Primary adenocarcinoma of the rectovaginal septum arising in pregnancy in the absence of endometriosis.

A case of primary adenocarcinoma of the rectovaginal septum (PARVS) is reported with clinical and pathological findings. A 37-year-old Caucasian woman with a history of sterility and small posterior leiomyoma, a few months after a cesarean section, was admitted because of vaginal spotting, abdominal pain and constipation. Her previous history did not reveal exposure to diethylstil bestrol (DES). Pelvic computed tomography showed a heterogeneous pelvic mass in the Douglas pouch, measuring 9 cm in diameter, located in the rectovaginal septum, involving the rectal and vaginal wall. Histological examination of neoplastic tissue revealed solid sheet structures, occasional tubular lumen, extensive necrotic areas and clear cells. The neoplastic elements showed immunoreactivity for Mullerian markers (cytokeratin 7, CA-125 and vimentin). Because, the present case of PARVS cannot be due to DES exposure, the clear appearance of the neoplastic elements could represent only one differentiation of Mullerian rests. Moreover, because no foci of endometriosis were identified in several sections of the neoplasm, uterine and cervical wall, and tissues nearby the neoplasm could represent a rare subtype of PARVS arising in the absence of endometriosis.

Behaviour of ovarian tumors of low malignant potential treated with conservative surgery.

OBJECTIVE: Fertility-sparing surgery has been proposed for the treatment of borderline ovarian tumors. The aim of this study was to evaluate the outcome of patients submitted to cystectomy (CYS) compared with patients treated by unilateral salpingo-oophorectomy (USO) or bilateral salpingo-oophorectomy with/without total hysterectomy (radical surgery, RS). METHODS: We reviewed retrospectively the data of patients treated in 3 institutions for borderline ovarian tumors. One hundred and sixty-eight patients underwent laparoscopic or laparotomic surgical treatment from 1985 to 2006. Tumor recurrence rate, disease-free survival and site of recurrences were evaluated. Specific prognostic factors, such as stage, histology, micropapillary subtype, exophytic tumor growth, intraoperative spillage, endosalpingiosis, staging procedures, and route of surgery were analysed. RESULTS: Thirty-five patients underwent cystectomy, 50 unilateral salpingo-oopohorectomy, and 83 radical surgery. Twelve patients in the CYS group (34.3%), 10 in the USO group (20.0%), and 5 (6.0%) in RS group relapsed. Five-year progression-free survival (PFS) was 59.6%, 78.4%, and 93.5% in CYS, USO and RS groups, respectively. None of the relapsed patients died of disease. CONCLUSIONS: Cystectomy is an effective surgical strategy for patients with borderline ovarian tumor. The higher risk of local relapses is not associated with a reduction in the overall survival. The procedure should be offered to young patients with bilateral tumors and to very young ones, considering the higher risk of local relapse.

Vaginal versus abdominal hysterectomy in endometrial cancer: a retrospective study in a selective population.

The purpose of this study was to analyze the outcome of vaginal and abdominal hysterectomy for the treatment of early-stage endometrial cancer in a selected group of elder patients. This retrospective study analyzed a total of 154 patients: 113 (group I) underwent vaginal surgery and 41 (group II) underwent laparotomy. In both groups, we investigated the following parameters: intra- and postoperative complications, mean operative time, mean hospital stay, disease-free survival (DFS), overall survival (OS), and time of local or retroperitoneal recurrence. Medically compromised patients were significantly more frequent in the vaginal surgery group (P = 0.005), and the operative duration in this group was significantly shorter (P = 0.01). Intra- and postoperative complications, along with local and distant recurrence, did not show a statistically significant difference in the two groups. Total survival in the two populations, 85% at 5 years, did not reach statistically significant difference either in terms of DFS or in terms of OS. Vaginal surgery compared to traditional abdominal approach is feasible also in patients with high surgical risk; it does not require general anesthesia, abolishes abdominal trauma correlated to laparotomy, and allows a quicker reprise of the bladder and rectal function; therefore, it achieves high eradication rates and low intra- and postoperative morbidity rates.

Detection of human papillomavirus in organs of upper genital tract in women with cervical cancer.

In this study, we evaluated the presence of human papillomavirus (HPV) DNA in organs of the female upper genital tract, using nine hysterectomy and salpingo-oophorectomy specimens affected by HPV-positive invasive cervical carcinomas, to establish if cervical HPV infection can spread to upper tracts of the female genital system. HPV DNA was evaluated by polymerase chain reaction (PCR) in all cervical carcinomas as well as in all tracts of the genital system. Then, these data were compared with the results obtained from PCR study of five other hysterectomy and salpingo-oophorectomy specimens (control cases). The criteria used for selection of the control cases were informed consent of the patients for research at the time of surgery, absence of neoplasms, absence of any anatomic lesion caused by HPV in cervix, and external genitalia. All selected cases were squamous cervical carcinomas. PCR analysis revealed HPV DNA in all cases of cervical carcinoma. The HPV DNA was detected as weak positivity on PCR analysis in other organs of the genital system. However, the distribution of HPV DNA varied in the various cases and in the different tracts of the same hysterectomy and salpingo-oophorectomy specimen. We believe that the HPV DNA, detected as a weakly positive signal, in the upper genital tract of patients who have a cervical squamous carcinoma could be a reflection of a latent HPV infection, as well as a sign of the existence of micrometastases containing HPV DNA, which cannot be detected by conventional histologic techniques.

Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial.

Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m(-2)), doxorubicin (45 mg m(-2)), cyclophosphamide (600 mg m(-2)) every 28 days for five cycles, or external RT (45-50 Gy on a 5 days week(-1) schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66-1.36; P = 0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63-1.23; P = 0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited.

Metastatic extragenital neoplasms to the uterus: a clinicopathologic study of four cases.

The aim of this study was to elucidate the clinicopathologic features, the differential diagnostic problems, and the prognostic consequences of patients with metastatic extragenital malignancies to uterus. The patients with metastatic extragenital malignancies to the uterus were evaluated. We considered the metastases in non-genital tract organs at diagnosis of primary neoplasm, the distribution of the metastases in the uterus, and the presence of concomitant metastases in other genital and non-genital tract organs. There were four cases of metastatic extragenital malignancies to the uterus. The breast was the most frequent primary site (two cases: 50%). The other two primary tumors were adenocarcinoma of the cecum and malignant melanoma of the skin. The diagnosis was facilitated by clinical history, revealing the previous primary neoplasm, and by specific immunohistochemical study. Almost all the patients died from disseminated disease. Thus, the prognosis of metastatic extragenital malignancies to the uterus alone or simultaneously to the uterus and other organs of the genital tract is poor. Thus, the metastases to the uterus and to other organs of the genital tract can be considered a preterminal event.

Radioguided sentinel lymph node detection in vulvar cancer.

Lymph node status is the most important prognostic factor in vulvar cancer. Histologically, sentinel nodes may be representative of the status of the other regional nodes. Identification and histopathologic evaluation of sentinel nodes could then have a significant impact on clinical management and surgery. The aim of this study was to evaluate the feasibility and diagnostic accuracy of sentinel lymph node detection by preoperative lymphoscintigraphy with technetium-99 m-labeled nanocolloid, followed by radioguided intraoperative detection. Nine patients with stage T1, N0, M0, and 11 patients with stage T2, N0, M0 squamous cell carcinoma of the vulva were included in the study. Only three cases had lesions exceeding 3.5 cm in diameter. Sentinel nodes were detected in 100% of cases. A total of 30 inguinofemoral lymphadenectomies were performed, with a mean of 10 surgically removed nodes. Histological examination revealed 17 true negative sentinel nodes, 2 true positive, and 1 false negative. In our case series, sentinel lymph node detection had a 95% diagnostic accuracy, with only one false negative. Based on literature evidence, the sentinel node procedure is feasible and reliable in vulvar cancer; however, the value of sentinel node dissection in the treatment of early-stage vulvar cancer still needs to be confirmed.

Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group.

BACKGROUND: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. PATIENTS AND METHODS: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m(2) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. RESULTS: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). CONCLUSIONS: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance status.

A multicentre collaborative study on the use of cold scalpel and electrocautery for midline abdominal incision.

BACKGROUND: Although studies in animals demonstrated a better wound healing after abdominal incision with cold scalpel than with electrocautery, clinical experiences did not confirm these findings. The purpose of this study was to compare early and late wound complications between diathermy and scalpel in gynecologic oncologic patients undergoing midline abdominal incision. METHODS: Patients undergoing midline abdominal incision for uterine malignancies were divided into two groups according to the method used to perform the abdominal midline incision: cold scalpel and diathermy in coagulation mode. Early and late complications were compared. Logistic regressions were used for statistical analysis. RESULTS: Nine hundred sixty-four patients were included, of whom 531 were in the scalpel group and 433 in the electrocautery group. Both groups were similar with respect to demographic, operative, and postoperative characteristics. Univariate analysis revealed a higher incidence of severe wound complications in the scalpel group than in the electrocautery group (8 of 531 versus 1 of 433, P <0.05). After adjustment for confounding variables (eg, age, body mass index) no differences were found between groups. CONCLUSIONS: Scalpel and diathermy are similar in terms of early and late wound complications when used to perform midline abdominal incisions. Therefore the choice of which method to use remains only a matter of surgeon preference.

Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer.

OBJECTIVE: The aim of the study was to analyze the benefit/toxicity profile of a second-line treatment with carboplatin alone or carboplatin plus another non-cross-resistant drug (epidoxorubicin) in ovarian cancer patients sensitive to cisplatin-based chemotherapy at first-line treatment. METHODS: We conducted a randomized clinical trial. Women with epithelial ovarian cancer FIGO Stage II--IV who had a complete or partial response to first-line treatment with cisplatin or carboplatin-based regiments and subsequently progressed or relapsed more than 6 months after discontinuation of first-line treatment were eligible for the study. A total of 190 subjects entered the study. They were randomly allocated to either 300 mg/m(2) of carboplatin every 28 days for five cycles (95 patients) or 120 mg/m(2) of epidoxorubicin and 300 mg/m(2) of carboplatin every 28 days for five cycles (95 patients). RESULTS: A complete response was reported, respectively, in 32 (36%) women allocated to carboplatin alone and in 28 (31.8%) of those allocated to carboplatin plus epidoxorubicin. The corresponding figures for partial response were 18 (20.2%) and 26 (29.9%). Comparing the frequency of complete response, partial response, no change, and progression, the differences between the two groups were not significant (chi(2)(3) 5.10, P = 0.16). The median duration of response was 16 months in the carboplatin alone and 20 months in the carboplatin plus epidoxorubicin group (P = not significant). The 3-year percentage of survival was 29% in the carboplatin alone and 42% in the carboplatin plus epidoxorubicin group; this difference was not statistically significant. The frequency of leukopenia, anemia, and thrombocytopenia grade 3-4 was higher in the epidoxorubicin plus carboplatin than in the carboplatin alone group. Alopecia G3 was present in 88% of women treated with epidoxorubicin plus carboplatin. CONCLUSIONS: The general results of this study do not show any marked differences in response to second-line treatment among women treated with single-agent (carboplatin) or multiagent (carboplatin plus epidoxorubicin) schedules. Toxicity, particularly hematological, was more relevant in women treated with the multiagent schedule.

Clinical value of intraoperative gross examination in endometrial cancer.

We present the largest multicenter study evaluating whether intraoperative visual estimation can accurately assess the depth of myometrial invasion in patients with endometrial cancer. The study population consisted of 403 consecutive women who underwent total hysterectomy for endometrial cancer. After the uterus was removed, a visual estimate of depth of gross myometrial invasion was recorded. The uterus was opened, the endometrial cavity was inspected, and one or more full-thickness incisions were made through the tumor, myometrium, and serosa. An intraoperative estimation of gross myometrial invasion was made and classified as more or less than 50% of the uterine wall. Gross visual estimation accurately identified the microscopic myometrial invasion in 85.3% (344/403) of cases. Sensitivity, specificity, and positive and negative predictive values of gross estimation in determining a microscopic myometrial invasion greater than 50% were 73.0, 92.5, 85.0, and 85.5%, respectively. Among patients in whom the myometrial invasion was underestimated at gross examination the tumoral invasion was limited to the inner two thirds of the myometrium in 45% (18/40) of cases and the distance from the tumor-myometrial junction to the uterine serosa was greater than 3 mm in 65% (26/40) of cases. We conclude that gross estimation of myometrial invasion is a reliable and inexpensive method for evaluating the invasiveness of uterine carcinomas and that deciding to perform an extensive surgical staging upon gross estimation will be in accordance with the final histopathologic report in about 9 of 10 cases.

Mature results of a prospective randomized trial comparing a three-weekly with an accelerated weekly schedule of cisplatin in advanced ovarian carcinoma.

In a retrospective analysis of a series of clinical trials by Levin and Hryniuk in 1987, the average relative dose intensity of first-line chemotherapy for advanced ovarian cancer correlated significantly with clinical response and survival, and cisplatin was the only drug for which the outcome correlated with the individual drug relative dose intensity. There was a need to test whether and to what extent this evidence would be confirmed in a prospective evaluation. In this study 101 patients with advanced ovarian carcinoma were randomized to receive the same total dose of cisplatin but at the conventional 3-weekly schedule (CTWS) (100 mg/m2 every 3 weeks for six cycles) (51 patients) or at an experimental accelerated weekly schedule (AWS) (100 mg/m2 every week for two triplets of three cycles separated by a 5-week interval) (50 patients). To benefit from a multidrug regimen at the same extent, patients in both arms sequentially received four cycles of doxorubicin and cyclophosphamide. The median follow-up period of this study is 9.7 years. In 42 and 40 patients of the two arms having evaluable response, the clinical complete response rates to cisplatin were 14% and 22% and the complete plus partial response rates were 48% and 55% in the CTWS and in the AWS arm, respectively. These differences were not statistically significant. However, the survival curves were similar during the first 2 years but clearly diverged thereafter in favor of the AWS arm (p = 0.07). At 5 years, 12% and 30% of the patients were still alive in the CTWS and in the AWS arm, respectively. Hematologic toxicity was not relevant in either arm of the study. Nonhematologic toxicity, especially ototoxicity, was substantial and significantly higher in the AWS arm. Although statistically nonsignificant, this AWS regimen of cisplatin is associated with long-term better survival compared to the CTWS regimen in advanced ovarian carcinoma. This accelerated approach administering cisplatin should be further investigated, especially in patients with low residual disease after primary surgery.

Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given for 5 months after cytoreductive surgery for advanced ovarian cancer.

PURPOSE: To compare the efficacy of a treatment with cisplatin plus cyclophosphamide given for 5 months and a short treatment with cisplatin alone in advanced ovarian cancer, we conducted a multicenter randomized clinical trial. PATIENTS AND METHODS: Eligibility criteria were as follows: first diagnosis of histologically confirmed invasive epithelial ovarian cancer of International Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2 plus cyclophosphamide 750 mg/m2 every 21 days for six courses. RESULTS: A total of 607 women were entered onto the study. There was no difference in the response to treatment. Pathologic complete response (CR) was documented in 63 of the weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi 1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and 148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms, respectively. Survival curves were similar in the two groups, with a 3-year percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) = 0.004; P = .96). CONCLUSION: This study found that 2-month monochemotherapy treatment with cisplatin was as effective as 5-month polychemotherapy including cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.

A phase I-II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer.

We conducted a phase I-II study with escalating paclitaxel doses plus carboplatin at a fixed dose for previously untreated patients with advanced ovarian cancer in order to define the maximum tolerated dose. Eligible for the study were women with a histologically confirmed diagnosis of ovarian cancer stage III-IV according to the FIGO classification. In the first phase of the study, 6 patients were allocated escalating paclitaxel doses with fixed-dose carboplatin in order to establish the maximum tolerated dose. The starting dose of paclitaxel was 150 mg/m2 given after carboplatin (300 mg/m2) every 4 weeks for a total of six courses. The paclitaxel dose step was 25 mg/m2 up to 250 mg/m2. The study then progressed to a phase II trial using the maximum tolerated paclitaxel dosage reached during the escalating dose phase. A total of 27 patients entered phase I and 23 phase II. Neurotoxicity was observed in 47 patients (94%; 29 grade 1, 17 grade 2, 1 grade 3, according to the WHO classification). The intensity of neurotoxicity tended to be dose related: out of the 15 patients who received < or = 200 mg paclitaxel, a total of 14 grade 1, but no grade 2 or 3 neurotoxicities, were observed. The frequency of grade 1, 2 and 3 neurotoxicity was 15, 17 and 1, respectively, in the 35 women who received > or = 225 paclitaxel +300 mg carboplatin. There was no clear relationship between median WBC and platelet nadir and dose level. Among other toxicities, alopecia was observed in all 50 cases, hypersensitivity in two (4%) and myalgia in 41 (82%; 34 grade 1 and 7 grade 2). These frequencies tended to increase with the dose, but the relationship was not statistically significant. The overall response rate was 78% (39/50) with a complete response rate of 62% (31/50). In conclusion, this study suggests that carboplatin and paclitaxel can be administered safely to patients with advanced ovarian carcinoma. The maximum dose reached was 250 mg/m2 paclitaxel and 300 mg/m2 for carboplatin, but from a clinical point of view the maximum paclitaxel dose we would consider safe is 225 mg/m2.

Survival of women with advanced ovarian cancer and complete pathologic response at second-look laparotomy.

BACKGROUND: The purpose of the study was to analyze the determinants of long term survival in women with advanced ovarian cancer and negative second-look laparotomy. METHODS: A series of 140 advanced (Stage III-IV) ovarian cancer patients (median age, 54 years; range, 22-74 years) with negative second-look laparotomy after primary surgery and chemotherapy is included in the analysis. At first diagnosis, all patients were treated with radical or debulking surgery. After primary surgery, the patients were treated with a chemotherapy regimen based on cisplatin or carboplatin alone or in combination with other drugs. All second-look laparotomies were performed 6-8 months after first surgery. RESULTS: The overall survival rates were 76% at 3 years, 66% at 5 years, and 51% at 8 years. The corresponding rates for disease free survival were 57, 50, and 43%, respectively. Survival rates were better for women with a residual tumor 1 cm or less after primary surgery. The 5-year probability of survival was 78% in this group, compared with 55% in women with a residual tumor more than 1 cm (log rank test, P < 0.05). Survival rates for women with tumor Grade 3 tended to be worse than Grades 1-2, but the difference was only of borderline statistical significance. No relationship emerged between survival and age, histotype, and presence of ascites at diagnosis. Women with a residual tumor 1 cm or less and positive lymph nodes had a 66% 5-year probability of survival, compared with 85% for women with a residual tumor 1 cm or less and negative lymph nodes. This difference was significant (log rank test, P = 0.05). The 5-year survival probabilities were 47 and 58%, respectively, in women with a residual tumor more than 1 cm and positive or negative lymph nodes. CONCLUSIONS: This analysis shows a favorable long term survival rate for women with advanced ovarian cancer and complete pathologic response after debulking surgery and postoperative chemotherapy. It further suggests that lymph nodal status is a prognostic factor for women with minimal residual tumor after surgery.

Relationship between epidermal growth factor receptor and other prognostic factors in gynecological cancers.

In 62 cases of gynecological malignancies, 16 of the ovarian, 31 of the endometrium and 15 of the cervix, the EGF-R status was evaluated in order to establish its prognostic value and its correlation with other classical prognostic factors. We have failed to demonstrate any correlation between EGF-R status and stage, grade and hormonal receptors, ER/PgR, in ovarian and cervical cancer. In contrast, in endometrial cancer, we observed significantly lower levels of EGF-R in poorly differentiated tumors. Moreover, a weak negative relationship between EGF-R and PgR status was found. Regarding survival, we noticed a better prognosis in patients with ovarian cancer EGF-R positive, but without statistical significance.

[Gynecological celioscopy: indications and findings]. / Celioscopia ginecologica: indicazioni e reperti.

The Authors have critically reviewed 1000 consecutive laparoscopies, performed in the Department of Obstetrics and Gynecology, University of Parma. The most common diseases of the genital tract are represented into the population of the patients studied. Conclusions are the safety and the usefulness of the described technique, particularly in discrimination of pelvic pain, pelvic masses and sterility. Concerning the latest field, the importance of ovarian biopsy in distinguishing hypergonadotropic anovulations is confirmed.