The role of computed tomography in the diagnosis of lung cancer - a case report

Introduction Lung cancer has been the main oncological problem in the world for years. It is extremely important to use appropriate diagnostic methods that enable its detection and implementation of appropriate treatment. Aim The presented case shows the advantage of computed tomography over chest X-ray (X-ray) in visualizing neoplastic changes in the lungs. Case Study The paper presents a description of a patient diagnosed with centrally located advanced lung adenocarcinoma with a strong expression of PD-L1 qualified for treatment with pembrolizumab. Results and Discussion Presented case confirms that X-ray is less sensitive, especially in the case of centrally located tumors. Therefore, the emergence of a new cough in a smoker or ex-smoker should raise concerns related to lung cancer despite a normal X-ray image. The central location of the tumor may cause dramatic course of the symptoms. In the presented case, a sudden significant deterioration of the condition was observed due to atelectasis of the entire lung. Haemoptysis observed during hospitalization was another symptom of centraly located tumor mass. Conclusions In conclusion, the history of cigarette smoking, presence of typical symptoms should provide an in-depth diagnosis of lung cancer, despite normal X-ray. Diagnostic procedures include computed tomography in the first place. The course of centrally localized disease may change rapidly during on first cycle of treatment. Due to the possibility of serious complications of the ongoing neoplastic disease, the patient should be under constant medical supervision.

Feline and Canine Cutaneous Lymphocytosis: Reactive Process or Indolent Neoplastic Disease?

Cutaneous lymphocytosis (CL) is an uncommon and controversial lymphoproliferative disorder described in dogs and cats. CL is generally characterized by a heterogeneous clinical presentation and histological features that may overlap with epitheliotropic lymphoma. Therefore, its neoplastic or reactive nature is still debated. Here, we describe clinicopathological, immunohistochemical, and clonality features of a retrospective case series of 19 cats and 10 dogs with lesions histologically compatible with CL. In both species, alopecia, erythema, and scales were the most frequent clinical signs. Histologically, a dermal infiltrate of small to medium-sized lymphocytes, occasionally extending to the subcutis, was always identified. Conversely, when present, epitheliotropism was generally mild. In cats, the infiltrate was consistently CD3+; in dogs, a mixture of CD3+ and CD20+ lymphocytes was observed only in 4 cases. The infiltrate was polyclonal in all cats, while BCR and TCR clonal rearrangements were identified in dogs. Overall, cats had a long-term survival (median overall survival = 1080 days) regardless of the treatment received, while dogs showed a shorter and variable clinical course, with no evident associations with clinicopathological features. In conclusion, our results support a reactive nature of the disease in cats, associated with prolonged survival; despite a similar histological picture, canine CL is associated with a more heterogeneous lymphocytic infiltrate, clonality results, and response to treatment, implying a more challenging discrimination between CL and CEL in this species. A complete diagnostic workup and detailed follow-up information on a higher number of cases is warrant for dogs.

A Comprehensive Review of Receptor-Type Tyrosine-Protein Phosphatase Gamma (PTPRG) Role in Health and Non-Neoplastic Disease

Protein tyrosine phosphatase receptor gamma (PTPRG) is known to interact with and regulate several tyrosine kinases, exerting a tumor suppressor role in several type of cancers. Its wide expression in human tissues compared to the other component of group 5 of receptor phosphatases, PTPRZ expressed as a chondroitin sulfate proteoglycan in the central nervous system, has raised interest in its role as a possible regulatory switch of cell signaling processes. Indeed, a carbonic anhydrase-like domain (CAH) and a fibronectin type III domain are present in the N-terminal portion and were found to be associated with its role as [HCO3−] sensor in vascular and renal tissues and a possible interaction domain for cell adhesion, respectively. Studies on PTPRG ligands revealed the contactins family (CNTN) as possible interactors. Furthermore, the correlation of PTPRG phosphatase with inflammatory processes in different normal tissues, including cancer, and the increasing amount of its soluble form (sPTPRG) in plasma, suggest a possible role as inflammatory marker. PTPRG has important roles in human diseases; for example, neuropsychiatric and behavioral disorders and various types of cancer such as colon, ovary, lung, breast, central nervous system, and inflammatory disorders. In this review, we sum up our knowledge regarding the latest discoveries in order to appreciate PTPRG function in the various tissues and diseases, along with an interactome map of its relationship with a group of validated molecular interactors.

Nasal Transmissible Venereal Tumor (TVT) with Bone Metastasis in a Dog

Background: Transmissible venereal tumor (TVT) is a highly contagious round cell neoplasm that affects dogs, and it is usually transmitted through coitus. The tumor is mainly located in the genital area; however, the neoplasm can also be extragenital, affecting the nose, mouth, and eyes, as well as the skin and superficial lymph nodes. Cytological examination is the most commonly used method for definitive diagnosis due to its low cost and fast execution. Chemotherapy, radiotherapy, surgical resection, and other procedures such as cryosurgery are the possible treatment options. The objective of this report was to describe a case of extragenital TVT with nasal primary site and metastasis in the bone tissue in a dog treated at a private veterinary hospital in the city of Belém, Pará, Brazil.Case: A 6-year-old male domiciliary Labrador Retriever dog, weighing 24.2 kg, received oncologic treatment in a private veterinary hospital in the city of Belém, Pará, Brazil. The animal had a history of neoplastic disease, and he had undergone TVT resection associated with chemotherapy treatment more than 3 years ago. The clinical examination revealed a volume increase in the periorbital region, left lateral ocular displacement, left nostril excessive epistaxis, recurrent sneezing, cough, and pain signs, and tumor metastasis was suspected. Complementary exams of oncological cytology, computed tomography (CT), hemogram, and serum biochemistry were requested for diagnosis and staging of the condition, and supportive therapy was prescribed. The cytological report showed a dense population of neoplastic round cells with characteristics of TVT. CT indicated the presence of a heterogeneous hypodense mass with irregular contours and partially defined limits, with slight uptake of the intravenously injected contrast medium that obliterated the nasal cavity, maxillary recess, nasopharyngeal meatus, frontal sinus, and sphenoid sinus on the left side. The hematological analysis revealed mild anemia, neutrophilia, and lymphopenia, while the biochemical analysis only showed hypocalcemia. The prescribed therapy was amoxicillin + potassium clavulanate, omega-3, firocoxib, tranexamic acid, and finally chemotherapy with lomustine. Since the patient did not return for follow-up, the outcome could not be determined.Discussion: The patient described in this report was a domiciliary dog who did not live with other pets, but had access to the community environment and contact with other animals. The animal’s history, clinical signs, and cytological and imaging findings were consistent with those of TVT. In extragenital presentations of TVT, the inguinal and sublumbar lymph nodes, lungs, and abdominal organs are most commonly affected. Furthermore, bone involvement is rare, as this has not been commonly described in the literature as compared to the other sites of metastases. An abrasive brush was used for the cytological sample collection, because it provides slides with richer cells as compared to the imprint samples. CT is an important tool for the diagnosis of neoformations in the skeleton, and this method demonstrated high efficiency in identifying the bone involvement and the degree of the invasion and lesion in this case. The therapeutic agents used in this case were different from the usual, since the patient was given lomustine (40 mg/capsule, orally) in the metronomic chemotherapy. This drug has been previously used as an alternative in a canine TVT case resistant to vincristine.Keywords: neoplasm, extragenital, computed tomography, TVT.Título: Tumor Venéreo Transmissível (TVT) nasal com metástase óssea em um cãoDescritores: neoplasia, extragenital, tomografia computadorizada, TVT.

Application of Machine Learning for the Prediction of Etiological Types of Classic Fever of Unknown Origin

Background: The etiology of fever of unknown origin (FUO) is complex and remains a major challenge for clinicians. This study aims to investigate the distribution of the etiology of classic FUO and the differences in clinical indicators in patients with different etiologies of classic FUO and to establish a machine learning (ML) model based on clinical data.Methods: The clinical data and final diagnosis results of 527 patients with classic FUO admitted to 7 medical institutions in Chongqing from January 2012 to August 2021 and who met the classic FUO diagnostic criteria were collected. Three hundred seventy-three patients with final diagnosis were divided into 4 groups according to 4 different etiological types of classical FUO, and statistical analysis was carried out to screen out the indicators with statistical differences under different etiological types. On the basis of these indicators, five kinds of ML models, i.e., random forest (RF), support vector machine (SVM), Light Gradient Boosting Machine (LightGBM), artificial neural network (ANN), and naive Bayes (NB) models, were used to evaluate all datasets using 5-fold cross-validation, and the performance of the models were evaluated using micro-F1 scores.Results: The 373 patients were divided into the infectious disease group (n = 277), non-infectious inflammatory disease group (n = 51), neoplastic disease group (n = 31), and other diseases group (n = 14) according to 4 different etiological types. Another 154 patients were classified as undetermined group because the cause of fever was still unclear at discharge. There were significant differences in gender, age, and 18 other indicators among the four groups of patients with classic FUO with different etiological types (P < 0.05). The micro-F1 score for LightGBM was 75.8%, which was higher than that for the other four ML models, and the LightGBM prediction model had the best performance.Conclusions: Infectious diseases are still the main etiological type of classic FUO. Based on 18 statistically significant clinical indicators such as gender and age, we constructed and evaluated five ML models. LightGBM model has a good effect on predicting the etiological type of classic FUO, which will play a good auxiliary decision-making function.

The Impact of Iron Chelators on the Biology of Cancer Stem Cells

Neoplastic diseases are still a major medical challenge, requiring a constant search for new therapeutic options. A serious problem of many cancers is resistance to anticancer drugs and disease progression in metastases or local recurrence. These characteristics of cancer cells may be related to the specific properties of cancer stem cells (CSC). CSCs are involved in inhibiting cells’ maturation, which is essential for maintaining their self-renewal capacity and pluripotency. They show increased expression of transcription factor proteins, which were defined as stemness-related markers. This group of proteins includes OCT4, SOX2, KLF4, Nanog, and SALL4. It has been noticed that the metabolism of cancer cells is changed, and the demand for iron is significantly increased. Iron chelators have been proven to have antitumor activity and influence the expression of stemness-related markers, thus reducing chemoresistance and the risk of tumor cell progression. This prompts further investigation of these agents as promising anticancer novel drugs. The article presents the characteristics of stemness markers and their influence on the development and course of neoplastic disease. Available iron chelators were also described, and their effects on cancer cells and expression of stemness-related markers were analyzed.

Canine and Feline Cutaneous Lymphocytosis: Reactive Process or Indolent Neoplastic Disease?

Cutaneous lymphocytosis (CL) is an uncommon and controversial lymphoproliferative disorder described in dogs and cats. CL is generally characterized by a heterogeneous clinical presentation and histological features that may overlap with epitheliotropic lymphoma. Therefore, its neoplastic or reactive nature is still debated. Here, we describe clinicopathological, immunohistochemical and clonality features of a retrospective case series of 19 cats and 10 dogs with lesions histologically compatible with CL. In both species, alopecia, erythema and scales were the most frequent clinical signs. Histologically, a dermal infiltrate of small to medium-sized lymphocytes, occasionally extending to the subcutis, was always identified. Conversely, when present, epitheliotropism was generally mild. In cats, the infiltrate was consistently CD3+; in dogs, a mixture of CD3+ and CD20+ lymphocytes was observed only in 4 cases. The infiltrate was polyclonal in all cats, while BCR and TCR clonal rearrangements were identified in dogs. Overall, cats had a long-term survival (median overall survival=1080 days) regardless of the treatment received, while dogs showed a shorter and variable clinical course, with no evident associations with clinicopathological features. In conclusion, our results support a reactive nature of the disease in cats, associated with prolonged survival; despite a similar histological picture, canine CL was associated with a more heterogeneous lymphocytic infiltrate, clonality results, and response to treatment.

An Orthotopic Model of Uveal Melanoma in Zebrafish Embryo: A Novel Platform for Drug Evaluation

Uveal melanoma is a highly metastatic tumor, representing the most common primary intraocular malignancy in adults. Tumor cell xenografts in zebrafish embryos may provide the opportunity to study in vivo different aspects of the neoplastic disease and its response to therapy. Here, we established an orthotopic model of uveal melanoma in zebrafish by injecting highly metastatic murine B16-BL6 and B16-LS9 melanoma cells, human A375M melanoma cells, and human 92.1 uveal melanoma cells into the eye of zebrafish embryos in the proximity of the developing choroidal vasculature. Immunohistochemical and immunofluorescence analyses showed that melanoma cells proliferate during the first four days after injection and move towards the eye surface. Moreover, bioluminescence analysis of luciferase-expressing human 92.1 uveal melanoma cells allowed the quantitative assessment of the antitumor activity exerted by the canonical chemotherapeutic drugs paclitaxel, panobinostat, and everolimus after their injection into the grafted eye. Altogether, our data demonstrate that the zebrafish embryo eye is a permissive environment for the growth of invasive cutaneous and uveal melanoma cells. In addition, we have established a new luciferase-based in vivo orthotopic model that allows the quantification of human uveal melanoma cells engrafted in the zebrafish embryo eye, and which may represent a suitable tool for the screening of novel drug candidates for uveal melanoma therapy.

Problems, Stressors and Needs of Children and Adolescents with Cancer

Background: Cancer diseases in children and adolescents are considered to be one of the most serious health problems in the world. It is estimated that about 151,435 cases are diagnosed in children annually. Children with cancer experience many comorbid symptoms related to diagnosis and treatment that can profoundly affect their lives. They experience physical and emotional suffering, which affects their well-being and physical fitness, influencing the prognosis and deteriorating their physical, mental and social functioning. Given the limited data, an attempt was made to assess the problems of the biopsychosocial sphere of need and stressors among children and adolescents treated for cancer. Accurate symptom assessment is essential to ensure high-quality care and effective treatment. Patients and Methods: The qualitative study was conducted in pediatric oncology of hospitals in Poland. Children diagnosed with cancer were invited to participate in the study to assess their problems, stressors and needs. Results: The study included 520 people, where female sex constituted 48% and male 52%. The mean age of the children is 13.2 SD = 2.5. Negative experiences related to the disease are experienced by 82% of children. Among the surveyed children, the most experienced were anxiety (61%). The conducted research shows that as many as 69% of all respondents experienced states that indicate severe depression. The most common somatic problems reported by children were pain (58%). The most dominant areas of life that had a negative impact was body image (85%). Conclusions: Children and adolescents diagnosed with neoplastic disease experience many problems and stressors in every sphere of life, which undoubtedly affects a high level of unmet needs. The main category of needs concerning the challenges faced by children with cancer was psychological and care problems. In the youth group, the needs were mainly related to education and social support.

A Cell Culture System to Investigate Marek’s Disease Virus Integration into Host Chromosomes

Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes a devastating neoplastic disease in chickens. MDV has been shown to integrate its genome into the telomeres of latently infected and tumor cells, which is crucial for efficient tumor formation. Telomeric repeat arrays present at the ends of the MDV genome facilitate this integration into host telomeres; however, the integration mechanism remains poorly understood. Until now, MDV integration could only be investigated qualitatively upon infection of chickens. To shed further light on the integration mechanism, we established a quantitative integration assay using chicken T cell lines, the target cells for MDV latency and transformation. We optimized the infection conditions and assessed the establishment of latency in these T cells. The MDV genome was efficiently maintained over time, and integration was confirmed in these cells by fluorescence in situ hybridization (FISH). To assess the role of the two distinct viral telomeric repeat arrays in the integration process, we tested various knockout mutants in our in vitro integration assay. Efficient genome maintenance and integration was thereby dependent on the presence of the telomeric repeat arrays in the virus genome. Taken together, we developed and validated a novel in vitro integration assay that will shed light on the integration mechanism of this highly oncogenic virus into host telomeres.