Sarcoma Botryoides: Optimal Therapeutic Management and Prognosis of an Unfavorable Malignant Neoplasm of Female Children

Embryonal rhabdomyosarcoma (ERMS) is a rare malignancy and occurs primarily in the first two decades of life. Botryoid rhabdomyosarcoma is an aggressive subtype of ERMS that often manifests in the genital tract of female infants and children. Due to its rarity, the optimal treatment approach has been a matter of debate. We conducted a search in the PubMed database and supplemented it with a manual search to retrieve additional papers eligible for inclusion. We retrieved 13 case reports and case series, from which we summarized that the current trend is to approach each patient with a personalized treatment plan. This consists of a combination of local debulking surgery and adjuvant or neoadjuvant chemotherapy (NACT). Effort is made in every approach to avoid radiation for the sake of preserving fertility. Radical surgeries and radiation still have a role to play in extensive disease and in cases of relapse. Despite the rarity and aggressiveness of this tumor, disease-free survival and overall prognosis is excellent, especially when it is diagnosed early, compared with other subtypes of rhabdomyosarcoma (RMS). We conclude that the practice of a multidisciplinary approach is appropriate, with favorable outcomes; however, larger-scale studies need to be organized to have a definite consensus on optimal management

Silent Myocardial Ischemia: From Pathophysiology to Diagnosis and Treatment

Silent myocardial ischemia (SMI), characterized by a lack of overt symptoms despite an inadequate blood supply to the myocardium, remains a challenging entity in cardiovascular medicine. The pathogenesis involves intricate interactions of vascular, neurohormonal, and metabolic factors, contributing to perfusion deficits without the characteristic chest pain. Understanding these mechanisms is pivotal for recognizing diverse clinical presentations and designing targeted interventions. Diagnostic strategies for SMI have evolved from traditional electrocardiography to advanced imaging modalities, including stress echocardiography, single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (MRI). Treating SMI is a matter of ongoing debate, as the available evidence on the role of invasive versus medical management is controversial. This comprehensive review synthesizes current knowledge of silent myocardial ischemia, addressing its pathophysiology, diagnostic modalities, and therapeutic interventions

HIPEC for gynaecological malignancies: A last update (Review)

Advanced-stage gynaecological cancer represents a clinical entity with challenging surgical treatment in an effort to optimize prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS) has been reported as a method potentially eligible to improve prognosis. However, no definitive conclusions have yet been made on which types of cancer and which context HIPEC may actually have a beneficial impact. The present review discusses the efficacy and safety of HIPEC as a treatment option for patients with primary/recurrent ovarian, endometrial and cervix cancer, as well as peritoneal sarcomatosis. A literature search was conducted using MeSH terms for each topic in the PubMed database and supplemented with a manual search to retrieve additional articles eligible for inclusion/fulfilling the inclusion criteria. The implementation of HIPEC appears to be beneficial in terms of survival in patients with epithelial ovarian carcinoma (EOC) following neoadjuvant chemotherapy, as well as in patients with recurrent EOC. Statistical superiority is not justified by current studies regarding other gynaecological malignancies with peritoneal dissemination. Furthermore, as regards safety, HIPEC following CRS does not appear to significantly increase the mortality and morbidity rates compared to the use of CRS alone. The rationale for using HIPEC and CRS in the treatment of ovarian cancer, particularly in the neoadjuvant setting, as well as for recurrences, is adequately evidenced, with acceptable safety and post-operative complication rate profiles. Its current place in the multimodal strategy for patients with peritoneal metastases remains uncertain, however. Randomized clinical trials are warranted to further examine the use of HIPEC and establish the optimal regimen and temperature settings. The role of optimal cytoreduction and no residual disease, as well as the proper patient selection remain basic parameters for maximizing survival parameters

Neoadjuvant chemotherapy in advanced-stage ovarian cancer - state of the art

: Ovarian cancer represents the fifth cause of cancer death among women, carrying one of the worst prognoses among gynaecological malignancies. The need to achieve no residual disease after surgery in order to optimize prognosis of advanced-stage ovarian cancer introduced the idea of neoadjuvant chemotherapy. The present review aims to summarize current state-of-the-art evidence regarding the efficacy and safety of neoadjuvant chemotherapy as well as novel insights regarding the usage of modern therapeutic regimens in the context of neoadjuvant chemotherapy. The last decade has been characterized by the breakthrough scientific evidence that neoadjuvant chemotherapy followed by interval debulking surgery for advanced-stage ovarian cancer may be comparable to primary debulking surgery. Neoadjuvant chemotherapy followed by interval debulking surgery is an acceptable - if not preferable - therapeutic approach in advanced-staged ovarian cancer patients because it is associated with higher optimal debulking surgery, fewer complications, and non-inferior survival outcomes. The addition of bevacizumab to chemotherapy contributes significantly to survival outcomes without causing side effects that outbalance the benefits. Patients with recurrent high-grade serous ovarian cancer and a germline or breast cancer mutation should be offered maintenance olaparib after a response to platinum-based chemotherapy. Finally, the role of hyperthermic intraperitoneal chemotherapy in the context of neoadjuvant chemotherapy remains unjustified

Combined pelvic and para-aortic is superior to only pelvic lymphadenectomy in intermediate and high-risk endometrial cancer: a systematic review and meta-analysis

BACKGROUND: Lymph node metastasis is a principal prognostic factor for the treatment of endometrial cancer. Added value of para-aortic lymphadenectomy to only pelvic lymphadenectomy for intermediate/high-risk endometrial cancer patients remains controversial. OBJECTIVE: A systematic review and meta-analysis was performed to assess the impact of combined pelvic and para-aortic lymph node dissection (PPALND) compared to only pelvic lymph node dissection (PLND) on survival outcomes of intermediate and/or high-risk patients. STUDY DESIGN: The systematic review and meta-analysis adhered to the PRISMA guidelines for meta-analyses of interventional studies. Pubmed, Scopus, EMBASE and Cochrane were searched up to April 20, 2018. Included studies were those comparing high-risk endometrial cancer patients that had performed pelvic and para-aortic lymph node dissection (PPALND) vs. only pelvic lymph node dissection (PLND) apart from standard procedure (total hysterectomy with bilateral salpingo-oophorectomy, TAHBSO). Primary outcomes of the study were overall survival and disease-free survival rates. Methodological quality of the included studies was assessed using the ROBINS-I tool. Overall quality of the evidence for the primary and secondary outcomes was evaluated as per GRADE guideline using the GRADE pro GD tool. RESULTS: There were 13 studies identified with 7349 patients included. All studies were retrospective observational as no RCTs or prospective studies adhering to inclusion criteria were retrieved. Combined pelvic and para-aortic lymphadenectomy was associated with 46% decreased risk for death (HR 0.54, 95% CI 0.35-0.83, I2 = 62.1%) and 49% decreased risk for recurrence (HR 0.51, 95% CI 0.28-0.93). It was also associated with increased 5-year OS rate (RR 1.13, 95% CI 1.04-0.24, I2 = 57.3%) and increased 5-year DFS rate (RR 1.23, 95% CI 1.14-1.31, I2 = 85.5) compared with only pelvic lymphadenectomy. CONCLUSION: Combined pelvic and para-aortic lymphadenectomy is associated with improved survival outcomes compared with only pelvic lymphadenectomy in women with intermediate/high-risk endometrial cancers. Further prospective studies should be performed.status: publishe

Long-term endothelial dysfunction after trans-radial catheterization: A meta-analytic approach

Background: Following cardiac catheterization using radial artery (RA) access, persistent endothelial dysfunction may limit the use of RA as a conduit during coronary artery bypass graft (CABG) surgery. We reviewed published literature to investigate the effects of transradial coronary catheterization on RA endothelial function. Methods: We searched PubMed from inception to April 2017 for published studies assessing RA endothelial function late (>= 1 month) after coronary catheterization. A total of 12 eligible published studies (n = 490 patients) were included in the final quantitative synthesis. Statistical heterogeneity among studies was assessed by the I-2. A random effects model was used to calculate the pooled estimate for standardized mean difference (SMD). Meta-regression analysis was used to explore predictors of change in RA endothelial function following catheterization. Results: In all studies, a significant reduction in endothelium dependent response was observed post-catheterization (SMD = -0.53, 95% confidence interval [CI]: -0.93 to -0.13, P = 0.01) and a marginal, non-significant, reduction in endothelium independent response (SMD = -0.38, 95%CI: -0.77, 0.01, P < 0.059). In controlled studies, using the contralateral RA as a control, a significant impairment in endothelial function was confirmed (SMD = -6.26, 95%CI: -9.71 to -2.81, P < 0.0001), while the change in endothelium-independent response was not significant (SMD = -4.46, 95%CI: -13.3 to 4.37, P = 0.32). In meta-regression analysis male gender (z = 2.36, P = 0.018) and increasing time following catheterization (z = 2.62, P = 0.009) were associated with less RA endothelial dysfunction. Conclusions: Transradial catheterization impairs endothelium dependent vasodilatory properties of the cannulated RA, which do not recover even several months post-catheterization. Non-recovery of vasomotor function of cannulated RAs may limit their use as arterial grafts during CABG surgery

Low-Grade Systemic Inflammation Interferes with Anabolic and Catabolic Characteristics of the Aged Human Skeletal Muscle.

Aging is associated with the development of chronic low-grade systemic inflammation (LGSI) characterized by increased circulating levels of proinflammatory cytokines and acute phase proteins such as C-reactive protein (CRP). Collective evidence suggests that elevated levels of inflammatory mediators such as CRP, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) are correlated with deteriorated skeletal muscle mass and function, though the molecular footprint of this observation in the aged human skeletal muscle remains obscure. Based on animal models showing impaired protein synthesis and enhanced degradation in response to LGSI, we compared here the response of proteolysis- and protein synthesis-related signaling proteins as well as the satellite cell and amino acid transporter protein content between healthy older adults with increased versus physiological blood hs-CRP levels in the fasted (basal) state and after an anabolic stimulus comprised of acute resistance exercise (RE) and protein feeding. Our main findings indicate that older adults with increased hs-CRP levels demonstrate (i) increased proteasome activity, accompanied by increased protein carbonylation and IKKα/β phosphorylation; (ii) reduced Pax7+ satellite cells; (iii) increased insulin resistance, at the basal state; and (iv) impaired S6 ribosomal protein phosphorylation accompanied by hyperinsulinemia following an acute RE bout combined with protein ingestion. Collectively, these data provide support to the concept that age-related chronic LGSI may upregulate proteasome activity via induction of the NF-κB signaling and protein oxidation and impair the insulin-dependent anabolic potential of human skeletal muscle

Combined pelvic and para-aortic is superior to only pelvic lymphadenectomy in intermediate and high-risk endometrial cancer: a systematic review and meta-analysis

Background Lymph node metastasis is a principal prognostic factor for the treatment of endometrial cancer. Added value of para-aortic lymphadenectomy to only pelvic lymphadenectomy for intermediate/high-risk endometrial cancer patients remains controversial. Objective A systematic review and meta-analysis was performed to assess the impact of combined pelvic and para-aortic lymph node dissection (PPALND) compared to only pelvic lymph node dissection (PLND) on survival outcomes of intermediate and/or high-risk patients. Study design The systematic review and meta-analysis adhered to the PRISMA guidelines for meta-analyses of interventional studies. Pubmed, Scopus, EMBASE and Cochrane were searched up to April 20, 2018. Included studies were those comparing high-risk endometrial cancer patients that had performed pelvic and para-aortic lymph node dissection (PPALND) vs. only pelvic lymph node dissection (PLND) apart from standard procedure (total hysterectomy with bilateral salpingo-oophorectomy, TAHBSO). Primary outcomes of the study were overall survival and disease-free survival rates. Methodological quality of the included studies was assessed using the ROBINS-I tool. Overall quality of the evidence for the primary and secondary outcomes was evaluated as per GRADE guideline using the GRADE pro GD tool. Results There were 13 studies identified with 7349 patients included. All studies were retrospective observational as no RCTs or prospective studies adhering to inclusion criteria were retrieved. Combined pelvic and para-aortic lymphadenectomy was associated with 46% decreased risk for death (HR 0.54, 95% CI 0.35-0.83, I-2 = 62.1%) and 49% decreased risk for recurrence (HR 0.51, 95% CI 0.28-0.93). It was also associated with increased 5-year OS rate (RR 1.13, 95% CI 1.04-0.24, I-2 = 57.3%) and increased 5-year DFS rate (RR 1.23, 95% CI 1.14-1.31, I-2 = 85.5) compared with only pelvic lymphadenectomy. Conclusion Combined pelvic and para-aortic lymphadenectomy is associated with improved survival outcomes compared with only pelvic lymphadenectomy in women with intermediate/high-risk endometrial cancers. Further prospective studies should be performed