Potential of molecular classification to guide fertility-sparing management among young patients with endometrial cancer.

The traditional histological classification system for endometrial carcinoma falls short in addressing the disease's molecular heterogeneity, prompting the need for alternative stratification methods. Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has emerged as a clinically efficient tool to categorize endometrial cancers according to mismatch repair deficiency, POLE exonuclease domain mutations, and p53 expression. However, the application of this classification to fertility-sparing treatments remains unexplored, and current guidelines lack specificity in how it should be used. In this review, we summarize the available literature and establish the framework for future investigations focused on molecular profiling-based risk assessment of endometrial cancer, with the goal of utilizing precision medicine to optimally counsel patients seeking fertility-sparing treatment. While the available evidence is limited and of low quality, it does provide insights and frames future perspectives for managing fertility-sparing approaches on the basis of molecular subtypes. Evidence suggests that mismatch repair-deficient tumors are likely to recur despite progestin therapy, emphasizing the need for alternative treatments, with targeted therapies being a new landscape that still needs to be explored. Tumors with POLE mutations exhibit a favorable prognosis, but the safety of hysteroscopic resection alone requires further investigation. p53 abnormal tumors have an unfavorable prognosis, raising questions about their suitability for fertility-sparing treatment. Lastly, the no specific molecular profile (or p53 wild-type) tumors, while having a relatively good prognosis, are heterogeneous and require more precise biomarkers to effectively guide therapy for those with poorer prognoses. Addressing these research gaps will lead to more precise guidelines to ensure optimal selection for fertility-sparing treatment.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Adjuvant external beam radiotherapy combined with brachytherapy for intermediate-risk cervical cancer.

OBJECTIVE: Patients with intermediate-risk cervical cancer receive external beam radiotherapy (EBRT) as adjuvant treatment. It is commonly administered with brachytherapy without proven benefits. Therefore, we evaluated the frequency of brachytherapy use, the doses for EBRT administered alone or with brachytherapy, and the overall survival impact of brachytherapy in patients with intermediate-risk, early-stage cervical cancer. METHODS: This retrospective cohort study was performed using data collected from the National Cancer Database. Patients diagnosed with cervical cancer from 2004 to 2019 who underwent a radical hysterectomy and lymph node staging and had disease limited to the cervix but with tumors larger than 4 cm or ranging from 2 to 4 cm with lymphovascular space invasion (LVSI) were included. Patients with distant metastasis or parametrial involvement were excluded. Patients who underwent EBRT alone were compared with those who also received brachytherapy after 2:1 propensity score matching. RESULTS: In total, 1174 patients met the inclusion criteria, and 26.7% of them received brachytherapy. After 2:1 propensity score matching, we included 620 patients in the EBRT group and 312 in the combination treatment group. Patients who received brachytherapy had higher equivalent doses than those only receiving EBRT. Overall survival did not differ between the two groups (hazard ratio (HR) 0.88 (95% confidence interval (CI), 0.62 to 1.23]; p=0.45). After stratification according to tumor histology, LVSI, and surgical approach, brachytherapy was not associated with improved overall survival. However, in patients who did not receive concomitant chemotherapy, the overall survival rate for those receiving EBRT and brachytherapy was significantly higher than that for those receiving EBRT alone (HR, 0.48 (95% CI, 0.27 to 0.86]; p=0.011). CONCLUSION: About one-fourth of the study patients received brachytherapy and EBRT. The variability in the doses and radiotherapy techniques used highlights treatment heterogeneity. Overall survival did not differ for EBRT with and without brachytherapy. However, overall survival was longer for patients who received brachytherapy but did not receive concomitant chemotherapy.

All-cause and cancer-specific mortality after fertility-sparing surgery for stage IA and IC epithelial ovarian cancer.

OBJECTIVE: To compare all-cause and cancer-specific mortality between women who underwent fertility-sparing surgery (FSS) versus standard surgery for stage IA and IC epithelial ovarian cancer. METHODS: Reproductive aged patients (18-45) with stage IA or IC epithelial ovarian cancer diagnosed between 2000 and 2015 were identified in the California Cancer Registry. FSS was defined as retention of the contralateral ovary and the uterus, and standard surgery included at least removal of both ovaries and the uterus. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. Inverse probability of treatment weighting (IPTW) was used to create two groups balanced on covariates of interest. The Kaplan-Meier method and Cox proportional hazards analysis were used to model survival outcomes. RESULTS: Among 1119 women who met inclusion criteria, 390 (34.9%) underwent FSS. IPTW yielded a balanced cohort of 394 women who underwent FSS and 723 women who underwent standard surgery. Among patients who underwent FSS, there were 45 deaths corresponding to an 85.4% (95% confidence interval [CI] 0.79-0.92) 10-year all-cause survival probability, compared to 81 deaths and 86.4% 10-year all-cause survival probability (95% CI 0.83-0.90) among patients who underwent standard surgery. FSS was not associated with increased all-cause mortality (HR 1.04, 95% CI 0.72-1.49) or cancer-specific mortality (HR 1.50, 95%CI 0.97-2.31). CONCLUSIONS: Among reproductive-aged patients with early-stage epithelial ovarian cancer fertility-sparing surgery was not associated with an increased risk of death compared to standard surgery.

Mapping sentinel lymph nodes in early-stage ovarian cancer (MELISA) trial - a further step towards lymphadenectomy replacement.

OBJECTIVE: Sistematic pelvic and para-aortic lymphadenectomy is part of the staging surgery for early-stage epithelial ovarian cancer, with no therapeutic value. The Mapping Sentinel Lymph Nodes In Early-Stage Ovarian Cancer (MELISA) trial prospectively assessed the SLN detection rate and the diagnostic accuracy of the SLN mapping technique in patients with early-stage epithelial ovarian cancer. METHODS: This prospective, single-arm study included patients diagnosed with early-stage epithelial ovarian cancer (FIGO stages I and II), via either primary surgery or re-staging surgery. SLN mapping was performed by injecting 0.2 mL of 37-mBq 99mTc-nanocoloid albumin and 2 mL of 2.5 mg/mL indocyanine green into the infundibulopelvic and utero-ovarian ligaments. After removal of SLNs, a complete systematic pelvic and para-aortic lymphadenectomy was performed. SLN Ultrastaging analysis was applied. The primary outcome was the overall SLN detection rate, either with one or both tracers. Secondary outcomes were the diagnostic accuracy of detecting lymph node metastases and factors that may influence SLN detection. RESULTS: Thirty patients were included. SLNs were identified in 27 patients (90%). Detection rates in primary and re-staging surgery were 89% and 92%, respectively. Para-aortic drainage was the predominant lymphatic spread, observed in 26 of 27 patients. Ultrastaging pathologic reports listed 1 SLN with macrometastasis, 1 with micrometastasis, and 5 with isolated tumor cells; the sensitivity of SLN mapping was 100%, with a false-negative rate of 0%. Univariate analysis showed a nonsignificant higher proportion of patients with uterine fibroids, adenomyosis, and endometriosis (100%, 67%, 67%, respectively) in patients in whom SLNs were not detected. CONCLUSION: SLN mapping has a high detection rate (90%) and is an accurate technique for detecting lymph node involvement in early-stage epithelial ovarian cancer. SLN mapping is a potential alternative to systematic lymphadenectomy to reduce associated morbidity, but further research is needed to evaluate the impact of SLN mapping on oncologic outcomes and its cost-effectiveness.

Diagnostic accuracy of sentinel lymph node frozen section analysis in patients with early-stage cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of intraoperative SLN frozen section analysis compared with ultrastaging in patients with early-stage cervical cancer. METHODS: A systematic literature review was conducted following the PRISMA checklist. MEDLINE (via Ovid), Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until February 2023. The inclusion criteria were patients with early-stage cervical cancer (2018 FIGO stage I-II), consisting of the histological subtype squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (≥90% of the patients in each study), who underwent SLN detection (with any tracer) and intraoperative frozen section followed by SLN ultrastaging. Randomized controlled trials, prospective and retrospective observational studies were considered. The detection rates and measures of diagnostic accuracy were pooled using a random effects univariate model. A preplanned subgroup meta-analysis was conducted, with isolated tumor cells excluded as positive lymph nodes. The review was registered in PROSPERO (CRD42023397147). RESULTS: The search identified 190 articles, with 153 studies considered potentially eligible after removing duplicates. Fourteen studies met the selection criteria, including a total of 1720 patients. Seven studies were retrospective, and the other seven were prospective. Frozen section analysis detected 159 of 292 (54.5%) patients with lymph node metastases. In 281 patients the type of volume metastasis was reported: 1 of 41 (2.4%) patients had isolated tumor cells, 21 of 78 (26.9%) patients had micrometastases, and 133 of 162 (82.1%) patients had macrometastases. The pooled sensitivity of intraoperative SLN frozen section analysis was 65% (95% CI, 51-77%) for macrometastases, micrometastases, and isolated tumor cells. When we excluded patients with isolated tumor cells, the pooled sensitivity increased to 72% (95% CI, 60-82%). CONCLUSION: SLN frozen section detects 65% of lymph node metastases compared with SLN ultrastaging and may prevent unnecessary radical surgery in some patients with early-stage cervical cancer.

Sentinel lymph node detection in early-stage ovarian cancer: a systematic review and meta-analysis.

BACKGROUND: A systematic pelvic and para-aortic lymphadenectomy remains the surgical standard management of early-stage epithelial ovarian cancer. Sentinel lymph node mapping is being investigated as an alternative procedure; however, data reporting sentinel lymph node performance are heterogeneous and limited. OBJECTIVE: This study aimed to evaluate the detection rate and diagnostic accuracy of sentinel lymph node mapping in patients with early-stage ovarian cancer. METHODS: A systematic search was conducted in Medline (through PubMed), Embase, Scopus, and the Cochrane Library. We included patients with clinical stage I-II ovarian cancer undergoing a sentinel lymph node biopsy and a pelvic and para-aortic lymphadenectomy as a reference standard. We conducted a meta-analysis for the detection rates and measures of diagnostic accuracy and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with identifying number CRD42022351497. RESULTS: After duplicate removal, we identified 540 studies, 18 were assessed for eligibility, and nine studies including 113 patients were analyzed. The pooled detection rates were 93.3% per patient (95% CI 77.8% to 100%; I2=74.3%, p<0.0001), and the sentinel lymph node technique correctly identified 11 of 12 patients with lymph node metastases, with a negative predictive value per patient of 100% (95% CI 97.6% to 100%; I2=0%). The combination of indocyanine green and 99mTc-albumin nanocolloid had the best detection rate (100% (95% CI 94% to 100%; I2=0%)) when injected into the utero-ovarian and infundibulo-pelvic ligaments. CONCLUSION: Sentinel lymph node biopsy in early-stage ovarian cancer showed a high detection rate and negative predictive value. The utero-ovarian and infundibulo-pelvic injection using the indocyanine green and technetium-99 combination could increase sentinel lymph node detection rates. However, given the limited quality of evidence and the small number of reports, results from ongoing trials are awaited before its implementation in routine clinical practice.

Cardiophrenic lymph nodes in advanced ovarian cancer.

Epithelial ovarian cancer most commonly presents at advanced stages, and prognosis is influenced by residual disease following cytoreduction. The significance of cardiophrenic lymph node resection at the time of cytoreductive surgery in advanced ovarian cancer remains a topic of debate. Enlarged cardiophrenic lymph nodes are detected through high-resolution imaging; however, the optimal imaging technique in determining feasibility of node resection remains uncertain. Similarly, the impact of excision of cardiophrenic lymph nodes on progression-free and overall survival remains elusive. The indications for resection of cardiophrenic lymph nodes are not addressed in standard ovarian cancer guidelines. Patients with cardiophrenic lymph nodes exceeding 1 cm in size may be considered for resection if complete intra-abdominal cytoreduction is feasible to no gross residual. The surgical approach might be either by open access or by video-assisted thoracoscopic surgery (minimally invasive approach), and major complications following cardiophrenic lymph nodes resection are low. Pathological cardiophrenic lymph nodes are associated with a poorer overall prognosis and can serve as a prognostic parameter; however, the therapeutic benefit of cardiophrenic lymph nodes resection remains inconclusive.

Beneficial effects of olive oil and Mediterranean diet on cancer physio-pathology and incidence.

Virgin olive oil is a characteristic component and the main source of fat of the Mediterranean diet. It is a mix of high-value health compounds, including monounsaturated fatty acids (mainly oleic acid), simple phenols (such as hydroxytyrosol and tyrosol), secoiridoids (such as oleuropein, oleocanthal), flavonoids, and terpenoids (such as squalene). Olive oil consumption has been shown to improve different aspects of human health and has been associated with a lower risk of cancer. However, the underlying cellular mechanisms involved in such effects are still poorly defined, but seem to be related to a promotion of apoptosis, modulation of epigenetic patterns, blockade of cell cycle, and angiogenesis regulation. The aim of this review is to update the current associations of cancer risk with the Mediterranean diet, olive oil consumption and its main components. In addition, the identification of key olive oil components involved in anticarcinogenic mechanisms and pathways according to experimental models is also addressed.

Evaluation of patients with advanced epithelial ovarian cancer before primary treatment: correlation between tumour burden assessed by [18F]FDG PET/CT volumetric parameters and tumour markers HE4 and CA125.

OBJECTIVES: Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. METHODS: We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. RESULTS: wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. CONCLUSION: HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. KEY POINTS: • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution.

Outcomes of open radical hysterectomy following implementation of an enhanced recovery after surgery program.

OBJECTIVE: Open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2018 IA1 with lymphovascular space invasion-IIA1). Our primary objective was to compare the length of stay in patients undergoing open radical hysterectomy before and after implementation of an enhanced recovery after surgery (ERAS) program. METHODS: This was a single center, retrospective, before-and-after intervention study including patients who underwent open radical hysterectomy for cervical cancer from January 2009 to December 2020. Two groups were identified based on the time of ERAS implementation: pre-ERAS group included patients who were operated on between January 2009 and October 2014; post-ERAS group included patients who underwent surgery between November 2014 and December 2020. RESULTS: A total of 81 patients were included, of whom 29 patients were in the pre-ERAS group and 52 patients in the post-ERAS group. Both groups had similar clinical characteristics with no differences in terms of median age (42 years (interquartile range (IQR) 35-53) in pre-ERAS group vs 41 years (IQR 35-49) in post-ERAS group; p=0.47) and body mass index (26.1 kg/m2 (IQR 24.6-29.7) in pre-ERAS group vs 27.1 kg/m2 (IQR 23.5-33.5) in post-ERAS group; p=0.44). Patients in the post-ERAS group were discharged from the hospital earlier compared with those in the pre-ERAS group (median 3 days (IQR 2-3) vs 4 (IQR 3-4), p<0.01). The proportion of patients discharged within 48 hours was significantly higher in the post-ERAS group (47.3% vs 17.3%, p=0.013). There were no differences regarding either overall complications (44.8% pre-ERAS vs 38.5% post-ERAS; p=0.57) or readmission rates within 30 days (20.7% pre-ERAS group vs 17.3% ERAS group; p=0.40). Adherence to the ERAS pathway since its implementation in 2014 has remained stable with a median of 70% (IQR 65%-75%). CONCLUSIONS: Patients undergoing open radical hysterectomy on an ERAS pathway have a shorter length of hospital stay without increasing overall complications or readmissions rates.

A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE).

BACKGROUND: Multimodal prehabilitation programs that combine exercise training, nutritional support, and optimize psychological status have demonstrated efficacy in reducing post-operative complications in non-gynecological abdominal surgeries; however, the benefit in advanced ovarian cancer is unclear. PRIMARY OBJECTIVE: To compare the post-operative complications of a multimodal prehabilitation program in patients undergoing cytoreductive surgery for advanced ovarian cancer with standard pre-operative care. STUDY HYPOTHESIS: Multimodal prehabilitation reduces post-operative complications in patients undergoing cytoreductive surgery for advanced ovarian cancer and subsequently reduces the length of hospital stay and time to initiation of adjuvant therapy. TRIAL DESIGN: This prospective, multi-institutional, randomized clinical trial will randomize candidates for surgery to either the standard of care or multimodal prehabilitation consisting of (1) 2- or 3-weekly supervised high-intensity resistance training sessions and promotion of physical activity through a mobile phone application; (2) respiratory physiotherapy; (3) nutrition counseling with supplementation as needed; and (4) weekly psychological and cognitive behavioral sessions. Baseline, pre-operative and 1 month post-operative data will be collected. An independent blinded evaluator will collect intra- and post-operative surgical data. MAJOR INCLUSION/EXCLUSION CRITERIA: Women with advanced ovarian cancer International Federation of Gynecology and Obstetrics (2014) stage III or IV scheduled to undergo primary debulking surgery, interval debulking surgery,or secondary or tertiary cytoreductive surgery will be included. Women are eligible if they are able to undergo a minimum of 2 weeks of prehabilitation prior to surgery. Patients with <75% adherence to the total program will be excluded. PRIMARY ENDPOINT: Post-operative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery according to the Comprehensive Complication Index. SAMPLE SIZE: 146 patients will be included, 73 in each group. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual should be completed in December 2024 with results reported soon thereafter. TRIAL REGISTRATION NUMBER: NCT04862325.

Implications of extraperitoneal paraaortic lymphadenectomy to the left renal vein in locally advanced cervical cancer. A Spanish multicenter study.

OBJECTIVE: Paraaortic lymph node involvement is an important prognostic factor in locally advanced cervical cancer (LACC), but the anatomic limit of aortic lymphadenectomy is controversial. We assessed the impact of extraperitoneal paraaortic lymphadenectomy up to the left renal vein in patients with LACC undergoing pretherapeutic staging. METHODS: A retrospective, multicenter study of patients with LACC stages FIGO 2009 IB2 and IIA2-IVA treated in 10 Spanish reference hospitals in gynecological oncology between 2000 and 2016. Sites of metastatic paraaortic lymph nodes above or below the inferior mesenteric artery were evaluated. Procedural-related intraoperative and early and late complications were assessed. RESULTS: We included 634 patients undergoing paraaortic lymphadenectomy, in 616 (97.2%) of which the left renal vein was the upper limit of dissection (laparoscopy 592, robotic-assisted 24). The median surgical time was 150 min (interquartile range (IQR) 120-180), blood loss was 50 mL (range 20-80), and the length of stay was 2 days (range 2-3). Metastatic paraaortic involvement was found in 114 patients (18.5%), with infrarenal metastases in 73 (64%) of them. There were 11 patients (9.6%) with infrarenal metastases only, whereas in the remaining 62 (54.4%) patients concomitant infrarenal and inframesenteric metastases were observed. Intraoperative, early, and late postoperative complications occurred in 3.6%, 7.0%, and 4.5% of patients, respectively. CONCLUSIONS: In this study of patients with LACC undergoing surgical staging, paraaortic lymphadenectomy up to the left renal vein detected skip or isolated infrarenal metastasis in 9.6% of patients, with an acceptable surgical morbidity.

Development and Biomass Composition of Ephestia kuehniella (Lepidoptera: Pyralidae), Tenebrio molitor (Coleoptera: Tenebrionidae), and Hermetia illucens (Diptera: Stratiomyidae) Reared on Different Byproducts of the Agri-Food Industry.

The aim of this study was to evaluate five agro-industrial byproducts (apricots, brewer's spent grains, brewer's spent yeast, feed mill byproducts including broken cereal grains, and hatchery waste including eggshell debris, fluff, infertile eggs, dead embryos, and egg fluids) or mixtures thereof as food diets of Ephestia kuehniella (Zeller), Tenebrio molitor (L.), and Hermetia illucens (L.). Eleven out of 26 tested combinations allowed the first instar larvae to reach the adult stage. Results showed that bioconversion parameters and biomass composition can vary depending on the diet composition, especially in the case of E. kuehniella and H. illucens, whose nutritional requirements seem more complex than those of T. molitor. Tenebrio molitor was able to develop in almost all byproducts. However, only when T. molitor was fed with suitable mixtures of byproducts the development parameters were similar to those obtained with the standard diet. The best results in terms of bioconversion parameters were obtained by feeding H. illucens with a diet including dried brewer's spent grain, feed mill byproducts and brewer's spent yeast. The larvae of these three species can be considered interesting from a nutritional point of view, because of their high protein and fat content. However, the fatty acids profile of H. illucens larvae, with high proportions of saturated fatty acids, seems less healthy for human consumption compared with those of E. kuehniella and T. molitor.

Long-term oncological outcomes of patients with negative sentinel lymph node in vulvar cancer. Comparative study with conventional lymphadenectomy.

INTRODUCTION: The aim of this study was to compare oncological outcomes and morbidity in patients with early-stage vulvar cancer with negative sentinel lymph node (SLN) biopsy vs negative inguinofemoral lymphadenectomy (IFL). MATERIAL AND METHODS: Study with retrospectively collected data in patients with squamous cell vulvar carcinomas ≤ 4 cm without suspected inguinofemoral lymph node metastases. Only patients with negative nodes after histopathology procedure were followed. Patients who underwent only SLN were compared with patients who underwent IFL ± SLN to compare recurrences, survival rates and morbidity. RESULTS: Ninety-three patients were eligible for follow up: 42 with negative SLN and 51 with negative IFL ± SLN. The median follow-up period was 60.4 months (range 6.7-160.7). The rate of isolated first groin recurrence was 4.8% in patients with negative SLN and 2.0% in patients with negative IFL ± SLN (P = 0.587) and the rates of first isolated local recurrence were 28.6% and 31.4%, respectively (P = 0.823). Only 1 patient (2.4%) in the group of negative SLN had distant recurrence. The disease-specific survival rate at 5 years was 83.3% in the negative SLN group and 92.2% in the negative IFL ± SLN group (P = 0.214). We observed a higher rate of wound breakdown and infection after IFL than SLN biopsy (17.6% vs 10.6%; P = 0.020) and lymphedema (33.3% vs 0%; P < 0.001). CONCLUSIONS: We report in the same population of patients with early-stage vulvar cancer that SLN biopsy does not have significantly higher rates of groin recurrences or lower survival rates compared with IFL. Moreover, the SLN procedure has less morbidity, which should encourage gynecologists to abandon IFL.

Patient Location and Disparities in Access to Fertility Preservation for Women With Gynecologic or Breast Cancer.

OBJECTIVE: To assess the effect of geographic factors on fertility-sparing treatment or assisted reproductive technology (ART) utilization among women with gynecologic or breast cancers. METHODS: We conducted a cohort study of reproductive-aged patients (18-45 years) with early-stage cervical, endometrial, or ovarian cancer or stage I-III breast cancer diagnosed between January 2000 and December 2015 using linked data from the California Cancer Registry, the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. Generalized linear mixed models were used to evaluate associations between distance from fertility and gynecologic oncology clinics, as well as California Healthy Places Index score (a Census-level composite community health score), and ART or fertility-sparing treatment receipt. RESULTS: We identified 7,612 women with gynecologic cancer and 35,992 women with breast cancer. Among all patients, 257 (0.6%) underwent ART. Among patients with gynecologic cancer, 1,676 (22.0%) underwent fertility-sparing treatment. Stratified by quartiles, residents who lived at increasing distances from gynecologic oncology or fertility clinics had decreased odds of undergoing fertility-sparing treatment (gynecologic oncology clinics: Q2, odds ratio [OR] 0.76, 95% CI, 0.63-0.93, P =.007; Q4, OR 0.72, 95% CI, 0.56-0.94, P =.016) (fertility clinics: Q3, OR 0.79, 95% CI, 0.65-0.97, P =.025; Q4, OR 0.67, 95% CI, 0.52-0.88, P =.004), whereas this relationship was not observed among women who resided within other quartiles (gynecologic oncology clinics: Q3, OR 0.81 95% CI, 0.65-1.01, P =.07; fertility clinics: Q2, OR 0.87 95% CI, 0.73-1.05, P =.15). Individuals who lived in communities with the highest (51 st -100 th percentile) California Healthy Places Index scores had greater odds of undergoing fertility-sparing treatment (OR 1.29, 95% CI, 1.06-1.57, P =.01; OR 1.66, 95% CI, 1.35-2.04, P =.001, respectively). The relationship between California Healthy Places Index scores and ART was even more pronounced (Q2 OR 1.9, 95% CI, 0.99-3.64, P =.05; Q3 OR 2.86, 95% CI, 1.54-5.33, P <.001; Q4 OR 3.41, 95% CI, 1.83-6.35, P <.001). CONCLUSION: Geographic disparities affect fertility-sparing treatment and ART rates among women with gynecologic or breast cancer. By acknowledging geographic factors, health care systems can ensure equitable access to fertility-preservation services.