Lymphovenous anastomosis and complex decongestive therapy for severe deformed lymphedema with recurrent infection: A case report.

BACKGROUND: Lower extremity lymphedema is a common complication following treatment for gynecological malignancies. Its incidence rate can reach up to 70%, affecting ~20 million people worldwide. However, specialized treatment centers are scarce, and there is a lack of consensus on treatment approaches. Furthermore, there are even fewer reports on the systematic and effective treatment of severe lymphedema with malformations. Effective management of this condition remains a significant challenge for clinicians. CASE SUMMARY: A 40-year-old woman developed bilateral leg swelling 6 years after receiving treatment for endometrial cancer. Since August 2018, she experienced > 30 episodes of lymphangitis. Upon presentation, she exhibited bilateral leg swelling and deformation, with four large swellings in the posterior thigh that impeded movement, and pain in the limbs. Skin manifestations included lichenoid lesions and features of deep sclerosis. Radionuclide lymphoscintigraphy confirmed the diagnosis of lower limb lymphedema. After 6 mo of complex decongestive therapy (CDT) and three lymphaticovenous anastomosis (LVA) treatments, the patient lost 49 kg in weight. She also experienced a maximum circumference reduction of 35.2 cm in the left lower limb and 37.5 cm in the right lower limb. The leg pain disappeared, her swelling significantly decreased, and she regained the ability to walk, cycle, and run normally. CONCLUSION: The combined application of CDT and LVA therapy demonstrates significant positive effects in the treatment of severe, deformed stage III lymphedema.

Ferroptosis: a novel strategy to overcome chemoresistance in gynecological malignancies.

Ferroptosis is an iron-dependent form of cell death, distinct from apoptosis, necrosis, and autophagy, and is characterized by altered iron homeostasis, reduced defense against oxidative stress, and increased lipid peroxidation. Extensive research has demonstrated that ferroptosis plays a crucial role in the treatment of gynecological malignancies, offering new strategies for cancer prevention and therapy. However, chemotherapy resistance poses an urgent challenge, significantly hindering therapeutic efficacy. Increasing evidence suggests that inducing ferroptosis can reverse tumor resistance to chemotherapy. This article reviews the mechanisms of ferroptosis and discusses its potential in reversing chemotherapy resistance in gynecological cancers. We summarized three critical pathways in regulating ferroptosis: the regulation of glutathione peroxidase 4 (GPX4), iron metabolism, and lipid peroxidation pathways, considering their prospects and challenges as strategies to reverse chemotherapy resistance. These studies provide a fresh perspective for future cancer treatment modalities.

Real-world drug treatment models of novel targeted drugs in Chinese patients with gynecological cancer from 2017 to 2021: A cross-sectional analysis.

Objective: The significance of novel anti-tumor pharmaceuticals in the treatment of gynecological tumors is growing, but there is no consensus regarding the optimal drug delivery strategy for gynecological tumors. This study seeks to investigate the treatment models of novel anti-tumor drugs in patients with gynecological cancer in China over the past five years, with a particular emphasis on the trend and rationality of their use. Method: We conducted a cross-sectional analysis of data from a China Medical Association-supervised hospital prescription analysis cooperation initiative. The data was derived from prescriptions written for patients diagnosed with cancer between January 2017 and December 2021. The required information for patients was extracted. Our study included 2308 patients that were diagnosed as gynecological tumors which were treated with novel antineoplastic targeted drugs. Patients were categorized by age and region. Then, the selection, application, and indications of the most essential treatment pharmaceuticals were investigated. We evaluated anti-tumor prescription information based on the recommended drug labeling protocol and the most recent domestic and international guidelines.Excel 2013 and SPSS (version 25; SPSS Inc., Chicago, IL, United States) were utilized to conduct statistical analysis.In addition，we also used Sankey diagram to evalute the relation between novel antineoplastic targeted drugs and corresponding diagnoses. Result: The top three cities for the 2308 patients included in this study were Guangzhou (28.51%), Hangzhou (21.79%), and Beijing (20.06%). In the past five years, the average age of medication patients was 55.61-year-old, with 37.86% of women aged of 51-60. Each patient's primary treatment regimens were statistically analyzed, yielding a total of 16 single-drug and combination-drug primary treatment regimens. Bevacizumab, Olaparib, Trastuzumab, Apatinib, and Arotinib were the top five treatment strategies. The maximum proportion, up to 0.74%, was attributed to the combination of human epidermal growth factor receptor-2 inhibitor (HER2i), including Trastuzumab and Parostuzumab. Vascular endothelial growth factor receptor inhibitor (VEGFRi), including Bevacizumab and Apatinib was the most frequently prescribed medication for outpatients in major cities across the country. According to the 5-year change in time, poly adenosine diphosphate ribose polymerase inhibitor (PARPi) rated first in terms of usage, with Olaparib ranking first with the highest concentration of 33.44% and Niraparib ranking second overall with the fastest growth in 2021. The quantity of VEGFRi variants utilized was the greatest, and their proportion of total usage increased annually. The top five drugs by total drug costs were Bevacizumab, Carelizumab, Olaparib, Trastuzumab, and Apatinib. However, the top five drugs by per capita drug cost were Olaparib + Bevacizumab, Bevacizumab + Sidilimab, Arrotinib + Olaparib, Olaparib, and Patuzumab + Trastuzumab. Conclusion: The incidence rate of gynecological tumor patients rises with age, and the cost of drug treatment has risen annually over the past five years, which is also related to the rising incidence rate of tumors in recent years. Bevacizumab rates first in the drug treatment scheme for the application of novel anti-tumor targeted drugs, which may be related to the widespread use of VEGFRi drugs in gynecological and reproductive tumors. Breast cancer and adenocarcinoma are at the top of the female cancer incidence spectrum, which may explain why HER2i multi-drug combination regimen rates highest among multi-drug combination regimens. Future research may concentrate on how novel anti-tumor targeted drugs can minimize the economic burden and maximize the benefits of patient treatment for patients with gynecological cancer.

Targeting WEE1 Kinase in Gynecological Malignancies.

WEE1 kinase is involved in the G2/M cell cycle checkpoint control and DNA damage repair. A functional G2/M checkpoint is crucial for DNA repair in cancer cells with p53 mutations since they lack a functional G1/S checkpoint. Targeted inhibition of WEE1 kinase may cause tumor cell apoptosis, primarily, in the p53-deficient tumor, via bypassing the G2/M checkpoint without properly repairing DNA damage, resulting in genome instability and chromosomal deletion. This review aims to provide a comprehensive overview of the biological role of WEE1 kinase and the potential of WEE1 inhibitor (WEE1i) for treating gynecological malignancies. We conducted a thorough literature search from 2001 to September 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of WEE1i and gynecologic oncology. WEE1i has been shown to inhibit tumor activity and enhance the sensitivity of chemotherapy or radiotherapy in preclinical models, particularly in p53-mutated gynecologic cancer models, although not exclusively. Recently, WEE1i alone or combined with genotoxic agents has confirmed its efficacy and safety in Phase I/II gynecological malignancies clinical trials. Furthermore, it has become increasingly clear that other inhibitors of DNA damage pathways show synthetic lethality with WEE1i, and WEE1 modulates therapeutic immune responses, providing a rationale for the combination of WEE1i and immune checkpoint blockade. In this review, we summarize the biological function of WEE1 kinase, development of WEE1i, and outline the preclinical and clinical data available on the investigation of WEE1i for treating gynecologic malignancies.

Reproductive concerns and its correlation with fear of recurrence and level of family support in patients of childbearing age with gynecologic malignancies.

BACKGROUND: To discuss the current status of reproductive concerns and its correlation with fear of recurrence and level of family support in patients of childbearing age with gynecologic malignancies. METHODS: A convenient sampling method was used to enroll 188 patients with gynecologic malignancies in Nanjing Maternity and Child Health Care Hospital, Nanjing Drum Tower Hospital, General Hospital of Ningxia Medical University, and Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from September 2022 to April 2023. Patients were assessed using general information questionnaire, Reproductive Concerns After Cancer Scale (RCAC), Fear of Cancer Recurrence Inventory (FCRI) questionnaire, and Perceived Social Support-Family (PSS-FA) Scale. RESULTS: Among patients of childbearing age with gynecologic malignancies, the total RCAC score was (54.35 ± 7.52), indicating a moderate level of reproductive concerns. Patients scored (20.98 ± 4.51) on FCRI, implying a moderate level of fear of recurrence. The PSS-FA score was (9.57 ± 2.76), denoting a moderate level of family support. The total score and each dimensional score of RCAC were positively correlated with FCRI total score (P < 0.05), and negatively correlated with PSS-FA total score (P < 0.05). Fear of recurrence, family support level, number of children, educational background, treatment modality, and fertility intention were influencing factors for reproductive concerns in patients of childbearing age with gynecologic malignancies (all P < 0.05). CONCLUSION: The reproductive concerns, fear of recurrence and family support are all at moderate levels in patients of childbearing age with gynecologic malignancies, and reproductive concerns are positively correlated with fear of recurrence and negatively correlated with family support.

Occurrence and Management of Immunotherapy-Associated Adverse Events in Patients with Gynecological Cancers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as an essential therapeutic approach in treating many solid tumors. ICIs enhance the body's anti-tumor T-cell activity, resulting in a novel spectrum of immunotherapy-related side effects. This novel spectrum of adverse events differs significantly from the side effects of conventional chemotherapy. It, therefore, requires special attention in the diagnosis and management of immunotherapy-related adverse events (irAEs). The present study aimed to retrospectively analyze the incidence, diagnosis, and management of irAEs in patients with gynecologic malignancies who received ICIs and to discuss these findings in the context of the recent literature. METHODS: In the present retrospective overview, we evaluated patients with gynecologic malignancies (breast, endometrial, cervical, ovarian) who received ICIs with regard to the incidence, type, and time to onset of irAEs. A total of 61 patients treated at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany, between 2018 and 2023 were included in the analysis. RESULTS: A total of 32.8% of patients developed an irAE of any grade or type. The median time to irAE was 24 weeks. The most frequently observed irAEs were grade 1 (20%) or 2 (35%). Immunotherapy-related grade 3 or 4 adverse events occurred in 45% of patients (40% grade 3, 5% grade 4). The most common type of irAE in our cohort was hypothyroidism, followed by hepatitis and colitis. Cox regression analysis identified the duration of ICI therapy as the only significant factor influencing the incidence of irAEs (p = 0.004). CONCLUSION: The broad spectrum of irAEs and the onset time of irAEs are important challenges of therapy with ICIs, requiring proactive monitoring and tailored management strategies to optimize the safety and efficacy of immunotherapy.

The impact of short-term multimodal prehabilitation on functional capacity in patients with gynecologic malignancies during the perioperative period: A prospective study.

PURPOSE: To explore the effect of a short-term, hospital-based, multimodal preoperative prehabilitation intervention on perioperative functional ability of patients with gynecological malignant tumors. METHODS: According to the order in which they underwent surgery, 97 patients were divided into the control group (48 cases) and the intervention group (49 cases). The control group was given routine preoperative guidance, whereas the intervention group was given short-term multimodal prehabilitation guidance on the basis of the control group intervention. The 6-min walk test was performed on the day of admission to the hospital, the day before surgery, and the 30th day after surgery. RESULTS: Compared with the control group, the intervention group had significantly better 6-min walk distance and superior physical and psychological status on the day before surgery and the 30th day after surgery (P < 0.001). For three consecutive days after surgery, the quality of recovery in the intervention group was significantly higher than that in the control group (P < 0.001), and the first ambulation time and exhaust time were achieved earlier in the intervention group than in the control group (P < 0.05). CONCLUSION: The preoperative intervention group showed improved preoperative exercise ability and reduced anxiety in patients with gynecological cancer. Furthermore, this intervention improved the overall health of patients and accelerated their postoperative recovery.

Causal Relationship between Immune Cells and Gynecological Cancers through Bidirectional and Multivariable Mendelian Randomization Analyses.

Background: Evidence suggests potential associations between gynecological malignancies and various immune cell chemicals and systems. However, establishing a causal relationship remains uncertain. Methods: This work employed Wald ratio for one single-nucleotide polymorphism (SNP) or the inverse-variance weighted method (IVW) for multiple SNPs to conduct bidirectional two-sample Mendelian randomization (MR) analysis by utilizing genome-wide association study (GWAS) data. We employed supplementary methods, including MR-Egger and weighted median methods, to detect and correct for the influence of horizontal pleiotropy. In addition, we also use colocalization analysis for further validation. Results: In IVW analysis, increases in relative count of circulating CD11c+ HLA-DR++ conventional dendritic cells (cDC) were associated with an elevated risk of breast cancer (OR [95% CI], 1.1295 [1.0632-1.2000], P = 8.044 × 10-5), while elevated levels of HLA-DR on plasmacytoid dendritic cells (DC) and HLA-DR on DC were protective against breast cancer. In addition, actual count of CD39+ resting Treg AC was also shown to be causally associated with the development of ovarian cancer, whereas a high relative count of CD28+ CD45RA- CD8+ T cells reduced the risk of cervical cancer. Sensitivity analysis revealed almost no evidence of bias in the current study. Multivariable MR (MVMR) analyses further confirmed a direct impact of the CD11c+ HLA-DR++ cDC immune phenotype on breast cancer. Colocalization analysis showed the lead SNP, rs780094, suggesting HLA-DR GWAS shared a common genetic mechanism with breast cancer. Conclusions: The MR study identified significant causal relationships between multiple immunophenotypes and breast cancer, aiming to provide clinicians with some reference for cancer prediction and explore further potential associations between immune phenotypes and gynecologic tumors.

Tumor immunity: A brief overview of tumor­infiltrating immune cells and research advances into tumor­infiltrating lymphocytes in gynecological malignancies (Review).

Tumor immunity is a promising topic in the area of cancer therapy. The 'soil' function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor-infiltrating immune cells in the TME, especially the tumor-infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: 'Tumor microenvironment'; 'TME'; 'tumor-infiltrating immunity cells'; 'gynecologic malignancies'; 'the adoptive cell therapy (ACT) of TILs'; and 'TIL-ACT' (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor-infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy.

Advances in the application of positron emission tomography in the diagnosis and treatment of gynecological malignancies / 中国辐射卫生

@#Positron emission tomography (PET) has been used for the diagnosis of gynecological malignancies and is superior to conventional imaging tools in detecting metastatic lesions, diagnosing local recurrence, and evaluating treatment outcome. Compared with the in vitro assessment of tumor biopsy materials, PET imaging has advantages in measuring <i>in vivo</i> tumor behaviors, characterizing overall tumor burden, and capturing the phenotypic heterogeneity of tumors. PET imaging provides precision data on tumor staging and recurrence through integrating the anatomic and functional data of metabolic features, thereby achieving the high-quality assessment of gynecological malignancies. This article reviews the advances in the application of PET imaging in the diagnosis and treatment of cervical cancer, ovarian cancer, and endometrial carcinoma.

Effect of the intervention based on Information-Motivation-Behavioral skills on the preoperative anxiety in patients with gynecological malignancies / 中国实用护理杂志

Objective To investigate the effect of interventions based on Information-Motivation-Behavioral skills on the preoperative anxiety in patients with gynecological malignancies. Methods A total of 64 patients with malignant tumor were divided into two groups by random digits table method with 32 cases each. The patients in the two groups received routine nursing. In addition, interventions based on Information-Motivation-Behavioral skills were provided in the intervention group. All patients were investigated by the following indexes such as the Self-Rating Anxiety Scale (SAS), sleep quality scale, blood pressure and heart rate before and after the intervention. Results After the intervention, the SAS scores in the intervention group was (49.47 ± 3.81) points, sleep quality score was (3.66 ± 0.97) points, and systolic blood pressure and heart rate were (128.56±5.93) mmHg (1 mmHg=0.133 kPa), (75.09 ± 3.78) beats/min, which were lower than those in the control group (57.38 ± 3.75) points, (5.50 ± 1.50) points, (134.97 ± 7.19) mmHg, (81.34 ± 4.88) beats/min, the differences were statistically significant (t=-8.350--3.887, P<0.05). Conclusions The intervention focused on Information-Motivation-Behavioral Skills can help patients to relieve anxiety, reduce stress response, improve quality of sleep.

Rresearch progress of androgens in gynecological malignancies / 中国综合临床

Gynecological malignancies have seriously affected women′s living quality and survival.In recent years,studies have shown that androgen is closely related to the occurrence and development of gynecologic malignancies.In this paper,we mainly discussed the mechanism of androgen on gynecologic malignancies.

Delineation of target volume in intensity-modulated radiotherapy for para-aortic lymph node metastases in patients with gynecological malignancies / 中华放射肿瘤学杂志

Objective To preliminarily explore the delineation of clinical target volume in intensity-modulated radiotherapy for para-aortic lymph node metastases in patients with gynecological malignancies.Methods A retrospective analysis was performed on 56 gynecological tumor patients with para-aortic lymph node metastases who were admitted to our department from January 2010 to September 2016.The number and distribution of metastatic para-aortic lymph nodes were determined by imaging method.Results A total of 108 positive para-aortic lymph nodes were found in the 56 patients,with 1-4(mean,2) positive para-aortic lymph nodes per patient.The mean diameter of positive para-aortic lymph nodes was 2.3 cm (1.2-4.0 cm).A total of 20 metastatic lymph nodes (19%) were located at the L4 level,38(35%) at the L3 level,44(41%) at the L2 level,and 6(5%) at the L1 level.There were 71 metastatic lymph nodes (66%) at the left side of the para-aortic region,20 metastatic lymph nodes (19%) between the abdominal aorta and the vena cava,and 17 metastatic lymph nodes (15%) at the right side of the inferior vena cava.Conclusions For patients with gynecological malignancies,nodal contouring for the para-aortic region should not be defined by a fixed circumferential margin around the vessels.The left side of the para-aortic region should be covered adequately;the upper target should be extended up to the renal artery,and needs to be further extended for patients who have nodal involvement near the renal arteries and veins.

CLINICAL VALUE OF CA125, CA153, HE4 JOINT DETECTION IN DIAGNOSIS OF GYNE-COLOGICAL MALIGNANCIES / 现代医院

Objective To investigate the clinical value of CA125, CA153, HE4 joint detection in diagnosis of gynecological malignancies.Methods 70 cases of gynecological malignancies were selected from our hospital in 2013, 72 cases of benign gynecological diseases selected in the same period, and 70 healthy controls were selected. The expression levels of CA125, CA153 and HE4 were detected and statistically analyzed.Results The positive rate of serum CA125 in the gynecological malignancies group was higher than that in the benign gynecological disease group (p <0.05).The positive rate of serum HE4 in the gynecological malignancies group was higher than that in the benign gynecological disease group (p <0.01).The positive rate of CA125, CA153, HE4 joint detection in the gy-necological malignancies group (up to 72.9%) was also significantly higher than that in the benign gynecological dis-ease group (p <0.01).Conclusion is a single tumor marker with the highest sensitivity and specificity for diagno-sis of gynecological malignancies.CA125, CA153, HE4 joint detection can improve the positive rate of diagnosis of gynecological malignancies.

Pelvic exenteration for recurrent cervical cancer: ten-year experience at National Cancer Center in Korea / 부인종양

OBJECTIVE: To evaluate survival and morbidity after pelvic exenteration (PE) for the curative management of recurrent cervical cancer. METHODS: We retrospectively evaluated patients with recurrent cervical cancer who underwent PE from January 2001 to April 2011. Patients were identified from the registry of our institution. The clinical status and demographic information was obtained by reviewing the medical records. RESULTS: Sixty-one recurrent cervical cancer patients underwent PE. Patients who received radiotherapy, operation, chemotherapy before PE were 98%, 41%, and 23%, respectively. The total morbidity rate was 44%; 10 (16%) patients had early complications (30 days or less after PE), whereas 22 (36%) patients had late complications. Wound problems were common early complications (7/18), and bowel fistulas were common late complications (9/30). The five-year overall survival and five-year disease-free survival were 56% and 49%, respectively. Median follow-up was 22 months (range, 1.8 to 60 months). Affecting factors for overall survival were resection margin status, pelvic wall and rectal involvement. CONCLUSION: Our overall 5-year survival is encouraging. Although the morbidity rate is still high, PE is a potentially curative opportunity in gynecological malignancies with no other treatment options. The most important factors for overall survival after PE are the resection margin status, pelvic wall involvement and rectal involvement.

Pelvic exenteration for recurrent cervical cancer: ten-year experience at National Cancer Center in Korea / 부인종양

OBJECTIVE: To evaluate survival and morbidity after pelvic exenteration (PE) for the curative management of recurrent cervical cancer. METHODS: We retrospectively evaluated patients with recurrent cervical cancer who underwent PE from January 2001 to April 2011. Patients were identified from the registry of our institution. The clinical status and demographic information was obtained by reviewing the medical records. RESULTS: Sixty-one recurrent cervical cancer patients underwent PE. Patients who received radiotherapy, operation, chemotherapy before PE were 98%, 41%, and 23%, respectively. The total morbidity rate was 44%; 10 (16%) patients had early complications (30 days or less after PE), whereas 22 (36%) patients had late complications. Wound problems were common early complications (7/18), and bowel fistulas were common late complications (9/30). The five-year overall survival and five-year disease-free survival were 56% and 49%, respectively. Median follow-up was 22 months (range, 1.8 to 60 months). Affecting factors for overall survival were resection margin status, pelvic wall and rectal involvement. CONCLUSION: Our overall 5-year survival is encouraging. Although the morbidity rate is still high, PE is a potentially curative opportunity in gynecological malignancies with no other treatment options. The most important factors for overall survival after PE are the resection margin status, pelvic wall involvement and rectal involvement.