RESUMEN
INTRODUCTION: A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. PATIENTS AND METHODS: A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samples t-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. RESULTS: Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08, p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10, p = 0.011). CONCLUSION: This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.
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Hemangiopericitoma , Neoplasias Meníngeas , Tumores Fibrosos Solitarios , Adulto , Hemangiopericitoma/radioterapia , Hemangiopericitoma/cirugía , Humanos , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Tumores Fibrosos Solitarios/radioterapia , Tumores Fibrosos Solitarios/cirugíaRESUMEN
BACKGROUND: Patients undergoing surgery for soft tissue sarcoma have high morbidity rates, particularly after preoperative radiation therapy (RT). An enhanced recovery after surgery (ERAS) programme may improve perioperative outcomes in abdominal surgery. This study reported outcomes of an ERAS programme tailored to patients with soft tissue sarcoma. METHODS: A prospective ERAS protocol was implemented in 2015 at a high-volume sarcoma centre. Patients treated within the ERAS programme from 2015 to 2018 were case-matched retrospectively with patients treated between 2012 and 2018 without use of the protocol, matched by surgical site, surgeon, sarcoma histology and preoperative RT treatment. Postoperative outcomes, specifically wound complications and duration of hospital stay, were reported. RESULTS: In total, 234 patients treated within the ERAS programme were matched with 237 who were not. The ERAS group had lower wound dehiscence rates overall (2 of 234 (0·9 per cent) versus 31 of 237 (13·1 per cent); P < 0·001), after preoperative RT (0 of 41 versus 11 of 51; P = 0·004) and after extremity sarcoma surgery (0 of 54 versus 6 of 56; P = 0·040) compared with the non-ERAS group. Rates of postoperative ileus or obstruction were lower in the ERAS group (21 of 234 (9·9 per cent) versus 40 of 237 (16·9 per cent); P = 0·016) and in those with retroperitoneal sarcoma (4 of 36 versus 15 of 36; P = 0·007). Duration of hospital stay was shorter in the ERAS group (median 5 (range 0-36) versus 6 (0-67) days; P = 0·003). CONCLUSION: Treatment within an ERAS protocol for patients with soft tissue sarcoma was associated with lower morbidity and shorter hospital stay.
ANTECEDENTES: Los pacientes sometidos a cirugía por sarcoma de tejido blando (soft tissue sarcoma, STS) tienen altas tasas de morbilidad, particularmente después de la radioterapia preoperatoria (RT). El programa de recuperación intensificada después de la cirugía (enhanced recovery after surgery, ERAS) puede mejorar los resultados perioperatorios en la cirugía abdominal. Este estudio analizó los resultados de un programa ERAS diseñado para pacientes con STS. MÉTODOS: Se implementó un protocolo prospectivo ERAS en el año 2015 en un centro de alto volumen de sarcomas. Los pacientes en ERAS desde 2015 hasta 2018 fueron emparejados retrospectivamente con pacientes sin ERAS desde 2012 hasta 2018, según la localización quirúrgica, el cirujano, la histología del sarcoma y el tratamiento con RT preoperatoria. Se analizaron los resultados postoperatorios, específicamente las complicaciones de la herida y la duración de la estancia hospitalaria (length of stay, LOS). RESULTADOS: En total, 234 pacientes tratados con ERAS se compararon con 237 pacientes no tratados con ERAS. Los pacientes con ERAS tuvieron tasas globales más bajas de dehiscencia de la herida (2 (0,9%) versus 31 (13,1%), P < 0,001)), después de la RT preoperatoria (0 versus 11 (21,6%), P = 0,004)), y después de la cirugía de STS de extremidades (0 versus 6 (0,7%), P = 0,04)) en comparación con los pacientes no ERAS. Las tasas de íleo u obstrucción postoperatorias fueron más bajas en el grupo ERAS (21 (9,9%) versus 40 (16,9%), P = 0,02)) y en aquellos pacientes con sarcoma retroperitoneal (4 (11,1%) versus 15 (41,7%), P = 0,007)). La mediana (rango) de la LOS fue más corta en los pacientes con ERAS que fue de 5 (0-36) días que en los pacientes sin ERAS que fue de 6 (0-67) días (P = 0,003). CONCLUSIÓN: ERAS para pacientes con STS se asoció con una menor morbilidad y una estancia hospitalaria más corta.
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Recuperación Mejorada Después de la Cirugía , Sarcoma/cirugía , Vías Clínicas , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Although cytoreductive surgery has been shown to be beneficial in carefully selected patients with metastatic gastrointestinal stromal tumours (GISTs) treated with tyrosine kinase inhibitors (TKIs), factors predictive of postoperative morbidity have not been investigated previously. METHODS: A surgical complexity score for GIST metastasectomy (GM-SCS) composed of patient-related and surgical factors was assigned retrospectively to patients with metastatic GIST treated with TKI therapy and surgery at two institutions between 2002 and 2014. The ability of clinicopathological factors and GM-SCS to predict postoperative morbidity was assessed by means of a multivariable logistic regression model. Postoperative complications were categorized using the Clavien-Dindo classification. RESULTS: Some 400 operations on 323 patients with metastatic GIST on TKIs were included. Complications were observed following 110 operations (27·5 per cent) including 70 major complications (grade III-V) (17·5 per cent of 400 operations). Patients were divided into low (5 points or less; 100 patients, 25·0 per cent), intermediate (6-9 points; 191, 47·8 per cent) and high (at least 10 points; 109, 27·3 per cent) complexity scoring groups based on the GM-SCS. An intermediate (odds ratio (OR) 2·88; P = 0·008) and high (OR 5·40; P < 0·001) GM-SCS were independent predictors of overall complications, whereas only a high GM-SCS was independently predictive of a major complication (OR 3·65; P = 0·018). Metastatic mitotic index was also an independent predictor of overall complications (OR 2·55; P = 0·047). GM-SCS did not predict progression-free or overall survival. CONCLUSION: A gastrointestinal stromal tumour metastastectomy surgical complexity score can predict morbidity, which may help in preoperative risk stratification and optimal treatment planning.
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Antineoplásicos/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/cirugía , Mesilato de Imatinib/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Anciano , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/terapia , Humanos , Metastasectomía , Persona de Mediana Edad , Factores de RiesgoRESUMEN
AIM: To describe the multidetector computed tomography (MDCT) features of primary, locally recurrent, and metastatic duodenal gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant, retrospective study, 25 patients [13 men, 12 women; mean age 56 years (34-74 years)] with histopathologically confirmed duodenal GISTs seen at Dana Farber Cancer Institute and Brigham and Women's Hospital from December 1999 to October 2009 were identified. The MDCT of primary tumours in six patients and follow-up imaging in all the 25 patients was reviewed by two radiologists in consensus. Electronic medical records were reviewed to document the clinical characteristics and management. RESULTS: The mean size of the primary tumour was 3.7 cm (range 2.5-5.6 cm). Three of six primary tumours were in the second and third portions of the duodenum, one in the third portion, one in the third and fourth portions, and one in the fourth portion. Three of six of the tumours were exophytic, two were both exophytic and intraluminal, and one was intramural. The tumours were well-circumscribed, round or oval masses, with few lobulations, and were either homogeneously hyper-enhancing or heterogeneously isodense at MDCT. None of the tumours had necrosis, haemorrhage, calcification, or loco regional lymphadenopathy on imaging. Sixteen of 25 (64%) patients developed metastatic disease, the most common sites being liver (14/16; 87.5%) and peritoneum (5/16; 31%). CONCLUSION: Duodenal GISTs are well-circumscribed, round or oval masses, and occur in the second through fourth portions of the duodenum, without lymphadenopathy or duodenal obstruction. Duodenal GISTS metastasize frequently to the liver and peritoneum.
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Neoplasias Duodenales/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Adulto , Anciano , Medios de Contraste , Neoplasias Duodenales/patología , Neoplasias Duodenales/secundario , Duodeno/diagnóstico por imagen , Femenino , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/secundario , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Intensificación de Imagen Radiográfica/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: To determine the timing of earliest, best and plateau response to neoadjuvant imatinib in patients with GIST. MATERIALS AND METHODS: In this IRB-approved retrospective study, we included all 20 patients (10 women; mean age 61 years, range 30-83 years) with KIT-positive primary GIST who received neoadjuvant imatinib and underwent surgery between January 2001 and December 2012. Earliest (earliest time to partial response), best (percentage reduction in longest axial diameter [LAD] and volume correlated with RECIST 1.1 and volumetric criteria) and plateau (time point when there was <10% change in treatment response between two consecutive scans beyond best response) responses were analyzed on review of imaging. RESULTS: Median tumor size at baseline was 7.2 cm (range, 3.0-31.4 cm). Median duration of neoadjuvant imatinib was 32 weeks (IQR, 16-36 weeks). Partial response was noted in 16/20 patients (median interval = 16 weeks; IQR, 7-26 weeks); 4/20 had stable disease. Median time to earliest PR was 16 weeks (IQR, 7-26 weeks). At best response, median decrease in LAD and volume were 43% (IQR, 31-48%) and 83% (IQR, 63-87%), (median interval = 28 weeks; IQR, 18-37 weeks), at which point 10 tumors were resected. Plateau response (45% [IQR, 35-45%] LAD reduction) was noted in the remaining 10 patients (median interval = 34 weeks; IQR, 26-41 weeks) before resection. Tumor size, location or risk category did not correlate with best response or time to best response. CONCLUSION: Best response to neoadjuvant imatinib was seen at 28 weeks irrespective of tumor size and location. Plateau response was seen at 34 weeks, beyond which further treatment may not be beneficial.
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Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Neoplasias Gastrointestinales/diagnóstico por imagen , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/cirugía , Terapia Neoadyuvante/métodos , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the imaging features of anorectal gastrointestinal stromal tumors (GISTs) with clinical and histopathologic correlation. MATERIALS AND METHODS: In this Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 16 patients (12 men; mean age 66 years (30-89 years)) with pathologically proven anorectal GISTs seen at our institution from January 2001 to July 2011 were identified. Electronic medical records were reviewed to obtain clinical data. Pretreatment imaging studies (computed tomography (CT) in 16 patients, magnetic resonance imaging (MRI) in 9 patients and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT in 8 patients) were evaluated by 2 radiologists until consensus. The location, size and imaging features of the primary tumor and metastases at presentation, if any, were recorded, and correlated with clinical data and pathologic features (histologic type, presence of necrosis, mitotic activity, risk category, immunohistochemical profile). RESULTS: The mean tumor size was 6.9 × 6.0 cm. Of the 16 tumors, 11 (68.7%) were infralevator, 4 (25%) supra and infralevator and 1 (6.3%) supralevator; 9 (56.2%) were exophytic, 6 (37.5%) both exophytic and intraluminal, and 1 (6.3%) was intraluminal. The tumors were iso- to minimally hypoattenuating to muscle on CT, iso- to minimally hypointense on T1-weighted images, hyperintense on T2-weighted images and showed variable enhancement. Necrosis was seen in 4 (25%), and hemorrhage and calcification in 2 (12.5%) patients each. The tumors were FDG avid with a mean maximum standardized uptake value of 11 (8.4-16.8). All tumors were positive for KIT and CD34. Distant metastasis to liver was seen in 1 patient (6.3%) at presentation. CONCLUSION: Anorectal GISTs are well-circumscribed, non-circumferential, predominantly infralevator, intramural or exophytic, FDG-avid, hypoattenuating masses, and present without lymphadenopathy or intestinal obstruction.
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Neoplasias Gastrointestinales/diagnóstico , Tumores del Estroma Gastrointestinal/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fluorodesoxiglucosa F18 , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The duodenum is a rare site of primary gastrointestinal stromal tumor (GIST). Overall (OS) and disease-free survival (DFS) after limited resection (LR) versus pancreaticoduodenectomy (PD) were studied. METHODS: All patients who underwent surgery for primary, localized duodenal GIST between 2000 and 2011 were identified from four prospective institutional databases. OS and DFS were calculated by Kaplan-Meier method. Univariate analysis was performed. RESULTS: Eighty-four patients (median follow-up 42 months) underwent LR (n = 56, 67%) or PD (n = 28, 33%). Patients in the PD group had a larger median tumor size (7 cm vs. 5 cm, p = 0.024) and higher mitotic count (39% vs. 19% >5/50 high-power fields, p = 0.05). Complications were observed in five patients (9%) in the LR group and ten patients (36%) in the PD group. OS and DFS for the entire cohort were 89% and 64% at 5 years, respectively. No difference in outcome between LR and PD were observed. Eleven patients were treated with preoperative IM. A major RECIST response was obtained in nine (80%), whereas two had stable disease. Twenty-three patients received postoperative Imatinib (IM). A trend toward a better OS in IM-treated patients could be detected only in the high-risk group. CONCLUSIONS: Type of duodenal resection does not impact outcome. The choice should be determined by duodenal site of origin and tumor size. IM may be considered in cases at high risk of recurrence; in neoadjuvant setting, IM might facilitate resection and possibly increase the chance of preserving normal biliary and pancreatic anatomy.
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Antineoplásicos/uso terapéutico , Neoplasias Duodenales/patología , Neoplasias Duodenales/terapia , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/terapia , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Benzamidas , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Mesilato de Imatinib , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Índice Mitótico , Pancreaticoduodenectomía/efectos adversos , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
The large-scale, persistent use of antibiotics has provoked microbes to evolve mechanisms to evade them. Pharmaceutical companies have found this to be counterproductive to their business economics. To maintain company interest to invest in this sector, innovative alternatives are needed. The availability of metabolic and genomic databases has opened up an avenue for such discoveries. Using these databases, potential producers of penicillin and cephalosporin have been traced. In addition, organisms that can be transformed from their present 'non'-producer status to antibacterial producers by supplementing their missing gene(s) by recombinant DNA technology have been revealed.
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BACKGROUND: Preoperative chemoradiation can potentially improve outcomes in patients with pancreatic cancer. This study addresses its effect on staging pancreatic cancer with multidetector computed tomography (MDCT). METHODS: Fifty-five patients underwent a dual-phase MDCT pancreas protocol for proved pancreatic cancer. Of these, 16 patients underwent preoperative chemoradiation. Three radiologists independently reviewed images to assess for locally advanced disease, liver and peritoneal metastases on baseline studies of all 55 patients, and on follow-up preoperative studies for the 16 patients receiving preoperative therapy. Overall score for resectability was graded on a scale from 1 to 5 (1, definitely resectable; 5. definitely unresectable). Receiver operating characteristic curves and weighted (kappa statistics were determined. RESULTS: The areas under the receiver operating characteristic curves for readers 1, 2, and 3 were 0.98, 0.96, and 0.90, respectively. Weighted kappa values for reader 1 versus reader 2, reader 1 versus reader 3, and reader 2 versus reader 3 were 0.90, 0.57, and 0.54, respectively. Interpreting scores of 1 to 3 for resectability as resectable disease, the mean values for sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 0.92, 0.91, 0.74, 0.98, and 0.92 respectively. CONCLUSION: The negative predictive value for MDCT for identifying unresectable pancreatic cancer in the setting of preoperative therapy is comparable to that reported in the absence of neoadjuvant therapy.
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Estadificación de Neoplasias/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Terapia Combinada , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Ácidos TriyodobenzoicosRESUMEN
The genes ARAF1, SYN1, TIMP, and PFC are clustered within 70 kb of one another, and, as reported in the accompanying paper (J. Knight et al., 1994, Genomics 21: 180-187), at least four more genes map within 400 kb: a cluster of Krüppel-type zinc finger genes (including ZNF21, ZNF41, and ZNF81) and ELK-1, a member of the ets oncogene superfamily. This gene-rich region is of particular interest because of the large number of disease genes mapping to Xp11.23: at least three eye diseases (retinitis pigmentosa type 2, congenital stationary night blindness CSNB1, and Aland Island eye disease), Wiskott-Aldrich syndrome, X-linked nephrolithiasis, and a translocation breakpoint associated with synovial sarcoma. We have constructed a 1.8-Mb YAC contig in this region, confirming the link between TIMP and OATL1 reported by Knight et al. (1994) and extending the map in the distal direction. To investigate the likelihood that more genes are located within this region, we have carried out detailed mapping of rare-cutter restriction sites in these YACs and identified seven CpG islands. At least six of these islands are located over 50 kb from any known gene locations, suggesting that the region contains at least this many as yet unidentified genes. We have also mapped the physical locations of six highly polymorphic CA repeats within the contig, thus integrating the physical, genetic, and transcriptional maps of the region and facilitating the mapping and identification of disease genes.(ABSTRACT TRUNCATED AT 250 WORDS)