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Objective. Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. Methods. The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and χ 2 tests. Results. Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC ( P Conclusion. Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.

Radical hysterectomy is a common and effective treatment of early cervical cancer. Modern advances include the use of robotic assistance to perform equivalent minimally invasive procedures. The purpose was to compare surgical and short-term outcomes, as well as margins, between robotic-assisted laparoscopic radical hysterectomy and open radical hysterectomy.The first 30 cases of robotically assisted type III radical hysterectomy for cervical cancer were compared with the 30 previous cases of open type III radical hysterectomy. Body mass index, length of operation, nodal yield, margins, estimated blood loss, hospital stay, and complications were all documented and compared.The 30 patients undergoing robotically assisted laparoscopic radical hysterectomy were similar in body mass index to the women undergoing open radical hysterectomy (34 kg/m robotic, 32 kg/m open, P = 0.22). The mean operating time was 154 minutes compared with 166 minutes in the open arm (P = 0.36). The mean blood loss was 165 mL compared with 323 mL in the open arm (P = 0.001). The mean pelvic nodal yield was 25 nodes compared with 26 nodes in the open group (P = 0.45). The mean parametrial margin size was not significantly different between groups. The mean postoperative length of stay was 1.4 days compared with 2.8 days for the open cases (P0.001). Urinary retention was significantly more common in the robotic arm.Radical surgery for cervical cancer can be accomplished using the da Vinci surgical system (Intuitive Surgical, Sunnyvale, Calif) with acceptable blood loss, operating time, parametrial margins, and nodal yield. Future studies need to address long-term outcomes.

Highlights • Aprepitant combined with ifosfamide may lead to encephalopathy. • Aprepitant–ifosfamide induced encephalopathy was of short duration in these cases.

Objectives The objective of this pilot study was to determine if the combination of CA 125, menopausal status and prealbumin can be used to accurately predict ovarian cancer in women with pelvic masses. Study design Preoperative serum CA 125, prealbumin and menopausal status were prospectively determined. Results were formulated into an ovarian cancer risk assessment (OCRA) score and compared with final surgical pathology. Results OCRA was studied in 130 women. No cancers were found in women with a score less than 200. For all cancers, an OCRA score ≥ 200 had a sensitivity of 96%, specificity of 95% and positive predictive value of 95%. When the OCRA score of ≥200 was evaluated for its ability to predict ovarian cancer, the sensitivity, specificity, and positive predictive value were 100%, 83%, and 78%, respectively. Conclusions In this pilot study, OCRA was able to predict which women with pelvic masses were more likely to have ovarian cancer. The scoring system easily applied clinically and may help facilitate appropriate referral of women to gynecologic oncologists for optimal care.

Objective. While uterine papillary serous carcinoma (UPSC) is an aggressive histologic subtype, it fortunately is not as common as some other histologic subtypes. Overall, patients with UPSC have a poor survival rate. Since the optimal surgical procedure to perform on patients with this tumor is unknown, the authors wanted to determine what the optimal surgical management of patients with UPSC should be. Methods. All patients with the preoperative or frozen section intraoperative diagnosis of UPSC were treated with a staging or cytoreductive procedure analogous to patients with serous carcinoma of the ovary. Patients analyzed underwent surgery from March 1983 to September 1995. Results. Sixty-five patients with UPSC were found. Twenty patients had FIGO stage I tumors, 6 stage II tumors, 8 stage III tumors, and 31 stage IV tumors. Twenty-nine patients had upper abdominal disease (17 gross disease and 12 microscopic disease only). Forty-eight patients underwent pelvic and paraaortic lymphadenectomy, with 6 of 48 having positive lymph nodes. All 14 patients with lymphovascular space invasion had stage IV disease. Thirty-one of sixty-five patients had positive cytology at the time of surgery. Conclusion. Based on the clinical experience of these investigators, patients with UPSC should undergo a staging laparotomy similar to the procedure undertaken for patients with ovarian carcinoma. The surgery should include at least partial omentectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal washings, peritoneal biopsies, and pelvic and paraaortic lymphadenectomy similar to an ovarian cancer staging procedure if no gross disease ≥2 cm is found at time of surgery. If disease ≥2 cm is found, cytoreduction should be undertaken when feasible.

Vulvar Paget's disease is a relatively rare gynecologic neoplasm that is problematic because of its propensity to recur.An 80-year-old woman was found to have recurrent Paget's disease of the vulva. She was initially diagnosed 12 years previously and had had multiple resections for the disease. She was found to have histologically proven Paget's disease and underwent a course of topical immune modulator therapy with imiquimod. Biopsy proved histologic regression of the disease progress. The patient remained without recurrence 12 months after therapy.In select patients imiquimod may be used to treat or facilitate treatment of vulvar Paget's disease.

To determine whether differences exist in clinicopathologic variables or survival between women with primary carcinoma of the fallopian tube (PCFT) and with epithelial ovarian carcinoma (EOC).University of Iowa Hospitals and Clinics (UIHC) tumor board records were analyzed from January 1, 1991, to April 30, 2001. No cases were knowingly excluded. Each case of PCFT was matched with 2 cases of EOC. Controls were the next 2 cases of EOC diagnosed at UIHC after each case of PFTC, with priority given to stage of disease, then histologic grade, followed by histology, with 1 year the limit for obtaining the closest match.Twenty-eight cases of PCFT were found. These were matched with 56 cases of EOC. The mean age at diagnosis was significantly older for women with PCFT (67 years) vs. women with EOC (60 years) (p = 0.005). The was no difference in prediagnosis hormonal contraceptive use (p=0.38), body mass index (p = 0.5) or rate of positive nodes (p = 0.19). Kaplan-Meier analysis revealed no difference in survival between PCFT and EOC (p = 0.5).There is no significant difference in clinical parameters or survival between patients with PCFT or EOC when matched for stage, grade and histology.

Late radiation cystitis is one of the most difficult complications of radiation therapy for pelvic malignancies.A 29-year-old woman with a history of cervical cancer presented with radiation-induced hemorrhagic cystitis. The patient received multiple units of packed red blood cells while undergoing several intravesical treatments, including continuous bladder irrigation, 4% formalin, 0.15% AgNO3 and Mg(OH)2 with Al(OH)3. The bleeding finally was stopped by the use of intravenous recombinant factor VIIa.When hemorrhagic cystitis related to late radiation complications is refractory to conventional management, intravenous recombinant factor VIIa may be of benefit.

Objective: Robotic hysterectomies are becoming increasingly common in the United States. Although benefits exist, risks are also present. The purpose of this study was to see what percentage of women with migraine headaches had a post-operative exacerbation.Study design: Records were examined for the diagnosis of migraine headaches as well as post-operative diagnosis of a headache. Records were also examined for age, estimated blood loss, total skin to skin operative time and body mass index.Results: Surgeries and records for 100 women were examined. Only 6% of women complained of post-operative headaches. However, 45% of women with history of migraines complained of post-operative headaches (p

The purpose of this study was to determine if serum prealbumin could be used to objectively determine which patients could not safely undergo cytoreductive surgery.Patients with suspected ovarian cancer in a 24-month period underwent nutritional assessment during their preoperative workup and were followed for development of postoperative complications.One hundred and eight of 114 patients underwent surgical cytoreduction. Of the 108 surgical patients, 88 patients had prealbumin levels18 mg/dl and 24 patients had prealbumin levels10 mg/dl. Postoperative complications increased with lower prealbumin levels. All complications occurred in group of patients with prealbumin18 mg/dl (P=0.013). A significantly increased number of complications occurred in patients with prealbumin10 mg/dl (61.5% vs. 6.4%, P0.001, RR 9.6). All postoperative mortality in this series occurred in patients with prealbumin10 mg/dl (23.1% vs. 0%, P0.001). Patients whose prealbumin started low but was able to be raised to10 mg/dl by TPN did not have significantly increased complications or EBL compared to patients whose initial prealbumin was10 mg/dl (18.2% vs. 4.8%, P=0.95 and 570 vs. 600 ml, P=0.87).Significantly more blood loss, morbidity, and mortality occurred in patients with abnormal preoperative prealbumin. This was especially true in patients with a prealbumin10 mg/dl. With these significantly increased risks, patients with extremely poor nutritional status (prealbumin10 mg/dl) may be better served by neoadjuvant chemotherapy with interval cytoreductive surgery if nutrition improves.

Objective. The platinum-free interval (PFI) is an important entity in the treatment of women with epithelial ovarian cancer. The purpose of this study was to determine on clinical samples whether a taxane-free interval (TFI), as defined by in vitro extreme drug resistance assay, existed in women previously exposed to platinum and taxane chemotherapy. Methods. Records were examined from 2003 to 2006 to find all patients with epithelial ovarian cancer who had previous exposure to platinum and taxane therapy. Further examination was done to find all patients who underwent secondary cytoreduction and had their tumor submitted for extreme drug resistance assay. Results. Thirty-four women meeting the above criteria were found. The mean PFI was 25 months (median 18). The mean TFI was 27 months (median 20). Over 44% of the patients have been exposed to more than just a course of platinum and a course of a taxane. In patients having a PFI of ≥12 months, 38.8% had extreme drug resistance (EDR) to carboplatin and 41.9% EDR to cisplatin. Conversely, in patients having a TFI of ≥12 months, 89.7% had EDR to paclitaxel and 82.8% EDR to docetaxel. Conclusions. While only a small percentage have EDR to carboplatin and cisplatin after a PFI of ≥12 months, almost 90% of patients with a TFI ≥12 months showed EDR to paclitaxel in vitro .

Objective. To determine whether neoadjuvant cisplatin and 5-fluorouracil chemotherapy can be used to preserve the anal sphincter and/or urethra in patients with advanced vulvar cancer involving these sites. Methods. Fourteen patients with advanced vulvar cancer (1997–2003) involving the anal sphincter and/or urethra were given 3–4 cycles of neoadjuvant chemotherapy to attempt preservation of these pelvic structures rather than undergoing a primary pelvic exenteration. Following 3 cycles, a radical vulvectomy and groin lymph node dissection were planned. All patients had lesion size documented by measurement and photograph prior to and following chemotherapy. Results. The median age was 63 years (range 39–88). Thirteen patients received a median of 3 cycles (range 2–4) of neoadjuvant chemotherapy. Ten patients received cisplatin and 5-fluorouracil, while three received cisplatin alone. The median time from diagnosis to surgery was 77 days (range 54–143). All patients with cisplatin and 5-fluorouracil chemotherapy underwent surgery except one patient who had a synchronous renal cell carcinoma and died prior to surgery. Patients receiving cisplatin alone showed no measurable response, while all patients receiving cisplatin and 5-fluorouracil demonstrated at least a partial response. Two patients had no residual invasive carcinoma on final pathology. All patients receiving cisplatin and 5-fluorouracil followed by surgery are disease-free, while two of three receiving cisplatin have progressive disease. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. Conclusion. Neoadjuvant cisplatin and 5-fluorouracil in advanced vulvar cancer demonstrated a response rate of 100%. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. Responders are disease-free at this time. This response rate demonstrates superior activity of 5-fluorouracil in vulvar cancer and spares these patients the morbidity of exenteration or radiation.

The purpose is to investigate the safety and efficacy of i.p. topotecan and oral etoposide as salvage treatment for patients with platinum-resistant ovarian or primary peritoneal cancer.Patients were treated with i.p. topotecan initial dose, 1 mg/m2 on days 1 to 5, followed by oral etoposide 100 mg on days 6 to 9 of a 28-day cycle for six cycles. Dose reduction of topotecan was used for severe bone marrow suppression. Peritoneal (topotecan) and plasma (topotecan and etoposide) levels were assessed at multiple time points using high-pressure liquid chromatography.Twenty-two patients (mean age, 61 years) with a median of 1.5 prior treatments were enrolled. Etoposide peak plasma concentrations ranged from 1.9 to 6.9 microg/mL (mean, 3.6 microg/mL). Topotecan plasma levels rose with increasing peritoneal concentration and were detectable within 1 hour but tended to decrease rapidly to below detectable levels within 24 hours. The peak plasma concentration of topotecan was 12.82 +/- 8.55 microg/mL with a plasma half-life of 6.17 +/- 2.75 hours. A total of 104 cycles was administered; 14 patients (64%) completed all six planned cycles. All patients were evaluable for toxicity, and 21 patients were evaluable for response. The most common grade 4 toxicities were neutropenia and thrombocytopenia in eight and four patients (36 and 18%), respectively. There were no treatment-related deaths. The overall response rate was 38% [complete response, three (14%); partial response, five (24%)]. Seven patients had stable disease and six progressed while on treatment.The combination of i.p. topotecan and oral etoposide is an active and well-tolerated regimen in platinum-resistant ovarian carcinoma. Additional studies investigating topotecan in combination with etoposide are warranted.

Objective: The authors, using image analysis, previously demonstrated nuclear size and summed optical density to be independent prognostic indicators of recurrence in patients with endometrial carcinoma. The same tumors were analyzed by studying the optical features in the G0–G1 peak to see if this changed the values found as well as their importance as prognostic features at greater than 5 years of follow-up. Methods: Tumors from 74 consecutive patients, surgically treated, with endometrial cancer, were evaluated. Survival, depth of invasion, lymphvascular space invasion, FIGO stage, grade, histology were analyzed. DNA index, progesterone receptor status, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD) were evaluated. NUSZ, NUSH, and NUSD were quantified using image analysis. Results: Fifteen patients died from disease during the observation period of the study. Mean follow-up was 82 months with a median of 84 months. Forty-nine patients had stage I cancers, five stage II, 17 stage III, and three stage IV. NUSZ and NUSD were all significantly different between the original (entire cell cycle) and the re-measured (G0G1 only) values (both P

Background Malignant mixed mullerian tumors (MMMTs) of the ovary are a rare, aggressive subtype of ovarian cancer without a clear relationship to familial breast–ovarian cancer syndromes. Case We present the case of a woman with bilateral breast cancers who subsequently developed a stage IIIc MMMT of the ovary. The patient had a first-degree female relative with breast and ovarian cancer (not MMMT), as well as second- and third-degree female relatives each with bilateral breast cancers. BRCA1 and BRCA2 sequencing of germline DNA revealed no evidence of a heritable mutation. Discussion Ovarian MMMTs may be a hallmark of breast/ovarian cancer secondary to genetic risk independent of classic BRCA1/2 pathways.

Objectives. The purpose of this study was to determine the recurrence rate, survival, and pregnancy outcome in patients with Stage IA and Stage IC invasive epithelial ovarian cancer treated with unilateral adnexectomy. Methods. A multi-institutional retrospective investigation was undertaken to identify patients with Stage IA and IC epithelial ovarian cancer who were treated with fertility-sparing surgery. All patients with ovarian tumors of borderline malignancy were excluded. Long-term follow-up was obtained through tumor registries and telephone interviews. The time and sites of tumor recurrence, patient survival, and pregnancy outcomes were recorded for every patient. Results. Fifty two patients with Stage I epithelial ovarian cancer treated from 1965 to 2000 at 8 participating institutions were identified. Forty-two patients had Stage IA disease, and 10 had Stage IC cancers. Cell type was distributed as follows: mucinous, 25; serous, 10; endometrioid, 10; clear cell, 5; and mixed, 2. Histologic differentiation was as follows: grade 1, 38; grade 2, 9; and grade 3, 5. Twenty patients received adjuvant chemotherapy (mean 6 courses, range 3–12 courses). Patients received the following chemotherapeutic agents: cisplatin/taxol or carboplatin/taxol, 11; melphalan, 5; cisplatin and cyclophosphamide, 3; and single-agent cisplatin, 1. Eight patients had second-look laparotomies and all were negative. Duration of follow-up ranged from 6 to 426 months (median 68 months). Five patients developed tumor recurrence 8–78 months after initial surgery. Sites of recurrence were as follows: contralateral ovary, 3; peritoneum, 1; and lung, 1. Nine patients underwent subsequent hysterectomy and contralateral oophorectomy for benign disease. At present, 50 patients are alive without evidence of disease and 2 have died of disease 13 and 97 months after initial treatment. The estimated survival was 98% at 5 years and 93% at 10 years. Twenty-four patients attempted pregnancy and 17 (71%) conceived. These 17 patients had 26 term deliveries (no congenital anomalies noted) and 5 spontaneous abortions. Conclusion. The long-term survival of patients with Stage IA and IC epithelial ovarian cancer treated with unilateral adnexectomy is excellent. Fertility-sparing surgery should be considered as a treatment option in women with Stage I epithelial ovarian cancer who desire further childbearing.

Background: Although BRCA1 and BRCA2 play important roles in hereditary ovarian cancers, the extent of their role in sporadic ovarian cancers and their mechanisms of inactivation are not yet well understood. Our goal was to characterize BRCA2 mutations and mRNA expression in a group of ovarian tumors previously evaluated for BRCA1 mutations and mRNA expression. Methods: The tumors of 92 unrelated women with “ovarian” cancer (i.e., ovarian, peritoneal, or fallopian tube cancer) were screened for BRCA2 null mutations using a protein truncation test. Methylation-specific polymerase chain reaction (PCR) was used to examine the BRCA2 promoter for hypermethylation in tumors that did not express BRCA2 mRNA. All statistical tests were twosided. Results: Nine tumors had a germline (n = 5) or somatic (n = 4) BRCA2 mutation; each was associated with loss of heterozygosity. All of the somatic (1445delC, E880X, 4286del8, and 5783delT) and one of the germline (5984ins4) mutations were unique to this study. One tumor had somatic mutations in both BRCA1 and BRCA2. Two tumors are, to our knowledge, the first cases of germline BRCA2-associated peritoneal cancer. Twelve additional tumors lacked detectable BRCA2 mRNA, but the BRCA2 promoter was hypermethylated in only one of them, suggesting that other mechanisms effect transcriptional silencing of BRCA2. Tumors lacking BRCA1 mRNA were more likely to lack BRCA2 mRNA than tumors expressing BRCA1 mRNA (P

Many factors modify ovarian cancer survival. There are conflicting reports regarding survival of individuals with hereditary BRCA1-related ovarian cancer. None have controlled for other mechanisms of BRCA1 silencing in the control cohort.Fifty-nine cancers with presumed BRCA1 dysfunction because of mutation (24 germ-line and 16 somatic) or absent BRCA1 mRNA because of promoter hypermethylation (n = 19) were identified among 250 consecutively screened ovarian cancers. Controls were matched from the same population based on p53 mutation type, age at diagnosis, Fédération Internationale des Gynaecologistes et Obstetristes surgical stage and histological grade, residual disease, preoperative CA125, disease site, and the presence of BRCA1 mRNA translatable in an in vitro protein expression assay. BRCA1 promoter hypermethylation was determined by the methylation-specific PCR technique. The significance of promoter hypermethylation was confirmed by the absence of detectable BRCA1 mRNA.The median survival for individuals with ovarian cancer BRCA1 dysfunction was 4.1 years versus 3.5 years in the case matched controls (P = 0.98). Grouped on the basis of the mechanism of BRCA1 dysfunction, median survival was 4.5, 2.8, and 2.3 years for germ-line, somatic, and BRCA1 promoter-silenced ovarian cancers. However, for the corresponding matched controls with wild-type BRCA1 sequence, the median survival was virtually identical: 4.6, 2.8, and 3.3 years, respectively. In a Cox proportional hazards analysis, only residual disease (P = 0.0001), age (P = 0.01), and Fédération Internationale des Gynaecologistes et Obstetristes stage (P = 0.011) entered the survival model.In contrast with other published reports, we are unable to detect large survival differences between matched case-control cohorts of ovarian cancers with BRCA1 inactivation by any of three independent mechanisms.

Background: Ovarian cancer is one of the most common hereditary cancers in women. Mutations in the BRCA1 gene increase a woman's risk of ovarian cancer. Testing for BRCA1 mutations is cumbersome and impractical for large populations. Therefore, we developed an efficient strategy to detect various types of BRCA1 dysfunction and also determined the relative frequency of BRCA1 dysfunction in ovarian cancer. Methods: Tumors from 221 patients with epithelial ovarian cancer were screened for loss of heterozygosity (LOH) at the BRCA1 locus. BRCA1 complementary DNA (cDNA) and genomic DNA from all cancers with BRCA1 LOH (106 tumors) or noninformative status (15 tumors) were polymerase chain reaction (PCR) amplified and analyzed for protein truncation in a coupled transcription/ translation test. When truncated BRCA1 protein was detected, the BRCA1 gene from both the tumor and a paired blood sample was sequenced. When BRCA1 expression in tumor cDNA was not detected with a protein truncation test, a methylation-specific PCR was used to determine whether the promoter region of BRCA1 was methylated and thus inactivated. All statistical tests were two-sided. Results: Fifty-one (23.1%) of 221 tumors had BRCA1 dysfunction, including 18 with germline mutations, 15 with somatic mutations, and 18 with monoallelic or biallelic hypermethylated promoters. By the consideration of only tumors with LOH or that were noninformative, the efficiency for detecting BRCA1 dysfunction improved to 45 (37.2%) of 121 tumors. Therefore, LOH/noninformative was a strong predictor of mutation status (Fisher's exact test, P

Geisler JP, Geisler HE, Miller GA, Wiemann MC, Zhou Z, Crabtree W.Markov optical texture parameters as prognostic indicators in ovarian carcinomas. Texture is a descriptive property of a surface describing the morphometric heterogeneity of complex structures. Computer aided image analysis allows optical texture measurement and analysis of gray-scale images. The authors, utilizing image analysis, prospectively studied Markov nuclear texture features to determine their relevance as prognostic indicators of survival in patients with epithelial ovarian carcinoma. Ninety-nine consecutive patients with ovarian cancer, treated initially with surgery were evaluated for their length of survival, level of cytoreduction, FIGO stage, grade, histology, and DNA index, as well as 20 Markov texture features. Markov nuclear texture features were quantified using image analysis. Mean follow-up for the study population was 64 months (median 59) with a range from 51 to 89 months. Five optical texture features showed significant correlation with length of survival. Difference entropy (P = 0.033) and information measure A (P = 0.041) were both indirectly correlated with survival while information measure B (P = 0.030), correlation coefficient (P = 0.045), and the maximum correlation coefficient (P = 0.041) were directly correlated. Only sum entropy (P = 0.035), FIGO stage (P = 0.0031), and level of cytoreduction (P < 0.0001) were independent predictors of survival in this population. Optical texture can be quantified by image analysis. Utilizing multivariate analysis, the Markov texture feature, sum entropy, was demonstrated to be an independent prognostic indicator of survival in patients with epithelial ovarian cancer. FIGO stage and optimal cytoreduction also were independent prognostic indicators of survival.

p53 is the most common tumor suppressor gene involved with human malignancies. Mutations in p53 are present in approximately 50% of human malignancies. bcl-2 is a protooncogene. Expression of its protein product is related to better prognosis in several malignancies.One hundred and three patients with epithelial ovarian carcinoma were studied. Immunohistochemical staining using the pAb1801 monoclonal antibody to p53 and the anti-bcl-2 124 monoclonal antibody to bcl-2 was performed. Image analysis was used to measure percentage positive nuclear area staining of mutant p53. In addition to bcl-2 and p53, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. Univariate as well as Cox regression analysis was performed.One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO stage I disease, 4 stage II, 59 stage III, and 20 stage IV. Immunohistochemical staining for mutant p53 was not significantly related to DNA index (P = 0.99) but was related to increasing FIGO stage (P0.001) and increasing histologic grade (P = 0.039). Using Cox regression analysis, increased mutant p53 staining was an independent predictor of survival in these patients (P = 0.0032), along with stage (P0. 0001) and level of cytoreduction (P0.0001). Although by itself bcl-2 was not an independent prognostic indicator (P = 0.18), the combination of p53 and bcl-2 was independently predictive of survival (P = 0.038).This study confirms the authors' earlier report on the importance of p53 as a prognostic indicator of survival in ovarian carcinoma. Cox regression analysis reveals mutant p53 staining to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than the combination of bcl-2 and p53.

Primary carcinoma of the fallopian tube (PCFT) has been traditionally assessed and treated following epithelial ovarian carcinoma (EOC) guidelines despite the paucity of supporting data. A previous population-based study reported a better prognosis for PCFT, but no case match data has been published evaluating clinical parameters and outcomes. To analyze clinical similarities and differences between women with PCFT and EOC in case control fashion, the investigators examined records in the tumor registry database of the University of Iowa Hospitals and Clinics from 1991 to 2001. Cases of PCFT were matched with EOC controls according to the chronology of diagnosis. Each case of PCFT was matched with the next two cases of EOC with an 1-year limit for finding the closest match. Priority was given to stage of disease and histological grade, followed by histology. Twenty-eight cases of PCFT were matched with 56 cases of EOC. PCFT patients were 7 years older at diagnosis than the EOC patients (mean age, 67 versus 60 years, P = .005). No significant differences between the two diseases were found in the prediagnosis use of oral contraceptives (P = .38); body mass index (P = .5); percentage of positive nodes (P = .19); or survival based on Kaplan-Meier analysis (P = .5). The investigators conclude that the apparent lack of differences between PCFT and EOC in clinical parameters or survival indicates that PCFT should be treated according to protocols designed for EOC.

Objective. Heat shock protein 27 (HSP27) is a relatively small protein produced in response to pathophysiologic stress. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors in patients with endometrial carcinoma. Methods. One hundred fifty-three consecutive patients with endometrial carcinoma were studied. Slides were prepared from fresh tissue. HSP27 was analyzed using a semiquantitative measurement. Patient records were examined for FIGO stage, grade, depth of myometrial invasion, histology, lymphovascular space invasion, time to recurrence, and survival. Results. The mean follow-up was 53 months (median 56 months, range 30–68 months). Endometrioid tumors showed significantly higher HSP27 staining than nonendometrioid tumors ( P = 0.005). Patients alive at the conclusion of this study had significantly higher mean HSP27 staining than patients who were deceased ( P P = 0.02), FIGO stage ( P = 0.014), and lymphovascular space invasion ( P = 0.046) to be independently predictive of survival. Conclusion. HSP27 staining is significantly higher in endometrioid than nonendometrioid tumors. HSP27 staining is an independent prognostic indicator in patients with endometrial carcinoma, the most common gynecologic malignancy in the United States.

bcl-2 is a protein which prohibits programmed cell death. The purpose of this study was to determine whether bcl-2 staining was related to traditional prognostic factors and/or recurrence in patients with endometrial carcinoma.One hundred twenty consecutively surgically treated patients with endometrial carcinoma had their tumors studied immunohistochemically for bcl-2 staining.The mean follow-up of the patients was 53 months with a median of 56 months (range 30 to 68 months). bcl-2 staining was positive in 44.0% of patients with endometrioid carcinomas and in 23. 1% of patients with nonendometrioid carcinomas (P0.001). Increasing depth of invasion (P = 0.014), grade (P = 0.011), and FIGO stage (P = 0.018) were each correlated with decreasing bcl-2 staining. bcl-2 staining was positive in 44.1% of patients whose tumors showed no lymphovascular space invasion and in 11.1% of patients with lymphovascular space invasion (P0.001). Only 1 of 26 patients with recurrent disease had persistence of bcl-2 staining. Multivariate analysis revealed FIGO stage (P = 0.0051), histologic grade (P = 0.050), and lack of staining for bcl-2 (P = 0.012) to be independent predictors of recurrence.bcl-2 persistence is more common in endometrioid than in nonendometrioid adenocarcinomas of the endometrium. It appears to be inversely correlated with the universally recognized prognostic factors of depth of invasion, histologic grade, and FIGO stage. Lack of bcl-2 persistence was an independent predictor of recurrence of disease. This group of patients continues to be followed to determine the role of bcl-2 persistence or lack of persistence as a predictor of 5-year survival of patients with endometrial carcinoma.

Objective. Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors as well as survival in patients with epithelial ovarian carcinoma. Methods. Ninety-nine patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction, and survival. Results. Immunohistochemical staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant difference in HSP27 staining was found in relation to FIGO stage ( P = 0.013). HSP27 staining was found to be an independent predictor of 2-year survival in these patients ( P = 0.041). Conclusion. The level of HSP27 significantly decreases as the FIGO stage increases and is an independent prognostic indicator of survival in patients with epithelial ovarian carcinoma.

Texture is a descriptive property of a surface distinct from color and shape. Image analysis allows gray-scale images to have their optical texture measured and analyzed. The authors, utilizing image analysis, prospectively studied Markov texture parameters to determine their relevance as prognostic indicators of disease recurrence in endometrial cancer.Seventy-four consecutive patients, surgically treated, with endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as 21 Markov parameters. DI and the Markov parameters were quantified using image analysis.Median follow-up for the study population was 31 months with a range from 1 to 44 months. Fifteen patients had recurrence of their cancer and 12 patients died from disease during the observation period of the study. Eleven Markov parameters showed significant correlation with increasing FIGO stage (P0.05), while 14 Markov parameters showed significant correlation with survival (P0.05). Three Markov parameters, difference entropy (P = 0.025), information measure B (P = 0.01), and diagonal moment (P = 0.046), were demonstrated to be independent prognostic indicators along with the more traditional prognostic indicators, stage (P = 0.006), grade (P = 0.029), and depth of myometrial invasion (P = 0.03).Image analysis is able to quantify optical texture. Utilizing bivariate correlations and multivariate analysis, three of these parameters were demonstrated to be independent prognostic indicators in endometrial cancer, specifically difference entropy, information measure B, and diagonal moment.

Background: Steroid receptor status as a prognostic indicator in gynecologic malignancies has been a focus of study for almost 20 years. Although shown to be of importance in assessing prognosis in some patients with endometrial cancer, their importance in assessing prognosis in patients with serous cystadenocarcinoma of the ovary is not established. Methods: All cases of stage IIIc serous cystadenocarcinoma of the ovary operated on by the gynecologic oncology service from January 1, 1981, through December 31, 1989, were evaluated for their estrogen and progesterone receptor status, time to recurrence, length of survival, and level of primary cytoreduction as well as FIGO stage, grade, and histology. Fresh tissue was obtained and frozen at the time of surgery for the steroid assays. Results: Ninety-six patients who had optimal primary cytoreductive surgery for their stage IIIc serous cystadenocarcinomas of the ovary and had their estrogen and progesterone receptor status established were found. Patients with an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein were shown to have a better mean survival (41 months) than patients with estrogen receptor levels greater than 10 fmol/mg cytosol protein (34 months) ( P = 0.015). Five-year survival in the former group (38 patients) was 39.5% while 5-year survival in the latter group (58 patients) was 10.3% ( P = 0.001). The was no correlation between progesterone status and survival ( P > 0.05) in that same cohort of patients. Conclusions: In patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary, an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein may be indicative of a better prognosis. Progesterone receptor status does not appear to affect survival.

Juvenile granulosa cell tumor (JGCT) of the ovary, if diagnosed at an early stage, has a favorable prognosis. Recurrences are uncommon but typically occur within the first year. The patient presented here was treated with a left oophorectomy after initial presentation. Tumor recurrence in the left adnexa, diagnosed 48 months later, was treated with cytoreductive surgery followed by chemotherapy; she remains disease free 19 months after this recurrence. Late recurrences of JGCT can occur and continued close surveillance is recommended.

Pelvic exenteration has usually been employed as salvage treatment for gynecologic malignancies which have failed primary radiotherapy. The therapeutic mainstay for vulvar melanomas has become wide local excision with or without concurrent regional node dissection. Patients with primary melanoma of the vagina who undergo exenteration as primary therapy may experience 50% 5-year survival if the pelvic nodes are free of metastases. However, the overall 5-year survival for vaginal melanoma is 15%. In our patient population, there have been four patients with vaginal or urethral melanomas treated primarily with pelvic exenteration. The purpose of this study was to report that patients with vaginal or urethral melanomas over 3 mm in thickness may benefit from primary pelvic exenteration. Four patients underwent pelvic exenteration at Indiana University Medical Center for malignant melanoma of the vagina or urethra between 1986 and 1992. The pathologic specimens of all patients were analyzed for thickness, growth pattern, and nodal metastases. Patient age ranged from 50 to 71. Thickness of the melanomas ranged from >3 to 12 mm. All four patients underwent exenterations, three total and one anterior. All patients had negative pelvic and inguinal nodes at the time of surgery. None of the patients has experienced a recurrence. Three of four patients are alive without evidence of disease at 31 to 97 months following their exenteration. One patient died postoperatively of cardiopulmonary complications. Patients with melanomas of the vagina and female urethra, greater than 3 mm in thickness, may benefit from primary pelvic exenteration.

Central nervous system metastases from epithelial ovarian carcinoma are uncommon. A retrospective study was undertaken to see if there was a difference in brain metastases from ovarian cancer in our patient population as compared to the literature. A retrospective study of all patients diagnosed with brain metastases from epithelial ovarian carcinoma at two institutions was performed. All patients were analyzed for stage, grade, type of chemotherapy, sites of recurrence, time to relapse, and survival after relapse. The results were compared to a compilation of reported cases from the literature. Sixteen patients with central nervous system metastases of 479 patients treated for ovarian carcinoma between January 1, 1979 and December 31, 1992 were identified. All 16 patients were diagnosed with serous cystadenocarcinoma, and all were either stage III or IV on presentation. Fifteen of the 16 patients had grade 2 or 3 disease. Histologic grade, at the time of diagnosis, did not influence survival after central nervous system recurrence; however, stage at original diagnosis did influence survival after brain metastases (P < 0.001). Eight of 11 patients undergoing second-look laparotomy had no evidence of disease. The most common presenting symptom of central nervous system disease was a slowly worsening headache of several weeks duration. The median time from original diagnosis to diagnosis of central nervous system disease was 19 months with a median survival after diagnosis of central nervous system disease of 3 months. The incidence of brain metastases in patients with epithelial ovarian carcinoma in our institutions was 3.3%. In conclusion, our incidence of brain metastases of 3.3% was not statistically significant from other reported rates. Patients who underwent radiation therapy with either craniotomy or chemotherapy for their brain metastases fared better than those who received radiation alone.

Malignant mixed mesodermal tumors of the ovary occur in less than 1% of cases of ovarian cancer. They have a dismal prognosis and the most effective type of therapy is still not known. All cases of malignant mixed mesodermal tumor of the ovary between January 1, 1985 and May 1, 1994 operated on by the gynecologic oncology service are the subject of this report. Data were obtained from the hospital and office records of the patients. Nine patients who had their primary surgery by the gynecologic oncology service were found to have the diagnosis of malignant mixed mesodermal tumor of the ovary. Homologous tumors were found in five patients and heterologous tumors in four. Homologous tumors (mean survival 15.2 months) showed a better survival than heterologous tumors (mean survival 6.5 months; P = 0.001). An elevated estrogen receptor status was shown to correspond to longer survival (P < 0.0001). Six specimens were considered to be estrogen receptor positive and three were receptor negative. The mean survival in those patients who had a positive estrogen receptor status, 13.7 months, with a median of 7.5 months was significantly higher than those who were not positive, 6.7 months (P = 0.019) with a median of 6.25 months. All specimens were progesterone receptor negative. Malignant mixed mesodermal tumors of the ovary have a dismal prognosis, no effective therapy, and controversial prognostic indicators. Increasing estrogen receptor status appeared to correlate with longer mean survival. Larger, multi-institutional studies need to be done to determine the overall significance of these findings.

Extramammary Paget's disease of the vulva is an uncommon vulvar neoplasm with a high rate of recurrence. A 64-year-old white female with a history of extramammary Paget's disease of the vulva, excised in 1987 by skinning vulvectomy and treated again in 1993 by skinning vulvectomy with split-thickness skin grafting, presented in 1994 with recurrent Paget's disease in the area of the skin graft. Extramammary Paget's disease of the vulva may recur in an area previously totally excised and transplanted with autologous skin. Therefore, close follow-up is necessary in all patients with this pathologic entity.

The authors conducted a review of the medical records of all patients less than 40 years of age who were treated with unilateral oophorectomy for stage IA and stage IC epithelial ovarian cancer at one of the eight participating institutions from 1965 to 2000. Fifty-two patients were identified, and they or their families were contacted to provide long-term outcome information. The patients averaged 26 years of age (range, 11-40). The most common cell type was mucinous (48%), followed by serous and endometrioid (19% each), clear cell (10%), and mixed (4%). Seventy-three percent of the tumors were well differentiated, 17% were moderately differentiated, and 10% were poorly differentiated. Eleven patients with stage IA and 8 with stage IC disease received adjuvant chemotherapy. Five of the 52 patients (4 with stage IA and 1 with stage IC disease) experienced a tumor recurrence at 78, 69, 13, 9, and 8 months. Three of the recurrences were in the contralateral ovary. These three women were treated by reparation, and one also received postoperative chemotherapy. They are all alive with no evidence of disease after a mean follow-up of 21 months. One patient had a recurrence in the abdominal peritoneum 9 months after treatment. A second had a pulmonary metastasis diagnosed 78 months after initial treatment. Despite additional chemotherapy or chemoradiation, both of these women died of disease. One patient developed a distinctly different second primary ovarian tumor in the contralateral ovary. Another patient developed an adenosquamous cancer of the endometrium. Twenty-four of the 52 patients reported having attempted pregnancy. Seventeen of them were able to conceive, and these patients have had 26 term pregnancies with 5 spontaneous abortions. No congenital anomalies were reported.

Ovarian carcinoma commonly has an insidious onset. By the time the diagnosis is made, advanced disease is usually present. Rarely does a patient have acute symptoms which require immediate medical attention and lead to the correct diagnosis. A 40-year-old white female presented with lower abdominal pain, nausea, and light-headedness. Physical examination revealed a markedly tender lower abdomen with the right lower quadrant slightly more tender than the left. Hemoglobin level was noted to have decreased 2.6 g/dl over 16 hr. At exploratory laparotomy, 1500 cc of blood and a ruptured right ovarian mass were found. Pathologic analysis revealed a malignant mixed mesodermal tumor of the right ovary and an endometrioma of the left ovary. In conclusion, ovarian carcinoma may present as an acute abdomen because of intra-abdominal hemorrhage. It should be part of the differential diagnosis in a woman with an acute surgical abdomen and a hemoperitoneum.

Purpose. Docetaxel is a relatively new taxane that has not been associated with significant tissue injury after extravasation. We present a case of a patient who had grade 4 tissue toxicity after extravasation of docetaxel infused through a peripheral intravenous site. Case report. A 71-year-old female was being treated for recurrent ovarian cancer with docetaxel and carboplatin. Shortly after the docetaxel infusion began, she experienced docetaxel extravasation into the dorsum of her left hand. The infusion was halted, and then the administration was continued in a peripheral intravenous site in the other upper extremity. Erythema was noted by the patient on the dorsum of her left hand 6 days after infiltration. The following day, the patient noted severe pain, decreased function, and blistering along with increased erythema. The patient presented to the gynecology oncology clinic 11 days after the extravasation injury occurred. Conservative management was undertaken, and over the next 4 weeks the patient had resolution of the skin changes and full return of function. Conclusion. Docetaxel can cause significant delayed tissue injury if extravasation occurs.