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1.
Ann Surg Oncol ; 30(2): 1017-1025, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36161375

RESUMEN

BACKGROUND: The American Society of Breast Surgeons recommends genetic testing (GT) for all women with breast cancer (BC), but implementation and uptake of GT has not been well-described. METHODS: A retrospective chart review was performed for newly diagnosed BC patients or patients with a newly identified recurrence of BC seen in a multidisciplinary clinic (MDBC) who were offered genetic counseling (GC) and GT. RESULTS: The 138 women attending the MDBC had a median age of 54 years and comprised non-Hispanic whites (46%), Asians (28%), Hispanics (17%), blacks (4%), and other (5%). Of the 105 (76%) patients without prior GT, 100 (95%) accepted GC, with 93 (93%) of these 100 patients undergoing GT. The patients meeting the National Comprehensive Cancer Network (NCCN) guidelines for GT were more likely to undergo GT. Testing was performed with a 67- to 84-gene panel, together with an 8- to 9-gene STAT panel if needed. Among 120 patients with reports available, including 33 patients previously tested, 15 (12%) were positive (1 BLM, 1 BRCA1, 3 BRCA2, 1 BRIP1, 1 CFTR, 1 CHEK2, 1 MUTYH, 1 PALB2, 1 PRSS1, 1 RAD50, 1 RET, and 2 TP53), 44 (37%) were negative, and 61 (51%) had an uncertain variant. The median time to STAT results (n = 50) was 8 days. The STAT results were available before surgery for 47 (98%) of the 48 STAT patients undergoing surgery. CONCLUSIONS: New BC patients attending the MDBC demonstrated high rates of acceptance of GC and GT. The combination of GC and GT can offer timely information critical to patient risk assessment and treatment planning.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico , Estudios Retrospectivos , Pruebas Genéticas/métodos , Genes BRCA2 , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal
2.
J Surg Oncol ; 128(1): 9-15, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36933187

RESUMEN

BACKGROUND: Although sentinel lymph node dissection (SLND) after neoadjuvant chemotherapy (NAC) is feasible, axillary management for patients with pretreatment biopsy-proven axillary metastases and who are clinically node-negative after NAC (ycN0) remains unclear. This retrospective study was performed to determine the rate of axillary lymph node recurrence for such patients who had wire-directed (WD) SLND. METHODS: Patients treated with NAC from 2015 to 2020 had axillary nodes evaluated by pretreatment ultrasound. Core biopsies were done on abnormal nodes, and microclips were placed in nodes during biopsy. For patients with biopsy-proven node metastases who received NAC and were ycN0 by clinical exam, WD SLND was done. Patients with negative nodes on frozen section had WD SLND alone; those with positive nodes had WD SLND plus axillary lymph node dissection (ALND). RESULTS: Of 179 patients receiving NAC, 62 were biopsy-proven node-positive pre-NAC and ycN0 post-NAC. Thirty-five (56%) patients were node-negative on frozen section and had WD SLND alone. Twenty-seven (43%) patients had WD SLND + ALND. Forty-seven patients had postoperative regional node irradiation. With median follow-up of 40 months, there were recurrences in 4 (11%) of 35 patients having WD SLND and 5 (19%) of 27 having WD SLND + ALND, but there was only one axillary lymph node recurrence, identified by CT scan. CONCLUSIONS: Axillary node recurrence was very uncommon after WD SLND for patients who had pretreatment biopsy-proven node metastases and were ypN0 after NAC. These patients would be unlikely to derive clinical benefit from the addition of completion ALND to SLND.


Asunto(s)
Neoplasias de la Mama , Ganglio Linfático Centinela , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/etiología , Terapia Neoadyuvante , Estudios Retrospectivos , Escisión del Ganglio Linfático/efectos adversos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Biopsia del Ganglio Linfático Centinela , Axila/patología , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología
3.
Ann Surg ; 274(6): 1073-1080, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32427760

RESUMEN

OBJECTIVE: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy. BACKGROUND: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined. METHODS: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards. RESULTS: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS. CONCLUSIONS: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Metastasectomía/métodos , Neoplasias de las Glándulas Suprarrenales/mortalidad , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Estudios Retrospectivos , Tasa de Supervivencia , Estados Unidos
4.
J Surg Res ; 246: 139-144, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31569035

RESUMEN

BACKGROUND: Ex vivo aspiration of parathyroid glands for the measurement of intraoperative parathyroid hormone (IOPTH) levels is a rapid point-of-care method to confirm parathyroid tissue during parathyroidectomy and an alternative to frozen section (FS). This study sought to determine the awareness and utilization of this technique among endocrine surgeons. MATERIALS AND METHODS: A de-identified 12-question survey regarding techniques for intraoperative identification/confirmation of parathyroid tissue and the use of IOPTH monitoring was distributed to all 608 members of the American Association of Endocrine Surgeons. RESULTS: Among the 182 (30%) respondents, FS was the most common primary technique utilized by 115 (63%) respondents to confirm parathyroid tissue; only 12 (7%) utilized ex vivo aspiration, although 78 (42%) were familiar with the technique. Availability and familiarity were the principal reasons for use of the primary technique; the most common barrier was time. Serum IOPTH monitoring was routinely used by 124 (74%). Of respondents who utilized FS, serum IOPTH monitoring was routinely used by 75% (86/115), including 71% (45/63) who reported time as a barrier to FS. Of these 45, only 15 (33%) were familiar with ex vivo parathyroid aspiration. Only 48% of surgeons knew how PTH samples were charged. CONCLUSIONS: FS was the most common method of identification/confirmation of parathyroid tissue. Although most respondents routinely performed IOPTH monitoring, relatively few utilized ex vivo aspiration as a technique for parathyroid identification and less than 50% were familiar with this technique. Broader dissemination about novel techniques such as ex vivo aspiration and cost awareness are recommended.


Asunto(s)
Hiperparatiroidismo/cirugía , Cuidados Intraoperatorios/métodos , Monitoreo Intraoperatorio/métodos , Glándulas Paratiroides/patología , Paratiroidectomía/métodos , Biopsia con Aguja/estadística & datos numéricos , Competencia Clínica/estadística & datos numéricos , Secciones por Congelación/estadística & datos numéricos , Humanos , Cuidados Intraoperatorios/estadística & datos numéricos , Monitoreo Intraoperatorio/estadística & datos numéricos , Glándulas Paratiroides/cirugía , Hormona Paratiroidea/sangre , Paratiroidectomía/estadística & datos numéricos , Sistemas de Atención de Punto/estadística & datos numéricos , Cirujanos/estadística & datos numéricos , Encuestas y Cuestionarios/estadística & datos numéricos , Factores de Tiempo
5.
J Surg Res ; 246: 335-341, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31635835

RESUMEN

BACKGROUND: Persistent/recurrent hyperparathyroidism occurs in 2%-5% of patients with sporadic primary hyperparathyroidism (PHPT). In this study, the incidence and time to recurrence in patients with single-gland disease (SGD), double adenomas (DAs), or four-gland hyperplasia (FGH) at initial parathyroidectomy were compared. METHODS: This retrospective review included adult patients with sporadic PHPT who underwent initial parathyroidectomy with intraoperative parathyroid hormone monitoring (IOPTH) from 1/2000 to 12/2016 with ≥6 mo follow-up. An abnormal parathyroid was defined by a gland weight of ≥50 mg. A concurrent serum calcium >10.2 mg/dL and parathyroid hormone >40 pg/mL was defined as persistent PHPT if present <6 mo and recurrent PHPT if present ≥6 mo postoperatively after initial normocalcemia. RESULTS: Of 1486 patients, 1203 (81%) had SGD, 159 (11%) DA, and 124 (8%) FGH. Among the 3 groups, there was no difference in the percent decrease from the baseline or time of excision to final postexcision IOPTH levels between groups (79% versus 80% versus 80%, respectively; P = 0.954) or in the proportion of patients with a final IOPTH ≥40 (22% versus 18% versus 14%; P = 0.059). Overall, 22 (1.5%) had persistent PHPT and 26 (1.7%) had recurrent PHPT. Persistent PHPT was more frequent with DAs (6; 3.8%) than other groups (SGD: 16, 1.3%; FGH: 0; P = 0.02). At median follow-up of 33 mo (IQR, 18-60), there was no difference in recurrence rate (1.6% versus 2.5% versus 2.4%; P = 0.57) or median time (mo) to recurrence (SGD: 59 [IQR, 21-86], DAs: 36 [IQR, 29-58], FGH: 23 [IQR, 17-40]; P = 0.46). CONCLUSIONS: Recurrent PHPT occurred in 1.7% of patients who underwent curative initial parathyroidectomy, with no difference in incidence or time to recurrence between groups based on the number of glands removed. Patients with DA more commonly had persistent PHPT, raising the possibility of unrecognized FGH.


Asunto(s)
Adenoma/epidemiología , Hiperparatiroidismo Primario/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Glándulas Paratiroides/patología , Neoplasias de las Paratiroides/epidemiología , Adenoma/complicaciones , Adenoma/cirugía , Anciano , Femenino , Estudios de Seguimiento , Humanos , Hiperparatiroidismo Primario/etiología , Hiperparatiroidismo Primario/cirugía , Hiperplasia/complicaciones , Hiperplasia/cirugía , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/cirugía , Glándulas Paratiroides/cirugía , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/cirugía , Paratiroidectomía/métodos , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Tiempo
7.
J Surg Res ; 213: 138-146, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28601306

RESUMEN

BACKGROUND: Surgical resection remains the mainstay of treatment for patients with adrenocortical carcinoma (ACC). The aim of the present study is to examine disparities in access to surgical resection and identify factors associated with overall survival following surgical resection. METHODS: The National Cancer Database was queried for patients with ACC (2004-2013). Patient characteristics and disease details were abstracted. Logistic regression analysis was performed to examine the factors associated with surgical resection, and a multivariate Cox proportional hazards model was used to identify predictors of survival in the surgical cohort. RESULTS: Surgical resection was performed in 2007/2946 (68%) ACC patients. On multivariate logistic regression analysis controlling for clinicodemographic factors, surgery was less likely to be performed in patients ≥56 y, males, African-Americans, patients with government insurance, or those treated at community cancer centers (P < 0.05). On a multivariate Cox proportional hazards model adjusting for clinicodemographic and treatment variables, older age (≥56 y) and presence of comorbidities were associated with worse overall survival. CONCLUSIONS: These findings suggest that there are demographic and socioeconomic disparities in access to surgical resection for ACC. However, after adjusting for patient and clinical characteristics, only patient age and presence of comorbidities were predictors of worse survival in patients undergoing surgery for ACC. More data are needed to determine the factors driving these disparities.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/cirugía , Adrenalectomía , Carcinoma Corticosuprarrenal/cirugía , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Adolescente , Neoplasias de la Corteza Suprarrenal/economía , Neoplasias de la Corteza Suprarrenal/etnología , Neoplasias de la Corteza Suprarrenal/mortalidad , Adrenalectomía/economía , Carcinoma Corticosuprarrenal/economía , Carcinoma Corticosuprarrenal/etnología , Carcinoma Corticosuprarrenal/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Accesibilidad a los Servicios de Salud/economía , Disparidades en Atención de Salud/economía , Disparidades en Atención de Salud/etnología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Estados Unidos/epidemiología , Adulto Joven
8.
J Surg Res ; 209: 162-167, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28032553

RESUMEN

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) level monitoring is a useful adjunct to parathyroidectomy for primary hyperparathyroidism (pHPT). Occasionally, increases ("spikes") in IOPTH levels from the preoperative baseline parathyroid hormone may occur, which may lead to longer operative times or more extensive neck exploration or both. The aim of this study was to determine if the extent of IOPTH level increase predicts single gland disease (SGD). METHODS: This is a retrospective review of a prospective parathyroid database of patients undergoing parathyroidectomy for sporadic pHPT from 1999-2013. Extent of parathyroid hormone spike was calculated by the difference in IOPTH level at the time of gland excision and baseline: group 1 had a decrease in IOPTH level, group 2 had IOPTH level increase one to three times above the baseline, and group 3 had IOPTH level increase greater than three times above the baseline. RESULTS: Of the 900 patients in the cohort, there were 634 patients (70%) in group 1, 234 (26%) in group 2, and 32 (4%) in group 3. SGD was identified in 88%, 78%, and 100% of patients in groups 1, 2, and 3, respectively. The median gland weight in group 3 (920 mg) was significantly larger than those in groups 1 and 2 (440 and 460 mg, respectively; P < 0.001). CONCLUSIONS: IOPTH level spikes occur in nearly one-third of patients undergoing parathyroidectomy for sporadic pHPT. Patients with extensive IOPTH level increase are more likely to have larger SGD, whereas patients with moderate IOPTH level increases have increased incidence of multigland disease. In patients with a significant increase in IOPTH levels and larger glands, no further surgical exploration may be indicated.


Asunto(s)
Hiperparatiroidismo Primario/cirugía , Monitoreo Fisiológico/métodos , Hormona Paratiroidea/sangre , Paratiroidectomía , Adulto , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas , Femenino , Humanos , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Estudios Retrospectivos , Adulto Joven
9.
J Surg Res ; 211: 107-113, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28501106

RESUMEN

INRODUCTION: The number of endocrine procedures, specifically parathyroidectomy, thyroidectomy, and adrenalectomy, being performed is increasing. There is a paucity of literature on the feasibility of combining these procedures with other surgical procedures. Therefore, the aim of this study was to determine the effect of performing concurrent surgical procedures on postoperative outcomes. METHODS: This is a single institution retrospective review of multiple prospectively maintained databases of patients who underwent elective thyroidectomy, parathyroidectomy, and/or adrenalectomy in combination with another procedure. The other procedures included soft tissue, breast or hernia, abdominal major, abdominal minor, cervical, and "other". Demographics, operative details, length-of-stay, and 30-d outcomes were reviewed. "Endocrine-specific" complications included recurrent laryngeal nerve injury, hypoparathyroidism, cervical wound infection, hematoma, and other. RESULTS: The cohort comprised 104 patients. Overall, 19 (18%) patients had 21 complications, including endocrine-specific complications in eleven (11%) patients. These eleven complications included recurrent laryngeal nerve injury (n = 3; 3%), hematoma (n = 2; 2%), wound infection (n = 1; 1%), transient hypoparathyroidism (n = 2; 2%), and other (n = 3; 3%). The remaining complications included three (3%) general complications, six (6%) patients with complications related to the concurrent procedure, and one patient who underwent an open adrenalectomy and hysterectomy and developed a midline wound dehiscence, which could not be specifically attributed to either procedure. CONCLUSIONS: Less than 5% of patients undergoing a surgical endocrine procedure underwent a concurrent procedure, ranging from soft tissue to major abdominal. Short-term endocrine-specific complications were managed safely, suggesting that concurrent procedures can be considered, with minimal effect on patient outcomes.


Asunto(s)
Procedimientos Quirúrgicos Endocrinos , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Estudios de Factibilidad , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo
10.
Ann Surg Oncol ; 23(7): 2310-4, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27006125

RESUMEN

BACKGROUND: Following parathyroidectomy for primary hyperparathyroidism (pHPT), serum calcium levels typically normalize relatively quickly. The purpose of this study was to identify potential factors associated with delayed normalization of calcium levels despite meeting intraoperative parathyroid hormone (IOPTH) criteria and to determine whether this phenomenon is associated with higher rates of persistent pHPT. METHODS: This was a retrospective review of 554 patients who underwent parathyroidectomy for sporadic pHPT from January 2009 to July 2013. Patients who underwent presumed curative parathyroidectomy and had elevated POD0 calcium levels (>10.2 mg/dL) were matched 1:2 for age and gender to control patients with normal POD0 calcium levels. RESULTS: Of the 554 patients, 52 (9 %) had an elevated POD0 Ca (median 10.7, range 10.3-12.2). Compared with the control group, these patients had higher preoperative calcium (12 vs. 11.1, p < 0.001) and PTH (144 vs. 110 pg/mL, p = 0.004) levels and lower 25OH vitamin D levels (26 vs. 31 pg/mL; p = 0.024). Calcium normalization occurred in 64, 90, and 96 % of patients by postoperative days (POD) 1, 14, and 30, respectively. There was no difference in rates of single-gland disease or cure rates between the groups. CONCLUSIONS: After presumed curative parathyroidectomy, nearly 10 % of patients had transiently persistent hypercalcemia. Most of these patients had normal serum calcium levels within the first 2 weeks and did not have increased rates of persistent pHPT. Immediate postoperative calcium levels do not predict the presence of persistent pHPT, and these patients may not require more stringent follow-up.


Asunto(s)
Calcio/sangre , Hipercalcemia/sangre , Hiperparatiroidismo Primario/cirugía , Paratiroidectomía/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Hipercalcemia/etiología , Hipercalcemia/patología , Hiperparatiroidismo Primario/patología , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Periodo Posoperatorio , Pronóstico , Estudios Prospectivos , Recurrencia , Estudios Retrospectivos
11.
J Surg Res ; 202(1): 132-8, 2016 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-27083959

RESUMEN

INTRODUCTION: Multigland disease (MGD) accounts for 15% of sporadic primary hyperparathyroidism (pHPT). Several studies have reported a link between obesity and calcium metabolism (e.g., increased incidence of pHPT, higher levels of parathyroid hormone, lower vitamin D levels, and larger parathyroid glands). Obese patients have also been shown to require reoperation for persistent/recurrent pHPT more often than nonobese controls. We hypothesize that obese patients may have a higher prevalence of MGD. METHODS: This was a retrospective review of a prospectively collected parathyroid database that included adult patients with sporadic pHPT, who underwent initial parathyroidectomy between 1999 and 2013. Demographic, clinicopathologic, operative, and laboratory data were assessed for associations with MGD. RESULTS: Of 1305 consecutive patients, 200 (15%) had MGD. Median age was 59 y. Univariate analyses demonstrated that MGD was associated with age > 60 y, higher body mass index (BMI), history of lithium therapy, lower 24-h urine calcium excretion, higher serum alkaline phosphatase levels, and smaller size of the first excised parathyroid gland. On multivariate analyses, predictors of MGD were BMI 30-39.9 kg/m(2) (odds ratio [OR] 1.5; 95% confidence interval [CI] 1.2-2.5), BMI ≥ 40 kg/m(2) (OR 1.8; 95% CI 1.3-3.1), and smaller size of the first excised parathyroid (OR 0.7; 95% CI 0.6-0.8). CONCLUSIONS: This study demonstrates a higher incidence of MGD in obese and morbidly obese patients. Due to a higher risk of MGD, surgeons should have a lower threshold to perform bilateral exploration in obese patients, especially if the first excised parathyroid gland is relatively small.


Asunto(s)
Índice de Masa Corporal , Hiperparatiroidismo Primario/etiología , Obesidad/complicaciones , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Hiperparatiroidismo Primario/epidemiología , Hiperparatiroidismo Primario/cirugía , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Paratiroidectomía , Estudios Retrospectivos , Factores de Riesgo
12.
J Biol Chem ; 289(36): 25306-16, 2014 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-25037223

RESUMEN

The histone deacetylase inhibitor (HDACi) sodium butyrate promotes differentiation of colon cancer cells as evidenced by induced expression and enzyme activity of the differentiation marker intestinal alkaline phosphatase (ALPi). Screening of a panel of 33 colon cancer cell lines identified cell lines sensitive (42%) and resistant (58%) to butyrate induction of ALP activity. This differential sensitivity was similarly evident following treatment with the structurally distinct HDACi, MS-275. Resistant cell lines were significantly enriched for those harboring the CpG island methylator phenotype (p = 0.036, Chi square test), and resistant cell lines harbored methylation of the ALPi promoter, particularly of a CpG site within a critical KLF/Sp regulatory element required for butyrate induction of ALPi promoter activity. However, butyrate induction of an exogenous ALPi promoter-reporter paralleled up-regulation of endogenous ALPi expression across the cell lines, suggesting the presence or absence of a key transcriptional regulator is the major determinant of ALPi induction. Through microarray profiling of sensitive and resistant cell lines, we identified KLF5 to be both basally more highly expressed as well as preferentially induced by butyrate in sensitive cell lines. KLF5 overexpression induced ALPi promoter-reporter activity in resistant cell lines, KLF5 knockdown attenuated butyrate induction of ALPi expression in sensitive lines, and butyrate selectively enhanced KLF5 binding to the ALPi promoter in sensitive cells. These findings demonstrate that butyrate induction of the cell differentiation marker ALPi is mediated through KLF5 and identifies subsets of colon cancer cell lines responsive and refractory to this effect.


Asunto(s)
Fosfatasa Alcalina/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Epiteliales/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Factores de Transcripción de Tipo Kruppel/metabolismo , Fosfatasa Alcalina/genética , Benzamidas/farmacología , Sitios de Unión/genética , Western Blotting , Ácido Butírico/farmacología , Diferenciación Celular/genética , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Islas de CpG/genética , Metilación de ADN , Resistencia a Antineoplásicos/genética , Perfilación de la Expresión Génica , Células HCT116 , Células HT29 , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Regiones Promotoras Genéticas/genética , Unión Proteica , Piridinas/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
13.
Am J Pathol ; 180(4): 1509-21, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22349300

RESUMEN

Colorectal cancers (CRCs) are classified as having microsatellite instability (MSI) or chromosomal instability (CIN); herein termed microsatellite stable (MSS). MSI colon cancers frequently display a poorly differentiated histology for which the molecular basis is not well understood. Gene expression and immunohistochemical profiling of MSS and MSI CRC cell lines and tumors revealed significant down-regulation of the intestinal-specific cytoskeletal protein villin in MSI colon cancer, with complete absence in 62% and 17% of MSI cell lines and tumors, respectively. Investigation of 577 CRCs linked loss of villin expression to poorly differentiated histology in MSI and MSS tumors. Furthermore, mislocalization of villin from the membrane was prognostic for poorer outcome in MSS patients. Loss of villin expression was not due to coding sequence mutations, epigenetic inactivation, or promoter mutation. Conversely, in transient transfection assays villin promoter activity reflected endogenous villin expression, suggesting transcriptional control. A screen of gut-specific transcription factors revealed a significant correlation between expression of villin and the homeobox transcription factor Cdx-1. Cdx-1 overexpression induced villin promoter activity, Cdx-1 knockdown down-regulated endogenous villin expression, and deletion of a key Cdx-binding site within the villin promoter attenuated promoter activity. Loss of Cdx-1 expression in CRC lines was associated with Cdx-1 promoter methylation. These findings demonstrate that loss of villin expression due to Cdx-1 loss is a feature of poorly differentiated CRCs.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Proteínas de Microfilamentos/metabolismo , Animales , Biomarcadores de Tumor/genética , Diferenciación Celular/fisiología , Membrana Celular/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Metilación de ADN/genética , ADN de Neoplasias/genética , Regulación hacia Abajo , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Humanos , Estimación de Kaplan-Meier , Ratones , Ratones SCID , Proteínas de Microfilamentos/genética , Inestabilidad de Microsatélites , Repeticiones de Microsatélite , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Trasplante de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Pronóstico , Regiones Promotoras Genéticas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Células Tumorales Cultivadas
14.
Am J Surg ; 223(3): 539-542, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34801227

RESUMEN

BACKGROUND: This study was designed to assess prognostic factors associated with relapse-free survival (RFS) after neoadjuvant chemotherapy (NAC) for breast cancer. METHODS: A single-institution retrospective analysis was performed including clinical, radiographic, and pathologic parameters for all breast cancer patients treated with NAC from 2015 to 2018. All patients had pre-and post-NAC MRI. RESULTS: For 102 patients, median follow-up was 47.4 months, and the five-year RFS was 74%. The 41 (40%) patients who achieved pathologic complete response (pCR) after NAC had a significantly higher five-year RFS than the 61 not achieving pCR. For 31 patients with triple-negative cancers, the five-year RFS was significantly higher in those achieving pCR vs. no pCR. The 44 (43%) patients who achieved radiographic complete response (rCR) after NAC had similar five-year RFS to the 58 (57%) not achieving rCR. CONCLUSION: pCR, node-negativity after NAC, and triple-negative subtype were prognostic factors associated with relapse-free survival after NAC.


Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos
16.
Surgery ; 164(4): 746-753, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30072256

RESUMEN

BACKGROUND: An institutional protocol for selective calcium/calcitriol supplementation after completion/total thyroidectomy was established based on the 4-hour postoperative parathyroid hormone level. The aim of this study was to evaluate the outcomes of this protocol 5 years after implementation. METHODS: All patients who underwent completion/total thyroidectomy from January 2012 to December 2016 were reviewed. Predictors of a 4-hour parathyroid hormone level <10 pg/mL and symptomatic hypocalcemia were assessed. RESULTS: Of 591 patients, 448 (76%) had a 4-hour parathyroid hormone ≥10, 72 (12%) had a 4-hour parathyroid hormone of 5-10, and 71 (12%) had a 4-hour parathyroid hormone <5. Hypocalcemic symptoms were infrequent (30/448, 7%) if the 4-hour parathyroid hormone was ≥10; 56% (40/71) of those with a 4-hour parathyroid hormone <5 reported symptoms. With 4-hour parathyroid hormone of 5-10, symptoms were reported in 32 of 72 (44%) patients; supplementation at discharge included calcium (n = 55, 76%), calcium and calcitriol (n = 12, 17%), or none (n = 5, 7%). Ten patients subsequently received calcitriol for persistent symptoms. On multivariate analysis, predictors of 4-hour parathyroid hormone <10 included incidental parathyroidectomy, malignancy, and thyroiditis; predictors of hypocalcemic symptoms included age <55 and 4-hour parathyroid hormone <10. CONCLUSION: After completion/total thyroidectomy, patients with a 4-hour parathyroid hormone ≥10 can be safely discharged without routine supplementation. The addition of calcitriol to calcium supplementation should be strongly considered for patients with a 4-hour parathyroid hormone of 5-10.


Asunto(s)
Algoritmos , Hipocalcemia/etiología , Hipocalcemia/prevención & control , Hormona Paratiroidea/sangre , Complicaciones Posoperatorias/etiología , Tiroidectomía/efectos adversos , Adulto , Calcitriol/uso terapéutico , Calcio/uso terapéutico , Hormonas y Agentes Reguladores de Calcio/uso terapéutico , Femenino , Humanos , Hipocalcemia/diagnóstico , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos
17.
Thyroid ; 28(11): 1462-1467, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30215297

RESUMEN

BACKGROUND: Previous studies have suggested that oncocytic variant papillary thyroid carcinoma (PTC) may be more aggressive, with higher rates of recurrent disease. The aim of this study was to evaluate characteristics and outcomes of patients with oncocytic variant PTC compared to classical PTC. METHODS: Patients with oncocytic variant PTC were retrospectively identified from 519 patients who underwent thyroidectomy for PTC between January 2009 and August 2015. Data collected included patient demographics, laboratory and pathology findings, imaging studies, treatment, and follow-up. Patients were matched 1:1 by age, sex, and TNM stage with patients who underwent total thyroidectomy for classical PTC during the same time period. RESULTS: The cohort included 21 patients, of whom 18 (86%) were female, with a median age of 53 years (range 23-68 years). All patients underwent total thyroidectomy, and 17 (81%) had a central compartment neck dissection (8 [38%] prophylactic). The median tumor size was 2.0 cm (range 0.9-6.5 cm), and four (19%) patients had extrathyroidal extension. There was no significant difference in histopathologic characteristics, including extrathyroidal extension and lymphovascular invasion, between the two groups except for an increased incidence of thyroiditis in oncocytic variant PTC (90.5% vs. 57%; p = 0.01). In oncocytic variant PTC patients who underwent central compartment neck dissection, malignant lymph nodes were found in 12 (57%) patients compared to 13 (62%) classical (p = 0.75). Lateral neck dissection was performed in 5 (24%) oncocytic variant and classical PTC patients, with metastatic lymphadenopathy found in four (a median of four malignant lymph nodes; range 1-6) and five (a median of 2.5 malignant lymph nodes; range 1-9), respectively. Radioactive iodine was administered to 18 (86%) oncocytic variant PTC and 18 (86%) classical PTC patients. At a median follow-up of 51 months (interquartile range 38-61), one oncocytic variant PTC patient had recurrent disease and underwent reoperation at 24 months. In classical PTC patients with a median follow-up time of 77 months (range 56-87 months), two (9.5%) patients had detectable thyroglobulin levels indicating early recurrence, but neither has undergone reoperation. CONCLUSIONS: Oncocytic variant PTC was present in 5% of PTC patients. Most (95%) patients remain disease-free at four years, similar to classical PTC outcomes, suggesting that oncocytic variant may not represent a more aggressive variant.


Asunto(s)
Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Femenino , Humanos , Cooperación Internacional , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adulto Joven
18.
Surgery ; 161(1): 25-34, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27865592

RESUMEN

BACKGROUND: This prospective survey study assessed changes in sleep quality in patients with primary hyperparathyroidism after parathyroidectomy. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism (n = 110) or thyroidectomy for benign euthyroid disease (control group; n = 45) were recruited between June 2013 and June 2015 and completed the Pittsburgh Sleep Quality Index preoperatively and at 1- and 6 months postoperatively. "Poor" sleep quality was defined as a score >5; a clinically important and relevant improvement was a ≥3-point decrease. RESULTS: Preoperatively, parathyroid patients had worse sleep quality than thyroid patients (mean 8.1 vs 5.3; P < .001); 76 (69%) parathyroid and 23 (51%) thyroid patients reported poor sleep quality (P = .03). Postoperatively, only parathyroid patients demonstrated improvement in sleep quality; mean scores did not differ between the parathyroid and thyroid groups at 1 month (6.3 vs 5.3; P = .12) or 6 months (5.8 vs 4.6; P = .11). The proportion of patients with a clinically important improvement in sleep quality was greater in the parathyroid group at 1 month (37% vs 10%; P < .001) and 6 months (40% vs 17%; P = .01). Importantly, there was no difference in the proportion of patients with poor sleep quality between the 2 groups at 1 month (50% vs 40%; P = .32) and 6 months (40% vs 29%; P = .22). CONCLUSION: More than two-thirds of patients with primary hyperparathyroidism report poor sleep quality. After parathyroidectomy, over one-third experienced improvement, typically within the first month postoperatively.


Asunto(s)
Hiperparatiroidismo Primario/cirugía , Paratiroidectomía/métodos , Calidad de Vida , Trastornos del Sueño-Vigilia/prevención & control , Sueño/fisiología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/diagnóstico , Masculino , Persona de Mediana Edad , Polisomnografía/métodos , Periodo Posoperatorio , Estudios Prospectivos , Valores de Referencia , Índice de Severidad de la Enfermedad , Trastornos del Sueño-Vigilia/etiología , Tiroidectomía/métodos
19.
Surg Oncol Clin N Am ; 25(1): 139-52, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26610779

RESUMEN

Minimally invasive adrenalectomy has become the gold standard for removal of benign adrenal tumors. The imaging characteristics, biochemical evaluation, and patient selection for laparoscopic transabdominal and posterior retroperitoneoscopic approaches are discussed with details of surgical technique for both procedures.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Laparoscopía/métodos , Humanos
20.
Surgery ; 159(1): 259-65, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26422766

RESUMEN

BACKGROUND: Secondary adrenal insufficiency (AI) can occur after unilateral adrenalectomy for adrenal-dependent hypercortisolism. Postoperative glucocorticoid replacement (GR), although given routinely, may not be necessary. We sought to identify factors that, in combination with postoperative day 1 cosyntropin stimulation testing (POD1-CST), would predict the need for GR. METHODS: We reviewed 31 consecutive patients who underwent unilateral adrenalectomy for hypercortisolism (study patients) or hyperaldosteronism (control patients). A standard POD1-CST protocol was used. Hydrocortisone was started for clinical evidence of AI, basal plasma cortisol ≤ 5 (µg/dL), or a stimulated plasma cortisol <18. RESULTS: A normal POD1-CST was found in all nine control patients and 11 of 22 patients (50%) with Cushing's syndrome; the other 11 study patients (50%) received GR based on the POD1-CST. These patients were younger (51 vs 62 years; P = .017), had a higher body mass index (BMI; 31 vs 29 kg/m(2)), and smaller adrenal neoplasms (16.9 vs 33.0 g; P = .009) than non-GR study patients. CONCLUSION: After unilateral adrenalectomy for hypercortisolism, only 50% of patients received GR. No preoperative biochemical characteristics were associated with postoperative AI, although patients who received GR were younger, and tended to have a higher BMI and smaller adrenal nodules. Use of this novel protocol for postoperative dynamic adrenal function testing prevented unnecessary GR in 50% of patients and allowed for individualized patient care.


Asunto(s)
Corticoesteroides/administración & dosificación , Neoplasias de la Corteza Suprarrenal/cirugía , Insuficiencia Suprarrenal/diagnóstico , Adrenalectomía/efectos adversos , Cosintropina/administración & dosificación , Síndrome de Cushing/cirugía , Pruebas de Función de la Corteza Suprarrenal , Neoplasias de la Corteza Suprarrenal/complicaciones , Insuficiencia Suprarrenal/dietoterapia , Insuficiencia Suprarrenal/etiología , Adulto , Anciano , Protocolos Clínicos , Síndrome de Cushing/etiología , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
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