Mexican consensus about surgical treatment in early-stage cervicouterine cancer.

Introduction: Cervical cancer is a public health problem in our country and worldwide. Less than 25% of cases are diagnosed in the early stages, where survival is more remarkable than 90% at five years. Here, we review surgical treatment in the early stages of cervical cancer. Methodology: A literature review was carried out in the MEDLINE database. The search was mainly limited to the English language, with priority given to systematic reviews with or without meta-analysis and randomized studies. However, only retrospective or observational evidence was found for some topics. Results: The standard treatment for early-stage cervical cancer is hysterectomy, and its radical nature will depend on the tumor size, lymphovascular permeation, and tumor-specific prognostic factors. Furthermore, the type of surgery (hysterectomy or trachelectomy) will rely on the patient's desire to preserve fertility. Nodal evaluation is indicated as part of the treatment from stage IAI with PLV. However, the sentinel lymph node is more relevant in the treatment. The incidental finding of cervical cancer after a hysterectomy requires a multidisciplinary evaluation to determine the therapeutic approach. Less radical surgery has been described as oncologically safe in low-risk groups. Conclusion: Surgical treatment in its early stages has evolved in recent decades, making it more individualized and seeking less morbidity in patients without compromising their survival.

Role of palliative care intervention in patients with vulvar cancer: a retrospective study.

OBJECTIVE: To describe the experience of a Mexican cancer centre in vulvar cancer and the opportunity to incorporate palliative care (PC) during treatment. PATIENTS AND METHODS: A retrospective study of clinical and sociodemographic characteristics of women with vulvar cancer referred to the PC service (PCS) between 2010 and 2021 is reported. Frequencies were estimated, as well as medians and IQRs, accordingly. Referral time and overall survival were estimated using the Kaplan-Meier method. RESULTS: 125 women with vulvar cancer were seen between 2010 and 2021, but only 42% were seen at PCS, mostly polysymptomatic, after several visits to the emergency room. 89% of the patients seen at PCS died at home. CONCLUSIONS: Vulvar cancer is a rare type of cancer, while squamous cell carcinoma is the most frequent type. At the time of referral, almost half of the patients had severe pain, bleeding, malodor, infection and urinary incontinence. Most of these patients lived in poverty, were poorly educated and had multiple surgeries. PC may play an important role in the care of patients with advanced vulvar cancer, relieving the physical and psychological symptoms, avoiding unnecessary hospitalisation and favouring death at home without pain and other symptoms.

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.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Insurance status and access to cervical cancer treatment in a specialized cancer center in Mexico.

To describe access to complete treatment in women with cervical cancer and state-sponsored insurance versus no insurance. We conducted a retrospective observational study. The source population consisted of women treated for cervical cancer from January 2000 to December 2015 in a tertiary care hospital. We included 411 women with state-sponsored insurance and 400 without insurance. We defined access to cervical cancer treatment as complete treatment (according NCCN/ESMO (National Comprehensive Cancer Network/European Society for Medical Oncology) standards) and timely initiation of treatment (less than 4 weeks). Clinical and sociodemographic characteristics were described and analyzed with logistic regression using complete treatment as the main outcome. A total of 811 subjects were included, the median age was 46 (IQR (Interquartile range) 42-50) years. Most of them were married (36.1%), unemployed (50.4%), and had completed primary school (44.0%). The most common clinical stages at diagnosis were II (38.2%) and III (24.7%). In the adjusted regression model, being married (OR (odds ratio): 4.3, 95% CI (confidence interval): 1.74-10.61) and having paid employment (OR: 2.79, 95% CI: 1.59-4.90) or state-sponsored insurance (OR: 1.54, 95% CI: 1.04-2.26) were positively associated with the possibility of having a complete treatment. Women with insurance were likely to be younger and receive timely treatment compared with uninsured women. Complete treatment was associated to insurance status and advanced stages of cervical cancer. State-sponsored insurance improves access to complete treatment. Government policies are needed to avoid social and economic inequity and provide better management of cervical cancer in our country.

Time intervals to care and health service use experiences of uninsured cancer patients treated under public financing in Mexico City.

BACKGROUND: The present study assesses the time intervals from symptom discovery to treatment start and describes the health service use experiences of uninsured patients with cancer of the breast, cervix uteri, testicle, and prostate before their arrival to the cancer hospital. METHODS: This cross-sectional study included 1468 patients who were diagnosed between June 2016 and May 2017 and received treatment for the selected cancers in two of the largest public cancer hospitals in Mexico City, financed through Seguro Popular. Data was collected through a survey administered via face-to-face interviews with patients and a review of their medical files. RESULTS: The median time between detection (symptom discovery or first abnormal screening test) and treatment start was 6.6 months. For all types of cancer, the longest interval was the diagnostic interval -between the first use of healthcare services and the confirmation of cancer. Less than 20% cancer patients were diagnosed in the earliest stages that are associated with the best chances of long-term survival. The participants described a high use of private services for their first consultation, the use of several different types of health services and multiple consultations before arrival to the cancer centers, and 35% perceived being misdiagnosed by the first doctor they consulted. CONCLUSIONS: Most cancer patients treated in the two largest public institutions available for the uninsured faced long delays to get diagnosed and started treatment at advanced stages. Strengthening quality and access for effective early cancer diagnosis and treatment is key to improve patient outcomes in low and middle-income settings.

Cervical cancer prevention program in Mexico disrupted due to COVID-19 pandemic: Challenges and opportunities.

Introduction: The COVID-19 pandemic disrupted the preventive services for cervical cancer (CC) control programs in Mexico, which will result in increased mortality. This study aims to assess the impact of the pandemic on the interruption of three preventive actions in the CC prevention program in Mexico. Methods: This study is a retrospective time series analysis based on administrative records for the uninsured population served by the Mexican Ministry of Health. Patient data were retrieved from the outpatient service information system and the hospital discharge database for the period 2017-2021. Data were aggregated by month, distinguishing a pre-pandemic and a pandemic period, considering April 2020 as the start date of the pandemic. A Poisson time series analysis was used to model seasonal and secular trends. Five process indicators were selected to assess the disruption of the CC program, these were analyzed as monthly data (N=39 pre-pandemic, N=21 during the pandemic). HPV vaccination indicators (number of doses and coverage) and diagnostic characteristics of CC cases were analyzed descriptively. The time elapsed between diagnosis and treatment initiation in CC cases was modeled using restricted cubic splines from robust regression. Results: Annual HPV vaccination coverage declined dramatically after 2019 and was almost null in 2021. The number of positive Papanicolaou smears decreased by 67.8% (90%CI: -72.3, -61.7) in April-December 2020, compared to their expected values without the pandemic. The immediate pandemic shock (April 2020) in the number of first-time and recurrent colposcopies was -80.5% (95%CI:-83.5, -77.0) and -77.9% (95%CI: -81.0, -74.4), respectively. An increasing trend was observed in the proportion of advanced stage and metastatic CC cases. The fraction of CC cases that did not receive medical treatment or surgery increased, as well as CC cases that received late treatment after diagnosis. Conclusions: Our analyses show significant impact of the COVID-19 pandemic with declines at all levels of CC prevention and increasing inequalities. The restarting of the preventive programs against CC in Mexico offers an opportunity to put in place actions to reduce the disparities in the burden of disease between socioeconomic levels.

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.

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer.

PURPOSE: Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. METHODS: Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. RESULTS: Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. CONCLUSION: The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

Snapshot of symptoms of advanced cervical cancer patients referred to the palliative care service in a cancer center in Mexico.

OBJECTIVE: To report the clinical and demographic characteristics of patients with advanced cervical cancer referred to the palliative care service (PC) at a major cancer center in Mexico. METHODS: This is a retrospective cohort study of patients with advanced cervical cancer referred to the PC of INCan, between January 2011 and December 2015. Demographic and clinical characteristics at the time of admission to the INCan, time to referral to PC, initial Edmonton Symptom Assessment System evaluation, and follow up were recorded. RESULTS: In all, 359 patients were included, median age 51 years, predominantly poor with low education. Most patients 322 (90%) received tumor-specific treatment; presence of nephrostomies and other tumor-related complication was frequent. Median time to referral was 335 days, more than 180 (50%) had five or more symptoms, pain and fatigue were the most prevalent. CONCLUSION: Women with advanced cervical cancer have a high burden of symptoms; PC is only considered at the end of life. Efforts for an early referral to PC should be made.

Cervical Cancer in Young Women: Do They Have a Worse Prognosis? A Retrospective Cohort Analysis in a Population of Mexico.

BACKGROUND: Cervical cancer (CC) is a global problem; it is among the five leading causes of cancer death in women. Several studies have examined the association between age and disease prognosis; however, controversy still exists. The objective of the present study is to determine if age at diagnosis has an impact on overall survival (OS) and disease-free survival (DFS). MATERIALS AND METHODS: Retrospective cohort of 2,982 patients with CC treated at the National Cancer Institute of Mexico from 2005 to 2015. We collected demographic, clinical, and treatment data, as well as current status, of 2 groups: women under and over 40 years of age. We calculated OS and DFS rates with Kaplan-Meier estimates. Cox proportional hazards modeling was used to determine risks. RESULTS: The median follow-up time was 26.5 months (percentile [P]25 -P75 , 11-60.23). When comparing DFS, OS, stage, and histologic subtype between young patients <40 and adult patients >40, we did not observe any difference. We found that in both groups, locally advanced and advanced stage, neuroendocrine subtype, hydronephrosis, and positive inguinal lymph nodes increased the risks of death and recurrence. Having been pregnant was identified as protective factor in DFS (hazard ratio, 0.54; 95% confidence interval, 0.04-0.71). CONCLUSION: We corroborated that age at diagnosis is not a prognostic factor for decreased or increased OS or DFS, and in both groups, the stage, histologic subtype, hydronephrosis, and node involvement were identified as factors adverse to OS and DFS, and pregnancy history was a protective factor in DFS. IMPLICATIONS FOR PRACTICE: The present study directly affects everyday clinical practice because it allows us to focus on the most relevant prognostic factors in patients with cervical cancer. When planning treatment and follow-up, clinicians should focus on stage at diagnosis, histologic subtype, hydronephrosis, and distant metastasis instead of patients' age. They should also be aware of any previous pregnancies and poor response, or nonresponse, to treatment, which results in disease progression and persistence. Paying attention to these factors affecting overall survival and disease-free survival will help treat patients better and increase their chances of survival and improve their quality of life.

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.

Experiencia con el uso de olaparib en pacientes con cáncer de ovario.

INTRODUCTION: More than the twenty percent of ovarian cancers are hereditary, and most have BRCA mutations. The 30% of Mexican patients with the BRCA1 mutation have the BRCA1 gene exon 9-12del deletion founder mutation (BRCA1 ex9-12del). BRCA-mutated tumors are more sensitive to PARP inhibitors such as olaparib. OBJECTIVE: To show the clinical experience on the use of olaparib at Instituto Nacional de Cancerología in Mexico. METHOD: Ovarian cancer patients treated with olaparib from November 2016 to December 2018 were studied, and their characteristics, clinical response, progression-free survival (PFS) and toxicities were described. RESULTS: Nineteen patients were assessed, with BRCA1 mutation being found in 78.9%, out of which 21.1% were carriers of the ex9-12del founder mutation. The median of PFS was 12 months; for patients treated on second and third line it was > 15 months, and for those treated with a fourth and subsequent line it was 8.3 months. Patients with the founder mutation had better results. Toxicities were like those reported in previous studies. CONCLUSIONS: Olaparib offers greater PFS benefit as maintenance therapy after a first and second relapse. Patients with founder mutation have had sustained PFS.

INTRODUCCIÓN: Más del 20 % de los cánceres de ovario puede ser hereditario y la mayoría tiene mutaciones BRCA. El 33 % de las pacientes mexicanas con mutación BRCA1 tiene la mutación fundadora deleción del exón 9-12del del gen BRCA1 (BRCA1 ex9-12del). Los tumores BRCA mutados son más sensibles a inhibidores PARP como olaparib. OBJETIVO: Mostrar la experiencia clínica del uso de olaparib en el Instituto Nacional de Cancerología de México. MÉTODO: Se estudiaron las pacientes con cáncer de ovario tratadas con olaparib de noviembre de 2016 a diciembre de 2018 y se describieron sus características, respuesta clínica, supervivencia libre de progresión y toxicidades. RESULTADOS: Se evaluaron 19 pacientes, 78.9 % presentó mutación BRCA1, del cual 21.1 % era portador de la mutación fundadora ex9-12del. La mediana de supervivencia libre de progresión global fue de 12 meses, para las pacientes tratadas tratadas con olaparib de mantenimiento posterior a segunda y tercera línea fue de > 15 meses y para las de cuarta línea o más fue de 8.3 meses. Las pacientes con mutación fundadora presentaron mejores respuestas. Las toxicidades fueron similares a las de estudios con el uso de olaparib. CONCLUSIONES: Olaparib ofrece mayor beneficio en supervivencia libre de progresión como tratamiento de mantenimiento después de la primera y segunda recaída. Las pacientes con mutación fundadora han tenido respuesta sostenida.

Prognostic factors associated with uterine sarcomas: the experience of a single institution.

Uterine sarcomas are infrequent and heterogeneous mesenchymal tumours, associated with aggressive characteristics and a poor clinical outcome. The aim of the study is to describe the prognostic factors associated with uterine sarcomas. The clinical records between 2000 and 2014 of women diagnosed with uterine sarcomas and initially treated surgically were reviewed. A histological comparison was performed. The overall survival (OS) and disease-free survival (DFS) were calculated and compared. Seventy-three women had surgery (12.3% had endometrial stromal sarcomas, 24.7% undifferentiated endometrial sarcomas, 49.3% leiomyosarcomas and 13.7% other subtypes). Complete cytoreduction had a mean DFS of 25.1 months, while the incomplete cytoreduction averaged in a DFS of 4.33 months (p = .04). The median five-year OS with a complete cytoreduction was not reached; the incomplete cytoreduction OS was 10.1 months (p = .002). Our data suggests that undifferentiated endometrial sarcomas have the lowest DFS (p = .004); while OS was negatively influence by stage IV (p < .001). Impact statement What is already known about this subject? Uterine sarcomas compared with the more common endometrial carcinomas (epithelial neoplasms), behave aggressively and are associated with a poorer prognosis. The rarity of uterine sarcoma has made it difficult to perform large studies to identify risk factors. What do the results of this study add? Complete cytoreduction improves the DFS and OS and may be a valuable prognostic factor. Poorer DFS and OS prognosis was observed in undifferentiated endometrial sarcomas. What are the implications of these findings for clinical practice and/or further research? Our results demonstrate the importance of an early diagnosis, and thus an early identification of disease that benefits from complete cytoreduction regardless of histology. For the advanced clinical stage of uterine sarcomas further research is necessary and participation in clinical trials should be encouraged.

[Resultados quirúrgicos de histerectomía radical laparoscópica en pacientes con cáncer de cérvix en etapa temprana: experiencia inicial en Instituto de Cáncer]. / Surgical outcomes of laparoscopic radical hysterectomy for patients with early cervical cancer: Initial experience in Cancer Institute.

ANTECEDENTES: La histerectomía radical abierta con linfadenectomía pélvica bilateral es el tratamiento estándar para el cáncer de cérvix uterino (CACU) en etapas temprana (1A2-1B1); la histerectomía radical por laparoscopia (HRL) es una opción segura y viable. OBJETIVO: Evaluar la seguridad y la factibilidad de la HRL en un centro hospitalario de atención de cáncer. MÉTODO: Estudio retrospectivo que incluyó 17 pacientes con CACU en etapa temprana intervenidas con HRL entre abril de 2013 y noviembre de 2016 en el Instituto Nacional de Cancerología de México. RESULTADOS: Las 17 pacientes se encontraban en etapa clínica IB1, en 10 (58.8%) fue subtipo epidermoide, en 4 (23.5%) adenocarcinoma y en 3 (17.6%) adenoescamoso. La media de edad fue de 42 ± 8 años. El tamaño del tumor fue de 2.3 ± 0.9 cm, y en el 94.1% los márgenes quirúrgicos estaban libres de enfermedad. El promedio de tiempo operatorio fue de 341 ± 65 minutos, con una pérdida sanguínea de 107 ± 64 ml, no requirieron trasfusión sanguínea y no hubo conversión a cirugía abierta. La media de estancia hospitalaria fue de 2.7 días (rango: 2-7 días). No se presentaron complicaciones intraoperatorias ni posoperatorias. CONCLUSIONES: La HRL es una alternativa segura y confiable para el tratamiento del CACU en etapa temprana. BACKGROUND: Open radical hysterectomy with bilateral pelvic lymphadenectomy is the standard treatment in early stages (1A2-1B1) of uterine cervical cancer (UCC); laparoscopic radical hysterectomy (LRH) is a safe and viable option. OBJECTIVE: To evaluate the safety and feasibility of LRH in a hospital cancer care center. METHOD: Retrospective study that included the first 17 patients with UCC in an early stage operated with LRH in the period from April 2013 to November 2016 at the National Cancer Institute of Mexico. RESULTS: The 17 patients were stage IB1 clinical, of which 10 (58.8%) was epidermoid subtype, 4 (23.5%) adenocarcinoma and 3 (17.6%) adenoescamoso. The mean age was 42 ± 8 years. The tumor size was 2.3 ± 0.9 cm, and in 94.1% the surgical margins were free of disease. The average operative time was 341 ± 65 minutes and blood loss of 107 ± 64 ml, no patient required blood transfusion and there was no case of conversion to open surgery. The average length of hospital stay was 2.7 days (range: 2-7 days). There were no intraoperative or postoperative complications. CONCLUSIONS: LRH is a safe and reliable alternative for the treatment of early stage UCC.

let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer.

Altered expression of microRNAs contributes to the heterogeneous biological behavior of human malignancies and it may correlate with the clinical pathological features of patients. The let-7 microRNA family is frequently downregulated in human cancers and its aberrant expression may be a useful marker for prediction of the clinical response to therapy in patients. In the present study, we analyzed the expression of three members of the let-7 family (let-7a-3p, let-7d-3p and let-7f), which remains largely uncharacterized in ovarian cancer tissues. We also investigated the function of let-7d-3p in the apoptosis and sensitization to chemotherapy in ovarian cancer cells. Our data from stem-loop quantitative RT-PCR showed that expression of let-7a-3p and let-7d-3p, but not let-7f, was significantly (P<0.04) upregulated in ovarian tumors relative to that noted in normal ovarian tissues. Markedly, an increased expression of let­7d-3p (also known as let-7d-3*) was associated with positive response to carboplatin/paclitaxel treatment in ovarian cancer patients. To investigate the biological relevance of let­7d-3p, we knocked down its expression in SKOV-3 ovarian cancer cell line using antagomiRs. Loss of function analysis showed that inhibition of let-7d-3p significantly (P<0.05) impaired cell proliferation and activated apoptosis. In contrast, scratch/wound healing and Transwell chamber assays showed that migration and invasion abilities were not affected in the let-7d-3p-deficient SKOV-3 cancer cells. Notably, Annexin V assays showed a significant (P<0.05) increase in cell death of cancer cells treated with the let-7d-3p inhibitor plus carboplatin indicating a synergistic effect of the drug with antagomiR therapy. Gene ontology classification of predicted targets of let-7d-3p identified a number of genes involved in cellular pathways associated with therapy resistance such as ABC transporters, HIF-1, RAS and ErbB signaling. In summary, our findings showed that inhibition of let-7d-3 activates apoptosis and that its upregulation is associated with a positive response of ovarian cancer patients to carboplatin/paclitaxel chemotherapy.

MicroRNA-125 modulates radioresistance through targeting p21 in cervical cancer.

Cervical cancer (CC) is one of the most common cancers diagnosed in women worldwide, and it is estimated that ~500,000 new patients are diagnosed with cervical cancer annually and that ~270,000 deaths occur each year. Patients with cervical cancer are treated with different radiotherapy schedules, either alone or with adjuvant chemotherapy. Unfortunately, nearly 50% of all patients with cervical cancer do not respond to standard treatment due to tumor radioresistance. In this scenario, several microRNAs (miRNAs) have been associated with the acquisition of the radioresistance phenotype. The aim of the present study was to evaluate the possible role of miR­125a in the acquisition of radioresistance in cervical cancer. The expression of miR­125a was assessed by means of RT­qPCR in 30 cervical cancer samples from patients receiving standard treatment and 3 induced radioresistant cervical cancer cell lines. In addition, we employed miR­125a mimics and inhibitors to evaluate its function in the induction of radioresistance. We showed that miR­125a was downregulated in patients with cervical cancer who did not respond to standard treatment. Concordantly, radioresistant SiHa, CaSki and HeLa cell lines had low levels of miR­125a with respect to the sensitive cell lines. Finally, we demonstrated that overexpression of miR­125a sensitized cervical cancer cells to radiation therapy through the downregulation of CDKN1A. Our data corroborate previously published studies in which it was demonstrated that miRNAs could play a role in the regulation of the process of radioresistance. Additionally, we showed that overexpression of miR­125a could be used as a radioresistance biomarker in patients with cervical cancer.

Histology as Prognostic Factor in Early-Stage Cervical Carcinoma. Experience in a Third-Level Institution.

BACKGROUND: Cervical carcinoma (CC) is one of the most frequent neoplasms, especially in developing countries. The most common histopathological type is squamous cell carcinoma (SCC), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC). Prognosis according to histological type is controversial. OBJECTIVE: The objective of this study is to describe and compare the prognoses of the most common histologies of CC in the early stages. MATERIALS AND METHODS: We reviewed records of patients attended at the Instituto Nacional de Cancerología of Mexico with CC surgically treated Stages IA2-IB1 and IIA1, including the histological types SCC, AC, and ASC. Patients who had another malignant neoplasm, cervical cancer in situ, locally advanced neoplasm, and metastatic neoplasm were excluded from the study. A descriptive and comparative analysis was conducted. Overall survival (OS) and disease-free period were calculated for each histological type with the Kaplan-Meier method and were compared with the log-rank test. RESULTS: A total of 202 records were obtained, of which 131 (64.9%) had SCC, 57 (28.2%) AC, and 14 (6.9%) ASC. The 5-year DFS was 94.4% for SCC, 98.1% for AC, and 92.3% for ASC, without a statistically significant difference (p = 0.55). The 5-year OS for SCC was 97.9%, for AC was 97.8%, and for ASC was 100%, without a statistically significant difference (p = 0.702). CONCLUSIONS: DFS and OS did not differ between the most common histological types of CC at the early stages.