Michael J. Worley

Endometriosis-Associated Ovarian Cancer: A Review of Pathogenesis

Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC). Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC) develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.

Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm.

MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.

Minimally invasive staging of endometrial cancer is feasible and safe in elderly women.

STUDY OBJECTIVE To compare the surgical outcome of elderly and younger patients undergoing laparoscopic or robotic surgical staging of endometrial cancer. DESIGN Retrospective analysis (Canadian Task Force classification II-2). SETTING University-affiliated hospital. PATIENTS One hundred twenty-nine patients comprised the study group. Sixty patients were aged 65 years or older (elderly group), and 69 patients were younger than 65 years (younger group). INTERVENTION Abdominal, laparoscopic, or robotic hysterectomy. MEASUREMENTS AND MAIN RESULTS Among the 109 patients who underwent laparoscopic or robotic staging, there were no differences in estimated blood loss, lymph node count, surgical time, complications, rate of blood transfusion, conversion to laparotomy, and mean postoperative stay between elderly and younger patients. CONCLUSION Minimally invasive surgical staging for endometrial cancer is both feasible and safe in the elderly population and offers similar outcomes as in younger patients.

Adolescent Understanding and Acceptance of the HPV Vaccination in an Underserved Population in New York City.

Background. HPV vaccination may prevent thousands of cases of cervical cancer. We aimed to evaluate the understanding and acceptance of the HPV vaccine among adolescents. Methods. A questionnaire was distributed to adolescents at health clinics affiliated with a large urban hospital system to determine knowledge pertaining to sexually transmitted diseases and acceptance of the HPV vaccine. Results. 223 adolescents completed the survey. 28% were male, and 70% were female. The mean age for respondents was 16 years old. Adolescents who had received the HPV vaccine were more likely to be female and to have heard of cervical cancer and Pap testing. Of the 143 adolescents who had not yet been vaccinated, only 4% believed that they were at risk of HPV infection and 52% were willing to be vaccinated. Conclusions. Surveyed adolescents demonstrated a marginal willingness to receive the HPV vaccine and a lack of awareness of personal risk for acquiring HPV.

Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole‐exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies

OBJECTIVE Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers. METHODS This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment. RESULTS From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5 days (range 0-22 days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44 days (range 9-99). CONCLUSION Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.

Does neoadjuvant chemotherapy decrease the risk of hospital readmission following debulking surgery

OBJECTIVE To compare primary debulking surgery (PDS) vs. neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) among elderly patients with ovarian/fallopian tube/primary peritoneal carcinoma. METHODS Medical records of patients ≥70 years old with epithelial ovarian/fallopian tube/primary peritoneal carcinoma between January 2000 and December 2010 were reviewed. Patients were separated by PDS or NACT-IDS. Preoperative characteristics, surgical procedures and postoperative and oncologic outcomes were compared. Surgical procedures were given a complexity score based on a previously published method. RESULTS Of 165 patients, 125 (75.8%) underwent PDS and 40 (24.2%) underwent NACT-IDS. Patients undergoing NACT-IDS were more likely to have a pleural effusion (without cytology) and stage 4 disease. Median CA-125 at diagnosis was greater for those undergoing NACT-IDS. The NACT-IDS group was associated with less intraoperative blood loss (250 vs. 400 mL, p=0.001), a greater chance of achieving no residual disease (40% vs. 16%, p=0.005) and a shorter hospital length of stay (LOS) (5 vs. 7 days, p<0.001). PFS (17 vs. 15 months, p=0.708) and OS (29 vs. 33 months, p=0.827) were similar between the two groups. Readmission rates within 30 days of surgery were greater in those undergoing PDS (17.6% vs. 2.5%, p=0.016). After readmission, the median hospital LOS was 6 days (range: 1-41). CONCLUSIONS Elderly patients undergoing PDS have similar oncologic outcomes when compared to patients undergoing NACT-IDS. The risk of readmission within 30 days of surgery is significantly greater among patients undergoing PDS.

The significance of preoperative leukocytosis in endometrial carcinoma

OBJECTIVE To evaluate the impact of preoperative leukocytosis among patients with endometrial carcinoma. METHODS The medical records of all patients that underwent surgical treatment for endometrial carcinoma between January 2005 and December 2010 were retrospectively reviewed. Patients were separated into two groups based on the presence or absence of preoperative leukocytosis (WBC ≥ 10,000 cells per μl). The groups were then compared with respect to pathologic findings, progression-free survival and overall survival. RESULTS 1144 patients were identified, 156 (13.6%) with preoperative leukocytosis and 988 (86.4%) without leukocytosis. The leukocytosis group had a greater percentage of patients with stage 3 (15.4% vs. 9.8%, crude p=0.02) and 4 (7.1% vs. 3.0%, crude p=0.007) disease. Leukocytosis was associated with a greater mean tumor size (4.4 vs. 3.4 cm, p=0.0002) and a greater percentage of patients with cervical stromal involvement (14.8% vs. 8.7%, crude p=0.02), adnexal involvement (14.1% vs. 7.5%, crude p=0.007) and lymphvascular space invasion (24% vs. 16.3%, crude p=0.02). On multivariate analysis, mean tumor size (OR, 95% CI; 1.10, 1.02-1.18) remained significantly associated with preoperative leukocytosis. There was no difference between groups, with respect to time to recurrence. However, leukocytosis was independently associated with an increased risk of death (HR, 95% CI; 1.69, 1.07-2.68). CONCLUSIONS Preoperative leukocytosis, among endometrial cancer patients, was independently associated with increasing tumor size and independently imposed an increased risk of death.

The significance of a thickened endometrial echo in asymptomatic postmenopausal patients

OBJECTIVE The purpose of this study was to evaluate the significance of a thickened endometrial echo in an asymptomatic, postmenopausal patient. STUDY DESIGN A retrospective review was conducted of all women who underwent transvaginal ultrasonography between January 2003 and August 2008, were found to have an endometrial thickness of at least 5mm and were subjected to endometrial sampling. RESULTS Sixty-five postmenopausal women, without vaginal bleeding underwent ultrasonographic evaluation with subsequent endometrial sampling. The mean endometrial stripe thickness was 9.7 mm (range: 5.4-22). Four (6.2%) cases of simple/complex hyperplasia were identified and two (3.1%) cases of atypical hyperplasia were diagnosed. Zero (0%) specimens were identified as adenocarcinoma. Twenty-eight (43.1%) polyps and eleven (16.9%) leiomyomata were identified. CONCLUSION The use of transvaginal sonography as a screening tool in this population is not validated and need not trigger routine evaluation.

Venous thromboembolism prophylaxis for laparoscopic surgery: a survey of members of the Society of Gynecologic Oncology.

Objective This study aimed to evaluate the use of venous thromboembolism (VTE) prophylaxis for laparoscopic surgery among members of the Society of Gynecologic Oncology (SGO). Methods A 23-item questionnaire was sent to all working/eligible SGO member e-mail addresses (n = 1356). Data were collected and analyzed using descriptive statistics. χ2 was used to determine differences in responses between groups. Results Of the 287 (21.2%) responding SGO members, most (61.3%) estimated the risk of VTE for laparoscopic surgery between 1% and 2%. Most (51.2%) of respondents did not routinely use preoperative pharmacoprophylaxis, and most discontinued prophylaxis upon hospital discharge, regardless of benign (73.5%) or malignant (53.3%) pathology. Combination prophylaxis was preferred for procedures in the setting of intermediate- (50.2%) or high-complexity (78%), malignancy (70.7%), obesity (71.4%), multiple medical comorbidities (76%), or the elderly (64.5%). When compared with respondents of greater surgical volume, respondents who performed less than 5 laparoscopic cases per month were more likely to use sequential compression devices alone in the setting of malignancy (52.6%, P = 0.025). The omission of VTE prophylaxis was rare and varied depending on the patient scenario (0.7%–3.5%). When compared with younger respondents, those who were 61 to 70 years old more frequently omitted VTE prophylaxis in the setting of low-complexity procedures (22.2%, P = 0.003), obesity (11.1%, P = 0.021), multiple medical comorbidities (11.1%, P = 0.008), and the elderly (11.1%, P = 0.009). Conclusions Among SGO members, the preferred method of VTE prophylaxis during laparoscopic surgery for several high-risk patient scenarios was combination prophylaxis. The use versus nonuse and the preferred method of VTE prophylaxis were influenced by respondent age and surgical volume.