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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.

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.

Among gynecological pathologies, cervical cancer has always represented a health problem with great social impact. The giant strides made as a result of both the screening programs perfected and implemented over the years and the use of new and accurate technological equipment have in fact significantly improved our clinical approach in the management and personalized diagnosis of precancerous lesions of the cervix. In this context, the advent of artificial intelligence and digital algorithms could represent new directions available to gynecologists and pathologists for the following: (i) the standardization of screening procedures, (ii) the identification of increasingly early lesions, and (iii) heightening the diagnostic accuracy of targeted biopsies and prognostic analysis of cervical cancer. The purpose of our review was to evaluate to what extent artificial intelligence can be integrated into current protocols, to identify the strengths and/or weaknesses of this method, and, above all, determine what we should expect in the future to develop increasingly safer solutions, as well as increasingly targeted and personalized screening programs for these patients. Furthermore, in an innovative way, and through a multidisciplinary vision (gynecologists, pathologists, and computer scientists), with this manuscript, we highlight a key role that AI could have in the management of HPV-positive patients. In our vision, AI will move from being a simple diagnostic device to being used as a tool for performing risk analyses of HPV-related disease progression. This is thanks to the ability of new software not only to analyze clinical and histopathological images but also to evaluate and integrate clinical elements such as vaccines, the composition of the microbiota, and the immune status of patients. In fact, the single-factor evaluation of high-risk HPV strains represents a limitation that must be overcome. Therefore, AI, through multifactorial analysis, will be able to generate a risk score that will better stratify patients and will support clinicians in choosing highly personalized treatments overall. Our study remains an innovative proposal and idea, as the literature to date presents a limitation in that this topic is considered niche, but we believe that the union of common efforts can overcome this limitation.

Objective: Colorectal cancer (CRC) during pregnancy is a rare occurrence, with a reported incidence of 0.8 cases per 100,000 pregnancies. Managing CRC during pregnancy poses substantial challenges for clinicians: the diagnosis is often complicated and delayed due to symptom overlap with pregnancy-related manifestations, and medical imaging is constrained by safety concerns for the foetus. Methods: This article presents two cases of advanced CRC diagnosed and managed during pregnancy. Additionally, we conducted a systematic review of the literature to assess diagnostic and prognostic factors involved in CRC in pregnant individuals. The systematic review, with pre-registration and approval through Prospero, involved an extensive search of medical databases (Pubmed, Web of Science, Scopus and Scholar) and statistical analysis using t-test for continuous variables and chi square for dichotomous variables. Results: A total of 1058 studies were identified. After applying exclusion criteria, sixty-six studies were included. Women whose initial symptoms were severe abdominal pain not responsive to common medical treatments and constipation (acute abdomen) had a mean gestational age at delivery lower than those who presented with paucisymptomatic onset. In our study groups, women who underwent chemotherapy during pregnancy had a higher mean gestational age at delivery and did not experience worse neonatal outcomes compared to those who did not undergo chemotherapy. Conclusions: CRC during pregnancy poses unique diagnostic and therapeutic challenges. Collaborative efforts among various medical disciplines are essential to manage CRC during pregnancy.

The objective of this research is to evaluate cervical regeneration after large loop excision of the transformation zone (LLETZ) through the identification of a new sonographic reference point at the level of the uterine margins. In the period March 2021–January 2022, a total of 42 patients affected by CIN 2–3 were treated with LLETZ at the University Hospital of Bari (Italy). Before performing LLETZ, cervical length and volume were measured with trans-vaginal 3D ultrasound. From the multiplanar images, the cervical volume was obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL™) program with manual contour mode. The line that connects the points where the common trunk of the uterine arteries reaches the uterus splitting into the ascending major branch and the cervical branch was considered as the upper limit of the cervical canal. From the acquired 3D volume, the length and the volume of the cervix were measured between this line and the external uterine os. Immediately after LLETZ, the removed cone was measured using Vernier’s caliper, and before fixation in formalin, the volume of the excised tissue was evaluated by the fluid displacement technique based on the Archimedes principle. The proportion of excised cervical volume was 25.50 ± 17.43%. The volume and the height of the excised cone were 1.61 ± 0.82 mL and 9.65 ± 2.49 mm corresponding to 14.74 ± 11.91% and 36.26 ± 15.49% of baseline values, respectively. The volume and length of the residual cervix were also assessed using 3D ultrasound up to the sixth month after excision. At 6 weeks, about 50% of cases reported an unchanged or lower cervical volume compared to the baseline pre-LLETZ values. The average percentage of volume regeneration in examined patients was equal to 9.77 ± 55.33%. In the same period, the cervical length regeneration rate was 69.41 ± 14.8%. Three months after LLETZ, a volume regeneration rate of 41.36 ± 28.31% was found. For the length, an average regeneration rate of 82.48 ± 15.25% was calculated. Finally, at 6 months, the percentage of regeneration of the excised volume was 90.99 ± 34.91%. The regrowth percentage of the cervical length was 91.07 ± 8.03%. The cervix measurement technique that we have proposed has the advantage of identifying an unequivocal reference point in 3D cervical measurement. Ultrasound 3D evaluation could be useful in the clinical practice to evaluate the cervical tissue deficit and express the “potential of cervical regeneration” as well as provide the surgeon useful information about the cervical length.

Dilatation of the fetal cerebral ventricles (ventriculomegaly) is a generic sonographic sign that is common to several pathological entities carrying different prognoses. The main causes of fetal ventriculomegaly are aqueductal stenosis, Chiari II malformation, Dandy-Walker complex, and agenesis of the corpus callosum. Ventriculomegaly is easily recognized by ultrasound by measuring the atrial width. This simple measure allows the recognition of mild forms of ventricular dilatation and is used in screening for ventriculomegaly. However, although the diagnosis of ventriculomegaly is easy, the prenatal identification of the cause of ventricular dilatation is a more difficult task. For this purpose the evaluation of the posterior fossa in association with the visualization of the corpus callosum is useful. Research into the causes of ventriculomegaly is clinically useful, since the prognosis mainly depends on the etiology and on the presence of associated abnormalities. In this article the role of prenatal sonography in determining the cause of the ventriculomegaly is reviewed, as well as the prognostic value of the prenatal sonographic findings.

All cancers develop as a result of mutations in genes. DNA damage induces genomic instability and subsequently increases susceptibility to tumorigenesis. Women who carry mutations of BRCA 1 and BRCA2 genes have an augmented risk of breast and ovarian cancer and a markedly augmented probability of dying because of cancer compared to the general population. As a result, international guidelines recommend that all BRCA1\\2 mutation carriers be offered risk-reducing bilateral salpingo-oophorectomy at an early age to reduce the risk of cancer and decrease the mortality rate of this high-risk population. NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy in pre-menopausal women, between 35–40 years in BRCA1 mutation carriers and between 40–45 years in BRCA2 mutation carriers. Unfortunately, the well-documented reduction of cancer risk is counterbalanced by early sterility and premature ovarian failure with an early onset of secondary menopausal syndromes such as neuromotor, cardiovascular, cognitive and urogenital deficiency. Hormonal replacement therapy significantly compensates for hormonal deprivation and counteracts menopausal syndrome morbidity and mortality; however, some data suggest a possible correlation between hormonal medications and cancer risk, especially in BRCA1\\2 carriers who undergo long-term regimens. Conversely, short-term treatment before the age of natural menopause does not appear to increase the cancer risk in BRCA1 mutation carriers without a personal history of breast cancer after prophylactic surgery. Few data are available on BRCA2 mutation carriers and more well-designed studies are needed. In conclusion, clinicians should propose short-term hormone replacement therapy to BRCA 1 carriers to counteract hormonal deprivation; personalized counselling should be offered to BRCA2 mutation carriers for a balance between the risks and benefits of the treatment.

Background: Vulvar lymphangiectasia (VLA) is a rare condition characterized by the abnormal dilation of lymphatic vessels in the vulvar region, often secondary to surgery or radiation therapy for malignancies. Its clinical presentation closely resembles other dermatological conditions, posing challenges for accurate diagnosis and appropriate management. This study aims to present a rare case of VLA occurring decades after cervical carcinoma surgery, contributing to the limited literature on this condition and offering insights into its differential diagnosis and management. Methods: A 70-year-old female patient presented with multiple fluid-filled vesicles in the vulvar region appearing 36 years after undergoing radical hysterectomy with pelvic lymphadenectomy for cervical carcinoma. The lesions were biopsied, and histopathological and immunohistochemical analyses were performed to confirm the diagnosis. A review of the existing literature on VLA was conducted to contextualize this case. Results: A histopathological examination revealed papillomatous lesions with hyper-keratosis, dilated lymphatic vessels, and no signs of atypia, consistent with VLA. An immunohistochemical analysis confirmed the lymphatic nature of the lesions. Due to the patient’s comorbidities, asymptomatic presentation, and lesion stability, conservative management with regular follow-up was chosen. No progression or complications were observed during the 12-month follow-up period. Conclusions: This case highlights the importance of considering VLA in patients presenting with vulvar vesicles, especially those with a history of lymphatic disruption. An accurate diagnosis through histopathological and immunohistochemical techniques is essential to distinguish VLA from other conditions. Conservative management may be appropriate for asymptomatic cases, but tailored therapeutic strategies are needed to address symptomatic or disfiguring lesions.

Introduction/BackgroundManaging pregnancy-associated colorectal cancer (PACrC) poses substantial challenges: the diagnosis is complicated due to symptom overlap with pregnancy-related manifestations and medical imaging, chemotherapy and surgery are constrained by safety concerns for the foetus.MethodologyThe case report was extracted from our hospital records. The literature review was conducted with PRISMA methodology.ResultsA 33-year-old, 19 weeks-of-gestation (WG) pregnant patient presented to the emergency room due to severe abdominal pain and underwent urgent laparotomy with Hartmann sigmoid resection and colostomy due to sigmoid volvulus; the histopathology unveiled a sigmoid adenocarcinoma G2pT3bN0. At 23WG, an abdominal MRI showed a placental neoformation and multiple hepatic nodules suggestive of neoplastic lesions (Figure 1). Our multidisciplinary team proposed adjuvant chemotherapy with infusion of five cycles of FOLFOX biweekly (75%dosage). The foetus exhibited steady growth throughout-the-treatment and the caesarean section was conducted at 37WG, resulting in the birth of a 2940 g infant with arterial pH of 7.32, Apgar 8–10. The placental histopathology was negative. Given the favourable response to first-line-chemotherapy, hepatic metastasectomy was performed and twelve cycles of FOLFOX (100%dosage) plus BEVACIZUMAB were administered. One-year post-diagnosis, the patient continues the chemotherapy, with optimal performance-status. Additionally, her infant achieved normal developmental milestones.ConclusionPACrC poses unique diagnostic and therapeutic challenges. Our statistical analysis on 66 studies revealed the importance of early diagnosis of PACrC: a delay of diagnosis often led to urgent surgery, and poor maternal\\neonatal outcomes with higher caesarean rates and earlier WG at-delivery. We found that women with an early diagnosis were more likely to undergo chemotherapy during pregnancy, resulting in better control of the disease and later WG at-delivery. Chemotherapy during pregnancy is a feasible and safe treatment for PACrC: despite the uncertainties about the effects on the foetus, we did not find different neonatal outcomes between those exposed those who did not.DisclosuresThe authors declare no conflicts of interests.Abstract 739 Figure 1A: MRI images showing the formation in amniotic sac; B: TC image showing the hepatic metastases

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.