Prognostic Relevance of Preoperative Immune, Inflammatory, and Nutritional Biomarkers in Patients Undergoing Gastrectomy for Resectable Gastric Adenocarcinoma: An Observational Multicentre Study.

Background: The aim of this study was to evaluate different preoperative immune, inflammatory, and nutritional scores and their best cut-off values as predictors of poorer overall survival (OS) and disease-free survival (DFS) in patients who underwent curative gastric cancer resection. Methods: This was a retrospective observational multicentre study based on data of the Spanish EURECCA Esophagogastric Cancer Registry. Time-dependent Youden index and log-rank test were used to obtain the best cut-offs of 18 preoperative biomarkers for OS and DFS. An adjusted Cox model with variables selected by bootstrapping was used to identify the best preoperative biomarkers, which were also analysed for every TNM stage. Results: High neutrophil-to-lymphocyte ratio (NLR), high monocyte systemic inflammation index (moSII), and low prognostic nutritional index (PNI) were identified as independent predictors of poor outcome: NLR > 5.91 (HR:1.73; 95%CI [1.23-2.43]), moSII >2027.12 (HR:2.26; 95%CI [1.36-3.78]), and PNI >40.31 (HR:0.75; 95%CI [0.58-0.96]) for 5-year OS and NLR > 6.81 (HR:1.75; 95%CI [1.24-2.45]), moSII > 2027.12 (HR:2.46; 95%CI [1.49-4.04]), and PNI > 40.31 (HR:0.77; 95%CI [0.60,0.97]) for 5-year DFS. These outcomes were maintained in the whole cohort for NLR and moSII (p < 0.05) but not in stage II and for PNI in all tumoral stages. The associations of NLR-PNI and moSII-PNI were also a relevant prognostic factor for OS. Conclusions: High NLR, high moSII (for stages I and III), and low PNI (regardless of tumour stage) were the most promising preoperative biomarkers to predict poor OS and DFS in gastric cancer patients treated with curative intent.

Short-term effects of gastric bypass versus sleeve gastrectomy on high LDL cholesterol: The BASALTO randomized clinical trial.

BACKGROUND: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). METHODS: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications. RESULTS: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques. CONCLUSION: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient. TRIAL REGISTRATION: Clinicaltrials.gov number, NCT03975478).

Recurrence and Survival After Minimally Invasive and Open Esophagectomy for Esophageal Cancer: A Post Hoc Analysis of the Ensure Study.

OBJECTIVE: To determine the impact of operative approach [open (OE), hybrid minimally invasive (HMIE), and total minimally invasive (TMIE) esophagectomy] on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer. BACKGROUND: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear. METHODS: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009 and 2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield, and overall survival (OS). RESULTS: In total, 3199 patients were included. Of these, 55% underwent OE, 17% HMIE, and 29% TMIE. DFS was independently increased post-TMIE [hazard ratio (HR): 0.86 (95% CI: 0.76-0.98), P = 0.022] compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to the operative approach [HMIE vs OE, odds ratio (OR): 0.79, P = 0.257; TMIE vs OE, OR: 0.84, P = 0.243]. The probability of systemic recurrence was independently increased post-HMIE (OR: 2.07, P = 0.031), but not TMIE (OR: 0.86, P = 0.508). R0 resection rates ( P = 0.005) and nodal yield ( P < 0.001) were independently increased after TMIE, but not HMIE ( P = 0.424; P = 0.512) compared with OE. OS was independently improved following both HMIE (HR: 0.79, P = 0.009) and TMIE (HR: 0.82, P = 0.003) as compared with OE. CONCLUSION: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, whereas both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer.

Western European Variation in the Organization of Esophageal Cancer Surgical Care.

Reasons for structural and outcome differences in esophageal cancer surgery in Western Europe remain unclear. This questionnaire study aimed to identify differences in the organization of esophageal cancer surgical care in Western Europe. A cross-sectional international questionnaire study was conducted among upper gastrointestinal (GI) surgeons from Western Europe. One surgeon per country was selected based on scientific output and active membership in the European Society for Diseases of the Esophagus or (inter)national upper GI committee. The questionnaire consisted of 51 structured questions on the structural organization of esophageal cancer surgery, surgical training, and clinical audit processes. Between October 2021 and October 2022, 16 surgeons from 16 European countries participated in this study. In 5 countries (31%), a volume threshold was present ranging from 10 to 26 annual esophagectomies, in 7 (44%) care was centralized in designated centers, and in 4 (25%) no centralizing regulations were present. The number of centers performing esophageal cancer surgery per country differed from 4 to 400, representing 0.5-4.9 centers per million inhabitants. In 4 countries (25%), esophageal cancer surgery was part of general surgical training and 8 (50%) reported the availability of upper GI surgery fellowships. A national audit for upper GI surgery was present in 8 (50%) countries. If available, all countries use the audit to monitor the quality of care. Substantial differences exist in the organization and centralization of esophageal cancer surgical care in Western Europe. The exchange of experience in the organizational aspects of care could further improve the results of esophageal cancer surgical care in Europe.

Effects of Preoperative Quadruple Therapy for Helicobacter pylori on Bariatric Surgery Metabolic Outcomes.

PURPOSE: To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS). METHODS: Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated. RESULTS: HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (-14.6 ± 27.5 mg/dL HP-treated vs -22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (-13.7 ± 29.4 mg/dL HP-treated vs -26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023). CONCLUSIONS: Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS.

Clinical Features of Gastric Signet Ring Cell Cancer: Results from a Systematic Review and Meta-Analysis.

BACKGROUND: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. METHODS: A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. RESULTS: A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. CONCLUSIONS: Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.

YAP Activation Is Associated with a Worse Prognosis of Poorly Cohesive Gastric Cancer.

Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA-YAP axis in these mechanisms. The present observational multicenter retrospective study included 133 patients with PC GC treated at two dedicated European surgical centers between 2004 and 2014. YAP nuclear localization was measured by immunohistochemical (IHC) analysis of tissue biopsies. The complete absence of nuclear reactivity was coded as negative expression; we considered "any positive" as low nuclear expression (>0% but <10% of cells) and high nuclear expression (≥10% of cells). Women represented about half of the present series (52%), and the median age was 64 years (p25-p75 range: 53-75). Neoadjuvant and adjuvant treatments were administered to 10% and 54% of the cases, respectively. Extended systemic lymphadenectomy (D2) was the most common (54%). In nearly all cases, the number of retrieved nodes was ≥15, i.e., adequate for tumor staging (94%). An R0 resection was achieved in 80% of the cases. Most patients were pathological T stage 3 and 4 (pT3/pT4 = 79.0%) and pathological N stage 2, 3a, and 3b (pN2/pN3a/pN3b = 47.0%) at the pathological examination. Twenty patients (15%) presented distant metastases. Five-year overall survival (OS) was significantly higher (p = 0.029) in patients with negative YAP (46%, 95% CI 31.1-60.0%) than in the other patients (27%, 17.5-38.1%). Moreover, when controlling for sex, age, pT, pN, and percentage of signet ring cells in the multivariable analysis, YAP expression was a significant predictor of OS (HR 2.03, 95% CI: 1.18-3.51, p = 0.011). Our results provide new insights into the role of the YAP signaling cascade, as its activation was associated with a worse prognosis in PC GC.

Textbook Oncological Outcome in European GASTRODATA.

OBJECTIVE: To assess the rate of textbook outcome (TO) and textbook oncological outcome (TOO) in the European population based on the GASTRODATA registry. BACKGROUND: TO is a composite parameter assessing surgical quality and strongly correlates with improved overall survival. Following the standard of treatment for locally advanced gastric cancer, TOO was proposed as a quality and optimal multimodal treatment parameter. METHODS: TO was achieved when all the following criteria were met: no intraoperative complications, radical resection according to the surgeon, pR0 resection, retrieval of at least 15 lymph nodes, no severe postoperative complications, no reintervention, no admission to the intensive care unit, no prolonged length of stay, no postoperative mortality and no hospital readmission. TOO was defined as TO with the addition of perioperative chemotherapy compliance. RESULTS: Of the 2558 patients, 1700 were included in the analysis. TO was achieved in 1164 (68.5%) patients. The use of neoadjuvant chemotherapy [odds ratio (OR) = 1.33, 95% CI: 1.04-1.70] and D2 or D2+ lymphadenectomy (OR = 1.55, 95% CI: 1.15-2.10) had a positive impact on TO achievement. Older age (OR = 0.73, 95% CI: 0.54-0.94), pT3/4 (OR = 0.79, 95% CI: 0.63-0.99), ASA 3/4 (OR = 0.68, 95% CI: 0.54-0.86) and total gastrectomy (OR = 0.56, 95% CI: 0.45-0.70), had a negative impact on TO achievement. TOO was achieved in 388 (22.8%) patients. Older age (OR = 0.37, 95% CI: 0.27-0.53), pT3 or pT4 (OR = 0.52, 95% CI: 0.39-0.69), and ASA 3 or 4 (OR = 0.58, 95% CI: 0.43-0.79) had a negative impact on TOO achievement. CONCLUSIONS: Despite successively improved surgical outcomes, stage-appropriate chemotherapy in adherence to the current guidelines for multimodal treatment of gastric cancer remains poor. Further implementation of oncologic quality metrics should include greater emphasis on perioperative chemotherapy and adequate lymphadenectomy.

5-Year Collis-Nissen Gastroplasty Outcomes for Type III-IV Hiatal Hernia with Short Esophagus: A Prospective Observational Study.

BACKGROUND: To assess the 5-year outcomes of patients undergoing Collis-Nissen gastroplasty for type III-IV hiatal hernia with short esophagus. STUDY DESIGN: From a prospective observational cohort of patients who underwent antireflux surgery for type III-IV hiatal hernia between 2009 and 2020, those with short esophagus (abdominal length <2.5 cm) in whom a Collis-Nissen procedure was performed and reached at least 5 years of follow-up were identified. Hernia recurrence, patients' symptoms, and quality of life were assessed annually by barium meal x-ray, upper endoscopy, and validated symptoms and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaires. RESULTS: Of the 114 patients with Collis-Nissen gastroplasty, 80 patients who completed a 5-year follow-up were included (mean age 71 years). There were no postoperative leaks or deaths. Recurrent hiatal hernia (any size) was identified in 7 patients (8.8%). Heartburn, regurgitation, chest pain, and cough were significantly improved at each follow-up interval (p < 0.05). Preoperative dysphagia disappeared or improved in 26 of 30 patients, while new-onset dysphagia occurred in 6. Mean postoperative QOLRAD scores significantly improved at all dimensions (p < 0.05). CONCLUSIONS: Collis gastroplasty combined with Nissen fundoplication provides low hernia recurrence, good control of symptoms, and improved quality of life in patients with large hiatal hernia and short esophagus.

Research protocol for the Paraesophageal hernia symptom tool, a prospective multi-center cohort study to identify the need and threshold for surgery and assess the symptom response to surgery.

Large hiatus hernias with a significant paraesophageal component (types II-IV) have a range of insidious symptoms. Management of symptomatic hernias includes conservative treatment or surgery. Currently, there is no paraesophageal hernia disease-specific symptom questionnaire. As a result, many clinicians rely on the health-related quality of life questionnaires designed for gastro-esophageal reflux disease (GORD) to assess patients with hiatal hernias pre- and postoperatively. In view of this, a paraesophageal hernia symptom tool (POST) was designed. This POST questionnaire now requires validation and assessment of clinical utility. Twenty-one international sites will recruit patients with paraesophageal hernias to complete a series of questionnaires over a five-year period. There will be two cohorts of patients-patients with paraesophageal hernias undergoing surgery and patients managed conservatively. Patients are required to complete a validated GORD-HRQL, POST questionnaire, and satisfaction questionnaire preoperatively. Surgical cohorts will also complete questionnaires postoperatively at 4-6 weeks, 6 months, 12 months, and then annually for a total of 5 years. Conservatively managed patients will repeat questionnaires at 1 year. The first set of results will be released after 1 year with complete data published after a 5-year follow-up. The main results of the study will be patient's acceptance of the POST tool, clinical utility of the tool, assessment of the threshold for surgery, and patient symptom response to surgery. The study will validate the POST questionnaire and identify the relevance of the questionnaire in routine management of paraesophageal hernias.

State of the art of enhanced recovery after surgery (ERAS) protocols in esophagogastric cancer surgery: the Western experience.

Enhanced recovery after surgery (ERAS) programs provide a framework to standardize care processes and improve outcomes. The results of this multimodal and multidisciplinary approach based on actions focused on reducing physiological surgical stress in the preoperative, intraoperative, and postoperative periods are beneficial in reducing morbidity and hospital stay, without increasing readmissions across different surgical settings. The implementation of ERAS in resection procedures of esophageal and gastric cancer has been challenging due to the complexity of these surgical techniques and the high risk of complications. Despite the limited evidence of ERAS in esophagectomy operations, systematic reviews and meta-analysis have confirmed a reduction of pulmonary complications and hospital stay without increasing readmissions. In gastrectomy operations, the implementation of ERAS reduces the use of nasogastric tubes and intraabdominal drains, facilitates early diet, and reduces the length of hospital stay, without increasing complications. There is, however, wide heterogeneity and absence of standardization in the number and definition of the ERAS components. The development of ERAS consensus guidelines including procedure-specific components may reduce this variability. Regardless growing evidence of the effectiveness of ERAS, the adherence rate is still low. The commitment of the multidisciplinary team and leadership is critical in the application and refinement of ERAS protocols in parallel with periodic audits. Pre- and post-habilitation methods are emerging concepts to be incorporated in ERAS protocols.

Cost analysis of a patient blood management program for patients undergoing gastric cancer surgery.

Patient Blood Management (PBM) programs have probed to reduce blood transfusions and postoperative complications following gastric cancer resection, but evidence on their economic benefit is scarce. A recent prospective interventional study of our group described a reduction in transfusions, infectious complications and length of stay after implementation of a multicenter PBM program in patients undergoing elective gastric cancer resection with curative intent. The aim of the present study was to analyze the economic impact associated with these clinical benefits. The mean [and 95% CI] of total healthcare cost per patient was lower (-1955 [-3764, -119] €) after the PBM program implementation. The main drivers of this reduction were the hospital stay (-1847 [-3161, -553] €), blood transfusions (-100 [-145, -56] €), and post-operative complications (-162 [-718, 411] €). Total societal cost was reduced by -2243 [-4244, -210] € per patient. These findings highlight the potential economic benefit of PBM strategies.

Machine Learning Risk Prediction Model of 90-day Mortality After Gastrectomy for Cancer.

OBJECTIVE: To develop and validate a risk prediction model of 90-day mortality (90DM) using machine learning in a large multicenter cohort of patients undergoing gastric cancer resection with curative intent. BACKGROUND: The 90DM rate after gastrectomy for cancer is a quality of care indicator in surgical oncology. There is a lack of well-validated instruments for personalized prognosis of gastric cancer. METHODS: Consecutive patients with gastric adenocarcinoma who underwent potentially curative gastrectomy between 2014 and 2021 registered in the Spanish EURECCA Esophagogastric Cancer Registry database were included. The 90DM for all causes was the study outcome. Preoperative clinical characteristics were tested in four 90DM predictive models: Cross Validated Elastic regularized logistic regression method (cv-Enet), boosting linear regression (glmboost), random forest, and an ensemble model. Performance was evaluated using the area under the curve by 10-fold cross-validation. RESULTS: A total of 3182 and 260 patients from 39 institutions in 6 regions were included in the development and validation cohorts, respectively. The 90DM rate was 5.6% and 6.2%, respectively. The random forest model showed the best discrimination capacity with a validated area under the curve of 0.844 [95% confidence interval (CI): 0.841-0.848] as compared with cv-Enet (0.796, 95% CI: 0.784-0.808), glmboost (0.797, 95% CI: 0.785-0.809), and ensemble model (0.847, 95% CI: 0.836-0.858) in the development cohort. Similar discriminative capacity was observed in the validation cohort. CONCLUSIONS: A robust clinical model for predicting the risk of 90DM after surgery of gastric cancer was developed. Its use may aid patients and surgeons in making informed decisions.

Development of the ParaOesophageal hernia SympTom (POST) tool.

BACKGROUND: The aim of this study was to develop a symptom severity instrument (ParaOesophageal hernia SympTom (POST) tool) specific to para-oesophageal hernia (POH). METHODS: The POST tool was developed in four stages. The first was establishment of a Steering Committee. In the second stage, items were generated through a systematic review and online scoping survey of international experts. In the third stage, a three-round modified Delphi consensus process was conducted with a group of international experts who were asked to rate the importance of candidate items. An a priori threshold for inclusion was set at 80 per cent. The modified Delphi process culminated in a consensus meeting to develop the first iteration of the tool. In the final stage, two international patient workshops were held to assess the content validity and acceptability of the POST tool. RESULTS: The systematic review and scoping survey generated 64 symptoms, refined to 20 for inclusion in the modified Delphi consensus process. Twenty-six global experts participated in the Delphi consensus process. Five symptoms reached consensus across two rounds: difficulty getting solid foods down, chest pain after meals, difficulty getting liquids down, shortness of breath only after meals, and an early feeling of fullness after eating. The subsequent patient workshops deemed these five symptoms to be relevant and suggested that reflux should be included; these were taken forward to create the final POST tool. CONCLUSION: The POST tool is the first instrument designed to capture POH-specific symptoms. It will allow clinicians to standardize reporting of symptoms of POH and evaluate the response to surgical intervention.

Definitions and treatment of oligometastatic oesophagogastric cancer according to multidisciplinary tumour boards in Europe.

BACKGROUND: Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking. OBJECTIVE: To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe. MATERIAL AND METHODS: European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (<50%), fair (50%-75%), or consensus (≥75%). RESULTS: A total of 47 MDTs across 16 countries fully discussed the cases (96%). Oligometastatic disease was considered in patients with 1-2 metastases in either the liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue or bone (consensus). At follow-up, oligometastatic disease was considered after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after a median of 18 weeks of systemic therapy the number of lesions progressed, this was not considered as oligometastatic disease (fair agreement). There was no consensus on treatment strategies for oligometastatic disease. CONCLUSION: A broad consensus on definitions of oligometastatic oesophagogastric cancer was found among MDTs of oesophagogastric cancer expert centres in Europe. However, high practice variability in treatment strategies exists.

Preoperative neutrophil-to-lymphocyte ratio behaves as an independent prognostic factor even in patients with postoperative complications after curative resection for gastric cancer.

PURPOSE: The aim of this study was to determine if the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) could be modified by the presence of postoperative complications (POC) and their severity in patients with gastric adenocarcinoma resected with curative intent. METHODS: A retrospective study based on a prospective database of patients with resectable gastric adenocarcinoma treated with radical intention (R0) between January 1998 and February 2012. The primary endpoint was overall survival according to preoperative peripheral blood NLR and postoperative complications. Clinicopathological variables, preoperative blood tests, POC and its severity (Clavien-Dindo classification), type of POC (infectious or not infectious) and mortality were registered. A univariate and multivariate analysis (step forward Cox regression) was performed. The Kaplan-Meier method was used to assess overall survival. RESULTS: The 147 patients with gastric cancer who had undergone radical resection were included from an initial cohort of 209 patients. Univariant analysis: type of surgery, pT, pN, postoperative complications (Clavien-Dindo ≥ 3) and preoperative NLR ≥ 2.4 were significantly associated with survival (p < 0.05). Patients with POC showed worse long-term survival (p = 0.000), with no difference (p = 0.867) between infectious or non-infectious POC. NLR ≥ 2.4 was associated with infectious POC (p < 0.001). Patients with preoperative NLR ≥ 2.4 (p = 0.02) had a worse prognosis. Multivariate analysis: pN (p < 0.001), postoperative complications (p < 0.001) (HR 3.04; 95% CI: 1.97-4.70) and NLR ≥ 2.4 (p = 0.04) (HR = 1.55; 95% CI: 1.02-2.3) were independent prognostic factors. CONCLUSION: The preoperative inflammatory state of patients with gastric cancer measured by NLR behaves as an independent prognostic factor, even in patients with POC.

Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials.

OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098.Trial registration number: ISRCTN59036820, ISRCTN10386621.

Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study.

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ±â€Š0.02 and 0.82 ±â€Š0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.