Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey.

BACKGROUND: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). PATIENTS AND METHODS: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. RESULTS: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). CONCLUSIONS: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

Systemic treatment in advanced phyllodes tumor of the breast: a multi-institutional European retrospective case-series analyses.

BACKGROUND: We aimed at investigating outcome of systemic treatments in advanced breast PT. METHODS: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed. RESULTS: 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months. CONCLUSION: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active.

Thymidine phosphorylase expression is associated with time to progression in patients receiving low-dose, docetaxel-modulated capecitabine for metastatic breast cancer.

BACKGROUND: Preclinical data have indicated a synergistic interaction between docetaxel and capecitabine by means of taxane-induced up-regulation of thymidine phosphorylase (TP). On the basis of such premises, we conducted a phase II trial to determine the activity and tolerability of weekly docetaxel plus capecitabine in patients with metastatic breast cancer (MBC). Furthermore, we explored the relationship between TP tumor expression and benefit from this regimen. PATIENTS AND METHODS: Patients received docetaxel 36 mg/m(2) i.v. on days 1, 8, and 15 and capecitabine orally 625 mg/m(2) b.i.d. from days 8 to 21. Cycles were repeated every 4 weeks. In the correlative study, we evaluated the TP expression by immunohistochemistry and the TP messenger RNA expression by real-time RT-PCR in the primary tumor. RESULTS: Forty-seven women were enrolled. In the intention-to-treat analysis, objective responses were achieved in 24 patients (51%). Fourteen additional patients (30%) had stable disease. The median time to progression (TTP) was 6 months (range 1-44 months). Median survival was 17 months (range 1-48 months). Overall, the treatment was well tolerated. The most common clinical adverse events (all grades) were alopecia (55%), nail changes (53%), fatigue/asthenia (51%), nausea/vomiting (51%), neutropenia (49%), and neuropathy (49%). A significantly higher TTP was observed in patients with TP-positive tumors (log-rank test, P = 0.009). Interestingly, a subgroup analysis confirmed this TTP benefit in patients with TP-positive tumors obtaining a tumor response (log-rank test, P = 0.03), whereas the statistical significance was lost in nonresponders (log-rank test, P = 0.3). CONCLUSIONS: This study indicates that a regimen with low doses of capecitabine plus weekly docetaxel is active against MBC. The correlative analysis provides preliminary evidence that TP expression may be a predictive marker for therapeutic benefit.

Baseline staging tests after a new diagnosis of breast cancer: further evidence of their limited indications.

BACKGROUND: Bone scanning (BS), liver ultrasonography (LUS) and chest radiography (CXR) are commonly used in patients with newly diagnosed breast cancer as part of baseline staging. However, in the absence of symptomatic disease, the usefulness of this routine diagnostic work-up is not evidence-based. METHODS: We selected the study sample from 516 consecutive patients with newly diagnosed invasive breast cancer. For each diagnostic test (BS, LUS, CXR), we analyzed the prevalence defined as the number of patients with diagnosis of metastatic disease after an imaging technique divided by the total number of patients tested. In addition, sensitivity and specificity were calculated. Initial suspicion was confirmed by other independent tests (bone X-ray, computerized tomography scan, magnetic resonance imaging) in order to identify "true" positive diagnoses. RESULTS: At baseline, BS was carried out in 412 patients, LUS in 412 patients and CXR in 428 patients. Thirty-three patients were correctly diagnosed by the initial staging investigations as having metastatic disease (true positive cases). BS detected skeletal metastases in 6.31% of patients, LUS detected liver metastases in 0.72% of patients and CXR detected lung metastases in 0.93% of patients. Before imaging tests, all patients with either LUS or CXR evidence of metastases were previously classified as having stage III disease. On the other hand, only 26.9% of bone metastases were detected in patients with stage III. Accordingly, the detection rate in stage III patients was 14%, 5.6% and 7.2%, respectively for BS, LUS and CXR. CONCLUSIONS: These findings indicate that a complete diagnostic work-up to detect metastases is unnecessary in the majority of patients with newly diagnosed breast cancer, whereas it may be indicated for specific patient categories such as those with stage III disease.

Effects of a cable car trip on blood pressure and cardiovascular hormones in lowlander and highlander normotensives.

The effects of a cable car trip from 1370 m (4500 ft) to 3460 m (11350 ft) were studied in 6 lowlanders (3 men and 3 women, mean age 31 +/- 4 years, living at an altitude of less than 500 m) and in 10 highlanders (all males, mean age 37 +/- 12 years, ski teachers and cable car workers working for greater than or equal to 6 months/year at a greater than 3000 m). Cuff blood pressure (BP), heart rate, plasma catecholamines, serum renin, aldosterone, ACTH and cortisol were measured immediately before and 20 min after the trip, at rest and at the same air temperature. A handgrip test was also performed under the same conditions. At baseline, lowlanders and highlanders showed significant differences in diastolic BP (86 +/- 5 mmHg in lowlanders and 91 +/- 4 mmHg in highlanders, p = 0.05), plasma noradrenaline (323 +/- 114 pg/ml in lowlanders and 585 +/- 255 in highlanders, p less than 0.05), serum renin (10 +/- 6 pg/ml in lowlanders and 17 +/- 8 in highlanders, p less than 0.05), and serum cortisol (163 +/- 54 ng/ml in lowlanders and 120 +/- 25 in highlanders, p less than 0.01). The acute exposure to high altitude did not modify BP, heart rate or any of the measured cardiovascular hormones in either group. The handgrip test provoked a significant increase in systolic and diastolic BP in both lowlanders and highlanders (p less than 0.01), and this response was not modified by the change in altitude; however, highlanders showed significantly smaller increases in systolic BP than lowlanders at both altitudes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive effect of slow-release nicardipine. A placebo-controlled cross-over study.

The magnitude and duration of the antihypertensive effect of slow-release nicardipine (SR-Nicardipine) have been compared with placebo in 36 uncomplicated essential hypertensives (diastolic BP 95 to 115 mm Hg after 1-month placebo washout). According to a double-blind, randomized, cross-over design they received SR-Nicardipine 40 mg b.d. and placebo for 1 month. At the end of each treatment period, blood pressure and heart rate were measured 12 h after the evening dose and 1, 2, 3 and 4 h after the morning dose. SR-Nicardipine significantly reduced systolic (SBP) and diastolic (DBP) blood pressure at each time after dosing. The absolute decrements peaked 4 h after dosing (-18.3 and -11.7 mm Hg, respectively) and more than 90% of the peak effect persisted 12 h after dosing, both for SBP and DBP. The heart rate was slightly increased by SR-Ni-cardipine. Adverse effects monitored with a check-list occurred in 31% of patients during SR-Nicardipine treatment and in 28% on placebo. Thus, SR-Nicardipine 40 mg b.d. has a maintained and significant antihypertensive effect lasting up to 12 h in essential hypertension.

Alveolo-arterial gradients of O2 and CO2 in hyperlipidemic subjects.

In 20 hypertriglyceridemic normocholesterolemic patients, mean age 51 years (range 42-62), +/- 10% ideal body weight, and in 18 normolipidemic controls, mean age 49 years (range 42-63), +/- 10% ideal body weight, the following tests were performed: spirometry, flow-volume curves, arterial blood gases, alveolo-capillary transfer of CO, alveolo-arterial gradients of O2 and arterio-alveolar gradients of CO2. A significant decrease in the arterial partial pressure of O2 and in the transfer of CO, with a significant increase in the alveolo-arterial gradient of O2 were found. Hypertriglyceridemia seems to compromise the alveolo-capillary gas exchange.

[Action of heparin on pulmonary lipids and alveolar surfactant in rabbits]. / Azione dell'eparina sui lipidi polmonari e sul surfactant alveolare di conigli.

The effect of subcutaneous 1000 IU/kg calcic heparin every 12 hr for 7 days on lung lipids and pulmonary surfactant was examined in 10 male rabbits weighing 2.5-3.5 kg. Comparison with an identical control group showed a decrease in phospholipids and lecithins in the lung homogenate extract and in the alveolar liquid bubble stability index. The difference in the means was highly significant (P less than 0.001) for all three parameters.

[The arterio-alveolar CO2 gradient. Physiopathological and clinical significance]. / Il gradiente arterio-alveolare di CO2. Significato fisiopatologico e clinico.

The arterio-alveolar CO(2) gradient was examined in 20 patients with various ventilation diseases. It increased or became negative in obstruction. The tendency to increase was attributable to distribution disturbances, particularly the marked increase in the "dead space" effect. The same picture, though to a lesser degree, owing to a smaller dead space increase, was even more frequent in restriction cases. The appearance of a gradient in healthy subjects is referable to uneven air and blood distribution in the alveoli under physiological conditions. The physiopathological significance of negative gradients is discussed in the light of the results and the findings of other workers.

[Alveolar surfactant and experimental diabetes (protective action of citicoline)]. / Surfactant alveolare e diabete sperimentale (azione portettiva della citicolina).

Above normal or normal S.R. values (0,70-0,90) (S.R. = 0,81 +/- 0,11), were noted in 13 alloxaneinduced diabetic rabbits treated with CDP-choline, and decreased values (S.R. = 0,57 +/- 0,06) in 9 diabetic rabbits not so treated. This difference was statistically significant (P less than 0,001). The results show that CDP-choline can protect surfactant from damage caused by alloxane-induced diabetes. The most likely explanation is increased synthesis of dipalmitoyllecithin, by intervention of CDP-choline, as cofactor, on lipid metabolism in the lung.

[Allergological study of subjects with chronic rhinitis]. / Studio allergologico in soggetti affetti da rinite cronica.

The following parameters were considered in an allergological study of 362 subjects with chronic rhinitis unaccompanied by bronchial asthma: sex, age at onset, residence, familial allergy, personal history, season in which distrubances occurred, nasal polyps, concomitance of conjunctivitis, appear of chronic bronchitis, skin tests for dusts, vegetable fibres, skin derivatives, pollens and moulds. A positive allergometric response was noted in 60.77% and familial allergy in 30.93%. Skin manifestations were observed in 20.99%. Conjunctivitis was present in 55.24%, most of whom were skin-positive; nasal polyps were present in 4.69%, most of whom were skin-negative. 1.65% had chronic bronchitis. 79.54% of the skin-positive subjects were sensitive to pollens, 47.72% to "inhalants" (28.18% to household dust), and 30% to moulds.

[Allergological findings in rhinitis-asthmatic subjects]. / Indagini allergologiche in soggetti rinoasmatici.

A comparison was made between skin-positive and skin-negative subjects in an allergological study of 404 patients with rhinitis and asthma. The two diseases had appeared simultaneously in 52.72% of cases, while rhinitis had appeared first in 35.14%. Respiratory disturbances had occurred more frequently before the age of 30 yr in allergic subjects and between 20 and 50 yr in skin-negative subjects. Familial allergy was noted in 34% and a personal history of skin allergy in 21%. Associations with conjunctivitis, chronic bronchitis and nasal polyposis were noted in about 50%, 13% and 4% respectively. Nearly all skin-negative subjects had disturbances the whole year round, as did 47.67% of the skin-positives, while 36.53% of the latter had disturbances in spring and summer only. A positive reaction to at least one allergen was noted in 79.95%. Pollens were positive in 70.58%, dusts, vegetables fibres and skin derivatives in 66.25%, and moulds in 33.12%. The allergens used and the number of positives obtained with each are listed. It is felt that reaction to pollen should be investigated in such subjects, even when their symptoms are not sea sonal.

[Corticoids and alveolar surfactant. Experimental study]. / Cortisonici e surfactant alveolare. Studio sperimentale

The effect of cortisone on the production of surfactant was studied by measuring the tensioactive property of the alveolar fluid, evaluated with Pattle's method. The stability ratio (R.S.) values obtained in 12 guinea-pigs following cortisone administration were all within normal limits. In rabbits treated with prednisolone during a number of fast days, S.R. values were lower than normal in 9 cases out of 10. The results of this study would seem to exclude any influence of the administration of cortisone on the activity of the alveolar surfactant.