bluuebunny/crossref_metadata_2025_split huggingface dataset:
72 PHASE II ADJUVANT CANCER-SPECIFIC VACCINE THERAPY FOR ESOPHAGEAL CANCER PATIENTS CURATIVELY RESECTED AFTER PREOPERATIVE THERAPY WITH PATHOLOGICALLY POSITIVE NODES
Authors: Yasuda Takushi , Nishiki Kohei , Hiraki Yoko , Kato Hiroaki , Iwama Mitsuru , Shiraishi Osamu , Yasuda Atsushi , Shinkai Masayuki , Kimura Yutaka , Sukegawa Yasushi , Chiba Yasutaka , Imano Motohiro , Takeda Kazuyoshi , Satou Takao , Shiozaki Hitoshi , Nakamura Yusuke 
Published: September 2021

Abstract

Esophageal squamous cell carcinoma (ESCC) patients with pathologically positive nodes have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. To elucidate the efficacy of adjuvant vaccine monotherapy using three HLA-A*24-restricted tumor-specific peptide antigens for ESCC, up-regulated lung cancer 10, cell division cycle associated 1 and KH domain-containing protein overexpressed in cancer 1, we conducted an exploratory prospective phase II clinical trial (UMIN000003557).

Methods
Patients with ESCC who underwent curative resection after preoperative therapy and were found pathologically positive lymph node metastasis were enrolled from December 2009 to September 2014 and allocated into the control and vaccine groups (CG and VG) based on the HLA-A*2402 positive or negative. One mg each of three epitope peptides mixed with 1 mL of Montanide ISA 51 VG was administered the first 10weekly injections followed by 10 additional biweekly injections to VG. No other adjuvant therapy was given until recurrence occurred. The primary endpoint was relapse-free survival (RFS) and the secondary endpoint was esophageal cancer-specific survival (ECSS).

Results
Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs. 45.3%, p = 0.205 (one-sided)), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs. 32.4%, p = 0.045 (one-sided)) probably due to the better clinical responses in patients of the VG to the post-recurrence therapy and this difference was more prominent in patients with CD8+ and programmed death-ligand 1 double negative tumor (68.0% vs. 17.7%, p = 0.010 (two-sided)).

Conclusion
Our results suggested that the cancer peptide vaccine suppressed the postoperative recurrence, enhanced the post-recurrence therapy and improved the survival of ESCC patients, particularly in the cases without CD8 infiltration and PD-L1 expression. A phase III randomized controlled study has been conducted in response to these results, and the results are waiting to be published.
734 PL11.06 PROGNOSTIC FACTORS FOR MORTALITY IN PATIENTS WITH ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY FOR CANCER (TENTACLE—ESOPHAGUS STUDY)
Authors: Ubels Sander , Verstegen Moniek , Bouwense Stefan , Hannink Gerjon , Klarenbeek Bastiaan , Siersema Peter , Workum Frans , Rosman Camiel ,   on behalf of the TENTACLE - Esophagus Collaborative group
Published: September 2021

Abstract

Anastomotic leakage (AL) is a common and potentially life-threatening complication after esophagectomy. In patients with AL it is largely unknown which patient parameters and leakage characteristics are associated with leak severity and mortality. We aimed to identify prognostic factors for mortality in patients with anastomotic leakage after esophagectomy.

Methods
The TENTACLE—Esophagus study is an international retrospective cohort study, in which 1451 patients with AL after esophagectomy between 2011 and 2019 were included in 71 centers from 20 countries. Potential prognostic factors were selected from literature and a hypothetical association with mortality. Confounders of (individual) prognostic factors were identified using a directed acyclic graph approach to minimize bias. Primary outcome was 90-day mortality. Logistic regression analysis was performed to estimate crude and adjusted odds ratios (AOR) and 95% confidence intervals (95%CI). The study protocol is accessible at www.tentaclestudy.com.

Results
Overall 90-day mortality rate was 11.6%. Leakage characteristics with the largest prognostic effect on mortality were gastric conduit ischemia/necrosis (AOR 2.23, 95%CI 1.43-3.49), defect circumference ≥ 25% (AOR 2.10, 95%CI 1.32-3.36) and intrathoracic fluid collections (drained AOR 1.98, 95%CI 1.05-3.75; undrained AOR 2.43, 95%CI 1.57-3.75). Patient parameters with the largest prognostic effect were ASA-score ≥ 3 (AOR 4.18, 95%CI 1.67-10.51), ECOG-score ≥ 2 (AOR 2.83, 95%CI 1.56-5.14) and respiratory failure (AOR 3.89, 95%CI 2.67-5.66), hemodynamic failure (AOR 3.09, 95%CI 1.96-4.88) or renal failure (AOR 4.08, 95%CI 2.20-7.59) at time of AL diagnosis.

Conclusion
Defect circumference, intrathoracic fluid collections, gastric conduit condition and several patient parameters were identified as prognostic factors for mortality in patients with AL. Adjusting for these prognostic factors may reduce confounding bias in future studies assessing efficacy of AL treatments. The identified prognostic factors contribute to the understanding of the severity of anastomotic leakage after esophagectomy and may be used to recognize the severity of an anastomotic leak in individual patients.
756 LONG-TERM OUTCOME AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ENTIRE CIRCUMFERENTIAL CT1AN0M0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Inaba Atsushi , Kadota Tomohiro , Nishihara Keiichiro , Sato Daiki , Nakajo Keiichiro , Yukami Hiroki , Mishima Saori , Sawada Kentaro , Kotani Daisuke , Fujiwara Hisashi , Nakamura Masaki , Hojo Hidehiro , Yoda Yusuke , Kojima Takashi , Fujita Takeo , Yano Tomonori 
Published: September 2021

Abstract

Endoscopic submucosal dissection (ESD) is the standard treatment for cT1a esophageal squamous cell carcinoma (ESCC), however its indication for the entire circumferential lesions is still controversial because of the risk of severe stricture after ESD. Therefore, several treatment options are performed based on physicians’ choice, however, each clinical course is unclear. This study aimed to clarify the long-term outcome after ESD for patients with entire circumferential cT1aN0M0 ESCC, comparing with esophagectomy or chemoradiotherapy.

Methods
Patients with entire circumferential cT1aN0M0 SESCC treated with ESD, chemoradiotherapy, or esophagectomy as the initial treatment between January 2010 and December 2016 in our institution were included. Patients who had a history of any malignancy at cStage II-IV within 5 years were excluded. The 5-year overall survival (OS), 5-year disease-free survival (DFS), stricture rate, refractory stricture rate (defined as requiring &gt;6 dilations), curative resection (defined as pT1a without lymphovascular invasion and negative for vertical margin in the pathological evaluation) rate of ESD, and complete response rate of chemoradiotherapy were evaluated for each treatment.

Results
Of the 48 eligible patients, 25/13/10 patients were performed ESD/chemoradiotherapy/esophagectomy as an initial treatment. Curative resections rate of ESD was 72%, and additional esophagectomy and chemoradiotherapy were performed in three and one patients with non-curative resection. Complete response rate of chemoradiotherapy was 100%, however, 4 patients had recurrence thereafter. No recurrences occurred after esophagectomy in all patients treated with esophagectomy. During median follow-up of 83 months, stricture and refractory stricture rate was 80/44% after ESD, 0/0% after chemoradiotherapy, and 20/10% after esophagectomy. The 5-year OS/DFS was 91/87% after ESD, 92/59% after chemoradiotherapy, and 90/90% after esophagectomy.

Conclusion
While some patients required additional treatments due to non-curative resection, the long-term survival after ESD for circumferential cT1aN0M0 ESCC was similar as those after chemoradiotherapy or esophagectomy. In contrast, the stricture and refractory stricture rate after ESD was higher than others. Further investigation in a large cohort is necessary to clarify the indication criteria of ESD for patients with the lesion.
761 PATIENT PREFERENCES FOR ACTIVE SURVEILLANCE VERSUS STANDARD SURGERY AFTER NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL CANCER TREATMENT
Authors: Hermus Merel , Wilk Berend , Collee Gerlise , Chang Rebecca , Noordman Bo , Dekker Jan Willem , Esser Stijn , Nieuwenhuijzen Grard , Luyer Misha , Rosman Camiel , Klarenbeek Bastiaan , Coene Peter-Paul , Harst Erwin , Wijnhoven Bas , Busschbach Jan , Lanschot Jan , Lagarde Sjoerd , Kranenburg Leonieke 
Published: September 2021

Abstract

The need for standard surgical resection in esophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) is subject of debate. Possibly, active surveillance (AS) is an option for patients with a clinically complete response (cCR), in whom no vital tumor cells are detected after nCRT. In a large Dutch multicenter randomized trial (SANO trial), standard surgery is compared to AS in patients with a cCR. Within this trial, we performed a side-study on patient treatment preferences.

Methods
Esophageal cancer patients, who declined participation in the SANO-trial due to a strong treatment preference for either AS or surgery were included. In-depth interviews were held on patient’s motives for their treatment choice. First, personal motives were addressed in an open manner, and later specific topics were addressed: earlier experiences with illness and health care, future health expectations, emotional motives, religious or spiritual believes and values in life. Data was recorded, transcribed verbatim and qualitatively analyzed according to the grounded theory principles. In addition, questionnaires on health literacy, coping, anxiety and decision regret were administered at two time points.

Results
Forty patients participated: twenty preferred AS and twenty standard surgery. The central principle for all patients is striving for safety while dealing with the threat of cancer. However, patients express different coping strategies in dealing with this threat. Patients preferring AS rely on trusting their bodies and good outcomes, while questioning the need for surgery. Patients preferring surgery try to minimize insecurity by eliminating the source of the cancer, while arguing that chances for undergoing surgery are high anyway. Interestingly, for either treatment option comparable arguments were used, with the most striking one of wishing ‘not to become a patient’.

Conclusion
Patients’ preferences in the treatment of esophageal cancer are determined by the way they cope with the threat of cancer. Since the arguments given for either AS or standard surgery can be comparable or even similar, the need for healthcare professionals to discuss what truly matters to their patients is of high importance. Subsequently, attuning to the personal needs of esophageal cancer patients will benefit the decision making process on future treatment.
780 ISOLATED BRAIN METASTASIS OF ESOPHAGEAL CARCINOMA AFTER MINIMALLY INVASIVE ESOPHAGECTOMY MIGHT NOT HAVE A DISMAL PROGNOSIS
Authors: Stuart S , Kuypers T , Martijnse I , Heisterkamp J , Matthijsen R 
Published: September 2021

Abstract

After esophagectomy for esophageal carcinoma, 2–13% of patients develop brain metastases (BM) which are associated with a poor prognosis. Further investigation into treatment and prognosis is beneficial given the scarce publications and varying outcomes.

Methods
Case files of all 339 patients who underwent esophagectomy in a single high-volume centre between January 2015 and December 2020 were retrospectively reviewed, all procedures were minimally invasive esophagectomies (MIE). Patients with BM and isolated brain metastases (iBM) were identified and a Kaplan–Meier analysis was performed.

Results
15 out of 339 patients (4,4%) undergoing MIE developed BM of which 9 (60,0%) were iBM. Most patients were diagnosed with squamous cell carcinoma (55,6%), localised in the middle third of the esophagus (66,7%) and had a pathologic complete response (66,7%). Treatment consisted of gamma knife (GK) radiosurgery (44,4%), surgical resection (22,2%), GK and surgical resection (11,1%) and best supportive care (22,2%). Median time to diagnose iBM was 8,4 months (95% CI 0,0–17,2) and survival after recurrence was 14,3 months (95% CI 0,0–45.9). 2 patients (22,2%) remain disease-free after at least 2 years of follow-up.

Conclusion
iBM after esophagectomy for esophageal carcinoma is rare, but when encountered should be treated with a curative intent in selected cases. More research should be conducted on the benefits of screening for iBM after esophagectomy, especially in patients diagnosed with a squamous cell carcinoma in the middle third of the esophagus with a pathological complete response.
782 PATTERNS OF FAILURE AND ADEQUACY OF CLINICAL TARGET VOLUME (CTV) MARGINS IN PATIENTS TREATED WITH DEFINITIVE CHEMO-RADIATION IN ESOPHAGEAL CANCER
Authors: Tahmeed Tahseena , Tibdewal Anil , Ghosh-Laskar Sarbani , Mummudi Naveen , Noronha Vanita , Prabhash Kumar , Agarwal Jai Prakash 
Published: September 2021

Abstract

Esophageal cancer is a locally aggressive malignancy with dismal overall survival (OS) rates. Approximately 50–60% of patients fail loco-regionally after definitive chemoradiation (CTRT). There is a lack of consensus regarding clinical target volume (CTV) margins. Improved diagnostic investigations and patterns of failure (POF) data, suggested scope of reduced CTV margins. In this retrospective study, we evaluated the POF (defined as first site of failure) and the adequacy of CTV margins.

Methods
All patients treated with CTRT between Jan 2013 to Dec 2017 were included. CTV margin was given as 3–5 cm cranio-caudal and 1–1.5 cm radial from gross tumor volume (GTV). Patients were treated either with combined technique (anterior–posterior followed by conformal) or with volumetric arc radiotherapy to a dose of 60-63Gy in 30–35 fractions. PET-CT/CT thorax and upper GI-endoscopy were performed at regular intervals. Loco-regional failure (LRF) was defined as recurrence at local site or regional nodes respectively and classified as infield, marginal and out-field. CT was co-registered with planning CT to document these failures.

Results
158 patients were eligible. Twenty-one patients were excluded as they either progressed or did not attend the first follow-up. Median age was 57 years, &gt;90% had squamous histology, and most common subsite was upper third. Median follow-up was 45.8 months, 53 patients (41.7%) had progression. Local recurrence (LR) was seen in 37 (69.8%), followed by regional in 25 (47.1%) and distant in 21 patients (39.6%). All LR were within the GTV. Of regional failures, 50% were within GTV and 50% were outside the radiotherapy portals. This suggest that 3 cm cranio-caudal CTV margin was adequate.

Conclusion
Our study demonstrated that loco-regional recurrence was the most common pattern of failure after definitive CTRT. As majority of loco-regional failures were within the GTV, hence, 3 cm cranio-caudal CTV margins appear to be adequate enough for control of microscopic disease. Further prospective studies are needed to validate the use of 3 cm CTV margins in definitive CTRT for esophageal cancer.
784 TRANSHIATAL HERNIA: AN UNDERDIAGNOSED BUT OVER-TREATED COMPLICATION AFTER MINIMALLY INVASIVE ESOPHAGECTOMY
Authors: Kuypers Toon , Stuart Sanne , Martijnse Ingrid , Heisterkamp Joos , Matthijsen Robert 
Published: September 2021

Abstract

Postoperative transhiatal hernia is a possible life-threatening complication following esophagectomy. The incidence and indications to treat remain open to debate with apparently an increase after minimally invasive esophagectomy (MIE). The aim of this study is to analyze a large series of patients after MIE in a single high-volume center with a transhiatal herniation after minimally invasive esophagectomy (THAMIE) and obtain new insights in this pathology.

Methods
We included all patients who underwent a MIE (Ivor Lewis and McKeown procedure) in our hospital between 2015 and 2020. Retrospective analysis of demographic, clinical and surgical data was performed. Outcomes of measure were incidence, initial clinical presentation, treatment of choice, postoperative complications and symptoms, herniation recurrence.

Results
In 341 MIE 25 (7.3%) patients were diagnosed with a THAMIE postoperatively. 4 patients (16.0%) were asymptomatic at the time of presentation. 5 patients (20%) were treated conservatively because of recurrent carcinoma. 20 patients received a laparoscopic reduction of the transhiatal hernia and cruraplasty (19 non-absorbable sutures, 1 mesh) regardless whether they were symptomatic or not. 25.0%(5/20) of the patients were operated in emergency settings and 5.0% (1/20) was converted to a laparotomy. Postoperatively 6 of the 18 symptomatic patients (33.3%) experienced no relief of symptoms and 40.0% (8/20) of the THAMIE recurred. 35% had serious postoperative complications (clavien-dindo IIIa or more) and mortality was 0.0%.

Conclusion
The incidence of 7.33% found in our data suggests that THAMIE is a common complication after MIE. We almost exclusively (95.0%) treated patients in a laparoscopic way. Due to the high percentage of morbidity (35.0% ≥ CD IIIa), recurrence (40.0%) and patients with unrelieved symptoms(33.3%) we recommend a conservative treatment for the asymptomatic patients, and further analysis of predictive symptoms associated with a THAMIE to evolve to a shared decision making algorithm for elective symptomatic patients.
793 PATIENTS’ PREFERENCES FOR ACTIVE SURVEILLANCE OR STANDARD ESOPHAGECTOMY AFTER NEOADJUVANT CHEMORADIOTHERAPY: A DISCRETE CHOICE EXPERIMENT IN PATIENTS AFTER STANDARD ESOPHAGECTOMY
Authors: Van Der Wilk Berend , Spronk Inge , Noordman Bo J , Eyck Ben M , Haagsma Juanita , Coene Peter-Paul L O , Harst Erwin , Heisterkamp Joos , Lagarde Sjoerd M , Wijnhoven Bas P L , Lanschot J Jan B 
Published: September 2021

Abstract

Active surveillance after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal cancer is currently topic of investigation. In a discrete choice experiment, patients’ preferences can be quantified by asking patients to state their preference over hypothetical treatment alternatives. The aim of the present study was to assess patients’ preferences for either active surveillance or standard esophagectomy in patients who underwent neoadjuvant chemoradiotherapy followed by surgery without signs of recurrence.

Methods
A discrete choice experiment was performed in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by standard esophagectomy at least one year earlier. Patients completed a questionnaire consisting of eighteen choice sets considering active surveillance or standard esophagectomy. Treatment alternatives were characterized by attributes with varying attribute levels hypothesized to influence treatment choice: five-year survival, short-term and long-term health related quality of life (HRQOL), annual number of diagnostics required and the risk that esophagectomy is still necessary later in time. The importance of attributes and willingness to trade-off 5-year survival for other attributes were assessed using panel latent class model.

Results
A total of 107 patients were consecutively included, of whom 100 (93%) responded between August 2018 and October 2020. Regardless of the attribute levels, 28 patients preferred active surveillance and 28 patients preferred standard esophagectomy. When considering both treatments, five-year survival and long-term HRQOL were considered most important attributes. Patients were willing to trade-off 5.4% five-year overall survival to obtain a better long-term HRQOL.

Conclusion
At least one year after neoadjuvant chemoradiotherapy and esophagectomy, over a quarter of patients would choose not to undergo standard esophagectomy again, regardless of the attribute levels. Patients were willing to trade-off five-year survival chance in order to achieve an HRQOL which was much better than their own situation. When considering both treatments, five-year survival and long-term HRQOL were the most important determinants in the choice for treatment.
801 EXOSOMES CONTAINING LUNG SELF-ANTIGENS COLLAGEN-V AND Kα1-TUBULIN ARE PREVALENT IN PATIENTS WITH SYMPTOMATIC GASTROESOPHAGEAL REFLUX: RESULTS FROM A PILOT STUDY
Authors: Razia Deepika , Ravichandran Ranjithkumar , Bansal Sandhya , Fournier Sarah , Baboli Komeil , Bremner Ross M , Mohanakumar Thalachallour , Mittal Sumeet K 
Published: September 2021

Abstract

Gastroesophageal reflux disease (GERD) has been associated with aspiration-induced pulmonary injury; however, good clinical or laboratory markers are not available. Increased serum levels of exosomes containing normally sequestered primary lung self-antigens (collagen-V, Kα1-tubulin) have been associated with lung injury in the lung transplant population. The aim of this pilot study was to assess the prevalence of exosomes containing collagen-V and/or Kα1-tubulin in patients with severe GERD.

Methods
After IRB approval, the institutional biobank database was queried to identify non-lung transplant patients who underwent primary anti-reflux surgery (ARS) from 2019 to 2020. Serum samples were retrieved from the repository. Exosome pellets were isolated using the Invitrogen® kit using the manufacturer’s protocol. The size of exosomes in the pellet was confirmed using NanoSight. Western blot of the exosomes was used to isolate and quantify collagen-V and Kα1-tubulin, using CD-9 as the standard. A ratio &gt; 1 was considered abnormal.

Results
Ten patients (6 females) with a median (IQR) age of 53 (42, 63) years were included in this study. All patients had symptomatic GERD as an indication for ARS. Five patients (50%) had exosomes containing abnormal levels of collagen-V and/or Kα1-tubulin (Figure 1). There was a mean 2.9- and 8.2-fold increase in collagen-V and Kα1-tubulin, respectively.

Conclusion
Humoral factors associated with lung injury are highly prevalent in patients undergoing elective ARS for GERD. This suggests that detection of exosomes containing lung self-antigens collagen-V and Kα1-tubulin could be useful as a biomarker of GERD-induced lung injury.