Nutrition as Personalized Medicine against SARS-CoV-2 Infections: Clinical and Oncological Options with a Specific Female Groups Overview.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is acknowledged that vulnerable people can suffer from mortal complications of COVID-19. Therefore, strengthening the immune system particularly in the most fragile people could help to protect them from infection. First, general nutritional status and food consumption patterns of everyone affect the effectiveness of each immune system. The effects of nutrition could impact the level of intestinal and genital microbiota, the adaptive immune system, and the innate immune system. Indeed, immune system cells and mediators, which are crucial to inflammatory reaction, are in the structures of fats, carbohydrates, and proteins and are activated through vitamins (vit) and minerals. Therefore, the association of malnutrition and infection could damage the immune response, reducing the immune cells and amplifying inflammatory mediators. Both amount and type of dietary fat impact on cytokine biology, that consequently assumes a crucial role in inflammatory disease. This review explores the power of nutrition in the immune response against COVID-19 infection, since a specific diet could modify the cytokine storm during the infection phase. This can be of vital importance in the most vulnerable subjects such as pregnant women or cancer patients to whom we have deemed it necessary to dedicate personalized indications.

Primary surgical cytoreduction in advanced ovarian cancer: An outcome analysis within the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group.

OBJECTIVE: To draw a reliable picture of the surgical management of advanced ovarian cancer (AOC) within the MITO Group, trying to correlate the disease extent at presentation, the category of center, and surgical outcome. METHODS: Three tertiary referral centers for gynecologic oncology and four non-oncologic referral gynecologic surgical centers, participated in the project. A questionnaire was adopted to register perioperative data on AOCs (FIGO Stage IIICIV) consecutively operated on for a period of 12months. RESULTS: A total of 205 patients were registered into the study: 140 and 65 were recruited in oncological referral centers and non-referral centers, respectively. Following a multivariate analysis, the Eisenkop score and the category of center resulted the most potent predictors of complete surgical cytoreduction followed by PCI, preoperative CA125, and ASA score. Complete surgical cytoreduction was associated with oncological referral centers (60% vs 24.6%, p<0.001). The proportion of patients undergoing additional surgical procedures was significantly different comparing the two categories of centers (at least one additional procedure was performed in 81.4% vs 50.8% in oncological referral centers compared to the others, p<0.001). Despite the more aggressive surgery performed in oncological referral centers, the perioperative outcome measures were not significantly different in the two groups. CONCLUSIONS: The chance of obtaining a complete cytoreduction mainly depends on patient characteristics, tumor spread, and quality of treatment. The latter is amenable for direct influence, and therefore, seems to be of utmost importance when considering efforts aiming at improvement in the outcome of this disease.

Association between Cervical Microbiota and HPV: Could This Be the Key to Complete Cervical Cancer Eradication?

The heterogeneity of the cervico-vaginal microbiota can be appreciated in various conditions, both pathological and non-pathological, and can vary according to biological and environmental factors. Attempts are still in course to define the interaction and role of the various factors that constitute this community of commensals in immune protection, inflammatory processes, and the onset of precancerous lesions of the cervical epithelium. Despite the many studies on the relationship between microbiota, immunity, and HPV-related cervical tumors, further aspects still need to be probed. In this review article, we will examine the principal characteristics of microorganisms commonly found in cervico-vaginal specimens (i) the factors that notoriously condition the diversity and composition of microbiota, (ii) the role that some families of organisms may play in the onset of HPV-dysplastic lesions and in neoplastic progression, and (iii) possible diagnostic-therapeutic approaches.

Lactobacillus crispatus M247 oral administration: Is it really an effective strategy in the management of papillomavirus-infected women?

BACKGROUND: Recent studies have shown the importance of the microbiota in women's health. Indeed, the persistence of Human Papilloma Virus (HPV)-related lesions in patients with dysbiosis can be the antechamber to cervical cancer. The aim of this study was to evaluate whether long term administration of oral Lactobacillus crispatus can restore eubiosis in women with HPV infections and hence achieve viral clearance. METHODS: In total, 160 women affected by HPV infections were enrolled at the Department of Gynecological Obstetrics of "San Paolo" Hospital, Italy between February 2021 and February 2022. The women were randomly assigned to two groups, one in treatment with oral Lactobacillus crispatus M247 (group 1, n = 80) versus the control group, that hence only in follow-up (Group 2, n = 80). RESULTS: After a median follow-up of 12 months (range 10-30 months), the likelihood of resolving HPV-related cytological anomalies was higher in patients in treatment with the long term oral probiotic (group 1) versus the group that perfom only follow-up (group 2) (60.5% vs. 41.3%, p = 0.05). Total HPV clearance was shown in 9.3% of patients undergoing only follow-up compared to 15.3% of patients in the group taking long term oral Lactobacillus crispatus M247 (p = 0.34). However, the percentage of HPV-negative patients, assessed with the HPV-DNA test, documented at the end of the study period was not significantly different from the control group. CONCLUSIONS: Despite the limitations of our analysis, we found a higher percentage of clearance of PAP-smear abnormalities in patients who took long term oral Lactobacillus crispatus M247 than in the control group. Larger studies are warranted, but we believe that future research should be aimed in this direction. Trial registration This study is retrospectively registered.

SARS-CoV-2 Vaccines and Adverse Effects in Gynecology and Obstetrics: The First Italian Retrospective Study.

The most common effects reported by the Italian Medicine Agency following administration of SARS-CoV-2 vaccine are myalgia, soreness to the arm of inoculation, fever, and asthenia. To date, there are no specific and official reports registered by the Italian Medicine Agency on possible alterations of the menstrual cycle, or of the female reproductive system, following the vaccine. Actually, clinical experience showed a spread of transient adverse drug reactions of the menstrual cycle, following the administration of all COVID-19 vaccine types, both mRNA and Adenovirus vectored ones. In this work, we conducted the first retrospective study on Italian patients vaccinated for SARS-CoV-2 in the period between April 2021 and April 2022, to report the onset of menstrual changes after the vaccine in order to understand: etiology, duration of possible adverse effects, and the extent of the phenomenon. We recruited 100 women aged 18-45, vaccinated for SARS-CoV-2, who were asked to complete a questionnaire consisting of 12 multiple choice questions about the effects of the vaccine on the reproductive system. Thirty-seven of them received three doses of the vaccine, while the remaining 63 received two doses. Symptoms such as delayed menstruation and abnormal uterine bleeding (metrorrhagia, menometrorrhagia, and menorrhagia) were generally reported within the first three weeks of vaccination, especially after the second dose, with a percentage of 23% and 77%, respectively. These preliminary data suggest that this problem may be broader and deserving of further investigation in the future.

Communications Is Time for Care: An Italian Monocentric Survey on Human Papillomavirus (HPV) Risk Information as Part of Cervical Cancer Screening.

Human papilloma virus (HPV) infection could be considered a social disease, both for its high incidence, especially in younger subjects, and for the risk of neoplastic evolution linked to viral infection. Therefore, the National Health System, in collaboration with the state, must help women to understand the oncological risk of HPV and suitable methods of prevention. We conducted an Italian monocentric survey on HPV risk information as part of cervical cancer screening. An anonymous questionnaire was administered to 200 women with high-risk positive HPV and low-grade cervical lesions during second-level cervical cancer screening at the Gynecology and Obstetrics Unit of the "San Paolo" Hospital. From this survey, the need to improve communication for patients has emerged, as currently it is not exhaustive. In response to this need, organizational changes have been implemented to centralize the moment of counseling in the second levels of screening and to improve the training of health workers in level I as well as family doctors. In addition, psychological support was also proposed to patients who requested it, as was the dissemination of material such as that produced by GISCI (Italian Cervico-Carcinoma Screening Group) and updated in May 2018, which provides 100 answers to questions on HPV in order to achieve effective and comprehensive communication. This investigation requires further development, and the expansion of this investigation to the multicenter level is already underway. Therefore, this survey will represent a cornerstone for further discussion on the topic considering the necessity of appropriate communication in the oncological context.

Effects of Oral Supplementation with Myo-Inositol and D-Chiro-Inositol on Ovarian Functions in Female Long-Term Survivors of Lymphoma: Results from a Prospective Case-Control Analysis.

The progressive improvement of lymphoma treatment has led to an important prolongation of patient survival and life expectancy. The principal international scientific societies of oncology now therefore recommend that long-term survivors of lymphoma join fertility programs. Specifically, fertile-age patients should be assisted by a multidisciplinary team, including specialists dedicated to fertility preservation in oncology, in order to support the completion of their reproductive project. In the general population, the use of Myo-Inositol and D-Chiro-Inositol (MI/DCI) has been demonstrated to be an effective choice to treat ovarian dysfunctions, with a consequent improvement in reproductive outcomes, so it may represent an adjuvant strategy for this purpose. We therefore conducted a pilot prospective case-control study to evaluate the potentialities of this nutritional supplement, with the aim of optimizing reproductive function in female long-term survivors of lymphoma. One group underwent oral supplementation with MI 1200 mg and DCI 135 mg per day for 12 months, compared with controls who underwent no treatment in the same period. After 12 months, FSH, LH, and progesterone levels, as well as oligomenorrhea and antral follicle count (AFC), were significantly improved in the MI/DCI group. In addition, a significantly higher mean value in FSH and LH and a significantly lower mean AFC value in the right ovary were observed in controls compared to the MI/DCI group. Despite the need for further investigation, MI/DCI could be considered a potential adjuvant strategy to restore ovarian function in female long-term survivors of lymphoma.

Conservative treatment of early endometrial cancer: preliminary results of a pilot study.

OBJECTIVE: This study evaluated the feasibility and efficacy of combined operative hysteroscopy (HSC) and hormone therapy as fertility-preserving treatment in a cohort of selected young women with early endometrial carcinoma (EC). METHODS: Fourteen patients (median age 38 years, range 26-40) with FIGO stage IA (intramucous) EC wishing to preserve fertility were enrolled with the following inclusion criteria: age ≤40 years; no evidence of Lynch II syndrome; well-differentiated estrogen/progesterone receptor positive (ER+/PR+) endometrioid EC; no evidence of myoinvasion, multifocal tumor, node metastasis, ovarian mass; normal serum CA 125. Treatment consisted of hysteroscopic ablation of the lesion and the myometrial tissue below, followed by oral megestrol acetate (MA) 160 mg/day for 6 months (6 pts) or 52 mg levonorgestrel-medicated intrauterine device (LNG-IUD) for 12 months (8 pts). RESULTS: With a median follow-up of 40 months (range 13-79), one patient recurred after 5 months from operative HSC and underwent definitive surgery, one patient showed an endometrial hyperplasia without atypia at the 3 and 6 month HSC control, with negative controls thereafter. Three patients have attempted to conceive and one of them conceived and term delivered a healthy baby. CONCLUSIONS: Combined operative HSC and progestin therapy may have a role for safe and effective conservative management of early EC in selected patients wishing to preserve fertility.

Correlation between factors involved in the local haemostasis and angiogenesis in full term human placenta.

INTRODUCTION: Few studies have been carried out to investigate whether distinct areas of full term placenta express different amounts of markers involved in the placental haemostasis and angiogenesis. A possible relationship between the expression of genes involved in the haemostasis and angiogenesis of human placenta has not been investigated. MATERIALS AND METHODS: Twenty-eight fresh human placentas (35-41 weeks of gestation) from uneventful pregnancies were dissected with two different methods. Quantitative mRNA expression of the tissue factor (TF), TF pathway inhibitor (TFPI), TFPI-2, plasminogen activator inhibitor (PAI-2), annexin V (Anx V), vascular endothelial growth factor (VEGF), and thrombomodulin (TM) genes was evaluated by quantitative real time PCR system. Histology of each sample was graded. RESULTS: Gene expression of all the considered markers was not significantly different in each area, using both the different methods of dissection. A significant correlation (p<0.05) was found between the expression of TF and TFPI-2. TF and TFPI-2 were significantly (p<0.05) associated with VEGF, whereas a stronger association (p<0.01) was found between TFPI and TFPI-2. TFPI and TFPI-2 were strongly associated with PAI-2 expression (p<0.01). CONCLUSIONS: In placentas with central cord insertion, gene expression is not dependent on the method of sampling site. A significant relationship between haemostasis and angiogenesis in at term placentas was shown.

Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study.

BACKGROUND: Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. METHODS: 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute--Common Toxicity Criteria. RESULTS: 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7-58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy. CONCLUSION: A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease.

Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study.

PURPOSE: Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. PATIENTS AND METHODS: To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. RESULTS: Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. CONCLUSION: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

Asynclitism: a literature review of an often forgotten clinical condition.

Asynclitism is defined as the "oblique malpresentation of the fetal head in labor". Asynclitism is a clinical diagnosis that may be difficult to make; it may be found during vaginal examination. It is significant because it may cause failure of progress operative or cesarean delivery. We reviewed all literature for asynclitism by performing an extensive electronic search of studies from 1959 to 2013. All studies were first reviewed by a single author and discussed with co-authors. The following studies were identified: 8 book chapters, 14 studies on asynclitism alone and 10 papers on both fetal occiput posterior position and asynclitism. The fetal head in a laboring patient may be associated with some degree of asynclitism; this is seen as usual way of the fetal head to adjust to maternal pelvic diameters. However, marked asynclitism is often detected in presence of a co-existing fetal head malposition, especially the transverse and occipital posterior positions. Digital diagnosis of asynclitism is enhanced by intrapartum ultrasound with transabdominal or transperineal approach. The accurate diagnosis of asynclitism, in an objective way, may provide a better assessment of the fetal head position that will help in the correct application of vacuum and forceps, allowing the prevention of unnecessary cesarean deliveries.

Review role of topotecan in gynaecological cancers: current indications and perspectives.

BACKGROUND: Ovarian cancer is the fourth cause of death from gynaecological cancer and cervical cancer is the first in women <45 years old in developing countries. The aim of this article is to review the role of topotecan (Hycamtin), a semi-synthetic alkaloid derivative of camptothecin, in ovarian and cervical cancer in monotherapy and in combination. METHODS: This article reviews the mechanism of action, pharmacokinetics, toxicity and efficacy of topotecan. The paper also reports the principal phases II and III studies of topotecan in advanced or recurrent ovarian and cervical cancer. RESULTS: Topotecan (Hycamtin), currently indicated for the treatment of relapsed ovarian cancer, has demonstrated activity both in platinum-sensitive and in platinum-resistant disease. The combination cisplatin-topotecan for the treatment of advanced and recurrent cervical cancer has demonstrated a clinical benefit in terms of response rate, overall survival and progression free survival. Haematological toxicity of topotecan also is easy to manage and not cumulative, especially with the weekly scheduled recently introduced in clinical practice. CONCLUSION: Topotecan (Hycamtin) will continue to play a role in the treatment of advanced ovarian and cervical cancer, in monotherapy or in combination with other cytotoxic agents.

Skin metastases in ovarian carcinoma: a report of nine cases and a review of the literature.

OBJECTIVE: Cutaneous involvement is unusual at presentation and during the course of ovarian carcinoma. The aim of the present study was to determine the incidence, clinicopathologic characteristics and prognostic factors of skin metastases in ovarian cancer patients. METHODS: A retrospective chart review was conducted on 220 patients with epithelial ovarian carcinoma treated at our unit between 1991 and 2001. Pertinent clinical information, pathologic data, treatment, and prognostic factors for survival following documentation of skin metastases were collected. Survival time was calculated from the time of diagnosis of ovarian cancer and from the time of diagnosis of the cutaneous metastasis. RESULTS: FIGO stage at the time of ovarian cancer diagnosis was stage III = five patients (56%), and stage I and stage IV = two patients each (22%). Most patients had serous papillary cystoadenocarcinoma of the ovary (78%), and one each had endometrioid and mucinous carcinomas (12%). Seven patients (78%) had poorly differentiated tumors. Only one patient had a skin metastasis at the time of ovarian cancer diagnosis; in the remaining patients the average time of appearance of skin metastases after the diagnosis of ovarian cancer was 23.4 +/- 12 months (range 4 to 37). The diameter of the skin lesions ranged between 0.5 and 3 cm. Three patients had a single skin nodule, while six had multiple skin lesions. Eight patients (89%) have died of disease and median survival after diagnosis of the skin metastases was 4 months (range 2 to 65). One patient (Cases 1) is alive without tumor 4 months after diagnosis of the skin metastases. Overall survival after diagnosis of skin metastasis from ovarian cancer was 4 months (range 2 to 65). CONCLUSION: Skin involvement is a late complication that occurs rarely in ovarian cancer patients. Prognosis after skin metastases is poor and the most important prognostic factor associated with survival is the interval time between diagnosis of ovarian cancer and documentation of cutaneous involvement.

A retrospective study of preoperative CA 125 levels in 82 patients with ovarian cancer.

INTRODUCTION: The aim of our study was to investigate preoperative serum CA 125 as a prognostic factor in patients with ovarian carcinoma. METHODS: A retrospective analysis was conducted on 82 patients with ovarian carcinoma treated at our Unit between 1998 and 2000 who had a serum CA 125, evaluated by a commercially available radioimmunoassay, prior to cytoreductive surgery. We looked for an association between preoperative CA 125 and known prognostic factors of ovarian cancer. We compared outcomes of patients with preoperative CA 125 at or below to 500 U/ml with outcomes of patients with preoperative CA 125 above 500 U/ml. RESULTS: A significant ( p<0.002) correlation between stage and CA 125 serum levels was found as 16 out of 18 stage I-II patients (89%) had CA 125 level 500 U/ml. Among stage III and IV patients there was nonstatistically significant relation between serum CA 125 and histologic grade (G1+G2 vs. G3) and residual disease (<1 cm vs. >1 cm) after primary cytoreductive surgery. Preoperative serum CA-125 level did not predict either recurrences or disease free interval. CONCLUSION: Preoperative CA 125 correlated well with FIGO stage but not with age, grade, residual disease after primary surgery, relapse and disease free interval.

Gynecological malignancies in elderly patients: is age 70 a limit to standard-dose chemotherapy? An Italian retrospective toxicity multicentric study.

OBJECTIVE: One hundred and forty-eight consecutive gynecological oncological patients aged >or=70 were administered chemotherapy during the years 1990-2000. METHODS: Median age was 73 years (range 70-84). Fifty-five (37.2%) women were over 75 years old. One or more comorbid conditions were present in 118 (79.7%) patients. Standard schedules were administered to 97.3% of cases, with a total number of 1046 cycles of therapy administered (median, 6; range, 1-35, per patient). RESULTS: Of a total of 233 chemotherapy regimens globally administered, G3-G4 hematological toxicity was documented in 38.2% of cases. Only 10 (6.8%) of the 148 patients discontinued treatment because of G3-G4 hematological toxicity. No severe nonhematological toxicity was observed. Two dose reductions and three treatment delays, but no discontinuation of treatment, were required during second-line regimens. Treatment delay >7 days was required in 16.9% of cases. CONCLUSIONS: Chronological age did not adversely influence the ability to receive aggressive treatment.