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Archives of Pathology & Laboratory... Jul 2020Preoperative neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant therapy...
CONTEXT.—
Preoperative neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant therapy often induces extensive fibrosis in tumor, adjacent pancreatic parenchyma, and peripancreatic tissue. Histopathologic evaluations and histologic tumor response grading (HTRG) of posttherapy pancreatectomy specimens are very difficult and challenging. Studies on prognostic significance of posttherapy pathologic staging, optimal system for HTRG, and other pathologic parameters in treated PDAC patients are limited.
OBJECTIVE.—
This review is to provide a timely update of the prognostic values of posttherapy pathologic staging, HTRG, and other pathologic parameters in PDAC patients who received neoadjuvant therapy and pancreas resection.
DATA SOURCES.—
Systemic review of major studies on pathologic evaluation and its clinicopathologic implications in treated PDAC patients.
CONCLUSIONS.—
Systemic pathologic examination, histologic tumor regression grading, pathologic evaluation of the margins, tumor involvement of superior mesenteric vein/portal vein, accurate pathologic staging, and reporting of posttherapy pancreatectomy specimens provide highly valuable prognostic information for postoperative patient care. Our findings suggest for the first time that tumor size of 1.0 cm, instead of 2.0 cm, is a better cutoff for ypT2 in PDAC patients. The newly proposed 3-tier MD Anderson HTRG system not only has proved to be an independent prognostic marker for PDAC patients who received neoadjuvant therapy and pancreatectomy, but also improves interobserver agreement among pathologists in evaluation of tumor response. This grading system should be considered in future editions of the College of American Pathologists protocol for PDAC.
Topics: Biopsy; Carcinoma, Pancreatic Ductal; Humans; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Observer Variation; Pancreatectomy; Pancreatic Neoplasms; Predictive Value of Tests; Reproducibility of Results; Treatment Outcome
PubMed: 32023088
DOI: 10.5858/arpa.2019-0477-RA -
Cureus Dec 2021Meningiomas have been classified as the most commonly occurring primary brain tumors. Although the majority of meningiomas are benign and slow-progressing, the tumors... (Review)
Review
Meningiomas have been classified as the most commonly occurring primary brain tumors. Although the majority of meningiomas are benign and slow-progressing, the tumors that grow to a larger size are associated with various risks during surgical procedures. Early detection of meningiomas is crucial to the treatment as those detected early can be treated through non-invasive methods. Due to their benign nature, meningiomas contain homogeneous protein biomarkers that can be easily identified. Cerebrospinal fluid (CSF) has a high protein composition which can be used to diagnose various brain tumors. Because CSF comes into direct contact with the brain during its functioning, it is one of the factors that makes it an important source of different biomarkers. An analysis of biochemical changes occurring in the CSF can be useful in assessing the condition of the periventricular white matter and the parenchyma. In this review, PubMed, Medline, PubMed Central, and Google Scholar were used to identify studies discussing meningiomas regarding their assessment, types, diagnosis, and treatment, with more attention directed towards the application of CSF proteome analysis in diagnosis. Priority was given to studies published within the last 15 years. The following keywords were used in the literature search: "cerebrospinal fluid," "meningiomas," "brain tumors," "primary brain tumors," "protein biomarkers," "proteome analysis," and "diagnosis." Subsequently, the 15 most relevant studies were selected for inclusion in the review. We excluded studies discussing different types of non-brain tumors as well as older articles. The selected studies also underwent a quality appraisal process using corresponding assessment tools. The selected articles were highly informative about meningiomas and the processes of diagnosis and treatment that are currently in use as well as those that are being developed or implemented. The use of CSF proteins in the diagnostic process is also discussed in this review. The studies also describe proteomics as a less invasive procedure that allows for the analysis of entire proteins and the projection of diagnostic images with higher resolutions that aid in the diagnosis.
PubMed: 34966627
DOI: 10.7759/cureus.20707 -
Journal of Neurological Surgery Reports Oct 2023Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an...
Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an illustrative case and systematic review of rare, predominantly extra-axial World Health Organization (WHO) grade 4 astrocytomas located within the cerebellopontine angle (CPA) and explore the impact of anatomic location on diagnosis, management, and outcomes. A systematic review of adult patients with predominantly extra-axial WHO grade 4 CPA astrocytomas was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through December 2022. Eighteen articles were included comprising 21 astrocytomas: 13 exophytic tumors arising from the cerebellopontine parenchyma and 8 tumors originating from a cranial nerve root entry zone. The median OS was 15 months with one-third of cases demonstrating delayed diagnosis. Gross total resection, molecular genetic profiling, and use of ancillary treatment were low. We report the only patient with an integrated isocitrate dehydrogenase 1 (IDH-1) mutant diagnosis, who, after subtotal resection and chemoradiation, remains alive at 40 months without progression. The deep conical-shaped corridor and abundance of eloquent tissue of the CPA significantly limits both surgical resection and utility of device-based therapies in this region. Prompt diagnosis, molecular characterization, and systemic therapeutic advances serve as the predominant means to optimize survival for patients with rare skull base astrocytomas.
PubMed: 37854309
DOI: 10.1055/a-2172-7770 -
Membranes Jul 2021(1) Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used for acute respiratory failure with few absolute but many relative contraindications. The... (Review)
Review
Contraindications to the Initiation of Veno-Venous ECMO for Severe Acute Respiratory Failure in Adults: A Systematic Review and Practical Approach Based on the Current Literature.
(1) Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used for acute respiratory failure with few absolute but many relative contraindications. The provider in charge often has a difficult time weighing indications and contraindications to anticipate if the patient will benefit from this treatment, a decision that often decides life and death for the patient. To assist in this process in coming to a good evidence-based decision, we reviewed the available literature. (2) Methods: We performed a systematic review through a literature search of the MEDLINE database of former and current absolute and relative contraindications to the initiation of ECMO treatment. (3) Results: The following relative and absolute contraindications were identified in the literature: absolute-refusal of the use of extracorporeal techniques by the patient, advanced stage of cancer, fatal intracerebral hemorrhage/cerebral herniation/intractable intracranial hypertension, irreversible destruction of the lung parenchyma without the possibility of transplantation, and contraindications to lung transplantation; relative-advanced age, immunosuppressed patients/pharmacological immunosuppression, injurious ventilator settings > 7 days, right-heart failure, hematologic malignancies, especially bone marrow transplantation and graft-versus-host disease, SAPS II score ≥ 60 points, SOFA score > 12 points, PRESERVE score ≥ 5 points, RESP score ≤ -2 points, PRESET score ≥ 6 points, and "do not attempt resuscitation" order (DN(A)R status). (4) Conclusions: We provide a simple-to-follow algorithm that incorporates absolute and relative contraindications to the initiation of ECMO treatment. This algorithm attempts to weigh pros and cons regarding the benefit for an individual patient and hopefully assists caregivers to make better, informed decisions.
PubMed: 34436348
DOI: 10.3390/membranes11080584 -
Frontiers in Neurology 2022The glymphatic system has been described as one that facilitates the exchange between the cerebrospinal fluid (CSF) and interstitial fluid, and many recent studies have...
BACKGROUND
The glymphatic system has been described as one that facilitates the exchange between the cerebrospinal fluid (CSF) and interstitial fluid, and many recent studies have demonstrated glymphatic flow based on magnetic resonance imaging (MRI). We aim to systematically review the studies demonstrating a normal glymphatic flow in a human population using MRI and to propose a detailed glymphatic imaging protocol.
METHODS
We searched the MEDLINE and EMBASE databases to identify studies with human participants involving MRI-based demonstrations of the normal glymphatic flow. We extracted data on the imaging sequence, imaging protocol, and the targeted anatomical structures on each study.
RESULTS
According to contrast-enhanced MRI studies, peak enhancement was sequentially detected first in the CSF space, followed by the brain parenchyma, the meningeal lymphatic vessel (MLV), and, finally, the cervical lymph nodes, corresponding with glymphatic flow and explaining the drainage into the MLV. Non-contrast flow-sensitive MRI studies revealed similar glymphatic inflow from the CSF space to the brain parenchyma and efflux of exchanged fluid from the brain parenchyma to the MLV.
CONCLUSION
We may recommend T1-weighted contrast-enhanced MRI for visualizing glymphatic flow. Our result can increase understanding of the glymphatic system and may lay the groundwork for establishing central nervous system fluid dynamic theories and developing standardized imaging protocols.
PubMed: 35693018
DOI: 10.3389/fneur.2022.827398 -
Sarcoidosis, Vasculitis, and Diffuse... Mar 2023To outline the observations of studies evaluating the prominence of Neutrophil to Lymphocyte Ratio (NLR) in sarcoidosis.
BACKGROUND AND AIM
To outline the observations of studies evaluating the prominence of Neutrophil to Lymphocyte Ratio (NLR) in sarcoidosis.
METHODS
The search was performed on PubMed, Scopus, and web of science up until November 21, 2021. Eventually, a number of 17 papers were incorporated into this review.
RESULTS
The results of this analysis showed no significant difference of NLR values between sarcoidosis patients and tuberculosis patients (SMD=-0.36, 95% CI= -0.92-0.21). The results showed high heterogeneity (I2=90.83%, p<0.001). So, we used random-effects model. However, NLR can be utilized to identify the radiological severity and staging of pulmonary sarcoidosis due to statistically significant variations. An elevation in NLR values may assist both sarcoidosis diagnosis and lung parenchyma involvement. Also, extra-pulmonary involvement was just more probable to be found in individuals diagnosed with sarcoidosis inhibiting high rates of NLR. High NLR levels were found to be associated with an accelerated rate of progression, revealing that NLR might be used to detect Pulmonary Hypertension (PH) as a complication of sarcoidosis.
CONCLUSIONS
In the visualizations of the disease, NLR was revealed to be a beneficial and straightforward fundamental laboratory biomarker connected to disease severity and requirement for therapy.
PubMed: 36975052
DOI: 10.36141/svdld.v40i1.13824 -
Frontiers in Neurology 2020Within the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from...
Within the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings.
PubMed: 33613412
DOI: 10.3389/fneur.2020.577312 -
Advanced Drug Delivery Reviews 2020Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain...
Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.
Topics: Animals; Biological Transport; Blood-Brain Barrier; Cerebral Ventricles; Cerebrospinal Fluid; Drug Delivery Systems; Humans; Injections, Spinal; Liposomes; Micelles; Nanoparticles; Subarachnoid Space
PubMed: 32142739
DOI: 10.1016/j.addr.2020.02.006 -
Annals of Surgical Oncology Jul 2024Pancreatoduodenectomy (PD) has a considerable surgical risk for complications and late metabolic morbidity. Parenchyma-sparing resection of benign tumors has the... (Meta-Analysis)
Meta-Analysis
Long-Term Oncologic Outcome following Duodenum-Preserving Pancreatic Head Resection for Benign Tumors, Cystic Neoplasms, and Neuroendocrine Tumors: Systematic Review and Meta-analysis.
BACKGROUND
Pancreatoduodenectomy (PD) has a considerable surgical risk for complications and late metabolic morbidity. Parenchyma-sparing resection of benign tumors has the potential to cure patients associated with reduced procedure-related short- and long-term complications.
MATERIALS AND METHODS
Pubmed, Embase, and Cochrane libraries were searched for studies reporting surgery-related complications following PD and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. A total of 38 cohort studies that included data from 1262 patients were analyzed. In total, 729 patients underwent DPPHR and 533 PD.
RESULTS
Concordance between preoperative diagnosis of benign tumors and final histopathology was 90.57% for DPPHR. Cystic and neuroendocrine neoplasms (PNETs) and periampullary tumors (PATs) were observed in 497, 89, and 31 patients, respectively. In total, 34 of 161 (21.1%) patients with intraepithelial papillar mucinous neoplasm exhibited severe dysplasia in the final histopathology. The meta-analysis, when comparing DPPHRt and PD, revealed in-hospital mortality of 1/362 (0.26%) and 8/547 (1.46%) patients, respectively [OR 0.48 (95% CI 0.15-1.58); p = 0.21], and frequency of reoperation of 3.26 % and 6.75%, respectively [OR 0.52 (95% CI 0.28-0.96); p = 0.04]. After a follow-up of 45.8 ± 26.6 months, 14/340 patients with intraductal papillary mucinous neoplasms/mucinous cystic neoplasms (IPMN/MCN, 4.11%) and 2/89 patients with PNET (2.24%) exhibited tumor recurrence. Local recurrence at the resection margin and reoccurrence of tumor growth in the remnant pancreas was comparable after DPPHR or PD [OR 0.94 (95% CI 0.178-5.34); p = 0.96].
CONCLUSIONS
DPPHR for benign, premalignant neoplasms provides a cure for patients with low risk of tumor recurrence and significantly fewer early surgery-related complications compared with PD. DPPHR has the potential to replace PD for benign, premalignant cystic and neuroendocrine neoplasms.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Pancreaticoduodenectomy; Duodenum; Organ Sparing Treatments; Pancreatic Cyst; Postoperative Complications; Prognosis; Pancreatectomy
PubMed: 38578553
DOI: 10.1245/s10434-024-15222-y -
Neurosurgical Review Oct 2022Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use....
Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcomes. A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Fifteen studies were included, reporting 699 patients. Most patients were male (71.7%), and the pooled mean age was 40.8 years; 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in the parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes, and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcomes, one found them to predict better outcomes and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number: CRD42021271200.
Topics: Adult; Biomarkers; Brain Injuries, Traumatic; Female; Humans; Interleukin-6; Male; Prognosis; Prospective Studies
PubMed: 35790656
DOI: 10.1007/s10143-022-01827-y