Cancer Treatment and Research Communications

Effectiveness of sentinel lymph node biopsy and bilateral pelvic nodal dissection using methylene blue dye in early-stage operable cervical cancer—A prospective study

To evaluate the effectiveness of methylene blue dye in detecting sentinel lymph nodes (SLNs) in women with early-stage operable (defined as FIGO I-IIA) cervical cancer. It also aims to evaluate procedural challenges and accuracy. This prospective study, which focused on 20 women with early-stage cervical cancer, was carried out between June 2016 and December 2017. These patients had SLN mapping with methylene blue dye injections and thorough examinations, including imaging. All patients underwent radical hysterectomy and complete bilateral pelvic lymphadenectomy. No additional investigation was done on the lymph node in cases where a metastasis was found in the first H&E-stained segment of the sentinel node. 20 patients were included in the analysis. The median age of the subjects was 53, and 95 % of them had squamous cell carcinoma. 90 % of the time, the identification of SLNs was effective, and 55 SLNs were found, of which 52.7 % were on the right side of the pelvis and 47.3 % on the left. The obturator group had the most nodes, followed by the external and internal iliac groups in descending order of occurrence. Metastasis was detected in 3 patients, resulting in a sensitivity of 100 % and a specificity of 93.75 % for SLN biopsy. Notably, no false-negative SLNs were found. Complications related to methylene blue usage included urine discoloration in 30 % of patients. This trial highlights the promising efficacy and safety of methylene blue dye alone for SLN identification in early-stage operable cervical cancer, with a notably higher success rate. Despite limitations like a small sample size, healthcare professionals and researchers can build upon the insights from this study to enhance cervical cancer management.

Transcriptomes of cervical cancer provide novel insights into dysregulated pathways, potential therapeutic targets, and repurposed drugs

Cervical cancer ranks as the fourth most prevalent gynaecological malignancy and is a significant contributor to mortality among women globally. With the exception of HPV-mediated oncogenesis, the molecular etiology of the disease is poorly understood, and there is a critical dearth of knowledge concerning cancer that is not caused by HPV. Moreover, none of the options presently accessible for the treatment of cancers specifically target cervical cancer. In context with this, this research aims to identify the critical genes, regulators, and pathways that contribute to the pathogenesis of cervical cancer, in addition to prospective pharmacological targets and repurposed therapeutic agents that can be directed against the targets. A total of eleven different global gene expression (transcriptome) datasets were subjected to analysis utilizing a variety of in silico tools. The present study reveals a previously unknown correlation between cervical cancer and five genes: SHC1, CBL, GNAQ, GNA14, and PPP2CA. Significant dysregulation was observed in four crucial transcription factors (KLF4, E2F1, FOXM1, and AR) that modulate the expression of numerous genes in cervical cancer. Furthermore, it was observed that AKT1, MAPK1, and MAPK3 ranked the highest among the regulatory genes that hold promise as therapeutic targets in the context of cervical cancer. Additional research, both in vitro and in vivo, is required to validate and establish the therapeutic potential of these crucial genes in the context of cervical cancer.

Exploring the prognostic impact of tumor sidedness in ovarian cancer: A population-based survival analysis of over 10,000 patients

Very recently, emerging evidence demonstrated that laterality might be an independent prognostic factor in patients with advanced ovarian cancer (OC). Based on preliminary provocative observations, our study aimed to investigate the prognostic impact of sidedness in a large cohort of women with OC. Survival was estimated based on Kaplan-Meier method and survival curves were compared using Log-rank test. Cox proportional-hazards model was used to study the association between survival and covariates. A total of 10,177 women with OC were included. Mean age at diagnosis was 59.58 years (±13.5); 36.7% OC right-sided, 36.9% were left- sided, and 26.4% had bilateral OC. The median overall survival (OS) for the entire population was 77 months, with the lowest median OS observed in bilateral OC (median OS: 34 months). The prognostic value of OC sidedness was not confirmed at the univariable analysis (HR = 0.958; 95% CI: 0.888-1.033, p = 0.268). However, women with bilateral OC has a 45% higher risk of death as compared with unilateral diagnosis (HR = 1.453; 95% CI: 1.410-1.497; p< 0.001). The independent prognostic value was further confirmed on multivarible analysis after adjusting for covariates including age, marital status, histological type, CA-125 at diagnosis, grade, stage, chemotherapy and surgery (HR = 1.087; 95% CI: 1.043-1.136, p = 0.02). However, the ultimate prognostic significance appeared less prominent, with bilateral OC conferring a relative increase of 8.7% of mortality. Our real-world study demonstrated that impact of tumor sidedness has no prognostic implication (right vs left OC) but bilateral OCs might be marginally more prognostically unfavorable. Prospective validation might be warranted, to confirm the prognostic significance of OC sidedness, including for the presence of key genetic alterations and lymph nodes asymmetry, to better stratify patients with OC and predict outcomes according to tumor sidedness at diagnosis.

Clonal origins and divergent evolutionary relationships of synchronous multiple malignant neoplasms in gynecology revealed by next-generation sequencing

Synchronous multiple malignant neoplasms (SMMNs) in gynecology involving the ovary, endometrium, and cervix are rare and pose a significant diagnostic challenge when the primary lesion is unclear. We performed targeted genomic sequencing, immunohistochemical analysis and copy number analysis on multiple samples from one patient with simultaneous cancerous lesions in ovary, endometrium and cervix, to clarify tumor clonal origin and divergent evolutionary relationships. Using blood-derived genomic DNA as reference, targeted sequencing of 1012 genes across endometrial, ovarian, and cervical sites identified two germline and 96 somatic mutations. A germline MSH2 splice acceptor site mutation confirmed Lynch syndrome. Tumor across distinct anatomical sites shared three genetic mutations: an MSH2 missense mutation, a FAT1 missense mutation, and an SH3GL1 in-frame deletion. These rare mutations of uncertain clinical significance support a shared clonal origin. Ovarian lesions showed the highest shared somatic mutation frequency, indicating an ovarian origin. Phylogenetic reconstruction revealed branched evolution, indicating metastasis from ovary to endometrium and cervix. Diverse mutation forms in ARID1A, PTEN, ERBB2, and PIK3CA across different lesions suggest convergent phenotypic evolution. Next-generation sequencing precisely resolved the diagnostic dilemma of gynecologic SMMNs by delineating an ovarian origin and a complex evolutionary pattern, thereby proving critical for guiding personalized treatment and screening strategies, particularly in hereditary cancer syndromes.

Role of aspirin in cancer prevention

Investigating the quality of sexual function in women with genital cancers: A structural equation analysis approach

Investigating the quality of sexual function in women with genital cancers: A structural equation analysis approach

Human malignant ovarian germ cell tumor cell lines derived from peritoneal cytology retrieving from circulating tumor cell system

Malignant ovarian germ cell tumor (MOGCT) is a rare neoplasm predominantly affecting adolescent and young adult females. Establishing personalized permanent tumor cell lines is crucial for understanding tumor behavior and optimizing precision treatment for these patients. We developed a novel procedure for isolating and culturing human MOGCT cells from peritoneal wash cytology using the circulating cell extraction technique (Labyrinthbiotech Co. LLC, LABYRINTHCE01, China). Peripheral blood and peritoneal washings were collected from 15 patients, including those with yolk sac tumor (n = 6), dysgerminoma (n = 2), immature teratoma (n = 5), and mixed germ cell tumor (n = 2). After washing and centrifugation, samples were processed using the labyrinth technique to achieve high-purity cell cultures. The isolated tumor cells were characterized by immunofluorescence microscopy and flow cytometry. Immunohistochemical analysis enabled specific discrimination from primary peritoneal human fibroblasts. Cultures were established from peritoneal cytology with cell densities ranging from 10² to 10⁵ cells per well, with 5 samples showing over 10⁵ cell growth, 3 samples over 10⁴ cell growth, and others at 10³ cell growth. The longest cell culture has been maintained for 18 generations. Short tandem repeat (STR) analysis of cultured cells confirmed their germ cell tumor origin. Preliminary assessments of chemosensitivity in cultured cells have been found to reflect similar clinical responses in the corresponding patients. The MOGCT cell lines derived from peritoneal washings using the circulating tumor cell chip represent the tumor characteristics. This method holds promise for functional studies on rare ovarian tumors and for evaluating chemo-sensitivity for potential therapeutic applications.

Immunohistological localization of MDM2, MCM2, Fascin, PCNA, EGFR in paraffin section; in the normal and cancerous human ovary

Many protein markers have been investigated in human tissues such as; Fascin, MDM2, MCM2, EGFR, and PCNA. These markers have important physiologic roles in cell proliferation, motility, adhesion, invasion, and survival. up to date, some researchers focused on these markers in ovarian cancer. However, the mentioned markers have not been investigated in the normal human ovary. Using the immunohistochemical technique we tried to localize these markers in the normal, and cancerous ovarian tissues. Paraffin-embedded from 10 normal ovarian tissue and 1 case with histologically confirmed ovarian cancer, underwent an immunohistological process, and five mentioned markers were localized in the human ovary. At first, each marker presentation was assessed and then it tried to quantify the amount of presentation. Fascin, PCNA, and MCM2 are presented high in the normal ovarian tissue, while EGFR is restricted to the epithelium and very rarely in the granulosa cells. Also, MDM2 was negative for all normal ovaries. All markers had overexpression in ovarian cancer in different patterns. Ovarian cancer tissue showed over-expression of the cell proliferation and motility markers compared with the normal ovary. These markers may have prognostic value in ovarian cancer.

An evaluation of the utility of computed tomography in high-risk endometrial cancer surveillance

Endometrial cancer is a collection of heterogeneous histologies and molecular subtypes with different risk profiles. High-risk endometrial cancer surveillance regimens vary amongst providers. The National Comprehensive Cancer Network (NCCN) recommends symptom and exam-based surveillance for all endometrial cancers after remission, regardless of cancer stage and histology. Our objective was to identify the first method of detection of recurrence in high-risk endometrial cancers and examine disease recurrence and treatment patterns. A retrospective review of patients diagnosed with high-risk endometrial cancer between November 2013 and February 2020 was conducted at a large academic institution. High-risk endometrial cancers were classified by histology and pathologic stage and were categorized by primary method of detection. Two hundred and twenty-nine patients were identified with high-risk endometrial cancer, 63 (28 %) of whom had a recurrence. Most recurrences were first detected with routine imaging in 31 patients (49.2 %) and symptom surveillance in 24 patients (38.15 %). Regardless of the detection method, most patients underwent systemic treatment. The average survival after recurrence was 2.0 years in the imaging cohort and 1.6 years in the non-imaging surveillance cohort. The most common site of recurrence in our cohort of high-risk endometrial cancer was in the lung, and most recurrences were identified with asymptomatic imaging. Though there was no statistically significant difference between the survival of those who underwent imaging surveillance vs. standard of care, there was a trend toward survival that deems further exploration with a larger cohort.

First-trimester miscarriage in the background of endometrial carcinoma

Endometrial cancer in young women (less than 40-year-old) is associated with anovulatory menses, polycystic ovarian syndrome (PCOS) and subfertility. Endometrial cancer occurring in a miscarriage is rare. We highlight a case of endometrial cancer occurring during miscarriage of a non-viable pregnancy, its management and the outcome. A 32-year-old woman, Gravida 1 Para 0, was referred to our center at 7 weeks gestation in 2018 for uncontrolled diabetes mellitus diagnosed during investigation for subfertility. Her poor compliance with the treatment is consistent with an HbA1c of 8%. During the assessment, she was already complaining of lower abdominal pain. Ultrasound showed irregular IUGS with no fetal echo. She had a miscarriage soon; however, due to ultrasound evidence of thickened and irregular endometrium (17 mm) with mixed echogenicity, dilatation and curettage (D + C) were commenced. The first and second tissues were reported as the product of conception (POC) and well differentiated endometrioid adenocarcinoma, respectively. The first hysteroscopy showed foci area of polypoidal growth at the right posterior endometrium, obscuring the right ostium, with similar histology report. She was commenced on high-dose progestogen with hysteroscopy surveillance 6 months later, which showed disease regression. After two normal hysteroscopies and endometrial biopsies with continuous progestogen therapy for 12 months, cyclical progestogen for 12 months and follow-up for another 6 months, she had spontaneous conception and is currently pregnant at 16 weeks gestation. Endometrial cancer should be suspected in high-risk patients with first-trimester miscarriage. Individualized treatment with high dose progestogen and follow-up with the proper patient and partner counselling and education has high successful regressionand later on, pregnancy rate.

Genome-wide cell-free DNA methylation profiling in advanced stage ovarian cancer. Are we looking at the tumor or the patient's immune response to the tumor?

The aim of this study was to identify differentially methylated regions in cell-free DNA (cfDNA) between healthy persons and patients with advanced stage ovarian cancer (ASOC) and to identify differences in cfDNA methylation before and after cytoreductive surgery. Plasma-derived cfDNA was analyzed by a high-throughput genome wide DNA methylation sequencing technique: MeD-seq. A training set of therapy naïve cfDNA samples of patients with ASOC (≥FIGO stage IIIB, n=10) was compared with cfDNA of healthy controls (n=10) to define a ASOC specific cfDNA methylation signature. A cumulative hypermethylation score was constructed and a validation set of pre- and postoperative samples of 39 patients were compared using this score. MeD-seq results of tumor tissue samples were correlated with cfDNA results. Patients with ASOC showed a clear distinct cfDNA methylation signature from healthy controls (p<0.0001). This cfDNA-methylation signature resulted in preoperative hypermethylation scores (135; interquartile range 110-163) that were significantly higher than postoperative hypermethylation scores (91; interquartile range 76-101) (p<0.001). The cfDNA methylation signature at baseline differed from tumor tissue and was more closely related to DNA methylation of immune-related cells (T-lymphocytes, neutrophil granulocytes, monocytes, and B-lymphocytes) than to ASOC tissue. MeD-seq provides a promising method for genome wide methylation profiling of cfDNA. Patients with ASOC could clearly be distinguished from healthy controls and differed pre- and postoperatively.

Synchronous endometrial and ovarian cancer and its recurrent risk factors: Case series

Synchronous endometrial and ovarian cancer (SEOC) is a relatively rare entity with indistinct clinical manifestation but have a better prognosis compared to metastatic malignancy of each organ. The aim of the study is to determine the prognosis and factors associated with recurrence of SEOC. This case-series study was performed on 37 histologically confirmed SEOC, diagnosed and treated in our tertiary hospital from March 2009 to September 2021. Disease-free survival (DFS) and overall survival (OS) rates following indicated procedure were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to determine risk factors of recurrence. The mean age of participants was 49.38 (age range: 26-78). The most common complaints and symptoms were abdominal pain (40.5%), followed by abnormal uterine bleeding (29.7%). Most common histological presentation was endometroid type for both ovarian (46%) and endometrial (97.3%) cancers. Over the mean follow-up period of 85.54 months, 11 patients developed recurrence without mortality. Non-endometrioid histology of ovarian cancer, higher grade and stage of ovarian cancer, and omentum invasion were significantly associated with worse DFS in unvariate analysis. Lymphovascular invasion was the sole predictor of DFS in multivariate analysis. While this study was not able to investigate the risk factors of overall survival associated with SEOC, the results of this study provides an overview of clinicopathological presentation of the disease and emphasizes the importance of lymphovascular invasion in determining prognosis and DFS in SEOC.

Estrogen receptor and programmed death ligand-1 expression in type 1 endometrial cancer and its associated clinicopathological characteristics

This study aimed to determine the association of estrogen receptor (ER) and programmed death ligand-1 (PD-L1) expression with the clinicopathological characteristics of type 1 endometrial cancer. A total of 85 patients with type 1 endometrial cancer who underwent surgery at the Dr. Soetomo Hospital, Surabaya, Indonesia were retrospectively studied. Data about the age, menopausal status, body mass index, disease stage, cell differentiation, angiolymphatic invasion, myometrial invasion, and adjuvant therapy of the patients were collected from medical records. Immunohistochemistry with ER and PD-L1 antibodies was performed on all samples. The association between ER and PD-L1 expression and clinicopathological characteristics was statistically analyzed. The positivity rates of ER and PD-L1 in type 1 endometrial cancer were 68.2 % and 78.5 %, respectively. ER positivity was significantly correlated with body mass index (BMI) ≥25, premenopausal status, early stage of disease, <1/2 myometrial invasion, negative nodal metastasis, and lack of adjuvant therapy. It was also associated with age <55 years, low-grade cells, and angiolymphatic invasion, but the correlation was not significant. Meanwhile, PD-L1 positivity was significantly correlated with BMI <25, menopausal status, advanced stage of disease, high-grade cells, angiolymphatic invasion, and adjuvant therapy. It was also associated with age ≥55 years and nodal metastasis, but the correlation was not significant. ER and PDL-1 positivity is associated with the clinicopathological characteristics of type 1 endometrial cancer.

Artemin affects the survival and prognosis of endometrial cancer patients via regulating tumor cell proliferation

The main aim of the study is to analyze the impact of Artemin on survival and prognosis in endometrial cancer (EC) patients by bioinformatics methods. As a member of the glial-derived neurotrophic factor (GDNF) family, Artemin is not only important in the repair process of nerve damage, but also involved in tumorigenesis and metastasis. In this study, we demonstrated that Artemin mRNA was overexpressed in EC tissues. Artemin expression was closely related to the FIGO stage, pathologic differentiation, deep myometrial infiltration, lymphatic metastasis, and survival status. Univariate and multivariate Cox regression analysis showed that ectopic overexpression of Artemin predicted poor survival prognosis. Artemin expression could be used as an independent risk factor for the prognosis of EC patients. The proliferation of EC cells was significantly downregulated by silencing of Artemin. Artemin promotes tumor progression by regulating the proliferation of EC cells, thereby affecting the prognosis of EC patients.

miR-150 in cancer metastasis: Orchestrating migration, invasion, and angiogenesis through context-dependent mechanisms

ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway

Through comprehensive analysis of cisplatin-resistant HeLa cervical cancer cells, we reveal that curcumin exerts potent anti-cancer effects by modulating autophagic processes, and further identify Endoplasmic reticulum oxidoreductase 1-alpha (ERO1α) as a key regulator mediating this biological response. Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8). The immunoblotting analysis measured the Phosphoinositide 3-Kinase/ Protein Kinase B (PI3K/AKT) pathway-related proteins, Microtubule-associated protein 1A/1B-light chain 3 (LC3II/I) ratio, and Beclin-1 expression. The cell migration ability was evaluated through a scratch assay. Curcumin significantly inhibits the proliferation and migration of cisplatin-resistant HeLa cells. It promotes autophagy in these cells, as shown by the upregulation of autophagy-related proteins Beclin-1 and LC3II/I. Curcumin also downregulates ERO1α expression, subsequently modulating the PI3K/AKT pathway. Interestingly, the overexpression of ERO1α or activation of PI3K negated the autophagy-promoting effects of curcumin, indicated by the absence of changes in autophagy-related proteins and phosphorylation levels of PI3K/AKT. Our study provides compelling evidence that curcumin inhibits the proliferation and migration of cisplatin-resistant HeLa cells by promoting autophagy through the downregulation of ERO1α and inhibition of the PI3K/AKT pathway.

Combined single cell and spatial transcriptome analysis reveals hedgehog pathway-related genes as potential therapeutic targets for cervical cancer

Cervical cancer (CC) remains one of the most common and deadly malignancies among women worldwide, with exceptionally high morbidity and mortality rates. The aberrant activation of the hedgehog pathway is intimately associated with tumor development and progression. Nevertheless, the potential therapeutic targets within the hedgehog pathway in CC have yet to be clearly identified. In this study, we conducted an in-depth investigation of hedgehog pathway-related genes in CC, integrating single-cell sequencing data and spatial transcriptomics. Utilizing a comprehensive scoring algorithm, we identified that myofibroblasts within CC tissue exhibit a highly enriched hedgehog pathway. Our analysis of the myofibroblast development process revealed that MYH9 plays a crucial role. Further exploration using spatial transcriptome data allowed us to delve into the role of MYH9 in myofibroblasts. We discovered that MYH9-negative and MYH9-positive myofibroblasts display distinct profiles. Validation using extensive transcriptome data demonstrated that a high infiltration of MYH9-positive myofibroblasts is a risk factor for CC patients, significantly impacting prognosis and immunotherapeutic efficacy. Our study provides unique insights into the relationship between CC and the hedgehog pathway, offering new directions for cancer treatment strategies.

Utilization of cervical cancer screening and determinant factors among female nurses in selected public hospitals in Addis Ababa, Ethiopia

Cervical cancer is one of the top cause of death among childbearing women globally and public health issue for underdeveloped nations.It is the world's second most prevalent cancer among women. In 2018, 311,000 women died due to cervical cancer.Approximately 80 % of these deaths occurred in developing countries.However, there has been insufficient research on cervical cancer screening utilisation among Ethiopian nurses, despite the fact that nurses promote women's health and play a key role in cervical cancer education. As a result, evaluating utilization of cervical cancer screening among nurses is critical for program effectiveness. To assess the magnitude of utilization of cervical cancer screening and determinant factors among female Nurses in selected public hospitals in Addis Ababa, Ethiopia. An institutional-based cross-sectional study design was employed from October 1 to November 30, 2022. Data was collected using an interviewer-administered questionnaire. The data was entered into Epi data version 3.1 and then exported to SPSS version 22 for data management and analysis. Bivariate and multi-variable logistic regressions were employed to identify the predictor variables. Statistical significance was considered at P 8 years (AOR = 16.78; 95 % CI: 4.82, 58.44), history of STI (AOR = 53.72; 95 % CI: 14.18, 203.45) and having multiple sexual partners (AOR = 12.74; 95 % CI: 4.15, 39.11) were significantly associated with utilization of cervical cancer screening among female nurses. The overall cervical cancer screening rate among female nurses was low compared to the WHO strategy for cervical cancer elimination, which asks for 70 % of women worldwide to be checked for cervical illnesses regularly by 2030. According to the study findings, respondents' work experience, STI history, and having multiple sexual partners influenced their utilization of cervical cancer screening among nurses. To boost the utilization of screening services, female nurses should place a strong emphasis on maintaining screening awareness through education and knowledge sharing.Finally, we recommend future researchers to do comparative study design to draw any scientific and credible conclusions.

Optimized cancer gene selection using armadillo optimization algorithm and support vector machine

Feature selection is a crucial step in improving classification performance for high dimensional cancer datasets, which often contain numerous irrelevant or redundant features that can negatively impact model accuracy and increase computational load. The proposed hybrid AOA-SVM method effectively reduces the gene pool to a subset of highly informative features by implementing AOA's capability for efficient local optimization and diversity maintenance. Within the AOA framework, gene selection is refined through local optimization within smaller subgroups, followed by a shuffling phase to preserve solution diversity. This dual-phase strategy allows the identification of key genes that optimally distinguish between cancerous and healthy tissues. Selected gene subsets are then classified using SVM for high accuracy. The approach was evaluated on three major cancer datasets: leukaemia (AML, ALL), ovarian, and CNS. The method demonstrated impressive performance across all datasets. In the ovarian dataset, the model achieved 99.12 % accuracy and an AUC-ROC score of 98.83 % with only 15 selected genes. The leukaemia dataset achieved perfect classification with 100 % accuracy and an AUC-ROC score with 34 genes. For the CNS dataset, the approach maintained 100 % accuracy using 43 genes. These results validate the AOASVM method's effectiveness in producing accurate, informative gene subsets, enabling high-precision classification. The AOA-SVM hybrid presents a highly accurate and computationally efficient tool for cancer diagnostics, demonstrating significant potential for application in precision medicine by identifying minimal, biologically relevant gene markers.

Characteristics, treatment patterns, and outcomes in patients with high-risk locally advanced cervical cancer

To characterize the real-world treatment patterns and outcomes of patients with high-risk locally advanced cervical cancer (HR-LACC). This retrospective study identified and randomly selected adults diagnosed between 2010 and 2018 from the ConcertAI Oncology Dataset. For patients initially treated with concurrent chemoradiotherapy (CCRT), we estimated real-world progression-free survival (rwPFS) among those with persistent disease, real-world time on CCRT, and recurrence-free survival (rwRFS) using Kaplan-Meier methods. The cohort included 300 patients. Median age at diagnosis was 51 years. 53.7 % were White and 30.0 % were Black; 52.0 % were premenopausal; 89.3 % had squamous cell histology; 75.3 % had stage III disease, and 92.7 % had no evidence of performance status impairment. Initial treatment included CCRT (N = 229), surgery (N = 28), antineoplastics only (N = 11), and radiation only (N = 5). Twenty-seven patients were untreated. Baseline characteristics for the CCRT-first patients were similar to the overall cohort; their median real-world time on treatment was 1.6 months; 78.2 % received cisplatin for a median of 1.2 months; 28.4 % received antineoplastics after CCRT, and 11.8 % initiated a second antineoplastic therapy. Of the CCRT-first patients, 27/143 with a complete response had subsequent recurrent disease (median rwRFS not reached). 179 patients had persistent disease, among whom median (95 % confidence interval [CI]) rwPFS was 29.7 (16.9-59.3) months. In this study of United States-based clinical practices, most HR-LACC patients received CCRT as initial treatment. Many patients developed persistent disease after CCRT indicating a need for improved first treatment and maintenance options.

A case of neoadjuvant chemotherapy in pregnancy with cervical cancer (IB3)

Compared with the early symptoms of non-pregnancy, the early pregnancy with cervical cancer is often confused with threatened abortion, so it is difficult to diagnose and delay the time of treatment. At present, compared with cervical cancer, there is no clear and standard treatment for cervical cancer in pregnancy. At present, the diagnosis and treatment plan is mainly made according to the pathological examination, staging, fetal development (whether there is abnormality on ultrasound and whether the chromosome karyotype is normal or not) and the pregnant women and their family members' pregnancy wishes. A case of pregnancy complicated with cervical cancer who was terminated by planned cesarean section after neoadjuvant chemotherapy (NACT) with irregular vaginal bleeding as the first symptom was analyzed retrospectively.

The effect of postoperative chemotherapy on blood glucose and prognosis in patients with advanced ovarian cancer

Recent studies have shown that chemotherapy can cause abnormal glucose metabolism in cancer patients; however, little is known about the association of blood glucose (BG) with chemotherapy in ovarian cancer. In this study, we investigated the effect of chemotherapy on glucose metabolism in patients with advanced ovarian cancer and its effect on patient prognosis. We retrospectively analyzed blood glucose and other clinical data from 100 patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics, FIGO III/IV) before and after chemotherapy. Kaplan-Meier survival curves were used to calculate OS Overall Survival) survival curves for patients in the BG-High and BG-Low groups, and logarithmic rank statistics (Mantel-Cox) to assess associations between clinical outcomes and related indicators of patients. Of the 100 patients with advanced ovarian cancer (OC) included in this study, 49 patients (49 %) had stage III disease, and 51 had stage IV disease according to FIGO classification. In total, 65 patients (65 %) achieved R0 surgical resection, while 35 patients (35 %) achieved R1, after complete surgical resection or satisfactory cytoreductive surgery followed by paclitaxel-carboplatin chemotherapy every three weeks for a total of six cycles. According to blood glucose (BG) levels after chemotherapy, patients were divided into two groups: blood glucose ≥ 6.1mmol/L (BG High) and blood glucose < 6.1mmol/L (BG Low). Thirty-two patients (BG High) had elevated fasting blood glucose levels after chemotherapy. Of these, six patients were definitively diagnosed with diabetes, fasting BG ≥7.0 mmol/L, and 26 patients had impaired fasting blood glucose, fasting BG 6.1-6.9 mmol/L; this difference was statistically significant (P < 0.05). Kaplan-Meier analysis showed that the mean 5-year OS (probability of survival from diagnosis to 5 years post-treatment) of 100 patients with OC in this study were 33 months. The mean OS of patients in the BG-LOW group was 37 months compared to 28 months in the BG-High group; this difference was statistically significant (P <0.01). The Cox regression model indicated that post-chemotherapy blood glucose levels exerted an independent effect on OS in OC patients (hazard ratio [HR]: 3.4; 95 % confidence interval [CI]: 2.0-5.7; P < 0.01). In addition, FIGO staging and surgical R0 resection also exerted independent effects on patient survival. Patients with advanced ovarian cancer experience hyperglycemia during adjuvant chemotherapy. Furthermore, an increase in blood glucose after chemotherapy is associated with a poor prognosis. Our findings identified potential chemotherapy risks and highlighted the importance of preventing hyperglycemia.

Knowledge and practice of health promotive lifestyle toward cervical cancer prevention among women in Africa: A scoping review

Cervical cancer remains a significant public health concern among women globally, with a high burden of morbidity and mortality. Despite the existence of empirical evidence about various preventive strategies, the burden of cancer continues to rise, particularly in developing countries like Nigeria. This scoping review aimed to examine the existing literature on the knowledge and practice of health-promotive lifestyle factors for the prevention of cervical cancer among women in Nigeria. This review is driven by the acknowledgment that early detection and prevention are crucial in mitigating the impact of cervical cancer. A systemic search of databases; PubMed, Embase, Google Scholar, Medline, Semantic Scholars was also conducted to identify relevant studies published between 2019 and 2023. Relevant articles were screened for eligibility, and 46 papers were selected. The Joanna Briggs Institute and Preferred Reporting Items for Systematic Review and Meta-analysis Scoping Review Extension (PRISMA-ScR) guidelines were used to analyze the quality of the articles. The study affirmed that various studies have been done concerning knowledge and practice of cervical cancer prevention among women in Africa. The knowledge, attitude and practice of cervical cancer prevention was poor among these women, which has had a direct influence in the poor uptake of cervical cancer screening among Africa women. However, nurse led interventions has been proven to increase knowledge level and screening uptake in experimental groups post intervention. While some women have good knowledge of cervical prevention, the attitude and practice of prevention is poor in many of the studies reviewed. The uptake of screening was low, and some barriers identified encompasses socio-cultural concerns, cost, insufficient health education, limited availability of healthcare services, and consent from partners, while family history of cervical cancer is one of the reasons for uptake of screening in some women.

Epithelial ovarian cancer: Review article

Epithelial ovarian cancer is the second commonest cause of death amongst all gynaecological cancers. Treatment is challenging because almost 75% of cases are diagnosed in advanced stages. Front line treatment with aggressive cytoreduction and adjuvant treatment decides the outcome. Despite the complete response to primary treatment majority will relapse with disease. Treatment options of recurrent disease depends on platinum free interval. Systemic therapy is the mainstay of treatment and secondary cytoreduction may be beneficial in selected patients Newer therapeutic agents are being added in the front line and recurrent setting to improve outcome.

Hyperthermic intraperitoneal chemotherapy (HIPEC) after primary debulking surgery in advanced epithelial ovarian cancer: Is BRCA mutational status making the difference?

The role of a molecular pattern predictive of hyperthermic intraperitoneal chemotherapy (HIPEC) efficacy in advanced ovarian cancer (AOC) patients has been poorly investigated. We aimed to assess the effect of HIPEC after primary debulking surgery (PDS) in AOC according to patient's Breast Cancer Gene (BRCA) mutational status. This is a retrospective, single center, case-control study. Data on AOC patients receiving HIPEC at the end of PDS as previously enrolled in a phase II monocentric trial (HIPEC group), were retrieved and matched for clinical and surgical characteristics with a group of cases who underwent PDS without receiving HIPEC between 01/2010 and 01/2015 (No HIPEC group). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage ≥IIIB disease, aged between 18 and 70 years, with a laparoscopic Predictive Index value (PIV) ≤8 and residual disease ≤2.5 mm were included. 70 patients were included. With the except of age (p = 0.012), the populations were balanced for the main characteristics. At a median follow-up of 48 months, no differences in Progression Free Survival (PFS) (p = 0.968) and Overall Survival (OS) (p = 0.789) were recorded. Survival analysis according to HIPEC administration and BRCA mutational status showed an improved PFS (p = 0.011) and OS (p = 0.003) in BRCA mutated compared to wild-type patients when HIPEC was not administered, whilst they were superimposable in case of HIPEC administration (p = 0.857 vs p = 0.372; respectively). No differences in terms of neither intra-operative (p = 1.0) nor early post-operative complications (p = 0.920) were detected. Our results show that HIPEC in AOC may be a promising treatment in BRCA wild-type patients, as it seems to balance their decreased chemosensitivity compared to mutation carriers.

Factors associated with health seeking delay in the screening of cervical cancer among women in Imo state, south Eastern Nigeria

Cervical cancer is a curable disease if diagnosed early. The mortality rate due to cervical cancer is high worldwide, mainly because of the absence of a functioning screening process and the advanced stage of the disease at diagnosis. The aim of this study was to assess the factors associated with health-seeking delay in the screening of cervical cancer among women in Owerri Municipal LGA, Imo State. A descriptive cross-sectional research design was employed in this study on factors associated with health-seeking delay in the screening of cervical cancer among women in Owerri Municipal LGA. A semi-structured questionnaire was used for the study, and Statistical Package for the Social Sciences (SPSS) version 20 was used in the analysis of the data gotten from the study. A probability-based multi-stage sampling method was adopted for the study in recruiting 432 women who participated in it. Results from the study showed that most of the women, 117 (27.1 %), were between the ages of 22 and 27. The study found that a high percentage of the respondents, 350 (81.0 %), had heard about cervical cancer screening, and when they were asked who they thought should be screened for cervical cancer, 154 (35.6 %) said women between the ages of 15 and 40. Further findings revealed that, 420 (97.2 %) said they had not been screened for cervical cancer. The study also demonstrated that 260 (60.2 %) believe long distance has an impact on your access to health care. The findings of this study revealed that age (P = 0.0247), educational level of women (P = 0.0214), and monthly income of the women (P = 0.0062) were all significantly associated with health-seeking delay in cervical screening. The study concluded that there is no limited knowledge about cervical cancer among women in Owerri Municipal. Long distance to screening facilities, educational background, and monthly income are significantly associated with the delay in seeking health services for cervical screening. The study recommended that there should be massive awareness and participation in the screening program across the state.

The effect of distance from cancer facility on advanced clinical stage at diagnosis in patients with cervical cancer

In the United States, cervical cancer remains a significant cause of morbidity and mortality. The effect of distance has a complicated relationship with disease characteristics and outcomes in other cancers. The purpose of this study is to investigate the relationship between distance from cancer facility on clinical stage at diagnosis in women with cervical cancer. Data were obtained from the National Cancer Database which include patient demographics, disease characteristics, and treatment details. Persons diagnosed with cervical cancer from 2004 to 2015 were included. Subjects were excluded if they had missing information, variant histology, or lived >1,000 miles from their facility resulting in 51,413 persons. Disease was classified as localized (stage 1a-2a) or advanced (stage 2b-4b). Univariate comparisons were performed using analysis of variance and chi-square test. Multivariable logistic regression was used to investigate the effect of distance quartiles on advanced stage while adjusting for other significant variables. Mean age was 51.0 years, 16.9% of women were black, 14.7% were Hispanic, 45.0% had private insurance, and 10.7% were uninsured. Overall, 50.9% of women presented with advanced disease. In multivariable analysis, greater distance demonstrated a stepwise risk reduction of advanced disease where those in the farthest quartile had odds ratio of 0.73 (p<0.001) relative to the closest. Additionally, age, race, income, and insurance status significantly affected risk of advanced disease. Distance from cancer facility resulted in lower risk of advanced stage disease at diagnosis. Additional research could elucidate the nuanced relationship between distance, disease characteristics and outcomes in cervical cancer.

Knowledge, attitude and perception on cervical cancer screening among women attending ante-natal clinic in Owerri west L.G.A, South-Eastern Nigeria: A cross-sectional study

Cancer of the cervix is the second most common cancer in women globally, and it is a major cause of morbidity and mortality among women in developing countries such as Nigeria. The study assessed the knowledge, attitude and perception on cervical cancer screening among women attending ante-natal clinic in Owerri West, south eastern Nigeria. This cross-sectional study was conducted using a random sampling technique among 231 respondents attending ante-natal clinic in a cluster of 4 selected public primary healthcare centres. A structured questionnaire was used for data collection, and data obtained was analysed using a descriptive technique, while the chi-square test was used to test for the influence of age and education level on cervical cancer screening. The result showed that there was a high level of awareness (68.8%) of cervical cancer screening. The majority of women (122 (52.8%)) received this information from friends. Although the majority of the participants had heard about the screening, few of them had basic information on the cause of the disease 44 (19%), prevention 32 (13.9%), risk factors 48 (20.8%) and treatment (23.4%) of the disease. Of the 231 women, 59 (25.5%) strongly agreed they were too young to have cervical cancer and hence there was no need for the screening, while a greater proportion (53 (22.9%)) agreed that the screening is only meant for older women (30-45 years). Expensive cost of screening (68 (29.4%)) and invasion of privacy by male doctors (34.6%) were also strong reasons for avoiding screening. The study revealed strong influence of age (χ2 = 104.37; DF = 10; P<0.001) and level of education (χ2=31.63; DF = 6; P<0.001) on awareness of cervical cancer screening. Moreover, educational status had a significant positive influence (χ2= 54.71; P<0.001) on the cause of cervical cancer, with a higher proportion of participants with post-secondary education. Awareness of cervical cancer is high, but the perception that it can be treated is quite low, along with fear of the screening outcome. Age and level of education are significant factors of screening for cervical cancer. Educational programmes encouraging participation in cervical cancer screening should consider involving the use of close peers and friends to educate the women on the importance of screening program.

Whole exome sequencing of low risk endometrial cancer patients with isolated local recurrences

A small proportion of clinicopathologically low-risk endometrial cancer (EC) patients who omitted adjuvant radiotherapy (RT) may subsequently develop a local recurrence. Molecular profile for those clinically low-risk yet recurred EC patients is unavailable. A total of 442 EC patients treated from 2014 to 2020 at Northwestern Memorial Hospital were studied. Among them, 28 patients clinically low risk or low-intermediate risk per GOG-99 criteria developed an isolated local recurrence after hysterectomy, bilateral salpingo-oophorectomy, and omitted RT. Whole exome sequencing (WES) was performed on 22 patients whose pathologic specimen were retrievable. The majority of the cases studied were molecularly No Specific Molecular Profile (NSMP) cohort (91%). We identified CTNNB1, FGFR2, PTEN, and KRAS as the most frequently altered pathogenic or likely pathogenic genes with 5 (22.7%), 5 (22.7%), 4 (18.2%), and 3 (13.6%) out of 22 patients carrying these alterations, respectively. TP53 somatic alterations were identified in 2 (9.1%) out of 22 cases. Analysis of The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) dataset identified 53 EC patients with pathologically Grade 1 molecularly NSMP cohort. Within this cohort, CTNNB1 alterations were identified in 31 patients (58%) and prognosticated worse progression free survival (p<0.05). NSMP molecular group constitutes the majority of clinically low-risk EC patients with isolated local recurrences. The CTNNB1 alteration was validated as a biomarker in prognostication in this independent cohort and may help guide adjuvant treatment decisions.

Outcomes in patients of carcinoma cervix Stage IIIB treated with definitive radiotherapy

Cervical cancer is the fourth most common cancer in women. Although cervical cancer screening is available in India, there is lack of awareness and access to screening services. Consequently, most cancers are diagnosed in advanced stagesoften with obstructive uropathy. This was a retrospective study of stage III B (as per pre-2018 FIGO staging) cervical cancer patients who received radiotherapy at our center between 2012 and 2019. Patients with or without obstructive uropathy, age group between 18 and 85 years, were included. Definitiveradiotherapy (RT) was delivered with 3D CRT to a dose of 50 Gy in 25 fractions over 5weeks given to whole pelvis and boost of 54 Gy was given to para-aortic or retroperitoneal lymph nodes when enlarged. All patients received intracavitary brachytherapy. 3-year overall survival rates for patients who received only RT was 24% versus 71% for those who received chemoradiotherapy (p = 0.0001). 5-year survival for patients who received RT alone was 12% versus 63% for those who received chemoradiotherapy (p = 0.0001). 3-year PFS was 77% versus 83% and those with and without obstructive uropathy respectively. (p = 0.0001). Overall, 37(56%) patients were alive without any evidence of recurrence. Early recognition and appropriate intervention for obstructive uropathy can potentially limit the detriment to outcomes in these patients and result is good long-term cure rates in these patients.

Endometrial Stem/Progenitor cell (ES/PC) Marker Expression Profile in Adenosarcoma and Endometrial Stromal Sarcoma

The uterus is one of the most dynamic organs in the human body, and this dynamic homeostasis is supported by endometrial stem/progenitor cells (ES/PCs), which are heterogeneous in their phenotype and degree of differentiation. ES/PCs are generally localized in the endometrial stroma, the site of origin for adenosarcoma and endometrial stromal sarcoma (ESS). Subsets of ESSs and adenosarcomas harbor SUZ12 or DICER1 gene alterations, two genes with roles in embryonic stem cell biology. However, the possible contribution of ES/PCs to tumorigenesis is unexplored. We examined the expression of eleven ES/PC markers, along with three proteins expressed in the mature endometrial stroma (ER, PR and CD10) in 60 uterine tumors (24 low-, 11 high-grade ESS, 25 adenosarcomas). Protein expression profiles were assessed by unsupervised hierarchical clustering. miRNA expression profiles were examined in a subset of adenosarcoma with/without DICER1 mutations, using the NanoString platform. ES/PC markers were variably expressed, and the tumors exhibited limited immunophenotypic resemblance to different ES/PCs. Within the ESSs, the ES/PC marker clustering pattern was prognostic for both overall and disease-free survival. Comparing adenosarcomas and ESSs, most high-grade ESSs clustered with one another, while low-grade ESSs and adenosarcomas tended to cluster with one another. Among the adenosarcomas, the miRNA expression profiles were varied with respect to the DICER1 mutation status, with pathway analysis pointing to dysregulated signal transduction and stem cell biology. ESSs and adenosarcomas exhibit varying immunophenotypic resemblance to ES/PCs. These expression profiles have prognostic implications and may be genetically driven.

Serum CYFRA21–1 and SCC-Ag levels in women during pregnancy and their diagnostic value for cervical cancer

The incidence of cervical cancer increases every year during pregnancy. Cervical cytology in pregnant women has a unique morphology and liquid-based cytology methods are prone to cause false positives. The aim of this study was to investigate the serum cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and squamous cell carcinoma associated antigen (SCC-Ag) concentrations in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy. In this prospective study, 165 healthy non-pregnant women, 441 healthy pregnant women and 22 patients with cervical cancer in pregnancy were recruited. The healthy pregnant women group included 143 women in the first trimester (T1), 147 in the second (T2) and 151 in the third (T3). Both SCC-Ag and CYFRA21-1 levels were significantly different in the healthy pregnant women group compared to the control group. The CYFRA21-1 and SCC-Ag were higher in the T1 and T3 than in the control groups. However, there was no statistically significant difference in serum CYFRA21-1 and SCC-Ag levels in the T2 group compared to the control group. The AUCs of CYFRA21-1, SCC-Ag and CYFRA21-1 combined with SCC-Ag were 0.674, 0.792, and 0.805, respectively. The cut-off values of CYFRA21-1 and SCC-Ag were 6.64 ng/mL and 1.75 ng/mL, respectively. Serum CYFRA21-1 and SCC-Ag levels were higher in pregnant women during early and late pregnancy compared to non-pregnant individuals, while they were not statistically different from non-pregnant women during mid-trimester. CYFRA21-1 and SCC-Ag have diagnostic value for cervical cancer in pregnancy.

Human papilloma virus vaccines: A comprehensive narrative review

Cervical cancer is one of the most common cancers in women aged 15-44 years in the world, with more than three-quarters of cases diagnosed at a locally advanced clinical stage with minor prospects of survival. Although only a small percentage of women with Human Papilloma Virus (HPV) develop cervical cancer and most of the HPV infections are cleared subsequently at primary stage itself, but seroconversion not always guarantees that the individual is immune to HPV. The advent of the cervical carcinoma vaccine has raised the expectations that eradication of cervical carcinoma might be possible in the near future as it exhibited remarkably high efficacy against the vaccine-specific types in naive women with no serious vaccine-related adverse events. Few prophylactic HPV vaccines are currently licensed in over 100 countries. It has also been suggested that vaccinating both men and women is more beneficial than vaccinating only females. Vaccination is a cost-effective strategy to reduce the incidence of cervical cancer and mortality compared to no vaccination based on the cost of cancer treatment. Well-coordinated vaccination strategy with focus on adolescent girls and if possible, boys can lead to dramatic impact on disease reduction around the world.

Patient profiles, treatment patterns, and outcomes among persistent, recurrent, or metastatic cervical cancer patients under routine care in the United States

Patients with persistent, recurrent, or metastatic cervical cancer have poor prognosis. While recent advances have expanded treatment options, real-world data on treatment patterns and outcomes in this population are lacking. This retrospective study identified adult females with persistent, recurrent, or metastatic cervical cancer from the ConcertAI Oncology Dataset who received systemic therapy on or after August 15, 2014. Patients were followed from persistent, recurrent, or metastatic diagnosis through third-line (3 L) therapy, death, end of record, or study end (June 2021). Data collection included patient characteristics, treatment patterns, and clinical outcomes. Kaplan-Meier methods were used for the three most common first-line (1 L) regimens to analyze real-world time on treatment (rwToT), real-world progression-free survival (rwPFS), and real-world overall survival (rwOS). Analyses were stratified by bevacizumab receipt by treatment line. 307 patients were included (mean [standard deviation] age 51.5 [13.2] years, 70.7% White). 91.2% of patients had metastatic disease, 8.5% had persistent disease, and <1% had recurrent disease. The most common 1 L regimen was carboplatin+paclitaxel+bevacizumab (40.7%) with median (95% confidence interval [CI]) rwToT of 3.5 (2.9-4.4) months. 57.0% of patients proceeded to second line (2 L), and 25.7% went to 3 L. Median (95% CI) rwPFS was 7.2 (6.4-8.1) months, and median (95% CI) rwOS was 16.5 (14.2-19.9) months, from initiation of 1 L. 1 L regimens received in patients with persistent, recurrent, or metastatic cervical cancer generally followed clinical guidelines, and the rwOS agrees with clinical trials. This study highlights the burden of disease and unmet need for specific treatments in these patients.

HPV testing for cervical cancer screening: Should reflex cytology be performed after a positive test for HPV 16 and 18?

At Portuguese-organized cervical cancer (CC) screening programs, all women testing positive for human papillomavirus (HPV) 16 and/or 18 are referred for immediate colposcopy. This study aimed to evaluate the utility of reflex cytology in women who test positive for HPV 16 and/or 18 to improve the efficiency of CC screening. A cross-sectional and retrospective study was performed based on data from the routine CC screening protocol in force at Cova da Beira University Hospital Center, Portugal between August 2012 and June 2021. The screening method was the Cobas 4800 HPV test using the liquid medium Surepath. In all the selected cases, the patient's HPV test results and the cytology and histology findings of the biopsies obtained using colposcopy were analyzed. This study included 339 women who first tested positive for HPV 16 and/or 18 and were referred for immediate colposcopy, in whom 40 (11.8%) cases of high-grade squamous intraepithelial lesion (HSIL+) were diagnosed. Of these, 12 (30%) had reflex cytology negative for intraepithelial lesion or malignancy (NILM) and 14 (35%) had HSIL+ cytology. After 3 years, 14 (9.3%) of the 150 women who were still undergoing follow-up were diagnosed with histologic HSIL+ lesions, of which 5 (35.7%) had baseline NILM cytology. Despite the small sample, the results of this study allow us to conclude that reflex cytology is not useful for discrimination to immediate referral for colposcopy in women who test positive for HPV 16 and/or 18, as most women with a histologic diagnosis of an HSIL+ lesion had <HSIL reflex cytology.

Involvement of small extracellular vesicle-derived TIE-1 in the chemoresistance of ovarian cancer cells

Ovarian cancer is the most lethal gynecologic malignancy due to the tumor's acquisition of chemoresistance to platinum-based chemotherapy. To solve this problem, we conducted RNAi-based large-scale screening and determined that tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) is a key molecule involved in the platinum resistance of ovarian cancer cells. Recently, a variety of studies have investigated that small extracellular vesicles (sEVs) contribute to the communication between cancer cells, including the development of chemoresistance in ovarian cancer. The purpose of our study is to determine if sEVs-derived TIE-1 is involved in the chemoresistance of ovarian cancer cells. TIE-1-overexpressed TOV112D cells, termed TOV112D TIE-1 was contained within sEV Our findings suggest that sEV-derived TIE-1 could be a new therapeutic target for refractory ovarian cancer.

Evaluating the tozzi classification system in diaphragm surgeries for advanced ovarian cancer: Clinical applicability and perioperative outcomes

Over 70 % of advanced ovarian cancer cases involve metastasis to the peritoneum, diaphragm, and liver. Standardised diaphragm surgeries are vital for achieving complete cytoreduction and enhancing patient prognosis. This study evaluates the clinical utility of Tozzi's classification for diaphragm surgeries and examines perioperative outcomes in advanced ovarian cancer debulking. Patients who underwent diaphragm surgery during cytoreductive procedures for ovarian cancer were classified using Tozzi's classification based on disease extent, and liver mobilisation and perioperative outcomes were analysed. Among 38 patients (71 % stage III; 52.6 % interval surgeries), 39.4 % were Type I, 28.9 % Type II, and 31.5 % Type III. Ascites was more common in Type II (77.8 %, p = 0.04), while Type III had more imaging-detected lesions (83.3 %, p = 0.03). Type III surgeries required longer durations (405 ± 136 min, p = 0.04) and more intraoperative interventions (58.3 %, p = 0.01). ICU care was needed in 50 % of cases, with a median stay of two days, mainly for Type III. Pulmonary complications occurred in 10.5 %, and the median hospital stay was six days. Tozzi's classification predicts surgical complexity and morbidity, particularly for Type III cases, aiding surgical planning and optimising patient outcomes.

The impact of multiple neoadjuvant chemotherapy cycles in patients with advanced epithelial ovarian cancer: A single center experience

Three to four cycles of neoadjuvant chemotherapy prior to interval debulking surgery is a common treatment of ovarian cancer. This study aimed to determine the impact of increasing the number of neoadjuvant chemotherapy cycles on overall survival), progression-free survival, and disease responses in patients diagnosed with epithelial ovarian cancer. Twenty-eight patients who underwent NACT for advanced-stage EOC were enrolled in a retrospective cohort study conducted at Princess Noorah Oncology Center and King Abdulaziz Medical City between 2010 and 2021 and divided into two groups. Patients in the first group received fewer than six cycles of NACT while those the second group were treated with six or more cycles. Differences in the OS, PFS, and NACT responses were compared. The median OS was 22.50 months ([IQR], 35.75 months) among patients in the group who received fewer than six cycles of NACT and 29.5 months (IQR, 28.75 months) for those treated with six cycles or more (P = 0.67). The median PFS was 12 months (IQR, 16) for the group that received fewer than six cycles, and nine months (IQR, 21.5 months) for patients assigned to the group that received six or more cycles (P = 0.88). Six of the patients from the group that received fewer than six cycles of NACT and five of the patients from the group that received six cycles or more achieved a complete response to therapy (P = 0.81). Increasing the number of NACT cycles did not significantly impact OS, PFS, or the overall response to therapy. However, the study's small patient population presents a limitation.

Dendrosomal Curcumin Nanoformulation induces apoptosis via Bax/Bcl-2 in human ovarian cancer OVCAR3 cells

Curcumin (Cur), a yellow polyphenolic compound derived from the rhizome of turmeric, exhibits potent chemopreventive and chemotherapeutic properties. However, its clinical application as an anticancer agent is hindered by poor water solubility and low bioavailability. To overcome these limitations, the present study introduces a novel nanoformulation in which curcumin is effectively encapsulated within 142 nm spherical dendrosomes, which serve as a non-toxic nanocarrier. The morphological changes in OVCAR3 ovarian cancer cells were assessed using both inverted light microscopy and fluorescence microscopy. Cell cycle distribution was analyzed by flow cytometry using the MultiCycler software. Cells were treated with dendrosomal curcumin (DNC), oxaliplatin (Oxa), or a combination of both for 48 hours. Protein expression levels were analyzed by western blotting using enhanced chemiluminescence (ECL) detection. Dendrosomal curcumin improves curcumin's bioavailability and therapeutic potential in cancer treatment. Treatment with DNC and Oxa individually resulted in significant induction of apoptosis in OVCAR3 cells. The combination therapy further amplified this effect compared to either agent alone. Molecular analyses revealed upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2 at both mRNA and protein levels, supporting the activation of apoptotic pathways. Our findings demonstrate that both DNC and Oxa induce apoptosis in OVCAR3 ovarian cancer cells through modulation of Bax and Bcl-2 expression. The enhanced efficacy observed in combination therapy highlights the therapeutic potential of DNC, in conjunction with conventional chemotherapeutics, as a promising strategy for ovarian cancer treatment.

Modified swede colposcopic index versus modified reid index in colposcopic screening for premalignant &amp; malignant lesions of the cervix: a cross-sectional analysis

Cervical cancer cases in India account for one-fourth of the worldwide burden. Colposcopy is used to evaluate the cervix of women with abnormal screening test results. For standardized reporting, various scores were introduced of those, Reid Colposcopic Index (RCI) and Swede score are the most commonly used. This study is undertaken to determine the diagnostic efficacy and clinical relevance of the newly introduced MSCI and compare MSCI and Modified Reid Index. 225 women out of 237 were analyzed. MSCI score 9 perform best for colposcopic diagnosis of CIN 2 or higher lesions. The sensitivity, specificity, PPV, and NPV for threshold score 9 for CIN 2 or higher lesions were 94.92 %, 67.88 %, 51.38 %, and 97.39 % respectively. Modified Reid Index threshold 3 performed best for the detection of CIN 2 or higher lesions with a sensitivity, specificity, PPV, and NPV of 84.75 %, 44.85 %, 35.46 %, and 89.16 % respectively. On comparing the area under the curve (AUC) for MSCI and MRI, we found that the difference between the AUC of MSCI (0.854) and Modified Reid Index (0.657) was significant (P < 0.05). MSCI performs better than the modified reid index for the diagnosis of both HGL and LGL or higher. Also, the omission of impractical measurements and inclusion of easier and more practical parameters than the Swede score or Modified Reid Index makes MSCI a simple and effective screening tool.

Small cell neuroendocrine carcinoma of vagina: Report of a unique case with literature review

Small cell carcinoma (SCC) of vagina is extremely rare. The association between this tumor and high-risk HPV infection is unclear. To our knowledge, HPV status has been reported in only 3 previous cases of SCC of vagina. Herein, we present a unique case of vaginal small cell carcinoma with discordant HPV testing results between vaginal and cervical samples. We also review and discuss findings from previously reported cases of small cell carcinoma of vagina.

Case report: Response to platinum agents and poly (adenosine diphosphate-ribose) polymerase inhibitor in a patient with BRCA1 c.5096G&gt;A (R1699Q) intermediate-risk variant

BRCA1 c.5096G>A (p. Arg1699Gln) (hereinafter BRCA1 R1699Q) is classified as a pathogenic genetic variant despite its lower penetrance of breast and ovarian cancers compared to other BRCA1 variants. However, this mutation is currently reported as a 'special interpretation' variant in the BRACAnalysis® because the response to platinum agents and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors remains unknown in patients with this mutation. We present a case of stage IIIc high-grade primary peritoneal cancer in a 69-year-old woman with germline BRCA1 R1699Q variant. She received platinum-containing chemotherapy followed by surgery. Eight months later, the patient experienced recurrence and received six cycles of chemotherapy and olaparib maintenance therapy. However, the disease progressed after only 5 months, and she received another chemotherapy drug. This patient responded slightly to platinum agents and had shorter progression-free survival on olaparib compared with clinical trial data. myChoice® CDx also showed Genomic Instability Score (GIS) was 50. This patient had no other gene mutations which could cause homologous recombination deficiency. This is the first report of the clinical outcome of PARP inhibitor and platinum-containing chemotherapy in a patient with a BRCA1 R1699Q variant. Despite BRCA1 mutation and high GIS, used as indicators of drug sensitivity, the recurrent tumor did not respond well to platinum agents and olaparib. BRCA1 R1699Q variant could differ from others in cancer risk and in drug response. Further studies are needed to confirm these observations.

Does muscle invasive bladder cancer following pelvic radiotherapy portend worse prognosis? A seer-based study

Although emerging evidence demonstrates increased risk of secondary bladder cancer following pelvic radiotherapy, the aggressiveness of these tumors is not well-characterized. A search of the Surveillance, Epidemiology, and End Results (SEER) 18 Database, identified 25,734 patients diagnosed with bladder cancer following definitive therapy for previous pelvic malignancy. Kaplan-Meier curve analyses were utilized to determine overall survival with significance set at p<0.05. Of the 25,734 patients, 11,376 (44.2%) received radiation treatment for their first cancer. Overall survival of bladder cancer was found to be 80%, 69.5%, and 49.2% at 1,2 and 5 years, respectively. There was no significant survival difference between groups whose first cancer was treated with or without radiation (p=0.8). A survival advantage was seen for the bladder cancer patients not treated with radiation for cervical (p=0.004), uterine (p=0.0006), and vaginal cancers (p<0.0001). Bladder cancer patients treated with radiation for prostate cancer showed a survival advantage (p=0.002). The average time to second cancer diagnosis was 6.5±6.1 years. Patients treated with radiation for first primary cancer showed a longer time to second cancer (7.2±6.0 years) compared to those treated without radiation (5.9±6.0 years) (p<0.01). Patients with prior history of female cancers treated without radiation demonstrated significant survival advantage in second primary bladder cancer. A small significant survival advantage was seen in bladder cancer patients previously treated for prostate cancer with radiation. This data suggests that second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy. The overall survival of 25,734 patients diagnosed with bladder cancer following definitive therapy for a previous pelvic malignancy was 49.2% at 5 years. There was no significant survival difference between groups whose first cancer was treated with or without radiation. Second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy.

A randomized controlled trial comparing large versus small stitch incision closure in gynaecological malignancies (CLaSSIC Study)

The study aimed to compare Small Stitch Closure (SSC) and Large Stitch Closure (LSC) techniques for reducing incisional ventral hernia (IVH) and surgical site infection (SSI) rates in gynaecological malignancies. We conducted a single-blind, randomised controlled trial at our gynaecological oncology department. Patients aged ≥18 years scheduled for elective oncological surgery with midline laparotomy were randomly assigned to receive small stitches of 5 mm every 5 mm or large stitches of 1 cm every 1 cm. Between March 1, 2022, and August 13, 2023, 218 patients were randomly assigned to either the LSC group (n = 110) or the SSC group (n = 108). Follow-up ended on August 20, 2024, with 213 patients completing it. After one year, the SSC group had significantly lower rates of IVH at 3.7 % compared to 12.1 % for the LSC group (p = 0.02); this difference remained significant in multivariate analysis (p = 0.04, OR: 5.78). SSI rates were similar, with the LSC group at 2.8 % and the SSC group at 3.5 % (p = 0.11). In the multivariate analysis, preoperative chemotherapy was significantly associated with IVH (p = 0.04, OR: 3.83), while a postoperative hospital stay of 72 h or more increased the risk of SSI (p = 0.02, OR: 11.51). LSC was associated with a significantly higher rate of IVH compared to SSC, while SSI rates were similar between both groups. Preoperative chemotherapy was a key factor influencing IVH, and a longer postoperative hospital stay led to increased SSI rates.

Pre-treatment hematological parameters as a cost effective predictive marker for response to concurrent chemo radiation in locally advanced cervical cancer

Locally advanced cervical cancer is still a major cause of mortality in developing countries. Recently, personalized medicine has changed the treatment paradigm for many solid cancers but no robust biomarkers has yet been validated for predicting response to chemo radiation in cervical cancer patients. To assess the role of hematological parameters as a cost-effective predictive marker of response to concurrent chemo radiation in cervical cancer patients. This is a retrospective analysis of 90 cervical cancer patients treated with concurrent chemo radiation in a tertiary cancer center. Clinical details of the patients were extracted from the case records. For end point evaluation, the pre-treatment levels of hemoglobin, neutrophil, lymphocyte, platelet, platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) were compared and statistically analyzed between responders and non-responders. The optimal cutoff values of hematological parameters were estimated by the receiver operating characteristics (ROC) curve. Out of 90 patients, 60 (66.66%) were complete responders and remaining 30 (33.33%) were non-responders. The mean value of platelet, NLR, and PLR was significantly higher in the non-responder group. ROC curve analysis showed the optimal cut-off value of pre-treatment Hb, PLT, NLR and PLR to be 11 gm/dl, 3, 177 × 109/L, and 70 respectively. Our study suggests that simple hematological markers like NLR, PLT count and PLR could be used as a cost effective pretreatment predictive marker for response to chemo radiation in cervical cancer patients.

Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer,

Uterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. Whole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. Serum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P < 0.05), stage (P < 0.16), tumor size, and parametrial invasion. Negative result was seen with vaginal invasion, lymph node involvement & cases which had recurrence. Various histological types showed variable results. So the serum level of HE4 (sHE) level may play a role in the diagnosis & therapeutic monitoring of UCC. But the prognostic evaluation needs further studies. sHE4 is useful in the diagnosis of cervical cancer, but its prognostic significance is under the question marks. It may be associated with higher values in higher stages. Higher parity of the patient is associated with higher level of HE4 in UCC.

Obstetric outcomes after cervical loop electrosurgical excision procedure

This study aimed to investigate whether a history of loop electrosurgical excision procedure (i.e., conisation) affects obstetric and neonatal outcomes. A retrospective cohort study was carried out in Västernorrland county, Sweden. 57 nulliparous women with singleton pregnancies and previous conisation were compared with 100 age-matched pregnant controls without history of conisation. There was significantly lower gestational age by delivery (p = 0.036), however, the premature delivery rate was not different. Caesarean section was also less frequent (OR: 0.29, 95% CI: 0.081-1.04, p = 0.047) in the conisation group than those in the control group. There were no differences in neonatal outcomes. Previous conisation does not affect the risk of prematurity or cervical dilatation during the first stage of labour. Women with history of conisation had a lower rate of caesarean section, and lower gestational age by delivery.

OTUB1/SLC7A11 axis promoted AKT signaling activation to mediate ovarian cancer progression

Exploring the application of PD-1/PD-L1 inhibitors for ovarian cancer

Ovarian cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although standard treatment regimens, including cytoreductive surgery combined with platinum-based chemotherapy, have achieved certain therapeutic advances, the high recurrence rate and the emergence of platinum resistance continue to represent significant clinical challenges. This highlights the urgent need to explore novel therapeutic strategies.As an emerging modality of immunotherapy, PD-1/PD-L1 inhibitors enhance anti-tumor immune responses by modulating the immune system. Although ovarian cancer has traditionally been regarded as a tumor with low immunogenicity, studies have demonstrated that the presence of tumor-infiltrating lymphocytes and the expression of PD-L1 indicate a potential response to immune checkpoint inhibitors.This review focuses on the application of PD-1/PD-L1 inhibitors in the treatment of ovarian cancer, summarizing their mechanisms of action, clinical research progress, potential combination strategies, and future perspectives. A deeper understanding of the role of immune checkpoint inhibitors in ovarian cancer will contribute to optimizing therapeutic strategies and improving patient outcomes. Despite the potential of PD-1/PD-L1 inhibitors in ovarian cancer treatment, overcoming resistance mechanisms, refining patient selection criteria, and improving safety profiles remain key challenges for clinical application.