Endometrial Cancer: Analysing Patterns of Recurrence and Real-Life Outcome Data Using the 2020 ESGO-ESTRO-ESP Risk Stratification System.

AIMS: To evaluate patterns of recurrence and explore the prognostic differences between the 2018 FIGO staging system and the 2020 ESGO-ESTRO-ESP risk stratification system of endometrial cancer with an emphasis on early-stage disease. BACKGROUND: The incidence of endometrial cancer has risen by around 60% since the 90's. It is projected that by 2035 endometrial cancer will be the sixth most common cause of cancer-related death amongst females. METHODS: This was a retrospective cohort study which included patients treated between 2010 and 2017. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meyer survival analysis was used to assess OS and RFS across different risk groups. Cox proportional hazards regression was used to evaluate prognostic risk factors implicated in recurrence. Different recurrence patterns across the subgroups were analysed with Pearson's chi-square test. RESULTS: The study included 692 patients with a recurrence rate of 14.9%. The median time to recurrence was 17.1 months (IQR:8.8-28.4). The mean OS varied between 97.2 months in the low-risk group to 63.1 months in the high-risk group (p < 0.001). Mean RFS was 96.1 in the low-risk group and 58.9 in the high-risk group (p < 0.001). RFS was predicted by the following factors; high risk group (OR=3.87; p = 0.041), LVSI (OR=2.54, p = 0.005), carcinosarcoma (OR=2.20, p = 0.021) and serous subtype (OR=1.91, p = 0.01). Logistic regression was used to evaluate risk factors for loco-regional and distant recurrence. Patients in the low-risk group were less likely to have distant recurrence (OR=0.08, p = 0.004). Similarly, negative LVSI and Grade 1 cancers were associated with decreased risk of distant recurrence (OR=0.34, p = 0.006 and OR=0.33, p = 0.007, respectively). There were no significant risk factors for loco-regional recurrence. CONCLUSIONS: The 2020 ESGO-ESTRO-ESP risk stratification provides accurate estimates of recurrence risk and survival. Those treated in line with current guidance have significantly better outcomes.

Laparoscopic and Robotic Surgery for Endometrial and Cervical Cancer.

Minimally invasive surgery (MIS) has many benefits, in the form of reduced postoperative morbidity, improved recovery and reduced inpatient stay. It is imperative, however, when new techniques are adopted, in the context of treating oncology patients, that the oncological efficacy and safety are established rigorously rather than assumed based on first principles. Here we have attempted to provide a comprehensive review of all the contentious and topical themes surrounding the use of MIS in the treatment of endometrial and cervix cancer following a thorough review of the literature. On the topic of endometrial cancer, we cover the role of laparoscopy in both early and advanced disease, together with the role and unique benefits of robotic surgery. The surgical challenge of patients with a raised body mass index and the frail and elderly are discussed and finally the role of sentinel lymph node assessment. For cervical cancer, the role of MIS for staging and primary treatment is covered, together with the interesting and highly specialist topics of fertility-sparing treatment, ovarian transposition and the live birth rate associated with this. We end with a discussion on the evidence surrounding the role of adjuvant hysterectomy following radical chemoradiation and pelvic exenteration for recurrent cervical cancer. MIS is the standard of care for endometrial cancer. The future of MIS for cervix cancer, however, remains uncertain. Current recommendations, based on the available evidence, are that the open approach should be considered the gold standard for the surgical management of early cervical cancer and that MIS should only be adopted in the context of research. Careful counselling of patients on the current evidence, discussing in detail the risks and benefits to enable them to make an informed choice, remains paramount.

Incisional site metastasis in a patient with cervical carcinoma: a case report and review of the literature.

Abdominal wall metastasis either incisional, drain, or port is rather rare in patients treated for cervical carcinoma. We present a case of a patient who underwent an abdominal radical hysterectomy for a moderately differentiated cervical adenocarcinoma stage Ib1 and presented an incisional site metastasis 36 months after her operation. Moreover, we performed a literature search for abdominal wall metastases after radical hysterectomy for cervical cancer, and we present a table of the relative case reports. After our literature search, we clarified that the median time of recurrence was 14 months (range 1.5 month to 45 months). Thirty-three out of 42, 8/42, and 1/42 were squamous, adeno-, and adenosquamous carcinomas, respectively. Wide excision was performed in 30/37 cases of which we have information regarding the treatment option, while 11/37 and 13/37 underwent radiotherapy and chemotherapy, respectively. The possible mechanism of such a metastasis as well as the treatment options is discussed.

Sister Mary Joseph's Nodule as a First Manifestation of Primary Peritoneal Cancer.

Sister Mary Joseph's nodule metastasis is a rather rare finding. The primary malignancy in women is usually ovarian, endometrial, gastric, or pancreatobiliary tree cancer. We present a case of an 87-year-old patient with Sister Mary Joseph's nodule metastasis caused by a primary peritoneal malignancy. Through a literature search, we also discuss the pathophysiology, diagnostic approach, management, and prognosis of such a condition.

The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer.

BACKGROUND: Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches. METHODS: Cytotoxicity testing (MTT) and cell cycle blockade assessed drug responsiveness. Methylation specific PCR and pyrosequencing identified sites of promoter methylation in p57(Kip2). siRNA to p57(Kip2) was used to look at the changes in apoptosis of carboplatin treated EOC cells. EOC tissues (20 cases) were assessed for mRNA levels of p57(Kip2). RESULTS: Carboplatin resistance was reversed using 5-aza-cytidine in vitro. Promoter methylation sites and preferential sensitivity to seliciclib were seen in PEO1CarbR cells. Silencing p57(Kip)2 decreased the apoptotic response to the effects of platinum but produced sensitisation to seliciclib. EOC biopsies indicated an association of high levels of p57(Kip2)mRNA with complete responses to chemotherapy and improved outcome. CONCLUSION: We conclude that p57(Kip2) is a candidate biomarker of platinum sensitivity/resistance in EOC and such cases may show preferential response to the cyclin-dependent kinase inhibitor seliciclib.

Liver resection for metastases arising from recurrent granulosa cell tumour of the ovary--a case series.

Ovarian granulosa cell tumours (GCT) occur rarely and represent 2-3% of all ovarian tumours. Regarded as tumours with low malignant potential and renowned for late recurrences, these tumours occasionally metastasize to the liver. We present our experience with three patients who underwent secondary cytoreductive surgery including liver resection for recurrence of the disease resulting in greatly improved quality of life and disease-free interval.

Use of surgical sealant in debulking surgery for advanced ovarian carcinoma--case report.

Haemostatic sealants are frequently used in gynaecological surgery. Several commercial products are available with similar mechanisms of action and chemical structure. We report the use of Floseal in a laparotomy for ovarian cancer to achieve haemostasis. This is the first reported case with the successful use of Floseal in gynaecological oncology.

Intraoperative haemostasis with new fibrin surgical sealant (Quixil) in gynaecological oncology.

We evaluated the effectiveness and safety of Quixil in gynaecological oncology with a prospective observational study over 11 months in a gynaecological oncology centre. Quixil was opportunistically used when conventional haemostatic techniques failed, in 35 laparotomies and four laparoscopies. A total of 26 operations were performed for malignant disease and 13 for benign indications. Demographic, intraoperative and postoperative data were collected. Haemostasis was accomplished within 5 min from sealant application. No hypersensitivity reactions were noted. Bowel recovery and postoperative pain were usual. In the laparotomy group, the mean hospital stay was 11 days and mean operating time, 164 min. In the laparoscopy group, the mean hospital stay was 3 days and mean operating time 165 min. In both groups, the incidence of complications and recurrence rates were in line with the expected population rates of these treated patients. We conclude that Quixil is an efficient, safe and effective haemostatic agent, which has a role to play in gynaecological surgery for benign and malignant disease.

Debulking hepatectomy for an unusual case of a grade 1 stage 1 granulosa cell tumour of the ovary with late metastases.

Granulosa cell tumours of the ovary are rare. They are considered low-grade malignant cancers and infrequently metastasise to the liver. We present our experience of a case with a grade 1, stage 1 granulosa cell tumour of the ovary that systemically recurred 15 years following surgical resection. The patient went on to have a debulking hepatic resection 21 years following initial surgery despite a 6-year-long palliative diagnosis.

Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma.

BACKGROUND: Primary debulking surgery (PDS) and paclitaxel-platinum chemotherapy remains the mainstay of treatment for advanced ovarian cancer. However, there is considerable morbidity and even mortality associated with this approach. The concept of primary chemotherapy followed by interval debulking surgery (IDS) has emerged for advanced stage disease with the aim of improving sensitivity to chemotherapy and improving survival. The purpose of our study was to examine the impact of IDS on clinical outcomes of patients considered unsuitable for PDS and compare them with outcomes of women that had conventional PDS followed by chemotherapy. PATIENTS AND METHODS: A non-randomised prospective cohort study of 35 patients who underwent IDS and 29 patients treated with PDS were included. All patients had Stage IIIC or IV disease. The IDS patients were considered unresectable based on an initial laparoscopy or preoperative computed tomography findings. All patients were treated by the same lead surgeons and received the same regimen of chemotherapy. RESULTS: The median intraoperative blood loss, the incidence of pelvic lymphadenectomies, the median hospital stay and the possibility of admission to the Intensive Care Unit were significantly less in the IDS group. Optimal cytoreduction was higher in the IDS compared to the PDS group, but did not reach statistical significance. CONCLUSIONS: IDS for advanced ovarian cancer may be associated with less morbidity compared to PDS and appears to require less use of hospital resources. If the ongoing randomised studies confirm that IDS does not adversely affect the long-term survival of these patients, morbidity related to ovarian cancer surgery may evolve as a crucial factor for choosing treatment options.

Prevalence of high-grade CIN following mild dyskaryotic smears in different age groups.

OBJECTIVE: The new guidelines of the British Society of Colposcopy and Cervical Pathology suggest that women should be offered colposcopy after only one mildly dyskaryotic smear. This is expected to generate increased workload for the colposcopy clinics, at least in the short term. The main objective of this study was to estimate the incidence of high-grade cervical intraepithelial neoplasia (CIN) in women with mildly dyskaryotic smears and investigate whether there is any variation in different age groups. The rationale was to determine whether we could reduce the burden on colposcopy services by prioritizing the mild dyskaryotic referrals by age, as we hypothesized that high-grade CIN is less frequent in younger women. METHODS: The study sample included all women who were referred for colposcopy with a cervical smear suggesting mild dyskaryosis (with or without koilocytosis) from April 2000 to March 2003. RESULTS: We studied 510 women. They were divided into three age groups (<20, 20-25 and >25 years). The overall prevalence of high-grade CIN (CIN II and III) was 28.7%. The positive predictive value of a mildly dyskaryotic smear for high-grade CIN was similar in all groups. CONCLUSIONS: Our results show that we are not in a position to prioritize our referrals by age group and reduce the initial pressure for colposcopies. We are also concerned that with the implementation of the new guidelines, a significant number of women <25 years will be carrying high-grade CIN for more than 5 years before they are first screened.