BACKGROUND:Measurement of autoantibodies (AAbs) to tumor associated antigens has been proposed to aid in the early detection of ovarian cancer with high specificity. Here we describe a multiplex approach to evaluate selected peptide epitopes of p53 protein, and propose a novel approach to increase specificity and potentially sensitivity for discrimination between healthy women and women with cancerous masses. MATERIALS AND METHODS:20-mer overlapping peptide epitopes of p53, generated by mapping the complete p53 sequence, were evaluated in a multiplex immunoassay for their detection of serum AAbs in patients with ovarian cancer, using Luminex technology. AAbs to the selected peptides and to p53 full length protein were then detected in a multiplex immunoassay evaluating 359 sera from healthy women and 285 sera from patients with early and late stage ovarian cancer. CA-125 levels were measured in all p53 AAb-positive sera. RESULTS:We considered the AAb results together to identify sera where both the full length protein and at least one selected peptide epitope were positive and chose cutoffs that reduced false positives from these AAbs to 1/359 samples, improving specificity. Using this combined approach, we could identify 7 AAb-positive patients that were negative for CA-125 (concentrations below 35 IU/mL); this represents 26% of the p53 positive patients in the total population. CONCLUSION:By detecting p53 AAbs in CA-125-negative sera, we demonstrated that combining measurement of AAbs to the full length p53 protein and one or more selected epitopes can potentially improve sensitivity and specificity for ovarian cancer detection.
OBJECTIVE:The aim of this study was to clarify the clinical, laboratory, and imaging findings of ovarian cancer in association with endometriotic cysts by detailed comparison of the findings of benign and malignant tumors.METHODS AND MATERIALS:This was a retrospective study of 138 women who had an operation for ovarian tumors at the Department of Obstetrics and Gynecology of Kochi Health Sciences Center between September 1, 2011, and July 30, 2015. The ovarian tumors were divided into two groups: the benign group (endometriotic cysts) and the malignant group (ovarian cancer in association with endometriotic cysts).RESULTS:Of the 138 patients, 28 had malignant disease, and 110 had benign endometriotic cysts. Patients in the malignant group were significantly older than patients in the benign group. The mean maximum tumor diameter was also significantly larger for the malignant tumors. Unilocular-solid and multilocular-solid type tumors were present in 25.0% and 75.0% of malignant tumors, and in 9.1% and 19.1% of benign tumors, respectively. The mean maximum solid component diameter and height were significantly larger in the malignant tumors than in the benign tumors. The solid components were present on the abdominal side of the cyst wall in 12.5% of benign tumors and in 51.9% of malignant tumors.CONCLUSION:In elderly patients, the presence of large solid components in large endometriotic cysts, especially the abdominal side of the cyst wall, might suggest malignancy.MICRO ABSTRACT:The aim of this study was to clarify the findings of ovarian cancer in association with endometriotic cysts by detailed comparison of the findings of benign and malignant tumors. The presence of solid components in large endometriotic cysts, especially the abdominal side of the cyst wall, might suggest malignancy.
The Journal Clinical Ovarian and Other Gynecologic Cancer has now expired and as a result, this article has transferred to Clinical Breast Cancer and can be found via http://dx.doi.org/10.1016/j.clbc.2017.09.009. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
Concurrent chemoradiation causes toxicities such as enteritis, hematologic toxicities which may lead to treatment interruptions, and therefore inferior outcomes. Adequate supportive care is very important to complete the scheduled protocol. Most of our patients are from rural background with a heterogeneous social background (nutrition and social support). There is paucity of literature to evaluate the tolerance of this intense treatment in these groups of patients, and hence, this study was undertaken. In this observational study, 30 rural women having carcinoma cervix treated with concurrent chemoradiation between January and July 2013 were reviewed retrospectively. They were assessed weekly for dyselectrolytemia, enteritis, and hematologic toxicity using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. Treatment gaps along with reasons were recorded and correlated. Median age of patients was 54 years. Of the patients, 43.3% were International Federation of Gynecology and Obstetrics stage II and 46.7% stage III. Grade 3 enteritis was seen in 7 of 30 patients (23.3%). None (0%) had grade 3 or higher hematologic toxicity. Dyselectrolytemia–hyponatremia (46.66%), hypokalemia (26.66%), hypocalcemia (6.66%), and hypomagnesemia (10%) were noted. Two of thirty patients (6.66%) received the planned 5 cycles, cisplatin 40 mg/m2 weekly. There were treatment interruptions in radiation in 6 (20%) and treatment delays in chemotherapy in 10 (33.33%) patients. Concurrent chemoradiation for patients from rural areas is associated with higher acute toxicities. Regular monitoring for enteritis and dyselectrolytemias and timely intervention can help improve compliance and decrease treatment interruptions and thereby achieve the optimum treatment outcome.
To identify the impact of weight, table surface, and table type on slipping in a simulation of minimally invasive gynecologic surgery. A mannequin was placed into increasing Trendelenburg until a slip was observed; the table angle at the time of the event was measured (slip angle). The influence of mannequin position (supine vs. lithotomy), weight, table surface, and model was evaluated. A linear regression model was used to analyze the data. Mannequin weight, bed surface, and bed type all significantly impacted the slip angles. In general, higher mannequin weights tolerated significantly more Trendelenburg before slipping in the supine position but less in lithotomy compared to lower weights. In lithotomy, the disposable sheet and gelpad performed worse than the bean bag, egg crate foam, and bedsheet. There was no difference in slipping because of bed surface in the supine model. The Skytron operating table performed significantly better than the Steris operating table when tested with the bedsheet. Operative position, patient weight, and bed surface together influence the slipping propensity. In lithotomy, heavier patients were more prone to slipping while the inverse was true in supine. The egg crate foam, bean bag, and bedsheet were the best antislip surfaces. Operating room table choice can mitigate slippage.
The optimal therapy to treat relapsed, platinum-sensitive ovarian cancer remains elusive. Because most patients receive initial therapy with paclitaxel and platinum, there is a lack of cross-reaction of docetaxel and paclitaxel and retreatment with platinum is standard of care; we evaluated the toxicity and efficacy of docetaxel and carboplatin as salvage therapy for relapsed, platinum-sensitive ovarian cancer. This phase II study treated the first-relapsed, platinum-sensitive, stage III/IV ovarian cancer patients with docetaxel 80 mg/m2 intravenous (IV) over 60 minutes followed by carboplatin area under the curve 6 IV over 30 minutes every 21 days, for 6 cycles. End points were toxicity, response rates, relapse rates, event-free survival, and survival rates. Thirty-six patients were enrolled and 35 were evaluable. Twenty-three percent of patients were age ≥ 70 years. A total of 170 cycles of therapy were given. Ten patients required dose reduction. Thirty-eight percent had a delay in starting subsequent planned cycles. Most delays were due to hematologic recovery. Hematologic toxicity was most common and significant; 77% grade 4 neutropenia. One patient died from typhilitis. Total complete remission (38%) and partial remission (27%) rate was 65%. Median time to progression was 261 days (60-717). Five (14%) patients remain alive without ovarian cancer, with median follow-up of 5.1 years. Patients who entered the study with ≥ 12-month duration of initial remission had best response. The combination of docetaxel and carboplatin has toxicity, especially hematologic, and requires growth factor support and close monitoring for infections. Its role for treating ovarian cancer patients was better in patients in whom initial response to therapy was ≥ 12 months.
To investigate the methylation pattern in promoter region of RASSF1A and PTEN genes in epithelial ovarian cancer patients in North India. Fifty patients and 20 healthy controls were studied. Isolation of genomic DNA from peripheral blood and methylation-specific polymerase chain reaction (MSP) were applied for analysis. 17 of 50 patients (34.0%) were found to be methylated for RASSF1A gene, whereas methylation of the PTEN gene occurred in 8 of 50 cases (16.0%). A statistically significant result was obtained (P = .01) for RASSF1A gene and correlated with the patients' clinicopathologic features. Hypermethylation of both RASSF1A and PTEN genes in blood DNA from ovarian cancer patients might offer an exposition for early diagnosis of the malignancy.
The aim of this study was to validate the risk-of-malignancy index (RMI) incorporating menopausal status, serum CA 125 levels, and imaging findings for discriminating benign from malignant pelvic masses and to evaluate the ability of 4 different RMIs. This is a prospective study of 296 women admitted to the Department of Obstetrics and Gynecology of Kochi Health Sciences Center, between September 2011 and April 2014, for surgical exploration of pelvic masses. The RMI 1, 2, 3, and 4 methods were calculated for all patients together with the sensitivity, specificity, positive predictive value, and negative predictive value. The sensitivity of RMIs 1, 2, 3, and 4 was 73.0%, 81.1%, 73.0%, and 77.0%, respectively, and the specificity was 93.7%, 89.6%, 93.7%, and 92.3%, respectively. The RMI 2 was significantly better at predicting malignancy than RMIs 1 3; however, there was no statistically significant difference in performance of RMIs 2 4. The RMI method is a valuable and applicable method in diagnosing pelvic masses with high risk of malignancy and a simple technique that can be used in gynecology clinics and less-specialized centers.
Ovarian cancer as the most lethal gynecologic malignancy in women is poorly detected during early stages of carcinogenesis. Therefore, there is an emergent need to look for specific and sensitive biomarkers for early diagnosis of ovarian cancer. In this study, we performed real-time polymerase chain reaction (PCR) to evaluate the expression of six proapoptotic genes, CASP8, BAK, APAF1, BAX, BID, and BAD, which contain CpG islands in their promoter regions. Afterward, the significantly downregulated genes were investigated by HpaII-PCR and methylation-specific PCR (MSP) to determine the methylation status between tumoral and adjacent normal tissues. The real-time PCR results in 24 tumoral and 9 normal adjacent tissues showed decreased expression of CASP8 and BAD genes in tumoral relative to normal samples. Furthermore, the methylation analysis showed no significant methylation between tumoral and normal samples. Taken together, this could be concluded that downregulation of CASP8 and BAD genes in ovarian cancer may be as important causes for ovarian cancer carcinogenesis via inducing resistance to apoptosis; however, the downregulations are not due to promoter hypermethylation.
About 10% to 15% of ovarian cancers are linked to genetic abnormalities, including breast cancer susceptibility gene (BRCA) mutations, and Lynch syndrome. The aim of this work was to provide comprehensive and updated review of this distinct type of ovarian cancer that carries genetic alterations in relation to its pathology, prevention, prognosis, and management. Genetic ovarian cancer has a distinct pathologic and molecular biology features. BRCA1 and BRCA2 mutation ovarian cancers are most likely to be high-grade serous adenocarcinomas. Many BRCA1-mutated tumors harbor a mutant p53 gene, c-myc overexpression, and epidermal growth factor receptor overexpression. Clinically, genetic ovarian cancer presents at a younger age than sporadic ovarian cancer. For prevention, risk-reduction salpingo-oophorectomy is an effective tool. Chemoprevention by oral contraceptives may represent an option. A recent study demonstrates improved progression-free survival and overall survival in patients whose ovarian cancer displays BRCA1 and BRCA2 mutation, relative to those who have normal BRCA1 and BRCA2 function. Recent management advances include PARP (poly[adenosine diphosphate {ADP}–ribose] polymerases) inhibitors. Significant progress has been recently made in elucidating the role of BRCA1 and BRCA2 mutation and Lynch syndrome on ovarian cancer prognosis and management.
Female adnexal tumors of probable wolffian origin are very rare neoplasms that coincide with abdominal pain and swelling. These lesions are typically considered to be of low malignant potential, but they are periodically aggressive and can metastasize. Immunohistochemistry is not always effective in determining the clinical diagnosis of these tumors, and standard treatment is indeterminate. This report presents a patient diagnosed with a female adnexal tumor of probable wolffian origin who intraoperatively developed incidental disseminated intravascular coagulation that was successfully addressed with pressure, microfibrillar collagen hemostat, and blood products. Regrettably, she died of disease progression 4 weeks postoperatively. Despite the uncharacteristic coexistence of a female adnexal tumor of probable wolffian origin and disseminated intravascular coagulation, oncology surgeons should be prepared for these 2 conditions in an attempt to confer an optimal patient outcome.
This study was aimed at evaluating the efficacy and tolerability of oxaliplatin/doxorubicin combination therapy in patients with platinum-sensitive and platinum-resistant ovarian cancer. Patients with recurrent ovarian cancer after 1 regimen of platinum-based chemotherapy received doxorubicin (50 mg/m2 intravenously) and oxaliplatin (130 mg/m2 intravenously) on day 1 every 3 weeks. The platinum-free interval was set to be < 24 months. A total of 33 patients were enrolled (21 platinum-resistant and 12 platinum-sensitive relapses). The response rate in platinum-resistant ovarian cancer was lower than in platinum-sensitive disease (33.4% vs. 54.5%), although the difference was not statistically significant (P = .59). The median progression-free survival (PFS) and overall survival in the whole cohort were 7.4 and 24.3 months, respectively. PFS in platinum-sensitive cancer was longer than in platinum-resistant cancer (10.8 vs. 6.7 months); however, this difference did not reach statistical significance (P = .14). The combination of oxaliplatin/doxorubicin is an active regimen for patients with platinum-sensitive and platinum-resistant recurrent ovarian cancer.
Objective: Survival outcomes in most patients with recurrent cervical cancer that is not amenable to radical excision or curative local radiation is usually less than 1 year. These patients are generally candidates for cytotoxic chemotherapy and clinical trials are recommended in an attempt to improve the prognosis of these patients. The objective of this study was to compare survival outcomes in patients with recurrent cervical cancer treated on versus off clinical trial.
The purpose of this study was to determine the effect of time interval between debulking surgery to adjuvant chemotherapy on the short-term morbidity and carcinoma antigen (CA)-125 level. A total of 43 patients with primary debulking surgery for operable stage epithelial ovarian cancer (stage IB to IIIC) from January 2008 to January 2010 were analyzed prospectively. The participants were randomized into 2 groups. The surgical–chemotherapy interval group 2 (SCI2) (n = 22) received adjuvant chemotherapy (carboplatin and paclitaxel) within 2 weeks after primary debulking surgery and the SCI6 (n = 21) group received the same chemotherapy agents 6 weeks after the primary surgery. A computerized randomization technique was used. Participants in the SCI2 group had a better CA-125 reduction after 6 cycles of chemotherapy (P < .005) compared with the SCI6 group. The incidence of anemia was more significant in the SCI2 group (P < .005) than in the other group. However, there were no significant differences in wound breakdown, neutropenia, thrombocytopenia, and clinical response of chemotherapy between the 2 groups. Time interval between primary surgery to the commencement of adjuvant chemotherapy had no significant effect on short-term morbidity, but had an improved effect on biochemical (CA-125) response.
Malignant transformation of mature cystic teratoma (MCT) is a rare event, occurring in 1% to 2% of cases. Small-cell carcinoma arising from an MCT is particularly rare, with only 3 other cases described in the English literature. We report a case of a 54-year-old para 1 female who was found to have advanced-stage small-cell carcinoma of the ovary in association with a MCT. The clinicopathological features, treatment regimen, and outcome of this patient were compared with the other cases described in the literature to evaluate the prognostic significance of this unusual subtype of ovarian cancer. Small-cell carcinoma of the ovary arising from a mature cystic teratoma is a rare form of ovarian cancer. It is usually of the pulmonary subtype and is treated with the same chemotherapeutic regimen as small-cell lung cancer. The prognostic significance of this unusual cancer subtype remains uncertain.
5055 Background: There has been conflicting data regarding the relationship between obesity and progression free survival in patients with ovarian cancer. There has been some evidence to suggest that obesity results in altered tumor biology and a poorer prognosis in these patients. The aim of this study was to examine whether obesity is a risk factor for time to recurrence in primary epithelial ovarian cancer. Methods: A multicenter retrospective chart review was performed at Mercy Medical Center and University of Michigan Medical Center. 591 patients were diagnosed with primary epithelial ovarian cancer between 2004-2009. However, 221 patients were excluded from the analysis because of persistent or progressive disease, treatment with neoadjuvant chemotherapy, presence of synchronous tumors or incomplete follow-up data. 370 patients were eligible for analysis. Data collected included: height and weight at the time of surgery, age, race, medical co-morbid illnesses, tumor stage, grade and histology. Treatment related data such as number of cycles of adjuvant chemotherapy; and optimal versus suboptimal tumor debulking was also collected. Body mass index (BMI) was defined according to WHO 2004 criteria. Women with a BMI greater than 30 were categorized as obese. The diagnosis of recurrence was made by positive radiological or pathological diagnosis of cancer recurrence after patient had surgery, received adjuvant chemotherapy and had no clinical, radiological or serological evidence of recurrence during this time. The time to recurrence was then quantified in terms of months from the initial surgery. Survival analyses were performed with the Kaplan-Meier method and compared using log-rank testing. Time to recurrence was analyzed using Mann-Whitney U and Wilcox W tests. Results: 130 (35%) obese patients were compared with 240 (65%) non obese patients. A recurrence was documented in 125 (47.9%) non obese patients and 49 (37.7%) obese patients. Time to recurrence between both BMI groups was found to be identical, at 15 months (p=1.0). The progression free survival was similar in both obese and non obese subjects (p=0.118). Conclusions: Obesity does not impact the time to recurrence in patients with primary ovarian cancer.
This study aimed to determine the postoperative fever index in the gynecologic oncology patient associated with significant infectious morbidity. A retrospective analysis was performed of 355 patients who underwent abdominal surgery. Charts were reviewed to evaluate postoperative temperature and risk factors for infectious morbidity. Statistical analyses were performed as indicated by the data type, including the Student t test, Mann-Whitney U test, χ2 test, and 1-way analysis of variance. A value of P < .05 was considered significant. There were 210 patients with temperatures < 100.5°F (group 1), 69 with a temperature ≥ 100.5°F to < 101°F (group 2), and 76 with a temperature ≥ 101°F (group 3). Demographic data were similar among groups. There were 285 diagnostic tests performed, with 51 test results indicative of infectious morbidity. Patients in group 3 underwent more testing and had more positive test results compared with groups 1 and 2. The majority of diagnostic testing and positive test results (60%) were in patients from group 3. Groups 1 and 2 were statistically similar in the number of positive test results and antibiotic duration, demonstrating a lower risk of infectious morbidity compared with group 3. This study suggests that a postoperative temperature of ≥ 101°F appears to be a better predictor of significant infectious morbidity compared with the prior definition of a temperature ≥ 100.5°F. Furthermore, this illustrates the need for the development of a postoperative temperature evaluation protocol to avoid expensive evaluations and empiric treatment of benign causes of postoperative fever.
