Annexin A1 based inflammation resolving mediators and nanomedicines for inflammatory bowel disease therapy.

Inflammatory bowel diseases (IBD) such as Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic, progressive, and relapsing disorders of the gastrointestinal tract (GIT), characterised by intestinal epithelial injury and inflammation. Current research shows that in addition to traditional anti-inflammatory therapy, resolution of inflammation and repair of the epithelial barrier are key biological requirements in combating IBD. Resolution mediators include endogenous lipids that are generated during inflammation, e.g., lipoxins, resolvins, protectins, maresins; and proteins such as Annexin A1 (ANXA1). Nanoparticles can specifically deliver these potent inflammation resolving mediators in a spatiotemporal manner to IBD lesions, effectively resolve inflammation, and promote a return to homoeostasis with minimal collateral damage. We discuss these exciting and timely concepts in this review.

A nationwide population-based study on the clinical and economic burden of anastomotic leakage in colorectal surgery.

AIM: Anastomotic leakage (AL) is one of the most dreaded complications in colorectal surgery. In 2013, the International Classification of Diseases code K91.83 for AL was introduced in Germany, allowing nationwide analysis of AL rates and associated parameters. The aim of this population-based study was to investigate the current incidence, risk factors, mortality, clinical management, and associated costs of AL in colorectal surgery. METHODS: A data query was performed based on diagnosis-related group data of all hospital cases of inpatients undergoing colon or sphincter-preserving rectal resections between 2013 and 2018 in Germany. RESULTS: A total number of 690,690 inpatient cases were included in this study. AL rates were 6.7% for colon resections and 9.2% for rectal resections in 2018. Regarding the treatment of AL, the application of endoluminal vacuum therapy increased during the studied period, while rates of relaparotomy, abdominal vacuum therapy, and terminal enterostomy remained stable. AL was associated with significantly increased in-house mortality (7.11% vs. 20.11% for colon resections and 3.52% vs. 11.33% for rectal resections in 2018) and higher socioeconomic costs (mean hospital reimbursement volume per case: 14,877€ (no AL) vs. 37,521€ (AL) for colon resections and 14,602€ (no AL) vs. 30,606€ (AL) for rectal resections in 2018). CONCLUSIONS: During the studied time period, AL rates did not decrease, and associated mortality remained at a high level. Our study provides updated population-based data on the clinical and economic burden of AL in Germany. Focused research in the field of AL is still urgently necessary to develop targeted strategies to prevent AL, improve patient care, and decrease socioeconomic costs.

[Co-occurrence of Whipple's disease and hyperparathyroidism - coincidence or causal relationship?] / Gemeinsames Auftreten von Morbus Whipple und Hyperparathyreoidismus ­ Zufall oder kausaler Zusammenhang?

Whipple's disease is a rare infectious disease with multiple clinical manifestations. The disease is named after George Hoyt Whipple, who first recorded the illness in 1907 after conducting the autopsy of a 36-year-old man with weight loss, diarrhea, and arthritis. Under the microscope, Whipple discovered a rod-shaped bacterium in the patient's intestinal wall, which was not confirmed as a new bacterial species until 1992, when it was named Tropheryma whipplei.Recurrence of Whipple's disease can occur years after an initial diagnosis and often manifests with extraintestinal symptoms such as arthritides or skin efflorescences, years before a gastrointestinal complaint. However, the simultaneous occurrence of primary hyperparathyroidism in the present case is a hitherto unknown clinical picture and opens up new questions and perspectives in the context of diagnostics and therapy.

Crohn's disease: a population-based study of surgery in the age of biological therapy.

PURPOSE: Despite primary conservative therapy for Crohn's disease, a considerable proportion of patients ultimately needs to undergo surgery. Presumably, due to the increased use of biologics, the number of surgeries might have decreased. This study aimed to delineate current case numbers and trends in surgery in the era of biological therapy for Crohn's disease. METHODS: Nationwide standardized hospital discharge data (diagnosis-related groups statistics) from 2010 to 2017 were used. All patients who were admitted as inpatient Crohn's disease cases in Germany were included. Time-related development of admission numbers, rate of surgery, morbidity, and mortality of inpatient Crohn's disease cases were analyzed. RESULTS: A total number of 201,165 Crohn's disease cases were included. Within the analyzed time period, the total number of hospital admissions increased by 10.6% (n = 23,301 vs. 26,069). While gender and age distribution remained comparable, patients with comorbidities such as stenosis formation (2010: 10.1%, 2017: 13.4%) or malnutrition (2010: 0.8%, 2017: 3.2%) were increasingly admitted. The total number of all analyzed operations for Crohn's disease increased by 7.5% (2010: n = 1567; 2017: n = 1694). On average, 6.8 ± 0.2% of all inpatient patients received ileocolonic resections. Procedures have increasingly been performed minimally invasive (2010: n = 353; 2017: n = 687). The number of postoperative complications remained low. CONCLUSION: Despite the development of novel immunotherapeutics, the number of patients requiring surgery for Crohn's disease remains stable. Interestingly, patients have been increasingly hospitalized with stenosis and malnutrition. The trend towards more minimally invasive operations has not relevantly changed the rate of overall complications.

[Endometriosis and Menopause]. / Endometriose und Klimakterisches Syndrom.

Endometriosis and Menopause Abstract. Endometriosis is supposed to affect only women in their reproductive years, but endometriotic lesions can reactivate in menopause and cause significant complaints in these patients. Altered needs and co-morbidities of the women request a different approach in therapy than in the younger ages. Reduction in chronic pain on the one hand and alleviation of climacteric symptoms, like hot-flushes and vaginal dryness, on the other hand, are main concerns to the physician in charge. Consequently, keeping the balance between the hypoestrogenic state, which is necessary to reduce activity and size of endometriotic lesions, and hormone replacement therapy (HRT) to relief menopausal complaints, depicts the key in treating these women. Progesterons, GnRH-analoga (with addback) and intrauterine devices depict the basic therapeutic strategy in perimenopausal women. In case of uncertain sonographic findings or intractable symptoms, a surgical approach (and histology) should be performed. Aromatase inhibitors, melatonin, oral GnRH-antagonists and ablation of the endometrium (in bare dysmenorrhea) represent promising alternatives to the established therapy. Requesting an HRT, it is important to add progesterone for at least two years, even in the patients with a prior hysterectomy to avoid a recurrence of residual lesions.

A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro.

Adequate tissue engineered models are required to further understand the (patho)physiological mechanism involved in the destructive processes of cartilage and subchondral bone during rheumatoid arthritis (RA). Therefore, we developed a human in vitro 3D osteochondral tissue model (OTM), mimicking cytokine-induced cellular and matrix-related changes leading to cartilage degradation and bone destruction in order to ultimately provide a preclinical drug screening tool. To this end, the OTM was engineered by co-cultivation of mesenchymal stromal cell (MSC)-derived bone and cartilage components in a 3D environment. It was comprehensively characterized on cell, protein, and mRNA level. Stimulating the OTM with pro-inflammatory cytokines, relevant in RA (tumor necrosis factor α, interleukin-6, macrophage migration inhibitory factor), caused cell- and matrix-related changes, resulting in a significantly induced gene expression of lactate dehydrogenase A, interleukin-8 and tumor necrosis factor α in both, cartilage and bone, while the matrix metalloproteases 1 and 3 were only induced in cartilage. Finally, application of target-specific drugs prevented the induction of inflammation and matrix-degradation. Thus, we here provide evidence that our human in vitro 3D OTM mimics cytokine-induced cell- and matrix-related changes-key features of RA-and may serve as a preclinical tool for the evaluation of both new targets and potential drugs in a more translational setup.

Androgens sensitise mice to glucocorticoid-induced insulin resistance and fat accumulation.

AIMS/HYPOTHESIS: Chronic glucocorticoid therapy causes insulin resistance, dyslipidaemia, abnormal fat accumulation, loss of muscle mass and osteoporosis. Here we describe a hitherto unknown sexual dimorphism in the metabolic response to chronic glucocorticoid exposure in mice. This led us to investigate whether glucocorticoid-induced insulin resistance and obesity were dependent on sex hormones. METHODS: Male and female CD1 mice were treated for 4 weeks with supraphysiological doses (~250 µg/day) of corticosterone, the main glucocorticoid in rodents, or equivalent volume of vehicle (drinking water without corticosterone). To investigate the effects of sex hormones, a separate group of mice were either orchidectomised or ovariectomised prior to corticosterone treatment, with or without dihydrotestosterone replacement. Body composition was determined before and after corticosterone treatment, and insulin tolerance was assessed after 7 and 28 days of treatment. Adipocyte morphology was assessed in white and brown adipose tissues by immunohistochemistry, and fasting serum concentrations of NEFA, triacylglycerols, total cholesterol and free glycerol were measured using colorimetric assays. Obesity- and diabetes-related hormones were measured using multiplex assays, and RNA and protein expression in adipose tissues were measured by RT-PCR and immunoblotting, respectively. RESULTS: Chronic corticosterone treatment led to insulin resistance, fasting hyperinsulinaemia, increased adiposity and dyslipidaemia in male, but not female mice. In males, orchidectomy improved baseline insulin sensitivity and attenuated corticosterone-induced insulin resistance, but did not prevent fat accumulation. In androgen-deficient mice (orchidectomised males, and intact and ovariectomised females) treated with dihydrotestosterone, corticosterone treatment led to insulin resistance and dyslipidaemia. In brown adipose tissue, androgens were required for corticosterone-induced intracellular lipid accumulation ('whitening'), and dihydrotestosterone specifically exacerbated corticosterone-induced accumulation of white adipose tissue by increasing adipocyte hypertrophy. Androgens also suppressed circulating adiponectin concentrations, but corticosterone-induced insulin resistance did not involve additional suppression of adiponectin levels. In white adipose tissue, androgens were required for induction of the glucocorticoid target gene Gilz (also known as Tsc22d3) by corticosterone. CONCLUSIONS/INTERPRETATION: In mice, androgens potentiate the development of insulin resistance, fat accumulation and brown adipose tissue whitening following chronic glucocorticoid treatment.

Is it really penetration? Part 2. Locomotion of Enterococcus faecalis cells within dentinal tubules of bovine teeth.

OBJECTIVE: The aim of the present vitro study was to examine the question whether devitalized Enterococcus faecalis (E. faecalis) cells can migrate into dentinal tubules and if that process takes place in a time-dependent manner. DESIGN: Sixty bovine root canals were incubated with devitalized and vital streptomycin-resistant E. faecalis strains after root canal enlargement (size 80, taper .02) with 3% NaOCl solution. Incubation times 7, 14, 21, 28, 35, and 42 days. Samples were processed for analysis by scanning electron microscopy (SEM) and DAPI (4',6-diamidino-2-phenylindole) staining. The penetration depth was calculated with the measurement tool of the Axio Vision program (Zeiss, Jena, Germany). Statistical analysis was performed by Kruskal-Wallis (α = 0.05) and Mann-Whitney U test (p < 0.05). RESULTS: Devitalized E. faecalis strains were able to migrate into dentinal tubules. The total number and penetration depth of devitalized E. faecalis cells was lower compared to the vital suspension of E. faecalis. It was noted, that bacterial penetration was not common to all of the dentinal tubules in the vital E. faecalis control and especially in the devitalized control. The migration took place in a time-dependent migration characteristic. CONCLUSIONS: Devitalized E. faecalis cells are still able to migrate into the dentinal tubules due to possible electrokinetic and osmotic processes. Thereby, increased exposure times lead to a time-dependent penetration characteristic. CLINICAL RELEVANCE: Since devitalized bacteria can migrate as well into dentinal tubules, the presence of bacteria within dentinal tubules cannot be interpreted as a failure of tested preparation regimens.

[Can Pravastatin influence Pregnancies at High-risk for Preeclampsia?] / Pravastatin ­ Ein Lipidsenker zur Präeklampsie-Prophylaxe und Therapieoption?

Statins seem to positively influence the inflammatory, anti-angiogenic milieu of pregnancies with underlying placental ischemia by their pleiotropic effects. This might prevent, ameliorate and delay preeclampsia. To confirm the benefits of pravastatin on gestational age at birth as well as clinic and angiogenic markers in pregnancies at high-risk for preeclampsia, the Department of Obstetrics at the University Hospital Leipzig plans a randomized, double-blinded, placebo-controlled feasibility study.

Effect of Sonic Application of Self-etch Adhesives on Bonding Fiber Posts to Root Canal Dentin.

PURPOSE: To evaluate the effect of sonic application of 5 different self-etch adhesives on the push-out bond strength of fiber posts in root canals. MATERIALS AND METHODS: In a preliminary test, 24 teeth were treated with manual and sonically assisted bonding, then a composite cylinder was built up to test the shear bond strength as a proof of principle. In the main test, 120 root canals were endodontically prepared and divided into 10 groups: 5 self-etch adhesives (Futurabond DC, Futurabond M, Futurabond U, Optibond XTR, Universalbond), each applied under manual and sonic application modes. After insertion of the fiber posts using the specific adhesive and a dual-curing composite, the teeth were sectioned and the push-out test was performed. The specimens were analyzed by light and scanning electron microscopy. Statistical analysis was performed using the Shapiro-Wilk test, one-way ANOVA and the Tamhane test. RESULTS: Sonic application of self-etch adhesive systems did not increase the bond strength of fiber posts in root canals. In general, the bond strength decreased from the coronal to the apical part of the root canal, irrespective of the applied method. The best post retention was achieved with Futurabond U and Optibond XTR. CONCLUSION: Sonic application of self-etch adhesives did not improve the fiber post retention in the root canal and can therefore not be recommended. Nevertheless, sonic application of etch-and-rinse adhesives can increase the bond strength to coronal dentin.

Pediatric Colorectal Carcinoma is Associated With Excellent Outcome in the Context of Cancer Predisposition Syndromes.

INTRODUCTION: Colorectal carcinoma (CRC) is the second most common adult cancer in Germany, however, it is extremely rare in children and adolescents. In these patients, previous literature describes aggressive behavior and diagnosis at advanced stage. METHOD: Thirty-one patients with CRC age ≤ 18 years and treated between 1990 and 2012 have been identified through the structures and registries of the German Society for Pediatric Oncology and Hematology. RESULTS: The age range was 9-18 years (median 13.5 years); the median follow-up time was 43.9 months (range 1-124 months). Twenty-six patients (84%) were tested for a genetic tumor syndrome (GTS); of these, 11 patients (35% of all patients) tested positive (eight cases of Lynch syndrome, one patient with familial adenomatous polyposis, two patients with constitutional mismatch repair deficiency). An unfavorable histology was reported in 55% of the records (n = 17), a poor differentiation (grade III) in 68% of carcinoma (n = 21). Overall survival (OS) and event-free survival at 5 years was 52.0% and 65.6%, respectively. Five-year survival according to stage was 100% in stage II (n = 2), 100% in stage III (n = 13), and 12.9% in stage IV (n = 15; P < 0.001). Five-year OS in patients with and without a defined GTS was 100% and 36.5% (P = 0.019), respectively. CONCLUSION: Children and adolescents with CRC are frequently diagnosed in advanced stages and have an unfavorable prognosis. In this study, a high percentage of pediatric CRC patients presented with a tumor predisposition syndrome and showed an especially favorable OS.

Application of Plant Extracts for the Prevention of Dental Erosion: An in situ/in vitro Study.

OBJECTIVES: Antiadherent and antibacterial effects of certain plant extracts have been proven to be beneficial in preventive dentistry. In the present in situ/in vitro crossover study, the impact of plant extracts rich in polyphenols on the erosion-protective properties of the in situ pellicle was evaluated. METHODS: Individual splints were prepared for 12 subjects for intraoral exposure of bovine enamel specimens. Following formation of a 1-min pellicle, watery plant extracts (leaves of the wild form of Ribes nigrum, the wild form of Origanum as well as a combination of both) were administered for 10 min in situ. Alternatively, a mouth rinse with fluorides (Elmex Kariesschutz) was performed for 1 min. After further oral exposure for 19/28 min, respectively, slabs were removed and incubated with HCl in vitro over 120 s (pH 2, 2.3, 3). The resulting calcium and phosphate release was quantified photometrically. Slabs with and without a 30-min in situ pellicle served as controls. The modification of pellicle ultrastructure was evaluated by transmission electron microscopy (TEM). RESULTS: Plant extracts modulated the erosion-protective properties of the native in situ pellicle in all test groups in a pH-dependent manner. The combination of R. nigrum leaves and Origanum enhanced the protective properties of the pellicle at all pH values; the administration of this preparation was comparable, yet superior, to the effect of the fluoridated mouth rinse. TEM images indicated that rinsing with R. nigrum leaves/Origanum yielded a distinctly thicker and more electron-dense pellicle. CONCLUSION: The combination of certain plant extracts offers a novel approach to the complementary prevention of dental erosion.

Fractal analysis of extracellular matrix for observer-independent quantification of intestinal fibrosis in Crohn's disease.

Prevention of intestinal fibrosis remains an unresolved problem in the treatment of Crohn's disease (CD), as specific antifibrotic therapies are not yet available. Appropriate analysis of fibrosis severity is essential for assessing the therapeutic efficacy of potential antifibrotic drugs. The aim of this study was to develop an observer-independent method to quantify intestinal fibrosis in surgical specimens from patients with CD using structural analysis of the extracellular matrix (ECM). We performed fractal analysis in fibrotic and control histological sections of patients with surgery for CD (n = 28). To specifically assess the structure of the collagen matrix, polarized light microscopy was used. A score to quantify collagen fiber alignment and the color of the polarized light was established. Fractal dimension as a measure for the structural complexity correlated significantly with the histological fibrosis score whereas lacunarity as a measure for the compactness of the ECM showed a negative correlation. Polarized light microscopy to visualize the collagen network underlined the structural changes in the ECM network in advanced fibrosis. In conclusion, observer-independent quantification of the structural complexity of the ECM by fractal analysis is a suitable method to quantify the degree of intestinal fibrosis in histological samples from patients with CD.

B cell-mediated CD4 T-cell costimulation via CD86 exacerbates pro-inflammatory cytokine production during autoimmune intestinal inflammation.

Dysregulated B cell responses have been described in inflammatory bowel disease (IBD) patients; however, the role of B cells in IBD pathology remained incompletely understood. We here provide evidence for the detrimental role of activated B cells during the onset of autoimmune intestinal inflammation. Using Wiskott-Aldrich Syndrome interacting protein deficient (Wipf1-/-) mice as a mouse model of chronic colitis, we identified clusters of differentiation (CD)86 expression on activated B cells as a crucial factor exacerbating pro-inflammatory cytokine production of intestinal CD4 T cells. Depleting B cells through anti-CD20 antibody treatment or blocking costimulatory signals mediated by CD86 through cytotoxic T lymphocyte antigen-4-immunoglobulin (CTLA-4-Ig) diminished intestinal inflammation in our mouse model of chronic IBD at the onset of disease. This was due to a reduction in aberrant humoral immune responses and reduced CD4 T cell pro-inflammatory cytokine production, especially interferon-g (IFN-g) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, in addition to B cells isolated from the inflamed colon of Wipf1-/- mice, we also found CD86 mRNA and protein expression upregulated on activated B cells isolated from inflamed tissue of human patients with IBD. B cell activation and CD86 expression were boosted by soluble CD40L in vitro, which we found in the serum of mice and human patients with IBD. In summary, our data provides detailed insight into the contribution of B cells to intestinal inflammation, with implications for the treatment of IBD.

Perioperative Low-Dose Prednisolone Treatment Has Beneficial Effects on Postoperative Recovery and Anastomotic Healing in a Murine Colitis Model.

BACKGROUND AND AIMS: High-dose glucocorticoid treatment has been identified as a risk factor for anastomotic leakage in patients with inflammatory bowel disease [IBD] undergoing bowel resection surgery. By contrast, active disease during surgery is also associated with elevated morbidity. Perioperative low-dose treatment might be beneficial regarding postoperative outcomes by controlling disease activity. The present study is the first to investigate the dose-dependent effect of perioperative prednisolone therapy in a murine IBD model combining dextran sodium sulphate [DSS] colitis with intestinal anastomosis surgery. METHODS: In 84 10-week-old wild-type mice, a colorectal anastomosis was performed using a microsurgical technique. Half the animals received induction of chemical colitis with 2% DSS via drinking water prior to surgery. In both groups, one-third of the animals received daily oral administration of high-dose [0.533 mg/kg] and one-third low-dose [0.133 mg/kg] prednisolone. Evaluation was performed on postoperative days 3 and 7. RESULTS: While high-dose prednisolone treatment led to an increased anastomotic leakage rate in mice under colitis, low-dose prednisolone treatment limited preoperative disease activity and did not influence the leakage rate. Histological examination showed a beneficial effect of low-dose prednisolone treatment on microscopic abscess formation at the anastomotic site in DSS mice as well as an increased anastomotic healing score. CONCLUSIONS: We demonstrate a beneficial effect of perioperative short-term low-dose prednisolone treatment on intestinal anastomotic healing in the context of colitis. Perioperative use of short-term low-dose prednisolone treatment might be beneficial in IBD patients who need to undergo surgery during active disease.

CT Attenuation of Hepatic Pancreatic Cancer Metastases Correlates with Prognostically Detrimental Metastatic Necrosis.

Percutaneous CT-guided biopsy is a frequently performed procedure for the confirmation and molecular workup of hepatic metastases of pancreatic ductal adenocarcinoma (PDAC). Tumor necrosis of primary PDAC has shown a negative prognostic impact in recent studies. This study aims to examine predictability in CT scans and the prognostic impact of necrosis in hepatic metastases of PDAC. In this tertiary-center retrospective cohort study, we included 36 patients with hepatic metastases of PDAC who underwent CT-guided hepatic biopsies. Normalized attenuation of the biopsied metastasis was determined in venous phase contrast-enhanced planning scans obtained prior to biopsy by automatic, threshold-based 3D segmentation and manual, blinded 2D segmentation. A board-certified pathologist specialized in hepatic pathology histologically quantified the tumor necrosis and cellularity of the biopsy cylinders. We found a significant inverse-linear correlation between normalized attenuation and the fraction of necrosis (Pearson's r = 0.51, p < 0.001 for automatic 3D segmentation or Pearson's r = 0.52, p < 0.001 for manual 2D segmentation), whereas no correlation was found with tumor cellularity. Additionally, we discovered that patients with a fraction of necrosis ≥ 20% in metastases had a significantly shorter overall survival (p < 0.035). In summary, tumor necrosis of PDAC metastases can be estimated from contrast-enhanced CT scans, which could help to improve biopsy sample pattern planning. In addition, liver metastatic necrosis may serve as a prognostic biomarker in PDAC.

Gastrectomy for cancer beyond life expectancy. A comprehensive analysis of oncological gastric surgery in Germany between 2008 and 2018.

Introduction: Major gastric surgery for distal esophageal and gastric cancer has a strong impact on the quality of life, morbidity, and mortality. Especially in elderly patients reaching their life expectancy, the responsible use and extent of gastrectomy are imperative to achieve a balance between harm and benefit. In the present study, the reimbursement database (German Diagnosis Related Groups (G-DRG) database) of the Statistical Office of the Federal Republic of Germany was queried to evaluate the morbidity and mortality of patients aged above or below 75 years following gastrectomy. Material and methods: All patients in Germany undergoing subtotal gastrectomy (ST), total gastrectomy (T), or gastrectomy combined with esophagectomy (TE) for gastric or distal esophageal cancer (International Statistical Classification of Diseases and Related Health Problems Version 10 (ICD-10) C15.2, C15.5, and C16.0-C16.9) between 2008 and 2018 were included. Intraoperative and postoperative complications as well as comorbidities, in-hospital mortality, and the extent of surgery were assessed by evaluating ICD-10 and operation and procedure key (Operationen- und Prozedurenschlüssel) codes. Results: A total of 67,389 patients underwent oncologic gastric resection in Germany between 2008 and 2018. In total, 21,794 patients received ST, 41,825 received T, and 3,466 received TE, respectively. In 304 cases, the combinations of these, in fact, mutually exclusive procedures were encoded. The proportion of patients aged 75 years or older was 51.4% (n = 11,207) for ST, 32.6% (n = 13,617) for T, and 28.1% (n = 973) for TE. The in-hospital mortality of elderly patients was significantly increased in all three groups. (p < 0.0001) General complications such as respiratory failure (p = 0.0054), acute renal failure (p < 0.0001), acute myocardial failure (p < 0.0001), and the need for resuscitation (ST/T: p < 0.0001/TE: p = 0.0218) were significantly increased after any kind of gastrectomy. Roux-en Y was the most commonly applied reconstruction technique in both young and elderly patients. Regarding lymphadenectomy, systematic D2 dissection was performed less frequently in older patients than in the younger collective in the case of ST and T as well as D3 dissection. Peritonectomy and hyperthermic intraperitoneal chemotherapy were uncommon in elderly patients alongside ST and T compared to younger patients (p < 0.0001). Conclusion: The clinical outcome of major oncological gastric surgery is highly dependent on a patient's age. The elderly show a tremendously increased likelihood of in-hospital mortality and morbidity.