Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Lung cancer is the most common cause of mortality from malignant tumors worldwide. The five-year survival rate for people with advanced stages varies considerably, from 35.4% to 6.9%. The angiogenic potential of bcl2 is not well known, nor is the way in which tumor cells with excessive bcl2 expression affect VEGF production. Hypothetically, given that tumor growth, progression and metastasis are dependent on angiogenesis, the antiapoptotic effect is expected to form a link between these two molecules. The aim of this study was to evaluate the relationship between bcl-2 and VEGF expression, clinicopathological features and survival in 216 patients with advanced NSCLC. Archival tumor tissues were examined by immunohistochemistry for the expression of bcl-2 and VEGF. Immunoreactivity for bcl-2 was observed in 41.4% of NSCLCs, 51% of squamous and 34.8% of adenocarcinomas-expressed Bcl-2. There was an inverse correlation of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (p < 0.0005). A total of 71.8% NSCLCs were VEGF positive, 56% of squamous and 82.2% of adenocarcinomas. High level of VEGF expression was significantly associated with histology type (p = 0.043), low histology grade (p = 0.014), clinical stage IV (p = 0.018), smoking history (p = 0.008) and EGFR mutations (p = 0.026). There was an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC patients (p = 0.039, r = -0.163). Two-year survival of patients with unresectable NSCLC was 39.3%, and 50% of patients were alive at 17 months. Our results demonstrated no difference in survival for patients in advanced NSCLC grouped by bcl-2 and VEGF status. Additionally, we observed an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC and mononuclear reaction and bcl-2 expression in adenocarcinomas.

Vitamin D, Albumin, and D-Dimer as Significant Prognostic Markers in Early Hospitalization in Patients with COVID-19.

SARS-CoV-2 continues to pose a major challenge to scientists and clinicians. We examined the significance of the serum concentrations of vitamin D, albumin, and D-dimer for the severity of the clinical picture and mortality in COVID-19. MATERIALS AND METHODS: A total of 288 patients treated for COVID-19 infection participated in the research. The patients were treated in the period from May 2020 to January 2021. All patients were divided based on the need for oxygen therapy (Sat > 94%) into patients with mild or severe clinical pictures. The biochemical and radiographic parameters of the patients were analyzed. Appropriate statistical methods were used in the statistical analysis. RESULTS: In patients with COVID-19 with confirmed severe clinical pictures, lower values of serum albumin (p < 0.0005) and vitamin D (p = 0.004) were recorded, as opposed to elevated values of D-dimer (p < 0.0005). Accordingly, the patients with fatal disease outcomes had lower levels of albumin (p < 0.0005) and vitamin D (p = 0.002), while their D-dimer (p < 0.0005) levels were elevated. An increase in the radiographic score, as a parameter for assessing the severity of the clinical picture, was accompanied by a decrease in serum albumin (p < 0.0005) and a simultaneous increase in D-dimer (p < 0.0005), without a change in the vitamin D concentration (p = 0.261). We also demonstrated the interrelations of the serum levels of vitamin D, albumin, and D-dimer in patients with COVID-19 as well as their significance as predictors of the outcome of the disease. CONCLUSION: The significance of the predictive parameters in our study indicates the existence of an important combined role of vitamin D, albumin, and D-dimer in the early diagnosis of the most severe patients suffering from COVID-19. Reduced values of vitamin D and albumin, in combination with elevated values of D-dimer, can be timely indicators of the development of a severe clinical picture and death due to COVID-19.

Metastatic Breast Cancer Presenting as Acute Appendicitis: A Rare Case Study and Review of Current Knowledge.

This manuscript discusses a rare case of acute appendicitis caused by metastasis from invasive breast carcinoma of no special type in a 70-year-old female previously diagnosed with breast cancer. It delves into the diagnostic challenges and management complexities of such unusual clinical presentations. The paper includes an analysis of 19 documented cases, enriching the understanding of metastatic patterns and treatment strategies in breast cancer. It underlines the importance of considering a history of malignancy when diagnosing acute abdominal conditions and emphasizes a comprehensive approach in interpreting diagnostic imaging in patients with past oncological issues to effectively manage metastatic breast cancer exhibiting atypical manifestations.

Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy.

Several Serratia species are widely distributed in nature, but Serratia marcescens is the only species frequently isolated in hospitals. This pathogen is mainly responsible for nosocomial infection, mostly in immunocompromised hosts. A 26-year-old woman with a twin pregnancy, regularly controlled, was hospitalized at 24 + 5 weeks of gestation due to scant vaginal bleeding, lower abdominal pain, and body temperature up to 37.5°C. Gynecological examination revealed bleeding accompanied by dilatation of the cervix. The laboratory analyses revealed leukocytosis with elevated C-reactive protein (CRP). Treatment was initiated with intravenous antibiotic administration. After admission, fetal membranes spontaneously ruptured, and an extremely preterm dichorionic female twin birth occurred at 25 + 0 weeks of gestation. Both infants died two days after labor. Pathological and microbiological analyses revealed chorioamnionitis caused by S. marcescens. According to the antibiogram, antibiotic treatment was continued for the next 7 days. The examination of cervical and vaginal discharge samples was negative three days and two weeks after therapy. S. marcescens may cause spontaneous miscarriages and, in this important case, caused loss of discordant twins in an extremely preterm birth by an immunocompetent patient. Infection by S. marcescens cannot be excluded as a cause of discordant growth and needs to be confirmed by further research.

Breast Cancer and p16: Role in Proliferation, Malignant Transformation and Progression.

The definition of new molecular biomarkers could provide a more reliable approach in predicting the prognosis of invasive breast cancers (IBC). The aim of this study is to analyze the expression of p16 protein in IBC, as well as its participation in malignant transformation. The study included 147 patients diagnosed with IBC. The presence of non-invasive lesions (NIL) was noted in each IBC and surrounding tissue. p16 expression was determined by reading the percentage of nuclear and/or cytoplasmic expression in epithelial cells of IBC and NIL, but also in stromal fibroblasts. Results showed that expression of p16 increases with the progression of cytological changes in the epithelium; it is significantly higher in IBC compared to NIL (p < 0.0005). Cytoplasmic p16 expression is more prevalent in IBC (76.6%), as opposed to nuclear staining, which is characteristic of most NIL (21.1%). There is a difference in p16 expression between different molecular subtypes of IBC (p = 0.025). In the group of p16 positive tumors, pronounced mononuclear infiltrates (p = 0.047) and increased expression of p16 in stromal fibroblasts (p = 0.044) were noted. In conclusion, p16 protein plays an important role in proliferation, malignant transformation, as well as in progression from NIL to IBC.

Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma.

Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth.

Hypercalcemic type of small cell carcinoma of the ovary.

INTRODUCTION: Extrapulmonary small cell carcinoma is a rare, prognostically bad tumor category. Primary, it can be localized in every organ, even in the ovary, where, due to its clinical specificities, it represents a challenge in diagnosis, as well as in therapy. Small cell ovarian carcinoma (SCOC) is biologically very aggressive malignant tumor of unknown histogenesis. We presented a rare case of SCOC with hypercalcemia of aggressive course and fatal outcome in a postmenopausal woman at International Federation of Gynecology and Obstetrics (FIGO) Ia stage. CASE REPORT: A 60-year-old woman, Caucasian, came to the doctor because of discomfort in the lower abdomen and pain of greater intensity in last few days. Ultrasound examination and CT scan of the abdomen confirmed the presence of large adnexal masses of cystic-solid appearance with the largest diameter of 13 cm, regular structure of the other gynecological organs, without verifying the existence of metastatic deposits. All the results of laboratory analysis gave normal values, except for calcium, which was elevated. Explorative laparotomy with complete hysterectomy, bilateral salpingo-oophorectomy, dissection of lymph nodes and omentectomy were conducted. Based on pathohistological analysis of the operative material, SCOC at FIGO Ia stage was diag- nosed. No complications were observed in a postsurgery period and after 10 days the patient was discharged in a good condition and with normal calcemia. The treatment was continued with concurrent radiotherapy and chemotherapy. However, in spite of overall treatment, the disease progressed, and the patient died of disseminated metastatic disease, 26 months after the diagnosis. CONCLUSION: Small cell carcinoma localized in the ovary is generally a tumor category with bad prognosis depending on the stage of the disease.

Dysplasia epiphysealis hemimelica: a case report.

INTRODUCTION: Dysplasia epphysealis hemimelica, also known as Trevor's disease, is an extremely rare skeletal developmental disorder of unknown etiology, characterized by an osteocartilaginous outgrowth of one or more epiphyses or of a tarsal bone during childhood. CASE REPORT: We presented a sporadic case of dysplasia Epipysealis hemimelica developed in the talus. A 6-year-old boy complained of swelling of his right ankle joint, with painful and reduced movements. Radiographies suggested excessive overgrowth of the dorsomedial aspect of the talus. The tumor was surgically excised and the gross and histological findings were consistent with those of osteochondroma. CONCLUSION: Dysplasia epphysealis hemimelica is diagnosed by clinical, radiographic and histopathological examination. Early diagnosis is important for the condition to be treated before the deformity becomes disabling.

Gestational choriocarcinoma of the cervix.

Choriocarcinoma is the most aggressive, malignant form of gestational trophoblastic disease and has varying incidence, increasing in patients older than 40 years. It usually develops after a malignant alteration in a molar pregnancy, but rarely after an abortion or normal or ectopic pregnancies. The most common localization is the uterus, but it can also be found rarely in the ovaries, fallopian tubes, vagina, vulva, cervix or pelvic region. A 38-year-old multiparous woman, with no complications in three previous labors and four miscarriages, presented to her gynecologist one year after the last miscarriage complaining of abnormal vaginal bleeding. Clinical examinations showed normal ultrasound and histopathology findings. Blood analysis demonstrated moderate anemia and low elevated serum b-human chorionic gonadotropin. Due to profuse hemorrhage and anemia after the curettage, the medical council decided that a total hysterectomy should be performed. Macroscopic examination of the post-operative material showed regular morphology of the uterus, fallopian tubes and ovaries. However, a whitish brown lesion with a maximum diameter of 22 mm was noted in a longitudinal section of the cervix. Using standard histopathology and immunohistochemical analysis, a cervical gestational choriocarcinoma was diagnosed. Knowledge of the characteristics of the choriocarcinoma is very important for accurate diagnosis and treatment, especially when the tumor is localized on the rare locations and where a high level of serum b-human chorionic gonadotropin is absent.

Cancer of ectopic parathyroid gland presentation of the disease with a case report.

Tc-99m-methoxyisobutylisonitril (MIBI) scintigraphy is localizing diagnostic methods that is used for detection of sicken parathyroid gland (PT). The use of this method for PT diseases diagnosis makes surgical treatment of a patient more successful. This is a report about the patient who was surgically treated for primary hyperparathyroidism caused by hyperplasia of parathyroid glands and cancer of ectopic parathyroid gland. He was operated in two acts. The first surgical intervention was performed without preoperative diagnostics of Tc-99m-MIBI scintigraphy, while the second surgical intervention was preceded by Tc-99m-MIBI scintigraphy which clearly showed the existence of tumor in the back mediastinum (ectopic parathyroid gland). Pathophysiological analysis of the extirpated parathyroid gland showed the case of ectopic parathyroid gland cancer. The use of Tc-99m-MIBI scintigraphy as a localizing method before the first surgical intervention could have saved the patient from the second one and from risks it could have caused, as well.

Foreign body extraction through the rigid bronchoscopy.

INTRODUCTION: Foreign body aspiration into tracheobronchial tree represents an urgent condition at high level of risk. Etiology is different, and this condition is typical for all ages with highest incidence in pediatric population. CASE REPORT: A successful foreign body removal (partial denture) in a 34-year old man was presented. Radiography and computerized tomography of the chest showed a foreign body localized at the level of the right bronchus including the right middle lobe bronchus. By the use of rigid bronchoscopy, a foreign body was visualized and mobilized from the segmental bronchus in the first act, and then completely extracted. CONCLUSION: Efficient diagnostics and extraction are imperative for the aspirated foreign body preventing life-threatening complications.

Giant dumbbell tumor of the posterior mediastinum.

BACKGROUND: Giant dumbbell-shaped tumors are very rare and characterized by intra- and extraspinal propagation of different dimensions. In thoracal localization, invasive growth can lead up to rib and vertebra erosion. CASE REPORT: We presented a 54-year-old woman with a giant dumbbell schwannoma in the posterior mediastinum. The tumor was removed by the posterior approach with hemilaminectomy and costotransversectomy. By microscopic examination the diagnosis of benign schwannoma was made. A year after the surgery, the patient was without neurological deficiency and without radiological signs of illness relapse. CONCLUSION: Treatment of dumbbell schwannoma is surgical, dilemmas of the optimal surgical approach. When it is thoracally located the posterior approach with hemilaminectomy and costotransversectomy is safe and effective for its removal.