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Current Oncology (Toronto, Ont.) Nov 2023Basal cell carcinoma (BCC) is the most common skin cancer, with a lifetime risk currently approaching up to 40% in Caucasians. Among these, some clinical and... (Review)
Review
Basal cell carcinoma (BCC) is the most common skin cancer, with a lifetime risk currently approaching up to 40% in Caucasians. Among these, some clinical and pathological BCC variants pose a higher risk due to their more aggressive biological behavior. Morpheaform BCC (morBCC), also known as sclerosing, fibrosing, or morpheic BCC, represents up to 5-10% of all BCC. Overall, morBCC carries a poorer prognosis due to late presentation, local tissue destruction, tumor recurrence, and higher frequency of metastasis. In this systematic review, we review the epidemiological, clinical, morphological, dermatoscopical, and molecular features of morBCC. After the title and abstract screening of 222 studies and the full-text review of 84 studies, a total of 54 studies met the inclusion criteria and were thus included in this review.
Topics: Humans; Neoplasm Recurrence, Local; Carcinoma, Basal Cell; Skin Neoplasms; Transcription Factors
PubMed: 37999140
DOI: 10.3390/curroncol30110720 -
Autoimmunity Reviews Jun 2023Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50.... (Review)
Review
Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50. Aggressive wall inflammation, neoangiogenesis and consecutive remodeling processes are the hallmark of the disease. Though etiology is unknown, cellular and humoral immunopathological processes are well understood. Matrix metalloproteinase-9 mediated tissue infiltration occurs through lysis of basal membranes in adventitial vessels. CD4+ cells attain residency in immunoprotected niches, differentiate into vasculitogenic effector cells and enforce further leukotaxis. Signaling pathways involve the NOTCH1-Jagged1 pathway opening vessel infiltration, CD28 mediated T-cell overstimulation, lost PD-1/PD-L1 co-inhibition and JAK/STAT signaling in interferon dependent responses. From a humoral perspective, IL-6 represents a classical cytokine and potential Th-cell differentiator whereas interferon-γ (IFN- γ) has been shown to induce chemokine ligands. Current therapies involve glucocorticoids, tocilizumab and methotrexate application. However, new agents, most notably JAK/STAT inhibitors, PD-1 agonists and MMP-9 blocking substances, are being evaluated in ongoing clinical trials.
Topics: Humans; Giant Cell Arteritis; Autoimmunity; Programmed Cell Death 1 Receptor; CD4-Positive T-Lymphocytes; Cytokines; Takayasu Arteritis
PubMed: 36990133
DOI: 10.1016/j.autrev.2023.103328 -
Frontiers in Pharmacology 2023Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced (LA) at diagnosis. The combination of radiotherapy (RT), chemotherapy, targeted therapy, and immunotherapy are the primary LA-HNSCC treatment options. Nevertheless, the choice of optimal LA-HNSCC treatment remains controversial. We systematically searched public databases for LA-HNSCC-related studies and assess treatment effectiveness and safety by assessing the objective response rate (ORR), ≥3 adverse events (AEs), overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), local-region control (LRC), and disease-specific survival (DSS). 126 randomized controlled clinical trials (RCTs) were included in this study. We show that concurrent RT with nimotuzumab or conventional concurrent chemo-radiotherapy (CCRT) had significantly better efficacy and long-term survival without increasing AEs than RT alone. Accelerated fractionated radiotherapy (AFRT) showed better efficiency than conventional fractionated RT, although it had higher AEs. In addition, concurrent cetuximab combined with RT failed to show a significant advantage over RT alone. PROSPERO CRD42022352127.
PubMed: 37795033
DOI: 10.3389/fphar.2023.1269863 -
The Lancet. Planetary Health Sep 2021Non-Hodgkin lymphoma comprises a heterogeneous group of cancers with unresolved aetiology, although risk factors include environmental exposures to toxic chemicals.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-Hodgkin lymphoma comprises a heterogeneous group of cancers with unresolved aetiology, although risk factors include environmental exposures to toxic chemicals. Although the ubiquitous pollutant benzene is an established leukemogen, its potential to cause non-Hodgkin lymphoma has been widely debated. We aimed to examine the potential link between benzene exposure and risk of non-Hodgkin lymphoma in humans by evaluating a wide array of cohort and case-control studies using electronic systematic review.
METHODS
We did a comprehensive systematic review and meta-analysis of all qualified human epidemiological studies that assessed the relationship between benzene exposure and non-Hodgkin lymphoma. We queried the PubMed and Embase databases for relevant articles published before June 5, 2019, and applied the SysRev platform for study selection. All peer-reviewed human cohort and case-control studies that reported non-Hodgkin lymphoma risk estimates specifically for benzene exposure were eligible for inclusion. Studies that calculated relative risks (RRs) for industries or job types without identifying those specifically exposed to benzene, that combined non-Hodgkin lymphoma with other cancer types, or that reported many different solvent exposures together were excluded. From each study, two investigators independently extracted information on the study design, location, years, sample size, participation rates, age, sex, sources of cases and controls, diagnosis, histological verification, exposure assessment, results, adjustment, and statistical analysis, and subsequently assessed study quality. We calculated the meta-analysis relative risk (meta-RR) and CIs using the fixed effect and random effect models, as well as assessing publication bias.
FINDINGS
Our search yielded 2481 articles. After screening and removal of duplicates, 20 case-control studies and eight cohort studies were included in our meta-analysis, which included a total of 9587 patients with non-Hodgkin lymphoma. We reported an increased meta-relative risk (meta-RR) of 33% in highly exposed groups, when data were available (meta-RR 1·33 [95% CI 1·13-1·57], n=28). The meta-RR rose to 1·51 (1·22-1·87, n=18) in the studies that provided results specifically for highly exposed individuals. In particular, we reported a doubling of this risk for diffuse large B-cell lymphoma, a major non-Hodgkin lymphoma subtype (1·67 [1·01-2·77]). We also detected increased risks for follicular lymphoma (1·47 [0·95-2·27]) and hairy cell leukaemia (1·77 [0·99-3·16]), though they were not statistically significant. Funnel plot, Egger's test (p=0·77) and Begg's test (p=0·98) did not show evidence of publication bias. We evaluated the major aspects of causal inference and found evidence to support all the Hill considerations for assigning causation.
INTERPRETATION
Our findings suggest a causal link between benzene exposure and non-Hodgkin lymphoma, especially for diffuse large B-cell lymphoma.
FUNDING
National Institute of Environmental Health Sciences.
Topics: Benzene; Case-Control Studies; Cohort Studies; Humans; Lymphoma, Non-Hodgkin; Risk Factors
PubMed: 34450064
DOI: 10.1016/S2542-5196(21)00149-2 -
Asian Pacific Journal of Cancer... Dec 2023Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be...
INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management.
METHOD
We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies.
RESULTS
A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue.
CONCLUSION
The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.
Topics: Adult; Humans; Child; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; B-Lymphocytes; Fatigue
PubMed: 38156834
DOI: 10.31557/APJCP.2023.24.12.4025 -
Human Mutation Sep 2022The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues.... (Review)
Review
The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues. Recent advances in whole-genome sequencing of patients with undiagnosed genetic disorders have identified several rare pathogenic variants in DOCK genes. We conducted a systematic review and performed a patient database and literature search of reported DOCK pathogenic variants that have been identified in association with clinical pathologies such as global developmental delay, immune cell dysfunction, muscle hypotonia, and muscle ataxia among other categories. We then categorized these pathogenic DOCK variants and their associated clinical phenotypes under several unique categories: developmental, cardiovascular, metabolic, cognitive, or neuromuscular. Our systematic review of DOCK variants aims to identify and analyze potential DOCK-regulated networks associated with neuromuscular diseases and other disease pathologies, which may identify novel therapeutic strategies and targets. This systematic analysis and categorization of human-associated pathologies with DOCK pathogenic variants is the first report to the best of our knowledge for a unique class in this understudied gene family that has important implications in furthering personalized genomic medicine, clinical diagnoses, and improve targeted therapeutic outcomes across many clinical pathologies.
Topics: Ataxia; Genomics; Guanine Nucleotide Exchange Factors; Humans; Intellectual Disability; Multigene Family; Muscle Hypotonia; Transcription Factors
PubMed: 35544951
DOI: 10.1002/humu.24398 -
Nutrients Dec 2023Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products. It participates in cellular energy metabolism and modulates multiple cellular survival and death pathways. Nicotinamide has been widely studied as a safe chemopreventive agent that reduces actinic keratosis (AKs) and non-melanoma skin cancers (NMSC).
METHODS
We used the Medline, EMBASE, PubMed, and Cochrane databases to search the concepts "nicotinamide", "chemoprevention", and "skin cancer" up to August 2023. Three independent authors screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. The primary outcome was the impact of oral nicotinamide on the incidence of NMSC in high-risk patients. We also conducted a systematic search to identify relevant epidemiological studies published evaluating dietary niacin intake and the risk of NMSC.
RESULTS
Two hundred and twenty-five studies were reviewed, and four met the inclusion criteria. There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48-1.37; I = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50-1.55; I = 63%), and NMSC (RR 0.82, 95% CI 0.61-1.12; I = 63%). Adverse events were rare and acceptable, allowing optimal compliance of patients to the treatment. We found only one article evaluating the association between niacin dietary intake and NMSC risk, supporting a potential beneficial role of niacin intake concerning SCC but not BCC or melanoma.
CONCLUSIONS
The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.
Topics: Animals; Humans; Niacinamide; Niacin; Chemoprevention; Skin Neoplasms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell
PubMed: 38201930
DOI: 10.3390/nu16010100 -
Critical Reviews in Oncology/hematology Jan 2022This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Neoplasm; Humans; Mutation; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins p21(ras)
PubMed: 34843928
DOI: 10.1016/j.critrevonc.2021.103548 -
Public Health Aug 2023To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits,... (Review)
Review
OBJECTIVE
To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits, hospitalizations, and deaths due to substance use, injury, and mental health among those aged 11 years and older.
METHODS
A systematic review of six electronic databases up to February 1, 2023. Original, peer-reviewed articles with interrupted time series or before and after designs were included. Four independent reviewers screened articles and assessed risk of bias. Outcomes with 'critical' risk of bias were excluded. Protocol registered on PROSPERO (# CRD42021265183).
RESULTS
After screening and risk of bias assessment, 29 studies were included which examined ED visits or hospitalizations for cannabis use or alcohol (N = 10), opioid mortality (N = 3), motor vehicle fatalities or injury (N = 11), and intentional injury/mental health (N = 5). Rates or number of cannabis-related hospitalizations increased after RCL in Canada and the USA. Immediate increases in rates of cannabis-related ED visits were found after both RCL and RCC in Canada. Rates of traffic fatalities increased after RCL and RCC in certain jurisdictions in the USA.
CONCLUSIONS
RCL was associated with increased rates of cannabis-related hospitalizations. RCL and/or RCC was associated with increased rates of cannabis-related ED visits, consistently shown across sex and age groups. The effect on fatal motor vehicle incidents was mixed, with observed increases found after RCL and/or RCC. The effect of RCL or RCC on opioids, alcohol, intentional injury, and mental health is not clear. These results inform population health initiatives and international jurisdictions considering RCL implementation.
Topics: Humans; Cannabis; Mental Health; Carcinoma, Renal Cell; Substance-Related Disorders; Analgesics, Opioid; Legislation, Drug; Ethanol; Kidney Neoplasms
PubMed: 37429043
DOI: 10.1016/j.puhe.2023.06.012 -
Cancers Jan 2022Rhabdoid liver tumors in children are rare and have a devastating prognosis. Reliable diagnosis and targeted treatment approaches are urgently needed.... (Review)
Review
Rhabdoid liver tumors in children are rare and have a devastating prognosis. Reliable diagnosis and targeted treatment approaches are urgently needed. Immunohistochemical and genetic studies suggest that tumors formerly classified as small cell undifferentiated hepatoblastoma (SCUD) belong to the entity of malignant rhabdoid tumors of the liver (MRTL), in contrast to hepatoblastomas with focal small cell histology (F-SCHB). This may have relevant implications on therapeutic approaches. However, studies with larger cohorts investigating the clinical relevance of the histological and genetic similarities for patients are lacking. To analyze possible similarities and differences in patient characteristics, tumor biology, response to treatment, and clinical course of patients with MRTL, SCUD and F-SCHB. Applied therapeutic regimens and prognostic factors are investigated. A systematic literature search of MEDLINE, Web of Science, and CENTRAL was performed for this PRISMA-compliant systematic review. All studies of patients with MRTL, SCUD and F-SCHB that provided individual patient data were included. Demographic, histological, and clinical characteristics of the three subgroups were compared. Overall survival (OS) was estimated with the Kaplan-Meier method and prognostic factors investigated in a multivariable Cox regression model. PROSPERO 2021 CRD42021258760. Fifty-six studies with a total of 118 patients were included. The two subgroups MRTL and SCUD did not differ significantly in baseline patient characteristics. However, heterogenous diagnostic and therapeutic algorithms were applied. Large histological and clinical overlap between SCUD and MRTL could be shown. Two-year OS was 22% for MRTL and 13% for SCUD, while it was significantly better in F-SCHD (86%). Chemotherapeutic regimens for hepatoblastoma proved to be ineffective for both SCUD and MRTL, but successful in F-SCHB. Soft tissue sarcoma chemotherapy was associated with significantly better survival for MRTL and SCUD, but was rarely applied in SCUD. Patients who did not undergo surgical tumor resection had a significantly higher risk of death. While F-SCHB is a subtype of HB, SCUD should be classified and treated as a type of MRTL. Surgical tumor resection in combination with intensive, multi-agent chemotherapy is the only chance for cure of these tumors. Targeted therapies are highly needed to improve prognosis. Currently, aggressive regimens including soft tissue sarcoma chemotherapy, extensive resection, radiotherapy or even liver transplantation are the only option for affected children.
PubMed: 35053437
DOI: 10.3390/cancers14020272