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1.
Am Surg ; 89(11): 4379-4387, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35762831

RESUMEN

BACKGROUND: Driving physician behavior change has been an elusive goal for quality improvement efforts aimed at reducing low-value care. We proposed the use of "nudge" interventions at the surgeon level in order to reduce post-surgical opioid overprescribing in accordance with consensus guidelines. METHODS: We used 2017 Medicare data to identify outlier surgeons. A peer data benchmarking report that showed each surgeon the average number of opioid tablets they prescribed for an open inguinal hernia repair procedure from January 1, 2017 to December 31, 2017. We conducted a 1:1 randomized controlled trial providing outlier surgeons a report of their opioid prescribing patterns for a standard operation compared to the national average and prescribing guidelines. RESULTS: There were 489 surgeons randomized to the intervention, of which 180 (36.8%) had data in the post-intervention period. Data was available for 87 surgeons in the intervention group and 93 surgeons in the control group. 97.7% of surgeons in the intervention group reduced their opioid prescribing pattern compared to 95.7% in the control group. Surgeons who received the data benchmarking report intervention prescribed 14.3% less opioids than surgeons in the control group (10.54 (SD 5.34) vs. 12.30 (SD 6.02), P = .04). The intervention was associated with a 1.83 lower mean number of opioid tablets prescribed per patient in the multivariable linear regression model after controlling for other factors (Intervention group vs. control group 95% CI [-3.61, -.04], P = .04). DISCUSSION: The implementation of a peer data benchmarking intervention can drive physician behavior change towards high-value care.


Asunto(s)
Analgésicos Opioides , Dolor Postoperatorio , Anciano , Humanos , Estados Unidos , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Benchmarking , Prescripción Inadecuada , Pautas de la Práctica en Medicina , Medicare
2.
Med Care Res Rev ; 79(1): 133-140, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33327861

RESUMEN

Insurance agents and brokers play an important role in facilitating the contracting of fully insured health insurance and pharmacy benefit plans for U.S. employers. They are primarily compensated with a commission charged back to the plan. Using a national sample that covered 11.7 million employees enrolled in 33,689 health plans in 2017, we found that a plan's commission (median: $178) was positively associated with a plan's premium (coefficient: 0.01 for the full sample and 0.03 for small plans, p < .001) after controlling for the number of enrollees. The commission-to-premium ratio was greater for smaller plans and plans offered by nonmajor insurance companies, and varied by geographic region. Policy makers should consider improving transparency of the commission to facilitate employers making efficient broker contracting and plan purchasing decisions. The fee-based brokerage model has the potential to help employers and workers contain health care spending.


Asunto(s)
Planes de Asistencia Médica para Empleados , Atención a la Salud , Humanos , Seguro de Salud , Salarios y Beneficios , Estados Unidos
3.
Pediatr Surg Int ; 36(11): 1339-1343, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32915274

RESUMEN

BACKGROUND: Opioid misuse continues to be a major source of morbidity and mortality in the US, in both the adult and pediatric populations. Post-operative opioid prescriptions are often the first exposure children have to opioids and increases their risk of chronic use. There is significant variation in the number of opioids following identical procedures and measures have been taken within the adult population to limit this. However, specific post-operative opioid prescription guidelines are not present in the pediatric population. METHODS: Seven common pediatric surgery procedures were selected for inclusion. The recommended number of opioid doses following each procedure was determined by a multi-disciplinary expert panel. All surgery residents were sent an initial survey to determine the number of opioids they would prescribe for each procedure. They were then shown the guidelines and the survey repeated to determine changes in response. RESULTS: 35 and 27 general surgery residents took part in and pre- and post-educational surveys respectively. In all procedures, there was a decrease in the mean number of post-operative opioids prescribed. In addition, there was an increase in the number of residents who prescribed within the guidelines and a decrease in the number who overprescribed post-operative opioids. CONCLUSION: Pediatric postoperative opioid prescribing guidelines derived from expert opinion increase resident compliance with appropriate dosing; this has the potential to decrease the classic problem of general surgery residents accustomed to treating adults overprescribing opioids to children. These results are promising, and we aim to expand on this work and incorporate these guidelines into our clinical practice. LEVEL OF EVIDENCE: III/IV.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Dolor Postoperatorio/tratamiento farmacológico , Cuidados Posoperatorios/normas , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adolescente , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
4.
J Gastrointest Surg ; 24(7): 1590-1596, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31270718

RESUMEN

BACKGROUND: Introduction of effective systemic therapies for pancreatic ductal adenocarcinoma (PDAC) has demonstrated survival benefit. However, chemotherapy remains underutilized in these patients. We sought to investigate the implications of disparities on the trends in utilization of chemotherapy. METHODS: A retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database identified patients who underwent surgical resection for PDAC from 1998 to 2014. Clinicopathologic, demographic, racial, and geographical factors were analyzed to assess associations with receipt of chemotherapy and disease-specific survival. RESULTS: A total of 15,585 patients were included in the study. A majority (N = 9953, 63.9%) received chemotherapy. Factors associated with poorer odds of receiving chemotherapy included older age (p < 0.001), African-American race (p = 0.003), and living in the Southwest region of the USA (p < 0.001). Married patients were at higher odds of receiving chemotherapy (all p < 0.001). Receipt of chemotherapy was independently associated with improved disease-specific survival (p < 0.001). CONCLUSIONS: Receipt of chemotherapy results in an improved survival in patients with resected PDAC. Demographic, racial, and geographic factors influence the rate of receipt of chemotherapy. Despite prior reports, these trends have not changed over the recent decades.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Anciano , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Quimioterapia Adyuvante , Disparidades en Atención de Salud , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Tasa de Supervivencia
6.
Drugs Aging ; 37(1): 57-65, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31782129

RESUMEN

BACKGROUND: Polypharmacy in older patients increases the risk of medication-related adverse events and can be a marker of unnecessary care. OBJECTIVES: The aim of this study was to describe the frequency of polypharmacy among patients 65 years of age or older and identify factors associated with the occurrence of patient-level and physician-level polypharmacy. METHODS: We performed a cross-sectional analysis of 100% Medicare claims data from January 1, 2016 to December 31, 2016. All patients with continuous Medicare coverage (Parts A, B, and D) throughout 2016 who were 65 years of age or older and who were prescribed at least one medication for at least 30 days were included in the analysis. Each patient was attributed to the primary care physician who prescribed them the most medications. Physicians treating fewer than ten patients were excluded. We defined polypharmacy based on the highest number of concurrent medications at any point during the year. We used hierarchical linear regression to study patient- and physician-level characteristics associated with high prescribing rates. RESULTS: We identified 25,747,560 patients attributed to 147,879 primary care physicians. The patient-level mean [standard deviation (SD)] concurrent medication rate was 5.6 (3.3), and the physician-level mean (SD) was 5.6 (1.1). A total of 6108 physicians (4.1% of sample) had a mean concurrent number of medications greater than two SDs above the physician-level mean. At the patient level in the adjusted model, a history of HIV/AIDS, diabetes mellitus, solid organ transplant, and systolic heart failure were the comorbidities most strongly associated with polypharmacy. The relative difference in number of medications associated with these comorbidities were 1.89, 1.39, 1.32, and 1.06, respectively. At the physician level, increased time since medical school graduation and smaller practice size were associated with lower rates of polypharmacy. CONCLUSIONS: Patterns of high prescribing to older patients is common and measurable at the physician level. Addressing high outlier prescribers may represent an opportunity to reduce avoidable harm and excessive costs.


Asunto(s)
Utilización de Medicamentos/tendencias , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Polifarmacia , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Comorbilidad , Estudios Transversales , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Masculino , Medicare , Persona de Mediana Edad , Pronóstico , Estados Unidos
8.
JAMA Dermatol ; 155(8): 906-913, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31055597

RESUMEN

IMPORTANCE: Mohs micrographic surgery (MMS) is a skin cancer treatment that uses staged excisions based on margin status. Wide surgeon-level variation exists in the mean number of staged resections used to treat a tumor, resulting in a cost disparity and question of appropriateness. OBJECTIVE: To evaluate the effectiveness of a behavioral intervention aimed at reducing extreme overuse in MMS, as defined by the specialty society, by confidentially sharing stages-per-case performance data with individual surgeons benchmarked to their peers nationally. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized controlled intervention study included 2329 US surgeons who performed MMS procedures from January 1, 2016, to March 31, 2018. Physicians were identified using a 100% capture of Medicare Part B claims. The intervention group included physicians affiliated with the American College of Mohs Surgery, and the control group included physicians not affiliated with the American College of Mohs Surgery. INTERVENTIONS: Individualized performance reports were delivered to all outlier surgeons, defined by the specialty society as those with mean stages per case 2 SDs above the mean, and inlier surgeons in the intervention group. MAIN OUTCOMES AND MEASURES: The primary outcome was surgeon-level change in mean stages per case between the prenotification (January 2016 to January 2017) and postnotification (March 2017 to March 2018) periods. A multivariable linear regression model was used to evaluate the association of notification with this surgeon-level outcome. The surgeon-level metric of mean stages per case was not risk adjusted. The mean Medicare cost savings associated with changes in practice patterns were calculated. RESULTS: Of the 2329 included surgeons, 1643 (70.5%) were male and 2120 (91.0%) practiced in metropolitan areas. In the intervention group (n = 1045), 53 surgeons (5.1%) were outliers; in the control group (n = 1284), 87 surgeons (6.8%) were outliers. Among the outliers in the intervention group, 44 (83%) demonstrated a reduction in mean stages per case compared with 60 outliers in the control group (69%; difference, 14%; 95% CI of difference, -1 to 27; P = .07). There was a mean stages-per-case reduction of 12.6% among outliers in the intervention group compared with 9.0% among outliers in the control group, and outliers in the intervention group had an adjusted postintervention differential decrease of 0.14 stages per case (95% CI, -0.19 to -0.09; P = .002). The total administrative cost of the intervention program was $150 000, and the estimated reduction in Medicare spending was $11.1 million. CONCLUSIONS AND RELEVANCE: Sharing personalized practice pattern data with physicians benchmarked to their peers can reduce overuse of MMS among outlier physicians.

9.
J Am Coll Surg ; 228(4): 504-512.e2, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30703538

RESUMEN

BACKGROUND: To better understand re-excision practice patterns after breast-conserving therapy (BCT), we evaluated variation in surgeon-specific re-excision rates and associated factors. STUDY DESIGN: We performed a retrospective analysis using Medicare claims from 2012 to 2018 to identify patients undergoing BCT and subsequent breast resection procedures within 12 months. We compared rates before and after the 2014 "no tumor on ink" consensus guideline. A hierarchical logistic regression model was also used to evaluate patient and physician characteristics associated with re-excision. RESULTS: We identified 291,065 female Medicare beneficiaries who underwent an initial BCT procedure, of which 19.0% had a re-excision. The overall re-excision rate was 22.1% in the pre-guideline period and 17.2% in the post-guideline period. For the 5,337 physicians that performed more than 10 initial BCT procedures during the study period, their physician-level re-excision rate ranged from 0% to 91.7% (median 18.2%). In total, 17.5% of the physicians had a re-excision rate greater than the expert consensus cutoff of 30%. The percentage of outlier physicians decreased from 22.2% in 2012 to 8.8% in 2017. High surgeon volume of BCT was associated with a lower re-excision odds (≥51 cases vs ≤20 cases: adjusted odds ratio 0.78; 95% CI 0.74 to 0.82; 21 to 50 cases vs ≤20 cases: adjusted odds ratio 0.92; 95% CI 0.88 to 0.96). Patient factors associated with decreased odds of re-excision were age older than 75 years and Northeast region of the US (adjusted odds ratio 0.93; 95% CI 0.89 to 0.98). CONCLUSIONS: Marked variation exists in surgeon re-excision rates among patients undergoing BCT, which might represent unnecessary operations for patients and a financial burden to the healthcare system. Formalizing a re-excision frequency metric could have implications for quality improvement and data-driven surgeon feedback aimed at reducing unwarranted variation.


Asunto(s)
Competencia Clínica/estadística & datos numéricos , Adhesión a Directriz/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Mastectomía Segmentaria/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Indicadores de Calidad de la Atención de Salud/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Logísticos , Medicare , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Garantía de la Calidad de Atención de Salud , Estudios Retrospectivos , Estados Unidos
10.
Am J Surg ; 216(4): 793-799, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30177240

RESUMEN

BACKGROUND: Patients often have an incomplete understanding of the levels of training and roles of the various surgical providers in teaching hospitals, leading to patient confusion and dissatisfaction. METHODS: Pre-intervention discharge surveys were administered to gastrointestinal surgery inpatients (10/2016-02/2017) to evaluate sentiments regarding their surgical team. During the intervention period (02/2017-05/2017), patients at admission received "facesheets" containing team member profiles, photos, training level, and roles. These patients were evaluated using the survey, and pre- and post-intervention scores compared. RESULTS: 153 pre- and 100 post-intervention surveys were collected. There was a significant increase in patients reporting it was important to know the surgical team members and that they knew team member roles (p ≤ 0.05). Scores in every domain of the satisfaction survey improved in the post-intervention period, although not reaching statistical significance. CONCLUSIONS: Improving how patients perceive their interactions with their surgical team has implications on patient satisfaction and hospital quality metrics.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Internado y Residencia , Grupo de Atención al Paciente/normas , Educación del Paciente como Asunto/normas , Satisfacción del Paciente/estadística & datos numéricos , Mejoramiento de la Calidad/organización & administración , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Encuestas de Atención de la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Relaciones Enfermero-Paciente , Educación del Paciente como Asunto/métodos , Educación del Paciente como Asunto/organización & administración , Relaciones Médico-Paciente , Estudios Prospectivos , Cirujanos/normas
11.
J Am Coll Surg ; 227(4): 411-418, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30118896

RESUMEN

BACKGROUND: One in 16 surgical patients prescribed opioids becomes a long-term user. Overprescribing opioids after surgery is common, and the lack of multidisciplinary procedure-specific guidelines contributes to the wide variation in opioid prescribing practices. We hypothesized that a single-institution, multidisciplinary expert panel can establish consensus on ideal opioid prescribing for select common surgical procedures. STUDY DESIGN: We used a 3-step modified Delphi method involving a multidisciplinary expert panel of 6 relevant stakeholder groups (surgeons, pain specialists, outpatient surgical nurse practitioners, surgical residents, patients, and pharmacists) to develop consensus ranges for outpatient opioid prescribing at the time of discharge after 20 common procedures in 8 surgical specialties. Prescribing guidelines were developed for opioid-naïve adult patients without chronic pain undergoing uncomplicated procedures. The number of opioid tablets was defined using oxycodone 5 mg oral equivalents. RESULTS: For all 20 surgical procedures reviewed, the minimum number of opioid tablets recommended by the panel was 0. Ibuprofen was recommended for all patients unless medically contraindicated. The maximum number of opioid tablets varied by procedure (median 12.5 tablets), with panel recommendations of 0 opioid tablets for 3 of 20 (15%) procedures, 1 to 15 opioid tablets for 11 of 20 (55%) procedures, and 16 to 20 tablets for 6 of 20 (30%) procedures. Overall, patients who had the procedures voted for lower opioid amounts than surgeons who performed them. CONCLUSIONS: Procedure-specific prescribing recommendations may help provide guidance to clinicians who are currently overprescribing opioids after surgery. Multidisciplinary, patient-centered consensus guidelines for more procedures are feasible and may serve as a tool in combating the opioid crisis.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Manejo del Dolor/normas , Dolor Postoperatorio/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Consenso , Técnica Delphi , Humanos , Estados Unidos
12.
Ann Surg Oncol ; 25(8): 2209-2217, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29855832

RESUMEN

BACKGROUND: Although well described for gastrointestinal and pelvic cancers, use of minimally invasive surgery (MIS) for the management of retroperitoneal soft tissue sarcoma (RPS) remains unknown. The current study aimed to describe patterns of MIS use and assess the association between MIS and clinical outcomes among patients undergoing surgery for RPS. METHODS: Patients undergoing a primary resection for RPS between 2010 and 2014 were identified using the National Cancer Database. Multivariable logistic and Cox proportional hazards models were used to assess the association between use of MIS and clinical outcomes. Sensitivity analysis was performed using propensity score-matching (PSM). RESULTS: This study identified 3844 patients who met the inclusion criteria. Of these patients, 89.3% (n = 3432) underwent an open surgery, whereas 10.7% (n = 412) underwent MIS. The patients undergoing MIS were more likely to present with smaller tumors (open vs MIS: median tumor size, 17 cm; interquartile range [IQR, 9.8-26.0] vs 10.5 cm [IQR, 6.5-18.0]) and to undergo surgery at community hospitals (26.8% vs 36.1%; both P < 0.001). Although MIS was associated with a shorter hospital length of stay [LOS] (median LOS, 6 days [IQR, 5-9 days] vs 4 days [IQR, 2-7]; P < 0.001), postoperative mortality and overall survival were comparable between the two treatment groups (all P > 0.05). These findings were confirmed using PSM. CONCLUSIONS: MIS was associated with a shorter LOS, however, postoperative mortality and overall survival were comparable by operative approach. Future research is required to evaluate the use of MIS for the management of RPS. Policies are required to ensure that patients receive care in accordance with best practices and recommended guidelines.


Asunto(s)
Bases de Datos Factuales , Procedimientos Quirúrgicos Mínimamente Invasivos/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Complicaciones Posoperatorias/mortalidad , Puntaje de Propensión , Neoplasias Retroperitoneales/mortalidad , Sarcoma/mortalidad , Anciano , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/cirugía , Sarcoma/patología , Sarcoma/cirugía , Tasa de Supervivencia
13.
J Surg Oncol ; 118(1): 127-137, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29878363

RESUMEN

BACKGROUND: Margin negative resection offers the best chance of long-term survival in retroperitoneal sarcoma (RPS). En-bloc resection of adjacent structures, including the inferior vena cava (IVC), is often required to achieve negative margins. We review our 20-year experience of en-bloc IVC and RPS resection. METHODS: Retrospective review of patients with RPS resection involving the IVC were matched 1:3 by age and histology to RPS without IVC resection. Prognostic factors for overall survival (OS) and disease free survival (DFS) were assessed. RESULTS: Thirty-two patients underwent RPS resection en-bloc with IVC. They were matched with 96 cases of RPS without IVC resection. Median OS of 59 months and DFS 18 months in IVC resection group was comparable to RPS resection without vascular involvement: median OS 65 months, DFS 18 months (P = 0.519, P = 0.604). On multivariate analyses, R2 margin (OS: HR = 6.52 [95%CI: 1.18-36.09], P = 0.032) was associated with inferior OS. R2 margin and increased number of organs resected (DFS: HR = 5.07, [1.15-22.27], P = 0.031, HR = 1.28 [1.01-1.62], P = 0.014) were associated with inferior DFS. Reconstructions included graft (n = 19, 59%), patch (n = 4, 13%), primary repair (n = 6, 19%), and ligation (n = 4, 13%). CONCLUSIONS: RPS resection en-bloc with IVC can achieve equivalent rates of DFS and OS to patients without vascular involvement.


Asunto(s)
Leiomiosarcoma/cirugía , Liposarcoma/cirugía , Neoplasias Retroperitoneales/cirugía , Vena Cava Inferior/cirugía , Anciano , Puente Cardiopulmonar/métodos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos
16.
Int J Oncol ; 49(4): 1541-1552, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27634112

RESUMEN

Field effect or field cancerization denotes the presence of molecular aberrations in structurally intact cells residing in histologically normal tissues adjacent to solid tumors. Currently, the etiology of prostate field­effect formation is unknown and there is a prominent lack of knowledge of the underlying cellular and molecular pathways. We have previously identified an upregulated expression of several protein factors representative of prostate field effect, i.e., early growth response-1 (EGR­1), platelet-derived growth factor­A (PDGF­A), macrophage inhibitory cytokine­1 (MIC­1), and fatty acid synthase (FASN) in tissues at a distance of 1 cm from the visible margin of intracapsule prostate adenocarcinomas. We have hypothesized that the transcription factor EGR­1 could be a key regulator of prostate field­effect formation by controlling the expression of PDGF­A, MIC­1, and FASN. Taking advantage of our extensive quantitative immunofluorescence data specific for EGR­1, PDGF­A, MIC­1, and FASN generated in disease­free, tumor­adjacent, and cancerous human prostate tissues, we chose comprehensive correlation as our major approach to test this hypothesis. Despite the static nature and sample heterogeneity of association studies, we show here that sophisticated data generation, such as by spectral image acquisition, linear unmixing, and digital quantitative imaging, can provide meaningful indications of molecular regulations in a physiologically relevant in situ environment. Our data suggest that EGR­1 acts as a key regulator of prostate field effect through induction of pro­proliferative (PDGF­A and FASN), and suppression of pro­apoptotic (MIC­1) factors. These findings were corroborated by computational promoter analyses and cell transfection experiments in non­cancerous prostate epithelial cells with ectopically induced and suppressed EGR­1 expression. Among several clinical applications, a detailed knowledge of pathways of field effect may lead to the development of targeted intervention strategies preventing progression from pre-malignancy to cancer.

17.
PLoS One ; 10(3): e0119314, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25767870

RESUMEN

Prostate field cancerization denotes molecular alterations in histologically normal tissues adjacent to tumors. Such alterations include deregulated protein expression, as we have previously shown for the key transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS). Here we add the two secreted factors macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) to the growing list of protein markers of prostate field cancerization. Expression of MIC-1 and PDGF-A was measured quantitatively by immunofluorescence and comprehensively analyzed using two methods of signal capture and several groupings of data generated in human cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and PDGF-A expression in tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01 to p = 0.23, respectively). In support of field cancerization, MIC-1 and PDGF-A expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x, respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC-1 and PDGF-A expression were similar in tumor and adjacent tissues (0.3x to 1.0x; p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for PDGF-A). All analyses indicated a high level of inter- and intra-tissue heterogeneity across all types of tissues (mean coefficient of variation of 86.0%). Our data shows that MIC-1 and PDGF-A expression is elevated in both prostate tumors and structurally intact adjacent tissues when compared to disease-free specimens, defining field cancerization. These secreted factors could promote tumorigenesis in histologically normal tissues and lead to tumor multifocality. Among several clinical applications, they could also be exploited as indicators of disease in false negative biopsies, identify areas of repeat biopsy, and add molecular information to surgical margins.


Asunto(s)
Factor 15 de Diferenciación de Crecimiento/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Próstata/metabolismo , Neoplasias de la Próstata/metabolismo , Adulto , Anciano , Expresión Génica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Próstata/patología , Neoplasias de la Próstata/patología
18.
Int J Surg Case Rep ; 5(12): 1271-4, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25460491

RESUMEN

INTRODUCTION: Pancreatic neuroendocrine tumors (PNET) are rare, often indolent malignancies. PNET are classified as functional or nonfunctional based on the secretion of hormones without a negative feedback loop; the latter account for up to 60% of PNET. Although PNET are associated with a better prognosis compared to pancreatic adenocarcinomas, they are often diagnosed in advanced stages, making them a significant source of morbidity for patients. Here we present a rare case of venous tumor thrombus arising from a nonfunctional PNET. PRESENTATION OF CASE: A 44-year-old woman was referred for evaluation and treatment of a possible tail of pancreas PNET discovered during work-up for a 9 year history of intermittent subcostal pain. Previous endoscopic ultrasound with fine needle aspiration revealed a 3.5cm×3cm mass, with cytological diagnosis of neuroendocrine tumor. Patient was scheduled for laparoscopic distal pancreatectomy. During surgery the mass was found to encase the splenic vein leading the surgeon to perform an en bloc distal pancreatectomy and splenectomy. Pathologic analysis revealed a 1.8cm×5cm tumor thrombus lodged in the splenic vein. DISCUSSION: Nonfunctional PNET usually present in advanced stages and can be associated with venous tumor thrombi. Preoperative imaging may not accurately predict the presence of venous tumor thrombi. CONCLUSION: En bloc resection of primary tumor, involved organs and thrombus is the recommended treatment option and often results in long term survival. New multi-modality strategies are needed for detection of venous involvement in nonfunctional PNET to better assist with preoperative planning and counseling.

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