Extended-field radiation therapy with whole pelvis radiotherapy and cisplatin chemosensitization in the treatment of IB2-IIIB cervical carcinoma: a retrospective review.

OBJECTIVE: This retrospective study evaluated the toxicity of extended-field radiation therapy (EFRT), whole pelvis radiotherapy, and concurrent chemotherapy in patients treated with IB2-IIIB cervical carcinoma. STUDY DESIGN: Patients treated with EFRT, whole pelvis radiotherapy, and concurrent chemotherapy were analyzed for toxicity. Median prescribed dose to the whole pelvis was 45 Gy (45-50 Gy). Median prescribed dose to the paraaortic lymph nodes was 45 Gy (36-50). Thirty-five patients received cisplatin chemosensitization at a median dose of 40 mg/m(2) (40-51), with a median of 5 cycles (2-6). RESULTS: Thirty-six patients were treated, 3 with positive paraaortic lymph nodes. The median follow-up interval was 32 months. Twenty-four patients (66.7%) had no evidence of disease at last follow-up. Thirteen patients (36.1%) had recurrence. Fifteen patients (41.7%) experienced acute grade 3 toxicity. CONCLUSION: Increased toxicity in patients warrants careful patient selection.

Cervical adenocarcinoma in situ: the predictive value of conization margin status.

OBJECTIVE: We evaluated the impact of conization margin status on outcomes of patients diagnosed with cervical adenocarcinoma in situ. STUDY DESIGN: A retrospective chart review identified patients at a University hospital from 1988-2006 with adenocarcinoma in situ (AIS) on conization. RESULTS: Seventy-four patients were included. Median follow-up was 26 months. Twenty-two of 74 patients (30%) had positive margins, 46 patients (62%) had negative margins, and 6 patients had indeterminate margins. Of patients with positive margins, 55% (12/22) were diagnosed with residual or recurrent disease, including 3 patients diagnosed with adenocarcinoma on hysterectomy. Thirteen percent of patients with negative conization margins (6/46) were diagnosed with residual or recurrent disease, including 2 patients diagnosed with adenocarcinoma during follow-up. Cold knife conization resulted in a significantly higher number of negative margins compared to other conization procedures (P = .013). CONCLUSIONS: Even with negative conization margins, women still face a risk of residual, recurrent, or invasive disease.

Initial chemotherapy followed by surgical cytoreduction for the treatment of stage III/IV epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to evaluate differences in morbidity, progression-free interval, and survival in women with advanced epithelial ovarian cancer treated with initial chemotherapy versus initial surgery. STUDY DESIGN: All women with epithelial ovarian cancer who were treated surgically at our hospital between January 1, 1995, and January 1, 2003, were eligible; the cases of 200 patients met the criteria and underwent retrospective chart review. RESULTS: Ninety-eight patients (49%) had initial chemotherapy, and 102 patients (51%) had initial surgery. Patients who received initial chemotherapy were more likely to have stage IV disease (initial chemotherapy, 27%, vs initial surgery, 8%; P = .042) and grade 3 disease (initial chemotherapy, 73%, vs initial surgery, 61%; P = .025). Optimal cytoreduction was achieved more often in patients who received initial chemotherapy (initial chemotherapy, 86%, vs initial surgery, 54%; P < .001). Only optimal cytoreduction (P = .022), and not treatment choice (P = .089), had an impact on median survival. CONCLUSION: Initial chemotherapy is a reasonable alternative to initial surgery for the treatment of selected patients with advanced epithelial ovarian cancer.

Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: To determine if circadian timed (CT) chemotherapy results in improved response, progression-free survival (PFS), overall survival (OS), and lower toxicity, when compared with standard timed (ST) chemotherapy. MATERIALS AND METHODS: Eligibility criteria were stage III, IV, or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery; measurable disease; and no prior chemotherapy. Therapy was randomized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2, or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm. Cycles were repeated every 3 weeks to a maximum of eight cycles. RESULTS: The ST arm included 169 patients, and the CT arm included 173 patients. The objective response rate (complete responses plus partial responses) was 46% in the ST group compared with 49% in the CT group (P =.26, one tail). Median PFS and OS were 6.5 and 11.2 months, respectively, in the ST group; and 5.9 and 13.2 months, respectively, in the CT group (PFS: P =.31; OS: P =.21, one tail). Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group, versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group. Grade 3 or 4 leukopenia occurred in 73% of patients in the ST arm and in 63% of patients in the CT arm. There were eight treatment-related deaths. CONCLUSION: In this trial, no significant benefit in terms of response rate, PFS or OS, or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma.

Minimizing the risk of neurologic injury in gynecologic surgery.

OBJECTIVE: The association of intraoperative neurologic injuries with gynecologic surgical procedures is well established. The sequelae of such injuries are usually transient and resolve with minimal intervention, although long-term disability can and does occasionally occur. The purpose of this study was to examine the mechanisms by which these injuries occur in order to reduce the risk of their occurrence. DATA SOURCES: A MEDLINE search was performed cross-referencing the index terms "neurological injury" and "gynecological surgery," from January 1, 1960 to December 31, 2002. METHODS OF STUDY SELECTION: This article, based on the data and results (Level I-III) obtained from the MEDLINE search, examined the most common neurologic injuries that occur in association with abdominal and vaginal surgical procedures routinely performed by gynecologists. TABULATION, INTEGRATION, AND RESULTS: Neurologic injuries after pelvic surgery all generally share a common etiology, specifically injury to one or more components of the lumbosacral nerve plexus. Three major factors that predispose to neurologic injury at the time of gynecological surgery are 1) the improper placement or positioning of self-retaining or fixed retractors, particularly those with deep lateral retractor blades; 2) improper positioning of patients in lithotomy position preoperatively; and 3) radical surgical dissection resulting in autonomic nerve disruption. Level I data strongly implicate the improper placement of self-retaining or fixed retractors as the most common cause of femoral nerve injury arising in association with abdominal surgical procedures. CONCLUSION: A thorough understanding of the anatomy of the lumbosacral nerve plexus and the mechanisms by which operative injuries to this plexus occur will enable the gynecologic surgeon to reduce the subsequent risk of their occurrence in his or her own surgical practice.

Effects of adjunctive Swedish massage and vibration therapy on short-term postoperative outcomes: a randomized, controlled trial.

OBJECTIVE: To examine the effects of adjunctive postoperative massage and vibration therapy on short-term postsurgical pain, negative affect, and physiologic stress reactivity. DESIGN: Prospective, randomized controlled trial. The treatment groups were: (1) usual postoperative care (UC); (2) UC plus massage therapy; or (3) UC plus vibration therapy. SETTING: The University of Virginia Hospital Surgical Units, Gynecology-Oncology Clinic, and General Clinical Research Center. SUBJECTS: One hundred and five (N = 105) women who underwent an abdominal laparotomy for removal of suspected cancerous lesions. INTERVENTIONS: All patients received UC with analgesic medication. Additionally, the massage group received standardized 45-minute sessions of gentle Swedish massage on the 3 consecutive evenings after surgery and the vibration group received 20-minute sessions of inaudible vibration therapy (physiotones) on the 3 consecutive evenings after surgery, as well as additional sessions as desired. OUTCOME MEASURES: Sensory pain, affective pain, anxiety, distress, analgesic use, systolic blood pressure, 24-hour urine free cortisol, number of postoperative complications, and days of hospitalization. RESULTS: On the day of surgery, massage was more effective than UC for affective (p = 0.0244) and sensory pain (p = 0.0428), and better than vibration for affective pain (p = 0.0015). On postoperative day 2, massage was more effective than UC for distress (p = 0.0085), and better than vibration for sensory pain (p = 0.0085). Vibration was also more effective than UC for sensory pain (p = 0.0090) and distress (p = .0090). However, after controlling for multiple comparisons and multiple outcomes, no significant differences were found. CONCLUSIONS: Gentle Swedish massage applied postoperatively may have minor effects on short-term sensory pain, affective pain, and distress among women undergoing an abdominal laparotomy for removal of suspected malignant tissues.

Endocervical curettage. Does it contribute to the management of patients with abnormal cervical cytology?

OBJECTIVE: To conduct a prospective analysis of whether endocervical curettage contributes to the management of patients with abnormal cervical cytology. STUDY DESIGN: Three hundred four consecutive patients being evaluated for abnormal squamous cervical cytology at the University of Virginia underwent routine endocervical curettage at the time of diagnostic colposcopy. RESULTS: Among the 304 patients evaluated colposcopically, the information provided by endocervical curettage changed treatment planning in only 13, or 4.27%. In none of these 13 patients would the omission of endocervical curettage at the time of diagnostic colposcopy have resulted in overlooking an occult invasive or microinvasive carcinoma. CONCLUSION: This prospective analysis did not find the information provided by the routine application of endocervical curettage at the time of diagnostic colposcopy to be helpful in the subsequent treatment planning of patients undergoing evaluation for cervical intraepithelial disease.

"See-and-treat" loop electrosurgical excision. Has the time come for a reassessment?

OBJECTIVE: To review the results of a policy decision to offer selected women with cervical high grade squamous intraepithelial lesions (HSILs) loop electrosurgical excision (LEEP) at the time of their initial colposcopic evaluation. STUDY DESIGN: Sixty-one patients with newly diagnosed cytologic cervical HSIL were evaluated for inclusion in a "see-and-treat" protocol. Fifty of these patients met inclusion criteria and underwent immediate loop excision of the cervical transformation zone at their initial colposcopic visit. RESULTS: Forty-eight of 50 patients that underwent see-and-treat management at their initial colposcopic evaluation had histologic evidence of cervical dysplasia/neoplasia. The positive predictive value of diagnostic colposcopy in this setting was 96%, with a 95% confidence interval (88-99%). Two patients had no pathologic abnormality, for an overtreatment incidence of 4%. CONCLUSION: The selected use of see-and-treat management of cytologic cervical HSIL is feasible, highly predictive and associated with an extremely low incidence of overtreatment. Such management has the potential to increase patient satisfaction and compliance while drastically reducing health care dollars currently directed toward the management of HSIL. Strong consideration should be given to accepting see-and-treat management as a viable alternative in the care of patients with documented cervical cytologic HSIL.

The utility of HPV DNA triage in the management of cytological AGC.

OBJECTIVE: Given the demonstrated utility of human papilloma virus DNA triage in the management of atypical squamous cells of undetermined significance, this study sought to evaluate the potential role of human papilloma virus DNA testing in the evaluation and management of cytological atypical glandular cells. STUDY DESIGN: Following institutional review board approval, 28 women presenting with cytological atypical glandular cells underwent repeat thin-prep cytology, Hybrid Capture 2 human papilloma virus DNA testing, colposcopic evaluation, Fisher electrosurgical conization, and endometrial sampling. Human papilloma virus test results in each patient were then correlated with histologic lesions, if present. RESULTS: Sixteen of the 28 study patients had pathologic lesions (11/28 high-grade squamous intraepithelial lesion, 3/28 low-grade squamous intraepithelial lesion, 1/28 adenocarcinoma in situ, 1/28 simple endometrial hyperplasia). Human papilloma virus DNA testing was available in 24 of 28 subjects (86%). The sensitivity of human papilloma virus positivity to predict the presence of cervical intraepithelial neoplasia was 100% (confidence interval 77% to 100%), specificity 64% (confidence interval 35% to 85%), positive predictive value 76%, and negative predictive value 100%. Women who tested human papilloma virus positive were 12 times more likely to have cervical intraepithelial neoplasia than women who were human papilloma virus negative (Fisher P<.001). Human papilloma virus positivity was not predictive of endometrial pathology; women who were human papilloma virus positive were less likely to have endometrial pathology than were women who were human papilloma virus negative (risk ratio 1.6, 95% confidence interval 0.01-1.7). CONCLUSION: Atypical glandular cells can represent a variety of lesions. The majority of the lesions will be squamous intraepithelial lesions of the cervix (50%), with high-grade squamous intraepithelial lesion present in 40% of subjects. Human papilloma virus DNA testing is a sensitive test for the presence of squamous intraepithelial lesion, with excellent negative predictive value for the absence of squamous intraepithelial lesion. The results of this study suggest human papilloma virus DNA testing might be an effective screening test in the initial evaluation and management of cytological atypical glandular cells.

Leiomyosarcoma of the cervix.

BACKGROUND: Epithelioid leiomyosarcoma arising from the uterine cervix is extremely rare, with only three cases reported in the world literature. We present the case report of a 14-cm epithelioid leiomyosarcoma arising from the uterine cervix. CASE: A 47-year-old female presented with a 1-year history of worsening menorrhagia and was found to have a large pelvic mass extending into and filling the upper vagina. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, revealing a 14 x 10 x 9 cm cervical epithelioid leiomyosarcoma. CONCLUSION: Although exceedingly rare, leiomyosarcoma is able to arise primarily from the uterine cervix. Given its extreme rarity, management of cervical LMS must be extrapolated from the currently accepted management for uterine LMS.

Uterine perforation at the time of brachytherapy for carcinoma of the cervix.

OBJECTIVE: The reported incidence of uterine perforation by tandems at the time of vaginal brachytherapy for management of cervical cancer ranges from 1.75% to 10% per application. The potential ramifications of afterloading a tandem that is outside the uterine cavity within the pelvis are sufficiently severe, in terms of bowel injury, that a reliable means of determining tandem positioning at the time of placement is essential. METHODS: We examined a representative patient that underwent tandem placement for Federation Internationale of Gynecologic Oncologist (FIGO) stage Ib1 cervical Squamous Cell Carcinoma (SCCA). The information provided by conventional radiographic assessment and clinical impression was not helpful in ultimately determining tandem placement. RESULTS: Direct endoscopic visualization provided accurate and irrefutable evidence of tandem location and positioning prior to leaving the operating room. CONCLUSION: A variety of techniques have been described to assist in accurate placement of the uterine tandem prior to afterloading, when utilizing definitive chemoradiation in the management of cervical carcinoma. These include postoperative plain films or computerized tomography, versus intraoperative transabdominal or transrectal ultrasound guidance at the time of placement. Postoperative techniques that confirm perforation necessitate a second visit to the operating room, a second general anesthetic, as well as a treatment delay that may impact negatively upon central control rates in the long term. Intraoperative techniques have their limitations as well, particularly in the obese patient. With difficult or questionable insertions, direct endoscopic evaluation at the time of tandem insertion is the only means of knowing definitively the location of the tandem prior to leaving the operating room.

Evaluation of paclitaxel in previously treated leiomyosarcoma of the uterus: a gynecologic oncology group study.

OBJECTIVE: The purpose of this phase II trial was to evaluate the efficacy of intravenous paclitaxel in patients with recurrent or advanced leiomyosarcoma of the uterus. METHODS: To be eligible, patients with recurrent or persistent leiomyosarcoma of the uterus were to have measurable disease not previously treated with paclitaxel and adequate hematologic (WBC >or=3000/microl, platelet count >or=100000/microl), renal (serum creatinine

Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: To estimate the objective response rate and toxicity associated with alternating megestrol acetate (MA) and tamoxifen citrate (T) in women with endometrial carcinoma. METHODS: Consenting patients with measurable recurrent or advanced endometrial carcinoma were eligible if they had not received prior cytotoxic or hormonal treatment. MA 80 mg BID x 3 weeks alternating with T 20 mg BID x 3 weeks orally was given. RESULTS: Of 61 patients entered, 56 eligible patients were evaluable for toxicity and response. Fifteen patients responded (12 complete, 3 partial) for an overall response rate of 27% (90% Confidence Interval: 17-38%). In 8 of 15 (53%) responders, response duration exceeded 20 months. The response rate was 38% in patients with histologic grade 1 tumors (n = 16), 24% in those with grade 2 disease (n = 17), and 22% among patients with grade 3 disease (n = 23). Women less than or equal to 60 years (n = 16) appear to have a better response rate than those >60 years (n = 40), 44% versus 20%. The response rate in patients with extra pelvic disease (n = 42) was 31% as compared to 14% in those with strictly pelvic and/or vaginal disease (n = 14). The median progression-free survival (PFS) was 2.7 months and median overall survival was 14.0 months. Two patients experienced a grade 4 thromboembolic event. Additional toxicities included one of each grade 3 gastrointestinal, grade 3 neurologic, and grade 3 genitourinary. CONCLUSION: A regimen of alternating megestrol acetate and tamoxifen is active in treating endometrial cancer and may result in a prolonged complete response (CR) in some patients.