Factors associated with emergency room readmission after elective surgery for ovarian carcinoma.

BACKGROUND: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors. METHODS: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors. RESULTS: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45). CONCLUSION: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems. TRIAL REGISTRATION: researchregistry7882.

Molecular Differences between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers.

The most frequently diagnosed histological types of cervical cancer (CC) are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Clinically, the prognosis of both types is controversial. A molecular profile that distinguishes each histological subtype and predicts the prognosis would be of great benefit to CC patients. METHODS: The transcriptome of CC patients from The Cancer Genome Atlas (TCGA) was analyzed using the DESeq2 package to obtain the differentially expressed genes (DEGs) between ADC and SCC. The DEGs were validated on a publicly available Mexican-Mestizo patient transcriptome dataset (GSE56303). The global biological pathways involving the DEGs were obtained using the Webgestalt platform. The associations of the DEGs with Overall Survival (OS) were assessed. Finally, three DEGs were validated by RT-qPCR in an independent cohort of Mexican patients. RESULTS: The molecular profiles of ADC and SCC of the CC patients of the TCGA database and the Mexican-Mestizo cohort (GSE56303) were determined obtaining 1768 and 88 DEGs, respectively. Strikingly, 70 genes were concordant-with similar Log2FoldChange values-in both cohorts. The 70 DEGs were involved in IL-17, JAK/STAT, and Ras signaling. Kaplan-Meier OS analysis from the Mexican-Mestizo cohort showed that higher GABRB2 and TSPAN8 and lower TMEM40 expression were associated with better OS. Similar results were found in an independent Mexican cohort. CONCLUSIONS: Molecular differences were detected between the ADC and SCC subtypes; however, further studies are required to define the appropriate prognostic biomarker for each histological type.

LncRNAs driving feedback loops to boost drug resistance: sinuous pathways in cancer.

Feedback loops mediate signaling pathways to maintain cellular homeostasis. There are two types, positive and negative feedback loops. Both are subject to alterations, and consequently can become pathogenic in the development of diseases such as cancer. Long noncoding RNAs (lncRNAs) are regulators of signaling pathways through feedback loops hidden as the dark regulatory elements yet to be described with great impact on cancer tumorigenesis, development, and drug resistance. Several feedback loops have been studied in cancer, however, how they are regulated by lncRNAs is hardly evident, setting a trending topic in oncological research. In this review, we recapitulate and discuss the feedback loops that are regulated by lncRNAs to promote drug resistance. Furthermore, we propose additional strategies that allow us to identify, analyze and comprehend feedback loops regulated by lncRNAs to induce drug resistance or even to gain insight into novel feedback loops that are stimulated under the pressure of treatment and consequently increase its efficacy. This knowledge will be useful to optimize the therapeutic use of oncological drugs.

Gene Promoter-Methylation Signature as Biomarker to Predict Cisplatin-Radiotherapy Sensitivity in Locally Advanced Cervical Cancer.

Despite efforts to promote health policies focused on screening and early detection, cervical cancer continues to be one of the leading causes of mortality in women; in 2020, estimated 30,000 deaths in Latin America were reported for this type of tumor. While the therapies used to treat cervical cancer have excellent results in tumors identified in early stages, those women who are diagnosed in locally advanced and advanced stages show survival rates at 5 years of <50%. Molecular patterns associated with clinical response have been studied in patients who present resistance to treatment; none of them have reached clinical practice. It is therefore necessary to continue analyzing molecular patterns that allow us to identify patients at risk of developing resistance to conventional therapy. In this study, we analyzed the global methylation profile of 22 patients diagnosed with locally advanced cervical cancer and validated the genomic results in an independent cohort of 70 patients. We showed that BRD9 promoter region methylation and CTU1 demethylation were associated with a higher overall survival (p = 0.06) and progression-free survival (p = 0.0001), whereas DOCK8 demethylation was associated with therapy-resistant patients and a lower overall survival and progression-free survival (p = 0.025 and p = 0.0001, respectively). Our results suggest that methylation of promoter regions in specific genes may provide molecular markers associated with response to treatment in cancer; further investigation is needed.

Time in range and HbA1C after 6 months with a multidisciplinary program for children and adolescents with diabetes mellitus, real world data from Mexico City.

BACKGROUND: Multidisciplinary interventions may be useful for children and adolescents with diabetes mellitus (DM), especially in areas where new blood glucose monitoring and control technologies are difficult to access. METHODS: PAANDA, a care program for adolescents and children with diabetes, was implemented in patients aged 0 to 18 years and 11 months. The effect of the intervention was determined by self-blood glucose monitoring (SBGM) and glycosylated hemoglobin (HbA1C ) levels at start and after 6 months. RESULTS: A total of 121 patients with DM were evaluated, mean age of 14.27 years (SD: 4.60 years). Blood glucose measurements in range (70-120 mg/dL pre-prandial or 70-180 mg/dL post-prandial) increased by 20.67% before breakfast, 8.14% after breakfast (both P-value <.001), 5.02% before lunch (P-value = .02), 8.66% after lunch (P-value <.001), 11.50% before dinner (P-value <.001), 11.87% after dinner (P-value <.001), and 8.00% at dawn (P-value = .001). This change was accompanied by fewer values in the hyperglycemic category (-19.49% before breakfast, -7.73% after breakfast, both P-value <.001) and hypoglycemia (-1.18%). HbA1C levels decreased significantly 1.8% (P-value = .018). Multivariate logistic regression analysis showed an increase in glycemic control associated with each month after the intervention time in the PAANDA program (P-value <.001 for all the time points evaluated) and a significant decrease in glycemic variability. CONCLUSIONS: The multidisciplinary PAANDA intervention had a beneficial effect on glycemic control, with an improved time in range in a population of children and adolescents with DM.

Advancing clinical research globally: Cervical cancer research network from Mexico.

Cervical cancer is the fourth most common cancer in women with 85% of the mortality burden occurring in less-developed regions of the world. The Cervix Cancer Research Network (CCRN) was founded by the Gynecologic Cancer InterGroup (GCIG) with a mission to improve outcomes in cervix cancer by increasing access to high-quality clinical trials worldwide, with particular attention to less-developed, underrepresented sites. The CCRN held its second international educational symposium in Mexico City with ninety participants from fifteen Latin America countries in January 2017. The purpose of this symposium was to advance knowledge in cervix cancer therapy, promote recruitment to CCRN clinical trials, and to identify relevant future CCRN clinical trial concepts that could improve global care standards for women with cervical cancer.

CTCF-KDM4A complex correlates with histone modifications that negatively regulate CHD5 gene expression in cancer cell lines.

Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5, and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood. Here, we show that CTCF and KDM4A form a protein complex, which is recruited into the first intron of CHD5. This is related to a decrease in H3K36me3/2 histone marks and is associated with its transcriptional downregulation. Depletion of CTCF or KDM4A by siRNA, triggered the reactivation of CHD5 expression, suggesting that both proteins are involved in the negative regulation of this gene. Furthermore, the knockout of KDM4A restored the CHD5 expression and H3K36me3 and H3K36me2 histone marks. Such mechanism acts independently of CHD5 promoter DNA methylation. Our findings support a novel mechanism of epigenetic repression at the gene body that does not involve promoter silencing.

PAX8 is transcribed aberrantly in cervical tumors and derived cell lines due to complex gene rearrangements.

The transcription factor PAX8, a member of the paired box-containing gene family with an important role in embryogenesis of the kidney, thyroid gland and nervous system, has been described as a biomarker in tumors of the thyroid, parathyroid, kidney and thymus. The PAX8 gene gives rise to four isoforms, through alternative mRNA splicing, but the splicing pattern in tumors is not yet established. Cervical cancer has a positive expression of PAX8; however, there is no available data determining which PAX8 isoform or isoforms are present in cervical cancer tissues as well as in cervical carcinoma-derived cell lines. Instead of a differential pattern of splicing isoforms, we found numerous previously unreported PAX8 aberrant transcripts ranging from 378 to 542 bases and present in both cervical carcinoma-derived cell lines and tumor samples. This is the first report of PAX8 aberrant transcript production in cervical cancer. Reported PAX8 isoforms possess differential transactivation properties; therefore, besides being a helpful marker for detection of cancer, PAX8 isoforms can plausibly exert differential regulation properties during carcinogenesis.

Multiple human papillomavirus infections are highly prevalent in the anal canal of human immunodeficiency virus-positive men who have sex with men.

BACKGROUND: Anal cancer has become one of the most common non-AIDS-defined tumors among Human Immunodeficiency Virus-positive (HIV+) individuals, and a rise in its incidence among HIV+ Men who have Sex with Men (MSM) has been shown, despite the introduction of Highly Active Anti-Retroviral Therapy (HAART). Human Papillomavirus (HPV) infections are highly prevalent among HIV+ MSM and recent studies have shown high rates of HPV-associated anal intraepithelial neoplasia (AIN) and anal cancer among this population. METHODS: In the present study we determined the prevalence and nature of HPV co-infections in the anal canal of 324 HIV+ MSM attending a high specialty medical center in Mexico City, DNA extraction and amplification with generic primers for HPV was performed, followed by detection of specific types and co-infections with INNO-Lipa, and identification of variants by amplification and sequencing of the E6 and LCR region of HPV 16. RESULTS: We found a very high prevalence of HPV infections among this cohort (86%), with more than one fourth of them (28%) positive for type 16. Among HPV16-positive patients, European variants were the most prevalent, followed by Asian-American ones. Among these individuals (HPV-16+), we identified co-infections with other 21 HPV types namely; 11, 51, 52, 6, 66, 68, 74, 18, 45, 35, 26, 44, 70, 53, 54, 82, 31, 33, 56, 58, 59. CONCLUSIONS: HIV+ MSM show a very high rate of HPV infections in the anal canal and those with type 16 exhibited a multiplicity of associated types. This study emphasizes the need for an early detection of HPV infections among HIV+ MSM in order to establish its utility to prevent anal neoplasia and cancer.

MicroRNAs in cervical cancer: evidences for a miRNA profile deregulated by HPV and its impact on radio-resistance.

Cervical carcinoma (CC) is one of the most common cancers and a leading cause of mortality in women worldwide. Epidemiologic and experimental data have clearly demonstrated a causal role of high-risk Human Papillomavirus (HR-HPV) types in CC initiation and progression, affecting the cellular processes by targeting and inactivating p53 and pRB host proteins. HR-HPV E5, E6 and E7 oncoproteins have the ability to deregulate several cellular processes, mostly apoptosis, cell cycle control, migration, immune evasion, and induction of genetic instability, which promote the accumulation of mutations and aneuploidy. In this scenario, genomic profiles have shown that aberrant expression of cellular oncogenic and tumor suppressive miRNAs have an important role in CC carcinogenesis. It has been stated that HPV infection and E6/E7 expression are essential but not sufficient to lead to CC development; hence other genetic and epigenetic factors have to be involved in this complex disease. Recent evidence suggests an important level of interaction among E6/E7 viral proteins and cellular miRNA, and other noncoding RNAs. The aim of the current review is to analyze recent data that mainly describe the interaction between HR-HPV established infections and specific cellular miRNAs; moreover, to understand how those interactions could affect radio-therapeutic response in tumor cells.

Importance of tumor size in soft tissue sarcomas: a proposal for a nomogram based on a score system to staging soft tissue sarcomas in the postoperative setting.

In order to adequately stage patients with extremity soft tissue sarcomas (ESTS), it is mandatory to include all adverse prognostic factors and create an integral staging system. We were able to evaluate a nomogram based on a score (STSSS), to improve ESTS staging. We retrospectively evaluated 596 patients with ESTS in stages I-III, of the American Joint Committee on Cancer (AJCC), who had a complete resection. We analyzed the influence of clinicopathological factors on metastasis, recurrence, and disease-specific survival. The STSSS was based on histologic grade (HG), profundity, tumor size (TS), and surgical margins; we also compared STSSS versus AJCC systems in their ability to stage ESTS. The mean TS was 11.8 cm, with 50%>10 cm. Large TS and high HG were independent but adverse prognostic factors for metastasis. In addition, large TS, high grade, and R1 resection were independent adverse prognostic factors for decreased survival. There was a progressive decline in survival as TS increased, although AJCC staging did not correlate well between stages (IA vs. IB p=0.233, IA vs. IIA p=0.123, IA vs. IIB p=0.075, IB vs. IIA p=0.472, IB vs. IIB p=0.211). STSSS showed differences between these categories for 5-year survival (I vs. II p=0.003, II vs. III p=0.002, III vs. IV p<0.001). Surgical margins, HG, and TS are important determinants for metastases and survival. We also found a strong correlation between survival and prognosis with the use of STSSS in the immediate postoperative setting.

The MAD1 1673 G → A polymorphism alters the function of the mitotic spindle assembly checkpoint and is associated with a worse response to induction chemotherapy and sensitivity to treatment in patients with advanced epithelial ovarian cancer.

BACKGROUND: Mitotic arrest deficient 1 (MAD1), a protein of the mitotic spindle assembly checkpoint (SAC), recognizes MAD2 through two leucine zippers, transporting and activating MAD2, which promotes a metaphase arrest signal. A single nucleotide polymorphism of MAD1 was found to affect the SAC function that could be involved in a poor response to therapeutic agents that alter the dynamics of microtubules. OBJECTIVE: The aim of this study was to examine the relationship of the polymorphism MAD1 1673 G → A (rs1801368) with the efficiency of the SAC and the generation of aneuploidies and with the therapeutic response of patients with ovarian cancer. METHODS: The polymorphism was evaluated in 144 healthy individuals and 91 patients. Mitotic arrest and the presence of errors in segregation were analyzed in cultured human lymphocytes treated with nocodazole and paclitaxel. Errors in segregation were also evaluated in 27 biopsies of patients. RESULTS: Allele frequencies in healthy individuals were G: 50%, A: 50%, whereas in the patients they were G: 38%, A: 62% (P<0.05). The percentage of cells with mitotic arrest was higher among GG cells (P<0.05). The frequency of micronuclei and nondisjunction events increased in AA cells (P<0.05). Tumors from polymorphic patients had a higher percentage of aneuploid cells (P<0.05). The GG patients showed a higher biochemical response, optimal cytoreduction, and sensitivity to the treatment. There were no differences in progression-free or overall survival between both groups. CONCLUSION: The polymorphism MAD1 1673 G → A affects SAC functionality, increasing the frequency of aneuploid cells. This polymorphism modifies the response to agents that alter the dynamics of microtubules in patients with ovarian cancer.

A high body mass index is not a worse prognostic factor for endometrial carcinoma in a predominantly obese population.

AIM: We investigate if body mass index (BMI, kg × m(2)) is related to clinical-pathological characteristics in primary tumor and disease outcome in endometrial cancer. BACKGROUND: Endometrial cancer incidence is increasing in industrialized countries. High BMI is associated with worse prognosis for many diseases. INTRODUCTION: Endometrial carcinoma is the most common gynecological malignancy in industrialized countries and the incidence has been increasing over the last few decades associated with obesity, however, it is not clear if a high BMI is associated with poor prognosis. PATIENTS AND METHODS: In total, 147 women primarily treated for endometrial carcinoma at the Instituto Nacional de Cancerología during 2000-2005 were studied. Body mass index was available for all patients and related to comprehensive clinical and histopathological data. RESULTS: High BMI was related to endometrioid histology and low/intermediate grade, and overweight/obese women had the same survival as the normal/underweight women. In survival analysis adjusting for age, histological subtype and grade, BMI showed no independent prognostic impact. CONCLUSION: High BMI was significantly associated with markers of non-aggressive disease and women with high BMI had the same survival time in univariate analysis.

Adenocarcinoma metastatic to the uterine cervix: a case series.

AIMS: The objectives of this report are, first, to describe the clinical behavior of cases of carcinoma metastatic to the uterine cervix treated at our institution in order to carry out a systematic review to establish the behavioral patterns of the most frequent metastases to the cervix and, second, to generate guidelines for their diagnosis and treatment. METHODS: At the National Institute of Cancer of Mexico (INCan), we performed a review of the clinical files with a diagnosis of malignant neoplasm metastatic to the uterine cervix between 1990 and 2009. For a systematic review, we conducted a PubMed search between the years 1970 and 2009 of case reports and series of cases of patients with metastatic gastric, breast, ovarian and colorectal cancer. We analyzed each report individually and extracted the patients' clinical data from our cases and reports, including the primary tumor, cervical metastases and survival rates. RESULTS: There were 10 cases of tumors metastatic to the uterine cervix. Metastasis was documented in one-half of the patients during follow up, with two of these cases having the cervix as the only site. We included the following reports in the systematic review: 13 reports of gastric-associated cancer, 30 related to breast cancer, nine with ovarian-associated cancer and 10 related to colorectal cancer. CONCLUSIONS: Metastatic cervical activity is an infrequent event. The prognosis of survival is poor in the presence of gastric or ovarian cancer and cervical metastases.

Perivascular epithelioid cell tumor of abdominal origin.

Perivascular epithelioid tumor is not a common disease; therefore, large series are not available in the literature, and most are case reports. Histologic characteristics of these neoplasms are positivity to melanogenic (HMB-45) and muscle stains. All these neoplasms have the characteristic perivascular epithelioid cell or "PEC," but the term myomelanocyte tumor has been proposed because of the immunohistochemistry expression. Females are affected more commonly than males. The uterus seems to be one of the most common organs affected. Its clinical behavior is uncertain, and standard treatment has not been established as well as criteria for malignancy. We report 3 cases of abdominal PEComa, 1 of them with benign clinical outcome and 2 with an aggressive behavior.

Human papillomavirus (HPV) in breast tumors: prevalence in a group of Mexican patients.

BACKGROUND: Breast cancer is one of the main health problems in developed countries, occupying first place in mortality in women. It is well-known that there are risk factors associated with breast cancer development. Nonetheless, in 50-80% of cases known risk factors have not been identified, this has generated the attempt to identify new factors related with this neoplasia as viral infections. The aim of this work is investigate the prevalence of HPV DNA in patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico. METHODS: Fifty-one cases of breast cancer were selected from the files of the institute and compared by age and tumor size with 43 cases of non malignant breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor). Paraffin embedded specimens were selected, HPV DNA was analyzed by polymerase chain reaction (PCR) and sequenced for different types of HPV in case of positivity for HPV-DNA. Descriptive analysis of clinical and pathological variables was performed and comparisons between positive and negative cases was done. RESULTS: All patients were mexican, mean age was 53.3, median age of menarche was 13 and median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1 patient (1.9%) of cancer group had HPV and none in the other group, no cases were diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5%) were negative and 15 (29.4%) were positive to HPV-DNA, 10(66.6%) were positive for HPV 16, 3(20%) for HPV 18, two cases (13.4%) were positive for both. In the group of benign conditions all were negative to HPV-DNA. CONCLUSION: Presence of HPV in breast cancer in our group of cases is high in comparison to other authors; larger numbers of cases need to be analyzed in order to establish the exact role of this virus in the pathogenesis of breast cancer.

Primary retroperitoneal mucinous cystadenocarcinoma: report of two cases.

BACKGROUND: Retroperitoneal cystadenocarcinomas are rare lesions, the majority of cases presented as one-patient reports. METHODS: We present two cases of retroperitoneal cystadenocarcinoma, both in women of reproductive age: one with aggressive behavior, and the remaining case, with a more indolent clinical evolution. RESULTS: One case presented as pelvic tumor, was treated with surgical resection of the disease, but manifested with recurrent disease a few months later despite use of chemotherapy. The second case involved a patient with diagnosis of abdominal tumor; during laparotomy, a retroperitoneal tumor was found and was totally removed. At follow-up, the patient is disease-free with no other treatment. CONCLUSION: The behavior and treatment of retroperitoneal cystadenocarcinoma are controversial. We suggest aggressive surgery including radical hysterectomy and bilateral salpingoopherectomy with adjuvant chemotherapy in these cases.