Evaluation of Pulmonary Complications in Robotic-Assisted Gynecologic Surgery.

STUDY OBJECTIVE: To conduct a study to assess the incidence of pulmonary complications associated with robotic-assisted surgeries in women with various gynecologic conditions. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: There were 296 patients included in this study. Patient characteristics and comorbidities were noted. Surgical characteristics and respiratory parameters were recorded for all patients. Intraoperative complications and postoperative complications were noted for up to 30 days after surgery. Patients were followed for a median of 231 days in an effort to detect any long-term complications. The primary outcome was postoperative pulmonary complications, and the secondary outcome measure was all complications. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study was composed of 296 patients. Only 5 patients (2%) experienced a pulmonary complication. Overall, 38 patients (13%) experienced complications, including both major and minor complications. Average airway pressure and maximum airway pressure were both associated with a significantly higher risk of pulmonary complications (p = .02 and p = .008, respectively). Age, body mass index, tidal volume, respiratory rate, estimated blood loss, and length of procedure were all found to not be statistically significant in patients who experienced a pulmonary complication versus patients who did not experience one. CONCLUSION: Robotic gynecologic surgery is safe and tolerated well by most patients. This study supports that there is a low rate of pulmonary complications in those who undergo robotic-assisted surgery for gynecologic indications, as well as a low overall complication rate.

A Delay from Diagnosis to Treatment Is Associated with a Decreased Overall Survival for Patients with Endometrial Cancer.

OBJECTIVES: While Caucasian women are more likely to be diagnosed with endometrial cancer compared to African-American women, the rate of mortality is higher for African Americans. The cause of this disparity is unknown. We analyzed the time interval from diagnosis of endometrial cancer to treatment as it pertains to race and socioeconomic factors and its possible impact on survival. METHODS: This was a retrospective, single institution chart review using a cancer registry database. We identified 889 patients who were diagnosed with endometrial cancer between January 2005 and June 2012. Clinicopathologic characteristics, demographics, insurance status, distance from medical center, body mass index (BMI), dates of diagnosis, and treatment were obtained from the medical records. Survival and association was determined by a one-way ANOVA test. RESULTS: At the time of the study, 699 patients were alive and 190 dead. The average age was noted to be 62 years (24-91 years). Stages I-IV disease accounted for 69, 6, 15, and 10%, respectively. White race accounted for 64%, African Americans 24%, and Hispanics 7% of our study population. Majority of patients were privately insured (n = 441) followed by Medicare (n = 375). The mean interval time from diagnosis to treatment was 47.5 days (0-363). A statistically significant difference was noted for this time interval with regard to both race and insurance status: white and African Americans (42.6 vs. 57.3 days, p = 0.048), privately insured and Medicare (38.4 vs. 54.1 days, p < 0.001). There was a significant association with increased risk of death with a longer delay (43.3 vs. 64.8 days, p < 0.001). No statistically significance was noted for distance from medical center or BMI. CONCLUSION: A significant increase in interval of time from diagnosis to treatment of endometrial cancer was seen in both race and insurance status. A longer interval from diagnosis to treatment was associated mortality. The causes of these delays are likely multifactorial but deem further investigation given these data.

Central-type primitive neuroectodermal tumor of the uterus: Case report of remission of stage IV disease using adjuvant cisplatin/etoposide/bevacizumab chemotherapy and review of the literature.

•Bevacizumab was an effective agent in one case of advanced uterine PNET.•VEGF was expressed by the tumor, supporting a mechanism for effectiveness.•Cisplatin/etoposide/bevacizumab should be further studied in clinical trials.•Patient remains disease-free forty-eight months following intervention.

Interleukin 16 expression changes in association with ovarian malignant transformation.

OBJECTIVE: Long-term unresolved inflammation has been suggested as a risk factor for the development of various malignancies. The goal of this study was to examine whether the expression of interleukin (IL)-16, a proinflammatory cytokine, changes in association with ovarian cancer (OVCA) development. STUDY DESIGN: In an exploratory study, changes in IL-16 expression in association with OVCA development and progression were determined using ovarian tissues and serum samples from healthy subjects (n = 10) and patients with benign (n = 10) and malignant ovarian tumors at early (n = 8) and late (n = 20) stages. In the prospective study, laying hens, a preclinical model of spontaneous OVCA, were monitored (n = 200) for 45 weeks with serum samples collected at 15-week interval. Changes in serum levels of IL-16 relative to OVCA development were examined. RESULTS: The frequency of IL-16-expressing cells increased significantly in patients with OVCA (P < .001) compared to healthy subjects and patients with benign ovarian tumors. The concentration of serum IL-16 was higher in patients with benign tumors (P < .05) than in healthy subjects and increased further in patients with early-stage (P < .05) and late-stage (P < .03) OVCA. Increase in tissue expression and serum levels of IL-16 in patients with early and late stages of OVCA were positively correlated with the increase in ovarian tumor-associated microvessels. Prospective monitoring showed that serum levels of IL-16 increase significantly (P < .002) even before ovarian tumors become grossly detectable in hens. CONCLUSION: This study showed that tissue expression and serum levels of IL-16 increase in association with malignant ovarian tumor development and progression.

Use of cervical mucus to screen for gynecological malignancies: a pilot study.

High-grade malignancies are the leading cause of death from gynecological tumors. Unfortunately, no efficient screening method is available for these tumors. In this paper we report the results of a pilot study based on the frequency of TP53 mutations in these cancers. Mucus from the cervix of 32 hysterectomy specimens with no grossly visible cervical or serosal involvement were included in this study. TP53 exons 5-9 mutations were screened for mutations using single strand conformation polymorphism (SSCP). Immunostain for p53 protein was performed in all fallopian tubes and in a sample from the tumors that were identified prospectively. A total of 32 cases including 19 malignant, and 13 benign cases were included. P53 immunostain was positive in only 5 cases including 3 high grade malignant tumors and 2 precancerous lesions (serous tubal intraepithelial lesion or p53 signature) in the fallopian tubes. A TP53 mutation band pattern was detected by SSCP in 2/3 and 2/2 cases respectively. Twenty-seven cases were negative for p53 imunostain, 4 of which were positive for TP53 mutation by SSCP including 3 low-grade malignancies. The results of this study provide evidence that DNA from precursor lesions of high grade ovarian, fallopian tube and endometrial carcinomas can be detected in cervical mucus. Further studies using different markers, in preoperative setting and large scale screening studies will determine the utility of using cervical mucus to screen for gynecological malignancies.

Immunohistochemical characterization of squamous differentiation and morular metaplasia in uterine endometrioid adenocarcinoma.

Squamous differentiation (SD) and morular metaplasia (MM) are frequently present in uterine endometrioid adenocarcinoma (EAC) and can mimic areas of solid tumor. We used immunohistochemical stains to further characterize these lesions, and to determine which markers would help to distinguish these metaplasias from areas of solid growth in EAC. The pathology database was searched for diagnoses of EAC from 1997 to 2007, the hematoxylin and eosin-stained slides were reviewed, and 143 cases with SD, MM, or both (SD+MM) were identified. A panel of immunohistochemical stains was performed. In particular, we were interested in PAX2 and PAX8, recently studied markers of Müllerian tissue as potential markers for differentiation of metaplasias and tumor. In addition, estrogen receptor and progesterone receptor, and Her-2/neu, were examined to determine whether there was a differential expression between the metaplasias and solid tumor that may be diagnostically useful. In addition, to further characterize MM and SD, bcl-2 as a marker of cell regulation and inhibition of apoptosis, p16 as a surrogate marker for human papillomavirus, and p63 as a marker of mature SD were studied. Adjacent normal endometrium (NEM), when present, and 20 EAC cases (FIGO Grades 1-3) without SD or MM served as controls. PAX2 was positive in NEM (58/61, 95%) and was lost in SD (15/136, 11%), MM (1/25, 4%), and EAC (57/163, 35%), whereas PAX8 was positive in all NEM (61/61, 100%) and in the majority of SD (125/136, 92%), MM (19/25, 73%), and EAC (162/163, 99%). The estrogen receptor and the progesterone receptor were expressed by the majority of EAC (148/163, 91% and 144/163, 88%, respectively), whereas both were markedly diminished in SD (56/136, 41% and 58/136, 43%) and MM (4/25, 16% and 2/25, 8%). Approximately half of the MM was positive for bcl-2 (12/25, 48%), making it an unreliable marker. Her-2/neu was negative in all cases (0%). p16 was patchy in SD (111/136, 82%), MM (22/25, 88%), and EAC (154/163, 94%), whereas p63 was predominantly positive only in SD (96/136, 71%). Estrogen receptor and progesterone receptor, PAX2, and PAX8 were helpful in differentiating MM from SD, EAC, or NEM (P<0.05). In addition, p63 distinguished between SD and MM, supporting the theory that morules do not show characteristic mature SD.

Differential analysis of ovarian and endometrial cancers identifies a methylator phenotype.

Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer.

Optimal surgical debulking in uterine papillary serous carcinoma affects survival.

OBJECTIVE: UPSC is similar to papillary serous ovarian carcinoma in its histology and pattern of spread. The survival advantage with optimal debulking for ovarian cancer has been demonstrated. We examined our experience with UPSC. METHODS: Seventy-eight UPSC patients were seen between 1995 and 2008 at Rush University Medical Center for surgery and/or adjuvant treatment. Information was obtained retrospectively from the Rush computer system, National Death Registry, and charts from chemotherapy, radiation, and gynecologic oncology. RESULTS: Mean survival was 67.1 months for all stages (95% CI 52.8-81.2), 47.6 months for stage III (95% CI 26.7-68.3), and 21.7 months for stage IV (95% CI 14.5-29.1). No deaths occurred in stages I and II. No significant survival difference was found between African-Americans and Whites (log-rank test, p=0.62), nor between full serous and mixed pathology (log-rank test, p=0.52). Optimally debulked stage IV patients had a mean survival of 30.9 months, compared to 10.3 months in suboptimally debulked patients (p<0.001). Optimal debulking had no significant effect on stage III survival (p=0.47). Although weight was not statistically significant (p=0.059), there was a trend associated with suboptimal debulking. The mean time to recurrence for stage I was 79.9 months (95% CI 12.8-54.9), stage III was 27.4 months (95% CI 7.8-47.1), and stage IV was 20.2 months (95% CI 11.1-29.4) (p<0.001). There were no recurrences in stage II. CONCLUSION: Our results suggest that UPSC should be optimally debulked. Weight is a risk factor for suboptimal debulking, which decreases mean survival and time to recurrence.

Use of gene expression profiles to stage concurrent endometrioid tumors of the endometrium and ovary.

OBJECTIVE: The objectives of this study were to determine whether there are distinct gene expression profiles for endometrial and ovarian endometrioid carcinomas and to create a statistical model using these profiles to predict their organ of origin. METHODS: Expression profiles of seven stage I, grades 1 and 2, endometrioid endometrial carcinomas and seven stage I ovarian endometrioid carcinomas were analyzed as the training set. The test set included seven advanced endometrial carcinomas and nine dual primary endometrial and ovarian primary tumors of endometrioid histology. Unsupervised hierarchical clustering, multidimensional scaling (MDS) and predictive analysis of microarrays (PAM) were used to analyze the data. RESULTS: We identified 163 differentially expressed (DE) genes between endometrial and ovarian tumors. Both unsupervised hierarchical clustering and multidimensional scaling showed clear separation of the two groups. Pathway analysis of the 163 DE genes revealed significant biological differences between the two groups, which included metabolic and biosynthetic pathways. Further classification analysis on the training data using predictive analysis of microarray generated a 119-gene predictive model with 100% cross-validation accuracy. When the 119-gene model was applied to the test set of 16 samples, we found concordance in 11/16 samples and discordance in 5/16 samples with the pathologic classification. CONCLUSION: We conclude that, although similar in histologic appearance, endometrioid carcinomas of the ovary and endometrium have distinct gene expression patterns. A larger test set is needed to prospectively evaluate this prediction model further.

Epithelioid angiosarcoma of the mons after chemoradiation for vulvar cancer.

Angiosarcomas are rare malignant tumors of endothelial origin with morphological properties similar to the vascular and lymphatic endothelium. Associated risk factors include chronic lymph edema and previously irradiated areas. Our patient is the first case report of an angiosarcoma of the mons pubis after chemoradiation and the second reported angiosarcoma of the mons. She was a 74-year-old woman who initially presented with stage II keratinizing squamous cell carcinoma of the vulva that underwent neoadjuvant chemoradiation followed by a radical vulvectomy with bilateral inguinal-femoral lymphadenectomy. She presented 4 years later with a lesion on her mons, consistent with an angiosarcoma. Angiosarcomas are rare malignant tumors of endothelial origin with morphological properties similar to the vascular and lymphatic endothelium. Our patient is the first case report of an angiosarcoma of the mons pubis after chemoradiation for vulvar cancer and the second reported angiosarcoma of the mons. Time to presentation was approximately 4 years from the time of completion of chemoradiation. She recurred within 6 months of surgical resection and required a reexcision. She currently is undergoing systemic chemotherapy after being diagnosed with a metastatic pelvic lymph node. As the treatment of vulvar cancer evolves, and more radiation therapy is given, the incidence of angiosarcomas will rise, requiring better diagnostic and treatment protocols.

The use of colorectal stents for palliation of large-bowel obstruction due to recurrent gynecologic cancer.

OBJECTIVE: Acute large-bowel obstruction (LBO) is considered a surgical emergency. In gynecologic oncology patients with LBO due to recurrent tumor, surgery has been the standard treatment. However, operative intervention has significant associated morbidity and mortality. Recent reports have addressed the use of colorectal stents for the treatment of colonic malignancies. We are reporting our experience with colorectal stents in gynecologic oncology patients. METHODS: We reviewed the records of all patients who underwent colorectal stent placement for palliation of LBO due to recurrent gynecologic malignancy from August 2001 to January 2003. RESULTS: Six patients were identified; five patients had recurrent ovarian cancer and one had recurrent endometrial cancer. The mean age of the six patients at the time of stent placement was 51.5 years (range, 22-83 years). The length of LBO ranged from 2 to 10 cm. Two patients had a lumen of 1 to 2 mm before stent placement, while the other four had a complete obstruction and needed balloon dilatation before the deployment of the stent. Four (67%) of six patients had immediate relief, with passage of stool and flatus noted at the time of the colorectal stent placement. Stent placement failed to relieve the LBO in two patients (33%); these patients went on to receive colostomies. Of the four patients who had successful stent placement, the mean survival after stent placement was 120 days. One patient had a contained sigmoid bowel perforation noted 12 days after stent placement, which resolved with conservative measures. CONCLUSION: Colonic stents appear to be a useful option in the management of patients with LBO due to recurrent gynecologic malignancy.