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BACKGROUND: The aim of this study was to investigate the patterns of recurrence and their associated risk factors in patients who underwent resection for pancreatic carcinoma. METHODS: This retrospective study included 272 patients, who underwent Ro/R1-resection of PDAC from 2005 to 2020 at the University Hospital Erlangen. Risk factors for different recurrence patterns and the prognostic value of recurrence pattern on the overall survival after recurrence were evaluated. RESULTS: 61 % of the patients experienced recurrence, mostly within the first 12 postoperative months (62 %) and in the form of metastases (87 %). The median overall survival from recurrence was 9.2 months. The preoperative absence of diabetes and the presence of lymph node metastasis were independent risk factors for recurrence and a preoperative CA19-9 exceeding 97 U/ml for early recurrence. Additionally, lymph node metastases were associated with a higher risk of metastatic recurrence. Early recurrence, but not the site of recurrence, was identified as an independent prognostic factor for worse overall survival from recurrence. CONCLUSION: The occurrence of recurrence and especially of early and metastatic recurrence are associated with a worse overall survival. Patients lacking preoperative diabetes, having high preoperative CA19-9 values and lymph node metastases are particularly at risk for (early) recurrence.
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Molecular phylogenetic research has relied on the analysis of the coding sequences by genes or of the amino acid sequences by the encoded proteins. Enumerating the numbers of mismatches, being indicators of mutation, has been central to pertinent algorithms. Specific amino acids possess quantifiable characteristics that enable the conversion from "words" (strings of letters denoting amino acids or bases) to "waves" (strings of quantitative values representing the physico-chemical properties) or to matrices (coordinates representing the positions in a comprehensive property space). The application of such numerical representations to evolutionary analysis takes into account not only the occurrence of mutations but also their properties as influences that drive speciation, because selective pressures favor certain mutations over others, and this predilection is represented in the characteristics of the incorporated amino acids (it is not born out solely by the mismatches). Besides being more discriminating sources for tree-generating algorithms than match/mismatch, the number strings can be examined for overall similarity with average mutual information, autocorrelation, and fractal dimension. Bivariate wavelet analysis aids in distinguishing hypermutable versus conserved domains of the protein. The matrix depiction is readily subjected to comparisons of distances, and it allows the generation of heat maps or graphs. This analysis preserves the accepted taxa order where tree construction with standard approaches yields conflicting results (for the protein S100A6). It also aids hypothesis generation about the origin of mitochondrial proteins. These analytical algorithms have been automated in R and are applicable to various processes that are describable in matrix format.
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INTRODUCTION: The purpose of this analysis was to investigate the most appropriate duration of postoperative antibiotic treatment to minimize the incidence of intraabdominal abscesses and wound infections in patients with complicated appendicitis. MATERIALS AND METHODS: In this retrospective study, which included 396 adult patients who underwent appendectomy for complicated appendicitis between January 2010 and December 2020 at the University Hospital Erlangen, patients were classified into two groups based on the duration of their postoperative antibiotic intake: ≤ 3 postoperative days (group 1) vs. ≥ 4 postoperative days (group 2). The incidence of postoperative intraabdominal abscesses and wound infections were compared between the groups. Additionally, multivariate risk factor analysis for the occurrence of intraabdominal abscesses and wound infections was performed. RESULTS: The two groups contained 226 and 170 patients, respectively. The incidence of postoperative intraabdominal abscesses (2% vs. 3%, p = 0.507) and wound infections (3% vs. 6%, p = 0.080) did not differ significantly between the groups. Multivariate analysis revealed that an additional cecum resection (OR 5.5 (95% CI 1.4-21.5), p = 0.014) was an independent risk factor for intraabdominal abscesses. A higher BMI (OR 5.9 (95% CI 1.2-29.2), p = 0.030) and conversion to an open procedure (OR 5.2 (95% CI 1.4-20.0), p = 0.016) were identified as independent risk factors for wound infections. CONCLUSION: The duration of postoperative antibiotic therapy does not appear to influence the incidence of postoperative intraabdominal abscesses and wound infections. Therefore, short-term postoperative antibiotic treatment should be preferred.
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Abscesso Abdominal , Antibacterianos , Apendicectomia , Apendicite , Infecção da Ferida Cirúrgica , Humanos , Apendicectomia/efeitos adversos , Apendicite/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Abscesso Abdominal/prevenção & controle , Abscesso Abdominal/etiologia , Antibacterianos/uso terapêutico , Adulto , Infecção da Ferida Cirúrgica/prevenção & controle , Pessoa de Meia-Idade , Incidência , Fatores de Risco , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologiaRESUMO
Gastrointestinal (GI) tumors pose a significant global health burden, necessitating the exploration of novel therapeutic approaches. Plasmacytoid dendritic cells (pDCs) play a crucial role in tumor immunity, exhibiting both anti-tumor and pro-tumor effects. This review aims to summarize the role of pDCs in different types of GI tumors and assess their potential as therapeutic targets. In gastric cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma, increased infiltration of pDCs was associated with a worse outcome, whereas in esophageal cancer, pancreatic cancer, and colorectal cancer, pDC infiltration improved the outcome. Initial animal studies of gastric cancer and hepatocellular carcinoma showed that pDCs could be a successful therapeutic target. In conclusion, pDCs play a multifaceted role in GI tumors, influencing both anti-tumor immunity and tumor progression. Further research is needed to optimize their clinical application and explore combinatorial approaches.
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PURPOSE: Nutrition status of patients with pancreatic ductal adenocarcinoma (PDAC) has gained an increasing importance - especially in the preoperative setting. The aim of the present study was to evaluate different preoperative nutritional parameters including body composition parameters regarding their impact on short- and long-term outcome in patients with resectable PDAC. METHODS: This retrospective single center study included 162 patients, who underwent primary resection of PDAC from January 2003 to December 2018 at the University Hospital of Erlangen. The influence of different preoperative nutrition parameters as well as different CT-based body composition parameters on short- (major morbidity, postoperative pancreatic fistula (POPF) and longer hospital stay) as well as on long-term outcome (overall and disease-free survival) were tested using multiple regression analysis. RESULTS: Major morbidity and POPF occurred in 30% respectively 18%. Median length of hospital stay was 18 days. Median overall and disease free survival were 20.3 respectively 12.0 months. Multivariate analysis revealed among the different nutritional parameters following independent predictors: PMTH (psoas muscle thickness/height) for major morbidity (HR 2.1, p = 0.038), PMA (psoas muscle area) for a prolonged hospital stay >18 days (HR 7.3, p = 0.010) and NRS (nutritional risk score) for overall survival (HR 1.7, p = 0.043). CONCLUSION: In our cohort, nutritional parameters played a minor role in predicting short- and long-term outcome in patients with primary resectable PDAC, as there were only significant associations between selected psoas muscle parameters and short-term outcome parameters and the nutritional risk score (NRS) with the overall survival.
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Carcinoma Ductal Pancreático , Estado Nutricional , Neoplasias Pancreáticas , Humanos , Masculino , Feminino , Estudos Retrospectivos , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Idoso , Pessoa de Meia-Idade , Prognóstico , Tempo de Internação , Composição Corporal , Complicações Pós-Operatórias , Resultado do Tratamento , Avaliação Nutricional , Pancreatectomia , Intervalo Livre de DoençaRESUMO
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters. Methods: Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed. Results: PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482). Conclusion: With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.
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Líquido Ascítico , Biomarcadores Tumorais , Carcinoma Ductal Pancreático , Exossomos , Neoplasias Pancreáticas , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Humanos , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Exossomos/metabolismo , Masculino , Líquido Ascítico/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Feminino , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Prognóstico , Idoso , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/metabolismo , Adulto , Estudos ProspectivosRESUMO
BACKGROUND: We previously reported that metastases are generally characterized by a core program of gene expression that activates tissue remodeling/vascularization, alters ion homeostasis, induces the oxidative metabolism, and silences extracellular matrix interactions. This core program distinguishes metastases from their originating primary tumors as well as from their destination host tissues. Therefore, the gene products involved are potential targets for anti-metastasis drug treatment. METHODS: Because the silencing of extracellular matrix interactions predisposes to anoiks in the absence of active survival mechanisms, we tested inhibitors against the other three components. RESULTS: Individually, the low-specificity VEGFR blocker pazopanib (in vivo combined with marimastat), the antioxidant dimethyl sulfoxide (or the substitute atovaquone, which is approved for internal administration), and the ionic modulators bumetanide and tetrathiomolybdate inhibited soft agar colony formation by breast and pancreatic cancer cell lines. The individual candidate agents have a record of use in humans (with limited efficacy when administered individually) and are available for repurposing. In combination, the effects of these drugs were additive or synergistic. In two mouse models of cancer (utilizing 4T1 cells or B16-F10 cells), the combination treatment with these medications, applied immediately (to prevent metastasis formation) or after a delay (to suppress established metastases), dramatically reduced the occurrence of disseminated foci. CONCLUSIONS: The combination of tissue remodeling inhibitors, suppressors of the oxidative metabolism, and ion homeostasis modulators has very strong promise for the treatment of metastases by multiple cancers.
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Indazóis , Pirimidinas , Sulfonamidas , Animais , Humanos , Camundongos , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Linhagem Celular Tumoral , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirimidinas/administração & dosagem , Feminino , Indazóis/farmacologia , Indazóis/uso terapêutico , Indazóis/administração & dosagem , Metástase Neoplásica , Molibdênio/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: The optimal management of colorectal lung metastases (CRLM) is still controversial. The aim of this study was to compare surgical and non-surgical treatment for CRLM regarding the prognostic outcome. METHODS: This retrospective single-center cohort study included 418 patients, who were treated from January 2000 to December 2018 at a German University Hospital due to their colorectal carcinoma and had synchronous or metachronous lung metastases. Patients were stratified according the treatment of the CRLM into two groups: surgical resection of CRLM versus no surgical resection of CRLM. The survival from the time of diagnosis of lung metastasis was compared between the groups. RESULTS: Two- and 5-year overall survival (OS) from the time of diagnosis of lung metastasis was 78.2% and 54.6%, respectively, in our cohort. Patients undergoing pulmonary metastasectomy showed a significantly better 2- and 5-year survival compared to patients with non-surgical treatment (2-year OS: 98.1% vs. 67.9%; 5-year OS: 81.2% vs. 28.8%; p < 0.001). Multivariate Cox regression revealed the surgical treatment (HR 4.51 (95% CI = 2.33-8.75, p < 0.001) and the absence of other metastases (HR 1.79 (95% CI = 1.05-3.04), p = 0.032) as independent prognostic factors in patients with CRLM. CONCLUSION: Our data suggest that patients with CRLM, who qualify for surgery, benefit from surgical treatment. Randomized controlled trials are needed to confirm our findings. CLINICAL TRIAL REGISTRY NUMBER: The work has been retrospectively registrated at the German Clinical Trial Registry (DRKS00032938).
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Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Estudos de Coortes , Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/cirurgia , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Current diagnostics for the detection of pancreato-biliary cancers (PBCs) need to be optimized. We therefore propose that methylated cell-free DNA (cfDNA) derived from non-invasive liquid biopsies serves as a novel biomarker with the ability to discriminate pancreato-biliary cancers from non-cancer pancreatitis patients. METHODS: Differentially methylated regions (DMRs) from plasma cfDNA between PBCs, pancreatitis and clinical control samples conditions were identified by next-generation sequencing after enrichment using methyl-binding domains and database searches to generate a discriminatory panel for a hybridization and capture assay with subsequent targeted high throughput sequencing. RESULTS: The hybridization and capture panel, covering around 74 kb in total, was applied to sequence a cohort of 25 PBCs, 25 pancreatitis patients, 25 clinical controls, and seven cases of Intraductal Papillary Mucinous Neoplasia (IPMN). An unbiased machine learning approach identified the 50 most discriminatory methylation markers for the discrimination of PBC from pancreatitis and controls resulting in an AUROC of 0.85 and 0.88 for a training (n = 45) and a validation (n = 37) data set, respectively. The panel was also able to distinguish high grade from low grade IPMN samples. CONCLUSIONS: We present a proof of concept for a methylation biomarker panel with better performance and improved discriminatory power than the current clinical marker CA19-9 for the discrimination of pancreato-biliary cancers from non-cancerous pancreatitis patients and clinical controls. This workflow might be used in future diagnostics for the detection of precancerous lesions, e.g. the identification of high grade IPMNs vs. low grade IPMNs.
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Carcinoma Ductal Pancreático , Ácidos Nucleicos Livres , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Pancreatite , Humanos , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Pancreatite/diagnóstico , Pancreatite/genética , Biópsia Líquida , Carcinoma Ductal Pancreático/patologiaAssuntos
Pancreaticoduodenectomia , Pancreaticojejunostomia , Procedimentos Cirúrgicos Robóticos , Pancreaticoduodenectomia/métodos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fístula Pancreática/prevenção & controle , Fístula Pancreática/etiologia , Anastomose Cirúrgica/métodos , Neoplasias Pancreáticas/cirurgia , Técnicas de SuturaRESUMO
Metastasizing cells display a unique metabolism, which is very different from the Warburg effect that arises in primary tumors. Over short time frames, oxidative phosphorylation and ATP generation are prominent. Over longer time frames, mitochondrial biogenesis becomes a pronounced feature and aids metastatic success. It has not been known whether or how these two phenomena are connected. We hypothesized that Osteopontin splice variants, which synergize to increase ATP levels in deadherent cells, also increase the mitochondrial mass via the same signaling mechanisms. Here, we report that autocrine Osteopontin does indeed stimulate an increase in mitochondrial size, with the splice variant -c being more effective than the full-length form -a. Osteopontin-c achieves this via its receptor CD44v, jointly with the upregulation and co-ligation of the chloride-dependent cystine-glutamate transporter SLC7A11. The signaling proceeds through activation of the known mitochondrial biogenesis inducer PGC-1 (which acts as a transcription coactivator). Peroxide is an important intermediate in this cascade, but surprisingly acts upstream of PGC-1 and is likely produced as a consequence of SLC7A11 recruitment and activation. In vivo, suppression of the biogenesis-inducing mechanisms leads to a reduction in disseminated tumor mass. This study confirms a functional connection between the short-term oxidative metabolism and the longer-term mitochondrial biogenesis in cancer metastasis - both are induced by Osteopontin-c. The results imply possible mechanisms and targets for treating cancer metastasis.
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Neoplasias , Biogênese de Organelas , Humanos , Trifosfato de Adenosina/metabolismo , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Osteopontina/genética , Osteopontina/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fatores de Transcrição/metabolismoRESUMO
INTRODUCTION: Bacteria play an important role not only in pathogenesis of appendicitis but also in the postoperative course of patients. However, the usefulness of an intraoperative swab during appendectomy is controversial. The primary aim of this study was to investigate the impact of intraoperative swab during appendectomy on the postoperative outcome in patients with uncomplicated and complicated appendicitis. METHODS: A retrospective analysis was conducted on a consecutive series of 1570 adult patients who underwent appendectomy for acute appendicitis at the University Hospital Erlangen between 2010 and 2020. Data regarding the intraoperative swab were collected and analyzed for the entire cohort as well as for patients with uncomplicated and complicated appendicitis. RESULTS: An intraoperative swab was taken in 29% of the cohort. The bacterial isolation rate in the obtained intraoperative swabs was 51%, with a significantly higher rate observed in patients with complicated appendicitis compared to those with uncomplicated appendicitis (79% vs. 35%, p < 0.001). The presence of a positive swab was significantly associated with worse postoperative outcomes, including higher morbidity, increased need for re-surgery, and longer hospital stay, when compared to patients without a swab or with a negative swab. A positive swab was an independent risk factor for postoperative morbidity (OR 9.9 (95% CI 1.2-81.9), p = 0.034) and the need for adjustment of postoperative antibiotic therapy (OR 8.8 (95% CI 1.1-72.5), p = 0.043). However, a positive swab resulted in postoperative antibiotic therapy adjustment in only 8% of the patients with bacterial isolation in the swab. CONCLUSION: The analysis of swab samples obtained during appendectomy for acute appendicitis can help identify patients at a higher risk of a worse postoperative outcome. However, the frequency of antibiotic regime changes based on the swab analysis is low.
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Apendicectomia , Apendicite , Adulto , Humanos , Apendicectomia/efeitos adversos , Apendicite/complicações , Apendicite/diagnóstico , Apendicite/cirurgia , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Hospitais UniversitáriosRESUMO
Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. In mice with FHL2 deficiency (FHL2KO), WTD feeding resulted in reduced body weight gain paralleled by enhanced energy expenditure and uncoupling protein 1 (UCP1) expression, indicative of activated thermogenesis. In human VAT, FHL2 was inversely correlated with UCP1 expression. Furthermore, macrophage infiltration and the expression of the chemokine MCP-1, a known promotor of macrophage accumulation, was significantly reduced in WTD-fed FHL2KO mice compared with wild-type (wt) littermates. While FHL2 depletion did not affect the differentiation or lipid metabolism of adipocytes in vitro, FHL2 depletion in macrophages resulted in reduced expressions of MCP-1 and the neuropeptide Y (NPY). Furthermore, WTD-fed FHL2KO mice showed reduced NPY expression in VAT compared with wt littermates, and NPY expression was enhanced in VAT resident macrophages of obese individuals. Stimulation with recombinant NPY induced not only UCP1 expression and lipid accumulation but also MCP-1 expression in adipocytes. Collectively, these findings indicate that FHL2 is a positive regulator of NPY and MCP-1 expression in macrophages and herewith closely linked to the mechanism of obesity-associated lipid accumulation and inflammation in VAT. Thus, FHL2 appears as a potential novel target to interfere with the macrophage-adipocyte crosstalk in VAT for treating obesity and related metabolic disorders.
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Gordura Intra-Abdominal , Neuropeptídeo Y , Animais , Humanos , Camundongos , Tecido Adiposo/metabolismo , Dieta , Dieta Hiperlipídica , Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Lipídeos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Neuropeptídeo Y/metabolismo , Obesidade/metabolismo , Fatores de Transcrição/metabolismoRESUMO
(1) Background: The aim of the present study was to identify risk factors associated with postoperative morbidity, suture/anastomotic insufficiency, re-surgery, and mortality in patients undergoing surgery for gastroduodenal perforation. (2) Methods: A retrospective analysis of 273 adult patients who received surgical treatment for gastroduodenal perforation from January 2006 to June 2021 at the University Hospital Erlangen was performed. The patient demographics and preoperative, intraoperative, and postoperative parameters were collected and compared among the different outcome groups (in-hospital morbidity, suture/anastomotic insufficiency, re-surgery, and 90-day mortality). (3) Results: In-hospital morbidity, suture/anastomotic insufficiency, need for re-surgery, and 90-day mortality occurred in 71%, 10%, 26%, and 25% of patients, respectively. The independent risk factors for morbidity were a significantly reduced general condition, a lower preoperative hemoglobin level, and a higher preoperative creatinine level. The independent risk factors for suture/anastomotic insufficiency could be identified as an intake of preoperative steroids and a perforation localization in the proximal stomach or duodenum. The four parameters were independent risk factors for the need for re-surgery: a significantly reduced general condition, a perforation localization in the proximal stomach, a higher preoperative creatinine level, and a higher preoperative CRP level. An age over 66 years and a higher preoperative CRP level were independent risk factors for 90-day mortality. (4) Conclusions: Our study could identify relevant risk factors for the postoperative outcome of patients undergoing surgical treatment for gastroduodenal perforation. Patients exhibiting the identified risk factors should receive heightened attention in the postoperative period and may potentially benefit from personalized and tailored therapy.
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(1) Background: Since its introduction in the 1990s, laparoscopic appendectomy has become established over the years and is today considered the standard therapy for acute appendicitis. In some cases, however, a conversion to the open approach is still necessary. The primary aim of this study was to identify risk factors for the need to convert from the laparoscopic to an open approach during appendectomy for acute appendicitis. (2) Methods: A retrospective analysis of 1220 adult patients who underwent laparoscopic appendectomy for acute appendicitis from 2010 to 2020 at the University Hospital Erlangen was performed. Data, including patient demographics and pre-, intra-, and postoperative findings, were collected and compared between patients with and without conversion. (3) Results: The conversion rate in our cohort was 5.5%. A higher preoperative WBC count and CRP (OR 1.9, p = 0.042, and OR 2.3, p = 0.019, respectively), as well as the presence of intraoperative perforation, necrosis or gangrene, perityphlitic abscess and peritonitis (OR 3.2, p = 0.001; OR 2.3, p = 0.023; OR 2.6, p = 0.006 and OR 2.0, p = 0.025, respectively) were identified as independent risk factors for conversion from the laparoscopic to the open approach. Conversion was again independently associated with higher morbidity (OR 2.2, p = 0.043). (4) Conclusion: The laparoscopic approach is feasible and safe in the majority of patients with acute appendicitis. Only increased inflammatory blood markers could be detected as the preoperative risk factors potentially influencing the choice of surgical approach but only with low specificity and sensitivity. For the decision to convert, intraoperative findings are additionally crucial. However, patients with conversion should receive special attention in the postoperative course, as these have an increased risk of developing complications.
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Robot-assisted systems have been increasingly used in general surgery for several years. Accordingly, the number of systems installed in Germany has also rapidly increased. While around 100 robot-assisted systems were used in German hospitals in 2018, this figure had already risen to more than 200 by 2022. The aim of this article is to present the current state of development and trends in robotic surgery in Germany. For this purpose, data from the StuDoQ|Robotics register were analyzed. Furthermore, a descriptive analysis of concomitant diagnosis-related groups (DRG) data was carried out via the Federal Statistical Office (Destatis), for a better assessment of the representativeness of the StuDoQ|Robotics register data. In both data sets, the annual number of robot-assisted visceral surgery procedures in Germany steadily increased. Compared to the DRG data, only 3.7% up to a maximum of 36.7% of all robot-assisted procedures performed were documented in the StuDoQ|Robotics register, depending on the type of procedure. Colorectal resections were the most frequent robot-assisted procedures (StuDoQ: 32.5% and 36.7% vs. DRG data: 24.2% and 29.7%) and had, for example, low mortality rates (StuDoQ: 1% and 1% vs. DRG data: 2.3% and 1.3%). Due to the low coverage rates of robot-assisted esophageal, gastric, pancreatic and liver interventions, no valid statements could be derived from the StuDoQ data for these areas. With the current coverage rates, the informative value of the StuDoQ|Robotics register is considerably limited for some types of intervention. In the future, measures should therefore be explored that lead to a significant increase in the coverage rates.
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Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Robóticos , Robótica , Alemanha/epidemiologia , Sistema de RegistrosRESUMO
Inflammatory bowel diseases (IBDs) are a global health issue with an increasing incidence. Although the pathogenesis of IBDs has been investigated intensively, the etiology of IBDs remains enigmatic. Here, we report that interleukin-3 (Il-3)-deficient mice are more susceptible and exhibit increased intestinal inflammation during the early stage of experimental colitis. IL-3 is locally expressed in the colon by cells harboring a mesenchymal stem cell phenotype and protects by promoting the early recruitment of splenic neutrophils with high microbicidal capability into the colon. Mechanistically, IL-3-dependent neutrophil recruitment involves CCL5+ PD-1high LAG-3high T cells, STAT5, and CCL20 and is sustained by extramedullary splenic hematopoiesis. During acute colitis, Il-3-/- show, however, increased resistance to the disease as well as reduced intestinal inflammation. Altogether, this study deepens our understanding of IBD pathogenesis, identifies IL-3 as an orchestrator of intestinal inflammation, and reveals the spleen as an emergency reservoir for neutrophils during colonic inflammation.
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Colite Ulcerativa , Interleucina-3 , Animais , Camundongos , Colite/patologia , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/patologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Camundongos Endogâmicos C57BL , Neutrófilos/patologia , Baço/patologiaRESUMO
(1) Background: The intake of aspirin (ASS) has been demonstrated to have a relevant impact on the pathogenesis, incidence and outcome in different solid gastrointestinal tumors. However, data on the effect of ASS on the short-term outcome and the long-term survival in patients with pancreatic carcinoma are still limited. (2) Methods: A total of 213 patients who underwent primary resection of PDAC at the University Hospital of Erlangen from January 2000 to December 2018 were included in this retrospective single-center study in total. Patients were stratified according to the aspirin intake into three groups: continuous aspirin intake (cASS), perioperatively interrupted aspirin intake (iASS) and no aspirin intake (no ASS) at the timepoint of surgery. The postoperative outcome as well as long-term survival were compared between the groups. (3) Results: There were no differences regarding postoperative morbidity (iASS: 54% vs. cASS: 53% vs. no ASS: 64%, p = 0.448) and in-hospital mortality (iASS: 4% vs. cASS: 10% vs. no ASS: 3%, p = 0.198) between the groups. The overall survival (OS) and disease-free survival (DFS) did not differ in the groups when comparing the ASS-intake status (OS: iASS 17.8 months vs. cASS 19.6 months vs. no ASS 21.6 months, p = 0.489; DFS: iASS 14.0 months vs. cASS 18.3 months vs. no ASS 14.7 months, p = 0.957). Multivariate analysis revealed that age (hazard ratio (HR) 2.2, p < 0.001), lymph node-positive status (HR 2.0, p < 0.001), R status 1 or 2 (HR 2.8, p < 0.001) and differentiation with a grading of 3 (HR 1.7, p = 0.005) were significant independent prognostic factors regarding the OS. Moreover, age (HR 1.5, p = 0.040), lymph node-positive status (HR 1.8, p = 0.002) and high-grade (G3) carcinomas (HR 1.5, p = 0.037) could be identified as independent prognostic parameters for DFS. (4) Conclusions: In patients undergoing primary surgery for curative resection of pancreatic carcinoma, the perioperative intake of ASS had no significant impact on postoperative outcome, overall and disease-free survival.