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1.
Ann Oncol ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38866180

RESUMEN

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer. At the first interim analysis, the trial met one of its dual-primary endpoints with statistically significant progression-free survival benefits in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase 3, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer who were randomly assigned (1:1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual-primary endpoint. RESULTS: A total of 494 patients were randomized (245 in dostarlimab arm; 249 in placebo arm). In the overall population, with 51% maturity, RUBY met the dual-primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death (HR = 0.69; 95% CI, 0.54-0.89; P = 0.0020) in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32; 95% CI, 0.17-0.63; nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair proficient/microsatellite stable (MMRp/MSS) population (HR = 0.79; 95% CI, 0.60-1.04; nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful overall survival benefit in the overall population of patients with primary advanced or recurrent endometrial cancer while demonstrating an acceptable safety profile.

2.
Gynecol Oncol ; 163(2): 312-319, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34563366

RESUMEN

OBJECTIVE: Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers. METHODS: A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts. RESULTS: Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types. CONCLUSIONS: The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMBH. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMBH. The incidence of 'triple positive" cases was less than 2%.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de los Genitales Femeninos/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inestabilidad de Microsatélites , Antígeno B7-H1 , Toma de Decisiones Clínicas/métodos , Resistencia a Antineoplásicos/genética , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Mutación , Selección de Paciente
3.
Ann Oncol ; 30(5): 721-732, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30887020

RESUMEN

BACKGROUND: Ovarian cancer remains the most deadly gynecologic cancer with the majority of patients relapsing within 3 years of diagnosis. Traditional treatment paradigms linked to platinum sensitivity or resistance are currently being questioned in the setting of new diagnostic methods and treatment options. DESIGN: Authors carried out review of the literature on key topics in treatment of recurrent epithelial ovarian cancer (EOC) when platinum is still an option; including secondary surgical cytoreduction, chemotherapy, novel treatment options, and maintenance therapy. A treatment algorithm is proposed. RESULTS: Molecular characterization of EOC is critical to help guide treatment decisions. The role of secondary cytoreductive surgery is currently being evaluated with results from Gynecologic Oncology Group (GOG) 213 and anticipated results from DESKTOP III clinical trials. Chemotherapy backbone has remained relatively unchanged but utilizing non-platinum-based regimens is under investigation. In addition, maintenance therapy with anti-angiogenic therapy and Poly (ADP-ribose) Polymerase (PARP) inhibitors has emerged as the standard of care. Novel combinations, including immunotherapy and anti-angiogenesis agents, may further change the current landscape. CONCLUSIONS: The treatment of recurrent EOC is rapidly changing. Clinical trial design will need to continue to evolve as many novel therapies move to the upfront setting. Ultimately, the treatment of patients with recurrent EOC must incorporate individual patient and tumor factors.


Asunto(s)
Carcinoma Epitelial de Ovario/terapia , Recurrencia Local de Neoplasia/terapia , Compuestos Organoplatinos/uso terapéutico , Neoplasias Ováricas/terapia , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Humanos , Inmunoterapia/métodos , Terapia Molecular Dirigida , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología
4.
Gynecol Oncol ; 155(2): 186-191, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31519320

RESUMEN

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Anciano , Carcinoma Epitelial de Ovario/mortalidad , Supervivencia sin Enfermedad , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Indazoles , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Calidad de Vida , Resultado del Tratamiento , Adulto Joven
5.
Ann Oncol ; 29(3): 737-743, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29267856

RESUMEN

Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.


Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Quimioterapia de Mantención/efectos adversos , Neoplasias Ováricas/tratamiento farmacológico , Pirimidinas/efectos adversos , Calidad de Vida , Sulfonamidas/efectos adversos , Adulto , Inhibidores de la Angiogénesis/efectos adversos , Método Doble Ciego , Femenino , Humanos , Indazoles , Quimioterapia de Mantención/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Supervivencia sin Progresión , Tiempo de Tratamiento
7.
Zentralbl Chir ; 141(6): 625-629, 2016 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-27501071

RESUMEN

Background: Postoperative pancreatic fistulas (POPF) remain a major concern after distal pancreatectomy. Irrespective of the technique to close the pancreatic remnant, pancreatic fistulas will occur in approximately 30 % of patients undergoing distal pancreatectomy. For the first time ever, autologous fibrin sealant (Vivostat®) was used to additionally seal the pancreatic remnant after a distal pancreatectomy. The aim was to analyse whether this changes the postoperative outcome. Patients/Material and Methods: In 2015, a technical case series was performed in 15 patients who underwent distal pancreatectomy. The pancreatic remnant was additionally sealed with autologous fibrin sealant (Vivostat®). Results: A postoperative pancreatic fistula (POPF) occurred in 5/15 patients (33 %). One patient had a POPF grade A (1/15, 6.7 %), whereas a POPF grade B occurred in 4/15 patients (26.7 %). 75 % (3/4) of the patients with a POPF grade B were sufficiently treated with antibiotics, whereas a CT-guided percutaneous drainage had to be placed only in one case. Conclusion: Autologous fibrin sealant is simple to apply and seems to be well tolerated. However, it does not seem to avoid the development of postoperative pancreatic fistulas after distal pancreatectomy.


Asunto(s)
Adhesivo de Tejido de Fibrina/uso terapéutico , Pancreatectomía/métodos , Fístula Pancreática/prevención & control , Neoplasias Pancreáticas/secundario , Neoplasias Pancreáticas/cirugía , Pancreatitis Crónica/cirugía , Complicaciones Posoperatorias/prevención & control , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fístula Pancreática/clasificación , Fístula Pancreática/terapia , Resultado del Tratamiento
8.
Sci Rep ; 14(1): 3861, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38360826

RESUMEN

Laser beam directed energy deposition (DED-LB) is an attractive additive manufacturing technique to produce versatile and complex 3D structures on demand, apply a cladding, or repair local defects. However, the quality of manufactured parts is difficult to assess by inspection prior to completion, and parts must be extensively inspected post-production to ensure conformance. Consequently, critical defects occurring during the build go undetected. In this work, a new monitoring system combining three infrared cameras along different optical axes capable of monitoring melt pool geometry and vertical displacement throughout deposition is reported. By combining multiple sensor data, an automated algorithm is developed which is capable of identifying the formation of structural features and defects. An intersecting, thin-walled geometry is used to demonstrate the capability of the system to detect process-induced porosity in samples with narrow intersection angles, which is validated using micro-CT observations. The recorded results indicate the root cause of this process-induced porosity at the intersection, and it is shown that advanced toolpath planning can eliminate such defects. The presented methodology demonstrates the value of multi-axis monitoring for identifying both defects and structural features, providing an advancement towards automated detection and alert systems in DED-LB.

9.
Zentralbl Chir ; 137(6): 559-64, 2012 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-23264197

RESUMEN

BACKGROUND: After pancreatic head resection the reconstruction of small and fragile bile ducts is technically demanding, resulting in more postoperative bile leaks. One option for the reconstruction is the placement of a T-tube drainage at the site of the anastomosis. MATERIAL AND METHODS: Standard reconstruction after pancreatic head resection was an end-to-side hepaticojejunostomy with PDS 5.0, 15-25 cm distally from the pancreaticojejunostomy. For patients with a small bile duct diameter (≤ 5 mm) or a fragile bile duct wall the reconstruction was performed with PDS 6.0 and a T-tube drainage at the side of the anastomosis. RESULTS: The reconstruction with a T-tube drainage at the site of the anastomosis is technically easy to perform and offers the opportunity for immediate visualisation of the anastomosis in the postoperative period by application of water soluble contrast medium. If a bile leak occurs, biliary deviation through the T-tube drainage can enable a conservative management without revisional laparotomy in selected patients. Whether or not a conservative management of postoperative bile leaks will lead to more bile duct strictures is a subject for further investigations. CONCLUSION: A T-tube drainage at the site of the anastomosis can probably not prevent postoperative bile leaks from a difficult hepaticojejunostomy, but in selected patients it offers the opportunity for a conservative management resulting in less re-operations. Therefore we recommend the augmentation of a difficult hepaticojejunostomy with a T-tube drainage.


Asunto(s)
Anastomosis Quirúrgica/instrumentación , Conductos Biliares Extrahepáticos/cirugía , Fístula Biliar/cirugía , Colestasis Extrahepática/cirugía , Drenaje/instrumentación , Yeyunostomía/instrumentación , Pancreatectomía , Complicaciones Posoperatorias/cirugía , Implantación de Prótesis/instrumentación , Fístula Biliar/diagnóstico , Fístula Biliar/prevención & control , Pancreatocolangiografía por Resonancia Magnética , Colestasis Extrahepática/diagnóstico , Constricción Patológica/cirugía , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quiste Pancreático/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control , Diseño de Prótesis , Reoperación , Factores de Riesgo , Tomografía Computarizada por Rayos X
10.
Acta Chir Belg ; 111(6): 378-83, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22299325

RESUMEN

INTRODUCTION: Diverticular disease of the colon is a common condition in developed countries. For perforated diverticulitis Hartmann's procedure is a safe and quick treatment option. But intestinal restoration needs further interventions. This leads to high complication rates and cost. Therefore a critical evaluation of surgical treatment options is necessary. METHODS: During a period of 18 months 88 patients underwent surgical resection for diverticulitis. Forty patients had emergency surgery. Among those a primary anastomosis was performed in 21 patients. The other 19 patients had interval colostomy. Among 21 patients with primary anastomosis major complications occurred in two patients, vs. twelve in patients with Hartmann's operation (p = 0.03). In the Hartmann group eight patients had major general complications, vs. one patient in the group with primary anastomosis (p = 0.06). The mean hospital stay was 38 days after Hartmann's procedure, vs. 13 days for patients with primary anastomosis (p < 0.01). CONCLUSION: In emergency surgery for complicated diverticulitis primary anastomosis is not associated with an increased postoperative morbidity. A primary anastomosis reduces the need for further surgical interventions and complex re-operations. Thus, an overall reduction of morbidity, cost, complication rate and hospital stay is possible. Therefore this technique is advantageous for patients and hospitals.


Asunto(s)
Colostomía , Diverticulitis del Colon/mortalidad , Diverticulitis del Colon/cirugía , Ileostomía , Enfermedades del Sigmoide/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/métodos , Colostomía/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Diverticulitis/mortalidad , Diverticulitis/cirugía , Urgencias Médicas , Femenino , Estudios de Seguimiento , Humanos , Ileostomía/efectos adversos , Perforación Intestinal/complicaciones , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Peritonitis/complicaciones , Peritonitis/etiología , Peritonitis/cirugía , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
11.
Eur J Med Res ; 15(12): 525-32, 2010 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-21163727

RESUMEN

The management of severe intra-abdominal infections remains a major challenge facing surgeons and intensive care physicians, because of its association with high morbidity and mortality. Surgical management and intensive care medicine have constantly improved, but in the recent years a rapidly continuing emergence of resistant pathogens led to treatment failure secondary to infections with multi-drug resistant bacteria. In secondary peritonitis the rate of resistant germs at the initial operation is already 30 %. The lack of effective antibiotics against these pathogens resulted in the development of new broad-spectrum compounds and antibiotics directed against resistant germs. But so far no "super-drug" with efficacy against all resistant bacteria exists. Even more, soon after their approval, reports on resistance against these novel drugs have been reported, or the drugs were withdrawn from the market due to severe side effects. Since pharmaceutical companies reduced their investigations on antibiotic research, only few new antimicrobial derivates are available. - In abdominal surgery you may be in fear that in the future more and more patients with tertiary peritonitis secondary to multi-drug resistant species are seen with an increase of mortality after secondary peritonitis. - This article reviews the current treatment modalities for complicated intra-abdominal infections with special reference to the antibiotic treatment of complicated intra-abdominal infections with multi-drug resistant species.


Asunto(s)
Abdomen/patología , Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Microbiana , Resistencia a Múltiples Medicamentos , Humanos
12.
J Phys Chem A ; 113(6): 1033-9, 2009 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-19143542

RESUMEN

The dynamics of the ring-closure reaction of three different bis(thiophen-3-yl)maleimides are investigated using ultrafast spectroscopy in the visible range. The structures of the molecules differ with respect to substitution of the thiophene ring and the maleimide. The experiments reveal reaction kinetics which point to the population of an excited electronic state for several nanoseconds. In the case of completely unsubstituted thiophene rings, a long excited-state lifetime (biexponential decay with 3 and 15 ns) can be observed. The remaining ultrafast absorption transients of this molecule are due to relaxational processes on the excited electronic potential energy surface. The ring-closure reaction has a small yield (<1%) and does not show up in the ultrafast absorption experiments. A dimethyl substitution of the thiophene ring results in completely different behavior: after transients related to relaxation in the excited electronic state, one finds pronounced absorption transients with tau = 16 ps which represent the partial decay of the excited electronic state and the formation of the ring-closed isomer. Another fraction of the emitting excited electronic state decays again on the few nanosecond time scale. The experiments suggest that the open isomer of the dimethyl-substituted imides exists in two conformations.


Asunto(s)
Luz , Maleimidas/química , Color , Etilenos/química , Fluorescencia , Procesos Fotoquímicos , Espectrofotometría Ultravioleta , Factores de Tiempo
13.
Int J Gynecol Cancer ; 18(5): 879-90, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18053062

RESUMEN

Epidermal growth factor receptor (EGFR) inhibitors are a new biologically targeted therapy, which may offer new hope in the treatment of patients with advanced or recurrent ovarian cancers. In this review, we summarize and discuss the results of research to date on EGFR inhibitors with particular emphasis on ovarian cancer. We reviewed data identified by searches of MEDLINE, PubMed, and abstracts from the proceedings of the American Society of Clinical Oncology meetings from 1998 to 2006, with the search terms "Ovarian Cancer,""EGFR,""gefitinib, ZD1839, Iressa,""erlotinib, OSI-774, Tarceva,""CI-1033,"" GW 572016, lapatinib,""PKI-166,""EKB 569,""anti-EGFR antibodies,""trastuzumab, Herceptin,""cetuximab, Erbitux, IMC-C225,""matuzumab, EMD 72000,""panitumamab, ABX-EGF,""pertuzumab," and "vandetanib, rINN, Zactima, ZD6474." Phase II trials of both small molecule inhibitors of EGFR- and antibody-based inhibitors are currently ongoing in ovarian cancer and emerging data suggest that their activity in unselected women with advanced or recurrent ovarian cancer is modest, when utilized as a single agent. It is possible that these agents will be highly effective in smaller subsets of patients whose tumors are dependent on EGFR signaling, perhaps through activating mutations in EGFR or its downstream pathway. Targeted therapy with EGFR inhibitors is an untapped potential resource in the treatment of advanced or recurrent ovarian cancer. Ongoing trials will elucidate the most effective strategies to use these agents individually or in combination with traditional chemotherapeutic agents.


Asunto(s)
Antineoplásicos/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Ováricas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Ensayos Clínicos como Asunto , Receptores ErbB/metabolismo , Femenino , Humanos , Ligandos , Neoplasias Ováricas/enzimología
15.
J Med Case Rep ; 12(1): 85, 2018 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-29576017

RESUMEN

BACKGROUND: Pancreatic injuries are rare in cases of blunt abdominal trauma and therefore easily misdiagnosed at time of hospital admission. They are associated with a significantly elevated morbidity and lethality. Bicycle handlebar injuries are the most common cause of pancreatic trauma in children and adolescents. CASE PRESENTATION: We report two cases of a 23-year-old Caucasian woman and a 15-year-old Caucasian boy who presented to our clinic with a similar history of a bicycle accident on 2 consecutive days. Both suffered from a fall from a bicycle with bicycle handlebar injury 4 and 6 days prior to admission in our clinic. Emergency distal pancreatectomies were performed in both cases. CONCLUSIONS: Pancreatic injuries must be highly suspected in bicycle handlebar injuries, even if amylase/lipase levels or ultrasound findings seem unremarkable. The best initial strategies are early computed tomography and a quick referral to a level 1 trauma center. Distal pancreatectomy is the treatment of choice in cases of complete rupture of the pancreatic body.


Asunto(s)
Traumatismos Abdominales/complicaciones , Traumatismos Abdominales/cirugía , Ciclismo/lesiones , Páncreas/lesiones , Pancreatectomía , Rotura/cirugía , Heridas no Penetrantes/complicaciones , Adolescente , Cuidados Críticos/métodos , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Páncreas/cirugía , Rotura/etiología , Resultado del Tratamiento , Heridas no Penetrantes/cirugía , Adulto Joven
16.
Clin Nephrol ; 68(6): 357-66, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18184517

RESUMEN

AIMS: There are discrepant data on the prevalence of vascular compression of the rostral ventrolateral medulla, discussed as a possible cause of essential hypertension, in patients with essential and secondary hypertension. We therefore evaluated the comparative prevalence of neurovascular compression in two large and well defined patient groups with severe essential and secondary hypertension. PATIENTS AND METHODS: 121 patients with long-standing severe (requiring at least three antihypertensive agents for adequate control of blood pressure) essential or secondary hypertension and extensive examination for causes of secondary hypertension were recruited. The presence of neurovascular compression was assessed independently by a neuroradiologist and a neurosurgeon in MRI images for all patients. The subgroup of patients with the highest prevalence of neurovascular compression was identified by CART-analysis. RESULTS: 5 of 121 formerly included patients (4.1%) were excluded for diverging MRI assessments. Neurovascular compression was diagnosed in 50 of 68 patients (73.5%) with essential hypertension and 6 of 48 patients (12.5%) with secondary hypertension. The odds ratio for diagnosis of neurovascular compression in patients with essential hypertension was 19.4 (95%-confidence interval 7.9-47.9) compared to patients with secondary hypertension. CART-analysis identified the highest prevalence of neurovascular compression in patients with severe essential hypertension younger than 67.5 years. CONCLUSIONS: Since successful decompression or implantation of a carotid sinus stimulator in patients eligible for surgery may lead to substantial improvement in blood pressure in patients in whom blood pressure could not be lowered below 140/90 mmHg by antihypertensive treatment alone MRI screening for the presence of neurovascular compression is justified in patients meeting all of the following three criteria: exclusion of secondary hypertension after extensive examination; hypertension uncontrollable with antihypertensive treatment alone, and age younger than 67.5 years.


Asunto(s)
Hipertensión/complicaciones , Síndromes de Compresión Nerviosa/epidemiología , Síndromes de Compresión Nerviosa/etiología , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia
17.
Eur Eat Disord Rev ; 15(6): 430-8, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17726661

RESUMEN

There are contradictory results concerning the frequency of borderline personality disorder (BPD) in bulimic patients and its impact on eating pathology and treatment outcome. We evaluated 240 patients with bulimia nervosa using EDI-2, SIAB and SCL-90-R. Only a minority of patients had a BPD (13.8%). There were no differences in binging or purging behaviour between patients with and without BPD, but borderline patients had significantly more feelings of ineffectiveness and more disturbances in interoceptive awareness. Bulimic patients with BPD showed significantly more general psychopathology. Although, BPD patients started with higher levels of pathology, there were similar reductions of symptoms over the course of treatment in both groups. Psychotherapy in bulimic patients with a BPD has to focus not only on eating pathology but also on aspects that are caused by the severe personality disturbance.


Asunto(s)
Trastorno de Personalidad Limítrofe , Bulimia Nerviosa , Adolescente , Adulto , Edad de Inicio , Trastorno de Personalidad Limítrofe/diagnóstico , Trastorno de Personalidad Limítrofe/epidemiología , Trastorno de Personalidad Limítrofe/terapia , Bulimia Nerviosa/diagnóstico , Bulimia Nerviosa/epidemiología , Bulimia Nerviosa/terapia , Comorbilidad , Femenino , Humanos , Masculino , Prevalencia , Psicoterapia de Grupo , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
18.
J Gastrointest Surg ; 21(2): 344-351, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27826941

RESUMEN

PURPOSE: Circumportal pancreas is a rare congenital pancreatic anomaly with encasement of the portal vein and/or the superior mesenteric vein by pancreatic tissue. It is often overlooked on cross-sectional imaging studies and can be encountered during pancreatic surgery. Pancreatic head resection with circumportal pancreas is technically difficult and bears an increased risk of postoperative pancreatic fistula. MATERIALS AND METHODS: A retrospective chart review of our data base for all patients who had undergone pancreatic head resection between 2004 and 2015 was performed. RESULTS: We identified six patients out of 1102 patients who had undergone pancreatic head surgery in the study period. CT-scan and MRI were never able to identify circumportal pancreas prior to surgery. The right hepatic an artery derived from the superior mesenteric artery in four cases (67%). Additional resection of the pancreatic body was always performed. Postoperative course was uneventful in all cases without occurrence of pancreatic fistula. CONCLUSIONS: Circumportal pancreas is a rare entity every pancreatic surgeon should be aware of. It is difficult to identify on cross-sectional imaging studies. A right hepatic artery arising from the superior mesenteric artery should raise suspicion of circumportal pancreas. Additional pancreatic tissue resection should be performed during pancreatic head resections to avoid pancreatic fistula.


Asunto(s)
Páncreas/anomalías , Páncreas/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Femenino , Arteria Hepática , Humanos , Masculino , Arteria Mesentérica Superior , Venas Mesentéricas , Persona de Mediana Edad , Páncreas/cirugía , Pancreatectomía , Vena Porta , Estudios Retrospectivos
20.
Cancer Res ; 55(9): 1922-6, 1995 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-7728760

RESUMEN

Thirty-seven endometrial cancers were subjected to an allelotype analysis in an attempt to identify chromosomal regions that are lost in a significant portion of tumors and to identify tumors characterized by replication errors. Thirty-nine highly polymorphic microsatellite markers representing all chromosomal arms, excluding the X and the short arms of the acrocentrics, were examined. An average of 20 informative cases were evaluated for each marker. Genetic alterations were detected in 30 of the 37 tumors. Replication errors were identified in 8 tumor specimens. Loss of heterozygosity was observed for loci on all chromosomes examined with the exception of chromosomes 4 and 20. The two most frequent sites of loss were at the marker loci examined on 10q (40%) and 17p (29%). Six additional simple sequence repeat markers from 10q were genotyped in an effort to refine the region of 10q loss. The chromosome 10 markers used in these studies were physically mapped with the use of a panel of somatic hybrids that retain defined portions of chromosome 10. The observed patterns of loss of sequences on 10q suggest a role for a tumor suppressor gene in the 10q23-26 region in the development or progression of endometrial cancers.


Asunto(s)
Alelos , Cromosomas Humanos Par 10 , Replicación del ADN , Neoplasias Endometriales/genética , Eliminación de Gen , Mapeo Cromosómico , ADN/genética , ADN de Neoplasias/genética , ADN Satélite/genética , Femenino , Genes Supresores de Tumor , Humanos , Cariotipificación , Polimorfismo Genético
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