 82-year-old man with a past medical history of treated pulmonary tuberculosis in his 20s, Crohn’s colitis and gastroesophageal reflux disease presented to clinic with worsening dysphagia for the past few years with chronic dysphagia symptoms for the past 50 years. Barium esophagram demonstrated a stricture in the upper to mid esophagus and a corkscrew pattern of the mid-esophagus (Figure 1). Esophagogastroduodenoscopy demonstrated an esophageal stricture and multiple traction diverticula distal to the stricture. Computed tomography of the chest showed homogeneous soft tissue encasing the trachea and esophagus consistent with fibrosing mediastinitis. Serial dilation of the esophageal stricture was performed, but mucosal disruption was never achieved with no improvement in stricture diameter. The case was discussed in a multi-disciplinary conference where esophageal stenting was not felt to be feasible given multiple traction diverticula, and esophageal resection would be high risk given the fibrosing mediastinitis. Risks and benefits were discussed with the patient, and the patient opted to do dietary modifications as he did not have dysphagia on a pureed diet.

Discussion

Fibrosing mediastinitis is often idiopathic but can be due to infectious/inflammatory processes, sarcoidosis, or radiation exposure. The most common cause of fibrosing mediastinitis is prior infection with Histoplasma capsulatum. In this case, fibrosing mediastinitis from remote Mycobacterium tuberculosis infection resulted in a focal stricture and traction diverticula of the esophagus causing dysphagia. Barium esophagram revealed a corkscrew pattern of the esophagus, a pattern usually seen in diffuse esophageal spasm but was due to multiple traction diverticula. Fibrosing mediastinitis causing dysphagia is rare, and no prior reports in the literature describe a case causing concomitant esophageal stricture and traction diverticula in a patient.
218. INITIAL EXPERIENCES WITH VACUUM-STENT AS NOVEL TREATMENT OPTION FOR TRANSMURAL DEFECTS IN THE UPPER GASTRO-INTESTINAL TRACT: A SINGLE-CENTER CASE SERIES
Authors: Pattynama Lisanne , Eshuis Wietse J , Bergman Jacques J , Berge Henegouwen Mark I , Pouw Roos
Published: August 2023

Background

Transmural defects in the upper gastro-intestinal (GI) tract (anastomotic leak, Boerhaave syndrome, iatrogenic defects) are associated with severe morbidity. Recently, a vacuum-stent was introduced as novel treatment device, combining the benefits of negative pressure wound therapy and an intraluminal stent, while allowing for oral intake of a soft diet. The aim of this prospective case series was to describe the first experiences with the vacuum-stent for the upper GI tract in an academic hospital.

Methods

All patients treated with a vacuum-stent between March 2022 and March 2023 were included. Patients who were already treated with vacuum-sponge and received a vacuum-stent when it became available were also included. Outcome measures included successful closure of the defect, adverse events, number of EVT-related endoscopies and treatment duration.

Results

23 patients were included (18 male, median age 65 years). Fourteen patients had anastomotic leakage after esophagectomy, five patients an iatrogenic perforation and four had Boerhaave syndrome. Twelve patients were treated with vacuum-stent alone and eleven with a combination of vacuum-stent and vacuum-sponge (Table 1), which was mostly due to the later availability of or limited experience during the implementation period of the vacuum-stent. Success rate was 91%, median 4 (IQR 3–8) EVT-related endoscopies were performed during median 14 (IQR 12–31) days of treatment in successful cases. During median 120 (IQR 15–221) days follow-up, four patients developed an anastomotic stricture treated with endoscopic dilation. No other adverse events were observed.

Conclusion

The vacuum-stent combines the benefits of EVT and an intraluminal stent and shows great feasibility and efficacy in treatment of transmural defects in the upper GI tract. More research is necessary, as this device could possibly prevent major (re-)surgery in these patients.
221. INTERVAL METASTASES AFTER NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED ESOPHAGEAL CANCER: A MULTICENTER OBSERVATIONAL COHORT STUDY
Authors: Zijden Charlène , Sluis Pieter , Mostert Bianca , Nuyttens Joost , Lanschot Jan , Spaander Manon , Valkema Roelf , Coene Peter-Paul , Dekker Jan-Willem , Fiets Willem , Hartgrink Hendrik , Hazen Wouter , Kouwenhoven Ewout , Nieuwenhuijzen Grard , Rosman Camiel , Sandick Johanna , Sosef Meindert , Zaag Edwin , Lagarde Sjoerd , Wijnhoven Bas
Published: August 2023

Background

Despite trimodality treatment, 10–20% of patients with esophageal cancer develop metastases after surgery. Re-staging after neoadjuvant chemoradiotherapy (nCRT) may be useful to identify these patients who should not have proceeded to surgery. In this multicenter observational cohort study, we assessed the proportion of patients with interval metastases after nCRT. Secondary outcomes were overall survival (OS), location and treatment of metastases.

Methods

Between 2013–2021, patients with cT2-4aN0–3 M0 esophageal/junctional cancer who underwent nCRT were identified from three prospective study-databases. Re-staging with 18F-FDG-PET/CT ≤14 weeks after completion of nCRT was performed in all patients. Metastases detected on imaging or during surgery were categorized into oligometastatic (≤3 lesions located in one single organ or in one extra-regional lymph node station) or non-oligometastatic. Treatment of metastases was based on pretreatment multidisciplinary tumor board reports for patients with oligometastatic disease and consisted of systemic therapy, loco(regional) therapy or best supportive care. OS was calculated from completion of nCRT until date of death or last day of follow-up.

Results

Metastases were detected in 100 of 973 patients (10.3%). The majority (84%) were detected by 18F-FDG-PET/CT and in 16% during surgery of which 60% were peritoneal metastases. Oligometastatic disease was seen in 30% of patients and 12 patients (40%) were treated with potentially curative intent. Median OS of patients with oligometastatic disease who were treated with potentially curative intent was 22.8 months (95% CI 10.4-NA), compared to 13.8 months (95% CI 9.2–27.1) in patients treated with palliative intent. Oligometastases were mostly located in non-regional lymph nodes (33.3%) or bones (26.7%). Median OS non-oligometastatic disease 9.0 months (95% CI 7.4–10.9).

Conclusion

Interval metastases were detected in about 10% of esophageal cancer patients after nCRT and the majority had non-oligometastatic disease. This underlines the benefit of restaging to select patients who are not candidates for esophagectomy. Treatment of oligometastases might lead to favorable survival in selected patients.
223. UNDERSTANDING POTENTIALLY PREVENTABLE MORTALITY FOLLOWING ESOPHAGO-GASTRIC CANCER SURGERY: ANALYSIS OF A NATIONAL AUDIT OF SURGICAL MORTALITY
Authors: Liu David , Fayed Aly , Evans Penelope , Bright Tim , Aly Ahmad , Duong Cuong , Spillane John , Weinberg Laurence , Watson David
Published: August 2023

Introduction

At a national level, understanding preventable mortality after esophago-gastric cancer surgery can direct quality-improvement efforts. Here, we utilized the Australian and New Zealand Audit of Surgical Mortality (ANZASM) database to 1) determine the causes of death following esophago-gastric cancer resections in Australia, 2) quantify the proportion of potentially preventable death, and 3) identify clinical management issues contributing to preventable mortality.

Methods

All in-hospital mortalities following esophago-gastric cancer surgery from 01/01/2010 to 31/12/2020 were analyzed from ANZASM data. Potentially preventable and non-preventable cases were compared. Thematic analysis was used classify clinical management issues. Overall, we reviewed 636 complications and 123 clinical management issues in 105 mortalities.

Results

The most common causes of death were cardio-respiratory in etiology. Forty-nine (46.7%) mortalities were potentially preventable. These cases were characterized by higher rates of sepsis (59.2% vs. 33.9%, p = 0.011), multiorgan dysfunction syndrome (40.8% vs. 25.0%, p = 0.042), reoperation (63.3% vs. 41.1%, p = 0.031), and other complications compared with non-preventable mortality. Potentially preventable mortalities also had more clinical management issues per patient [median (IQR): 2 (1–3) vs. 0 (0–1), p < 0.001), which adversely impacted preoperative (30.6% vs. 7.1%, p = 0.002), intraoperative (18.4% vs. 5.4%, p = 0.037), and postoperative (51.0% vs. 17.9%, p < 0.001) care. Thematic analysis highlighted recurrent areas of deficiency in patient management.

Conclusions

Almost 50% of deaths following esophago-gastric cancer resections were potentially preventable. These were characterized by higher complication rates and clinical management issues. We highlighted recurrent themes in patient management to improve future quality-of-care.
228. THORACOACROMIAL ARTERY PERFORATOR FLAP REPAIR OF ACQUIRED INTRATHORACIC NONMALIGNANT TRACHEOESOPHAGEAL FISTULAS THROUGH A MIDSTERNAL INCISION APPROACH
Authors: Yuan Pei-song , Wu Na , Xia Qi , Hu Yang
Published: August 2023

Background

Acquired intrathoracic nonmalignant tracheoesophageal fistulas (TEFs) are rare and challenging surgical problems. They can constitute a life-threatening condition due to severe pulmonary complications and poor nutrition. The current treatment strategy for TEFs is controversial, and postoperative mortality and complication morbidity have been ignored in recent studies. Here, we introduce our innovative experience repairing acquired tracheoesophageal fistulas with a thoracoacromial artery perforator flap, in which no mortality or complications were observed within 180 days after the operation.

Methods

Surgical repair with a thoracoacromial artery perforator flap through a midsternal incision approach was performed in 3 patients. During the procedure, a midsternal incision was made. After the thymus and anterior mediastinal fat were resected, and the left innominate vein was transected, the trachea and esophagus were mobilized. The trachea was incised and pulled to the cranial and caudal sides. Then, the thoracoacromial artery perforator flap was harvested and transferred into the superior mediastinum for esophageal reconstruction. Subsequently, the trachea was anastomosed end to end after debridement, and the left innominate vein was either anastomosed or not.

Results

Two patients developed esophageal anastomotic leakage postoperatively and healed well after nonsurgical treatment. No mortality or other complications were observed at 180 days after the operation.

Conclusion

Repair of acquired tracheoesophageal fistulas using a thoracoacromial artery perforator flap through a midsternal incision approach is an effective, safe surgical treatment.
246. SPATIAL HETEROGENEITY OF PD-L1 EXPRESSION INFLUENCE ITS ASSESSMENT IN ESOPHAGEAL SQUAMOUS CARCINOMA (ESCC)
Authors: Yu Boyao , Liu Zhichao , Ma Ning , Pan Jie , Li Zhigang
Published: August 2023

Background

Anti-PD-1/PD-L1 immunotherapy is a promising treatment for ESCC. High PD-L1 expression is a theoretical predictive biomarker, but the poor response is also observed in some patients with high PD-L1 expression. Biopsies assessment of PD-L1 expression always focuses on a single region which may be influenced by spatial heterogeneity of tumor microenvironment. This study investigates whether the PD-L1 expression by biopsy assessment in the different spatial regions is related to its paradoxical predictive value.

Methods

We prospectively included 30 consecutive patients with treatment-naïve, stage II-III ESCC who underwent upfront esophagectomy. Multi-region sampling was taken with endoscopic biopsy forceps (Fig. A) from four regions (A/B/C/D) from the proximal, distal, midpoint of tumor surface, and internal center, respectively. Each region was spaced ≥1 cm apart and avoided areas of severe necrosis. We compared the PD-L1 expression at different endoscopic-biopsy regions and the overall surgical-resected tumor specimen. PD-L1 expression was evaluated by immunohistochemistry using combined positive score (CPS). PD-L1 expression positive and negative is defined as CPS ≥ 1 and CPS < 1, respectively.

Results

Based on surgical-resected tumor, PD-L1 positive and high were 66.7% and 10% of 30 patients, respectively. PD-L1 positive/negative discordance rate of four sampling regions was 66.7% with poor concordance (kappa = 0.206) (Fig. B). Correlations between four biopsy regions of PD-L1 expression (Fig. C) revealed high in B and D (r = 0.77) but relatively low in others. Combining multi-region sampling for evaluation improved the correlation consistency of PD-L1 expression assessment (Fig. D). Comparing PD-L1 expression based on the endoscopic-biopsy region with the gold standard surgical-resected specimen, the sensitivity was increased by 12.5% for multi-region versus single-region assessment.

Conclusion

PD-L1 expression was spatially heterogeneous in ESCC, and a single region cannot reflect the PD-L1 status of the tumor, consistent with the observation of suboptimal prediction of PD-L1 expression for ESCC immunotherapy. Multi-region biopsy could help improve the assessment bias of PD-L1 expression related to spatial heterogeneity, and may help to improve the identification of the candidate for immunotherapy.
255. EARLY COST-EFFECTIVENESS MODELLING STUDY COMPARING MINIMALLY INVASIVE TRANSCERVICAL ESOPHAGECTOMY (MICE) AND TRANSTHORACIC MINIMALLY INVASIVE ESOPHAGECTOMY (TMIE) IN OESOPHAGEAL CANCER PATIENTS
Authors: Klarenbeek Bastiaan , Leijten Lars , Scholte Mirre , Veenendaal Linde , Rovers Maroeska , Rosman Camiel
Published: August 2023

Introduction

Minimally Invasive transCervical Esophagectomy (MICE) is a novel transcervical approach to esophagectomy with the possible advantage of decreased pulmonary complications. MICE is in an early stage of introduction in patients which are treated with the McKeown procedure in regular practice. The aim of this study was to provide insight in the potential cost-effectiveness of MICE and its sensitivity to different complications.

Methods

A decision tree modelled the postoperative outcomes of recurrent laryngeal nerve paresis, anastomotic leakage, pulmonary complications and 30-day mortality. Subsequently, we developed a Markov state transition model to calculate the effects of these input parameters on health outcomes (QALYs) and costs. The results were analysed with a sensitivity analysis and a scenario analysis of a clinical trial of a similar procedure.

Results

Preventing complications seemed to be effective in reducing hospital costs, but resulted in a limited improvement of health outcomes. Improving 30-day survival demonstrated to have a larger effect on health outcomes. A scenario analysis of data from a clinical trial studying similar procedures resulted in a cost reduction of €2974 and an increase of 0.016 QALYs per patient.

Conclusion

Reduced healthcare costs and improved health outcomes from reducing complications and 30-day mortality could offset the increased cost of MICE and lead to a cost-effective innovation. We advise close monitoring of short and long term survival outcomes in future studies.
268. DEVELOPMENT OF A NOVEL ESOPHAGUS-ON-A-CHIP MODEL: A HIGH-FIDELITY PLATFORM FOR DIRECTING PERSONALIZED THERAPY IN ESOPHAGEAL ADENOCARCINOMA
Authors: Pal Sanjima , Shimshoni Elee , Flores-Torres Salvador , Bérubé Julie , Kong Mingyang , Giannias Betty , Hall Sean , Bertos Nicholas , Sangwan Veena , Ingber Donald , Ferri Lorenzo
Published: August 2023

Background

80% of patients diagnosed with esophageal adenocarcinoma (EAC) die of disease. Current standard of care for EAC is systemic cytotoxic, platinum-based neoadjuvant chemotherapy followed by resection and additional rounds of chemotherapy. Locally advanced, resectable patients often fail to respond due to intrinsic and/or acquired chemoresistance. Traditional preclinical models fail to offer alternative salvage options. To our knowledge, this is the first high-fidelity dynamic 3D platform implemented to study esophageal function, pathophysiology, and drug effects.

Methods

Primary tissues obtained from EAC patients at diagnostic biopsy were propagated into patient-derived organoids (PDOs). The upper (mucosal) channel of the esophagus-chip was designated for PDO-derived epithelial cells, while the lower stromal channel was designated for matched fibroblasts. Autologous cell types were exposed to a physiologically relevant flow of nutrient media and microtissues were formed. Epithelial permeability was determined by cascade blue assay. Using this model, a clinically relevant chemotherapy protocol was administered to study patient-specific tumor response. To determine microtissue development and cellular fate in response to chemotherapy, level of several epithelial/mesenchymal biomarkers were evaluated.

Results

Study cohort consisted of both chemo-sensitive and -resistant EAC patients. Esophagus-chip models were developed with samples from patient-matched tumor and normal tissue. Chips recapitulated morphological and histological features of their parental tissues. Epithelial barrier integrity was established within 5 days on-chip. Scanning electron microscopy revealed the presence of pleomorphic cells and mature microvilli in EAC-chips. In vitro administration of docetaxel triplet chemotherapy demonstrated efficacy similar to that observed in the clinical setting when assessed directly or indirectly. Confocal imaging revealed treatment-associated differential expression of epithelial (CK7, CK19), and mesenchymal (vimentin) markers.

Conclusion

3D-organoids conserve cellular heterogeneity of source patients, whereas esophagus-on-chip expand on this diversity by adding microphysiological relevance, stromal influence & flexible complexity. This high-fidelity biomimetic platform enables clinical mimicry and can predict patient-specific chemosensitivity within a clinically relevant timeframe. This esophagus-chip system is a promising potential replacement for both inefficient preclinical animal models and existing tumor-only avatars lacking stromal and microphysiological context.
303. THE TISSUE SYSTEMS PATHOLOGY-9 TEST PROVIDES CLINICALLY-IMPACTFUL RISK STRATIFICATION IN PATIENTS WITH BARRETT’S ESOPHAGUS: CLINICAL EXPERIENCE IN A MULTICENTER COHORT
Authors: Villa Nicolas A , Ordonez-Castellanos Miguel , Yodice Michael , Smolko Christian , Arora Meenakshi , Critchley-Thorne Rebecca J , Khara Harshit S , Diehl David L
Published: August 2023

Background

Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Society guidelines recommend surveillance of BE by endoscopy with biopsies with the goal of detecting dysplasia and EAC at early, treatable stages. However, current practices have limited ability to predict which patients with BE will progress to EAC. This study evaluated the use of the validated, commercially-available tissue systems pathology test (TissueCypher, TSP-9) to risk-stratify BE patients in a large clinical practice cohort.

Methods

TSP-9 test results ordered by 475 physicians from June 2016 to January 2023 for 3935 patients with BE with clinicopathologic data were analyzed. The test orders were from private practices and integrated healthcare systems (92.8%) and academic medical centers (7.2%). Submitted diagnoses were non-dysplastic BE (NDBE, n = 3553, 90.3%), indefinite for dysplasia (IND, n = 190, 4.8%), low-grade dysplasia (LGD, n = 112, 2.8%), or other (BE with sub-category not clearly specified, n = 80, 2.0%). The TSP-9 results (risk classes of low-, intermediate- or high-risk and predicted probability of progression to HGD/EAC within 5 years) were evaluated in all patients.

Results

The TSP-9 test scored 3267 (83.0%), 377 (9.6%), and 291 (7.4%) low-, intermediate- and high-risk, respectively. The TSP-9 test identified risk for progression in NDBE, IND, and LGD subsets, in males and females, and in patients with short- and long-segment BE (Fig. 1). The test scored 15.2% of NDBE patients as intermediate or high-risk. Patients with NDBE who received TSP-9 intermediate- and high-risk scores had predicted 5-year risk of progression to HGD/EAC of 8.1% and 16.2%, respectively, which are higher than progression rates in BE patients with LGD (6.7% in 5 years) for whom guidelines recommend endoscopic eradication therapy.

Conclusions

TSP-9 risk-stratified for progression independently of clinicopathologic features in a cohort of 3935 BE patients. The majority of BE patients scored low-risk, providing support for surveillance-only management. The test identified 15.2% of NDBE patients as intermediate/high-risk for progression, indicating that the test can enable early detection of patients who will benefit from escalation of care to prevent EAC. The TSP-9 test provides objective results to enable risk-aligned management to improve health outcomes for BE patients.
346. IMPACT OF VIRTUAL POST-OPERATIVE CARE ON ESOPHAGECTOMY PATIENTS DURING THE COVID-19 PANDEMIC
Authors: Xiao Karren , Bolger Jarlath , Ristic Ivan , Darling Gail , Yeung Jonathan
Published: August 2023

Background

The SARS-CoV-2 pandemic has resulted in disruptions to oncology practices amongst healthcare institutions globally. To adapt, telehealth has been increasingly implemented into oncologic care, including that of esophageal cancer patients, which has been met with overall success. However, there remains a lack of evidence in the literature pertaining to the outcomes of virtual postoperative appointments for esophagectomy patients.

Methods

We conducted a retrospective cohort study to assess the clinical outcomes of esophageal cancer patients attending phone call follow-up (virtual) visits compared to standard in person care after esophagectomy. Demographic data, clinical and disease characteristics, and hospital visit data within 6 months of operation were collected. This included surgical clinic visits, endoscopies, and emergency room (ER) admissions.

Results

168 esophagectomy patients underwent follow-up care between March 2020 to May 2022; 70 virtual and 98 in-person. Patients attending virtual appointments had significantly fewer ED admissions (−0.48, p = 0.005*, 95%CI [−0.80, −0.14]). Number of endoscopy visits (0.36, p = 0.110, 95%CI [−0.08, 0980]) and the number of clinic visits (0.42, p = 0.118, 95%CI [−0.11, 0.93]) were similar between the two cohorts. ER visits for virtual cohort included feeding tube complications (20.0%), dysphagia (20.0%), and abdominal pain (13.3%). For the in-person cohort, feeding tube complications (12.8%) and chest pain or cardiac features (9.3%) were the most common reasons.

Conclusion

The results of this study provide evidence for the increased use of telehealth following esophagectomy. The reduction in emergency admissions in the virtual cohort may be due to increased comfort with phone call appointments or increased fear of hospital visitation during the pandemic.