Cancer in pregnancy: maternal and fetal implications on decision-making.

BACKGROUND: Cancer complicates one out of 1,000 pregnancies. No standardized therapeutic interventions have been reported for these patients. METHODS: Fifteen patients with cancer during pregnancy were diagnosed between 6.5 and 36 weeks of gestational age between January 1991 and December 2007. RESULTS: Among the 15 cases one patient with early diagnosis (11 weeks) asked for interruption of pregnancy, two patients rejected chemotherapy in order to avoid fetal effects, seven patients underwent surgery during the first or second trimester, and two patients agreed to start the treatment only after delivery. Standard platinum-based chemotherapy (cisDDP) was postponed in six patients to the second trimester (administered after surgery in 2 cases). Chemotherapy was started between 18.3 and 29.6 weeks (median 22.3 weeks). One patient had pPROM (22.3 weeks) after chemotherapy with cisDDP. Ten patients were delivered by elective cesarean section and three by vaginal delivery. Mean gestational age at delivery was 33.5 weeks (range 32.1-40.0); mean weight at birth was 2,550 g (range 1,250-3,450). None of the newborns showed congenital malformations, and all had normal Apgar scores. Anemia occurred in two newborns. At a median follow-up of 56 months (range 2-198 months) all children were well and healthy. Eleven out of 15 mothers are alive and well, and one is alive with disease. An advanced neoplasm was diagnosed in three patients who died. CONCLUSION: When platinum-based chemotherapy is administered during the 2nd-3rd trimester, adverse effects in newborns are comparable to those in the general population. Deliberate treatment delay to achieve fetal viability or to improve fetal outcome may be reasonable for patients with early-stage cancer.

Preoperative diagnosis of 221 consecutive ovarian masses: scoring system and expert evaluation.

OBJECTIVE: The aim of our work was to assess the diagnostic accuracy of a scoring system versus subjective assessment of the risk of malignancy of pelvic masses achieved by gynecologist/sonologists in the preoperative triage of a busy gynecology department. METHODS: One hundred and eighty-two consecutive patients who underwent surgical removal of ovarian neoplasms were examined. In 39 patients pelvic masses were bilateral. The total number of neoplasms analyzed in this series was 221. Lesions were examined and scored according to the sonographic characteristics. Gynecologist/sonologists also recorded a subjective evaluation of the adnexal masses defining them as "probably benign", and "suspicious/probably malignant". Preoperative ultrasound risk assessment was compared to the final pathologic report and diagnostic accuracy was calculated. CA125 was obtained in all patients and its independent and combined accuracy was calculated. RESULTS: The sensitivity of the scoring system and subjective evaluation was 86% and 95% respectively, specificity was 79% and 91% with a positive predictive value of 41% and 53%. The frequency of positive diagnoses for CA125 was 44% due to the high prevalence of endometrosis in this series (48%). In premenopausal patients (75%) the specificity was 93% and 89% for scoring and subjective evaluation, respectively. The combined use of morphological scoring and CA125 achieved higher specificity and positive predictive values both for the whole series and in premenopausal patients. CONCLUSIONS: These results confirmed that the experience of gynecological surgeons with ultrasound skills, outperforms the morphological indexing assessment of ovarian masses. Nonetheless an easy sonographic descriptive scoring system is not significantly lower in accuracy than the expertise achieved by gynecologists with sonographic skills.

Severe factor X deficiency in pregnancy: case report and review of the literature.

Isolate factor X deficiency is an extremely rare clotting factor disorder inherited in autosomal recessive fashion and pregnancy in a homozygous patient is frequently complicated by recurrent miscarriage, uterine bleeding and premature labour. Eleven pregnancies in seven patients affected by FX deficiency have been reported in the literature. Two additional pregnancies have been reported in a FX variant (FX Friuli). We present a new case of successful at term pregnancy in a homozygous patient.

An analysis of different approaches to ovarian cysts in Italy.

UNLABELLED: The management of pelvic masses represent a rising problem due to the need to obtain an early diagnosis and treatment of ovarian cancers. MATERIALS AND METHODS: In order to evaluate the clinical and surgical approach to ovarian cysts in Italy, we sent a multiple choice questionnaire to 214 members of the Italian Society of Gynecologic Oncology (SIOG) and to 230 members of the Italian Society of Gynecologic Endoscopy (SEGi). Ninety-six resulted evaluable. RESULTS: Transabdominal and transvaginal ultrasound associated with CA125 determination represent the basis for the diagnosis, even if there is no univocal agreement on the ultrasound aspects that may define an ovarian cyst as doubtful. If an ovarian cyst, classified as suspicious, has been diagnosed in a postmenopausal woman, a wide range of therapeutic options have been reported: laparotomic hysterectomy and bilateral salpingo-oophorectomy represent the treatment of choice for 49% of SIOG members, whereas laparoscopic bilateral (45%) or monolateral (39%) salpingo-oophorectomy represents the standard for SEGi members. Ultrasound criteria to distinguish among benign or probably malignant or doubtful ovarian cysts, the treatment of an ovarian cyst during pregnancy, and the management of an unexpected intraoperative diagnosis of borderline ovarian neoplasia are discussed on the basis of answers received by SIOG and SEGi members.

Synchronous fallopian tube and breast cancers: case report and literature review.

A case of fallopian tube cancer was intraoperatively diagnosed in a patient submitted to laparoscopic hysterectomy and bilateral salpingo-oophorectomy because of an ultrasound diagnosis of a probable endometriotic cyst of the right ovary. Postoperatively a complete staging was performed and a synchronous carcinoma of the breast was diagnosed. Consequently the patient completed laparotomic debulking and a left mastectomy. A case of a premenopausal woman with fallopian tube cancer and synchronous breast cancer is reported together with a review of the most recent literature.

Small-bowel occlusion after operative laparoscopy: our experience and review of the literature.

Bowel complications as a consequence of laparoscopic surgery are usually due to direct injuries; on the other hand, bowel occlusion is a rarely described event. We have retrospectively analyzed our data in this field. Out of 2652 laparoscopies performed between July 1996 and March 2000, three cases of small-bowel occlusion were observed. Two cases were due to bowel hernia through a 5-mm trocar port incision, the third was a consequence of an adhesion between the ileum and lost fragment of myoma. Two cases were treated laparoscopically, while in the third a laparotomy was required. At the time of writing, all the patients are well after a mean follow-up of 6 months. It appears important to also perform closure of the fascia and peritoneum after a 5-mm trocar port incision where there has been extensive manipulation.

Prospective multicenter study on urologic complications after radical surgery with or without radiotherapy in the treatment of stage IB-IIA cervical cancer.

A national collaborative group has conducted a multicenter prospective study on the use of a specific glossary for the complications associated with the treatment of cervical cancer, which were analytically described in 1989. This report analyzes the urologic complications with particular reference to radical surgery in stage IB-IIA cancer cases. In the prospective multicenter clinical study 2024 patients with frankly invasive cervical cancer were enrolled (IB = 1041; IIA = 308; IIB = 384; IIIA-B = 237; IV = 54). This report considers 1349 patients with stage IB-IIA disease. Treatment modalities in this group of patients were: type III radical surgery in 21.9%; type III radical surgery followed by radiotherapy in 20.8%; type III radical surgery preceded by radiotherapy in 7.3%; type II radical surgery in 3.1%; type II radical surgery followed by radiotherapy in 8.4%; type II radical surgery preceded by radiotherapy in 18.8%; surgery plus chemotherapy plus radiotherapy in 3.5%; radiotherapy alone in 16%. In this case series 873 complications were registered, and among these 341 (39.1%) were described in the urinary tract. Among 277 bladder complications 47.3% were grade 1; 47.3% grade 2, and 5.4% grade 3. Among 64 ureter complications 59.4% were grade 1; 17.2% grade 2, and 23.4% grade 3. Distribution of severe urinary complications was different according to site (bladder or ureter) and treatment modalities (radical surgery alone: bladder 1.3%, ureter 1.3%; radical surgery followed by radiotherapy: 1.4% bladder, 2.8% ureter; radical surgery preceded by radiotherapy: 3% bladder, 0% ureter). Different distributions of severe urinary complication were also observed in respect to stage (IB vs IIA); treatment: elective vs nonelective. In 673 patients treated with radical surgery plus or minus radiotherapy 123 relapses were registered (18.2%). Incidence of relapse was not different in patients suffering from mild/severe complications vs patients without complications. Disease-free survival, death from tumor, and death from other causes were not different in the group with complications in comparison to the group without complications.

Uterine leiomyoma metastasis as a first sign of breast cancer.

Uterine metastases from extragenital cancer are rarely reported in the literature. More frequently, the female genital tract is involved by direct extension from an adjacent pelvic organ. A 37-year-old woman had a myoma of the uterine wall and hypermenorrhea. The mass was laparoscopically enucleated, and frozen section examination was performed because it was macroscopically suspicious for sarcomatoid degeneration. The final diagnosis was metastatic carcinoma in the uterus of probable breast origin.

An analysis of approaches to the management of endometrial cancer in North America: a CTF study.

OBJECTIVE: The aim of this study was to define the clinical-therapeutical approach to endometrial cancer now being followed in some of the most important centers of reference for gynecological cancer in North America by means of a questionnaire. STUDY DESIGN: The questionnaire focused on four principal areas: (1) surgical staging and therapy; (2) adjuvant treatment; (3) treatment modifications; and (4) management of advanced stages (FIGO III-IV). RESULTS: There were 48 evaluable responses (77%) received by the end of December 1994 which were considered for this analysis. Lymphadenectomy is utilized routinely in 26/48 centers (54.2%) and in selective clinical-pathological conditions in another 21/48 centers (43.5%). In the majority of centers (31/48; 64.6%) radical surgery is utilized for selected indications such as cervical involvement. Only 3/48 (6.2%) centers consider the vaginal approach totally inappropriate. The great majority (40/48; 83.3%) of the centers considered postsurgical adjuvant therapy to be necessary in FIGO Stage Ic. Brachytherapy is routinely performed in 3 centers (6.2%) in postsurgical management of Stage I endometrial cancer, while the majority of the centers (31/48; 64.6%) perform brachytherapy of the vaginal vault in certain clinical-pathological conditions. A wide variety of treatments are used for advanced stages (FIGO III-IV). CONCLUSIONS: It emerges that some controversial aspects exist on endometrial cancer treatment, and these conflicting data need a large-scale multicenter randomized clinical trial.

Uterine leiomyosarcoma: analysis of treatment failures and survival.

The objective of this retrospective multicenter study was to assess the rates, times, and sites of recurrences of 126 patients with uterine leiomyosarcomas. Surgery was the initial therapy for all patients. Median follow-up of survivors was 50 months (range, 3-168 months). Of the 90 patients with stage I-II disease, 26 received postoperative irradiation and/or chemotherapy. Thirty-five (38.9%) patients developed recurrent disease after a median time of 16 months (range, 2-102 months). Recurrence was pelvic in 5 (14.3%) patients, distant in 23 (65.7%), and pelvic plus distant in 7 (20.0%). The overall recurrence rate was similar in patients who received adjuvant treatment and in those who did not. None of the 15 patients who underwent pelvic irradiation developed local recurrences, but 5 of them failed in distant sites. Of the 16 patients with stage III leiomyosarcomas, 2 died of intercurrent disease within 1 month from surgery and 11 received postoperative irradiation and/or chemotherapy. Thirteen patients developed recurrent tumor after a median time of 8 months (range, 1-21 months). Recurrence was pelvic in 3, distant in 4, and pelvic plus distant in 6 patients. Of the 20 patients with stage IV leiomyosarcomas, after surgery 6 were clinically free of disease (group A) and 14 had clinically evaluable residual disease (group B). With regard to group A, 3 patients received postoperative irradiation and/or chemotherapy. Five patients developed recurrent disease after a median time of 11 months (range, 8-16 months). Recurrence was distant in 3 patients and pelvic plus distant in 2. With regard to group B, 11 patients underwent postoperative chemotherapy. Eleven patients died after a median time of 6 months (range, 1-15 months), and 3 are still alive with clinical evidence of disease after 4, 5, and 8 months, respectively, from surgery. Cox model showed that stage (P = 0.0001), mitotic count (P = 0.0002), and age (P = 0.0048) were independent prognostic variables for disease-free survival. In conclusion, uterine leiomyosarcomas have an aggressive clinical behavior, with a propensity to recur both locally and moreover at distant sites. Tumor stage is the strongest prognostic variable. Only patients with early-stage disease have a chance of surviving, whereas the treatment of patients with advanced or recurrent disease is palliative.

Transdermal estroprogestins versus transdermal estrogen plus oral dihydrogesterone replacement in menopause.

We studied 18 early (6 to 36 months) postmenopausal patients with a mean age of 51 years (47-53), who had never undergone hormone replacement therapy before and had no contraindications to hormone replacement. All cases of menopause were spontaneous. The treatment consisted in the continuous transdermal administration of 17-beta-estradiol (50 microg/daily) by skin patch to be replaced every 84 hours. The patients were further treated with a two-week progestogen administration every fortnight. This consisted of transdermal norethisterone acetate (0.25 mg/daily) combined with estradiol in the same patch in the first year, and oral dihydrogesterone (10 mg/daily) in the second year, without wash-out period. Before treatment (T0), and at the 12th (T1) and 24th (T2) month we measured the body mass index, the arterial blood pressure (AP), lipoproteins, coagulation parameters and bone metabolism parameters. The systolic pressure presented mean values (+/-SD) equal to 128.5+/-10.2 mmHg (T0), 131.1+/-7.4 mmHg (T1) and 130.4+/-7.5 mmHg (T2). Diastolic pressure values showed mean value ranging from 85.4+/-8.7 mmHg (T0) to 83.9+/-5.3 (T1) and 83.4+/-5.8 mmHg (T2). The detailed analysis of values of triglycerides, HDL cholesterol, apolipoprotein A1, apolipoprotein B and coagulation parameters at different times of therapy showed no statistically significant changes. With regard to bone metabolism, no statistically significant changes from baseline values were observed in parathormone, alkaline phosphatase, calcitonin, urinary calcium/creatinine ratio, and bone mineral content expressed by the bone density.

Gynaecological aspects of primary Sjogren's syndrome.

UNLABELLED: Female patients affected with Sjogren's Syndrome (SS) frequently describe symptoms such as vaginal dryness and dyspareunia; however, only a few controlled studies have regarded clinical involvement of the female external genitalia. OBJECTIVE: The present study was undertaken in order to: (1) Evaluate the involvement of external genitalia in a large number of female patients affected with primary SS (pSS) by semi-quantitative methods covering subjective symptoms and clinical evaluation. (2) Compare pSS patients with a matched healthy control group (pre- and post-menopausal women were separately studied). (3) Correlate the gynaecological involvement with salivary and lacrimal abnormalities in pSS patients. METHODS: We evaluated 36 patients with primary SS (18 pre- and 18 post-menopausal women) and 43 healthy controls using a questionnaire regarding vulvar and vaginal dryness and a complete gynaecological examination. Subsequently, three scores related to vulvar and cervical status plus a global score were obtained. In primary SS patients, salivary and lacrimal involvement was also evaluated. RESULTS: Dyspareunia was present in 61% and vaginal dryness in 55% of SS patients versus 39% and 33% of healthy controls. No significant differences regarding gynaecological scores were found between SS patients and controls, in both pre- and post-menopausal women, nor correlation was observed between gynaecological and lacrimal or salivary involvement. CONCLUSIONS: Our data suggest that although SS patients frequently complain of dyspareunia and vaginal dryness they do not greatly differ from healthy subjects in regard to some major gynaecological aspects.

An analysis of approaches to the treatment of endometrial cancer in western Europe: a CTF study.

The role of this research is to define the clinical-therapeutic approach to endometrial cancer currently being followed in some of the most important centres of reference for gynaecological cancer in Western Europe. Data was collected by means of a questionnaire, concerning specific diagnostic and therapeutic options, sent to 115 leading centres for gynaecological oncology in Western Europe, and 82 responses were received. The analysis of the management of this neoplasia in Western European countries shows significant differences regarding some particular clinical conditions. Only 24.4% of the interviewed centres stated that they perform lymphadenectomy routinely, whereas it is most commonly reserved for specific pathological conditions. The presence of lymph node spread is generally considered to be the most important prognostic element, and currently, radiotherapy of the pelvis appears to be the treatment of choice either as the sole postsurgical therapy (57%) or in combination with systemic treatment. An adjuvant treatment in stage I lymph node-negative patients is adopted in the large majority of the centres (70.5%) when poorly differentiated cancer (46%) and/or deep myometrial invasion (33.3%) are present. In this condition, radiotherapy appears to be the therapy of choice. Histotype and grading are generally recognised as important risk factors and result in treatment modification; the high percentage of primary surgical modifications is considerable (63.4%) in stage I grade 3 cancers that primarily require lymphadenectomy or recourse to radical hysterectomy. The results of our study indicate that there is no leading therapy in the advanced stages of endometrial cancers, but each therapeutic modality is adopted to more or less the same extent.

Prospective multicenter study on the clinical utility of ca-72.4 in postmenopausal patients with pelvic mass.

The study objective was to evaluate the sensitivity and specificity as well as the positive predictive value and negative predictive value of CA 72.4 and CA 125 determination, separately and in combination, for diagnosing ovarian tumors in post-menopausal women with pelvic mass. The 299 patients recruited in this study underwent gynecological examination, plasma determination of CA 72.4 and CA 125, and laparotomy with histological definition of pelvic mass. CA 72.4 assay values were under 3.9 U/ml in 194 cases (70.8%); values ranged from 3.9 to 4.5 U/ml in 7 cases (2.5%) and were greater than 4.5 U/ml in 73 cases (26.6%). CA 72.4 assay was positive (>4.5 U/ml) in 56 cases (57.1%) of malignant ovarian pathology, in 4 cases (25%) of malignant extra-ovarian pathology as well as in 9 cases (7.1%) of benign ovarian pathology and in 4 cases (11.8%) of benign extra-ovarian pathology. With a cut-off at 3.9 U/ml, CA 72.4 showed a specificity of 91.3% and a sensitivity of 62.2%, whereas with a cut-off at 4.5 U/ml specificity was 92.9% and sensitivity 57.1%. Results of CA 125 assay for diagnosing a pelvic neoplasia (ovarian or extra-ovarian), showed a specificity of 85.3% and sensitivity of 68.8%. The agreement of the two markers (CA 125 and CA 72.4) as negative or positive shows a specificity of 77% and a sensitivity of 84.7% for ovarian cancer and a specificity of 73.5% and sensitivity of 75% for the diagnosis of pelvic neoplasias.

Melatonin-induced decrease of body temperature in women: a threshold event.

Whether the biological effect of melatonin in humans is directly related to the circulating levels of the hormone, has not heretofore been investigated. In this study, we investigated whether previously described hypothermic melatonin properties are dose related. The nocturnal decline of the body temperature (BT) observed in 16 early follicular phase women, following placebo administration at 18.00 h, was compared with that observed during the preceding or following night, after melatonin suppression with the beta 1-adrenergic antagonist atenolol (100 mg). In 6 subjects (37.5%) with lower nocturnal melatonin levels (p < 0.05) atenolol induced a complete melatonin suppression and an attenuation of the nocturnal BT decline (p < 0.02), whereas in the remaining 10 subjects (62.5%) atenolol induced an incomplete melatonin suppression with no modification of the nocturnal BT decline. During a 3rd night, 2 of the 6 subjects with complete and 6 of the 10 subjects with incomplete melatonin suppression blindly received atenolol plus melatonin (1 mg at 19.30 h and 0.75 mg at 21.00 and 23.00 h). Exogenous melatonin restored the full expression of the nocturnal BT decline in the 2 subjects with complete melatonin suppression, but did not modify the BT decline in the 6 subjects with atenolol-induced incomplete melatonin suppression. Our data show that markedly, but not completely attenuated nocturnal melatonin levels are sufficient to exert maximal thermoregulatory effects, indicating rather a threshold than a dose-response effect of melatonin action on human BT.

Prospective multicenter study on CA 125 in postmenopausal pelvic masses.

The purpose of this study was to determine the diagnostic value of CA 125 in comparison with transabdominal ultrasound (US) in the evaluation of postmenopausal women with pelvic mass to detect malignant epithelial ovarian tumors. Postmenopausal patients with pelvic mass were studied with gynecologic examination, US and CA 125 determination. Three hundred eighty-eight patients were entered in the study. According to stratification based on US (probably benign, equivocal, possibly malignant) and CA 125 (< 35 U/ml, negative; between 35 and 65 U/ml, borderline; > 65 U/ml, positive), 290 patients were considered eligible for surgery. Specificity, sensitivity, positive and negative predictive value, and accuracy of US and CA 125 were calculated with respect to histological examination. Out of 290 operated patients, 134 had a benign ovarian pathology, 34 had extraovarian benign pathology, 106 had an ovarian malignancy, and 16 presented with an extraovarian malignant pathology. The results according to ovarian malignant pathology were as follows. CA 125 (> 65 U/ml): Specificity, 92.5%; sensitivity, 71.7%; accuracy, 83.3%. CA 125 (> 35 U/ml): Specificity, 82.0%; sensitivity, 78.3%; accuracy, 80.4%. US: Specificity, 77.6%; sensitivity, 84.9%; accuracy, 80.3%. Combination of US and CA 125 (> 65 U/ml): Specificity, 96.1%; sensitivity, 91.7%; accuracy, 94.3%. Determination of CA 125 is a highly specific method in predicting ovarian cancer in postmenopausal women with a pelvic mass. The association with US significantly improves the overall accuracy and may support therapeutical decision making by distinguishing between a significant percentage of women most likely to benefit from prompt intervention and women who may be managed following minor surgical diagnostic approach, such as fine-needle aspiration.

Times and sites of relapses after negative second look in advanced epithelial ovarian cancer.

In the present work the Authors analyse the role and significance of second-look laparotomy in the management of epithelial ovarian cancer. Eighty-three patients with advanced epithelial ovarian cancer (stage III-IV) followed at the Institutes of Gynecology of Padua and Pisa Universities underwent a negative second-look at a median time of 6 months after first surgery. The incidence of relapse after the negative second-look was 45.8% and the mean time of relapse was 27.4 months. Advanced surgical-pathological stage, the presence of residual disease > 2 cm and serous histotype are risk factors for relapse after a negative second-look. These data confirm that, because of its poor prognostic value, a negative second-look laparotomy should not influence the choice of second line chemotherapy and, consequently is no longer routinely performed in our Institutes.

Histopathological characterization in carcinoma of the endometrium. Comparison between biopsy and pathological examination of specimen.

On the basis of a case series of 577 patients affected by carcinoma of the endometrium treated during the period 1963-1989 in the Gynecologic Institute of the Padua University, the present work examines the reliability of endometrial biopsy aiming at the correct histopathologic diagnosis, through comparison with the subsequent histologic examination of the surgical specimen. It is shown how simple biopsy alone allows for correct diagnosis of histotype in 91.6% of cases of adenocarcinoma, while the reliability of such an examination is reduced, respectively, to 30.7% in adenoacanthoma and to 37.5% in adenosquamous histotypes.

The role of insulin and renin in the pathogenesis of hormone-dependent neoplasias. b). Renin.

Recently, a prorenin-renin-angiotensin system which could be correlated to the reproductive function, although independent from the renal renin-angiotensin complex, has been observed also at ovarian level. It had been supposed that the renin itself by influencing the metabolism of steroid hormones is responsible for the pathogenesis of hormone-dependent neoplasias, endometrial and breast carcinoma. This would lead to the consideration of hypertension as a primary risk factor for such pathologies and not only as secondary to obesity. This research has not, however, revealed significant relations between the plasmatic concentration of renin and the hormone variation responsible for the pathogenesis of hormone-dependent neoplasias.

The role of insulin and renin in the pathogenesis of hormone-dependent neoplasias. a). Insulin.

Weight increase is frequently observed in women of menopausal age and the androgens secreted at the ovarian level are converted into estrogens at adipose tissue level, because of the presence of specific enzymes, the aromatases. Insulin and the androgens reduce the synthesis of Sex Hormone Binding Globulin (SHBG) at the hepatic level, thus increasing the amount of free steroids able to act at the level of the hormone-dependent tissues. Besides, the insulin stimulates androgenic synthesis at the level of the ovarian stroma in postmenopausal women. In this research, we studied 83 postmenopausal women, 41 with hormone-dependent pathologies and 42 affected by other pathologies, and we observed that women affected by breast and endometrial neoplasias presented a reduced tolerance to glucose, a higher level of circulating androgens, a large quantity of fatty tissue and a SHBG concentration inversely proportional to insulin level. These results suggest that the ovarian synthesis of androgens increase in women in postmenopausal age affected by hormone-dependent pathologies, and that insulin may play a part in the pathogenesis of such neoplasias.