bluuebunny/crossref_metadata_2025 huggingface dataset:
94: HEALTH RELATED QUALITY OF LIFE OF PATIENTS WITH ESOPHAGEAL CANCER FOLLOWING ESOPHAGECTOMY TREATED WITH NEOADJUVANT CHEMORADIOTHERAPY OR CHEMOTHERAPY: A EUROPEAN MULTICENTER STUDY
Authors: Schuring N , Markar S , Hagens E , Jezerskyte E , Sprangers M , Johar A , Gisbertz S , Van Berge Henegouwen M
Published: April 2022

Background and aim

Curative treatment for patients with esophageal cancer consists of neoadjuvant treatment followed by an esophagectomy. Different neoadjuvant strategies exist; perioperative chemotherapy (pCT) and neoadjuvant chemoradiotherapy (nCRT). Both strategies improve the 5-year overall survival rate, however, whether differences exist in long-term health related Quality of Life (HR-QoL) has not been studied. The aim of this study is to compare HR-QoL between perioperative chemotherapy and neoadjuvant chemoradiotherapy in esophagectomy for cancer patients.

Methods

Disease-free patients following esophagectomy for cancer in one of the participating LASER study centers between 2010 and 2016, following neoadjuvant treatment with chemoradiotherapy or chemotherapy, were extracted for analysis from the LASER study database. Included patients completed the LASER, EORTC-QLQ-C30 and QLQ-OG25 questionnaires at least one year following surgery. Primary outcome was to assess long-term HR-QoL between patients treated with pCT or nCRT, using univariable and multivariable logistic regression analysis.

Results

Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) patient were perioperatively treated with chemotherapy. The mean age was 63.7 years (± SD 8.6) with a mean time since surgery of 4.3 (± 1.7) years. After multivariable analysis patients treated with pCT reported worse outcomes on the ‘Social Functioning’ domain (∆means 4.56 P-value<0.05) and more symptomatology on the domains ‘Insomnia’ (∆means 5.65 P-value<0.05) and ‘Diarrhea’ (∆means 5.93 P-value<0.05) of the QLQ-C30, and more symptomatology on the domains ‘Reflux’ (∆means 7.40 P-value<0.05), ‘Odynophagia’(∆means 4.66 P-value<0.05) and ‘Pain and discomfort’(∆means 4.34 P-value<0.05) of the QLQ-OG25. No statistically significant differences were observed for the LASER key symptoms. None of the observed differences in mean scores of HR-QoL domains were clinically relevant (∆means≠ ≥ 10 points).

Conclusion

Some differences in favor of nCRT were observed in long-term HR-QoL domains for patients following esophagectomy for cancer. However, none of the observed differences was clinically relevant (∆means≠ ≥ 10 points). HR-QoL is unhelpful when deciding on neoadjuvant strategy.
102: EFFECT OF A MULTIMODAL PREHABILITATION PROGRAM ON POSTOPERATIVE RECOVERY AND MORBIDITY IN PATIENTS UNDERGOING A MINIMALLY INVASIVE ESOPHAGECTOMY
Authors: Janssen H , Fransen L , Heesakkers F , Dolmans-Zwartjes A , Moorthy K , Nieuwenhuijzen G , Luyer M
Published: April 2022

Background and aim

Despite recent advancements in perioperative care, postoperative morbidity following an esophagectomy remains substantial. Studies in other major abdominal surgery, have shown that prehabilitation can improve short-term outcomes. This single-center cohort study investigated the effect of prehabilitation in patients undergoing minimally invasive Ivor-Lewis esophagectomy (MIE-IL).

Methods

Data were collected on consecutive patients receiving a standardized ERAS program that included direct start of oral feeding following MIE-IL (from postoperative day one), between October 2015 and February 2020. The intervention group comprised patients enrolled in the PREPARE prehabilitation program that was implemented in 2018 as the standard care pathway for all patients. The control group comprised a retrospective cohort prior to implementation of PREPARE. Postoperative outcomes included (functional) recovery, length of hospital stay (LOHS), cardiopulmonary complications (CPC) and other predefined outcomes.

Results

The PREPARE group comprised 52 patients and control group 43 patients. Median time to functional recovery was 6 vs. 7 days (P = 0.074) and LOHS 7 vs. 8 days (P = 0.039) in the PREPARE and control group, respectively. Hospital readmission rate was 9.6% vs. 14.3% (P = 0.484). Although thirty-day overall postoperative complication rate did not differ statistically significantly (P = 0.106), a clinically relevant reduction of 17% was observed in PREPARE patients. Similarly, CPC rate was 14% lower in the PREPARE group (P = 0.190). Anastomotic leakage rate was similar (9.6% vs 14.0%; P = 0.511). Despite no difference in severity (Clavien-Dindo) of complications (P = 0.311), ICU readmission rate was lower in PREPARE patients (3.8% vs. 16.3%, P = 0.039). In the PREPARE group wherein maximum oxygen uptake capacity (VO2max) was assessed preoperatively during a Steep Ramp Test, VO2max was lower at baseline in patients diagnosed with postoperative complications (P = 0.011). There were no data on VO2max in the control group.

Conclusion

Prehabilitating patients prior to a MIE-IL led to a shorter LOHS and reduced ICU readmission rate. Additionally, a clinically relevant improvement in (functional) recovery and reduction in postoperative morbidity was observed in patients that were prehabilitated.
103: EARLY OUTCOMES OF ROBOTIC GASTRECTOMY COMPARED WITH OPEN GASTRECTOMY FOR GASTRIC CANCER WITH DESCRIPTION OF THE ROBOTIC TECHNIQUE
Authors: Jung M K , Biasco B , Chevallay M , Wassmer C H , Toso C , Mönig S P
Published: April 2022

Background and aim

Minimally invasive gastrectomy for gastric cancer shows slower adoption in Western countries, probably due to more advanced stages and a more frequently proximal localization, which requires a total gastrectomy. We aimed to assess the perioperative outcomes in early and locoregional advanced gastric cancer.

Methods

We retrospectively reviewed a prospectively collected database. A total of 51 patients who underwent oncologic total gastrectomy or subtotal gastrectomy by robotic or open approach of stage pT1-T4a, pN0–3 were identified from June 2016 until June 2020. Nine patients were operated on robotically, and 42 patients by laparotomy.

Results

The age of the patients in the robotic group was comparable to that of the open group (64.7 ± 9.2 versus 62.8 ± 12.9, P = 0.685). Endoscopic tumor size was smaller in the robotic group (24.3 ± 10.4 mm versus 43.1 ± 27.0 mm, P = 0.081). Blood loss was significantly smaller with the robotic approach (185 ± 180 mL versus 425 ± 257 mL, P = 0.038). Pathologic tumor stage included stages pT1–pT4b in the open group, while stages pT1–pT3 were operated by robotic approach. Fewer tumors were localized in the upper body in the robotic group (0, 0%) than in the open group (12, 28.6%). The length of the proximal margin was comparable in the two groups (104.29 ± 50.29 versus 86.88 ± 64.66, P = 0.516). The mean number of retrieved lymph nodes was comparable in the robotic group and the open group (42.89 ± 12.119 versus 43.22 ± 20.271, P = 0.963). The mean number of metastatic nodes was significantly lower in the robotic group (0.33 ± 0.707 versus 7.02 ± 14.313, P = 0.171). Diffuse-type cancers were significantly more frequent in the robotic group (3 (33.3%) versus 3 (8.6%), P = 0.040). Significantly fewer high-grade complications (Clavien>3a) appeared in the robotic group (0 (0%) versus 2 (4.8%), P = 0.019). Length of hospital stay was comparable in the two groups.

Conclusion

The gold standard of oncologic gastrectomy is still the open approach. The minimally invasive approach must show comparable pathohistological results in regards to lymph node harvest and proximal tumor margins to be accepted in future European guidelines.
106: DOUBLE TRACT RECONSTRUCTION VS POSTERIOR ESOPHAGO-GASTROSTOMY WITH PARTIAL NEO-FUNDOPLICATION AFTER PROXIMAL GASTRECTOMY IN ADVANCED GASTRIC CANCER
Authors: Sedlak K , Rawicz-Pruszynski K , Geca K , Mlak R , Polskowski W
Published: April 2022

Background and aim

There is an upward shift in the incidence and localization of gastric cancer (GC). Proximal gastrectomy (PG) has been advocated as an alternative operation for the upper third GC that may be performed as a function-preserving procedure with various new reconstruction techniques. Uneventful postoperative course is currently measured using well-defined textbook outcome (TO), which represents a composite of surgical quality metrics. The aim of this report was to compare the TO of the two reconstruction methods following PG: double tract reconstruction (DTR) and posterior esophago-gastrostomy with partial neo-fundoplication (EGF).

Methods

TO was defined as (1) radical resection according to the surgeons’ assessment at the end of the operation, (2) no intraoperative complications, (3) negative resection margins, (4) harvest of min. 15 lymph nodes (5) no severe postoperative complications, (6) no re-interventions, (7) no readmission to intensive care unit, (8) no prolonged hospital stay, (9) no hospital readmission and (10) no postoperative mortality. Some 44 patients were eligible for analysis.

Results

The DTR and EGF were performed in 21 and 23 patients, respectively. Detailed results of TO in DTR and EGF are shown in Table 1. Patients reconstructed with DTR had a nearly six-fold increased chance of achieving the TO compared to patients with EGF (OR = 5.80; P = 0.0090). Comparison of both reconstruction methods demonstrated no statistically significant differences in terms of postoperative complications and CCI score, and overall survival.

Conclusion

TO is more likely to be achieved in DTR than in EGF. Randomized controlled trials are warranted to indicate the preferred reconstruction technique after PG.
109: THE IGREENGO STUDY. CLINICAL ROLE OF INDOCYANINE GREEN IMAGING FLUORESCENCE IN SURGICAL TREATMENT OF ADVANCED GASTRIC CANCER. STUDY PROTOCOL
Authors: Lombardi P M , Mazzola M , Nicastro V , De Martini P , Gualtierotti M , Ferrari G C
Published: April 2022

Background and aim

Near infra-red/indocyanine green imaging fluorescence (NIR/ICG) technology is showing promising results in several fields of surgical oncology. However, the clinical value of NIR/ICG technology in the surgical treatment of advanced gastric cancer (AGC) is not clearly established. Indeed, although lymphadenectomy is one of the main steps in curative-intent surgery for gastric cancer and lymph node status is the most important prognostic factor for survival, several questions have risen in literature on considering the overall number of harvested lymph nodes as the best indicator of the NIR/ICG technology clinical value. At present, no data exist regarding the ability of NIR/ICG technology to modify the surgical conduct at the moment of lymphadenectomy.

Methods

This is the ‘iGreenGO’ (indocyanine Green Gastric Observation) study protocol: an international, prospective, multicentre study. Study population will be a cohort of Western patients undergoing preoperative upper gastrointestinal endoscopy with submucosal peritumoral ICG injection followed by curative-intent minimally invasive gastrectomy with D2 lymphadenectomy for locally AGC. High-volume western academic and non-academic hospitals will be allowed to participate in the study. The primary endpoint will be the ‘change of the surgical conduct’ (CSC) at the moment of intraoperative NIR/ICG technology activation after completing a D2 lymphadenectomy ‘with the naked eye’. Key secondary endpoints will be the identification of preoperative clinical variables potentially associated with CSC, the number of additional LNs retrieved and pTNM stage migration using NIR/ICG technology, abdominal fluorescence location according to patient’s and tumor’s characteristics.

Results

The sample size was calculated by considering the estimated incidence of intraoperative change of the surgical conduct when using NIR/ICG technology. Data from the literature indirectly suggest an approximate rate of such event around 17%. A sample size of 350 patients will be necessary to obtain a measurement with an estimated precision of 4% with a confidence level of 1-alfa = 95%.

Conclusion

The iGreenGO study will be the first western study to investigate the intraoperative clinical role of NIR/ICG technology in surgical treatment of AGC in a large cohort of Western patients. Results from the present study can further clarify the role of the NIR/ICG technology in helping the surgeon during lymphadenectomy for AGC.
113: THE PARA-OESOPHAGEAL HERNIA SYMPTOM TOOL (POST): A MODIFIED DELPHI CONSENSUS STUDY
Authors: Puri A , Patel N , Sounderajah V , Ferri L , Griffiths E , Low D , Maynard N , Mueller C , Pera M , Van Berge Henegouwen M , Zaninotto G , Hanna G , Markar S
Published: April 2022

Background and aim

Patients with a para-oesophageal hernia (POH) report a range of symptoms and quality of life (QOL) issues. Clinicians often utilise existing health-related quality of life tools to identify patients eligible for surgical management and to evaluate the benefit of surgical intervention. However, the most commonly used tools for this purpose are not disease specific. Therefore, crucial POH-specific symptoms which impact QOL may not be captured. To address this, a modified Delphi consensus study was undertaken to establish a HRQOL instrument specific to POH.

Methods

A two-round modified Delphi consensus study was conducted with a group of international experts. Participants were identified through their authorship in landmark POH studies and the professional networks of the study investigators. Before the Delphi process, a scoping survey was undertaken to generate a list of candidate items. Participants were asked to rate the items’ importance in assessing patients with POH using a 5-point Likert scale. The a priori threshold for inclusion was 80% for scores of 4 or 5. If consensus was not achieved, the item was carried through to the next round.

Results

The candidate list of items consisted of 64 symptoms, refined to 20 for inclusion within the first modified Delphi round. Four symptoms; ‘difficulty getting solid foods down’, ‘chest pain after meals’, ‘difficulty getting liquids down’ and ‘shortness of breath only after meals’, reached consensus threshold of 80% in the first round and additionally, ‘early feeling of fullness after eating’, reached consensus in the second. A total of 26 participants took part in the first and 24 in the second round. These five symptoms form the initial version of the Para-Oesophageal Hernia Symptom Tool (POST).

Conclusion

POST is the first tool that aims to capture POH-specific symptoms that impact HRQOL. Prior to clinical use, this tool will be presented in international patient workshops to assess its construct validity. Thereafter, we aim to assess the content validity of the tool through a longitudinal study in a cohort of patients with undergoing POH repair. This tool aims to serve as a decision-support tool for clinicians when evaluating the risk–benefit of surgical intervention in this cohort of patients.
123: SEVERE LYMPHOPENIA ACQUIRED DURING CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER: INCIDENCE AND EXTERNAL VALIDATION OF A PREDICTION MODEL
Authors: Kroese T , Jairan J , Ruurda J , Lin S , Mohan R , Mook S , Haitjema S , Hoefer I , Haj Mohammad N , Van Hillegersberg R , Van Rossum P
Published: April 2022

Background and aim

The incidence of grade 4 lymphopenia in patients treated with chemoradiotherapy (CRT) according to Chemoradiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) regimen is unclear. The primary aim was to determine the incidence of grade 4 lymphopenia during CROSS for esophageal cancer. Secondary aims were to externally validate a prediction model for grade 4 lymphopenia and compare overall survival between patients with and without grade 4 lymphopenia.

Methods

Patients who underwent CRT for esophageal cancer between 2014 and 2019 were eligible for inclusion. Patients with a planned radiation dose of 41.4 Gy (CROSS) or 50.4 Gy (‘extended-CROSS’) and concurrent carboplatin and paclitaxel were included. The primary outcome was the incidence of grade 4 lymphopenia during CRT defined according to Common Terminology Criteria for Adverse Events version 5.0 (i.e. lymphocyte count nadir <0.2 μL). The secondary outcome measures were the prediction model’s external performance (i.e. discrimination and calibration). Overall survival for patients with versus without grade 4 lymphopenia was compared using Kaplan–Meier analysis.

Results

A total of 219 patients were included of whom 176 patients (80%) underwent CROSS and 43 patients (20%) extended-CROSS. The incidence of grade 4 lymphopenia was 11% in CROSS and 33% in extended-CROSS (P < 0.001). External discrimination yielded a c-statistic of 0.80 (95% confidence interval: 0.70–0.89). External calibration of the model was poor in CROSS but fair in extended-CROSS. Adjusted calibration using intercept correction (adjusted for the lower a-priori risk for grade 4 lymphopenia in CROSS) showed fair agreement between the observed and predicted risk for grade 4 lymphopenia. Median overall survival in patients with versus without grade 4 lymphopenia was 12.7 versus 42.5 months (P = 0.045).

Conclusion

The incidence of grade 4 lymphopenia is significantly higher in esophageal cancer patients receiving extended-CROSS compared to those receiving CROSS. The prediction model demonstrated good external performance in the setting of the CROSS-regimen and could be used to identify patients at high-risk for grade 4 lymphopenia who might be eligible for lymphopenia–mitigating strategies.
147: MAJOR PATHOLOGIC RESPONSE IN ESOPHAGEAL ADENOCARCINOMA: IS THE TIME RIPE FOR A NEW PARADIGM IN DEFINING RESPONSE TO TREATMENTS?
Authors: Scarton A , Capovilla G , Pierobon E S , Moletta L , Zanchettin G , Salvador R , Costantini M , Merigliano S , Grimminger P , Valmasoni M
Published: April 2022

Background and aim

Adenocarcinoma of the esophagus is still burdened by low 5-year survival. A complete pathologic response after neoadjuvant treatment is associated with improved long-term survival, however this result is rarely achieved.

The aim of this study was to evaluate the impact of tumor regression grade (TRG), according to Mandard, on long-term survival. The primary endpoint was to determine whether the survival benefit associated with a complete tumor regression could be achieved also with a subtotal tumor response (TRG2). Secondly, we analyzed how TRG predicts survival in chemotherapy (CT) or chemoradiotherapy (CRT) treated patients and the relationship with nodal status (ypN).

Methods

We evaluated all consecutive patients who underwent esophagectomy for cancer at Padova University Hospital and Mainz University Hospital. Inclusion criteria were histologically confirmed ADK involving the thoracic esophagus or Siewert I and II cancers, treated by neoadjuvant CT or CRT and surgery. Patients with Siewert III or cervical cancer and those who underwent upfront surgery were excluded from the study. Kaplan-Maier analysis was used to estimate overall survival (OS) according to the TRG and ypN.

Results

Overall, 270 patients were recruited in the study period. The median OS was 50 months (range 1–134). TRG 1 and 2 were associated with improved survival (P < 0.0001), this finding was further confirmed in the CRT patients’ subgroup (P < 0.0001) (Figure). Survival curves for TRG 1 and TRG 2 patients were similar, both among ypN0 (P = 0.0185) and ypN+ patients (P = 0.013). In the CT group these findings were confirmed in the whole subgroup (P = 0.0001) and ypN+ (P = 0.007) but not in patients without lymph node involvement (P = 0.58).

Conclusion

Tumor regression after neoadjuvant treatment is significantly associated with long term survival irrespective of the nodal status. In the overall study population and among CRT treated patients, the long-term survival was comparable between TRG 1 and TRG 2 patients. This finding allowed us to support the criterion of a Major Pathologic Response, which includes both TRG 1 and 2 ypN0 patients, potentially creating a homogeneous and larger subgroup of subjects to be evaluated in future clinical trials and studies.
149: CONVERSION DURING MINIMALLY INVASIVE ESOPHAGECTOMY DOES NOT AFFECT ONCOLOGICAL AND SURGICAL OUTCOMES
Authors: Froiio C , Capovilla G , Tagkalos E , Berlth F , Hadzijusufovic E , Uzun E , Mann C , Lang H , Grimminger P P
Published: April 2022

Background and aim

We evaluated causes and implications of conversion during minimally invasive (MI) esophagectomy and the feasibility of MI surgery in patients with ‘risk indications’ that would potentially prompt the referral to open surgery.

Methods

We analyzed 371 patients treated with esophagectomy for cancer, between January 2016 and April 2021. We identified three groups: (I) non-MI surgery group including patients with planned open/hybrid esophagectomy (n = 26); (II) the MI surgery group including patients with totally MI procedures, both thoracoscopic/laparoscopic and robotic esophagectomy (n = 335); (III) the MI converted group with patients who had unplanned conversion (n = 10). Pre- and postoperative data were compared. ‘Risk indications’ motivating open/hybrid surgery were evaluated to define two subgroups of high- and low-risk patients treated with MI surgery, and to compare the surgical outcomes between these 2 groups.

Results

Overall, 345 patients were approached via MI surgery: 335 had completed MI esophagectomy (RAMIE = 63.28%; MIE = 36.72%). The conversion-rate was 2.9% (n = 10): 6.1% in MIE, 0.9% in RAMIE (P = 0.008). Postoperative leakage was higher in converted patients compared to the non-MI and the totally MI groups (P < 0.001). Surgical radicality, readmission rate and mortality were comparable. Patients with and without ‘risk indication’ for open surgery showed a similar conversion rate and post-operative outcomes following MI esophagectomy.

Conclusion

Conversion does not significantly affect the oncological outcomes and short-term mortality after MI esophagectomy. A MI approach could be safely offered also to patients with ‘risk indications’ that would potentially lead the choice of an open surgery.
155: ENDOSCOPICALLY DERIVED OESOPHAGEAL ADENOCARCINOMA ORGANOIDS TO ASSESS POTENTIAL RESPONSE TO NEO-ADJUVANT THERAPY AND VIROTHERAPY
Authors: Rayner C , Wooldridge T , Bagwan I , Preston S , Pandha H , Annels N , Abbassi-Ghadi N
Published: April 2022

Background and aim

Organoids are 3D models that retain the architecture and function of the organ from which they are derived. Culture of oesophageal adenocarcinoma organoids from individual’s standard endoscopic biopsies to assess response to therapy could dramatically alter the neo-adjuvant treatment paradigm, giving clarity over who will benefit from preoperative therapy, including novel treatment methodologies. Immune checkpoint blockade (ICB) has been shown to be effective in oesophageal adenocarcinoma. Combining Oncolytic Virotherapy with ICB could enhance the action of ICB alone, through selective infection of tumour cells accompanied by immunogenic cell death, with release of neo-tumour antigens and alteration of the tumour microenvironment.

Methods

This study uses organoids derived from endoscopic biopsies to assess the viability of an oncolytic herpes simplex virus in the treatment of oesophageal adenocarcinoma. Samples were taken at routine staging endoscopy using standard biopsy forceps. Tissue specimens were dissociated using the Miltenyi tumour dissociation kit before being suspended in Matrigel in Oesophageal adenocarcinoma conditioned media. Media was changed every 48 hours with domes being split every 7–10 days. After >6 passages organoids were incubated with an oncolytic herpes simplex virus lacking ICP 34.5 and 47. Growth was monitored, and green fluorescence protein expression measured using the Incucyte SX5 Live Cell Analysis system.

Results

Organoids were successfully established and cultured beyond 6 passages for patients with oesophageal adenocarcinoma. Organoids incubated with an oncolytic herpes simplex virus demonstrated significantly reduced growth compared to untreated organoids with increased expression of green fluorescence protein indicating viral infection.

Conclusion

We have demonstrated a successful methodology to culture Oesophageal adenocarcinoma organoids from endoscopic biopsies. Further work to determine their responses to standard chemotherapy used in the perioperative phase will help to assess their potential for providing bespoke therapy in the future. Oncolytic herpes simplex virus is able to infect and cause lysis of OAC organoids supporting its potential use in driving an increased inflammatory tumour microenvironment which could be combined with immune checkpoint blockade to induce durable responses for patients.
156: PHYSIOTHERAPY REGIMENS IN ESOPHAGECTOMY AND GASTRECTOMY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tukanova K , Chidambaram S , Guidozzi N , Hanna G , Mcgregor A , Markar S
Published: April 2022

Background and aim

Esophageal and gastric cancer surgery are associated with considerable morbidity, specifically postoperative pulmonary complications (PPC), potentially accentuated by underlying challenges with malnutrition and cachexia affecting respiratory muscle mass. Physiotherapy regimens aim to increase the respiratory muscle strength and may prevent postoperative morbidity. This review and meta-analysis is to assess the impact of physiotherapy regimens following esophagectomy or gastrectomy.

Methods

An electronic literature search was performed in MEDLINE, EMBASE, CENTRAL, CINAHL and Pedro databases, to identify articles evaluating the effect of physiotherapy interventions following esophagectomy or gastrectomy. A meta-analysis was performed to assess the impact of prehabilitation and peri- or postoperative rehabilitation on the functional capacity, incidence of PPC and postoperative morbidity, in-hospital mortality rate, the Length of Hospital Stay (LOS) and the Health-Related Quality of Life (HRQoL).

Results

Seven RCTs and 7 cohort studies assessing prehabilitation totalling 960 patients, and 5 RCTs and 5 cohort studies assessing peri- or postoperative physiotherapy with 703 total patients, were included. Prehabilitation resulted in a lower incidence of postoperative pneumonia and morbidity (Clavien-Dindo score > II). No significant difference was observed in functional exercise capacity, and in-hospital mortality following prehabilitation. Meanwhile, peri- or postoperative rehabilitation resulted in a lower incidence of pneumonia, a shorter LOS and better HRQoL scores for dyspnea and physical functioning, while no differences were found for the QoL summary score, global health status, fatigue and pain scores.

Conclusion

Our meta-analysis shows that implementation of an exercise intervention may be beneficial in both the preoperative and peri- or postoperative period. Further investigation is needed to understand the mechanism through which exercise interventions improve clinical outcomes and which subgroup of patients will gain the most benefit.
159: DEFINITIVE CHEMORADIOTHERAPY VERSUS NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY RADICAL SURGERY FOR LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kamarajah S K , Evans R , Gossage J , Griffiths E , Pucher P
Published: April 2022

Background and aim

Debate exists surrounding definitive chemoradiotherapy (dCRT) over neoadjuvant chemoradiotherapy and surgery (nCRS) as a primary treatment for esophageal squamous cell carcinoma (ESCC) owing to the heterogeneity in the quality of current evidence. This study aimed to compare long-term survival of dCRT with nCRT for ESCC from high-quality studies.

Methods

This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus and Cochrane CENTRAL databases up to 23rd July 2021. Primary outcome was overall survival (OS) and secondary outcomes were disease-free survival (DFS) and recurrence rates. A meta-analysis was conducted using random-effects modelling to determine pooled adjusted multivariable hazard ratios (HRs).

Results

This review included ten high-quality studies including 14,092 patients, of which 30% received nCRT. Three studies were randomized controlled trials (RCT), six studies were single-center. dCRT and nCRT regimens were reported in six studies and surgical quality control were reported in two studies. Outcomes for OS and DFS were reported in eight and three studies, respectively. nCRT had significantly longer OS (HR: 0.68, CI95%: 0.54–0.87, P < 0.001) and DFS (HR: 0.50, CI95%: 0.36–0.70, P < 0.001) than dCRT.

Conclusion

nCRS followed by planned esophagectomy appears to remain the optimum curative treatment regime in patients with loco-regional ESCC. Thus, surgery remains an integral component of the management of patients with ESCC. As adjuvant and immunotherapy treatment regimens develop, ongoing prospective assessment of the role of radiotherapy in combination with modern treatment modalities should be studied.
187: EFFECT OF PERI-OPERATIVE CHEMOTHERAPY REGIMEN ON SURVIVAL IN THE TREATMENT OF LOCALLY ADVANCED GASTRO-OESOPHAGEAL ADENOCARCINOMA—FLOT VS ‘MAGIC’
Authors: Moore J , Kumar S , Patel P , Santaollala A , Kapiris M , Van Hemelrijk M , Maisey N , Lagergren J , Gossage J , Kelly M , Baker C , Allum W , Cunningham D , Davies A
Published: April 2022

Background and aim

Peri-operative chemotherapy has been shown to improve survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two commonly used regimens are epirubicin, cisplatin plus capecitabine or fluorouracil (MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). The primary aim of this study was to evaluate the effect of chemotherapy regimen (FLOT vs MAGIC) on survival. We also aimed to assess pathological response, surgical complications, chemotherapy associated adverse events and chemotherapy completion rates.

Methods

Cohort study including 946 patients treated with peri-operative FLOT or MAGIC chemotherapy who underwent oesophagectomy or gastrectomy for oesophageal or gastric adenocarcinoma between 2002–2021 at St Thomas’ Hospital, London, UK or The Royal Marsden Hospital, London, UK. Survival analysis was performed using Kaplan–Meier and Cox regression.

Results

Patients treated with MAGIC had worse overall and disease-free survival compared with FLOT on multivariable analysis (overall survival HR 1.353 95% CI 1.039–1.763, disease-free survival HR 1.335 95% CI 1.025–1.739). Stratified analysis by tumour location revealed similar results for both oesophageal and gastric tumours. Patients treated with FLOT were more likely to have a favourable pathological response (Mandard 1–2) (11.1% MAGIC vs 21.8% FLOT, P < 0.001). Patients treated with FLOT were less likely to have a positive resection margin (19.1% FLOT vs 32.2% MAGIC, P < 0.001). Surgical complications, chemotherapy associated adverse events and chemotherapy completion rates were comparable between groups.

Conclusion

Patients with oesophageal and gastric adenocarcinoma treated with peri-operative FLOT had improved survival compared with those treated with peri-operative MAGIC. Surgical complications, chemotherapy associated adverse events and chemotherapy completion rates were comparable between groups.

Table

https://secure.sem-2000.it/semUpload/OLC/file/9203828791100911681076702/94509_Table.jpg.
196: SARCOPENIA AND PATIENT’S BODY COMPOSITION: NEW MORPHOMETRIC TOOLS TO PREDICT CLINICAL OUTCOME AFTER IVOR-LEWIS ESOPHAGECTOMY
Authors: Battaglia S , Cossu A , Palumbo D , De Pascale S , Gualtierotti M , Vecchiato M , Parise P , Puccetti F , Barbieri L , Elmore U , De Cobelli F , Fumagalli Romario U , Ferrari G , Petri R , Rosati R
Published: April 2022

Background and aim

Anastomotic leakage represents one of the most dreadful complications following esophagectomy. Although preoperative body composition has been identified as an independent predictor of prognosis for esophageal cancer patients after esophagectomy, its actual contribution to subsequent anastomotic leakage development is still unclear. The aim of the study was to further explore such a relationship.

Methods

We conducted a multicenter retrospective study from a prospectively acquired database on consecutive patients who underwent Ivor Lewis esophagectomy in four italian high volume centers from May 2014. All patients who were evaluated with at least one preoperative CT scan were enrolled. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA) and subcutaneous fat area (SFA) were determined based on two consecutive axial CT images extending upwards from the level of the third lumbar vertebra; sarcopenia was defined using predetermined sex specific values: 52.4 cm2/m2 for men, 38.5 cm2/m2 for women. Perioperative variables (ASA, neoadjuvant treatment, tumour site, anastomosis type were systematically collected.

Results

237 patients were enrolled. Preoperative BMI: 25.16 kg/m2; 23.6% of patients suffered from anastomotic leakage. According to CT morphometric assessment, 64.1% were classified as sarcopenic; these patients were more vulnerable in terms of postoperative death (within 90 days, P = 0.028). The mean VFA/TAMA and VFA/SFA ratios were 2.93 ± 1.87 and 0.93 ± 0.59, respectively. Both these ratios demonstrated a linear correlation with the Clavien Dindo classification of postoperative complications (R = 0.311 and 0.239, respectively); specifically, patients with anastomotic leakage had significantly higher VFA/TAMA (3.56 ± 1.86 vs. 2.75 ± 1.83, P = 0.006) and VFA/SFA (1.18 ± 0.68 vs. 0.87 ± 0.54, P = 0.003) ratios. In patients suffering from anastomotic leakage, the highest VFA/TAMA ratio values were found in those experiencing type III (P = 0.044). No significant correlation was found between preoperative BMI and subsequent anastomotic leakage development (P = 0.154).

Conclusion

Analytical morphometric assessment represents a useful non invasive tool for preoperative risk stratification. The concurrent association of sarcopenia and visceral obesity seems to be the best predictor of anastomotic leakage, far better than simple BMI evaluation, and potentially modifiable if targeted with prehabilitation programs.
209: ROLE OF ADJUVANT CHEMOTHERAPY IN LOW BURDEN (YPT0-T1N0) GASTRIC ADENOCARCINOMA AFTER NEOADJUVANT CHEMOTHERAPY
Authors: Voron T , Lambert C , Piessen GError! Bookmark not defined , Bonnet S , Gualtierotti M , Guiramand J , Souadka A , Pezet D , Gronnier C
Published: April 2022

Background and aim

Since 2006, perioperative chemotherapy(periCT) has become an established treatment for patients with resectable gastric adenocarcinoma in Europe after the demonstration of a survival benefit in two randomized clinical trials. However, only half of patients included in the periCT arm started adjuvant chemotherapy(adjCT), suggesting a preponderant effect of neoadjuvant chemotherapy(neoCT) on the survival benefit observed. The aim of this study was to assess the benefit of adjCT on disease-free survival in patients with low tumor burden(LTB) (ypT0N0 or ypT1N0) after neoCT.

Methods

Data were collected from 30 European centres from 2007 to 2017. Among 2131 included patients, 762 patients received neoCT and 135 had LTB (17.7%), including 40 patients (5.3%) with complete pathological response. Among patients with LTB, 85 (63%) received adjCT(adjCT+) and 50 patients (37%) did not (adjCT-). Propensity score matching analyses were used to compensate for differences in baseline characteristics between ajdCT+ and adjCT- patients.

Results

NeoCT regimen was mainly based on platinum-fluoropyrimidine doublet or triplet regimen(88.1%). In univariate analysis, predictive factors for LTB after neoCT were antro-pyloric location, pretherapeutic stage≤cT2, well-differentiated tumor, ≥2 cycles of preoperative chemotherapy, intestinal or mixt-type according to Lauren’s classification and non poorly-cohesive cells tumor. Patients in adjCT- group were older and had more frequently severe postoperative complications (≥ grade 3a according to Dindo-Clavien’s classification) than patients in adjCT+ group. Despite this, 5-years overall(OS) and disease-free survival(DFS) rates were comparable between adjCT+ and adjcCT- groups, respectively 92% vs. 82% and 89% vs.83%. After propensity score analysis, OS and DFS remain comparable between adjCT+ and adjCT- groups. In adjCT+ group, patients received mostly the same chemotherapy as that received preoperatively (82%). However, severe toxicity was described in 11 patients (13%). Among patients with ypT0N0 response with a follow-up longer than 3 months, 4 patients experienced tumor recurrence or death (11.4%). All of these patients had received adjuvant chemotherapy.

Conclusion

Performing adjCT in patients with LTB after neoCT does not seem to provide any benefit on OS or DFS, with non-negligible toxicity rates in counterpart.
210: SHORT-TERM RESULTS AFTER ROBOTIC SURGERY FOR GASTRIC CANCER: A SINGLE-CENTER, PROSPECTIVE STUDY
Authors: Barbato G , Staderini F , Coratti F , Bottari A , Badii B , Indennitate G , Pasqualini E , Cianchi F
Published: April 2022

Background and aim

Gastric cancer is the fifth most frequent cancer globally. The mainstay of curative treatment is surgical resection with or without (neo)adjuvant therapy. Minimally invasive surgery for gastric cancer was introduced as to reduce post-operative morbidity and hospital length of stay. While the role of laparoscopic gastrectomy has been definitively established, only recently robotic gastric surgery has been gaining increasing application. This is mainly due to the assumption that robotic technology can overcome some of the technical limitations of conventional laparoscopic. The purpose of this study was to assess the feasibility and safety of robotic gastrectomy for gastric cancer and report the short-term results of a single-center prospective study.

Methods

From April 2017 to June 2020, 103 consecutive patients underwent robotic gastrectomy by a single surgeon at the Digestive Surgery Unit, Careggi University Hospital. There were 57 males and 46 females. The median age was 72 years (range 44–90). Seventy nine distal and 24 total gastrectomies were performed. A D2 lymphadenectomy was performed in all the patients. Tumors were staged as follows: 32 (31.0%) were stage I, 18 (17.5%) stage II and 53 (51.5%) stage III.

Results

The mean operative time was 323 (range: 250–525) and 445 (range:155–555) minutes for distal and total gastrectomy, respectively. There were no intraoperative complications and no conversions to laparoscopic or open surgery occurred. The rate of postoperative morbidity was 14.1% while no postoperative 30-day mortality was registered. Overall, 5 patients required reintervention. All patients received R0 resection. The mean total number of harvested lymph nodes was 45.6 (range: 18–112). A significant increase in the number of examined lymph nodes was observed during the learning curve (Figure 1). In particular, the mean values were 34.7 during the initial learning phase (case 1–25), 48.7 during the proficiency phase (case 26–88) and 50.4 during the mastery phase (case 89–103).

Conclusion

Our findings demonstrate the safety and the oncological adequacy of the robotic approach in the treatment of gastric cancer. However, further randomized clinical trials are required to confirm our results.
With a Little Help from My Peer Clique: Mitigating the Intergenerational Transmission of Poverty
Authors: Fischer-Neumann Marion , Böhnke Petra
Published: April 2022

Driven by two theoretical models of the resiliency framework, this paper examines the compensatory and protective role of interacting with peers in late adolescence in inhibiting the intergenerational transmission of poverty into young adulthood. We suggest different compensatory and protective effects of three peer contexts, referring to specific advantages of group-based friendship networks (i.e. cliques) in comparison with dyadic best friendships and romantic relationships. Further, we assume heterogeneity in the peer resilience mechanisms by age, migration background, and gender. Using longitudinal data from the German Socio-Economic Panel and random-effects linear probability models, we indeed find conditional compensatory influences as well as an unconditional protective effect of clique interaction in late adolescence for the intergenerational transmission of poverty. Hence, frequent interaction within friendship cliques compensates the deleterious effect of long-term poverty in adolescence on the risk of poverty in young adulthood with increasing age as well as particularly for first-generation immigrants. Further, the engagement with peer cliques in late adolescence attenuates the association between long-term youth poverty and adulthood poverty and thus helps to protect against the intergenerational transmission of poverty.
Temporary Employment, Employee Representation, and Employer-Paid Training: A Comparative Analysis
Authors: Adolfsson Maja , Baranowska-Rataj Anna , Lundmark Anneli
Published: April 2022

This article examines the moderating role of employee representation on the chances of receiving employer-paid training among temporary and permanent workers from a cross-country, comparative perspective. The impact of employee representation is considered at the individual level and at the country level. The statistical analyses are performed using data from the 2015 European Working Conditions Survey and multilevel modelling. Our results suggest that temporary workers receive less employer-paid training than permanent workers. Access to employee representation increases workers’ access to employer-paid training, regardless of contract type. At the country level, we found that the training-related benefits from union coverage are larger for permanent than for temporary workers. Our findings suggest that employee representation in the workplace could operate as an equalizer between temporary and permanent workers; while at the country level, the lobbying effect of union coverage is more beneficial for permanent workers.
Down-regulation of ABCB1 by collateral sensitivity drugs reverses multidrug resistance and up-regulates enolase I
Authors: Limniatis Georgia , Georges Elias
Published: April 2022

The emergence of drug resistance remains an obstacle in the clinical treatment of cancer. Recent developments in the studies of drug resistance have identified compounds such as verapamil and tamoxifen that specifically target ABCB1-expressing multidrug-resistant (MDR) cells, through an ATP-dependent ROS-generating mechanism. In this report, we demonstrate that treatment of ABCB1-expressing MDR cells (CHORC5 or MDA-Doxo400) or individual clones of the latter with sub-lethal concentrations of tamoxifen or verapamil down-regulates ABCB1 protein and mRNA expression in surviving clones. Consequently, tamoxifen- and verapamil-treated cells show increased sensitivity to chemotherapeutic drugs (e.g., colchicine and doxorubicin) and decreased sensitivity to collateral sensitivity drugs (e.g., verapamil and tamoxifen). Importantly, we show for the first time that down-regulation of ABCB1 expression resulting from tamoxifen treatment and CRISPR-knockout of ABCB1 expression up-regulate α-enolase (enolase I) protein levels and activity. These findings demonstrate a possible effect of ABCB1 expression on the metabolic homeostasis of MDR cells. Moreover, given the use of tamoxifen to prevent the recurrence of oestrogen receptor-positive breast cancer, the findings of this study may be clinically important in modulating activity of other drugs.
Products in Disguise: Communicating Product Benefits with Surface Mimicry
Authors: Van Kerckhove Anneleen , De Bondt Caroline , Geuens Maggie
Published: April 2022

In an effort to find a novel way to enhance the attractiveness of healthy food, this article proposes surface mimicry—that is, designing a product to visually resemble another product—as an effective intervention to communicate property information to consumers. Specifically, it advances the notion that exposure to surface mimicry primes property mapping, a thinking style that leads consumers to transfer property information from one product onto another. To this end, three studies show that exposure to a target food product (e.g., kiwifruit) mimicking visual characteristics of another, modifier food product (e.g., popsicle) induces a transfer of attribute values of the modifier onto the target product for salient, alignable attributes on which the products differ (e.g., tastiness). A fourth study points to the activation of a property-mapping mindset as the underlying process. Finally, the effect is shown to persist, but it attenuates when the difference in belief(s) about the target and mimicked product is substantial (e.g., the taste expectations for Brussels sprouts and popsicles).
Influence by Intimidation: Business Lobbying in the Regulatory Process
Authors: Acs Alex , Coglianese Cary
Published: April 2022

Interest group influence in the policy process is often theorized to occur through a mechanism of exchange, persuasion, or subsidy. Here, we explore how business groups may also exert influence by intimidating policymakers—a form of persuasion, but one based on the provision not of policy information but of political information. We develop a theory in which a business firm lobbies a regulator to communicate political information about its capacity to commit to future influence-seeking activities that would sanction the regulator. The regulator assesses the credibility of this message by evaluating the firm’s commitment to lobbying. Guided by our theory, we present empirical evidence consistent with expectations that intimidation can shape regulatory outcomes to the advantage of certain firms, both through a chilling effect, by which lobbying derails nascent regulatory plans, as well as a retreating effect, by which opposition to published proposals leads to their withdrawal.
Preface to JSSAM Privacy, Confidentiality, and Disclosure Protection Special Issue
Authors: Shlomo Natalie , Charest Anne-Sophie
Published: April 2022

This article is an introduction to the 13 articles in the JSSAM special issue on Privacy, Confidentiality, and Disclosure Protection. We also provide background information to place the articles into context.
Missplicing suppressor alleles of Arabidopsis PRE-MRNA PROCESSING FACTOR 8 increase splicing fidelity by reducing the use of novel splice sites
Authors: Cabezas-Fuster Adrián , Micol-Ponce Rosa , Fontcuberta-Cervera Sara , Ponce María Rosa
Published: April 2022

Efficient splicing requires a balance between high-fidelity splice-site (SS) selection and speed. In Saccharomyces cerevisiae, Pre-mRNA processing factor 8 (Prp8) helps to balance precise SS selection and rapid, efficient intron excision and exon joining. argonaute1-52 (ago1-52) and incurvata13 (icu13) are hypomorphic alleles of the Arabidopsis thaliana genes ARGONAUTE1 (AGO1) and AUXIN RESISTANT6 (AXR6) that harbor point mutations creating a novel 3′SS and 5′SS, respectively. The spliceosome recognizes these novel SSs, as well as the intact genuine SSs, producing a mixture of wild-type and aberrant mature mRNAs. Here, we characterized five novel mutant alleles of PRP8 (one of the two Arabidopsis co-orthologs of yeast Prp8), naming these alleles morphology of ago1-52 suppressed5 (mas5). In the mas5-1 background, the spliceosome preferentially recognizes the intact genuine 3′SS of ago1-52 and 5′SS of icu13. Since point mutations that damage genuine SSs make the spliceosome prone to recognizing cryptic SSs, we also tested alleles of four genes carrying damaged genuine SSs, finding that mas5-1 did not suppress their missplicing. The mas5-1 and mas5-3 mutations represent a novel class of missplicing suppressors that increase splicing fidelity by hampering the use of novel SSs, but do not alter general pre-mRNA splicing.