Función pronóstica de los parámetros derivados de FDG PET en la estadificación preoperatoria del cáncer de endometrio / Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer

Objetivo: Investigar el papel pronóstico preoperatorio de la PET/TC con 18F-FDG en pacientes con carcinoma de endometrio (CE). Material y métodos: Se realizó PET/TC con 18F-FDG en 57 pacientes para el estudio preoperatorio del CE. Se evaluaron los valores de captación estandarizados máximos y medios (SUVmax, media), volumen tumoral metabólico (MTV) y glicólisis de lesión total (TLG) de tumores primarios, a diferentes umbrales de 40%, 50%, 60% (40-50-60), comparándose con las características anatomopatológicas. Se evaluó el rendimiento diagnóstico de los parámetros PET (categorizados por análisis ROC) en la discriminación de la enfermedad de bajo y mediano riesgo y el papel pronóstico en la supervivencia (supervivencia global-OS, supervivencia libre de enfermedad-SSE). Resultados: Los TLG40-50-60 categorizados fueron los únicos parámetros relacionados con FIGO estadio I versus II-III-IV (p = 0,0035 para todos). Los puntos de corte para la estratificación del riesgo fueron 83,69, 61,81 y 41,32, respectivamente (sensibilidad: 60%; especificidad, 71,43% para todos los parámetros. El estadio patológico 1 (pT1) del tumor primario se predijo con MTV60 y TLG40-50 (p = 0,0328, 0,0240 y 0,0147, respectivamente). Los umbrales óptimos fueron 7,795, 99,55 y 77,58, respectivamente (sensibilidad: 38,46%, 53,85% y 53,85%, respectivamente; especificidad: 88,64%, 79,55% y 81,82%, respectivamente). SUVmax y SUVmean40-50-60 fueron los únicos parámetros que discriminaron el subtipo endometrioide del no endometrioide. La sensibilidad fue del 64,86% y 62,16% para SUVmax y SUVmean50-60, y 62,16% para SUVmean40; la especificidad fue del 70% para todos los parámetros. La SG media (DE) fue del 79,77% (3,34%) y la SSE media fue del 77,89% (3,73%). El tipo de tumor fue la única variable significativamente asociada a la SG (p = 0,0486). TLG50 > 77,58 cm3 fue la única variable asociada a un mayor riesgo de recaída (p = 0,0472). Conclusión: TLG40-50-60 y MTV60 de EC primaria tienen valor pronóstico para discriminar FIGO y estadificación patológica. Estos resultados sugieren un posible papel de estos parámetros en la predicción de la agresividad de la CE, mejorando así la caracterización preoperatoria del cáncer de endometrio

Purpose: To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). Methods: 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40-50-60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival -OS; disease free survival - DFS) was evaluated. Results: The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). Conclusion: TLG40-50-60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer

Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer. / Función pronóstica de los parámetros derivados de FDG PET en la estadificación preoperatoria del cáncer de endometrio.

PURPOSE: To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). METHODS: 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40-50-60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival -OS; disease free survival - DFS) was evaluated. RESULTS: The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). CONCLUSION: TLG40-50-60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study.

OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

Sarcoidosis imitando metástasis de cáncer ginecológico: ¿un reto diagnóstico y terapéutico? / Sarcoidosis mimicking metastatic gynaecological malignancies: a diagnostic and therapeutic challenge?

Se han publicado casos clínicos que describen la asociación entre el cáncer y la sarcoidosis; por esta razón, la sarcoidosis siempre debe ser incluída en el diagnóstico diferencial cuando un paciente con cáncer presenta linfadenopatía. La tomografía de emisión de positrones (PET) con 2-[18F]-fluoro-2-desoxi- d -glucosa (FDG) combinada con la tomografía computarizada (TC) se utiliza ampliamente para la estadificación y la vigilancia del cáncer, ya que permite la localización de tejido maligno metabólicamente activo; los resultados de la PET/TC o TC en pacientes con sospecha de recurrencia de cáncer se pueden utilizar para guiar un tratamiento temprano y agresivo. Sin embargo, una adenopatía hipermetabólica benigna puede ser similar a una adenopatía maligna tanto en la TC como en la PET/TC por lo que es importante disponer de un diagnóstico histológico antes de iniciar una terapia antineoplásica basada en las imágenes. En este estudio se presentan cuatro pacientes con tumores ginecológicos malignos y sarcoidosis y se menciona la importancia clínica del diagnóstico diferencial entre recidiva tumoral y enfermedad granulomatosa(AU)

Several case reports describing the coexistence of sarcoidosis and malignancy have been published. Therefore, sarcoidosis should always be considered as a differential diagnosis when a cancer patient develops lymphadenopathy. Positron-emission tomography (PET) 2-[18F]-fluoro-2-deoxy- d -glucose (FDG) combined with computed tomography (CT) is widely used for cancer staging and surveillance because it permits localization of metabolically active malignant tissue. PET/CT or CT findings in patients with suspected cancer recurrence can be used to guide early and aggressive therapy. However, benign hypermetabolic lymphadenopathy can mimic malignant lymphadenopathy, both on a conventional CT scan and on PET/CT. Thus, it is important to obtain a histological diagnosis before initiating antineoplastic therapy based on imaging findings. Four cases of patients affected by gynaecological malignancies and coexisting sarcoidosis are reported in this study. Furthermore, the clinical relevance of making a differential diagnosis between gynaecological cancer recurrence and granulomatous disorder is given specific mention(AU)

Role of 18F-FDG PET in the management of gestational trophoblastic neoplasia.

PURPOSE: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. METHODS: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (ßHCG) and in 4 with ßHCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. RESULTS: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after ßHCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with ßHCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative ßHCG. CONCLUSION: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of ßHCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment.

Sarcoidosis mimicking metastatic gynaecological malignancies: a diagnostic and therapeutic challenge?

Several case reports describing the coexistence of sarcoidosis and malignancy have been published. Therefore, sarcoidosis should always be considered as a differential diagnosis when a cancer patient develops lymphadenopathy. Positron-emission tomography (PET) 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) combined with computed tomography (CT) is widely used for cancer staging and surveillance because it permits localization of metabolically active malignant tissue. PET/CT or CT findings in patients with suspected cancer recurrence can be used to guide early and aggressive therapy. However, benign hypermetabolic lymphadenopathy can mimic malignant lymphadenopathy, both on a conventional CT scan and on PET/CT. Thus, it is important to obtain a histological diagnosis before initiating antineoplastic therapy based on imaging findings. Four cases of patients affected by gynaecological malignancies and coexisting sarcoidosis are reported in this study. Furthermore, the clinical relevance of making a differential diagnosis between gynaecological cancer recurrence and granulomatous disorder is given specific mention.

Follow-up in pulmonary sarcoidosis: comparison between HRCT and pulmonary function tests.

PURPOSE: The authors assessed the clinical usefulness of high-resolution computed tomography (HRCT) for monitoring sarcoidosis by comparing changes on HRCT with those on pulmonary function test (PFT) results over time. MATERIALS AND METHODS: The baseline and follow-up (after 13 months, range 15-63 months) HRCT scans of 14 consecutive patients with sarcoidosis were reviewed by a single observer. Each follow-up HRCT examination was assessed as stable, improved (when the extent of HRCT findings was reduced compared with baseline) and worsened (when the extent of HRCT findings was increased and/or when HRCT pattern had become fibrotic compared with baseline). Any increase or decrease in forced vital capacity (FVC)≥10% from baseline was considered significant. Changes on HRCT were then compared with those on FVC. RESULTS: During a median follow-up of 33 (range 15-63) months, HRCT findings worsened in 8/14 (58%) cases, improved in 3/14 (21%) and remained stable in 3/14 (21%). Agreement between changes on HRCT and FVC was moderate (κ=0.49). In 9/14 (64%) cases, HRCT changes were in line with those on FVC. In 4/5 discordant cases, the worsened HRCT findings were not mirrored by FVC changes. CONCLUSIONS: Despite the small size of our study population, our results suggest that HRCT may provide clinicians with additional information about the evolution of sarcoidosis.

Advantages of multidetector-row CT with multiplanar reformation in guiding percutaneous lung biopsies.

PURPOSE: This study aimed to assess the usefulness of multiplanar reformations (MPR) during multidetector-row computed tomography (MDCT)-guided percutaneous needle biopsy of lung lesions difficult to access with the guidance of the native axial images alone owing to overlying bony structures, large vessels or pleural fissures. MATERIALS AND METHODS: MDCT-guided transthoracic needle biopsy (TNB) was performed on 84 patients (55 men and 29 women; mean age 65 years) with suspected lung neoplasm by using a spiral MDCT scanner with the simultaneous acquisition of six slices per rotation. We determined the site of entry of the 22-gauge Chiba needle on native axial images and coronal or sagittal MPR images. We took care to ensure the shortest needle path without overlying large vessels, main bronchi, pleural fissures or bony structures; access to the lung parenchyma as perpendicular as possible to the pleural plane; and sampling of highly attenuating areas of noncalcified tissue within the lesion. RESULTS: Diagnostic samples were obtained in 96% of cases. In 73 patients, lesions appeared as a solid noncalcified nodule <2 cm; 11 lesions were mass-like. In 22, the biopsy required MPR guidance owing to overlying ribs (18), fissures (2) or hilar-mediastinal location (2). CONCLUSIONS: MDCT MPR images allowed sampling of pulmonary lesions until now considered unreachable with axial MDCT guidance because of overlying bony structures (ribs, sternum and scapulae) or critical location (hilar-mediastinal, proximity to the heart or large vessels). Compared with the conventional procedure, the use of MPR images does not increase the rate of pneumothorax or the procedure time.

Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of regional cooling.

OBJECTIVE: Palmar-plantar erythrodysesthesia (PPE) is a characteristic cutaneous toxicity associated with pegylated liposomal doxirubicin (PLD). Different therapies have been proposed to alleviate PPE onset. We performed a prospective study to evaluate preventive strategies to reduce PPE incidence in patients treated for gynecologic cancers. METHODS: Fifty-three patients were treated from 2001 to 2006 with PLD as single agent therapy or in combination with carboplatin or paclitaxel. PLD dosages were in the range of 30-50 mg/m2 every 21-28 days. All patients received premedication with dexamethasone and pyridoxine. Twenty-eight patients received application of ice packs on extremities during PLD infusion. RESULTS: PPE was observed in 11 patients (20.8%). PLD administration as single agent or in combination and schedule of PLD therapy did not affect PPE incidence. A significant reduction in PPE onset was observed if PLD dosage was 30-35 mg/m2 (p=0.03) and when patients were submitted to regional cooling protocol (p=0.0097). CONCLUSIONS: The use of ice packs around wrists and ankles is a simple and well tolerated prevention strategy and its efficacy is demonstrated in this study.

Integrated PET/CT as a first-line re-staging modality in patients with suspected recurrence of ovarian cancer.

PURPOSE: The aims of this study were to compare CT with PET/CT results in patients with suspected ovarian cancer recurrence and to assess the impact of the PET/CT findings on their clinical management. METHODS: Thirty-two consecutive patients with suspected ovarian cancer recurrence were retrospectively included in the study. Abdominal contrast-enhanced CT and PET/CT with [(18)F]FDG, in addition to conventional follow-up, were performed in all 32 patients. After the comparison between CT and PET/CT results, based on clinical reports, changes in the clinical management of patients (intermodality changes) due to PET/CT information were analysed. RESULTS: Twenty of the 32 patients were positive at CT (62.5%) versus 29 (90.6%) at PET/CT. Intermodality changes in management, i.e. use of a different treatment modality, after PET/CT examination were indicated in 14/32 (44%) patients. In particular, before PET/CT study, the planned management was as follows: wait-and-see in 7/32 (22%), further instrumental examinations in 4/32 (12%), chemotherapy in 10/32 (31%), diagnostic surgical treatment in 6/32 (19%) and surgical treatment in the remaining 5/32 (16%). After PET/CT study, wait-and-see was indicated in 1/32 (3%), further instrumental examinations in 7/32 (22%), chemotherapy in 16/32 (50%), diagnostic surgical treatment in 2/32 (6%) and surgical treatment in the remaining 6/32 (19%). CONCLUSION: Integrated PET/CT could detect tumour relapse in a higher percentage of patients than could CT. A change in the clinical management was observed in 44% of cases when PET/CT information was added to conventional follow-up findings.

Epidoxorubicin versus no treatment as consolidation therapy in advanced ovarian cancer: results from a phase II study.

To compare the effect of epidoxorubicin given for 4 months versus no treatment in the survival of patients with advanced ovarian cancer and complete pathologic response after first-line surgery and chemotherapy with platinum-based schedules, we conducted a multicenter randomized clinical trial. Patients with histologic diagnosis of epithelial ovarian cancer FIGO stage III or IV at first diagnosis; complete pathologic response at second-look laparotomy/laparoscopy or complete clinic response; and those who have had first-line therapy including surgery and one regimen containing cisplatin or carboplatinum were eligible for the study and were randomly allocated to epidoxorubicin 120 mg/sqm or no treatment. A total of 64 women were allocated to epidoxorubicin and 74 to no treatment. There were 20 and 19 deaths, respectively, in the epidoxorubicin and no-treatment groups. The 3-year percent overall survival was 79.0% and 78.7%, respectively, in the no-treatment and epidoxorubicin groups (log-rank test, P= 0.93).

Early smoking-induced lung lesions in asymptomatic subjects. Correlations between high resolution dynamic CT and pulmonary function testing.

PURPOSE: To evaluate the prevalence and significance of the pathological effects of cigarette smoking on the lung and the sensitivity of high-resolution CT (HRCT) in the recognition of early smoking-induced lesions in asymptomatic former or current smokers. MATERIALS AND METHODS: We performed a prospective and consecutive analysis of 36 volunteers (16 males, 20 females), 10 non-smokers (3 males; 7 females) and 26 smokers (13 males; 13 females / 17 current smokers; 9 former smokers), all asymptomatic and with normal respiratory flows. These subjects underwent lung function testing and HRCT, after providing written informed consent for the study. The HRCT scans were obtained at three pre-selected levels (aortic arch, tracheal carina and venous hilum). The same scans were obtained in post-expiration phase. At the level of the apical segmental bronchus of the right upper lobe, we measured on the monitor wall thickening, and the total and internal diameters using the techniques reported in literature. Each study was independently evaluated by two radiologists that were blinded to all clinical and functional data; they also evaluated the presence, prevalence and type of emphysema, areas of patchy hyperlucency and oligoemia in the inspiration phase and areas of expiratory air trapping. The extension was evaluated with the visual score method. The data obtained were analysed with the Windows SPSS package for statistical analysis. RESULTS: The two groups (non smokers and smokers) showed significant differences in some functional tests such as FEV1 (p<0.005) and Tiffeneau index (p<0.005), which were lower in current-smokers or former-smokers, although still within the normal range. The HRCT study did not show areas of emphysema or air trapping in non smokers. In the smokers' group, air trapping was observed in 30.7% of cases: 33.3% former-smokers and 29.4% current smokers (mean extension was 21.36% in former smokers and 9.48% in current smokers). Mean extension in the smokers' group was 13.94%. Pulmonary emphysema was found in 34.6% of cases in the smokers' group: 33.3% former-smokers and 35.2% current-smokers. Emphysema was prevalent in the upper lobes (88.8%). Mean extension was 8.76% in the former smokers group and 18.81% in current-smokers, with a total mean extension of 15.47% in the smokers' group. Statistically, there was a significant difference between non-smokers and smokers as regards emphysema extension and expiratory air trapping (p=0.034 and p=0.050, respectively). The smokers' group had a significantly wider diameter of the apical segmental bronchus of the right upper lobe than the controls. There was no significant statistical correlation between this dilatation and the emphysema score (r=0.051; p=0.81). The entity of smoking history did not correlate with emphysema extension or air trapping or with the size of the apical segmental bronchus of the right upper lobe. CONCLUSIONS: Our study demonstrates that HRCT is more sensitive and specific than commonly-used functional tests for the evaluation of initial emphysema in asymptomatic smokers. We observed expiratory air trapping only in the smokers' group, and only of the lobular type, without evidence of disease in inspiratory scans. Among the smokers and former-smokers, air trapping was found in 30.7% of subjects, with a mean extension lower than 10%. Our results therefore suggest that, even in asymptomatic subjects, expiratory air trapping is probably pathological and, once bronchial asthma has been excluded, it may be related to cigarette smoking and indicate early inflammatory bronchiolar damage. HRCT may therefore be regarded as a useful tool in the early diagnosis of smoking-related lung disease.

Identification of high risk patients with endometrial carcinoma. Prognostic assessment of endometrial cancer.

OBJECTIVES: To verify the importance of DNA ploidy on clinical outcome in endometrial carcinoma and to investigate whether the prognostic information obtained by this variable is independent from other clinical-pathologic features. MATERIALS AND METHODS: Univariate and multivariate analysis of clinical and pathologic prognostic factors obtained from 203 consecutive cases of endometrial cancer, that had been surgically treated in our hospital, were performed. RESULTS: Significant prognostic factors according to the Kaplan-Meier method were age at the time of diagnosis, grade of differentiation, peritoneal cytology, node involvement, vascular invasion, myometrial infiltration and ploidy. At multivariate analysis only DNA ploidy resulted to be an independent variable. CONCLUSIONS: In our analysis DNA content is the only parameter which preserved prognostic significance in multivariate analysis.

Paclitaxel vs epidoxorubicin plus paclitaxel as second-line therapy for platinum-refractory and -resistant ovarian cancer.

We conducted a randomized clinical trial to compare the efficacy and safety of paclitaxel and a combination including paclitaxel and epidoxorubicin as second-line treatment in platinum-refractory or -resistant ovarian cancer. Patients who had progressive or stable disease during first-line therapy with regimens containing cisplatin or carboplatin (platinum-refractory patients) or who responded and subsequently relapsed within 6 months after discontinuation of first-line platinum-based regimen (platinum-resistant patients) were eligible for the study. They were randomly allocated to paclitaxel 175 mg/m2 every 28 days (41 women) for five cycles or epidoxorubicin 120 mg/m2 iv plus paclitaxel 150 mg/m2 iv every 28 days (40 women). The overall response rates (complete plus partial response) were, respectively, 17.1% in the paclitaxel and 34.2% in the epidoxorubicin plus paclitaxel group (P = 0.10). The 2-year percentage survival was 18 in the paclitaxel group and 10 in the epidoxorubicin plus paclitaxel group. A higher frequency of leukopenia and thrombocytopenia was reported in women allocated to epidoxorubicin plus paclitaxel than in the paclitaxel alone group, but the frequency of neurotoxicity was higher in the paclitaxel alone group. An important limitation of the study is the small sample size. With this sample size we can exclude that multiagent therapy in comparison with single-agent therapy improves response in platinum-refractory and -resistant ovarian cancer of more than 25%.

Prognostic factors in patients with with locally advanced cervical cancer treated with radical hysterectomy and adjuvant radiotherapy.

The purpose of this study was to investigate the presence of risk factors for node metastases and to estimate survival in patients with cervical cancer, stages IB and IIA. In a retrospective study of 103 patients with cervical cancer stages IB and IIA, all treated with radical hysterectomy and adjuvant radiotherapy, we estimated survival curves according to different prognostic parameters. Mean follow-up time was 97 months. A significant difference between clinical pre-operative assessment and histological determination of real extent of the disease was evidenced. Pelvic lymph node metastases (P = 0.0005) significantly correlated with survival. This study shows that only lymph node involvement is an independent prognostic factor. Stage acts through nodal status in its impact on survival. A surgical-pathological staging in early stage cervical cancers is found to be more appropriate to correctly estimate patients' survival and prognosis.

Octreotide in the management of bowel obstruction in terminal ovarian cancer.

Intestinal obstruction is a common and distressing clinical complication in ovarian cancer. The aim of our study was to assess vomit control in terminal ovarian cancer patients with inoperable gastrointestinal obstruction, using a symptomatic pharmacological treatment with octreotide which obviates the need for nasogastric tube placement. We studied 13 patients, all of whom had advanced ovarian cancer FIGO stage IIIc. Seven patients were treated in the Gynecology Department of S. Raffaele Hospital, at the University of Milan, and 6 were managed in the University of Varese Hospital. Octreotide was administered at doses starting with 0.3 up to 0.6 mg (mean 0.44 mg) a day by subcutaneous bolus or continuous infusion. Octreotide controlled vomiting in all cases to grade 0 on the WHO emesis scale. Complete relief of symptoms was achieved within 3.07 days (range 1-6 days). Vomiting stopped within 2-3 days of starting treatment in most patients. In 8 patients with a nasogastric tube, drainage decreased from 2000 to under 100 ml/day after the start of octreotide treatment. No side effects were reported. All patients died with minimal distress or pain.

Adjunctive radiotherapy after radical hysterectomy in high risk early stage cervical carcinoma. Assessment of morbidity and recurrences.

Morbidity and prognostic factors were reviewed in 145 patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between January 1976 and December 1986. Ninety five patients received adjuvant postoperative external radiotherapy (average 4800 cGY). One hundred twenty patients were F.I.G.O. stage IB, and 25 were clinical stage IIA. Indications for adjuvant radiotherapy included 3 categories of patients with high risk factors: 1) pelvic lymph node metastases, 2) parametrial invasion and/or surgical margins involvement, 3) large volume, deep stromal penetration or uterine extension. Four percent of the patients suffered major gastrointestinal complications, 8.9% had major genito-urinary complications, 19 patients had lymphocytes and 2 patients complained of thromboembolic episodes. Of the 19 patients with major gastrointestinal or genito-urinary morbidity, 7 (38.8%) were related to radiotherapy. Thirty-nine patients had node involvement, 38 of these patients received radiotherapy and 5-year survival rate was 43.5% versus 87.7% in other cases (p < 0.001). Of the 14 patients with parametrial invasion and/or surgical margins involvement, 10 received radiotherapy and overall 5-yrs survival was 85.8%. Of the 37 patients related to third category of risk, 18 received adjuvant radiotherapy with 83.3% 5-yrs survival versus 94.7% of other 19 cases (n.s.). Patients treated with surgery alone had a better 5-yrs survival (96%) than those who received combination therapy (66.3%) (p < 0.001). Adjuvant radiotherapy increases the morbidity of radical hysterectomy, while it has a relative value in preventing local and distant recurrences. In view of reduced survival in high risk patients with node involvement, consideration should be given to adjuvant systemic chemotherapy in high risk cases.

Risk factors for varicose disease before and during pregnancy.

Risk factors for varicose disease before and during pregnancy have been analyzed by use of data from a survey on venous disease in pregnancy conducted in 611 women (mean age thirty years, range fifteen to forty-seven) who consecutively delivered at the Obstetric-Gynecologic Clinic "L. Mangiagalli" of Milan between January and April, 1989. In total, 137 women (22%) reported varicose disease before the index pregnancy. The relative risk (RR) of varicose disease before the index pregnancy increased with age, being, as compared with women aged twenty-nine years or less, 1.6 in those aged thirty to thirty-four and 4.1 in those aged thirty-five years or more (chi 2(1) trend 25.28, p < 0.001). Compared with nulliparae, women reporting a full-term pregnancy before the index pregnancy had an RR of venous disease of 1.2, and the risk increased to 3.8 in women reporting two or more births (chi 2(1) trend 25.28, p < 0.001). A family history of varicose disease was associated with an RR of venous disease of 6.2 (95% confidence interval, CI, from 4.1 to 9.6). No relationship emerged between varicose disease and overweight. Of the 474 women who did not report venous disease before the index pregnancy, 132 (28%) developed venous disease during the index pregnancy. The risk of developing venous disease in pregnancy increased with age, being, as compared with women aged twenty-four years or less, 4.0 in those aged thirty-five years or more, and the trend in risk was statistically significant (chi 2(1) trend 16.25, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Primary carcinoma of the fallopian tube.

BACKGROUND: Because of the rarity of fallopian tube cancer, clinical approaches have changed during the last 18 years. METHODS: Twenty-nine patients with fallopian tube cancer were treated at the Gynecologic Oncology Department of Milan University from 1970 to 1988. The mean patient age was 59 years. Parity, symptomatology and histology were considered. Distribution by stage was as follows: I, 11 (37%); II, 10 (34%); III, 8 (27%) according to the Dodson classification. Twenty patients (69%) underwent surgery followed by pelvic irradiation. Adjuvant chemotherapy was performed in the treatment of 5 women with stage I disease, 6 with stage II, and all 8 with stage III. RESULTS: Five-year overall survival was 41.38%: 47.6% at stages I and II, 25% at stage III. Radiotherapy has not been replaced by cisplatin-based multiagent chemotherapy. Optimal surgical debulking combined with accurate lymph node sampling are not followed by systematic use of repeat laparotomy. CONCLUSIONS: The procedures described in this work improve the clinical assessment and patient survival, and make different series comparable.

[Assessment of the use of Pap test in a sample of pregnant women]. / Valutazione della pratica del Pap-test in un campione di donne gravide.

Four hundred and ninety-nine women were interviewed who gave birth in the "L. Mangiagali" Obstetrics-Gynaecological Clinic between March and April 1989. 22% of these women had never had a Pap-test, 37% reported having had 1-2 cervical smears and 41% 3 or more. In the group of patients that contacted a private gynaecologist during pregnancy, the percentage of women who had never had a Pap-test was 18% versus 30% in the group of subjects followed in the public health service. Although pluriparas reported a greater number of Pap-test than primiparas, this difference was not statistically significant. Youth is significantly related to the probability of never having had a cervical smear. Social and economic factors were also clearly important. In particular, women with a low educational level represented the group with the highest risk for the lack of cervical screening. The role of the gynaecologist and preventive programmes aimed at the higher risk levels play an important role in terms of heightening awareness.