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.

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.

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.

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.

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.

Fertility after ovarian cancer treatment.

Considering the important improvement of surgical techniques and chemotherapy in the last few years, it is possible today, in selected cases of patients previously treated for ovarian cancer, to support their desire for motherhood, thus improving the quality of life for them. The major problem for the Gynecologic Oncologist in treating young women for ovarian tumour is the lack of statistically significant experience world-wide, because of the very few cases in which the reproductive function is preserved, and pregnancy is subsequently possible. In this report the problem is discussed, and the results obtained in our Institute are presented.

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.

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.

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.

Management of cervical cancer and surgical-pathological staging (SPS). Report of our clinical case series.

FIGO staging is imprecise in a relevant number of cases of cervical cancer, especially in advanced stages, when the prognosis and the choice of the therapy are most delicate. The Authors examine their case series about the index of correction of FIGO staging after Surgical Pathological Staging (SPS). Surgical Pathological Staging was applied systematically in 788 cases and revealed errors in FIGO staging in 16% of cases at stage I; 77% at stage II; and 96% at stage III. SPS allows a more precise knowledge of neoplastic diffusion and consequently to the elimination of many false advanced stages and to adequate the treatment. Furthermore 5 year survival rate confirms the role of SPS and Surgical therapy alone or combined with Radiotherapy and Chemotherapy in every stages of diffusion of cervical cancer.

Quality of life in gynaecological oncology.

In the last twenty years a new philosophy in the management of gynaecological cancer has begun: the goal of the therapy is now not only to save the life but also the patient's quality of life. To this end, on the basis of a century's experience and of progress in the oncologic field, therapies have been progressively personalized and modulated, considering both the surgical pathological staging and the effective possibilities in terms of survival and quality of life, in order to avoid over or undertreatments. Moreover, in the last few years also the patients submitted to surgery for gynaecological malignancies are beginning to ask gynaecologists for access to hormonal replacement therapy in order to prevent the symptoms typical of menopause, and physicians have to decide when that is possible. Consequently gynaecologist oncologists have to bear in mind the therapy's real cost/benefit balance for the patients, also from a psychological point of view, and in any case, treatments must be performed only if they are unquestionably useful and if they involve the patient's consciousness in choices and decisions.

Fertility after ovarian cancer treatment.

Considering the important improvement of surgical techniques and chemotherapy in the last few years, it is possible today, in selected cases of patients previously treated for ovarian cancer, to support their desire for motherhood, thus improving the quality of life for them. The major problem for the Gynecologic Oncologist in treating young women for ovarian tumour is the lack of statistically significant experience world-wide, because of the very few cases in which the reproductive function is preserved, and pregnancy is subsequently possible. In this report the problem is discussed, and the results obtained in our Institute are presented.

Antiblastic chemotherapy and reproductive life.

In the present work the Authors, on the basis of most recent literature have tried to show some general outline with regard to the effects of antiblastic chemotherapy on the "ovarian function" in patients of pre-puberal and fertile age, understood that this would mean complex interference between endocrine and gametogenic; they have besides faced the problem of the gestational capacity of such patients. Notable difficulties have derived from the fact that the data in Literature are often non-comparable among themselves and, at times, discordant. However, although they have been unable to reach unequivocal conclusions, they hope to have made some practical contribution to those who, ever more often, find themselves having to face such problems.

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.

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.