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We have previously shown in a phase 3 trial that tamoxifen 5 mg/day for 3 years decreased by 52% the incidence of recurrence of invasive breast cancer or DCIS after a median follow-up of 5.1 years in women with excised non invasive breast disease, including atypical ductal hyperplasia, DCIS or LCIS (DeCensi et al. JCO 2019; 37:1629). Toxicity was negligible with only an extra hot flash per day in the tamoxifen arm compared with the placebo arm. These findings were incorporated into the ASCO clinical practice guidelines for breast cancer risk reduction as an alternative option to standard doses and duration of tamoxifen or aromatase inhibitors in women with non-invasive disease (Visvanathan et al. JCO 2019; 37:3152). In the present study we update the findings on breast cancer recurrence after a median of 9.14 years (interquartile range, IQR, 7.16-10.73) and a total of 10.57 person years of follow up to see if the treatment effect is retained with more events and after a median of approximately 6 years from treatment cessation. We conducted a national multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. Between November 1, 2008, and March 31, 2015, 1,160 women were screened and 500 aged 75 years of age or younger were included in the study. Women with high-grade or comedo/necrotic DCIS received adjuvant radiotherapy of 50 Gy in 25 courses. The mean age was 54 years (standard deviation, 9 years), and 55% of participants were postmenopausal. The mean (SD) body mass index, kg/m2, was 25.7 (4.8) on tamoxifen and 25.3 (4.2) on placebo. Twenty percent had ADH, 11% had LCIS, and the remaining 69% had DCIS. After a median follow-up of 9.14 years, there were 22 neoplastic events (invasive breast cancer or DCIS) with tamoxifen and 37 with placebo (annual rate 11.09, 95% CI, 7-30-16.84 on T vs 19.71, 95% CI, 14.28-27.21 on P per 1,000 person-years; hazard ratio, 0.56; 95% CI, 0.33 to 0.95; P = .03), which resulted in a 5-year number needed to treat of 18. Overall, 71% of the recurrences were invasive breast cancer. The follow-up was updated with the most recent visit within 12 months in two thirds of the participants, so an update of all participants will be performed by Sept 30th with full analysis of neoplastic events, annual risk rate ratio, serious adverse events and deaths. Moreover, an updated analysis of potential effect modifiers will be conducted, including menopausal status, baseline estradiol levels, menopausal symptoms, BMI, smoking status and Ki-67 of the primary lesion. In conclusion, our findings indicate that low dose tamoxifen given for 3 years still significantly prevents recurrences from non-invasive breast cancer after a median of 6 years from treatment cessation, providing a valid prevention/interception option in this disease group. Supported by Ente Ospedaliero Ospedali Galliera, Genova, Italy, the Italian Ministry of Health (RFPS-2006-1-339898), the Italian Association for Cancer Research (IG 2008 Grant No. 5611), and the Italian League against Cancer (LILT 7-08). Citation Format: Andrea De Censi, Matteo Lazzeroni, Matteo Puntoni, Luca Boni, Aliana Guerrieri Gonzaga, Tania Buttiron Webber, Marianna Fava, Irene Maria Briata, Livia Giordano, Maria Digennaro, Laura Cortesi, Fabio Falcini, Franca Avino, Francesco Millo, Katia Cagossi, Elisa Gallerani, Alessia De Simone, Anna Cariello, Giuseppe Aprile, Maria Renne, Bernardo Bonanni. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-08.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. METHODS We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. RESULTS The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. CONCLUSION Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

Pediatric malaria, even in countries considered as free as Italy, is an important problem of public health because children have a high variability of the clinical picture. The objective of this brief note is to determine the incidence of pediatric malaria in the Piedmont Region during the period 1989-2015.All cases of pediatric malaria notified were considered thanks to the regional information flow over the period 1989-2015. Cases of congenital malaria, unconfirmed malaria cases, and aged 14 and older were excluded of the study.In Piedmont in the period 1989-2015, pediatric malaria accounts for 8.8% of the total (172/1946 cases). 74% of patients are of foreign nationality, to which must be added the 14% represented by those born in Italy from foreign parents, while it is 100% the fraction of patients who have made a trip to the abroad. The notification of cases is greater in the autumn months. Only 7.6% of the sample carried out a complete chemoprophylaxis. In 79% of cases, the primary care physician advised chemoprophylaxis on trips to endemic areas.At present, lacking an effective vaccine, the prevention and implementation of standard precautions such as chemoprophylaxis, represent the safest strategy to put into practice to eradicate the disease especially for the groups at greater risk as visiting friends and relatives.

Background Delirium after cardiac surgery is associated with adverse outcomes, including prolonged hospital stay, prolonged intensive care unit stay, and increased mortality. Effective preventive interventions and treatments still are largely unknown. Aim This systematic review aimed to gather and summarize the existing evidence from randomized trials concerning interventions studied in the prevention or treatment of delirium in adult patients undergoing cardiac surgery. Methods A systematic review of the literature using a key word strategy and Boolean operators was performed. PubMed and the Cochrane and Scopus databases were searched for pertinent studies until July 2018 (no inception limit). Results Of 2,556 articles identified, 56 studies met the inclusion criteria and were included in the review—39 addressed pharmacologic strategies and 17 nonpharmacologic interventions. Interestingly, 51 (91%) trials focused on delirium prevention and only 5 (9%) on delirium treatment. Most of the analyzed studies were recent double-blind, single-center trials conducted in Europe or North America, with a low risk of bias. Overall, 38 different interventions were identified: 15 (26%) interventions were performed before surgery, 20 (36%) in the operating room, and 21 (38%) after surgery. The most frequently analyzed strategies were the administration of dexmedetomidine, ketamine, antipsychotics, glucocorticoids, propofol, opioids, volatile anesthetics, local anesthetics, and remote ischemic preconditioning. The analyzed strategies were extremely heterogenous, and dexmedetomidine was the most promising measure able to prevent the development of postoperative delirium. Conclusions In the present systematic review of 56 randomized controlled trials that examined 38 interventions, the authors found that dexmedetomidine was the most frequently studied agent and that it might reduce the occurrence of delirium after cardiac surgery.

Post-traumatic chylothorax needs surgical approach when conservative treatment is not successful to reduce chyle leakage. Thoracic duct ligation requires thoracoscopic or thoracotomic access. The authors report on a surgical thoracotomic approach to a severe and unremitting thoracic duct lesion after IX and X ribs and vertebral fractures.

The development of clinical and histopathological criteria for the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC), pushed the scientists to identify a new category: the indeterminate colitis (CI). This term is used when definitive diagnosis of UC or CD has not been made by colonoscopy, colonic biopsy or colectomy. The distinction between these forms has major implications including the choice of medical treatment, timing of surgery, prognosis and disease course. The role of surgery in inflammatory bowel disease differs between the three main forms: in CD is primarily to treat complications of the disease process; in UC surgery is curative for intestinal manifestations and nearly eliminates the risk of future malignancy; in IC is actually discussed: the current guidelines identify in surgery the best treatment for fulminate disease, intractability of disease symptoms or failure of medical therapy. Although there is a few number of studies in the literature, selective criteria for the diagnosis and successful treatment must be revisited. The term CI should be used as a pending tray diagnosis, representing diagnostic inadequacy and not as specific nosological entity. Evidence emerging from the studies of serological markers (ASCA and P-ANCA) suggests that a subgroup of patients initially diagnosed as IC maybe identified as a separate group, and so they need a specific treatment for their disease.

Lipofilling is becoming part of the breast reshaping after quadrantectomy or mastectomy in breast cancer patients, but there are open questions of its safety.