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Objective/Background: Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied. Methods: MiTG and miDG patients were selected from 9356 oncological gastrectomies performed in 2017--2021 in 43 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis. Results: Three major anastomotic techniques [circular stapled (CS); linear stapled (LS); and hand sewn (HS)], and 3 major bowel reconstruction types [Roux (RX); Billroth I (BI); Billroth II (BII)] were identified in miTG (n= 878) and miDG (n=3334). Postoperative complications, including AL (5.2% vs 1.1%), overall (28.7% vs 16.3%), and major morbidity (15.7% vs 8.2%), as well as 90-day mortality (1.6% vs 0.5%) were higher after miTG compared with miDG. After miTG, the AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, and HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as a predictive factor for AL, overall, and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, and RX 1.2%), overall (BI: 14.5%, BII: 15.0%, and RX: 18.7%), and major morbidity (BI: 7.9%, BII: 9.1%, and RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, and RY: 1.1%%) were not affected by bowel reconstruction. Conclusions: In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to the surgeon's preference. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care. [ABSTRACT FROM AUTHOR]

This document provides a list of references to studies and articles that focus on surgical outcomes and benchmarking in various areas of surgery, including esophagogastric cancer surgery, gastrectomy for cancer, liver transplantation, and bariatric surgery. The studies aim to establish benchmarks and evaluate the quality of surgical interventions, with a particular emphasis on measuring surgical morbidity and complications. The articles offer insights into different surgical techniques, outcomes, and risk factors associated with different surgical procedures. [Extracted from the article]

Background: Aurora kinase A (AURKA) plays a pivotal role in regulating cell mitosis and tumor progression. However, its prognostic significance across diverse cancer types remains relatively unexplored. Methods: We conducted a comprehensive analysis of AURKA expression in various cancers using data from The Cancer Genome Atlas, Genotype-Tissue Expression, and The Human Protein Atlas databases. Our investigation encompassed an exploration of the associations between AURKA expression and clinical characteristics, shedding light on potential functional roles of AURKA. Additionally, we delved into the relationship between AURKA and the tumor microenvironment. To substantiate the role of AURKA, we carried out in vitro experiments in esophageal adenocarcinoma (EAC), prostate cancer (PRAD), and pancreatic cancer (PAAD) cells. Results: Our analysis revealed that AURKA is prominently overexpressed in a majority of the cancer types under investigation. Elevated AURKA expression correlated closely with poorer prognosis and advanced tumor stages. AURKA was found to be associated with key pathways involved in the cell cycle and arachidonic acid metabolism. Moreover, AURKA expression exhibited significant correlations with immunoregulatory genes and immune cell profiles. Notably, in vitro experiments demonstrated that silencing AURKA expression resulted in reduced cell viability in EAC, PRAD, and PAAD cells, as well as a decrease in clone formation, cell cycle elongation, diminished cell invasion and reduced spheroid size in EAC cells (OE33 and OE19). Conclusion: Our study elucidates the oncogenic role of AURKA and underscores its prognostic value across a spectrum of cancers, including EAC. These findings suggest that AURKA holds promise as a predictive biomarker for EAC and various other tumor types. [ABSTRACT FROM AUTHOR]

Intraoperative near-infrared fluorescence angiography with indocyanine green (ICG-FA) is a well-established modality in gastrointestinal surgery. Its main drawback is the application of a fluorescent agent with possible side effects for patients. The goal of this review paper is the presentation of alternative, non-invasive optical imaging methods and their comparison with ICG-FA. The principles of ICG-FA, spectral imaging, imaging photoplethysmography (iPPG), and their applications in gastrointestinal surgery are described based on selected published works. The main applications of the three modalities are the evaluation of tissue perfusion, the identification of risk structures, and tissue segmentation or classification. While the ICG-FA images are mainly evaluated visually, leading to subjective interpretations, quantitative physiological parameters and tissue segmentation are provided in spectral imaging and iPPG. The combination of ICG-FA and spectral imaging is a promising method. Non-invasive spectral imaging and iPPG have shown promising results in gastrointestinal surgery. They can overcome the main drawbacks of ICG-FA, i.e. the use of contrast agents, the lack of quantitative analysis, repeatability, and a difficult standardization of the acquisition. Further technical improvements and clinical evaluations are necessary to establish them in daily clinical routine. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer (OC) is the primary cause of mortality in women diagnosed with gynecological cancer. Our study assessed pressurized intraperitoneal aerosol chemotherapy (PIPAC) as treatment for peritoneal surface metastases (PSM) from recurrent or progressive OC and conducted survival analyses to identify prognostic factors. Material and methods: This retrospective cohort study, conducted across 18 international centers, analyzed the clinical practices of patients receiving palliative treatment for PSM from OC who underwent PIPAC. All patients were initially treated appropriately outside any clinical trial setting. Feasibility, safety, and morbidity were evaluated along with objective endpoints of oncological response. Multivariate analysis identified prognostic factors for OS and PFS. Results: From 2015-2020, 234 consecutive patients were studied, from which 192 patients were included and stratified by platinum sensitivity for analysis. Patients with early recurrence, within one postoperative month, were excluded. Baseline characteristics were similar between the groups regarding platinum sensitivity (platinum sensitive (PS) and resistant (PR)), but chemotherapy frequency differed, as did PCI before PIPAC. Median PCI decreased in both groups after three cycles of PIPAC (PS 16 vs. 12, p < 0.001; PR 24 vs. 20, p = 0.009). Overall morbidity was 22%, with few severe complications (4-8%) or mortality (0-3%). Higher pathological response and longer OS (22 vs. 11m, p = 0.012) and PFS (12 vs. 7m, p = 0.033) were observed in the PS group. Multivariate analysis (OS/PFS) identified ascites (HR 4.02, p < 0.001/5.22, p < 0.001), positive cytology at first PIPAC (HR 3.91, p = 0.002/1.96, p = 0.035), and ≥ 3 PIPACs (HR 0.30, p = 0.002/0.48, p = 0.017) as independent prognostic factors of overall survival/progression-free survival. Conclusions: With low morbidity and mortality rates, PIPAC is a safe option for palliative treatment of advanced ovarian cancer. Promising results were observed after 3 PIPAC, which did improve the peritoneal burden. However, further research is needed to evaluate the potential role of PIPAC as an independent prognostic factor. [ABSTRACT FROM AUTHOR]

α-Aminoxy peptides represent an interesting group of peptidomimetics with high proteolytic stability and the ability to fold into specific, predictable secondary structures. Here, we present a series of hybrid peptides consisting of α-aminoxy acids and α-amino acids with cationic and aromatic, hydrophobic side chains in an alternating manner synthesized using an efficient protocol that combines solution- and solid-phase synthesis. 2D ROESY experiments with a representative hexamer suggested the presence of a 7/8 helical conformation in solution. Biological evaluation revealed a significant impact of the peptide chain length and the N-terminal cap on the antimicrobial and anticancer properties of this series of hybrid peptides. The Fmoc-capped peptide 6e displayed the most potent antimicrobial activity against a panel of Gram-negative and Gram-positive bacterial strains (e. g. against E. Coli: MIC=8 mg/L; S. aureus: MIC=4 mg/L). [ABSTRACT FROM AUTHOR]

Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. Results: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (rg = 0.13, P = 2 × 10-04) and a rg of 0.12 between WHR and BE/EA (P = 1 × 10-02). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females (rg = 0.17, P = 1.2 × 10-03), and WHR and EA in males (rg = 0.18, P = 1.51 × 10-02). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10-03) and WHR and BE/EA risk variants (P = 2 × 10-02). Conclusions: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. [ABSTRACT FROM AUTHOR]

Despite improvements in operative strategies for esophageal resection, anastomotic leaks, fistula, postoperative pulmonary complications, and chylothorax can occur. Our review seeks to identify potential risk factors, modalities for early diagnosis, and novel interventions that may ameliorate the potential adverse effects of these surgical complications following esophagectomy. Surgical complications, such as anastomotic leaks, fistulas, postoperative pulmonary complications, and chylothoraxes, can occur following esophagectomy. This review seeks to identify potential risk factors, modalities for early diagnosis, and novel interventions that may ameliorate the potential adverse effects of these complications. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer (GC) patients with peritoneal metastasis (PM) have poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with systemic chemotherapy is a novel treatment option for patients in stage IV of the disease. Materials and Methods: Between November 2015 and June 2018, prospective data collection was performed in 24 patients with GC and PM (median age, 57; range, 44-75 years). These patients underwent 46 PIPAC procedures with a median number of 2 interventions per patient (range, 1-6). A laparoscopic access was used and a combined therapy of cisplatin and doxorubicin aerosol was administered. Results: The median peritoneal carcinomatosis index before the 1st PIPAC was 14 (range, 2-36), and the median ascites volume in patients before the 1st PIPAC was 100 mL (range, 0-6 mL, 300 mL). Eleven patients, who received 2 or more PIPAC procedures, had decreased and stable volumes of ascites, while only 3 patients displayed increasing volume of ascites. The median overall survival was 121 days (range, 66-625 days) after the 1st PIPAC procedure, while 8 patients who received more than 3 PIPAC procedures had a median survival of 450 days (range, 206-481 days) (P=0.0376). Conclusions: Our data show that PIPAC is safe and well tolerated, and that the production of ascites can be controlled by PIPAC in GC patients. Patients, who received 2 or more PIPAC procedures, reported a stable overall quality of life. Further studies are required to document the significance of PIPAC as a palliative multimodal therapy. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin complex 1 (mTORC1) is known to be a central cellular nutrient sensor and master regulator of protein metabolism; therefore, it is indispensable for normal embryonic development. We showed previously in a diabetic pregnancy that embryonic mTORC1 phosphorylation is increased in case of maternal hyperglycaemia and hypoinsulinaemia. Further, the preimplantation embryo is exposed to increased L-leucine levels during a diabetic pregnancy. To understand how mTOR signalling is regulated in preimplantation embryos, we examined consequences of L-leucine and glucose stimulation on mTORC1 signalling and downstream targets in in vitro cultured preimplantation rabbit blastocysts and in vivo. High levels of L-leucine and glucose lead to higher phosphorylation of mTORC1 and its downstream target ribosomal S6 kinase 1 (S6K1) in these embryos. Further, L-leucine supplementation resulted in higher embryonic expression of genes involved in cell cycle (cyclin D1; CCND1), translation initiation (eukaryotic translation initiation factor 4E; EIF4E), amino acid transport (large neutral amino acid transporter 2; Lat2: gene SLC7A8) and proliferation (proliferating cell nuclear antigen; PCNA) in a mTORC1-dependent manner. Phosphorylation of S6K1 and expression patterns of CCND1 and EIF4E were increased in embryos from diabetic rabbits, while the expression of proliferation marker PCNA was decreased. In these embryos, protein synthesis was increased and autophagic activity was decreased. We conclude that mammalian preimplantation embryos sense changes in nutrient supply via mTORC1 signalling. Therefore, mTORC1 may be a decisive mediator of metabolic programming in a diabetic pregnancy. [ABSTRACT FROM AUTHOR]

During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling. [ABSTRACT FROM AUTHOR]

Influenza A viruses recruit components of the nuclear import pathway to enter host cell nucleus and promote viral replication. Here, we analyzed the role of the nuclear import factor importin-α7 in H1N1 influenza virus pulmonary tropism using various ex vivo imaging techniques (magnetic resonance imaging, confocal laser-scanning microscopy and correlative light-electron microscopy). We infected importin-α7 gene deficient mice (α7-/-) with a recombinant H1N1 influenza virus and assessed in vivo viral kinetics in comparison to wild type (WT) mice. In WT mice, influenza virus replication occurred in bronchial and alveolar epithelium already a few days after infection. Accordingly, extensive mononuclear infiltration and alveolar destruction was present in lungs of infected WT mice followed by 100% lethality. Conversely, in α7-/- mice, virus replication was mostly restricted to bronchial epithelium with marginal alveolar infection resulting in significantly reduced lung damage and enhanced animal survival. To investigate the host immune response during alveolar virus replication, we studied the role of primary macrophages in virus propagation and clearance. The ability of macrophages to support or clear virus infection as well as the host cellular immune responses did not significantly differ between WT and α7-/- mice. However, cytokine and chemokine responses were generally elevated in WT mice likely reflective of increased viral replication in the lung. In summary, these data show that a cellular factor, importin-α7, is required for enhanced virus replication in the alveolar epithelium resulting in elevated cytokine and chemokine levels, extensive mononuclear infiltration and thus, severe pneumonia and enhanced virulence in mice. [ABSTRACT FROM AUTHOR]