In Vivo

The Impact of the COVID-19 Pandemic on Breast and Cervical Cancer Screening: A Systematic Review

COVID-19 has dramatically impacted non-pandemic-related care, including preventive medicine. Our objective was to quantify the alterations in the volume of screening tests for breast and cervical cancer during the COVID-19 era compared to pre-pandemic levels. Secondarily, we discussed the causes responsible for this change, presented suggestions for screening optimization and conducted a targeted search of the relevant literature for worsening of future mortality due to screening setback. We systematically searched Pubmed, Google Scholar and Epistemonikos for articles in English or Greek, published from March 11th, 2020, until September 14th, 2022, that illustrated quantitative variations of mammograms or Pap/HPV tests. Preprint articles, editorials and speeches were excluded. Quality of included studies was assessed via the JBI critical appraisal checklist for studies reporting prevalence data. The evidence was narratively synthesized. A total of 56 articles were included, being either observational studies or reports from cancer registries. Large reductions were universally identified, peaked during the first wave but partially persisted after easing of the restrictions. Our systematic review provides an updated record of the variations in screening volume and approaches screening neglect from a multidimensional perspective answering why it happened and how we could achieve recovery. A strong awareness campaign is proposed, in conjunction with triaging citizens more likely to benefit from screening. Cervical self-sampling is emphasized in the literature. Various studies displayed a potential increase in cancer mortality in the future based on predictive statistical models.

The Influence of the Metabolic Syndrome on Early Postoperative Outcomes of Patients With Advanced-stage Endometrial Cancer

Endometrial cancer is one of the most commonly encountered malignancies among obese women worldwide, a strong causality relationship being established between the two entities. Furthermore, obesity is also associated with metabolic syndrome; the aim of this study was to investigate the effect of metabolic syndrome on the postoperative outcomes of patients with endometrial cancer. Data of 23 patients diagnosed with endometrial cancer and metabolic syndrome were retrospectively reviewed and compared to the those of a control group of patients diagnosed with endometrial cancer in the absence of metabolic syndrome. Patients in the first group presented significantly higher values of body mass index when compared to the control group. There were no significant differences in terms of stage, histopathological subtype or degree of differentiation between the two groups. The completeness of cytoreduction was lower among patients with metabolic syndrome, however, this did not reach statistical significance (p=0.08). Although the rate of complete debulking was lower among those with metabolic syndrome, the rates of postoperative complications were significantly higher. The association of metabolic syndrome significantly influences the risk of postoperative complications in patients with endometrial cancer; moreover, in certain cases, it might preclude the achievement of freedom from residual disease.

Urinary Tract Resections as Part of Debulking Surgery for Locally Advanced Endometrial Stromal Sarcomas

Although very rare tumors, uterine sarcomas are extremely aggressive gynecologic malignancies being responsible for a significant number of gynecological cancer-related deaths. However, in such cases, it seems that cytoreductive surgery might increase the lifespan if debulking to no residual disease is achieved. We present a case series of three patients diagnosed with endometrial stromal sarcomas in which urinary tract resections were needed in order to maximize the debulking effort. In all cases total hysterectomy with bilateral adnexectomy was performed; in the meantime, urinary tract resection was needed due to the local extension of the neoplastic disease and consisted of unilateral ureteral resection followed by reimplantation through ureteroneocystostomy in one case, bilateral ureteral resection en bloc with partial cystectomy and ureteral reimplantation in one case and total cystectomy with bilateral ureterectomy followed by cutaneous ostomy in the third case. Moreover, one case also necessitated rectosigmoidian resection followed by colorectal anastomosis. In all cases no residual disease was encountered at the end of the debulking surgery. Urinary tract resections might be needed in order to maximize the debulking effort in patients presenting endometrial stromal sarcomas.

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

This research was aimed to evaluate the association between three selected single nucleotide polymorphisms (SNPs) within the CDKN2A (P14ARF) tumour suppressor gene and the incidence of endometrial cancer (EC) in postmenopausal women. The study included 194 postmenopausal women; 144 with EC and 50 non-cancer controls. Genotypes in P14ARF rs3088440, rs3731217 and rs3731245 polymorphisms were assayed using PCR-RFLP and confirmed by sequencing. Regarding the rs3088440 polymorphism, CT, and CT-TT genotypes, were more prevalent among EC patients than in controls (OR=5.55, p=0.023, OR=5.29, p=0.027; and OR=2.92, p=0.023, respectively). The T allele within rs3088440 was more prevalent in EC females than in controls (χ Polymorphisms in the CDKN2A gene are associated with EC in postmenopausal women.

Upper Abdominal Resections as Part of Tertiary Cytoreduction for Relapsed Ovarian Cancer

The role of upper abdominal resection as part of debulking surgery for advanced-stage or relapsed ovarian cancer has been widely debated. The aim of this study was to investigate the safety and efficacy of upper abdominal resection as part of tertiary cytoreduction. Between 2005 and 2019, 11 cases presenting upper abdominal recurrences after surgically treated ovarian cancer were submitted to surgery with radical intent. Complete debulking surgery was feasible in eight cases, optimal debulking was performed in two cases, while in one case a suboptimal resection was performed. The most commonly performed upper abdominal resections consisted of liver resection in seven cases, splenectomy in four cases, diaphragmatic resection in three cases, pancreatic tail resection in two cases and partial gastrectomy in another two cases. Postoperative complications were encountered in two cases, while postoperative mortality was null. Extended upper abdominal resection can be safely performed in order to increase the chances of optimal debulking surgery at the time of tertiary cytoreduction.

Extended Pelvic Resections as Part of Secondary Cytoreduction for Relapsed Ovarian Adenocarcinoma

Ovarian cancer presents an aggressive tumor biology, a significant number of patients experiencing recurrent disease. The aim of this study was to examine the feasibility and effectiveness of secondary debulking surgery for relapsed ovarian cancer. Between 2014 and 2018, debulking surgery for relapsed ovarian cancer was performed in 40 cases. Debulking surgery to no residual disease was achieved in 31 cases; among the remaining cases, an R1 resection was feasible in six cases, while in the remaining three cases an R2 resection was performed. The most commonly performed visceral resections were represented by rectosigmoidian resection, right colon resection, total or partial cystectomy and unilateral or bilateral ureteral resection. The early postoperative morbidity rate was 32.5% while the postoperative mortality rate was 2.5%. Extended pelvic resections are feasible in patients with relapsed ovarian cancer and might be performed with acceptable rates of postoperative complications.

Overexpression of Annexin A1 Is an Independent Predictor of Longer Overall Survival in Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the major gynecological cause of cancer deaths. Annexin A1 (ANXA1) protein has been implicated in the aggressiveness of several cancer types. This study retrospectively assessed ANXA1 expression in epithelial cells of 156 pre-chemotherapy EOC samples and 34 normal ovarian samples from patients treated at Salah Azaiez Institute. Using immunohistochemistry, ANXA1 expression was compared in normal versus cancer samples; correlations with clinicopathological features, including overall survival, were sought. Fifty-two percent of tumor samples showed epithelial ANXA1 staining versus only 26% of normal samples (Fisher's exact test, p=0.00794). Epithelial ANXA1 expression was correlated with better overall survival in both univariate and multivariate analyses. The possible contribution of ANXA1 overexpression to EOC outcome may be relevant to therapeutic strategies.

Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma

We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC). A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA. Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.

Clinicopathological Characteristics of Microscopic Tubal Intraepithelial Metastases from Adenocarcinoma and Small Cell Neuroendocrine Carcinoma of the Uterine Cervix

Some metastatic tumors that involve the fallopian tube show intraepithelial spread, mimicking primary tubal neoplasm and representing a potential diagnostic pitfall. In this study, we aimed to investigate the clinicopathological characteristics of tubal intraepithelial metastasis (IEM) from cervical carcinoma. We analyzed the clinical features, histological features, and immunophenotypes of IEMs in five patients with cervical carcinoma. This study included usual-type (1/5), mucinous-type (1/5), and gastric-type (2/5) endocervical adenocarcinomas and small cell neuroendocrine carcinoma (1/5) cases. None of the patients had ovarian metastasis, but metastatic tumor cells spread along the tubal mucosal surface and partially replaced the lining epithelium. Histological features of metastatic tumors closely resembled those of the primary tumors in all cases. Tubal IEM can mimic various tubal lesions including serous tubal intraepithelial carcinoma. Morphological consistency between the primary and metastatic tumors and immunostaining help guide the differential diagnosis of challenging intraepithelial lesions of the fallopian tube.

Lymphangioleiomyomatosis of the Pelvic Lymph Nodes Detected Incidentally During Surgical Staging of Gynecological Malignancies: Comprehensive Clinicopathological Analysis of 17 Consecutive Cases from a Single Institution

Clinicopathological Characteristics of Gastric-type Endocervical Adenocarcinoma Misdiagnosed as an Endometrial, Ovarian or Extragenital Malignancy, or Mistyped as Usual-type Endocervical Adenocarcinoma

The diagnosis of gastric-type endocervical adenocarcinoma (GEA) is challenging because its differential diagnosis includes not only gynecological tumors, but also extragenital tumors. We reviewed the electronic medical records and all available slides to investigate the clinicopathological characteristics of eight misdiagnosed GEA cases. Three tumors were initially misdiagnosed as endometrial carcinoma. They displayed extensive endomyometrial involvement and complex glandular architecture, but no severe nuclear pleomorphism. Another three tumors were misclassified as usual-type endocervical adenocarcinoma because of mucin-poor, pseudoendometrioid glands, apical mitotic figures, and karyorrhectic debris. The two remaining tumors presenting as adnexal masses mimicked primary ovarian mucinous tumor and metastatic cholangiocarcinoma. The varying pathological characteristics of GEA reflect the variability in clinical manifestations and its diagnostic difficulties. It is challenging to make an accurate diagnosis based solely on histological features. When suspecting GEA, clinicians should consider more comprehensively the clinicopathological context, along with immunostaining results.

Risk Factors for Severe Complications in Ovarian Cancer Surgery

Backround: Due to extensive surgical intervention for macroscopic complete cytoreduction in epithelial ovarian cancer (EOC) patients, severe complications in the postoperative course are possible. A total of 345 EOC patients who underwent cytoreductive surgery were retrospectively evaluated regarding risk factors for an unfavorable postoperative course. Possible pre-, intra- and postoperative risk factors were statistically analyzed performing multivariate ordinal logistic regression. A total of 345 EOC patients underwent cytoreductive surgery. There were no complications in 114 patients, mild complications in 114 patients and severe complications in 117 patients. The risk factor evaluation identified age (p=0.049), smoking (p=0.032) and duration of surgery (p<0.0001) as significant factors for severe postoperative morbidity. In EOC patients age, smoking and the duration of surgery have significant impact on the postoperative course. Only the duration of surgery can be positively influenced by a well-trained EOC team.

Subtotal Colectomy as Part of Debulking Surgery for Advanced-stage Ovarian Cancer

The presence of extensive lesions of peritoneal carcinomatosis is found in a significant number of cases of extended digestive resection surgery, such as subtotal colectomy. The aim of this study was to report a series of 17 cases that necessitated performing subtotal colectomy as part of cytoreductive surgery for advanced-stage ovarian cancer. Between 2012 and 2020 subtotal colectomy was associated as part of the debulking effort in 17 cases. The median age at the time of surgery was 59 years, while the initial stage at the time of diagnosis was IIIC in 14 cases, and respectively IV in three cases. Optimal debulking surgery was achieved in all cases. The continuity of the digestive tract was reestablished in 11 cases, while in the remaining 6 cases a terminal ileostomy was performed. Extended digestive tract resections may be needed in certain cases in order to maximize the debulking effort in patients with advanced-stage ovarian cancer.

The Influence of “Omental Cake” Presence on the Completeness of Cytoreduction in Advanced-stage Ovarian Cancer

The presence of "omental cake" has been considered since long as a negative prognostic factor in patients diagnosed with advanced-stage ovarian cancer. The aim of this paper was to study the impact of "omental cake" presence on the perioperative outcomes in advanced-stage ovarian cancer. Between 2015 and 2020, 85 patients were submitted to surgery for advanced-stage ovarian cancer. Among cases diagnosed with "omental cake" the rate of complete cytoreduction was significantly diminished when compared to cases in which this entity was not revealed. In the meantime, the presence of omental cake among cases in which complete debulking was achievable was significantly associated with a higher number of digestive resections when compared to the other cases submitted to surgery and in which tumoral transformation of the omentum was encountered. The presence of "omental cake" is associated with a higher rate of incomplete resections. However, in cases in which complete debulking was achieved, the presence of omental cake was associated with a significantly higher number of digestive tract resections.

Risk Factors for Postoperative Complications After Vulvar Surgery

Although the trends of surgical treatment in vulvar cancer patients are towards less extended resections, a significant number of cases are still diagnosed with locally advanced diseases imposing performing extended resections. The aim of this paper is to identify the prognostic factors for the development of early postoperative complications following vulvar surgery. Between 2017 and 2019, 145 patients with vulvar cancer were submitted to surgery with a curative intent. Among these cases there were 93 cases diagnosed with early stages of the disease and 52 cases diagnosed with advanced stages. The risk of postoperative complications was significantly influenced by: i) the stage of the disease, ii) the preoperative levels of serum albumin, iii) the status of the resection margins, iv) previous history of irradiation, v) length of hospital stay and vi) association of comorbidities. Vulvar cancer surgery for locally advanced disease is still associated with high rates of postoperative complications, and an attentive selection of cases submitted to surgery is mandatory.

Squamous Cell Carcinoma from Abscessed, Mature Cystic Ovarian Teratoma – A Case Report and Literature Review

Malignant transformation of mature cystic ovarian teratoma is a scarce eventuality, only rare cases being reported so far. Furthermore, development of this transformation in the setting of an abscessed tumor is even scarcer. The aim of this study was to report the case of a 47-year-old patient submitted to surgery for such a lesion. The patient was investigated for diffuse pelvic pain and diagnosed with a 10×7×8 cm mass at the level of the left adnexa with imaging findings suggesting the presence of an ovarian teratoma. The patient was submitted to surgery involving a total hysterectomy with bilateral adnexectomy, lymphadenectomy and peritoneal biopsies. The histopathological examination demonstrated the presence of squamous cell carcinoma areas transformation in association with areas of abscess. Postoperatively the patient was submitted to six cycles of platinum-based chemotherapy and concurrent external radiotherapy. At one-year follow-up she is free of recurrent disease. Although malignisation of mature cystic ovarian teratoma is a rare event, it should not be omitted when mature ovarian teratoma is suspected; however, association between malignant transformation and abscess is a scarcer eventuality.

Neoadjuvant Chemotherapy for Patients With Diaphragmatic Lesions: A Prognostic Postoperative Analysis

We aimed to analyse the prognosis of patients who underwent primary debulking surgery (PDS) and those who underwent interval debulking surgery (IDS) following four courses of paclitaxel+ carboplatin as preoperative chemotherapy to examine the usefulness of preoperative chemotherapy. We included 45 patients with epithelial ovarian and peritoneal cancers accompanied with diaphragmatic lesions who underwent standard surgery combined with diaphragmatic surgery at two related institutions in January 2010-December 2013. Using medical records, we surveyed the recurrence period, recurrence site, and date of last confirmed survival, and analysed prognosis. The PDS and IDS groups comprised 32 and 13 patients (overall survival, 61.2 and 43.2 months), respectively. Progression-free survival in the PDS and IDS groups was 31.2 and 16.8 months, respectively. NAC-IDS can be a standard treatment option for patients with a tumour in the triangular ligament, in whom complete surgery is difficult.

Tolerability and Efficacy of Bevacizumab Monotherapy in Older Patients With Recurrent Ovarian Cancer

The aim of this study was to compare the tolerability and efficacy of bevacizumab monotherapy between older and younger patients with recurrent ovarian cancer. We enrolled 32 patients with recurrent ovarian cancer who were treated with bevacizumab monotherapy and divided them into those who were 65 years and older (n=12) and those younger than 65 years (n=20). Except for grade ≥3 proteinuria, incidences of adverse events did not differ significantly between the groups. Although older patients exhibited more frequently cycle delay caused by non-hematological toxicities, this difference was not significant. There was no significant difference in tumor response and survival between the groups. Bevacizumab monotherapy was tolerable and effective for older patients with recurrent ovarian cancer compared with younger patients.

Ovarian Seromucinous Borderline Tumors Are Histologically Different from Mucinous Borderline Tumors

To examine the clinicopathological features of ovarian seromucinous borderline tumors (SMBTs) and compare them with those of mucinous borderline/atypical proliferative mucinous tumors (MB/APMTs). Patients with SMBT between 2014 and 2018 and those with MB/APMT between 1988 and 2018 who underwent surgery at our Institution were identified. Pathological review was conducted using the 2014 World Health Organization criteria. Clinical features were compared retrospectively between SMBT and MB/APMT. In total, 11 (12.9%) patients with SMBT and 74 (87.1%) patients with MB/APMT were included in our study. The diagnosis of six patients with SMBT and 73 patients with MB/APMT was not revised on review. SMBT was diagnosed at a younger age (p=0.04), was of smaller size (p<0.01) and bilateral (p=0.03), coexisted with endometriosis (p<0.01), and more frequently recurred than MB/APMT (p=0.04). SMBT might be more aggressive than MB/APMT.

Right Upper Abdominal Resections in Advanced Stage Ovarian Cancer

The right upper abdominal involvement is frequently encountered in patients with advanced stage ovarian cancer. The aim of this paper is to study the safety and efficacy of extended resections at this level as well as to determine the sites of residual disease. Between January 2016 and December 2019, 26 patients submitted to right upper abdominal resections were identified. Peritoneal stripping and full thickness resections were the most commonly performed resections (in 57% and 19% of cases, respectively), followed by capsular liver resection and atypical liver resection (in 30% and 23% of cases, respectively) while the most common sites where resection was incomplete were the liver pedicle and porta hepatis. Exceptionally, one case necessitated performing a pancreatoduodenectomy as part of debulking surgery. Postoperatively, two cases developed serious complications and required reintervention; however, the overall mortality was null. Right upper abdominal resections seem to be feasible and effective in order to maximize the debulking effort with acceptable risks arising from perioperative complications.

Outcome of Radiation Therapy for Locally Advanced Vulvar Carcinoma: Analysis of Inguinal Lymph Node

The aim of this study was to define the outcome of radiation therapy for vulvar carcinoma, and to investigate the effectiveness of therapeutic and prophylactic inguinal lymph node (ILN) irradiation. Because reports about the treatment of ILN were limited. Thirty consecutive vulvar carcinoma patients were treated using external beam radiation therapy (EBRT) for definitive disease (n=25) or postoperatively (n=5). Twenty-four (80%) had squamous cell carcinoma (SCC). Tumor stages (2002 UICC) ranged from 0 to IVB, with no distant metastases. The median total prescribed dose for primary tumor was 64.8 Gy. The 2-year overall survival rate was 25.3%. The outcome was significantly better in patients with ILNs60 Gy (p=0.002). ILN diameters ≤30 mm and prescribed doses over 60 Gy were associated with ILN control in patients with vulvar carcinoma.

The Influence of the Preoperative Status on the Risk of Postoperative Complications After Cytoreductive Surgery for Advanced-stage Ovarian Cancer

The aim of this study was to analyze the influence of preoperative status on the risk of developing further postoperative complications after debulking surgery for advanced-stage ovarian cancer. A total of 80 consecutive patients submitted to surgery between 2014 and 2019 for advanced-stage ovarian cancer were retrospectively reviewed. Among the 80 cases there were seven patients who developed serious postoperative complications requiring reintervention. Among these cases it seems that association of obesity, poor nutritional status (defined as a lower than 3.5 g/dl serum albumin level) and elderly age were significantly associated with the risk of developing further complications. When selecting the candidates for debulking surgery for advanced-stage ovarian cancer attention should be focused on excluding cases presenting such preoperative risk factors in order to decrease the postoperative morbidity.

Identification of Stably Expressed Reference microRNAs in Epithelial Ovarian Cancer

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression and have been associated with the development of various cancers, including epithelial ovarian cancer (EOC). Accurate quantification of miRNA levels is important for determining their role in tumorigenesis and as biomarkers. Currently, U6 is widely used as a normalization control when investigating miRNAs in EOC; however, its variable expression across cancers has been reported. As only a few studies have been published to date on the identification of endogenous miRNA controls in EOC, our aim was to identify stable miRNAs based on global microarray profiling of 197 EOC patients and verify their stability in external datasets. We collected miRNA-microarray data from four datasets: the in-house "Pelvic Mass", and three public datasets with primary EOC patients: The Cancer Genome Atlas, GSE47841, and GSE73581. The expression stability of endogenous control candidates was evaluated by their coefficient of variation. All miRNA results in the used cohorts were produced by either Affymetrix or Agilent technologies, which show similar intra-platform patterns. Nonetheless, a clear difference in a cross-platform comparison was observed. We identified hsa-miR-92b-5p and hsa-miR-106b-3p as stable candidates shared between four datasets. Moreover, we investigated the stability performance of eight miRNAs that have been previously reported as stable endogenous controls in EOC and various performance was observed in four datasets. The selection of suitable endogenous miRNA normalization controls in EOC remains to be resolved, as variability in miRNA performance between platforms might have a crucial impact on the biological interpretation of data.

Malignant Struma Ovarii Τreated With Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Malignant struma ovarii is an extremely rare tumor entity among ovarian tumors. In the presence of ascites and peritoneal metastases, the preoperative appearance may resemble the most common epithelial ovarian carcinoma (EOC) and accordingly, the surgical therapy may be identical if a preoperative histology diagnosis is not possible. The objective of this case report is to present a patient with histopathologically confirmed malignant struma ovarii who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) with the aim of complete tumor resection. This study reports on a patient with preoperatively proven peritoneal metastasis of an 18 cm ovarian tumor with large struma ovarii and papillary thyroid carcinoma within the struma, who was treated with CRS and HIPEC after neoadjuvant chemotherapy. This disease has a significantly better prognosis than EOC, however, HIPEC could provide an additional effect in examining the presence of peritoneal metastasis.

Clinical Availability of Tumour Biopsy Using Diagnostic Laparoscopy for Advanced Ovarian Cancer

Tumour biopsy using laparoscopy before neoadjuvant chemotherapy for advanced ovarian cancer has been widely accepted. However, there are few reports about its operative outcome compared to biopsy with laparotomy. We investigated the advantage of laparoscopic biopsy for advanced ovarian cancer. We included 23 patients who underwent laparoscopy and 27 who underwent exploratory laparotomy before neoadjuvant chemotherapy between January 2012 and August 2020. We reviewed their medical records and evaluated their operative outcomes. Blood loss was significantly lower in the laparoscopy group (5 ml vs. 320 ml, p<0.05). The period until the initiation of neoadjuvant chemotherapy was significantly shorter in the laparoscopy group (12 days vs. 16 days, p<0.05). Overall survival did not differ significantly between the two groups (25.4 months vs. 24.7 months, p=0.53). Laparoscopic tumour biopsy is useful and safe for histological diagnosis, thereby allowing for early introduction to neoadjuvant chemotherapy.

Areas to Improve Quality of Life After Ovarian Tumor Surgery and Adjuvant Treatment

To evaluate quality of life (QoL) in women treated for ovarian tumors one year after laparotomy. The validated quality of life questionnaires (EORTC QLQ-C30 and QLQ-OV28) were sent to women who had undergone laparotomy due to ovarian tumors 12 months after surgery. The answers were analyzed and grouped according to the ovarian tumor histology (benign, borderline and cancer). A total of 621 patients (87.5% out of 710) agreed to participate in the study. Ovarian cancer patients experienced statistically worse QoL one year after laparotomy in several analyzed parameters, including financial difficulties, compared to patients treated for benign and borderline tumors. Women with ovarian cancer still need further cancer rehabilitation and support one year after diagnosis to improve their QoL. The novel finding was that ovarian cancer patients suffered from financial difficulties even in a free of charge health care system.

Aggravation of Hemorrhoids in Patients With Cervical Cancer Undergoing Radiotherapy: A Nationwide Population-based Study

Anal canal toxicity tends to be ignored in pelvic radiotherapy (RT). However, patients with hemorrhoids can be troubled by lower radiation dose. We tried to determine whether a correlation exists between hemorrhoids and anal symptoms in patients with cervical cancer undergoing RT. The insurance claim data of patients who underwent definitive treatment for cervical cancer from 2015 to 2019 were analyzed. Adverse events including bleeding, proctitis, and hemorrhoids, were documented for 1 year after treatment completion. Odds ratios (ORs) were estimated by unconditional Poisson regression and adjusted for age, treatments, chemotherapy, and comorbidities. Details of 67,114 insured cervical cancer patients treated between 2015 and 2019 were obtained. Among them, 5,919 patients with follow-up data for at least one year, treated with curative intent, were analyzed. The OR of the definitive radiotherapy group (DRT group) for anal bleeding was 10.57 higher than that of the operation alone group (surgical group) (p<0.01). Newly developed hemorrhoids gradually increased in the surgical group (3.17%), the postoperative radiotherapy group (5.38%), and the DRT group (7.58%). The OR of the DRT group for newly developed hemorrhoids was 2.38 higher than that of the surgical group (p<0.01), and ORs increased to 1.99 and 1.61 in patients that received chemotherapy and patients with diabetes, respectively (p<0.01). Pelvic RT increased anal bleeding and symptomatic hemorrhoids. In particular, chemotherapy and diabetes also increased the risk. If patients with hemorrhoids receive pelvic RT, attention is required to prevent hemorrhoid aggravation.

Pelvic Insufficiency Fractures in Cervical Cancer After Radiation Therapy: A Meta-Analysis and Review

The aim of the study was to estimate the prevalence of pelvic insufficiency fractures (PIFs) after radiation therapy (RT) in patients with cervical cancer. A total of 3,633 patients from 15 cohort studies were included. Proportion meta-analysis was performed to estimate prevalence and subgroup analysis was performed according to imaging modalities for diagnosis of PIF. For continuous variables (age and length of follow-up), meta-regression analysis was performed. Pooled prevalence estimate of PIF was 14% (95% CI=10-19). Incidence of PIF was higher in studies that used MRI as a diagnostic tool (17%, 95% CI=12-22) than non-MRI (8%, 95% CI=2-14). In meta-regression, we found a significant association of prevalence of PIF with age (p=0.021) but not with length of follow-up (p=0.118). PIF after RT in patients with cervical cancer is not rare. Physicians need to pay attention to PIFs, especially in patients with high-risk factors for osteoporotic fracture.

Outcome of Radiation Therapy for Stage IVB Uterine Cervical Cancer With Distant Lymph Nodes Metastases; Sequential Irradiation for Distant Lymph Nodes Metastases

This study aimed to evaluate the outcome of radiation therapy for patients with distant lymph node (LN) metastases, without organ metastases from uterine cervical cancer (UCC). Twenty-six patients with UCC with distant LN metastases received radiotherapy and were retrospectively analyzed. The sites of distant LN metastasis were as follows; Supraclavicular in 19, inguinal in nine, axillary in four, and others in three. The mean dose prescribed for these was 50 (range=40-60) Gy. The 2-year overall, cause-specific, and progression-free survival, and local control of primary tumor rates were 51.3%, 51.3%, 46.9%, and 67.9%. In multivariate analysis, performance status ≥1 (p=0.007), para-aortic LN metastases (p=0.001), and lack of high-dose-rate intracavitary brachytherapy (p=0.033) were significantly associated with poor overall survival. Performance status ≥1 (p=0.004), and para-aortic LN metastases (p=0.014) were significantly associated with poor cause-specific survival. This study demonstrated favorable local control in patients with UCC with distant LN metastases.

Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: The Role of Immune-related Factors

Treatment of locally advanced cervical cancer (LACC) consists of concomitant chemoradiation or neoadjuvant chemotherapy (NACT) plus radical surgery (RS). This study analyzed the prognostic role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), tumor infiltrating lymphocytes (TILs), and PD-L1 expression in LACC patients, treated with NACT+RS. We prospectively analyzed 37 LACC patients treated from December 2016 to September 2019. Patients were submitted to pelvic examination, biopsy and imaging. In 65% of cases, a nodal involvement was present at pre-treatment MRI. All cancers showed the presence of stromal TILs and PD-L1 staining of inflammatory cells. No significant correlations were found between clinicopathological parameters and the number of TILs and PDL-1 at baseline. After NACT, 29 patients (78%) were submitted to RS; 28% of patients showed pathological complete response, 62% partial response and 10% stable disease. Seven (24%) patients reported a positive node. Patients with high levels of stromal TILs and low NLR and PLR showed a significantly better response to NACT. No significant correlation was observed between PD-L1 expression and response to NACT. The number of TILs, the expression of PDL1, and NLR and PLR ratios correlate significantly with the response of LACC patients to NACT.

Human Papillomavirus Modulates Matrix Metalloproteinases During Carcinogenesis: Clinical Significance and Role of Viral Oncoproteins

Human papillomavirus (HPV) infections are associated with cervical cancer and other anogenital cancers. Despite progresses in HPV vaccination and screening, these cancers still show high incidence and mortality, requiring improved prognostic markers and tailored therapies. This review addresses the role of Matrix metalloproteinases (MMPs) in HPV-induced cancers and the modulation of MMP expression by HPV oncoproteins. Scientific literature indexed in PubMed and ScienceDirect about Human papillomavirus modulates matrix metalloproteinases was retrieved and critically analyzed, to obtain an overview of expression patterns and their implications for carcinogenesis and patient prognosis. Matrix metalloproteinases such as MMP1, MMP9 and MMP13 have been associated with patient prognosis in HPV-induced cancers and play a major role in the degradation of the extracellular matrix, tumor invasion and metastasis. The HPV E2 and E7 oncoproteins regulate MMP expression via AKT, MEK/ERK and AP-1 signaling among other mechanisms. Increased expression of MMPs is associated with cancer progression and poor prognosis in multiple HPV-induced cancers, suggesting their potential use as prognostic markers. The identification of specific signaling pathways that mediate MMP regulation by HPV is essential for developing efficient new cancer therapies.

Synchronous Anal Canal Cancer and Cervical Cancer: Report of a Case and Management Implication

This is the case report of a synchronous anal canal cancer and cervical cancer in a patient who underwent definitive chemoradiotherapy (CRT) and radical surgery for anal canal and cervical carcinoma, respectively. A 55-year-old woman was diagnosed with cT4a cN1 Mx anal canal squamous cell carcinoma and stage IA2 cervical squamous cell carcinoma, based on biopsy and imaging. Definitive CRT consisted of radiotherapy (total dose of 59.4 Gy) and concomitant mitomycin (10 mg/m There is limited information in the literature regarding treatment strategy and outcome of patients with synchronous anal canal and cervical cancer. A two-step treatment, including CRT and radical hysterectomy, is likely to be accepted as valid option.

Prevalence and Determinants of Vaginal Infection With Human Papillomavirus Among Female University Students in Vietnam

Cervical cancer is the second most common malignancy among women in Vietnam, but the country is yet to introduce a national human papillomavirus (HPV) vaccine programme targeted at adolescents. We determined HPV prevalence and HPV vaccine knowledge among female university students in Vietnam. We surveyed and screened 1,491 female university students in Hanoi, Hue, and Ho Chi Minh City for their sexual behaviours, HPV knowledge and low- and high-risk HPV infection. The prevalence of any HPV infection and any high-risk HPV infection were 4.2% (95%CI=3.3%-5.4%) and 3.4% (95%CI=2.5%-4.4%), respectively. Being sexually active [adjusted prevalence ratio (aPR): 6.22; 95%CI=3.4-11.37] and having ever been pregnant (aPR: 4.82; 95%CI=1.93-12.04) were positively associated with high-risk HPV infection. Whilst 60% of participants had heard of HPV vaccine, only 4.6% had received the vaccine. The low HPV prevalence found in university students in Vietnam indicates that they can benefit from HPV vaccination, along with a well-designed HPV health promotion programme.

Colposcopic Alterations Are More Frequent in Smokers and Appear at a Younger Age

Tobacco use is a recognized cofactor risk for cervical cancer induced by high-risk Human Papilloma Virus (HR-HPV). This study aimed to evaluate the specific influence of tobacco use on colposcopic examination results in women infected by HR-HPV. HR-HPV-positive women undergoing a loop electrosurgical excision procedure (LLETZ) after colposcopic examination were considered for this study. A total of 819 patients from a regional screening program were included, of whom 320 were smokers and 499 non-smokers. Smokers were significantly younger (41.1 Smoking in any amount is associated with worse colposcopic and histopathological findings, and this occurs at younger ages.

SERPINB11Expression Is Associated With Prognosis of High-grade Serous and Clear Cell Carcinoma of the Ovary

To evaluate the role of serine protease inhibitor B11 (SERPINB11) expression as a prognostic biomarker in high-grade serous carcinoma (HGSC) and clear cell carcinoma of the ovary (CCC). We obtained tumor tissues from patients with HGSC (n=145) and CCC (n=59). We evaluated immunohistochemically the expression of SERPINB11 and investigated whether SERPINB11 expression affects platinum-resistance and the prognosis of HGSC and CCC. High expression of SERPINB11 was more common in CCC than in HGSC (57.6% vs. 28.3%; p<0.01), and SEPRINB11 expression did not correlate with platinum-resistance of HGSC and CCC. High expression of SERPINB11 was associated with worse progression-free survival and overall survival with marginal significance in HGSC; no relation between SERPINB11 expression and the prognosis of CCC was found. SERPINB11 expression maybe a prognostic biomarker for HGSC.

Treatment Outcome of the Combination Therapy of High-dose rate Intracavitary Brachytherapy and Intensity-modulated Radiation Therapy With Central-shielding for Cervical Cancer

This study aimed to evaluate the clinical outcome of intensity-modulated radiation therapy (IMRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) in uterine cervical cancer (UCC). IMRT consisted of whole-pelvic radiation therapy (WPRT) and sequential WPRT with central-shielding (WPRT-CS). Thirty UCC patients treated with IMRT using TomoTherapy, were retrospectively analyzed. The median dose of WPRT and WPRT-CS was 36 and 14.4 Gy and the median total dose of these was 50 Gy in 25 fractions (Fr). Median HDR-ICBT dose/Fr to Point A was 25 Gy/5 Fr. Median 2 Gy per fraction-equivalent dose (EQD2) of combined WPRT and HDR-ICBT to Point A (α/β=10) was 71.0 Gy. The 3-year local control, disease-free survival, and overall survival rates were 89.9%, 83.3%, and 86.3%. IMRT of WPRT and WPRT-CS given in combination with HDR-ICBT was a feasible therapy resulting in good disease control and tolerance in patients with UCC.

Impact of Bevacizumab on Clinical Outcomes in Patients With Platinum-resistant Relapsed Ovarian Cancer

Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinum-resistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. We retrospectively divided patients with PR-ROC into two groups: bevacizumab plus chemotherapy (BEV-CT group) and chemotherapy alone (CT group). Progression-free survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity.

Pegfilgrastim Maintains Relative Dose Intensity and Decreases Hospitalisations in Patients With Endometrial Cancer

Data are limited regarding the use of pegfilgrastim in gynaecologic oncology. We evaluated its efficacy for maintaining dose intensity during chemotherapy. We retrospectively examined the data of 65 women (26 pegfilgrastim users) who underwent primary surgical treatment for stages IB-IV endometrial cancer and had adjuvant chemotherapy containing platinum and taxane; the primary outcome was a relative dose intensity ≥85%. In the pegfilgrastim vs. the control group, body mass index (26.6±5.9 vs. 23.4±4.4), rate of relative dose intensity ≥85% (88.5% vs. 15.4%), plus other adverse event incidences were significantly higher; rate of neutropenia, total hospital visits during chemotherapy (11.0±2.1 vs. 18±5.6 days), unscheduled hospital visits (1.1±1.8 vs. 5.8±5.1 days), and unscheduled granulocyte colony-stimulating factor injections (0.58±1.7 vs. 6.4±5.1 days) were significantly lower. Pegfilgrastim can maintain a dose intensity of ≥85% during chemotherapy for the treatment of gynaecologic cancers and decrease hospital-visit frequency.

Volume Index Measured Using Magnetic Resonance Imaging for Diagnosing Cervical Cancer Tumors &lt;2 cm

Diagnosis of cervical cancer with tumor diameter <2 cm using magnetic resonance imaging alone has not been investigated. Moreover, whether tumor volume can be used for diagnosing the true tumor diameter remains unknown. Here, we investigated the utility of early cervical cancer volume index in diagnosing cervical cancer with a tumor diameter of <2 cm, which can be treated using more conservative surgery. This single-center retrospective study analyzed women who underwent radical hysterectomy for cervical cancer with a tumor diameter of <2 cm and clinical stages IA2, IB1, IB2, IB3, and IIA1 at our institute between January 2009 and April 2022. The volume index, defined as the product of the maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter (thickness) on a sagittal section image, and maximum horizontal diameter on a horizontal section image, was evaluated using either T2-weighted magnetic resonance imaging or gadolinium-enhanced T1-weighted imaging. The receiver operating characteristic curve for the volume index was also calculated. The sensitivity and specificity of magnetic resonance imaging for measuring the tumor diameter were 0.92 and 0.84, respectively. The calculated cut-off value was 2.60, whereas the volume index area under the curve was 0.955, with a sensitivity of 0.92 and specificity of 0.93. Considering the specificity and low incidence of false-negative results, the volume index can be used for preoperative diagnosis of pT1B1 cervical cancer, which can be treated with more conservative surgery.

Survival Outcomes With Reduced Doses of Adjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer

There have not been enough recent studies investigating the incidence or efficacy of dose reduction in adjuvant chemotherapy for epithelial ovarian cancer. This study examined whether patients who needed dose reduction showed poorer survival outcomes. From 2011 to 2021, 102 patients were included in the study. Patients who underwent neoadjuvant chemotherapy and those with early-stage disease were excluded. Patients were divided into two groups: those who had a ≥60% dose reduction during the whole period of first-line adjuvant chemotherapy, and those with dose reductions <60%. Of the 102 patients, 38 (37.3%) underwent dose reduction ≥60%. PFS was significantly longer in the group whose dose reductions were ≥60%, whereas OS was not significant. A dose reduction of ≥60%, determined by patients' medical conditions, during first-line of adjuvant chemotherapy does not negatively influence survival outcomes, such as OS and PFS, in advanced epithelial ovarian cancer.

A Phase II Trial to Evaluate the Efficacy of Bortezomib and Liposomal Doxorubicin in Patients With BRCA Wild-type Platinum-resistant Recurrent Ovarian Cancer (KGOG 3044/EBLIN)

The majority of targeted therapies are focused on BRCA mutations, homologous recombination repair deficiency, and BRCA wild-type platinum-sensitive recurrent ovarian cancer. There is a growing need for platinum-resistant patients without BRCA mutations. Herein, we conducted a phase II multicenter study evaluated the efficacy and safety of bortezomib plus pegylated liposomal doxorubicin (PLD) in patients with BRCA wild-type platinum-resistant recurrent ovarian cancer (NCT03509246). Ovarian cancer patients with wild-type BRCA who experienced platinum-resistant recurrence after three or less prior treatment cycles from three Institutions were included. All patients received bortezomib, 1.3 mg/m The trial was terminated after 23 patients were recruited because of slow accrual. The median follow-up was 29.5 months. The overall ORR was 8.7% (2/23); partial response was observed in two patients. The median duration of response was 10.5 months, and median PFS was 2.9 months. Treatment-related adverse events (TRAEs) of grade 3/4 were reported in 43.5% of patients. One patient who exhibited TRAEs discontinued treatment. However, grade 4/5 TRAEs were not observed. Mutations in TP53 and CDK12 were detected in 67% (14/21) and 24% (12/21) of patients, respectively. Two patients with partial response harbored mutations in genes related to homologous recombination repair deficiency, including BRCA2, ATM, and CDK12. The combination of bortezomib and PLD was well tolerated; however, antitumor activity was not sufficient to warrant further investigation in ovarian cancer.

Comparison of Survival Outcomes According toBRCA1/2Variant Type in High-grade Serous Ovarian Cancer

Mutations of BRCA1/2 improve cancer prognosis due to their better response to platinum-based chemotherapy. This study evaluated overall survival (OS) and progression-free survival (PFS) under similar conditions of first-line adjuvant chemotherapy within seven years in high-grade serous ovarian cancer (HGSOC). A total of 160 patients were enrolled. The pathogenic BRCA1/2 variant group included pathogenic variant and likely-pathogenic variant, while the non-pathogenic group included wild-type and variant of uncertain significance. For first-line chemotherapy, delivered dose intensity, relative dose intensity, and delay of duration were calculated in all patients. Of the tested variants, 108 (67.5%) were non-pathogenic and 52 (32.5%) were pathogenic. No significant difference was found in various clinical factors of cancer stage, surgery, or chemotherapy. There was no significance for OS or PFS within five or seven years. In patients with HGSOC, the OS and PFS for germline BRCA1/2 pathogenic and non-pathogenic variants were not significantly different under similar conditions of first-line adjuvant chemotherapy within seven years.

Patient Preferences With Regard to Care Structures for Cervical or Vulvar Dysplasia in Certified Dysplasia Clinics in Germany

The aim of this study was to evaluate patient preferences regarding cervical dysplasia clinics. Specifically, preferences in terms of diagnostic and therapeutic pathways as well as logistical and structural aspects were addressed to recognize unmet needs and improve existing structures of cervical dysplasia care. This questionnaire-based study was conducted between June and December 2022 at an academic medical center in Southwestern Germany. A total of 226 patients who had an appointment at the certified dysplasia clinic were included. The vast majority of patients (74.8%) preferred counseling at the certified dysplasia clinic in the case of an abnormal finding of the cervix or labia. A prompt appointment (within a maximum of 4 weeks), a timely notification about test results (within a maximum of 2 weeks), a travel time <60 minutes and seeing the same doctor during follow-up appointments were recognized as important aspects. While about half of the patients (53.5%) were indifferent to the sex of the gynecologist, almost all of the remaining patients stated they would prefer to be seen by a female doctor (44.3% female doctor vs. 2.2% male doctor). Most women expect very timely appointments and result notifications. Moreover, they favor short travel times and continuity of care. The identified patient preferences should be considered to increase patient satisfaction and quality of care when developing and optimizing management at specialized dysplasia clinics.

Identification of Predictive Factors for Post-operative Recurrence and Clinical Outcomes of Primary Vulvar Extramammary Paget Disease

Data regarding the clinicopathological factors predicting recurrence and prognosis in patients with vulvar extramammary Paget disease (VPD) are limited. Therefore, we aimed to identify predictive factors for recurrence and outcomes in patients with VPD. Forty-five patients with VPD were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological information. Eighteen cases (40.0%) had resection margin (RM) involvement. Twelve patients (26.7%) received adjuvant radiation therapy (RT). Ten patients (22.2%) experienced recurrence. The recurrence rate was higher in patients who underwent wide local excision or simple vulvectomy than in those who underwent radical vulvectomy. Positive RM involvement was a significant and independent predictive factor for worse recurrence-free survival (RFS). The overall survival rate of patients who received adjuvant RT was significantly higher than that of those who underwent surgery alone. A positive RM involvement independently predicted worse RFS. The recurrence rate was significantly associated with the type of surgical procedure performed. Additionally, adjuvant RT can improve the prognosis of patients with VPD.

Evaluation of ChatGPT’s Potential in Tailoring Gynecological Cancer Therapies

ARID1 and BRG1 Expression in Endometrial Cancer

Endometrial cancer (EC) is the predominant malignancy among gynecologic cancers and ranks fourth among all types of cancer. Recently, researchers have focused on the development of new prognostic biomarkers. Subunits of the SWI/SNF protein complex, like the ARID1 and BRG1, have been associated with the development of endometrial cancer. The present study aimed to evaluate the expression patterns of ARID1A and BRG1 in a collection of endometrioid adenocarcinomas of the uterus using immunohistochemistry. The study comprised a total of thirty-three individuals diagnosed with stage I endometrioid endometrial cancer, treated with radical hysterectomy. The histological material was then examined to assess the cytoplasmic and nuclear expression of the proteins. ARID1A exhibited expression in both the cytoplasm and nucleus of cancer cells, whereas BRG1 was mainly expressed in the nuclei. In addition, ARID1A exhibited a notable decrease in expression in grade 3 histology, with no significant correlation with the depth of myometrial invasion. The reduced expression was highly related to tumor expansion into the endocervix. The findings demonstrated a total absence of ARID1A expression in 27% of endometrioid carcinomas, with a significant reduction in expression in an additional 51% of cancer cells. These findings align with the most recent published data. In contrast, in the current study, BRG1 was rarely down-regulated and was extensively expressed in the majority of endometrioid carcinomas, preventing the possibility of statistical analysis. In summary, ARID1A expression loss can be used as a biomarker to guide post-operative therapy; however, further investigation is needed, especially for early-stage endometrial cancer.

Concomitant [18F]F-FAZA and [18F]F-FDG Imaging of Gynecological Cancer Xenografts: Insight into Tumor Hypoxia

Herein we assessed the feasibility of imaging protocols using both hypoxia-specific [ CoCl Elevated GLUT-1, and hexokinase enzyme-II expression driven by CoCl The addition of [

Successful Management of Ovarian Cancer Progressing on Olaparib by Niraparib Following Cytoreduction: A Case Report

Polyadenosine 5'-diphosphoribose polymerase inhibitors (PARP-Is) are novel, effective agents for treating newly diagnosed epithelial ovarian cancer (EOC). However, the effect of PARP-I on the progression of recurrent EOC has not yet been determined. In particular, there is limited evidence regarding retreatment with PARP-I for recurrent EOC that has progressed on PARP-I in the short term. A 69-year-old woman with a BRCA1 mutated EOC relapsed five months after starting olaparib maintenance following neoadjuvant chemotherapy and interval debulking surgery. Although the platinum-free interval was within six months, secondary cytoreductive surgery was performed because the tumor was locoregional. Following two cycles of weekly nedaplatin, niraparib induced a complete response, and the patient maintained a progression-free status for 15 months. Even with short-term progression on PARP-I, local control combined with different platinum agents and PARP-I can be used to achieve good responses.

Current Position of Oncofertility in Adolescent Female Cancer Patients: A Comparative Review on Society Guidelines

PD-L1 and PD-1 Expression in Early Stage Uterine Endometrioid Carcinoma

Immune checkpoint inhibitors (ICI) and tumor-infiltrating lymphocytes (TILs) for cancer treatment in clinical oncology have revolutionized patient care. However, no gold standard exists for the criteria of analytical validity of TILs of different types of cancer. Clinicopathological data from 60 patients with endometrioid carcinoma (EC) who had undergone surgical treatment at the Gyeongsang National University Hospital between January 2002 and December 2009, were investigated. The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PDL1) expression levels were characterized by immunohistochemical staining patterns, and the interpretations derived from machine learning morphometric analysis (Genie) and the pathologists' assessments were compared. In solid tumors, pathologists assessed the proportion of positive cells in each core of the tissue microarray. For Genie, the proportion of positive cells in the entire core and the number of positive cells per 1 mm Both the pathologists and Genie identified the same trend in association with tumor size, with significant differences (p=0.026, p=0.033). Genie expression showed a significant association with PD1 expression, and pathologists identified a significant association with PDL1 expression in immune cells. The PD1 expression levels identified in immune cells of EC specimens were similar between the pathologists and Genie, suggesting that there is little resistance to the introduction of morphometric analysis. To our knowledge, this is the first study to introduce and validate machine learning as an integrated method for predicting prognosis and treatment based on PD1 expression in EC tumor microenvironments.

Robotic Versus Laparoscopic Pelvic Lymphadenectomy for Endometrial Cancer Under the Japanese Public Health Insurance System

Surgery is the preferred treatment modality for endometrial cancer. In recent years, minimally invasive surgery (MIS) has become increasingly popular, and in Japan, robotic surgery has been covered by national insurance in addition to laparoscopic surgery for apparent stage IA cases since 2018. We conducted a comparative analysis of laparoscopic and robotic surgeries, including pelvic lymphadenectomy for stage IA endometrial cancer, with the aim of evaluating the efficacy of robotic surgery. A retrospective analysis was conducted for patients who underwent MIS pelvic lymphadenectomy between January 2018 and December 2023. Sixty-nine patients who underwent robotic surgery and 29 who underwent laparoscopic surgery were included in the study. All the patients underwent total hysterectomy and pelvic lymph node dissection, with preoperative diagnosis of stage 1A and G1-G2 endometrial cancer. Operative time was longer in the robotic group (median=316 This retrospective analysis suggests that robotic surgery is a feasible and safe procedure for total hysterectomy and pelvic lymph node dissection in patients with preoperative diagnosis of stage IA and G1-G2 endometrial cancer.

Metastatic Invasive Lobular Breast Carcinoma Involving Tamoxifen-related Endometrial Polyp in a Patient With Metachronous Bilateral Breast Carcinomas: A Case Report

Metastasis of extragenital malignancies to the female genital tract, particularly the uterus, is exceedingly rare. Invasive lobular carcinoma (ILC) is the most common histological type of breast carcinoma that metastasizes to gynecologic organs. A 42-year-old woman receiving tamoxifen presented with an irregularly thickened endometrium on transvaginal ultrasonography. She had previously undergone bilateral partial mastectomies - eight years prior for right-sided invasive ductal carcinoma, and three years prior for left-sided ILC. Hysteroscopic evaluation revealed an endometrial polyp. Microscopic examination of the polypectomy specimen showed variably sized, irregularly shaped branching glands embedded in densely fibrotic stroma. Within the stroma, monomorphic tumor cells with hyperchromatic, eccentrically located nuclei were arranged in single files, thin cords, or nests. Immunostaining revealed that the tumor cells were positive for GATA-binding protein 3 and negative for paired box 8, supporting a diagnosis of metastatic carcinoma from the breast. The final pathological diagnosis was metastatic ILC involving a tamoxifen-associated endometrial polyp. Although rare, breast carcinoma may metastasize to endometrial polyps. Clinicians and pathologists should consider this possibility when evaluating abnormal ultrasonographic findings in the female genital tract, particularly in patients with a history of breast carcinoma receiving tamoxifen therapy. Abnormal ultrasonographic findings in the uterus of such patients warrant a comprehensive diagnostic workup to exclude metastatic disease.

Cervical Cytology Preserves Histologically Detected Surface Epithelial Slackening, Unique to the POLE Mutation-subtype in Endometrial Cancer

Among the four genomic subtypes of endometrial cancer, distinguishing between the DNA polymerase epsilon mutation (POLEmut) and no specific molecular profile (NSMP) subtypes requires genomic profiling owing to the lack of surrogate immunohistochemical markers. We have previously found that, histologically, the POLEmut-subtype exhibits surface epithelial slackening (SES). Therefore, to improve subtype identification, we aimed to extract cytological features corresponding to SES in POLEmut-subtype cervical cytology specimens. We analyzed 104 endometrial cancer cervical cytology specimens, with integrative diagnosis confirmation via histology, immunohistochemistry, and genomic profiling. Cytological features were evaluated for the presence of atypical glandular cells, atypical cell appearance in single cells and clusters, and cytological SES and the presence of tumor-infiltrating inflammatory cells in clusters. Based on cervical cytology, the POLEmut- and p53mut-subtypes exhibited more frequent atypical cells in smaller clusters, giant tumor cells, and cytological SES patterns than the NSMP-subtype. Tumor-infiltrating lymphocytes were frequent in the POLEmut- and mismatch repair-deficient subtypes. Histologically-detected SES as well as other endometrial cancer features may be preserved in the atypical cell clusters observed in cervical cytology specimens. Cytological detection of SES and of smaller clusters of atypical cells and inflammatory cells with moderate atypia are suggestive of POLEmut-subtype. Integrative diagnosis including genomic profiling remains critical for diagnostic confirmation.

Validity of the 2014 FIGO Stage IIIA1 Subclassification for Ovarian, Fallopian Tube, and Peritoneal Cancers

The 2014 International Federation of Gynecology and Obstetrics (FIGO) classification subdivides patients with stage IIIA1 ovarian, fallopian tube, and peritoneal cancers by the greatest dimension of metastatic lymph node without supporting evidence. This study aimed to assess the validity of this subdivision. A retrospective single-institution cohort study was performed in patients with ovarian, fallopian tube, or peritoneal cancer from 2009 to 2020. We compared outcomes between patients diagnosed with IIIA1(i) (metastasis ≤10 mm in the greatest dimension) and IIIA1(ii) (metastasis >10 mm in the greatest dimension). Of the 895 patients, 46 (5.1%) were classified as stage IIIA1, 20 as IIIA1(i), and 26 as IIIA1(ii). In stage IIIA1(ii), there were significantly more cases of serous carcinoma (p<0.001), and the number of positive nodes and lymph node ratio were significantly higher than those in stage IIIA1(i) (p=0.001, p=0.002). Five-year progression-free survival was 68.7% in patients with stage IIIA1(i) cancer and 58.1% in those with stage IIIA1(ii) (p=0.58). Five-year overall survival was 83.1% in patients with stage IIIA1(i) cancer and 80.2% in those with stage IIIA1(ii) (p=0.44). Among other patient characteristics and pathologic findings, there were no prognostic factors for patients with stage IIIA1 cancer. In this retrospective cohort study, further classification of FIGO stage IIIA1 cancer was not significantly associated with patient outcomes.

Licoricidin Enhances Paclitaxel-induced Apoptosis Through Endoplasmic Reticulum Stress in Human Cervical Cancer Cells

The adverse side effects associated with chemotherapeutic agents have prompted the exploration of natural compounds as adjuvants to chemotherapy, offering more effective therapeutic alternatives. Licoricidin, a bioactive constituent of licorice, possesses diverse pharmacological properties. However, the antitumor mechanisms underlying the therapeutic effects of Licoricidin combined with paclitaxel in cervical cancer remain unclear and further investigations are warranted. Cell growth and apoptosis were assessed using the MTT assay and Annexin V/PI staining. Endoplasmic reticulum (ER) stress was evaluated using the ER-ID assay. The expression of apoptosis- and ER stress-related proteins in response to the combined treatment was analyzed using western blotting. Combined treatment with licoricidin and paclitaxel effectively inhibited cell growth and induced apoptosis in human HeLa and C-33A cells. We further revealed that this combined treatment increased the expression of apoptotic proteins (c-PARP, Bax, and DR5) while decreasing the expression of pro-caspase proteins (pro-caspase-3 and pro-caspase-9) in HeLa cells. In addition, the combined treatment induced ER stress, as evidenced by decreased expression levels of ERp44, ERp57, and ERp72, whereas the expression of GRP78 was increased in HeLa cells. The combination of licoricidin and paclitaxel induced ER stress-mediated apoptosis and may serve as a potential antitumor therapeutic strategy against human cervical cancer cells.

Liquid-based Cytological Features of Adenocarcinoma Not Otherwise Specified, Extrauterine Adenocarcinoma, and Other Malignant Neoplasms of The Uterine Cervix: A 5-year Single-institutional Experience With 30 Consecutive Patients

The adenocarcinoma (ADC) and other malignant neoplasm (OMN) terminologies of The Bethesda System represent various histological types of uterine and extrauterine malignancies. This study aimed to clarify the incidences of ADC not otherwise specified (ADC-NOS), ADC extrauterine (ADC-EXT), and OMN in our institution and describe their characteristic cytomorphological features. We searched the database to identify all patients diagnosed with carcinoma, including those diagnosed through cervical liquid-based cytology (LBC), between January 2019 and December 2023. The electronic medical records and all available slides were reviewed. Overall, 30 of the 149,197 (0.02%) patients were diagnosed with ADC-NOS, ADC-EXT, and OMN. All three groups included various histological types of both gynecological and non-gynecological origin. More than two-thirds (23/30; 76.7%) were of uterine origin, but seven patients had metastatic carcinoma of extrauterine organ origin, including the ovary, lung, stomach, breast, colon, urethra, and pancreas. In all patients, the cytological features were concordant with the histological features. In LBC, ADC-NOS does not only encompass uterine cervical tumors, but also various types of extrauterine malignancies. ADC-EXT and OMN also represent both extrauterine and uterine tumors. Awareness of the morphological features observed in LBC samples of non-gynecological malignancies may be helpful in obtaining the correct diagnosis.

Waikato Environment for Knowledge Analysis (WEKA) as a Data Analysis Method Identifying Potential Hematological Parameters for Early Diagnosis of Cervical Cancer

The present study explored the use of Waikato Environment for Knowledge Analysis (WEKA) to analyze hematological parameters for distinguishing potential development and progression of cervical cancer. Specifically, we aimed to identify significant biomarkers capable of differentiating atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSIL) from cervical cancer-negative and advanced conditions such as cervical adenocarcinoma. Hematological and biochemical data were collected from patients and analyzed using data-mining algorithms available in WEKA. The random forest algorithm was employed to identify patterns among key hematological and biochemical biomarkers, alongside one-way analysis of variance to determine significant alterations in these parameters across cancer-negative, ASC-US, LSIL and adenocarcinoma groups. Random forest was the classifier model that demonstrated superior performance metrics with high recall (1.000) and accuracy (0.843), Matthews correlation coefficient (0.510) and area under the curve (0.708), effectively identifying significant patterns within the datasets. One-way analysis of variance indicated significant alterations in red and white blood cell counts, platelet count, hemoglobin, hematocrit and other white blood cell parameters between cancer-negative, ASC-US, LSIL and adenocarcinoma, emphasizing the role of hematological parameters in identifying progression risk. The consistency in conclusions drawn from data mining and statistical analyses highlight the utility of hematological parameters as potential non-invasive biomarkers for cervical cancer screening and progression monitoring. These findings suggest that integrating machine-learning algorithms, particularly random forest, with hematological analysis might enhance early diagnosis and improve clinical outcomes for patients with cervical abnormalities.

Clinical Outcomes of Pleomorphic High-grade Squamous Intraepithelial Lesions of the Uterine Cervix: A Single-institutional Experience of 44 Cases

Pleomorphic high-grade squamous intraepithelial lesions (PHSILs) of the uterine cervix are characterized by strikingly pleomorphic and enlarged nuclei with brisk mitotic activity. The aim of this study was to analyze the clinical outcomes of patients with PHSIL. Clinical data were collected from the electronic medical records of 44 patients with PHSIL. The patients' mean age was 52.1 years. The initial cytological diagnosis was HSIL in 43.2% of patients. High-risk human papillomavirus was detected in 89.5% of patients. The human papillomavirus type was not predominated by one specific type. The patients were treated with conization alone or with conization with subsequent hysterectomy. Two cases of squamous cell carcinoma coexisting with PHSIL, and one case of adenoid basal carcinoma were detected among the surgical specimens. Follow-up cytology revealed negative results for intraepithelial lesions in all patients, except for one patient who experienced recurrent PHSIL 41 months after hysterectomy and underwent laser ablation. The incidence rates of concurrent squamous cell carcinoma (4.5%) and recurrence (2.3%) in our PHSIL cohort were lower than those previously reported in patients with conventional HSIL. Our findings suggest that pleomorphic nuclear change alone in PHSIL was not associated with worse clinical outcomes than conventional HSIL and support the notion that PHSIL does not require more aggressive clinical management than conventional HSIL. However, close follow-up with cytological examination may be necessary to determine the potential risk of recurrence.

Neoadjuvant Chemotherapy With the Angiogenesis Inhibitor Bevacizumab for Locally Advanced Cervical Cancer

We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy - whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven - could optimize the therapy regimen, leading to improved response rates and survival outcomes. Forty patients with histologically confirmed cervical cancer with FIGO stage IB3-IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated. Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progression-free survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098). While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach.

Impact of the Corona Pandemic on Cervical Cancer Screening Assessment

The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many countries. There have been no reports on cervical cancer screening in Germany. This study aimed to describe changes in the numbers of colposcopies, cytology examinations, HPV tests, and histological results during the pandemic compared to the pre-pandemic years in order to evaluate the impact of the COVID-19 pandemic on cervical cancer screening. The numbers of colposcopies, cytology examinations, HPV tests, and histologic results were analyzed retrospectively for the period January 2018 to December 2022. The 2 years period before the pandemic (2018 and 2019) were compared with the 3 years period of the pandemic (2020-2022). In total, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies, cytology examinations, and high-risk HPV (hrHPV) tests increased during the pandemic years. The number of biopsies per year taken was stable (range=450-554). The relative numbers of cervical intraepithelial neoplasia (CIN) III/HSIL findings were stable, while the numbers of cervical cancers identified increased slightly from 15 (6.6%) in 2018 to 22 (7.4%) in 2022. Increases in numbers of women examined and colposcopies were observed in the years 2021 and 2022 during the pandemic, in comparison to the preceding years. These also led to increases in the figures for cytology, hrHPV, histology, and operations. The onset of the pandemic occurred in the same year as a newly organized screening program started in Germany. The increases might therefore be due to the newly organized screening system.

Clinicopathological Characteristics of Atypical Polypoid Adenomyoma of the Uterus in Association With Endometrial Atypical Hyperplasia and Endometrioid Carcinoma

Atypical polypoid adenomyoma (APA) is an uncommon biphasic uterine tumor characterized by irregularly shaped, atypical endometrial glands haphazardly distributed within a fibromuscular stroma. APA is frequently associated with atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) and endometrioid endometrial carcinoma (EC). This study aimed to characterize the clinicopathological features and outcomes of APA concomitant with AH/EIN and EC. Nineteen cases of APA coexisting with AH/EIN or EC were retrospectively analyzed. Clinical presentation, pathological findings, treatment modalities, and outcomes were reviewed. Most patients (78.9%) were of reproductive age (26-45 years). The most common presenting symptom was abnormal uterine bleeding (47.4%), while 26.3% were asymptomatic. EC and AH/EIN were identified in 14 (73.7%) and five (26.3%) patients, respectively. Compared with AH/EIN, EC more often demonstrated cribriform architecture, papillary intraluminal growth, and stromal desmoplasia. Six of the 14 patients with EC underwent hysterectomy and remained recurrence-free. Of the eight patients managed with progestin therapy, four had persistent EC or AH/EIN on follow up curettage at three months. Similarly, one of the five patients with AH/EIN treated conservatively showed persistent disease after three months of progestin therapy. Nevertheless, all patients were disease-free at the last follow-up. In APA, meticulous pathological evaluation is essential to detect concurrent AH/EIN or EC. Although conservative management may be appropriate for selected patients, close surveillance is necessary to monitor for persistence or recurrence. Hysterectomy remains a definitive and reliable therapeutic option.

Ovarian Granulosa Cell Tumor Initially Presenting as a Giant Liver Mass Radiologically Mimicking Primary Cystic Cholangiocarcinoma

Ovarian granulosa cell tumor (GCT) is a rare type of malignant sex-cord stromal tumor, with adult and juvenile types. The ovarian GCT initially presented as a giant liver mass clinically mimicking primary cholangiocarcinoma is exceedingly rare. We report such a case of a 66-year-old woman who presented with right upper quadrant pain. Abdominal magnetic resonance imaging (MRI) and a subsequently fused positron emission tomography/computed tomography (PET/CT) showed a solid and cystic mass with hypermetabolic activity concerning intrahepatic primary cystic cholangiocarcinoma. A fine-needle core biopsy of the liver mass showed coffee-bean-shaped tumor cells. The tumor cells were positive for Forkhead Box L2 (FOXL2), inhibin, Wilms tumor protein 1 (WT-1), steroidogenic factor 1 (SF1), vimentin, estrogen receptor (ER), and smooth muscle actin (SMA). The histologic features and immunoprofile supported a metastatic sex-cord stromal tumor favoring granulosa cell tumor, adult type. Strata next-generation sequencing test was performed on the liver biopsy and FOXL2 c.402C>G (p.C134W) mutation was present, consistent with granulosa cell tumor. To the best of our knowledge, this is the first documented case of ovarian granulosa cell tumor with FOXL2 mutation initially presenting as a giant liver mass clinically mimicking primary cystic cholangiocarcinoma.

Highly Invasive and Metastatic High-grade Endometrial Stromal Sarcoma WithBCORGene Alterations: A Case Report

The coexistence of a uterine leiomyosarcoma and a high-grade endometrial stromal sarcoma (HGESS) is extremely rare, especially when one of the components causes metastasis. A 46-year-old female with aggravated abdominal pain for more than 4 months was diagnosed with uterine malignant mesenchymal tumor composed of predominantly a leiomyosarcoma (99%) and a minor component of HGESS with BCL6 corepressor (BCOR) gene alterations (1%), with ovarian and pelvic metastases. The volume of HGESS with BCOR gene alterations accounted for less than 1% of the tumor mass but caused ovarian and pelvic metastases. HGESS with BCOR gene alterations is extremely aggressive. We suggest that when both components of HGESS with BCOR gene alterations and uterine leiomyosarcoma are present in one patient, the HGESS with BCOR gene alterations needs to be highlighted in the pathological report, even if it accounts for less than 1% of the tumor volume.

Detection of 14 High-risk Human Papillomavirus (HPV) Genotypes Within the Italian Cervical Cancer Screening

The identification of high-risk human papillomavirus (HR HPV) genotypes is important both for epidemiological purposes and because the persistence of an HPV infection with the same genotype is a necessary condition for the development of cervical cancer. The purpose of this study was to analyze the prevalence of HR HPV genotypes in women enrolled in the national program for cervical cancer screening in Lazio Region, Italy. From April to November 2022, we evaluated 30,445 samples using the Anyplex TM II HPV HR Detection test (Seegene), which identifies 14 HR HPV: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. The data were analyzed using the SG STATS platform. In total, 4,244 samples tested positive (13.9%); 3,290 samples (77.5%) were positive for one of the genotypes tested, and 954 (22.5%) were positive for more than one HPV genotype. The total prevalence (considering both single infection and co-infections) of the different genotypes was: HPV 16 755 cases (13.8%), HPV 31 704 (12.9%), HPV 68 580 (10.6%), HPV 66 436 (8.0%), HPV 52 413 (7.5%), HPV 58 411 (7.5%), HPV 51 400 (7.3%), HPV 56 366 (6.7%), HPV 39 293 (5.3%), HPV 59 260 (4.8%), HPV 45 231 (4.2%), HPV 33 230 (4.2%), HPV 18 222 (4.0%), HPV 35 173 (3.2%). Our results indicate that HPV 16 and 31 are the most prevalent genotypes in the Lazio region followed by HPV 68, 66, 52, 58, and 51. The extended genotyping test allows a better risk stratification and the identification of multiple HPV infections.

L1CAM Is Not a Predictive Factor in Early-stage Squamous-cell Cervical Cancer

Our study aimed to assess expression of L1 cell adhesion molecule (L1CAM) in early-stage cervical squamous-cell cancer as a prognostic factor. This retrospective, single-institution study included 154 patients who underwent radical hysterectomy for early-stage squamous cell cervical cancer between 2007 and 2017. Tumor samples from 154 patients were available for L1CAM analysis by immunohistochemistry. Among all patients, radical abdominal hysterectomy was performed in 144 cases. L1CAM expression was positive in 24 tumors (15.6%) of the whole group. In relation to the grade of differentiation and the presence of lymphovascular invasion, L1CAM expression did not show an association (p=0.154 and p=0.306, respectively). The disease-free interval and overall survival also did not significantly differ between L1CAM-positive and L1CAM-negative cases (p=0.427 and p=0.240, respectively). For histopathological characteristics, L1CAM-positive cases had a significantly higher median tumor size (p=0.015). Even in the selected group of 115 cases without nodal infiltration, L1CAM status had no effect on the relapse rate during follow-up. Our study did not confirm the results of previous studies showing L1CAM expression to be a negative prognostic factor in cervical cancer. In our study, increased L1CAM expression in early-stage squamous-cell cervical cancer was not associated with adverse prognosis regarding disease recurrence, disease-free survival, nor overall survival. L1CAM expression was correlated only with the size of the tumor.

Supportive Care for HDR Brachytherapy in Gynecological Cancer: A Single Center Experience

Brachytherapy (BT) is a standard component of treatment for patients with gynecological cancers, particularly cervical and endometrial cancer. This study aimed to evaluate the potential benefits of local supportive therapies for vaginal toxicity administered during and after vaginal or intracervical BT, within a standardized supportive care framework. A retrospective analysis was conducted on 105 patients treated between 2010 and 2016 for endometrial, cervical, or vaginal cancer with primary indication for BT. All patients underwent BT using an Iridium-192 source. Treatment protocols varied by diagnosis: patients with endometrial cancer received 25 Gy in five fractions, while patients with cervical cancer received 20 Gy in 4 fractions and were additionally treated with external beam radiotherapy. Patients were advised to follow a supportive care regimen including local estrogen, topical steroids, and moisturizing agents ( Vaginal toxicity is a well-known complication of radiation therapy. In our cohort, 51% of patients experienced Grade I vaginal late toxicity according to the LENTSOMA scale. No Grade II or higher acute or late toxicities were reported. Adherence with the recommended supportive care was suboptimal; 26% (n=11) of patients did not perform any local supportive therapy despite repeated counseling. Effective patient education and consistent guidance are crucial for ensuring adherence to supportive care protocols. Properly implemented, local supportive therapy may help mitigate both acute and late toxicity associated with BT. In our collective, a rate of 51% vaginal dryness was observed. However, the specific benefit of adding local vaginal steroid therapy or local estrogen remains inconclusive and requires further investigation.

Oral Administration of Itraconazole Induces M1 Polarization of Tumor-associated Macrophages in Gynecological Cancer

Itraconazole (ITZ), an antifungal agent with reported anticancer properties, has been shown to induce phenotypic repolarization of tumor-associated macrophages (TAMs) from an M2-like to an M1-like phenotype Nineteen patients with cervical, vaginal, or vulvar cancer received oral ITZ (20 ml of 10 mg/ml solution, twice daily) in a window-of-opportunity trial (jRCTs051190006). Tumor response was assessed using transvaginal ultrasound. Paired tumor biopsy specimens obtained before and after ITZ treatment from patients with ≥20% tumor reduction within two weeks of ITZ treatment were analyzed by immunohistochemistry using anti-CD163 and anti-CD86 antibodies to identify M2-like and M1-like TAMs, respectively. Quantitative image analysis was performed using the Vectra3 system and inForm software. Among the 19 patients, four [21.1%; 95% confidence interval (CI)=6.1-45.6%] showed ≥20% tumor reduction within two weeks of ITZ treatment, including one patient who achieved complete macroscopic regression. Immunohistochemical analysis of paired tumor samples from the remaining three responders demonstrated an increase in CD86 single-positive and CD163/CD86 double-positive TAMs after ITZ administration. ITZ treatment was associated with increased infiltration of M1-like TAMs in cancer tissues, suggesting an immunomodulatory effect. These findings support further investigation of ITZ as a potential adjunct in cancer therapy.

Evaluation of CD4+:CD8+ Ratio in Patients With Cervical Cancer and the Levels of Inflammatory Markers

Cervical cancer remains a major public health concern. The ratio of CD4+:CD8+ T-cells is used to evaluate the immune system function. This study aimed to explore the CD4+:CD8+ T-cell ratio in relation to the glycemic status, inflammatory markers, vitamin D, and vitamin B12 in patients with early diagnosed cervical cancer. This is a cross-sectional study. Blood samples were collected for flow cytometry analysis. Information regarding Papanicolaou (Pap) smears and colposcopy investigations were collected from 152 women with type 2 diabetes admitted to East Jeddah Hospital, Jeddah, Saudi Arabia, between January 2018 and January 2021. Patients with early cervical carcinoma and a higher CD4+:CD8+ ratio (>1.2) had a higher C-reactive protein (CRP) level than those with a lower CD4+:CD8+ ratio (Mean±SD=13.75±13.3 vs. 10.85±8.1; p-value=0.034). Patients with early cervical carcinoma, diabetes, and higher CD4+:CD8+ ratio (>1.2) had a higher blood HbA1c percent than those with a lower CD4+:CD8+ ratio. A high CD4+:CD8+ T-cells ratio was associated with an increased HbA1c% and CRP levels in women with diabetes diagnosed with early cervical carcinoma, which can induce inflammation in early diagnosed patients with cervical cancer.

Claudin 18.2 Expression in Gastric Tumors and Other Tumor Types With Gastric Epithelium-like Differentiation

Ethyl β-Carboline-3-Carboxylate Increases Cervical Cancer Cell Apoptosis Through ROS-p38 MAPK Signaling Pathway

Ethyl β-carboline-3-carboxylate (β-CCE) is one of the effective ingredients of Picrasma quassioides (P. quassioides). As a β-carboline alkaloid, it can antagonize the pharmacological effects of benzodiazepines by regulating neurotransmitter secretion through receptors, thus affecting anxiety and physiology. However, its efficacy in cancer treatment is still unclear. We explored the effect of b-CCE on SiHa cells using MTT assay, western blot, flow cytometry, LDH release, T-AOC, SOD, and MDA assays. We investigated the cytotoxicity of β-CCE in SiHa cells and verified that β-CCE could induce cell apoptosis in a time- and concentration-dependent manner. In this process, treatment with β-CCE significantly increased the levels of cytoplasmic and mitochondrial reactive oxygen species (ROS), which disturb the oxidation homeostasis by regulating the total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) production. Notably, the addition of N-acetylcysteine (NAC) (ROS scavenger) effectively alleviated β-CCE-induced apoptosis in SiHa cells. In addition, β-CCE might activate the p38/MAPK signaling pathway, as the pre-treatment with SB203580 (p38 inhibitor) significantly reduced β-CCE-induced apoptosis in SiHa cells. β-CCE has an anti-tumor activity. It activates the p38/MAPK signaling pathway by increasing intracellular ROS levels, which subsequently induce SiHa cell apoptosis. Our results provide a novel therapeutic target for treatment of cervical cancer.

Splenectomy in Ovarian Cancer Cytoreductive Surgery: Pre-operative Prediction of Disease, Peri-operative Outcomes and Post-operative Adherence to Antimicrobial Prophylaxis and Immunisation

Is There a Correlation Between Platelet Count, Mesenteric Lymph Node Involvement, and Hematogenous Metastases in Advanced Stage Ovarian Cancer?

Ovarian cancer remains a major cause of death in women worldwide, mainly due to late diagnosis and the lack of a reliable screening test for early detection of the disease. In this context, attention has been focused on the identification of other prognostic factors that might allow a better identification of cases with worse long-term outcome. Data of patients who underwent cytoreductive surgery between 2014-2019 were retrospectively reviewed and 57 patients were considered eligible for this study. These cases were further classified according to preoperative platelet count, with a cut-off value of 335,000/μl as a positive predictive value for long-term survival. According to this value, there were 27 cases with a preoperative platelet count lower than 335,000/μl and 30 cases with a preoperative platelet count higher than 335,000/μl. Cases in the second group had a significantly higher peritoneal carcinomatosis index (p=0.002), a higher proportion of digestive serosa involvement (p<0.001), and a higher proportion of mesenteric lymph node involvement and hematogenous metastases (p=0.005 and p=0.001, respectively). When analyzing long-term outcomes, all these factors had a significant impact on overall survival. Preoperative thrombocytosis appears to be positively associated with gastrointestinal serosa involvement, mesenteric lymph node invasion, and the presence of hematogenous metastases, thus significantly influencing the long-term outcome of patients with advanced ovarian cancer.

Ovarian Cancer and the Risk of Cataract Episodes: A Nationwide Cohort Study

The aim of this study was to explore the potential association between ovarian cancer and cataracts using the Longitudinal Health Insurance Research Database (LHIRD) of Taiwan. A retrospective cohort study was conducted, and patients with ovarian cancer were age-matched with non-ovarian cancer patients in a 1:4 ratio. A total of 4,980 and 19,920 participants were classified into the ovarian cancer and non-ovarian cancer groups, respectively. The primary outcome was the presence of cataracts and cataract surgery. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (aHR) and the 95% confidence intervals (CIs) of the primary outcomes between the groups. A total of 484 and cataract events were recorded in the ovarian cancer group, while 2,383 cataract events were recorded in the non-ovarian cancer group. The ovarian cancer group had a non-significantly higher incidence of cataracts compared to the non-ovarian cancer group (aHR=1.07, 95%CI=0.97-1.19, Ovarian cancer is associated with a marginally higher incidence of cataracts and cataract surgery.

Clinicopathological Significance of Claudin-6 Immunoreactivity in Low-grade, Early-stage Endometrioid Endometrial Carcinoma

Dysregulation of claudin 6 (CLDN6) expression has been widely documented in various malignancies. CLDN6 is aberrantly expressed in many types of human carcinomas; however, its clinical significance in endometrial carcinoma has seldom been investigated. This study aimed to examine the immunohistochemical expression status of CLDN6 in low-grade, early-stage endometrioid endometrial carcinoma (LGES-EEC) and to assess its clinicopathological significance. We performed immunostaining for CLDN6 in 118 tissue samples from LGES-EECs. Protein expression levels were interpreted using a semi-quantitative histoscore method. All statistical analyses were performed. CLDN6 was primarily localized along the membranes of the tumor cells. We considered histoscore ≥10 (the staining proportion ≥5% and intensity ≥2) as positive immunoreactivity for CLDN6. Twenty-six of the 118 patients (22.0%) showed CLDN6 positivity. Positive CLDN6 expression was significantly associated with deeper myometrial invasion (p=0.001), higher initial stage (p=0.015), and substantial lymphovascular space invasion (p=0.018). Aberrant CLDN6 expression is involved in tumor progression in LGES-EECs. In addition, targeting CLDN6 may offer clinical utility in patients with endometrial carcinoma.

Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor

Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA. Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed. Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up. Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.

Platinum-free Interval May Predict Duration of Maintenance Bevacizumab and Survival in Platinum-sensitive Recurrent Ovarian Cancer

We investigated factors affecting the long-term duration of bevacizumab-based maintenance therapy (BMT) and survival in patients with the first platinum-sensitive recurrence of ovarian cancer (PSR). We included patients with the first PSR in two tertiary centers from January 2015 till August 2021. All patients received six cycles of paclitaxel, carboplatin, and bevacizumab followed by BMT. We collected data including age at recurrence, histologic types, the status of BRCA mutation, platinum-free interval (PFI), extent of secondary cytoreductive surgery (SCS), presence of extra-abdominal disease, numbers of recurred lesions, cycles of BMT, progression-free survival (PFS), and cancer-specific survival (CSS). The median cycles of BMT were 13 (range=1-108). A total 103 patients were included, who consisted of the short-term (12 months, and optimal cytoreduction during SCS were favorable factors for the long-term duration of BMT. Moreover, PFI >12 months and the long-term duration of BMT were factors for improved PFS, and HGSC and PFI >12 months were related to improved CSS. PFI >12 months may be associated with the long-term duration of BMT and improved survival in patients with the first PSR.

Effect and Safety of Diluted Vasopressin Injection for Bleeding Control During Robot-assisted Laparoscopic Myomectomy in Reproductive Women With Uterine Fibroids: A Randomized Controlled Pilot Trial (VALENTINE Trial)

Vasopressin injected during myomectomy is known to effectively reduce bleeding but is sometimes associated with intraoperative vasoconstriction and hypertension due to systemic absorption. Although there is a growing preference for the use of diluted vasopressin, evidence of its effect and safety is still lacking. We performed a randomized controlled pilot trial to evaluate the effect and safety of vasopressin diluted in a constant volume during robot-assisted laparoscopic myomectomy (RALM), where a total of 39 women with uterine fibroids were randomly assigned into the following three groups (group 1, 0.2 IU/ml; group 2, 0.1 IU/ml; group 3, 0.05 IU/ml with a total of 100 ml of normal saline). The primary endpoint was to compare estimated blood loss (EBL), and the secondary endpoints were to compare postoperative value and drop ratio of hemoglobin, operation time, transfusion, hospitalization, and complications among the three groups. There were no differences in the number and largest size of uterine fibroids, total weight of uterine fibroids, console time, and volumes of intravenous fluid administered during RALM among the three groups, whereas combined operation was performed more commonly in group 2 than in groups 1 and 3 (53.9% vs. 0 to 7.7%; p=0.01). The primary and secondary endpoints were also not different among the three groups. However, two patients in group 1 (15.4%) showed vasopressin-related hypertension. Vasopressin diluted in a volume of 100 ml showed an effective hemostatic effect and safety during RALM (Trial No. NCT04874246 in ClinicalTrial.gov).

Endometriosis: A Retrospective Analysis on Diagnostic Data in a Cohort of 4,401 Patients

Endometriosis is a gynecological estrogen-dependent inflammatory disease due to ectopic endometrial tissue and often associated with pelvic pain. Despite its high prevalence, there are still uncertainties about its pathogenesis, diagnosis, and therapy. This study presents a retrospective study conducted on 4,401 endometriosis patients, 584 of which underwent laparoscopic procedures. The archived data about clinical signs, magnetic resonance imaging (MRI) results, topography of the endometriosis lesions (obtained via laparoscopy) associated diseases, sample analysis and histological findings were analyzed. Next, the statistical associations between the information for each case, provided by these diagnostic tools were determined. MRI is the most sensitive and specific diagnostic system for ovarian lesions, but poor in sensitivity and specificity for deep endometriosis lesions and not indicated for peritoneal lesions which remain the exclusive prerogative of laparoscopy. Clinical signs are essential for diagnosing deep lesions. The Ca125 and Ca19.9 markers have a poor reliability and their negativity in symptomatic patients has no clinical value, while in positive cases it could probably be used as a monitoring parameter. The results generated will help provide an accurate picture of the topography and distribution of endometriotic lesions. Correlation analyses between the data generated by the clinical-instrumental examinations and those on the site of the disease identified by laparoscopy, allow to define the predictive value of the clinical-instrumental signs in the diagnosis and localization of endometriotic disease.

miRNA Expression in Ovarian Cancer in Fresh Frozen, Formalin-fixed Paraffin-embedded and Plasma Samples

MicroRNAs (miRNAs) are small noncoding RNAs involved in gene expression regulation and have been investigated as potential biomarkers for various diseases, including ovarian cancer (OC). However, lack of standardized protocols regarding e.g., RNA isolation, cDNA synthesis, spike-in controls for experimental steps, and data normalization, impacts cross validation of results across research groups and hinders implementation of miRNAs as clinical biomarkers. RNA was isolated from matching fresh-frozen tissue (FF), formalin-fixed paraffin embedded (FFPE) tissue, and plasma samples from twenty women diagnosed with OC using three commercial kits: miRNeasy Tissue/Cells, miRNeasy FFPE, and miRNeasy Serum/Plasma (Qiagen, Copenhagen, Denmark). RNA isolation, cDNA synthesis, and PCR performance were tested using miRCURY LNA miRNA Quality Control PCR (QC) Panels (Qiagen). Finally, miRNA stability was assessed using five algorithms: BestKeeper, Normfinder, GeNorm, comparative delta-Ct and comprehensive ranking provided by a web-based RefFinder tool. RNA from FF, FFPE and plasma was extracted using commercially available kits and the differences in yield and purity were examined. We developed a simple method for identifying and potentially excluding samples based on their crossing point values from RT-qPCR data, which could improve existing manufacture guidelines. Moreover, we discussed how assessment of miRNA stability differs between algorithms, possibly leading to inconsistent results. We present guidelines for RNA isolation, cDNA synthesis, and data normalization for successful miRNA expression profiling using RT-qPCR in corresponding biological OC specimens. We recommend QC panels in combination with spike-in controls and interplate controls to monitor process efficiencies.

Mode of Referral of Ovarian Cancer Patients: Does it Alter Treatment and Survival?

Some studies have shown that ovarian cancer patients admitted after referral to the emergency department had a worse prognosis than those referred through non-emergency pathways. We believe that our study is the first in the UK to explore this difference and aimed to compare the 1-year, 3-year, and 5-year overall survival rates of ovarian cancer patients referred non-urgently from the general practitioner (GP) vs. patients referred urgently to the emergency department (ED). This was a retrospective cohort study conducted at the University Hospitals of Leicester (UHL) from 1 There was no significant difference in the 1-year, 3-year, and 5-year overall survival in ovarian cancer patients referred from the GP compared to patients referred to the ED, 84.8%, 62.2%, and 48.4% versus 80.2%, 64.8%, and 43.5%, respectively (p=0.732). The mode of referral for ovarian cancer patients may not affect their prognosis. Prompt referral to the gynaecological oncology multidisciplinary team, a good acute oncology service, early imaging and image-guided diagnostic pathways, timely appointment, and timely initiation of treatment in our centre may have minimized the difference in outcome in the two groups.

The Impact of COVID-19 Infection During the Postoperative Period After Surgery for Ovarian Cancer

The COVID-19 pandemic has significantly influenced the management of oncogynecologic patients in regard to time of diagnosis, to delay of treatment, therapeutic strategy and postoperative complications. The aim of the study was to investigate the impact of preoperative SARS-Cov2 infection on the postoperative outcome after debulking surgery for ovarian cancer. Between June 2021 and September 2021, 12 patients with antecedents of COVID-19 infection and ovarian cancer were submitted to surgery at "Dr. I. Cantacuzino" Hospital, Bucharest, Romania. Their outcomes were compared to those reported in a similar group of patients submitted to surgery during the same period in the absence of COVID-19 infection. Although preoperative data showed no statistically significant differences between the two groups, intraoperative length and estimated blood loss were higher in the COVID-19 group and so were the postoperative complications, the most commonly encountered ones being reported by wound infection, postoperative hemoperitoneum and pneumonia. However, the differences did not reach statistical significance. Preoperative COVID-19 infection seems to slightly increase the risk of postoperative complications after debulking surgery for ovarian cancer.

Hypoxia-induced Maspin Expression Affects the Prognosis of Ovarian Clear Cell Carcinoma

To investigate the role of the expression of hypoxia-related genes on the prognosis of ovarian clear cell carcinoma (OCCC). Basal mRNA levels of eight hypoxia-related genes were compared. Cell viability was assayed after treating ES-2 cells under hypoxic conditions. The mRNA and protein levels were evaluated after the induction of hypoxia and administration of increased doses of N-acetylcysteine (NAC). Finally, the prognostic role of their expression levels was evaluated in 61 patients with OCCC. The mRNA and protein levels of maspin increased gradually with the induction of hypoxia. Maspin protein expression decreased after treatment with paclitaxel and NAC. High expression of maspin was related to poor progression-free and overall survival in patients with OCCC (adjusted hazard ratios, 3.97 and 7.47; 95% confidence intervals=1.34-11.81, and 1.98-28.13). High expression of maspin induced by hypoxia might be associated with poor prognosis of OCCC.

Extraperitoneal Approach During Peritonectomy in the Right Upper Quadrant for Peritoneal Metastases from Ovarian Malignancies

To present the extraperitoneal approach for the removal of peritoneal metastases in the right upper abdomen in patients with ovarian cancer and to evaluate safety and potential advantages with comparison with the traditional approach. Detailed description of the right upper quadrant peritonectomy as extraperitoneal approach. Procedure-specific short-term complications were retrospectively analyzed in a cohort of patients. Sixty-four patients were included. Full-thickness diaphragmatic resection was performed in 17% of primary cases, and in 44% of the patients with recurrent ovarian carcinoma. The rate of complete cytoreduction (CC-0) was 70%. The most common postoperative complication was pleural effusion (32%). The extraperitoneal approach for peritonectomy of the right upper quadrant in patients with ovarian cancer is feasible, with improved access to the right subdiaphragmatic area. This enables a high rate of complete cytoreduction, and simplified and safe surgical dissection in an uncontaminated area under secured vascular structures. The early postoperative outcomes are comparable to those of the traditional transperitoneal approach.

Long Non-coding RNA LOC285194 Promotes Epithelial Ovarian Cancer Progressionviathe Apoptosis Signaling Pathway

To explore the molecular mechanism and clinical significance of a newly identified lncRNA LOC285194 in epithelial ovarian cancer (EOC). LOC285194 transcript levels were analyzed in EOC cells compared to normal cells. Small interfering RNAs were used to suppress LOC285194 expression. Levels of apoptosis-related proteins were determined by western blot. LOC285194 expression in ovarian cancer and non-tumor tissues were compared with clinicopathologic and survival data. Knockdown of LOC285194 decreased cell migration and proliferation, enhanced reactive oxygen species production and resulted in increased levels of proteins of the extrinsic apoptotic signaling pathway. LOC285194 expression level was higher in ovarian cancer tissues compared to control. Overall survival was significantly shorter in patients with high LOC285194 expression. Lymph node metastasis and high LOC285194 expression were significant prognostic factors of mortality (HR=4.614 and 5.880; p=0.026 and p=0.002, respectively). LOC285194 can promote the progression of EOC via an anti-apoptotic mechanism. It may serve as a novel biomarker for predicting prognosis of EOC.

Plan-Optimization Method for Central-shielding Pelvic Volumetric-modulated Arc Therapy for Cervical Cancer

To establish a method of plan optimization in pelvic volumetric-modulated arc therapy (VMAT) for cervical cancer using the central-shielding (CS) principle. We created external beam VMAT plans for eight cases with non-bulky stage I-IIb using the CS principle based on the Japanese standard guideline. Clinical target volumes (CTVs) for whole-pelvis (WP) irradiation were created using published guidelines, and CTVs for CS irradiation were created by subtracting the uterus corpus and 4 cm-wide regions centered at the cervix and vagina from the CTVs for WP irradiation. For plan optimization of CS irradiation, a 4-cm diameter cylindrical volume centered in the cervix and vagina was created as the volume receiving a high dose in brachytherapy, and the volume overlapping with the rectum was defined as the Ant-Rectum. Dose-volume histogram (DVH) parameters of two CS VMAT plans with and without (VMAT VMAT In the implementation of IMRT/VMAT as the standard treatment for cervical cancer in Japan, our optimization method may be an essential step toward fully benefitting from the CS principle.

Long-term Outcomes of Cervical Adenocarcinoma Treated With Concurrent Chemoradiotherapy Using Paclitaxel and Cisplatin

We retrospectively analyzed the locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) of the uterine cervix treated with concurrent chemoradiotherapy using cisplatin plus paclitaxel (TP-CCRT). Thirty patients with stage IB-IVA AC/ASC were treated with whole pelvis external beam radiotherapy. A high-dose-rate intracavitary brachytherapy was delivered once per week at a fractional dose of 6 Gy. For TP-CCRT, the patients received cisplatin and paclitaxel. A complete response was achieved in 17 patients (77.3%) in the TP-CCRT group and 4 patients (50.0%) in the P-CCRT group. The 5-year OS rate in the TP-CCRT and P-CCRT groups was 74.2% and 25.0% (p=0.0094), the central DFS rate was 58.0% and 12.5% (p=0.0267), and the distant DFS rate was 63.6% and 12.5% (p=0.0042), respectively. TP-CCRT achieves a considerably better disease control for AC of the cervix, leading to a better OS.

Clinicopathological Characteristics of Squamous Cell Carcinoma and High-grade Squamous Intraepithelial Lesions Involving Endocervical Polyps

To investigate the clinicopathological characteristics of high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas (SCCs) involving endocervical polyps (ECPs). We collected the endocervical polypectomy cases and performed pathological examination and cytohistological correlation. During a period of 12 years, 21 (1.1%) HSILs and two (0.1%) SCCs involving ECPs were identified in 1,905 cases. Twelve (63.1%) of the 19 cases were cytohistologically concordant. In five HSILs and one SCC with polypectomy margin involvement, residual HSIL was identified in conization or hysterectomy specimens. Furthermore, in two HSIL patients and one SCC patient with negative polypectomy margins, residual HSILs were found in the conization specimens. The prevalence of HSIL and SCC involving ECP in our cohort was similar to the rates found in previous studies. The presence of residual HSIL in nonpolypoid cervical tissue regardless of the polypectomy margin involvement suggests that conization or hysterectomy is needed for diagnostic or treatment purposes.

Demethoxycurcumin Inhibits In Vivo Growth of Xenograft Tumors of Human Cervical Cancer Cells

Demethoxycurcumin (DMC), a derivate of curcumin from natural plants, exerts antitumor effects on various human cancer cells in vitro and in vivo. Nevertheless, no reports have disclosed whether DMC can affect the growth of human cervical cancer cells in vivo. Therefore we investigated the antitumor effects of DMC on a HeLa cell xenograft model in nude mice in this study. Twenty-four nude mice were subcutaneously injected with HeLa cells. All mice were randomly divided into control, low-dose DMC (30 mg/kg), and high-dose DMC (50 mg/kg) groups and individual mice were treated intraperitoneally accordingly every 2 days. DMC significantly reduced tumor weights and volumes of HeLa cell xenografts in mice, indicating the suppression of growth of xenograft tumors. These effects and findings might provide evidence for investigating the potential use of DMC as an anti-cervical cancer drug in the future.

Hysterectomy for Recurrent/Residual Cervical Cancer Following Definitive Radiotherapy

Radical hysterectomy has been used for local recurrent or persistent (LR) cervical cancer after radiotherapy (RT), but the rate of serious complications is high and tolerance is low. This study determined the efficacy, safety, and prognostic factors of adjuvant simple hysterectomy in LR cervical cancer post-RT. A total of 21 patients who underwent hysterectomy for LR cervical cancer post-RT in our Department between May 2007 and September 2018 were included in the study. Primary, definitive RT was performed. Histological response by definitive RT in the extirpated uterus was classified on the basis of histological response criteria: effect (Ef) 0-3. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 51.9% and 50.1%, respectively. Ef 1 was significantly associated with poorer prognosis compared to Ef 2 or Ef 3. Adjuvant hysterectomy could be a treatment of choice for LR cervical cancer post-RT.

Radical Hysterectomy for Cervical Cancer in Patients With Uterine Prolapse

Association between cervical cancer and uterine prolapse represents a scarce eventuality. This is a case series of 11 patients diagnosed with different stages of cervical cancer in association with uterine prolapse. Between 2014 and 2020, 11 patients were diagnosed with cervical cancer on prolapsed uterine cervix. The mean age of patients at the time of uterine cervix diagnosis was 68 years. In six cases, the first intent treatment was surgery, while in the remaining five cases it consisted of radio-chemotherapy, followed by radical surgery. The perioperative and postoperative outcomes were compared to those reported in a similar series of patients diagnosed in similar stages of the disease, but in the absence of uterine prolapse, no significant differences being encountered. Although it represents an unusual situation, malignant transformation of the uterine cervix might be encountered even in cases presenting uterine prolapse. In such cases, the therapeutic strategy should be tailored according to the stage of the disease.

Volume Delineation in Cervical Cancer With T2 and Diffusion-weighted MRI: Agreement on Volumes Between Observers

To delineate cervical cancer gross tumor volume (GTV) on T2-magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) maps, assessing volumes and inter-observer agreement between two observers. A radiologist and a radiation oncologist delineated GTV on T2 (T2 Mean T2 GTV delineation was smaller in the ADC maps compared to T2-MRI, reaching an almost perfect agreement between observers. Thanks to this acceptable variability, adding functional imaging might provide more information for tumor delineation, improving reproducibility for image-guided adaptive radiotherapy.

Picrasma quassioides Extract Elevates the Cervical Cancer Cell Apoptosis Through ROS-Mitochondrial Axis Activated p38 MAPK Signaling Pathway

Picrasma quassioides (P. quassioides) is used in traditional Asian medicine widely for the treatment of anemopyretic cold, eczema, nausea, loss of appetite, diabetes mellitus, hypertension etc. In this study we aimed to understand the effect of P. quassioides ethanol extract on SiHa cervical cancer cell apoptosis. The P. quassioides extract-induced apoptosis was analyzed using the MTT assay, fluorescence microscopy, flow cytometry and western blotting. P. quassioides extract induced cellular apoptosis by increasing the accumulation of cellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting ATP synthesis. Pretreatment with N-Acetylcysteine (NAC), a classic antioxidant, decreased the intracellular ROS production and inhibited apoptosis. In addition, the P38 MAPK signaling pathway is a key in the apoptosis of SiHa cells induced by the P. quassioides extract. The P. quassioides extract exerts its anti-cancer properties on SiHa cells through ROS-mitochondria axis and P38 MAPK signaling. Our data provide a new insight for P. quassioides as a therapeutic strategy for cervical cancer treatment.

BRM270 Suppresses Cervical Cancer Stem Cell Characteristics and Progression by Inhibiting SOX2

Cervical cancer is one of the leading causes of cancer death in women worldwide. BRM270 (BRMLife) has therapeutic potential for cancer treatment owing to its ability to inhibit cell proliferation, and expression of cluster of differentiation (CD) 133 in CD133 The expression of sex-determining region Y-box 2 (SOX2) was tested in four different cervical cancer cell lines, HeLA, SiHa, Caski and C33A. SOX2-expressing SiHa and C33A cell lines were selected for further experiments on the in vitro and in vivo effects of BRM270 on cervical cancer progression using western blotting, flow cytometry, sphere-formation assay, magnetic-activated cell sorting of CD133 In the present study, in cervical cancer stem cells (CSCs), we found that BRM270 inhibited expression of SOX2, which is associated with cervical cancer initiation and metastasis. BRM270 also inhibited CD133 expression and induced apoptosis of CSCs and suppressed CD133 BRM270 might be an effective agent for cervical cancer treatment.

Cervical Pathology Following HPV Vaccination in Greece: A 10-year HeCPA Observational Cohort Study

In Greece the population-level impact of HPV vaccination is unknown due to lack of official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy. This is an observational prospective cohort study performed in 7 academic Obstetrics and Gynaecology Departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected. A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated. HPV vaccination at a proper age can markedly reduce development of severe cervical precancers and consequently the need for treatment, as well as their long-term related obstetrical morbidity.

Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer

Ubiquitin-associated protein 2-like (UBAP2L) has been demonstrated to be associated with the progression of multiple types of cancer. However, the function of UBAP2L in uterine cervical cancer remains unclear. Between 2005 and 2015, 84 patients who underwent surgery were included in this study. The patients were stratified into two groups on the basis of immunohistochemical staining for UBAP2L, and survival analysis was performed. Moreover, loss-of-function analysis was performed using the cervical cancer cell lines CaSki and SiHa. Based on immunohistochemistry, the overall survival in patients with low UBAP2L expression was significantly longer than that of those with high UBAP2L expression (p=0.045). The in vitro experiment revealed that knockdown of UBAP2L remarkably inhibited cell proliferation in both live cell imaging and the MTS assay. Patients with high UBAP2L expression had unfavorable prognosis and UBAP2L appears to play an important role in proliferation.

Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy

The aims of the study were: i) to assess the incidence of perineural invasion (PNI) in squamous cell carcinoma of the vulva and ii) to correlate PNI with common pathological prognostic variables and clinical outcome of patients. The hospital records of 64 patients with vulvar squamous cell carcinoma who underwent primary radical surgery were reviewed. PNI was significantly related to stage (p=0.038), size (p=0.038), lymph-vascular space involvement (p=0.013) and nodal status (p=0.038), but not to patient age, tumor grade and stromal invasion. Five-year disease-free survival was 30.0% in patients with PNI and 53.1% in those without PNI (p=0.018), and the corresponding 5-year overall survival was 50.0% and 77.1% (p=0.031), respectively. PNI was associated with common pathological prognostic variables and with a poorer clinical outcome in patients with vulvar squamous cell carcinoma.

Negative Pressure Wound Therapy (NPWT) in Groin Wounds After Lymphadenectomy in Vulvar Cancer Patients

Vulva cancer surgery is associated with a high level of morbidity mostly due to wound healing disorders in the inguinal region following lymphadenectomy. Our aim is to evaluate the feasibility of negative pressure wound therapy (NPWT) using the PICO™ device in groin wounds after lymphadenectomy. The groins of twenty patients who underwent bilateral lymph node dissection were dressed with the PICO™ device. All patients were followed prospectively with clinical controls up to three months postoperatively using a standardized study protocol. A total of 11 patients (55%) developed a surgical site complication (SSC). One patient suffered from a wound rupture two days after surgery, six a lymphocele and four a surgical site infection. Operation time, blood loss, number of lymph nodes removed, length of hospital-stay and duration of PICO™ treatment did not differ between women with and without SSCs. NPWT using the PICO™ device seems to be a feasible method to reduce the severity of healing disorders in the groin after lymphadenectomy in vulva cancer patients.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Recurrent Endometrial Cancer With Peritoneal Carcinomatosis

Peritoneal carcinomatosis of recurrent endometrial cancer (EC) is a rare clinical entity with dismal prognosis. The purpose of this study was the presentation of the outcomes of patients with peritoneal carcinomatosis from recurrent endometrial cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The files of the patients with recurrent EC and peritoneal carcinomatosis treated with CRS and HIPEC between 2000 and 2024 were retrospectively reviewed. Clinical and histopathological variables were correlated to survival, morbidity, and mortality. CRS plus HIPEC was performed in 23 female patients, mean age 60.4±7.9 (48-75) years. The mean peritoneal cancer index was 10.6±6 (3-39). Complete or near-complete cytoreduction was possible in 82.6% of patients. The incidence of severe morbidity and hospital mortality was 8.68% and 0%, respectively. Recurrence was recorded in 47% of patients. The overall 5- and 10-year survival was 78%. The completeness of cytoreduction score was identified as the single possible prognostic variable of survival. Complete cytoreduction combined with HIPEC appears to offer significant survival benefit with low morbidity in patients with recurrent EC and peritoneal carcinomatosis.

Significance of HER2 and VEGFR2 in Early-stage Endometrial Cancer

The majority of patients with early-stage endometrial cancer (EC) have a good prognosis, but recurrence does occur despite diagnosis at an early stage. There is a growing need for early diagnosis of EC and novel treatment options. Human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor receptor 2 (VEGFR) expression in microarrays of patient EC tissue was examined in association with clinicopathological data. HER2 and VEGFR2 expression in Ishikawa cells and differences in migration and proliferation of cells with HER2-knockdown were evaluated. Higher expression of VEGFR2 was associated with lower International Federation of Obstetrics and Gynecology grades (p=0.044). The positive correlation between HER2 and VEFR2 expression was statistically significant in T1 stage (p=0.002) and International Federation of Obstetrics and Gynecology grade 1 tumors (p=0.004). Wound-healing assays revealed that HER2 loss in Ishikawa cells reduced confluence compared to that of control cells. The association of VEGFR2 and HER2 expression in early EC was elucidated. This study shows that the measurement of VEGFR2 expression may be useful in the preoperative assessment of EC and suggests the possibility of anti-HER2 therapy for EC.

The Expression of NRIP1 and LCOR in Endometrioid Endometrial Cancer

The aim of the study was to analyze the expression of nuclear receptor interacting protein 1 (NRIP1) and its partner ligand-dependent nuclear receptor co-repressor (LCOR) in endometrioid endometrial cancer and to investigate their association with estrogen receptor (ER), progesterone receptor (PR), Ki-67, clinicopathological parameters and patient survival. Immunohistochemical evaluation was carried out to investigate the subcellular expression of NRIP1 and LCOR in endometrioid endometrial cancer samples. Statistical analysis was used to identify the correlations of NRIP1 and LCOR expression with clinicopathological variables and to estimate the survival rates. Endometrial cancer tissues exhibited higher expression of NRIP1 and LCOR in comparison with the normal tissues. Cytoplasmic LCOR expression was positively associated with ER and PR expression, while cytoplasmic NRIP1 expression was positively associated with ER expression. Moreover, cytoplasmic expression of NRIP1 was positively associated with Ki-67. Our study demonstrated that high cytoplasmic expression of LCOR may predict a longer overall survival of patients with endometrioid endometrial cancer. Patients with tumors expressing low levels of LCOR showed a worse survival compared to those expressing high levels.

Controversies in the Management of Early-stage Serous Endometrial Cancer

Early-stage uterine serous carcinoma (USC) has one of the highest recurrence rates and mortality among early-stage uterine epithelial cancers. Research into the clinical management of USC has begun to progress, guided by surgical and pathological advances. This article summarizes the available literature regarding diagnosis, management, and possible future uses of molecular analysis of women with early-stage USC. PubMed was searched for all pertinent English language research articles published from January 1, 2006 through March 1, 2020 which included a study population of women diagnosed with stage 1 USC. Due to the scarcity of prospective or large-scale data, studies were not limited by design or numbers of patients. Studies performed at earlier dates were incorporated to provide context. A total of 86 studies were included in the review. Multiple well-designed studies have confirmed the safety of a minimally invasive surgical approach for surgical management of USC. The role of sentinel node biopsy has been validated with both prospective and retrospective multi-center data. Stage I USC is associated with a highly variable risk of recurrence, even following completion of adjuvant chemoradiation. This aggressive phenotype has been linked to high numbers of somatic copy number alterations, tumor protein 53, and phosphatidylinositol 3 kinase mutations, which have been shown to be predictive of prognosis. Early-stage USC demonstrates a lack of predictable recurrence patterns, with reports noting distant recurrence in patients with disease confined to polyps. Unless no residual tumor is found on hysterectomy, chemotherapy and radiotherapy should be discussed and individualized by stage and treatment goals.

The Advantage of Pinpoint Camera System With Indocyanine Green for Sentinel Lymph Node Micrometastasis Detection in Low Risk Endometrial Cancer

This report outlines our experience in the management of 10 cases of low-risk endometrial cancer with Indocyanine Green for sentinel lymph node (SLN) mapping using the Pinpoint 30-degree 4K S1 SPY real-time camera system (Stryker). This system offers simultaneous, real-time, high-definition white light and fluorescence imaging through a single laparoscope, without the need to change camera filters. In our retrospective case series we included all endometrioid endometrial cancers of grade G1 and pre-operative radiological staging FIGO 1A reported on magnetic resonance imaging (MRI) that were treated laparoscopically from October 2019 to April 2020. Bilateral sentinel lymph node excision was achieved in 9 out of 10 cases. In one patient, one sentinel lymph node featuring a micrometastasis of <2 mm was identified. A specialist minimal access team can safely and reliably reproduce this technique for sentinel lymph node excision.

Grade 1 Endometrioid Carcinoma With an Area of Serous Carcinoma Less than 5% Is More Aggressive than Stage IA Pure-type Grade 1 Endometrioid Carcinoma

In 2020, the percentages were removed from the World Health Organization's criteria for mixed carcinoma. The aim was to examine the clinical significance of an area of serous carcinoma (SC) <5%. Our study included 236 patients with the 2009 International Federation of Obstetrics and Gynecology (FIGO) stage IA grade 1 endometrioid carcinoma (EG1) from multiple hospitals. EG1 patients with an area of SC <5% and those with pure-type EG1 were retrospectively compared. In the multivariate analysis for recurrence, an area of SC <5% was an independent risk factor [hazard ratio (HR)=101.51, p<0.01]. In the multivariate analysis for progression-free survival, an area of SC <5% was identified as a negative prognostic factor (HR=62.43, p<0.01). EG1 with an area of SC <5% may be more aggressive than pure-type EG1 at FIGO stage IA.