Protein Supplementation in a Prehabilitation Program in Patients Undergoing Surgery for Endometrial Cancer.

Enhanced recovery after surgery (ERAS) and prehabilitation programs are multidisciplinary care pathways to reduce stress response and improve perioperative outcomes, which also include nutritional interventions. The aim of this study is to assess the impact of protein supplementation with 20 mg per day before surgery in a prehabilitation program in postoperative serum albumin, prealbumin, and total proteins in endometrial cancer patients undergoing laparoscopic surgery. METHODS: A prospective study including patients who underwent laparoscopy for endometrial cancer was conducted. Three groups were identified according to ERAS and prehabilitation implementation (preERAS, ERAS, and Prehab). The primary outcome was levels of serum albumin, prealbumin, and total protein 24-48 h after surgery. RESULTS: A total of 185 patients were included: 57 in the preERAS group, 60 in the ERAS group, and 68 in the Prehab group. There were no basal differences in serum albumin, prealbumin, or total protein between the three groups. After surgery, regardless of the nutritional intervention, the decrease in the values was also similar. Moreover, values in the Prehab group just before surgery were lower than the initial ones, despite the protein supplementation. CONCLUSIONS: Supplementation with 20 mg of protein per day does not impact serum protein levels in a prehabilitation program. Supplementations with higher quantities should be studied.

Prehabilitation in an ERAS program for endometrial cancer patients: impact on post-operative recovery.

OBJECTIVES: Enhanced recovery after surgery (ERAS) and prehabilitation programs are multidisciplinary care pathways that aim to reduce stress response and improve perioperative outcomes. However, literature is limited regarding the impact of ERAS and prehabilitation in gynecologic oncology surgery. The aim of this study was to assess the impact of implementing an ERAS and prehabilitation program on post-operative outcomes of endometrial cancer patients undergoing laparoscopic surgery. METHODS: We evaluated consecutive patients undergoing laparoscopy for endometrial cancer that followed ERAS and the prehabilitation program at a single center. A pre-intervention cohort that followed the ERAS program alone was identified. The primary outcome was length of stay, and secondary outcomes were normal oral diet restart, post-operative complications and readmissions. RESULTS: A total of 128 patients were included: 60 patients in the ERAS group and 68 patients in the prehabilitation group. The prehabilitation group had a shorter length of hospital stay of 1 day (p<0.001) and earlier normal oral diet restart of 3.6 hours (p=0.005) in comparison with the ERAS group. The rate of post-operative complications (5% in the ERAS group and 7.4% in the prehabilitation group, p=0.58) and readmissions (1.7% in the ERAS group and 2.9% in the prehabilitation group, p=0.63) were similar between groups. CONCLUSIONS: The integration of ERAS and a prehabilitation program in endometrial cancer patients undergoing laparoscopy significantly reduced hospital stay and time to first oral diet as compared with ERAS alone, without increasing overall complications or the readmissions rate.

Impact of prehabilitation during neoadjuvant chemotherapy and interval cytoreductive surgery on ovarian cancer patients: a pilot study.

BACKGROUND: Cytoreductive surgery followed by systemic chemotherapy is the standard of treatment in advanced ovarian cancer where feasible. Neoadjuvant chemotherapy (NACT) followed by surgery is applicable where upfront cytoreductive surgery is not feasible because of few certain reasons. Nevertheless, surgical interventions and the chemotherapy itself may be associated with postoperative complications usually entailing slow postoperative recovery. Prehabilitation programs consist of the patient's preparation before surgery to improve the patient's functional capacity. The aim of this study was to evaluate the impact of a prehabilitation program during neoadjuvant treatment and interval cytoreductive surgery for ovarian cancer patients. METHODS: A retrospective observational pilot study of patients with advanced ovarian cancer treated with NACT and interval cytoreductive surgery was conducted. The prehabilitation group received a structured intervention based on physical exercise, nutritional counseling, and psychological support. Nutritional parameters were assessed preoperatively and postoperatively, and functional parameters and perioperative and postoperative complications were also recorded. RESULTS: A total of 29 patients were included in the study: 14 in the prehabilitation group and 15 in the control group. The patients in the prehabilitation program showed higher mean total protein levels in both preoperative (7.4 vs. 6.8, p = 0.004) and postoperative (4.9 vs. 4.3, p = 0.005) assessments. Up to 40% of controls showed intraoperative complications vs. 14.3% of patients in the prehabilitation group, and the requirement of intraoperative blood transfusion was significantly lower in the prehabilitation group (14.3% vs. 53.3%, p = 0.027). The day of the first ambulation, rate of postoperative complications, and length of hospital stay were similar between the groups. Finally, trends towards shorter time between diagnosis and interval cytoreductive surgery (p = 0.097) and earlier postoperative diet restart (p = 0.169) were observed in the prehabilitation group. CONCLUSION: Prehabilitation during NACT in women with ovarian cancer candidates to interval cytoreductive surgery may improve nutritional parameters and thereby increase postoperative recovery. Nevertheless, the results of this pilot study are preliminary, and further studies are needed to determine the clinical impact of prehabilitation programs.

Predictor factors for conservative management of cervical intraepithelial neoplasia grade 2: Cytology and HPV genotyping.

OBJECTIVE: The purpose of this study was to evaluate the role of HPV genotyping and previous cytology result to predict the evolution of CIN2 histological lesions managed conservatively. METHODS: A prospective observational study was conducted at Hospital del Mar in Barcelona from January 2012 to May 2017. Women with new diagnosis of CIN2 were invited to undergo conservative management for 24 months. Complete regression, partial regression, persistence and progression to CIN3 were defined as final outcomes. Univariate and multivariate analyses combining HPV genotyping and cytology were used to establish progression predictors of CIN2. RESULTS: A total of 300 patients were included in the study, and 291 patients completed the 24-months follow-up. Of them, 214 patients (73.5%) showed regression; 43 (14.8%) persistence to CIN2, and 34 (11.7%) progression to CIN3. In multivariable analysis, HPV-16 infection (odds ratio [OR] 1.97, [95% confidence interval {CI} 1.13-3.43]) and previous HSIL cytology (OR 3.46, [95% CI 1.99-6.02]) significantly increased the risk of persistence or progression (CIN2+) of CIN2 lesions. In contrast, all HPV-negative lesions regressed (p < 0.001). CONCLUSIONS: The regression rate of CIN2 lesions supports conservative management in selected patients regardless of their age. Patients with a CIN2 biopsy and negative HPV test had a high rate of regression and should be offered follow-up without excisional treatment. In contrast, patients with HPV-16 and HSIL cytology had an increased risk of CIN2+, their treatment should be individualized and excisional treatment should be considered. The age may not be considered a criterion to decide the best management. New markers may help in the future to select the best management of CIN2.

Influence of age on treatment and prognosis of invasive cervical cancer.

OBJECTIVE: Invasive cervical cancer is considered a young women's disease, however up to 20 % of cases develop cervical cancer at advanced ages. The aim was to characterize invasive cervical cancer in women aged 65 and older assessing age-specific survival differences. STUDY DESIGN: A retrospective study including cervical cancer patients was conducted at Hospital del Mar Barcelona from July-2007 to December-2016. Women were stratified: <65 or ≥65years. Clinical and pathological data were collected. Multivariate analysis was used to compare outcomes. Adjusted hazard ratios with 95 % confidence intervals for disease-free survival, and overall survival were estimated using Cox proportional hazards models. RESULTS: 124 patients with invasive cervical cancer (n = 87 < 65years and n = 37 ≥ 65years) were included. At diagnosis, 48.3 % of <65years patients were diagnosed at advanced stages, while 64.9 % in ≥65years (p = 0.018). Standard treatment was given to 83.9 % of patients in <65years group compared to 62.2 % in ≥65years (p = 0.015). Disease-free survival and overall survival showed no significant differences between groups. Age ≥65 did not predict worse disease-free survival (HR: 0.3 95 %CI, 0.04-3.1, p = 0.347) or overall survival (HR: 0.82 95 %CI, 0.3-2.3, p = 0.729). CONCLUSION: Invasive cervical cancer was diagnosed at advanced stages and was treated less frequently with radical intention in patients ≥65years; overall survival and disease-free survival were similar to those cervical cancer diagnosed at younger ages.

Gynecologic cancer surveillance in the era of SARS-CoV-2 (COVID-19).

The SARS-CoV-2 (COVID-19) pandemic has significantly impacted the management of patients with gynecologic cancers. Many centers have reduced access to routine visits to avoid crowded waiting areas and specially to reduce the infection risk for oncologic patients. The goal of this review is to propose a surveillance algorithm for patients with gynecologic cancers during the COVID-19 pandemic based on existing evidence and established guidelines. It is time to consider strategies based on telemedicine and to adapt protocols in this new era. We hereby propose a strategy for routine surveillance both during and beyond the pandemic.

Role and impact of multimodal prehabilitation for gynecologic oncology patients in an Enhanced Recovery After Surgery (ERAS) program.

Patients undergoing major surgery are predisposed to a decrease in functional capacity as a response to surgical stress that can delay post-operative recovery. A prehabilitation program consists of patient preparation strategies before surgery, and include pre-operative measures to improve functional capacity and enhance post-operative recovery. Multimodal prehabilitation may include exercise, nutritional counseling, psychological support, and optimization of underlying medical conditions, as well as cessation of unfavorable health behaviors such as smoking and drinking. Currently, there are no standardized guidelines for prehabilitation, and the existent studies are heterogeneous; however, multimodal approaches are likely to have a greater impact on functional outcomes than single management programs. We have reviewed the literature on prehabilitation in general, and in gynecologic surgery in particular, to identify tools to establish an optimal prehabilitation program within an Enhanced Recovery After Surgery (ERAS) protocol for gynecologic oncology patients. We suggest a safe, reproducible, functional, and easy-to-apply multimodal prehabilitation program for gynecologic oncology practice based on patient-tailored pre-operative medical optimization, physical training, nutritional counseling, and psychological support. The analysis of the prehabilitation program implementation in an ERAS protocol should undergo further research in order to test the efficacy on surgical outcome and recovery after surgery.

Role of Chlamydia trachomatis serology in conservative management of cervical intraepithelial neoplasia grade 2.

OBJECTIVE: To evaluate the spontaneous progression of cervical intraepithelial neoplasia grade 2 (CIN2) in accordance with Chlamydia trachomatis (chlamydia) serology. METHODS: A prospective observational study included women diagnosed with CIN2 by cervical biopsy and managed conservatively for 24 months at Hospital del Mar, Barcelona, between December 2011 and October 2013. Serum anti-chlamydia immunoglobulin G (IgG), previous cytology, and high-risk human papillomavirus (HPV) genotyping were recorded at baseline. The outcome was regression, persistence, or progression of CIN2. RESULTS: Overall, 93 women aged 18-56 years were enrolled. Spontaneous regression was observed for 61 (66%) women, and 21 (23%) progressed to CIN3. Eight (9%) women had chlamydia seropositivity at baseline. Multivariate analysis showed that anti-chlamydia IgG seropositivity (odds ratio [OR], 19.1; 95% confidence interval [CI], 1.9-189.7), previous high-grade squamous intraepithelial lesion cytology (OR, 5.0; 95% CI, 1.7-14.6), and HPV16 (OR, 4.8; 95% CI, 1.7-13.7) increased the risk of CIN2 persistence or progression. CONCLUSION: Women with CIN2 and chlamydia IgG seropositivity had increased risk of progression to CIN2+ and immediate treatment may be recommended for these women. Larger clinical studies are needed to confirm the results, but chlamydia serology might be introduced into CIN2 management to better individualize treatment.

Utility of Human Papillomavirus Genotyping in the Management of Low-Grade Squamous Intraepithelial Lesions.

OBJECTIVE: The aim of the study was to determine the usefulness of human papillomavirus (HPV) partial genotyping test in the triage of newly diagnosed low-grade squamous intraepithelial lesions (LSILs). MATERIALS AND METHODS: We analyzed 143 patients with LSIL diagnosed de novo. Lesions were classified as positive for HPV 16 or HPV 18, positive for HPV but not HPV 16 or HPV 18 (HPVno16no18) or no HPV detected (HPVneg). Patients were followed for a period of 2 years or until the lesion progressed. We calculated absolute and relative risks for progression and regression according to the HPV result. RESULTS: The mean (SD) age was 33.8 (11.1) years. A total of 19.6% were positive for HPV 16, 4.9% for HPV 18, and 63.6% for HPVno16no18. The absolute risk of HPV 16 for progression to cervical intraepithelial neoplasia grade 2 or more (CIN 2+) was 32.1%, 14.3% for HPV 18, and 5.8% for HPVno16no18. None of the HPVneg cases evolved to CIN 2+. The presence of HPV 16 conferred a 7.4 (95% CI = 2.7-20.3) times greater risk of developing CIN 2+ than its absence. The absolute risks for HPV 16, HPV 18, HPVno16no18, and HPVneg for regression were 53.6%, 57.1%, 75.4%, and 87.5%, respectively. Relative risks for regression were 0.7 (95% CI = 0.5-0.9) for HPV 16 and 1.3 (95% CI = 1.1-1.5) for HPVneg. CONCLUSIONS: The HPV 16 LSILs are more likely to progress to CIN 2+, so tight control and immediate colposcopy are crucial, whereas when HPV 16 is not present, follow-up could be less strict. Low-grade squamous intraepithelial lesions in which high-risk HPV is not detected do not progress to CIN 2+, so its control should be different from other LSIL, and conservative management could be an acceptable strategy.

Usefulness of p16INK4a staining for managing histological high-grade squamous intraepithelial cervical lesions.

p16INK4a (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining. Patients diagnosed with HSIL/CIN2 colposcopy-directed biopsy, were recruited prospectively between December 2011 and October 2013. p16 staining was performed in all HSIL/CIN2 diagnostic biopsies. Follow-up was conducted every 4 months by cytology, colposcopy and biopsy if suspicion of progression and once the 12 months of follow-up completed. Complete regression, partial regression, persistence, and progression rates of HSIL/CIN2 were defined as a final outcome. A total of 96 patients were included in the analysis. The rate of spontaneous regression was 64%, while 28% had persistent disease, and 8% progressed at 12 months of follow-up. p16 was positive in 81 (84%) initial HSIL/CIN2 biopsies. Regression was observed in all 15 p16 negative cases and in 46 of 81 (57%) p16 positive cases (P=0.001). In conclusion, patients with p16 negative HSIL/CIN2 biopsy had a high rate of regression during first 12 months of follow-up. Status of p16 staining could be considered for HSIL/CIN2 management.

Value of p16(INK4a) and Ki-67 Immunohistochemical Staining in Cervical Intraepithelial Neoplasia Grade 2 Biopsies as Biomarkers for Cervical Intraepithelial Neoplasia Grade 3 in Cone Results.

OBJECTIVE: To evaluate the usefulness of p16(INK4a) (p16) and Ki-67 staining in high-grade cervical intraepithelial neoplasia (CIN2) biopsies in order to predict CIN3 results in cone specimens, thereby sparing those not likely at risk for CIN3 from unnecessary cone excision. STUDY DESIGN: We retrospectively recruited patients with CIN2 colposcopy-directed biopsy treated by loop electrosurgical excision procedure. The expression of p16 and Ki-67 was qualitatively and quantitatively analyzed in all biopsies and cone specimens. RESULTS: A total of 123 patients from January 2009 to December 2010 were included in the study. CIN3 in cone specimens was observed in 35 patients (28.5%). Ki-67 positive immunostaining in > 50% of epithelial cells was related to CIN3 diagnoses in cone specimens (p = 0.043). However, p16+ and Ki-67+ evaluated by thirds of the epithelial thickness in CIN2 biopsies did not show a significant correlation with the cone results. In multivariate analysis, Ki-67 cell expression over 50% in CIN2 biopsies and high-grade squamous intraepithelial lesion (HSIL) in the previous cytology were statistically associated with CIN3 results in the cone (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.04-6.29; OR 2.68, 95% CI 1.07-6.72, respectively). CONCLUSION: Patients with HSIL in the previous cytology and Ki-67 cell expression over 50% in their CIN2 biopsies could be considered in need of treatment by cone for their higher risk of underlying CIN3 lesions.

A call for new standard of care in perioperative gynecologic oncology practice: Impact of enhanced recovery after surgery (ERAS) programs.

Enhanced recovery after surgery (ERAS) programs aim to hasten functional recovery and improve postoperative outcomes. However, there is a paucity of data on ERAS programs in gynecologic surgery. We reviewed the published literature on ERAS programs in colorectal surgery, general gynecologic surgery, and gynecologic oncology surgery to evaluate the impact of such programs on outcomes, and to identify key elements in establishing a successful ERAS program. ERAS programs are associated with shorter length of hospital stay, a reduction in overall health care costs, and improvements in patient satisfaction. We suggest an ERAS program for gynecologic oncology practice involving preoperative, intraoperative, and postoperative strategies including; preadmission counseling, avoidance of preoperative bowel preparation, use of opioid-sparing multimodal perioperative analgesia (including loco-regional analgesia), intraoperative goal-directed fluid therapy (GDT), and use of minimally invasive surgical techniques with avoidance of routine use of nasogastric tube, drains and/or catheters. Postoperatively, it is important to encourage early feeding, early mobilization, timely removal of tubes and drains, if present, and function oriented multimodal analgesia regimens. Successful implementation of an ERAS program requires a multidisciplinary team effort and active participation of the patient in their goal-oriented functional recovery program. However, future outcome studies should evaluate the efficacy of an intervention within the pathway, include objective measures of symptom burden and control, study measures of functional recovery, and quantify outcomes of the program in relation to the rates of adherence to the key elements of care in gynecologic oncology such as oncologic outcomes and return to intended oncologic therapy (RIOT).

Alcohol consumption and in vitro fertilization: a review of the literature.

The aim of our study is to determine whether alcohol consumption affects the results of in vitro fertilization. A review of the literature was performed to find prospective cohort studies of couples undergoing in vitro fertilization in which alcohol intake was recorded. A primary search returned 389 studies, 2 of which were finally considered eligible. A total of 2908 couples were analyzed in terms of pregnancy outcomes depending on drinking habits. The risk of IVF failure increased 4.14-fold and 2.86-fold with an increased alcohol intake of 12 gr/d in women during the week and month before, respectively. The odds ratio (OR) of live birth rate in women who drank at least four drinks per week compared with women who drank fewer was 0.84; this difference was statistically significant. Paternal alcohol use levels 1 month, 1 week and during the attempts were also associated with worse reproductive effects. Our review, though including a small number of studies that were heterogeneous in design, revealed decreased rates of pregnancy and fertilization outcomes for couples who drank before or during their in vitro fertilization techniques. This suggests that couples undergoing IVF should be advised to abstain from alcohol prior to and during their procedures.

Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of luteal phase support with vaginal progesterone in women undergoing intrauterine insemination (IUI). METHODS: Systematic review and meta-analysis. Randomized controlled trials (RCT) comparing supplementation of luteal phase with vaginal progesterone among women undergoing IUI versus a control group were included. The main outcome assessed was live birth rate. RESULTS: Five RCT met the inclusion criteria. In all 1,271 patients were included (951 IUI cycles in the progesterone group, 935 in the control group). Women treated with vaginal progesterone achieved significantly higher live birth rate (risk ratio [RR] 1.94, 95 % confidence interval [CI] 1.36 to 2.77,), and clinical pregnancy rate (RR 1.41, 95 % CI 1.14 to 1.76) as compared with controls. In the subgroup analysis per stimulation protocol, this beneficial effect of receiving progesterone was only observed in the group stimulated with gonadotropins (RR 2.28, 95 % CI 1.49 to 3.51), compared to the group stimulated with clomiphene citrate (CC) (RR 1.30, 95 % CI 0.68 to 2.50). No differences were observed in the miscarriage and multiple pregnancy rates. CONCLUSIONS: The supplementation of luteal phase with vaginal progesterone significantly increases live birth among women undergoing IUI when receiving gonadotropins for ovulation induction. Women receiving CC to induce ovulation do not seem to benefit from this treatment.