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The global distribution of germline CDH1 mutations in hereditary diffuse gastric cancer families, is highly heterogenous. The aim of this study was to determine if there is any geographic clustering of CDH1 mutations in families with the hereditary diffuse gastric cancer syndrome. Data from 1998 to 2021 were collected systematically according to the PRISMA guidelines. 571 germline CDH1 mutations were recorded worldwide, with 387 (67.8%) of them reported in 108 families. The largest clusters of CDH1 mutations were identified in central Europe, north America, northern Europe, New Zealand (Māori), and south America. A high penetrance risk for GC development was observed for c.1008G T in New Zealand (Māori), c.1565 + 2insT in northern Europe, c.1901C T in Portugal, and c.1003C T in the USA. Our observations are consistent with a specific local clustering of some recurrent CDH1 mutations within specific countries.

Recent observations regarding long-term outcomes among patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS) plus whole-breast irradiation (WBI) or mastectomy are from a small number of registry-based studies. Therefore, these findings may overestimate differences in survival between the two groups, compared with randomized controlled trials conducted in the 1980s. The aim of this study is to compare long-term outcomes and clinicopathologic characteristics between patients treated with BCS + WBI or mastectomy for BC.We performed a propensity score-matched analysis in a cohort of 9710 patients aged 70 years who underwent BCS + WBI or mastectomy without external radiotherapy for a first primary BC (pT1-2, N0-3a) at the European Institute of Oncology between 2000 and 2008. Patients were matched by propensity score.Median follow-up was 8.4 years (interquartile range 6.5-10.2). The cumulative incidence of axillary lymph node recurrence at 10 years was lower in the BCS + WBI group [2.4% (95% CI, 1.7-3.3%)] than in the mastectomy group [4.4% (95% CI, 3.5-5.5%)] (P = .0005), and the cumulative incidence of contralateral BC was higher in the BCS + WBI group [3.9% (95% CI, 2.8-5.1%)] than in the mastectomy group [2.5% (95% CI, 1.7-3.4%)] (P = .01). Among the 366 patients with HER2 subtype BC, BCS + WBI was associated with a fivefold higher risk [hazard ratio 4.97 (95% CI, 2.28-10.8)] of ipsilateral breast tumor recurrence (IBTR), compared with mastectomy (P .0001); however, among patients with other BC subtypes, the rates of IBTR were not statistically significantly different.Patients with HER2 subtype BC (T1-2, N0-3) who underwent BCS + WBI had a statistically significantly higher risk of IBTR than patients who underwent mastectomy. Survival was not statistically significantly different between the groups.

The objective of this study was to determining the frequency of different sub-types of pathogenic CDH1 germline mutations in healthy and asymptomatic individuals from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations. The collected variants were classified according to their subtype into the following classes: missense, non-sense, splicing, insertions and deletions. The χ2 test was used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was statistically significant. CDH1 genetic screening data were retrieved for 224 patients with GC and 289 healthy individuals. Among the subjects that had tested CDH1 positive, splicing mutations were found in 30.4% of the healthy individuals and in 15.2% of the patients with GC (p=0.0076). Missense mutations were also found to occur in healthy subjects with higher frequency (22.2%) than in GC-affected individuals (18.3%), but the difference was not significant in this case. In families meeting the clinical criteria for the HDGC syndrome, CDH1 splicing and missense germline mutations have been reported to occur with higher frequency in healthy subjects than in patients with cancer. This preliminary observation suggests that not all pathogenic CDH1 germline mutations confer the same risk of developing GC.

Background and objectives The oncological benefit of axillary surgery (AS), with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND), in elderly women affected by breast cancer (BC) is controversial. We evaluated AS trends over a 10-year follow-up period as well as locoregional and survival outcomes in this subset of patients. Methods Patients aged 70 years or older, treated between 1994 and 2008, were selected and divided in two groups, depending on whether or not AS was performed. A (1:1) matched analysis for all relevant clinicopathological features was performed. Outcomes were analyzed using the Kaplan–Meier method and univariate Cox-proportional hazard ratio analysis. Results A total of 1.748 patients were identified and stratified by age (70–74, 75–79, 80–84). A matched analysis was performed for 252 patients: 122 who underwent AS and 122 who did not. At 10-year follow-up, ipsilateral breast tumor recurrence, distant metastasis and contralateral BC were similar, p = 0.83, p = 0.42 and p = 0.28, respectively. In the no-AS group, a significant increased risk of axillary lymph-node recurrence was identified at 5- and confirmed at 10-years (p = 0.038), without impact on overall survival at 5- and 10-years (p = 0.52). In the non-AS group, higher rate of axillary recurrence at 10-years was observed in patients with poorly differentiated (24.1%, 95% CI 7.2–46.2), highly proliferative (Ki67 ≥ 20%: 17.1%, 95% CI 0.6–33.3) and luminal B tumors (16.8%, 95% CI 5.9–35.5). Conclusions Axillary staging in elderly women does not impact long-term survival. Tailoring surgery according to tumor biology and age may improve locoregional outcome.

Aims: The clinical significance of nonvisualized sentinel lymph nodes (non-vSLNs) is unknown. The authors sought to determine the incidence of non-vSLNs on lymphoscintigraphy, the identification rate during surgery, factors associated with non-vSLNs and related axillary management. Patients & methods: A total of 30,508 consecutive SLN procedures performed at a single institution from 2000 to 2017 were retrospectively studied. Associations between clinicopathological factors and the identification of SLNs during surgery were assessed. Results: Non-vSLN occurred in 525 of the procedures (1.7%). In 73.3%, at least one SLN was identified intraoperatively. Nodal involvement was only significantly associated with SLN nonidentification (p

BACKGROUND. Around 7% of women who undergo breast-conserving surgery (BCS) or mastectomy are at risk of developing ipsilateral breast tumor recurrence (IBTR). When assessing risks that, like that of IBTR, depend on multiple clinicopathological variables, nomograms are the predictive tools of choice. In this study, we constructed two independent nomograms to estimate the individualized risk of IBTR after breast surgery. METHODS. 18,717 consecutive patients with primary invasive breast cancer were enrolled in this retrospective study. The training set used for building the nomograms comprised 15,124 patients (11,627 treated with BCS and 3,497 with mastectomy), while the validation set included 3,593 women (2,565 BCS and 1,028 mastectomy). Median follow-up time was 8 years in the training set and 6 years in the validation set. Multivariable Cox proportional Hazards regression was used to identify independent factors for IBTR. Two separated nomograms were constructed on multivariate models for BCS and mastectomy, respectively. RESULTS. We identified the factors that associated with IBTR after either BCS or mastectomy. The two multivariable models were used to build nomograms for the prediction of IBTR 1 year, 5 years, and 10 years after BCS or after mastectomy. 5-year and 10-year IBTR rates in the BCS training set were equal to 3.50% and 7.00%, respectively and to 5.39% and 7.94% in the mastectomy training set. The nomograms were subsequently validated with c-index values of 0.77 and 0.69 respectively in the BCS and mastectomy validation sets. CONCLUSION. The nomograms presented in this study provide clinicians and patients with a valuable decision-making tool for choosing between different treatment options for invasive breast cancer.

Objective To compare robotic mastectomy with open classical technique outcomes in breast cancer patients. Summary Background Data As the use of robotic nipple sparing mastectomy continues to rise, improved understanding of the surgical, oncologic and quality of life outcomes is imperative for appropriate patient selection as well as to better understand indications, limits, advantages and dangers. Methods In a phase III, open label, single center, randomized controlled trial involving 80 women with breast cancer (69) or with BRCA mutation (11), we compared the outcome of robotic and open nipple sparing mastectomy. Primary outcomes were surgical complications and quality of life using specific validated questionnaires. Secondary objective included oncologic outcomes. Results Robotic procedure was 1 hour and 18 minutes longer than open (P < 0.001). No differences in the number or type of complications (P = 0.11) were observed. Breast-Q scores in satisfaction with breasts, psychosocial, physical and sexual well-being were significantly higher after robotic mastectomy vs open procedure. Respect to baseline, physical and sexual well-being domains remained stable after robotic mastectomy while they significantly decreased after open procedure (P

Simple Summary Diffuse gastric cancer is the hallmark of the hereditary diffuse gastric cancer syndrome related with the E-cadherin germline mutations. Other cancers (non-gastric) are described in association with the CDH1 gene germline alterations. In this study, we aimed to assess the overall frequency of CDH1 mutations in non-gastric tumors reported in literature so far. Abstract Hereditary Diffuse Gastric Cancer (HDGC) is a complex inherited syndrome caused by CDH1 germline mutations. DGC is the hallmark cancer of this genetic predisposition, but several other cancers are associated with these CDH1 mutations. In this review, we revised all studies reporting CDH1 mutations in non-GC patients. The selected studies included: (a) families aggregating with GC and other cancers, both, and (b) families presenting only non-gastric tumors association. Among non-gastric tumors, our results show that CDH1 mutations are most frequently identified in breast cancer. The frequency of missense mutations is higher in the non-GC group, as the age at diagnosis in this group. Moreover, the predominant CDH1 mutation affects the extracellular domain. Our data suggest that CDH1 genetic testing should be considered also in other cancers, especially breast tumors.

PURPOSE: Robotic nipple-sparing mastectomy (RNSM) may allow for more precise anatomic dissection and improved cosmetic outcomes over conventional open nipple-sparing mastectomy; however data about the feasibility and safety of the procedure is limited. The aim of this study is to present and discuss peri-operative surgical outcomes and early oncologic follow-up data on consecutive patients undergoing RNSM from June 2014 to January 2019. METHODS: Women underwent RNSM and immediate robotic breast reconstruction through an axillary incision at a single institution. Peri-operative data, complications at 3 months postoperatively, pathological data, and adjuvant therapies were recorded. Local recurrence free survival, disease free survival and overall survival were analyzed. RESULTS: Seventy-tree women underwent 94 RNSM procedures. Indications were invasive breast cancer in 39 patients, ductal carcinoma in situ in 17 patients, and BRCA mutation in 17 patients. Mean surgery time was 3 hours and 32 minutes. One-step reconstruction with implant occurred in 89.4% of procedures. The rate of complications requiring re-operation was 4.3%. The rate of flap or nipple necrosis was 1.1% The median follow up was 19 months (range: 3.1–44.8). No local recurrences occurred. The overall survival at 12 months, 24 or 60 months was 98% (95% CI 86–100%). DISCUSSION: We observed low complication rate in 94 consecutive RNSM procedures demonstrating the procedure is technically feasible and safe. We found no early local failures at 19 months follow-up. Long-term follow-up is needed to confirm oncologic safety. Future clinical trials to study the advantages and disadvantages of RNSM are warranted.

BackgroundMicroinvasive breast cancer is an uncommon pathological entity. Owing to the rarity of this condition, its surgical axillary management and overall prognosis remain controversial.MethodsA database was analysed to identify patients with microinvasive ductal carcinoma in situ (DCIS) who had surgery for invasive breast cancer at the European Institute of Oncology, Milan, between 1998 and 2010. Women who had undergone axillary staging by sentinel lymph node biopsy were included in the study.ResultsOf 257 women with microinvasive breast cancer who underwent sentinel lymph node biopsy (SLNB), 226 (87·9 per cent) had negative sentinel lymph nodes (SLNs) and 31 had metastatic SLNs. Twelve patients had isolated tumour cells (ITCs), 14 had micrometastases and five had macrometastases in sentinel nodes. Axillary lymph node dissection was performed in 16 of the 31 patients with positive SLNs. After a median follow-up of 11 years, only one regional first event was observed in the 15 patients with positive SLNs who did not undergo axillary lymph node dissection. There were no regional first events in the 16 patients with positive SLNs who had axillary dissection.ConclusionGood disease-free and overall survival were found in women with positive SLNs and microinvasive DCIS. This study is in line with studies showing that SLNB in microinvasive DCIS may not be useful, and supports the evidence that less surgery can provide the same level of overall survival with better quality of life.

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC). This manuscript was supported by the Italian Ministry of Health (Project Code GR-2016-02361655) and was partially supported by the Ricerca Corrente and 5 × 1000 funds.

Purpose: Around 7% of women who undergo breast-conserving surgery (BCS) or mastectomy are at risk of developing ipsilateral breast tumor recurrence (IBTR). When assessing risks that, like that of IBTR, depend on multiple clinicopathological variables, nomograms are the predictive tools of choice. In this study, we constructed two independent nomograms to estimate the individualized risk of IBTR after breast surgery. Patients and Methods: 18,804 consecutive patients with primary invasive breast cancer were enrolled in this retrospective study. The training set used for building the nomograms comprised 15,168 patients (11,648 treated with BCS and 3520 with mastectomy), while the validation set included 3636 women (2581 BCS and 1055 mastectomy). Median follow-up time was 8 years in the training set and 6 years in the validation set. Multivariable Cox proportional Hazards regression was used to identify independent factors for IBTR. Two separated nomograms were constructed on multivariate models for BCS and mastectomy, respectively. Results: We identified the factors that associated with IBTR after either BCS or mastectomy. The 2 multivariable models were used to build nomograms for the prediction of IBTR 1 year, 5 years, and 10 years after BCS or after mastectomy. The nomograms were validated on the patients in the validation set. A relative score was associated to each variable. The final number predicted the risk of IBTR. Conclusion: The nomograms presented in this study provide clinicians and patients with a valuable decision-making tool for choosing between different treatment options for invasive breast cancer. Funding: The preparation of this study was supported in part by NIH/NCI Cancer Center Support Grant No. P30 CA008748 to Memorial Sloan Kettering Cancer Center. Declaration of Interest: The authors have no conflict of interest disclosures to report. Ethical Approval: This study was approved by the review board/ethics committee of the European Institute of Oncology.

Purpose The aim of this study was to report the rate of survivorship in patients with osteonecrosis of the femoral head treated with core decompression in association with mesenchymal stem cells (MSCs) implantation, platelet-rich plasma (PRP) injection, and synthetic bone graft. Methods We evaluated 24 hips in 16 patients, according to Ficat classification, treated by core decompression, injection of PRP and MSCs, and backfilling of the core tract with synthetic bone graft. Survivorship was estimated using Kaplan–Meier curves. Results The survivorship of core decompression in association with the procedure is 50% at 75 months of follow-up. The survival rate was 80% for patients in early stage and 28.6% for patients in advanced stage at 75 months. When we compared Kaplan–Meier survival curves of patients in stage III + IV and patients in stage I + II, we noticed that the survival functions are statistically different (p Conclusion This technique is safe and good preliminary results were obtained in patients with early stages of the disease with no reported complications. Level of Evidence Level IV, therapeutic case series.

L'articolo esamina il fenomeno delle fusioni di Comuni, anche in chiave comparata, riconnettendolo alla recente crisi economica-finanziaria e inserendolo nel contesto delle politiche di riforma territoriale adottate in Italia negli ultimi anni.

Studying the role of the media in the process of Italian cultural unification, the Internet comes to light for its distinctive status: its relatively short life is, in effect, counterbalanced by an exceptional pervasivity and an impressive innovatory force. The attitude of the Web to facilitate the enjoyment of individual freedoms and democratic participation raises the question whether Net access should be considered a fundamental right and consequently protected by the Constitution. After having dealt with the questionable constitutionalization of the right to access the Internet and once showed the penetration of the medium in Italy, the essay dwells on the close matter of access to digital contents, which should be granted to any user with no restrictions at all. Then the article introduces the debate on Net neutrality and tries to demonstrate that an equal treatment of data packets flowing online is a necessary and sufficient condition for the defense of informative pluralism, naturally occurring on the Internet.

Ultrafast broadband network infrastructures, the so-called Next Generation Access Networks (NGAN), enable a speed of connection much higher than the one made possible by DSL technologies and hence are looked upon as excellent tools to drive economic growth and social progress. Considering that, the essay reviews EU initiatives aimed towards their promotion and examines more specifically the Italian regulator’s choices and the telecom operators’ reactions, with a particular focus on the factors which prevent from increasing the band’s width and the optic fiber’s spread. This paper, therefore, illustrates how and in which ways the New Generation Networks’ development has been encouraged, in order to define the current state of art and to describe the possible future scenarios.

La forma degli atti promananti da organi amministrativi collegiali: forma orale o scritta? La verbalizzazione delle delibere.

Introduzione agli organi collegiali. Applicabilità agli organi collegiali del cd. preavviso di rigetto

L'applicazione della legge n. 241/1990 agli organi amministrativi collegiali: peculiarità e limiti