Search Results (718)

In today’s oncology, immunotherapy arises as a potent complement for conventional cancer treatment, allowing for obtaining better patient outcomes. B7-H3 (CD276) is a member of the B7 protein family, which emerged as an attractive target for the treatment of various tumors. The molecule modulates anti-cancer immune responses, acting through diverse signaling pathways and cell populations. It has been implicated in the pathogenesis of numerous malignancies, including melanoma, gliomas, lung cancer, gynecological cancers, renal cancer, gastrointestinal tumors, and others, fostering the immunosuppressive environment and marking worse prognosis for the patients. B7-H3 targeting therapies, such as monoclonal antibodies, antibody–drug conjugates, and CAR T-cells, present promising results in preclinical studies and are the subject of ongoing clinical trials. CAR-T therapies against B7-H3 have demonstrated utility in malignancies such as melanoma, glioblastoma, prostate cancer, and RCC. Moreover, ADCs targeting B7-H3 exerted cytotoxic effects on glioblastoma, neuroblastoma cells, prostate cancer, and craniopharyngioma models. B7-H3-targeting also delivers promising results in combined therapies, enhancing the response to other immune checkpoint inhibitors and giving hope for the development of approaches with minimized adverse effects. However, the strategies of B7-H3 blocking deliver substantial challenges, such as poorly understood molecular mechanisms behind B7-H3 protumor properties or therapy toxicity. In this review, we discuss B7-H3’s role in modulating immune responses, its significance for various malignancies, and clinical trials evaluating anti-B7-H3 immunotherapeutic strategies, focusing on the clinical potential of the molecule. Full article

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

Mature teratomas account for approximately 20% of all ovarian tumors identified in pathological studies. Benign or malignant somatic neoplasms developing within teratomas can arise from any tissue in up to 2% of mature cystic teratomas, including low-grade malignant mucinous neoplasms. This report presents the case of a 34-year-old woman with no previous gynecological or general health issues, who was admitted to our Hospital after an asymptomatic pelvic mass was detected during a routine exam. A transvaginal ultrasound revealed a unilateral pelvic mass in the left adnexal region, measuring 8 cm. The CT scan showed a cystic-appearing formation measuring nearly 12 cm, which indented the bladder dome. Final diagnosis indicated a mucinous carcinoma arising from a mucinous borderline lesion within the context of a mature ovarian teratoma. No other involvement or lymphadenopathies were detected on 18FDG-PET CT scan, and the patient is now well and free of recurrences. Full article

Ovarian cancer is a deadly gynecological malignancy that will affect about 21,000 women and result in almost 153,000 deaths in the United States in 2025. New clinical tools that facilitate early diagnosis and treatment of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. We utilized a previously identified single-strand DNA aptamer RLA01 that binds and internalizes into target epithelial ovarian cancer cells to label PLGA-based nanoparticles and determine their ability to selectively target EOC cells and deliver payloads for cellular internalization. Nanoparticles labeled with RLA01 significantly enhanced cellular uptake 20–85% by receptor-mediated endocytosis into target EOC Caov-3 cells and inhibited cellular uptake in non-target HOSE 6-3 cells. Further, labeling of paclitaxel-loaded nanoparticles with RLA01 significantly decreased cell proliferation and induced apoptosis. A preliminary pilot study looking at the in vivo stability of aptamers demonstrated their ability to promote retention and honing of nanoparticles at tumors. These data demonstrate the effective combinatorial use of aptamer RLA01 and nanoparticle technologies for the direct targeting of tumor cell populations both in vitro and in vivo. Full article

Background and Objectives: The causes and clinical outcomes of renal perfusion abnormalities occurring after para-aortic lymphadenectomy (PANDx) for gynecologic malignancies are unknown. We investigated the potential involvement of accessory renal artery (ARA) obstruction in their development by reassessing perioperative contrast-enhanced computed tomography (CECT). Materials and Methods: This retrospective study investigated a clinical database to identify urinary contrast defects using CECT in all patients who had undergone PANDx between January 2020 and December 2024. The perfusion defects in the kidney detected by CECT were extracted by a gynecologic oncologist and evaluated by a radiologist and urologist for suspected obstruction of ARAs. Results: Postoperative renal contrast defects were observed in 3.8% (6/157) of patients. Renal parenchymal fibrosis, cortical atrophy, and parenchymal thinning were observed as universal findings in all patients showing renal contrast defects. In five of the six cases, ARAs supplying the infarcted renal segments were identified on preoperative CECT, and arterial obstruction was confirmed on postoperative imaging. The remaining case was considered to be latent pyelonephritis. All five patients underwent laparotomy, and preoperative CECT failed to detect ARAs. The median resected para-aortic lymph node was 23 nodes (range: 15–33) in five patients, showing no statistically significant difference compared to patients without perfusion abnormalities (p = 0.19). Postoperative serum creatinine levels remained stable. Conclusions: ARA obstruction appears to be a risk factor for segmental renal infarction after para-aortic lymphadenectomy in gynecological malignancies; however, the clinical impact on urinary function may be limited. Awareness of this potential complication is essential for gynecologic oncologists performing PANDx. Full article

Background and Clinical Significance: Endometriosis is a common gynecological disease that can occasionally be associated with malignant transformation. The most common site of malignant transformation is the ovary, but there can also be rare extragonadal endometriosis-associated malignancy sites, such as the intestines, rectovaginal septum, and abdominal wall. A low number of malignant degenerations of rectal endometriosis are described in the literature. However, the majority of these cases report endometrioid adenocarcinoma as the most frequent histopathological type of tumor. On the other hand, Müllerian clear cell carcinoma is sporadic. Case Presentation: We present the case of a 43-year-old woman with clear cell carcinoma of the rectum, which developed on an endometriosis nodule, and the surgical outcome. Imaging of the case was performed by MRI. The patient was offered curative surgery. The pathology report confirmed a clear cell carcinoma developed on an endometriosis lesion, and immunochemistry helped in the characterization of the tumor. The patient developed a rectovaginal fistula. An ileostomy and surgical repair of the fistulous opening were performed, with a favorable postoperative recovery. Conclusions: Malignant transformation of endometriosis lesions is possible and should be taken into consideration. Müllerian clear cell carcinoma development within rectovaginal endometriosis is extremely rare. Full article

Background: Lower limb lymphedema (LLL) is a frequent complication after gynecological cancer treatment, with a significant impact on quality of life. Despite the common use of compression therapy in managing established lymphedema, its role in prevention remains insufficiently explored. Methods: In this prospective randomized study, 64 women treated for gynecological malignancies were assigned to either a compression group (CG) using medium-pressure stockings (23–32 mmHg) or a no-compression group (NCG). All participants received standard education and physical activity guidance. Limb volume, symptom burden, and quality of life were assessed over 12 months. Results: The incidence of LLL was significantly lower in the CG (3.4%) compared to the NCG (38%, p = 0.003). Compression use resulted in significant reductions in limb volume and symptom severity, as well as improved physical functioning. Compliance with compression therapy was high, and patients reported good comfort and usability. Conclusions: Medium-pressure compression stockings combined with education and physical activity are effective and well-tolerated in preventing LLL following gynecological cancer treatment. Full article

Endometrial cancer is one of the most prevalent gynecologic malignancies in developed countries, with its incidence steadily increasing each year. Early diagnosis is crucial for a favorable prognosis; however, certain patients experience recurrence and distant metastasis after surgery, similar to advanced cancer patients, with limited treatment options. Therefore, effective strategies for early screening, diagnosis, predicting local recurrence, and guiding rapid treatment interventions are essential for improving survival rates and prognosis. Liquid biopsy, a method known for being non-invasive, safe, and effective, has attracted widespread attention for cancer diagnosis and treatment. Although its clinical application in endometrial cancer is less established than in other cancers, research on biomarkers using liquid biopsy in endometrial cancer patients is currently in progress. This review examines the latest advancements in non-invasive biomarkers identified through liquid biopsy and provides a comprehensive overview of their clinical applications in endometrial cancer. Additionally, it discusses the challenges and future prospects of liquid biopsy, offering valuable insights into the diagnosis and personalized treatment of endometrial cancer. Full article

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation. Full article

Background/Objectives: Endometrial cancer (EC) is the most prevalent gynecological malignancy, with increasing incidence and mortality. HOXA5, a developmental transcription factor, has been linked to prognosis in various cancers, but its role in EC remains unclear. This study aimed to evaluate the prognostic potential of HOXA5 in EC and to explore its association with common tumor-related proteins. Methods: We analyzed 75 EC tissue samples using immunohistochemistry to evaluate HOXA5 expression and its association with clinicopathological features and tumor-related biomarkers, including Ki-67, CD31, and fibronectin. Statistical analyses included logistic regression and Kaplan–Meier survival analysis. Results: High HOXA5 expression was significantly associated with elevated Ki-67 levels (p = 0.001) but paradoxically correlated with improved overall survival (p = 0.026). CD31 and fibronectin levels were significantly lower in the high-HOXA5 group (p = 0.007 and p = 0.001, respectively), suggesting reduced angiogenic and invasive potential. However, neither marker remained significant in multivariable analysis. Conclusions: HOXA5 may exert a dual role in EC by promoting proliferation while limiting tumor progression via suppression of angiogenesis and matrix remodeling. It holds potential as a prognostic biomarker and therapeutic target. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy, increasingly affecting premenopausal women. While hysterectomy is the standard treatment, it eliminates reproductive potential, highlighting the need for effective fertility-sparing alternatives. Current ESHRE/ESGO/ESGE guidelines recommend progestin-based therapies, often with hysteroscopic resection. However, these are based on limited pharmacological options and moderate to low-quality evidence. Novel and combination therapies have shown promise but remain absent from current clinical guidelines. This review aims to evaluate the efficacy and safety of fertility-preserving treatments for early-stage EC, emphasizing the need to update current strategies based on emerging data. Methods: A systematic review and meta-analysis will follow PRISMA guidelines and the Cochrane Handbook. Eligible studies, including randomized and non-randomized designs, will assess fertility-preserving treatments for early-stage EC. Data will be extracted on complete response, recurrence, and long-term fertility outcomes. The GRADE system will assess evidence certainty. Risk of bias will be evaluated using RoB 2 for RCTs and ROBINS-I for non-randomized studies. Meta-analysis will be performed if sufficient data are available. Conclusions: This review will provide a comprehensive analysis of fertility-sparing treatments for early-stage EC, support personalized strategies, identify evidence gaps, and guide future research. Trial registration—Prospero: CRD420251032161. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC and explored clinical moderators of change. Methods: Eighty-eight consecutive patients (mean age 59.1 ± 10.7 years) completed the SF-36, WHOQOL-BREF, EORTC QLQ-C30, and 10-item Perceived Stress Scale (PSS-10) at baseline (pre-therapy) and six months after cytoreductive surgery ± platinum-based chemotherapy. Stage (FIGO I–II vs. III–IV) and treatment pathway (primary debulking surgery, neoadjuvant chemotherapy plus interval debulking, chemotherapy only) data were recorded. Results: Global QoL improved significantly (EORTC Global Health +5.9 ± 7.7 points; p < 0.001) while perceived stress declined (ΔPSS −3.6 ± 5.1; p < 0.001). SF-36 Physical Functioning rose 4.7 ± 7.9 points (p < 0.001) and Mental Health 4.4 ± 7.9 points (p = 0.004). The WHOQOL Physical and Psychological domains gained 4.7 ± 7.1 and 4.3 ± 7.4 points, respectively (both p < 0.01). Advanced-stage patients experienced larger stress reductions than early-stage patients (−4.1 ± 2.7 vs. −2.9 ± 2.2; p = 0.028) but comparable QoL gains. Greater stress relief correlated with greater mental-health improvement (r = −0.51) and global-health gains (r = −0.45) (all p < 0.001). Treatment pathway did not significantly influence trajectories. Conclusions: Early survivorship after first-line ovarian-cancer therapy was characterized by the clinically meaningful recovery of physical and emotional functioning together with the moderate alleviation of perceived stress. Improvements were observed irrespective of stage and treatment strategy, suggesting that contemporary multimodal regimens do not inevitably compromise patient-reported outcomes. Our estimates provide preliminary effect sizes that should be validated in multi-center cohorts with longer follow-up. Full article

High-grade serous ovarian cancer (HGSOC) is an aggressive gynecological malignancy characterized by intraperitoneal spread and chemotherapy resistance. Chemotherapies have demonstrated limited effectiveness in HGSOC, underscoring the urgent need to evaluate how the tumor microenvironment (TME) was reshaped by chemotherapy in different sites of tumor foci. In this study, we performed single-cell transcriptomic analysis to explore the TME in samples obtained from various sites of tumor foci, with or without the history of Neoadjuvant chemotherapy (NACT). We discovered that chemotherapy reshaped the tumor immune microenvironment, evident through the reduction in human leukocyte antigen (HLA) diversity and the increase in PDCD1/CD274 in CD8_ANXA1, LAMP3+ dendritic cell (DC_LAMP3), and EREG+ monocytes (mono_EREG). Moreover, cancer.cell.2, cancer-associated C3+ fibroblasts (CAF_C3), and Fibrocyte_CD34, which are prone to accumulate in the metastatic site and post-NACT group, harbored poor clinical outcome, reflected in the immune exclusion and tumor progression signaling. Cell–cell communication identified a stronger interaction between cancer.cell.2 and CAF_C3, as well as Fibrocyte_CD34, in post-NACT samples, indicating that chemotherapy reshapes pre-existing cell clusters in a site-dependent manner. Our findings suggest that chemotherapy and sites of foci were critical for the transcriptional reprogramming of pre-existed cell clusters. Our study offers a single-cell phenotype data substrate from which to develop a personalized combination of chemotherapy and immunotherapy. Full article

Background: Liposarcoma (LPS) is a rare malignant tumor, but it is also one of the most common adult soft-tissue sarcomas. Myxoid liposarcoma (MLPS) accounts for 30% of all LPS cases. Diagnosis during pregnancy and the puerperium is very rarely reported, and only a few cases have been reported in the thigh. Case presentation: We report the case of a 36-year-old female patient on the 11th day of the puerperium after a cesarean section. The patient presented to the gynecology ward owing to the sudden appearance of a tumor in the medial part of her right thigh. The lesion was non-painful, mobile, soft, approximately 20 cm in diameter, and protruded above the level of the rest of the thigh surface. A suspicion of hematoma was raised. The final diagnosis was high-grade MLPS. Conclusions: An MLPS diagnosis is uncommon in female patients and even rarer during pregnancy. This case represents a novel occurrence, as the first instance in which symptoms manifested during the puerperium. Proper treatment and early detection could improve disease outcomes. Full article

Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit from local treatments; Stereotactic Body Radiotherapy (SBRT) might be considered in selected patients with oligometastatic presentation. Materials/Methods: Oligometastases were defined according to recent ESTRO/EORTC consensus. Inclusion criteria were as follows: ECOG PS ≤ 2, written informed consent, up to five lesions to be treated at the same time, patients treated with radiotherapy schedules applying minimum 6 Gy per fraction. The primary endpoint of the study was local control (LC); acute and late toxicity, distant progression-free survival (DPFS), time-to-next systemic treatment (TNST), polymetastatic-free survival (PMFS) and overall survival (OS) were secondary endpoints. Toxicity was assessed according to CTCAE criteria v5.0. Statistical associations between clinical variables and outcomes were assessed using Fisher’s exact test, and Kruskal–Wallis test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Between April 2020 and September 2024 a total of 26 oligometastatic lesions located in the peritoneum or in the abdominal wall detected in 20 patients received SBRT with Helical Tomotherapy. All cases have been assessed by a multidisciplinary team. Only in three patients out of twenty did more than one lesion receive SBRT: two lesions in two patients, and five lesions in a single case of colorectal cancer with ongoing third-line systemic treatment. Median total dose was 30 Gy (27–35 Gy) in five fractions (3–5). The most frequent primary neoplasm was ovarian cancer in 14/20, endometrial in 2/20, while the remaining were colorectal, vaginal, pancreatic and non-small cell lung cancer. Four lesions were located in the abdominal wall, while the remaining twenty-two were located in the peritoneum. Concurrent systemic therapy was administered in 18/20 patients. With a median follow-up of 15 months (range, 6–59), our 1-year LC was 100%, while 1-year DPFS, PMFS, TNTS and OS rates were 54%, 69%, 61% and 83%, respectively. Abdominal wall location and treatment of a subsequent oligometastatic recurrence with a second course of SBRT were both significantly associated with improved OS (p = 0.03 and p = 0.04, respectively). No G ≥ 3 adverse events occurred. Conclusion: Our preliminary data support the use of SBRT in selected cases of oligometastatic disease located in the peritoneum or in the abdominal wall with excellent results in terms of tolerability and promising clinical outcomes. Full article