Sociodemographic characteristics and their association with survival in women with cervical cancer.

BACKGROUND: In 2020, the highest incidence and mortality from cervical cancer (CC) were detected in low and middle-income countries. CC remains a health problem for women living in them. In Mexico, CC ranks second in cancer incidence and mortality in women. The main characteristics of this population are low income, low educational level, and inadequate medical coverage. The present study characterized the Mexican population by CC, and the sociodemographic variables that impacted overall survival (OS) were identified. METHODS: A retrospective study that included a cohort of patients with a confirmed diagnosis of CC at the Instituto Nacional de Cancerologia between 2003 and 2016. Information was collected on sociodemographic variables related to the disease and OS. RESULTS: Four thousand six hundred thirty-one patients were included. The median age was 51 years, 78.5% were unemployed, 44.4% lived in a rural/suburban area, 50.8% had a partner when collecting this information, and 74.3% were classified as having low socioeconomic status. Age, living in a rural/suburban area, more advanced stages of the disease, and not receiving cancer treatment were associated with lower OS. CONCLUSION: CC continues to affect mainly women with minimal resources, low educational levels, and living in marginalized areas. These characteristics influence the OS. Prevention and timely detection programs, education, and training focused on this population and with broader coverage are required to identify patients with CC at earlier stages.

Quality of life but not cachexia definitions are associated with overall survival in women with cervical cancer: a STROBE-compliant cohort study.

BACKGROUND: Cancer-related cachexia (CRC) has a profound impact on health-related quality of life (HRQL), and both were reported to be associated with overall survival (OS). We hypothesize that HRQL and CRC are associated with OS. This study analyzed the impact of CRC on HRQL and its prognostic value in women with cervical cancer (CC). METHODS: A cohort study including consecutive women with CC treated from October 2020 to October 2021 in a cancer center. Cox's model defined the associations of immune, biochemical and nutritional parameters, clinical cachexia classifications and HRQL with OS. RESULTS: Two hundred forty-four consecutive women with CC were included. Cachexia classifications and several scales of the QLQ-C30 were associated with OS by bivariate but not by multivariate analysis. QLQ-CX24 scales were not associated with OS. The prognostic nutritional index (PNI) (hazard ratio (HR) 0.828; 95% confidence interval (CI) 0.766-0.896), Food aversion (HR 0.95; 95% CI 0.924-0.976), Eating difficulties (HR 1.041; 95% CI 1.013-1.071), Loss of control (HR 4.131; 95% CI 1.317-12.963), Forced self to eat (1.024; 95% CI 1.004-1.044) and Indigestion (HR 0.348; 95% CI 0.131-0.928) scales of the QLQ-CAX24 were independently associated with OS by multivariate analysis (p = 1.9×10-11). CONCLUSION: This model permitted a clear stratification of prognostic subgroups. The PNI and several QLQ-CAX24 scales were associated with OS in women with CC. CRC, defined by several cachexia classifications, was not an independent prognostic factor. These findings require confirmation because of their possible diagnostic, therapeutic and prognostic implications.The prognostic nutritional index and several QLQ-CAX24 scales were associated with overall survival in women with cervical cancer. Cancer-related cachexia, defined by several cachexia classifications, was not an independent prognostic factor, neither The International Federation of Gynecology and Obstetrics (FIGO) stage classifications.

Validation of the QLQ-CAX24 instrument in cervical cancer and its association with cachexia classifications.

Cancer-related cachexia (CRC) is a common phenomenon in cervical cancer (CC), severely affecting clinical response, drug toxicity and survival. The patients' point of view should be evaluated to quantify the impact of CRC, and adequate instruments to do so are required. Thus, the study aimed to validate the Mexican-Spanish version of the QLQ-CAX24 instrument in women with CC. A cohort of women with CC answered the EORTC QLQ-C30 and QLQ-CAX24 instruments. The psychometric and clinimetric properties of the instruments were assessed. Two hundred and forty-four women were included; the mean age was 50 years (IQR: 41-60) and 188 (77%) were first diagnosed in locally advanced stages. The QLQ-CAX24 internal consistency test demonstrated adequate convergent (Spearman correlation coefficient 0.08-0.709) and divergent validity (Spearman correlation coefficient 0.006-0.471). Cronbach's alpha coefficients of the three multi-item scales were >0.5 (minimum 0.539, maximum 0.84). Patients with decreased handgrip strength, low fat-free mass, or high C-reactive protein levels had worse QLQ-CAX24 scale scores. Cachexia was diagnosed with the SCRINIO, Fearon and Evans criteria, and 31.5, 32.4 and 38.5% of women had cachexia, respectively. Patients with cachexia had the worst scores in terms of quality of life. The test re-test analysis did not show differences between visits in patients without malnutrition. The Mexican-Spanish version of the QLQ-CAX24 instrument is reliable and valid. Low handgrip strength, low fat-free mass and high C-reactive protein levels were associated with poor scale scores.

Functional foods modulating inflammation and metabolism in chronic diseases: a systematic review.

Chronic diseases are responsible for approximately 71% global deaths. These are characterized by chronic low-grade inflammation and metabolic alterations. "Functional foods" have been attributed with anti-inflammatory properties, demonstrated in cell lines and murine models; however, studies in humans are inconclusive. The purpose of this systematic review is to identify clinical trials that analyzed changes in inflammatory and metabolic mediators, in response to consumption of specific functional foods. A total of 3581 trials were screened and 88 were included for this review. Foods identified to regulate inflammation included cranberries, grapes, pomegranate, strawberries, wheat, whole grain products, low fat dairy products, yogurt, green tea, cardamom, turmeric, soy foods, almonds, chia seeds, flaxseed, pistachios, algae oil, flaxseed oil and grape seed oil. Clinical trials that focus on a dietary pattern rich in functional foods are necessary to explore if the additive effect of these foods lead to more clinically relevant outcomes.

Treatment of Locally Advanced Cervical Cancer With Kidney Failure and Comorbidities.

A woman aged 63 years presented at the gynecological oncology outpatient clinic with the following medical history: smoking history (smoking index of 10); systemic arterial hypertension diagnosed 6 years ago; menarche at 16 years; menopause at 52 years; 4 pregnancies, 4 deliveries; beginning of active sexual life at 18 years; 3 sexual partners; and no early cancer detection method in her life. Her performance status per ECOG criteria was 1. The patient presented with transvaginal bleeding with 5 months of evolution. Upon physical exploration, a 5 x 5 cm tumor in the cervix was detected, with the following characteristics: exophytic, friable, bleeding, with invasion to the lower third of the vagina, affection to the cul-de-sac and parametria, and bilaterally fixed to the pelvic wall. A biopsy of the cervix showed moderately differentiated invasive squamous cell carcinoma.

Validation of the QLQ-CX24 questionnaire for the assessment of quality of life in Mexican women with cervical cancer.

OBJECTIVE: Cervical cancer is the fourth most frequent neoplasm among women in terms of incidence and mortality. Health-related quality of life (HRQL) is an important outcome in oncology. The QLQ-CX24 instrument was developed to measure HRQL in patients with cervical cancer, and its Mexican-Spanish version had not been validated. METHODS: Between March 2018 and May 2019, Mexican women older than 18, with any-stage cervical cancer were invited to participate in the study. Patients answered the QLQ-C30 and QLQ-CX24 questionnaires. Current tests for psychometric and clinical validation were performed. RESULTS: Three hundred and thirty patients with cervical cancer were included in this study. All women invited to participate accepted and were included. The QLQ-CX24 internal consistency test demonstrated adequate convergent (Spearman correlation coefficient 0.001-0.847) and divergent validity (Spearman correlation coefficient <0.0001-0.45). Cronbach's alpha coefficients of the three multi-item scales were >0.7 (minimum 0.76, maximum 0.89). Four scales of the QLQ-CX24 distinguished patients in different clinical stages. The evaluation of responsiveness demonstrated that the peripheral neuropathy scale was sensitive to change over time during chemo-radiation therapy. Six scales of the QLQ-CX24 instrument were associated with survival. CONCLUSION: The Mexican-Spanish version of the QLQ-CX24 questionnaire is reliable and valid for the assessment of HRQL in patients with cervical cancer.

Consensus Report on the Prevention, Diagnosis, and Treatment of Cervical Cancer - a Perspective from the Immune System Toward Immunotherapy.

According to GLOBOCAN 2018 data1, cervical cancer (CC) is the fourth most common cancer in women worldwide and the third most frequent cancer in Mexican women. In recent years, incidence and mortality rates have been declining worldwide at a rate of 1.6% per year2.

IMMUNONUTRITION IN CERVICAL CANCER: IMMUNE RESPONSE MODULATION BY DIET.

In the development of cervical cancer (CC), the immune response plays an essential role, from the elimination of human papillomavirus (HPV) infection to the response against the tumor. For optimal function of the immune response, various factors are required, one of the most important being an adequate nutrition. The complex interaction between nutrients and microbiota maintains the immune system in homeostasis and in case of infection, it provides the ability to fight against pathogen invasion, as occurs in HPV infection. The purpose of this article is to describe the role of diet, food, and specific nutrients in the immune response from the onset of infection to progression to precancerous lesions and CC, as well as the role of diet and nutrition during oncological treatment. The immunomodulatory role of microbiota is also discussed. A detailed analysis of the evidence leads us to recommend a nutritional pattern very similar to the Mediterranean diet or the prudent diet for an optimal immune response. Moreover, pre- and probiotics favorably modulate the microbiota and induce preventive and therapeutic effects against cancer.

THERAPEUTIC USE OF HUMAN PAPILLOMAVIRUS VACCINES IN CERVICAL LESIONS.

Human papillomavirus (HPV) has been associated with the development of precancerous lesions of the cervix and cervical cancer (CC). Prophylactic HPV vaccination induces the development of a specific memory immune response that facilitates HPV elimination once the natural infection occurs. At present, in addition to the prophylactic vaccine, therapeutic vaccines are being developed and researched with the aim of inducing an immune response that allows the elimination of HPV-infected cells. The purpose of this study is to describe the current evidence on the use of therapeutic vaccines and their effect on cervical precancerous lesions, to establish recommendations on their clinical use. So far, the studies that have generated results have described a marginal beneficial effect of the prophylactic vaccine in the management of infection and pre-invasive lesions. Based on the evidence, continuing research on the efficacy and safety of therapeutic vaccines for the treatment of cervical intraepithelial lesions is recommended. The use of the HPV prophylactic vaccine as treatment for pre-existing lesions is not advised, but it is recommended to prevent new lesions.

Use of Functional Foods and Oral Supplements as Adjuvants in Cancer Treatment.

In cancer patients treated with radiotherapy to the abdominopelvic region, dietary modifications and the use of functional foods (fortified food with added ingredients to provide specific health improving benefits, such as antioxidants, omega-3 fatty acids, and glutamine), may contribute to the improvement of the toxic effects of treatment, including nausea, diarrhea, and constipation, among others. With the aim of analyzing which coadjuvant foods benefit these patients, scientific evidence was gathered by a group of experts. For these patients, the authors recommend a diet that includes sufficient foods rich in antioxidants and polyphenols instead of supplements. Docosahexaenoic and eicosapentaenoic acids have proven useful for the management of anorexia/cachexia in pancreatic cancer patients. Probiotics composed of Lactobacillus spp. and Bifidobacterium spp. are regarded as safe even in patients with neutropenia and have been proven to decrease gastrointestinal symptoms. Several factors should be considered before probiotic supplementation, these include the stage of the disease, radiation dose, and symptomatology of each patient. There is no demonstrated clear benefit to the use of glutamine, so it is not recommended due to its high cost.

Nutrient Recommendations for Cancer Patients Treated with Pelvic Radiotherapy, with or without Comorbidities.

Radiotherapy is one of the main treatment options used in pelvic cancers. Ionizing radiation induces damage to surrounding tissues, resulting in disruption of normal physiological functions and symptoms such as diarrhea, tenesmus, incontinence, and rectal bleeding, which can all significantly alter the patient's quality of life. These patients are at increased risk of developing protein-calorie malnutrition and micronutrient deficiencies. Therefore, designing a proper nutritional intervention plan, with an optimal proportion of protein, fat, and carbohydrates, is required to reduce or even reverse the patients' poor nutritional status, increase their tolerance and response to oncology treatment, decrease the rate of complications and improve their quality of life. The aim of this review was to establish a nutritional plan that includes recommendations on macronutrient proportions and micronutrient intake in patients receiving pelvic radiotherapy. The following nutritional plan has been recommended in the literature: Energy: 28-31 kcal/kg/day, using the Harris-Benedict formula adjusted for body weight in obese patients; protein: 20-30%; fat: 30-40%; and carbohydrates: 40-50%. The maintenance of adequate levels of Vitamin D, Vitamin E, Vitamin A, calcium, magnesium, thiamin, riboflavin, and niacin must be emphasized. Physical activity must also be increased to maintain muscle mass. Nutrient requirements must be established in an integral manner, considering the patient's age, nutritional status, and the presence of comorbidities. Unnecessary dietary restrictions should be avoided to ensure an adequate nutritional status.

Nutritional Assessment Tools for the Identification of Malnutrition and Nutritional Risk Associated with Cancer Treatment.

Malnutrition and muscle wasting are common features of cancer cachexia that may interfere with the patient's response to cancer treatment, survival, and quality of life. An accurate nutritional screening at the time of diagnosis and throughout the patient's treatment fosters better control of the disease. Several screening tools have proven to be useful for this purpose. Nevertheless, nutritional evaluation is not a routine practice in this clinical setting and procedures must be standardized. Nutritional risk screening (NRS), malnutrition screening tool (MST), and patient-generated subjective global assessment (PG-SGA) are the most common screening tools, and each one possesses some benefits when screening patients for malnutrition; however, weight loss over a specific time period, dietary intake and anorexia must also be considered. The body mass index-adjusted weight loss grading system predicts survival. We recommend the application of MST or NRS, followed by PG-SGA, food intake determination, measurement of body weight, and its changes as well as body composition, biochemical nutritional markers, muscle function, and physical performance.

Effects of Dietary Components During and After Concomitant Chemoradiotherapy, Radiotherapy, or Sequential Chemoradiotherapy to the Abdominopelvic Area.

Radiotherapy is a fundamental part of the treatment of pelvic neoplasms. Up to 90% of patients develop gastrointestinal symptoms as a result of acute injury to the small and large intestine, particularly in the mucosa. Radiotherapy leads to atrophy of the intestinal epithelium, acute crypt inflammation, inflammatory infiltration of the epithelium, malabsorption of lactose, and biliary salts as well as alterations in pancreatic enzymes and biliary salts, resulting in the malabsorption syndrome and dysbiosis. The most commonly reported symptoms of pelvic radiation disease include changes in bowel habits (94%), decreased fecal consistency (80%), frequency of bowel movements (74%), bowel urgency (39%), and fecal incontinence (37%). Although nutritional interventions with dietary modifications have been reported to prevent and treat gastrointestinal symptoms, the evidence remains inconclusive.

Epidemiological Data on the Nutritional Status of Cancer Patients Receiving Treatment with Concomitant Chemoradiotherapy, Radiotherapy or Sequential Chemoradiotherapy to the Abdominopelvic Area.

Cancer patients are particularly susceptible to undernourishment so associated weight loss is frequent. Approximately 15% of patients lose >10% of their usual body weight, 40-80% become undernourished, and about 20% die as a result. Well-nourished patients have a higher survival rate when compared with patients at risk of undernourishment (19.9 vs. 3.7 months); hence, nutritional intervention is pivotal. Undernourishment negatively influences the patient's prognosis, and its prevalence depends on the tumor type and location, disease stage, treatment, and the applied nutritional evaluation tool. During abdominopelvic radiotherapy, up to 90% of patients experience symptoms of varying severity; weight loss during radiotherapy is an early indicator of nutritional deterioration, and he the use of radiation is associated with a higher likelihood of undernourishment. In patients with gynecological malignancies, 12.5-54% are malnourished before receiving oncological treatment, worsening after treatment in 35.8-82% of cases. There is also deterioration of the nutritional status in patients with colorectal cancer once pelvic radiotherapy is initiated, whereby 50% of cases are malnourished at the beginning of treatment, and 66.7% are so when it ends. Although there are notable differences in the impact of radiotherapy on weight according to the radiated region, 88% patients receiving abdominal radiotherapy were found to lose weight compared to 38% of patients whose treatment was limited to the pelvis.

Epidemiological Profile, Gastrointestinal Toxicity, and Treatment of Pelvic Cancers in Patients Managed with Radiotherapy to the Abdominal Pelvic Area.

Mexico has seen an increase in cancer prevalence in its entire population as well as particular age ranges, predominantly the older segment. The most frequently reported pelvic cancers in Mexico are cervical, endometrial, bladder, prostate, rectum, and anal canal. Approximately 80% of the population diagnosed with pelvic cancers present with locally advanced tumors and require concomitant chemoradiotherapy, sequential chemoradiotherapy, or radiotherapy alone. The toxicity of any of these treatment modalities may be manifested as intestinal injury, a significant problem that can compromise the response to treatment, the patient's nutritional state, quality of life, and survival. In this article, we will approach key aspects in nutrition as well as the epidemiological characteristics and toxicities in patients affected by these pelvic tumors.

Effects of prebiotics, probiotics, and synbiotics on the prevention and treatment of cervical cancer: Mexican consensus and recommendations.

Gut microbiota plays a crucial role in modulating immune responses, including effector response to infection and surveillance of tumors. This article summarizes the current scientific evidence on the effects of supplementation with prebiotics, probiotics, and synbiotics on high-risk human papillomavirus (HPV) infections, precancerous lesions, and various stages of cervical cancer development and treatment while also examining the underlying molecular pathways involved. Our findings indicate that a higher dietary fiber intake is associated with a reduced risk of HPV infection, while certain probiotics have shown promising results in clearing HPV-related lesions. Additionally, certain strains of probiotics, prebiotics such as inulin and fructo-oligosaccharides, and synbiotics decrease the frequency of gastrointestinal adverse effects in cervical cancer patients. These agents attain their results by modulating crucial metabolic pathways, including the reduction of inflammation and oxidative stress, promoting apoptosis, inhibiting cell proliferation, and suppressing the activity of oncogenes, thus attenuating tumorigenesis. We conclude that although further human studies are necessary, robust evidence in preclinical models demonstrates that prebiotics, probiotics, and synbiotics play an essential role in cervical cancer, from infection to carcinogenesis and its medical treatment. Consequently, we strongly recommend conducting high-quality clinical trials using these agents as adjuvants since they have proven safe.

Metabolic Recovery with the Persistence of Proinflammatory Leucocyte Dysfunction After Bariatric Intervention for Obesity.

PURPOSE: A suitable option for severe obesity treatment is a surgical approach. After surgery, metabolic markers and weight frequently return to adequate values; however, concerning systemic inflammatory mediators, the results are inconsistent. Furthermore, it has been suggested that leucocyte function may be affected even after weight normalization. This study aimed to determine if the surgical treatment of obesity influences the production of cytokines by LPS-stimulated as a function of leucocytes. MATERIALS AND METHODS: We performed a cross-sectional study that investigated the production of cytokines in response to lipopolysaccharide (LPS) along a kinetic of simulation by leucocytes recovered from individuals with normal weight (NW, n = 8), persons living with obesity (Ob, n = 7), persons living with obesity and diabetes mellitus (Ob-DM, n = 17), and persons that used to live with obesity who underwent bypass surgery (fOb + bypass, n = 8) and recover normal weigh. RESULTS: IL-6 levels were significantly higher in the Ob and fOb + bypass groups than in NW (p = 0.043). IL-10 secretion without LPS was significantly higher in the NW group than in the other groups explored (p < 0.05). When exposed to LPS, the IL-10 levels increased in all groups except the NW group. As also observed for IL-18 and IL-33, the secretion curve of the fOb + bypass group was more similar to the Ob group, even when they had reached normal weight, as opposed to the NW group. CONCLUSION: Our results show that in patients with fOb + bypass, inflammatory and anti-inflammatory cytokine production dynamics remain disrupted even with improved metabolic control and normal weight recovery.

Chemoradiotherapy treatment with gemcitabine improves renal function in locally advanced cervical cancer patients with renal dysfunction.

BACKGROUND: Cervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients. METHODS: This retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival. RESULTS: 351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84). CONCLUSION: CCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.

Splenocytes and thymocytes migration patterns between lymphoid organs in pregnancy.

Background: Cell migration is essential for the immune system and is frequently analyzed in adult non-pregnant animals but poorly explored in pregnant animals. However, a physiologic increased size in the spleen and periaortic lymph nodes had been reported in pregnant mice. Methods: Using a mouse model, we transferred PKH26-stained thymocytes and splenocytes from pregnant or non-pregnant animals to receptor mice in the presence or absence of pregnancy. Percentage of PKH-26 cells and Mean Fluorescence Intensity were calculated. Non-parametric ANOVA analysis was performed. Results: We detected that the percentage of PKH26+ thymocytes in the spleen, lymph nodes, and peripheral blood is higher in females than in males (p = 0.039). Our results showed a similar frequency of thymocytes and splenocytes from pregnant and non-pregnant mice located in receptor lymphoid organs (p > 0.05). Also, the location of marked cells was similar during the perinatal period (p > 0.05). Conclusions: The mobility of thymocytes and splenocytes in pregnant and non-pregnant mice is similar. Therefore, we suggest that the larger size of the spleen and periaortic lymph nodes noted previously in pregnant mice could result from the retention of leukocytes in the secondary lymphoid organs.