Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC.

Uterine leiomyosarcoma in asian patients: validation of the revised Federation of gynecology and obstetrics staging system and identification of prognostic classifiers.

BACKGROUND: In 2008, the Federation of Gynecology and Obstetrics (FIGO) revised their 1988 staging system for uterine leiomyosarcomas. In this article, we compare performance of the 2008 and 1988 FIGO systems. METHODS: Individual case data were manually culled. Staging was retrospectively assessed according to revised and 1998 FIGO criteria. Overall survival distribution was assessed by the Kaplan-Meier method. Harrell's concordance index was used to assess the discriminative ability of a fitted Cox model to predict overall survival. RESULTS: A total of 110 cases of uterine leiomyosarcomas were reviewed and data from 88 patients were analyzed. In all, 71% of cases were classified as stage I, 7% as stage II, 3% as stage III, and 19% as stage IV under the revised FIGO staging system. Nine patients (10.2%) were downstaged and none were upstaged. The revised FIGO system did not show a significant improvement over the 1988 FIGO system in the ability to discriminate the risk of death of patients between stages, with concordance indexes of 0.70 and 0.71, respectively. Most patients were classified as stage I with age, tumor grade, tumor size, and lymphovascular invasion as prognostic factors. CONCLUSION: The 2008 revised FIGO staging system for uterine leiomyosarcomas does not perform better than the 1988 system for uterine endometrial carcinomas. A better staging system is needed for these cases.

Concurrent chemoradiotherapy incorporating high-dose rate brachytherapy for locally advanced cervical carcinoma: survival outcomes, patterns of failure, and prognostic factors.

BACKGROUND: This is a retrospective study evaluating the survival outcomes, patterns of failure, and prognostic factors of chemoradiotherapy incorporating high-dose rate brachytherapy in the treatment of locally advanced cervical cancer. METHODS: A review of 120 consecutive patients with Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stages IB2 to IVA cervical cancer treated with concurrent cisplatin-based chemoradiotherapy between April 1999 and January 2005. Overall (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. RESULTS: The 5-year OS and DFS rates were, respectively, 65.0% (35.0% IB2, 65.7% IIA-B, 71.0% IIIA-B, and 40.0% IVA) and 57.3% (30.0% IB2, 58.2% IIA-B, 64.0% IIIA-B, and 40.0% IVA). Most patients had squamous cell carcinoma (89.2%) and belonged to FIGO stages IIB (40.8%) and IIIB (30.8%). All but 4 patients completed the planned radiotherapy regimen. There were 48 documented recurrences, of which 13 were locoregional only, 26 were distant only, and 9 were both sites. Five patients (4.2%) experienced late grade 3 to 4 gastrointestinal toxicity. On multivariate analysis, a preradiotherapy hemoglobin level of less than 10 g/dL and tumor size of 4 cm or greater or bulky on computed tomography were independently significant variables for OS, whereas a nadir hemoglobin level of less than 10 g/dL and presence of radiologically enlarged pelvic or paraaortic lymph nodes were independently significant variables for DFS. CONCLUSIONS: We conclude that this regimen is efficacious and feasible, but the safety profile about concurrent administration of high-dose rate brachytherapy and chemotherapy should be studied further. Finally, for cervical cancer patients selected for nonsurgical treatment, radiological assessment of tumor size and lymph node status can provide valuable prognostic information over and above FIGO staging alone.

Lessons learnt from two women with morbidly adherent placentas and a review of literature.

INTRODUCTION: Pathologically adherent placentas occur when there is a defect of the decidua basalis, typically arising from previous caesarean section, resulting in abnormally invasive implantation of the placenta. The depth of placental invasion varies from the superficial (accreta), to transmural and possibly beyond (percreta). CLINICAL PICTURE: We report on 2 cases, one treated "conservatively", the other with a caesarean hysterectomy, both of which led to a safe outcome for both mother and baby. CONCLUSIONS: Management relies on accurate early diagnosis with appropriate perioperative multidisciplinary planning to anticipate and avoid massive obstetric haemorrhage at delivery.

HER2 amplification and clinicopathological characteristics in a large Asian cohort of rare mucinous ovarian cancer.

Mucinous epithelial ovarian cancer has a poor prognosis in the advanced stages and responds poorly to conventional chemotherapy. We aim to elucidate the clinicopathological factors and incidence of HER2 expression of this cancer in a large Asian retrospective cohort from Singapore. Of a total of 133 cases, the median age at diagnosis was 48.3 years (range, 15.8-89.0 years), comparatively younger than western cohorts. Most were Chinese (71%), followed by Malays (16%), others (9.0%), and Indians (5%). 24% were noted to have a significant family history of malignancy of which breast and gastrointestinal cancers the most prominent. Majority of the patients (80%) had stage I disease at diagnosis. Information on HER2 status was available in 113 cases (85%). Of these, 31 cases (27.4%) were HER2+, higher than 18.8% reported in western population. HER2 positivity appeared to be lower among Chinese and higher among Malays patients (p = 0.052). With the current standard of care, there was no discernible impact of HER2 status on overall survival. (HR = 1.79; 95% CI, 0.66-4.85; p = 0.249). On the other hand, positive family history of cancer, presence of lymphovascular invasion, and ovarian surface involvements were significantly associated with inferior overall survival on univariate and continued to be statistically significant after adjustment for stage. While these clinical factors identify high risk patients, it is promising that the finding of a high incidence of HER2 in our Asian population may allow development of a HER2 targeted therapy to improve the management of mucinous ovarian cancers.

Caesarean section scar pregnancy: a case series at a single tertiary centre.

We present a case series of four patients with Caesarean scar pregnancies (CSPs) managed at our gynaecological unit between October 2008 and May 2009. Three patients were detected while asymptomatic, and were treated with elective intragestational sac methotrexate injections. The last patient had presented following complications from a termination of pregnancy for a CSP that was misdiagnosed as intrauterine. Following treatment, this patient and another developed arteriovenous malformation, which responded to bilateral uterine artery embolisations and gonadotropin releasing hormone (GnRH)-agonist treatment.