Comparing Surgical and Oncological Outcomes between Indocyanine Green (ICG) Sentinel Lymph Node Mapping with Routine Lymphadenectomy in the Surgical Staging of Early-Stage Endometrioid Endometrial Cancer.

Methods: A retrospective single-centre cohort study of patients with early-stage endometrioid endometrial cancer undergoing staging surgery (total hysterectomy, bilateral salpingo-oophorectomy with/without pelvic lymph node, and/or para-aortic lymph node dissection (PLND)) with either SLN mapping or routine lymphadenectomy between July 2017 and December 2018. Results: 203 cases with clinical and radiological International Federation of Gynaecology and Obstetrics (FIGO) stage I endometrioid endometrial cancer were included, out of which 109 cases underwent SLN mapping and 94 cases complete lymphadenectomy. Compared to the PLND group, the SLN group had shorter operative time (129 vs. 162 minutes), less blood loss (100 vs. 300 ml), and decreased length of postoperative hospital stay (3 vs. 4 days) (p < 0.001). The lymph node metastases detection rate was 4.6% and 7.4% for the SLN and PLND groups, respectively (p = 0.389). With a median follow-up of 14 months for the SLN and 15 months for the PLND group, the disease-free (DFS) and overall survival (OS) were comparable for both at 13 months (p = 0.538 and p = 0.333, respectively). Conclusion: SLN mapping has been shown to be an acceptable alternative to routine lymphadenectomy in the surgical staging of early-stage endometrial cancer in our centre, with a comparable lymph node metastases detection rate, DFS and OS, and reduction in operative morbidity. Our results with SLN mapping reproduce comparable outcomes to those reported in the literature.

The Characteristics of Real-time Transvaginal Sono-elastography in Endometrial Cancer.

Background: Endometrial cancer is the most common gynecological cancer among women in developed countries. Sono-elastography is an extended ultrasonographic technique that has been shown to be useful in a wide range of conditions ranging from breast, prostate, and thyroid nodules to chronic liver disease and musculoskeletal conditions. The aim of this study is to compare the sonoelastographic features of endometrial malignancy and normal endometrium. Methods: This case-control observational study was conducted at a single institution. Participants with histologically proven endometrial cancer according to the results from microcurettage or hysteroscopic biopsy and scheduled for total hysterectomy were included as cases, while asymptomatic women scheduled for routine screening ultrasound examination were recruited as controls. Both cases and controls underwent conventional B-mode transvaginal ultrasonography and strain elastography. Demographic, ultrasonographic, and histopathologic findings were analyzed. Results: A total of 29 endometrial cancer patients (cases) and 28 normal females (controls) were included in the analysis. There was no significant difference in the mean age between the two groups, but the mean body weight was significantly higher in the case group (P < 0.001). The strain ratio and elastographic thickness ratio of the endometrium were statistically significantly different between the case and the control group (P ≤ 0.05) due to increased endometrial stiffness in cancer patients as compared to the normal group. Conclusion: Our results suggest that endometrial cancer can result in increased stiffness that is detectable by transvaginal sonoelastography. Sonoelastography may serve as an adjunct to conventional ultrasound in evaluating the endometrium of women with abnormal uterine bleeding.

Benign metastasising leiomyoma: a rare disease and a diagnostic challenge.

Benign metastasising leiomyoma (BML) is a rare tumour characterised by extrauterine metastasis of histologically benign leiomyomas. We present a case of BML with pulmonary involvement. A 49-year-old woman presented with large pelviabdominal masses complicated by gross abdominal and lower limb swelling 6 years following open myomectomy. Preoperative CT imaging showed pelviabdominal masses and multiple bilateral pulmonary nodules. Initial impression was that of a stage 4 gynaecological malignancy. Palliative total hysterectomy bilateral salpingo-oophorectomy was performed. Histopathology confirmed benign uterine leiomyomas. Biopsy of pulmonary nodules showed benign leiomyomas, strongly positive for oestrogen and progesterone receptors. Definitive diagnosis of BML was made on histopathology and immunohistochemistry. The patient declined letrozole treatment as she had just undergone bilateral oophorectomy. She opted for conservative monitoring of her lung nodules. CT imaging 7 months postsurgery showed disease regression. She will require long-term surveillance scans to detect disease progression.

Labor Complicated by Cervical Stenosis Following a Laser Cone Biopsy.

A 34-year-old lady, with three previous spontaneous vaginal deliveries, presented in labor at 37 + 0 weeks' gestation. Following the birth of her third child, she underwent a laser cone biopsy for cervical intraepithelial neoplasia (CIN) 3. Despite sustained regular contractions and augmentation with Syntocinon, progressive cervical dilatation beyond 1 cm failed to occur in this multiparous lady. A delayed diagnosis of cervical stenosis was made. She eventually underwent a cesarean section where her internal cervical os was found to be thin and fibrotic. This case describes an uncommon occurrence of cervical stenosis presenting in labor and seeks to increase awareness of this condition so as to allow preemptive counselling of similar patients, early recognition in a labor with poor progress and a swift, better-informed decision to deliver via an emergency cesarean section. We review the existing literature on cervical stenosis following cervical conization and analyze the various definitions available.

Biallelic NF1 inactivation in high grade serous ovarian cancers from patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a multisystem disorder caused by germline heterozygous NF1 loss-of-function variants. The NF1 gene encodes neurofibromin, a RAS GTPase-activating protein, which functions by down-regulating RAS/RAF/MAPK-signalling pathways. Somatic NF1 aberrations frequently occur in sporadic ovarian cancer (OC), but the incidence of OC in NF1 patients is rare. Here we report the germline and somatic findings for two unrelated patients with NF1 and high-grade serous OC. Germline testing revealed a heterozygous NF1 pathogenic variant in each patient, c.7096_7101del (p.Asn2366_Phe2367del) and c.964delA (p.Ile322Leufs*54), respectively. No germline variants in well-established OC predisposition genes were detected, including BRCA1 and BRCA2. Tumor loss-of-heterozygosity analysis demonstrated loss of the wild type NF1 allele for both patients. Biallelic NF1 inactivation occurs as part of OC pathogenesis in NF1 patients. Although the penetrance of NF1-associated OC is insufficient to warrant risk-reducing interventions, our findings highlight the potential for therapies targeting the RAS/RAF/MAPK-signalling pathway for these cases.

A Cervical Smear Scare due to Monsel's Solution: A Case Report.

Monsel's solution has been in use since the end of the 19th century for its valuable property of creating hemostasis in minor disruptions of the epithelium. Its styptic effect was first described by Leon Monsel, a pharmacist in the French army, in a letter dated on October 13, 1852. Containing ferric subsulphate, it is used as a topical hemostatic agent in minor procedures such as biopsies in gynecology, proctology, dermatology, otorhinolaryngology and odontology. A 28-year-old nulliparous woman, with a known history of adenomyosis, had presented for sudden heavy intermenstrual vaginal bleeding. Examination revealed a bleeding Nabothian cyst. Monsel's solution application helped stop the bleeding. She returned 3 days later with persistent heavy vaginal bleeding. Examination showed active oozing from the Nabothian cyst. A cervical smear and a human papillomavirus (HPV) swab were taken, and vaginal packing was inserted. The cervical smear result was reported as atypical cells, suspicious for malignancy. Colposcopy performed showed a grade 2 acetowhite lesion, suspicious for cervical intraepithelial neoplasia (CIN) III/microinvasive disease. However, punch biopsies of the cervix revealed only CIN I/koilocytosis. The patient was counselled and subsequently underwent a laser cone biopsy, which showed CIN I with clear margins. The discrepant results between the cervical smear and the cone biopsy prompted a review of the cervical smear and cervical histology; and a relook at the chronology of events. The cytological features observed in the initial cervical smear could be explained by the interference from the Monsel's solution, which was applied just 3 days before the cervical smear. In cases where Monsel's solution has been used for hemostasis, it is best to delay taking a cervical smear or a biopsy for at least 3 weeks as the histologic effect of Monsel's solution may persist for up to that duration of time in tissues.

Surgical and Oncological Outcome of Total Laparoscopic Radical Hysterectomy versus Radical Abdominal Hysterectomy in Early Cervical Cancer in Singapore.

INTRODUCTION: The Wertheim's radical abdominal hysterectomy (RAH) has been the traditional surgical approach for operable Stage IB cervical cancer in Singapore whereas total laparoscopic radical hysterectomy (TLRH) was introduced only in 2009. In this study, we aimed to compare the long-term surgical outcome between the two routes of surgery in our center. METHODS: This is a prospective study performed in a single large tertiary institution in Singapore. Inclusion criteria included surgically fit patients with early cervical cancer and no radiological evidence of regional or distant metastases. RESULTS: From November 2009 to December 2014, 51 TLRHs and 85 RAHs were performed. Median blood loss in the TLRH group was significantly lower than in the RAH group (300 vs. 500 mL; P = 0.002) as was median hospital stay (5 vs. 6 days; P = 0.001). Operative time was significantly higher in the TLRH group (262 vs. 228 min; P < 0.001). There was no significant difference in bladder recovery. Intraoperative complications were encountered in 2 (3.9%) TLRH patients and 1 (1.2%) RAH patient. Postoperative complications occurred in 3 (5.9%) TLRH patients and 8 (9.4%) RAH patients. With a median follow-up of 117 (range 1.6-314.6) weeks in the TLRH group and 143.3 (range 0.4-304.7) weeks in the RAH group, 9 (17.6%) TLRH patients and 7 (8.2%) RAH patients had recurrence. There was no significant difference in the overall 3-year survival between the TLRH group and the RAH group for tumor size ≤2 cm (100.0% vs. 97.0%; P = 0.37). However, there was a trend toward lower survival for the TLRH group for tumor size >2 cm (61.9% vs. 85.4%; P = 0.06). CONCLUSION: The results of our study suggest that with appropriate patient selection, TLRH can be a safe and effective procedure for the management of early cervical cancer in Singapore, especially in women with small tumors ≤2 cm but should be used with caution in women with larger tumors.

Comparison of outcomes following laparoscopic and open hysterectomy with pelvic lymphadenectomy for early stage endometrial carcinoma.

INTRODUCTION: Endometrial carcinoma is the most common gynaecological malignancy. Studies have shown that laparoscopic total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection was advantageous compared to laparotomy in reducing length of stay and intraoperative blood loss. However, these studies had a predominantly Caucasian population. A comparison study was conducted among the Singapore population to investigate the differences in oncological and surgical outcomes between these two methods. METHODS: A retrospective, single-centre cohort study was conducted. Records of hospitalised patients with Stage 1 endometrioid carcinoma from 2008 to 2014 were extracted for review. Demographic data and study-specific parameters, including operative time, length of hospitalisation, intraoperative and postoperative complications, pain scores, final staging and recurrence rates, were compared between the two groups. RESULTS: 475 endometrioid carcinoma patients were admitted for surgical staging, among whom 374 fulfilled our inclusion criteria. Out of these patients, 229 underwent laparotomy and 145 underwent laparoscopy. The race, parity and body mass index of both groups were comparable. Patients who underwent laparoscopic surgery reported reduced pain score within two hours postoperatively (p = 0.007) and at Postoperative Days 1, 2 and 3 (p < 0.001). Laparoscopic surgery also illustrated better outcomes such as reduced length of stay (p < 0.001) and reduced intraoperative blood loss (p < 0.001). The operative time, recurrence rate and disease-free intervals were comparable between both groups. CONCLUSION: Laparoscopy offered similar oncological outcomes with superior surgical outcomes compared to laparotomy. It provides a suitable alternative in the surgical staging of endometrioid carcinoma.

Mutation spectrum of POLE and POLD1 mutations in South East Asian women presenting with grade 3 endometrioid endometrial carcinomas.

OBJECTIVE: Somatic POLE mutations have been found in a subset of endometrioid ECs particularly in FIGO grade 3 tumors while POLD1 mutations are reportedly rare in ECs. While it has been suggested that POLE mutation confers good prognosis, the data remains conflicting. Our study aims to determine the mutation spectrum of somatic and germline POLE and POLD1 gene mutations in South East Asian (SEA) women with FIGO grade 3 endometrioid ECs. METHODS: Forty-seven patients diagnosed with FIGO grade 3 endometrioid EC, diagnosed between 2009 and 2013 were included. Next generation sequencing (NGS) using formalin fixed embedded (FFPE) tissue was utilized to sequence tumor and matched normal tissue. Tumors were also assessed for other clinicopathologic and microsatellite status phenotype. Survival curves for pathogenic somatic POLE mutated and wild-type tumors were estimated by Kaplan-Meier method. RESULTS: Pathogenic POLE (somatic or germline) and POLD1 (germline) mutations were detected in 29.7% (14/47) and 4.3% (2/47) patients, respectively. Three pathogenic germline mutations; one POLE and two POLD1 mutations were novel. Pathogenic germline and somatic POLE and POLD1 mutations were associated with 100% recurrence free survival. In contrast, among the wild-type POLE and POLD1 patients, 25% (8/32) had recurrence with 15.6% (5/32) subsequently dying of the disease. Somatic POLE-mutated tumors were more commonly associated with microsatellite stable (MSS) ECs (83% vs 49%; p=0.04) and peritumoral lymphocytic infiltration (75% vs 42%; p=0.05). All tumors with tumoral infiltrating lymphocytes exhibited peritumoral lymphocytic infiltrate but not vice versa. CONCLUSION: Mutations in POLE and POLD1 in SEA women with grade 3 endometrioid ECs are associated with improved recurrence free survival. Notably, germline mutations in either POLE/POLD1 were seen in 8.5% of patients who will require appropriate genetic counseling regarding risk of developing colorectal carcinoma and on the need for additional surveillance for colonic changes. MSS and peritumoral lymphocytic infiltration may be useful histological features for distinguishing POLE mutated grade 3 endometrioid ECs.