Evaluation of Clinical and Pathologic Risk Factors May Reduce the Rate of Multimodality Treatment of Early Cervical Cancer.

OBJECTIVE: To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. METHODS: This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. RESULTS: We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10 mm received RT, and 87% of patients with tumors depth of invasion >10 mm and lymph-vascular space invasion received RT. CONCLUSIONS: This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation.

Endometrial Cancer Surgery for Elderly Women--The Early Postoperative Period.

OBJECTIVE: The aim of this study was to examine the early postoperative period and assess whether elderly patients recuperate differently than do their younger counterparts after surgery for endometrial cancer. METHODS: This retrospective chart review comprised all women older than 75 years who underwent laparotomy for endometrial cancer staging at our center from January 2005 through December 2010 and a consecutive control group of women younger than 74 years. Parameters included demographic variables, surgical procedure/findings, postoperative morbidity, and pathology. RESULTS: Ninety patients older than 75 years and 88 younger patients were identified. The elderly patients had a statistically significant prolonged wait for bowel movement (5.9 vs 3.1 days, P = 0.002) and ambulated later (4.1 vs 1.1 days, P < 0.001). Postoperative hospital stay was similar in both groups (5.8 vs 4.2 days, P = 0.37). Early postoperative complications (fever, bowel, wound, eventration, cardiopulmonary) occurred at a similar rate in both groups. CONCLUSIONS: Elderly patients after laparotomy for endometrial cancer staging ambulated later and recovered bowel function later than did the younger patients. This did not translate into prolonged hospital stay or excessive complications. Earlier intervention with physical therapy and stool softeners can possibly close this gap in recovery.

Uterine papillary serous carcinoma pre-operatively diagnosed as endometrioid carcinoma: Is omentectomy necessary?

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is a relatively rare but aggressive uterine malignancy comprising approximately 10% of endometrial cancers. Many women pre-operatively misdiagnosed as having endometrioid carcinoma have ultimately UPSC on final pathology. These women receive inadequate surgical staging without omentectomy. AIM: To assess the value of omentectomy on disease-free interval and overall survival in women with UPSC who had an initial diagnosis of endometrioid carcinoma. METHODS: This retrospective study included all women treated for the final diagnosis of UPSC in our centre from January 2007 to December 2012. Data regarding patient demographics, staging procedures, histology results, adjuvant therapy and follow-up outcomes were recorded. RESULTS: Of the 52 women with a final diagnosis of UPSC, more than 45% had an initial diagnosis of endometrioid carcinoma. All women underwent hysterectomy and removal of the adnexa. Lymph node evaluation was performed in 75% of women. Omentectomy was performed in 30/52 women (58%). Of those, three women (10%) had omental involvement. Mean disease-free interval with omentectomy was 24.5 months versus 30.5 months without (P = 0.29). Mean overall survival was 33 months with an omentectomy and 29 months without (P = 0.32). Recurrence patterns did not differ between groups. CONCLUSION: Women diagnosed pre-operatively with endometrioid carcinoma and eventually found to have UPSC can expect no change in prognosis despite not having undertaken a full staging procedure. Repeat surgery for omentectomy is probably of no benefit.

The significance of paracardiac lymph-node enlargement in patients with newly diagnosed stage IIIC ovarian cancer.

OBJECTIVE: Extra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis. METHODS: A retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease-free interval (DFI) and overall survival (OS) were recorded. RESULTS: Thirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p=.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0 months, p=.0097) and overall survival was shorter (median 31.7 vs. 61.3 months, p=.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS. CONCLUSION: The presence of enlarged PCLN at presentation appears to be associated with poor prognosis in stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment.

Integration of PET/CT into the preoperative evaluation of patients with early cervical cancer does not decrease the proportion of patients with positive lymph nodes found after surgery.

PURPOSE: The aim of this study was to evaluate whether preoperative positron emission tomography/computed tomography (PET/CT) in patients with early-stage cervical carcinoma reduced the proportion of patients with metastatic lymph nodes identified after surgery. PATIENTS AND METHODS: This is a multicenter case-control study of 599 patients with early cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy at 1 of 10 gynecological oncology units in Israel. The patients were divided into 2 groups according to whether or not they underwent a preoperative PET/CT. The primary outcome was the proportion of patients with nodal involvement. The 2 groups were compared with regard to the clinical and histological variables. RESULTS: Of the 599 patients who underwent surgery, 180 (36%) had preoperative PET/CT study. There were no significant differences between the PET/CT and control groups with regard to clinical and histological risk factors. The proportion of patients with involved nodes was similar in the control and PET/CT groups (20.8% vs 19%; P = 0.73) as well as the proportion of patients receiving adjuvant radiotherapy/chemoradiation (58.3% vs 55.1%; P = 0.55). CONCLUSIONS: Preoperative PET/CT in patients with early cervical cancer does not reduce proportion of patients with metastatic nodal involvement and the employment of multimodality treatment. Prospective clinical trials comparing management based on PET/CT findings are warranted.

Clinical course of patients treated for advanced ovarian carcinoma without surgical intervention.

OBJECTIVE: To describe the clinical course and outcome of patients with non-surgically-treated advanced ovarian cancer attending a single institute. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed the medical charts of all patients with advanced epithelial ovarian cancer who underwent chemotherapy at a tertiary medical center between January 2005 and December 2010 but were never operated. Data on patient characteristics, disease course, and outcome were collected from patient files. Sixteen patients met the inclusion criteria. Eight (50%) were diagnosed with apparent FIGO stage IIIC disease, and 8 with stage IV. Five patients (31%) achieved a complete clinical response, and 11 (69%) achieved a partial response. Among the complete responders, the median disease-free interval was 8 months (range 7-11 months). In all of them, the disease recurred and second-line chemotherapy was administered. Of them, four (80%) achieved a second complete response. Partial responders had up to four lines of chemotherapy, with continued disease progression. The median overall survival of the whole group was 19.5 months, and of the complete responders, 28 months. CONCLUSIONS/SIGNIFICANCE: Most patients with advanced ovarian carcinoma who will not undergo surgery respond only partially to first-line chemotherapy. Having no surgery is associated with a short disease-free interval.

The use of Fluorouracil (5-FU) and leucovorin in women with heavily pretreated advanced ovarian carcinoma.

BACKGROUND: Women suffering from recurrent platinum-resistant ovarian carcinoma go through several lines of chemotherapy, but eventually fail all conventional chemotherapy options. After failing multiple other regimens, we offer patients fluorouracil (5-FU) in a weekly regimen with leucovorin. For those women who failed to react to multiple lines of treatment, 5-FU has been shown to be a reasonable option with reported response rates of 10% to 33%. We report our experience with 5-FU+leucovorin in this patient population. METHODS: This is a retrospective chart review of women treated for recurrent ovarian carcinoma between January 2003 and December 2009. Women with recurrent ovarian carcinoma who had been treated with at least 3 previous chemotherapy regimens and had received 5-FU were eligible for the study. 5-FU and leuocovorin are given at 600 mg/m weekly for 6 weeks of an 8-week cycle. Patient charts were reviewed for demographics and disease history relevant to the administration of 5-FU. Response was assessed clinically and by CA125 levels. RESULTS: Fifty-three patients matching inclusion criteria received 5-FU during the study period. Twenty-five percent of patients achieved a partial response and 17% stable disease for an overall response rate of 42%. A median of 4 weekly doses was administered (range, 1 to 26). The median survival of the whole cohort was 10 weeks after the last dose of 5-FU was administered. CONCLUSIONS: In this population of heavily pretreated patients, a significant response to 5-FU can be achieved. Unfortunately, the response is short lived and mostly partial.

Platinum-resistance in ovarian cancer cells is mediated by IL-6 secretion via the increased expression of its target cIAP-2.

Ovarian carcinoma patients are initially responsive to platinum-based therapy, but eventually become refractory to treatment due to the development of platinum chemoresistance. Elevated levels of interleukin-6 (IL-6) in the sera and ascites of these patients predict poor clinical outcome. Our goal was to analyze the interaction between cisplatin and cisplatin-resistant ovarian cancer cells, and to identify means of circumventing platinum resistance. We studied ovarian carcinoma cell lines and cells drawn from ovarian carcinoma patients. Gene array analyses were performed on ovarian carcinoma cells upon treatment with cisplatin, and the results were validated by ELISA and Western blotting (WB). Cytotoxicity assays were performed on anti-IL-6 Ab-, IL-6-, and cellular inhibitor of apoptosis 2 (cIAP-2) siRNA-treated cells, following cisplatin addition. Our results revealed a highly significant increase in IL-6 and cIAP-2 mRNA and protein levels upon treatment with cisplatin. WB analysis of cisplatin-treated cells exhibited decreased cIAP-2 expression level following anti-IL-6 Ab addition. Furthermore, IL-6 by itself, significantly increased cIAP-2 levels in ovarian carcinoma cells. Finally, cytotoxicity assays showed sensitization to cisplatin following the addition of IL-6 and cIAP-2 inhibitors. In conclusion, cisplatin treatment of ovarian carcinoma cells upregulates IL-6 and cIAP-2 levels while their inhibition significantly sensitizes them to cisplatin. Here, we present cIAP-2 as a novel inducer of platinum resistance in ovarian carcinoma cells, and suggest an axis beginning with an encounter between cisplatin and these cells, mediated sequentially by IL-6 and cIAP-2, resulting in cisplatin resistance. Consequently, we propose that combining IL-6/cIAP-2 inhibitors with cisplatin will provide new hope for ovarian carcinoma patients by improving the current treatment.

Burkitt's lymphoma of the ovary: case report and review of the literature.

Primary Burkitt's lymphoma of the ovary is extremely rare. We report the case of a 39-year-old woman who presented with a 1-month history complaints of night sweats, abdominal pain and dyspnea. Physical examination demonstrated pleural effusions, ascites and an abdominal mass. Imaging showed enlargement of both ovaries extending to the surrounding tissue. Frozen sections on explorative laparotomy suggested granulosa cell tumor of the ovary, and thus extensive debulking was carried out. The final pathological report was compatible with Burkitt's lymphoma. A systematic literature review revealed another 16 cases of ovarian Burkitt's lymphoma. Characteristics predictive for the diagnosis of Burkitt's lymphoma were: younger age, bilateral ovarian involvement, a rapidly progressive course and high LDH levels.

Laparoscopic adnexal transposition: novel surgical technique.

Treatment of some cancers diagnosed at an early stage with expectation of prolonged survival has permitted the consideration of salvaging the reproductive and hormonal function of premenopausal female patients. When radiation to the pelvic area is part of treatment, this will almost always result in ovarian failure. To protect the ovaries, an oophoropexy may be performed, which involves moving the ovaries away from the radiation field. This procedure may be performed via laparoscopy. Some women undergoing laparoscopic radical hysterectomy may also be candidates for laparoscopic transposition. Because failure rates are still reported to be high, we developed a novel technique to mobilize the adnexa, which we present in this paper and attached movie.After separating the adnexa from the uterus and developing the infundibulopelvic (IP) ligament, a retroperitoneal tunnel is developed from the pelvis to the transposition opening laterally. The adnexa are moved through this tunnel, avoiding torsion of the vessels, and are brought through the opening back into the peritoneum. The adnexa are now fixed securely to the posterolateral abdominal wall with nonabsorbable sutures.Several issues permit better results using this technique. The IP ligament remains retroperitoneal and itself is outside the field of radiation. There is no kinking of the ovarian blood supply on the peritoneal fold. The location of the transposition is way above the field of radiation, preventing scatter injury. Even if one or both of the sutures fail, placement of the ovary will not change because of the peritoneum it has been brought through. This and the final location of the IP ligament retroperitoneally may enforce the ovary to it outside of the radiation field and prevent possible migration of the ovary back to the pelvis. This technique has advantages, which may offer the ovaries a better chance to resume hormonal function.

Human papilloma vaccination to adolescents.

Infection with the Human Papilloma Virus (HPV) is extremely common worldwide. Persistent infection with high-risk strains can lead to genital tract premalignant and malignant lesions. Two licensed prophylactic HPV vaccines against cervical malignancy are commercially available. In naive patients both vaccines showed close to 100% efficacy against persistent infection and genital disease associated with the vaccine-targeted HPV types, as well as excellent safety over several years of study. Here we present a discussion on the appropriate age and gender in which to propose vaccination, and conclude that the most suitable recommendation is for vaccination of adolescents.

Should simple hysterectomy be added after chemo-radiation for stage IB2 and bulky IIA cervical carcinoma?

BACKGROUND AND AIMS: Management of bulky cervical tumours is controversial. We describe the addition of high dose rate brachytherapy with concomitant chemotherapy to an attenuated protocol of radiation followed by simple hysterectomy in the management of bulky cervical tumours. METHODS: Between January, 2003 and December, 2006, 23 patients diagnosed with bulky cervical tumours underwent a fixed chemo-radiation protocol followed by simple hysterectomy. Fractionated external beam pelvic radiation (4500 cGy) followed by two high-dose rate applications of brachytherapy (700 cGy - prescription dose to point A) was given with weekly concomitant cisplatin (35 mg/m(2)). Patients then underwent simple hysterectomy. Clinical information was prospectively collected and patient charts were then further reviewed. RESULTS: Twenty patients had stage IB2 and three bulky IIA. Median tumour size was 5 cm. Sixteen patients (70%) achieved a clinical complete and seven (30%) a clinical partial response. All patients had a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH BSO). On final pathology, 12 patients (52%) had a pathological complete response, whereas 11 patients (48%) had residual carcinoma in the cervix. Surgical margins were not involved. With a median follow-up time of 20 months (range 10-50 months), four patients (17.4%), all from the pathological partial response group, have suffered a pelvic recurrence, within 6 months from therapy; nineteen patients (82.6%) remain free of disease. CONCLUSIONS: This attenuated protocol of chemo-radiation using HDR brachytherapy followed by simple hysterectomy is a viable option in the treatment of bulky cervical carcinomas. The rate of residual cervical disease after chemo-radiation is substantial, but simple hysterectomy achieved negative surgical margins in all cases.

A new computer-aided diagnostic tool for non-invasive characterisation of malignant ovarian masses: results of a multicentre validation study.

OBJECTIVES: To prospectively assess an innovative computer-aided diagnostic technology that quantifies characteristic features of backscattered ultrasound and theoretically allows transvaginal sonography (TVS) to discriminate benign from malignant adnexal masses. METHODS: Women (n = 264) scheduled for surgical removal of at least one ovary in five centres were included. Preoperative three-dimensional (3D)-TVS was performed and the voxel data were analysed by the new technology. The findings at 3D-TVS, serum CA125 levels and the TVS-based diagnosis were compared with histology. Cancer was deemed present when invasive or borderline cancerous processes were observed histologically. RESULTS: Among 375 removed ovaries, 141 cancers (83 adenocarcinomas, 24 borderline, 16 cases of carcinomatosis, nine of metastases and nine others) and 234 non-cancerous ovaries (107 normal, 127 benign tumours) were histologically diagnosed. The new computer-aided technology correctly identified 138/141 malignant lesions and 206/234 non-malignant tissues (98% sensitivity, 88% specificity). There were no false-negative results among the 47 FIGO stage I/II ovarian lesions. Standard TVS and CA125 had sensitivities/specificities of 94%/66% and 89%/75%, respectively. Combining standard TVS and the new technology in parallel significantly improved TVS specificity from 66% to 92% (p < 0.0001). CONCLUSIONS: Computer-aided quantification of backscattered ultrasound is a highly sensitive for the diagnosis of malignant ovarian masses.

The counseling and management of young healthy BRCA mutation carriers.

Although more than 15 years have elapsed since the discovery of the BRCA1 and BRCA2 genes and the associated increased risk of breast and ovarian cancers in mutation carriers, our understanding of the syndrome is still evolving. With the accumulation of knowledge, more questions arise regarding the proper approach to mutation carriers diagnosed as having cancer. Moreover, the number of questions regarding the recommended management methods for healthy carriers and the potential risk-reducing measures is increasing constantly.In this review, we discuss these issues and summarize contemporary recommendations.

Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients.

BACKGROUND: Ovarian cancer, the leading cause of gynecologic cancer deaths, is usually diagnosed in advanced stages. Prognosis relates to stage at diagnosis and sensitivity to platinum based chemotherapy. We aimed to assess the expression of microRNAs in ovarian tumors and identify microRNA expression patterns that are associated with outcome, response to chemotherapy and survival. METHODS: Patients, who were surgically treated for ovarian cancer between January 2000 and December 2004 were identified. Patient charts were reviewed for clinicopathologic information, follow-up and survival. Total RNA was extracted from tumor samples and microRNA expression levels were measured by microarrays. Expression levels were compared between groups of samples and statistically analyzed. RESULTS: Fifty-seven patients were identified to fit study criteria. Of them, 19 patients had stage I disease at diagnosis, and 38 patients, stage III. All patients received platinum based chemotherapy as first line treatment. 18 microRNAs were differentially expressed (p<0.05) between stage I and stage III disease. Seven microRNAs were found to be significantly differentially expressed in tumors from platinum-sensitive vs. platinum-resistant patients (p<0.05). Five microRNAs were associated with significant differences (p<0.05) in survival or recurrence-free survival. High expression of hsa-mir-27a identified a sub-group of patients with very poor prognosis. CONCLUSIONS: We have found an array of tumor specific markers that are associated with response to platinum based first line chemotherapy. Expression of some of these miRNAs also correlated closely with prognosis. This approach can potentially be used to tailor chemotherapy and further management to specific patient needs.

Labial edema following treatment of condyloma acuminata with CO(2) laser in an adolescent: a case report and literature review.

PURPOSE: To describe a case of bilateral labial edema in an adolescent patient and review the literature on this rare occurrence. MATERIAL: A 16-year-old girl was treated for widespread genital condyloma acuminata with CO(2) laser under general anesthesia and local lidocaine injections. Severe bilateral labial edema occurred after 48 hours. RESULTS: Lidocaine and Latex dermal patch tests for delayed hypersensitivity were negative. The edema resolved following treatment with local ice packs and magnesium sulfate compresses for 2 weeks. CONCLUSION: This is the first description of severe bilateral labial edema after CO(2) laser treatment for condyloma acuminata. We suggest that transient local lymphatic obstruction was the reason for this complication. The literature on this rare occurrence is reviewed.

Granular cell tumor of the vulva: six new cases.

Granular cell tumors are rare neoplastic skin and soft tissue lesions: only 1-2% are malignant. Five to sixteen percent occur in the vulva. We present our experience with granular cell tumors of the vulva in six patients, all of whom had wide local excisions and were followed-up in our outpatient clinic for 3-171 months. One died of an unrelated cause. None of the others has evidence of the disease.