Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Diabetes Obes Metab ; 20(8): 1859-1867, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29569324

RESUMEN

AIMS: Our current understanding of the pathogenesis of type 1 diabetes (T1D) arose, in large part, from studies using the non-obese diabetic (NOD) mouse model. In the present study, we chose a human-focused method to investigate T1D disease mechanisms and potential targets for therapeutic intervention by directly analysing human donor pancreatic islets from individuals with T1D. MATERIALS AND METHODS: We obtained islets from a young individual with T1D for 3 years and from an older individual with T1D for 27 years and performed unbiased functional genomic analysis by high-depth RNA sequencing; the T1D islets were compared with islets isolated from 3 non-diabetic donors. RESULTS: The islets procured from these T1D donors represent a unique opportunity to identify gene expression changes in islets after significantly different disease duration. Data analysis identified several inflammatory pathways up-regulated in short-duration disease, which notably included many components of innate immunity. As proof of concept for translation, one of the pathways, governed by IL-23(p19), was selected for further study in NOD mice because of ongoing human trials of biologics against this target for different indications. A mouse monoclonal antibody directed against IL-23(p19) when administered to NOD mice resulted in a significant reduction in incidence of diabetes. CONCLUSION: While the sample size for this study is small, our data demonstrate that the direct analysis of human islets provides a greater understanding of human disease. These data, together with the analysis of an expanded cohort to be obtained by future collaborative efforts, might result in the identification of promising novel targets for translation into effective therapeutic interventions for human T1D, with the added benefit of repurposing known biologicals for use in different indications.


Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Regulación de la Expresión Génica , Islotes Pancreáticos/metabolismo , Adulto , Animales , Anticuerpos Monoclonales/uso terapéutico , Cadáver , Niño , Análisis por Conglomerados , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/prevención & control , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunidad Innata , Subunidad p19 de la Interleucina-23/antagonistas & inhibidores , Subunidad p19 de la Interleucina-23/genética , Subunidad p19 de la Interleucina-23/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/patología , Masculino , Ratones Endogámicos NOD , Prueba de Estudio Conceptual , Donantes de Tejidos
2.
Dis Colon Rectum ; 53(11): 1467-72, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20940593

RESUMEN

PURPOSE: Single-port laparoscopic surgery has evolved from an effort to minimize tissue trauma, limit morbidity, and maximize cosmesis. Limited data exist comparing single-port with conventional laparoscopy for right colectomy. Our aim is to compare single-port with laparoscopic colectomy with regard to safety and feasibility. We assert that this approach can be adopted in a safe and efficacious manner while using standard laparoscopic instrumentation. METHODS: This is a retrospective analysis of prospectively gathered data regarding 16 single-port and 27 conventional laparoscopic right hemicolectomies performed by a single surgeon between January 2008 and February 2009. Demographics, operative outcomes, and morbidity were included and analyzed using either Student t test or Fisher exact probability test. RESULTS: Single-port and conventional laparoscopic groups were similar with regard to age, gender, body mass index, prior abdominal surgery, and co-morbidity. Seventy-five percent and 70% of the operations were performed for malignancy in the single-port and the conventional laparoscopy group, respectively (P = .69). Operative duration was 106 minutes in the single-port group vs 100 minutes in the conventional group (P = .64). Blood loss was 54 mL and 90 mL, respectively (P = .07). No conversions or additions of ports occurred. Hospital stay was 5.3 days in the single-port group vs 6 days in the conventional group (P = .53). Margins were negative in both groups. Mean lymph node number was 18 and 16 nodes (P = .92). There was one death in the conventional group (P = .44). Morbidity including wound infection was 18.8% and 14.9%, respectively (P = .73). CONCLUSIONS: These findings support single-port right colectomy as a safe and efficacious approach to right colon resections in patients eligible for laparoscopy with minimal additional equipment or learning curve for experienced laparoscopic colorectal surgeons. The single port was undertaken without an increase in morbidity or mortality. There was no increase in operative time with use of the single-port approach. Finally, adequate lymph node harvest and margin clearance was maintained.


Asunto(s)
Colectomía/métodos , Enfermedades del Colon/cirugía , Laparoscopía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Colectomía/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
3.
JSLS ; 14(3): 325-31, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21333183

RESUMEN

BACKGROUND AND OBJECTIVES: As minimally invasive colon and rectal resection has become increasingly prevalent over the past decade, the role that fellowship training plays has become an important question. This analysis examines the learning curve of one fellowship-trained colorectal surgeon in his first 100 cases. METHODS: This was a prospectively collected retrospective analysis of the first 100 laparoscopic colon and rectal resections performed between July 2007 and July 2008 by a colorectal (CRS) fellowship trained surgeon at a Veteran's Administration (VA) and county hospital. Included were all emergent and nonemergent laparoscopic cases. RESULTS: Mean age was 63(range, 36 to 91). The 100 resections included 42 right, 6 left, 32 sigmoid, 13 rectal, and 7 total abdominal colectomies. Indications were 55% cancer, 20% unresectable polyp, 18% diverticular, 4% inflammatory, and 3% other. Overall mortality was 3%. Overall morbidity including wound infection was 24%. Early and late groups were similar in age, ASA score, and indication. Conversion rate was 4%. No statistical difference was seen in mortality, morbidity, EBL, LOS, margin, lymph nodes, or conversions between the first and second 50 cases (P<0.05). Right and sigmoid colectomy operative time decreased by 40.0% and 19.6%, respectively. CONCLUSION: Prior investigators have demonstrated a significant learning curve for laparoscopic colorectal surgery. In the first 100 cases, there is no difference in mortality or morbidity between early and late cases. Alternatively, operative times decreased with experience. Laparoscopic training during CRS fellowship surpasses the learning curve in regard to safety and outcome, whereas operative efficiency improves over the first year of practice.


Asunto(s)
Colectomía/educación , Enfermedades del Colon/cirugía , Cirugía General/educación , Internado y Residencia , Laparoscopía/educación , Curva de Aprendizaje , Enfermedades del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Competencia Clínica , Colectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
4.
Mol Cancer Res ; 4(6): 387-99, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16778086

RESUMEN

Chemotherapy to date has not been effective in the treatment of human hepatocellular carcinoma. More effective treatment strategies may involve combinations of agents with activity against hepatocellular carcinoma. Parthenolide, a nuclear factor-kappaB (NF-kappaB) inhibitor, and NS398, a cyclooxygenase (COX)-2 inhibitor, have been shown to individually suppress the growth of hepatocellular carcinoma cells in vitro. To investigate their effects in combination, three human hepatocellular carcinoma lines (Hep3B, HepG2, and PLC) were treated with parthenolide and/or NS398. Parthenolide (0.1-10 micromol/L) and NS398 (1-100 micromol/L) each caused concentration-dependent growth inhibition in all cell lines. The addition of parthenolide to NS398 reduced the concentration of NS398 required to inhibit hepatocellular carcinoma growth. Because parthenolide and COX-2 inhibitors have been reported to influence NF-kappaB activity, the effects on this pathway were investigated. The combination of parthenolide/NS398 inhibited phosphorylation of the NF-kappaB-inhibitory protein IkappaBalpha and increased total IkappaBalpha levels. NF-kappaB DNA-binding and transcriptional activities were inhibited more by the combination than the single agents in Hep3B and HepG2 cells but not in PLC cells. The response of PLC cells to NS398 was augmented by p65 small interfering RNA to inhibit NF-kappaB p65 protein expression. The combination of parthenolide/NS398 increased apoptosis only in PLC cells, suggesting that the combination may decrease the apoptotic threshold in these cells. In Hep3B and HepG2 cells, combination treatment with NS398/parthenolide altered the cell cycle distribution resulting in more G0-G1 accumulation. Cyclin D1 levels were further decreased by combination treatment in all cell lines, correlating with the cell cycle alterations. Our results suggest that parthenolide may be effective in combination with COX-2 inhibitors for the treatment of hepatocellular carcinoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/patología , Interfase/efectos de los fármacos , Nitrobencenos/farmacología , Sesquiterpenos/farmacología , Sulfonamidas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Proteínas de Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Ciclooxigenasa/uso terapéutico , Proteínas de Unión al ADN/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Proteínas I-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Nitrobencenos/uso terapéutico , Sesquiterpenos/uso terapéutico , Sulfonamidas/uso terapéutico , Transcripción Genética/efectos de los fármacos
5.
J Gastrointest Surg ; 10(10): 1338-45; discussion 1345-6, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17175452

RESUMEN

Pancreatic cancer has a poor prognosis with complete surgical resection being the only therapy to offer a realistic chance for long-term survival. The aim of this study is to identify surgery-related variables that influence long-term survival. Between 1990 and 2002, 226 consecutive patients (mean age of 64+/-11 years) had resection for pancreatic adenocarcinoma. Prognostic variables in these patients were analyzed using univariate and multivariate analysis. Two hundred four patients (90%) had pancreaticoduodenectomy, 13 patients (6%) had distal pancreatectomy, and 9 patients (4%) had a TP. Stage I disease was present in 50 (22%), stage II disease in 170 (75%), and stage III disease in 6 (3%). R0 resections were achieved in 70%. Operative morbidity was 36% and 30-day mortality was 6%. Actual 1-year, 3-year, and 5-year survival rates were 49% (n=111), 14% (n=31), and 4% (n=9). Using multivariate analysis: tumor size, tumor differentiation, obtaining an R0 resection, and lack of postoperative complications were variables associated with long-term survival. Long-term survival in patients with pancreatic cancer after resection remains poor. Achieving a margin negative resection (R0) with no postoperative complications are prognostic variables that can be affected by the surgeon.


Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Pancreatoyeyunostomía , Adenocarcinoma/patología , Anciano , Femenino , Humanos , Masculino , Venas Mesentéricas/cirugía , Persona de Mediana Edad , Análisis Multivariante , Pancreatectomía , Neoplasias Pancreáticas/patología , Vena Porta/cirugía , Pronóstico , Factores de Riesgo , Análisis de Supervivencia
7.
Mol Cancer Ther ; 4(4): 587-94, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15827332

RESUMEN

Activation of the transcription factor nuclear factor-kappa B (NF-kappa B) has been implicated in pancreatic tumorigenesis. We evaluated the effect of a novel NF-kappa B inhibitor, parthenolide, a sesquiterpene lactone isolated from the herb feverfew, in three human pancreatic tumor cell lines (BxPC-3, PANC-1, and MIA PaCa-2). Parthenolide inhibited pancreatic cancer cell growth in a dose-dependent manner with substantial growth inhibition observed between 5 and 10 micromol/L parthenolide in all three cell lines. Parthenolide treatment also dose-dependently increased the amount of the NF-kappa B inhibitory protein, I kappa B-alpha, and decreased NF-kappa B DNA binding activity. We have previously shown that nonsteroidal anti-inflammatory drugs (NSAID) suppress the growth of pancreatic cancer cells. To determine whether inhibition of the NF-kappa B pathway by parthenolide could sensitize pancreatic cancer cells to NSAID inhibition, BxPC-3, PANC-1, and MIA PaCa-2 cells were treated with parthenolide and the NSAID sulindac, either alone or in combination. Treatment with the combination of parthenolide and sulindac inhibited cell growth synergistically in MIA PaCa-2 and BxPC-3 cells and additively in PANC-1 cells. In addition, treatment with the parthenolide/sulindac combination lowered the threshold for apoptosis. Increased levels of I kappa B-alpha protein were detected, especially in MIA PaCa-2 cells, after treatment with parthenolide and sulindac compared with each agent alone. Similarly, decreased NF-kappa B DNA binding and transcriptional activities were detected in cells treated with the combination compared with the single agents, demonstrating cooperative targeting of the NF-kappa B pathway. These data provide preclinical support for a combined chemotherapeutic approach with NF-kappa B inhibitors and NSAIDs for the treatment of pancreatic adenocarcinoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Sinergismo Farmacológico , FN-kappa B/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Sesquiterpenos/administración & dosificación , Sulindac/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Apoptosis , Western Blotting , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Modelos Biológicos , Fosforilación , Unión Proteica , Transcripción Genética , Transfección
8.
Surgery ; 136(4): 909-16, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15467678

RESUMEN

BACKGROUND: Successful surgical management of pancreatic necrosis can result in structural changes that cause recurrent pancreatitis. The purpose of this study is to review our clinical experience managing recurrent pancreatitis in patients after successful pancreatic debridement. METHODS: We retrospectively reviewed 98 patients with pancreatic necrosis treated by debridement who made a complete recovery at our institution over an 8-year period (January 1995 to January 2003). RESULTS: Fourteen patients (14%) developed recurrent pancreatitis 5 to 39 months (median, 15 months) after recovery. Five patients (36%) had pancreatic pseudocysts and 9 (64%) had radiologic evidence of obstructive pancreatitis. All patients had either a high-grade pancreatic duct stricture (N=7) or complete duct cutoff (N=7), localized to the pancreatic neck (N=10) or proximal pancreatic body (N=4) identified by either endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. Two patients failed endoscopic stent therapy. All patients required re-operative treatment: 6 distal pancreatectomy, 6 pancreatico-jejunostomy Roux-en-Y, and 2 cystojejunostomy Roux-en-Y with no recurrence of pancreatitis after a median follow-up of 22 months. CONCLUSIONS: Recurrent pancreatitis occurs in 14% of patients after successful pancreatic debridement. Pancreatic duct obstruction in the neck or proximal body is the primary etiologic factor. Re-operation directed at alleviating this ductal obstruction by resection or drainage is effective.


Asunto(s)
Desbridamiento/métodos , Páncreas/patología , Conductos Pancreáticos/patología , Pancreatitis Aguda Necrotizante/cirugía , Adulto , Anciano , Constricción Patológica/etiología , Constricción Patológica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Páncreas/cirugía , Enfermedades Pancreáticas/etiología , Enfermedades Pancreáticas/cirugía , Pancreatitis Aguda Necrotizante/complicaciones , Recurrencia , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
9.
Arch Surg ; 138(6): 610-7; discussion 617-8, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12799331

RESUMEN

HYPOTHESIS: Malignant intraductal papillary mucinous neoplasms (IPMNs) can be predicted before surgery. DESIGN: Retrospective review of a prospectively collected database. SETTING: Academic, urban, tertiary care hospital. PATIENTS: Sixty-four consecutive patients with a pathological diagnosis of IPMN. INTERVENTIONS: All 64 patients underwent surgical intervention for IPMN between December 8, 1988, and October 16, 2002. MAIN OUTCOME MEASURES: Reliable predictors of malignancy. RESULTS: The 64 patients underwent 69 operations: 39 pancreaticoduodenectomies, 18 distal pancreatectomies, 7 total pancreatectomies, 4 neck and/or body pancreatectomies, and 1 cystgastrostomy with pancreatic biopsy. Twenty-three of 69 specimens were malignant-12 in situ (high-grade dysplasia) and 11 invasive. In a univariate analysis of 12 clinical signs or symptoms recorded, diabetes mellitus and jaundice showed a significant association with malignancy of IPMN. Of 24 serum chemistry studies, hematologic studies, and tumor marker analyses (in serum, bile, and pancreatic fluid), elevation of serum alkaline phosphatase and glucose levels showed correlation with malignancy. Computed tomography, ultrasound, and endoscopic retrograde cholangiopancreatography findings did not distinguish between benign and malignant tumors. Atypia on preoperative cytologic analysis was specific for malignancy (93%) but lacked the same degree of sensitivity (40% in situ, 91% invasive, and 67% overall). CONCLUSIONS: Malignancy of IPMNs is suggested by new-onset diabetes mellitus, jaundice, and elevations in serum glucose or alkaline phosphatase levels. Atypia on preoperative cytologic testing is the finding most predictive of malignancy. The absence of these features does not predict benign disease. These findings may help guide patient and physician decision making.


Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Papilar/diagnóstico , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , Neoplasias Pancreáticas/diagnóstico , Lesiones Precancerosas/diagnóstico , Adenocarcinoma Mucinoso/sangre , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Papilar/sangre , Adenocarcinoma Papilar/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/cirugía , Lesiones Precancerosas/sangre , Lesiones Precancerosas/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos
10.
Arch Surg ; 139(7): 718-25; discussion 725-7, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15249403

RESUMEN

HYPOTHESIS: Pancreaticoduodenectomy (PD) is a safe procedure for a variety of periampullary conditions. DESIGN: Retrospective review of a prospectively collected database. SETTING: Academic tertiary care hospital. PATIENTS: A total of 516 consecutive patients who underwent PD. MAIN OUTCOME MEASURES: Patient outcomes and survival factors. RESULTS: Pathological examination demonstrated 57% periampullary cancers, 22% chronic pancreatitis, 12% cystic neoplasms, 4% islet cell neoplasms, and 5% other. Fifty-one percent of patients underwent pylorus preservation. Median operating time was 5 hours; blood loss, 1300 mL; and transfusion requirement, 1.5 U. Postoperative complications occurred in 43% of patients, including cardiopulmonary events (15%), fistula (9%), delayed gastric emptying (7%), and sepsis (6%). Additional surgery was required in 3% of patients, most commonly because of bleeding. Perioperative mortality was 3.9% overall but only 1.8% in patients with chronic pancreatitis; 25% of patients who died had preoperative complications associated with their periampullary condition. Three-year survival was 15% after resection for pancreatic cancer, 42% for duodenal cancer, 53% for ampullary cancer, and 62% for bile duct cancer. Univariate predictors of long-term survival in patients with periampullary adenocarcinoma included elevated glucose levels, liver function test results, abnormal tumor markers, blood loss, transfusion requirement, type of operation, and pathologic findings (periampullary adenocarcinoma type, differentiation, and margin and node status). Multivariate predictors were serum total bilirubin level, blood loss, operation type, diagnosis, and lymph node status. CONCLUSIONS: Pancreaticoduodenectomy continues to be associated with considerable morbidity. With careful patient selection, PD can be performed safely. Long-term survival in patients with periampullary adenocarcinoma can be predicted by preoperative laboratory values, intraoperative factors, and pathologic findings.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática , Neoplasias de los Conductos Biliares/cirugía , Quimioterapia Adyuvante , Neoplasias Duodenales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomía/métodos , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Estudios Retrospectivos
11.
Am J Surg ; 186(5): 468-71, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14599608

RESUMEN

BACKGROUND: Because of limited resources and common barriers to widespread screening, the Surgery Service of the Indianapolis Veterans Affairs Medical Center has focused its colorectal screening program on patients undergoing hernia repair. Our objective was to examine the success, safety, pathology results, and educational benefit of this nontraditional screening program. METHODS: The study was a retrospective analysis of a prospectively collected database (1991 to 2002). Initial screening colonoscopy was performed on 263 average-risk Veterans Affairs patients, 217 (83%) in conjunction with hernia repair. Visualized polyps were removed or biopsied during colonoscopy and pathology reports for all specimens were examined. Results were compared with published screening studies. RESULTS: Complete colonoscopy, defined as cecal intubation, was performed in 93% of initial screening colonoscopies. There were no major complications, including perforation, excessive bleeding, or death, from colonoscopy. Initial colonoscopy showed adenomas in 67 patients (25%), hyperplastic polyps in 34 (13%), and invasive cancer in 4 (1.5%). Follow-up endoscopies revealed cancer in 2 additional patients, 3 and 5 years after initial screening. CONCLUSIONS: This program is an important training resource for surgical residents. Screening colonoscopy performed in conjunction with hernia repair has produced results consistent with more conventional methods. The Surgery Service at the Indianapolis Veterans Affairs Medical Center is providing colorectal cancer screening with a high degree of safety and success in the face of limited resources and common barriers to implementation of widespread screening.


Asunto(s)
Neoplasias del Colon/diagnóstico , Colonoscopía , Tamizaje Masivo/economía , Neoplasias del Recto/diagnóstico , Colonoscopía/economía , Costos y Análisis de Costo , Bases de Datos Factuales , Femenino , Herniorrafia , Hospitales de Veteranos , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , United States Department of Veterans Affairs
12.
Am J Surg ; 186(5): 486-92, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14599612

RESUMEN

BACKGROUND: Prognostic markers for pancreas cancer, such as CEA, CA19-9, ploidy analysis, and S-phase determination using flow cytometry, have not been consistently predictive. We chose to evaluate nuclear proliferation, as measured by the MIB-1 monoclonal antibody and digital image analysis, as a prognostic marker in pancreatic carcinoma, and compare the findings with DNA ploidy and S-phase analysis. MIB-1 identifies the Ki67 antigen present in nuclei of cells in all phases of the cell cycle except G0. METHODS: We retrospectively reviewed 33 patients with pancreatic adenocarcinoma resected for cure between 1989 and 1994 with available fixed tissue. Sectioned tissue was stained with MIB-1, and the number of positively stained nuclei determined and expressed as a MIB-1 labeling index (LI) by quantitative image analysis. Disaggregated nuclei were analyzed by flow cytometry using standard techniques. RESULTS: MIB-1 LI for pancreas cancers was heterogeneous within and between cancers. The MIB-1 LI for the cancers was 28 +/- 15 (median 29). There was no correlation between survival and MIB-1 expression (R(2) = 0.03). Likewise, there was no correlation between MIB-1 LI and percentage of cells in S-phase, G(2)/M, or total proliferating cells (S+G(2)/M; R(2) = 0.01), nor was there a difference between MIB-1 LI and ploidy (P = 0.88). CONCLUSIONS: We conclude that in our patient population, nuclear proliferation in pancreatic cancer, as determined by expression of Ki67 nuclear antigen, does not appear to correlate with survival and is not a useful prognostic marker. Despite intuitive thoughts to the contrary, there is no correlation between cell cycle analysis as determined by flow cytometry and Ki67 expression in pancreas cancer. Current methods of assessing prognosis after curative resection of cancer of the pancreas, including lymph node and margin status, tumor size, and possibly DNA ploidy as determined by flow cytometry, are not augmented by the assessment of nuclear proliferation by image analysis using the MIB-1 monoclonal antibody.


Asunto(s)
Carcinoma Ductal Pancreático/mortalidad , ADN de Neoplasias/análisis , Antígeno Ki-67/metabolismo , Pancreatectomía , Anticuerpos Antinucleares , Anticuerpos Monoclonales , Biomarcadores de Tumor/análisis , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirugía , Ciclo Celular , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Ploidias
13.
JAMA Surg ; 148(3): 285-91; discussion 291, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23552812

RESUMEN

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) and risk-reducing mastectomy are widely used for BRCA1 and BRCA2 mutation carriers to reduce the risk of ovarian and breast cancer. To our knowledge, no risk-reduction therapy has addressed the BCRA1/2 carrier lifetime risk of intra-abdominal peritoneal carcinoma from an appendix source. We identified a BRCA1 carrier in a hereditary breast and ovarian cancer kindred who developed a low-grade malignant appendiceal mucocele 2 years after risk-reducing salpingo-oophorectomy. Our retrospective meta-analysis assessed the risk of intraperitoneal appendiceal cancer in BRCA1/2 carriers after RRBSO to determine whether elective risk-reduction appendectomy could reduce the incidence of intraperitoneal cancer. Data sources included the case report and 12 reports of BRCA1 and BRCA2 carriers after RRBSO with ovarian, fallopian tube, breast, and peritoneal cancer published from January 1, 1985, through April 30, 2012. Main outcome measures were nonovarian, non-fallopian tube, nonbreast, positive intra-abdominal peritoneal carcinoma in previously cancer-free BRCA1/2 carriers after RRBSO. The source of intraperitoneal cancer in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy is highly likely the appendix. Use of risk-reduction appendectomy with RRBSO in younger BRCA1/2 carriers may reduce lifetime risk of malignant tumor and eliminate intraperitoneal cancer.


Asunto(s)
Apendicectomía , Neoplasias del Apéndice/genética , Neoplasias del Apéndice/prevención & control , Genes BRCA1 , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/prevención & control , Adulto , Femenino , Humanos , Conducta de Reducción del Riesgo
14.
Case Rep Oncol ; 5(1): 202-7, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22649340

RESUMEN

Metastatic colorectal cancer represents a major health problem in the US and worldwide. Forty percent of patients undergoing resection of the primary tumor will experience relapse. In this brief review, we describe a case of a woman with metastatic disease and long-term survival culminating with an unusual myocardial recurrence. Over three decades, a multimodality approach has evolved to allow for long-term survival in selected patients with metastatic colorectal cancer. In this case report, the role of multiple aggressive surgical resections is emphasized.

15.
Ann Gastroenterol ; 25(4): 361-364, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-24714263

RESUMEN

We report a rare case of right-sided colobronchial fistula in a 47-year-old, severely malnourished male with a history of regional enteritis and recurrent right lower and middle lobe pneumonias medically managed with the addition of the immunomodulator infliximab prior to surgery. On admission, evaluation of sputum cultures and chest radiograph pattern of pneumonia led to the suspicion of colobronchial fistula. This diagnosis was confirmed by abdominal CT enteroclysis. This patient's pneumonia was initially treated with empiric antibiotics, then focused antibiotics based on culture results. The treatment for the regional enteritis and the secondary colobronchial fistula consisted of immunosuppression with infliximab, bowel rest, and total parenteral nutrition. The patient was discharged on a limited course of prednisone and received maintenance therapy with 3mg/kg IV infliximab infusions for four additional treatments with dramatic improvement in his clinical condition. Surgical therapy consisted of only bowel resection; no thoracic surgery or lung resection was necessary. The patient has had a dramatic improvement in his clinical condition and is currently disease-free on no maintenance therapy. The use of TNF-blocking agents such as infliximab may simplify the surgical approach in patients with complicated fistulous Crohn's disease.

17.
AMIA Annu Symp Proc ; 2012: 154-63, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23304284

RESUMEN

Perioperative care is complex and involves multiple interconnected subsystems. Delayed starts, prolonged cases and overtime are common. Surgical procedures account for 40-70% of hospital revenues and 30-40% of total costs. Most planning and scheduling in healthcare is done without modern planning tools, which have potential for improving access by assisting in operations planning support. We identified key planning scenarios of interest to perioperative leaders, in order to examine the feasibility of applying combinatorial optimization software solving some of those planning issues in the operative setting. Perioperative leaders desire a broad range of tools for planning and assessing alternate solutions. Our modeled solutions generated feasible solutions that varied as expected, based on resource and policy assumptions and found better utilization of scarce resources. Combinatorial optimization modeling can effectively evaluate alternatives to support key decisions for planning clinical workflow and improving care efficiency and satisfaction.


Asunto(s)
Toma de Decisiones , Quirófanos/organización & administración , Atención Perioperativa , Flujo de Trabajo , Técnica Delphi , Eficiencia Organizacional , Humanos , Entrevistas como Asunto , Modelos Organizacionales , Sistemas de Información en Quirófanos
18.
J Gastrointest Surg ; 14(11): 1813-9, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20697832

RESUMEN

AIM: The aim of the study was to determine the impact of replaced or accessory right hepatic artery (RARHA) during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). METHODS: Four hundred seventy-one consecutive patients underwent PD for PA at the two institutions; 47 patients (10%) had RARHA: 16 patients (neoRARHA group) received neoadjuvant chemoradiation, and 31 patients did not receive preoperative treatment (RARHA group). Thirty-one matched patients without RARHA comprised our control group. RESULTS: RARHA was preserved in 44 patients; three patients with involved RARHA had reconstruction (n = 2) or ligation (n = 1). Patients with R1 resection (n = 8) had tumor size ≥3 cm. Patients in the neoRARHA group had identical positive margin rate when compared with patients in RARHA group (p = 0.6). No difference was noted in median or 3-year overall survival times between RARHA group and control group. Two patients in RARHA group with involved RARHA died of disease progression after 6 and 12 months of follow-up. One patient in neoRARHA group with involved RARHA was still alive without recurrence after 28 months' follow-up. CONCLUSIONS: Pathologic findings did not show increased positive margins despite preservation of RARHA. In contrast, patients with frank RARHA involvement seemed to have poor survival. Thus, patients with suspicion of involved RARHA should be considered for neoadjuvant chemoradiation.


Asunto(s)
Adenocarcinoma/cirugía , Arteria Hepática/anomalías , Arteria Hepática/cirugía , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía/métodos , Tasa de Supervivencia
19.
Surgery ; 148(4): 814-23, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20797748

RESUMEN

BACKGROUND: Minimally invasive techniques and even robotics in pancreaticobiliary surgery are being used increasingly. Cost-effectiveness is a practical burden associated with the introduction of surgical innovation. This study compares the costs and the outcomes of open, laparoscopic, and robotic distal pancreatectomies. We hypothesized that robotic distal pancreatectomy is cost-effective. METHODS: Between August 2008 and August 2009, 77 distal pancreatectomies were performed at a single academic medical center. A retrospective analysis of prospectively collected data on demographics, short-term outcomes, and direct cost was performed. RESULTS: Thirty-two open distal pancreatectomies, 28 laparoscopic distal pancreatectomies, and 17 robotic distal pancreatectomies were performed. Age, American Society of Anesthesia preoperative risk score, and specimen length were similar. Indications for laparoscopic distal pancreatectomies and robotic distal pancreatectomies included more cystic neoplasms (49%) and fewer malignancies (29%) versus open distal pancreatectomies (16% and 47%). Spleen preservation occurred in 65% robotic distal pancreatectomies versus 12% and 29% in open distal pancreatectomies and laparoscopic distal pancreatectomies (P < .05). The operative time averaged 298 minutes in robotic distal pancreatectomies versus 245 and 222 minutes in open distal pancreatectomies and laparoscopic distal pancreatectomies (P < .05). Blood loss and morbidity were similar with no mortality. The length of stay was 4 days in robotic distal pancreatectomies versus 8 and 6 in open distal pancreatectomies and laparoscopic distal pancreatectomies (P < .05). The total cost was $10,588 in robotic distal pancreatectomies versus $16,059 and $12,986 in open distal pancreatectomies and laparoscopic distal pancreatectomies. CONCLUSION: These data suggest direct hospital costs are comparable among all groups. They suggest a shorter length of stay in robotic versus laparoscopic or open approaches. Finally, spleen and vessel preservation rates may improve with a robotic approach at the expense of increased operative time. In summary, robotic distal pancreatectomy is safe and cost effective in selected cases.


Asunto(s)
Laparoscopía/economía , Pancreatectomía/economía , Robótica/economía , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía
20.
HPB Surg ; 2009: 404520, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19461951

RESUMEN

Pancreatic fistula continues to be a common complication following PD. This study seeks to identify clinical factors which may predict pancreatic fistula (PF) and evaluate the effect of PF on outcomes following pancreaticoduodenectomy (PD). We performed a retrospective analysis of a clinical database at an academic tertiary care hospital with a high volume of pancreatic surgery. Five hundred ten consecutive patients underwent PD, and PF occurred in 46 patients (9%). Perioperative mortality of patients with PF was 0%. Forty-five of 46 PF (98%) closed without reoperation with a mean time to closure of 34 days. Patients who developed PF showed a higher incidence of wound infection, intra-abdominal abscess, need for reoperation, and hospital length of stay. Multivariate analysis demonstrated an invaginated pancreatic anastomosis and closed suction intraperitoneal drainage were associated with PF whereas a diagnosis of chronic pancreatitis and endoscopic stenting conferred protection. Development of PF following PD in this series was predicted by gender, preoperative stenting, pancreatic anastomotic technique, and pancreas pathology. Outcomes in patients with PF are remarkable for a higher rate of septic complications, longer hospital stays, but in this study, no increased mortality.


Asunto(s)
Fístula Pancreática/etiología , Pancreaticoduodenectomía , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anastomosis Quirúrgica , Femenino , Humanos , Incidencia , Indiana/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Fístula Pancreática/epidemiología , Complicaciones Posoperatorias/epidemiología , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no Paramétricas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA