bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; 0.0001), this finding was further confirmed in the CRT patients’ subgroup (P &lt; 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

Abstract

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 &lt; 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

Abstract

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 &gt;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

Abstract

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 &gt; 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

Abstract

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 &lt; 0.001) and DFS (HR: 0.50, CI95%: 0.36–0.70, P &lt; 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

Abstract

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 &lt; 0.001). Patients treated with FLOT were less likely to have a positive resection margin (19.1% FLOT vs 32.2% MAGIC, P &lt; 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
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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

Abstract

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

Abstract

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

Abstract

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

Abstract
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.