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3.
NPJ Breast Cancer ; 10(1): 71, 2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39098868

RESUMEN

New approaches are needed to determine which ductal carcinoma in situ (DCIS) is at high risk for progression to invasive ductal carcinoma (IDC). We retrospectively studied DCIS patients who declined surgery (2002-2019), and received endocrine therapy (ET) and breast MRI. Baseline MRI and changes at 3 months and 6 months were analyzed by recursive partitioning to stratify IDC risk. Sixty-two patients (63 DCIS; 1 bilateral) with a mean follow-up of 8.5 years were included. Fifty-one percent remained on active surveillance (AS) without evidence of IDC, with a mean duration of 7.6 years. A decision tree based on MRI features of lesion distinctness and background parenchymal enhancement (BPE) at baseline and change after 3 months of ET stratified patients into low, intermediate, and high risk for progression to IDC. MRI imaging features in patients treated with ET and undergoing AS, may help determine which DCIS lesions are at low versus high risk for IDC.

5.
Ann Surg Oncol ; 31(11): 7326-7334, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39034365

RESUMEN

BACKGROUND: Inflammatory breast cancer (IBC) is rare and biologically aggressive. We sought to assess diagnostic and management strategies among the American Society of Breast Surgeons (ASBrS) membership. PATIENTS AND METHODS: An anonymous survey was distributed to ASBrS members from March to May 2023. The survey included questions about respondents' demographics and information related to stage III and IV IBC management. Agreement was defined as a shared response by >80% of respondents. In areas of disagreement, responses were stratified by years in practice, fellowship training, and annual IBC patient volume. RESULTS: The survey was administered to 2337 members with 399 (17.1%) completing all questions and defining the study cohort. Distribution of years in practice was 26.0% 0-10 years, 26.6% 11-20 years and 47.4% > 20 years. Overall, 51.2% reported surgical oncology or breast fellowship training, 69.2% maintain a breast-only practice, and 73.5% treat < 5 IBC cases/year. Agreement was identified in diagnostic imaging, trimodal therapy, and mastectomy with wide skin excision for stage III IBC. Lack of agreement was identified in surgical management of the axilla; respondents with < 10 years in practice or fellowship training were more likely to perform axillary dissection for cN0-N2 stage III IBC. Locoregional management of stage IV IBC was variable. CONCLUSIONS: Among ASBrS members, there is consensus in diagnostic evaluation, treatment sequencing and surgical approach to the breast in stage III IBC. Differences exist in surgical management of the cN0-2 axilla with uptake of de-escalation strategies. Clinical trials are needed to evaluate oncologic safety of de-escalation in this high-risk population.


Asunto(s)
Consenso , Neoplasias Inflamatorias de la Mama , Autoinforme , Sociedades Médicas , Cirujanos , Humanos , Neoplasias Inflamatorias de la Mama/terapia , Neoplasias Inflamatorias de la Mama/patología , Neoplasias Inflamatorias de la Mama/cirugía , Femenino , Cirujanos/estadística & datos numéricos , Cirujanos/normas , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Mastectomía , Encuestas y Cuestionarios , Estados Unidos , Persona de Mediana Edad , Pronóstico , Oncología Quirúrgica/normas , Adulto , Estudios de Seguimiento
6.
Ann Surg Oncol ; 31(11): 7339-7346, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39048903

RESUMEN

BACKGROUND: Axillary dissection is the standard of care for patients with positive sentinel lymph nodes (SLNs) following neoadjuvant systemic therapy. Frozen section can provide intraoperative information regarding the need for axillary dissection during the index operation. However, there are limited data on the utility of frozen section in patients with clinically node-negative (cN0) HER2-positive or triple-negative breast cancer. METHODS: We conducted a single-institution observational cohort study including patients with non-inflammatory, cN0, HER2-positive or triple-negative breast cancer treated with neoadjuvant systemic therapy between 2015 and 2019. We estimated the prevalence of SLN positivity and the diagnostic test characteristics of SLN frozen section. RESULTS: Overall, 662 patients were eligible for inclusion, and 44 patients had one or more positive SLNs (prevalence: 6.6%, 95% confidence interval [CI] 4.9-8.8). There were 490 (74.0%) patients who had intraoperative frozen section, and 19 (3.9%) tested positive among 33 (6.7%) with positive final pathology. Frozen section sensitivity was 57.6% (95% CI 39.2-74.5), specificity was 100% (95% CI 99.2-100), positive predictive value was 100% (95% CI 82.4-100), and negative predictive value was 97.0% (95% CI 95.1-98.4). The sensitivity of frozen section for detection of micrometastases or isolated tumor cells was 35.3% (95% CI 14.2-61.7). CONCLUSION: In patients with cN0 HER2-positive or triple-negative breast cancer who have been treated with neoadjuvant therapy, positive SLNs are uncommon and frozen section sensitivity is modest. Decisions to defer SLN evaluation to final pathology, which may be reasonable in many settings, can be informed, in part, by these findings.


Asunto(s)
Secciones por Congelación , Terapia Neoadyuvante , Receptor ErbB-2 , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/cirugía , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/metabolismo , Anciano , Adulto , Estudios de Seguimiento , Prevalencia , Pronóstico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Metástasis Linfática , Anciano de 80 o más Años , Escisión del Ganglio Linfático
7.
JAMA Netw Open ; 7(6): e2418486, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38916888

RESUMEN

Importance: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. Objective: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. Design, Setting, and Participants: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Main Outcomes and Measures: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. Results: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. Conclusions and Relevance: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.


Asunto(s)
Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Adulto , Proteína BRCA2/genética , Proteína BRCA1/genética , Estudios de Cohortes , Resultado del Tratamiento , Supervivencia sin Enfermedad
9.
J Robot Surg ; 16(6): 1391-1399, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35147841

RESUMEN

Robotic proctectomy has become increasingly popular for both benign and malignant indications. The purpose of this study was to determine if the robotic approach has a distinct advantage over laparoscopy in obese patients, which has been suggested by previous subgroup analyses. We performed a retrospective review of 2016-2018 National Surgery Quality Improvement Program (NSQIP) data to compare outcomes between patients who underwent robotic versus laparoscopic proctectomy, stratified by Body Mass Index (BMI) subgroups. We also compared outcomes of converted minimally invasive proctectomy to planned open operations. Four thousand four hundred eighteen (69.3%) patients underwent laparoscopic proctectomy, and 1956 (30.7%) patients underwent robotic proctectomy. Robotic proctectomy was associated with a significantly lower conversion rate compared to laparoscopic proctectomy (5.1% vs 12.3%; p = 0.002), and this relationship was maintained on an adjusted model. Obese (BMI > 30) patients were more likely to require conversion in both laparoscopic and robotic groups with the greatest difference in the conversion rate in the obese subgroup. Patients who underwent conversion had higher composite morbidity compared to patients who underwent planned open operations (50.8% vs 41.3%; p < 0.001). And among patients with rectal cancer, robotic proctectomy was associated with a greater incidence of positive radial tumor margins compared to laparoscopic proctectomy (8.0% vs 6.4%; p = 0.039), driven primarily by the obese subgroup. Our study demonstrates that robotic proctectomy is associated with a 7% lower conversion rate compared to laparoscopy and that obese patients are more likely to require conversion than non-obese patients. Among obese patients with rectal cancer, we identified an increased risk of positive radial margins with robotic compared to laparoscopic proctectomy.


Asunto(s)
Laparoscopía , Proctectomía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Mejoramiento de la Calidad , Neoplasias del Recto/cirugía , Laparoscopía/efectos adversos , Estudios Retrospectivos , Márgenes de Escisión , Obesidad/complicaciones , Obesidad/cirugía , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología
10.
Cancer Res Commun ; 2(12): 1579-1589, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36970720

RESUMEN

Ductal carcinoma in situ (DCIS) is a biologically heterogenous entity with uncertain risk for invasive ductal carcinoma (IDC) development. Standard treatment is surgical resection often followed by radiation. New approaches are needed to reduce overtreatment. This was an observational study that enrolled patients with DCIS who chose not to pursue surgical resection from 2002 to 2019 at a single academic medical center. All patients underwent breast MRI exams at 3- to 6-month intervals. Patients with hormone receptor-positive disease received endocrine therapy. Surgical resection was strongly recommended if clinical or radiographic evidence of disease progression developed. A recursive partitioning (R-PART) algorithm incorporating breast MRI features and endocrine responsiveness was used retrospectively to stratify risk of IDC. A total of 71 patients were enrolled, 2 with bilateral DCIS (73 lesions). A total of 34 (46.6%) were premenopausal, 68 (93.2%) were hormone-receptor positive, and 60 (82.1%) were intermediate- or high-grade lesions. Mean follow-up time was 8.5 years. Over half (52.1%) remained on active surveillance without evidence of IDC with mean duration of 7.4 years. Twenty patients developed IDC, of which 6 were HER2 positive. DCIS and subsequent IDC had highly concordant tumor biology. Risk of IDC was characterized by MRI features after 6 months of endocrine therapy exposure; low-, intermediate-, and high-risk groups were identified with respective IDC rates of 8.7%, 20.0%, and 68.2%. Thus, active surveillance consisting of neoadjuvant endocrine therapy and serial breast MRI may be an effective tool to risk-stratify patients with DCIS and optimally select medical or surgical management. Significance: A retrospective analysis of 71 patients with DCIS who did not undergo upfront surgery demonstrated that breast MRI features after short-term exposure to endocrine therapy identify those at high (68.2%), intermediate (20.0%), and low risk (8.7%) of IDC. With 7.4 years mean follow-up, 52.1% of patients remain on active surveillance. A period of active surveillance offers the opportunity to risk-stratify DCIS lesions and guide decisions for operative management.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Estudios Retrospectivos , Carcinoma Ductal de Mama/patología , Terapia Neoadyuvante , Espera Vigilante , Neoplasias de la Mama/diagnóstico por imagen
11.
J Am Coll Surg ; 233(3): 395-414, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34166838

RESUMEN

BACKGROUND: Hepatopancreatobiliary (HPB) Fellowship training in the Americas consists of 3 distinctive routes with variable curricula: Surgical Oncology Fellowship via the Society of Surgical Oncology (SSO), Abdominal Transplant Surgery Fellowship via the American Society of Transplant Surgeons (ASTS), and HPB Fellowship via the Americas Hepato-Pancreato-Biliary Association (AHPBA). Our objective was to establish a pan-American consensus among HPB surgeons, surgical oncologists, abdominal transplant surgeons, and general surgery residency program directors (GSPDs) on a core knowledge curriculum for HPB fellowship, and to identify topics appropriate for general surgery residency and subspecialty beyond HPB fellowship. STUDY DESIGN: A 3-round modified Delphi process was used. Baseline statements were developed by the Education and Training Committee of the AHPBA, in collaboration with representatives of the SSO, ASTS, and GSPDs. The expert panel, consisting of members of the 3 societies together with GSPDs, rated the statements on a 5-point Likert scale and suggested editing or adding new statements. A statement was included in the final curriculum when Cronbach's alpha value was ≥ 0.8 and ≥ 80% of the panel agreed on inclusion. RESULTS: The response rate was 100% for the first round, and 98% for the second and third rounds. Eighty-nine of 138 proposed statements were included in the final HPB fellowship curriculum. Curricula for general surgery residency and subspecialty beyond HPB fellowship included 50 and 29 statements, respectively. CONCLUSIONS: A multinational consensus on core knowledge for an HPB fellowship curriculum was achieved via the modified Delphi method. This core curriculum may be used to standardize HPB fellowship training across different pathways in the Americas.


Asunto(s)
Enfermedades de las Vías Biliares/cirugía , Curriculum/normas , Procedimientos Quirúrgicos del Sistema Digestivo/educación , Educación de Postgrado en Medicina/normas , Gastroenterología/educación , Consenso , Técnica Delphi , Becas , Humanos , Estados Unidos
12.
NPJ Breast Cancer ; 7(1): 59, 2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34035311

RESUMEN

Ductal carcinoma in situ (DCIS) is a risk factor for the subsequent development of invasive breast cancer. High-risk features include age <45 years, size >5 cm, high-grade, palpable mass, hormone receptor negativity, and HER2 positivity. We have previously shown that immune infiltrates are positively associated with these high-risk features, suggesting that manipulating the immune microenvironment in high-risk DCIS could potentially alter disease progression. Patients with high-risk DCIS were enrolled in this 3 × 3 phase 1 dose-escalation pilot study of 2, 4, and 8 mg intralesional injections of the PD-1 immune checkpoint inhibitor, pembrolizumab. Study participants received two intralesional injections, three weeks apart, prior to surgery. Tissue from pre-treatment biopsies and post-treatment surgical resections was analyzed using multiplex immunofluorescence (mIF) staining for various immune cell populations. The intralesional injections were easily administered and well-tolerated. mIF analyses demonstrated significant increases in total T cell and CD8+ T cell percentages in most patients after receiving pembrolizumab, even at the 2 mg dose. T cell expansion was confined primarily to the stroma rather than within DCIS-containing ducts. Neither cleaved caspase 3 (CC3) staining, a marker for apoptosis, nor DCIS volume (as measured by MRI) changed significantly following treatment. Intralesional injection of pembrolizumab is safe and feasible in patients with DCIS. Nearly all patients experienced robust total and CD8+ T cell responses. However, we did not observe evidence of cell death or tumor volume decrease by MRI, suggesting that additional strategies may be needed to elicit stronger anti-tumor immunity.

13.
Transplantation ; 105(6): 1297-1302, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33347261

RESUMEN

BACKGROUND: The use of living donor liver transplantation (LDLT) for primary liver transplantation (LT) may quell concerns about allocating deceased donor organs if the need for retransplantation (re-LT) arises because the primary LT did not draw from the limited organ pool. However, outcomes of re-LT after LDLT are poorly studied. The purpose of this study was to analyze the Adult to Adult Living Donor Liver Transplantation Study (A2ALL) data to report outcomes of re-LT after LDLT, with a focus on long-term survival after re-LT. METHODS: A retrospective review of A2ALL data collected between 1998 and 2014 was performed. Patients were excluded if they received a deceased donor LT. Demographic data, postoperative outcomes and complications, graft and patient survival, and predictors of re-LT and patient survival were assessed. RESULTS: Of the 1065 patients who underwent LDLT during the study time period, 110 recipients (10.3%) required re-LT. In multivariable analyses, hepatitis C virus, longer length of stay at LDLT, hepatic artery thrombosis, biliary stricture, infection, and disease recurrence were associated with an increased risk of re-LT. Patient survival among re-LT patients was significantly inferior to those who underwent primary transplant only at 1 (86% versus 92%), 5 (64% versus 82%), and 10 years (44% versus 68%). CONCLUSIONS: Approximately 10% of A2ALL patients who underwent primary LDLT required re-LT. Compared with patients who underwent primary LT, survival among re-LT recipients was worse at 1, 5, and 10 years after LT, and re-LT was associated with a significantly increased risk of death in multivariable modeling (hazard ratios, 2.29; P < 0.001).


Asunto(s)
Trasplante de Hígado , Donadores Vivos , Reoperación , Adulto , Factores de Edad , Femenino , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , América del Norte , Reoperación/efectos adversos , Reoperación/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
14.
Transplantation ; 105(4): 824-831, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32433235

RESUMEN

BACKGROUND: Share 35 was a policy implemented in 2013 to increase regional sharing of deceased donor livers to patients with model for end-stage liver disease ≥ 35 to decrease waitlist mortality for the sickest patients awaiting liver transplantation (LT). The purpose of this study was to determine whether live donor liver transplantation (LDLT) volume was impacted by the shift in allocation of deceased donor livers to patients with higher model for end-stage liver disease scores. METHODS: Using Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files, we identified all adults who received a primary LT between October 1, 2008, and March 31, 2018. LT from October 1, 2008, through June 30, 2013, was designated as the pre-Share 35 era and July 1, 2013, through March 31, 2018, as the post-Share 35 era. Primary outcomes included transplant volumes, graft survival, and patient survival in both eras. RESULTS: In total, 48 779 primary adult single-organ LT occurred during the study period (22 255 pre-Share 35, 26 524 post). LDLT increased significantly (6.8% post versus 5.7% pre, P < 0.001). LDLT volume varied significantly by region (P < 0.001) with regions 2, 4, 5, and 8 demonstrating significant increases in LDLT volume post-Share 35. The number of centers performing LDLT increased only in regions 4, 6, and 11. Throughout the 2 eras, there was no difference in graft or patient survival for LDLT recipients. CONCLUSIONS: Overall, LDLT volume increased following the implementation of Share 35, which was largely due to increased LDLT volume at centers with experience in LDLT, and corresponded to significant geographic variation in LDLT utilization.


Asunto(s)
Técnicas de Apoyo para la Decisión , Selección de Donante , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado , Donadores Vivos/provisión & distribución , Enfermedad Hepática en Estado Terminal/diagnóstico , Femenino , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
15.
Future Oncol ; 8(11): 1383-96, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23148612

RESUMEN

Advances in targeted therapies have improved progression-free and overall survival in women with metastatic breast cancer; however, regardless of efficacy, resistance almost always occurs eventually. Upregulation of the PI3K/AKT/mTOR pathway, which promotes cell growth and proliferation, is a means of escaping responsiveness to hormone therapy in hormone receptor-positive disease, or trastuzumab in HER2-positive disease. Everolimus, an inhibitor of mTOR, has shown promise in early clinical trials in metastatic breast cancer and is currently being studied in larger Phase II and III clinical trials, combined with hormone therapy or trastuzumab with or without cytotoxic chemotherapy. In this article, we discuss the mechanistic and preclinical data for everolimus, efficacy and safety results of clinical trials, and the landscape looking forward.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Sirolimus/análogos & derivados , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Resistencia a Antineoplásicos , Everolimus , Femenino , Humanos , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor ErbB-2/metabolismo , Transducción de Señal/efectos de los fármacos , Sirolimus/efectos adversos , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo , Trastuzumab , Resultado del Tratamiento
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