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Background Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival. Methods From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the Iog-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided. Results The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively). Conclusion Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.

Background: The role of systematic aortic and pelvic lymphadenectomy in patients with optimally debulked advanced ovarian cancer is unclear and has not been addressed by randomized studies. We conducted a randomized clinical trial to determine whether systematic aortic and pelvic lymphadenectomy improves progression-free and overall survival compared with resection of bulky nodes only. Methods: From January 1991 through May 2003, 427 eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-C and IV epithelial ovarian carcinoma were randomly assigned to undergo systematic pelvic and para-aortic lymphadenectomy (n = 216) or resection of bulky nodes only (n = 211). Progression-free survival and overall survival were analyzed using a log-rank statistic and a Cox multivariable regression analysis. All statistical tests were two-sided. Results: After a median follow-up of 68.4 months, 292 events (i.e., recurrences or deaths) were observed, and 202 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for first event was statistically significantly lower in the systematic lymphadenectomy arm (hazard ratio [HR] = .75, 95% confidence interval [CI] = 0.59 to 0.94; P = .01) than in the no-lymphadenectomy arm, corresponding to 5-year progression-free survival rates of 31.2 and 21.6% in the systematic lymphadenectomy and control arms, respectively (difference = 9.6%, 95% CI = 1.5% to 21.6%), and to median progression-free survival of 29.4 and 22.4 months, respectively (difference = 7 months, 95% CI = 1.0 to 14.4 months). The risk of death was similar in both arms (HR = 0.97, 95% CI = 0.74 to 1.29; P = .85), corresponding to 5-year overall survival rates of 48.5 and 47%, respectively (difference = 1.5%, 95% CI = -8.4% to 10.6%), and to median overall survival of 58.7 and 56.3 months, respectively (difference = 2.4 months, 95% CI = -11.8 to 21.0 months). Median operating time was longer, and the percentage of patients requiring blood transfusions was higher in the systematic lymphadenectomy arm than in the no-lymphadenectomy arm (300 versus 210 minutes, P

Draining the space created during a minilaparotomy can reduce the number of surgical complications as well as the length of hospital stay, according to a study of 72 women who had this operation. The women whose surgical incision was drained had fewer complications and shorter hospital stays than women who did not receive this postoperative treatment. The incision created during a minilaparotomy contains a small space that can grow bacteria.

Patients with pelvic cancer who have radiation treatment before surgery may have a worse outcome from surgery, according to a study of 77 patients who had pelvic surgery. Of 36 who had radiation treatment before surgery, 30% developed problems with the anastomosis that was created between the colon and rectum after surgeons removed much of their colon.

Autologous blood transfusion may be beneficial for women having a hysterectomy for cervical cancer. In a study of 156 women, only 12% of the women who received autologous blood required further blood transfusions compared to 30% of those who did not.

Non-surgical methods may be effective in managing the urinary complications of a Miami pouch. The Miami pouch is a surgical technique used to create an artificial bladder in cancer patients who have had their bladder and possibly other abdominal organs removed. In a study of 77 patients who had a Miami pouch, the most common complications were obstruction of the ureters, difficult catheterization to remove urine from the pouch, and kidney infection. Eighty percent were treated non-surgically, with stents, balloon dilatation, catheters and antibiotics.

The sacrospinous ligament fixation procedure to correct vaginal and uterine prolapse may be effectively performed by gynecology residents and should be taught in residency programs. The surgery is commonly performed to support pelvic organs that descend into the vagina. Doctors reviewed the medical records of 160 patients who underwent the surgery at Jackson Memorial Hospital in Miami, FL. The surgery was successful in most patients, and complications were not significant. Several years after surgery, 85% of patients had no recurrence of any defect in pelvic support.

Thorough dissection may be necessary during surgery to remove remnants of ovarian tissue left behind from previous operations and to avoid injuring the ureters. Remnants of ovarian tissue may resume the functions of the removed ovary and develop cysts that cause pain. Researchers reviewed eight cases of ovarian remnant syndrome at a Miami hospital. Most patients described their abdominal pain as persistent, dull, and localized rather than as sharp and intermittent. All patients had surgery to remove residual ovarian tissue. Ovarian remnant syndrome is most commonly treated by surgery, but may still recur in 8% to 10% of cases. The use of ultrasound before surgery may be helpful in locating tissue masses and determining their size. Clomiphene administration may help to identify an ovarian tissue mass before surgery by making it larger.

Background. This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation-modulation effects of recombinant [alpha]-IFN and [beta]-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated. Methods. Control cells and cells pretreated with either [alpha]-IFN or [alpha]-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear-quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents. Results. The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments. Conclusions. Recombinant [alpha]-IFN and [beta]-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations. Cancer 1993; 71:3717-25.

Background. Interferon (IFN) has been reported to increase hormone receptor expression in breast cancer cells and to sensitize them to antiproliferative hormones. Endometrial cancer cells with high progesterone receptor (PR) level respond better to progesterone therapy than cells with either low or absent PR level. The effect of four different interferons ([Alpha] and [Beta], both natural [n] and recombinant [r]) on cell proliferation and steroid receptor levels was investigated in the PR positive AE-7 human endometrial cancer cell line over a period of 12 days. Methods. Cells were exposed to 10,100 and 1000 IU/ ml of each IFN either for 3 days or continuously for 12 days. Hormone receptors were determined by the monoclonal enzyme immunoassay. Chemosensitivity was evaluated with the adenosine triphosphate-cell viability assay. Results. AE-7 has a low level of estrogen receptors, which was not significantly affected by IFN exposure. The four IFN showed significantly enhanced PR levels over 12 days in both the 3-day and continuous-exposure experiments. No significant difference of PR enhancement was observed between 3 days and continuous exposure to IFN. This increase of receptors did not appear to be dose related. IFN enhanced PR level to a maximum level of about two times control cells. IFN did not produce significant cytotoxicity. Antiproliferative activity was observed with nIFN[Beta] and rIFN[Beta] at 1000 IU/ml dose in continuous-exposure experiments, which showed survival values of 79% and 69% respectively, compared with control at day 12. Conclusions. These preliminary data on PR expression modulation support other studies, which have shown that IFN modulate hormone receptor expression and, therefore, may play a role in the treatment of endometrial cancer. Cancer 1993; 71:2776-81.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1067/mob.2000.105403 Byline: Roberto Angioli, Orlando Gomez-Marin, Guilherme Cantuaria, Mary J. O'Sullivan Keywords: Episiotomy; forceps; perineal lacerations; vacuum; vaginal delivery Abstract: Objective: After childbirth-related third- or fourth-degree perineal lacerations, the estimated incidence of wound disruption, fecal incontinence, or fistula ranges from 1% to 10%. Risk factors associated with severe laceration were analyzed at a single large teaching institution. Study Design: This study consisted of an analysis of data from the delivery database of Jackson Memorial Hospital, University of Miami, from 1989 through 1995. Included were vaginal deliveries for which complete information was available on maternal age, parity, ethnicity (white, black, or Hispanic), birth weight, episiotomy versus no episiotomy, type of episiotomy, and delivery (normal spontaneous, vacuum, or forceps). Multiple gestations, cases of shoulder dystocia, cesarean deliveries, patients with a history of cesarean delivery, and babies weighing Author Affiliation: Miami, Florida From the Departments of Obstetrics and Gynecology,.sup.a Epidemiology and Public Health,.sup.b and Pediatrics,.sup.c Jackson Memorial Hospital, University of Miami School of Medicine Article Note: (footnote) [star] Reprint requests: Roberto Angioli, MD, Department of Obstetrics and Gynecology, University of Miami School of Medicine (D-52), 1611 NW 12th Ave, ET 7007, Miami, FL 33136.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.05.018 Byline: Innocenza Palaia (a), Roberto Angioli (b), Filippo Bellati (a), Stefano Basile (a), Carla Rabitti (c), Pierluigi Benedetti Panici (a) Abstract: Palmar plantar erythrodysesthesia is a cutaneous drug reaction induced by chemotherapy. We present a case of a patient with neurosensorial deficit affected by ovarian cancer who experienced a painless necrosis of a distal phalange of the hand during treatment with pegylated liposomal doxorubicin. Palmar plantar erythrodysesthesia may be underestimated by physicians in paucisymptomatic patients. Author Affiliation: (a) Department of Obstetrics and Gynecology, 'La Sapienza' University, Rome, Italy (b) Departments of Obstetrics and Gynecology (c) Pathology, Campus BioMedico University, Rome, Italy Article History: Received 9 December 2005; Revised 19 April 2006; Accepted 11 May 2006

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Abstract: Background: This is the first case–control study on the use of a fibrin sealant (Tisseel®) on uterine suture during laparoscopic myomectomy (LM), with the primary endpoint to evaluate the intraoperative bleeding and postoperative blood loss. In addition, we evaluated the time required to achieve hemostasis using Tisseel® and how much it can influence operative time. Methods: From December 2009 to January 2011, consecutive patients older than 18 years with symptomatic isolate intramural myoma with maximal diameter ≤6 cm and ≥4 cm and with a sonographically diagnosed free myometrium margin ≥0.5 cm were included in the study. We selected from our institute’s database a group of consecutive patients with homogeneous features of the study group, who underwent laparoscopic myomectomy without Tisseel® application. Results: Fifteen women with symptomatic myoma were enrolled in the study (group A). Regarding the control group (group B), we selected a homogenous group of 15 patients with the same preoperative characteristics of the study group. Mean operative time was 47.7 min and 62.1 min, for groups A and B respectively (p < 0.05). Mean time required to achieve complete haemostasis was 195.5 s in group A and 361.8 in control group B (p < 0.0001). Mean estimated blood loss was 111.3 mL and 230 mL in groups A and B, respectively (p < 0.05). Mean hemoglobin decrease was 1.36 g/dL and 2.04 g/dL in groups A and B, respectively (p < 0.05). Conclusions: The use of Tisseel® during LM may represent a valid alternative solution for obtaining hemostasis, reducing intra- and postoperative bleeding. Furthermore, it may help the surgeon to obtain a rapid healing of the injured surfaces, probably reducing the use of electrocoagulation and traumatisms.

Carcinosarcomas of the female genital tract are rare tumors with an aggressive clinical behavior. Trastuzumab, a humanized monoclonal antibody, acts by binding to HER2neu extracellular domain and exhibits therapeutic efficacy in HER2neu-overexpressing cancers. Two uterine carcinosarcomas (UMMT-ARK-1, UMMT-ARK-2) and 2 ovarian carcinosarcomas (OMMT-ARK-1, OMMT-ARK-2) were established as primary tumor cell lines in vitroand evaluated for HER2neu expression by immunohistochemistry, fluorescent in situhybridization analysis, quantitative real-time polymerase chain reaction, and for membrane-bound complement regulatory proteins CD46, CD55, and CD59 by flow cytometry. Sensitivity to trastuzumab-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was studied in 5-hr chromium release assays. HER2neu expression was demonstrated in OMMT-ARK-1 and OMMT-ARK-2. OMMT-ARK-2 demonstrated an amplification of the c-erbB2 gene by fluorescent in situhybridization analysis and a high sensitivity to ADCC (mean killing, 45.6; range, 32.3–72.6). A lower level of killing was detected against the fluorescent in situhybridization analysis-negative OMMT-ARK-1 cell line (mean, 26.5; range, 21.0–31.8). CD46, CD55, and CD59 membrane-bound complement regulatory proteins were expressed at high levels in all primary mixed müllerian tumor cell lines, and all these tumors were found to be highly resistant to complement-dependent cytotoxicity with or without trastuzumab. Addition of untreated and heat-inactivated plasma did not significantly decrease ADCC against OMMT-ARK-2 cell line, suggesting that while the cell line is highly resistant to complement, irrelevant IgG does not significantly alter the ability of trastuzumab to mediate ADCC. Our results suggest that HER2neu may represent a novel target for the immunotherapy of a subset of human carcinosarcomas refractory to salvage chemotherapy.

Pelvic and para-aortic lymphnode sampling is an integral part of the staging system of ovarian cancer. The issue concerning lymphadenectomy in the management of the disease is still debated, however. The purpose of this paper is to review the role of systematic lymphadenectomy in patients affected by early and advanced-stage ovarian cancer.

To evaluate whether the frequency of overactive bladder (OAB) symptoms increases in menopause patients after a tension-free vaginal tape (TVT) procedure, and to determine if topical estrogen therapy can help prevent these symptoms.

The objective of the current study was to evaluate the incidence of long-term bladder dysfunction after type 3–4 radical hysterectomy in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy (NACT). A case–control study was conducted to evaluate the occurrence of long-term bladder dysfunction in 76 patients with International Federation of Gynecology and Obstetrics Stage IB–IIA (> 4 cm), Stage IIB, and Stage III cervical carcinoma who underwent type 3–4 radical hysterectomy after NACT. Preoperative assessment included acquisition of a standardized urogynecologic history, evaluation of severity of urinary incontinence symptoms, maintenance of a 3-day voiding diary, pelvic examination, urogynecologic physical examination, urodynamic assessment, and estimation of hydronephrosis. Follow-up was carried out at least 12 months after surgery. Urinary symptoms (sensory loss, difficult micturition, severe urinary incontinence) were reported by 20 patients (26%). Eighteen patients (24%) had a normal urodynamic profile, 16 patients (21%) had detrusor overactivity, 22 patients (29%) had urodynamic stress incontinence, 2 patients (2%) had aconctractile detrusor, and 18 patients (24%) had mixed urinary incontinence. The length of vagina removed was significantly greater among patients who had detrusor overactivity and mixed urinary incontinence compared with patients who had a normal diagnosis. The observed rate of bladder dysfunction was higher than the corresponding rate reported in the literature (76%). Three main disturbances were found: detrusor overactivity (21%), mixed urinary incontinence (24%), and de novo stress incontinence (21%). Detrusor overactivity was related to a prevalence of hypertonic bladder. Among patients who underwent type 4 radical hysterectomy, the extent of caudal resection of rectovaginal ligaments and vaginal tissue was found to be more strongly associated with bladder dysfunction than was the extent of lateral parametrial resection. Despite the fact that 76% of patients had abnormal urodynamic parameters, most patients were satisfied with their voiding condition. Cancer 2004. © 2004 American Cancer Society.

The exact role of lymphadenectomy in the management of ovarian cancer has been the object of controversy during recent years. The International Federation of Obstetrics and Gynecology has indicated that pelvic and para-aortic lymph node sampling is an integral part of the staging system of ovarian cancer. On the other hand the advantage of systematic sampling, resection of bulky nodes only, or no lymphadenectomy in terms of recurrence rate and survival of ovarian cancer patients has not yet been clearly defined. Thanks to the analysis of clinical studies on systematic lymphadenectomy, detailed anatomical studies to assess the location of lymph nodes and lymphatic spread have been recently reported.

Objective.Cancer cells have increased rates of glucose metabolism when compared to normal cells. One of the mechanisms proposed for the accelerated glucose use in malignant cells is the overexpression of glucose transporters. In this study we evaluated the expression of the GLUT-1 glucose transporter in borderline and malignant epithelial neoplasms of the ovary.

Since the early 1940s, the incidence of cervical cancer has dramatically decreased due in large part to the work of Papanicolaou and Traut. Successful treatment can now be done using simple or radical surgical intervention for early invasive lesions and radiation therapy for more advanced lesions. However, despite current advances in screening and early treatment, local recurrences still happen and are difficult to treat. The natural history of cervical cancers is that of a slowly growing, locally invasive tumor. As such, it lends itself to radical surgical resection in selected patients prior to distant metastasis. Current advances in intra-operative and postoperative monitoring, as well as improved surgical techniques and devices, have decreased the morbidity and mortality of radical surgical procedures to acceptable levels. Current data associated with these procedures for advanced or recurrent cervical cancer are described. Semin. Surg. Oncol. 16:236–241, 1999. © 1999 Wiley-Liss, Inc.

Objective.The aim of this study was to report the first case of primary uterine angiosarcoma described in a Hispanic American woman and to review the literature on uterine angiosarcomas. We review characteristic presenting symptoms, gross and microscopic pathologic findings, and treatment outcomes where available.

This is a case report and review of the literature on primary melanoma of the cervix. There have been only 26 published cases of primary cervical melanoma and most are poorly documented and doubtful. The patients' ages ranged from 26 to 78 years old with a mean age of 55 ± 13 years. The main presenting symptom was vaginal bleeding (83.0%). The majority of the patients, 88%, presented in stage I or II. Treatment varied from a simple excision of a cervical mass to a radical hysterectomy with lymph node dissection and adjuvant radiation or chemotherapy. Our patient presented with vaginal bleeding and was diagnosed as having stage IIa cervical melanoma. She underwent a radical hysterectomy, partial vaginectomy, and pelvic and paraaortic lymph node dissection. She received adjuvant radiation therapy and her survival was 29 months. The prognosis of primary cervical melanoma is usually poor and unpredictable. We recommend a radical hysterectomy and vaginectomy, if necessary, to obtain negative surgical margins of at least 2 cm. We advocate lymphadenectomy only for grossly positive nodes.

Preliminary clinical data show promising activity regarding the combination of paclitaxel (TaxolTM) (TAX) and doxorubicin (AdriamycinTM) (ADR) in the treatment of breast cancer. This combination needs both further preclinical and clinical investigations to better understand the drug interaction, and to optimize the dose and schedule of these drugs. This study was done to evaluate the combination effect of TAX and ADR in three human breast cancer cell lines. The ATP-Cell-Viability Assay was used to evaluate the chemosensitivity profiles and to obtain dose response curves. For quantitation of synergism and antagonism the median-effect principle was applied and the corresponding combination index values were calculated. Drug synergism/antagonism was shown to be dose-related; synergism was enhanced at higher fractions affected. From this preclinical data, we have concluded that TAX-ADR is highly effective and partly synergisticin vitro. In spite of severe initial toxicities in early clinical trials in metastatic breast cancer patients, further clinical studies appear to be justified in order to define a tolerable dosage.

Purpose.The object of this study is to review our experience and formulate a plan for early recognition and effective management of early and late complications seen in patients who have undergone construction of the ileocolonic continent urinary reservoir.Method.Charts of patients who underwent continent urinary diversion at the Division of Gynecologic Oncology, University of Miami School of Medicine, from 1988 to 1996 were reviewed. We analyzed our data in terms of early and late (beyond 6 weeks) complications resulting directly from the operation or from this form of urinary diversion.Results.Urinary diversion via the continent ileocolonic reservoir has been performed at our institution since February 1988. Sixty-six women have undergone construction of the Miami pouch over the past 81 years. Sixty-three of 66 patients needed a reservoir as a part of total pelvic exenteration for persistent or recurrent gynecologic malignancy. Three patients underwent reservoir construction for repair of vesicovaginal fistula. Sixty-two of 66 patients (95%) have a history of prior pelvic radiation. A total of 35 patients (53%) suffered early complications resulting in an operative mortality rate of 9% (6 of 66 patients). Early complications related to the construction of the reservoir included ureteral stricture/obstruction [10], anastomotic leak [4], reservoir-cutaneous fistula [4], difficulty in catheterization [5], pyelonephritis [10], sepsis [6], DIC [2], and ARDS [1]. Nonsurgical management strategies used for reservoir-related complications in these cases included percutaneous nephrostomy, peripheral hyperalimentation, intravenous antibiotics, and ultrasound-guided catheter placement. Eighty-four percent (16/19) of functional complications of the reservoir resolved with conservative management, whereas 3/19 patients needed surgical revision. One or more late complications (beyond 6 weeks) occurred in 25 patients (37%). Late complications seen included ureteral stricture/obstructions [6], incontinence [8], difficulty in catheterization [7], and urinary stones [4]. Nonsurgical management strategies used included percutaneous nephrostomy, balloon dilation, scheduled catheterization, ultrasound-guided catheter placement, and endoscopic/percutaneous lithotripsy. Four of 25 patients needed reoperation, whereas in 84% (21/25) of patients problems resolved with initial conservative management.Conclusion.Successful conservative therapy constitutes establishment of drainage, adequate nutrition, avoidance of sepsis, close observation, and patience. This article reviews the complications of the continent ileocolonic form of urinary diversion and formulates a treatment outline emphasizing an initial conservative approach that offers optimal management of early and late complications seen in this patient group.

Background.The presence of p53 mutations and associated mutant p53 overexpression has been demonstrated in many cancer systems. Whether the overexpression of mutant p53 represents cause or effect, and whether p53 mutation contributes actively to the malignant phenotype is a matter of controversy. We examined the growth effects of oligonucleotides designed to interfere with p53 expression and/or activity in p53-mutant/overexpressing endometrial cancer cell lines.

U-73, 975 (U-73), U-77, 779 (U-77), and U-80, 244 (U-80) are analogs of the potent antitumor compound CC-1065. This class of drugs act us alkylating agents binding to DNA preferentially. Using the ATP-chemosensitivity assay, this study wus designed to compare the potencies of U-73, U-77, and U-80 with cisplatin (DDP) or adriamycin (DXR) in 10 gynecologic cancer cell lines. The mean IC50s were: U-73, 0.173 2 0.115 ng/ml; U-77, 0.650 ± 0.209 ng/ml; U-80, 3.0 ± 3.0 ng/ml; DDP, 4.40 ± 2.83 μg /ml; and DXR, 0.286 ± 0.040 μg /ml. U-73 appears the most potent analog, being 103 to 104 times more cytotoxic than DDP and DXR. U-77 and U-80 were somewhat comparable, demonstrating approximately 102 to 103 greater potency than DDP and DXR. All the cervical, endometrial, und ovarian cell lines were sensitive to U-73, with decreasing sensitivity to U-77, U-80, DXR, and DDP in that order. U-73 as well as the other analogs appear promising chemotherapeutic agents.

Taxol is an exciting antineoplastic agent with a novel mechanism of action. Taxol has been shown to prolong the G2/M phase of the cell cycle. This cell cycle perturbation has been the explanation given for the radiation-sensitizing effects seen with taxol in vitro. The aim of this study is to evaluate the cell kinetics of the BG-1 human ovarian cancer cell line after treatment with nontoxic doses of taxol and radiation (RT). This cell line was treated in the proliferative state for 90 min with 5 nM taxol and then irradiated 48 hr later with 2 Gy of Cobalt60. Flow cytometric evaluations of cell cycle perturbations were performed at 24-hr intervals from 0 through 216 hr. ATP cell viability assay was performed in parallel to obtain survival data. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. At this nontoxic dose of taxol no cell cycle perturbations as compared to control were seen. Radiation sensitization was still found. Sensitizer enhancement ratio was 2.3 at 10% survival. The RT-related G2/M block peaked at 24 h after RT and then resolved. The combination of taxol and radiation resulted in a large prolonged block in G2/M that did not resolve through the duration of the experiment. In summary, taxol sensitized cells to radiation at a dose that was not cytotoxic and that did not cause cell cycle perturbations. Copyright 1993, 1999 Academic Press

The treatment of adenocarcinoma of the cervix has traditionally followed that of squamous cancer. A 25-year review of 88 radical hysterectomies for Stage IB adenocarcinoma of the cervix at the University of Miami/Jackson Medical Center (UM) is compared to over 1600 cases reported in the literature. Adenocarcinoma represented 10.4% of 978 radical hysterectomies performed at UM from July 1965 to December 1990. In a survey of the literature, patients with Stage IB cervical adenocarcinoma treated by radical surgery alone had a statistically better 5-year survival than those treated by radiation alone (79% vs 67%, respectively; P  0.05). Futhermore, no additional benefit was achieved by combining the two therapeutic modalities. The corrected 5-year survival at UM is 81% for Stage IB adenocarcinoma of the cervix treated with radical hysterectomy, a number consistent with the cumulative data base. Radical surgery is an acceptable primary therapy in Stage IB adenocarcinoma of the cervix. Copyright 1993, 1999 Academic Press

Taxol is an exciting antineoplastic agent with a novel mechanism of action. This study was designed to explore the potential use of taxol as a radiation sensitizer. Three human ovarian cancer cell lines were used: BG-1, SKOV-3, and OVCAR-3. These cell lines were treated in the proliferative and confluent state with taxol doses of 0.0001X, 0.0005X, 0.001X, 0.005X, and 0.01X peak plasma concentration of taxol for 90 min and then irradiated either 24 or 48 hr later. Doses of cobalt were 0, 2, 5, 8, and 10 Gy. ATP bioluminescence assays were performed on Day 7 after irradiation. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with ttest and analysis of variance was performed. Taxol was found to have a significant radiosensitizing effect on all cell lines. Proliferating cells were more sensitive to taxol, radiation, and the combination than confluent cells. Treatment of proliferating cells with taxol 48 hr prior to irradiation had a greater radiosensitizing effect than treatment 24 hr prior to irradiation. In summary, taxol is a potent radiosensitizer in ovarian cancer cell lines and should be considered for further study.

This study evaluates the in vitrosensitivities of 42 ovarian cancer specimens to the new anticancer agent Paclitaxel (taxol, Tx), cisplatin (DDP), and the combination Tx-DDP with the adenosine triphosphate cell viability assay (ATP-CVA). In vitroresponse is defined by ⩾50% ATP decrease compared to untreated controls 6-7 days after drug treatment with 20% of the peak plasma concentration (PPC). Response rates were 12% to Tx, 19% to DDP, and 27% to Tx + DDP. The mean IC50's of Tx, DDP, and the combination Tx-DDP were (2.6×, 1.0×, and 0.38× PPC, respectively). The mean inhibition of cell viability was significantly greater with drug combinations compared to single drugs. In 7/11 tumors synergistic effects and in 2/11 additive effects were found between Tx and DDP. We conclude that based on ATP-CVA in vitroresults, Tx-DDP shows significantly better activity compared to each of the single drugs in ovarian cancer.

The value of DNA index as a prognostic factor in early cervical cancers was investigated. A total of 124 patients who underwent radical hysterectomy for stages IB-IA cervical cancers from 1/1982 to 12/1985 were included. Paraffin blocks were available in only 98 patients for the analysis. After dewaxing, rehydrating, and enzyme disaggregation, cells were subjected to dual parameter flow cytometry. Tumor DNA index was calculated and the results were correlated with 5-year survival, stage, grade, tumor size, nodal metastasis, surgical margins, and lymphovascular invasion. There were 1% hypoploid, 7.3% diploid, 72.9% aneuploid, 16.7% tetraploid, and 2.1% hyperploid. At the end of 5 years, there were 69 alive and 27 dead patients with mean DNA indices of 1.50 ± 0.3 and 1.70 ± 0.3, respectively, t Test analysis revealed that mean DNA index of deceased patients was significantly higher than that of alive ones (P = 0.008). Survival analysis demonstrated the prognostic significance of DNA index 1.70 (P = 0.017). Median survival of patients with DNA index of 1.70 or greater was 36 months in contrast to 73.5 months for those with DNA index less than 1.70. Multivariate analysis subsequently confirmed DNA index of 1.70 as an independent prognostic indicator with a hazard ratio of 2.05. Copyright 1993, 1999 Academic Press

From 1965 to 1995, at the University of Miami/Jackson Memorial Medical Center, 1223 patients with stage IA2, IB, or IIA cervical cancer have undergone a radical hysterectomy. The charts of these patients were reviewed retrospectively for pathology reports showing positive or close surgical margins. Fifty-one of these cases had final pathology results interpreted as close vaginal margins (CVM), which we define as tumor less than or equal to 0.5 cm from the vaginal margins of resection. All slides of blocks with close vaginal margins were found and reviewed by a single pathologist. Twenty-eight (54.9%) had parametrial involvement or positive lymph nodes and received adjuvant radiation therapy (RT). Of the remaining 23 cases, only 6 had other high risk factors, tumor greater than 4 cm, poorly differentiated, greater than 50% invasion, or lymphovascular space involvement. Sixteen of 23 received radiation. The 5-year survival was significantly greater with RT, 81.3%, than without RT, 28.6% (P< 0.05). The recurrence rate was also decreased from 85.7 to 12.5% (P< 0.01). Although present in less than 2% of radical hysterectomy specimens, CVM without other high risk factors may be an important prognostic variable that should be considered when making adjuvant therapy decisions.

The incidence and prognostic significance of positive intraperitoneal cytology taken during a radical hysterectomy was reviewed. A prospective study looking at intraperitoneal cytology was conducted by using 400 consecutive radical hysterectomies from January 1988 through June 1996. All selected patients had peritoneal washings performed prior to a radical hysterectomy with pelvic and para-aortic lymphadenectomy. A single pathologist reviewed all cytological and histologic specimens. A total of 400 patients were included in the study. Only 7 of 400 (1.8%) had positive intraperitoneal cytology. Four had squamous cell cancer and 3 had adenocarcinoma. Five had stage IB cervical cancer and the remainder were stage IIA. Three had positive nodes. Six of 7 had tumor size greater than 3 cm. Three of 7 had >50% invasion and 2 of 7 had lymphovascular space invasion. No other risk factors were present in these specimens. Six of 7 recurred within 18 months of surgery. Recurrences were local or retroperitoneal; none were upper abdomen or intraperitoneal. The incidence of positive peritoneal cytology during radical hysterectomy is 1.8%. The cost of these cytology specimens did not offer an advantage to the current surgical–pathological factors used to determine prognosis and adjuvant therapy.

Although laparoscopic pelvic lymphadenectomy has several potential advantages for patients with early-stage cervical cancer, laparotomy still is viewed as the standard approach because laparoscopic surgery may not remove a sufficient number of diseased lymph nodes. This randomized study compared three surgical approaches in 168 consecutive patients proved to have invasive cervical carcinoma, all of whom were scheduled for radical hysterectomy and systematic pelvic lymphadenectomy. The participants, aged 70 or younger, had stage IB1 or stage IB2-IIB disease and had responded objectively to neoadjuvant chemotherapy. The methods evaluated were transperitoneal (TPL), extraperitoneal (EPL), and laparoscopic pelvic lymphadenectomy (LPL). Conventional radical hysterectomy was performed in all cases, and patients were evaluated 15 days and 1 and 2 months after surgery. The final study population numbered 161 patients.

Improved surgical techniques have led to agreement that optimal primary cytoreductive surgery (OPCS) is, along with adjuvant chemotherapy, the preferred management of advanced ovarian cancer (AOC). The best survival can be expected if no gross macroscopic disease is left behind, but there is considerable variation in reported rates of OPCS. This study evaluated diagnostic open laparoscopy (DOL) as a means of predicting the best candidates to undergo OPCS. DOL was carried out in 87 patients with newly diagnosed AOC. Those who were not considered candidates for OPCS received 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery (IDS). Among 87 women having DOL were 53 (61%) who were thought to be operable and who underwent primary cytoreductive surgery (group A). The remaining 34 patients (group B) had a partial clinical response and were scheduled to undergo IDS and receive neoadjuvant and then adjuvant chemotherapy. An attempt was made at DOL to systematically examine the entire abdominal cavity using atraumatic forceps.

Objective:To evaluate the safety and effectiveness of 5% Imiquimod cream in the treatment of external anogenital warts in adolescent girls.