Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer.

BACKGROUND: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin-paclitaxel (CP) or carboplatin-liposomal doxorubicin (CPLD). METHODS: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 10(9) per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. RESULTS: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008).Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). CONCLUSION: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity.

Nonclosure of peritoneum at radical abdominal hysterectomy and pelvic node dissection: a randomized study.

OBJECTIVE: To compare closure and nonclosure of the peritoneum at radical abdominal hysterectomy and pelvic node dissection with respect to postoperative morbidity. METHODS: Women with uterine cancer who underwent radical abdominal hysterectomy and node dissection type II or III of Piver-Rutledge were assigned randomly to have a standard closure of pelvic and parietal peritoneum and placement of a T-shaped suction drain or to have the peritoneum left open but the vagina closed and two abdominal drains placed. Adjuvant radiotherapy was given to patients with risk factors. The postoperative incidence of lymphocysts (within 8 weeks from the operation and after 1 year) and infection-related and non-infection-related complications were analyzed. RESULTS: One hundred twenty subjects were enrolled, of whom 59 had peritoneal closure and 61 did not. Both groups were similar with regard to age, weight, nodes removed, nodal metastases, operative time, type of surgery, need for transfusion, and incidence of postoperative radiotherapy. The median follow-up was 36 months (range 11-72). Eleven patients died, four because of treatment-related complications. The amount of drainage was significantly higher in the closed group than in the unclosed group (median 740 mL, range 50-5980 versus median 340 mL, range 40-4000; P < .005). The incidence of asymptomatic lymphocysts was similar in the closed and open groups at 2 weeks (17 of 59 versus 15 of 6, respectively), at 8 weeks (eight of 56 versus ten of 61, respectively), and after 1 year (one of 21 versus four of 22, respectively). No difference was found between closed and open groups in terms of symptomatic lymphocysts (one of 59 versus two of 61, respectively), wound and pelvic infection (seven of 59 versus 11 of 61, respectively), febrile morbidity (two of 59 versus 11 of 61, respectively), and obstruction (zero of 59 versus one of 61, respectively). CONCLUSION: Nonclosure of the peritoneum at radical abdominal hysterectomy and node dissection is not hazardous and is not associated with an increased incidence of infection- or adhesion-related complications.

Endometrial thickness in tamoxifen-treated patients: an independent predictor of endometrial disease.

OBJECTIVE: To assess the independent contribution of transvaginal ultrasound in identifying women at risk for endometrial disorders, and determine whether a cutoff value identifies women who need endometrial histologic assessment. METHODS: Postmenopausal women with breast cancer who were receiving tamoxifen, with ultrasonographic endometrial thickness greater than 4 mm or vaginal bleeding, had hysteroscopy with selective endometrial biopsies. Endometrial thickness, duration of tamoxifen therapy, and endometrial histology were studied. Parametric and nonparametric tests and logistic regression and receiver operating characteristic curves were used for statistical analysis. RESULTS: The study population consisted of 163 women, 46 with vaginal bleeding. The proportion of women with abnormal histologic findings was greater among those with endometrial thicknesses exceeding 9 mm compared with those with endometrial thicknesses 9 mm or less (60% versus 6.1%, P < .001) and among women who received tamoxifen for more than 27 months than those who received it for less time (46% versus 16%, P < .005). Logistic regression showed that endometrial thickness greater than 9 mm and vaginal bleeding were independent predictors of abnormal findings at hysteroscopy. CONCLUSION: In women taking tamoxifen, sonographic endometrial thickness exceeding 9 mm and the presence of vaginal bleeding are independent predictors of endometrial disease. If either exists, hysteroscopy and biopsy should be done.

DNA-ploidy and proliferative activity in uterine-tumors - an in-vivo study using bromodeoxyuridine and flow-cytometry.

We have studied the DNA ploidy and the proliferative activity in 102 patients with endometrial and cervical carcinoma, by flow cytometry. Samples were excised 1 hour after bromodeoxyuridine (BrdU, 250 mg/) e.v. infusion and fixed in 70% ethanol. Nuclear DNA content and BrdU incorporation, were simultaneously determined to obtain ploidy (DNA index) and proliferative activity (BrdU-labeling index, LI). No acute toxicity or side effects related to BrdU injection were recorded. The overall feasibility of the determinations was higher than 90% (93/102). Twenty-two out of 59 (37.2%) endometrial neoplasms and 23 out of 34 (67.6%) cervical neoplasms were aneuploid, with a median DNA-index of the aneuploid peak of 1.3 and 1.4, respectively. Overall median BrdU LIs were 4.8% and 7.2%. Proliferative activity was found to be higher in aneuploid tumors (p<.05). DNA ploidy and/or BrdU-LI were not significantly related either with the clinical stage or the histopathologic grading in either tumor type. The BrdU in vivo administration coupled with bivariate FCM for measurement is a simple method that can be performed in clinical settings to better evaluate the prognostic significance of proliferative parameters in gynecological tumors.

Pelvic exenteration in gynecologic oncology. Review.

Pelvic exenteration is still indicated in the treatment of gynecological cancer, in patients with pelvic resectable disease, after the failure of standard treatment. The reported survival ranges from 20 to 60% and has been increasing in the last 15 years; the prognostic factors more frequently described are margin status, time from diagnosis or radiotherapy, lesion size, preoperative side-wall fixation. The role of palliative exenteration in patients with non-resectable disease and/or nodal metastases is discussed. Survival and morbidity in elderly patients are comparable to the younger group and age cannot be considered as an exclusion criteria. Gastrointestinal, urinary and infectious complications are still considerable, but morbidity and mortality have been reduced by surgical and intensive care developments. New surgical techniques, i.e. vaginal reconstruction and continent urinary diversions, have improved quality of life, especially in younger patients, with longer expected survival.

Adenocarcinoma of the uterine cervix.

From 1970 to 1989, 39 patients with cervical adenocarcinoma (9.3% of all cervical cancers) were treated in the Department of Gynecology - University of Pavia. Adenocarcinoma seemed to be a disease epidemiologically different from epidermoid carcinoma. Treatment included radical hysterectomy, radiotherapy, radical hysterectomy and radiotherapy. In stage I disease survival was not significantly influenced by treatment modality. However in young patients without risk factors surgery seemed to obtain the best results; in high risk patients adjuvant radiotherapy did not apparently improve survival. Prognosis for adenocarcinoma seemed to be worse than for its squamous counterpart. The main prognostic factors were grading and lymph node status. Relapse occurred also a long time after treatment. In 2 cases we observed Cervical Intraepithelial Neoplasia grade 3 (CIN 3) in association with adenocarcinoma.

Microlaparoscopy: a new approach to the reassessment of ovarian cancer patients.

BACKGROUND: The purpose of the work was to determine the feasibility and accuracy of microlaparoscopy as diagnostic method for the reassessment of ovarian cancer patients. METHODS: Eight patients scheduled for second-look laparoscopy who had undergone primary surgery for ovarian cancer followed by 6 cycles of chemotherapy were included in the study. Microlaparoscopy was performed using a 2.8 mm laparoscope followed by conventional 10-mm laparoscopy. Three additional 5-mm ancillary trocars were inserted to perform intraabdominal biopsies. Pelvic washings were performed in all cases. RESULTS: Microlaparoscopy was feasible in all cases and as accurate as conventional laparoscopy in seven cases. In one case the procedure was terminated before conventional laparoscopy because of positive biopsies at frozen section examination. There were no intra-operative complications related to microlaparoscopy. The median time from skin incision to the removal of the microlaparoscope was 47 minutes (range 30-70). CONCLUSION: Microlaparoscopy seems to be a safe, accurate, minimally invasive method and therefore we suggest its use as primary approach to the reassessment of ovarian cancer patients.

Oral ondansetron and intravenous dexamethasone in the prevention of cisplatin-induced emesis. A phase II trial in women.

Fifty-eight previously untreated patients with gynecological cancer, assigned to cisplatin-based chemotherapy (40-80 mg/m2), received the following antiemetic treatment: day 0, oral ondansetron 8 mg 3 times/day + intravenous dexamethasone 16 mg; days 1-7, oral ondansetron 8 mg twice/day. In cycle 1 complete or major control (0-2 emetic episodes) was achieved in 94.6% of the patients in the acute phase (day 0) and in 89.2% in the delayed phase (day 1-7). In the subgroup receiving cisplatin > or = 75 mg/m2 the effect on acute and delayed emesis decreased significantly with subsequent courses. Reversible side effects were observed in 8.9% of the cases. Oral ondansetron was efficacious, well tolerated and is worth testing further in randomized trials with intravenous therapy.

[Lymph node metastasis of carcinoma of the cervix uteri. Role of lymphography and computerized tomography]. / Metastasi linfonodali nel carcinoma della cervice uterina. Ruolo della linfografia e della tomografia computerizzata.

The presence of lymph nodal metastases in the patients affected with carcinoma of the uterine cervix is of the utmost clinical relevance. In the Radiology, Obstetrics and Gynecology Departments of Pavia University we have evaluated the accuracy of lymphangiography and CT in recognizing lymph nodal metastases in 95 patients, 58 of them evaluated preoperatively (49 subsequently submitted to radical hysterectomy). CT accuracy was also evaluated in 37 patients with a clinically suspected relapse of cervical cancer. In the first group the overall results were: 91% accuracy, 88% sensitivity, 92.5% specificity for lymphangiography and 87.9% accuracy, 72.2% sensitivity, and 95% specificity for CT (in 49 patients, stage I-II, submitted to lymphadenectomy, lymphangiographic accuracy was 91%, sensitivity was 88%, specificity 92% versus CT accuracy 85.7%, 44.4% sensitivity, and 95% specificity). In the second group (relapse) CT accuracy, sensitivity and specificity were 94%, 100%, and 91%, respectively. In conclusion, lymphangiography gives better results than CT in the patients with early stages (I-II) of the disease. In advanced stages and relapses CT was found to have high accuracy in demonstrating lymph node status. This information is useful for treatment planning and for avoiding unnecessary surgical exploration.