bluuebunny/crossref_metadata_2025_split huggingface dataset:
233 POSTOPERATIVE DELIRIUM AFTER OESOPHAGECTOMY FOR CANCER: HOW CAN WE PREVENT AND MANAGE IT?
Authors: Rita A , Pinto E , Pomba L , Tolin F , Mattara G , Mazza M , Turchet F , Pilati P 
Published: September 2020

Abstract

Oesophagectomy is associated with high morbidity. One of the postoperative complication observed after esophageal resection is Post Operative Delirium (POD), a psychiatric disease caused by major surgical stress and pharmacological treatments. POD can jeopardize patient healing-process since patients are not collaborative to perioperative care but also because they can harm themselves. Thus the aim of this systematic review was to identify POD factors and its effective management in patients undergone oesophagectomy for oesophageal/oesophagogastric-junction cancer.

Methods
A comprehensive systematic literature search was conducted using PubMed, Cochrane Library, Scopus, psycINFO and psycARTICLES in order to identify all articles published until January 2020. The following combinations of terms were used for the search strategy: neoplasm; esophagus; gastro-esophageal junction; oesophagectomy; delirium. The following inclusion criteria were set: full article published in English; patients with esophageal cancer undergone oesophagectomy; POD observed. Two researchers independently selected studies matching the inclusion criteria. Duplicate studies, non-relevant topic, data from abstracts or unpublished were excluded. Any disagreements between the researchers’ evaluation concerning inclusion of studies were resolved by consensus.

Results
Of 235 studies yielded by systematic literature search, 21 met inclusion criteria. POD incidence was observed between 3 and 38% of patients and was precursor of other complications in 1/3 of POD patients. Preoperative risk factors were older age, cerebrovascular disease and pulmonary disfunction. Anxiety and depression resulted predisposing factors. Perioperative risk factors were duration of surgery, ICU length of stay, colloids infusion and blood transfusion. Open-surgery seemed to influence POD more than minimally-invasive and robotic surgery. Interventions identified to treat POD were pharmacological (prophylactic haloperidol, insomnia treatment) and behavioral (patient reorientation by family involvement, bright-light therapy, early mobilization).

Conclusion
This systematic review identified preoperative, intraoperative and postoperative risk factors of POD after oesophagectomy. No standardized prevention nor treatment of POD was identified.
POD impacts patients’ ability in perceiving postoperative symptoms. The difficulty in communicating with health professionals may lead to delay the diagnosis of others complications and prolong hospital stay. Therefore further trials are required to assess efficacy of different POD treatments aimed to enhance postoperative management.
252 HETEROGENEITY OF CLINICAL LYMPH NODE INVOLVEMENT (CN+) IN ESOPHAGEAL CANCER: A PERSPECTIVE BASED ON METABOLIC VOLUME
Authors: Lin D , Liu G , Tan L 
Published: September 2020

Abstract

Esophageal cancer with clinical lymph node involvement (cN+) is a heterogeneous disease. Although the cN+ category is of vital importance, preclinical staging cannot establish the number of positive nodes. In this study, we aimed to measure the heterogeneity of esophageal cancer with cN+ based on metabolic volume. We investigated its influence on the response to neoadjuvant treatment.

Methods
We retrospectively reviewed the patients received neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy during January 2016 and November 2018. All patients had received baseline 18F-FDG PET/CT. All patients were restaged according to the 8th TNM Staging System. We measured the metabolic tumor volume (MTV, cm3) of the whole body (MTVwb) and the primary tumor (MTVp) on the workstation. We also calculated the difference of MTVwb and MTVp (MTVn) and the ratio of MTVwb and MTVp (MTVratio). Logistic regression was used to determine the association between the heterogeneity and the response to neoadjuvant treatment.

Results
Among the 102 patients enrolled in this study, 54 patients had clinically suspicious lymph nodes in small diameters with lower uptake (MTVn as 0). The median MTVwb, MTVp, and MTVn of the patients were 22.34 (2.09 to 105.24), 19.62 (1.93 to 98.06), and 0 (0 to 89.00), respectively. In nCT and nCRT groups (all patients), 15 (37.5%) and 38 (61.3%) achieved ypN0, respectively. In nCT and nCRT groups (MTVn as 0), 12 (42.9%) and 20 (76.9%) patients achieved ypN0, respectively. Logistic regression revealed that MTVn (0 vs. &gt;0) was independently associated with ypN status in nCRT group (P = 0.035).

Conclusion
nCRT compared with nCT achieved more effective disease control. In esophageal cancer treated with nCRT, the heterogeneity of cN+ measured by metabolic volume was associated with ypN status. A prospective study was in demand to further validate the findings.

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268 LIQUID BIOPSY IN ESOPHAGEAL ADENOCARCINOMA: ROLE OF LINE-1 HYPOMETHYLATION
Authors: Alfieri R , Boldrin E , Mazza M , Realdon S , Fassan M , Pilati P , Curtarello M 
Published: September 2020

Abstract

Esophageal Adenocarcinoma (EADC) prognosis is still poor. Clinical staging doesn’t allow accurate prediction of response to neoadjuvant treatment and survival. Molecular characterization of EADC is an expanding field aimed to predict treatment response and prognosis. Hypomethylation of Long Interspersed Nuclear Element 1 (LINE-1) sequences recently emerged as a frequent epigenetic alteration in EADC. Aim of the study was to evaluate methylation patterns of LINE-1 that is considered a good surrogate of global DNA methylation.

Methods
We investigated cell free DNA (cfDNA) of 21 patients, 19 with EADC and 2 with Barrett’s esophagus (BE). To verify the possibility to use LINE-1 methylation status to predict tumor behaviour, we extended the analysis to a few longitudinal cases, one EADC and two BE. One BE patient progressed to low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/EADC during surveillance, while the other remains stable. LINE-1 promoter methylation was analyzed using restriction enzymes and DNA amplification.

Results
Using this approach, we were able to detect the presence of hypomethylated LINE-1 sequences in EADC cfDNA. The difference in methylation level between cfDNA and constitutive DNA was statistically significant (p = 0.0001). In one EADC patient, treated with esophagectomy, LINE-1 hypomethylation was found at lower level after resection and at higher level at recurrence. In another patient affected by BE, LINE-1 hypomethylation increased during the progression from metaplastic epithelium to EADC, switching back to the level of constitutive DNA after endoscopic resection. The third patient, with stable BE during 4 years follow-up, showed non-significant variations in methylation status of LINE-1.

Conclusion
Our study demonstrated the feasibility of our methodological approach to detect hypomethylation events in EADC patient cfDNA. Longitudinal preliminary analysis suggested a correlation between methylation status of LINE-1 and tumor progression. Further studies on larger population are needed to confirm these encouraging data.
LINE-1 methylation analysis could be useful as a new molecular assay to integrate patient monitoring.
272 10-YEAR FOLLOW-UP OF A RANDOMISED CONTROLLED TRIAL COMPARING NEOADJUVANT CHEMORADIOTHERAPY PLUS SURGERY VERSUS SURGERY ALONE FOR OESOPHAGEAL CANCER (CROSS)
Authors: Eyck B , Lanschot J , Hulshof M , Wilk B , Shapiro J , Hagen P , Nieboer D , Berge Henegouwen M , Wijnhoven B , Laarhoven H , Nieuwenhuijzen G , Hospers G , Bonenkamp J , Cuesta M , Blaisse R , Busch O , Kate F , Creemers G , Punt C , Plukker J , Verheul H , Spillenaar Bilgen E , Dekken H , Sangen M , Rozema T , Biermann K , Beukema J , Piet A , Rij C , Reinders J , Tilanus H , Gaast A 
Published: September 2020

Abstract

Neoadjuvant chemoradiotherapy according to the Dutch randomised controlled ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) has become standard of care for patients with cancer of the oesophagus or oesophagogastric junction. The aim of this study was to provide more insight into the ultra-long-term impact of CROSS neoadjuvant chemoradiotherapy on survival and disease recurrence for patients with oesophageal cancer.

Methods
Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction were randomised between neoadjuvant chemoradiotherapy (five weekly cycles of intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m2 of body-surface area]) with concurrent 41.4 Gy radiotherapy given in 23 fractions of 1.8 Gy, 5 days per week) plus surgery (nCRT arm) versus surgery alone (surgery arm). Primary endpoint was overall survival, defined from date of randomisation to date of all-cause death or to last day of follow-up. Secondary endpoints were cause-specific mortality and conditional survival. Analysis was by intention-to-treat.

Results
From 2004 through 2008, 178 patients were randomized to the nCRT arm and 188 to the surgery arm. Median follow-up for surviving patients was 146.6 months (IQR 133.5–157.2). Ten-year overall survival was 38% in the nCRT arm and 25% in the surgery arm (HR 0.68 [95%CI 0.53–0.87]). For patients with squamous cell carcinoma ten-year overall survival was 46% in the nCRT arm compared to 23% in the surgery arm. For patients with adenocarcinoma ten-year overall survival was 36% in the nCRT arm and 26% in the surgery arm. In the nCRT arm, ten-year oesophageal cancer-specific mortality was 47%.

Conclusion
Survival benefit of patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction receiving neoadjuvant chemoradiotherapy persists for at least 10 years compared to patients undergoing surgery alone.
274 ASSESSMENT OF THE ANTI-PROLIFERATIVE EFFECTS OF STANDARD CHEMOTHERAPY AND PAN-HER FAMILY TYROSINE KINASE INHIBITORS IN ESOPHAGEAL CANCER CELL LINE MODELS.
Authors: Al Azzawi M , Gaynor N , Crown J , Collins D , Robb W 
Published: September 2020

Abstract

Esophageal cancer is the 9th most common cause of cancer globally with a mortality:incidence ratio of 0.88 and a 5 year mortality rate of 19%. Herceptin, a HER2 targeted monoclonal antibody, is approved for use in metastatic HER2+ gastroesophageal carcinoma. To further examine the benefits of HER family inhibition in esophageal cancer, the effects of pan-HER family TKIs and standard chemotherapy in HER2+ and HER2-low cell line models were examined.

Methods
Two cell lines, OE19 (HER2+) and FLO-1 (HER2-low) were used to examine the effect of the standard FLOT chemotherapy regimen (5 flurouracil (5FU), oxaliplatin and docetaxel) and pan-HER TKIs neratinib and poziotinib. All compounds were from commercial sources. 2D acid phosphatase-based proliferation assays were utilised to assess the anti-proliferative effects of these agents. Triplicates of each assay were performed and standard deviations were determined. IC50 values were calculated using Calcusyn ® software.

Results
The OE19 cell line demonstrated a high sensitivity to neratinib and poziotinib with IC50 values of 3.426+/−0.187 nM and 0.307 +/−0.051 nM), respectively. IC50 values for neratinib (0.147+/−0.080 μM) and poziotinib (2.4+/−0.471 μM) were significantly higher (p &lt; 0.05) in the FLO-1 cell line compared to OE19. The IC50 values for oxaliplatin and docetaxel were comparable between the OE19 and FLO-1. However, both cell lines were insensitive to 5FU with IC50 values greater than 10 μM.

Conclusion
The HER2+ cell line was significantly more sensitive to the pan-HER family TKIs neratinib and poziotinib, compared to the HER2-low cell line. This may indicate a potential use for pan-HER family TKIs in HER2+ esophageal cancer. Further work is being conducted to assess potential synergy between pan-HER family TKIs and chemotherapy in these models.
275 POSTOPERATIVE COMPLICATIONS DO NOT AFFECT QUALITY OF LIFE AFTER ESOPHAGECTOMY
Authors: Jezerskyte E , Laarhoven H , Sprangers M , Eshuis W , Hulshof M , Berge Henegouwen M , Gisbertz S 
Published: September 2020

Abstract

Despite the attempts to reduce postoperative complication incidence after esophageal cancer surgery, up to 60% of patients endure postoperative complications. These patients often have a reduced health related quality of life (HR-QoL) and it may also have a negative effect on long-term survival. The aim of this study is to investigate the difference in short- and long-term HR-QoL in patients with and without a complicated postoperative course.

Methods
A retrospective comparative cohort study was performed with data from the Dutch Cancer Registry (IKNL) and QoL questionnaires from POCOP, a longitudinal patient reported outcomes study. All patients with esophageal and gastroesophageal junction (GEJ) cancer after an esophagectomy with or without neoadjuvant chemo(radio) therapy in the period of 2015–2018 were included. Exclusion criteria were palliative surgery, patients with a recurrence, reconstruction with a colonic or jejunal interposition, no reconstruction and emergency surgery. HR-QoL was investigated at baseline and at 3, 6, 9, 12, 18 and 24 months postoperatively between patients with and without complications following an esophagectomy.

Results
A total of 486 patients were included: 270 with and 216 without postoperative complications. The majority of patients were male (79.8%) with a median age of 66 years (IQR 60–70.25). Significantly more patients had comorbidities in the group with postoperative complications (69.6% vs 57.3%, p = 0.001). A significant difference in HR-QoL over time was found between the two groups in “choked when swallowing” score (p = 0.028). Patients that endured postoperative complications reported more problems with choking when swallowing at 9 months follow-up (mean score 12.9 vs 8.4, p = 0.047). This difference was not clinically relevant with a mean score difference of 4.6 points.

Conclusion
Postoperative complications do not significantly influence the short- and long-term HR-QoL in patients following an esophagectomy. Only one HR-QoL domain showed difference over time, however, this was not clinically relevant.
288 RISK STRATIFICATION OF POSTOPERATIVE DELIRIUM BY SIMPLE QUESTIONNAIRE IN GERIATRIC PATIENTS WITH ESOPHAGEAL CANCER
Authors: Terayama M , Yamada K , Mita H , Wake H , Kataoka A , Enomoto N , Nohara K , Kokudo N 
Published: September 2020

Abstract

Geriatric patients often have cognitive decline which might cause postoperative complications, including delirium, therefore, it is very important to evaluate mental ability before surgery. The Flemish version of the triage Risk Screening Tool (fTRST), which focuses on the assessment of cognitive function, is reported to be useful for identifying patients with geriatric risks. The aim of our study is to predict postoperative delirium easily in geriatric patients with esophageal cancer (EC).

Methods
Patients aged ≥70 years old with EC were retrospectively included who received an operation at National Center for Global Health and Medicine from February 2016 to November 2019. The fTRST were administered to all patients. To evaluate objectively, Yamaguchi University Mental Disorder Scale (YDS), one of the famous exams to assess the patient’s cognitive function, were also performed. The impaired were defined as fTRST ≥2 and YDS ≤ 12. We evaluated postoperative delirium and compared the fTRST with YDS.

Results
Overall, 40 patients were included. Median age was 76 years (range, 70 to 89 years), and 37 patients (85%) were male. Twenty-three patients (58%) were fTRST impaired, 6 patients (15%) were YDS impaired. 21 patients (52%) had postoperative delirium. The abnormal fTRST (p = 0.001) and YDS (p = 0.02) were both at risk for postoperative delirium. In multivariable analysis, the abnormal fTRST was significantly associated with postoperative delirium (OR 5.96; CI 1.33–26.7, p = 0.02).

Conclusion
The fTRST is useful tools to predict postoperative delirium and prior to YDS in elderly patients with EC. Further studies are needed to design interventions to prevent postoperative delirium for those vulnerable patients.
294 LONG TERM OUTCOMES OF THORACOSCOPIC-ASSISTED OESOPHAGECTOMY FOR EARLY OESOPHAGEAL CANCER
Authors: Frankel A , Lamb P , Deans C , McDonald A , Couper G 
Published: September 2020

Abstract

Oesophageal cancer is the 9th most common cancer in Scotland, yet is ranked 5th for cancer mortality. This is in part due to most new patients presenting with locally-advanced or metastatic disease. Early disease is often found during Barrett's surveillance or serendipitously. There is a paucity of literature describing the outcomes of patients who undergo resection for early disease in Europe, particularly morbidity, actual five-year survival rate, recurrence patterns and ultimate causes of death.

Methods
Data for fifty consecutive patients from the Royal Infirmary Edinburgh (RIE) with cN0 disease who underwent thoracoscopically-assisted McKeown (three-stage) oesophagectomy between 2005 and 2013 were recorded in a prospectively-maintained database. 20/50 were in a formal endoscopic surveillance program for Barrett’s oesophagus. Endoscopic ultrasound (EUS) became widely used at RIE in 2007 with the introduction of an endoscopic mucosal resection service, with 39/40 patients operated on since 2007 undergoing pre-operative EUS.

Results
Median age was 67 (range 46–81) with 34 males and 16 females. 44 had ≤pT1b, while 48 patients were pN0 (median node yield of 12). There were 4 anastomotic leaks, 4 recurrent laryngeal nerve palsies and 2 tracheo-oesophageal fistulas. There was one in-hospital death secondary to intra-operative and post-operative myocardial infarctions. As of January 2020, 16/50 patients had died, with a median survival of 9 years; five year survival was approximately 85%. 5 patients died of metastatic disease (1.3 to 6.8 years post-resection). 10 patients died of other causes, the most common being alcoholic liver disease (n = 3).

Conclusion
Patients in this case series received high quality surgery and peri-operative care, and survival rates were high. This dataset demonstrates that a holistic approach to healthcare is vitally important in the long-term care of such a cohort, because most deaths were not related to their cancer. This should be kept in mind when counselling patients with early disease and when liaising with their primary care provider.
349 LAPAROSCOPIC MANAGEMENT OF ACHALASIA CARDIA IN CHILDREN
Authors: Haravu Ramprasad K , Agarwal P 
Published: September 2020

Abstract

Achalasia Cardia is a rare motility disorder of esophagus and is characterized by increased pressure of Lower Esophageal Sphincter (LES) and reduced motility of the body. This results in functional obstruction and failure of relaxation of LES. This condition is relatively rare in young children (about 0.11/100,000 children)

Methods
A retrospective study was done on 16 Paediatric patients with Achalasia Cardia over a 9 year period from 2010–2018. All patients underwent Barium Swallow and also upper GI endoscopy. Among the 16 patients, 8 of the patients underwent CT scanning and 6 patients had undergone manometry which is the gold standard method for diagnosis. Laparoscopic Heller’s Cardiomyotomy is the primary treatment modality for Achalasia Cardia. All patients underwent Cardiomyotomy along with Anterior Dor Fundoplication. Of the 16 patients, 6 had undergone Pneumatic Dilation previously.

Results
Of the 16 patients, 14 underwent Laparoscopic Heller’s Cardiomyotomy and 2 had open surgery. There were no intraoperative or postoperative complications. Normal feeds were started after 24 hours and the feeds were well tolerated. All the patients had complete resolution of dysphagia with score reducing from 4 to 0. All of them were discharged within 2–3 days.

Conclusion
Laparoscopic Heller’s Cardiomyotomy is the gold standard treatment for treating Achalasia Cardia. It is a safe, successful and efficient treatment modality for children with Achalasia Cardia due to shorter hospital stay, lower complication rates due to increased level of expertise and immediate and long lasting symptomatic relief.
356 DIVERTICULECTOMY WITH EXTEND MYOTOMY AND ANTERIOR FUNDOPLICATION AS TREATMENT OF INTRATHORACIC ESOPHAGEAL DIVERTICULUM. CASE REPORT AND REVIEW!
Authors: Szachnowicz S , Lopes L , Fernandes F , Edno Tales B , Sallum R , Cecconello I 
Published: September 2020

Abstract

Diverticula of the thoracic esophagus are uncommon disorders and its most appropriate treatment continues unclear. The majority of these diverticula are results of underlying esophageal motility disorders, but some cases are results of periesophageal inflammation. The patients can be asymptomatic, or present dysphagia, regurgitation, aspirated pneumonia, retrosternal pain and weight loss. The barium esophagogram is considered the best study to show and evaluate these cases. Esophageal manometry allow study the esophageal motility abnormality.

Methods
Patients with small and asymptomatic diverticula could not require any treatment. Patients with symptomatic or big diverticula should be submitted a diverticulectomy and often with an esophageal myotomy. However the necessity, the esophageal extension and local of the myotomy are still unclear. We describe a case of a 70 yo woman with a intrathoracic esophageal diverticulum. She presented progressive dysphagia to solids in the last two years, associated to regurgitation, retrosternal pain, nausea and weight loss of 10 kilograms. She has no history of aspirated pneumonia.

Results
The upper GI endoscopy showed the diverticulum in middle esophagus (25 cm from superior dental arch) and the size in barium esophagogram was 6,5 x 4,8 cm. The high resolution esophageal manometry was normal and the patient had no tuberculosis history. She was submitted a thoracoscopic diverticulectomy with extend myotomy (intrathoracic and abdominal) and Dor’s fundoplication. She was able to resume a liquid diet by day 3, after a normal barium esophagogram, and was discharged at the 4 post-operative day. After 9 months the patient remains asymptomatic.

Conclusion
In our experience, the diverticulectomy associated with an extend myotomy bring excellent results at the esophageal function, allowing an adequate emptying of the esophagus, avoiding severe complications as mediastinitis or esophageal leakage even in patients without severe motility disorder.

References
1. Altorki N K, Sunagawa M, Skinner D B. Thoracic esophageal diverticula. Why is operation necessary? J Thorac Cardiovasc Surg 1993 Feb; 105(2): 260–4.
2. Rice T W, Baker M E. Midthoracic esophageal diverticula. Semin Thorac Cardiovasc Surg 1999 Oct; 11(4): 352–7.