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1.
Ann Biomed Eng ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403451

RESUMO

The burden of cancer continues to increase in society and negatively impacts the lives of numerous patients. Due to the high cost of current treatment strategies, there is a crucial unmet need to develop inexpensive preclinical platforms to accelerate the process of anti-cancer drug discovery to improve outcomes in cancer patients, most especially in female patients. Many current methods employ expensive animal models which not only present ethical concerns but also do not often accurately predict human physiology and the outcomes of anti-cancer drug responsiveness. Conventional treatment approaches for cancer generally include systemic therapy after a surgical procedure. Although this treatment technique is effective, the outcome is not always positive due to various complex factors such as intratumor heterogeneity and confounding factors within the tumor microenvironment (TME). Patients who develop metastatic disease still have poor prognosis. To that end, recent efforts have attempted to use 3D microengineered platforms to enhance the predictive power and efficacy of anti-cancer drug screening, ultimately to develop personalized therapies. Fascinating features of microengineered assays, such as microfluidics, have led to the advancement in the development of the tumor-on-chip technology platforms, which have shown tremendous potential for meaningful and physiologically relevant anti-cancer drug discovery and screening. Three dimensional microscale models provide unprecedented ability to unveil the biological complexities of cancer and shed light into the mechanism of anti-cancer drug resistance in a timely and resource efficient manner. In this review, we discuss recent advances in the development of microengineered tumor models for anti-cancer drug discovery and screening in female-related cancers. We specifically focus on female-related cancers to draw attention to the various approaches being taken to improve the survival rate of women diagnosed with cancers caused by sex disparities. We also briefly discuss other cancer types like colon adenocarcinomas and glioblastoma due to their high rate of occurrence in females, as well as the high likelihood of sex-biased mutations which complicate current treatment strategies for women. We highlight recent advances in the development of 3D microscale platforms including 3D tumor spheroids, microfluidic platforms as well as bioprinted models, and discuss how they have been utilized to address major challenges in the process of drug discovery, such as chemoresistance, intratumor heterogeneity, drug toxicity, etc. We also present the potential of these platform technologies for use in high-throughput drug screening approaches as a replacements of conventional assays. Within each section, we will provide our perspectives on advantages of the discussed platform technologies.

2.
Ann Plast Surg ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33470624

RESUMO

BACKGROUND: Same-day discharge after mastectomy is a recently described treatment approach. Limited data exist investigating whether same-day discharge can be successfully implemented in patients undergoing mastectomy with immediate implant-based breast reconstruction (IBR). METHODS: Patients having mastectomy with IBR from 2013 to 2019 were reviewed. Enhanced recovery with same-day discharge was implemented in 2017. Patient characteristics, oncologic treatments, surgical techniques, and 90-day postoperative complications and reoperations were analyzed comparing enhanced recovery patients with historical controls. RESULTS: A total of 363 patients underwent nipple-sparing (214, 59%) or skin-sparing (149, 41%) mastectomy with 1-stage (270, 74%) or tissue expander (93, 26%) IBR. Enhanced recovery was used for 151 patients, with 79 of these patients (52%) discharged same-day. Overall, enhanced recovery patients experienced a significantly lower rate of 90-day complications (21% vs 41%, P < 0.001), including hematoma (3% vs 11%, P = 0.002), mastectomy flap necrosis (7% vs 15%, P = 0.02), seroma (1% vs 9%, P < 0.001), and wound breakdown (3% vs 9%, P = 0.05). Postoperative complication rates did not significantly differ among enhanced recovery patients discharged same day. Postoperative admissions significantly decreased after enhanced recovery implementation (100% to 48%, P < 0.001), and admitted enhanced recovery patients experienced a lower length of stay (1.2 vs 1.8, P < 0.001). Enhanced recovery patients experienced a lower incidence of ≥1 unplanned reoperation (22% vs 33%, P = 0.01); overall average unplanned and total reoperations did not significantly differ between groups. CONCLUSIONS: In conjunction with enhanced recovery practices, same-day discharge after mastectomy with IBR is a safe and feasible treatment approach.

3.
Ann Plast Surg ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33196535

RESUMO

BACKGROUND: The purpose of this study is to evaluate how prior breast augmentation impacts rates of complications and risk for reoperation after mastectomy with concurrent breast reconstruction. METHODS: Patients undergoing nipple-sparing, skin-sparing, or simple mastectomy with implant-based reconstruction from 2008 to 2018 were identified in a prospective database. Postoperative complications and reoperations were then analyzed comparing patients with prior augmentation to patients without history of previous breast surgery. RESULTS: A total of 468 patients were identified with a median follow-up of 4 years. Of these, 72 had prior augmentation mammoplasty. These patients underwent nipple-sparing (52, 72%), skin-sparing (15, 21%), or simple (5, 7%) mastectomy with immediate direct-to-implant (46, 61%) or tissue expander (26, 35%) reconstruction. On univariate analysis, this cohort had a lower body mass index (23.3 vs 25.3, P = 0.003), a higher rate of nipple-sparing mastectomy (72% vs 54%, P = 0.01), and a higher prevalence of stage I disease (44% vs 33%, P = 0.04). Differences in age, comorbidities, reconstructive techniques, tumor size, and neoadjuvant/adjuvant therapies were not significant. Overall complication rate between patients with or without prior augmentation did not significantly differ (51% vs 50%, P = 0.83); no significant differences in rates of surgical site infection, hematoma, mastectomy skin flap/wound necrosis, nipple complications, implant loss, or capsular contracture were found. Analysis of reoperations between patients with and without prior augmentation revealed no significant differences in average number of subsequent planned, unplanned, or total reoperations. On multivariate analysis, prior breast augmentation was found to be associated with significantly increased risk for undergoing ≥1 unplanned reoperation (odds ratio, 2.28; 95% confidence interval, 1.28-4.05, P = 0.005). CONCLUSIONS: Prior augmentation mammoplasty does not significantly affect rates of postoperative complications after mastectomy with concurrent reconstruction. Although prior augmentation does not affect number of subsequent reoperations on average, it does increase the risk of experiencing 1 or more unplanned reoperation after mastectomy with reconstruction.

4.
Am J Surg ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32988607

RESUMO

BACKGROUND: Capsular contracture causes pain, poor cosmesis, and reoperations. This study analyzes its incidence and risk factors in a more modern treatment era. METHODS: Patients undergoing mastectomy with implant reconstruction from 2010 to 18 were reviewed. Univariate and multivariate analysis evaluated rates and risk factors for capsular contracture. RESULTS: Among 451 patients, the majority underwent nipple-sparing mastectomy (262, 58.1%) with one-stage reconstruction (283, 62.7%) utilizing subpectoral implants (353, 77.4%) and acellular dermal matrix (354, 78.5%). Overall capsular contracture incidence was 9.8%; the rate after post-mastectomy radiation therapy (PMRT) was 18.7%, and 7.5% for patients without PMRT. Significant factors included neoadjuvant chemotherapy (P = 0.006), hematoma (P = 0.047), and PMRT (P = 0.001). Multivariate analysis showed that PMRT increased risk of capsular contracture (OR = 3.12, 95% CI 1.55-6.26, P = 0.001), and adjuvant chemotherapy was protective (OR = 0.289, 95% CI 0.114-0.731, P = 0.01). CONCLUSIONS: Incidence of capsular contracture is lower than previously reported. Advancing therapeutic techniques may reduce the risk of this complication.

5.
Am J Surg ; 220(6): 1422-1427, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32921402

RESUMO

BACKGROUND: Ramifications of postoperative complications on long-term survival after mastectomy are uncertain. METHODS: Overall complications (Clavien-Dindo Grades I-IIIB) and wound complications were analyzed using the Kaplan-Meier method for impact on 5-year overall (OS) and disease-free survival (DFS). RESULTS: A total of 378 patients underwent mastectomy alone (157, 41%) or mastectomy with reconstruction (221, 59%) for Stage I-III disease with a median follow-up of 5 years. Postoperative complications occurred in 186 patients (49%), requiring non-surgical (I/II = 83, 22%) or surgical (IIIa/IIIb = 103, 27%) management. Wound complications occurred in 140 patients (37%). Reconstruction was associated with a higher rate of complication (P < 0.001). Postoperative complications after mastectomy (with or without reconstruction) did not significantly affect OS or DFS. Wound complications also showed no significant effect on OS or DFS following mastectomy alone, or mastectomy with reconstruction. CONCLUSIONS: Postoperative complications after mastectomy, with or without reconstruction, bear no significant impact on 5-year survival.

6.
Cancer ; 126(24): 5239-5246, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931029

RESUMO

BACKGROUND: The goal of this study was to assess the impact of trastuzumab on locoregional failure. METHODS: The analysis included 2763 patients with HER2-positive (HER2+) breast cancer who were randomly assigned to adjuvant doxorubicin (A), cyclophosphamide (C), paclitaxel (T) and trastuzumab (H) (arm A, AC→T [n = 922]; arm B, AC→T→H [n = 988]; arm C, AC→T+H→H [n = 853]). Radiotherapy was given after AC→T concurrently with H. Radiotherapy was given after lumpectomy (L) or after mastectomy (M) with ≥4 positive lymph nodes but was optional for 1 to 3 positive lymph nodes. Locoregional failures at 10 years (LFR10) as first events were compared using competing risk analysis. RESULTS: The median follow-up was 13.0 years. The first site of failure was local-only in 96 cases, locoregional in 16 cases, regional in 32 cases, and not specified in 2 cases; LFR10 was 4.8% (95% CI 4.1%-5.7%). LFR10 was 5.5% (95% CI 4.3%-7.2%), 4.9% (95% CI 3.7%-6.4%), and 2.8% (95% CI 1.9%-4.1%) in arms A, B, and C (B vs A: hazard ratio [HR] 0.91, P = .62; C vs A: HR 0.72, P = .12). For estrogen receptor-positive patients, LFR10 was 3.7% (95% CI 2.8%-4.8%) and for estrogen receptor-negative patients, it was 6.1% (95% CI 5.0%-7.4%; HR 0.61, P = .004). Local treatment included L+RT (n = 1044 [38%]), M+RT (n = 1025 [37%]), and M (n = 694 [25%]). LFR10 was 6.% (95% CI 5.0%-7.8%), 3.0% (95% CI 2.1%-4.3%), and 5.5% (95% CI 4.0%-7.4%) for L+RT, M+RT, and M, respectively (M+RT vs L+RT: HR 0.43, P < .001; M vs L+RT: HR 0.88, P = .57). For 1 to 3 positive lymph nodes, LFR10 was 6.5% (95% CI 4.8%-8.9%), 4.1% (95% CI 2.4%-7.0%), and 4.3% (95% CI 2.9%-6.5%) in L+RT, M+RT, and M, respectively (M vs L+RT: HR 0.68, P = .14; M vs M+RT: HR 1.2, P = .6). CONCLUSION: Low 10-year LFRs were seen regardless of trastuzumab use. Differences in local therapy in patients with 1 to 3 positive lymph nodes did not appear to improve local control. Local therapy studies for HER2+ and other tumor characteristics are important as the role of local therapies continues to evolve.

8.
Surgery ; 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32814633

RESUMO

BACKGROUND: Thyroid nodules discovered incidentally during transplant may prolong time to transplantation. Although data suggest that incidence of thyroid cancer increases after solid organ transplantation, the impact on prognosis in differentiated thyroid cancer is not well characterized. METHODS: We performed a retrospective review of patients with history of thyroid cancer and solid organ transplantation at our institution. RESULTS: A total of 13,037 patients underwent solid organ transplantation of which there were 94 patients with differentiated thyroid cancer (0.7%). Of these, 50 patients (53%) had cancer pre-solid organ transplantation, whereas 44 patients (47%) developed cancer post-solid organ transplantation. Papillary histology was most common (88%), followed by follicular (3%), Hurthle cell (3%), and medullary (2%) carcinomas. One patient in the post-transplant cohort died from metastatic thyroid cancer 11.8 years after transplantation. There were 5 patients in the pre-transplant group and 4 patients in the post-transplant group who had recurrent thyroid disease. There were no patients treated for differentiated thyroid cancer pre-solid organ transplantation that experienced disease recurrence after transplantation. Disease-free survival at 5 and 10 years was 95.8% and 92.1% (confidence interval 84.9-99.2%, 80.0-97.4%) in the pre-solid organ transplantation group vs 89.7% and 84.4% in the post (confidence interval: 80.0-96.3% and 79.0-93.1%, P = .363), respectively. CONCLUSION: Survival outcomes and recurrence rates in patients with thyroid cancer are not significantly affected by solid organ transplantation. A history of thyroid cancer or discovery of thyroid nodules during transplant screening should not be a contraindication for transplant listing.

9.
Surgery ; 168(3): 518-526, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32669204

RESUMO

BACKGROUND: It is unknown whether all thick melanomas share the same prognostic features. We present a large, multi-institutional study on thick melanoma, evaluating for factors prognostic of survival. METHODS: We queried the database of the Sentinel Lymph Node Working Group for patients with thick melanoma (>4 mm) who had a sentinel lymph node biopsy from 1993 to 2018. Clinicopathologic characteristics were correlated with overall survival. RESULTS: There were 1,235 patients with a median follow-up of 28 months. Median thickness was 5.9 mm, with 713, 356, and 166 cases having a thickness of >4 to 6, >6 to 10, and >10 mm, respectively. Ulceration was seen in 51.2% of cases, while sentinel lymph node metastases were seen in 439 of 1,235 (35.5%) cases. For melanomas >4 to 6 mm, age, thickness, ulceration, lymphovascular invasion, and sentinel lymph node metastasis were correlated with overall survival (all P < .05), but for melanomas >6 to 10 mm, only sex and sentinel lymph node metastasis were prognostic of overall survival (both P < .05). For melanomas >10 mm, only sentinel lymph node metastasis predicted overall survival on multivariable analyses (P < .05). CONCLUSION: Prognostic markers of overall survival for thick melanoma include thickness, ulceration, and sentinel lymph node metastasis, but also include other unique factors such as lymphovascular invasion. Moreover, certain prognostic markers for survival are associated with different subgroups of thick melanoma, which vary based on thickness group.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Melanoma/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/mortalidade , Pele/patologia , Idoso , Vasos Sanguíneos/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral
10.
Sci Rep ; 10(1): 12190, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699259

RESUMO

Lynch syndrome (LS) arises in patients with pathogenic germline variants in DNA mismatch repair genes. LS is the most common inherited cancer predisposition condition and confers an elevated lifetime risk of multiple cancers notably colorectal and endometrial carcinomas. A distinguishing feature of LS associated tumors is accumulation of variants targeting microsatellite repeats and the potential for high tumor specific neoepitope levels. Recurrent somatic variants targeting a small subset of genes have been identified in tumors with microsatellite instability. Notably these include frameshifts that can activate immune responses and provide vaccine targets to affect the lifetime cancer risk associated with LS. However the presence and persistence of targeted neoepitopes across multiple tumors in single LS patients has not been rigorously studied. Here we profiled the genomic landscapes of five distinct treatment naïve tumors, a papillary transitional cell renal cell carcinoma, a duodenal carcinoma, two metachronous colorectal carcinomas, and multi-regional sampling in a triple-negative breast tumor, arising in a LS patient over 10 years. Our analyses suggest each tumor evolves a unique complement of variants and that vaccines based on potential neoepitopes from one tissue may not be effective across all tumors that can arise during the lifetime of LS patients.

11.
J Surg Oncol ; 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506815

RESUMO

BACKGROUND AND OBJECTIVES: Neoadjuvant endocrine therapy (NET) for ER+ breast cancer can downstage primary tumors. We evaluated NET efficacy in node-positive patients. METHODS: Node-positive patients undergoing NET for ER+ breast cancer from 2012 to 2019 were reviewed. Primary endpoints included rates of axillary lymphadenectomy (ALND), pathologic complete response (pCR), and final nodal staging. RESULTS: Thirty-nine patients were included. Before NET, all were clinically node-positive (cN1 = 36, 94%; cN2 = 2, 5%; cN3 = 1, 3%; Stage II = 23, 59%, Stage III = 16, 41%). After NET, nine (23%) had clinically persistent axillary disease necessitating ALND. The remaining 30 (77%) underwent sentinel lymph node biopsy (SLNB). Of these, 25 (83%) were SLNB+ on frozen section, undergoing immediate ALND. Five patients were negative on frozen section: one had a confirmed axillary pCR, and four had residual nodal disease on permanent pathology. One underwent delayed ALND, and for the remaining three patients, decision was made to forgo ALND. Final overall axillary staging was: N0 (pCR) = 1, 3%, pN1mic = 1, 3%, pN1 = 20, 51%, pN2 = 12, 30%, pN3 = 5, 13%; Stage II = 16, 41%, Stage III = 23, 59%. CONCLUSIONS: While NET is reported to downstage primary tumors, downstaging of the axilla was unsuccessful in the majority of patients.

12.
Plast Surg (Oakv) ; 28(2): 117-126, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32596187

RESUMO

Worldwide, millions of women live with breast implants. Therefore, it is important that physicians be aware of an uncommon but possibly serious complication arising from breast implants: breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Breast implant-associated anaplastic large-cell lymphoma most commonly presents as a delayed fluid collection around a textured breast implant or as a mass in the capsule surrounding the implant. The exact pathogenesis of the disease remains unclear. The neoplastic cells of BIA-ALCL show strong uniform staining for CD30 and are consistently negative for activin receptor-like kinase 1. Patients with confirmed cases should be referred to a lymphoma specialist or breast medical oncologist for a complete oncologic evaluation before any surgical intervention. For disease confined to the fluid accumulation or capsule, or both, surgical removal of the implant and complete capsulectomy is the preferred treatment. Postoperative chemotherapy or radiation, or both, are not considered necessary for patients with limited-stage disease and are reserved for advanced disease stages. Generally, BIA-ALCL is a local disease that follows an indolent course and has an excellent prognosis. Although complete remission of disease has occurred in patients with BIA-ALCL, median overall survival is reduced. As of March 2018, approximately 529 unique, confirmed BIA-ALCL cases had been reported in 23 countries. To date, 16 patients have died from BIA-ALCL, and all had extracapsular involvement. The aim of this article is to summarize the diagnosis, evaluation, and management of BIA-ALCL, based on established guidelines, for all practitioners who may care for patients with breast implants.

13.
Ann Surg Oncol ; 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32524460

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for intermediate thickness melanoma, but for thick melanoma, guidelines are less definitive about the use of SLNB in this population. We present a study on thick melanoma evaluating for prognostic factors. PATIENTS AND METHODS: The Sentinel Lymph Node Working Group database was queried for thick (> 4 mm) melanoma cases that had a SLNB from 1993 to 2018. Clinicopathologic characteristics were correlated with SLN status and melanoma-specific survival (MSS). RESULTS: There were 1235 patients. Median follow-up was 28 months. Median thickness was 5.9 mm, with 956, 175, and 104 cases presenting thickness > 4-8, > 8-12, and > 12 mm, respectively. SLN metastases were seen in 439 of 1235 (35.5%) cases and in 33.9%, 40.6%, and 42.3% of melanomas > 4-8, > 8-12, and > 12 mm, respectively. In each thickness group, MSS was significantly worse for SLN-positive compared with SLN-negative cases (all P < 0.005). Multivariable analysis showed that SLN metastasis, male gender, increasing thickness, lymphovascular invasion, and microsatellitosis significantly predicted worse MSS for melanomas > 4-8 mm, with SLN metastasis showing the greatest risk (HR 2.17, 95% CI 1.64-2.87, P < 0.0001). For melanomas > 8 mm, only SLN metastasis significantly predicted MSS (> 8-12 mm: HR 3.93, 95% CI 2.00-7.73, P < 0.0001; > 12 mm: HR 3.58, 95% CI 1.56-8.22, p < 0.0027). CONCLUSIONS: Thick melanoma patients with SLN metastasis have significantly worse MSS compared with SLN-negative patients, even in the thickest cases, and SLN status is the most powerful and/or only predictor of MSS. Given these results, SLNB shows important prognostic value in this population and is indicated for clinically localized thick melanoma.

14.
JCO Precis Oncol ; 4: 319-334, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32405608

RESUMO

Purpose: More than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here we describe a model that combines clinicopathologic and molecular variables to identify patients with thin and intermediate thickness melanomas who may forgo the SLN biopsy procedure due to their low risk of nodal metastasis. Patients and Methods: Genes with functional roles in melanoma metastasis were discovered by analysis of next generation sequencing data and case control studies. We then used PCR to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin and intermediate thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross validation scheme to predict the presence of SLN metastasis from molecular, clinical and histologic variables. Results: Expression of genes with roles in epithelial-to-mesenchymal transition (glia derived nexin, growth differentiation factor 15, integrin ß3, interleukin 8, lysyl oxidase homolog 4, TGFß receptor type 1 and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model which included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age; AUC, 0.82; 95% CI, 0.78-0.86; SLN biopsy reduction rate of 42% at a negative predictive value of 96%. Conclusion: A combined model including clinicopathologic and gene expression variables improved the identification of melanoma patients who may forgo the SLN biopsy procedure due to their low risk of nodal metastasis.

16.
Pancreas ; 49(4): 568-573, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32282771

RESUMO

OBJECTIVES: We compared risk-adjusted short- and long-term outcomes between standard pancreaticoduodenectomy (SPD) and a pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The National Cancer Database was queried for the years 2004 to 2014 to identify patients with adenocarcinoma of the pancreatic head undergoing SPD and PPD. Margin status, lymph node yield, length of stay (LOS), 30- and 90-day mortality, and overall survival were compared. RESULTS: A total of 11,172 patients were identified, of whom 9332 (83.5%) underwent SPD and 1840 (16.5%) PPPD. There was no difference in patient age, sex, stage, tumor grade, radiation treatment, and chemotherapy treatment between the 2 groups. Total number of regional lymph nodes was examined, and surgical margin status and overall survival were also comparable. However, patients undergoing PPPD had a shorter LOS (11.3 vs 12.3 days, P < 0.001), lower 30-day mortality (2.5% vs 3.7%, P = 0.02), and 90-day mortality (5.5% vs 6.9%, P = 0.03). On multivariate analyses, patients undergoing SPD were at higher risk for 30-day mortality compared with PPPD (odds ratio, 1.51; 95% confidence interval, 1.07-2.13). CONCLUSIONS: Standard pancreaticoduodenectomy and PPPD are oncologically equivalent, yet PPPD is associated with a reduction in postoperative mortality and shorter LOS.

18.
Ann Surg Oncol ; 27(9): 3436-3445, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32221736

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS®) principles have been beneficial in major abdominal surgery. ERAS® was instituted in our breast surgery practice in 2017. The goal of this study was to evaluate the feasibility of outpatient mastectomies before and after ERAS®. METHODS: A retrospective review of all mastectomies between 1/2013 and 6/2018 was performed. Patients receiving autologous flap reconstruction were excluded. The institution-specific ERAS® pathway began on February 1, 2017. Patient characteristics, operative intervention, and postoperative outcomes were compared between pre-ERAS® and post-ERAS® groups and between outpatient and inpatient subgroups. Continuous and categorical variables were compared using Wilcoxon rank-sum and Chi-square analyses. RESULTS: A total of 487 patients were analyzed. Three hundred and forty-seven (71%) were prior to ERAS® and 140 after (29%). The two groups were not significantly different in background characteristics. Same-day discharge occurred in 58.6% of post-ERAS® patients versus 7.2% of pre-ERAS® patients (p < 0.001). Liposomal bupivacaine block was used for pain control more in the post-ERAS® group, 62.1% versus 6.1% (p < 0.001). Reconstruction type differed with 45.7% of the post-ERAS® group undergoing direct-to-implant reconstruction versus 34.3% of pre-ERAS® patients (p < 0.001) and with higher rates of submuscular implant and tissue expander placement in the pre-ERAS® versus post-ERAS® group (p < 0.001). Complications rates were lower in the post-ERAS® group versus pre-ERAS® group, 32.9% versus 52.4% (p < 0.001). The outpatient subgroup had higher rates of liposomal bupivacaine administration 74.4% versus 44.8% (p < 0.001). Baseline characteristics and complication rates did not differ between outpatient and admitted subgroups. CONCLUSION: ERAS® principles can be applied to breast cancer patients and allow for outpatient mastectomies with no increase in postoperative morbidity.

19.
Support Care Cancer ; 28(5): 2139-2143, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31402403

RESUMO

PURPOSE: Survivors of estrogen receptor-expressing breast cancer generally do not receive estrogen-based therapy for menopausal symptoms due to concern for provoking recurrence of disease. Single-dose depomedroxyprogesterone acetate has been shown to be among the most effective non-estrogen strategies for treatment of menopausal hot flashes, but long-term evidence for safety in survivors is lacking. METHODS: We conducted an institutional review board approved, retrospective, case-control cohort study at a tertiary, academic referral center. Patients with estrogen receptor-expressing early-stage operable breast cancer who received depomedroxyprogesterone acetate for hot flashes between January 2005 and December 2012 were identified. We confirmed 75 patients who met strict inclusion criteria who were matched 1:1 with controls for age, stage of disease, HER2 status, and year of diagnosis. Overall survival, loco-regional recurrence-free survival, and progression-free survival assessments for cases were compared with controls. RESULTS: Median follow-up duration was 68.4 months in cases and 57.6 months in controls. Estimated local-regional recurrence-free survival at 10 years was 97% (95% CI, 92-100%) in cases and 98% (95% CI, 95-100%) in controls. Estimated progression-free survival at 10 years was 89% (95% CI, 80-100%) in cases and 83% (95% CI, 73-95) in controls. The majority (75%) of case patients experienced satisfactory relief of hot flashes from depomedroxyprogesterone injection. DISCUSSION: In this retrospective case-control study, we were unable to identify a detrimental effect of depomedroxyprogesterone acetate therapy for hot flashes in survivors of estrogen receptor-expressing breast cancer. Depomedroxyprogesterone acetate may be acceptable for management of hot flashes in this population.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Contraceptivos Hormonais/uso terapêutico , Fogachos/tratamento farmacológico , Acetato de Medroxiprogesterona/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Estudos de Casos e Controles , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão , Estudos Retrospectivos
20.
Appl Immunohistochem Mol Morphol ; 28(9): 661-668, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31517642

RESUMO

The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells' expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non-small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.

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