Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.

A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

OBJECTIVE: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. PATIENTS & METHODS: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. RESULTS: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. CONCLUSIONS: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.

A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study.

BACKGROUND: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. PATIENTS AND METHODS: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. RESULTS: The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. CONCLUSIONS: The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. TRIAL REGISTRATION: Clinicaltrials.gov, NCT 01666444.

A phase I trial of paclitaxel, cisplatin, and veliparib in the treatment of persistent or recurrent carcinoma of the cervix: an NRG Oncology Study (NCT#01281852).

Background: Preclinical studies demonstrate poly(ADP-ribose) polymerase (PARP) inhibition augments apoptotic response and sensitizes cervical cancer cells to the effects of cisplatin. Given the use of cisplatin and paclitaxel as first-line treatment for persistent or recurrent cervical cancer, we aimed to estimate the maximum tolerated dose (MTD) of the PARP inhibitor veliparib when added to chemotherapy. Patients and methods: Women with persistent or recurrent cervical carcinoma not amenable to curative therapy were enrolled. Patients had to have received concurrent chemotherapy and radiation as well as possible consolidation chemotherapy; have adequate organ function. The trial utilized a standard 3 + 3 phase I dose escalation with patients receiving paclitaxel 175 mg/m2 on day 1, cisplatin 50 mg/m2 on day 2, and escalating doses of veliparib ranging from 50 to 400 mg orally two times daily on days 1-7. Cycles occurred every 21 days until progression. Dose-limiting toxicities (DLTs) were assessed at first cycle. Fanconi anemia complementation group D2 (FANCD2) foci was evaluated in tissue specimens as a biomarker of response. Results: Thirty-four patients received treatment. DLTs (n = 1) were a grade 4 dyspnea, a grade 3 neutropenia lasting ≥3 weeks, and febrile neutropenia. At 400 mg dose level (DL), one of the six patients had a DLT, so the MTD was not reached. Across DLs, the objective response rate (RR) for 29 patients with measurable disease was 34% [95% confidence interval (CI), 20%-53%]; at 400 mg DL, the RR was 60% (n = 3/5; 95% CI, 23%-88%). Median progression-free survival was 6.2 months (95% CI, 2.9-10.1), and overall survival was 14.5 months (95% CI, 8.2-19.4). FANCD2 foci was negative or heterogeneous in 31% of patients and present in 69%. Objective RR were not associated with FANCD2 foci (P = 0.53). Conclusions: Combining veliparib with paclitaxel and cisplatin as first-line treatment for persistent or recurrent cervical cancer patients is safe and feasible. Clinical trial information: NCT01281852.

A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: a Gynecologic Oncology Group study.

OBJECTIVES: Vascular endothelial growth factors (VEGF) and their receptors have a critical role in stimulating the growth of ovarian cancer cells. Motesanib is a small molecule inhibitor of multiple receptor tyrosine kinases including VEGF receptors 1-3, as well as c-KIT and platelet-derived growth factor which are related to the VEGF family. PATIENTS AND METHODS: Twenty-two eligible patients with recurrent ovarian, fallopian tube or primary peritoneal carcinoma were treated with an oral daily dose of 125 mg of motesanib. Peripheral blood was analyzed for circulating tumor cells (CTC) and circulating endothelial cells/circulating endothelial progenitors (CEC/CEP), VEGF levels and cell-free circulating DNA (cfDNA). RESULTS: The study was abruptly halted after four patients developed posterior reversible encephalopathy syndrome. One patient had a partial response and seven patients had stable disease at the time they were removed from study treatment. Twelve of the 22 patients (50%) had indeterminate responses at trial closure. Early closure without clinical efficacy data precludes meaningful correlative studies. CONCLUSIONS: The serious central nervous system toxicity observed in patients with recurrent ovarian cancer precluded full examination of this agent in this population. There were no clear cut explanations for the high incidence of this known class effect in the study population compared with patients with other cancers.

Do uterine risk factors or lymph node metastasis more significantly affect recurrence in patients with endometrioid adenocarcinoma?

OBJECTIVES: Controversy continues over the importance of lymph node (LN) status in treating and predicting recurrence in endometrial cancer. Several predictive models are available which use uterine factors to stratify risk groups. Our objective was to determine how LN status affects recurrence and survival compared to uterine factors alone. METHODS: A retrospective review was performed of patients undergoing complete surgical staging for clinical stage 1 endometrioid adenocarcinoma of the uterus. Patients were assessed based on PORTEC 1 high intermediate risk (H-IR) criteria (2 factors : age>60, grade 3, >50% DOI), GOG-99 H-IR criteria (age >70+1 factor, age 50-70+2 factors, any age +3 factors: grade 2 or 3, LVSI, >50% DOI), and PORTEC 2 criteria. Rates of nodal involvement, recurrence rates, PFS, and OS were compared. RESULTS: We identified 352 clinical stage I patients with positive LN in 24% (87). 175 patients met PORTEC 1 eligibility and 66 met H-IR criteria. Rates of LN positivity were similar among groups (18.4% vs 19.7%, p=0.83) but recurrence rates were dissimilar (7.4% vs 27.3%, p=0.0004). Only 93 met PORTEC 2 criteria for treatment with no association between LN status, recurrence, and eligibility. 188 patients met H-IR eligibility criteria for GOG-99 with LN positive and recurrence rates higher in the H-IR group compared to GOG-99 eligible (34.6% vs 16.3%, p=0.0004, 28.3% vs. 10.6%, p=0.0002). CONCLUSIONS: Patients with H-IR disease based on uterine characteristics alone have substantial risk of nodal involvement. Knowledge of LN status may better define risk, prognosis, and postoperative treatment.

Human immunodeficiency virus testing in patients with invasive cervical carcinoma: a prospective trial of the gynecologic oncology group.

To determine the frequency of positive human immunodeficiency virus (HIV) serostatus among North American women 50 years of age or younger with invasive cervical cancer and to define their tolerance to treatment. Consenting patients with newly diagnosed invasive cervical cancer, age 50 or younger were tested by enzyme-linked immunosorbent assay. The study design anticipated that approximately 3% of patients would be HIV positive. After the accrual of 913 eligible and evaluable patients, interim analysis revealed that only 9/913 ( approximately 1%) patients were HIV seropositive, indicating that it would not be feasible to achieve the study objective. The study was closed to further accrual. Between 1994 and 1997, the frequency of positive HIV serostatus among North American women with newly diagnosed cervical cancer was quite low. As a consequence, no evaluation of response to treatment or treatment tolerance can be made.

Surgical management of early-stage endometrial cancer in the elderly: is laparoscopy feasible?

OBJECTIVE: To give insight into the utility of laparoscopic staging of endometrial cancer in the elderly population by reviewing the surgical management of clinically stage I endometrial cancer patients. METHODS: A retrospective analysis evaluating patients that were > or =65 years old and had planned laparoscopic staging, traditional staging via a laparotomy, or a transvaginal hysterectomy as management of their early endometrial cancer. The laparoscopic group had complete staging with bilateral pelvic and paraaortic lymph node dissections and was compared to the group who had staging performed via laparotomy. Patients were identified by our institution's database and data were collected by review of their medical records. Data were collected on demographics, pathology, and procedural information including completion rates, operating room (OR) time, estimated blood loss (EBL), transfusions, lymph node count, complications, and length of stay. Associations between variables were analyzed by Student's t tests and chi(2) testing using Excel v. 9.0. RESULTS: From February 25, 1994, through December 21, 2000, 125 elderly patients were identified. Sixty-seven patients had planned laparoscopic staging (Group 1), 45 patients had staging via planned laparotomy (Group 2), and 13 patients had a transvaginal hysterectomy (Group 3). Group 1 and Group 2 were compared regarding surgical and postoperative data. Age was not different between these groups (75.9 vs 74.7 years, P = NS). Quetelet index was also similar (29.4 vs 29.9, P = NS) 32.8% of Group 1 had > or =1 previous laparotomy compared to 51.1% in Group 2 (P = NS). In Group 1, 53/67 (79.1%) had stage I or II disease compared to 29/45 (64.4%) in Group 2 (P = NS). Laparoscopy was completed in 52/67 (77.6%) attempted procedures. The reasons for conversion to laparotomy were obesity 7/67 (10.4%), bleeding 4/67 (6.0%), intraperitoneal cancer 3/67 (4.5%), and adhesions 1/67 (1.5%). OR time was significantly longer in successful Group 1 patients compared to Group 2 patients (236 vs 148 min, p = 0.0001). EBL was similar between these groups (298 vs 336 ml, P = NS). Ten of 52 (19.2%) of successful Group 1 patients received a blood transfusion compared to 1/45 (2.2%) of Group 2 patients (P < 0.0001). Pelvic, common iliac, and paraaortic lymph node counts were similar between successful Group 1 patients and those in Group 2 combined with those that received a laparotomy in Group 1 (17.8, 5.2, 6.6 vs 19.1, 5.1, 5.2, P = NS). Length of stay (LOS) was significantly shorter in Group 1 versus Group 2 (3.0 vs 5.8 days, P < 0.0001). There were less fevers (6.0 vs 15.6%, P = 0.01), less postoperative ileus's (0 vs 15.6%, P < 0.001), and less wound complications (6.0 vs 26.7%, P = 0.002) in Group 1 compared to Group 2. Group 3 average age was 77.5 years. Concurrent medical comorbidities were the main reason for the transvaginal approach. OR time averaged 104.5 min. The average length of stay was 2.1 days with no procedural or postoperative complications. CONCLUSIONS: The favorable results from this retrospective study refute the bias that age is a relative contraindication to laparoscopic surgery. Laparoscopic staging was associated with an increased OR time and an increased rate of transfusion but equivalent blood loss and lymph node counts. Possible advantages are decreased length of stay, less postoperative ileus, and less infections complications. Transvaginal hysterectomy still remains a proven option for women with serious comorbid medical problems with short OR times, minimal complications, and short lengths of stay.

Ovarian cancer metastatic to the brain: what is the optimal management?

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.

Laparoscopic pelvic and paraaortic lymph node dissection: analysis of the first 100 cases.

OBJECTIVE: The aim of this study was to analyze the first 100 cases of planned laparoscopic pelvic and paraaortic lymph node dissection (LND) done for staging of gynecologic cancers. The goal of the study was to assess prognostic factors for conversion to laparotomy and document complications. METHODS: A retrospective review of patients who had planned laparoscopic bilateral pelvic and bilateral paraaortic LND for staging of their gynecologic cancer was performed. Patients were identified by our institutional database and data were collected by review of their medical records. Data were obtained regarding demographics, stage, histology, length of stay, and procedural information including completion rates, operating room time, estimated blood loss, assistant, lymph node count, and complications. Associations between variables were analyzed using Student t tests, analysis of variance, and chi(2) testing (Excel v7.0). RESULTS: A total of 103 patients were identified from 12/15/95 to 8/28/00. Demographics included mean age of 66.2 (25-92) and mean Quetelet index (QI) of 30.8 (15.9-56.1). A total of 34/103 (33.0%) had > or =1 previous laparotomy. Ninety-five patients had endometrial cancer and 8 had ovarian cancer. Eighty-six of 103 (83.5%) were stage I or II. The length of stay was shorter for those who had laparoscopy than for those who needed conversion to laparotomy (2.8 vs 5.6 days, P < 0.0001). Laparoscopy was completed in 73/103 (70.9%) of the cases. Completion rates were 62/76 (81.6%) with QI < 35 vs 11/27 (40.7%) with QI > or = 35, P < 0.001. Significantly more patients had their laparoscopy completed when an attending gynecologic oncologist was the first assistant compared to a fellow or a community obstetrician/gynecologist (92.9%, 69.0%, 64.5%, P < 0.0001). The top three reasons for conversion to laparotomy were obesity, 12/30 (29.1%), adhesions, 5/30 (16.7%), and intraperitoneal disease, 5/30 (16.7%). Pelvic, common iliac, and paraaortic lymph node counts did not differ when compared to those of patients who had conversion to laparotomy (18.1, 5.1, 6.8 vs 17.3, 5.7, 6.8, P = ns). Complications included 2 urinary tract injuries, 2 pulmonary embolisms, and 6 wound infections (all in the laparotomy group). Two deaths occurred, 1 due to a vascular injury on initial trocar insertion and 1 due to a pulmonary embolism after a laparotomy for bowel herniation through a trocar incision. CONCLUSION: Laparoscopic bilateral pelvic and paraaortic LND can be completed successfully in 70.9% of patients. Age, obesity, previous surgery, and the need to perform this procedure in the community were not contraindications. Advantages include a shorter hospital stay, similar nodal counts, and acceptable complications.

A retrospective analysis of radical hysterectomies done for cervical cancer: is there a role for the Pfannenstiel incision?

OBJECTIVE: The goal of this work was to review patients with early-stage cervical cancer undergoing radical hysterectomy, comparing Pfannenstiel and vertical midline incisions for surgical feasibility, complications, and length of stay. METHODS: Patients were identified by searching our institutional database. Data were collected from review of each patient's medical record, including demographics, cancer stage, histology, procedural information, length of stay, and complications. Associations between variables were studied using chi(2) and two-tailed t tests. Multivariate analysis was performed using logistic regression. RESULTS: Between March 1996 and June 2000, 113 patients from the University and Presbyterian Hospitals, Oklahoma City, Oklahoma, underwent radical hysterectomy and pelvic and paraortic lymph node dissection with records available for review. Group 1 consisted of 40 patients who had vertical incisions and group 2 consisted of 73 patients who had Pfannenstiel incisions. There was no difference in race, number of previous abdominal surgeries, distribution of stage, histology, percentage of type III hysterectomies, estimated blood loss, nodal counts, pathologic margin positivity, and postoperative complications among the two groups. Group 2 were younger (41.6 vs 46.5, P = 0.02) and had a lower average QI than group 1 (24.9 vs 28.9, P = 0.001). Group 2 also had a shorter average hospital stay (4.6 days vs 5.8 days, P = 0.04) and shorter operative time (215 min vs 273 min, P = 0.09). Multivariate analysis resulted in Pfannenstiel incisions (P = 0.002), younger age (P = 0.004), and smaller body mass index (P = 0.01) being significant predictors of length of stay. CONCLUSIONS: Pfannenstiel incisions are feasible without increased morbidity and equal nodal retrieval as compared with vertical midline incisions in patients with early-stage cervical cancer. Pfannenstiel incisions may offer an advantage besides cosmesis in the form of shorter operating room time and earlier discharge from the hospital.

Treatment of cervical intraepithelial neoplasia levels 2 and 3 with adapalene, a retinoid-related molecule.

OBJECTIVES: This study examined dose scheduling, safety, and efficacy of adapalene in the treatment of CIN2 and CIN3. METHODS: Patients were instructed on insertion and removal of an adapalene delivery system. Treatment regimens of 4, 8, and 14 days were utilized. Biopsies were performed on day 90 to assess efficacy. Safety was evaluated with toxicity questionnaires and patient interviews. RESULTS: Two patients treated for 4 days had stable disease. Twenty-three patients treated for 8 days demonstrated an overall 61% (14 of 23) response rate. Twenty-four patients treated for 14 days had an overall 38% (9 of 24) response rate. No patient had disease progression. Compared to untreated historical controls, significantly improved efficacy was demonstrated for patients with CIN2. Patients with CIN3 had improved efficacy, though not statistically significant. CONCLUSIONS: The lack of side effects and practicality of home use make adapalene a nontoxic and safe alternative to surgical therapy in patients with CIN2 and CIN3.

Cisplatin and pentoxifylline in advanced or recurrent squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group.

OBJECTIVE: The aim of this study was to determine the antitumor activity and toxicity of cisplatin and pentoxifylline in previously treated patients with squamous cell carcinoma of the cervix. METHODS: A Gynecologic Oncology Group (GOG) Phase II trial of recurrent squamous cell cervical cancer using standard GOG response and toxicity criteria was performed. RESULTS: A total of 47 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered. The starting dose was 75 mg/m(2) of cisplatin every 21 days and 1600 mg of pentoxifylline PO every 8 h for nine doses during each course. Forty patients were evaluable for response and 44 were evaluable for toxicity. Of the 40 evaluable patients, 37 had received prior radiotherapy and 35 had received prior chemotherapy. A median of three courses were given (range: 1-7). Among evaluable patients, 1 had a complete response (2.5%) and 3 had a partial response (7.5%) for an overall objective response rate of 10%. The complete responder had not previously had chemotherapy. Grade 3 or 4 toxicity was predominantly nausea and vomiting (32%) and hematologic toxicity (23%). CONCLUSIONS: The combination of cisplatin and pentoxifylline at the dose and schedule tested has limited activity in previously treated advanced or recurrent cervical cancer.

Cost analysis of laparoscopy versus laparotomy for early endometrial cancer.

OBJECTIVE: The purpose of this study was to determine whether the cost associated with treatment of early stage endometrial cancer differs on the basis of the surgical approach. METHODS: A retrospective analysis was performed on a series of women with presumed early stage endometrial cancer treated between 5/96 and 1/99 at a single institution. The patients were grouped according to the surgical approach utilized. The first group consisted of 19 patients who underwent laparoscopic assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and laparoscopic pelvic and paraaortic lymph node dissection. The second group consisted of 17 patients who underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymph node dissection. The two groups were compared with a two-tailed Student t test. Variables analyzed included age, Quetelet index (QI), surgical stage, number of lymph nodes, surgical time, estimated blood loss, postoperative complications, number of days in the hospital, and costs. The cost analysis was divided into room and board, pharmacy, ancillary services, operating room equipment, operating room services, and anesthesia. RESULTS: Both groups were similar in age, QI, and distribution of stage. The laparoscopic group required more OR time (237 vs 157 min, P < 0.001); however, the number of lymph nodes, estimated blood loss, and postoperative complications were not significantly different between the groups. The laparoscopic group required significantly shorter hospitalization than the laparotomy group (3.7 vs 5.2 days, P < 0.001) resulting in less room and board ($299 vs $454, P < 0.001) as well as pharmacy costs ($443 vs $625, P < 0.02). The cost of anesthesia was higher in the laparoscopic group ($696 vs $444, P < 0.001) but the costs of OR equipment, OR services, and total costs were not statistically different between the groups. CONCLUSION: Laparoscopic surgical management of early stage endometrial cancer is feasible with minimal morbidity. The cost savings of early hospital discharge is offset by longer surgical time and higher anesthetic costs. The total costs for each surgical approach are not statistically different. The presumed advantages of less pain, early resumption of normal activities, and overall improvement of quality of life await further investigation.

Laparoscopic paraaortic lymphadenectomy using laparosonic coagulating shears.

With marked innovations in endosurgical instrumentation, operative laparoscopy to include lymphadenectomy has become feasible and has a valuable role in the management of gynecologic malignancy. We used laparosonic coagulating shears (LCS) for laparoscopic paraaortic lymphadenectomy in two women with cervical carcinoma. Operating times for the laparoscopic portion were 55 and 65 minutes and blood loss was 20 and 30 ml, respectively. No surgical complications were encountered. Lymphatic tissues were evaluated histologically and no thermal artifacts were identified. The major advantage of the ultrasonically activated scalpel of the LCS is the ability to cut and coagulate tissues simultaneously without electrical current. The LCS may afford the surgeon a greater margin of safety than unipolar electrocoagulation scissors by eliminating potential thermal and electrical injury to vital structures. Ultrasonic-activated technology deserves extended clinical investigation in laparoscopic lymphadenectomy to substantiate our preliminary findings, as well as to explore its potential in gynecologic oncology.

Primary endodermal sinus tumor of the vulva: a case report and review of the literature.

BACKGROUND: Extragonadal endodermal sinus tumors arising in the external genitalia represent an exceedingly rare malignancy in women. Six cases of endodermal sinus tumors of the vulva have been reported to date, with three cases failing to respond to conservative surgery and vincristine-based chemotherapy. We report a seventh case of vulvar endodermal sinus tumor that was treated with radical surgery and platinum-based chemotherapy. CASE: RT is an 18-year-old female who presented with a vulvar mass that was diagnosed as endodermal sinus tumor at the time of biopsy. She was subsequently treated with modified radical vulvectomy and ipsilateral groin lymphadenectomy, followed by bleomycin, etoposide, and cisplatin chemotherapeutic regimen. She has since remained free of disease for 18 months as evidenced by serum alpha-fetoprotein and physical exam at 18 months. CONCLUSIONS: Vulvar endodermal sinus tumors represent a very small number of germ cell tumors in women. Based on the previous accounts, this disease appears to be more fatal than endodermal sinus tumor arising at other sites. These tumors also have a predilection for local metastasis. Due to the previous accounts, we chose to treat this patient with radical surgery and platinum-based chemotherapy. This treatment regimen has resulted in a disease-free state for 18 months.

P-glycoprotein as a prognostic indicator in pre- and postchemotherapy ovarian adenocarcinoma.

P-glycoprotein (P-gp) is a plasma membrane efflux transporter that maintains the intracellular concentration of chemotherapeutic agents at low levels. Since the clinical outcome of ovarian adenocarcinoma depends largely on its response to chemotherapy, an objective assessment of P-gp expression could serve as a prognostic indicator. Eighty-five patients were studied. Available tissue sections from the primary tumor (n = 75) and persistent or recurrent lesions (n = 19) were tested with anti-P-gp (JSB-1) monoclonal IgG. Multivariate survival analysis using Cox regression was performed controlling for fixed covariates (age, surgical stage, and presence of residual tumor) and included occurrence of postchemotherapy tumors and P-gp positivity in postchemotherapy neoplasms as time-dependent variables. P-gp was expressed in 49 prechemotherapy (65.3%) and 14 postchemotherapy (73.7%) tumors. After controlling for potentially confounding factors, patients with P-gp-positive postchemotherapy neoplasms were at three times greater risk of dying within 2 years than their counterparts with P-gp-negative tumors (hazard ratio = 3.1: 95% confidence interval = 1.2, 9.1; p < 0.05). Detection of P-gp-expressive subclones can serve as an independent poor prognostic indicator for patients with postchemotherapy tumors.

Immunohistochemical assessment of proliferation markers and altered gene expression in archival specimens of ovarian epithelial tumors.

Recently reported morphologic and molecular genetic evidence suggests that some ovarian carcinomas arise from their benign and low malignant potential (LMP) counterparts. In order to help reach a better understanding of ovarian tumorigenesis, we studied a wide range of gene products involved in cellular growth regulation in archival material obtained from three groups of tumors with graduated malignant potential. Immunohistochemical staining was performed for Ki-67, proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), HER-2/neu-encoded receptor protein, p53 gene product, and multidrug resistance gene product (P-glycoprotein). The expression of EGFR, HER-2/neu-encoded receptor protein, and mutant p53 product was significantly lower in LMP tumors than in carcinomas (p < 0.05). HER-2/neu immunopositivity was more prevalent in adenocarcinomas than in LMP tumors, and the proportion of HER-2/neu-positive adenocarcinomas increased with the progression of the disease. The staining differences between LMP tumors and adenocarcinomas with antibodies against Ki-67, PCNA, and P-glycoprotein were not statistically significant. Immunohistochemical detection of EGFR, HER-2/neu, and p53 in ovarian epithelial tumor is relevant to ovarian tumorigenesis. It could serve as a powerful tool for the pursuit of retrospective studies focused on these important biologic markers.

Hepatic venoocclusive disease as a complication of whole abdominopelvic irradiation and treatment with the transjuglar intrahepatic portosystemic shunt: case report and literature review.

We report the novel use of the transjugular intrahepatic portosystemic shunt (TIPS) procedure for the treatment of intractable ascites due to hepatic venooclusive disease as a result of whole abdominopelvic radiotherapy. A patient with Stage III endometrioid carcinoma of the endometrium treated with postoperative whole abdominopelvic irradiation developed intractable ascites. Multiple paracenteses and computerized tomography were negative for recurrent carcinoma. Liver biopsy demonstrated hepatic venoocclusive disease, a rare complication of therapeutic radiation involving the liver. Successful relief of ascites and its adverse symptomology were achieved with the transjugular intrahepatic portosystemic shunt. Relevant literature regarding the pathogenesis, prognosis, and treatment of radiotherapy-related hepatic venoocclusive disease are reviewed.

Use of ileocecal continent urinary reservoir in patients with previous pelvic irradiation.

OBJECTIVE: To assess the results of the use of ileocecal continent urinary reservoirs in patients with previous pelvic irradiation. METHODS: A retrospective analysis for morbidity and clinical outcome was undertaken for 37 female patients with prior therapeutic pelvic irradiation who underwent continent urinary diversion with a detubularized right colonic segment as the urinary reservoir, a plicated ileocecal valve as the continence mechanism, and a tapered distal ileum for efferent catheterization. RESULTS: Thirty-one patients had persistent or recurrent pelvic malignancies, 17 of whom had total pelvic exenteration and 14 had anterior exenteration. The remaining 6 patients had radiation-induced vesicovaginal fistulas without evidence of recurrence and underwent urinary diversion alone. Follow-up ranged from 2 to 33 months (median 11 months). Postoperative radiographic evaluation revealed no evidence of urinary extravasation. Of the 74 implanted ureters, 4 had reflux (5%), 2 developed stricture (3%), and 5 had mild to moderate hydronephrosis (7%). All patients achieved daytime continence with catheterization intervals of 3-8 hr (median 4 hr) and capacities of 200-1000 cc (median 500 cc). Nighttime continence was reported by 33 of 37 patients (89%). Reoperation was required in 3 patients (8%), 2 with stoma stenosis and 1 with difficulty in catheterization. CONCLUSIONS: The use of the ileocecal continent urinary reservoir in patients with previous pelvic irradiation achieves results comparable to those reported for nonirradiated patients, thus supporting its use in this select group of patients.