The Proper Ki-67 Cut-Off in Hormone Responsive Breast Cancer. A Monoinstitutional Analysis with Long-Term Follow-Up

Introduction: Breast cancer is a heterogeneous disease. Our study focuses on a monoinstitutional series of patients affected by Hormone Responsive carcinomas (luminal A and luminal B) and aims to define an optimal Ki-67 cut-off, to correctly stratify these patients into risk classes, using the ImmunoHistoChemical (IHC) surrogates of the Molecular Subtypes, according to the St. Gallen guidelines. Methods: We analyzed 1685 patients. These patients underwent both radical and conservative surgeries with Sentinel Lymph Node Biopsy eventually followed by Axillary Dissection (AD). Furthermore, all the patients underwent adjuvant therapies according to the guidelines. A retrospective univariate analysis was performed and survival curves (Disease-Related Survival, DRS, and Disease-Free Survival, DFS) were carried out according to the following ki-67 risk classes: Low Risk (Ki-67 ≤ 14%); Intermediate Risk (Ki-67 15% ÷ 20%); High Risk (Ki-67 > 20%). Results: 14 yy DRS was 98% in LA and 85% in LB with a ki-67 cut-off of 14% (p=0.037) vs 95% (LA) and 83% (LB) with a ki-67 cut-off of 20% (p=0.003). 14yy DFS was 85% in LA and 72% in LB with a ki-67 cut-off of 14% (p=0.017) vs 83% (LA) and 66% (LB) with a ki-67 cut-off of 20% (p<0.000). Discussion: Our results confirmed that the 20% Ki-67 cut-off is more reliable in differentiating patients at low or high risk of recurrence and death, and stratifying patients eligible for adjuvant chemotherapy. Thus, despite its poor reproducibility, the identification of the most accurate ki-67 index assumes a pivotal relevance in guiding a tailored strategy among patients with this specific profile of breast cancer, as well as the molecular surrogates, in order to avoid harmful overtreatments

Importance of perforating vessels in nipple-sparing mastectomy. an anatomical description

BACKGROUND: Nipple-sparing mastectomy (NSM), understood as an oncologically valid procedure, is relatively new, and is an evolution of traditional mastectomy, particularly in relation to breast-conserving surgery. The anterior perforating branches are responsible for the cutaneous vascularization of the breast skin, and their preservation is a fundamental step to avoid possible postoperative necrosis. Therefore, evaluating the potential complications of cancer-related reconstructive surgical procedures such as NSM, both the distance of the tumoral lesion from the skin and the surgical incision site should be carefully considered. The preferred site of incision corresponds to the inframammary fold or possibly the periareolar area. METHODS: We retrospectively reviewed 113 patients who underwent NSM from January 2005 to October 2012 to evaluate skin complications. The anatomical study was performed by magnetic resonance imaging of the breast. RESULTS: Only one of the 113 women who had undergone a NSM procedure had total necrosis (0.9%) and six patients had partial necrosis (5.8%) of the nipple-areola complex

The Breast-Q assessment: Sant'Andrea experience

Despite in the last 20 years breast surgery has become less mutilating, mastectomy is indicated in approximately 30% of cases, not only for large invasive carcinoma, but also for multicentric tumors and intraductal diffuse carcinomas. The nipple loss is experienced by the patients like a mutilation; we achieved a significant improvement of the aesthetic result performing Nipplesparing mastectomy (NSM), joined with reconstruction techniques. This approach has a positive impact on psychology and quality of life (QOL) of breast cancer patients. To evaluate these important aspects, we retrospectively applied the BREAST-Q questioner to 101 patients underwent a NSM. BREAST-Q is an instrument designed by the Evelyn H. Lauder Breast Center, MSKCC (NY), to assess outcomes among women undergoing different types of breast surgery: we chose reconstruction module that is comprised of two domains: patient satisfaction and QOL. There are six subthemes (physical, psychosocial and sexual well-being patient, satisfaction with breast, satisfaction with overall outcomes and satisfaction with care). From December 2003 to September 2013 we performed 157 NSMs with immediate breast reconstruction on a court of 117 patients. Selection criteria included women with preoperative diagnosis of breast cancer, tumor at least 1 cm from nipple- areola complex (NAC) without nipple discharge or NAC retraction. The median follow-up was 40 months with an age range between 19 and 72 y. We recorded 2 deaths for breast cancer, with a overall survival of 97% and a rate of local recurrence of 8.5% (10 cases). Our follow-up program included medical interview, examination of routine clinical and imaging findings, and collecting information by the BREAST-Q survey. 101 patients agreed the questioner. Our results confirm that BREAST-Q is an useful to evaluate QOL and obtain a more tailored surgery. Patients are very interested to a chance of explaining their point of view or suggesting improvements or propose grievances to the surgical equipe. This is a preliminary report, even if findings are tell now encouraging: the definitive results need greater casemix and longer follow-up. We are already satisfied about the contribution of our Breast Unit.Despite in the last 20 years breast surgery has become less mutilating, mastectomy is indicated in approximately 30% of cases, not only for large invasive carcinoma, but also for multicentric tumors and intraductal diffuse carcinomas. The nipple loss is experienced by the patients like a mutilation; we achieved a significant improvement of the aesthetic result performing Nipplesparing mastectomy (NSM), joined with reconstruction techniques. This approach has a positive impact on psychology and quality of life (QOL) of breast cancer patients. To evaluate these important aspects, we retrospectively applied the BREAST-Q questioner to 101 patients underwent a NSM. BREAST-Q is an instrument designed by the Evelyn H. Lauder Breast Center, MSKCC (NY), to assess outcomes among women undergoing different types of breast surgery: we chose reconstruction module that is comprised of two domains: patient satisfaction and QOL. There are six subthemes (physical, psychosocial and sexual well-being patient, satisfaction with breast, satisfaction with overall outcomes and satisfaction with care). From December 2003 to September 2013 we performed 157 NSMs with immediate breast reconstruction on a court of 117 patients. Selection criteria included women with preoperative diagnosis of breast cancer, tumor at least 1 cm from nipple- areola complex (NAC) without nipple discharge or NAC retraction. The median follow-up was 40 months with an age range between 19 and 72 y. We recorded 2 deaths for breast cancer, with a overall survival of 97% and a rate of local recurrence of 8.5% (10 cases). Our follow-up program included medical interview, examination of routine clinical and imaging findings, and collecting information by the BREAST-Q survey. 101 patients agreed the questioner. Our results confirm that BREAST-Q is an useful to evaluate QOL and obtain a more tailored surgery. Patients are very interested to a chance of explaining their point of view or suggesting improvements or propose grievances to the surgical equipe. This is a preliminary report, even if findings are tell now encouraging: the definitive results need greater casemix and longer follow-up. We are already satisfied about the contribution of our Breast Unit

Pediatric Pancreatitis. Not a Rare Entity

The incidence of acute pancreatitis is increasing in children and it should be considered as part of differential diagnosis in case of abdominal pain. The etiology of acute pancreatitis in this subpopulation is related to several conditions and risk factors, such as drugs, obesity, infections, trauma and anatomic abnormalities. In older children abdominal pain is the first symptom in more than 90% of cases, where as in younger children vomiting represents an early clinical manifestation. Diagnosis is based on laboratory investigation, such as serum levels of lipase, and imaging findings (ultrasonography, CT scanning or MRI) such as detecting edema, hemorrage or necrosis of pancreatic parenchyma or in peripancreatic fat. Treatments for adults and children are similar. Rapid and accurate assessment of the severity of pancreatitis is absolutely indicated for selecting the appropriate treatment and predicting the prognosis

Validazione del primo Tool Internazionale Multicentrico per predire il rischio di metastasi ascellari addizionali in caso di biopsia del linfonodo sentinella positiva

Introduzione: La biopsia del linfonodo sentinella (BLS) seguita da linfoadenectomia ascellare completa (CALND) in caso di positività, resta la procedura standard per stadiare le pazienti affette da cancro della mammella con linfonodi clinicamente negativi, nonostante i recenti risultati del trial ACOSOG Z0011. Il reperto di metastasi linfonodali ascellari addizionali oscilla in letteratura dal 35 al 50%. A partire dall’esperienza del Memorial Sloan Kettering Cancer Center (MSKCC), molte istituzioni hanno elaborato nomogrammi previsionali con l’intento di calcolare il rischio di ulteriore positività linfonodale ascellare in caso di LS metastatico e fornire un ausilio decisionale al clinico onde evitare CALND inutili. Scopo del presente lavoro è validare il primo Tool Internazionale Multicentrico costruito all’uopo e confrontarlo con i più diffusi simili strumenti statistici. Materiali e metodi: 206 casi di LS metastatico su un totale di 916 pazienti affette da carcinoma mammario invasivo. Le pazienti sono state tutte sottoposte a CALND, immediata o differita. È stato calcolato il rischio di trovare metastasi ascellari addizionali tramite l’International Multicenter Tool, il MSKCC nomogram, il Cambridge tool e il metodo originale basato sulla nostra casistica. La validazione è stata effettuata tramite l’area sotto la curva ROC e sono stati considerati valori > 0,70. Risultati: 125 sono state le macrometastasi (60%), 40% le micrometasi. In 124 casi (60%) non sono stati trovati altri linfonodi positivi, in 82 (40%) almeno un altro linfonodo metastatico. Il rilievo di metastasi addizionali è più frequente in caso di LS macrometastatico (52% vs 21% χ2 test p < 0,0001). I valori dell’area sottostante la ROC Curve sono stati 0,730 per l’International Tool, 0,726 per il MSKCC nomogram, 0,733 per il Cambridge e 0,750 per il nostro tool. Discussione e conclusioni: Nessuno dei metodi descritti in letteratura appare ideale, ma, tutti quelli analizzati, risultano superiori alla soglia di 0,70 che ne fa dei validi predittori di stato. Ovviamente il metodo statistico originale elaborato sulla propria casistica è più performante, ma il recente tool internazionale multicentrico vi si avvicina molto e può essere un valido aiuto decisionale. Bibliografia 1. Van Zee KJ, Manasseh D-ME, Bevilacqua JLB, et al: A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol 2003: 10: 1140-51. 2. Giuliano AE, Kelly KH, Ballman KV, et al: Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis. a randomized clinical trial. JAMA 2011; 305: 569-75. 3. Meretoja TJ, Leidenius MH, Heikkilä PS, et al: International Multicenter Tool to Predict the Risk of Nonsentinel Node Metastases in Breast Cancer. J Natl Cancer Inst 2012; 104: 1888-96. 4. Lombardi A, Maggi S, Lo Russo M, et al: Non-sentinel lymph node metastases in breast cancer patients with a positive sentinel lymph node: validation of five nomograms and development of a new predictive model. Tumori 2011; 97: 749-55

Le perforanti mediali dell’arteria toracica interna nella Mastectomia Nipple Sparing

Introduzione: Si può ormai considerare la Mastectomia Nipple Sparing un’evoluzione della mastectomia tradizionale, soprattutto in riferimento alla chirurgia conservativa della mammella. Preservando la cute e il CAC sovrastanti la lesione si ottiene una migliore ricostruzione e la mammella può in tal modo mantenere la sua forma naturale anche dopo una procedura chirurgica. Materiali e metodi: È noto che i rami perforanti anteriori sono i responsabili della vascolarizzazione cutanea della mammella da cui originano come rami collaterali in numero di tre: uno superiore, che emerge dalla fascia del muscolo grande pettorale circa in corrispondenza del 2°-3° spazio intercostale; uno mediale “maggiore” che emerge in corrispondenza del 3°-4° spazio intercostale e uno inferiore che emerge in corrispondenza del 5°-6° spazio intercostale. Questi si dirigono dapprima verso l’esterno (ventralmente) per qualche millimetro, piegano poi medialmente e in corrispondenza del margine sternale e si biforcano in un ramo cutaneo più ventrale e un ramo ghiandolare più dorsale. La variante di tecnica consiste nell’individuazione del peduncolo perforante a livello dei primi spazi intercostali in sede parasternale, una volta scollata la ghiandola dal piano cutaneo e muscolare per tutta la sua superficie escluso il margine mediale. Sottendendo la ghiandola si allarga l’angolo tra questa e la cute ed è quindi più semplice individuare il ramo ghiandolare sezionandolo con forbici ad ultrasuoni o legandola con un laccio sottile (preferiamo non usare il bisturi elettrico che può provocare lesioni indesiderate) preservando il ramo per la rete sottocutanea. Risultati: Nella nostra casistica di Mastectomia Nipple Sparing non sono state osservate necrosi del CAC là dove sono stati preservati almeno due peduncoli vascolari e dieci ischemie transitorie e/o parcellari là dove ne abbiamo preservato almeno uno e, nei casi in cui non siamo stati certi di averne preservato almeno uno, abbiamo avuto dieci casi di necrosi parcellari e 5 casi di necrosi totale della cute e del CAC. Con la RM della mammella abbiamo potuto valutare sia il numero che la portata delle perforanti avendo una guida pre operatoria all’intervento di Mastectomia Nipple Sparing. Gli interventi sono stati 128 in 94 pazienti, l’accesso è stato al solco mammario laterale in 92 casi (71,8 %), con un’incisione periareolare in 17 casi (13,2%) e sec. Wise in 11 casi pari al l’8,5% dei casi. Le complicanze sono state 25 (15,15) su 22 pazienti di cui 5 maggiori (necrosi del capezzolo e di più del 25% della cute) e 20 minori ovvero necrosi parcellari e comunque di meno del 25% della cute della mammella. Discussione e conclusioni: Lo studio anatomico e l’accuratezza della tecnica chirurgica ci ha permesso di ridurre considerevolmente le complicanze post operatorie

Positive margins (R1) risk factors in breast cancer conservative surgery

Background: The primary goal in conservative breast cancer surgery is the complete excision of the tumor, but at the same time attempting to obtain a satisfactory postoperative esthetic result. The notion of “No Ink on Tumor” that indicates exclusively the presence of tumor cells on the inked surface of the surgical specimen is now the gold standard; however, the problem of the free margin is still a fundamental topic of debate that has not yet found a definitive solution. Methods: Our retrospective analysis takes into account 1440 patients undergoing breast conservative surgery, from October 2004 to November 2018, all treated at the breast unit of our institution. Results: Positive margins (R1) rate was 10.2% (147 cases out of 1440). Overall survival was 95% at 5 years and 89% at 10 years. No differences in mortality and local recurrence rate between R0 and R1 patients were found. Half of the R1 patients underwent secondary surgery with enlargement of margins, while in the other half we performed direct mastectomy. Among the analyzed variables, age, histological size, histological type, grading, multifocality, lympho-vascular invasion and lymph node status were significantly correlated with the R1 status. The multivariate analysis shows the association of age and surgical technique (oncoplastic) with R1 status. Conclusion: Further studies will allow the creation of a statistical model, for better preoperative prediction of patients with higher risk of R1 and better selection of patients to be candidates for conservative surgery

Oncological outcomes in oncoplastic breast surgery. a single institution analysis

Oncoplastic surgery is a well-acknowledged technique that combines conserving treatment in breast cancer with plastic surgery reconstruction. The aim of our analysis is to evaluate the safety of this surgical procedure in the setting of invasive primary breast cancer, and then compare breast oncoplastic surgery with the Veronesi quadrantectomy.We have analyzed 1541 patients who underwent breast surgery for primary breast tumor between October 2004 and May 2018 at Sant'Andrea University Hospital in Rome: 880 women experienced the breast oncoplastic approach, while 660 patients received conservative surgery alone. The median follow-up time was 14 years with a completeness of 70% (1067 pts vs 1554). The statistic comparison across these subpopulations suggested that there are no statistically significant results in term of Overall Survival, Disease Related Survival, Local recurrence or positive margins. Therefore oncoplastic surgery for primary invasive breast cancer represents a feasible procedure and an oncological safe surgical option

La valutazione del BREAST-Q nella Nipple Sparing Mastectomy: esperienza dell’Ospedale Sant’Andrea

Introduzione: Nonostante negli ultimi vent’anni la chirurgia senologica sia divenuta sempre meno mutilante, la mastectomia è indicata nel 30% dei casi circa. La perdita del capezzolo è vissuta dalle pazienti come mutilazione ed eseguendo la Mastectomia Nipple Sparing (NSM) combinata con tecniche di ricostruzione si ha un impatto positivo sulla psicologia e sulla qualità di vita (QoL) delle pazienti. Il BREAST-Q è uno strumento progettato dall’ Evelyn H. Lauder Breast Center, MSKCC (NY), per valutare i risultati tra le donne sottoposte a diversi tipi di chirurgia senologica. Materiali e metodi: Abbiamo somministrato il BREAST-Q a 117 pazienti sottoposte a NSM con ricostruzione mammaria immediata. Hanno completato il questionario 101 pazienti. Il nostro follow-up (mediana 40 mm) ha compreso un colloquio medico, una visita clinica, il controllo degli esami strumentali effettuati. Risultati: Abbiamo registrato 2 decessi, con una sopravvivenza globale del 97% e un tasso di recidiva locale dell’8,5% (10 casi). Dalle risposte che riguardano il risultato della ricostruzione mammaria il 93% delle pazienti dichiarano che si risottoporrebbero all’intervento di mastectomia e ricostruzione e che non si pentono del percorso affrontato. Soltanto il 4% ha risposto che non si sottoporrebbe nuovamente alla ricostruzione e l’1% si dichiara pentita. Dall’analisi dei dati risulta che il 95% delle pazienti si è ritenuta soddisfatta ed è stata trattata con rispetto. La valutazione dello staff medico è stata valutata positivamente nel 93% dei casi. Il 94% delle pazienti si sono sentite a proprio agio nel colloquio con l’équipe di chirurgia senologica. Discussione e conclusioni: La NSM riassume in sé la radicalità oncologica e il migliore risultato estetico. I nostri risultati confermano che il BREAST-Q è utile per valutare la QoL ed ottenere un intervento chirurgico conforme alla paziente. Le pazienti sono molto interessate dalla possibilità di spiegare il loro punto di vista o suggerire miglioramenti all’équipe chirurgica. In questa maniera è possibile attuare una medicina basata sull’evidenza che sia al tempo stesso la più personalizzata possibile. Si tratta di una relazione preliminare, anche se i risultati sono, per ora, incoraggianti. I risultati definitivi verranno inclusi in uno studio multicentrico con un follow-up di maggior durata.Despite the fact that in the last twenty years senologic surgery has become less and less mutilating, mastectomy is indicated in about 30% of cases. Nipple loss is experienced by patients as mutilation and performing Mastectomy Nipple Sparing (NSM) combined with reconstruction techniques has a positive impact on patients' psychology and quality of life (QoL). BREAST-Q is a tool designed by Evelyn H. Lauder's Breast Center, MSKCC (NY), to evaluate the results of women undergoing various types of breast cancer surgery. Materials and Methods: We administered BREAST-Q to 117 patients undergoing NSM with immediate breast reconstruction. They completed the questionnaire for 101 patients. Our follow-up (median 40 mm) included a medical interview, a clinical visit, and the examination of the instrumental examinations performed. Results: We recorded 2 deaths, with a global survival of 97% and a local relapse of 8.5% (10 cases). Of the responses to the outcome of breast reconstruction, 93% of patients state that they will re-emerge for mastectomy and reconstruction and will not regret the path they are facing. Only 4% replied that it would not undergo reconstruction again and 1% declare it regretted. From the data analysis, 95% of the patients were satisfied and treated with respect. The medical staff evaluation was rated positively in 93% of cases