Correlation Studies between S100 Protein Level and Soluble MIA or Tissue MelanA and gp100 (HMB45) Expression in Cutaneous Melanoma.

(1) Background: Cutaneous melanoma (CM) originates from melanocytes and causes 90% of skin cancer deaths; therefore, the comparison of different soluble and tissue markers could be valuable in the detection of melanoma progression and therapy monitoring. The present study is focused on the potential correlations between soluble S100B and MIA protein levels in different melanoma stages or with tissue expression of S100, gp100 (HMB45), and MelanA biomarkers. (2) Methods: Soluble S100B and MIA levels were evaluated by means of immunoassay methods in blood samples from 176 patients with CM, while tissue expressions of S100, MelanA, and gp100 (HMB45) were detected by means of immunohistochemistry in 76 melanomas. (3) Results: Soluble S100B correlated with MIA in stages III (r = 0.677, p < 0.001) and IV (r = 0.662, p < 0.001) but not in stages I and II; however, 22.22% and 31.98% of stage I and II patients, respectively, had high values for at least one of the two soluble markers. S100 tissue expression correlated with both MelanA (r = 0.610, p < 0.001) and HMB45 (r = 0.476, p < 0.01), while HMB45 and MelanA also significantly positively correlated (r = 0.623, p < 0.001). (4) Conclusions: Blood levels of S100B and MIA corroborated with melanoma tissue markers expression could help to improve the stratification process for patients with a high risk of tumor progression.

Quantitative SPECT/CT Parameters in the Assessment of Transthyretin Cardiac Amyloidosis-A New Dimension of Molecular Imaging.

AIMS: Cardiac transthyretin amyloidosis (ATTR) represents the accumulation of misfolded transthyretin in the heart interstitium. Planar scintigraphy with bone-seeking tracers has long been established as one of the three main steps in the non-invasive diagnosis of ATTR, but lately, single-photon emission computed tomography (SPECT) has gained wide recognition for its abilities to exclude false positive results and offer a possibility for amyloid burden quantitation. We performed a systematic review of the existing literature to provide an overview of the available SPECT-based parameters and their diagnostic performances in the assessment of cardiac ATTR. Methods and Methods: Among the 43 papers initially identified, 27 articles were screened for eligibility and 10 met the inclusion criteria. We summarised the available literature based on radiotracer, SPECT acquisition protocol, analysed parameters and their correlation to planar semi-quantitative indices. RESULTS: Ten articles provided accurate details about SPECT-derived parameters in cardiac ATTR and their diagnostic potential. Five studies performed phantom studies for accurate calibration of the gamma cameras. All papers described good correlation of quantitative parameters to the Perugini grading system. CONCLUSIONS: Despite little published literature on quantitative SPECT in the assessment of cardiac ATTR, this method offers good prospects in the appraisal of cardiac amyloid burden and treatment monitoring.

Analysis of Efficacy-To-Safety Ratio of Angiogenesis-Inhibitors Based Therapies in Ovarian Cancer: A Systematic Review and Meta-Analysis.

(1) Background: Among new anti-angiogenesis agents being developed and ever-changing guidelines indications, the question of the benefits/safety ratio remains unclear. (2) Methods: We performed a systematic review combined with a meta-analysis of 23 randomized controlled trials (12,081 patients), evaluating overall survival (OS), progression free survival (PFS) and toxicity (grade ≥ 3 toxic effects, type, and number of all adverse effects. (3) Results: The analysis showed improvement of pooled-PFS (HR, 0.71; 95% CI, 0.64-0.78; I2 = 77%; p < 0.00001) in first-line (HR, 0.85; 95% CI, 0.78-0.93; p = 0.0003) or recurrent cancer (HR, 0.62; 95% CI, 0.56-0.70; p < 0.00001) and regardless of the type of anti-angiogenesis drug used (Vascular endothelial growth factor (VEGF) inhibitors, VEGF-receptors (VEGF-R) inhibitors or angiopoietin inhibitors). Improved OS was also observed (HR, 0.95; 95% CI, 0.90-0.99; p = 0.03). OS benefits were only observed in recurrent neoplasms, both platinum-sensitive and platinum-resistant neoplasms. Grade ≥ 3 adverse effects were increased across all trials. Anti-angiogenetic therapy increased the risk of hypertension, infection, thromboembolic/hemorrhagic events, and gastro-intestinal perforations but not the risk of wound-related issues, anemia or posterior leukoencephalopathy syndrome. (4) Conclusions: Although angiogenesis inhibitors improve PFS, there are little-to-no OS benefits. Given the high risk of severe adverse reactions, a careful selection of patients is required for obtaining the best results possible.

The Female Reproductive Tract Microbiome and Cancerogenesis: A Review Story of Bacteria, Hormones, and Disease.

The microbiota is the complex community of microorganisms that populate a particular environment in the human body, whereas the microbiome is defined by the entire habitat-microorganisms and their environment. The most abundant and, therefore, the most studied microbiome is that of the gastrointestinal tract. However, the microbiome of the female reproductive tract is an interesting research avenue, and this article explores its role in disease development. The vagina is the reproductive organ that hosts the largest number of bacteria, with a healthy profile represented mainly by Lactobacillus spp. On the other hand, the female upper reproductive tract (uterus, Fallopian tubes, ovaries) contains only a very small number of bacteria. Previously considered sterile, recent studies have shown the presence of a small microbiota here, but there are still debates on whether this is a physiologic or pathologic occurrence. Of particular note is that estrogen levels significantly influence the composition of the microbiota of the female reproductive tract. More and more studies show a link between the microbiome of the female reproductive tract and the development of gynecological cancers. This article reviews some of these findings.

Validation of a New Prognostic Score in Patients with Ovarian Adenocarcinoma.

Background and Objectives: This study aimed to assess the impact of clinical prognostic factors and propose a prognostic score that aids the clinician's decision in estimating the risk for patients in clinical practice. Materials and Methods: The study included 195 patients diagnosed with ovarian adenocarcinoma. The therapeutic strategy involved multidisciplinary decisions: surgery followed by adjuvant chemotherapy (80%), neoadjuvant chemotherapy followed by surgery (16.4%), and only chemotherapy in selected cases (3.6%). Results: After a median follow-up of 68 months, in terms of progression-free survival (PFS) and overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status of 1 and 2 vs. 0 (hazard ratio-HR = 2.71, 95% confidence interval-CI, 1.96-3.73, p < 0.001 for PFS and HR = 3.19, 95%CI, 2.20-4.64, p < 0.001 for OS), menopausal vs. premenopausal status (HR = 2.02, 95%CI, 1.35-3,0 p < 0.001 and HR = 2.25, 95%CI = 1.41-3.59, p < 0.001), ascites (HR = 1.95, 95%CI 1.35-2.80, p = 0.03, HR = 2.31, 95%CI = 1.52-3.5, p < 0.007), residual disease (HR = 5.12, 95%CI 3.43-7.65, p < 0.0001 and HR = 4.07, 95%CI = 2.59-6.39, p < 0.0001), and thrombocytosis (HR = 2.48 95%CI = 1.72-3.58, p < 0.0001, HR = 3.33, 95%CI = 2.16-5.13, p < 0.0001) were associated with a poor prognosis. An original prognostic score including these characteristics was validated using receiver operating characteristic (ROC) curves (area under the curve-AUC = 0.799 for PFS and AUC = 0.726 for OS, p < 0.001). The median PFS for patients with none, one, two, three, or four (or more) prognostic factors was not reached, 70, 36, 20, and 12 months, respectively. The corresponding median overall survival (OS) was not reached, 108, 77, 60, and 34 months, respectively. Conclusions: Several negative prognostic factors were identified: ECOG performance status ≥ 1, the presence of ascites and residual disease after surgery, thrombocytosis, and menopausal status. These led to the development of an original prognostic score that can be helpful in clinical practice.

Prognostic Role of Vascular Endothelial Growth Factor and Correlation with Oxidative Stress Markers in Locally Advanced and Metastatic Ovarian Cancer Patients.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in tumor progression in ovarian cancer, but the complex mechanism and interaction with oxidative stress are not fully understood. METHODS: A prospective study included 52 patients with ovarian adenocarcinoma stage IIIA-IV. Serum VEGF and reactive oxygen species (ROS) such as malondialdehyde and ceruloplasmin were measured. RESULTS: VEGF levels were elevated (mean 1014.7 ± 165 pg/mL), especially in patients with macroscopic residual disease (1058 vs. 810 pg/mL, p = 0.0001). Median progression-free survival (PFS) and overall survival (OS) were 6 and 40 months in patients with a very high VEGF (over 1200 pg/mL), 11 and 48 months in patients with VEGF between 1000-1200 pg/mL, 18 and 84 months in patients with VEGF between 800-1000 pg/mL, and not reached in patients with normal VEGF. Increased VEGF values were associated with a 2.6-fold increased risk of disease progression (HR = 2.60, 95% CI 1.69-3.99), and a 1.4-fold increased risk of death (HR = 1.4, 95% CI 1.15-1.91, p = 0.002). Receiver operator characteristic (ROC) curves were used to validate VEGF as a prognostic factor and the area under the curve (AUC) was 0.814, p = 0.036 for PFS and 0.729, p = 0.043, for OS. There was a positive correlation between VEGF and malondialdehyde, Pearson coefficient of 0.35, p = 0.0001. CONCLUSIONS: VEGF and malondialdehyde are important prognostic markers in ovarian cancer, especially in macroscopic residual disease, and there is a positive correlation between angiogenesis and oxidative stress.

Oncologic Outcome after Pulmonary Metastasectomy as Part of Multidisciplinary Treatment in a Tertiary Oncological Center.

(1) Background: Pulmonary metastases are encountered in approximately one-third of patients with malignancies, especially from colorectal, lung, breast, and renal cancers, and sarcomas. Pulmonary metastasectomy is the ablative approach of choice, when possible, as part of the multidisciplinary effort to integrate and personalize the oncological treatment. (2) Methods: The study includes 58 consecutive cases of pulmonary metastasectomies, retrospectively analyzed, performed in 12 consecutive months, in which the pathology reports confirmed lung metastases. (3) Results: Most frequent pathological types of metastases were: 14 of colorectal cancer, 10 breast, 8 lung, and 8 sarcomas. At the time of primary cancer diagnosis, 14 patients (24.14%) were in the metastatic stage. The surgical approach was minimally invasive through uniportal VATS (Video-Assisted Thoracic Surgery) in 3/4 of cases (43 patients, 74%). Almost 20% of resections were typical (lobectomy, segmentectomy). Lymphadenectomy was associated in almost 1/2 of patients and lymph node metastases were found in 11.11% of cases. The mortality rate (intraoperative and 90 days postoperative) is zero. The OS after pulmonary metastasectomy is 87% at 18 months, and the estimated OS for cancer is 90% at 5 years. The worst outcome presents the patients with sarcomas and the best outcome-colorectal and lung cancer. The patients with 1 or 2 resected metastases presented 96% survival at 24 months. (4) Conclusions: After pulmonary metastasectomy, survival is favored by the small number of metastases resected (1 or 2), and by the dimension of metastases under 20.5 mm. The non-anatomic (wedge) type of lung resection may present a lower risk of death compared to lobectomy. No statistical significance on survival has the presence of lymphadenectomy, the laterality right/left lung, the upper/lower lobes. In the future, longer follow-up and prospective randomized trials are needed for drawing definitive conclusions.

The Impact of Screening and Surgery on Life Expectancy in Breast Cancer - A Mathematical Model Case Study in the European Union.

Background: In the last 20 years in European Union states, the life expectancy did not change much. In the period 2012-2021 the average life expectancy remained almost constant at 82 years. Breast cancer represents the main cause of death by cancer in women The purpose of this research is to identify o identify and measure the influence of some medical interventions and procedures related to breast cancer on life expectancy. In our article, the target group is the feminine population from 27 EU countries. Methodology: For the analysis several indicators provided by Eurostat were considered: life expectancy for female population as a dependent variable and breast cancer screenings, surgical operations and procedures performed in hospitals (partial and total excision) were used as independent variables. The research used a mathematical model (regression panel) for 27 EU countries, for a 10 year period, to evaluate the impact of each independent variable on the life expectancy in EU as a whole. Results: From a statistical point of view, screening has a significant effect on life expectancy. On the other hand, surgical interventions have a role in the overall medical process and positively influence life expectancy. The panel model has shown that partial interventions contribute less than screening procedures to increase life expectancy. Conclusion: The development of mathematical models in health care is useful in the process of improving health care quality. In our days, the measurement and quantification of some medical methods is particularly difficult due to so many variables and observations. In these difficult circumstances, the mathematical models could bring some clarifications and structure.

Barriers and Facilitators of Romanian HPV (Human Papillomavirus) Vaccination.

BACKGROUND: Many countries had initial success with HPV vaccination campaigns worldwide. The HPV vaccine coverage during the COVID-19 pandemic dropped consistently. The aim of our research is to assess the barriers and facilitators of the current Romanian HPV vaccination campaign. METHODS: An analytical cross-sectional observational survey was conducted in the Romanian general population; a self-administered questionnaire was used. RESULTS: 1122 responders were interviewed; 666 (59.36%) were parents, and 67 (5.97%) HPV vaccinated themselves. A multinominal logistic regression carried out in the parents' category showed that women with university studies and informed from medical sources have greater chances to HPV vaccinate. Reticence regarding vaccination comes from the high cost of the vaccine and a lack of information. Only 118 (10.51%) vaccinated against HPV. From the logistic regression analysis, gender (ORa 0.461 = 95% CI: (0.196; 1.083)), geographic area of residence (ORa = 0.517; 95% CI: (0.331; 0.807)), and the inclusion of the HPV vaccine in the National Vaccination Program (ORa = 2.4; 95% CI: (1.361; 4.235)) were the factors found most associated with HPV vaccination. CONCLUSIONS: In the general population, the inclusion of HPV vaccination in the National Vaccination Program would be the most important facilitator of HPV vaccination in Romania. In parents that did not vaccinate their children, one important barrier to HPV vaccination was the high cost of the HPV vaccine and the lack of proper information. The acceptability of HPV vaccination in Romania is low; therefore, public health educational programs are needed.

Understanding COVID Vaccination and Its Implication in Cancer Patients' Imaging of Lymph Nodes by PET-CT.

(1) Background: The appearance of enlarged lymph nodes on imaging adds another layer of complexity to the differential diagnosis of disease progression versus immune response to COVID-19 vaccines. Our aim was to find an optimal timing between the vaccination and the PET-CT scan. (2) Methods: 25 cancer patients with 18F-FDG PET-CT evaluations and a history of COVID-19 vaccination between September 2021 and December 2021 were retrospectively analyzed to characterize the lymph nodes related to the time interval from COVID vaccination. (3) Results: All patients presented one or more adenopathies localized in the ipsilateral axilla (96%), ipsilateral cervical area (20%), ipsilateral retropectoral (20%) and pulmonary hilum (8%). The median value of SUVmax was 3.5 ± 0.5. There was a significant indirect correlation between SUVmax and the time passed between the vaccination and the PET CT (Pearson Correlation r = -0.54, p = 0.005). There was no significant difference (p = 0.19) in the SUVmax value in patients receiving Moderna mRNA-1273 vaccine vs. BNT162b2 mRNA Pfizer vaccine. (4) Conclusions: Lymph node enlargement is commonly seen in patients post-vaccination for COVID-19 and must be differentiated from disease progression. The data from our study strongly suggests that the minimum interval of time between an mRNA vaccine and a PET-CT should be more than six weeks.

Aspects Regarding the Influence of Obesity on the Molecular Characteristics of Breast Tumors.

The influence of excess adipose tissue on the evolution and prognosis of breast cancer has been evaluated in numerous papers over the years. The ways in which obesity can influence the development, progression, and prognosis of this neoplasia are complex and requires the design of new studies, both clinical and preclinical. The aim of this study is to highlight a possible correlation between obesity-specific tumor microenvironment markers (adipokine or leptin) and the different histological subtypes and aggressive characteristics of breast tumors. We prospectively monitored the prognostic values of 39 patients diagnosed with breast cancer who received oncologic-specific treatment or are in follow-up regarding some obesity markers. Our analysis included parameters such as age, body mass index, immunohistochemical characteristics, and plasma concentration of leptin. The methodology was designed to reveal a possible correlation between obesity (quantified by measuring body mass index and waist circumference), the plasma level of leptin, and breast tumor immunohistochemical characteristics. The patients diagnosed with aggressive tumors subtypes (HER2-positive and triple-negative) had a significantly higher body mass index than patients diagnosed with luminal type tumors (32 kg/sqm versus 27 kg/sqm), the difference being 5 kg/sqm. In patients with non-luminal type breast tumors (HER2-positive and triple-negative), serum concentration of leptin is 55 pg/ml compared to 48 pg/ml in luminal type, statistically significant, p=0.0168. Leptin plays an important role in the connection of specific microenvironment tumors to breast cancer. An increased serum concentration of this adipokine was found in patients with HER2-positive and triple-negative breast tumors compared with luminal-type breast tumors, which could open new directions in the research of breast cancer prognosis in obese patients.

Long-Term Outcome of Patients with Stage II and III Muscle-Invasive Urothelial Bladder Cancer after Multimodality Approach. Which Is the Best Option?

Background and Objectives: There is no consensus regarding the optimal therapy sequence in stage II and III bladder cancer. The study aimed to evaluate the long-term oncologic outcomes in patients with bladder cancer after a multimodality approach. Materials and methods: Medical files of 231 consecutive patients identified with stage II (46.8%), IIIA (30.3%), and IIIB (22.9%) transitional cell carcinoma of the bladder (BC) treated with a multimodality approach were retrospectively reviewed. The treatment consisted of transurethral resections or cystectomy, radiotherapy alone or concurrent chemoradiotherapy as definitive treatment, or neoadjuvant chemotherapy using platinum salt regimens. Results: Median age at diagnosis was 65 ± 10.98 years. Radical or partial cystectomy was performed in 88 patients (37.1%), and trans-urethral resection of bladder tumor (TURBT) alone was performed in 143 (61.9%) patients. Overall, 40 patients (17.3%) received neoadjuvant chemotherapy and 82 (35.5%) received definitive chemoradiotherapy. After a median follow-up of 30.6 months (range 3-146 months), the median disease-free survival (DFS) for an entire lot of patients was 32 months, and the percentage of patients without recurrence at 12, 24, and 36 months was 86%, 58%, and 45%, respectively. Patients receiving neoadjuvant chemotherapy had a better oncologic outcome compared to patients without neoadjuvant chemotherapy (median DFS not reached vs. 31 months, p = 0.038, HR = 0.55, 95% CI 0.310-0.951). There was a trend for better 3-year DFS with radical cystectomy vs. TURBT (60 months vs. 31 months, p = 0.064). Definitive chemoradiotherapy 3-year DFS was 58% compared to 44% in patients who received radiotherapy or chemotherapy alone. Conclusions: In patients with stages II and III, both neoadjuvant chemotherapy and concurrent radio-chemotherapy are valid options for treatment and must be part of a multidisciplinary approach.

Long-term oncological outcome in patients with cervical cancer after 3 trimodality treatment (radiotherapy, platinum-based chemotherapy, and robotic surgery).

ABSTRACT: Cervical cancer represents a general health issue spread all over the globe, which prompts the surge of scientific survey toward the rise of survival and condition of life of these patients. American and European guidelines suggest the open surgery, laparoscopic, and robotic surgery are the main therapeutic approaches for radical hysterectomy for patients with cervical cancer. This is the first survey to analyze the long-term oncological outcome of an extensive series of subjects cared for with multimodality treatment, here comprising robotic surgery.This study intents to evaluate the long-term oncological result in patients diagnosed with cervical cancer treated with radiotherapy (±chemotherapy) and robotic surgery compared with open surgery. Medical files of 56 patients diagnosed with cervical cancer who underwent a robotic hysterectomy and radiotherapy ± chemotherapy were retrospectively analyzed.The median age at diagnosis was 50.5 (range: 23-70). Eleven patients (19.6%) presented in an early stage (IB-IIA) and 80.4% advanced stage (IIB-IVA). Overall response rate after radiotherapy and chemoradiotherapy was 96.2%. Pathologic complete response was obtained in 64% of patients. After a median follow-up of 60 months (range: 6-105 months), 8 patients (14.2%) presented local recurrence or distant metastases. Disease-free survival (DFS) was 92% at 2 years and 84% at 3 and 5 years. Overall survival (OS) rates at 2, 3, and 5 years for patients with robotic surgery were 91%, 78%, and 73%, median OS not reached. OS was lower in the arm of open surgery (2, 3, and 5 years 87%, 71%, and 61%, respectively; median OS was 72 months P = .054). The multivariate analysis regarding the outcome of patients revealed an advantage for complete versus partial response (P < .002), for early versus advanced stages (P = .014) and a 10% gained in DFS at 3 years for patients in whom chemoradiotherapy was administered (DFS at 3 years 75% vs 85%) in patients with advanced stages.Robotic surgery has a favorable oncological outcome when associated with multimodal therapy.

When Should We Expect Curative Results of Neoadjuvant Treatment in Locally Advanced Rectal Cancer Patients?

This review on recently published literature aims to summarize published data on pathologic complete response following neoadjuvant treatment in biopsy proven locally advanced rectal cancer patients. Published articles referring to pCR rectal cancer patients were identified using PubMed search. Eleven relevant articles were selected, based on tumor, treatment, and patient characteristics reporting. As a conclusion, rectal cancer patients with the highest chances of complete clinical or pathological response to neoadjuvant treatment are males, who are around 60 years, diagnosed with well or moderate differentiated locally advanced rectal cancer.