The impact of ultra-radical surgery in the management of patients with stage IIIC and IV epithelial ovarian, fallopian tube, and peritoneal cancer.

OBJECTIVE: The aim of this study is to estimate the percentage of patients with metastatic ovarian, fallopian tube, and primary peritoneal cancer requiring ultra-radical surgery to achieve cytoreduction to less than 1 cm (optimal) or no macroscopic residual disease (complete). METHODS: Perioperative data were collected prospectively on consecutive patients undergoing elective cytoreductive surgery for metastatic epithelial ovarian, fallopian tube, or primary peritoneal cancer at the Norfolk and Norwich University Hospital, a tertiary referral cancer centre in the United Kingdom from November 2012 to June 2016. RESULTS: Over a 42-month period, 135 consecutive patients underwent cytoreductive surgery for stage IIIC and IV ovarian, fallopian tube, or primary peritoneal cancer. The median age of the patients was 69 years. 47.4% of the patients underwent diaphragmatic peritonectomy and/or resection, 20% underwent splenectomy, 14.1% had excision of disease from porta hepatis and celiac axis, and 5.2% of the patients had gastrectomy. Cytoreduction to no macroscopic visible disease (complete) and to disease with greater tumour diameter of less than 1 cm (optimal) was achieved in 54.1 and 34.1% of the cases, respectively. Without incorporating surgical procedures in the upper abdomen ('ultra-radical'), the combined rate of complete and optimal cytoreduction would be only 33.3%. CONCLUSIONS: Up to 50.4% of the patients in this study required at least one surgical procedure classified as ultra-radical, emphasizing the importance of cytoreductive surgery in the upper abdomen in management of women with stage IIIC and IV ovarian, fallopian tube, and primary peritoneal cancer.

Investigating vaginal bleeding in postmenopausal women found to have an endometrial thickness of equal to or greater than 10 mm on ultrasonography.

PURPOSE: This aim of this study is to determine the risk of endometrial cancer in symptomatic postmenopausal women, when endometrial thickness on transvaginal ultrasonography is equal to or greater than 10 mm, and subsequent office-based endometrial sampling histology is negative. METHODS: This is a prospective cross-sectional study, performed in a gynaecological oncology centre in the United Kingdom between February 2008 and July 2012. All postmenopausal women presenting with vaginal bleeding were investigated using transvaginal ultrasonography. Women with endometrial thickness measurements equal to or greater than 10 mm and negative office-based endometrial biopsy underwent hysteroscopy and endometrial biopsies. RESULTS: Over a 52-month period, 4148 women were investigated for postmenopausal vaginal bleeding. 588 (14.2%) women were found to have endometrial thickness measurements of equal to or greater than 10 mm on transvaginal ultrasonography. 170 (28.9%) cases of endometrial cancer were diagnosed in this group: 149 (87.6%) of the cancer cases were diagnosed in the outpatient setting with a Pipelle® endometrial sampler, whilst 21 (12.4%) had a negative Pipelle® sample and were diagnosed with hysteroscopy. The group diagnosed with hysteroscopy had lower BMI (32.7 kg/m2 versus 39.7 kg/m2, p < 0.001) whilst the group diagnosed with Pipelle was more likely to have a history of hypertension and diabetes mellitus (p = 0.019 for both). The sensitivity of Pipelle was 87.65%. CONCLUSION: For women presenting with postmenopausal bleeding and where the endometrial thickness is equal to or greater than 10 mm and Pipelle sampling is negative, hysteroscopic evaluation with directed biopsy is strongly recommended.

Subserosal uterine injection of blue dye for the identification of the sentinel node in patients with endometrial cancer: a feasibility study.

OBJECTIVE: To define the detection rate, sensitivity, and negative predictive value (NPV) of the sentinel node technique in patients with endometrial cancer. METHODS: Patients with endometrial cancer after informed consent underwent subserosal injection of blue dye during hysterectomy in a tertiary gynae/oncology department between 2010 and 2014. The procedure was performed in all cases by the same team including two gynae/oncologist consultants and one trainee. All relevant perioperative clinicopathological characteristics of the population were recorded prospectively. The identified sentinel nodes were removed separately and a completion bilateral pelvic lymphadenectomy followed in all cases. Simple statistics were used to calculate the sensitivity and NPV of the method on per patient basis. RESULTS: Fifty-four patients were included in this study. At least one sentinel node was mapped in 46 patients yielding a detection rate of 85.2%. Bilateral detection of sentinel nodes was accomplished in only 31 patients (57.4%). The mean number of sentinel nodes was 2.6 per patient and the commonest site of identification was the external iliac artery and vein area (66%). Six patients (11%) had a positive lymph node, and in five of them, this was the sentinel one yielding a sensitivity of 83.3% and an NPV of 97.5%. The overall detection rate improved significantly after the first 15 cases; however, this was not the case for the bilateral detection rate. CONCLUSION: Our study is in accordance with previous studies of sentinel node in endometrial cancer and further demonstrates and enhances the confidence in the technique. In the current era of an ongoing debate on whether a systematic lymphadenectomy in patients with endometrial cancer is still necessary, we believe that the sentinel node is an acceptable alternative and should be applied routinely in tertiary centres following a strict algorithm.

Serum CA 125, CA 15-3, CEA, and CA 19-9: a prognostic factor for uterine carcinosarcomas?

PURPOSE: There is a controversy in the literature regarding the role and the prognostic significance of serum markers in uterine carcinosarcomas (CSs). We attempted to determine the utility of serum CA 125, CA 15-3, CA 19-9, and CEA as prognostic factors and disease follow-up in patients with CS of the uterus. METHODS: Thirty-seven patients with CS of the uterus were included in this study. Information regarding demographic, clinical, pathologic, tumor marker data (CA 125, CA 19-9, CA 15-3, and CEA both pre- and postoperatively) treatment and outcome information was obtained, followed by Statistical analysis. RESULTS: The mean follow-up period was 3.5 years. None of the study serum markers showed significant association with the outcome. Greater hazard was found for cases that staged from IIIA to IV compared to those staged from IA to IIB (HR = 4.75, 95 % CI: 1.99-11.3). Also, greater hazard was found for adenosquamous histological type compared to the other histological types. When multiple Cox regression analysis with stepwise approach was implied, it indicated stage as the only significant factor for the outcome. Elevated CA19-9 was more frequent in cases with heterologous sarcoma (p = 0.036). CONCLUSION: In this retrospective study, none of the preoperative serum tumor markers, neither epithelial component, histological type, nor grade showed a significant association with prognosis. This null finding may have significant implications in the common clinical practice; given that there is a controversy in the literature regarding the role and the significance of the prognostic significance of serum CEA, CA 125, CA 19-9, and CA 15-3.

Endometrial stromal sarcoma arising from endometriosis of the terminal ileum: the role of immunohistochemistry in the differential diagnosis.

Low-grade endometrial stromal sarcoma (LESS) is an uncommon uterine malignancy. Occasionally, it may develop in extrauterine endometriotic lesions and present morphological characteristics mimicking various neoplasms, making its diagnosis very challenging. We report a rare case of a 56-year-old woman presenting with a pelvic mass, initially presumed to be of ovarian origin. After surgical excision the diagnosis of a LESS arising from foci of endometriosis of the terminal ileum was established. Pelvic lymph nodes and omentum were also infiltrated. The patient received adjuvant chemotherapy and medroxyprogesterone; she is alive with no evidence of disease after a follow-up of 38 months. Immunohistochemical characteristics of the tumor are very important for the differential diagnosis of this rare neoplasm and include diffuse strong positivity for CD 10, estrogen receptor expression and CD 34 negativity.

Abdominal radical trachelectomy for treatment of deep infiltrating endometriosis of the cervix.

Surgical management of deep infiltrating endometriosis can be very challenging even for experienced gynecologists. Radical procedures like bowel resection and nephrectomy have been reported for treatment of the disease. Our aim is to report abdominal radical trachelectomy for treatment of deep infiltrating endometriosis of the cervix causing obstructive uropathy and diminished kidney function. We present a 38-year-old woman who was treated in our department for cervical endometriosis involving the vagina and left parametrium. Abdominal radical trachelectomy, insertion of a pig-tail catheter in the left ureter and end-to-end anastomosis of the uterus with the vagina was performed to remove the endometriotic lesion. Cooperation between gynecologists, urologists and nephrologists enabled fertility preservation as well as improvement of renal function. Deep infiltrating endometriosis is a complex disease that requires a multidisciplinary approach. Abdominal radical trachelectomy for cervical lesions seems feasible in this setting and helps preserve fertility.

Clinicopathologic insight of simultaneously detected primary endometrial and ovarian carcinomas.

PURPOSE: To evaluate the clinicopathologic features in patients with synchronous primary carcinomas of the ovary and endometrium. METHODS: Clinical information and pathologic details were collected and analyzed from 30 women with synchronous endometrial and ovarian cancers. RESULTS: Median age at diagnosis was 51 years. Abnormal uterine bleeding was the most common presenting symptom (50%). More than half (53%) of the patients were premenopausal and 37% never had a pregnancy. Stage I disease was observed in 90 (27/30) and 73% (22/30) of the patients with endometrial and ovarian cancer, respectively. Endometrioid type was the most frequently observed histology for synchronous endometrial and ovarian cancer (n = 18/30, 60%). All patients were surgically staged and adjuvant treatment was considered when required according to our protocols. The mean follow-up period was 6.6 years (SD = 3.0 years), and the cumulative event-free rate for 5 years was 84.2% (SE 7.3%). No significant differences in the survival rates were found according to the histological subtype (p = 0.513). Women with synchronous primary cancers of the endometrium and ovary were generally younger than those developing either one of the above mentioned adenocarcinomas. They appeared to have a favorable prognosis with an estimated overall survival of 84.2% in 5 years. CONCLUSIONS: A gynecologist should always keep in mind the possibility of double primary carcinomas of the endometrium and ovary in a young, premenopausal, nulliparous woman presenting with abnormal uterine bleeding and prompt the patient for further evaluation.

Non-blood medical care in gynecologic oncology: a review and update of blood conservation management schemes.

This review attempts to outline the alternative measures and interventions used in bloodless surgery in the field of gynecologic oncology and demonstrate their effectiveness. Nowadays, as increasingly more patients are expressing their fears concerning the potential risks accompanying allogenic transfusion of blood products, putting the theory of bloodless surgery into practice seems to gaining greater acceptance. An increasing number of institutions appear to be successfully adopting approaches that minimize blood usage for all patients treated for gynecologic malignancies. Preoperative, intraoperative and postoperative measures are required, such as optimization of red blood cell mass, adequate preoperative plan and invasive hemostatic procedures, assisting anesthetic techniques, individualization of anemia tolerance, autologous blood donation, normovolemic hemodilution, intraoperative cell salvage and pharmacologic agents for controlling blood loss. An individualised management plan of experienced personnel adopting a multidisciplinary team approach should be available to establish non-blood management strategies, and not only on demand of the patient, in the field of gynecologic oncology with the use of drugs, devices and surgical-medical techniques.

Detection and credibility of sentinel node in vulvar cancer: a single institutional study and short review of literature.

PURPOSE: To evaluate the detectability and credibility of sentinel lymph node (SLN) in vulvar cancer. METHODS: With Tc99m-nanocolloid and methylene blue, we identified SLNs in 34 patients. In 27 cases both tracers were used, while in 7 only blue dye was used. Completion lymphadenectomy was performed in all patients. SLNs and non-SLNs were sent separately for pathologic evaluation. RESULTS: At least one SLN was identified in all patients. Detection rate per groin was not significantly higher in the combined versus blue dye only technique (42/50 vs. 10/14, p = 0.43). 99m-Tc was not superior to blue dye in detecting SLN (42/50 vs. 50/64, p = 0.65). Midline location of the tumor did not seem to negatively affect the procedure. Four false negatives were observed in three patients with tumors >4 cm. Negative predictive value of SLN was 100% for grade I tumors ≤ 4 cm in patients ≤ 71 years. CONCLUSION: Tc-99m does not seem to be superior to methylene blue in the detection of SLN in vulvar cancer. Patients of younger age with small, well-differentiated tumors appear to be the most suitable candidates for lymphatic mapping.

Survival after secondary cytoreduction for recurrent ovarian cancer: which are the prognostic factors?

OBJECTIVE: Significant controversy exists concerning the factors affecting survival after secondary cytoreduction (SCR) in recurrent ovarian cancer. This study aims to identify factors independently associated with survival after SCR. METHODS: We retrospectively retrieved 39 patients with recurrent ovarian cancer. All patients had been initially treated with primary cytoreduction in our institution and received platinum- and paclitaxel-based chemotherapy postoperatively. Disease-free interval (DFI) had to be longer than 6 months. A variety of clinicopathological factors were recorded. Multivariable Cox regression was performed to examine the associations of parameters with survival. RESULTS: Median survival was equal to 24 months, the median DFI was 22 months, and complete SCR had been achieved in 19/39 patients (48.7%, 95% CI: 32.4-65.2%). Higher number of recurrence sites, clear-cell histological type, and more advanced FIGO stage were independently associated with shorter survival; longer DFI was associated with longer survival. Noticeably, complete SCR lost its significance at the multivariable model, although it was associated with longer survival at the univariable analysis. CONCLUSIONS: Four factors seem capable of independently modifying survival after SCR: number of recurrence sites, DFI, FIGO stage, and clear cell histology. The two latter factors might reflect aggressive clinicopathological features of the tumor with long-term effect.

Risk factors in women 40 years of age and younger with endometrial carcinoma.

OBJECTIVE: To identify and compare risk factors among endometrial cancer patients ≤40 years of age, postmenopausal women with the same malignancy and women ≤40 years without malignancy. DESIGN: Retrospective case-control study. SETTING: Athens University, department of obstetrics and gynecology of a tertiary hospital serving a mainly urban population. POPULATION: Endometrial cancer patients ≤40 years (study group, n = 40), postmenopausal women with the same malignancy (positive controls, n = 40) and women ≤40 (negative controls, n = 40) without endometrial cancer. METHODS: Clinical history, treatment and follow-up of patients were evaluated. Factors studied included age, histology, stage, grade, lymphovascular space involvement, body mass index (BMI), cytology, lymph node status, parity, smoking, family history, hypertension recurrence and survival. MAIN OUTCOME MEASURES: Differences in risk factors and characteristics. RESULTS: Nulliparity, smoking and hypertension were significantly related with endometrial cancer in the study group compared to positive controls (p = 0.001, p < 0.01 and p < 0.001, respectively). BMI >30 significantly characterized patients in the study group compared to negative controls (p = 0.006). Finally, irregular menstruation and family history of cancer were observed more often in the study group compared to both control groups. Stage, grade, myometrial invasion, lymphovascular space involvement and lymph node status were comparable between the study and positive control groups. CONCLUSION: Nulliparity, obesity, unstable menstruation, smoking and cancer in the family are strongly correlated with endometrial cancer risk in women ≤40 years.

Intraoperative consultation in ovarian pathology.

Ovarian specimens are very commonly submitted for intraoperative consultation (frozen section diagnosis) in order to confirm the presence of malignancy, to give the surgeon all the information for the histologic type of the tumor and finally determine the extent of surgery. In most cases, intraoperative consultation regarding ovarian masses accurately determines the type of malignancy. The pathologist and the gynecologist must be aware of the applications, indications and limitations of frozen section. Despite its limitations, frozen section diagnosis represents a sensitive and specific technique that can play a very important role in the management of ovarian disease.

Learning curve for gynecological oncologists in performing upper abdominal surgery.

BACKGROUND: To assess the learning curve for gynecological oncologists in performing upper abdominal surgery for management of patients with advanced epithelial ovarian cancer (EOC). METHODS: Patients undergoing cytoreductive surgery for stage IIIC and IV EOC that required at least one surgical procedure in the upper abdomen were divided in three numerically equal groups: group 1, 2 and 3 that underwent surgery between December 2012 and July 2014, August 2014 to March 2016 and April 2016 to March 2018 respectively. RESULTS: One hundred and twenty-six patients were included. The percentage of patients undergoing primary surgery for group 1, 2 and 3 was 47.6%, 50.0% and 73.8%, respectively (P=0.02). There was significant increase in the percentage of patients undergoing cholecystectomy (P=0.02), resection of disease from porta hepatis (P=0.008), liver capsulectomy (P<0.001), lesser omentectomy (P<0.001) and celiac trunk lymphadenectomy (P<0.001) in the group 3. There was no difference in the percentage of patients undergoing splenectomy, diaphragmatic peritonectomy/resection and gastrectomy. Complete cytoreduction was achieved in 54.8%, 35.7% and 64.3% of patients in group 1, 2 and 3 respectively (P=0.028). There was no significant difference in the occurrence of grade 3-5 complications. Presence of a liver surgeon was required in 9.1%, 5.6% and 0% of cases in group 1, 2 and 3 respectively. CONCLUSIONS: The results reflect the evolution of surgical skills in the upper abdomen through the increase in the percentage of patients undergoing primary surgery, with the surgical team undertaking more complex procedures, less involvement of other specialties and simultaneously achieving higher rates of complete cytoreduction.

Cholecystectomy as Part of Cytoreductive Surgery for Advanced Ovarian Cancer: Perioperative Outcomes.

BACKGROUND/AIM: To assess the perioperative outcomes of cholecystectomy in cytoreductive procedures for epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Prospectively collected perioperative data of patients that underwent cytoreduction for advanced EOC, between 2014 and 2018, were analysed. Patients were divided in two groups on the basis of whether cholecystectomy was performed. RESULTS: A total of 144 patients with stage IIIC/IV EOC were included. Cholecystectomy was performed in 22 (15.3%) patients. Those who underwent cholecystectomy more likely required diaphragmatic peritonectomy, splenectomy, lesser omentectomy, excision of disease from the porta hepatis and liver's capsule (p<0.001). There was no difference in the cytoreductive outcomes (complete or optimal) and the rate of grade 3-5 complications between the two groups (p=0.10 & p=0.06, respectively). No direct complications related to cholecystectomy were observed. CONCLUSION: A significant percentage of patients with advanced EOC require cholecystectomy. Gynecologic oncologists should embrace the opportunity to develop advanced surgical skills including cholecystectomy.

The Role of Magnetic Resonance Imaging in the Pre-operative Evaluation of Women Diagnosed With Atypical Endometrial Hyperplasia.

BACKGROUND/AIM: To evaluate the role of MRI in patients with atypical endometrial hyperplasia (AEH) and incorporate MRI findings in predictive models estimating the risk of co-existent endometrial cancer (EC). PATIENTS AND METHODS: Data from 189 women diagnosed with AEH and had MRI scan prior to operation, over nine years, were retrospectively collected. RESULTS: Histology showed EC in 51 (27%) cases. Presence of myometrial invasion on MRI was more commonly detected in patients with EC compared to those with benign pathology (37.3% versus 10.9%, p<0.001). The sensitivity and specificity of MRI in identifying cancer were 37% and 89%, respectively. Age, menopausal status and presence of invasion on MRI were the best predictors for the presence of malignancy. CONCLUSION: Myometrial invasion on MRI is associated with increased risk of EC in women with AEH. Its accuracy in detecting malignancy improves when combined with clinical parameters. This could be of value for conservative-management candidates.

A pilot study of robotic uterine and vaginal vault manipulation: the ViKY Uterine Positioner™.

A pilot study of uterine and vaginal vault manipulation using a new surgical robot-The ViKY Uterine Positioner™--enrolled 36 cases comprising 31 hysterectomies, two myomectomies, two sacrocolpopexies and one excision of severe endometriosis performed between July 2010 and February 2012 in a tertiary referral District General Hospital in the UK. Mean age was 48 years, body mass index 25.7 kg/m(2) and uterine weight 231 g. Nine cases were foot-controlled and 27 by Bluetooth voice control. ViKY UP™ docking time once V-Care™ was inserted was 4.3 min. The device caused no peri-operative complications. Adequate mobilization, visualization and range of movement was possible in 81, 78 and 61 % of cases, respectively, with most of the problems arising in cases with uterine weight >350 g. ViKY UP™ was detached and an assistant was required in three cases, whilst V-Care™ came out of the uterus in one case. The learning curve led to various adjustments including optimizing patient position, increasing the device range of movement and adjusting device sensitivity. As a result, problems were minimized in our last nine cases. Adding robotic uterine manipulation is the obvious next step to give the gynecologist the ultimate control and stability of the uterus during robotic-assisted surgery without having to lift their head from the viewfinder or rely on a remotely situated perineal assistant. ViKY UP™ is the first device to deliver this. Pilot study results did not demonstrate compromised safety, and the device appears to be effective and easy to learn.

Merkel cell carcinoma in pelvic lymph nodes after surgical staging for endometrial cancer: A case report and review of the literature.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine tumor of the skin. PRESENTATION OF CASE: We present a case of MCC in pelvic lymph nodes, revealed after surgical staging for endometrial cancer. A 54-year-old Caucasian woman presented to our department with a three-month history of postmenopausal bleeding. After proper preoperative evaluation, the patient underwent total abdominal hysterectomy, bilateral salpingo-ophorectomy and pelvic lymph node dissection. The pathology report confirmed the presence of a small, grade I, endometrioid adenocarcinoma and MCC in the pelvic lymph nodes. Primary site of the disease could not been retrieved. The tumor board decided adjuvant chemotherapy (carboplatin and etoposide) and close follow-up every 2months. Our patient is alive with no evidence of disease 12months after surgery. DISCUSSION: It is noteworthy that 19% of the patients with MCC had lymph node metastasis with no apparent primary lesion. The mechanism of this regression remains unclear, although a higher apoptotic activity has been observed in MCC than other skin tumors. In addition, other co-malignancies have also been linked to MCC patients. The explanation for the frequent occurrence of other primary neoplasms in patients with MCC is still unclear. However, a reasonable cause could be an altered genetic profile or an immuno-compromised situation in these patients. CONCLUSION: Further analytic investigations are needed to clarify the role of various factors in the spontaneous regression or not of this neuroendocrine tumor as well as in the simultaneous genesis of other primary carcinomas.

Impact of placenta previa on obstetric outcome.

OBJECTIVE: To determine the maternal and perinatal outcome for different types of placenta previa (PP). METHODS: A retrospective review of 132 singleton pregnancies with PP. Outcome measures, including the incidence of obstetric hysterectomy, the neonatal Apgar score, and the neonatal weight, were evaluated by logistic regression analysis. RESULTS: The incidence of PP was 1.0%. Of the women with PP, 51.5% had complete PP, 20.5% had incomplete PP, 5.3% had marginal PP, and 22.7% had a low-lying placenta. Most (93.9%) women were delivered by cesarean delivery. In total, 19.7% women underwent obstetric hysterectomy; of these, 92.3% had complete PP. Mothers with 2 or more previous cesarean deliveries had an increased risk for obstetric hysterectomy (P<0.01). The gestational age at delivery was a significant linear predictor of the 5-minute Apgar score. Mothers with incomplete PP delivered neonates with lower Apgar scores than did mothers with complete PP. CONCLUSION: A history of multiple cesarean deliveries increased the risk for obstetric hysterectomy in women with PP. The type of PP had no effect on maternal and neonatal outcome, with exception of the fact that neonates in the incomplete PP group had lower Apgar scores than neonates in the complete PP group.

Isosexual pseudoprecocious puberty in a 2(1/2)-year-old girl presenting with intense skin pigmentation.

BACKGROUND: Ovarian follicular cyst producing estradiol is a rare cause of isosexual pseudoprecocious puberty. Intense pigmentation of breast papillae, areolae, and labia minora is also rarely reported in the literature. CASE: We describe a 2(1/2) year old girl presenting with signs of precocious puberty and advanced bone age due to a large follicular cyst. Estradiol and Dehydro-epiandrosterone sulfate (DHEAS) levels were remarkably elevated. Hyperpigmentation was also noted. Salpingoophorectomy resulted in regression of precocity and depigmentation, but DHEAS serum levels remained elevated. SUMMARY AND CONCLUSION: High levels of circulating estradiol due to an ovarian follicle can induce precocious puberty and pigmentation of the skin which regresses after surgical removal of the cyst. Elevated DHEAS levels may be the initiating event causing the formation of the large follicular cyst.