Clear cell endometrial cancer: a CTF multicentre Italian study.

UNLABELLED: Endometrial clear cell carcinoma (CCC) is a rare entity and only accounts for 1-6% of all endometrial cancers. CCC is considered an aggressive subtype of endometrial cancer with worse prognosis compared with type I cancer and more frequent relapses at distant and extrapelvic sites. These characteristics require specific treatment modalities, but rarity of the disease does not allow to identify evidence based indications for therapies. Objective of the present study is to analyse a series of cases treated in a multicentre Italian setting. MATERIALS AND METHODS: Sixty-five endometrial CCC were treated in the period 1990-2010 in the participating institutions. Slides of the pathological specimens were reviewed by a single pathologist of each institution and debatable cases were collegially reviewed. Clinical records were collected by a common database. Demographic, surgical pathological, and follow-up data were registered. Results: All patients received primary surgery. Stage of disease according FIGO 2009 was as follow: l a: 16.9%, lb: 35.4%, 2: 9.2%, 3a: 9.2%, 3b: 3.1%, 3c: 16.9%, 4a: 3.1%, and 4b: 6.1%. Adjuvant post-operative treatment was adopted in 53.8% of cases. A relapse was detected in 29.2% of cases with a majority of extrapelvic sites (68.4%). Five-year survival rate was significantly related to stage of disease with an excellent prognosis for Stage Ia e lb disease with a complete staging. In these cases adjuvant treatment does not show significant improvement of survival. Relapsed cases show a response rate to treatment in 26% of cases (predominantly chemotherapy). CONCLUSION: CCC requires extensive surgical staging. Stage I disease completely staged does not require adjuvant therapy. More advanced stages require adjuvant chemotherapy.

Adjuvant treatment and analysis of failures in patients with high-risk FIGO Stage Ib-II endometrial cancer: an Italian multicenter retrospective study (CTF study).

OBJECTIVES: The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion >50%, grade 2-3). METHODS: We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement. RESULTS: Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p=0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively). CONCLUSIONS: Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings.

Is there a role for postoperative treatment in patients with stage Ib2-IIb cervical cancer treated with neo-adjuvant chemotherapy and radical surgery? An Italian multicenter retrospective study.

PURPOSE: Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. PATIENTS AND METHODS: This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p<0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p=0.0001). On multivariate analysis, consolidation therapy (p=0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p=0.0169) and consolidation therapy (p=0.0016) were independent prognostic variables for overall survival. CONCLUSION: Optimal responders after chemo-surgical treatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment.

Pathological response on surgical samples is an independent prognostic variable for patients with Stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy: an Italian multicenter retrospective study (CTF Study).

OBJECTIVES: The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery. METHODS: This study was conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8-212 months). Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5-123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response. CONCLUSIONS: Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2-IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome.

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.

Non-hormonal treatment of vasomotor symptoms in gynecological cancer patients.

Gynaecological cancer patients generally suffer from an earlier and more severe menopausal syndrome than the general female population. Hormone replacement therapy is often contraindicated and there are non-hormonal treatments that are proven to be more effective than placebo in randomized controlled trials, e.g., some antidepressants, gabapentine and clonidine. The main limits to the use of these drugs in controlling hot flashes are the off-label use for this purpose, the very short follow-up and the fact that data come from studies performed on breast cancer, not on gynecological cancer patients. Patients believe that drugs derived from plants could be effective in relieving hot flashes and that they are harmless. Evidence is contrary to this belief and estrogen-sensitive cancer patients should be warned of the potential, though very weak, estrogenic effect of phytoestrogens and other "natural" drugs, and that their efficacy is close to that of a placebo.

Possible role of palliative surgery for bowel obstruction in advanced ovarian cancer patients.

OBJECTIVES: Bowel obstruction is a relatively common event (30-40%) in advanced or recurrent ovarian cancer patients. No definitive data are available on the optimal management of this serious complication and treatment is generally limited to adoption of palliative measures. These modalities include both surgical and medical procedures. The aim of this study was to define selection criteria for subjects who would benefit from palliative surgery. STUDY DESIGN: Out of 270 epithelial ovarian cancer patients treated in the period 1984-2005, 75 (28%) developed bowel obstruction related to progression/recurrence of the disease. Palliative treatment - both medical and surgical - was applied on an individual basis. A new score developed by these authors was retrospectivelly applied to this group of patients with the aim of defining a subgroup that could benefit from surgical treatment. RESULTS: Fifty cases (66.7%) were medically treated whereas 25 patients (33.3%) underwent surgery. Mean and median survival rates were 34 and 28 weeks in the surgical group versus 12 and four weeks in the medical group. Distribution according to score showed 53 cases (71%) in the low score group (< 14) and 22 (29%) in the high score group (> 14). A significantly better survival was observed in the low-score group (p < 0.0001) and in the surgically treated patients (p < 0.001). According to the risk score variables patients treated surgically for obstruction with low scores had a longer survival (p < 0.005) compared to medical treatment but this difference was not found in the high-risk group (p < 0.05). CONCLUSIONS: The prognosis of patients with bowel obstruction in relation to advanced ovarian cancer is best determined by comprehensive assessment of all prognostic parameters to define a subgroup of patients in a low-risk group that may benefit from surgical treatment.

Surveillance of endometrial pathologies, especially for endometrial cancer, of breast cancer patients under tamoxifen treatment.

Tamoxifen is the antihormonal treatment of choice for postmenopausal breast cancer patients with positive estrogen receptors. One of the most significant and deleterious side-effects of TAM treatment appears to be a proliferative effect on the endometrium, including endometrial cancer. Today no active screening for patients treated with tamoxifen other than routine annual gynecologic surveillance is recommended, however many investigators have recommended that those women should warrant closer gynecological surveillance for endometrial cancer during treatment, especially those with high-risk factors. This article evaluates the diagnostic flow chart for the surveillance of endometrial pathologies in tamoxifen-treated breast cancer patients, according to the literature and to the Committee Opinion of the Triveneto Directors of Gynecological and Obstetrical Departments (North-east Italy).

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.

The role of the French-Italian glossary of complications in the outcome evaluation of cervical cancer treatment: an Italian multicentric study.

UNLABELLED: The optimal treatment for cervical cancer is still a controversial matter: in the last two decades a lot of different modalities combining surgery, radiotherapy (RT) and chemotherapy (CHT) have been suggested and analysed in clinical trials. Nevertheless, analysis of treatment in cancer patients should be directed not only to survival, but also to the cost of complications and quality of life. In June 1988, a French-Italian co-operative group set up a glossary in which the complications of the treatment of cervical cancer are described and ranked. Nowadays, this is the only international system based upon an accurate description of symptoms and signs of complications following multidisciplinary treatment. The glossary was based on our previous experience in treating patients by surgery alone, RT or their combinations. Recently multimodality treatment includes also CHT. The aim of the present study was to verify whether the glossary is still a useful clinical instrument in outcome evaluation of cervical cancer treatment. MATERIALS AND METHODS: The analysis has been done on a retrospective consecutive series of 579 patients affected by cervical cancer, treated in five Italian institutions. A minimum of 12 months follow up was required. All medical records of the patients enrolled, were examined by two independent reviewers in order to classify the complications according to the glossary. RESULTS: Out of 579 patients 319 (55.1%) were free of complications and 260 (44.9%) experienced at least one complication. We found 436 complications. The distribution by Grade was: G1 58.9%, G2 27.5%, G3 13.5%. We had no fatal complication (G4). The glossary included all observed complications, except for pulmonary fibrosis. CONCLUSION: The glossary is still a useful instrument in evaluating the outcome of cervical cancer treatment, whatever the therapy, and should be considered in quality of life assessment.

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.

Serum CA125 assay in the early diagnosis of recurrent epithelial ovarian cancer.

The present retrospective study included 59 patients who had been treated for epithelial ovarian cancer and who showed an elevation of serum CA125 above 35 U/ml without clinical evidence of disease. Eight patients underwent chemotherapy at the time of serum antigen elevation (group A). The other 51 patients (group B) were periodically checked, and received further chemotherapy only when recurrent disease was detected. Forty-four of the 59 patients relapsed. One patient of group B experienced two different recurrences with two distinct time intervals. The median follow-up of survivors from CA125 elevation was 10 months (range 2-92 months). Of the 8 patients of group A, 3 (37.5%) developed recurrent disease after 14, 17 and 22 months, respectively, from antigen elevation. Of the 51 patients of group B, 41 (80.4%) relapsed. The overall recurrence rate was 82.4% (42/51). The median lead time between CA125 increase and clinical detection of relapse was 3 months (range 2-27 months). The present data confirmed the reliability of serum CA125 assay as predictor of clinical relapse in epithelial ovarian cancer. The recurrence rate seemed to be lower for patients who received chemotherapy at the time of CA125 elevation (37.5% versus 82.4%, p=0.02). However, the small number of patients, the short follow-up, and the non-randomized design of the study do not allow to draw any conclusion on the appropriate timing for second-line chemotherapy.

A conditioned medium from a human liposarcoma-derived cell line induces p53-dependent apoptosis in several tumor cell lines.

A novel cell line, named LSA, has been obtained, stabilized, and characterized from a human liposarcoma. These cells have morphological and biochemical features strongly resembling the adipocytes and were able to grow in the Ham's F12 medium, in presence or absence of FCS. A conditioned medium (LSA-CM) was obtained by growing the LSA cells in the F12 medium in the absence of FCS. LSA-CM had cytostatic and cytotoxic effects (apoptosis and necrosis) associated with down-regulation of c-myc and upregulation of p53 in several human cell lines (breast, lung, glioblastoma, etc. ). The MCF-7 and glioblastoma cells were killed by LSA-CM in 5-6 days, whereas the same cells were killed by LSA-CM co-incubated with low doses of cisplatin in 30 h. LSA-CM peri-tumoral injections for 15 days in Balb-c-fc3H mice affected by mammary tumors, resulted in the rapid disruption of tumors and absence of metastases. In contrast, in the untreated animals the tumor masses were 4 times larger than initial lesions, and numerous metastases were found in the lungs. The toxicity analysis of LSA-CM, performed on three different animal species, showed that LSA-CM is absolutely free of acute, subacute, and subchronic toxicity. The possible use of LSA-CM/cisplatin for cancer treatment is discussed.

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.

Efficacy of an acidic vaginal gel on vaginal pH and interleukin-6 levels in low-risk pregnant women: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Increased interleukin-6 (IL-6) levels and a vaginal pH of > 4.7 are associated with obstetric complications such as preterm delivery and low birth weight. Topical treatments, able to maintain a physiological vaginal pH, could help in the prevention of vaginal infections. STUDY AIM: In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of an acidic buffering vaginal gel (Miphil) on vaginal pH and IL-6 levels in pregnant women. PATIENTS AND METHODS: Seventy low-risk women pregnant with a singleton (second trimester) were enrolled in the trial. Thirty-five were randomized to the acidic gel, 2.5 g every 3 days for 12 weeks, and 35 to the corresponding placebo. Vaginal pH and vaginal IL-6 level were measured at baseline and after 12 weeks. Women were then followed until delivery. The main outcome measures were vaginal pH, vaginal pH normalization (pH < 4.5) and vaginal IL-6 levels. RESULTS: Vaginal pH at baseline was 4.6 +/- 0.4 and 4.4 +/- 0.3 in the acidic gel and the placebo group, respectively. At baseline, a total of 40% (14/35) and 22% (8/35) of women in each group, respectively, had a vaginal pH of > or = 4.7. At week 12, the vaginal pH was 4.3 +/- 0.3 in the acidic gel group and 4.3 +/- 0.3 in the placebo group (NS). The acidic gel normalized the vaginal pH in ten out of 14 women (p = 0.04) in comparison with only one out of eight women in the placebo group (NS). The acidic gel induced a significant (p < 0.02) reduction of vaginal IL-6 from 12.0 +/- 7 to 8.9 +/- 5 pg/l (-36%). In the placebo group, IL-6 increased from 9.0 +/- 5 to 13.5 +/- 6.8 pg/l (+50%) (p = 0.05). Birth weight was 2978 +/- 700 g in the placebo group and 3241 +/- 477 g in the acidic gel group (p = 0.06). CONCLUSIONS: The use of the acidic gel in low-risk pregnant women is able to maintain a physiological vaginal ecosystem and prevents the increases of vaginal pH and vaginal IL-6. Prospective and controlled trials are warranted to evaluate whether this acidic gel can reduce obstetric complications linked to vaginal inflammation during pregnancy.

Serum markers as prognostic factors in epithelial ovarian cancer: an overview.

A comprehensive review of the literature and the authors' personal experience on serum determination of tumour markers in epithelial ovarian cancer can be summarised as follows: CA 125 is the most reliable marker for monitoring the course of epithelial ovarian cancer; CA 125 assay is not an adequate screening test for this malignancy but it can represent an useful adjunct to clinical examination and ultrasound in the differential diagnosis of ovarian masses in postmenopausal women; Serial measurements of CA 125 are useful in monitoring the response to chemotherapy and follow-up. In patients with preoperative positive CA 125 assay, the concomitant determination of other tumour markers does not add further information when compared to CA 125 alone. Conversely in patients with preoperative negative assay the measurement of one or more of other antigens could be of clinical relevance.

Surgery as diagnostic and therapeutic moment in the management of cervical cancer.

Therapeutical program in cervical cancer usually include surgical or radiotherapeutical interventions or a combination of the two, variously integrated with techniques and sequences of application. Treatment planning and evaluation of results are normally based on the classification into clinical stages codified by the FIGO. But this classification, though providing useful prognostic standards of judgement, has proved to be inadequate to identify specific therapeutical guidance. Within a single clinical stage different risk factors have been identified which influence prognosis thus determining the therapeutical treatment more than staging itself. Furthermore clinical staging has failed to predict the surgical stage correctly in a significant number of cases. The index of correction after surgical staging shows discrepancy in about 1/3 of cases. In these cases a therapeutical program based on clinical examination exclusively may prove to be inadequate. The results reported by Authors warrant a rational resort to operative staging in cervical cancer in order to establish the real topography of the original focus more correctly. This indication is further strengthened by the need to identify lymphatic involvement, notably of para-aortic nodes, in locally advanced cases since such an occurrence bears a significant influence on the patient's prognosis and possibility of treatment. On the bases of these considerations the Authors suggest surgery as primary treatment in the management of cervical cancer.