Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

Prognostic nutritional index as a predictor of surgical complications in women with gynecological cancer.

OBJECTIVE: To analyze the association between the prognostic nutritional index and surgical morbidity in women with gynecologic cancers. METHODS: This is a retrospective cohort study of women with ovarian, endometrial, or cervical cancer who underwent surgery between January 2013 and December 2020 at a cancer center. Demographic and clinical data were extracted from electronic medical records. The prognostic nutritional index was calculated during the immediate pre-operative period. Binomial logistic regression was conducted to identify the association of the prognostic nutritional index with the outcome of surgical complications after Clavien-Dindo classification, adjusting for confounding variables. RESULTS: A total of 1000 women were included: 114 (11.4%) were diagnosed with cervical cancer, 551 (55.1%) with ovarian cancer, and 335 (33.5%) with endometrial cancer. Patients with a prognostic nutritional index >40 had a decreased possibility of surgical complications (OR=0.39, 95% CI 0.29 to 0.52); basal blood hemoglobin, volume of surgical bleeding, operative time, and length of hospital stay were also explanatory factors. The prognostic nutritional index has a significant effect on patients with endometrial and cervical cancer, but conversely is not significant in patients with ovarian cancer. CONCLUSION: The prognostic nutritional index is associated with surgical morbidity in endometrial and cervical cancers and thus can be a useful tool for predicting morbidity and guide pre-operative interventions in patients with gynecological cancers.

Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet).

Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< -1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA-miRNA-mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.

Influence of luminal and basal subtype in prognosis of high-grade non muscle invasive urothelial carcinoma.

BACKGROUND: Recent studies have shown that the classification of high-grade urothelial carcinoma non-muscle invasive (HGBCNMI) based on molecular subtypes might be a valuable strategy to identify patients with a worse clinical prognosis. OBJECTIVE: Determine the effect of the luminal and basal molecular subtype determined by immunistochemical on prognosis in patients with HGBC in Mexican population. METHODS: Phenotypes were evaluated by immunohistochemical staining of luminal (GATA3, FOXA1) and basal (CK5/6, CK14) markers in paraffin-embedded tissue samples from 45 patients with a diagnosis of HGBCNMI treated at Instituto Nacional de Cancerología-México (INCan) between 2009 and 2019. The association with prognosis was evaluated using Kaplan-Meier curves and multivariable-adjusted Cox models. RESULTS: HGBCNMI patients showed mean age of 58.77 years (SD: ±12.08 years). We identified expression of the luminal molecular subtype in 35 cases (77.78 %), and 10 cases (22.22 %) with "combined" expression of the molecular subtype (basal and luminal expression). The combined phenotype was statistically more frequent in metastatic cases (p-value = 0.028). In Kaplan-Meier curves, combined expression of luminal and basal molecular markers was associated with disease progression (p-value = 0.002, log-rank test). Cox regression models confirmed this association, which was not influenced by age (p-value = 0.007) or gender (p-value = 0.007). No association of phenotypes with overall survival (p-value = 0.860) or relapse (p-value = 0.5) was observed. CONCLUSION: The combined expression of immunohistochemical markers of the luminal and basal subtype might be considered as predictor for disease progression in patients with HGBCNMI in Mexican population.

Mutational Landscape of Bladder Cancer in Mexican Patients: KMT2D Mutations and chr11q15.5 Amplifications Are Associated with Muscle Invasion.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute-Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and exome sequenced. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

A Pathogenic Variant Reclassified to the Pseudogene PMS2P1 in a Patient with Suspected Hereditary Cancer.

The PMS2 gene is involved in DNA repair by the mismatch repair pathway. Deficiencies in this mechanism have been associated with Lynch Syndrome (LS), which is characterized by a high risk for colorectal, endometrial, ovarian, breast, and other cancers. Germinal pathogenic variants of PMS2 are associated with up to 5% of all cases of LS. The prevalence is overestimated for the existence of multiple homologous pseudogenes. We report the case of a 44-year-old woman diagnosed with breast cancer at 34 years without a relevant cancer family history. The presence of pathogenic variant NM_000535.7:c.1A > T, (p.Met1Leu) in PMS2 was determined by next-generation sequencing analysis with a panel of 322 cancer-associated genes and confirmed by capillary sequencing in the patient. The variant was determined in six family members (brothers, sisters, and a son) and seven non-cancerous unrelated individuals. Analysis of the amplified region showed high homology of PMS2 with five of its pseudogenes. We determined that the variant is associated with the PMS2P1 pseudogene following sequence alignment analysis. We propose considering the variant c.1A > T, (p.Met1Leu) in PMS2 for reclassification as not hereditary cancer-related, given the impact on the diagnosis and treatment of cancer patients and families carrying this variant.

Analysis of Mexican young women with primary ovarian insufficiency induced by gynaecological and haematological cancer management.

This was a retrospective study that included 114 women younger than 40 years with induced primary ovarian insufficiency. Patients who presented vasomotor symptoms had a higher proportion (26 [63.41%] versus 58 [79.45%], OR 2.23, 95% CI 0.95-5.23, p = .065) to initiate hormone replacement therapy. Vasomotor symptoms were present in patients with ovarian cancer (OR 0.27, 95% CI 0.09-0.8, p = .18), haematologic cancer (OR 0.11, 95% CI 0.2-0.65, p = .014), radiotherapy (OR 2.62, 95% CI 1.04-6.54, p = .039) and chemotherapy with radiotherapy (OR 2.72, 95% CI 1.01-7.35, p = .049). Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy, and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.Impact StatementWhat is already known on this subject? In young women with cancer, induced primary ovarian insufficiency can result as an ovarian surgery or as an adverse effect of chemotherapy or radiotherapy. Regardless of aetiology, patients are going to manifest early climacteric symptoms with an increased risk for cardiovascular disease, metabolic syndrome and osteoporosis.What do the results of this study add? Patients who presented vasomotor symptoms had initially a higher proportion of hormone replacement therapy. Patients that were treated exclusively with radiotherapy or with chemotherapy and concomitant radiotherapy have a significantly increased risk to manifest vasomotor symptoms.What are the implications of these findings for clinical practice and/or future research? Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.

Tumor histology is an independent prognostic factor in locally advanced cervical carcinoma: A retrospective study.

BACKGROUND: Even with different histologic origins, squamous cell carcinoma (SCC) and adenocarcinoma (AC) are considered a single entity, and the first-line treatment is the same. Locally advanced disease at the diagnosis of cervical cancer is the most important prognostic factor, the recurrence rate is high, making it necessary to evaluate prognostic factors other than clinical or radiological staging; histology could be one of them but continues to be controversial. The aim of this study was to evaluate tumor histology as a prognostic factor in terms of treatment outcomes, disease-free survival (DFS) and overall survival (OS) in a retrospective cohort of patients with Locally Advanced Cervical Carcinoma (LACC). METHODS: The records of 1291patients with LACC were reviewed, all of them were treated with 45-50 Gy of external beam radiotherapy with concurrent chemotherapy and brachytherapy. A descriptive and comparative analysis was conducted. Treatment response was analyzed by the chi-square test; DFS and OS were calculated for each histology with the Kaplan-Meier method and compared with the log-rank test; and the Cox model was applied for the multivariate analysis. RESULTS: We included 1291 patients with LACC treated from 2005 to 2014, of which 1154 (89·4%) had SCC and 137 (10·6%) had AC. Complete response to treatment was achieved in 933 (80·8%) patients with SCC and 113 (82·5%) patients with AC. Recurrence of the disease was reported in 29·9% of SCC patients and 31·9% of AC patients. Five-year DFS was 70% for SCC and 62·2% for AC. The five-year OS rates were 74·3% and 60% for SCC and AC, respectively. The mean DFS was 48·8 months for SCC vs 46·10 for AC (p = 0·043), the mean OS was 50·8 for SCC and 47·0 for AC (p = 0·002). CONCLUSION: Our findings support the hypothesis that SCC and AC are different clinical entities. TRIAL REGISTRATION: NCT04537273 .

Acantholytic squamous cell carcinomas of the cervix: A case series.

Squamous cell carcinoma of the uterine cervix is considered the most common histologic variant of cervical cancer, with well-established treatment protocols and prognosis. An infrequent histologic variant of cervical squamous cell carcinoma is the acantholytic variant (ASCC), which is characterized by discohesive cells that result in a pseudoglandular and/or angiomatoid pattern of growth. This variant of squamous cell carcinoma has been regarded as having a poor prognosis at certain anatomic sites such as the head and neck and vulva. In the uterine cervix, the importance of this variant has not been yet established. A ten-year retrospective review of squamous cell carcinoma of the uterine cervix was performed to identify this variant and correlate it with clinical characteristics to better define its prognostic implications. During the study period 19 cases were identified containing from 10 to 80% acantholytic component. Mean age at diagnosis was 49 years. Clinical stages were 1A2 (1 case), Ib1 (16), and IIA1 (2). Median follow-up was 92 months. When compared with controls, ASCC were larger in size (1.4 vs 3.5 cm), had deeper involvement of the cervical stroma (21 vs 47%), had more lymph node metastasis (8 vs 26%), more frequent recurrences (4 vs 15%) and a shorter disease-free survival; however, no statistical differences were identified in overall survival. ASCC is an infrequent variant of cervical cancer which seems to have an impact on disease-free survival but no in overall survival.

Somatic Mutational Landscape in Mexican Patients: CDH1 Mutations and chr20q13.33 Amplifications Are Associated with Diffuse-Type Gastric Adenocarcinoma.

The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets.

Expression of DNA Methyltransferase 3B Isoforms Is Associated with DNA Satellite 2 Hypomethylation and Clinical Prognosis in Advanced High-Grade Serous Ovarian Carcinoma.

Alterations in DNA methylation are critical for the carcinogenesis of ovarian tumors, especially ovarian carcinoma (OC). DNMT3B, a de novo DNA methyltransferase (DNMT), encodes for fifteen spliced protein products or isoforms. DNMT3B isoforms lack exons for the catalytic domain, with functional consequences on catalytic activity. Abnormal expression of DNMT3B isoforms is frequently observed in several types of cancer, such as breast, lung, kidney, gastric, liver, skin, leukemia, and sarcoma. However, the expression patterns and consequences of DNMT3B isoforms in OC are unknown. In this study, we analyzed each DNMT and DNMT3B isoforms expression by qPCR in 63 OC samples and their association with disease-free survival (DFS), overall survival (OS), and tumor progression. We included OC patients with the main histological subtypes of EOC and patients in all the disease stages and found that DNMTs were overexpressed in advanced stages (p-value < 0.05) and high-grade OC (p-value < 0.05). Remarkably, we found DNMT3B1 overexpression in advanced stages (p-value = 0.0251) and high-grade serous ovarian carcinoma (HGSOC) (p-value = 0.0313), and DNMT3B3 was overexpressed in advanced stages (p-value = 0.0098) and high-grade (p-value = 0.0004) serous ovarian carcinoma (SOC). Finally, we observed that overexpression of DNMT3B isoforms was associated with poor prognosis in OC and SOC. DNMT3B3 was also associated with FDS (p-value = 0.017) and OS (p-value = 0.038) in SOC patients. In addition, the ovarian carcinoma cell lines OVCAR3 and SKOV3 also overexpress DNMT3B3. Interestingly, exogenous overexpression of DNMT3B3 in OVCAR3 causes demethylation of satellite 2 sequences in the pericentromeric region. In summary, our results suggest that DNMT3B3 expression is altered in OC.

Long-term PM2.5 exposure before diagnosis is associated with worse outcome in breast cancer.

PURPOSE: Increasingly epidemiological evidence supports that environmental factors are associated with breast cancer (BC) outcomes after a BC diagnosis. Although evidence suggests that air pollution exposure is associated with higher mortality in women with BC, studies investigating potential mechanisms have been lacking. METHODS: We evaluated women with BC (N = 151) attended at the National Cancer Institute-Mexico from 2012 to 2015. We calculated 1-year average exposures to particulate matter < 2.5 µm (PM2.5) at home address before diagnosis. We used linear and logistic regression models to determine the associations between PM2.5 exposure and BC aggressiveness (tumor size, molecular phenotype). RESULTS: Average annual PM2.5 exposure of this population was 23.0 µg/m3 [standard deviation (SD)]: 1.90 µg/m3]. PM2.5 levels were positively correlated with tumor size at diagnosis (r = 0.22; p = 0.007). Multivariable linear models had a similar inference [risk ratio (RR): 1.32; 95% confidence interval (95% CI): 1.04, 1.674]. We did not observe differences in this association by age or menopause status. Further, women with triple-negative BC (TNBC) had significantly higher PM2.5 levels compared with other phenotypes (p = 0.015). Multivariable-adjusted logistic regression models assessing the association between PM2.5 and tumor size had a similar inference (RR 1.41; 95% CI 1.05, 1.89) overall for all ages and also for women who were ≤ 50 years old at diagnosis (RR 1.63; 95% CI 1.036, 2.57). CONCLUSIONS: Our findings suggest a significant association between long-term PM2.5 exposure and BC aggressiveness based on tumor size and phenotype, as well as a worse outcome.

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer.

OBJECTIVE: The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. METHODS: From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an 'inadvertent' simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only. RESULTS: 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). DISCUSSION: Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

Association of p16 and Ki-67 with Risk of Recurrence in Previously Treated Cervical High-Grade Squamous Intraepithelial Lesions.

OBJECTIVE: Our main objective was to assess the association between the markers p16 and Ki-67 and recurrence of disease in patients previously treated for cervical high-grade squamous intraepithelial lesion (HSIL). DESIGN: This is a case-control study at the National Cancer Institute conducted between 2005 and 2015. Of the patients with a pathologically confirmed diagnosis of HSIL, 107 cases were selected. They were divided into 2 groups: 28 cases with recurrence after treatment and a control group of 79 patients without recurrence. We identified clinical, pathological, and treatment variables. METHODS: Two experienced pathologists performed immunohistochemical analysis of biomarkers; they agreed on their interpretation, and we calculated the odds ratios (ORs) associated with recurrence. For group comparisons, we used the Wilcoxon signed-rank, χ2, or Fisher's exact test, depending on the type of variable. We conducted logistic regression models to estimate ORs and determine the factors associated with recurrence. The recurrence-free period was defined as the time frame between conization and either recurrence of disease or the last date the patient was seen. We used Kaplan-Meier plots to visualize survival curves and log-rank tests to compare the curves. We established a p value <0.05 as statistically significant. RESULTS: After pathologists performed immunohistochemical analysis, they achieved an agreement level of 83.7% for p16 and 60% for Ki-67. We did not find an association between recurrence and either p16 expression (p = 0.69) or the percentage of Ki-67 expression (p = 0.71). The recurrence-free period analysis did not reveal a difference in p16 expression (p = 0.57) nor in the percentage of Ki-67 expression in the 3-tiered scale (p = 0.56). LIMITATIONS: Our main limitation was a reduced sample size. CONCLUSION: We found no association between p16 and Ki-67 positivity and the risk of recurrence in previously treated HSIL.

Temperature should not be measured on forearm with infrared thermometers for Covid-19 screening.

Not available.

A Cohort Study of the Prognostic Impact of Exon-16 EZH2 Mutations in a Mexican-Mestizo Population of Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Novel prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) are required in the era of Rituximab. OBJECTIVE: The objective of the study was to study the prognostic impact of exon-16 enhancer-of-zeste homolog-2 (EZH2) mutations in patients with DLBCL. METHODS: In a cohort of patients with DLBCL treated between 2015 and 2017, we analyzed the presence of EZH2 mutations and their association with clinical response (CR), relapse, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 198 patients were included; of them, 30 (15.2%) had mutations at codon 641, in exon 16 of EZH2. Response was achieved in 151 patients (76.3%), and 43 (21.7%) relapsed or progressed during follow-up. EZH2 mutations were associated with relapse/progression (risk ratio [RR] 1.18; 95% confidence interval [CI] 0.98-1.42; p = 0.031), while a trend for not achieving a complete response was observed (RR: 0.876; 95%CI 0.74-1.038; p = 0.071). Of note, Tyr641His and Tyr641Ser EZH2 mutations were associated with shorter PFS (hazard ratio 3.234; 95% CI 1.149-9.1; p = 0.026). CONCLUSION: The presence of EZH2 mutations was negatively associated with relapse/progression and showed a trend for lack of complete response. Further studies are needed to define better the prognostic significance of these mutations in Mexican-Mestizo DLBCL patients.

Influence of social determinants, diabetes knowledge, health behaviors, and glycemic control in type 2 diabetes: an analysis from real-world evidence.

BACKGROUND: Although important achievements have been done in type 2 diabetes mellitus (T2D) treatment and glycemic control, new strategies may take advantage of non-pharmacological approaches and of other potential determinants of health (e.g., socioeconomic status, education, diabetes knowledge, physical activity, and self-care behavior). However, the relationships between these factors are not totally clear and have not been studied in the context of large urban settings. This study aimed to explore the relationship between these determinants of glycemic control (GC) in a low-income urban population from Mexico City, focused in exploring potential the mediation of self-care behaviors in the association between diabetes knowledge and GC. METHODS: A multicenter cross-sectional study was conducted in patients with type 2 diabetes (T2D) from 28 primary care outpatient centers located in Mexico City. Using multivariable-adjusted models, we determined the associations between diabetes knowledge, self-care behaviors, and GC. The mediation analyses to determine the pathways on glycemic control were done using linear regression models, where the significance of indirect effects was calculated with bootstrapping. RESULTS: The population (N = 513) had a mean age of 53.8 years (standard deviation: 11.3 yrs.), and 65.9% were women. Both socioeconomic status and level of education were directly associated with diabetes knowledge. Using multivariable-adjusted linear models, we found that diabetes knowledge was associated with GC (ß: -0.102, 95% Confidence Interval [95% CI] -0.189, - 0.014). Diabetes knowledge was also independently associated with self-care behavior (for physical activity: ß: 0.181, 95% CI 0.088, 0.273), and self-care behavior was associated with GC (for physical activity: ß: -0.112, 95% CI -0.194, - 0.029). The association between diabetes knowledge and GC was not observed after adjustment for self-care behaviors, especially physical activity (ß: -0.084, 95% CI -0.182, 0.014, p-value: 0.062). Finally, the mediation models showed that the effect of diabetes knowledge on GC was 17% independently mediated by physical activity (p-value: 0.049). CONCLUSIONS: Socioeconomic and educational gradients influence diabetes knowledge among primary care patients with type 2 diabetes. Self-care activities, particularly physical activity, mediated the effect of diabetes knowledge on GC. Our results indicate that diabetes knowledge should be reinforced in low-income T2D patients, with an emphasis on the benefits physical activity has on improving GC.

Diagnostic performance of intraoperative assessment in grade 2 endometrioid endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Grade 2 carcinoma is associated with pelvic lymph-node metastasis, depending on selected risk factors. Intraoperative assessment (IOA) can identify patients at risk for lymph node metastasis who should undergo staging surgery. Our objective was to establish the diagnostic precision of IOA in determining the need for surgical staging in grade 2 endometrioid endometrial carcinoma. METHODS: Two hundred twenty-two patients underwent IOA. Results were compared to the final pathology report. The accuracy of the IOA parameters was calculated. Variables were evaluated in patients with positive versus negative IOA. Overall and disease-free survivals were calculated according to IOA, lymphadenectomy, and nodal metastasis. RESULTS: IOA was positive in 80 patients. It showed an accuracy of 76.13% when compared with the postoperative assessment. The best individual parameter was myometrial invasion. Nodal metastasis was observed in 16 patients in the positive IOA group and 7 patients in the negative group. Patients with lymph node metastasis had a 5-year overall survival rate of 80.9%, whereas patients without metastasis had a 5-year overall survival rate of 97.9%. CONCLUSIONS: IOA is an adequate tool to identify high-risk patients in grade 2 endometrial carcinoma. Myometrial invasion is the individual parameter that yields the highest diagnostic precision.

What is the impact of radical hysterectomy on endometrial cancer with cervical involvement?

BACKGROUND: When endometrial carcinoma invades the cervical stroma, overall survival and disease-free survival decrease. However, it is still controversial whether patients in suspected stage II should be treated with radical hysterectomy. The goal of this study is to describe the role of radical hysterectomy in patients with endometrial carcinoma and cervical involvement. METHODS: This was a retrospective cohort study were a total of 239 patients with endometrial carcinoma with cervical involvement from Mexico City's National Cancer Institute were divided according to the type of hysterectomy, and the outcomes were compared using statistical analysis. RESULTS: The 5-year overall survival was 75.76% for the simple hysterectomy group and 89.19% for the radical hysterectomy group, without achieving statistical significance. The 5-year disease-free survival was 72.95% for the simple hysterectomy group and 64.31% for the radical hysterectomy group, without achieving statistical significance. Radicality was associated with longer surgical times, intraoperative complications, and bleeding over 500 ml. CONCLUSIONS: In patients with endometrial carcinoma with cervical involvement, radical hysterectomy does not improve prognosis or alter adjuvant therapy.

Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. OBJECTIVE: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. METHODS: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. RESULTS: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. CONCLUSIONS: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.