Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies.

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM-AIRO-AISP-ANISC-AURO-Fondazione AIOM-SIAPEC/IAP-SIBioC-SICO-SIF-SIGE-SIGU-SIU-SIURO-UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.

[Exclusive intra-operative radiation therapy (IORT) for early stage breast cancer: pilot study of feasibility]. / Radioterapia intraoperatoria (IORT) esclusiva nel carcinoma iniziale della mammella: studio pilota di fattibilità.

AIM: To evaluate feasibility, tolerability and cosmetic outcome of intra-operative radiation therapy (IORT) as an exclusive post-surgery treatment of early stage breast cancer. PATIENTS AND METHODS: From October 2008 to October 2009 30 patients underwent wide breast cancer excision or quadrantectomy followed by IORT on tumor bed with accelerated electrons at the dose of 21Gy. The characteristics of the patients were: ductal breast cancer or invasive lobular cT1, cT2 ≤ 2,5 cm, cN0, G1-2, age over 35 years, M0. RESULTS: The average age was 51.7 (range 38 - 75) with an average follow up of 11.7 months (range 6 - 18). The pathologic stage of the lesions resulted pT1 in 29 cases (96,6%), in particular: one case pT1a (3,3%), 21 cases pT1b (70,0%) and 7 cases pT1c (23,3%). One case (3,3%) was pT2 with a diameter of 2.5 cm. The grading was G2 in 20 cases (66,6%) and G1 in 10 cases (33,3%). The toxicity, evaluated according to the EORTC-RTOG criteria, was G0 (33.3%) in 10 cases, G1 (63,3%) in 19 cases, G2 in one case (3,4%); there was no G3 toxicity. The time needed for a complete healing of the wound was less than 10 days in 96,7% of the cases, with one case of limphocele (3,3%). There were no infections of the surgical wound nor any mastitis, neither in the treated quadrant nor in the other ones. We observed a light fibrosis in 5 cases (16,6%), moderate in 2 cases (6,6%) but never severe. Cosmetics, evaluated in four levels, according to Danoff et al., was excellent in 3 cases (43,3%), good in 15 cases (50%), sufficient in 2 cases (6,7%), never insufficient. As regards local control, there was no local relapse. The global survival was 100%. CONCLUSIONS: The IORT in early breast cancer, at the doses used in this study, proved itself as a secure technique, repeatable, with limited complications. The advantages of its use are the possibility of a direct control, by the surgeon and the radiotherapist, of the structures to treat and those to protect; the absence of time needed for cellular repopulation between surgery and radiotherapy; a good cosmetic outcome; and logistic advantages. It is necessary to have a long term follow up to evaluate the efficacy in terms of long term cosmetic and local control.

Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of Surgical Oncology (SICO) Breast Oncoteam survey.

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014-2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy. In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations.

[Colorectal cancer in old age. Our experience]. / Il cancro colorettale in età geriatrica. Nostra esperienza.

Two hundred and thirty-three patients treated for colorectal cancer during the period 1976-1991 were divided into three groups (A: < 65 yr; B: 65-74 yr; C: > 74 yr) in order to perceive possible statistically significant differences in patients older than 75 years. Epidemiological features are similar among the three groups, while a greater diagnostic delay (p = 0.013), a higher incidence of emergency procedures (p = 0.006) and a more advanced AP stage were found in group C. The high anesthesiological risk determined a conservative surgical approach only in 4.1% of patients, while a curative resection was performed on 51% of group C vs 72.7% of group A (p = 0.016). Postoperative complications and mortality for curative resections were 28% and 12% in group C vs 24.6% and 2.9% in group A (p = n.s.); the overall 5 years survival rate was 62.9%, 51.7% and 42.2% in groups A, B, and C. It is concluded that age alone should not be considered as a contraindication to curative surgery for colorectal cancer, for life expectancy and quality are considerably worse in the elderly undergoing derivative surgery.

Clinical management of soft tissue sarcomas.

The prognosis of soft tissue sarcomas has dramatically improved over the past few decades thanks to the use of increasingly suitable multidisciplinary therapeutic approaches. An assessment of the results of our series of 21 patients, carried out in the light of the most recent literature data, has led us to revise our approach to a number of problems regarding the natural history, the nosographical classification and the therapy of these cancers. This type of tumour arises in a muscle compartment and then spreads proximally and distally within the compartment without involving adjacent structures, except in a relatively advanced phase, while as regards remote metastases the preferential diffusion route is via the bloodstream. Thorough assessment of the clinical and morphological characteristics is essential for adequate treatment: echotomography, CT, and MRI are particularly useful in preoperative staging; a microscopic examination should always include precise classification and accurate assessment of the tumour grade. Surgical management consists in extensive en bloc resection, followed by radiotherapy in the event of unclear margins and/or high grade tumour even when dealing with small sarcomas. The main indications for chemotherapy are locally advanced cases or cases with distant metastases. Thanks to these therapeutic approaches today, good results can be achieved, with 5-year survival rates of 80 and 67%, respectively, in stages I and II, and of 12 to 50% in the more advanced stages.

[Sentinel lymph nodes in breast carcinoma: why, how, when]. / Lo studio del linfonodo sentinella nel carcinoma mammario: perché, come, quando.

Thanks to a retrospective analysis of the first 250 cases of sentinel lymph nodes in breast cancer assessed by the authors over the period from October 1998 to December 2000 in the light of a careful review of the literature, it has been possible to establish the importance of careful patient selection, strict compliance with the execution technique and, above all, the need for an adequate learning curve, before the procedure is used in particular protocols and/or in routine clinical practice in the near future. In particular, the training should first of all ensure that all personnel involved, i.e. surgeons, nuclear medicine specialists, and histopathologists, should attend specific courses at qualified Institutions followed by the actual management of a certain number of consecutive cases. In order to perfect the methodology and organisation, a preliminary study in a group of patients at different stages of evolution of the disease is recommended (50 cases in the study population reported). The next phase should include a group of highly selected patients, numbering at least 50-100. The training may be considered complete when in at least 20 cases, an identification rate of at least 90% is achieved with an incidence of false negatives of not more than 5%. In the authors' experience, these results were reached after 100 selected patients, and were later consistently confirmed after a further 50 cases.

[Acute complications of pulmonary hydatidosis. Apropos 44 cases]. / Le complicanze acute dell'idatidosi polmonare. A proposito di 44 osservazioni.

The authors examine a series of 44 patients with an acute complication of the hydatid disease of the lung. Clinical data, diagnostic features, surgical procedures and short and long term results are compared with those of 80 cases presenting no complications. Acute complication has in many cases a non specific clinical presentation and its evidence can only be found by means of radiology. The basic principles of surgical treatment are the same of the non complicated cysts, even though resection is more often performed (56.8%) since contextual lung and bronchial involvement is frequent. The authors report no significant difference between short- and long-term results in the two series.

Primary lactase deficiency and past malarial endemicity in Sardinia.

BACKGROUND: It has recently been suggested that primary lactase deficiency might have been selected for by malaria, as occurred for beta-thalassaemia and glucose 6-phosphate dehydrogenase deficiency. However, recently we have found that the prevalence of primary lactase deficiency in the area of Sassari (Northern Sardinia), where, in the past, there was intermediate malarial endemicity, is comparable to that observed in the adult population from other areas of Southern Italy where malaria was less endemic. AIMS: To address the problem further, we have determined the prevalence of primary lactase deficiency, glucose 6-phosphate dehydrogenase deficiency deficiency and beta-thalassaemia trait in the populations of three Sardinian villages which differ in altitude above sea-level, socioeconomic features, history of endemic malaria and prevalence of b-thalassaemia and glucose 6-phosphate dehydrogenase deficiency. SUBJECTS: We tested 138 adult males: 53 were from Fonni (a non-malarial mountain village, with a strong pastoral tradition), 38 from Lodé (a village with a similar pastoral tradition, but high malarial endemicity in the past) and 47 from Terralba (a lowland fishing village with an agricultural tradition and heavy malarial morbidity and mortality). METHODS: A blood sample was obtained in all subjects for determination of HbA2 and glucose 6-phosphate dehydrogenase activity. Lactase deficiency was assessed by measuring breath hydrogen production after oral administration of lactose (50 g), by gas-chromatography. RESULTS: The frequencies of glucose 6-phosphate dehydrogenase deficiency and of beta-thalassaemia trait in the non-malarial village of Fonni were strikingly low, compared to frequencies found in the two villages (Terralba and Lodé) with a very high past malarial morbidity. In contrast, there was no significant difference in the prevalence of lactase deficiency in the three groups of subjects from the three villages. CONCLUSIONS: These data obtained in Northern Sardinia do not support the hypothesis of a selection of primary lactase deficiency by malaria. For definitive conclusions, however, the malaria hypothesis should be tested in other parts of the world.