Impact of Dyslipidemia on Tear Film and Meibomian Gland Dysfunction: A Cross-Sectional Study of the Interplay between Serum Lipid Profile and Ocular Surface Health.

Purpose: To determine the relationship between dyslipidemia and dry eye disease (DED), as well as its influence on tear film and meibomian glands. Methods: This cross-sectional study included 40 patients with a mean age of 35.2 ± 13.9 years without any history of dyslipidemia. DED and serum lipid profile were evaluated after 8 hours of fasting. Patients were classified according to serum lipid levels with the following cut-off values: total cholesterol (TC) (200 mg/dl), high-density lipoprotein (HDL) (40 mg/dl), low-density lipoprotein (LDL) (130 mg/dl), and triglycerides (TG) (150 mg/dl). The relationship between serum lipid levels and DED was analyzed with the following variables: dry eye questionnaire-5 (DEQ-5), first (F-NIBUT) and average (A-NIBUT) noninvasive breakup time, tear meniscus height (TMH), lipid layer grade (LLG), conjunctival bulbar redness (CBR), and upper (U-LAMG) and lower (L-LAMG) loss area of meibomian glands. Results: Regarding tear film, patients with elevated TC and LDL levels reported significantly higher DEQ-5 scores and TMH (P < 0.05), while those with lower HDL levels showed significantly higher LLG (p < 0.05). Regarding MGD, patients with elevated TC, LDL, and TG, as well as lower HDL levels showed significantly higher L-LAMG (p < 0.05). HDL was correlated with LLG (p < 0.05), while TC was correlated with TMH (p < 0.05) and L-LAMG (p < 0.05), respectively. Conclusions: Disorders in TC, HDL, LDL, and TG levels were associated with DED, having an impact on the tear film and meibomian glands, specifically in DEQ-5 scores, LLG, and L-LAMG.

Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

BACKGROUND: Existing data on the impact of Hispanic ethnicity on outcomes for patients with renal cell carcinoma (RCC) is mixed. The authors investigated outcomes of Hispanic and non-Hispanic White (NHW) patients with advanced RCC receiving systemic therapy at large academic cancer centers using the International Metastatic Renal Cell Carcinoma Database (IMDC). METHODS: Eligible patients included non-Black Hispanic and NHW patients with locally advanced or metastatic RCC initiating systemic therapy. Overall survival (OS) and time to first-line treatment failure (TTF) were calculated using the Kaplan-Meier method. The effect of ethnicity on OS and TTF were estimated by Cox regression hazard ratios (HRs). RESULTS: A total of 1563 patients (181 Hispanic and 1382 NHW) (mostly males [73.8%] with clear cell RCC [81.5%] treated with tyrosine kinase inhibitor [TKI] monotherapy [69.9%]) were included. IMDC risk groups were similar between groups. Hispanic patients were younger at initial diagnosis (median 57 vs. 59 years, p = .015) and less likely to have greater than one metastatic site (60.8% vs. 76.8%, p < .001) or bone metastases (23.8% vs. 33.4%, p = .009). Median OS and TTF was 38.0 months (95% confidence interval [CI], 28.1-59.2) versus 35.7 months (95% CI, 31.9-39.2) and 7.8 months (95% CI, 6.2-9.0) versus 7.5 months (95% CI, 6.9-8.1), respectively, in Hispanic versus NHW patients. In multivariable Cox regression analysis, no statistically significant differences were observed in OS (adjusted hazard ratio [HR], 1.07; 95% CI, 0.86-1.31, p = .56) or TTF (adjusted HR, 1.06; 95% CI, 0.89-1.26, p = .50). CONCLUSIONS: The authors did not observe statistically significant differences in OS or TTF between Hispanic and NHW patients with advanced RCC. Receiving treatment at tertiary cancer centers may mitigate observed disparities in cancer outcomes.

Altered Lipid Moieties and Carbonyls in a Wistar Rat Dietary Model of Subclinical Fatty Liver: Potential Sex-Specific Biomarkers of Early Fatty Liver Disease?

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver. To date, there is a lack of knowledge about the subtype of lipid structures affected in the early stages of NAFLD. The aim of this study was to analyze serum and liver lipid moieties, specifically unsaturations and carbonyls, by nuclear magnetic resonance (NMR) in a subclinical Wistar rat model of NAFLD for detecting early alterations and potential sex dimorphisms. Twelve weeks of a high-fat diet (HFD) induced fat accumulation in the liver to a similar extent in male and female Wistar rats. In addition to total liver fat accumulation, Wistar rats showed a shift in lipid subtype composition. HFD rats displayed increased lipid carbonyls in both liver and serum, and decreased in unsaturated fatty acids (UFAs) and polyunsaturated fatty acids (PUFAs), with a much stronger effect in male than female animals. Our results revealed that the change in fat was not only quantitative but also qualitative, with dramatic shifts in relevant lipid structures. Finally, we compared the results found in Wistar rats with an analysis in a human patient cohort of extreme obesity. For the first time to our knowledge, lipid carbonyl levels and lipoproteins profiles were analyzed in the context of subclinical NAFLD. The association found between lipid carbonyls and alanine aminotransferase (ALT) in a human cohort of extremely obese individuals further supports the potential role of lipid moieties as biomarkers of early NAFLD.

Impact of Maternal Weight Gain on the Newborn Metabolome.

Pre-pregnancy obesity and excessive gestational weight gain (GWG) appear to affect birth weight and the offspring's risk of obesity and disease later in life. However, the identification of the mediators of this relationship, could be of clinical interest, taking into account the presence of other confounding factors, such as genetics and other shared influences. The aim of this study was to evaluate the metabolomic profiles of infants at birth (cord blood) and 6 and 12 months after birth to identify offspring metabolites associated with maternal GWG. Nuclear Magnetic Resonance (NMR) metabolic profiles were measured in 154 plasma samples from newborns (82 cord blood samples) and in 46 and 26 of these samples at 6 months and 12 months of age, respectively. The levels of relative abundance of 73 metabolomic parameters were determined in all the samples. We performed univariate and machine-learning analysis of the association between the metabolic levels and maternal weight gain adjusted for mother's age, Body Mass Index (BMI), diabetes, diet adherence and infant sex. Overall, our results showed differences, both at the univariate level and in the machine-learning models, between the offspring, according to the tertiles of maternal weight gain. Some of these differences were resolved at 6 and 12 months of age, whereas some others remained. Lactate and leucine were the metabolites with the strongest and longest association with maternal weight gain during pregnancy. Leucine, as well as other significant metabolites, have been associated in the past with metabolic wellness in both general and obese populations. Our results suggest that the metabolic changes associated to excessive GWG are present in children from early life.

Beyond FOXP3: a 20-year journey unravelling human regulatory T-cell heterogeneity.

The initial idea of a distinct group of T-cells responsible for suppressing immune responses was first postulated half a century ago. However, it is only in the last three decades that we have identified what we now term regulatory T-cells (Tregs), and subsequently elucidated and crystallized our understanding of them. Human Tregs have emerged as essential to immune tolerance and the prevention of autoimmune diseases and are typically contemporaneously characterized by their CD3+CD4+CD25high CD127lowFOXP3+ phenotype. It is important to note that FOXP3+ Tregs exhibit substantial diversity in their origin, phenotypic characteristics, and function. Identifying reliable markers is crucial to the accurate identification, quantification, and assessment of Tregs in health and disease, as well as the enrichment and expansion of viable cells for adoptive cell therapy. In our comprehensive review, we address the contributions of various markers identified in the last two decades since the master transcriptional factor FOXP3 was identified in establishing and enriching purity, lineage stability, tissue homing and suppressive proficiency in CD4+ Tregs. Additionally, our review delves into recent breakthroughs in innovative Treg-based therapies, underscoring the significance of distinct markers in their therapeutic utilization. Understanding Treg subsets holds the key to effectively harnessing human Tregs for immunotherapeutic approaches.

A phase II trial of weekly nab-paclitaxel for progressive and symptomatic desmoid tumors.

Desmoid fibromatosis (DF) are mesenchymal neoplasms, with potential aggressive course and relevant clinical impact. New systemic therapy modalities are needed in this symptomatic/progressive population. In this multicenter, phase II trial (NCT03275818), patients with symptomatic/progressing DF received three cycles of weekly nab-paclitaxel. Brief pain inventory short form (BPI-SF) was collected at baseline and in every visit. MRI was performed every 3 months. Primary composite endpoint was RECIST 1.1 overall response rate (ORR) and/or clinical response (improvement ≥ 2 points in BPI-SF). If 40% of patients achieved clinical/radiological response, further investigation would be warranted. Toxicity, progression-free survival (PFS), pattern of response and its correlation with clinical best response and BPI, variation of physical function, and analgesic consumption were secondary endpoints. The translational research reported was not a pre-specified secondary outcome. Forty eligible patients started therapy, being 35 radiologically and clinically evaluable. The study achieved its primary endpoint, as 7(20%) patients obtained RECIST partial response, whereas 31(89%) experienced pain reduction of ≥2 points in BPI-SF worst pain. Therapy was well tolerated. With a median follow-up of 30(14-44) months, median 12 and 24-months PFS rates were 91%(CI 95%, 82-100) and 84%(CI 95%, 71-97). For clinical progression, 12 and 24-months PFS rates were 85% (CI 95%, 73-97) and 74% (CI 95%, 58-90) respectively. Short course of nab-paclitaxel is active, safe and achieves quick and durable responses in progressing/symptomatic DF patients.

Expression of Programmed Death Ligand 1 in Breast Cancer in Mexican Women.

Background: Breast cancer is one of the most common malignant forms of neoplasia worldwide; programmed death protein 1 (PD-1), an inhibitory receptor of T lymphocytes, and its ligand programmed death ligand 1 (PD-L1), play an important role in the ability of tumor cells to evade the host's immune system. Methods: We conducted a descriptive, observational study using retrospective data and an open evaluation using immunohistochemistry to determine the general prevalence of PD-L1 expression in 63 women with breast cancer who underwent a modified radical mastectomy, or quadrantectomy, with axillary lymph node removal. Results: The prevalence of PD-L1 expression was 32% in patients with breast cancer treated with radical mastectomy. PD-L1 expression was higher in patients with large tumor size (19% for pT1, 37% for pT2, 50% for pT3, and 100% for pT4), metastasis in regional lymph nodes (25% for N0, 38% for N1, 75% for pN2, and 38% for pN3), and higher histological grade carcinoma (0% for grade 1, 23% for grade 2, and 50% for grade 3). Conclusions: These findings suggest that PD-L1 expression is heterogeneous in breast cancer tumors and that its expression varies highly in tumor regions over time. The evaluation of PD-L1 expression is significant, because of the therapeutical implications that could improve the outcomes and prognosis of these patients.

Metabolomic Analysis of Severe Osteoarthritis in a Spanish Population of Women Compared to Healthy and Osteoporotic Subjects.

Bone pathologies such as osteoporosis (OTP) and osteoarthritis (OA) are rising in incidence with the worldwide rise in life expectancy. The diagnosis is usually obtained using imaging techniques such as densitometry, but with both being multifactorial diseases, several molecular mechanisms remain to be understood. Metabolomics offers the potential to detect global changes which can lead to the identification of biomarkers and a better insight in the progress of the diseases. Our aim was to compare the metabolic profiles of a cohort of 100 postmenopausal women, including subcapital hip fragility fracture patients, women with severe OA of the hip that required the implantation of a hip prosthesis and controls, to find altered metabolites and networks. Nuclear magnetic resonance (NMR) spectroscopy was used to obtain the metabolomic profiles of peripheral blood derived serum, and statistical analysis was performed using MATLAB V.6.5. 30 of the 73 metabolites analysed showed statistically significant differences in a 3-way ANOVA, and 11 of them were present in the comparison between OA and controls after adjustment by covariates, including amino acids, energy metabolism metabolites and phospholipid precursors. PLS-DA analysis shows a good discrimination between controls and fracture subjects with OA patients, and ROC curve analysis demonstrates that control and fracture subjects were accurately discriminated using the metabolome, but not OA. These results point to OA as an intermediate metabolic state between controls and fracture, and suggest that some metabolic shifts that happen after a fracture are also present at weaker intensity in the OA process.

Desmoplastic infantile astrocytoma with atypical phenotype, PTEN homozygous deletion and BRAF V600E mutation.

Desmoplastic infantile astrocytoma (DIA) is rare, cystic and solid tumor of infants usually found in superficial cerebral hemispheres. Although DIA is usually benign, uncommon cases bearing malignant histological and aggressive clinical features have been described in the literature. We report a newborn patient who was diagnosed with a DIA and died postresection. Pathologic examination revealed that the main part of the tumor had benign features, but the internal region showed areas with a more aggressive appearance, with higher-proliferative cells, anaplastic GFAP positive cells with cellular polymorphism, necrosis foci, vascular hyperplasia with endothelial proliferation and microtrombosis. Genetic study, performed in both regions of the tumor, showed a BRAF V600E mutation and a homozygous deletion in PTEN, without changes in other relevant genes like EGFR, CDKN2A, TP53, NFKBIA, CDK4, MDM2 and PDGFRA. Although PTEN homozygous deletions are described in gliomas, the present case constitutes the first report of a PTEN mutation in a DIA, and this genetic feature may be related to the malignant behavior of a usually benign tumor. These genetic findings may point at the need of further and deeper genetic characterization of DIAs, in order to better understand the biology of this tumor and to obtain new prognostic approaches, a better clinical management and targeted therapies, especially in malignant cases of DIA.

Impact of the Discordance Between Scales of Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium in Patients' Prognosis With Metastatic Renal Cancer.

Background: In Mexico, about 30% of renal cancer patients are diagnosed in a metastatic state. Despite the recent advances in the treatment of cancer, metastatic renal cancer is still an incurable illness. Thus, identifying prognostic factors helps improve prognosis accuracy and survival prediction for patients. Methods: In this study, we retrospectively analyzed 26 patients with histological diagnosis of renal cell carcinoma, including clear cell and other subtypes in stage IV (metastatic), recurrent or unresectable disease. We performed a multivariate analysis of overall survival regarding the congruity between prognostic scales. Results: Our results showed a significant difference in favor of patients with congruity between scales for progression-free survival (18.9 vs. 3.1 months; P = 0.048) and a tendency towards better overall survival in patients with the congruity of both scales compared to the discordant patients (112 vs. 32 months; P = 0.99). Conclusion: This study highlights the discordance between Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium scales, which was associated with worse prognosis with a significant difference in progression-free survival but not in overall survival.

[An unusual association of malakoplakia and adenocarcinoma of the prostate]. / Asociación inusual de malacoplaquia y adenocarcinoma prostático.

Malakoplakia is a chronic inflammatory process caused by a lysosomal defect in bacterial digestion. Although rare, it occurs more frequently in the genitourinary tract and in patients with immune dysfunction. The bladder is the most commonly affected site, although cases have been reported in other organs, including the prostate gland. Clinically, this lesion can be confused with malignant tumours, both on physical examination and imagining techniques. This is particularly pronounced in the prostate, making the differential diagnosis challenging. Histologically, characteristic aggregates of histiocytes with basophilic intracytoplasmic inclusions composed of calcium and iron salts are found. We present a case diagnosed on transrectal biopsy as acinar adenocarcinoma with a Gleason 5 + 5 = 10 score. Prostatectomy revealed an unusual association of diffuse prostate malakoplakia and an area of acinar adenocarcinoma with a Gleason score of 3 + 4 = 7.

Efficacy of 0.1% crosslinked hyaluronic acid, coenzyme Q10 and vitamin E in the management of dry eye disease in menopause patients receiving antidepressants.

PURPOSE: The purpose of this study is to test non-inferiority of a lower dose of crosslinked hyaluronic acid (CLHA) to a higher dose of carmellose eye drop in menopause patients receiving antidepressant treatments. METHODS: This prospective, double-blind, single-center study enrolled sixty female patients. Mean age was 63.25 ± 9.13 years. We examined patients with Schirmer I, breakup time (TBUT) and the ocular surface disease index (OSDI) at the first visit. Tear A eyedrops were formulated with crosslinked hyaluronic acid, coenzyme Q10 and vitamin E. Control tear B was formulated with carmellose sodium. Posology was two and five times, respectively. RESULTS: After 2 months of treatment, the tear A obtained 14.12 ± 7.47 score points for OSDI (t = 11.74, p < 0.01), and tear B obtained 19.46 ± 10.03 score points (t = 7.59, p < 0.01). The tear A obtained 13.77 ± 7.78 score points for Schirmer test (t = 0.88, p > 0.05), and tear B obtained 14.20 ± 8.62 score points (t = 2.92, p < 0.01). The tear A obtained 8.30 ± 2.08 s for TBUT (t = 15.50, p < 0.01), and tear B obtained 7.23 ± 2.40 s (t = 8.79, p < 0.01). CONCLUSION: Lower total daily dose of crosslinked hyaluronic acid eyedrops obtained similar efficacy results in terms of tear stability and subjective dry eye sensation than higher carmellose total daily dose. A lower total daily dose of crosslinked eyedrops was sufficient to achieve better dry eye disease management compared to carmellose.

Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates.

BACKGROUND: Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants. METHODS: Prospective, observational, double-cohort study was conducted in very low birth weight infants with clinical signs and culture-positive sepsis. Blood samples were collected when clinical signs became apparent. Total RNA was processed for transcriptomic analysis. Results were validated by both reverse-transcription polymerase chain reaction and a mathematical model. RESULTS: We included 25 septic preterm infants, 17 with Gram-positive and 8 with Gram-negative bacteria. The principal component analysis identified these two clusters of patients. We performed a predictive model based on 21 genes that showed an area under the receiver-operating characteristic curve of 1. Eight genes were overexpressed in Gram-positive septic infants: CD37, CSK, MAN2B2, MGAT1, MOB3A, MYO9B, SH2D3C, and TEP1. The most significantly overexpressed pathways were related to metabolic and immunomodulating responses that translated into an equilibrium between pro- and anti-inflammatory responses. CONCLUSIONS: The transcriptomic profile allowed identification of whether the causative agent was Gram-positive or Gram-negative bacteria. The overexpression of genes such as CD37 and CSK, which control cytokine production and cell survival, could explain the better clinical outcome in sepsis caused by Gram-positive bacteria. IMPACT: Transcriptomic profiles not only enable an early diagnosis of sepsis in very low birth weight infants but also discriminate between Gram-positive and Gram-negative bacteria as causative agents. The overexpression of some genes related to cytokine production and cell survival could explain the better clinical outcome in sepsis caused by Gram-positive bacteria, and could lead us to a future, targeted therapy.

Impact of Testicular Germ Cell Tumor Laterality on Recurrence-Free Survival in the Mexican Population.

BACKGROUND: To date, the prognostic value of laterality for testicular germ cell tumors remains unknown. Herein, we describe this prognostic factor in the Mexican population. METHODS: A retrospective single-center study that included 37 patients with primary testicular germ cell tumors was conducted. Primary outcome was recurrence-free survival (RFS) at 2 years. Secondary outcomes were RFS by histology, progression-free survival by laterality, and 2-year overall survival. RESULTS: Thirty-seven patients were included, of which five showed relapses. By laterality, the 2-year RFS rate was 100% for left tumors and 77.3% for right tumors, with a trend toward statistical significance (P = 0.058). By histology, the RFS rate was higher for seminomas than non-seminomas (89% vs. 83%, respectively) without this difference being statistically significant. Progression-free survival was higher for right tumors than left tumors (91% vs. 80%, respectively) but without reaching statistical significance. The overall survival rate for the entire cohort was 94.5%. CONCLUSIONS: Our study shows that patients with primary germ cell tumors of the right testicle have a higher risk of recurrence than those with primary germ cell tumors of the left testicle, with a trend toward statistical significance.

Prevalence and Molecular Profile of Breast Carcinoma Using Immunohistochemistry Markers in Mexican Women.

BACKGROUND: In Mexico, breast cancer is the leading cause of death by malignant tumors in women aged 20 and older. The World Health Organization estimates that 69% of deaths caused by breast cancer occur in developing countries. Little is known about the prevalence of breast carcinoma in Mexico and its molecular subclassification. METHODS: This retrospective cross-sectional study included patients who underwent a mastectomy (single, radical or lumpectomy) or a breast tumor biopsy (core-needle or excisional) from January 2002 to December 2018. The primary purpose of the study was to determine the prevalence and molecular profile of breast in comprehensive cancer center in Mexico and compare our results with those published in the US. This study was approved by our scientific and bioethical committee. RESULTS: The final analysis included 379 patients. The youngest patient was 23 years old and the oldest patient was 89; the mean age at diagnosis was 54.63 years. Patients of 40 years old or younger accounted for 48 of the cases (12.66%) and those older than 40 accounted for 331 of the cases (87.33%). The molecular subclassification showed luminal A subtype in 139 cases (36.67%), luminal B subtype in 143 cases (37.73%), human epidermal growth factor receptor 2-positive carcinomas in 32 cases (8.44%) and triple-negative carcinomas in 65 cases (17.15%). Diabetes mellitus was present in 43 patients (11.34%), hypertension in 78 patients (20.58%), obesity in 82 patients (21.63%) and 66 patients reported being treated with exogenous hormone therapy (17.41%). CONCLUSIONS: Breast carcinoma occurs at an earlier age in Mexican women compared to women in the US. Hormone-positive tumors were found to be more prevalent in older patients, while high-grade tumors were more frequently identified in younger patients.

Interactive Data Visualization Tool for Patient-Centered Decision Making in Kidney Cancer.

PURPOSE: Patients and providers often lack clinical decision tools to enable effective shared decision making. This is especially true in the rapidly changing therapeutic landscape of metastatic kidney cancer. Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria, a validated risk prediction tool for patients with metastatic renal cell carcinoma, we created and user-tested a novel interactive visualization for clinical use. METHODS: An interactive visualization depicting IMDC criteria was created, with the final version including data for more than 4,500 patients. Usability testing was performed with nonmedical lay-users and medical oncology fellow physicians. Subjects used the tool to calculate median survival times based on IMDC criteria. User confidence was surveyed. An iterative user feedback implementation cycle was completed and informed revision of the tool. RESULTS: The tool is available at CloViz-IMDC. Initially, 400 lay-users and 15 physicians completed clinical scenarios and surveys. Cumulative accuracy across scenarios was higher for physicians than lay-users (84% v 74%; P = .03). Eighty-three percent of lay-users and 87% of physicians thought the tool became intuitive with use. Sixty-eight percent of lay-users wanted to use the tool clinically compared with 87% of physicians. After revisions, the updated tool was user-tested with 100 lay-users and 15 physicians. Physicians, but not lay-users, showed significant improvement in accuracy in the updated version of the tool (90% v 67%; P = .008). Seventy-two percent of lay-users and 93% of physicians wanted to use the updated tool in a clinical setting. CONCLUSION: A graphical method of interacting with a validated nomogram provides prognosis results that can be used by nonmedical lay-users and physicians, and has the potential for expanded use across many clinical conditions.

Neuroendocrine Tumor of the Common Bile Duct: Case Report.

Carcinoma of the extrahepatic biliary tract accounts for <2% of all cancers. Neuroendocrine tumor of the extrahepatic bile duct is very rare, and there are <200 cases reported since 1959. The preoperative diagnosis is infrequent (5.12%). The definite diagnosis relies on postoperative pathology which utilized immunohistochemistry study on many biomarkers to diagnose the histological subtypes of neuroendocrine neoplasms, such as chromogranin A, synaptophysin, and neuron-specific enolase. When the primary tumor has no metastases, radical removal of the lesion appears as curative treatment. The treatment of the carcinoid syndrome or other functioning syndrome is the first priority. We report a case of a 12-year-old Mexican woman with neuroendocrine tumor of the extrahepatic bile duct (common bile duct neuroendocrine tumor) seen in our hospital. Resection of the common bile duct, cholecystectomy, end to side Roux-en-y hepaticojejunostomy, and portal lymphadenectomy was performed. A review of the pertinent literature was performed. Given the rarity of the disease, treatment principles are based mainly on retrospective series and case reports. We present the eighth case in adolescence in the literature.

Acute Cardiac Tamponade Secondary to Cardiac Vascular-Type Pleomorphic Leiomyosarcoma: Case Report.

Soft tissue sarcomas represent <1% of all neoplasms. Leiomyosarcomas comprise only 5-7% of cases, and only 2% of these are vascular. Vascular leiomyosarcomas are extremely rare and represent only 0.001% of all neoplasms, the venous type being up to 5 times more frequent. Arterial leiomyosarcomas most frequently affect the great vessels, being fatal in most cases. In the reported cases of arterial leiomyosarcomas, the most frequently affected site is the pulmonary artery. We present the clinical case of 2 patients (a 42-year-old woman and a 36-year-old man) with a diagnosis of arterial pleomorphic leiomyosarcoma that conditioned cardiac tamponade as the initial manifestation. As it is an exceptionally rare neoplasm and with few cases reported in the literature, it is important to identify and describe this pathology which, due to the impossibility of offering surgical treatment, represents a therapeutic challenge.

Epithelial-Cadherin Expression Is Associated With Better Recurrence-Free and Overall Survival in Invasive Lobular Breast Cancer in Mexican Women.

BACKGROUND: There are different clinicopathological characteristics that are associated with the prognosis in patients with breast cancer. To date, the prognostic valor of for epithelial cadherin (E cadherin) expression in invasive lobular breast cancer remains unknown. METHODS: A retrospective single-center study that included 207 patients with primary invasive lobular breast cancer was conducted. The primary outcome was to report the correlation of the different clinical pathological characteristics including the expression of epithelial-cadherin (E-cadherin) in invasive lobular breast cancer in Mexican women with recurrence-free survival (RFS) and overall survival (OS). RESULTS: After 11 years of follow-up of patients with invasive lobular breast cancer, RFS was 89.4% and OS of 96.1%. The best prognosis in RFS was in patients with negative nodes 95.2% (P = 0.0001) and OS was 98.6-100% (P = 0.0001). Regarding tumor size, an RFS of 98.3% was observed in those measuring ≤ 2 cm (P = 0.0001) and OS of 99.2% (P = 0.0001). Negative Her2 was related to an RFS of 92.1% (P = 0.0001), and had better OS of 98.3% (P = 0.0001). Ki67 proliferation index ≤ 14% was associated with an RFS of 93.2% (P = 0.005). Negative lymph vascular invasion (LVI) increases the RFS of 91.8% (P = 0.032). The rate of positive expression of E-cadherin was associated with an increase in the RFS of 97.4%, with a mean of 128.6 ± 2.4 months (95% confidence interval (CI): 123.75 - 133.45 months) compared to the absence of expression E-cadherin: signal log ratio (SLR) 68.9%, a mean of 95 ± 6 months (95% CI: 83.28 - 106.88 months), P <0.001. When the OS was analyzed, the presence of E-cadherin expression increased the OS of 100% vs. 86.9% with the absence, P = 0.015. CONCLUSIONS: The prognostic impact of the different clinicopathological characteristics known worldwide was confirmed. Results of the analysis in the presented study indicate that positive expression of E-cadherin correlates with an improvement in OS and RFS in invasive lobular breast cancer in Mexican women.

A Risk-benefit Analysis of Prophylactic Anticoagulation for Patients with Metastatic Germ Cell Tumours Undergoing First-line Chemotherapy.

BACKGROUND: It remains unclear which patients with metastatic germ cell tumours (mGCTs) need prophylactic anticoagulation to prevent venous thromboembolic events (VTEs). OBJECTIVE: To assess the risk and onset of VTEs stratified by risk factors. DESIGN, SETTING, AND PARTICIPANTS: This multi-institutional retrospective dataset included mGCT patients treated with first-line platinum-based chemotherapy. INTERVENTION: Patients with prophylactic anticoagulation were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A regression analysis was performed to select risk factors for VTEs. The simulated number needed to treat (NNT) and the number needed to harm (NNH) with prophylactic anticoagulation were calculated based on the cumulative incidences retrieved from this study and hazard rates of recently published trials describing the efficacy of prophylactic anticoagulation to prevent VTEs and the risk of bleeding events. RESULTS AND LIMITATIONS: From 1120 patients, 121 (11%) had a VTE, which occurred prior to chemotherapy in 49 (4%) and on or after chemotherapy in 72 (6%). Six patients (<1%) had a bleeding event without anticoagulation. After backward regression, the one risk factor for a VTE during or after chemotherapy was the use of a venous access device. The simulated cumulative VTE incidence from prophylactic anticoagulation for patients on or after chemotherapy would translate into an NNT of 45 (95% confidence interval [CI] 36-56) and an NNH of 186 (95% CI 87-506). Limitations are mainly related to the retrospective nature of the study. CONCLUSIONS: The mGCTs associated VTEs are most common before and during, but not after, chemotherapy. Avoiding venous access device and/or prophylactic anticoagulation with an acceptable risk-benefit profile may decrease VTE occurring on chemotherapy. PATIENT SUMMARY: We found that venous thromboembolic events (VTEs) occur rarely after chemotherapy. Based on experience of prophylactic anticoagulation in other cancers, we conclude that the risk of VTE in men undergoing chemotherapy for metastatic germ cell tumours can be decreased by thromboprophylaxis with a reasonable risk-benefit profile and by avoidance of venous access devices.