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Certain integrins that control the growth of tumors may be missing in cancerous cervical tumors. Integrins are cell receptors that control cell reproduction and differentiation. Researchers analyzed 18 tissue samples from cervical tumors and four normal samples and found that the integrins alpha-3, -4, and -5 were missing in the cells lining the cervical tumors. The greater the lack of integrin alpha-5, the greater the number of cancerous cells. Future cancer treatments may be based on manipulating the activity of integrins, perhaps with fibronectin, a natural cell adhesive.

In spite of the use of cisplatin, other powerful anti-cancer drugs, and the development of chemotherapy using multiple drugs, the survival rate of women with ovarian cancer in later stages (from IIC to IV) is still under 25 percent. Recurrent ovarian cancer is often resistant to drugs and radiation, even if the tumor is small, and no therapy is known to be curative in the majority of these cases. Hexamethylmelamine is an anti-cancer drug that has been used since 1964. Over 30 percent of patients with new ovarian cancer, and up to 20 percent of those previously treated, respond to this agent. However, its use in ovarian cancer is not standardized, as it has not been rigorously evaluated. Eight years of experience in treating 49 patients with recurrent or persistent ovarian cancer is described. The average patient age was 59 years old, and 40 had stage III to IV disease at diagnosis. Forty-six of the 49 patients had previously received cisplatin-based chemotherapy. Of 24 women with non-measurable tumors, seven were alive at 10 to 35 months after start of hexamethylmelamine, five without sign of disease. Of 25 the women with measurable tumors, three had complete and two had partial responses to treatment, a response rate of 20 percent. Patients who did not respond to cisplatin-based chemotherapy did not respond to hexamethylmelamine. Side effects were mild and included numbness or tingling on arms or legs, nausea, weakness, muscle aches, and herpes zoster infections. The results indicate that hexamethylmelamine is generally well tolerated and is active against ovarian cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

In patients with locally advanced cervical cancer, cancer cells have spread from the primary cancer in the cervix to lymph nodes in the pelvic area, particularly the para-aortic lymph nodes in the back near the aorta. Such patients have a high risk of cancer recurrence after surgery, and radiotherapy is the mainstay of treatment for these patients. As a part of research evaluating the treatment of cervical cancer, data were collected from 626 patients with primary carcinoma of the cervix; all had surgical evaluation of the para-aortic lymph nodes and received radiation therapy. These data were analyzed to determine which factors bear most strongly on the risk of recurrence and upon the likelihood of long-term survival from this cancer. The data analysis revealed that the para-aortic lymph nodes were an especially strong prognostic factor. In most forms of cancer, the spread of cancer cells to neighboring lymph nodes indicates a worse prognosis. In the case of cervical cancer, the spread of cancer cells to the pelvic lymph nodes doubles the risk of suffering recurrence and dying within a given time. However, if cancer cells are found in the para-aortic lymph nodes, the relative risk of recurrence is 11 times greater and the relative risk of dying is over six times as great. It is important to always obtain pathological information on the para-aortic lymph nodes in cases of cervical cancer, as this is the single most meaningful prognostic factor. As would be expected, larger cancers and more advanced cancers are also significantly associated with an increased risk of recurrence and death. When conducting clinical trials of treatment programs for cervical cancer, the failure to pathologically examine the para-aortic lymph nodes would result in considering together patients with drastically different prognoses; this would very likely make interpretation of the effects of treatment difficult or impossible. In the present series of patients, two-thirds of the patients who have been followed for at least five years have died. (Consumer Summary produced by Reliance Medical Information, Inc.)

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2008.06.058 Byline: John F. Boggess, Paola A. Gehrig, Leigh Cantrell, Aaron Shafer, Mildred Ridgway, Elizabeth N. Skinner, Wesley C. Fowler Keywords: cervical cancer; da Vinci Surgical System; laparoscopy; radical hysterectomy; robotic technology Abstract: The purpose of this study was to compare robotically assisted hysterectomy (RAH) with open (ORH) type III radical hysterectomy in the treatment of early-stage cervical cancer. Author Affiliation: Division of Gynecology Oncology, Department of Obstetrics and Gynecology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC Article History: Received 7 January 2008; Accepted 19 June 2008 Article Note: (footnote) Cite this article as: Boggess JF, Gehrig PA, Cantrell L, et al. A case-control study of robot-assisted type III radical hysterectomy with pelvic lymph node dissection compared with open radical hysterectomy. Am J Obstet Gynecol 2008;199:357.e1-357.e7.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2008.08.012 Byline: John F. Boggess, Paola A. Gehrig, Leigh Cantrell, Aaron Shafer, Mildred Ridgway, Elizabeth N. Skinner, Wesley C. Fowler Keywords: endometrial cancer; hysterectomy; laparoscopy; laparotomy; robotic assistance Abstract: The purpose of this study was to compare outcomes in women who underwent endometrial cancer staging by different surgical techniques. Author Affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC Article History: Received 12 February 2008; Revised 19 May 2008; Accepted 7 August 2008 Article Note: (footnote) Cite this article as: Boggess JF, Gehrig PA, Cantrell L, et al. A comparative study of 3 surgical methods for hysterectomy with staging for endometrial cancer: robotic assistance, laparoscopy, laparotomy. Am J Obstet Gynecol 2008;199:360.e1-360.e9.

Serous components within endometrial carcinoma are reportedly poor prognosticators. However, to the authors' knowledge the percentage of tumors which must be comprised of a serous component in order to affect outcome is unknown. The authors compared overall survival (OS) in women with endometrial carcinomas comprised of various percentages of uterine serous carcinoma (USC) with that of women with International Federation of Gynecology and Obstetrics (FIGO) Grade 3 endometrioid carcinoma (G3EC) to determine whether outcomes varied between these two poorly differentiated histologies.Data concerning women with either G3EC or USC who were diagnosed between January 1990 and November 2000 were collected retrospectively. Cases were reviewed to confirm diagnosis and estimate the fraction of tumor comprised of USC. Variables assessed included patient age and race, tumor stage, and lymphovascular space invasion. Associations between variables were tested using the Fisher exact test. The Kaplan–Meier method was used to evaluate OS with comparisons performed using the log‐rank test.Fifty‐two women with G3EC and 87 women with USC were identified. The OS of women with tumors comprised of > 50% USC was found to be significantly worse compared with women with G3EC (hazard ratio [HR] of 2.4; 95% confidence interval [95% CI], 1.2–5.2). Women with USC were more likely to present with extrauterine disease (odds ratio of 2.2; 95% CI, 1.1–4.5). The 5‐year survival rate for women with G3EC was 75% compared with 41% for women with tumors that were > 50% USC (P = 0.01). There was a significant trend toward a worse OS in women with even 10% USC compared with women with G3EC.USC involving > 50% of an endometrial carcinoma was found to be predictive of worse OS compared with the OS of women with G3EC. In patients with early‐stage disease, a trend toward a worse prognosis was found to exist when USC comprised even 10% of a tumor. Investigation into the treatment of endometrial carcinoma should include and document tumors with any percentage comprised of USC. Cancer 2004. © 2004 American Cancer Society.

Objective: To determine the clinical course of noninvasive uterine papillary serous carcinoma and whether it indicates advanced metastatic disease.

Objectives.In vulvar carcinoma, the expression of Ki-67 has been previously found to correlate with patient outcome. The objective of the study was to determine whether a specific pattern of expression was associated with occult vulvar cancer in patients with vulvar intraepithelial neoplasia (VIN) III and whether patterns of Ki-67 expression correlated with other clinical prognostic factors.

Objective.The aims of this study were to assess the early and late toxicities of multiple-daily-fraction whole pelvic radiation plus concurrent chemotherapy with either hydroxyurea or 5-fluorouracil (5-FU)/cisplatin and to determine the maximum tolerated external radiation dose in conjunction with brachytherapy, when given with either of these drug regimens, as treatment for locally advanced carcinoma of the cervix.

The association between in utero diethylstilbestrol (DES) exposure and the development of clear-cell adenocarcinoma of the vagina and cervix has been well described. However, non-clear-cell mucin-secreting adenocarcinoma in women with DES exposure has not been previously reported. We present two cases of non-clear-cell mucinous adenocarcinoma in women having a history of in utero DES exposure. These cancers were found in older women and were more advanced than the clear-cell adenocarcinoma associated with DES. Histologic features of these tumors were notable for atypical, irregular glands lined by endocervical, intestinal, and endometrioid epithelium. The development of non-clear-cell adenocarcinoma of the vagina in these patients may be associated with DES exposure in utero. Long-term surveillance of DES-exposed women may be warranted. Copyright 1995, 1999 Academic Press

The menstrual and reproductive histories of 276 female offspring of women who had received diethylstilbestrol (DES) during pregnancy were evaluated. Mean age was 24.6 years, and mean age at menarche was 12.6 ± 0.3 years. Reported menstrual abnormalities included increased menstrual flow and cycle irregularities, primarily anovulation and oligomenorrhea. An apparent increased incidence of urinary tract manipulation was detected, and cervical stenosis was noted to follow cryosurgery in 75% of women treated. Of 106 women attempting pregnancy, there were 129 conceptions and 58 live births. The fetal wastage rates were 43% for the first pregnancy and 37% for all pregnancies. The losses were due to spontaneous abortions (25%), ectopic pregnancies (5%), molar pregnancies (2 of 129), and in utero fetal death (4%). In the subgroup of women with vaginal adenosis or cervical hoods, the fetal wastage rate was 53%. Of 35 women unable to conceive for more than 1 year, only three pregnancies have resulted after infertility evaluations. Although abnormalities of the uterine cavity were identified, tubal and/or ovulatory defects were also present. DES, given to mothers in hope of maintaining threatened pregnancies, appears to have a deleterious effect on the reproductive ability of female offspring. Menstrual and structural abnormalities identified in this study may be associated with the reported reproductive difficulties.

Clinical stage and pathological characteristics of endometrial cancer cases were related to several aspects of estrogen prescribing. In comparing 256 cases with 321 community control subjects, estrogen use of less than 3 1/2 years' duration did not increase the risk of endometrial cancer for any stage, grade, histological type, or extent of invasion. With long-term estrogen use (3 1/2 years or more), relative risks were significantly increased (5.2 to 7.6) for the early cancers—those clinically stage IA, histologically grade 1, and invading the endometrium only. These increases were seen with both high-dose (>0.625 mg) and low-dose (≤0.625 mg) preparations. Risks were only minimally increased for the more advanced cancers. However, long-duration estrogen use did produce an increased risk of advanced cancer when administration was continuous rather than cyclic.(JAMA 244:2419-2422, 1980)

A 25-year-old woman with Noonan syndrome presented with painful, bleeding lesions of the vulva and perineum. The histologic diagnosis was angiokeratoma. Chronic increased central venous pressure from the patient's underlying cardiac disease was felt to be etiologic. The Argon laser was used for ablation, with minimal blood loss despite the extreme vascularity of these lesions.

A retrospective study of 119 patients ranging from 30 to 69 years of age was undertaken to evaluate the effectiveness of preoperative radium treatment for patients with Stage IB (FIGO 1971) squamous cell carcinoma of the cervix undergoing radical hysterectomy. Results in 61 patients who had radical hysterectomy without preoperative radium treatment were compared to those in 58 patients who had received radium preoperatively. The patients receiving radium systems had an uncorrected 5-year survival rate of 89.7, while the patients without preoperative radium treatment had a 75.1 5-year rate of survival. This difference in survival rate was judged to be secondary to the greater incidence of lymphatic invasion and residual tumor in the surgical specimens of the patients who did not receive preoperative radium. The occurrence of significant gastrointestinal and urinary tract complications was identical in the 2 groups.

The Gynecologic Oncology Group (GOG), a program of ACOG, is one of 12 cooperative groups conducting clinical trials supported by the National Cancer Institute. Recently, an occurrence of research fraud was found in one of the other cooperative groups. The GOG maintains a quality assessment and assurance program that includes three primary functions Original source documentation is examined to verify accuracy of treatment modalities, all protocols are regularly scrutinized for consistency and validity, and regular on-site audits are conducted at all institutions. The group endeavors to reassure physicians and their patients that research fraud is not rampant in the cooperative group system and that data published by the cooperative groups are reliable. (Obstet Gynecol 1994;841059-62)

Objective: To determine the impact of margin status on disease recurrence and the incidence of occult cancer in women diagnosed with vulvar intraepithelial neoplasia (VIN) III and treated with surgical excision.

To assess the morbidity of lymph node sampling, medical records were reviewed for all patients with cancers of the uterine corpus and cervix who underwent primary surgical therapy between January 1, 1980 and December 31, 1986. Five hundred fifty-four patients were identified. Of the 292 patients with corpus cancer undergoing total abdominal hysterectomy, lymph node sampling was performed in 65.4. Operative blood loss, transfusion requirements, and length of hospital stay were not increased significantly (P>.05) in women having node sampling. Of the 262 patients with cervical cancer, 72 underwent abdominal hysterectomy, 111 underwent radical hysterectomy, and 79 underwent staging laparotomy, with lymph node sampling performed in 82, 100, and 92 of these groups, respectively. The incidence of perioperative complications in this group was similar to that in the corpus cancer group. Vascular injuries, hematomas, and lymphocysts were more frequent after lymph node sampling. One postoperative death was attributed to complications from node sampling, but there were no other long-term sequelae. The low overall risk associated with lymph node sampling supports its inclusion in the surgical evaluation of gynecologic malignancies.

We examined the utility of patient self-report forms in identifying those gynecologic oncology patients who would be diagnosed by an experienced consultation-liaison psychiatrist as suffering from major depression. Sixty-five women with gynecologic tumors were evaluated by a consultation-liaison psychiatrist, using standardized (DSM-III) criteria. Each patient also completed a Carroll Rating Scale for Depression (CRS). The CRS demonstrated sensitivity and specificity of 87 percent and 58 percent, respectively. Used as a screening instrument to rule out depression, the CRS yielded a negative predictive value of 94 percent. We identified a prioriforty items from the CRS which should not be influenced by the non-psychiatric biologic effects of gynecologic tumors, and compared the performance of this non-cancer related symptoms subscale (NCSG) to that of the CRS. The NCSG did not significantly outperform the CRS; its sensitivity and specificity were 87 percent and 62 percent, respectively. Because our study population was relatively homogeneous (i.e., non-ovarian gynecologic oncology patients without severe debilitation who were not receiving chemotherapy, radiation therapy, or other invasive procedures), the findings should not be generalized to other oncologic populations at this time. Our results suggest that patient self-report forms can be effective screening devices for identifying those non-ovarian, gynecologic oncology patients who should then be carefully evaluated for coexisting clinical depression.

Previous clinical investigations using interferons (IFNs) have shown activity against epithelial ovarian cancer. The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) IFN-α2bwhich could be administered in combination with intravenous (iv)cis-platinum plus cyclophosphamide chemotherapy. After comprehensive surgical staging and maximal cytoreduction, previously untreated patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels. IFN-α2b(5–30 × 106units) was administered ip on Day 1 (±Day 8).cis-Platinum (75 mg/m2) plus cyclophosphamide (750 mg/m2) were administered iv on Day 2 with prophylactic hydration and antiemetics. Courses were repeated every 3 weeks for 8 cycles. Adverse effects were recorded using standard Gynecologic Oncology Group toxicity scales. Fifteen patients with mean age 56 years (range 43–73) were entered and received a combined total of 100 treatment cycles. Catheter-related complications occurred in 8 patients, and in three cases lead to catheter removal and discontinuation of ip therapy. Two patients experienced grade 2–3 nephrotoxicity and 1 experienced grade 2 peripheral neuropathy. There was a single episode of chemical peritonitis. Myelosuppression was the dose-limiting toxicity with grade 3–4 leukopenia complicating 6, 5, 12, 11, and 17 cycles at dose levels 1–5, respectively. No patient completed planned treatment without interruption or dose reduction. Plannedcis-platinum dose intensity was most compromised at the fifth IFN-α2bdose level. The maximum tolerated dose of IFN-α2bwas determined to be 20 × 106units repeated on Days 1 and 8 of this 21-daycis-platinum plus cyclophosphamide chemotherapy cycle.

Endometrial cancer risk associated with exposure to exogenous estrogen was evaluated for 256 cases, 224 gynecology controls, and 321 community controls. The pathologic diagnosis on all cases and a sample of gynecology controls was verified independently by two outside pathologists. Data on estrogen use were obtained from interviews of patients or their relatives, physicians' office records, and hospital records. Consistent patterns of relative risks appeared with both control groups. Black women revealed no differences in estrogen use between cases and either set of controls. White women exhibited risks of 3.6 and 4.1 after 3½ years or more of estrogen use. No increased risk was observed for shorter durations of use, irrespective of dose, type of estrogen, mode of administration, stage or grade of cancer. Obese women, who presumably produce increased amounts of endogenous estrogen, did not have their risk increased further by exogenous estrogen. Nonobese, nonhypertensive women had the highest risks of 5 to 8 after 3½ years or more of estrogen use. A minimum latency period of 3 to 6 years subsequent to the first administration of estrogen was demonstrated, and an estrogen-free interval of 2 years was sufficient to reduce elevated risks to nonuser levels. These short latency and recency intervals are consistent with carcinogenic promoter rather than an initiator action. With estrogen use of long duration, risks of cancer were high for Stage IA and grade 1 lesions, and either small or not significant for more advanced disease. Increased medical surveillance that resulted in earlier diagnosis, or less aggressive biologic lesions, may account for these findings.

Described is the treatment of carcinoma of the vulva by means of the tensor fascia lata myocutaneous graft in the resurfacing of the surgical defect of radical vulvectomy and groin node dissection. Its use has been associated with a reduced rate of morbidity and hospital stay (11 days) in patients who undergo this procedure.

Background.Tumor hypoxia may be associated with treatment resistance, cell proliferation, and metastatic potential, which contribute to poor prognosis. Complementary techniques for detecting hypoxia, cell growth, and metastases are required to study these relationships.Objectives.The purpose of this study was to demonstrate the clinical feasibility of quantitative hypoxia detection with pimonidazole, a novel hypoxia marker, and to correlate hypoxia with S-phase markers of tumor proliferation.Methods.Pimonidazole binds to thiol-containing proteins specifically in hypoxic cells. Ten patients with cervical carcinoma received 0.5 g/m2pimonidazole intravenously followed by biopsy of the cervical carcinoma the next day. Hypoxic cells were recognized by immunohistochemical detection of pimonidazole using a mouse monoclonal antibody. Cell proliferation was detected with a commercially available monoclonal antibody for proliferating cell nuclear antigen (PCNA). Assessment of hypoxia and cell proliferation was made qualitatively with light microscopy and quantitatively using point counting and image analysis software methods.Results.No clinical toxic effects were associated with pimonidazole administration. Immunostaining with pimonidazole antibody was observed in 9 of 10 tumors, suggesting that hypoxia is a common occurrence in cervical carcinoma. Quantitatively, tumors that had large numbers of hypoxic cells had the greatest percentage of S-phase cells, but some tumors with smaller amounts of hypoxia also had substantial numbers of S-phase cells.Conclusion.Pimonidazole can be used for qualitative and quantitative assessment of tumor hypoxia.

A series of 877 patients with invasive squamous carcinoma of the cervix was evaluated to determine the value of chest films, intravenous pyelograms, barium enemas, cystoscopies, and sigmoidoscopies prior to treatment. It was found that intravenous pyelograms are the most important study for prognostic purposes and that both chest films and intravenous pyelograms are exceedingly important as base lines for follow up of treated cancer patients. Cystoscopies, sigmoidoscopies, and barium enemas are valuable primarily in patients with stage III or IV pelvic findings and use of these particular studies should be individualized to the situation of the particular patient.

Introital stenosis from both bony and soft tissue contracture is an unusual clinical problem not well addressed in the literature.

Objective.Malignant transformation of endometriosis has been well documented. Endometrioid adenocarcinoma is the most common malignancy to occur in this setting, although other carcinomas and rarely stromal tumors can be seen. We present the first case in the literature of adenosarcoma, a rare mixed mullerian or mesodermal tumor, arising in extrauterine vaginal endometriosis.

Objective.Ovarian hemangiomas are very rare with the majority being cavernous hemangiomas. We report a case of a capillary ovarian hemangioma.

Seventy-nine patients with endometrial carcinoma were compared with 203 control subjects regarding their use of combination-product oral contraceptives (OCs). Overall, 6.3% of patients and 15.3% of control subjects had used these products. The risk of endometrial cancer for users of OCs was less than half the risk for nonusers. Five years or more of use reduced the risk to a third. Recent users were strongly protected, whereas discontinuation resulted in risks returning to those of nonusers. Furthermore, OCs with predominantly progestational effects or intermediate formulations produced greater protection than those with predominantly estrogens. This pattern of results is biologically consistent with a protective effect of combination-product OCs against endometrial carcinoma.(JAMA 1982;247:475-477)