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.

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.

Simultaneous Approach of Colo-Rectal and Hepatic Lesions in Colo-Rectal Cancers with Liver Metastasis - A Single Oncological Center Overview.

Introduction: Management of synchronous colorectal cancer with liver metastases (SCLM) is still on debate, regarding timing, indications and complications of the 3 strategies: classic approach (first tumor resection), simultaneous resection and reverse approach (liver first). A retrospective single-centre evaluation of synchronous approach was accomplished, focusing on surgical technique, indications and complications. Material and Methods: Between 2017 and 2020, 31 SCLM patients benefited from synchronously colorectal and hepatic approach: segmental colectomies/rectal resections, simultaneously with liver metastasectomies (associated with radiofrequency ablation). Post-therapeutic imaging monitoring was performed from every 3 - 6 months. There were no perioperative complications related to the combination of the procedures, low morbidity and zero postoperative mortality. Results: The follow-up period was 10 - 40 months: 13 patients had no evidence of recurrence, 10 had hepatic metastases in regression, 4 patients had signs of peritoneal carcinomatosis and 4 showed progression of liver disease; all patients were on chemotherapy. During follow-up 4 patients died. Conclusions: Experience shows that the simultaneous approach of recto-colic and hepatic resections in colo-rectal cancers is a safe procedure, with low morbidity, the limits being dictated by the size of the liver metastases. The results at long-distance must be drawn by further consistent trials.

A Real-World Study to Compare the Safety and Efficacy of Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir, with or without Ribavirin, in 587 Patients with Chronic Hepatitis C at the Fundeni Clinical Institute, Bucharest, Romania.

BACKGROUND In the European Union, a tablet with fixed doses of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir is an authorized treatment for patients with chronic hepatitis C virus (HCV) infection. Ribavirin is a broad-spectrum antiviral used in several treatment regimens for patients with HCV infection. This real-world study aimed to compare the safety and efficacy of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin, in 587 patients with chronic hepatitis C attending the Fundeni Clinical Institute, Bucharest, Romania. MATERIAL AND METHODS This is an observational prospective study including 315 patients with F4 degree of fibrosis and compensated cirrhosis, 185 patients with F3 fibrosis, and 83 patients with F2 fibrosis. Liver fibrosis was evaluated by liver biopsy or Fibromax. Efficacy was defined as undetectable HCV-RNA at 12 weeks after the end of treatment. In terms of safety, we monitored the development of adverse reactions, liver cytolysis, cholestasis, and hematologic disorders. RESULTS Of the 587 patients, 2 patients with B-cell lymphoma died during therapy. In total, 3/585 patients (0.51%) did not achieve sustained virologic response. Common adverse effects were nausea and asthenia (especially in patients with other medical treatments; P=0.03 and P=0.04, respectively) and anemia in patients who received ribavirin (P<0.01). None of the patients discontinued antiviral treatment. Patients with kidney transplant or end-stage kidney disease did not receive or discontinued ribavirin. CONCLUSIONS Ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin had an efficacy rate of over 99% in HCV genotype 1b infection. We report no serious adverse reactions.

Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy.

Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients' daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient's daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma.

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.

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.

Tumor is an Oxidative Stress Factor in Ovarian Cancer Patients.

Introduction: Epithelial ovarian cancer is worldwide the second cause of gynaecological cancer but the commonest cause of gynaecological cancer-associated death. AIM: To determine the intensity of oxidative stress in ovarian cancer patients and to establish a connection between the presence of the tumor and reactive oxygen species (ROS). PATIENTS AND METHODS: Thirty-five patients diagnosed with epithelial ovarian carcinoma stage II-IV between 2010 and 2017, who underwent multimodality treatment (surgery and chemotherapy) were included in the study. ROS measured in dynamic (four determinations between every cycle) were malondialdehyde to evaluate the lipid peroxidation, ceruloplasmin, SH- albumin thiols groups and total antioxidants. Results: There was an increase in the value of ROS: malondialdehyde mean value was 8.1 µmol/100 ml (normal value 4 µmol/100 ml); ceruloplasmin mean value was 144.8U.I. (normal value 120U.I), both showing an active oxidative process in patients with ovarian cancer. A small decrease of the value of thiols (395 vs. 450 µmol/l) and a small increase of total antioxidants was noticed (1.44 vs. 1.4 µmol). All four compounds decrease between the first determination and the fourth one. There was a strong correlation between lipid peroxides levels and ceruloplasmin (Pearson correlation 0.315 p=0.005) and between lipid peroxides and thiols groups (Pearson correlation 0.23 p=0.039). There was a correlation between thiols and antioxidants (Pearson correlation 0.33 p=0.003). Lipid peroxidation and ceruloplasmin were significantly higher in patients with residual disease (p=0.039, p=0.046) emphasizing that the tumor is a generator of oxidative stress. CONCLUSION: Tumor produces ROS in excess in patients with advanced ovarian adenocarcinoma. Those ROS are corelated and acts as signalling molecules.

Distant Oncologic Outcome of Patients with Locally Advanced Unresectable and Metastatic Esophageal Cancer after Multimodality Treatment.

Background: Combined modality therapy has been employed for the treatment of choice for locally advanced esophageal and eso-gastric junction cancers all around the globe but a unanimous consensus is missing. Methods: Medical files of 132 patients with confirmed locally advanced un-resectable, and metastatic esophageal cancer who presented to our center between 2010-2015 were retrospectively reviewed. Multimodality treatment consisting of chemo-radiotherapy or chemotherapy or radiotherapy alone and surgery in patients who convert to operability was planned according to tumor extend and performance status of the patient. Results: Seventy seven percent of the patient presented with squamous carcinoma and 23 % were adenocarcinoma. At the diagnosis 22 patients (16.6%) were stage IV. Concurrent chemoradiotherapy was administered in 26 patients (19.7%), chemotherapy in 91 patients (68.9%), radiotherapy in 83 patients (62.9%). After combined treatment, surgery with radical intent was possible in 21 patients (15.9%). After a follow up of 17.3 months, overall survival (OS) was 12 months, with one and two-year survival rate of 49.2% and 17.4%. In metastatic patients OS was 10 months. Patients who were converted to operability had a OS of 20 months vs. 10 months in patients who doesn't undergo surgery (p=0.002). Chemo-radiotherapy was superior in terms of OS compare with chemotherapy or radiotherapy administered sequential (17 vs. 10 months, p=0.013). Conclusions: Multimodality treatment in locally advanced esophageal cancers (concurrent radiochemotherapy followed by surgery) can be considered superior to each method as single therapy and radiotherapy and chemotherapy can make certain locally advanced esophageal tumors resectable.

Effectiveness and safety profile of ipilimumab therapy in previously treated patients with unresectable or metastatic melanoma - the Romanian Patient Access Program.

PURPOSE: The Romanian Patient Access Program (Ro-PAP, CA 184-427), part of the European Expanded Access Program (EAP), was developed to evaluate the effectiveness and safety profile ipilimumab in previously treated patients with advanced melanoma (unresectable or metastatic melanoma). The objective of our retrospective observational study of patients included in this program was to provide data recorded in real-life settings. METHODS: We analysed 89 patients enrolled in Ro-PAP, CA 184-427 (54 men and 35 women) aged between 29 and 89 years. The patients received ipilimumab 3mg/kg, administered with short 30-min i.v. infusion every 3 weeks, having a total of 4 doses. Patients were assessed for tumor response, overall survival (OS) and progression-free survival (PFS), and were monitored for adverse events (AE). RESULTS: At 12 weeks after the completion of therapy, the complete and partial response rates were 6.74% each, stable disease 15.73%, with the best overall response rate 13.48% and disease control rate 29.21%. Median OS was 189.00 days (95% CI 69.50-308.49) and median PFS 124.00 days (95% CI 85.05-162.94). The level of patient functionality at the beginning of ipilimumab treatment showed to be an important predictor of outcome, as patients with ECOG performance status (PS) (0) before therapy with ipilimumab had a higher OS compared with those with impaired functionality. CONCLUSIONS: The use of ipilimumab in daily clinical practice demonstrated to be effective and safe, consistent with data coming from randomized clinical trials or other observational studies.

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.

Risk of Myelopathy Following Second Local Treatment after Initial Irradiation of Spine Metastasis.

Metastatic lesions of the spine occur in up to 40% of cancer patients and are a frequent source of pain and neurologic deficit due to cord compression. Palliative radiotherapy is the main first-intent local treatment in the form of single-fraction radiotherapy or fractionated courses. Reirradiation is a viable option for inoperable patients where spinal decompression is needed but with an increased risk of radiation-induced myelopathy (RM) and subsequent neurologic damage. This review summarizes reported data on local treatment options after initial irradiation in patients with relapsed spine metastasis and key dosimetric correlations between the risk of spinal cord injury and reirradiation technique, total dose, and time between treatments. The Linear Quadratic (LQ) model was used to convert all the published doses into biologically effective doses and normalize them to EQD2. For 3D radiotherapy, authors used cumulative doses from 55.2 Gy2/2 to 65.5 Gy2/2 EQD2 with no cases of RM mentioned. We found little evidence of RM after SBRT in the papers that met our criteria of inclusion, usually at the median reported dose to critical neural tissue around 93.5 Gy2/2. There is a lack of consistency in reporting the spinal cord dose, which leads to difficulty in pooling data.

Inequities in Screening and HPV Vaccination Programs and Their Impact on Cervical Cancer Statistics in Romania.

(1) Introduction: A Romanian woman is diagnosed with cervical cancer every two hours; the country ranks second in Europe in terms of the mortality and incidence rate of this disease. This paper aims to identify the main reasons that have led to this situation, focusing on the measures taken by the Romanian Ministry of Health for the prevention of this type of cancer-national programs for cervical cancer screening and HPV vaccination. (2) Materials and methods: We performed a study based on the available secondary data from the National Statistics Institute, World Health Organization and Bucharest Institute of Oncology in order to assess the burden associated with cervical cancer and place it in the context of known global and European incidence and mortality rates, thus evaluating the importance of this health issue in Romania. The second component of our study was a cross-sectional study. Here, we used a 14-question questionnaire applied to the women participating in the National Screening Program for Cervical Cancer and aimed to evaluate the women's level of knowledge about screening and HPV vaccination and their access cervical-cancer-specific healthcare services. (3) Results: The results of this research show that a high percentage of women postpone routine checks due to a lack of time and financial resources and indicate that a low level of knowledge about the disease and the specific preventive methods determines the low participation in screening and HPV vaccination programs implemented in Romania, contributing to the country's cervical cancer situation. (4) Conclusions: The national programs have complicated procedures, are underfunded and do not motivate healthcare workers enough. This, combined with the lack of information for the eligible population, adds up to an extremely low number of women screened and vaccinated. Our conclusion is that the Romanian Ministry of Health must take immediate action by conducting major awareness campaigns, implementing measures to make the programs functional and ensuring coherent funding.

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 Benefits and Challenges of the Multimodal Treatment in Advanced/Metastatic Malignant Melanoma.

Currently, the treatment of malignant melanoma offers the longest and the most studied experience of innovative treatments in malignant pathology. The algorithm of the therapeutic decision in advanced or metastatic melanoma must comprise: the timing of the therapeutic initiation, the sequencing of the specific oncological treatment (radiotherapy and chemotherapy still being therapeutic alternatives in selected cases), the diagnosis and the management of adverse reactions. We present the case of a patient diagnosed with metastatic malignant melanoma in November 2019, who progressed successively under new systemic treatment throughout the 3 years of treatment and experienced skin reactions of various degrees of severity. The comprehensive response to secondary hilar pulmonary lymphatic determinations under subsequent chemotherapy was specific to the presented case. The occurrence of vitiligo secondary to immunotherapy is a favorable prognostic factor, but the occurrence of secondary cerebral determinations is an extremely severe prognostic factor in malignant melanoma and a challenge in making the therapeutic decision. Previous treatment with immune checkpoint inhibitors may trigger a favorable response to systemic chemotherapy. The early and accurate diagnosis of the adverse events of the new therapies requires a multidisciplinary approach, because it can radically change the therapeutic decision.

A Decade of Therapeutic Challenges in Synchronous Gynecological Cancers from the Bucharest Oncological Institute.

The aim of our study is to present the particularities of a specific subset of gynecological cancer patients in Romania. We present a review of synchronous gynecological neoplasia (SGN) treated in the Bucharest Oncological Institute's surgery departments over a decade. Between 2012 and 2022, 7419 female patients with genital malignancies were treated. We identified 36 patients with invasive synchronous primary gynecological cancers (0.5%) and 12 cases with one primary gynecological and another primary invasive pelvic cancer (rectal/bladder). All recurrent, metastatic, or metachronous tumors detected were excluded. Demographic data, personal history, presenting symptoms, pathologic findings, staging, treatment, and evolution for each case were recorded. Usually, the most common SGN association is between ovarian and endometrial cancer of endometrioid differentiation (low-grade malignancies with very good prognosis). However, we noticed that, given the particularities of the Romanian medical system, the most frequent association is between cervical and endometrial, followed by cervical and ovarian cancers. Moreover, the cancer stage at diagnosis is more advanced. In countries with low HPV vaccination rate and low adherence to screening programs, SGNs can present as extremely advanced cases and require extensive surgery (such as pelvic exenterations) to achieve radicality. This multimodal treatment in advanced cases with high tumor burden determines a reduction in survival, time until progression, and quality of life.

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.

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.