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BackgroundGastric adenocarcinoma (GAC) imposes a considerable global health burden. Molecular profiling of GAC from the tumor microenvironment perspective through a multi-omics approach is eagerly awaited in order to allow a more precise application of novel therapies in the near future.MethodsTo better understand the tumor-immune interface of GAC, we identified an internal cohort of 82 patients that allowed an integrative molecular analysis including mutational profiling by whole-exome sequencing, RNA gene expression of 770 genes associated with immune response, and multiplex protein expression at spatial resolution of 34 immuno-oncology targets at different compartments (tumorous cells and immune cells). Molecular findings were validated in 595 GAC from the TCGA and ACRG external cohorts with available multiomics data. Prediction of response to immunotherapies of the discovered immunophenotypes was assessed in 1039 patients with cancer from external cohorts with available transcriptome data.ResultsUnsupervised clustering by gene expression identified a subgroup of GAC that includes 52% of the tumors, the so-called Inflamed class, characterized by high tumor immunogenicity and cytotoxicity, particularly in the tumor center at protein level, with enrichment of PIK3CA and ARID1A mutations and increased presence of exhausted CD8+ T cells as well as co-inhibitory receptors such as PD1, CTLA4, LAG3, and TIGIT. The remaining 48% of tumors were called non-inflamed based on the observed exclusion of T cell infiltration, with an overexpression of VEGFA and higher presence of TP53 mutations, resulting in a worse clinical outcome. A 10-gene RNA signature was developed for the identification of tumors belonging to these classes, demonstrating in evaluated datasets comparable clinical utility in predicting response to current immunotherapies when tested against other published gene signatures.ConclusionsComprehensive immunophenotyping of GAC identifies an inflamed class of tumors that complements previously proposed tumor-based molecular clusters. Such findings may provide the rationale for exploring novel immunotherapeutic approaches for biomarker-enriched populations in order to improve GAC patient’s survival.

The robotic approach to gastric cancer has been gaining interest in recent years; however, its benefit over the open procedure in total gastrectomy with D2 lymphadenectomy is still controversial. The aims of the study were to compare postoperative morbidity and mortality, hospital stay, and anatomopathological findings between the robotic and open approaches to oncologic total gastrectomy. We analyzed a prospectively collected database, which included patients who underwent total gastrectomy with D2 lymphadenectomy in our center using a robotic or an open approach between 2014 and 2021. Comparative analysis of clinicopathological, intraoperative, postoperative and anatomopathological variables between the robot-assisted group and the open group was performed. Thirty patients underwent total gastrectomy with D2 lymphadenectomy by a robotic approach and 48 patients by an open procedure. Both groups were comparable. The robot-assisted group presented a lower rate of Clavien-Dindo complications ≥ stage II (20 vs. 48%, p = 0.048), a shorter hospital stay (7 days vs. 9 days, p = 0.003) and had a higher total number of lymph nodes resected (22 nodes vs. 15 nodes, p = 0.001) compared to the open approach. Operative time was longer in the robotic group (325 min vs. 195 min, p < 0.001) compared to the open group. The robotic approach is associated with a longer surgical time, a lower rate of Clavien-Dindo complications ≥ stage II and a shorter hospital stay, and more lymph nodes were resected compared to the open approach.

Background Metastatic breast cancer is considered an incurable disease despite new therapies. Recent studies suggest that liver resection associated with systemic treatment may improve patient survival. Patients and methods Patient selection criteria were: good performance status, the feasibility of a complete and safe surgical procedure, and absence of uncontrolled extrahepatic metastases. The information was collected prospectively and analyzed retrospectively from our database. Results Between 1988 and 2006, 13 liver resections were performed in 12 patients owing to metastatic breast cancer. Two patients had synchronous metastases and ten metachronous metastases. One patient had extrahepatic bone metastases at the time of liver resection. Median follow-up was 35.9 months (range 12–113.4 months). Median age at liver resection was 58.4 years (range 36–76 years). Median hospital stay was 8 days (range 6–24 days); two patients had biliary leak but none died during the postoperative course. Seven patients (58.3%) developed hepatic recurrence. One-, 3-, and 5-year actuarial patient survival was 100%, 79%, and 33%, respectively. Patients who developed liver metastases within the first 24 months and after the first 24 months post-breast surgery had 1-, 3-, and 5-year actuarial patient survival of 100%, 0%, and 0% and 100%, 83%, and 60%, respectively ( P  < 0.025). Conclusion Liver resection for breast cancer liver metastases has an important role in the oncosurgical treatment of metastatic breast cancer with excellent 3-year survival.

Background/Objectives: Like many other countries, the management of pancreatic cancer in Spain has developed in a fragmented manner. This study analyzes clinical outcomes related to patient volume at different centers after left pancreatectomy (LP). Our goal is to determine whether our practices align with the standards established in the literature and assess whether centralization’s advantages significantly outweigh its disadvantages. Methods: The SPANDISPAN Project (SPANish DIStal PANcreatectomy) is an observational, prospective, multicenter study focused on LP conducted in Spanish Hepato-Pancreato-Biliary (HPB) Surgery Units from 1 February 2022 to 31 January 2023. HPB units were defined as high volume if they performed more than 10 LPs annually. Results: This study included 313 patients who underwent LP at 42 centers across Spain over the course of a year. A total of 40.3% of the procedures were performed in high-volume centers. Significant differences in preoperative variables were only observed in ASA scores, which were higher in the high-volume group. Intraoperatively, minimally invasive surgical techniques were performed more frequently in high-volume centers. Postoperatively, the administration of somatostatin, major complications, and B and C postoperative pancreatic fistula (POPF) were more frequent in low-volume hospitals. Conclusions: The findings revealed that high-volume centers had a higher rate of minimally invasive surgery, lower intraoperative bleeding, fewer complications, and reduced POPFs compared to low-volume centers. However, it is important to note that low-volume centers still demonstrated acceptable outcomes. Thus, the selective referral of more complex laparoscopic procedures could initiate a gradual centralization of surgical practices.

To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits. Both high- and low-grade esophagitis were induced in rabbits by the perfusion of acidified pepsin. Rabbits were treated with either a selective COX-2 inhibitor (DFU[3-(3-Fluorophenyl)-4-(4-Methanesulfonyl)-5,5-Dimethyl-5H-Furan-2-One];30 mg/Kg/day), a nonspecific COX inhibitor (indomethacin; 2 mg/Kg/day), or a COX-1 preferential inhibitor (piroxicam; 2 mg/Kg/12 h). Prostaglandins are derived from COX-1 activity in the normal esophagus. Both low- and high-grade esophagitis are associated with a progressive increase of COX activity, which is partially dependent on the COX-2 isoform. DFU reduced muscosal damage in both models of esophagitis. However, indomethacin did not affect significantly mucosal damage, and piroxicam increased damage in low-grade esophagitis. COX-1 activity is constitutive in the rabbit esophageal mucosa, but both COX-2 and COX-1 activity are increased under the impact of acidified pepsin. Treatment with the COX-2 inhibitor DFU is associated with improvement of mucosal damage, which may have therapeutic implications.

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p<0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

Background/Objectives: Palatability significantly influences food consumption, often leading to overeating and obesity by activating the brain’s reward systems. The nucleus accumbens (NAc) plays a central role in this process, modulating reward mechanisms primarily via dopamine through D2-like receptors (D2R, D3R, D4R). While the involvement of D2 receptors in feeding is well-documented, the role of D4 receptors (D4Rs) is less clear. Methods: Male Wistar rats received intra-NAc shell microinjections of the D4R agonist PD-168077 and the antagonist L-745870. This study also examined the modulation between D4R and glutamatergic transmission by administration of NMDA, NMDA receptor antagonist AP-5, AMPA, and AMPA receptor antagonist CNQX. Results: PD-168077 increased sweet solution intake by 46%, an effect that was reversed by L-745870. Pre-treatment with NMDA prevented the stimulatory effect of PD-168077, whereas the NMDA receptor antagonist AP-5 had no such effect. Additionally, AMPA administration reduced sweet solution intake by 63%, counteracting the effect of PD-168077, while the AMPA receptor antagonist CNQX, on its own, increased intake by 40%. Conclusions: These findings suggest that D4Rs promote hedonic feeding by modulating glutamatergic transmission in the NAc shell, highlighting the complexity of D4R involvement in food intake regulation. This study underscores the potential of targeting D4Rs for therapeutic interventions in eating disorders and obesity, though further research is essential to clarify the precise mechanisms through which D4R modulates AMPA and NMDA receptor activity in feeding behavior.

This article presents a Spanish adaption of the citizenship performance questionnaire of Coleman and Borman (2000) an analysis of its empirical structure. Once the original questionnaire was translated and adapted to a Spanish public administration context, it was administered to a sample of 135 public employees representing the complete staff ofa ´ Autonomic Government unit. Results show a high internal consistency of the questionnaire, although it seems to measure three related dimensions. Two of these dimensions are highly stable and coincide with those proposed by LePine, Erez, and Johnson (2002), Generalized Compliance and Altruism, while the third dimension is difficult to interpret. A second order factor analysis supports the existence of a unique underlying dimension of citizenship performance. These results have theoretical as well as practical implications that may help the interpretation and diagnosis in this domain. [PUBLICATION ABSTRACT]