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Head and Neck Pathology Mar 2022The 5 edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (2022) comes out only five years after the previous edition, however it...
The 5 edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (2022) comes out only five years after the previous edition, however it presents important updates that run in parallel with the rapid progression involving the increasingly sophisticated molecular investigation and its interpretation, some of which already have therapy-related impact. This manuscript provides an overview of the leading changes introduced in the classification of Odontogenic and Maxillofacial Bone Tumours that encompasses cysts of the jaws, odontogenic tumours, giant cell lesions and bone cysts, and bone and cartilage tumours. This is the first edition that Essential and Desirable Diagnostic Features were added for each entity, so that the most important clinical, microscopic and/or radiologic features were encapsulated and briefly highlighted. Surgical ciliated cyst was added to the group of odontogenic cysts, adenoid ameloblastoma was a newly recognized benign epithelial odontogenic tumour, and segmental odontomaxillary dysplasia was introduced in the group of fibro-osseous tumours and dysplasia. In addition, rhabdomyosarcoma with TFCP2 rearrangement, was introduced into the group of malignant jawbone tumours. The unique genetic aberrations distinguish it from other types of rhabdomyosarcomas. On the other hand, melanotic neuroectodermal tumour of infancy and osteoid osteoma were deleted from the benign bone and cartilageneous tumours, as was the hematolymphoid tumour of solitary plasmacytoma of bone. We systematically reviewed each entity in this chapter and provided important updated findings for selected topics that can further aid in the diagnostic process for challenging cases, broaden insights on the logic of the present classification, and finally, emphasize the potential that some of the molecular results may have in the near future to set new treatment approaches.
Topics: Bone Neoplasms; DNA-Binding Proteins; Head and Neck Neoplasms; Humans; Odontogenic Cysts; Odontogenic Tumors; Transcription Factors; World Health Organization
PubMed: 35312978
DOI: 10.1007/s12105-021-01404-7 -
European Urology Aug 2023Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external... (Review)
Review
CONTEXT
Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention.
OBJECTIVE
To perform an up-to-date systematic review of BC's epidemiology and external risk factors.
EVIDENCE ACQUISITION
Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018.
EVIDENCE SYNTHESIS
Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy.
CONCLUSIONS
We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention.
PATIENT SUMMARY
Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer.
Topics: Humans; Vehicle Emissions; Risk Factors; Urinary Bladder Neoplasms; Smoking; Tobacco Smoking; Occupational Exposure
PubMed: 37198015
DOI: 10.1016/j.eururo.2023.03.029 -
Virchows Archiv : An International... Feb 2021A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large...
A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.
Topics: Biomarkers, Tumor; Biopsy; Carcinoma; Endometrial Neoplasms; Evidence-Based Medicine; Female; Humans; Medical Oncology; Molecular Diagnostic Techniques; Neoplasm Staging; Predictive Value of Tests; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33604759
DOI: 10.1007/s00428-020-03007-z -
International Journal of Molecular... Aug 2022Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This... (Review)
Review
Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, in order to distinguish the biological and molecular origins. The authors performed a Medline and PubMed search for the years 1990-2022 using a combination of keywords on the topics to highlight the many genes and proteins involved in the pathogenesis of LMS. The mutation of these genes, in addition to the altered expression and functions of their enzymes, are potentially biomarkers of uterine LMS. Thus, the use of this molecular and protein information could favor differential diagnosis and personalized therapy based on the molecular characteristics of LMS tissue, leading to timely diagnoses and potential better outcomes for patients.
Topics: Female; Humans; Leiomyoma; Leiomyosarcoma; Pelvic Neoplasms; Uterine Neoplasms; Uterus
PubMed: 36077127
DOI: 10.3390/ijms23179728 -
International Journal of Molecular... Nov 2022Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory... (Review)
Review
Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory infection. This narrative overview aims to summarise and discuss current knowledge and previous evidence regarding triggers and pathophysiology of GBS. A systematic search of the literature was carried out using suitable search terms. The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in three quarters of cases, are previous infections. The most common infectious agents that cause GBS include , , and cytomegalovirus. is responsible for about a third of GBS cases. GBS due to is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signalling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space. In conclusion, GBS is a neuro-immunological disorder caused by autoantibodies against components of the myelin sheath or axolemma. Molecular mimicry between surface structures of pathogens and components of myelin or the axon is one scenario that may explain the pathophysiology of GBS.
Topics: Humans; Amantadine; Autoantibodies; Axons; Campylobacter jejuni; Guillain-Barre Syndrome
PubMed: 36430700
DOI: 10.3390/ijms232214222 -
Acta Neuropathologica Communications Mar 2023In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-α, IL-1α, and C1q induces a neurotoxic astrocytic phenotype, classified... (Review)
Review
In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-α, IL-1α, and C1q induces a neurotoxic astrocytic phenotype, classified as A1, A1-like, or neuroinflammatory reactive astrocytes. In contrast to typical astrocytes, which promote neuronal survival, support synapses, and maintain blood-brain barrier integrity, these reactive astrocytes downregulate supportive functions and begin to secrete neurotoxic factors, complement components like C3, and chemokines like CXCL10, which may facilitate recruitment of immune cells across the BBB into the CNS. The proportion of pro-inflammatory reactive astrocytes increases with age through associated microglia activation, and these pro-inflammatory reactive astrocytes are particularly abundant in neurodegenerative disorders. As the identification of astrocyte phenotypes progress, their molecular and cellular effects are characterized in a growing array of neuropathologies.
Topics: Humans; Astrocytes; Microglia; Central Nervous System; Blood-Brain Barrier; Chemokines; Neurotoxicity Syndromes
PubMed: 36915214
DOI: 10.1186/s40478-023-01526-9 -
Practical Radiation Oncology 2023With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the...
PURPOSE
With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling.
METHODS
The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation.
RESULTS
The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy.
CONCLUSIONS
These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.
Topics: Female; Humans; United States; Radiation Oncology; Endometrial Neoplasms; Brachytherapy; Combined Modality Therapy; Radiotherapy, Intensity-Modulated; Neoplasm Staging; Radiotherapy, Adjuvant
PubMed: 36280107
DOI: 10.1016/j.prro.2022.09.002 -
Advanced Biology Aug 2023Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss.... (Review)
Review
Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss. Intermittent fasting is a relatively new intervention that contributes to weight reduction. Considering the intimate relationship between obesity and inflammatory pathologies with gut microbiota alterations, a systematic review of the literature was herein conducted to elucidate the relationship between time-restricted food intake and gut microbiota diversity in humans. Searches are carried out in three databases (PubMed, MedLine/OVID, and Academic Search Complete) between April 2019 and April 2022. Nine studies (all with longitudinal design) were identified as eligible by presenting data about the impact of intermittent fasting schemes on gut microbiota. At the phylum level, Firmicutes and Bacteroidetes increase throughout follow-ups, while 16 bacteria genera change their abundance in response to intermittent fasting. Finally, some genera associated with clinical predictors such as weight change, abdominal circumference, and metabolic variables were reported. Changes induced by fasting schemes positively impact the diversity and abundance of gut microbiota and the biomarkers described here. However, the changes previously reported have been studied in short periods and some return to their basal state after fasting intervention.
Topics: Humans; Animals; Obesity; Gastrointestinal Microbiome; Intermittent Fasting; Inflammation; Bacteria
PubMed: 36950759
DOI: 10.1002/adbi.202200337 -
European Journal of Medical Genetics Oct 2021Hereditary Diffuse Gastric Cancer (HDGC) is a cancer predisposing syndrome mainly caused by germline inactivating variants in CDH1, encoding E-cadherin. Early-onset...
Hereditary Diffuse Gastric Cancer (HDGC) is a cancer predisposing syndrome mainly caused by germline inactivating variants in CDH1, encoding E-cadherin. Early-onset diffuse gastric cancer (DGC) and/or invasive lobular breast cancer (LBC) are the main phenotypes in CDH1-associated HDGC. CTNNA1, encoding for α-E-catenin, and E-cadherin-partner in the adherens junction complex, has been recently classified as a HDGC predisposing gene. Nevertheless, little is known about CTNNA1 tumor spectrum in variant carriers and variant-type associated causality. Herein, we systematically reviewed the literature searching for CTNNA1 germline variants carriers, further categorized them according to HDGC clinical criteria (HDGC vs non-HDGC), collected phenotypes, classified variants molecularly and according to CDH1 ACMG/AMP guidelines and performed genotype-phenotype analysis. We found 41 families carrying CTNNA1 germline variants encompassing in total 105 probands and relatives. All probands from 13 HDGC families presented DGC and their average age of onset was 40 ± 17 years; 10/13 (77%) HDGC families carried a pathogenic (P) variant. Most probands from 28 non-HDGC families developed unspecified-BC, as well as most of their relatives; 4/28 (14%) carried a P variant, 16/28 (57%) carried a likely pathogenic (LP) variant, 7/28 (25%) carried variants of unknown significance (VUS) and 1/28 (4%) carried a likely benign variant. Regardless of clinical criteria, 97% (32/33) of probands and relatives from P variant-carrier families had DGC/unspecified-GC. In LP variant-carrier families, 82% (28/34) of probands and relatives had unspecified-BC. Only 2/105 individuals had LBC. A cluster of frameshift and nonsense variants was found in CTNNA1 last exon of non-HDGC families and classified as VUS. In conclusion, current available data confirms an association of CTNNA1 P variants with early-onset DGC, but not with LBC. We demonstrate that in ascertained cohorts, CTNNA1 P variants explain <2% of HDGC families and support the use of ACMG/AMP CDH1 specific variant curation guidelines, while no specific guidelines are developed for CTNNA1 variant classification. Moreover, we demonstrated that truncating variants at the CTNNA1 NMD-incompetent last exon have limited deleteriousness, and that CTNNA1 LP variants have lower actionability than CDH1 LP variants. Current knowledge supports considering only CTNNA1 P variants as clinically actionable in HDGC carrying families.
Topics: Antigens, CD; Cadherins; Gene Frequency; Genetic Predisposition to Disease; Germ-Line Mutation; Heterozygote; Humans; Pedigree; Phenotype; Stomach Neoplasms; alpha Catenin
PubMed: 34425242
DOI: 10.1016/j.ejmg.2021.104316 -
The Journal of Craniofacial Surgery May 2022Primary oral mucosal melanoma (OMM) is a rare neoplasm accounting for the 0.2% to 0.8% of all melanomas. The aim of the present manuscript is (1) to describe 2 cases of...
PURPOSE
Primary oral mucosal melanoma (OMM) is a rare neoplasm accounting for the 0.2% to 0.8% of all melanomas. The aim of the present manuscript is (1) to describe 2 cases of primary OMM treated at our department, and (2) to perform a systematic literature review on primary OMM occurrence and treatment.
METHODS
Two cases of primary OMM were described. A systematic review is presented in order to assess the treatment options, recurrence, metastasis development, and survival rate of primary OMM.
RESULTS
Two patients were referred for the development of a lesion of the hard palate and the maxillary gingival mucosa, respectively. An incisional biopsy was performed in both patients, followed by extensive surgical resection after a thorough consideration of patient history and systemic involvement. The literature search retrieved 447 primary OMM cases. In the 30% of cases, distant metastases were already present at the time of diagnosis. The management of primary OMM most frequently involved surgical treatment and adjuvant radiotherapy.
CONCLUSIONS
Primary OMM still represents a challenge for the clinician, as the diagnosis is often performed when metastases have already developed. The prognosis is generally poor, thus highlighting the need for further investigations to improve early diagnosis.
Topics: Humans; Melanoma; Mouth Mucosa; Mouth Neoplasms; Prognosis; Retrospective Studies; Syndrome
PubMed: 34334749
DOI: 10.1097/SCS.0000000000008054