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The liver is innervated by primary sensory nerve fibres releasing the neuropeptide calcitonin gene-related peptide (CGRP). Elevated plasma levels of CGRP have been found in patients with liver fibrosis or cirrhosis. We hypothesised that signalling of CGRP and its receptors might regulate liver fibrosis and propose a novel potential target for the treatment. In this study, hepatic expression of CGRP and its receptor component, the receptor activity-modifying protein 1 (RAMP1), was dramatically increased in diseased livers of patients. In a murine liver fibrosis model, deficiency of RAMP1 resulted in attenuated fibrogenesis characterized by less collagen deposition and decreased activity of hepatic stellate cells (HSC). Mechanistically, activity of the TGFß1 signalling core component Smad2 was severely impaired in the absence of RAMP1, and Yes-associated protein (YAP) activity was found to be diminished in RAMP1-deficient liver parenchyma. In vitro, stimulation of the HSC line LX-2 cells with CGRP induces TGFß1 production and downstream signalling as well as HSC activation documented by increased α-SMA expression and collagen synthesis. We further demonstrate in LX-2 cells that CGRP promotes YAP activation and its nuclear translocation subsequent to TGFß1/Smad2 signals. These data support a promotive effect of CGRP signalling in liver fibrosis via stimulation of TGFß1/Smad2 and YAP activity.
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Many pancreatic neuroendocrine tumors (PanNETs) fall into two major prognostic subtypes based on DAXX/ATRX induced ALT phenotype and alpha and beta cell-like epigenomic profiles. However, these PanNETs are still flanked by other PanNETs that do not fit into either subtype. Furthermore, despite advanced genotyping, PanNETs are generally not well characterized in terms of their histological and hormonal phenotype. We aimed to identify new subgroups of PanNETs by extending the currently used transcription factor signatures and to investigate their correlation with histological, hormonal molecular and prognostic findings. 185 PanNETs (non-functioning 165, functioning 20) resected between 1996 and 2023 were classified into five subgroups (A1, A2, B, C, D) by cluster analysis based on ARX, PDX1, ISL1 and CDX2 expression and correlated with trabecular vs. solid histology, expression of insulin, glucagon, PP, somatostatin, serotonin, gastrin, calcitonin, ACTH, DAXX/ATRX, MEN1 and ALT status by FISH, and disease-free survival (DFS). A1 (46%, ARX+/ISL1+/PDX1-/CDX2-) and A2 (15%, ARX+/ISL1+/PDX1+/CDX2-) showed trabecular histology and glucagon/ PP expression, with A2 also showing gastrin expression. B (18%, PDX1+/ISL1+/ARX-/CDX2-) showed solid histology, insulin and somatostatin expression (p<0.001). It included all insulinomas and had the best outcome (p<0.01). C (15%, ARX-/PDX1-/ISL1-/CDX2-) showed solid histology and frequent expression of serotonin, calcitonin und ACTH. D (5%, PDX1+/CDX2+/ISL1-/ARX-) showed solid histology, expressed ACTH/serotonin and was an independent poor prognosticator (p<0.01). Differential expression of ARX, PDX1, ISL1 and CDX2 stratified PanNETs into five subgroups with different histology, hormone expression and outcome. Subgroups A1 and A2 resembled the alpha cell-like type, subgroup B the beta cell-like type. Subgroup C with almost a no transcription factor signature was unclear in cell lineage, while the PDX+/CDX2+ signature of subgroup D suggested a pancreatic/intestinal cell lineage. Assigning PanNETs to the subgroups may help to establish the diagnosis, predict the outcome, and guide the treatment.
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OBJECTIVE: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD). BACKGROUND: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience. METHODS: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSION: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries.
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INTRODUCTION: Surgical documentation has many implications. However, its primary function is to transfer information about surgical procedures to other medical professionals. Thereby, written reports describing procedures in detail are the current standard, impeding comprehensive understanding of patient-individual life-spanning surgical course, especially if surgeries are performed at a timely distance and in diverse facilities. Therefore, we developed a novel model-based approach for documentation of visceral surgeries, denoted as 'Surgical Documentation Markup-Modeling' (SDM-M). MATERIAL AND METHODS: For scientific evaluation, we developed a web-based prototype software allowing for creating hierarchical anatomical models that can be modified by individual surgery-related markup information. Thus, a patient's cumulated 'surgical load' can be displayed on a timeline deploying interactive anatomical 3D models. To evaluate the possible impact on daily clinical routine, we performed an evaluation study with 24 surgeons and advanced medical students, elaborating on simulated complex surgical cases, once with classic written reports and once with our prototypical SDM-M software. RESULTS: Leveraging SDM-M in an experimental environment reduced the time needed for elaborating simulated complex surgical cases from 354 ± 85 s with the classic approach to 277 ± 128 s. (p = 0.00109) The perceived task load measured by the Raw NASA-TLX was reduced significantly (p = 0.00003) with decreased mental (p = 0.00004) and physical (p = 0.01403) demand. Also, time demand (p = 0.00041), performance (p = 0.00161), effort (p = 0.00024), and frustration (p = 0.00031) were improved significantly. DISCUSSION: Model-based approaches for life-spanning surgical documentation could improve the daily clinical elaboration and understanding of complex cases in visceral surgery. Besides reduced workload and time sparing, even a more structured assessment of individual surgical cases could foster improved planning of further surgeries, information transfer, and even scientific evaluation, considering the cumulative 'surgical load.' CONCLUSION: Life-spanning model-based documentation of visceral surgical cases could significantly improve surgery and workload.
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The mandatory usage of extracellular matrix (ECM) gels in 3D cultures limits antibody penetration and increases background, while the removal of ECM gel causes disruption of morphology and sample loss. These factors pose challenges to effective immune labeling-based staining. Here, we present a protocol for whole-mount immunofluorescence staining of gel-embedded pancreatic organoids. We describe steps for sample fixation, blocking, and antibody incubation. We detail procedures for washing antibodies and mounting.
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Matriz Extracelular , Imunofluorescência , Organoides , Pâncreas , Organoides/citologia , Organoides/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Pâncreas/citologia , Pâncreas/metabolismo , Imunofluorescência/métodos , Animais , Coloração e Rotulagem/métodos , Humanos , Géis/química , CamundongosRESUMO
BACKGROUND: Pancreatic cancer is often accompanied by wasting conditions. While surgery is the primary curative approach, it poses a substantial risk of postoperative complications, hindering subsequent treatments. Therefore, identifying patients at high risk for complications and optimizing their perioperative general condition is crucial. Sarcopenia and other body composition abnormalities have shown to adversely affect surgical and oncological outcomes in various cancer patients. As most pancreatic tumours are located close to the neuronal control centre for the digestive tract, it is possible that neural infiltration in this area deranges bowel functions and contributes to malabsorption and malnutrition and ultimately worsen sarcopenia and weight loss. METHODS: A retrospective analysis of CT scans was performed for pancreatic cancer patients who underwent surgical tumour resection at a single high-volume centre from 2007 to 2023. Sarcopenia prevalence was assessed by skeletal muscle index (SMI), and visceral obesity was determined by the visceral adipose tissue area (VAT). Obesity and malnutrition were determined by the GLIM criteria. Sarcopenic obesity was defined as simultaneous sarcopenia and obesity. Postoperative complications, mortality and perineural tumour invasion, were compared among patients with body composition abnormalities. RESULTS: Of 437 patients studied, 46% were female, the median age was 69 (61;74) years. CT analysis revealed 54.9% of patients with sarcopenia, 23.7% with sarcopenic obesity and 45.9% with visceral obesity. Sarcopenia and sarcopenic obesity were more prevalent in elderly and male patients. Postoperative surgical complications occurred in 67.7% of patients, most of which were mild (41.6%). Severe complications occurred in 22.7% of cases and the mortality rate was 3.4%. Severe postoperative complications were significantly more common in patients with sarcopenia or sarcopenic obesity. Visceral obesity or malnutrition based on BMI alone, did not significantly impact complications. Perineural invasion was found in 80.1% of patients and was unrelated to malnutrition or body composition parameters. CONCLUSIONS: This is the first and largest study evaluating the associations of CT-based body mass analysis with surgical outcome and histopathological perineural tumour invasion in pancreatic cancer patients. The results suggest that elderly and male patients are at high risk for sarcopenia and should be routinely evaluated by CT before undergoing pancreatic surgery, irrespective of their BMI. Confirmation of the results in prospective studies is needed to assess if pancreatic cancer patients with radiographic sarcopenia benefit from preoperative amelioration of muscle mass and function by exercise and nutritional interventions.
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Composição Corporal , Pancreatectomia , Neoplasias Pancreáticas , Complicações Pós-Operatórias , Sarcopenia , Humanos , Masculino , Feminino , Idoso , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Sarcopenia/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pancreatectomia/métodos , Invasividade Neoplásica , Obesidade/complicações , Tomografia Computadorizada por Raios XRESUMO
Even after decades of research, pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease and responses to conventional treatments remain mostly poor. Subclassification of PDAC into distinct biological subtypes has been proposed by various groups to further improve patient outcome and reduce unnecessary side effects. Recently, an immunohistochemistry (IHC)-based subtyping method using cytokeratin-81 (KRT81) and hepatocyte nuclear factor 1A (HNF1A) could recapitulate some of the previously established molecular subtyping methods, while providing significant prognostic and, to a limited degree, also predictive information. We refined the KRT81/HNF1A subtyping method to classify PDAC into three distinct biological subtypes. The prognostic value of the IHC-based method was investigated in two primary resected cohorts, which include 269 and 286 patients, respectively. In the second cohort, we also assessed the predictive effect for response to erlotinib + gemcitabine. In both PDAC cohorts, the new HNF1A-positive subtype was associated with the best survival, the KRT81-positive subtype with the worst, and the double-negative with an intermediate survival (p < 0.001 and p < 0.001, respectively) in univariate and multivariate analyses. In the second cohort (CONKO-005), the IHC-based subtype was additionally found to have a potential predictive value for the erlotinib-based treatment effect. The revised IHC-based subtyping using KRT81 and HNF1A has prognostic significance for PDAC patients and may be of value in predicting treatment response to specific therapeutic agents.
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Biomarcadores Tumorais , Carcinoma Ductal Pancreático , Fator 1-alfa Nuclear de Hepatócito , Queratinas Tipo II , Neoplasias Pancreáticas , Valor Preditivo dos Testes , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Cloridrato de Erlotinib/uso terapêutico , Gencitabina , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Queratinas Específicas do Cabelo/metabolismo , Queratinas Específicas do Cabelo/análise , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/metabolismo , Prognóstico , Queratinas Tipo II/análise , Queratinas Tipo II/metabolismoRESUMO
BACKGROUND: Pancreaticoduodenectomy can entail a high complication rate, especially in patients who underwent preoperative bile duct drainage through bile duct stenting. Pancreaticoduodenectomy bile duct stenting patients frequently receive prophylactic antibiotic therapy in the postoperative period. However, the exact value and the benefit of prophylactic antibiotic therapy in pancreaticoduodenectomy bile duct stenting patients remains under-investigated and thus unclear. METHOD: We conducted a retrospective single-center study of pancreaticoduodenectomy bile duct stenting patients between January 2007 and December 2022. Demographic, clinical, laboratory, and pathology data of 370 patients were collected, and intraoperative swab cultures of the bile were obtained from all patients upon transection of the common bile duct. The groups to be investigated were formed on the basis of postoperative antibiotic prophylaxis. Postoperative complications and antibiotic resistance analysis were recorded. RESULTS: Postoperative antibiotic prophylaxis in stented patients after pancreaticoduodenectomy significantly reduced major complications (odds ratio: 0.547 [95% confidence interval 0.327-0.915]; P = .02) such as reoperation (P = .041) and readmission to the intensive care unit (P = .037). Patients with Enterococcus faecalis (odds ratio: 1.699 [95% confidence interval 0.978-2.950];P = .048), Enterococcus faecium (odds ratio: 1.808 [95% confidence interval 1.001-3.264]; P = .050), or Citrobacter (odds ratio: 2.211 [95% confidence interval 1.087-4.497]; P = .029) in their bile had a higher probability of developing wound infections. Appropriate antibiotic prophylaxis, according to the bile duct microbiome, significantly reduced the risk of wound infection (odds ratio: 2.239 [95% confidence interval 1.167-4.298]; P = .015). CONCLUSION: Postoperative antibiotic prophylaxis in pancreaticoduodenectomy bile duct stenting patients significantly reduced major complications such as intensive care stay and reoperation. Targeted antibiotic treatment according to the biliary microbiome reduced the incidence of wound infections.
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INTRODUCTION: Resection of colorectal liver metastasis has emerged as the standard treatment. Our study compares oncological outcomes of patients with resected synchronous bilobar versus unilobar colorectal liver metastasis. METHODS: This retrospective study presents long-term follow-up data of 105 consecutive patients with primary colorectal cancer and synchronous liver metastasis. All patients underwent primary tumor and metastasis resections between 2007 and 2019. RESULTS: Fifty-five patients with bilobar and 50 patients with unilobar colorectal liver metastases were included. No significant difference in overall, tumor-specific, or recurrence-free survival was observed between patients with bilobar and unilobar metastases. After case-control matching, the results were confirmed in patients with similar tumor burdens. In the multivariate analysis, chemotherapy following liver metastasis resection was a significant prognostic factor associated with improved overall survival (hazard ratio 0.518, 95% confidence interval: 0.302-0.888, p = 0.017). CONCLUSION: Overall survival, as well as tumor-specific and recurrence-free survival, did not differ between patients with unilobar and bilobar liver metastasis. These findings contribute to the understanding that primary tumor and metastasis resection in eligible patients improve long-term outcomes.
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PURPOSE: Gastrointestinal disorders frequently necessitate surgery involving intestinal resection and anastomosis formation, potentially leading to severe complications like anastomotic leakage (AL) which is associated with increased morbidity, mortality, and adverse oncologic outcomes. While extensive research has explored the biology of anastomotic healing, there is limited understanding of the biomechanical properties of gastrointestinal anastomoses, which was aimed to be unraveled in this study. METHODS: An ex-vivo model was developed for the biomechanical analysis of 32 handsewn porcine end-to-end anastomoses, using interrupted and continuous suture techniques subjected to different flow models. While multiple cameras captured different angles of the anastomosis, comprehensive data recording of pressure, time, and temperature was performed simultaneously. Special focus was laid on monitoring time, location and pressure of anastomotic leakage (LP) and bursting pressures (BP) depending on suture techniques and flow models. RESULTS: Significant differences in LP, BP, and time intervals were observed based on the flow model but not on the suture techniques applied. Interestingly, anastomoses at the insertion site of the mesentery exhibited significantly higher rates of leakage and bursting compared to other sections of the anastomosis. CONCLUSION: The developed ex-vivo model facilitated comparable, reproducible, and user-independent biomechanical analyses. Assessing biomechanical properties of anastomoses offers an advantage in identifying technical weak points to refine surgical techniques, potentially reducing complications like AL. The results indicate that mesenteric insertion serves as a potential weak spot for AL, warranting further investigations and refinements in surgical techniques to optimize outcomes in this critical area of anastomotic procedures.
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Fístula Anastomótica , Mesentério , Animais , Suínos , Fístula Anastomótica/prevenção & controle , Anastomose Cirúrgica , Mesentério/cirurgia , Técnicas de Sutura , CicatrizaçãoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at advanced stages and associated with early distant metastasis and poor survival. Besides clinical factors, the tumor microenvironment (TME) emerged as a crucial determinant of patient survival and therapy response in many tumors, including PDAC. Thus, the presence of tumor-infiltrating lymphocytes and the formation of tertiary lymphoid structures (TLS) is associated with longer survival in PDAC. Although neoadjuvant therapy (NeoTx) has improved the management of locally advanced tumors, detailed insight into its effect on various TME components is limited. While a remodeling towards a proinflammatory state was reported for PDAC-infiltrating T cells, the effect of NeoTx on B cell subsets, including plasma cells, and TLS formation is widely unclear. We thus investigated the frequency, composition, and spatial distribution of PDAC-infiltrating B cells in primary resected (PR) versus neoadjuvant-treated patients using a novel multiplex immunohistochemistry panel. The NeoTx group displayed significantly lower frequencies of pan B cells, GC B cells, plasmablasts, and plasma cells, accompanied by a reduced abundance of TLS. This finding was supported by bulk RNA-sequencing analysis of an independent fresh frozen tissue cohort, which revealed that major B cell pathways were downregulated in the NeoTx group. We further observed that plasma cells frequently formed aggregates that localized close to TLS and that TLS+ patients displayed significantly higher plasma cell frequencies compared to TLS- patients in the PR group. Additionally, high densities of CD20+ intratumoral B cells were significantly associated with longer overall survival in the PR group. While CD20+ B cells held no prognostic value for NeoTx patients, an increased frequency of proliferating CD20+Ki67+ B cells emerged as an independent prognostic factor for longer survival in the NeoTx group. These results indicate that NeoTx differentially affects PDAC-infiltrating immune cells and may have detrimental effects on the existing B cell landscape and the formation of TLS. Gaining further insight into the underlying molecular mechanisms is crucial to overcome the intrinsic immunotherapy resistance of PDAC and develop novel strategies to improve the long-term outcome of PDAC patients.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Linfócitos B , Linfócitos T/patologia , Microambiente TumoralRESUMO
Cell death is crucial for maintaining tissue balance and responding to diseases. However, under pathological conditions, the surge in dying cells results in an overwhelming presence of cell debris and the release of danger signals. In the liver, this gives rise to hepatic inflammation and hepatocellular cell death, which are key factors in various liver diseases caused by viruses, toxins, metabolic issues, or autoimmune factors. Both clinical and in vivo studies strongly affirm that hepatocyte death serves as a catalyst in the progression of liver disease. This advancement is characterized by successive stages of inflammation, fibrosis, and cirrhosis, culminating in a higher risk of tumor development. In this review, we explore pivotal forms of cell death, including apoptosis, pyroptosis, and necroptosis, examining their roles in both acute and chronic liver conditions, including liver cancer. Furthermore, we discuss the significance of cell death in liver surgery and ischemia-reperfusion injury. Our objective is to illuminate the molecular mechanisms governing cell death in liver diseases, as this understanding is crucial for identifying therapeutic opportunities aimed at modulating cell death pathways.
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Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11â¯700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.
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Biguanidas , Laparotomia , Infecção da Ferida Cirúrgica , Irrigação Terapêutica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Masculino , Feminino , Laparotomia/efeitos adversos , Pessoa de Meia-Idade , Biguanidas/uso terapêutico , Biguanidas/administração & dosagem , Idoso , Cuidados Intraoperatórios/métodos , AdultoRESUMO
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.
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Doença de Crohn , Humanos , Doença de Crohn/patologia , Fractais , Matriz Extracelular/patologia , Colágeno/uso terapêutico , FibroseRESUMO
INTRODUCTION: Cholangiocarcinoma is the second most common primary liver tumour worldwide with an increasing incidence in recent decades. While the effects of fibrosis on hepatocellular carcinoma have been widely demonstrated, the impact on cholangiocarcinoma remains unclear. The aim of this study was to evaluate the impact of liver fibrosis on overall survival (OS) and disease-free survival (DFS) in patients who have undergone liver resection for cholangiocarcinoma. METHODS: Eighty patients with cholangiocarcinoma who underwent curatively intended liver surgery between January 2007 and December 2020 were included in this retrospective single-centre study. Clinical and histopathological features were analysed. The primary endpoint was cause-specific survival. Secondary endpoints were DFS and identification of prognostic factors. RESULTS: The present study shows that the median OS is significantly reduced in patients with fibrosis (p < 0.001). The median OS in patients with fibrosis was three times shorter than in the group without fibrosis. In addition, a significantly shorter DFS was observed in patients with fibrosis (p < 0.002). Multivariate analysis showed that fibrosis is the strongest independent factor with a negative impact on OS and DFS. CONCLUSION: Liver fibrosis has a significant impact on OS and DFS in patients with cholangiocarcinoma. Patients with known liver fibrosis require thorough perioperative care and postoperative follow-up.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Cirrose Hepática/complicações , Fibrose , Ductos Biliares Intra-Hepáticos/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Prognóstico , Recidiva Local de Neoplasia/patologia , HepatectomiaRESUMO
Introduction: The SARS-CoV-2 pandemic has affected global public healthcare for several years. Numerous medical professionals have been infected since the outbreak in 2019, resulting in a shortage of healthcare providers. Since traditional personal protective wear was insufficient to eliminate the virus transmission reliably, new strategies to avoid cross-infection were imperative while enabling high-quality medical care. In the project ProteCT, we investigated the potential of robotic-assisted examination in providing medical examination via a telemedical approach. Material and Methods: We constructed a fully functional examination cabin equipped with cameras, microphones, screens and robotic arms to evaluate usability and perception. Therefore, we conducted a preliminary study with 10 healthy volunteers and 10 physicians to gain first insights and optimize the setup. In a second step, we performed telemedical examinations of actual patients from the local emergency department to compare the robotic approach with the classical method of measuring vital signs, auscultation, palpation and percussion. Results: The preliminary study identified basic requirements, such as the need for force-feedback and telemedical training for physicians. In the main study, acceptance was high and most patients indicated they would use a telemedical system again. Our setup enabled the physician to make the same diagnoses as by classic examination in the emergency department in most cases. Discussion: The potential acceptance of a telemedical system such as ProteCT is high. Robotic telemedical approaches could complement future healthcare beyond the Corona pandemic to reach rural areas or even war zones. Moreover, the daily clinical use of robotic telemedicine could improve patients' safety, the quality of perioperative management and the workflow in any medical facility. Conclusion: The development of telemedical and telerobotic systems is a multidisciplinary and complex challenge. However, acceptance of the proposed system was high among patients and physicians, indicating the potential use of similar systems for future healthcare.
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BACKGROUND: The minimum number of examined lymph nodes (ELN) required for adequate staging and best prediction of survival has not been established in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to investigate the influence of ELN on staging and survival in PDAC. METHODS: Patients undergoing partial or total pancreatectomy for PDAC at two European university hospitals between 2007 and 2018 were retrospectively reviewed. Multivariate Cox regression model and survival analyses were performed to verify adequate staging. RESULTS: Overall 341 (73 per cent) patients showed lymph node metastasis (N1/N2), whereas 125 (27 per cent) patients had no lymph node involvement (N0). With increasing number of ELN, the proportion of positive lymph nodes increased. The minimum number of ELN needed to detect lymph node involvement was 21. In multivariate analysis, examination of <21 lymph nodes was a significant negative predictor for survival. Examination of ≥21 ELN reversed this effect and ruled out possible misclassification. CONCLUSION: The number of ELN affects survival in PDAC. Possible misclassification was identified when <21 lymph nodes were examined. Therefore, at least 21 lymph nodes must be examined to avoid false lymph node classification in all types of resection.