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In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P 1⁄4 .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value 1⁄4 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Diagnostic criteria for juvenile myelomonocytic leukemia (JMML) are currently well defined, however in some patients diagnosis still remains a challenge. Flow cytometry is a well established tool for diagnosis and follow-up of hematological malignancies, nevertheless it is not routinely used for JMML diagnosis. Herewith, we characterized the CD34+ hematopoietic precursor cells collected from 31 children with JMML using a combination of standardized EuroFlow antibody panels to assess the ability to discriminate JMML cells from normal/reactive bone marrow cell as controls (n=29) or from cells of children with other hematological diseases mimicking JMML (n=9). CD34+ precursors in JMML showed markedly reduced B-cell and erythroid-committed precursors compared to controls, whereas monocytic and CD7+ lymphoid precursors were significantly expanded. Moreover, aberrant immunophenotypes were consistently present in CD34+ precursors in JMML, while they were virtually absent in controls. Multivariate logistic regression analysis showed that combined assessment of the number of CD34+CD7+ lymphoid precursors and CD34+ aberrant precursors or erythroid precursors had a great potential in discriminating JMMLs versus controls. Importantly our scoring model allowed highly efficient discrimination of truly JMML versus patients with JMML-like diseases. In conclusion, we show for the first time that CD34+ precursors from JMML patients display a unique immunophenotypic profile which might contribute to a fast and accurate diagnosis of JMML worldwide by applying an easy to standardize single eight-color antibody combination.

The prevention of chemotherapy-induced alopecia still represents an urgent need for every day clinical practice. In this regard, this prospective single-center study included breast cancer (BC) patients who underwent a scalp cooling device (Dignicap®) during (neo)adjuvant chemotherapy with the aim to evaluate the efficacy and safety of this device in preventing alopecia. One hundred and seventy-eight patients (median age 43 years) were enrolled. The chemotherapy regimen included anthracycline and taxane-based chemotherapy (68.1%), docetaxel and cyclophosphamide (25.8%), anthracycline and taxane-based plus carboplatin (3.9%), and paclitaxel alone (2.2%). In 25.3% of cases, a dose dense schedule was used. Overall, the success rate was 68.0%: 100% in paclitaxel alone, 87.0% in docetaxel-cyclophosphamide, 59.5% in anthracycline and taxane, and 71.4% in the sequential regimen plus carboplatin group (anthracycline and taxane-based chemotherapy versus taxane-based chemotherapy, p ≤ 001. No difference in terms of hair preservation between dose-dense or standard schedule was found (p = 0.557). Early discontinuation of the scalp cooling was observed in 50 patients (28.1%). Although 138 patients (77.5%) experienced adverse events, 70.2% of patients were satisfied with this device. In conclusion, this large prospective study confirmed the helpful effect of the scalp cooling system in preventing alopecia in BC patients also undergoing sequential anthracyclines and taxane-based chemotherapy.

Introduction: Paget’s disease (PD) represents 1%–3% of all breast cancers and mostly occurs in postmenopausal women. Multiple studies have confirmed that breast-conserving surgery (BCS) followed by radiotherapy is a safe option for patients with in situ or invasive PD, ensuring local control and survival rates similar to those achieved with mastectomy. Materials and methods: We retrospectively analyzed 115 patients affected by PD treated in our institution between January 2000 and May 2021. Median age at diagnosis was 60 years and median follow-up was 82 months; 69 patients were treated with BCS and 46 were treated with modified radical mastectomy or skin-sparing mastectomy. Results: At histological examination, 59 patients (59/115, 51.0%) had an underlying invasive carcinoma; in 11 patients (11/115, 9.0%), only PD was found. In 45 patients (45/115, 40.0%), only noninvasive cancer was found. Nine patients (9/115, 7.8%) developed a local recurrence, 7 patients (7/115, 6.0%) are alive with distant metastasis, and 10 patients (10/115, 8.6%) died. Discussion: In our series, no statistically significant differences were shown between PD alone, PD associated with in situ cancer, and PD with invasive cancer, regardless of the surgical procedure. BCS followed by radiotherapy appears to be an effective and safe option for patients with PD. Conclusion: PD is a rare form of breast cancer and, in half of the cases, is associated with an invasive carcinoma. Separating our sample into three subgroups based on tumor histology, there were no significant differences in terms of LC, DFS, and OS rate in patients treated with different types of surgery. This study presents some limitations due to its retrospective nature and being confined to a single institution.

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Hypodiploidy, defined as modal numbers (MNs) 45 or lower, has not been independently investigated in pediatric acute myeloid leukemia (AML) but is a well-described high-risk factor in pediatric acute lymphoblastic leukemia. We aimed to characterize and study the prognostic impact of hypodiploidy in pediatric AML. In this retrospective cohort study, we included children below 18 years of age with de novo AML and a hypodiploid karyotype diagnosed from 2000 to 2015 in 14 childhood AML groups from the International Berlin-Frankfurt-Münster (I-BFM) framework. Exclusion criteria comprised constitutional hypodiploidy, monosomy 7, composite karyotype, and t(8;21) with concurring sex chromosome loss. Hypodiploidy occurred in 81 patients (1.3%) with MNs, 45 (n = 66); 44 (n = 10) and 43 (n = 5). The most frequently lost chromosomes were chromosome 9 and sex chromosomes. Five-year event-free survival (EFS) and overall survival (OS) were 34% and 52%, respectively, for the hypodiploid cohort. Children with MN≤44 (n = 15) had inferior EFS (21%) and OS (33%) compared with children with MN = 45 (n = 66; EFS, 37%; OS, 56%). Adjusted hazard ratios (HRs) were 4.9 (P = .001) and 6.1 (P = .003). Monosomal karyotype or monosomy 9 had particular poor OS (43% and 15%, respectively). Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n = 18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5; P = .42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in the patients treated with SCT in CR1.

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Juvenile myelomonocytic leukemia (JMML) is a rare clonal stem cell disorder that occurs in early childhood and is characterized by the hyperactivation of the RAS pathway in 95% of the patients. JMML is characterized by a hyperproliferation of granulocytes and monocytes, and little is known about the heterogeneous nature of leukemia-initiating cells, as well as of the cellular hierarchy of the JMML bone marrow. In this study, we report the generation and characterization of a novel patient-derived three-dimensional (3D) in vitro JMML model, called patient-derived JMML Atypical Organoid (pd-JAO), sustaining the long-term proliferation of JMML cells with stem cell features and patient-specific hallmarks. JMML cells brewed in a 3D model under different microenvironmental conditions acquired proliferative and survival advantages when placed under low oxygen tension. Transcriptomic and microscopic analyses revealed the activation of specific metabolic energy pathways and the inactivation of processes leading to cell death. Furthermore, we demonstrated the pd-JAO-derived cells' migratory, propagation, and self-renewal capacities. Our study contributes to the development of a robust JMML 3D in vitro model for studying and defining the impact of microenvironmental stimuli on JMML disease and the molecular mechanisms that regulate JMML initiating and propagating cells. Pd-JAO may become a promising model for compound tests focusing on new therapeutic interventions aimed at eradicating JMML progenitors and controlling JMML disease.

PURPOSEA previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease.METHODSA total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (%0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS).RESULTSThe high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P <.0001), CIR (59.7% v 35.2%; P <.0001), and OS (49.2% v 70.5%; P <.0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P <.0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P <.0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P =.016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P =.00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS.CONCLUSIONEOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are nee

The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.

Introduction: The selection of surgery post-neoadjuvant chemotherapy (NACT) is difficult and based on surgeons’ expertise. The aim of this study was to create a post-NEoadjuvant Score System (pNESSy) to choose surgery, optimizing oncological and aesthetical outcomes. Methods: Patients (stage I–III) underwent surgery post-NACT (breast-conserving surgery (BCS), oncoplastic surgery (OPS), and conservative mastectomy (CMR) were included. Data selected were BRCA mutation, ptosis, breast volume, radiological response, MRI, and mammography pre- and post-NACT prediction of excised breast area. pNESSy was created using the association between these data and surgery. Area under the curve (AUC) was assessed. Patients were divided into groups according to correspondence (G1) or discrepancy (G2) between score and surgery; oncological and aesthetic outcomes were analyzed. Results: A total of 255 patients were included (118 BCS, 49 OPS, 88 CMR). pNESSy between 6.896–8.724 was predictive for BCS, 8.725–9.375 for OPS, and 9.376–14.245 for CMR; AUC was, respectively, 0.835, 0.766, and 0.825. G1 presented a lower incidence of involved margins (5–14.7%; p = 0.010), a better locoregional disease-free survival (98.8–88.9%; p < 0.001) and a better overall survival (96.1–86.5%; p = 0.017), and a better satisfaction with breasts (39.8–27.5%; p = 0.017) and physical wellbeing (93.5–73.6%; p = 0.001). Conclusion: A score system based on clinical and radiological features was created to select the optimal surgery post-NACT and improve oncological and aesthetic outcomes.

Background: The diffusion of screening programs has resulted in a decrease of cT4 breast cancer diagnosis. The standard care for cT4 was neoadjuvant chemotherapy (NA), surgery, and locoregional or adjuvant systemic therapies. NA allows two outcomes: 1. improve survival rates, and 2. de-escalation of surgery. This de-escalation has allowed the introduction of conservative breast surgery (CBS). We evaluate the possibility of submitting cT4 patients to CBS instead of radical breast surgery (RBS) by assessing the risk of locoregional disease-free survival, (LR-DFS) distant disease-free survival (DDFS), and overall survival (OS). Methods: This monocentric, retrospective study evaluated cT4 patients submitted to NA and surgery between January 2014 and July 2021. The study population included patients undergoing CBS or RBS without immediate reconstruction. Survival curves were obtained using the Kaplan-Meyer method and compared using a Log Rank test. Results: At a follow-up of 43.7 months, LR-DFS was 70% and 75.9%, respectively, in CBS and RBS (p = 0.420). DDFS was 67.8% and 29.7%, respectively, (p = 0.122). OS was 69.8% and 59.8%, respectively, (p = 0.311). Conclusions: In patients with major or complete response to NA, CBS can be considered a safe alternative to RBS in the treatment of cT4a-d stage. In patients with poor response to NA, RBS remained the best surgical choice.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). TNBC accounts for about 15% of breast cancers and has a poorer prognosis as compared with other subtypes of breast cancer. The more rapid onset of this cancer and its aggressiveness have often convinced breast surgeons that mastectomy could provide better oncological results. However, there is no relevant clinical trial that has assessed differences between breast-conserving surgery (BCS) and mastectomy (M) in these patients. This population-based study aimed to investigate the distinct outcomes between conservative treatment and M in a case series of 289 patients with TNBC treated over a 9-year period. This monocentric study retrospectively evaluated patients with TNBC who underwent upfront surgery at Fondazione Policlinico Agostino Gemelli IRCCS, in Rome, between 1 January 2013 and 31 December 2021. First, the patients were divided in two groups according to the surgical treatment received: BCS vs. M. Then, the patients were stratified into four risk subclasses based on combined T and N pathological staging (T1N0, T1N+, T2-4N0 and T2-4N+). The primary endpoint of the study was to evaluate locoregional disease-free survival (LR-DFS), distant disease-free survival (DDFS) and overall survival (OS) in the different subclasses. We analyzed 289 patients that underwent either breast-conserving surgery (247/289, 85.5%) or mastectomy (42/289, 14.5%). After a median follow-up of 43.2 months (49.7, 22.2–74.3), 28 patients (9.6%) developed a locoregional recurrence, 27 patients (9.0%) showed systemic recurrence and 19 patients (6.5%) died. No significant differences due to type of surgical treatment were observed in the different risk subclasses in terms of locoregional disease-free survival, distant disease-free survival and overall survival. With the limits of a retros

Clinical trials in cancer treatment are imperative in enhancing patients’ survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients’ accrual in clinical trials. We developed a specific platform, called “Digital Research Assistant” (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients’ records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients’ records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient’s data and clinical trial’s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.

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The presence of CBFA2T3-GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML-CBFA2T3-GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3-GLIS2-AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3-GLIS2-AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA-DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak-to-negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA-DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance.

Background: In the present study, we evaluated the prognostic value of TILs as well their relation with clinicopathological factors in patients affected by HER-2 positive breast cancer. Methods: We evaluated 47 patients with a histologically confirmed diagnosis of invasive breast carcinoma showing an immunohistochemically confirmed (score 3+) amplification of the c-erbB-2 gene for the presence of TILs and categorized in three predefined groups of low (0-10% immune cells in stromal tissue within the tumor), intermediate (11-40%), and high TILs (>40%). Results: Low, intermediate and high TILs were found in 17/47 (36%), 23/47 (49%) and 7/47(15%) cases, respectively. It was found that 6/47 cases treated with adjuvant chemotherapy plus trastuzumab underwent progression of the disease; none of these cases exhibited high TILs. It was found that 12/47 patients with a prognostically unfavorable stage of III and IV showed low and intermediate levels of TILs, while high TILs were never observed. A significant association between intermediate/high-levels of TILs, elevated KI 67 index and hormone receptors nuclear staining was observed. High concordance in TILs distribution was observed between preoperative breast biopsies and surgical samples. Conclusions: We observed a positive correlation between the TILs and the response to both adjuvant and neoadjuvant treatments in HER-2 positive BC. High TILs were also related to increased KI-67 index and to the expression of hormone receptors.

Sentinel lymph node biopsy (SLNB) following neoadjuvant treatment (NACT) has been questioned by many studies that reported heterogeneous identification (IR) and false negative rates (FNR). As a result, some patients receive axillary lymph node dissection (ALND) regardless of response to NACT, leading to a potential overtreatment. To better assess reliability and clinical significance of SLNB status on ycN0 patients, we retrospectively analyzed oncological outcomes of 399 patients treated between January 2016 and December 2019 that were either cN0-ycN0 (219 pa-tients) or cN1/2-ycN0 (180 patients). The Endpoints of our study were to assess, furthermore than IR: oncological outcomes as Overall Survival (OS); Distant Disease Free Survival (DDFS); and Regional Disease Free Survival (RDFS) according to SLNB status. SLN identification rate was 96.8% (98.2% in patients cN0-ycN0 and 95.2% in patients cN+-ycN0). A median number of three lymph nodes were identified and removed. Among cN0-ycN0 patients, 149 (68%) were confirmed ypN0(sn), whereas regarding cN1/2-ycN0 cases 86 (47.8%) confirmed an effective downstaging to ypN0. Three year OS, DDFS and RDFS were significantly related to SLNB positivity. Our data seemed to confirm SLNB feasibility following NACT in ycN0 patients, furthermore reinforcing its predictive role in a short observation timing.

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Background: CBL syndrome is a RASopathy caused by heterozygous germline mutations of the Casitas B-lineage lymphoma (CBL) gene. It is characterized by heterogeneous clinical phenotype, including developmental delay, facial dysmorphisms, cardiovascular malformations and an increased risk of cancer development, particularly juvenile myelomonocytic leukemia (JMML). Although the clinical phenotype has been progressively defined in recent years, immunological manifestations have not been well elucidated to date. Methods: We studied the genetic, immunological, coagulative, and clinical profile of a family with CBL syndrome that came to our observation after the diagnosis of JMML, with homozygous CBL mutation, in one of the members. Results: Variant analysis revealed the co-occurrence of CBL heterozygous mutation (c.1141 T > C) and SH2B3 mutation (c.1697G > A) in two other members. Patients carrying both mutations showed an ALPS-like phenotype characterized by lymphoproliferation, cytopenia, increased double-negative T-cells, impaired Fas-mediated lymphocyte apoptosis, altered cell death in PBMC and low TRECs expression. A coagulative work-up was also performed and showed the presence of subclinical coagulative alterations in patients carrying both mutations. Conclusion: In the reported family, we described immune dysregulation, as part of the clinical spectrum of CBL mutation with the co-occurrence of SH2B3.

Identification of pediatric patients with acute myeloid leukemia (AML) candidates to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) is still a matter of debate. Currently, transplantation is reserved to patients considered at high risk of relapse based on cytogenetics, molecular biology, and minimal residual disease (MRD) assessment. However, no randomized clinical trial exists in the literature comparing transplantation with other types of consolidation therapy. Here, we provide an up-to-date meta-analysis of studies comparing allo-HSCT in CR1 with chemotherapy alone as a post-remission treatment in high-risk pediatric AML. The literature search strategy identified 10 cohorts from 9 studies performing as-treated analysis. The quantitative synthesis showed improved overall survival (OS) (relative risk, 1.15; 95% confidence interval [CI], 1.06–1.24; P = 0.0006) and disease-free survival (relative risk, 1.31; 95% CI, 1.17–1.47; P = 0.0001) in the allo-HSCT group, with increased relapse rate in the chemotherapy group (relative risk, 1.26; 95% CI, 1.07–1.49; P = 0.006). Sensitivity analysis including prospective studies alone and excluding studies that reported the comparison only on intermediate-risk patients confirmed the benefit of allo-HSCT on OS. Further research should focus on individualizing allo-HSCT indications based on molecular stratification and MRD monitoring.

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Background: Conservative mastectomy with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that offers improved esthetic results and patient quality of life. Traditionally, implants have been placed in a submuscular (SM) plane beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of the prosthesis has been increasingly used in order to avoid morbidities related to manipulation of the PMM. The aim of this study was to compare outcomes of SM vs. PP IPBR after conservative mastectomy in patients with histologically proven breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: In this retrospective observational study, we analyzed two cohorts of patients that underwent mastectomy with IPBR after NAC in our institution from January 2018 to December 2021. Conservative mastectomy was performed in 146 of the 400 patients that underwent NAC during the study period. Patients were divided into two groups based on the positioning of implants: 56 SM versus 90 PP. Results: The two cohorts were similar for age (mean age 42 and 44 years in the SM and PP group respectively) and follow-up (33 and 20 months, respectively). Mean operative time was 56 min shorter in the PP group (300 and 244 min in the SM and PP group). No significant differences were observed in overall major complication rates. Implant loss was observed in 1.78% of patients (1/56) in the SM group and 1.11% of patients (1/90) in PP group. No differences were observed between the two groups in local or regional recurrence. Conclusions: Our preliminary experience, which represents one of the largest series of patients undergoing PP-IPBR after NAC at a single institution documented in the literature, seems to confirm that PP-IPBR after NAC is a safe, reliable and effective alternative to traditional SM-IPBR with excellent esthetic and oncological outcomes; it is easy to perform, reduces operative time and minimizes complications related to manip

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Background: The modern concept of lymphatic transfer includes vascularised lymph node transfer (VLNT), lymphatic vessels transfer (lymph interpositional flap transfer, LIFT) and lymphatic system transfer (vascularised lymph nodes and afferent lymphatics, LYST). The aim of this paper was to report our experience with different types of lymphatic transfer. Patients and Method: From June 2016 to June 2020, 30 consecutive patients affected by extremity lymphedema and 15 patients affected by post-traumatic lower extremity soft tissue defects, underwent lymphatic transfer (VLNT, LYST or LIFT). All cases were preoperatively evaluated by both high frequency and ultra-high frequency ultrasound. Flap features were recorded, as well as qualitative and quantitative outcomes at 1 year postoperative. Results: The mean postoperative lymphedema index reduction was 7.2 ± 5.7 for upper extremity and 20.7 ± 7.1 for lower extremity. No dismission of compression garments occurred, 12 patients (26%) referred more stable results of physical treatment and 1 case showed a 1-class compression reduction. All the LIFTs aimed as preventive did not develop post-traumatic lymphedema. In all cases of distal placement of VLNT and/or LYST, patients were dissatisfied with the aesthetic appearance of reconstruction, while no donor site scar disappointment was referred. Conclusion: When LVA is not feasible, LTT may represent a valid treatment option. This report was aimed at comprehensively describing and assessing how different lymphatic tissue transfer modalities may fulfil the different reconstructive needs of lymphedema patients.

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Background: Triple-negative breast cancer (TNBC) is a very heterogeneous disease. Several gene expression and mutation profiling approaches were used to classify it, and all converged to the identification of distinct molecular subtypes, with some overlapping across different approaches. However, a standardised tool to routinely classify TNBC in the clinics and guide personalised treatment is lacking. We aimed at defining a specific gene signature for each of the six TNBC subtypes proposed by Lehman et al. in 2011 (basal-like 1 (BL1); basal-like 2 (BL2); mesenchymal (M); immunomodulatory (IM); mesenchymal stem-like (MSL); and luminal androgen receptor (LAR)), to be able to accurately predict them. Methods: Lehman’s TNBCtype subtyping tool was applied to RNA-sequencing data from 482 TNBC (GSE164458), and a minimal subtype-specific gene signature was defined by combining two class comparison techniques with seven attribute selection methods. Several machine learning algorithms for subtype prediction were used, and the best classifier was applied on microarray data from 72 Italian TNBC and on the TNBC subset of the BRCA-TCGA data set. Results: We identified two signatures with the 120 and 81 top up- and downregulated genes that define the six TNBC subtypes, with prediction accuracy ranging from 88.6 to 89.4%, and even improving after removal of the least important genes. Network analysis was used to identify highly interconnected genes within each subgroup. Two druggable matrix metalloproteinases were found in the BL1 and BL2 subsets, and several druggable targets were complementary to androgen receptor or aromatase in the LAR subset. Several secondary drug–target interactions were found among the upregulated genes in the M, IM and MSL subsets. Conclusions: Our study took full advantage of available TNBC data sets to stratify samples and genes into distinct subtypes, according to gene expression profiles. The development of a data mining approach to acquire a large amo

Oncoplastic level II breast-conserving surgery (OPS2) allows for wider excisions than standard breast-conserving surgery, but the literature on this technique in the treatment of DCIS is scarce. This study compares OPS2 to conservative mastectomy (CM) in patients undergoing surgery for large DCIS. The clinical, radiological, surgical, and post-operative data of 147 patients who underwent either CM or OPS2 for large DCIS between 2007 and 2021 were retrospectively reviewed. The surgical, oncological, and patient-reported outcomes (PRO) were analyzed and compared between the two groups. The surgical outcomes were similar, in terms of margin involvement (p = 0.211), complication rate (p = 0.827), and re-excision rate (p = 1). The rate of additional surgery for cosmetic optimization was significantly lower in the OPS2 group: only 1 (1.8%) patient required surgical adjustments versus 24 (26.4%) patients in the CM group (p < 0.001). The mean hospital stay was lower in the OPS2 group (p < 0.001). The oncological outcomes did not differ between the two groups (p = 0.662). The PRO analysis showed better outcomes in the OPS2 group, which achieved statistical significance in the sexual well-being module (p = 0.015). Skin sensitivity loss was also significantly lower in the OPS2 group (p < 0.001). When feasible, OPS2 should be considered in the treatment of large DCIS, as it is safe and shows high levels of patient satisfaction.

Background. Immediate breast reconstruction is recommended for eligible patients undergoing mastectomy, raising the issue of economic sustainability of both mastectomy and breast reconstruction performed within the same hospitalization, as opposed to two surgical procedures in two different hospitalizations. Study design. A retrospective analysis was conducted to compare economic sustainability of mastectomies with or without immediate breast reconstruction. Methods. Economic data on hospitalizations for mastectomy in a Teaching Hospital between 1 January 2019 and 31 March 2021 were analyzed to assess their sustainability. Results. 338 admissions were selected (63.9% with immediate breast reconstruction (CI 99%: 57.2% to 70.6%). Compared to mastectomy alone, mastectomy with immediate breast reconstruction had higher cost of € 2,245 (p < 0.001), with operating rooms and devices as main cost drivers. Current reimbursements rates (which are the same for mastectomy alone and for mastectomy with immediate breast reconstruction) led to an average loss of € 1,719 for each mastectomy with immediate breast reconstruction. Conclusion. Current DRGs reimbursement rates for hospital admissions for breast cancer surgery do not guarantee immediate breast reconstruction’s economic sustainability. DRGs system should be revised, or other solutions as bundled payment should be implemented in the light of the costs of innovation in healthcare, considering mastectomy and breast reconstruction steps in a path of linked actions aimed at improving patients’ health.

Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC.