Prognostic Role of p53 Immunohistochemical Status in invasive Breast Cancer. A Retrospective Review of 1387 Cases With Luminal-Like/Her2 Negative Breast Tumors.

PURPOSE: The aim of this study was to evaluate the prognostic role of p53 immunohistochemical (IHC) expression in a large cohort of patients with hormone receptors (HR)-positive/Her2-negative primary invasive breast cancer. METHODS: Retrospective review of consecutive cases treated at our Breast Unit between 2003 and 2013. Patients were divided into 3 subgroups based on p53 IHC expression: null (0%), low (0.1%-49%), and high (≥50%) p53 expression. RESULTS: A total of 1387 patients were included in the study with a median follow-up of 86 months. After adjusting for age, size, node status, lymphovascular invasion, progesterone, and Ki67 expression, only null p53 immunophenotype was associated with worse disease-free survival (DFS) (OR 1.74, 95% IC, 1.11-2.71, P = .015) and distant recurrence-free survival (DRFS) (OR 1.73, 95% IC, 1.04-2.90, P = .036). Null p53 impacted significantly DFS and DRFS also in patients with early breast cancer. CONCLUSIONS: p53 IHC expression affects survival and, thus can be a valuable tool in the management of patients with HR-positive/Her2-negative breast cancer.

Use of dual-mobility cup in primary total hip arthroplasties: an Italian regional register (RIPO) study on three thousand, seven hundred and ten cases.

PURPOSE: The purpose of the study was to investigate the outcome of dual-mobility cup (DM) compared with a standard cup (SC) in primary total hip arthroplasty (THA) in the long-term follow-up based on a regional Italian joint registry (RIPO). METHODS: The Registry of Prosthetic Orthopaedic Implant (RIPO) was consulted, looking for all primary THAs implanted from 2000 to 2019. Three thousand seven hundred ten were dual-mobility cup (DM) total hip arthroplasties (THA) and 85.816 were standard cup (SC) THAs, on a total of 89.526 primary THA. Demographics, survival rates and causes of revision were evaluated and compared between the two groups. RESULTS: The use of DM progressively increased from 0.4% in 2000 to 7.5% in 2018 of all primary THAs. Revision rate was 3.5% (128 on 3710) for DMC and 4.7% (4061 on 85,816) for SC. DM presented lower dislocation rate if compared to SC with 22-28-mm femoral head diameter. However, DM showed a higher risk of revision for any causes than SC with 32-mm femoral head diameter in long-term follow-up. Nevertheless, no significant difference was measured in terms of demographics and surgical approach for dislocation rate. CONCLUSIONS: The DM cup represents a valid implant solution and has a lower dislocation rate than 22-28-mm SC. A slight increase in the use of DM implants over time was observed in the RIPO. However, a larger population and a longer follow-up are needed to further monitor the survival rate of new-generation DM implants.

Next-generation sequencing revealing TP53 mutation as potential genetic driver in dermal deep-seated melanoma arising in giant congenital nevus in adult patients: A unique case report and review of the literature.

Melanoma in giant congenital nevus (M-GCN) is a rare and potentially lethal neoplasm. In children, M-GCN appears as a dermal/deep-seated melanoma (DDM-GCN) with histopathologic features difficult to distinguish from proliferative nodules (PNs-GCN). DDM-GCN in adults is an anecdotal entity and only 8 cases have been described and genetically characterized. We report the first case of DDM-GCN in a 34-year-old man characterized with a large-panel next-generation sequence (NGS) highlighting a TP53 mutation with a UV-signature (C>T substitution) in DDM but not in PNs-GCN and GCN. Curiously, DDM showed an aberrant p16 overexpression without detection of CDKN2A mutation at NGS. In line with previous studies, it supports a different pathway in children and adults: UV-induced mutations may be involved in the latter not only by CDKN2A but also by TP53 mutations, with a potentially confusing overexpression of p16 protein. While these data need to be confirmed in larger cases series, our results show that NGS could be an additional genetic diagnostic tool in DDM-GCN.

Survivorship and clinical outcomes of 147 consecutive isolated or combined arthroscopic bone plug free meniscal allograft transplantation.

PURPOSE: To present the results of a survival analysis of a series of 147 arthroscopic MAT procedures. METHODS: One-hundred and forty-seven patients (117 males and 30 females) underwent arthroscopic MAT without bone plugs (82 medial MAT and 65 lateral MAT) using fresh-frozen, non-irradiated grafts. They were retrospectively reviewed at a mean of 4.0 ± 1.9-year follow-up. Mean age at surgery was 40.9 ± 11.2 (range 16.7-68.8) years; 70 patients (48 %) underwent combined procedures. Clinical evaluation was performed with KOOS, Lysholm and a 0-100 VAS for pain. Survival analysis was performed using two endpoints: surgical failure (revision procedure with direct relation to MAT) and clinical failure (revision procedure or poor Lysholm score, <65). RESULTS: There was a significant (p < 0.05) and clinically relevant decrease in the VAS and increase in KOOS and Lysholm from pre-operative mean score to post-operative mean score. Seven (5 %) patients (two medial and five lateral) experienced surgical failure (five meniscectomies, one lateral graft peripheral suture and one unicompartmental knee arthroplasty). The mean overall survival time was 9.7 years (CI 9.1-10.3). As 16 (11 %) patients presented poor Lysholm score, a total of 23 (16 %) patients were considered clinical failures. The mean overall survival time was 8 years (CI 7.1-8.8). No statistically significant differences in failure and survival rate were present between medial and lateral MAT, isolated or combined MAT, patients >50 or <50 years old and patients with body mass index <25 or >25. CONCLUSIONS: MAT, eventually associated with other needed procedures, was able to significantly relieve pain and improve function of the knee joint at midterm follow-up, with a survival rate from 9.7 to 8.0 years based on failure criteria. Most additional procedures were done in the first 2 post-operative years. MAT eventually associated with other needed procedures could represent an effective treatment for post-meniscectomy syndrome. LEVEL OF EVIDENCE: Therapeutic study, retrospective case series, Level IV.

Alterations of ribosomal RNA pseudouridylation in human breast cancer.

RNA modifications are key regulatory factors for several biological and pathological processes. They are abundantly represented on ribosomal RNA (rRNA), where they contribute to regulate ribosomal function in mRNA translation. Altered RNA modification pathways have been linked to tumorigenesis as well as to other human diseases. In this study we quantitatively evaluated the site-specific pseudouridylation pattern in rRNA in breast cancer samples exploiting the RBS-Seq technique involving RNA bisulfite treatment coupled with a new NGS approach. We found a wide variability among patients at different sites. The most dysregulated positions in tumors turned out to be hypermodified with respect to a reference RNA. As for 2'O-methylation level of rRNA modification, we detected variable and stable pseudouridine sites, with the most stable sites being the most evolutionary conserved. We also observed that pseudouridylation levels at specific sites are related to some clinical and bio-pathological tumor features and they are able to distinguish different patient clusters. This study is the first example of the contribution that newly available high-throughput approaches for site specific pseudouridine detection can provide to the understanding of the intrinsic ribosomal changes occurring in human tumors.

Effectiveness of sentinel lymph node intraoperative examination in 753 women with breast cancer: are we overtreating patients?

OBJECTIVE: The goal of our study was to evaluate the sensitivity and specificity of sentinel lymph node biopsy (SLNB) frozen section (FS) examinations to detect metastatic lymph nodes and also its potential role in avoiding unnecessary demolitive axillary surgery. BACKGROUND: SLNB is the standard of care in surgical oncology of the breast. Intraoperative evaluation of the SLN seems to achieve sufficient sensitivity for macrometastasis (Ma), leading to axillary lymph node dissection (ALND) only when strictly necessary. Is it equally as clear when to perform ALND if micrometastasis (Mi) or isolated tumor cells (ITCs) are detected? METHODS: All consecutive patients from January 2005 to September 2010 operated on for breast cancer were prospectively enrolled. All patients underwent an FS SLNB. The sensitivity and specificity of SLN FSs in detecting Ma, Mi, and ITCs was calculated. All patients with Ma or Mi at FS underwent ALND. For all patients who underwent ALND, the number of metastatic non-SLNs was recorded and correlated to the size of the SLN metastasis. RESULTS: A total of 753 patients were enrolled. FS examination had an overall 54% sensitivity and 100% specificity in detecting metastatic disease (Ma/Mi/ITCs). The sensitivity rises to 89% if only Mas were considered and to 64% if Mas and Mis were counted together. All patients with Mas or Mis detected at FS had a completion ALND during the same procedure (156/222). All patients with Mas detected at final pathology (16 false negatives, 2.6%) and 50 women with Mis or ITCs (119 false negatives, 20%) underwent a delayed ALND. When Mis or ITCs were detected in the SLN, only 8 of 73 (10.9%) and none of 4 (0%) patients, respectively, had at least 1 metastatic non-SLN after ALND. Two patients (2/460, 0.43%) who had negative SLNs showed local axillary recurrence. After a mean follow-up of 32 months, none of the 71 patients with Mis or ITCs who did not undergo a second operation showed local recurrence. CONCLUSIONS: SLNB FS is highly effective in detecting the subgroup of patients who may benefit from completion ALND during the same surgical procedure. The role of Mi/ITCs in the SLN(s) is still unclear, but our data lean toward a less aggressive surgical approach.

Successful management of diffuse bilateral pseudoangiomatous stromal hyperplasia of the mammary glands by reductive mammoplasty.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast condition commonly presented as an incidental microscopic finding. However, it can also manifest as a mass-forming lesion (tumorous PASH) or as gigantomastia (diffuse PASH). Most of the previously reported cases are unilateral tumorous PASH treated by mastectomy. In this article, we reported a rare case of diffuse bilateral PASH. A 21-year-old woman presented with a two-year history of bilateral breast enlargement and neck pain. Physical examination revealed asymmetrical bilateral macromastia with profound ptosis. Breast ultrasound demonstrated no cysts or masses in both breasts. The decision was made to perform an inverted T bilateral reductive mammoplasty which was performed successfully through a superior-central pedicle approach. Microscopic examination of the specimens confirmed the diagnosis of PASH without any evidence for malignancy. Nine months postoperatively, the size for both breasts was optimal the patient was satisfied. Recognition and reporting of this rare form of PASH is essential for proper investigation, pathology understanding, risk factors recognition, prognosis assessment and treatment methods selection.

Granular cell tumour of the breast: A rare presentation of a breast mass in an elderly female with a subsequent breast cancer diagnosis.

A 74-year-old female patient presented with a hard breast mass and dimpling with a clinical suspicion of a carcinoma. Histological evaluation revealed a granular cell tumour. Granular cell tumour is a rare neoplasm, mostly benign in origin that may arise in every body site, 5%-15% of cases occur in the breast. It is strongly suggested that granular cell tumours origin is Schwann cells. Clinically, granular cell tumours presentation may mimic mammary carcinoma and their similar features on mammography and ultrasound make it difficult to differentiate between them.

Current trends and outcomes of breast reconstruction following nipple-sparing mastectomy: results from a national multicentric registry with 1006 cases over a 6-year period.

BACKGROUND: Reconstruction options following nipple-sparing mastectomy (NSM) are diverse and not yet investigated with level IA evidence. The analysis of surgical and oncological outcomes of NSM from the Italian National Registry shows its safety and wide acceptance both for prophylactic and therapeutic cases. A further in-depth analysis of the reconstructive approaches with their trend over time and their failures is the aim of this study. METHODS: Data extraction from the National Database was performed restricting cases to the 2009-2014 period. Different reconstruction procedures were analyzed in terms of their distribution over time and with respect to specific indications. A 1-year minimum follow-up was conducted to assess reconstructive unsuccessful events. Univariate and multivariate analyses were performed to investigate the causes of both prosthetic and autologous failures. RESULTS: 913 patients, for a total of 1006 procedures, are included in the analysis. A prosthetic only reconstruction is accomplished in 92.2 % of cases, while pure autologous tissues are employed in 4.2 % and a hybrid (prosthetic plus autologous) in 3.6 %. Direct-to-implant (DTI) reaches 48.7 % of all reconstructions in the year 2014. Prophylactic NSMs have a DTI reconstruction in 35.6 % of cases and an autologous tissue flap in 12.9 % of cases. Failures are 2.7 % overall: 0 % in pure autologous flaps and 9.1 % in hybrid cases. Significant risk factors for failures are diabetes and the previous radiation therapy on the operated breast. CONCLUSIONS: Reconstruction following NSM is mostly prosthetic in Italy, with DTI gaining large acceptance over time. Failures are low and occurring in diabetic and irradiated patients at the multivariate analysis.

Recurrent periductal mastitis: Surgical treatment.

BACKGROUND: Recurrent periductal mastitis is a benign breast disorder that often features a mammary fistula that runs between periareolar skin and the ductal mammary system. Due to the high recurrence rate of this disease, its management is controversial. This study was designed to assess the efficacy of fistulectomy (Hadfield operation), particularly with regard to its long-term outcome. METHODS: We reviewed all women with recurrent periductal mastitis who underwent the Hadfield operation in the Breast Center in S.Orsola-Malpighi Hospital (Bologna University) from 2005 to 2015. All but one of the patients were heavy smokers and presented with a recurrent periareolar abscess and a periareolar mammary fistula. RESULTS: Eighteen women underwent the Hadfield surgical treatment. Mean age at the time of presentation was 42 years; 17 of 18 women smoked >10 cigarettes/d. All patients had a breast ultrasonography or mammography. Half of the patients had undergone antibiotic therapy with one or more prior abscess drainages or another form of operative treatment. All patients who underwent operative treatment had no postoperative events and were satisfied with the cosmetic results. Squamous metaplasia was always present in the specimens. After a median follow-up of 36 months, 2 patients developed a recurrence after a few months; neither had stopped smoking. CONCLUSION: Based on our review of the literature and taking into account the results of this study, it seems clear that the best treatment involves a combined total excision of the affected duct and the fistulous tract. Due to the important role of smoking in this disease, it is important to encourage patients to stop smoking.

Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period.

BACKGROUND: Nipple sparing mastectomy is deemed surgically and oncologically safe based on a long lasting literature data from reviews of single institution series. This study aims at evaluating surgical and oncological outcomes of NSM on a large multi-institutional scale, by means of the Italian National registry. METHODS: In July 2011 a panel of Italian specialists agreed upon and designed a National database of NSM. Centers with at least 150 cancers per year and following the National follow-up schedule guidelines could participate inserting any NSM case performed, retrospectively and prospectively from that moment on. In March 2015 analysis of data was accomplished. Dataset for this study consists of cases performed in the period between January 1st 2009 and December 31st 2014. RESULTS: 913 Women were included in the analysis, for a total of 1006 procedures. Prophylactic mastectomies were 124 (12.3%). MRI utilization increased over time. NSM failure rate, with NAC removal for any reason was 11.5%. NAC necrosis rate was 4.8%. Larger skin-flap necrosis rate was 2.3%. Major surgical complications rate was 4.4%. Oncological outcomes were calculated among primitive EBC cases only: locoregional recurrences rate was 2.9%, NAC recurrence 0.7%. Systemic recurrence rate was 1.0%. Five deaths (0.7%) were registered. CONCLUSIONS: More than 10% of NSM procedures are prophylactic mastectomies. MRI is gaining more importance over time. Surgical and oncological results show that NSM is effective. This National multicentric analysis enables a comparison of results with no geographical differences and a "safe" state of the art of NSM in Italy.

Return to sport after ACL reconstruction: how, when and why? A narrative review of current evidence.

Allowing a patient to return to sport and unrestricted physical activity after ACL injury and reconstruction is one of the most challenging and difficult decisions an orthopaedic surgeon has to make. Indeed, many factors have to be taken into account before it can be considered safe for a patients to load a reconstructed knee. The current literature contains plenty of studies aimed at evaluating return to sport, and the factors that may affect or predict this outcome, e.g. intrinsic factors like genetics, biology, type of lesion, anatomical features, motivation and psychology, and extrinsic factors such as graft type, surgical technique, rehabilitation protocols, and biological support. It is possible that awareness of these issues could help the clinician to optimise outcomes, and possibly avoid failures too, although as yet no universal criteria for resuming sport have been produced.