The Impact of Oral Microbiome Dysbiosis on the Aetiology, Pathogenesis, and Development of Oral Cancer.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Although the oral cavity is an easily accessible area for visual examination, the OSCC is more often detected at an advanced stage. The global prevalence of OSCC is around 6%, with increasing trends posing a significant health problem due to the increase in morbidity and mortality. The oral cavity microbiome has been the target of numerous studies, with findings highlighting the significant role of dysbiosis in developing OSCC. Dysbiosis can significantly increase pathobionts (bacteria, viruses, fungi, and parasites) that trigger inflammation through their virulence and pathogenicity factors. In contrast, chronic bacterial inflammation contributes to the development of OSCC. Pathobionts also have other effects, such as the impact on the immune system, which can alter immune responses and contribute to a pro-inflammatory environment. Poor oral hygiene and carbohydrate-rich foods can also increase the risk of developing oral cancer. The risk factors and mechanisms of OSCC development are not yet fully understood and remain a frequent research topic. For this reason, this narrative review concentrates on the issue of dysbiosis as the potential cause of OSCC, as well as the underlying mechanisms involved.

Aggregatibacter actinomycetemcomitans: From the Oral Cavity to the Heart Valves.

Aggregatibacter actinomycetemcomitans (A. actinomycetecomitans) is a Gram-negative bacterial species that is an essential component of the oral microbiota. Due to its aggregative properties, it plays a role in the pathogenesis of human diseases. The presence of the surface proteins Fim, Briae, and microvesicles enables the bacterium to adhere to the epithelial surface and the tooth's surface. The presence of leukotoxin A (LtxA), which plays an important role in the pathogenicity of the bacterium, has been associated with both periodontitis and the etiology of rheumatoid arthritis (RA). A. actinomycetecomitans is also associated with several other systemic diseases and complications, such as endocarditis and different abscesses. In addition to leukotoxin A, A. actinomycetecomitans possesses several different virulence factors, including bacteriocins, chemotaxis inhibitory factors, cytotoxic factors, Fc-binding proteins, immunosuppressive factors, lipopolysaccharide collagenase, fibroblast inhibitory factors, antibiotic resistance determinants, adhesins, invasive factors and factors that inhibit the function of polymorphonuclear leukocytes. The ability of A. actinomycetemcomitans lipopolysaccharide to induce macrophages to secrete the interleukins IL-1, IL-1ß, and tumor necrosis factor (TNF) is of considerable importance. The primary etiologic factor in the pathogenesis of periodontal disease is the oral biofilm colonized by anaerobic bacteria. Among these, A. actinomycetemcomitans occupies an important place as a facultative anaerobic bacterium. In addition, A. actinomycetemcomitans possesses many virulence factors that contribute to its potential to cause cancer. This article provides an overview of the virulence factors of A. actinomycetecomitans and its association with various systemic diseases, its oncogenic potential, and the treatment options for infections caused by A. actinomycetecomitans.

A rare presentation of leiomyosarcoma metastasis to the cervical spine: A case report and a brief review.

Background: Leiomyosarcoma (LMS) is a rare malignancy that originates from smooth muscle. The most common sites of metastases include the lungs, liver, kidney, and skin. Notably, metastases of LMS to the central nervous system/or spine are extremely rare. When a cervical spinal LMS lesion was encountered, the patient successfully underwent gross total tumor resection with negative margins. Case Description: A 63-year-old female had undergone an anterior cervical C5-C7 diskectomy and fusion 18 years ago and resection of a retroperitoneal LMS 3 years ago. She newly presented with right-sided numbness and pain of 2 months duration that correlated with a focal right-sided C5-level hemiparesis (i.e., 4/5 motor strength). When the cervical magnetic resonance demonstrated a right-sided C5 intralaminar mass with extension into the C5-C6 foramen, she underwent posterior tumor resection; pathologically, this proved to be an LMS metastasis. Respectively, 1- and six months postoperatively, follow-up magnetic resonance imaging scans showed no tumor recurrence; she tolerated adjuvant oncological treatment accompanied by physical therapy. However, in one postoperative year, the lesion recurred, and she is presently under consideration for additional surgical management. Conclusion: Gross total surgical resection is the first line of treatment for patients with metastatic LMS. Here, a patient with a C5 laminar/C5-C6 foraminal bony LMS metastasis underwent posterior tumor resection accompanied by adjuvant oncological treatment but exhibited disease recurrence within one postoperative year.

Health Effects of Ionizing Radiation on the Human Body.

Radioactivity is a process in which the nuclei of unstable atoms spontaneously decay, producing other nuclei and releasing energy in the form of ionizing radiation in the form of alpha (α) and beta (ß) particles as well as the emission of gamma (γ) electromagnetic waves. People may be exposed to radiation in various forms, as casualties of nuclear accidents, workers in power plants, or while working and using different radiation sources in medicine and health care. Acute radiation syndrome (ARS) occurs in subjects exposed to a very high dose of radiation in a very short period of time. Each form of radiation has a unique pathophysiological effect. Unfortunately, higher organisms-human beings-in the course of evolution have not acquired receptors for the direct "capture" of radiation energy, which is transferred at the level of DNA, cells, tissues, and organs. Radiation in biological systems depends on the amount of absorbed energy and its spatial distribution, particularly depending on the linear energy transfer (LET). Photon radiation with low LET leads to homogeneous energy deposition in the entire tissue volume. On the other hand, radiation with a high LET produces a fast Bragg peak, which generates a low input dose, whereby the penetration depth into the tissue increases with the radiation energy. The consequences are mutations, apoptosis, the development of cancer, and cell death. The most sensitive cells are those that divide intensively-bone marrow cells, digestive tract cells, reproductive cells, and skin cells. The health care system and the public should raise awareness of the consequences of ionizing radiation. Therefore, our aim is to identify the consequences of ARS taking into account radiation damage to the respiratory system, nervous system, hematopoietic system, gastrointestinal tract, and skin.

A Putative Role of Candida albicans in Promoting Cancer Development: A Current State of Evidence and Proposed Mechanisms.

Candida albicans is a commensal fungal species that commonly colonizes the human body, but it is also a pervasive opportunistic pathogen in patients with malignant diseases. A growing body of evidence suggests that this fungus is not only coincidental in oncology patients, but may also play an active role in the development of cancer. More specifically, several studies have investigated the potential association between C. albicans and various types of cancer, including oral, esophageal, and colorectal cancer, with a possible role of this species in skin cancer as well. The proposed mechanisms include the production of carcinogenic metabolites, modulation of the immune response, changes in cell morphology, microbiome alterations, biofilm production, the activation of oncogenic signaling pathways, and the induction of chronic inflammation. These mechanisms may act together or independently to promote cancer development. Although more research is needed to fully grasp the potential role of C. albicans in carcinogenesis, the available evidence suggests that this species may be an active contributor and underscores the importance of considering the impact of the human microbiome on cancer pathogenesis. In this narrative review, we aimed to summarize the current state of evidence and offer some insights into proposed mechanisms.

COVID-19 Pandemic Effects on Breast Cancer Diagnosis in Croatia: A Population- and Registry-Based Study.

BACKGROUND: Our objective was to assess the effects of COVID-19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers in the Republic of Croatia. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective, population- and registry-based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases. RESULTS: The average monthly percent change after the initial lockdown measures were introduced was -11.0% (95% confidence interval - 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017-2019. CONCLUSION: It seems that national health care system measures for controlling the spread of COVID-19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID-19 control measures were relaxed, and it has not reoccurred during the second COVID-19 wave. Although the COVID-19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020. IMPLICATIONS FOR PRACTICE: It is possible to compensate for the adverse effects of COVID-19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non-negligible extent.

PROGNOSTIC IMPACT OF LOW ESTROGEN AND PROGESTERONE POSITIVITY IN LUMINAL B (HER2 NEGATIVE) BREAST CANCER.

- Luminal B (HER2 negative) subtype is the most diversiform type of breast cancers, with a high Ki-67 proliferation index (>20%) or/and low progesterone (PR; <20%) with various intensity and distribution of hormone receptors. Considerable difference has also been noticed in disease outcome, wherefore there is the need for a more detailed classification of this tumor subtype. The clinical and pathologic parameters of 147 luminal B (HER2 negative) breast cancers were examined. The expression of hormone receptors in correlation with other prognostic factors and disease outcome was analyzed by Kaplan-Meier curves and multivariate Cox regression analysis. The Kaplan-Mayer analysis showed that low positivity of estrogen (ER) and PR receptors in tumors was associated with a significantly worse disease outcome (overall survival (ER), p=0.020; disease free survival (ER), p=0.019; overall survival (PR), p=0.026; disease free survival (PR), p=0.038)), unlike Ki-67, which did not show a statistically significant connection (overall survival, p=0.343; disease free survival, p=0.322). The intensity of receptor staining and Ki-67 relative to other histopathologic prognostic factors showed a statistically significant correlation solely with histologic grade of tumor. By using the Cox regression model, PR proved to be an independent prognostic factor for overall survival (p=0.004) and disease free survival (p=0.029). The luminal B (HER2 negative) breast cancer with low expression of hormone receptors, independent of the Ki-67 proliferation index, and in correlation with a higher histologic grade, could be a unique subtype of cancer.

High Tumor Stroma Proportion is a Worse Prognostic Factor in Colorectal Cancer

High stroma proportion appears to be a very important prognostic factor in esophageal and breast cancer. Previous researches have shown that it might have a similar effect on colorectal cancer. The aim of this study was to determine whether tumor stroma proportion influenced patient survival. This retrospective study included 236 patients with colorectal cancer having undergone surgery in 2006 and 2007 at Osijek University Hospital Center. Location with the highest stroma proportion at the site of deepest tumor invasion was determined. Patients were divided into the groups with high stroma proportion (>50%) and low stroma proportion (≤50%). Stroma proportion showed a statistically significant correlation with tumor stage. Kaplan-Meier survival curves yielded a statistically significant difference in patient overall survival (Cox ph model p=0.016) and progression-free survival (Cox ph model, p=0.0188) according to stroma proportion. Study results showed a statistically significantly shorter overall survival and progression-free survival in patients with high stroma proportion.