Feasibility and oncological safety of sentinel node biopsy in breast cancer patients with a local recurrence.

OBJECTIVES: To investigate the role and feasibility of sentinel lymph node biopsy (SLNB) in breast cancer patients with a local recurrence and no clinically positive axillary lymph nodes. MATERIALS AND METHODS: A total of 71 patients underwent SLNB for breast cancer recurrence. At first surgery, they had received SLNB (46.5%), axillary lymph node dissection (ALND) (36.6%) or no axillary surgery (16.9%). RESULTS: Lymphatic migration was successful in 53 out of 71 patients (74.6%) and was significantly higher in patients with previous SLNB or no axillary surgery than in those with previous ALND (87.9% vs. 53.8%; p = 0.009). Aberrant lymphatic migration pathways were observed in 7 patients (13.2%). The surgical SLNB was successfully performed in 51 patients (71.8%). In 46 patients (90.2%) the SLN was histologically negative, in 3 patients (5.9%) micrometastastatic and in 2 patients (3.9%) macrometastatic. The 2 patients with a macrometastates in SLN underwent ALND, In 4 out of the 18 patients with failure of tracer migration ALND, performed as surgeon's choice, did not find any metastatic node. After a median follow-up period of 39 months (range: 2-182 months), no axillary recurrence has been diagnosed. CONCLUSION: A SLNB in patients with locally recurrent breast cancer, no previous ALND and negative axillary lymph nodes is technically feasible and impacts on the ALND rate. In patients who at primary surgery received ALND, migration rate is significantly lower, aberrant migration is frequent and no clinically useful information has been obtained.

Diagnostic accuracy and cost-effectiveness of different strategies to triage women with adnexal masses: a prospective study.

OBJECTIVE: Transvaginal sonography (TVS) and serum biomarkers are used widely in clinical practice to triage women with adnexal masses, but the effectiveness of current biomarkers is weak. The aim of this study was to determine the best method of diagnosing patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: (1) the International Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with subjective assessment (SA) by an experienced ultrasound operator when TVS results are inconclusive (referred to hereafter as SR ± SA), (2) SR ± SA and cancer antigen 125 (CA 125), (3) SR ± SA and human epididymis protein 4 (HE4) and (4) SR ± SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was that the addition of the biomarkers to SR ± SA could improve triaging of these patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary analyses, we estimated the cost effectiveness of the four strategies and the diagnostic accuracy of SR ± SA at the study hospitals. METHODS: Between February 2013 and January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were enrolled in this multicenter prospective cohort study. Preoperative TVS was performed and preoperative CA 125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies and the cost of each strategy was calculated. RESULTS: A total of 391 patients were included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients and thus did not require SA; the overall performance of SR ± SA showed a sensitivity of 82%, specificity of 92% and positive and negative predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5 and 0.19, respectively. In premenopausal women, mean cost among the four triage strategies varied from €36.41 for SR ± SA to €70.12 for SR ± SA + ROMA. The addition of biomarkers to SR ± SA showed no diagnostic advantage compared with SR ± SA alone and was more costly. Among postmenopausal women, mean cost among the four triage strategies varied from €39.52 for SR ± SA to €73.23 for SR ± SA + ROMA. Among these women, SR ± SA + CA 125 and SR ± SA + ROMA had a higher sensitivity (both 92% (95% CI, 85-99%)) than SR ± SA (81% (95% CI, 71-91%)), but SR ± SA had a higher specificity (84% (95% CI, 77-91%)). SR ± SA + CA 125 and SR ± SA + ROMA improved diagnostic accuracy, each diagnosing a third more malignant adnexal masses. In postmenopausal women, compared with SR ± SA alone, SR ± SA + CA 125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13.00, while the extra cost for SR ± SA + ROMA was €33.71, with a comparable gain, in terms of NRI, as that of SR ± SA + CA 125. CONCLUSIONS: In our study sample, SR ± SA seems to be the best strategy to triage women with adnexal masses for surgical management. Among postmenopausal women, SR ± SA + CA 125 increased the NRI at a reasonable extra cost. Our data do not justify the use of HE4 and ROMA in the initial triage of women with adnexal masses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

CO2 laser vaporization for the treatment of vaginal intraepithelial neoplasia: effectiveness and predictive factors for recurrence.

OBJECTIVE: To evaluate the outcome of vaginal intraepithelial neoplasia (VaIN) treatment with CO2 laser vaporization in terms of local recurrence and progression to vaginal carcinoma. Additionally, the authors investigated the predictive factors for first recurrence. MATERIALS AND METHODS: The medical records of all patients treated for VaIN with CO2 laser vaporization at Sant'Anna Hospital in Turin (1995-2012), were retrospectively reviewed. A univariate logistic model was applied to evaluate selected clinical features as predictive factors for recurrence. A multivariate logistic regression analysis was then carried out including significant risk factors after univariate analysis (p < 0.05). RESULTS: The analysis included 285 out of 302 patients. Seventy-one (25%) women relapsed; of these 24 VaIN 1 (22%), 37 VaIN 2 (27%), and ten VaIN 3 (26%). The median time to the first recurrence was 5.2 months (1.4-127.8) for VaIN 1, 6.6 months (1-85.2) for VaIN 2, and 3.6 months (1.2-62) for VaIN 3. Sixty-one out of 71 patients were retreated with CO2 laser vaporization. At the last follow-up visit, 273 (96%) women were free from VaIN. No patients progressed to vaginal carcinoma. The multivariate model showed a higher risk of VaIN recurrence in the case of previous hysterectomy (HR 3.3, 95% CI 1.7-6.3, p < 0.001) and concomitant H-SIL on the Pap smear (HR 1.9, 95% CI 1.2-3.1, p = 0.008). CONCLUSION: CO2 laser vaporization is an effective low impact treatment for VaIN. Despite this, VaIN recur, in particular in cases of previous hysterectomy and concomitant H-SIL on the Pap smear. An intensive follow-up is proposed for women with a high risk of VaIN relapse.

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.

Palliative care in patients with ovarian cancer and bowel obstruction.

OBJECTIVE: Malignant bowel obstruction (MBO) is usually a pre-terminal event in patients with ovarian cancer. However, because of the lack of data in literature, decisions around surgical intervention, non-resectional procedures, or medical treatment of MBO in patients with ovarian cancer cannot be lightly undertaken. We analyzed medical and surgical procedures, performance status, nutritional status, cachexia, and their prognostic value in this group of patients. METHODS: We retrospectively selected all consecutive patients with recurrent ovarian cancer who received medical or surgical treatment for MBO between October 2008 and January 2014 at the Academic Department of Gynecological Oncology of Mauriziano Hospital of Turin (Italy). RESULTS: We found 40 patients: 18 of them underwent medical treatment and 22 of them were submitted to surgery. In the group of surgery, the hospitalization was shorter (p 0.02), the pain reduction was more effective (p 0.001), the number of chemotherapy lines was higher (p 0.03), and re-obstruction was more rare (p 0.02). Between the two groups, we did not find any differences in post-palliation episodes of vomit (p 0.83), type of diet (p 0.34), ability to return home (p 0.72), and death setting (p 0.28). Median survival after palliation was longer in the group of surgery (p 0.025). Cachexia, low performance status, and poor nutritional status were significant predictors of worse survival after MBO, independently by the treatment. CONCLUSIONS: Surgery has to be considered in patients without serious contraindications; otherwise, a medical protocol, including antisecretory drugs, is the standard of care in frail patients.

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.

Secondary cytoreductive surgery for isolated lymph node recurrence of epithelial ovarian cancer: a multicenter study.

INTRODUCTION: Chemotherapy is the standard treatment of recurrent epithelial ovarian cancer (EOC), but its use in nodal relapses is still debated. On the other hand, the role of secondary cytoreductive surgery (SCS) remains controversial. Aim of this study is to evaluate feasibility and outcomes of SCS for the specific setting of recurrent ovarian cancer, exclusively relapsing in lymph nodes. PATIENTS AND METHODS: We conducted a retrospective analysis in five Italian Institutions (University of Torino, INT of Milano, CRO of Aviano, University of Pisa and INT of Napoli) from 2000 to 2012. Patients with EOC who underwent secondary surgery for isolated lymph node recurrence (ILNR) were selected. RESULTS: Seventy-three patients were identified. At first diagnosis, patients received debulking surgery and platinum-based chemotherapy. The median disease free interval from completion of primary chemotherapy to nodal recurrence was 18 months. Nodal recurrence was para-aortic in 37 patients (50.7%), pelvic in 21 (28.8%), pelvic and para-aortic in 9 (12.3%), pelvic and inguinal in 3 (4.1%) and inguinal in 3 (4.1%). During SCS, in 1 patients nephrectomy was necessary for renal vein injury. No significant postoperative morbidity occurred. Median follow-up is 50 months. After secondary surgery, 32 (43.8%) are alive without disease, 18 (24.6%) are alive with disease and 23 patients (31.5%) are dead of disease. Five-year overall survival from the time of treatment of recurrent disease is 64%. CONCLUSIONS: Secondary surgery for ILNR of ovarian cancer is feasible, safe, with low morbidity and it is associated with a favorable outcome.

Long-acting beta-agonists and their association with inhaled corticosteroids in COPD.

Inhaled bronchodilators, including beta(2)-agonists and antimuscaric receptor antagonists, are the mainstay of pharmacotherapy in chronic obstructive pulmonary disease (COPD). The short-acting beta(2)-agonists, including salbutamol, and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand. The long-acting beta(2)-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a twice-daily dosing regimen for long-term COPD treatment. Unlike salmeterol, formoterol has a rapid onset of action. Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta(2)-adrenoceptors, rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance. Indacaterol, which has been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily dosing regimen. Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development. Combination with ICS (fluticasone/salmeterol, budesonide/formoterol, beclomethasone/formoterol) appears to provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often not clinically significant in all the endpoints assessed. In patients with COPD, treatment with ICS is associated with increased risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations. Subphenotyping of patients with COPD (e.g., frequent exacerbations, sputum eosinophilia, mixed asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating treatment. Ultra-LABA/ long-acting muscarinic receptor antagonist (LAMA) combination treatment is under development and is likely to become a standard pharmacological strategy for COPD. Dual-pharmacology inhaled muscarinic antagonist-beta(2) agonist (MABA) molecules provide a new approach to the treatment of COPD.

Inhaled muscarinic acetylcholine receptor antagonists for treatment of COPD.

Bronchodilators, generally administered via metered dose or dry powder inhalers, are the mainstays of pharmacological treatment of stable COPD. Inhaled long-acting beta-agonists (LABA) and anticholinergics are the bronchodilators primarily used in the chronic treatment of COPD. Anticholinergics act as muscarinic acetylcholine receptor antagonists and are frequently preferred over beta-agonists for their minimal cardiac stimulatory effects and greater efficacy in most studies. Their therapeutic efficacy is based on the fact that vagally mediated bronchoconstriction is the major reversible component of airflow obstruction in patients with COPD. However, bronchodilators are effective only on the reversible component of airflow obstruction, which by definition is limited, as COPD is characterized by a fixed or poorly reversible airflow obstruction. Inhaled anticholinergic antimuscarinic drugs approved for the treatment of COPD include ipratropium bromide, oxitropium bromide and tiotropium bromide. Ipratropium bromide, the prototype of anticholinergic bronchodilators, is a short-acting agent. Oxitropium bromide is administered twice a day. Tiotropium bromide, the only long-acting antimuscarinic agent (LAMA) currently approved, is administered once a day. Newer LAMAs including aclidinium bromide and glycopyrrolate bromide are currently in phase III development for treatment of COPD. Some new LAMAs, including glycocpyrrolate, are suitable for once daily administration and, unlike tiotropium, have a rapid onset of action. New LAMAs and their combination with ultra-LABA and, possibly, inhaled corticosteroids, seem to open new perspectives in the management of COPD. Dual-pharmacology muscarinic antagonist-beta2 agonist (MABA) molecules present a novel approach to the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a single molecule.

Pulmonary diffusing capacity for carbon monoxide: a marker of depressed hypercapnic drive in type 1 diabetes mellitus?

AIMS: Decreased chemosensitivity to hypercapnia, a common finding in Type 1 diabetes mellitus, seems related to autonomic neuropathy. We proposed to verify whether simple neuroautonomic cardiovascular tests or indexes of severity of diabetes and respiratory impairment can identify patients with such a dysfunction, but no clinical evidence of autonomic neuropathy. METHODS: Forty patients with Type 1 diabetes, 20 with autonomic neuropathy according to the results of a standardized test battery, were studied and compared with 40 normal subjects matched by age and sex. Spirometry and pulmonary diffusing capacity for carbon monoxide were performed. The chemosensitivity to hypercapnia was tested by the rebreathing method. RESULTS: There was no significant difference between patients with and without autonomic neuropathy in chemosensitivity to hypercapnia, as expressed by the ventilation response to increasing end-tidal pressure of carbon dioxide; however, it was lower in the whole group of patients with diabetes than in control subjects (1.71 ± 0.80 vs. 2.45 ± 1.11 l⁻¹ min⁻¹ mmHg, respectively, P=0.002). No significant correlation was found between ventilation response to increasing end-tidal pressure of carbon dioxide and the results of autonomic tests. In patients with diabetes mellitus, the ventilatory response to hypercapnia significantly correlated with pulmonary diffusing capacity for carbon monoxide (Spearman's rho=0.387, P=0.013) and this was the only variable significantly associated with ventilation response to increasing end-tidal pressure of carbon dioxide in a multiple regression model. CONCLUSIONS: Chemosensitivity to hypercapnia was depressed in patients with diabetes mellitus, irrespective of autonomic neuropathy, in comparison with control subjects. The correlation with pulmonary diffusing capacity for carbon monoxide suggests that microcirculatory damage might contribute to depress the central chemosensitivity.

Association between reduced pulmonary diffusing capacity and cardiac autonomic dysfunction in Type 1 diabetes.

BACKGROUND: In Type 1 diabetes mellitus (DM), it has been suggested that autonomic nervous system dysfunction (NAD) impairs lung diffusion capacity. Heart rate variability (HRV), a measure of cardiac autonomic function, is a sensitive method of detecting NAD. To our knowledge, no previous study has assessed whether cardiac sympatho-vagal balance is associated with lung diffusion capacity in diabetes. METHODS: Twenty Type 1 DM patients without pulmonary abnormalities and systemic NAD underwent measurement of lung diffusion capacity for carbon monoxide (DLCO) by single-breath method and assessment of cardiac autonomic function by HRV analysis on 24-h electrocardiographic Holter recordings. RESULTS: Standard respiratory function tests and peripheral autonomic tests were normal in all patients. DLCO was lower than normal reference values in six patients (30%). DLCO correlated significantly with most HRV variables, independent of the clinical and laboratory variables. The strongest correlation was found with standard deviation of all RR intervals (SDNN; r = 0.62, P = 0.003) in the time domain and low frequency (LF) power (r = 0.73, P < 0.001) in the frequency domain. CONCLUSIONS: In Type 1 diabetes, a significant association exists between cardiac NAD and reduced DLCO in the absence of clinical respiratory and autonomic abnormalities. Thus, NAD may be involved in the early reduction of DLCO in these patients, possibly through abnormalities in the regulation of pulmonary blood flow at the microvascular level.

Could follow-up different modalities play a role in asymptomatic cervical cancer relapses diagnosis? An Italian multicenter retrospective analysis.

OBJECTIVE: The aim of this study was to evaluate how much clinical surveillance performed by follow-up scheduled appointments may correctly identify asymptomatic recurrences and describe the pattern of relapse detected by procedures. METHODS: The records of 327 consecutive women with recurrent cervical cancer treated from 1980 to 2005 were retrospectively collected in 8 Italian Institutions. Primary disease and recurrence data were picked up: diagnosis, type of treatment, FIGO stage, tumour grade, histology, clinical lesion size, number of localizations and site of relapse, presence of symptoms and primary method of detection, the type of treatment of recurrence and follow-up data, such as appointment date, clinical status and procedure performed. A multivariate analysis was carried out using the Cox proportional hazards regression model. Survival curves were calculated using the Kaplan-Meier technique. Survival differences were evaluated by the log-rank test. RESULTS: Sixty-seven out of 327 patients (20.5%) had a local recurrence on vaginal vault, 120 (36.7%) in central pelvis, 31 (9.5%) in pelvic wall, 16 cases (4.9%) in lymph nodes. Seventy-nine patients (24.2%) showed a distant relapse while 14 (4.3%) developed both a distant and local relapse. Among patients with distant relapses 39 (49.4%) had lung metastasis, 41 (51.9%) an hepatic recurrence, 4 (5.1%) a bone relapse. Among distant sites 32 out of 79 patients (40.5%) had single relapse and 46 (58.2%) had multiple localizations. The site of relapse influenced survival since patients with vaginal vault recurrences lived significantly longer than patients with recurrences in other sites. Ninety-seven (29.7%) patients were symptomatic and anticipated the scheduled visit, 66 (20.2%) reported their symptoms during the follow-up visit and 164 (50.1%) were asymptomatic and the diagnostic path was introduced by a planned visit or exam. Between asymptomatic patients the first procedure was clinical visit for 85 patients out of 164 patients (51.8%), imaging for 60 patients (36.6%), both clinical visit and imaging for 14 (8.5%) and cytology for 5 (3%, Pap smear test). The median OS of symptomatic patients was 37 months versus 109 months of asymptomatic patients (Log rank, p=0.00001). The median survival since recurrence was 9 months for symptomatic patients and median was not reached for asymptomatic patients (p<0.0001). The median disease-free interval was 24 months for asymptomatic patients vs. 36 months for symptomatic patients (p=0.03). CONCLUSIONS: Our study helps demonstrate the great need of prospective cost-effectiveness studies which are lacking at the present time.

Follow-up strategies in gynecological oncology: searching appropriateness.

Nowadays, the cost for oncology diseases is growing rapidly, in particular as a consequence of the introduction of new drugs and new diagnostic procedures, and becoming a considerable percentage of the global healthcare expense. On the other hand, a substantial amount of that cost is considered to be imputable to the follow-up procedures. The aim of our paper is to introduce the debate about follow-up policies adopted in gynecological oncology throughout a literature review just based on cost-effectiveness and cost-efficacy in order to explore if the data are consistent with evidences available in this field. Furthermore, it is discussed if common practice fits the needs of patients, gynecological oncologists, and health service. Despite the fact that in gynecological oncology we must consider different clinical situations concerning each specific neoplasm with their peculiar natural history, some general considerations could be drawn in order to set up future initiatives properly.

Gemcitabine-carboplatin-paclitaxel combination as first-line therapy in advanced ovarian carcinoma: a single institution phase II study in 24 patients.

Single-agent gemcitabine demonstrated response rates of 11-60% in platinum/paclitaxel-resistant ovarian cancer. Twenty-four patients with epithelial ovarian cancer were treated with gemcitabine 800 mg/m2 on days 1 and 8, carboplatin area under the curve 5 on day 1, and paclitaxel 175 mg/m2 over 3 h on day 1 every 3 weeks for six cycles. Median age was 54 years, and FIGO stage distribution was IIC, 1 patient, III, 18, and IV, 5. A total of 22 (92%) patients completed all the six planned courses of chemotherapy. Doses were reduced in 8 out of 24 (33%) patients. Of the 17 patients with measurable disease, 15 underwent an interval debulking surgery. Prior to interval debulking surgery, all 15 patients had a partial response according to the response evaluation criteria in solid tumors criteria. Overall in the 17 patients with measurable disease, the response rate at the end of the first-line chemotherapy (including interval debulking) was 94% (14 [82%] complete response and 2 [12%], partial response). One patient (6%) received only one cycle due to early progression. Using the CA125 criteria as defined by the Gynecologic Cancer Intergroup, all patients had at least a partial response prior to interval debulking, and the overall response rate of the whole first-line chemotherapy and interval debulking (n= 15) was observed in 21 out of 23 patients (91%). The dose-limiting toxicity was bone marrow toxicity. Median overall survival was 28 months, and the 2-year actuarial survival was 73%. The gemcitabine, carboplatin, paclitaxel triplet has an acceptable toxicity with high response rates as first-line therapy in advanced ovarian cancer.

Autofluorescence bronchoscopy to identify pre-cancerous bronchial lesions.

BACKGROUND: This study aimed to assess the diagnostic yield of autofluorescence bronchoscopy (AFB) in the detection of pre-cancerous bronchial lesions in a non-selected sample of patients. METHODS: Both fiberoptic white-light bronchoscopy (WLB) and AFB using the Storz D-light system were performed on 166 consecutive patients. Biopsy specimens were taken in areas of the tracheobronchial tree judged as abnormal or suspicious at WLB and/or AFB. The bronchoscopic procedures were randomly performed by two operators. RESULTS: A total of 93 patients had a positive biopsy specimen: 80 for cancer and 13 for dysplasia. AFB was abnormal or suspicious in 85 of the 93 patients with a sensitivity of 91.4%. Specificity was 50.7%. In 16 patients with normal WLB examination, AFB identified abnormal or suspicious areas which had a positive biopsy. Thus AFB significantly improved sensitivity of WLB (100% vs 82.8%, respectively, p<0.001) in the entire sample of patients studied. Data was further analysed separately for patients with dysplasia and those with cancer. Indeed, 13 of 16 patients recognized only by AFB had a histological diagnosis of dysplasia. The remaining three patients had a diagnosis of cancer (small intraepithelial neoplastic lesions). Since no other patient with dysplasia was found, AFB had a sensitivity of 100% in diagnosing dysplasia. On the other hand, excluding the 13 patients with dysplasia, WLB had a high sensitivity in diagnosing cancer (93.7%). CONCLUSIONS: The AFB Storz system showed a high sensitivity. The increase in diagnostic yield of AFB in comparison with WLB was related to the power of AFB to identify pre-cancerous bronchial lesions so showing its usefulness in the early diagnosis of lung cancer.

Prevalence of asthma and atopy in Italian Olympic athletes.

This study aimed to assess the prevalence of asthma and atopy in the Italian athletes who were trying for a position on the Italian Olympic team for the 2000 Sydney Olympic Games. Overall, 1060 athletes (mean age 24 years, range 15 - 69 years, 729 males) were recruited and divided into three groups of sport activities: 1) anaerobic, 2) aerobic-anaerobic, 3) aerobic. Asthmatic and atopic athletes were identified by a self-administered, standardized questionnaire modified from the ISAAC questionnaire. Spirometry was performed in the athletes who reported wheezing or asthma and in an equal number of randomly selected controls. Athletes reporting wheezing or asthma were 15 %. However, only a minority of asthmatics had moderate or severe disease: indeed, 2.5 % reported more than 4 attacks in the last year. The prevalence of atopy was 18 %. Asthma was more common in athletes engaged in aerobic sport activities than in the other groups. Asthmatic athletes had a significantly lower value of some spirometric parameters in comparison with the control group. In conclusion, the prevalence of wheezing or asthma in a large sample of Italian competitive athletes was found higher than in general population; respiratory symptoms were more prevalent in athletes engaged in aerobic sport activities; a significant impairment of lung function was found in athletes suffering from mild and rarely symptomatic asthma.

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.

Quantitative real-time RT-PCR analysis of eight novel estrogen-regulated genes in breast cancer.

BACKGROUND: Biological markers capable of predicting the risk of recurrence and the response to treatment in breast cancer are eagerly awaited. Estrogen and progesterone receptors (ER, PgR) in tumor cells mark cancers that are more likely to respond to endocrine treatment, but up to 40% of such patients do not respond. Here, the expression of a group of estrogen-regulated genes, previously identified by microarray analysis of in vitro models, was measured in breast tumors and possible associations with other clinicopathological variables were investigated. METHODS: The expression of CD24, CD44, HAT-1, BAK-1, G1P3, TIEG, NRP-1 and RXRalpha was measured by quantitative real-time RT-PCR on RNA from eighteen primary breast tumors. Statistical analyses were used to identify correlations among the eight genes and the available clinicopathological data. RESULTS: Variable expression levels of all the genes were observed in all the samples examined. Significant associations of CD24 with tumor size, CD44 with lymph node invasion, and HAT-1 and BAK-1 with ER positivity were found. The possible combinatorial value of these genes was assessed. Unsupervised hierarchical clustering analysis demonstrated that the expression profile of these genes was able to predict ER status with an acceptable approximation. CONCLUSIONS: Eight novel potential markers for breast cancer have been preliminarily characterized. As expected from in vitro data, their expression is able to discriminate ER- versus ER+ tumors.

123I-MIBG radioaerosol lung clearance in COPD patients with fixed and partially reversible obstruction to evaluate the functional status of pulmonary adrenergic innervation.

In order to test the hypothesis that a greater sympathetic activity underlies partial reversibility of the bronchial obstruction in selected patients with chronic obstructive pulmonary disease (COPD), we assessed the pulmonary clearance of inhaled I-meta-iodobenzylguanidine ( I-MIBG) radioaerosol in 10 patients with fixed and nine with reversible obstruction. The clearance of inhaled I-MIBG is known to be inversely related to I-MIBG uptake by adrenergic terminals. Groups were matched for age and judged free from confounding comorbidity. The penetration index did not distinguish between the groups (fixed obstruction, 97.39+/-14.59%; reversible obstruction, 89.09+/-19.95%; P=0.659); this excludes the possibility that the inequality of tracer penetration could affect I-MIBG clearance. The I-MIBG clearance was 140.92+/-7.67 min in patients with fixed obstruction and 151.08+/-31.54 min in patients with reversible obstruction ( P=0.604). In conclusion, COPD patients with fixed and reversible obstruction show comparable binding of the tracer to adrenergic pulmonary receptors. Thus, a greater receptor responsiveness or post-receptor mechanism probably underlies the partial reversibility of bronchial obstruction.

Different types of hysterectomy in the radio-surgical treatment of early cervical cancer (FIGO Ib-IIa).

PURPOSE OF INVESTIGATION: Surgery and radiotherapy achieved equivalent results for FIGO stages Ib-IIa invasive cervical carcinoma. The integration of radiotherapy and surgery provided the same results for a selected series of patients without increasing the rate of complications. The aim of the study was to verify if, applying a radio-surgical protocol, the reduction of the surgery extension on the parametrium in one of two consecutive series might achieve the same results in terms of survival and recurrence rates with fewer complications. MATERIAL AND METHODS: We analysed actuarial survival (with >10-year follow-up), local control rates and morbidity of 390 patients who had different the kinds of surgery applied in the radio-surgical treatment protocol: Protocol A: brachytherapy plus type III radical hysterectomy vs Protocol B: brachytherapy plus type II radical hysterectomy. Patients were all included in an analysis of complications according to the French-Italian glossary. RESULTS: Analyses showed no differences in terms of survival, patterns of recurrences and onset time within the two protocols. Urinary complications were more frequent and severe in protocol A vs protocol B (G2: 26.5% vs. 6.1%; G3: 5.3% vs. 3.6%). CONCLUSION: Our study pointed out that the reduction of the surgery extension allowed the same overall survival and relapses with fewer complications particularly in terms of grade of severity.