The role of minimally invasive surgery in epithelial ovarian cancer treatment: a narrative review.

Objectives: The aim of this narrative review is to summarize the available evidence on the use of minimal invasive surgery (MIS) in the management of epithelial ovarian cancer (EOC). Background: MIS is currently performed to stage and treat EOC at different stage of presentation. We will evaluate risks and benefits of minimally invasive surgery for early stage EOC treatment, then potential advantages provided by staging laparoscopy in identifying patients suitable for primary cytoreductive surgery (PDS) will be discussed. Finally we will investigate the growing role of MIS in the treatment of advanced EOC after neoadjuvant chemotherapy (NACT) and in the treatment of EOC recurrence. Methods: An electronic database search was performed on PubMed, Medline, and Google Scholar for relevant studies up to December 2022. Conclusion: LPS represents a feasible surgical procedure for the staging and treatment in early, advanced and EOC relapse in selected patients treated in high-volume oncological centers by surgeons with adequate experience in advanced surgical procedures. Despite the increasing use of MIS over the last few years, randomized clinical trials are still needed to prove its effectiveness.

Impact of 2 years of COVID-19 pandemic on ovarian cancer treatment in IRCCS-AUSL of Reggio Emilia.

OBJECTIVE: To assess compliance with the 2019 regional recommendation to centralize epithelial ovarian cancer (EOC) patients and to assess whether the COVID-19 pandemic has affected the quality of care for EOC patients. METHODS: We compared data from EOC patients treated before the introduction of the 2019 regional recommendation (2018-2019) with data obtained from EOC patients treated after the regional recommendation was adopted during the first 2 years of the COVID-19 pandemic (2020-2021). Data were retrieved from the Optimal Ovarian Cancer Pathway records. R software version 4.1.2 (the R Foundation for Statistical Computing, Vienna, Austria) was used for the statistical analysis. RESULTS: 251 EOC patients were centralized. The number of EOC patients centralized increased from 2% to 49% despite the COVID-19 pandemic. During the COVID-19 pandemic, there was an increase in the use of neoadjuvant chemotherapy and interval debulking surgery. There was an improvement in the percentage of Stage III patients without gross residual disease following both primary and interval debulking surgery. The percentage of EOC cases discussed by the multidisciplinary tumor board (MTB) increased from 66% to 89% of cases. CONCLUSION: Despite the COVID-19 pandemic, centralization has increased and the quality of care has been preserved thanks to the MTB.

Should Endometrial Cancer Treatment Be Centralized?

Endometrial cancer (EC) is the most common malignancy of the female genital tract in Western and emerging countries. In 2012, new cancer cases numbered 319,605, and 76,160 cancer deaths were diagnosed worldwide. ECs are usually diagnosed after menopause; 70% of ECs are diagnosed at an early stage with a favorable prognosis and a 5-year overall survival rate of 77%. On the contrary, women with advanced or recurrent disease have extremely poor outcomes because they show a low response rate to conventional chemotherapy. EC is generally considered easy to treat, although it presents a 5-year mortality of 25%. Though the guidelines (GLs) recommend treatment in specialized centers by physicians specializing in gynecologic oncology, most women are managed by general gynecologists, resulting in differences and discrepancies in clinical management. In this paper we reviewed the literature with the aim of highlighting where the treatment of EC patients requires gynecologic oncologists, as suggested by the GLs. Moreover, we sought to identify the causes of the lack of GL adherence, suggesting useful changes to ensure adequate treatment for all EC patients.

An Italian National Survey on Ovarian Cancer Treatment at first diagnosis. There's None so Deaf as those who will not Hear.

Objective: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, crucial prognostic factors are no gross residual disease and centralization of cases. To evaluate the centralization of EOC patients, we report the results of a survey that shows the daily management of EOC patients in Italy. Methods: A 49-items electronic unblinded survey assessing demographics, practice characteristics, current opinions and approach to managing advanced EOC at first diagnosis was sent both to general gynecologists (GG) and gynecologic oncologists (GO). Differences in frequency distribution of answers between gynecologists with different expertise were evaluated using Fisher exact test. Multivariable analyses were performed applying generalized linear models. Results: 84/192 (44%) GG and 108/192 (56%) GO from all Italian regions answered to our survey. GOs declared to perform fertility sparing surgery in early EOC more frequently than GG (p=0.002). GOs can perform a frozen section and have both a gynecopathologist and a dedicated general surgeon. 89% of GOs consider as "optimal debulking" no gross residual disease and 81% achieve this at upfront cytoreduction in more than 40% of patients. Use of neoadjuvant chemotherapy decreases in higher volume centers (p<0.001) while it is lower in the group of GOs than in the GGs group (p<0.001). Conclusions: EOC patients are still treated by GGs. GOs perform more upfront surgery and achieve optimal debulking in a greater percentage of patients than GGs. In Italy an adequate centralization of cases has not yet been achieved, and this may have detrimental effects on the quality of treatment.

Impact of a Province-wide Endometrial Cancer Guideline on Daily Practice.

BACKGROUND/AIM: Most women are managed by a general gynaecologist rather than being centralized in an oncogynaecology unit, resulting in different clinical management. In 2006, a hub & spoke model was introduced in the Provincial Healthcare System of Reggio Emilia, and shared guidelines were written. We aimed to verify the adherence to guidelines and the consequent improvements in quality care. PATIENTS AND METHODS: All patients who underwent a hysterectomy for endometrial cancer in the Reggio Emilia Province hospitals from 2000 to 2016 were included in the study. Clinical and pathological data were carefully recorded for each patient included. RESULTS: This study included 132 and 277 patients in the periods before and after the implementation of the guideline, respectively. In the post-guideline period, the use of hysteroscopy, magnetic resonance, laparoscopy and adjuvant treatment significantly increased. CONCLUSION: Common shared guidelines and a clinical audit can help in improving centralization, resulting in an increased quality of care.

Accuracy of preoperative endometrial biopsy and intraoperative frozen section in predicting the final pathological diagnosis of endometrial cancer.

BACKGROUND: Histotype and grade of endometrial cancer (EC) are prognostic factors of nodal involvement and thus of survival. Preoperative biopsy (PB) and intraoperative frozen section (FS) are usually used to guide surgical staging on which the choice of adjuvant therapy will be based successively. OBJECTIVE: The aim of this study was to assess the agreement rate between PB and FS with final diagnosis (FD) in a series of surgically resected EC. MATERIALS: All patients submitted to hysterectomy for EC or atypical endometrial hyperplasia in the Reggio Emilia Province hospitals from 2007 to 2018 were included. Concordance rate differences in histotype, grading, myoinvasion, risk of recurrence between PB, FS and FD were assessed with Fisher's exact test and Mc Nemar contingency test. RESULTS: A total of 352 patients were identified. For 345 patients it was possible to compare PB and FD results. FS examination was performed in 201/352 (57%) cases, while for 21/352 (6%) patients only an intraoperative macroscopic evaluation was done; in the remaining women, FS-exam was omitted. In 14/201 (7%) cases the tumor wasn't grossly identifiable and the random FS-sampling wasn't able to find the tumor site. High diagnostic concordance of tumor type between PB and FD was observed: no significant differences were registered in type 1 and type 2-endometrial cancer identification (83%, 73%, p = 0.121). Significant differences (p = 0.005) were observed comparing FS and FD results: 95% of type 1-ECs were correctly diagnosed by FS, while only 76% of type 2-ECs received a correct diagnosis on FS. PB showed a concordance with FD among tumor grading close to 55% whilst concordance achieved 71% grouping low grade (G1-G2) EC. No significant differences in FS and FD concordance rate were observed between tumor grades. Concordance for low grade was significantly higher than for high grade ECs (89% vs 50%, respectively, p value = 0.014). The concordance rate in evaluating the myoinvasion status between FS and FD was 80% (n: 199 patients), reaching 99% after combining the first 2 groups (0-49% vs ≥ 50%). Twenty-two cases underwent only intraoperative macroscopic evaluation of the myoinvasion, with an accuracy of 91%: only in 1 case the invasion of the cervical stroma was not detected (Stage II), and 1 case the patient was overstaged as Ib. Discrepancies were observed in FS capacity to correctly predict the final ESMO risk group in stage I patients: FS resulted particularly reliable in predicting a low-risk (concordance with FD: 91%) while the accuracy sharply decreased for intermediate- and high-risk patients (62% and 40%, respectively). To investigate the usefulness of FS in EC management, we compared patients who underwent FS (FS-group) or not (no-FS-group). Especially for low risk patients, the FS significantly increased the adequacy of surgical treatment from 53% (no-FS-group) to 72% (FS-group) (p = 0.016). CONCLUSIONS: FS remains a useful tool to tailor surgery in EC-patients, avoiding secondary surgery to complete staging particularly in patients with AH + AHBA, low and intermediate risk ECs that could benefit from adjuvant therapy.

AB0 Blood Group and Ovarian Cancer Survival.

Background: Epithelial ovarian cancer is the most lethal gynecological malignancy because is usually diagnosed at advanced stage. New prognostic factors have been investigated but these biomarkers do not have a strong direct relationship with survival. Several studies investigated the association between AB0 blood group with ovarian cancer but with conflicting results. We investigated the association between AB0 blood group and epithelial ovarian cancer patients consecutively surgically treated at our department from 2004 to 2015. Methods: Clinical charts of ovarian cancer patients treated and followed from 2004 to 2015 were checked for inclusion and exclusion criteria. Clinical and pathological data were recorded in an electronic separate, anonymous, password-protected database. All relevant data were extrapolated and used for final analysis. Results: A population of 265 ovarian cancer patients was analyzed in this study. 121 (45.6%) patients presented blood type 0, 112 (42.3%) had blood type A, 23 (8.7%) B and 9 (3.4%) AB. A significantly lower percentage of death (8.7%) in patients with blood type B in comparison with patients presenting different genotypes (group 0: 34.7%, group A: 32.1%, group AB: 22.2%) was found. In invasive serous ovarian cancer patients the analysis showed a 5 fold significant reduction of the risk of death in patients with B genotype. However, postoperative residual tumor resulted the most important prognostic factor for overall survival. Conclusions: AB0 blood group might be a preoperative prognostic factor in epithelial ovarian cancer patients. According to the literature, postoperative residual disease remain the most important prognostic factor also in our study.

Uterine Papillary Serous Carcinoma Arising in a Polyp: A Multicenter Retrospective Analysis on 75 Patients.

OBJECTIVES: The objectives of this study were to evaluate whether the international recommendations on the management of uterine papillary serous carcinoma arising in a polyp are uniformly followed in Italian Oncologic Centers and whether the strategy adopted is effective. MATERIALS AND METHODS: Patients with uterine papillary serous carcinoma arising in a polyp and who had undergone a hysterectomy were identified in the 2003-2013 database of 7 Italian Gynecologic Oncology Centers. Clinical and pathologic characteristics and outcomes were compared between staging procedure types. Survival curves of the women were plotted using the Kaplan-Meier method and analyzed using Cox regression hazard model and the log-rank test. Associations between clinical parameters and the incidence of recurrence were assessed by generalized linear models and the Fisher test. RESULTS: A total of 75 patients met the inclusion criteria. Recurrence-free survival was affected positively by type of surgical staging and negatively by preoperative diagnosis of hypertension. The association between surgical staging and recurrence-free survival resulted significant at univariate survival analysis (P=0.048 and 0.045) and maintained a trend of significance (P=0.070) in multivariate analysis, whereas hypertension was demonstrated to be the principal influencing factor. CONCLUSIONS: The international recommendations on the management of uterine papillary serous carcinoma are not uniformly followed in daily practice, although the extension of the surgery seems to be associated with lower recurrence rates also when uterine papillary serous carcinoma is confined to a polyp or endometrial surface.

Prognostic Impact of ABO Blood Group on Type I Endometrial Cancer Patients- Results from Our Own and Other Studies.

Objectives: The ABO blood group antigens were found on most epithelial cells and in secretions. In the normal endometrium there is a variable expression of histo-blood group and related antigens suggesting a hormonal regulation. A relationship between ABO blood groups and endometrial cancer has been investigated with contradictory results. In this study we investigated the influence of blood types on clinical and pathological characteristics of endometrial cancer patients. Method: Retrospective cohort study. Clinical and pathological data were extrapolated and their association with blood groups were assessed. Results: A total of 203 type I endometrial cancer patients were included in the final analysis. Univariate analysis indicated that a lower frequency of G3 undifferentiated tumors was observed in patients with A blood group (P=0.027). Multivariate analysis, including also clinical features such as Age, BMI, parity, hypertension and diabetes confirmed that patients with A group present a lower risk of G3 tumors in comparison with not A patients. (OR=0.32, P=0.011). Conclusions: Patients with A genotype have a lower risk to develop G3 type I endometrial cancer. ABO blood group might represent a useful, easy access and cheap biomarker for patients' selection and for management personalization of endometrial cancer patients.

Impact of the Food and Drug Administration Safety Communication on the Use of Power Morcellator in Daily Clinical Practice: An Italian Survey.

STUDY OBJECTIVE: To assess the impact of the Food and Drug Administration (FDA) warning about power morcellation use on the daily clinical practice of Italian gynecologists. DESIGN: Electronic survey mailed to the main gynecologic centers (Canadian Task Force Classification type III). SETTING: Unit of Obstetrics and Gynecology, IRCCS - Arcispedale S. Maria Nuova di Reggio Emilia (Italy). PATIENTS: The study did not include patient data. INTERVENTION: There was no intervention. MEASUREMENTS AND MAIN RESULTS: From 490 surveys sent out, 426 replies were included in the final analysis (return rate = 86.9%). Four hundred of the 426 (93.9%) gynecologists were aware of the FDA warning. One hundred fifty of 302 (49.7%) of experienced gynecologists and 176 of 349 (50.4%) of oncology gynecologists considered laparoscopy the best approach for myomectomy. The FDA communication was considered overly restrictive by experienced and oncology gynecologists who declared that they had no intention of changing their surgical approach. Two hundred fifty of the 426 (58.7%) gynecologists declared that they would change their surgical approach only to prevent legal litigation. CONCLUSION: The FDA warning also affected Italian gynecologists. Particularly, less experienced gynecologists and those without oncologic practice seem to be more interested in avoiding legal litigation rather than a real clinical risk of upstaging an unexpected leiomyosarcoma. Fear of undiagnosed sarcoma could increase the number of laparotomies.

Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

HNF1B polymorphism influences the prognosis of endometrial cancer patients: a cohort study.

BACKGROUND: HNF1B (formerly known as TCF2) gene encodes for a transcription factor that regulates gene expression involved in normal mesodermal and endodermal developments. A close association between rs4430796 polymorphism of HNF1B gene and decreased endometrial cancer (EC) risk has been demonstrated. The aim of the current study was to test the hypothesis that rs4430796 polymorphism can influence the prognosis of EC patients. METHODS: Retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumour tissues. The influence of patients' genotype on overall survival and progression free survival were our main outcome measures. RESULTS: A total of 191 EC patients were included in the final analysis. Overall survival differed significantly (P = 0.003) among genotypes. At multivariate analysis, a significant (P < 0.05) effect on overall survival was detected for FIGO stage, and rs4430796 polymorphism of HNF1B gene. After grouping EC patients according to adjuvant treatment, rs4430796 polymorphism resulted significantly (P < 0.001) related to overall survival only in subjects who received radiotherapy plus chemotherapy. A significant (P = 0.014) interaction between rs4430796 polymorphism and chemo-radiotherapy was also detected. Finally, only a trend (P = 0.090) towards significance was observed for rs4430796 polymorphism effect on progression free survival. CONCLUSIONS: rs4430796 polymorphism of HNF1B gene influences independently the prognosis of EC patients with a potential effect on tumor chemo-sensitivity.

Clinical governance network for clinical audit to improve quality in epithelial ovarian cancer management.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several hospitals throughout the region provide primary treatment for these patients and it is well know that treatment quality is correlated to the hospital that delivers. The aim of this study was to investigate the management and treatment of EOC in a Region of the North Italy (Emilia-Romagna, Italy). METHODS: A multidisciplinary group made up of 11 physicians and 3 biostatisticians was formed in 2009 to perform clinical audits in order to identify quality indicators and to develop Region-wide workup in accordance with the principles of evidence-based medicine (EBM). The rationale was that, by setting up an oncogynecology network so as to achieve the best clinical practice, critical points would decrease or even be eliminated. Analysis of cases was based on the review of the medical records. RESULTS: 614 EOC patients treated between 2007 and 2008 were identified. We found only 2 high-volume hospitals (≥ 21 patients/year), 3 medium-volume hospitals (11-20 operated patients/year), and 7 low-volume hospitals (≤ 10 operated patients /year). Only 222 patients (76.3%) had a histological diagnosis, FIGO surgical staging was reported only in 206 patients (70.9%) but not all standard surgical procedures were always performed, residual disease were not reported in all patients. No standard number of neoadjuvant chemotherapy cycles was observed. CONCLUSIONS: The differences in terms of treatments provided led the multidisciplinary group to identify reference centers, to promote centralization, to ensure uniform and adequate treatment to patients treated in regional centers and to promote a new audit involving all regional hospitals to a complete review of the all the EOC patients.

Haptoglobin phenotype and epithelial ovarian cancer.

BACKGROUND: Haptoglobin (H) is a glycoprotein that regulates the immune response. Serum haptoglobin levels are significantly higher in patients with advanced epithelial ovarian cancer (EOC) with poor survival. Different isoforms of haptoglobin have been found in the serum of patients with EOC. We studied the genetic susceptibility and outcome of patients with EOC correlated to H phenotypes. MATERIALS AND METHODS: Analyses of the H phenotypes were performed on sera from patients stored at -70°C. A modified method based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of sera was used, followed by western blotting. RESULTS: Seventy-nine consecutive patients with EOC and 63 healthy women were enrolled. Their mean (± S.D.) age was 58.9 ± 12.46 years. Overall survival was 66 months (95% confidence interval=37.7-94.2). Similar distribution of haptoglobin phenotypes was observed in EOC and in healthy women. No significant correlation was found between haptoglobin phenotype, overall survival and time-to-progression. Fewer G3 tumors were found in patients with H2-2 compared with those with H1-2 (84.2% and 90.6%, respectively, p<0.04). No significant correlation was found between H phenotype and tumor markers or number of relapses. CONCLUSION: Although ours is a preliminary study based on a small population with scant significant findings, we hypothesize that patients with EOC with haptoglobin 2-2, might have a better prognosis because they present fewer G3 tumors and they may present a stronger immune response than patients with 1-1 and 1-2 phenotypes. Larger studies should be performed to assess the predictive value of haptoglobin phenotype in patients with EOC.

Province wide clinical governance network for clinical audit for quality improvement in endometrial cancer management.

BACKGROUND: According to the hub-and-spoke model introduced in the Provincial Healthcare System of Reggio Emilia, early endometrial cancer is treated in peripheral low-volume hospitals (spokes) by general gynecologist, whereas more complex cancers are treated by gynecological oncologists at the main hospital (hub). OBJECTIVE: To guarantee a uniformly high standard of care to all patients with endometrial cancer treated in hub and spoke hospitals of Reggio Emilia Province. METHODS: The specialists of the 5 hospitals of Reggio Emilia Province instituted an inter hospital and multidisciplinary oncology group to write common and shared guidelines based on evidence-based medicine through the use of clinical audit. They valued the process indicators before and after guidelines introduction identifying the site of improvement and verifying the standard achievement. RESULTS: Diagnostic hysteroscopy use increased significantly from preguideline period, 53%, to postguideline period, 74%. Magnetic resonance use and accuracy increased significantly from preguideline to postguideline periods: 8.1% to 35.3% and 37.3% to 74.7%, respectively. Laparoscopy use increased from 1.6% (preguideline) to 18.6 (postguideline). Early surgical complications decreased from 16% (preguideline) to 9% (postguideline). Radiotherapy use increased from 14.% (preguideline) to 32.3% (postguideline). CONCLUSION: It is possible for a provincial oncology group to build an oncology network providing an improvement in the assistance of patients with endometrial cancer through the use of clinical audit. Clinical audit made it possible to obtain the full attendance of specialists of various disciplines involved in the treatment of endometrial cancer to optimize response time schematizing process.

Gastric cancer in a pregnant woman presenting with low back pain and bilateral erythematous breast hypertrophy mimicking primary inflammatory breast carcinoma.

This report describes the first case of a pregnant woman presenting low-back pain and breast pain associated with bilateral erythematous breast hypertrophy, proving to be the result of metastatic disease from a gastric carcinoma. A 30-year-old pregnant woman was admitted complaining of persistent severe low back pain, breast pain and concomitant bilateral erythematous breast hypertrophy, mimicking primary inflammatory breast carcinoma. During the caesarean section, widespread disease was found and finally metastatic gastric cancer was detected. Pregnant women with gastric cancer may present symptoms that are considered common during pregnancy. Common symptoms that present warning characteristics, such as the persistent severe pain observed in the presented case, should be carefully investigated as they may be the only warning signs and symptoms of rare ominous conditions such as gastric cancer.

Tibolone and estradiol plus norethisterone acetate similarly influence endothelium-dependent vasodilatation in healthy postmenopausal women.

In healthy postmenopausal women, E(2) plus norethisterone acetate (1 mg + 0.5 mg) or tibolone (2.5 mg) similarly modify flow-mediated endothelium-dependent vasodilatation. The effect is dependent on baseline vasodilator reserve, with low values being augmented by either treatment.

Effect on insulin sensitivity of Implanon vs. GnRH agonist in women with endometriosis.

OBJECTIVES: To evaluate the influence of two medical treatments for endometriosis on insulin sensitivity. STUDY DESIGN: After surgery, 26 women with endometriosis were randomly allocated to a 6-month treatment with a GnRH agonist (Leuprorelin 3.75 mg/28 days) or a subdermal progestin implant (etonogestrel 68 mg). Insulin sensitivity (SI) and glucose utilization independent of insulin (Sg) were investigated at baseline and after 6 months by a frequently sampled intravenous glucose tolerance test (FSIGT) associated with the minimal model method. RESULTS: Both therapies tended to decrease SI, but the effect did not reach statistical significance in the GnRH agonist group (5.43+/-1.29 vs. 3.99+/-0.8) and was significant in the etonogestrel group (5.74+/-1.12 vs. 3.95+/-0,78; p=.046). Sg, fasting glucose, insulin, C-peptide and C-peptide/insulin were not modified by either treatment. CONCLUSIONS: The modifications of glucose-insulin metabolism induced by the GnRH agonist are of no relevance for the short-term use of this molecule. Even if the modification induced by the etonogestrel implant is subtle and of no major impact, it should be taken into consideration for the long-term treatment of individuals with abnormalities of glucose-insulin metabolism.