Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands: Novel pharmacological agents in the treatment of ischemia reperfusion injury

Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands constitute important insulin sensitizers that have already been used for the treatment of human metabolic disorders, exerting also pleiotropic effects on inflammatory related diseases and cancer. Ischemia-reperfusion injury that is mainly associated with organ transplantation constitutes a serious complication with a great relevance in clinical practice. Accumulating experimental data have recently revealed that natural and synthetic PPAR-γ ligands exert beneficial effects against ischemia-reperfusion injury. The present review summarizes the available information on the role of PPAR-γ ligands in ischemia-reperfusion injury amongst the different organ systems. Taking into consideration the data so far, PPAR-γ ligands seem to represent potential therapeutic agents in the aim to reduce or even prevent injury associated with ischemia-reperfusion. © 2008 Bentham Science Publishers Ltd

Neovascularization: an attractive but tricky target in thyroid cancer

Introduction: Neovascularization in carcinogenesis and tumor progression is well-established. Molecular mediators implicated in different modes of vascular remodeling and expansion (e.g. sprouting angiogenesis (SA), vasculogenesis, vascular mimicry) are evaluated as prognostic biomarkers and therapeutic targets in different malignant tumors. Significant progress has been made in the understanding of the complex interplay between thyroid cancer (TC) cells and the tumor microenvironment, thus unraveling the role of angiogenic mediators. Areas covered: This review summarizes current research on neovascularization and TC. Current knowledge on vascular remodeling, in the context of carcinogenesis, is presented. Preclinical and clinical data from TC studies are also discussed. Expert opinion: There is a remarkable effort to pharmacologically target several key molecules of vessel-forming cascades. Despite encouraging preclinical results, clinical outcomes in TC are not optimal, possibly reflecting knowledge gaps in the pathophysiology of neovascularization in thyroid tissue. Increasing amounts of data support the possibility that redundancy of pathways that regulate vascular network remodeling allows tumors to adapt in different conditions. Hypothesizing that alternative forms of neovascularization upregulate when SA is pharmacologically blocked, targeting two or more different pathways of neovascularization could be a promising future strategy. Further research is required to explore molecular mechanisms of neovascularization in TC. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

Tumor microenvironment in adrenocortical carcinoma: Barrier to immunotherapy success?

Adrenocortical carcinoma is a rare malignancy with aggressive behavior, with up to 40% of patients presenting with metastases at the time of diagnosis. Both conventional chemotherapeutic regimens and novel immunotherapeutic agents, many of which are currently being tested in ongo-ing clinical trials, have yielded modest results so far, bringing the need for a deeper understanding of adrenal cancer behavior to the forefront. In the recent years, the tumor microenvironment has emerged as a major determinant of cancer response to immunotherapy and an increasing number of studies on other solid tumors have focused on manipulating the microenvironment in the favor of the host and discovering new potential target molecules. In the present review we aim to explore the characteristics of adrenocortical cancer’s microenvironment, highlighting the mechanisms of immune evasion responsible for the modest immunotherapeutic results, and identify novel potential strategies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Exosomes in lung cancer diagnosis and treatment. From the translating research into future clinical practice

Lung cancer is one of the main causes of cancer-related death worldwide. Despite advances in lung cancer pathophysiology, diagnosis and prognosis, a better understanding of the disease is strongly needed in order to establish novel diagnostic and therapeutic approaches that should improve treatment outcomes. Exosomes are a type of cell-secreted extracellular vesicles, which transfer a wide variety of biomolecules, such as proteins, mRNAs, microRNAs, and lipids, are implicated in intercellular communication and modulate tumor-host interactions. The potential value of exosomes and their contents in lung cancer diagnosis, prognosis and prediction of treatment outcome is supported by ample literature. Growing attention has been drawn specifically to the critical role of exosomal miRNAs in lung cancer pathogenesis and their potential clinical utility, especially due to their ability to modulate gene expression post-transcriptionally. Owing to their universal presence in the blood and other bodily fluids, exosomes are considered candidate biomarkers. Furthermore, their ability to deliver biomolecules and drugs to recipient cells renders them possible drug delivery vehicles in lung cancer. Here we review the pathological functions of exosomes in cancer and discuss their possible clinical utility as biomarkers and therapeutic agents in the management of lung cancer. © 201

Farnesoid-X receptor (FXR) as a promising pharmaceutical target in atherosclerosis

Background: Atherosclerosis (AS) is a major cause of death and morbidity in Western world and is strongly connected with atherogenic lipoproteins and inflammation. Bile acids (BA) act as activating signals of endogenous ligands such as Farnesoid-X receptor (FXR). Primary data indicate a potential role of FXR in AS. The therapeutic value of FXR ligands in AS is unknown. Objective: With the present review, we analyzed the efficacy of FXR agonists as a therapeutic modalities against AS. In this aspect, we performed an electronic search through Pub- Med/MEDLINE database by using the key terms: FXR∗, Farnesoid X receptor∗, atherosclerosis∗, bile acids∗ and agonism∗. Conclusion: According to our analysis, the FXR seems to be a promising therapeutic target in the atherosclerosis natural history. FXR agonism could exert protective effects in the development and evolution of AS. However, concomitant side effects such as the reduction of plasma HDL have been reported. Finally, results from undergoing clinical trials with synthetic FXR agonists will shed more light to the precise role of FXR agonism in AS treatment. © 2017 Bentham Science Publishers

Polymorphous adenocarcinoma of the salivary glands: An overview of immunohistochemical features and insights on molecular pathology

Summary. Polymorphous adenocarcinoma (PAC), represents a common minor salivary gland tumor (SGT) characterized by local growth, low metastatic potential and non-aggressive biologic behavior. Due to the clinical aggressiveness noted in a subset of such tumors, the former term polymorphous low-grade adenocarcinoma (PLGA) was recently revised. PAC’s clinical features and histological diversity result in clinical overlap of this entity with several other SGTs including mainly adenoid cystic carcinoma (AdCC). Differential diagnosis among the entities is crucial, in terms of tumor management and patients’ prognosis. The aim of the present review is to summarize the histological, cytological, immunohistochemical and molecular features of PAC. Histopathological examination is usually adequate for PAC differential diagnosis from other SGTs, except of AdCC. Several immunohistochemical markers including c-Kit, S-100/ MG, Mcm-2 and Integrin β-1,-3,-4, are reported to be useful diagnostic aids in borderline cases. Limitations in sample numbers and study methodology issues of the immunohistochemical PAC studies complicate the identification and selection of appropriate markers useful in the differential diagnosis. Additionally, molecular analyses of PAC specimens indicate that the PAC spectrum phenotypes result from different genotypes (protein kinase D positive; PRKD(+) and PRKD(-) tumors). PAC pathogenesis remains to be determined in each particular genotype while the convergence issue should be addressed in future studies. © 2019, Histology and Histopathology. All rights reserved