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Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51-0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44-0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)-/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12-0.83; p = 0.02) and ER-/HER2- (OR = 0.41; 95% CI, 0.17-0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806.
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Importance: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent. Objective: To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography. Design, Setting, and Participants: The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023. Intervention: Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group). Main Outcomes and Measures: The primary end point of the study was distant disease-free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations. Results: Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor-positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group. Conclusions and Relevance: In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan. Trial Registration: ClinicalTrials.gov Identifier: NCT02167490.
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Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Humanos , Feminino , Pessoa de Meia-Idade , Biópsia de Linfonodo Sentinela/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/mortalidade , Estudos Prospectivos , Resultados Negativos , Recidiva Local de Neoplasia/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Ultrassonografia , RecidivaRESUMO
PURPOSE: Accurate evaluation of breast cancer on bioptic samples is of fundamental importance to guide therapeutic decisions, especially in the neoadjuvant or metastatic setting. We aimed to assess concordance for oestrogen receptor (ER), progesterone receptor (PR), c-erbB2/HER2 and Ki-67. We also reviewed the current literature to evaluate our results in the context of the data available at present. METHODS: We included patients who underwent both biopsy and surgical resection for breast cancer at San Matteo Hospital, Pavia, Italy, between January 2014 and December 2020. ER, PR, c-erbB2, and Ki-67 immunohistochemistry concordance between biopsy and surgical specimen was evaluated. ER was further analysed to include the recently defined ER-low-positive in our analysis. RESULTS: We evaluated 923 patients. Concordance between biopsy and surgical specimen for ER, ER-low-positive, PR, c-erbB2 and Ki-67 was, respectively, 97.83, 47.8, 94.26, 68 and 86.13%. Cohen's κ for interobserver agreement was very good for ER and good for PR, c-erbB2 and Ki-67. Concordance was especially low (37%) in the c-erbB2 1 + category. CONCLUSION: Oestrogen and progesterone receptor status can be safely assessed on preoperative samples. The results of this study advise caution in interpreting biopsy results regarding ER-low-positive, c-erbB2/HER and Ki-67 results due to a still suboptimal concordance. The low concordance for c-erbB2 1 + cases underlines the importance of further training in this area, in the light of the future therapeutic perspectives.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/tratamento farmacológico , Receptores de Progesterona , Antígeno Ki-67 , Biomarcadores Tumorais , Prognóstico , Imuno-Histoquímica , Receptor ErbB-2 , Biópsia , Receptores de EstrogênioRESUMO
Totally implanted venous access ports (TIVAPs) have been established as effective and safe devices for oncologic patients. In breast cancer setting, the implant of the reservoir at mid-arm allows the absence of additional scars on the chest and the easier access to the port with significant cosmetic and psychological advantages. In the last decades, breast surgery has made great progresses to ameliorate the cosmetic results even in mastectomy techniques. In fact, many studies have demonstrated that negative body image perception affects physical and psychological wellbeing of survivors. Despite this evidence, limited importance is still reserved to TIVAPs placement site, which is traditionally the chest. It is not unusual to see patients after a nipple-sparing mastectomy with excellent cosmetic result who show a disfiguring scar on their upper chest due to TIVAP placement. We report the case of a young woman with BRCA2-related breast cancer who underwent bilateral nipple sparing mastectomy with immediate reconstruction and adjuvant chemotherapy. Her TIVAP was located at the mid-arm, which is still an uncommon site compared to the upper chest. An optimal cosmetic result was obtained both in breast reconstruction and in the arm site of port, with high-rate patient satisfaction. This case presentation aims to raise awareness towards women's body image preservation, particularly in the choice of TIVAP placement: in most cases neckline and upper chest should be avoided for a better patient related outcome.
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BACKGROUND: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. PATIENTS AND METHODS: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). RESULTS: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. CONCLUSION: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.
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Neoplasias da Mama , Terapia Neoadjuvante , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Linfonodos , Mastectomia , Nomogramas , Biópsia de Linfonodo SentinelaRESUMO
PURPOSE: Breast lesions classified as of "uncertain malignant potential" represent a heterogeneous group of abnormalities with an increased risk of associated malignancy. Clinical management of B3 lesions diagnosed on vacuum-assisted breast biopsy (VABB) is still challenging: surgical excision is no longer the only available treatment and VABB may be sufficient for therapeutic excision. The aim of the present study is to evaluate the positive predictive value (PPV) for malignancy in B3 lesions that underwent surgical excision, identifying possible upgrading predictive factors and characterizing the malignant lesions eventually diagnosed. These results are compared with a subset of patients with B3 lesions who underwent follow-up. METHODS: A total of 1250 VABBs were performed between January 2006 and December 2017 at our center. In total, 150 B3 cases were diagnosed and 68 of them underwent surgical excision. VABB findings were correlated with excision histology. A PPV for malignancy for each B3 subtype was derived. RESULTS: The overall PPV rate was 28%, with the highest upgrade rate for atypical ductal hyperplasia (41%), followed by classical lobular neoplasia (29%) and flat epithelial atypia (11%). Only two cases of carcinoma were detected in the follow-up cohort, both associated with atypical ductal hyperplasia at VABB. CONCLUSION: Open surgery is recommended in case of atypical ductal hyperplasia while, for other B3 lesions, excision with VABB only may be an acceptable alternative if radio-pathological correlation is assessed, if all microcalcifications have been removed by VABB, and if the lesion lacks high-risk cytological features. KEY POINTS: ⢠Surgical treatment is strongly recommended in case of ADH, while the upgrade rate in case of pure FEA, especially following complete microcalcification removal by VABB, may be sufficiently low to advice surveillance as a management strategy. ⢠The use of 11-G- or 8-G-needle VABB, resulting in possible complete diagnostic excision of the lesion, can be an acceptable alternative in case of RS, considering open surgery only for selected high-risk patients. ⢠LN management is more controversial: surgical excision may be recommended following classical LN diagnosis on breast biopsy if an additional B3 lesion is concurrently detected while in the presence of isolated LN with adequate radiological-pathological correlation follow-up alone could be an acceptable option.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Mama/diagnóstico por imagem , Mama/cirurgia , Neoplasias da Mama/cirurgia , Humanos , Biópsia Guiada por Imagem , Mamografia , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
Recent developments in sentinel lymph node (SLN) and radio occult lesion localization (ROLL) highlight the need for a multimodal contrast agent, providing better presurgical PET imaging and improved intraoperative mapping thanks to fluorescence detection. For this reason, we have studied a trimodal SLN/ROLL targeting agent (99mTc-68Ga-ICG) with commercially available kits of macroaggregated or nanocolloidal albumin (MA/NC-HSA). 68Ga PET imaging does provide better spatial resolution and makes it possible to predict signal intensity during surgery. The presence of 99mTc assesses the efficacy of these compounds in vitro and also during the surgery procedure. The aim of this study was to optimise the labelling and tagging of these two radiopharmaceuticals and assess their yields and stability. Kits of MA/NC-HSA particles (Pulmocis® and NanoAlbumon®) were used for sequential radiolabelling with 99mTc and 68Ga. Fluorescent tagging was performed using indocyanine green, a tricarbocyanine dye. The ITLC radiochemical purity of the trilabelled MA/NC-HSA was >95%. Fluorescent purity was measured by scanning the strips with a PhotoDynamicEye probe. Finally, in vitro stability tests, performed with DTPA and human serum solutions, assessed the efficacy of fluorescent tagging and radiolabelling.
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Radioisótopos de Gálio/química , Verde de Indocianina/química , Nanopartículas/química , Compostos Organometálicos/química , Cintilografia , Kit de Reagentes para Diagnóstico , Albumina Sérica/química , Tecnécio/química , Coloides/química , Fluorescência , Humanos , Linfonodos/diagnóstico por imagem , Tamanho da Partícula , Controle de Qualidade , Radioatividade , Compostos Radiofarmacêuticos/químicaRESUMO
In this paper, we present the case of a 48-year-old woman diagnosed with early breast cancer. As candidate for mastectomy, she refused immediate reconstruction. She was referred to a psycho-oncologist for further evaluation and support. Psychological sessions helped reveal a history of intimate partner violence and helped clarify the reason for her refusal to undergo immediate reconstruction. Experience with this case highlights the importance of a multidisciplinary practice in which collaboration between surgeons, oncologists, and mental health professionals leads to a more in-depth understanding of the apparently paradoxical behaviors of patients, and to better care for their needs.
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Neoplasias da Mama/psicologia , Violência por Parceiro Íntimo/psicologia , Violência por Parceiro Íntimo/estatística & dados numéricos , Mastectomia/psicologia , Cônjuges/psicologia , Estresse Psicológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The surgical approach to the axilla in breast cancer has been a controversial issue for more than three decades. Data from recently published trials have provided practice-changing recommendations in this scenario. However, further controversies have been triggered in the surgical community, resulting in heterogeneous diffusion of these recommendations. The development of clinical guidelines for the management of the axilla in patients with breast cancer is a work in progress. A multidisciplinary team discussion was held at the research hospital Policlinico San Matteo from the Università degli Studi di Pavia with the aim to update recommendations for the management of the axilla in patients with breast cancer. An evidence-based approach is presented. Our multidisciplinary panel determined that axillary dissection after a positive sentinel lymph node biopsy may be avoided in cN0 patients with micro/macrometastasis to ≤2 sentinel nodes, with age ≥40y, lesions ≤3â¯cm, who have not received neoadjuvant chemotherapy and have planned breast conservation (BCS) with whole breast radiotherapy (WBRT). Cases with gross (>2â¯mm) ECE in SLNs are evaluated on individual basis for completion ALND, axillary radiotherapy or omission of both. Patients fulfilling the criteria listed above who undergo mastectomy, may also avoid axillary dissection after multidisciplinary discussion of individual cases for consideration of axillary irradiation. Women 70 years or older with hormone receptors positive invasive lesions ≤3â¯cm, clinically negative nodes, and serious or multiple comorbidities who undergo BCS with WBRT, may forgo axillary staging/surgery (if mastectomy or larger tumor, comorbidities and life expectancy are taken into account).
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Axila/patologia , Axila/cirurgia , Neoplasias da Mama/patologia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Consenso , Medicina Baseada em Evidências , Feminino , Humanos , Itália , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de NeoplasiasRESUMO
Breast cancer affects patients both emotionally and physically. It is time to consider distress as the sixth vital sign in breast cancer patients in Europe. Between 2012 and 2015, our EUSOMA-certified multi-disciplinary group conducted a study on emotional distress and quality-of-life in breast cancer patients at diagnosis, and observed their trend over the first 8 months of treatment. One hundred and forty-nine patients concluded the program. The psycho-oncologist and the breast nurses gave out SF36, Hospital Anxiety and Depression Scale and Distress Thermometer. Our Italian data go along with the reported literature on distress and quality-of-life. Despite modern advances, experiencing breast cancer impacts on overall quality-of-life.
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Neoplasias da Mama/psicologia , Qualidade de Vida , Estresse Psicológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Itália , Mastectomia , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Data from recently published trials have provided practice-changing recommendations for the surgical approach to the axilla in breast cancer. Patients with T1-2 lesions, treated with breast conservation, who have not received neoadjuvant chemotherapy and have 1-2 positive sentinel nodes (Z0011-criteria) may avoid axillary lymph node dissection (ALND). We aim to describe the dissemination of this practice in Europe over an extended period of time. METHODS: Our source of data was the eusomaDB, a central data warehouse of prospectively collected information of the European Society of Breast Cancer Specialists (EUSOMA). We identified cases fulfilling Z0011-criteria from 2005 to 2016 from 34 European breast centers and report trends in ALND. Data derived from Germany, Italy, Belgium, Switzerland, Austria, and Netherlands. RESULTS: 6671 patients fulfilled Z0011-criteria. Rates of ALND showed a statistically significant decrease from 2010 (89%) to 2011 (73%), reaching 46% in 2016 (pâ¯<â¯0.001). After multivariable analysis, factors associated with higher probability of ALND were earlier year of surgery, younger age, increasing tumor size and grade, and being operated in Italy (pâ¯<â¯0.001). The minimum and maximal rates of ALND in the most recent two-year period (2015-2016) were 0% and 83% in two centers located in different countries (pâ¯<â¯0.001). CONCLUSION: Our study demonstrates, a decrease in rates of ALND that started after year 2010 through the end of the study period. Wide differences were observed among centers and countries indicating the need to spread unified clinical guidelines in Europe to allow for homogeneous evidence-based practice patterns.
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Neoplasias da Mama/cirurgia , Excisão de Linfonodo/tendências , Padrões de Prática Médica/tendências , Adulto , Idoso , Axila , Mama/patologia , Neoplasias da Mama/patologia , Europa (Continente) , Feminino , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Pessoa de Meia-IdadeRESUMO
Distress could be often experienced by breast cancer patients with chemotherapy-induced alopecia. Those distress assessment is strategic to deliver care in a tailored way, enhancing the overall wellbeing. So far, those distress is measurable by the Chemotherapy-induced Alopecia Distress Scale (CADS), which is not yet available in Italian, due to there are no validation studies on this topic. For this reason, the aim of this study was to validate and adapt Chemotherapy-induced Alopecia Distress Scale within the Italian context (I-CADS). Specifically, the following validations were assessed: cultural-linguistic, qualitative and quantitative content validity, psychometrics and internal consistency (reliability) assessments. To answer to the specific aims, the study design was multiphase: 1) firstly, authors provided a linguistic and cultural validation; 2) then a panel of expert (n=16) was involved to assess qualitative and quantitative content validity, using CVR, I-CVIs, S-CVI; finally 3) a cross-sectional sampling was used to establish the psychometric proprieties and the internal consistency. In the third phase the data were analyzed through different exploratory factorial analysis models, using Maximum Likelihood Robust estimator and Geomin factor rotation. I-CADS has 16 items, measuring three domains, which are self-perception, emotivism and social engaging. The items internal consistency (α Cronbach was always major of 0.93) within their domain shows a good reliability. I-CADS could be routinely used to support clinical decision-making, due to it is useful to intercept distress related to low self-perception, emotivism and social engaging. Moreover, I-CAD clear psychometric structure could facilitate its usefulness in those researches where it is needed to measure distress amongst breast cancer patients with chemotherapy-induced alopecia.
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Alopecia/induzido quimicamente , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Estresse Psicológico/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/psicologia , Antineoplásicos/administração & dosagem , Neoplasias da Mama/psicologia , Estudos Transversais , Características Culturais , Feminino , Humanos , Itália , Idioma , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Estresse Psicológico/etiologia , Inquéritos e QuestionáriosAssuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/cirurgia , Predisposição Genética para Doença , Mastectomia Profilática/estatística & dados numéricos , Adulto , Neoplasias da Mama/psicologia , Feminino , Humanos , Itália , Mutação , Ovariectomia , Projetos Piloto , Procedimentos Cirúrgicos Profiláticos/estatística & dados numéricos , Salpingectomia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the long-term outcome of patients treated with serial intrafistular injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) for refractory Crohn fistulas in terms of safety and efficacy. PATIENTS AND METHODS: Starting from January 10, 2007, through June 30, 2014, clinical evaluation, calculation of the Crohn disease activity index (CDAI), therapeutic management, and documentation of adverse events in 8 of the 10 patients (5 men; median age, 37 years) who had been injected locally with MSCs were prospectively recorded for 72 months. Cumulative probabilities of fistula recurrence and medical or surgical treatment were estimated using a Kaplan-Meier method, whereas differences among the pre- and post-MSC CDAI values were calculated with the Mann-Whitney U test. RESULTS: Following disease remission observed after 12 months from MSC treatment (P<.001), the mean CDAI score increased significantly during the subsequent 2 years (P=.007), and was then followed by a gradual decrease, with the patients achieving remission again (P=.02) at the end of the 5-year follow-up. The probability of fistula relapse-free survival was 88% at 1 year, 50% at 2 years, and 37% during the following 4 years, and the cumulative probabilities of surgery- and medical-free survival were 100% and 88% at 1 year, 75% and 25% at 2, 3, and 4 years, and 63% and 25% at 5 and 6 years, respectively. No adverse events were recorded. CONCLUSION: Locally injected MSCs constitute a safe therapy that rescues refractory patients and regains responsiveness to drugs previously proved ineffective.
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Doença de Crohn/complicações , Doença de Crohn/terapia , Fístula Intestinal/etiologia , Fístula Intestinal/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease. PATIENTS AND METHODS: We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×106 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. RESULTS: MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p < 0.01 for both), and rectal mucosal healing were induced by treatment without any adverse effects. The percentage of mucosal and circulating regulatory T cells significantly increased during the treatment and remained stable until the end of follow up (p < 0.0001 and p < 0.01, respectively). Furthermore, MSCs have been proven to affect mucosal T cell apoptotic rate. CONCLUSIONS: Locally injected MSCs represent a feasible, safe and beneficial therapy in refractory fistulising Crohn's disease.
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Doença de Crohn/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Fístula Retal/terapia , Adolescente , Adulto , Doenças do Ânus/diagnóstico , Doenças do Ânus/etiologia , Doenças do Ânus/imunologia , Doenças do Ânus/terapia , Apoptose/imunologia , Técnicas de Cocultura , Doença de Crohn/complicações , Doença de Crohn/imunologia , Citocinas/biossíntese , Citocinas/sangue , Estudos de Viabilidade , Feminino , Humanos , Imunidade nas Mucosas , Imunofenotipagem , Imageamento por Ressonância Magnética , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/imunologia , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Fístula Retal/imunologia , Linfócitos T Reguladores/imunologia , Resultado do Tratamento , Cicatrização , Adulto JovemRESUMO
Fibromatosis-like spindle-cell metaplastic carcinoma (FLSpCC) is an atypical variant of spindle-cell carcinoma with a particular clinical behavior characterized by frequent local recurrence, very low potential for axillary lymph node metastasis, and uncommon distant metastases. Although it presents the typical immunoprofile of basal-like carcinomas, FLSpCC is associated with a favorable clinical outcome and conservative treatment is generally indicated. Because of the lack of specific clinical and radiological characteristics, the criteria for the differential diagnosis from other benign and malignant tumors are based only on histological findings and immunostaining. We report on two FLSpCC patients treated with wide local excision and mastectomy associated with axillary lymph node dissection. Although the biological behavior of this subtype of breast cancer has not been adequately evaluated, wide local excision or mastectomy with clear resection margins but no axillary dissection appears to be an adequate treatment approach.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Mama/patologia , Carcinoma/patologia , Carcinoma/cirurgia , Mastectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Axila , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Carcinoma/química , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Excisão de Linfonodo , Metaplasia/diagnóstico , Resultado do TratamentoRESUMO
Bortezomib is the first anticancer proteasome inhibitor introduced into clinical practice. It has been recently approved for the treatment of multiple myeloma, an incurable plasma cell tumour that accounts for 10-15% of all haematologic malignancies and for approximately 20% of deaths. Gastrointestinal toxicity associated with the use of this drug is common but generally mild to moderate. Paralytic ileus in patients undergoing bortezomib treatment has been reported, although a definite attribution to bortezomib administration has not been established. We report a myeloma patient who developed severe paralytic ileus during bortezomib therapy, which presented in the context of progressive constipation without other known causes and which regressed promptly with medical management after drug cessation, suggesting a direct causal relationship. Awareness of the various potential gastrointestinal toxic effects of bortezomib is of relevance given the growing number of patients undergoing treatment with this important and effective new cancer drug.