The Prognostic Impact of Minimally Invasive Esophagectomy on Survival after Esophagectomy following a Delayed Interval after Chemoradiotherapy; A Secondary Analysis of the DICE Study.

OBJECTIVE: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT). BACKGROUND: Previously, we established that a prolonged interval after CRT prior to esophagectomy was associated with poorer long-term survival. METHODS: This was an international multi-center cohort study involving seventeen tertiary centers, including patients who received CRT followed by surgery between 2010-2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approach. RESULTS: 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and two years after CRT. Significant differences were observed in ASA grade, radiation dose, clinical T stage, and histological subtype. There were no significant differences between the groups in age, sex, BMI, pathological T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate (P=0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI 1.14 to 2.5) and propensity matched analysis (P=0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE, in 40-50Gy dose groups (HR=1.9; 95% CI 1.2 to 3.0), and in patients having surgery within six months of CRT (HR=1.6; 95% CI 1.1 to 2.2). CONCLUSION: MIE was associated with an improved overall survival compared to OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

Neoadjuvant Chemotherapy Does Not Improve Survival in cT2N0M0 Gastric Adenocarcinoma Patients: A Multicenter Propensity Score Analysis.

BACKGROUND: According to current international guidelines, stage cT2N0M0 gastric adenocarcinoma warrants preoperative chemotherapy followed by surgery. However, upfront surgery is often preferred in clinical practice, depending on patient clinical status and local treatment preferences. OBJECTIVE: The aim of the present study was to assess the impact of neoadjuvant chemotherapy in overall survival (OS) and disease-free survival (DFS) of cT2N0M0 patients. METHODS: A retrospective analysis was performed among 32 centers, including gastric adenocarcinoma patients operated between January 2007 and December 2017. Patients with cT2N0M0 stage were divided into upfront surgery (S) and neoadjuvant chemotherapy followed by surgery (CS) groups. Inverse probability of treatment weighting (IPTW) was used to compensate for baseline differences between the groups. RESULTS: Among the 202 patients diagnosed with cT2N0M0 stage, 68 (33.7%) were in the CS group and 134 (66.3%) were in the S group. CS patients were younger (mean age 62.7 ± 12.8 vs. 69.8 ± 12.1 years for S patients; p < 0.001) and had a better health status (World Health Organization performance status = 0 in 60.3% of CS patients vs. 34.5% of S patients; p = 0.006). During follow-up, recurrence occurred in 27.2% and 19.6% of CS and S patients, respectively, after IPTW (p = 0.32). Five-year OS was similar between CS and S patients (78.9% vs. 68.3%; p = 0.42), as was 5-year DFS (70.4% vs. 68.5%; p = 0.96). Neoadjuvant chemotherapy was associated with neither OS nor DFS in multivariable analysis after IPTW. CONCLUSIONS: Patients with cT2N0M0 gastric adenocarcinoma did not present a survival or recurrence benefit if treated with perioperative chemotherapy followed by surgery as opposed to surgery alone.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Root cause analysis of mortality after esophagectomy for cancer: a multicenter cohort study from the FREGAT database.

BACKGROUND: Esophagectomy is associated with significant mortality. A better understanding of the causes leading to death may help to reduce mortality. A root cause analysis of mortality after esophagectomy was performed. METHODS: Root cause analysis was retrospectively applied by an independent expert panel of 4 upper gastrointestinal surgeons and 1 anesthesiologist-intensivist to patients included in the French national multicenter prospective cohort FREGAT between August 2014 and September 2019 who underwent an esophagectomy for cancer and died within 90 days of surgery. A cause-and-effect diagram was used to determine the root causes related to death. Death was classified as potentially preventable or non-preventable. RESULTS: Among the 1,040 patients included in the FREGAT cohort, 70 (6.7%) patients (male: 81%, median age 68 [62-72] years) from 17 centers were included. Death was potentially preventable in 37 patients (53%). Root causes independently associated with preventable death were inappropriate indication (odds ratio 35.16 [2.50-494.39]; P = .008), patient characteristics (odds ratio 5.15 [1.19-22.35]; P = .029), unexpected intraoperative findings (odds ratio 18.99 [1.07-335.55]; P = .045), and delay in diagnosis of a complication (odds ratio 98.10 [6.24-1,541.04]; P = .001). Delay in treatment of a complication was found only in preventable deaths (28 [76%] vs 0; P < .001). National guidelines were less frequently followed (16 [43%] vs 22 [67%]; P = .050) in preventable deaths. The only independent risk factor of preventable death was center volume <26 esophagectomies per year (odds ratio 4.71 [1.55-14.33]; P = .006). CONCLUSIONS: More than one-half of deaths after esophagectomy were potentially preventable. Better patient selection, early diagnosis, and adequate management of complications through centralization could reduce mortality.

Targeting metastasis-initiating cancer stem cells in gastric cancer with leukaemia inhibitory factor.

Gastric cancer's (GC) bad prognosis is usually associated with metastatic spread. Invasive cancer stem cells (CSC) are considered to be the seed of GC metastasis and not all CSCs are able to initiate metastasis. Targeting these aggressive metastasis-initiating CSC (MIC) is thus vital. Leukaemia inhibitory factor (LIF) is hereby used to target Hippo pathway oncogenic members, found to be induced in GC and associated with CSC features. LIF-treated GC cell lines, patient-derived xenograft (PDX) cells and/or CSC tumourspheres underwent transcriptomics, laser microdissection-associated proteomics, 2D and 3D invasion assays and in vivo xenograft in mice blood circulation. LIFR expression was analysed on tissue microarrays from GC patients and in silico from public databases. LIF-treated cells, especially CSC, presented decreased epithelial to mesenchymal transition (EMT) phenotype and invasion capacity in vitro, and lower metastasis initiation ability in vivo. These effects involved both the Hippo and Jak/Stat pathways. Finally, GC's high LIFR expression was associated with better clinical outcomes in patients. LIF treatment could thus represent a targeted anti-CSC strategy to fight against metastatic GC, and LIFR detection in primary tumours could constitute a potential new prognosis marker in this disease.

High Risk of Acute Kidney Failure in Kidney Transplant Recipients Early after Bariatric Surgery.

Bariatric surgery is routinely proposed to patients suffering from obesity including kidney transplant recipients. In this specific population, bariatric surgery has a positive impact in long-term outcomes in terms of patient and graft survival. We report here the cases of 4 patients with five post-kidney transplantation bariatric surgeries who experimented acute renal injury early after surgery. Creatinine rising occurred between day 14 and day 20 after surgery. In all cases, it was due to dehydration leading to a pre-renal acute renal failure. The specific care of kidney transplanted patients is discussed: single kidney associated with pre-existing altered kidney function associated with concomitant use of nephrotoxic drugs. Specific education intervention before surgery associated with careful early management of hydration after surgery is mandatory for these patients.

Total Versus Subtotal Gastrectomy for Distal Gastric Poorly Cohesive Carcinoma.

BACKGROUND: Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy. METHODS: A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS. RESULTS: The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34). CONCLUSIONS: At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer.

Robotic surgery for inguinal and ventral hernia repair: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis assessed the effectiveness of robotic surgery compared to laparoscopy or open surgery for inguinal (IHR) and ventral (VHR) hernia repair. METHODS: PubMed and EMBASE were searched up to July 2022. Meta-analyses were performed for postoperative complications, surgical site infections (SSI), seroma/hematoma, hernia recurrence, operating time (OT), intraoperative blood loss, intraoperative bowel injury, conversion to open surgery, length of stay (LOS), mortality, reoperation rate, readmission rate, use of opioids, time to return to work and time to return to normal activities. RESULTS: Overall, 64 studies were selected and 58 were used for pooled data analyses: 35 studies (227 242 patients) deal with IHR and 32 (158 384 patients) with VHR. Robotic IHR was associated with lower hernia recurrence (OR 0.54; 95%CI 0.29, 0.99; I2: 0%) compared to laparoscopic IHR, and lower use of opioids compared to open IHR (OR 0.46; 95%CI 0.25, 0.84; I2: 55.8%). Robotic VHR was associated with lower bowel injuries (OR 0.59; 95%CI 0.42, 0.85; I2: 0%) and less conversions to open surgery (OR 0.51; 95%CI 0.43, 0.60; I2: 0%) compared to laparoscopy. Compared to open surgery, robotic VHR was associated with lower postoperative complications (OR 0.61; 95%CI 0.39, 0.96; I2: 68%), less SSI (OR 0.47; 95%CI 0.31, 0.72; I2: 0%), less intraoperative blood loss (- 95 mL), shorter LOS (- 3.4 day), and less hospital readmissions (OR 0.66; 95%CI 0.44, 0.99; I2: 24.7%). However, both robotic IHR and VHR were associated with significantly longer OT compared to laparoscopy and open surgery. CONCLUSION: These results support robotic surgery as a safe, effective, and viable alternative for IHR and VHR as it can brings several intraoperative and postoperative advantages over laparoscopy and open surgery.

EAES Multidisciplinary Rapid Guideline: systematic review, meta-analysis, GRADE assessment and evidence-informed recommendations on the surgical management of paraesophageal hernias.

BACKGROUND: New evidence has emerged since latest guidelines on the management of paraesophageal hernia, and guideline development methodology has evolved. Members of the European Association for Endoscopic Surgery have prioritized the management of paraesophageal hernia to be addressed by pertinent recommendations. OBJECTIVE: To develop evidence-informed clinical practice recommendations on paraesophageal hernias, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: We performed three systematic reviews, and we summarized and appraised the certainty of the evidence using the GRADE methodology. A panel of general and upper gastrointestinal surgeons, gastroenterologists and a patient advocate discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost and use of resources, moderated by a Guidelines International Network-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests surgery over conservative management for asymptomatic/minimally symptomatic paraesophageal hernias (conditional recommendation), and recommends conservative management over surgery for asymptomatic/minimally symptomatic paraesophageal hernias in frail patients (strong recommendation). Further, the panel suggests mesh over sutures for hiatal closure in paraesophageal hernia repair, fundoplication over gastropexy in elective paraesophageal hernia repair, and gastropexy over fundoplication in patients who have cardiopulmonary instability and require emergency paraesophageal hernia repair (conditional recommendation). A strong recommendation means that the proposed course of action is appropriate for the vast majority of patients. A conditional recommendation means that most patients would opt for the proposed course of action, and joint decision-making of the surgeon and the patient is required. Accompanying evidence summaries and evidence-to-decision frameworks should be read when using the recommendations. This guideline applies to adult patients with moderate to large paraesophageal hernias type II to IV with at least 50% of the stomach herniated to the thoracic cavity. The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/j7q7Gn . CONCLUSION: An interdisciplinary panel provides recommendations on key topics on the management of paraesophageal hernias using highest methodological standards and following a transparent process. GUIDELINE REGISTRATION NUMBER: PREPARE-2023CN018.

A novel pathogenic variant in MRAP2 in an obese patient with successful outcome of bariatric surgery.

Mutations in genes encoding proteins located in the leptin/melanocortin pathway have been identified in the rare cases of genetic obesities. Heterozygous variants of MRAP2, encoding a G coupled-protein receptor accessory protein implicated in energy control notably via the melanocortin-4 receptor, have been recently identified. A 24-year-old patient with early-onset severe obesity (body mass index [BMI]: 64 kg/m2) associated with hypertension, respiratory complications, nonalcoholic fatty liver disease, and type 2 diabetes was referred to our department. Sleeve gastrectomy was successful. A new heterozygous variant in MRAP2 (NM_138409.4: c.154G>C/p.G52R) variant was identified in the patient DNA. Functional assessment confirmed that this new variant was pathogenic. We report a new pathogenic loss-of-function mutation in MRAP2 in a patient suffering from a severe multicomplicated obesity. This confirms the metabolic phenotype in patients with this monogenic form of obesity. Longer follow-up will be necessary. Our finding will allow a personalized medicine.

Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study.

OBJECTIVE: To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND: CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS: This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS: A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.

Gastro-Intestinal Disorders and Micronutrient Deficiencies following Oncologic Esophagectomy and Gastrectomy.

Primary surgical indications for the esophagus and stomach mainly involve cancer surgeries. In recent years, significant progress has been made in the field of esogastric surgery, driven by advancements in surgical techniques and improvements in perioperative care. The rate of resectability has increased, and surgical strategies have evolved to encompass a broader patient population. However, despite a reduction in postoperative mortality and morbidity, malnutrition remains a significant challenge after surgery, leading to weight loss, muscle mass reduction, and deficiencies in essential nutrients due to digestive complications. Malnutrition worsens quality of life and increases the risk of tumor recurrence, significantly affecting prognosis. Nevertheless, the nutritional consequences following surgery are frequently overlooked, mainly due to a lack of awareness regarding their long-term effects on patients who have undergone digestive surgery, extending beyond six months. Micronutrient deficiencies are frequently observed following both partial and total gastrectomy, as anticipated. Surprisingly, these deficiencies appear to be similarly prevalent in patients who have undergone esophagectomy with iron, vitamins A, B1, B12, D, and E deficiencies commonly observed in up to 78.3% of the patients. Recognizing the distinct consequences associated with each type of intervention underscores the importance of implementing preventive measures, early detection, and prompt management.

Risk factors for intraoperative complications, postoperative complications, and prolonged length of stay after laparoscopic adrenalectomy by transperitoneal lateral approach: a retrospective cohort study of 547 procedures.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard for the resection of most adrenal lesions. A precise delineation of factors influencing its outcomes is lacking. The aim of this study was to assess factors associated with intraoperative complications, postoperative complications, and prolonged length of stay (LOS) after LA. METHODS: Patients who underwent LA from 1999 to 2021 in a single-academic-institution were included. Patient and disease-specific data, intraoperative complications, postoperative complications according to Dindo-Clavien (DC) scale, and LOS were recorded. Predictive factors of complications and prolonged LOS were determined by logistic regression. RESULTS: We identified 530 patients who underwent 547 LA. Intraoperative complications occurred in 33 patients (6.0%). Postoperative complications ≥  DC grade 2 occurred in 73 patients (13.35%); severe postoperative complications ≥ DC grade 3 in 14 patients (2.56%). Postoperative complications were positively associated with age ≥ 72 (OR 1.14 [95% CI 1.02-1.29]), intraoperative complications (OR 1.36 [95% CI 1.14-1.63]), and negatively associated with non functional adenomas (OR 0.88 [95% CI 0.7-0.99]), and right adrenalectomy (OR 0.91 [95% CI 0.86-0.97]). Severe postoperative complications were positively associated with chronic obstructive pulmonary disease (COPD, OR 1.08 [95% CI 1.00-1.17]), and negatively associated with right adrenalectomy (OR 0.97 [95% CI 0.92-0.99]). Prolonged LOS was associated with age ≥ 72 (OR 1.21 [95% CI 1.05-1.41]), and COPD (OR 1.20 [95% CI 1.01-1.44]). CONCLUSIONS: LA remains safe when performed by surgeons with expertise. Right adrenalectomy resulted in less postoperative overall and severe complications. The risk-benefit equation should be carefully assessed before left LA in older patients with COPD.

Long-Term Results After Bariatric Surgery in Super-Super-Obese Patients.

Introduction: Despite addressing to high risk population, we can propose laparoscopic bariatric surgery to super-super-obese (SSO) patients (body mass index [BMI] ≥60 kg/m2). The aim of this study was to report our experience in terms of weight loss and improvement of medical comorbidities after a follow-up of 5 years in the SSO population who underwent different bariatric procedures. Methods: This retrospective study includes all SSO patients who underwent bariatric surgery (sleeve gastrectomy [SG] and/or gastric bypass) between 2006 and 2017. The population was divided in three groups (SG alone; Roux-en-Y gastric bypass [RYGB] alone and SG+RYGB). The rate of complication and the weight-loss results were analyzed. Results: Among 43 patients who underwent surgery, the mean age was 42[31-54]. There were more women (72%) with the mean preoperative BMI of 64.9 kg/m2 [59.6-70.1]. There were 9 SGs, 26 RYGB, and 8 SG revised to gastric bypass (SG+RYGB) after a median delay of 23.5 months [16.5-32]. The perioperative complication rate was 25%, and there was 1 postoperative death. The median follow-up was 69 months [1-128]. The mean percentage of excess weight loss (%EWL) was 39.2% [18.2-60.3] after 5 years. For the SG group, the %EWL was inferior -27.1 [-3.6 to 57.8], but with no significant difference. An improvement of comorbidities' rate was recorded in all groups of patients. Conclusion: Bariatric surgery in SSO patients leads to an improvement of comorbidities even if the weight-loss results, especially in the SG group, are less favorable. The two steps approach should be re-evaluated by shortening the interval between. Other surgical strategies than RYGB are needed to be evaluated to improve long-term weight loss.

Perioperative Cetuximab with Cisplatin and 5-Fluorouracil in Esogastric Adenocarcinoma: A Phase II Study.

PURPOSE: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. PATIENTS AND METHODS: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). RESULTS: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4-39.4] and 40.3 months [95% CI: 27.5-NA], respectively. CONCLUSION: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086).

A Comprehensive Review of Prognostic Factors in Patients with Gastric Adenocarcinoma.

Gastric adenocarcinoma remains associated with a poor long-term survival, despite recent therapeutical advances. In most parts of the world where systematic screening programs do not exist, diagnosis is often made at advanced stages, affecting long-term prognosis. In recent years, there is increasing evidence that a large bundle of factors, ranging from the tumor microenvironment to patient ethnicity and variations in therapeutic strategy, play an important role in patient outcome. A more thorough understanding of these multi-faceted parameters is needed in order to provide a better assessment of long-term prognosis in these patients, which probably also require the refinement of current staging systems. This study aims to review existing knowledge on the clinical, biomolecular and treatment-related parameters that have some prognostic value in patients with gastric adenocarcinoma.