Overexpression of COP9 signalosome subunits, CSN7A and CSN7B, exerts different effects on adipogenic differentiation

The COP9 signalosome (CSN) is an essential regulator of cullin-RING-ubiquitin (Ub) ligases (CRLs), which ubiquitinate important cellular regulators and target them for degradation by the Ub proteasome system (UPS). The CSN exhibits deneddylating activity localized on subunit CSN5, which removes the ubiquitin-like protein Nedd8 from the cullins of CRLs. CSN-mediated deneddylation is an important step in the process of CRL remodeling, in which new substrate recognition units are incorporated into Ub ligases to meet changed requirements for proteolysis in cells. For instance, extensive CRL remodeling occurs during adipogenic differentiation when new CRL3s are formed. Diversification of CSN complexes during evolution is most likely another adaptation to meet different cellular requirements. Best known CSN variants are formed by different CSN subunit isoforms. For instance, in plant cells, isoforms have been identified for the MPN-domain subunits CSN5 (CSN5A and CSN5B) and CSN6 (CSN6A and CSN6B) which form four distinct CSN variants. In mammalian cells CSNCSN7A and CSNCSN7B variants are generated by CSN7 isoforms. We demonstrate that the two variants coexist in human LiSa-2 cells and in mouse embryonic fibroblasts. During adipogenic differentiation of LiSa-2 cells CSN7B increases in parallel with an elevation of the total CSN complex. Permanent overexpression of Flag-CSN7B but not of Flag-CSN7A accelerates adipogenesis in LiSa-2 cells indicating a specific function of the CSNCSN7B variant in stimulating adipogenesis. Silencing of CSN7A as well as of CSN7B in LiSa-2 cells and in mouse embryonic fibroblasts (MEFs) reduces adipogenic differentiation demonstrating that both CSNCSN7A and CSNCSN7B variants are involved in the process

Laparoscopic liver resection: indications, limitations, and economic aspects

Background: Minimally invasive techniques have increasingly found their way into liver surgery in recent years. A multitude of mostly retrospective analyses suggests several advantages of laparoscopic over open liver surgery. Due to the speed and variety of simultaneous technical and strategic developments, it is difficult to maintain an overview of the current status and perspectives in laparoscopic liver surgery. Purpose: This review highlights up-to-date aspects in laparoscopic liver surgery. We discuss established indications with regard to their development over time as well as continuing limitations of applied techniques. We give an assessment based on the current literature and according to our own center experiences, not least with regard to a highly topical cost discussion. Conclusions: While in the beginning mainly benign tumors were laparoscopically operated on, liver metastasis and hepatocellular carcinoma are now among the most frequent indications. Technical limitations remain and should be evaluated with the overall aim not to endanger quality standards in open surgery. Financial aspects cannot be neglected with the necessity of cost-covering reimbursement

Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues

The autofluorescence (AF) characteristics of endogenous fluorophores allow the label-free assessment and visualization of cells and tissues of the human body. While AF imaging (AFI) is well-established in ophthalmology, its clinical applications are steadily expanding to other disciplines. This review summarizes clinical advances of AF techniques published during the past decade. A systematic search of the MEDLINE database and Cochrane Library databases was performed to identify clinical AF studies in extra-ophthalmic tissues. In total, 1097 articles were identified, of which 113 from internal medicine, surgery, oral medicine, and dermatology were reviewed. While comparable technological standards exist in diabetology and cardiology, in all other disciplines, comparability between studies is limited due to the number of differing AF techniques and non-standardized imaging and data analysis. Clear evidence was found for skin AF as a surrogate for blood glucose homeostasis or cardiovascular risk grading. In thyroid surgery, foremost, less experienced surgeons may benefit from the AF-guided intraoperative separation of parathyroid from thyroid tissue. There is a growing interest in AF techniques in clinical disciplines, and promising advances have been made during the past decade. However, further research and development are mandatory to overcome the existing limitations and to maximize the clinical benefits

Cost analysis of inguinal hernia repair: the influence of clinical and hernia-specific factors

Introduction: As in the rest of the world, in Germany, inguinal hernia operations are among the most common operations. From an economic standpoint, very little is known about the influence of demographic, clinical or hernia-related parameters on the cost of inguinal hernia repair. We, therefore, evaluated individual patient parameters associated with higher costs with a special focus on multimorbidity. Methods: A total of 916 patients underwent hernia repair for primary or recurrent inguinal hernia between 2014 and 2017 at a single university center and were included in the analysis. The clinical and financial data of these patients were analyzed to identify cost-increasing parameters. Results: A majority of patients were male (90.7%), with a mean age of 55 years. The surgical methods utilized were mainly the TAPP (57.2%) and Lichtenstein (41.7%) procedures, with an average duration of surgery of 85 min and an average duration of anesthesia of 155 min. The mean cost of all procedures was 3338.3 euro (+/- 1608.1 euro). Older age, multimorbidity, emergency operations with signs of incarceration, longer hospital stays and postoperative complications were significant cost-driving factors. On the other hand, sex, the side of the hernia (left vs. right) and the presence of recurrent hernias had no influence on the overall direct costs. Conclusion: From a purely economic point of view, older age and multimorbidity are demographic cost-driving factors that cannot be influenced. The national hospital reimbursement system needs to consider and compensate for these factors. Emergency operations need to be prevented by early elective treatment. Long postoperative stays and postoperative complications need to be prevented by proper preoperative check-ups and accurate treatment

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

BACKGROUND: Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 58 HCC patients received surgery with a curative intent. The abundance of TEMs, angiopoietin-1 and -2 were detected in tumor specimens of the HCC patients (n = 58), and together with the occurrence of histologic tumor necrosis, were associated with established clinicopathological characteristics and survival. RESULTS: Patients with HCC characterized by necrosis and TEMs revealed reduced both overall survival and recurrence-free survival (all p < 0.05). Angiopoietins and TEMs were associated with metastatic and recurrent HCC. Furthermore, the formation of histologic tumor necrosis was associated with advanced tumor stage and density of TEMs (all p < 0.05). CONCLUSIONS: Histologic tumor necrosis, TEMs, and related angiopoietins were associated with multiple HCC parameters and patient survival. The tumor necrosis-TEM-angiopoietin axis may offer a novel diagnostic modality to predict patient outcome after surgery for HCC

Risk factors for malignant transformation of hepatocellular adenoma to hepatocellular carcinoma: protocol for systematic review and meta-analysis

Introduction: Hepatocellular adenomas (HCAs) are solid liver tumours that are usually found incidentally during routine medical check-ups. Multiple modifiable and non-modifiable factors constitute a risk for the malignant transformation of HCAs to hepatocellular carcinoma (HCC), which has emerged to be one of the fastest growing causes of cancer-related mortality globally. This study protocol for a planned systematic review and meta-analysis documents the methodological approach to identify risk factors and their risk estimates for the transformation from HCA to HCC. Methods and analysis: Two independent reviewers will systematically search and extract data from studies in patients of all ages published between January 1970 and June 2021 on PubMed, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Scopus Web of Science, Ovid, The Cochrane Hepatobiliary Group Controlled Trials Register and The Cochrane Central Register of Controlled Trials by using an a priori defined search strategy. Study quality will be rated with the National Institute of Health quality assessment tools. Disagreements will be resolved by consensus with a third independent reviewer. The primary outcome will be the odds ratio (OR) of developing HCC in patients with prediagnosed HCA depending on the exposure to risk factors. HCC diagnosis must be inferred based on imaging techniques or pathology. We will use R V.4.0.2 to conduct meta-analyses and generate pooled ORs based on random effects models. Results will be presented as forest plots. Cochran’s Q and I2 test will be performed to assess heterogeneity between included studies. Funnel plots and Egger’s weighted regression will be used to evaluate publication bias. Ethics and dissemination: No ethical approval is required as we will use and analyse data from previously published studies in which informed consent was obtained. The results will be disseminated in a peer-reviewed journal on completion. PROSPERO registration number: CRD42020206578

Minimally invasive pancreatic surgery—will robotic surgery be the future?

Due to the complexity of the procedures and the texture of the organ itself, pancreatic surgery remains a challenge in the field of visceral surgery. During the past decade, a minimally invasive approach to pancreatic surgery has gained distribution in clinical routine, extending from left-sided procedures to pancreatic head resections. While a laparoscopic approach has proven beneficial for many patients with left-sided pancreatic pathologies, the complex reconstruction in pancreas head resections remains worrisome with the laparoscopic approach. The robotic technique was established to overcome such technical constraints while preserving the advantages of the laparoscopic approach. Even though robotic systems are still in development, especially in pancreatoduodenectomy, the current literature demonstrates the feasibility of this approach and stable clinical and oncological outcomes compared to the open technique, albeit only under the condition of such operations being performed by specialist teams in a high-volume setting (>20 robotic pancreaticoduodenectomies per year). The aim of this review is to analyze the current evidence regarding a minimally invasive approach to pancreatic surgery and to review the potential of a robotic approach. Presently, there is still a scarcity of sound evidence and long-term oncological data regarding the role of minimally invasive and robotic pancreatic surgery in the literature, especially in the setting of pancreaticoduodenectomy

Inguinal Lymph Node Metastasis of a Primary Serous Papillary Carcinoma of the Peritoneum One Year after CRS and HIPEC

Background: Primary peritoneal serous papillary carcinoma is a rare malignant epithelial tumor which was first described in 1959. Peritoneal serous papillary carcinoma arises from the peritoneal epithelium and originates from a single or multicentric focus of the peritoneum involving the peritoneum of the abdomen and pelvis. The involvement of retroperitoneal lymph nodes occurs in 64% of the patients diagnosed with this malignancy. So far, there is no report about inguinal lymph node metastasis in this disease. Case Report: We present a rare case of a 63-year-old female patient who developed singular inguinal lymph node metastasis 1 year after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy due to peritoneal serous papillary carcinoma. The lymph node metastasis was found by computed tomography (CT) scan and was resected and histologically confirmed. The postoperative course was uneventful, and the patient was discharged on postoperative day 1. The last CT scan 24 months after initial cytoreduction and 12 months after lymph node resection showed no further tumor recurrence. Conclusion: This case report should raise the awareness of potentially unexpected presentation of extraperitoneal metastasis and highlights the importance of patient follow-up including clinical examination and CT scans of thorax/abdomen/pelvis following a systematic schedule

Successful implementation of preventive measures leads to low relevance of SARS‐CoV‐2 in liver transplant patients: Observations from a German outpatient department

Background: Immunosuppressed liver transplant (LT) patients are considered to be at high risk for any kind of infection. What the outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) means for the transplant cohort is a question that, as of now, cannot easily be answered. Data on prevalence, relevance of the novel virus, and clinical course of the infection in stable LT patients are limited. Methods: Nasopharyngeal swabs were performed in our outpatient department during the shutdown between March and April 2020 in Germany. Results: The prevalence of SARS-CoV-2 was 3%. Three out of a cohort of 101 LT patients were asymptomatic for respiratory diseases. Respiratory complaints were common and not associated with SARS-CoV-2 infection. The overall monthly mortality rate was 0.22% and did not show alterations during the shutdown in Germany. Conclusions: If preventive measures are applied, LT patients do not seem to be at a higher risk for SARS-CoV-2 infection. Telemedicine in the outpatient setting may help to maintain distance and to reduce direct patient contact. However, standard of care must be guaranteed for patients with relevant comorbidities in spite of pandemics, because complications may arise from preexisting conditions

Analysis of outcomes and predictors of long-term survival following resection for retroperitoneal sarcoma

Background: Retroperitoneal sarcomas (RPS) include a heterogeneous group of rare malignant tumours, and various treatment algorithms are still controversially discussed until today. The present study aimed to examine postoperative and long-term outcomes after resection of primary RPS. Patients and methods: Clinicopathological data of patients who underwent resection of primary RPS between 2005 and 2015 were assessed, and predictors for overall survival (OS) and disease-free survival (DFS) were identified. Results: Sixty-one patients underwent resection for primary RPS. Postoperative morbidity and mortality rates were 31 and 3%, respectively. After a median follow-up time of 74 months, 5-year OS and DFS rates were 58 and 34%, respectively. Histologic high grade (5-year OS: G1: 92% vs. G2: 54% vs. G3: 43%, P = 0.030) was significantly associated with diminished OS in univariate and multivariate analyses. When assessing DFS, histologic high grade (5-year DFS: G1: 63% vs. G2: 24% vs. G3: 22%, P = 0.013), positive surgical resection margins (5-year DFS: R0: 53% vs. R1: 10% vs. R2: 0%, P = 0.014), and vascular involvement (5-year DFS: yes: 33% vs no: 39%, P = 0.001), were significantly associated with inferior DFS in univariate and multivariate analyses. Conclusions: High-grade tumours indicated poor OS, while vascular involvement, positive surgical resection margins, and histologic grade are the most important predictors of DFS. Although multimodal treatment strategies are progressively established, surgical resection remains the mainstay in the majority of patients with RPS, even in cases with vascular involvement