Cancer-related Survival Research Articles

Examination of Sarcopenia with Obesity as a Prognostic Factor in Patients with Colorectal Cancer Using the Psoas Muscle Mass Index

Background: Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods: We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results: CRRFS was significantly shorter in the SO group than in the non-SO group (p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions: Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients.

Impact of infectious complications after gastrectomy on non‑gastric cancer‑related deaths.

Infectious complications (ICs) have been reported as major causes of postoperative mortality in patients with cancer. However, to the best of our knowledge, the impact of ICs after gastrectomy on non-gastric cancer-related deaths (NGCDs) remains unexplored. The present study aimed to identify the impact of ICs after gastrectomy on NGCDs. A retrospective analysis of 712 patients with gastric cancer who underwent curative gastrectomy was conducted. The participants were categorized into IC and non-IC groups based on the incidence of postoperative IC. Clinicopathological factors and non-gastric cancer-related survival (NGCS) rates were compared between groups. Further NGCD and associated risk factor analyses were performed in a background factor-adjusted cohort using multivariate analysis. Among the 712 patients, 112 developed ICs (Clavien-Dindo classification grade ≥II). In the entire cohort, the IC group had a significantly worse 5-year cumulative incidence of NGCD (17.8 vs. 10.6%; Gray's P=0.021) compared with the non-IC group. Although a number of clinicopathological factors differed between the groups, including patient background, operative factors and tumor factors, the risk factors for NGCD identified in the multivariate analysis were older age, low prognostic nutritional index, low skeletal muscle index and Charlson comorbidity index ≥1, excluding IC incidents. The IC group exhibited more background factors contributing to NGCDs, suggesting a potential increase in NGCD regardless of IC incidence.

What alters prognosis in patients who were operated for lung cancer with lymph node metastasis?

In this study, we investigated the clinical outcomes of patients who underwent surgery with proven lymph node metastasis. Patients who were operated for lung cancer with pN1 or pN2 were examined in the study. The clinicopathological features and survival of the subjects were evaluated according to pN1-pN2 status, presence of neoadjuvant treatment, Positron emission tomography and computed tomography (PET/CT) avidity on mediastinal lymph nodes and specific lymph node stations. The study examines 100 patients operated from January 2016 to December 2021. Number of cases with pN1 and pN2 disease were 45 (45%) and 55 (55%) respectively. Thirty (30%) patients received neoadjuvant treatment. The 5-year overall survival (OS) and disease-free survival (DFS) of the patients were computed as 42.5% and 42.4% correspondingly. The 5-year cancer-related survival was 55.3%. In pN2 cohort, 5-year DFS was 67.9% in the neoadjuvant group and 15.9% in the non-neoadjuvant group (P = 0.042). In non-neoadjuvant group, 5-year DFS was 19.9% in cases with mediastinal PET/CT avidity and 56.3% in patients without mediastinal PET/CT avidity (P = 0.018). In pN2 disease, the presence of subcarinal or paratracheal lymph node metastasis did not create a significant difference in 5-year OS or DFS, but pulmonary ligament lymph node metastasis was found to be linked with worse survival in both 5-year OS (P = 0.005) and DFS (P = 0.017). The main elements related with poor prognosis were absence of neoadjuvant treatment and pulmonary ligament lymph node metastasis in pN2 disease, detecting PET/CT avid mediastinal lymph nodes in non-neoadjuvant group.

Chromosomal copy number based stratification of gastric cancer has added prognostic value to Lauren’s histological classification

BackgroundThe Cancer Genome Atlas (TCGA) recognizes four molecular subgroups of gastric cancer: Epstein-Barr virus (EBV) positive, microsatellite instable (MSI), genomically stable (GS), and chromosomal instable (CIN). Since a GS/CIN classifier is lacking, alternative markers such as Lauren’s histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods.Methods309 EBV negative and microsatellite stable tumors were included from the Dutch D1/D2 trial and assigned to subgroups by: (i) TCGA’s specific chromosomal copy number aberrations, (ii) genome instability index (GII), (iii) Lauren’s classification, and (iv) CDH1/p53 immunohistochemistry. Subgroups were associated with cancer-related survival (CRS).ResultsFive-year CRS was 42.0% for diffuse and 49.5% for patients with intestinal type tumors, and 57.8% for GS and 41.6% for patients with CIN tumors. Classification by GII or CDH1/p53 IHC did not correlate with CRS. The combination of TCGA and Lauren classifications resulted in four distinct subgroups. Five-year CRS for GS-intestinal (n = 24), GS-diffuse (n = 57), CIN-intestinal (n = 142) and CIN-diffuse (n = 86) was 61.4%, 56.5%, 47.6%, and 31.5%, respectively.ConclusionsTCGA’s GS and CIN subgroups have additional prognostic value to Lauren’s classification in resectable gastric cancer. GS-intestinal, GS-diffuse, CIN-intestinal and CIN-diffuse are suggested stratification variables for future studies.

Unveiling hidden outcomes in malignant gastric outlet obstruction research - insights from a "Pancreas 2000" review.

Malignant gastric outlet obstruction (mGOO) is a major condition affecting patients with periampullary tumors, including pancreatic cancer. The current treatment options include surgical gastroenterostomy, endoscopic stenting and more recently EUS-guided gastroenterostomy. Most studies comparing the outcomes of the three procedures focus on technical success, clinical success and safety. Several "occult" outcomes relevant to the patient's viewpoints and perspective may ultimately impact on cancer-related and overall survival, such as body mass composition, nutritional biomarkers, chemotherapy tolerance and patient-reported quality of life. The aim of this review is to provide an overview of potential key outcomes that should be explored in future comparative research around mGOO treatment options.

Automated Extraction of Patient-Centered Outcomes After Breast Cancer Treatment: An Open-Source Large Language Model-Based Toolkit.

Patient-centered outcomes (PCOs) are pivotal in cancer treatment, as they directly reflect patients' quality of life. Although multiple studies suggest that factors affecting breast cancer-related morbidity and survival are influenced by treatment side effects and adherence to long-term treatment, such data are generally only available on a smaller scale or from a single center. The primary challenge with collecting these data is that the outcomes are captured as free text in clinical narratives written by clinicians. Given the complexity of PCO documentation in these narratives, computerized methods are necessary to unlock the wealth of information buried in unstructured text notes that often document PCOs. Inspired by the success of large language models (LLMs), we examined the adaptability of three LLMs, GPT-2, BioGPT, and PMC-LLaMA, on PCO tasks across three institutions, Mayo Clinic, Emory University Hospital, and Stanford University. We developed an open-source framework for fine-tuning LLM that can directly extract the five different categories of PCO from the clinic notes. We found that these LLMs without fine-tuning (zero-shot) struggle with challenging PCO extraction tasks, displaying almost random performance, even with some task-specific examples (few-shot learning). The performance of our fine-tuned, task-specific models is notably superior compared with their non-fine-tuned LLM models. Moreover, the fine-tuned GPT-2 model has demonstrated a significantly better performance than the other two larger LLMs. Our discovery indicates that although LLMs serve as effective general-purpose models for tasks across various domains, they require fine-tuning when applied to the clinician domain. Our proposed approach has the potential to lead more efficient, adaptable models for PCO information extraction, reducing reliance on extensive computational resources while still delivering superior performance for specific tasks.

Short- and Long-Term Outcomes in Elderly Patients with Resectable Esophageal Cancer: Upfront Esophagectomy Compared to Surgery after Neoadjuvant Treatments.

Background/Objectives: Despite the increased incidence of esophageal cancer (EC) in elderly people, there are no clear guidelines for its treatment in these patients. The aim of this study was to compare the outcomes of patients ≥ 75 years with resectable EC, receiving either upfront esophagectomy or neoadjuvant treatment. Methods: We retrospectively identified 127 patients with resectable EC ≥ 75 years who underwent esophagectomy between January 2000 and December 2022 at our Clinic in the University Hospital of Padova. The included patients were stratified into two groups: patients undergoing upfront esophagectomy (SURG group) and patients receiving neoadjuvant treatment (NAT group). Results: There were no statistically significant differences in OS (p = 0.7708), DFS (p = 0.7827) and cancer-related survival (p = 0.0827) between the SURG and the NAT group, except for the OS of EAC with stage III-IV, where the NAT group experienced a significant benefit in OS (p = 0.0263). When comparing the two groups, patients receiving neoadjuvant treatment experienced a significantly higher rate of postoperative complications (p = 0.0266). At univariate analysis, neoadjuvant therapy was the only variable strongly associated with postoperative morbidity (p = 0.026). Conclusions: Considering the unique characteristics of elderly patients, the choice of a multimodal approach should be tailored to each case in a multidisciplinary setting and balanced with a potential higher risk of postoperative complications, as well as potential toxicity related to chemoradiation and reduced life expectancy.

Relevance of Cardiovascular Exercise in Cancer and Cancer Therapy-Related Cardiac Dysfunction.

Cancer therapy-related cardiac dysfunction (CTRCD) has been identified as a threat to overall and cancer-related survival. Although aerobic exercise training (AET) has been shown to improve cardiorespiratory fitness (CRF), the relationship between specific exercise regimens and cancer survival, heart failure development, and reduction of CTRCD is unclear. In this review, we discuss the impact of AET on molecular pathways and the current literature of sports in the field of cardio-oncology. Cardio-oncological exercise trials have focused on variations of AET intensity by using moderate continuous and high intensity interval training, which are applicable, safe, and effective approaches to improve CRF. AET increases CRF, reduces cardiovascular morbidity and heart failure hospitalization and should thus be implemented as an adjunct to standard cancer therapy, although its long-term effect on CTRCD remains unknown. Despite modulating diverse molecular pathways, it remains unknown which exercise regimen, including variations of AET duration and frequency, is most suited to facilitate peripheral and central adaptations to exercise and improve survival in cancer patients.

Time trends in surgical provision and cancer-specific outcomes in patients with stage T2-3 kidney cancer: a SEER-based study.

Surgery is the primary therapy that crucially affects the survival of patients with kidney cancer (KC). However, pertinent surgical decision criteria for individuals with stage T2-3 KC are lacking. This study aimed to display the practical choices and evolving trends of surgical procedures and elucidate their implied value. Through the Surveillance, Epidemiology, and End Results (SEER) dataset, the levels and evolving trends of different surgical methods were examined to determine cancer-specific risk of death (CSRD). Additionally, stratification analysis and survival rate analysis were performed to explore the effectiveness of partial nephrectomy (PN). In this study, 9.27% of patients opted for PN. Interestingly, an upward trend was observed in its decision, with an average annual percentage change (AAPC) of 7.0 (95% CI: 4.8-9.3, P < 0.05). Patients who underwent PN and were in a relatively less severe condition exhibited more favorable CSRD levels (0.17-0.36 vs. 0.50-0.67) and an improvement trend compared with those who underwent radical nephrectomy (RN) (AAPC: -1.9 vs. -0.8). Further analysis showed that the levels of CSRD and survival rates for patients opting for different surgical methods followed a similar pattern. This study showed that RN was still the most common surgical method. Patients with stage T2-3 KC had an increasing preference for PN and exhibited more favorable cancer-related survival outcomes, which underscores the need for further investigation and validation.

Prognostic Value of Tumor Deposits in Patients with Colorectal Cancer.

Tumor nodules or tumor deposits (TDs) are a histopathological prognostic factor that are associated with a negative evolutionary course in patients with colorectal cancer (CRC). There are still controversial aspects of TDs, including how they should be integrated into the TNM classification system. The objective of this study was to analyze the predictive value of TDs for cancer-related survival (CRS) and time-to-recurrence survival (TTR) and to evaluate the prognostic value of TDs in patients whose tumors also presented lymph node metastasis (LNM). In this retrospective observational study, all patients treated for CRC between January 2010 and December 2020 at the same hospital were included. CRS and TTR were classified by tumor stage. The results were compared between patients whose tumors had TDs and patients whose tumors did not. A total of 1426 patients met the criteria for inclusion in the analysis. TDs were detected in 178 patients (12.5%): 60 had tumors without LNM, and 118 had LNM. Patients with TD tumors had a lower CRS at 60 months after diagnosis (42% vs. 82%; p < 0.001) and a shorter TTR (34% vs. 79%; p < 0.001). Cox multiple regression analysis revealed that the presence of TD was associated with an increased risk of death from CRC (HR: 1.820; 95% CI: 1.327-2.496) and an increased risk of recurrence (HR: 2.315; 95% CI: 1.743-3.073). In each N stage category, the CRS was significantly lower in the subgroup with TD+: in patients with N1a tumors, the CRS was 44% when TD+ vs. 70% when TD- (p = 0.019); in the N1b group it was 36% vs. 66% (p < 0.001); in the N2a group it was 34% vs. 58% (p = 0.012); and in N2b tumors it was 23% vs. 53% (p = 0.031). The present study shows that the information on the presence of TDs is complementary to that provided by LNM and allows the identification of subgroups of patients in each N stage determined by two metrics, CRS and TTR. TDs should be included in the definition of TNM system categories in patients who simultaneously present with LNM.

The Naples Prognostic Score Is a Useful Tool to Assess Surgical Treatment in Non-Small Cell Lung Cancer.

Different prognostic scores have been applied to identify patients with non-small cell lung cancer who have a higher probability of poor outcomes. In this study, we evaluated whether the Naples Prognostic Score, a novel index that considers both inflammatory and nutritional values, was associated with long-term survival. This study presents a retrospective propensity score matching analysis of patients who underwent curative surgery for non-small cell lung cancer from January 2016 to December 2021. The score considered the following four pre-operative parameters: the neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, serum albumin, and total cholesterol. The Kaplan-Meier method and Cox regression analysis were performed to evaluate the relationship between the score and disease-free survival, overall survival, and cancer-related survival. A total of 260 patients were selected for the study, though this was reduced to 154 after propensity score matching. Post-propensity Kaplan-Meier analysis showed a significant correlation between the Naples Prognostic Score, overall survival (p = 0.018), and cancer-related survival (p = 0.007). Multivariate Cox regression analysis further validated the score as an independent prognostic indicator for both types of survival (p = 0.007 and p = 0.010, respectively). The Naples Prognostic Score proved to be an easily achievable prognostic factor of long-term survival in patients with non-small cell lung cancer after surgical treatment.

Comparison of the effects of sufentanil-dominant anaesthesia/analgesia and epidural anaesthesia/analgesia on postoperative immunological alterations, stress responses and prognosis in open hepatectomy: a randomized trial.

Both in vitro and in animal studies have shown immunosuppressive effects of opioids which might provoke tumour growth and metastasis, while no definite results were shown in previous clinical studies. To find out the effects between general anaesthesia combined with sufentanil target-controlled infusion (SGA) and general anaesthesia combined with epidural anaesthesia (EGA) on immunological alterations, stress responses and prognosis in patients undergoing open hepatectomy, a prospective, non-inferiority, randomized-controlled study was performed. Patients with liver neoplasms undergoing open hepatectomy were randomly assigned to either SGA (n=81) or EGA (n=81) group. The primary outcome was the ratio of interferon (IFN)-γ/interleukin (IL)-4 at 24 h after surgery (T3). The secondary outcomes included immune-related cytokines, circulating immune cells, stress-related cytokines, cortisol and blood glucose, visual analogue scale scores. Plasma was sampled at five-time points [baseline/before surgery (T0), 5 min after portal block release (T1), 1 h after surgery (T2), T3, and on a postoperative day (POD)5 (T4)]. Cancer-related outcomes, including recurrence, metastasis and survival, were followed up at 3 months and 1 year after surgery. The IFN-γ/IL-4 ratios were comparable between both groups at T3 {median [interquartile range (IQR)]: 20.78 (12.73-29.18) vs. 19.52 (13.98-29.29), P=0.607}. At T3, the proportions of circulating T cells were decreased, while those of B and natural killer cells were increased. The plasma level of tumour necrosis factor (TNF)-α at T2 was significantly higher in the SGA group [median (IQR): 7.45 (6.20-9.80) vs. 5.95 (4.95-7.45) pg/mL, P<0.001]. Patient-controlled intravenous analgesia was less effective than epidural analgesia on POD0 and POD2. For hepatocellular carcinoma (HCC)-related outcomes, no significant differences were found in either short- or long-term follow-ups. Although the levels of TNF-α were higher in the SGA group, the tumour-related immunological alterations and follow-ups showed no difference between groups. SGA appears not to be inferior to EGA regarding tumour-related immunity and prognosis. Intravenous opioid use appears not to be inferior to epidural anaesthesia, and can be used safely in HCC patients without worsening patients' prognosis. Chinese Clinical Trial Registry (No. ChiCTR2000035299).

Sertoli–Leydig cell tumor: a clinicopathological analysis in a comprehensive, national cohort

IntroductionSertoli–Leydig cell tumors are rare tumors of the ovary. Moderate and poorly differentiated tumors can metastasize and have a poor outcome. A pathogenic variant in DICER1 is associated with an...

Preventive and Therapeutic Effect of Metformin in Head and Neck Cancer: A Concise Review.

Head and neck cancer (HNC) is a complex affection. Nowadays, conventional treatments are associated with many side effects, reducing the patient's quality of life. Recent studies suggest that metformin, a first-line treatment for diabetes, could decrease cancer incidence and improve cancer-related survival rates. This systematic review summarizes important data from studies evaluating metformin's contribution to preventing and treating HNC. The results suggest a protective effect of metformin in HNC. However, no consensus has been found on its therapeutic effects. Metformin seems to confer an improved cancer-related survival rate in a diabetic population, but compared to a non-diabetic population, the review could not identify any advantages. Nevertheless, no studies presented a negative impact. In conclusion, the results of this systematic review suggest that HNC patients may benefit from metformin. Indeed, it would reduce the HNC incidence. However, more studies are required to evaluate the effect on cancer-related survival rates.

P21 Prevents the Exhaustion of CD4+ T Cells Within the Antitumor Immune Response Against Colorectal Cancer

Background and aimsT cells are crucial for the antitumor response against colorectal cancer (CRC). T cell reactivity to CRC is nevertheless limited by T cell exhaustion. However, molecular mechanisms regulating T cell exhaustion are only poorly understood. MethodsWe investigated the functional role of cyclin-dependent kinase 1a (Cdkn1a or p21) in CD4+ T cells using murine CRC models. Furthermore, we evaluated the expression of p21 in patients with stage I–IV CRC. In vitro co-culture models were used to understand the effector function of p21-deficient CD4+ T cells. ResultsWe observed that the activation of cell cycle regulator p21 is crucial for CD4+ T cell cytotoxic function and that p21-deficiency in Th1 cells leads to increased tumor growth in murine CRC. Similarly, low p21 expression in CD4+ T cells infiltrated into tumors of CRC patients is associated with reduced cancer-related survival. In mouse models of CRC, p21-deficient Th1 cells show signs of exhaustion, where an accumulation of effector/effector memory T cells and CD27/CD28 loss are predominant. Immune reconstitution of tumor-bearing Rag1-/- mice using ex vivo treated p21-deficient T cells with Palbociclib, an inhibitor of CDK4/6, restored cytotoxic function and prevented exhaustion of p21-deficient CD4+ T cells as a possible concept for future immunotherapy of human disease. ConclusionOur data reveal the importance of p21 in controlling cell cycle and preventing exhaustion of Th1 cells. Furthermore, we unveil the therapeutic potential of CDK inhibitors such as Palbociclib to reduce T cell exhaustion for future treatment of patients with colorectal cancer.

Novel Scoring Formula to Predict Survival in Patients of Primary Tongue Cancer Belonging to Tobacco Chewing Population.

Worldwide and in India head and neck malignancies are a major contributor to cancer mortality and morbidity. Tonguecancer predominates oral cavity cancers worldwide but in India it comes next to buccal mucosa. OPD patients after completing treatment tend to ask about the prognosis of their disease where they want an objective answer to "How long will I live?" His scoring system is intended to answer this question and guide patients for adjuvant therapy. This study enrolled all patients between 20 and 85years old with a history of tobacco chewing at least for the last 1year before diagnosis. Patients should have primary tongue cancer amenable to surgical resection. For survival calculation, date of diagnosis was taken as reference time. Using Kaplan-Meier survival analysis, clinicopathological factors significantly associated with survival were ascertained. Then using logit regression, a scoring system predicting patient survival in years based on clinicopathological risk factors was formulated and internal validation was done. A total 241 were enrolled and there were 69 cancer-related deaths. T stage, N stage, LVSI, and DOI were found to be significantly associated with cancer-related survival in tongue cancer patients. Another factor affecting survival was defaulting adjuvant radiation therapy. Using these variables, a survival predicting score was developed. On internal validation and regression, the score was found 80% accurate with error limits ± 6months. It is a concise comprehensive score applicable on Indian population with history of tobacco chewing. It will not only help clinicians to tell patients about their survival expectancy but also help to counsel them for adjuvant therapy. However, external validation and if required recalibration incorporating other factors need to be done for this score.

Pre-diagnostic prognostic value of leukocytes count and neutrophil-to-lymphocyte ratio in patients who develop colorectal cancer.

Emerging evidence is pointing towards a relevant role of immunity in cancer development. Alterations in leukocytes count and neutrophil-to-lymphocyte ratio (NLR) at diagnosis of colorectal cancer (CRC) seems to predict poor prognosis, but no data is available for the pre-diagnostic values. Retrospective analysis of patients who underwent surgery for CRC at our center (2005 - 2020). 334 patients with a complete blood count dating at least 24 months prior to diagnosis were included. Changes in pre-diagnosis values of leukocytes (Pre-Leu), lymphocytes (Pre-Lymph), neutrophils (Pre-Neut), and NLR (Pre-NLR) and their correlation with overall- (OS) and cancer-related survival (CRS) were analyzed. Pre-Leu, Pre-Neut and Pre-NLR showed an increasing trend approaching the date of diagnosis, while Pre-Lymph tended to decrease. The parameters were tested for associations with survival after surgery through multivariable analysis. After adjusting for potential confounding factors, Pre-Leu, Pre-Neut, Pre-Lymph and Pre-NLR resulted independent prognostic factors for OS and CRS. On sub-group analysis considering the interval between blood sampling and surgery, higher Pre-Leu, Pre-Neut, and Pre-NLR and lower Pre-Lymph were associated with worse CRS, and the effect was more evident when blood samples were closer to surgery. To our knowledge, this is the first study showing a significant correlation between pre-diagnosis immune profile and prognosis in CRC.

C7 COMBINATION OF SPIRULINA, GANODERMA LUCIDUM AND MORINGA OLEIFERA IMPROVES CARDIAC FUNCTIONS AND REDUCES PRO–INFLAMMATORY BIOMARKERS IN PRECLINICAL MODELS OF SHORT–TERM DOXORUBICIN–MEDIATED CARDIOTOXICITY

Abstract Background Anthracyclines are essential adjuvant therapies for a variety of cancers, particularly breast, and gastric and esophageal cancers. Whilst prolonging cancer–related survival, these agents can in–duce drug–related cardiotoxicity. Spirulina, Reishi (Ganoderma Lucidum) and Moringa are three nutaceuticals with anti–inflammatory effects that are currently used in cancer patients to improve quality of life and fatigue. Methods Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with short–term doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), Singo at 12 mg/kg (Singo, n=6) or doxorubicin combined to Singo (DOXO–Singo, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100, Fujifilm). Myocardial expression of NLRP3, DAMPs (galectine 3 and calgranulin S100) and 13 cytokines (IL–1α, IL–1β, IL–2, IL–4, IL–6, IL–10, IL–12, IL17–α, IL–18, IFN–γ, TNF–α, G–CSF, and GM–CSF) were quantified through selective mouse ELISA methods. Myocadial fibrosis, necrosis and hypertrophy were analyzed through Immunohistochemistry (IHC). Human cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination to Singo ( at 10, 25 and 50 µg/ml) for 24 and 48h. Cell viability studies were performed through MTS assay. Expression of NLRP3 and p65/NF–kB) were made through selective ELISA methods. Results In preclinical models of short–term DOXO cardiotoxicity, Singo improved significantly EF and FS and prevented the reduction of radial and longitudinal strain after 10 days of treatment with DOXO. A reduced expression of myocardial NLRP3 and NF–kB levels in cardiac tissues were seen in DOXO–Singo group compared to DOXO mice (p&amp;lt;0.05). Myocardial expression of pro–inflammatory cytokines were significantly reduced after treatment with Singo indicating anti–inflammatory properties. Myocardial levels of Cal–granulin S100 and galectine–3 were strongly enhanced in DOXO group; on the other hand their expression were reduced in Singo–DOXO group vs DOXO (p&amp;lt;0.05). Immunohistochemistry analysis indicates that Singo reduces fibrosis and hypertrophy in myocardial tissue of mice during exposure to DOXO. Conclusion Singo is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. Cardioprotective properties of Singo are mediated by the reduction of lipid peroxidation products and expression of NLRP3–NF–kB –cytokine pathways.

¿Se puede realizar la radioterapia intraoperatoria de forma asistencial en el tratamiento del cáncer de mama en estadios iniciales?

After conservative surgery in breast cancer adjuvant radiation therapy is indicated, such treatment can be performed as partial irradiation in well-selected cases and without risk factors for local relapse following the guidelines of international consensus. Partial irradiation is performed by several techniques such as interstitial brachytherapy, external radiation therapy, and also through intraoperative radiation therapy techniques at the same surgical act due to mobile electron accelerators or low-energy photons units. This allows local treatment to be performed in a single day, increasing the surgical time, but with advantages in terms of the tumor bed localization accuracy, immediacy of irradiation and greater patient satisfaction. There is extensive experience in the use of this technique with results comparable to other ways of partial irradiation in terms of local control, minimal side effects, good cosmetic results and even better no cancer related survival. This article reviews the evidence in the use of intraoperative radiation therapy in early-stage breast cancer derived from the main trials comparing it to whole breast irradiation, to confirm that it is already available for standard of care practice in patients who are candidates for partial irradiation.

Renal cell carcinoma with intracardiac tumor thrombus extension: Radical surgery yields 2 years of postoperative survival in a single-center study over a period of 30 years.

Renal cell carcinoma (RCC) with tumor thrombus extension into the right atrium (level IV) is a rare life-threatening clinical condition that can only be managed by means of a combined urological and cardiac surgical approach. The early and late outcomes of this radical treatment were analyzed in a large single-institution series over a period of 30 years. In 37 patients with RCC and intracardiac tumor thrombus extension, nephrectomy was performed followed by the extraction of the intracaval and intracardiac tumor thrombus under direct visual control during deep hypothermic circulatory arrest (DHCA). Recently, in 13 patients, selective aortic arch perfusion (SAAP) was instituted during DHCA. In all patients, precise removal of the tumor thrombus was accomplished in a bloodless field. The mean duration of isolated DHCA was 15 ± 6min, and 31.5 ± 10.2min in the case of DHCA + SAAP, at a mean hypothermia of 22.7 ± 4°C. In-hospital mortality was 7.9% (3 patients). In Kaplan-Meier analysis, the estimated median survival was 26.4 months whereas the 5-year cancer-related survival rate was 51%. Despite its complexity, this extensive procedure can be performed safely with a generally uneventful postoperative course. The use of cardiopulmonary bypass with DHCA, with the advantage of SAAP, allows for a safe, precise, and complete extirpation of intracaval and intracardiac tumor mass. Late outcomes after radical surgical treatment in patients with RCC and tumor thrombus reaching up in the right atrium in our series justify this extensive procedure.