Preservation of fertility in gynaecologic cancers

Gynecological malignancies may affect women in their reproductive age. New developments in surgical technique, new concepts on the radical management of gynaecologic cancers, and a trend towards early diagnosis increase the chances to preserve fertility at the time of surgical management of gynaecologic cancers. Data from the recent literature are reassuring about the safety of conservative management - involving the maintenance of at least the uterus and one ovary without radiation therapy - in early cervical cancers, selected early invasive epithelial tumors of the ovary, stage IA sex cord stromal tumors, and borderline tumors of the ovary whatever the stage. On the other hand, conservative management of endometrial cancers is not completely documented. Conservative management of germ cell tumors of the ovary and trophoblastic disease is standard, not an option. In addition, the field of assisted reproductive technology can be exploited when preservation of reproductive organs is not possible. Young patients presenting with gynaecologic cancers must be informed about fertility preserving options whenever applicable.     

Monitoring serial changes in circulating human breast cancer cells in murine xenograft models

Circulating tumor cells (CTC) are emerging as a powerful prognostic and predictive biomarker in several types of cancer, including breast, colon, and prostate. Studies of CTC in metastasis and further development of CTC as a biomarker in cancer have been limited by the inability to repetitively monitor CTC in mouse models of cancer. We have validated a method to enumerate CTC in blood samples obtained from living mice using a modified version of an in vitro diagnostic system for quantifying CTC in patients. Different routes of blood collection were tested to identify a method to reproducibly recover CTC from tumor-bearing mice without interference from contaminating normal murine epithelial cells. CTC are present in blood samples from mice bearing orthotopic xenografts of several different breast cancer cell lines and primary breast cancer cells from patient biopsies. We also show that this technology can be used for serial monitoring of CTC in mouse xenograft models of human breast cancer. These results establish a new method for studying CTC in mouse models of epithelial cancer, providing the foundation for studies of molecular regulation of CTC in cancer and CTC as biomarker for therapeutic efficacy.     

Peeling with 70% glicolic acid followed by 5% 5‐fluorouracil as well as 5% 5‐fluorouracil cream are effective methods for the treatment of actinic keratoses on upper limbs: A randomized clinical trial

The 5% 5‐fluorouracil (5‐FU) cream, considered the gold standard topical treatment, and peeling using 70% glycolic acid (GA) followed by 5% 5‐FU are methods for the treatment of actinic keratoses (AKs). However, the comparison of these two treatments had not yet been described and therefore was the objective of this study. A randomized clinical trial, intrapatient study in which 17 patients received a type of treatment in the right and left upper limb with 5% 5‐FU cream (twice daily) or a peeling application of 70% GA (every 15 days) followed by 5% 5‐FU cream. There was a significant reduction of 75% and 85.71% in the mean number of AK lesions and of 74.5% and 85.71% in the size of lesions on the upper limbs of patients treated with peeling and 5% 5‐FU cream (P‐value ≤.001), respectively. Neither treatment was superior to the other since there was no significant difference (P‐value ≥.05) between the treatments, both at the post‐intervention period as well as when comparing the difference between the pre and post‐intervention periods. The peeling with 70% GA followed by 5% 5‐FU as well as 5% 5‐FU cream are effective methods for the treatment of AKs on upper limbs.     

Resistance Training Improves Muscle Strength and Function,Regardless of Protein Supplementation,in the Mid- to Long-Term Period after Gastric Bypass

Inadequate protein intake and low levels of physical activity are common long-term sequelae after bariatric surgery and can negatively affect muscle strength (MS) and physical function (PF). The study investigated the effects of resistance training with or without protein supplementation on MS and PF. The study, which involved a 12-week controlled trial (n = 61) of individuals 2–7 years post-Roux-en-Y gastric bypass (RYGB), comprised four groups: whey protein supplementation (PRO; n = 18), maltodextrin placebo (control [CON]; n = 17), resistance training combined with placebo (RTP; n = 11), and resistance training combined with whey protein supplementation (RTP+PRO; n = 15). An isokinetic dynamometer was used to measure MS (peak torque at 60°/s and 180°/s). PF was measured with the 30-s sit-to-stand (30-STS), 6-min walk (6-MWT), and timed up-and-go (TUG) tests. There were improvements in the absolute and relative-to-bodyweight peak torque at 60°/s and 180°/s, TUG, 6-MWT and 30-STS in the RTP and RTP+PRO groups, but not in the CON and PRO groups. Changes in MS were significantly correlated with changes in PF between the pre- and post-intervention periods. A supervised resistance training program, regardless of protein supplementation, improved MS and PF in the mid-to-long-term period after RYGB and can lead to clinical benefits and improved quality of life.     

A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases

Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma, therefore often misdiagnosed and has no available standard treatment. Here, we report 3 cases of metastatic GNET with variable clinical courses. Our small case series as well as extensive literature review, further support that GNET is a spectrum of diseases with variable inherent biology and prognosis. Surgical management in the setting of recurrent/metastatic disease may be appropriate for GNET with indolent nature. Response to systemic treatments including chemotherapy and targeted treatments is variable, likely related to heterogenous biology as well. Furthermore, we retrospectively identified 20 additional GNET cases from Foundation Medicine’s genomic database and expanded on their clinicopathological and genomic features. Comprehensive genomic profiling (CGP) with DNA and RNA sequencing of this cohort, in the course of clinical care, demonstrated recurrent EWSR1 chromosomal rearrangements and a sparsity of additional recurrent or driver genomic alterations. All cases had low tumor mutational burden (TMB) and were microsatellite stable.     

Inflammatory cytokine gene polymorphisms and spontaneous preterm birth

The objective was to search for an association between spontaneous preterm birth (sPTB) and single and/or combined polymorphisms in genes TNFA −308 G > A, IL10 −1082 G > A, IL10 −819 C > T, IL10 −592 C > A, IL6 −174 G > C, and IFNG +874 A > T. Genotyping was performed on 410 Brazilian ethnically matched women managed at two hospitals (two independent case–control sets). One set consisted of 122 cases and 101 controls, and the other set comprised 82 cases and 105 controls. We compared genotype and genotype-combination frequencies between cases and controls using Fisher's exact or the χ² tests and confirmed results using logistic regression. Among the six SNPs studied, we found no independent association between any single SNP and sPTB risk. The multi-locus analysis revealed a significant association between sPTB and the TNFA(GG)/IL6(GG)/IFNG(AA) genotype combination (p = 0.002), confirmed by logistic regression. Our data suggest that the combination of TNF-α, IFN-γ, and IL-6 maternal gene polymorphisms might contribute to susceptibility to sPTB. This finding could be investigated as a possible genetic marker for the risk of spontaneous preterm birth.     

Exploring hTERT promoter methylation in cutaneous T‐cell lymphomas

Cutaneous T‐cell lymphomas (CTCLs) are telomerase‐positive tumors expressing hTERT, although neither gene rearrangement/amplification nor promoter hotspot mutations could explain the hTERT re‐expression. As the hTERT promoter is rich in CpG, we investigated the contribution of epigenetic mechanisms in its re‐expression. We analyzed hTERT promoter methylation status in CTCL cells compared with healthy cells. Gene‐specific methylation analyses revealed a common methylation pattern exclusively in tumor cells. This methylation pattern encompassed a hypermethylated distal region from −650 to −150 bp and a hypomethylated proximal region from −150 to +150 bp. Interestingly, the hypermethylated region matches with the recently named TERT hypermethylated oncogenic region (THOR). THOR has been associated with telomerase reactivation in many cancers, but it has so far not been reported in cutaneous lymphomas. Additionally, we assessed the effect of THOR on two histone deacetylase inhibitors (HDACi), romidepsin and vorinostat, both approved for CTCL treatment and a DNA methyltransferase inhibitor (DNMTi) 5‐azacytidine, unapproved for CTCL. Contrary to our expectations, the findings reported herein revealed that THOR methylation is relatively stable under these epigenetic drugs'' pressure, whereas these drugs reduced the hTERT gene expression.     

Assessment of Cardiorespiratory and Metabolic Responses in Women with Obesity After Surgically Induced Weight Loss: Results from a Pilot Study

Purpose

Bariatric surgery is effective in controlling severe obesity. However, studies investigating the impact of surgically induced weight loss on cardiorespiratory and metabolic responses during maximal effort are controversial. The aim of this study was to assess cardiorespiratory and metabolic responses in women with obesity after bariatric surgery.

Materials and Methods

We performed a secondary analysis on data from a pilot study with women with obesity submitted to bariatric surgery and who did not participate in a controlled physical training program. Anthropometry, pulmonary function (spirometry), and cardiorespiratory fitness (cardiopulmonary exercise testing [CPX]) were assessed before and after bariatric surgery.

Results

Thirty-four women were included (38.7 ± 9.6 years, body mass index = 44.1 ± 6.3 kg/m²). Postoperative assessment was conducted 9.4 ± 2.7 months after surgery. After surgery, we observed a reduction in all anthropometric measurements (mean loss of 28.6 kg, p < 0.001), and improvement in spirometry values (p < 0.001). Relative VO_2peak (mL/kg/min) increased slightly (Δ = 1.7; p = 0.06); however, absolute VO_2peak (L/min) reduced significantly (Δ =  − 0.398; p < 0.001). We also observed an increase of 1.3 min (p < 0.001) in CPX duration, a reduction of 11.3 bpm (p < 0.001) in resting heart rate, and a decrease of systolic (p = 0.02) and diastolic (p < 0.001) blood pressures at peak effort.

Conclusion

Surgically induced weight loss without exercise training improved cardiac reserve, ventilatory response, blood pressure, and resting heart rate. Cardiorespiratory fitness reflected by relative VO_2peak increased slightly, despite increased tolerance to CPX.

Graphical abstract