Range of Resection in Endometrial Cancer-Clinical Issues of Made-to-Measure Surgery.

Endometrial cancer (EC) poses a significant health issue among women, and its incidence has been rising for a couple of decades. Surgery remains its principal treatment method and may have a curative, staging, or palliative aim. The type and extent of surgery depends on many factors, and the risks and benefits should be carefully weighed. While simple hysterectomy might be sufficient in early stage EC, modified-radical hysterectomy is sometimes indicated. In advanced disease, the evidence suggests that, similarly to ovarian cancer, optimal cytoreduction improves survival rate. The role of lymphadenectomy in EC patients has long been a controversial issue. The rationale for systematic lymphadenectomy and the procedure of the sentinel lymph node biopsy are thoroughly discussed. Finally, the impact of the molecular classification and new International Federation of Gynecology and Obstetrics (FIGO) staging system on EC treatment is outlined. Due to the increasing knowledge on the pathology and molecular features of EC, as well as the new advances in the adjuvant therapies, the surgical management of EC has become more complex. In the modern approach, it is essential to adjust the extent of the surgery to a specific patient, ensuring an optimal, made-to-measure personalized surgery. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject, providing an up-to-date clinical guide.

Human Papillomavirus Infections and the Role Played by Cervical and Cervico-Vaginal Microbiota-Evidence from Next-Generation Sequencing Studies.

This comprehensive review encompasses studies examining changes in the cervical and cervico-vaginal microbiota (CM and CVM) in relation to human papillomavirus (HPV) using next-generation sequencing (NGS) technology. HPV infection remains a prominent global health concern, with a spectrum of manifestations, from benign lesions to life-threatening cervical cancers. The CM and CVM, a unique collection of microorganisms inhabiting the cervix/vagina, has emerged as a critical player in cervical health. Recent research has indicated that disruptions in the CM and CVM, characterized by a decrease in Lactobacillus and the overgrowth of other bacteria, might increase the risk of HPV persistence and the progression of cervical abnormalities. This alteration in the CM or CVM has been linked to a higher likelihood of HPV infection and cervical dysplasia. NGS technology has revolutionized the study of the cervical microbiome, providing insights into microbial diversity, dynamics, and taxonomic classifications. Bacterial 16S rRNA gene sequencing, has proven invaluable in characterizing the cervical microbiome, shedding light on its role in HPV infections and paving the way for more tailored strategies to combat cervical diseases. NGS-based studies offer personalized insights into an individual's cervical microbiome. This knowledge holds promise for the development of novel diagnostic tools, targeted therapies, and preventive interventions for cervix-related conditions, including cervical cancer.

Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts.

Carboplatin (CPT) and paclitaxel (PCT) are the optimal non-surgical treatment of epithelial ovarian cancer (EOC). Although their growth-restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental PMCs and PFBs. In addition, we tested whether PMC and PFB exposure to the drugs promotes the development of a pro-cancerogenic phenotype. The results showed that CPT and PCT induce G2/M growth arrest-associated senescence of normal peritoneal cells and that the strongest induction occurs when the drugs act together. PMCs senesce telomere-independently with an elevated p16 level and via activation of AKT and STAT3. In PFBs, telomeres shorten along with an induction of p21 and p53, and their senescence proceeds via the activation of ERK1/2. Oxidative stress in CPT + PCT-treated PMCs and PFBs is extensive and contributes causatively to their premature senescence. Both PMCs and PFBs exposed to CPT + PCT fuel the proliferation, migration, and invasion of established (A2780, OVCAR-3, SKOV-3) and primary EOCs, and this activity is linked with an overproduction of multiple cytokines altering the cancer cell transcriptome and controlled by p38 MAPK, NF-κB, STAT3, Notch1, and JAK1. Collectively, our findings indicate that CPT and PCT lead to iatrogenic senescence of normal peritoneal cells, which paradoxically and opposing therapeutic needs alters their phenotype towards pro-cancerogenic. It cannot be excluded that these adverse outcomes of chemotherapy may contribute to EOC relapse in the case of incomplete tumor eradication and residual disease initiation. © 2023 The Pathological Society of Great Britain and Ireland.

Expression of B7-H4 in endometrial cancer and its impact on patients' prognosis.

OBJECTIVES: The aim of the study was to evaluate the B7-H4 expression in endometrial cancer cells and to investigate its relationship with patient prognosis and clinicopathological features of the disease. MATERIAL AND METHODS: We performed a single-center, retrospective cohort study that included endometrial cancer patients treated between 2012 and 2019. B7-H4 expression in specimens obtained from 63 patients was examined by immunohistochemical staining. The evaluation of B7H4 immunoreactivity was assessed using Immunoreactivity Scoring (IRS) system. RESULTS: B7-H4 reactivity was observed in all, except one, endometrial cancer patients (98%). Staining intensity: no reaction in one case, weak in 16 (24%) patients, moderate in 25 (37%), and strong in 22 (35%). Twenty-nine (46%) patients showed B7-H4 immunoreactivity in more than 60% of cells, while, in 18 (29%) cases and 16 (25%) patients, the percentages were 30-60% and < 30% respectively. Median IRS was 2 (range 0-6). We found a significantly worse overall survival (OS) rate for patients with high versus low B7-H4 IRS (p = 0.03), however, in multivariate analysis, the difference in patient survival was close to the significance level (p = 0.052). B7-H4 expression was not related to histopathological type of the tumor, tumor grade, lymph node metastases, or the FIGO stage of the disease. CONCLUSIONS: Our result suggests that B7-H4 expression might be a useful prognostic factor in endometrial cancer.

Cancer Stem Cell Markers-Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis.

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients' clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10-3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10-3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.

FOXP3-positive cell infiltration in the chorionic villi is increased in the placenta accreta and decreased in the placental abruption.

OBJECTIVES: Growing data suggest a role of Treg cells in placentation. The aim of the study was to evaluate Treg cells (FOXP3-positive cells) placental bed infiltration in patients with placenta accrete syndrome (PAS) and patients who experienced placental abruption. MATERIAL AND METHODS: The study group included 13 patients with PAS and the control group consisted of 66 women who had caesarean (CD) delivery of whom, 44 patients with elective caesarean (EC) delivery, and 22 patients with urgent caesarean (UC) delivery due to placental abruption. FOXP3 cell infiltration was assessed by means of immunohistochemistry in placental chorionic villous (CV) and in the decidua (D) and cumulatively in the placental bed (PB). RESULTS: We observed significant difference in the degree of FOXP3-positive cell CV infiltration between studied groups (p = 0.04). FOXP3-positive cells were the most commonly observed in PAS patients, while, they were the least frequently presented in patients after UC. The immunoreactivity for FOXP3-positive cells in CV were as follows: PAS 5 (38%), urgent CS 1 (5%) and elective CS 8 (18%) subjects. We found no difference in the presence of FOXP3-positive cells in the D (p = 0.35) and in the PB (p = 0.23) of analyzed groups. FOXP3-cell infiltration was not related with patient age, BMI, gestational age and neonatal birth weight. CONCLUSIONS: Our study provides further evidence that abnormal invasive placentation is an associated disturbance of the maternal immune response. Accordingly, we have theorized that alteration of the FOXP3-positive Treg cell infiltration into the placental bed allows trophoblast cell invasion.

The impact of splenectomy and diaphragmatic surgery on perioperative morbidity and overall survival of ovarian cancer patients.

OBJECTIVES: The prognosis of ovarian cancer (OC), among other factors, depends on residual disease after primary debulking surgery (PDS) and initial disease advancement. The main aim of our study was to evaluate the survival benefits of splenectomy and diaphragmatic surgery in OC patients, when the procedures result in resection to no macroscopic residual disease or minimal residual disease [tumor nodules below 2.5 mm according to Sugarbaker's completeness of cytoreduction score (CC) = 1]. MATERIAL AND METHODS: The study included 25 OC patients after splenectomy procedures, 28 patients after diaphragmatic surgery and 17 patients who had undergone both splenectomy and diaphragmatic surgery. Patients' overall survival (OS) was compared with residual disease-matched controls (47 patients) who had upper abdomen involvement but no requirement for splenectomy and/or diaphragmatic surgery. RESULTS: Overall survival of patients after splenectomy was not significantly different from OS of patients who did not required splenectomy (36.1 vs 31.6 months; p = 0.85). No differences in OS were observed between patients who did and did not require diaphragmatic surgery (31.3 vs 41.8; p = 0.33). Similarly, we found no differences in OS between patients who underwent both splenectomy and diaphragmatic surgery and those patients who did not require either procedure (20.1 vs 31.6 months; p = 0.45). Splenectomies and diaphragmatic surgeries were associated with prolonged hospitalization and length of surgery, however, no specific morbidity related to the procedures was observed. CONCLUSIONS: In the cases of advanced OC, diaphragm and spleen involvement do not hamper patient prognosis when adequately resected.

The Prognostic Value of Cancer Stem Cell Markers (CSCs) Expression-ALDH1A1, CD133, CD44-For Survival and Long-Term Follow-Up of Ovarian Cancer Patients.

Recurrent disease and treatment-associated chemoresistance are the two main factors accounting for poor clinical outcomes of ovarian cancer (OC) patients. Both can be associated with cancer stem cells (CSCs), which contribute to cancer formation, progression, chemoresistance, and recurrence. Hence, this study investigated whether the expression of known CSC-associated markers ALDH1A, CD44, and CD133 may predict OC patient prognosis. We analyzed their expression in primary epithelial ovarian cancer (EOC) patients using immunohistochemistry and related them to clinicopathological data, including overall survival (OS) and progression-free survival (PFS). Expression of ALDH1A1 was detected in 32%, CD133 in 28%, and CD44 in 33% of cases. While Kaplan-Meier analysis revealed no association of the expression of CD133 and CD44 with PFS and OS, ALDH1A1-positive patients were characterized with both significantly shorter OS (p = 0.00022) and PFS (p = 0.027). Multivariate analysis demonstrated that the expression of ALDH1A1, FIGO stage III-IV, and residual disease after suboptimal debulking or neoadjuvant chemotherapy correlated with shorter OS. The results of this study identify ALDH1A1 as a potential independent prognostic factor of shorter OS and PFS in EOC patients. Therefore, targeting ALDH1A1-positive cancer cells may be a promising therapeutic strategy to influence the disease course and treatment response.

An analysis of the significance of the lymph node ratio and extracapsular involvement in the prognosis of endometrial cancer patients.

Introduction: The primary aim of our study was to analyse the impact of the lymph node ratio (LNR) and extracapsular involvement (ECI) on the prognosis of endometrial cancer (EC) patients. Material and methods: We carried out a retrospective analysis of 886 patients surgically treated for EC between 2000 and 2015. In the subgroup of patients with lymph node metastases (LNM), we evaluated the impact of the number and localization of the LNM, LNR, and ECI on patients' overall survival (OS). Results: In the group of patients with LNM, 0.3 was the optimal LNR cut-off for differentiating between short- and long-term survivors [HR = 2.94 (95% CI: 1.49-5.80)]. Patients with a LNR ≥ 0.3 had a significantly shorter OS period (35.0 months, range 0.2-175 months) compared to patients with a LNR < 0.3 [median OS - mOS, was 143, range 15-169 months; (p = 0.003]. We observed significant differences in the mOS of EC patients without LNM compared to patients with LNM, as well as those with both LNM and ECI (p < 0.0001). In the group of patients with LNM, we also found that a poorer prognosis depended on the extension of the primary tumour. Conclusions: Our results suggest that when LNM are found, the long-term outcomes of EC patients are worse in those who have a LNR ≥ 0.3, the presence of ECI, and a more advanced extension of the primary tumour.

Total Colectomy as a Part of Ultra-Radical Surgery for Ovarian Cancer-Short- and Long-Term Outcomes.

(1) Background: The aim of this study was to assess the outcomes for patients who underwent total colectomy (TC) as a part of surgery for ovarian cancer (OC). (2) Methods: We performed a retrospective analysis of 1636 OC patients. Residual disease (RD) was reported using Sugarbaker's completeness of cytoreduction score. (3) Results: Forty-two patients underwent TC during primary debulking surgery (PDS), and four and ten patients underwent TC during the interval debulking surgery (IDS) and secondary cytoreduction, respectively. The median overall survival (mOS) in OC patients following the PDS was 45.1 months in those with CC-0 (21%) resection, 11.1 months in those with CC-1 (45%) resection and 20.0 months in those with CC-2 (33%) resection (p = 0.28). Severe adverse events were reported in 18 patients (43%). In the IDS group, two patients survived more than 2 years after IDS and one patient died after 28.6 months. In the recurrent OC group, the mOS was 6.9 months. Patient age above 65 years was associated with a shortened overall survival (OS) and the presence of adverse events. (4) Conclusions: TC as a part of ultra-radical surgery for advanced OC results in high rates of optimal debulking. However, survival benefits were observed only in patients with no macroscopic disease.

The association between lymph node metastases and long-term survival in patients with epithelial ovarian cancer.

INTRODUCTION: A key survival prognosis factor for patients treated for ovarian cancer is complete cytoreductive surgery where all macroscopic neoplastic implants, including enlarged metastatic lymph nodes, are removed. We presume that investigating the involvement of the lymphatic system can result in a more individualized approach to the treatment of ovarian cancer patients. The main aim of our study was to analyze the relationship between the presence, number and types of lymph node metastases and ovarian cancer patient prognosis. MATERIAL AND METHODS: We carried out a retrospective analysis of patients who underwent cytoreduction due to primary ovarian cancer, between 2010 and 2015. We analyzed the number of metastatic lymph nodes, the lymph node ratio defined as the ratio of the number of metastatic lymph nodes to the total number of lymph nodes removed, extracapsular involvement, and the histopathological pattern of metastases. RESULTS: The study group included 651 patients. Of these, 377 had lymphadenectomy, 144 presented with lymph node metastases, and 233 had no lymph node metastases. We also included a group of 274 patients who did not have lymphadenectomy. Patients with more than 4 metastatic lymph nodes and a lymph node ratio of ≥ 0.1 had significantly poorer overall survival. Extracapsular involvement had no relation to patient overall survival. Multivariant survival analysis indicated that a lymph node ratio of ≥ 0.1 was an independent predictor of poor survival. CONCLUSIONS: The analysis of lymph node metastases in ovarian cancer patients can have predictive value for patient overall survival.

Analysis of long-term outcomes in 44 patients following pelvic exenteration due to cervical cancer.

BACKGROUND: Pelvic exenteration (PE) may be associated with prolonged overall survival (OS) in selected patients with advanced or recurrent cervical cancer. However, the factors related to improved survival following PE are not clearly defined. The aim of this study was to perform a retrospective analysis of OS rates in a group of patients undergoing PE in order to identify the factors related to improved long-term outcomes. METHODS: Our study group consisted of 44 patients, including 21 squamous cell cancer (SCC) patients, 22 patients with adenocarcinomas (AC) of the cervix, and one patient with undifferentiated cervical carcinoma. The patients were categorized according to the type of surgery, namely, primary surgery (12 patients) or surgery due to cancer recurrence (32 patients). RESULTS: In the group of patients with recurrent cervical cancer, we found that improved OS correlated with the SCC histological type and the presence of vaginal fistula. The need for reoperation within 30 days and the presence of severe adverse events significantly worsened the prognosis. We found a non significant trend toward improved survival in those patients with tumor-free margins. Lymph node metastases, the initial stage of the disease, the time to recurrence, and a history of hysterectomy had no impact on patients' OS. In the group of patients undergoing primary PE, we observed a trend toward improved survival among those diagnosed with vaginal fistula. CONCLUSIONS: Pelvic exenteration seemed to improve the long-term outcomes for patients with SCC cancer recurrence and vaginal fistula whose surgery was unrelated to severe adverse events.

Wilms' tumor 1 antigen immunoreactivity in epithelial ovarian cancer - diagnostic and prognostic value.

OBJECTIVES: Ovarian cancer is a heterogeneous disease, with a number of different histological subtypes with various responses to treatment. Wilms' tumor 1 (WT1) immunoreactivity is used to distinguish between OC's various subtypes. However, little is known about the protein's role as a prognostic factor. Thus, the main aim of our study was to evaluate the relationship between WT1 expression and patient overall survival (OS) and lymph node metastases. MATERIALS AND METHODS: Study group consisted of 164 women aged 22-84, diagnosed with epithelial ovarian cancer (EOC). WT1 expression in histological slides was assessed by immunohistochemistry. RESULTS: Serous tumors were the most common subtype among EOC (n = 126; 76.8%), followed by endometrioid (n = 20; 12.2%), clear-cell (n = 14; 8.5%) and mucinous cancer (n = 4; 2.4%). Of all serous EOC, WT1-positive tumors accounted for 75.6% of cases and this number was significantly higher than in other histological subtypes (p < 0.0001). Patients with lymph node metastases were more likely to have WT1-positive than WT1-negative tumors (p = 0.006). There was no significant correlation between WT1 immunoreactivity and OS across the whole study group of EOC patients (p = 0.6); however, in the group of non-serous (mucinous, endometrioid and clear-cell) EOC subjects, WT1 immunoreactivity was associated with shorter OS (p = 0.046). CONCLUSIONS: WT1 immunoreactivity may be helpful in differentiating primary epithelial serous carcinomas from non-serous ovarian cancers; however, its prognostic role in EOC is rather uncertain.

Psychiatric disorders and changes in immune response in labor and postpartum.

Women may present with psychiatric disorders during pregnancy, normal labor, following delivery by caesarean section, or in the postpartum period. The accumulating evidence suggests that these disorders may be due to changes in immune responses. During pregnancy complications such as the prolongation of cervical ripening or descent, placental abruption, premature labor, and preeclampsia increase the risk of postpartum psychiatric disorders. Women may exhibit depression and postpartum psychosis following either normal birth or caesarean section. Since psychiatric disorders like schizophrenia, major depression, and bipolar disorder are associated with both alterations in the immune response and changes in immune cell subpopulations, in this study we have chosen to examine whether the psychiatric disorders in women during labor or postpartum also lead to aberrant immune responses.

High post-treatment serum soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) levels is associated with poor survival of patients with cervical cancer.

AIM: Receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) is responsible for induction of selective immunosuppression. In addition, preclinical studies have shown that sRCAS1 levels may reflect cancer aggressiveness. The main aim of our study was to analyze pre- and post-treatment levels of sRCAS1 in the sera of patients treated for cervical cancer and to evaluate whether the levels change during treatment and their impact on patient prognosis. METHODS: The study included 49 patients suffering from cervical cancer. The early stage cervical cancer patients (14) were treated surgically, while the advanced stage patients (35) underwent radiochemotherapy. Serum sRCAS1 levels were evaluated both before and after intervention with the use of the ELISA method. RESULTS: We have found that median serum sRCAS1 levels of patients before intervention were not significantly different from the levels assessed after intervention. There were also no differences when pre- and post-treatment levels were compared within the group of early and of advanced stage patients. Serum sRCAS1 levels were not influenced by either the histopathological type of the tumor or the methods of treatment. High post-intervention sRCAS1 levels indicated shortened OS when compared to low sRCAS1 levels. Neither pre-intervention sRCAS1 levels nor the alteration in sRCAS1 levels during treatment were associated with patient prognosis. In multivariate analysis, post-treatment sRCAS1 levels and clinical stage of cervical cancer remained as independent predictors of survival. CONCLUSION: High post-treatment serum sRCAS1 level in cervical cancer patients seems to be a negative prognostic factor for patient overall survival.

Performance of Selected Models for Predicting Malignancy in Ovarian Tumors in Relation to the Degree of Diagnostic Uncertainty by Subjective Assessment With Ultrasound.

OBJECTIVES: The study's main aim was to evaluate the relationship between the performance of predictive models for differential diagnoses of ovarian tumors and levels of diagnostic confidence in subjective assessment (SA) with ultrasound. The second aim was to identify the parameters that differentiate between malignant and benign tumors among tumors initially diagnosed as uncertain by SA. METHODS: The study included 250 (55%) benign ovarian masses and 201 (45%) malignant tumors. According to ultrasound findings, the tumors were divided into 6 groups: certainly benign, probably benign, uncertain but benign, uncertain but malignant, probably malignant, and certainly malignant. The performance of the risk of malignancy index, International Ovarian Tumor Analysis assessment of different neoplasias in the adnexa model, and International Ovarian Tumor Analysis logistic regression model 2 was analyzed in subgroups as follows: SA-certain tumors (including certainly benign and certainly malignant) versus SA-probable tumors (probably benign and probably malignant) versus SA-uncertain tumors (uncertain but benign and uncertain but malignant). RESULTS: We found a progressive decrease in the performance of all models in association with the increased uncertainty in SA. The areas under the receiver operating characteristic curve for the risk of malignancy index, logistic regression model 2, and assessment of different neoplasias in the adnexa model decreased between the SA-certain and SA-uncertain groups by 20%, 28%, and 20%, respectively. The presence of solid parts and a high color score were the discriminatory features between uncertain but benign and uncertain but malignant tumors. CONCLUSIONS: Studies are needed that focus on the subgroup of ovarian tumors that are difficult to classify by SA. In cases of uncertain tumors by SA, the presence of solid components or a high color score should prompt a gynecologic oncology clinic referral.

An Analysis of Long-Term Outcomes in Patients Treated by Extensive Bowel Resection Due to Advanced Ovarian Cancer Relative to the Effectiveness of Surgery.

INTRODUCTION: Surgery for advanced ovarian cancer (AOC) often requires bowel resections. However, the impact of bowel surgery on patient overall survival (OS) has not yet been precisely determined. OBJECTIVE: The aim of the study was to analyze the OS rates in a group of AOC patients undergoing bowel resection. METHODS: We carried out a retrospective analysis of patients who had undergone low anterior resection of the rectum (LAR) during primary or interval debulking surgery for AOC. We divided the patients into 2 groups: Group 1 included 69 patients who underwent only LAR; Group 2 included 66 patients who underwent LAR and additional bowel resection. The control group included 71 AOC patients who did not required bowel resection. RESULTS: In the subgroup of patients with no gross residual disease (NGR), there were no differences in OS between Groups 1 and 2. In the subgroup of "optimally" (tumors <1 cm) debulked patients, Group 1 patients had a higher median OS than Group 2 patients. Additionally, there was no difference between Groups 1 and 2 as far as the number of severe adverse events. CONCLUSIONS: Multiple bowel resections seem to improve OS in patients when NGR is achieved but should be avoided when complete resection is not possible.

Ultrasound and Clinical Preoperative Characteristics for Discrimination Between Ovarian Metastatic Colorectal Cancer and Primary Ovarian Cancer: A Case-Control Study.

The aim of this study was to describe the clinical and sonographic features of ovarian metastases originating from colorectal cancer (mCRC), and to discriminate mCRC from primary ovarian cancer (OC). We conducted a multi-institutional, retrospective study of consecutive patients with ovarian mCRC who had undergone ultrasound examination using the International Ovarian Tumor Analysis (IOTA) terminology, with the addition of evaluating signs of necrosis and abdominal staging. A control group included patients with primary OC. Clinical and ultrasound data, subjective assessment (SA), and an assessment of different neoplasias in the adnexa (ADNEX) model were evaluated. Fisher's exact and Student's t-tests, the area under the receiver-operating characteristic curve (AUC), and classification and regression trees (CART) were used to conduct statistical analyses. In total, 162 patients (81 with OC and 81 with ovarian mCRC) were included. None of the patients with OC had undergone chemotherapy for CRC in the past, compared with 40% of patients with ovarian mCRC (p < 0.001). The ovarian mCRC tumors were significantly larger, a necrosis sign was more frequently present, and tumors had an irregular wall or were fixed less frequently; ascites, omental cake, and carcinomatosis were less common in mCRC than in primary OC. In a subgroup of patients with ovarian mCRC who had not undergone treatment for CRC in anamnesis, tumors were larger, and had fewer papillations and more locules compared with primary OC. The highest AUC for the discrimination of ovarian mCRC from primary OC was for CART (0.768), followed by SA (0.735) and ADNEX calculated with CA-125 (0.680). Ovarian mCRC and primary OC can be distinguished based on patient anamnesis, ultrasound pattern recognition, a proposed decision tree model, and an ADNEX model with CA-125 levels.

Cytoplasmic and membranous receptor-binding cancer antigens expressed on SiSo cells (RCAS1) immunoreactivity in epithelial ovarian cancer cells represent differing biological function of RCAS1.

INTRODUCTION: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a selective suppressor of the immune response that has been linked to the evasion of immune surveillance by cancer cells. However, the exact prognostic impact of RCAS1 on epithelial ovarian cancer (EOC) has not been fully elucidated. The main aim of our study was to evaluate the influence of RCAS1 immunoreactivity (RCAS1-Ir) in EOC cells and in tumor stroma cells on patient overall survival. We also focused on RCAS1-Ir and the structure of the tumor stroma. MATERIAL AND METHODS: RCAS1-Ir was evaluated by means of immunohistochemistry in 67 patients with EOC. We distinguished cytoplasmic and membranous immunoreactivity patterns. RESULTS: We found that high cytoplasmic RCAS1-Ir in cancer cells was associated with more than a two-time shortened period of overall survival. Membranous RCAS1-Ir in cancer cells, as well as in tumor stroma macrophages and fibroblasts, did not correlate with patient survival. RCAS1-Ir in the cytoplasm of cancer cells was positively correlated with the degree of tumor stroma infiltration by fibroblasts and macrophages, but not with RCAS1-Ir in these cells. On the other hand, membranous RCAS1-Ir in cancer cells was positively correlated with RCAS1-Ir in fibroblasts and macrophages, but not with their quantity. CONCLUSIONS: Due to their different impacts on patient prognosis and tumor stroma structure, it seems that cytoplasmic and membranous RCAS1-Ir in EOC cells may have different biological functions.

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes.

OBJECTIVES: There is growing evidence that Treg cell infiltration into the cancer nest is associated with poor prognosis. How- ever, the Treg cell population in the peripheral blood may change when a different type of anticancer therapy is applied. Since Treg cells may support tumor growth by enhancing the suppressive profile of the cancer microenvironment, the assessment of Treg cells can bring to light important information regarding prognosis. Thus we decided to analyze the Treg cell population in the peripheral blood in relation to long-term outcomes in the group of patients with ovarian cancer. MATERIAL AND METHODS: The 80 patients included in the study were treated surgically followed by chemiotherapy for ovar- ian cancer between October 2010 through May 2011.The peripheral blood samples from the patients were collected directly prior to chemotherapy. Information on any patients who died was retrieved from the database of the Cuiavia-Pomerania Regional Office of the National Health System of Poland. CD4+CD25+FOXP3+ lymphocytes T were assed by flow cytometry. We have analyzed the long term outcomes of treatment regarding to the level of Treg cells in peripheral blood. RESULTS: We found that patients with serous adenocarcinomas had significantly higher Treg levels compared to those patients with non-serous types. Patients who had a higher percentage of Treg cells within the CD4+ cell population prior to the beginning of the treatment had worse long-term outcomes from the applied therapy. CONCLUSIONS: The assessment of Treg levels prior to the start of chemotherapy is clinically useful and may predict overall survival in ovarian cancer patients.